bluuebunny/crossref_metadata_2025 huggingface dataset:
The adoption features of government initiatives for the Curriculum Reform in Hong Kong schools
Authors: Wong Ping-Man , Cheung Alan
Published: July 2014

This article is one of a series of papers generated from the Curriculum Reform study in Hong Kong with the purpose of understanding the impact of government’s role in the change process of the reform. This paper specifically examines the 17 government initiatives in the Curriculum Reform in terms of their adoption percentages of schools from before 2000 to 2006–7. These initiatives can be regarded as ‘soft’ measures of the Government, supplementing the hard policies on the Curriculum Reform. The adoption of these initiatives in schools reflects the extent of implementation of reform items and therefore should be crucial to the success of the Curriculum Reform. The study illustrates the impact of the government on the phase of adoption in the change process. The findings suggested that whereas the government initially played an important role in adoption of these initiatives it was not able to raise the adoption percentages further towards the end of the study. Other features of adoption and their impacts on policy and change are also discussed.
Women in educational leadership
Authors: Diko Nolutho
Published: July 2014

The Constitution of the Republic of South Africa, 1996 confers equality on all South African citizens regardless of race and gender. It has been reported that, under apartheid, gender inequality was a way of life and even social liberation movements observed it. Education is not exempt from gender inequality; the Department of Education in 2003 produced the Gender Equality In Education policy. The then Minister of Education committed to the policy and adopted the mainstreaming of gender and the training of education administrators in the implementation of gender equity programmes. Despite these efforts, male dominance continues in areas such as educational leadership. This paper employs a case study approach to investigate the role of institutional culture in undermining the constitutional aim of attaining gender equality. Using feminist critical policy analysis theory to study the mentoring and management style employed in a South African rural high school, the article concludes that despite the policy imperatives, the conservative and patriarchal tendencies within educational leadership undermine the attainment of gender equality. To attain success, implementation of gender policies needs to be strictly monitored.
Distributing leadership across people and objects in a collaborative research project
Authors: Mailhot Chantale , Gagnon Stéphanie , Langley Ann , Binette Louis-Félix
Published: July 2014

This paper examines how distributed leadership involving actor–object couplings may contribute to coordinated action across disparate thought worlds. We draw on ideas from French pragmatist sociology and on a case study of a successful collaborative research project involving participants from academia, government and practice settings to show how various kinds of objects (including material artifacts, more abstract concepts and human-material assemblages such as committees and procedures) come to participate in the leadership practices of multiple individuals, allowing the connection among different worlds. We suggest that adjustments between groups involved in collaborative work do not necessarily occur through the sharing of a common vision but through the ability of leaders to translate projects in terms that can be appreciated by the groups that must be mobilized. These translation activities are distributed widely between leaders and objects that co-construct each other. Objects frame action and give meaning to people, participating in the construction of leaders' roles.
Review of measurement instruments in research ethics in the biomedical sciences, 2008−2012
Authors: Redman Barbara K
Published: July 2014

There is an urgent need in biomedical science to understand whether regulations are being met, prerequisite to goals of subject protection and integrity in research practice. This article presents an update of a 2006 summary of measurement instruments in research ethics with psychometric information in the years 2008−2012. A review of 25 instruments identified seven used in the time period 2008−2012 and which had accumulated at least one study of its psychometric qualities beyond its developmental phase. Many of these instruments had been accumulating psychometric information over more than a decade. Two additional but still underdeveloped instruments addressing important bioethical issues − coercion and therapeutic misconception − are included because they address important issues in research ethics. Bioethicists use a wide range of methods for knowledge development and verification; each method should meet stringent standards of quality. Measurement instruments that meet these standards have the potential to greatly ease the work of institutional review boards and other regulatory bodies as well as to enhance empirical work on human research ethics.
Selection criteria for initiation and renewal of luteinizing hormone-releasing hormone agonist therapy in patients with prostate cancer: a French prospective observational study
Authors: Lebret Thierry , Davin Jean-Louis , Hennequin Christophe , Latorzeff Igor , Mignard Jean-Pierre , Moreau Jean-Luc , Rossi Dominique , Ruffion Alain , Zerbib Marc , Culine Stéphane
Published: July 2014

Objectives:

To define the profile of patients with prostate cancer (PCa) receiving a 3-month or 6-month formulation of luteinizing hormone-releasing hormone (LHRH) agonist in France and the reasons for choosing between formulations.

Methods:

This prospective 1-year observational study included patients with PCa starting LHRH agonist therapy in everyday practice. Reasons for prescription and patient preference were recorded at inclusion, 3 or 6 months, and 12 months. The percentage of patients with a renewed initial prescription was recorded during follow up.

Results:

A total of 1438 patients with PCa were included. Hormonotherapy was initiated more frequently with a 6-month ( n = 903; 62.8%) than with a 3-month formulation ( n = 535; 37.2%). The initial prescription was renewed in most patients after 3 or 6 months (86.1%) and 12 months (71%); 170 patients switched from a 3-month to a 6-month formulation during follow up. Presence of metastases influenced initial prescription (odds ratio 0.439; 95% confidence interval 1.095–1.892), with a 3-month formulation more often prescribed than a 6-month formulation to men with metastatic PCa at diagnosis (21.3% versus 15.8%, respectively). The most frequent reasons given by physicians for choosing the 6-month formulation were ‘simplification of therapeutic regimen’ (86.9%) or ‘fewer unnecessary visits’ (46.8%). Similar reasons were given for switching from a 3-month to a 6-month formulation during follow up. The most frequent reasons given by physicians to initiate therapy with a 3-month formulation were ‘usual practice/habit’ (55.5%) or ‘closer patient management’ (46.2%). ‘Closer patient management’ and ‘reassuring effect upon patient’ were the main reasons for switching from a 6-month to a 3-month formulation during follow up. Approximately 80% of patients were satisfied with the formulation they were prescribed and patients’ reasons for preferring one formulation over another were similar to the physicians’ reasons for prescribing these formulations.

Conclusions:

Slow-release formulations of LHRH agonists are useful therapies for physicians treating patients with PCa and there may be a preference for the 6-month formulation.
Does a Syrinx Matter for Return to Play in Contact Sports? A Case Report and Evidence-Based Review of Return-to-Play Criteria After Transient Quadriplegia
Authors: Milles Jeffrey L. , Gallizzi Michael A. , Sherman Seth L. , Smith Patrick A. , Choma Theodore J.
Published: July 2014

Transient quadriplegia is a rare injury that can change the course of an athlete’s career if misdiagnosed or managed inappropriately. The clinician should be well versed in the return-to-play criteria for this type of injury. Unfortunately, when an unknown preexisting syrinx is present in the athlete, there is less guidance on their ability to return to play. This case report and review of the current literature illustrates a National Collegiate Athletic Association (NCAA) Division I football player who suffered a transient quadriplegic event during a kickoff return that subsequently was found to have an incidental cervical syrinx on magnetic resonance imaging. The player was able to have a full neurologic recovery, but ultimately he was withheld from football.
Building sense out of situational complexity
Authors: Guarana Cristiano L. , Hernandez Morela
Published: July 2014

There is growing consensus among scholars that the organizational environment has become increasingly complex, dynamic, and socially demanding. Leaders and followers navigate through a cognitive paradox where assessments of the situation can be at once cognitively overpowering and cognitively deceiving. In this article, we propose that complex situations can lead to ambivalence, a psychological state caused by contrasting evaluative orientations toward an object or situation. We propose that ambivalence can become a functional cognitive process that provides cognitive discomfort and fluidity for joint contextual interpretation when leaders and followers share ambivalent cognitive states. We develop a theoretical model of how this process unfolds, highlighting how and when situational complexity can trigger leader and follower ambivalence leading to distinct interpretative processes. Taken together, we explain how ambivalence can facilitate collaborative contextual interpretation within complex situations. In so doing, we advance the current understanding of ambivalence by explicating its role in creating functional leadership processes.
On the role of experience in ethical decision making at work
Authors: Dane Erik , Sonenshein Scott
Published: July 2014

Previous research has produced contradictory results on whether and how “experience” relates to ethical decision making in the workplace. Maintaining that these divergent findings result from underspecified and inconsistent treatments of experience in the business ethics literature, we build theory around experience and its connection to ethical decision making. To this end, we draw upon and advance research on ethical expertise, defined as the degree to which one is knowledgeable about and skilled at applying moral values within a given work context. We also unpack the nature and consequences of two forms of ethical expertise, convergent and divergent. Building on this foundation—and seeking to reconcile the contradictory results around experience and ethical decision making—we theorize factors associated with the acquisition of ethical expertise in the workplace. We conclude by discussing the implications of our theorizing for business ethics scholarship and expertise research.
Implications of ventricular arrhythmia “bursts” with normal epicardial flow, myocardial blush, and ST-segment recovery in anterior ST-elevation myocardial infarction reperfusion: A biosignature of direct myocellular injury “downstream of downstream”
Authors: Majidi Mohamed , Kosinski Andrzej S , Al-Khatib Sana M , Smolders Lilian , Cristea Ecaterina , Lansky Alexandra J , Stone Gregg W , Mehran Roxana , Gibbons Raymond J , Crijns Harry J , Wellens Hein J , Gorgels Anton P , Krucoff Mitchell W
Published: July 2014

Aims:

Establishing epicardial flow with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is necessary but not sufficient to ensure nutritive myocardial reperfusion. We evaluated whether adding myocardial blush grade (MBG) and quantitative reperfusion ventricular arrhythmia “bursts” (VABs) surrogates provide a more informative biosignature of optimal reperfusion in patients with Thrombolysis in Myocardial Infarction (TIMI) 3 flow and ST-segment recovery (STR).

Methods and results:

Anterior STEMI patients with final TIMI 3 flow had protocol-blinded analyses of simultaneous MBG, continuous 12-lead electrocardiogram (ECG) STR, Holter VABs, and day 5–14 SPECT imaging infarct size (IS) assessments. Over 20 million cardiac cycles from >4500 h of continuous ECG monitoring in subjects with STR were obtained. IS and clinical outcomes were examined in patients stratified by MBG and VABs. VABs occurred in 51% (79/154) of subjects. Microcirculation (MBG 2/3) was restored in 75% (115/154) of subjects, of whom 53% (61/115) had VABs. No VABs were observed in subjects without microvascular flow (MBG of 0). Of 115 patients with TIMI 3 flow, STR, and MBG 2/3, those with VABs had significantly larger IS (median: 23.0% vs 6.0%, p=0.001). Multivariable analysis identified reperfusion VABs as a factor significantly associated with larger IS ( p=0.015).

Conclusions:

Despite restoration of normal epicardial flow, open microcirculation, and STR, concomitant VABs are associated with larger myocardial IS, possibly reflecting myocellular injury in reperfusion settings. Combining angiographic and ECG parameters of epicardial, microvascular, and cellular response to STEMI intervention provides a more predictive “biosignature” of optimal reperfusion than do single surrogate markers.
The Triple Test Markers Profile Among Fetuses and Children Diagnosed With Umbilical Vein Varix
Authors: Melcer Yaakov , Wiener Yifat , Ben-Ami Ido , Levinsohn-Tavor Orna , Feldman Noa , Maymon Ron
Published: July 2014

Umbilical vein varix (UVV) is defined as a focal enlargement of the umbilical vein and represents approximately 4% of fetal umbilical cord malformations. The reported neonatal outcome of fetuses with UVV varies widely due to its rarity, hence the small sample sizes of the case series in the literature. Earlier studies reported high fetal mortality, but more recent reports have demonstrated no association between UVV and intrauterine fetal death. A recent study has described a possible association between UVV diagnosed prenatally and child developmental delay. The present study of fetuses with UVV was done to evaluate and compare the levels of triple test serum biomarkers used for Down syndrome screening (human chorionic gonadotropin, α-fetoprotein, and unconjugated estriol) between a group of fetuses with uneventful obstetric outcome versus a subgroup of children with developmental delay.
Yield of tuberculosis contact investigations in Amsterdam: opportunities for improvement
Authors: Sloot Rosa , Schim van der Loeff Maarten F. , Kouw Peter M. , Borgdorff Martien W.
Published: July 2014

We aimed to determine the coverage and yield of tuberculosis contact investigation, and compliance with guidelines, and to identify opportunities for improvement.

Data were extracted from records on contacts of pulmonary tuberculosis patients at the Public Health Service (Amsterdam, the Netherlands) from 2008 to 2011. Additional data were obtained from the national tuberculosis register.

Among 3743 contacts of 235 pulmonary tuberculosis index patients, 2337 (62%) were screened for latent tuberculosis infection (LTBI). Those less likely to be screened for LTBI included contacts of sputum smear-negative index patients (adjusted odds ratio (aOR) 0.6, 95% CI 0.4–0.9) and bacille Calmette Guérin (BCG)-vaccinated contacts (aOR 0.06, 95% CI 0.04–0.09). Among BCG-vaccinated contacts, the proportion screened increased from 9% in 2008 to 43% in 2011 (p-value for trend <0.001). LTBI diagnosis among contacts screened was associated with non-Dutch nationality (aOR 2.8, 95% CI 1.9–4.1) and being a close contact (aOR 4.0, 95% CI 1.9–8.3). Of the 254 contacts with LTBI diagnosis, 142 (56%) started preventive treatment. Starting treatment was associated with Dutch nationality (aOR 2.6, 95% CI 1.2–5.4) and being a close contact (aOR 10.5, 95% CI 1.5–70.7). Treatment completion was achieved by 129 (91%) of the 142 contacts who started treatment.

Two areas for improvement were identified: further expanding LTBI screening, particularly among BCG-vaccinated contacts and contacts of sputum smear-negative index patients, and expanding preventive treatment among contacts with LTBI.
Changes in physical activity and all-cause mortality in COPD
Authors: Vaes Anouk W. , Garcia-Aymerich Judith , Marott Jacob L. , Benet Marta , Groenen Miriam T.J. , Schnohr Peter , Franssen Frits M.E. , Vestbo Jørgen , Wouters Emiel F.M. , Lange Peter , Spruit Martijn A.
Published: July 2014

Little is known about changes in physical activity in subjects with chronic obstructive pulmonary disease (COPD) and its impact on mortality. Therefore, we aimed to study changes in physical activity in subjects with and without COPD and the impact of physical activity on mortality risk.

Subjects from the Copenhagen City Heart Study with at least two consecutive examinations were selected. Each examination included a self-administered questionnaire and clinical examination.

1270 COPD subjects and 8734 subjects without COPD (forced expiratory volume in 1 s 67±18 and 91±15% predicted, respectively) were included. COPD subjects with moderate or high baseline physical activity who reported low physical activity level at follow-up had the highest hazard ratios of mortality (1.73 and 2.35, respectively; both p<0.001). In COPD subjects with low baseline physical activity, no differences were found in survival between unchanged or increased physical activity at follow-up. In addition, subjects without COPD with low physical activity at follow-up had the highest hazard ratio of mortality, irrespective of baseline physical activity level (p≤0.05).

A decline to low physical activity at follow-up was associated with an increased mortality risk in subjects with and without COPD. These observational data suggest that it is important to assess and encourage physical activity in the earliest stages of COPD in order to maintain a physical activity level that is as high as possible, as this is associated with better prognosis.
Gas exchange and ventilation–perfusion relationships in the lung
Authors: Petersson Johan , Glenny Robb W.
Published: July 2014

This review provides an overview of the relationship between ventilation/perfusion ratios and gas exchange in the lung, emphasising basic concepts and relating them to clinical scenarios. For each gas exchanging unit, the alveolar and effluent blood partial pressures of oxygen and carbon dioxide (PO2andPCO2) are determined by the ratio of alveolar ventilation to blood flow (V′A/Q′) for each unit. Shunt and lowV′A/Q′ regions are two examples ofV′A/Q′ mismatch and are the most frequent causes of hypoxaemia. Diffusion limitation, hypoventilation and low inspiredPO2cause hypoxaemia, even in the absence ofV′A/Q′ mismatch. In contrast to other causes, hypoxaemia due to shunt responds poorly to supplemental oxygen. Gas exchanging units with little or no blood flow (highV′A/Q′ regions) result in alveolar dead space and increased wasted ventilation,i.e.less efficient carbon dioxide removal. Because of the respiratory drive to maintain a normal arterialPCO2, the most frequent result of wasted ventilation is increased minute ventilation and work of breathing, not hypercapnia. Calculations of alveolar–arterial oxygen tension difference, venous admixture and wasted ventilation provide quantitative estimates of the effect ofV′A/Q′ mismatch on gas exchange. The types ofV′A/Q′ mismatch causing impaired gas exchange vary characteristically with different lung diseases.
Network medicine, multimorbidity and the lung in the elderly
Authors: Faner Rosa , Cruz Tamara , López-Giraldo Alejandra , Agustí Alvar
Published: July 2014

Noncommunicable diseases, including cardiovascular, metabolic and respiratory diseases, among others, are the major medical challenge of the 21st century. Most noncommunicable diseases are related to the ageing process and often co-occur in the same individual. However, it is unclear whether the index disease is somehow influencing the development of the other ones (comorbidity) or whether all of them (including the index disease) simply represent the clinical expression of pathological ageing (multimorbidity). The pathobiology of ageing, chronic obstructive pulmonary disease (COPD) and concomitant disorders is complex. A new field of research, known as systems biology if applied to model systems or network medicine if applied to human beings, has emerged over the past decade or so, to address biological complexity in a holistic, integrated way. It offers, therefore, great potential to decipher the relationship between ageing, COPD and comorbidities/multimorbidities. In this State of the Art review we present the basic concepts of systems biology, use some examples to illustrate the potential of network medicine to address complex medical problems, and review some recent publications that show how a systems-based research strategy can contribute to improve our understanding of multimorbidity and age-related respiratory diseases.
Smoking-related idiopathic interstitial pneumonia
Authors: Flaherty Kevin R. , Fell Charlene , Aubry Marie-Christine , Brown Kevin , Colby Thomas , Costabel Ulrich , Franks Teri J. , Gross Barry H. , Hansell David M. , Kazerooni Ella , Kim Dong Soon , King Talmadge E. , Kitachi Masanori , Lynch David , Myers Jeff , Nagai Sonoko , Nicholson Andrew G. , Poletti Venerino , Raghu Ganesh , Selman Moises , Toews Galen , Travis William , Wells Athol U. , Vassallo Robert , Martinez Fernando J.
Published: July 2014

Cigarette smoking is a key factor in the development of numerous pulmonary diseases.

An international group of clinicians, radiologists and pathologists evaluated patients with previously identified idiopathic interstitial pneumonia (IIP) to determine unique features of cigarette smoking. Phase 1 (derivation group) identified smoking-related features in patients with a history of smoking (n=41). Phase 2 (validation group) determined if these features correctly predicted the smoking status of IIP patients (n=100) to participants blinded to smoking history. Finally, the investigators sought to determine if a new smoking-related interstitial lung disease phenotype could be defined.

Phase 1 suggested that preserved forced vital capacity with disproportionately reduced diffusing capacity of the lung for carbon monoxide, and various radiographic and histopathological findings were smoking-related features. In phase 2, the kappa coefficient among clinicians was 0.16 (95% CI 0.11–0.21), among the pathologists 0.36 (95% CI 0.32–0.40) and among the radiologists 0.43 (95% CI 0.35–0.52) for smoking-related features. Eight of the 100 cases were felt to represent a potential smoking-related interstitial lung disease.

Smoking-related features of interstitial lung disease were identified in a minority of smokers and were not specific for smoking. This study is limited by its retrospective design, the potential for recall bias in smoking history and lack of information on second-hand smoke exposure. Further research is needed to understand the relationship between smoking and interstitial lung disease.
Treatment with pirfenidone for two years decreases fibrosis, cytokine levels and enhances CB2 gene expression in patients with chronic hepatitis C
Authors: Flores-Contreras Lucia , Sandoval-Rodríguez Ana S , Mena-Enriquez Mayra G , Lucano-Landeros Silvia , Arellano-Olivera Inmaculada , Álvarez-Álvarez Arnulfo , Sanchez-Parada M Guadalupe , Armendáriz-Borunda Juan
Published: July 2014

Background

The aim of this study was to assess whether two-years treatment with Pirfenidone influences necroinflammation, fibrosis and steatosis, serum levels of TGF-β1, IL-6, TNF-α and CB1 and CB2 gene expression, in patients with chronic hepatitis C (CHC).

Methods

Twenty-eight patients out of 34 with CHC virus infection were enrolled in the study and received Pirfenidone (1200 mg/day) for 24 months. Six patients dropped out after 12 months of PFD. Liver biopsies and serum samples were obtained at the beginning and end of treatment. Modified HAI was calculated. CB1 and CB2 gene expression was correlated with fibrosis progression alongside with necroinflammation and steatosis. TGF-β1, IL-6, TNF-α and liver transaminases were measured in serum at two-months intervals. HCV genotype and viral load were also assessed. Quality of life was evaluated by SF36 questionnaires and the prognosis of disease was assessed with Child-Pugh score. The Wilcoxon test matched-pair signed ranks were used to analyze the outcomes.

Results

Intention to treat analyses were performed for biochemistry and clinical parameters. At the end of treatment, necroinflammation grading was reduced in an average of 3.2 points in 82% of patients (p < 0.05) and Ishak’s fibrosis stage decreased 2-points average in 67% of patients (p < 0.05). Steatosis decreased in 61% of patients. IL-6 and TGF-β1 serum levels decreased significantly in 93% and 67% of patients (p < 0.05), respectively, while TNF-α diminished in 47% of patients. ALT and AST tended to normalize in 81% of patients; CB2 mRNA levels increased in 86% and CB1 expression diminished in 29% of patients. Both, quality of life and Child-Pugh score improvements were reported in all patients.

Conclusions

Pirfenidone for two years benefits CHC patients and improves inflammation, fibrosis and steatosis in higher number of patients as previously shown for 12-months treatment with PFD. Additionally, PFD improved TGFβ1 and IL-6 levels and diminished liver expression of anti-fibrogenic receptor CB2.

Trial registration

ClinicalTrials.gov identifier: NCT02161952. Protocol Registration Date: 06/11/2014.
Pain, motor function and health-related quality of life in children with cerebral palsy as reported by their physiotherapists
Authors: Badia Marta , Riquelme Inmaculada , Orgaz Begoña , Acevedo Raquel , Longo Egmar , Montoya Pedro
Published: July 2014

Background

Children and adolescents with cerebral palsy suffer from higher levels of pain than their peers without disability. The aim of this study was to explore the impact of pain on health-related quality of life and motor function in individuals with cerebral palsy as reported by health professionals.

Methods

Cross-sectional study carried out in Associations for Care of Individuals with Cerebral Palsy and Related Disabilities (ASPACE) in Balearic Islands and Castile Leon (Spain). Thirty-five physiotherapists rated pain, health-related quality of life and motor function in 91 children and adolescents with cerebral palsy [8-19y]. A semi-structured interview was used to collect demographic and clinical data according with the Study of Participation of Children with Cerebral Palsy Living in Europe (SPARCLE).

Results

Physiotherapists reported that 51% of individuals with cerebral palsy suffered from pain. Physiotherapists also perceived that pain in individuals with cerebral palsy was responsible for reductions of psychological but not physical domains of health-related quality of life. According with physiotherapists’ estimations, motor impairment scores were not correlated with pain scores in individuals with cerebral palsy, but they were significantly associated with physical and autonomy domains of health-related quality of life.

Conclusions

These findings highlighted the importance of assessing and providing interventions for pain relief in persons with cerebral palsy even at an early age.
Lung fibrotic tenascin-C upregulation is associated with other extracellular matrix proteins and induced by TGFβ1
Authors: Estany Susanna , Vicens-Zygmunt Vanesa , Llatjós Roger , Montes Ana , Penín Rosa , Escobar Ignacio , Xaubet Antoni , Santos Salud , Manresa Frederic , Dorca Jordi , Molina-Molina Maria
Published: July 2014

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical component in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to determine the expression profile of highlighted ECM proteins in IPF lungs.

Methods

ECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and western-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as chronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and fibrotic patients were studied to evaluate tenascin-C (TNC) synthesis.

Results

A total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost undetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP. Furthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient pattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin glycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients constitutively synthesized higher levels of TNC than normal fibroblasts. TNC and α-sma was induced by TGF-β1 in both fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant increased α-sma mRNA.

Conclusions

The difference in ECM glycoprotein content in interstitial lung diseases could contribute to the development of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in the altered wound healing.
Essential pediatric hypertension: defining the educational needs of primary care pediatricians
Authors: Cha Stephen D , Chisolm Deena J , Mahan John D
Published: July 2014

Background

In order to better understand the educational needs regarding appropriate recognition, diagnosis and management of pediatric hypertension (HTN), we asked practicing pediatricians questions regarding their educational needs and comfort level on this topic.

Methods

We conducted 4 focus group sessions that included 27 participants representing pediatric residents, adolescent medicine physicians, clinic based pediatricians and office based pediatricians. Each focus group session lasted for approximately an hour and 90 pages of total transcriptions were produced verbatim from audio recordings.

Results

Four reviewers read each transcript and themes were elucidated from these transcripts. Overall, 5 major themes related to educational needs and clinical concerns were found: utilization of resources to define blood pressure (BP), correct BP measurement method(s), co-morbidities, barriers to care, and experience level with HTN. Six minor themes were also identified: differences in BP measurement, accuracy of BP, recognition of HTN, practice pattern of care, education of families and patients, and differences in level of training. The focus group participants were also questioned on their preferences regarding educational methods (i.e. e-learning, small group sessions, self-study, large group presentations) and revealed varied teaching and learning preferences.

Conclusions

There are multiple methods to approach education regarding pediatric HTN for primary care pediatricians based on provider preferences and multiple educational activities should be pursued to achieve best outcomes. Based on this data, the next direction will be to develop and deliver multiple educational methods and to evaluate the impact on practice patterns of care for children and adolescents with HTN.
Green synthesis of protein capped silver nanoparticles from phytopathogenic fungus Macrophomina phaseolina (Tassi) Goid with antimicrobial properties against multidrug-resistant bacteria
Authors: Chowdhury Supriyo , Basu Arpita , Kundu Surekha
Published: July 2014

In recent years, green synthesis of nanoparticles, i.e., synthesizing nanoparticles using biological sources like bacteria, algae, fungus, or plant extracts have attracted much attention due to its environment-friendly and economic aspects. The present study demonstrates an eco-friendly and low-cost method of biosynthesis of silver nanoparticles using cell-free filtrate of phytopathogenic fungus Macrophomina phaseolina. UV-visible spectrum showed a peak at 450 nm corresponding to the plasmon absorbance of silver nanoparticles. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM) revealed the presence of spherical silver nanoparticles of the size range 5 to 40 nm, most of these being 16 to 20 nm in diameter. X-ray diffraction (XRD) spectrum of the nanoparticles exhibited 2θ values corresponding to silver nanoparticles. These nanoparticles were found to be naturally protein coated. SDS-PAGE analysis showed the presence of an 85-kDa protein band responsible for capping and stabilization of the silver nanoparticles. Antimicrobial activities of the silver nanoparticles against human as well as plant pathogenic multidrug-resistant bacteria were assayed. The particles showed inhibitory effect on the growth kinetics of human and plant bacteria. Furthermore, the genotoxic potential of the silver nanoparticles with increasing concentrations was evaluated by DNA fragmentation studies using plasmid DNA.
The effectiveness of lasers in the treatment of onychomycosis: a systematic review
Authors: Bristow Ivan R
Published: July 2014

Background

Onychomycosis is a common nail pathology which has proven to be a treatment challenge to healthcare professionals. Antifungal drugs have been the mainstay of therapy for many years. Recently, laser technologies have been introduced as a treatment for onychomycosis avoiding the disadvantages of systemic and topical drug therapies, offering a rapid treatment for an often persistent nail condition. The purpose of this study was to review published evidence regarding the effectiveness of laser technologies in the treatment of onychomycosis.

Methods

The primary question for this review was “what evidence is there for the use of lasers in the treatment of onychomycosis”? A systematic literature search of published papers indexed on Pubmed and Web of Science® was undertaken in June 2014 for original, published research. The primary outcome measures for efficacy were mycological cure and clearance of the affected nail (clinical cure).

Results

This review returned a total of twelve eligible published studies evaluating the use of lasers in the treatment of onychomycosis. Two were randomised controlled trials, four were comparative design studies (with no placebo/control groups) and the remainder were case series. The level of evidence was generally low level reflecting predominantly small sample size and lack of control groups. The results from studies were conflicting and follow up periods for patients in studies were generally short. Many studies excluded patients with severe or dystrophic onychomycosis.

Conclusions

The evidence pertaining to the effectiveness of laser treatment of onychomycosis is limited and of poor methodological quality. Future studies using a randomised controlled trial designs with larger study populations and clear procedures are required to permit a full evaluation of this emerging technology.
Tonsillotomy versus tonsillectomy on young children: 2 year post surgery follow-up
Authors: Ericsson Elisabeth , Graf Jonas , Lundeborg-Hammarstrom Inger , Hultcrantz Elisabeth
Published: July 2014

Objectives

To study the long-term effect of tonsillotomy and tonsillectomy in young children after two years in comparison to the results after six months.

Method

Children, age 4-5 with Sleep Disordered Breathing (SDB) and tonsil hyperplasia, were randomized to TE (32) or TT (35). TT was performed ad modum Hultcrantz with radiofrequency technique (Ellman). An adenoidectomy with cold steel was performed in the same session for 80% of cases. The patients were assessed prior to surgery, at six and 24 months postoperatively. Effects of surgery were evaluated clinically, through questionnaire (general health/snoring/ENT-infections), Quality of Life (QoL), survey of pediatric obstructive sleep apnea with OSA-18, and children's behavior with the Child Behavior Checklist.

Results

After two years there was still no difference between the groups with respect to snoring and frequency or severity of upper airway infections. Both TT and TE had resulted in large improvement in short and long term QoL and behavior. Three TT-children and one TE child had been re-operated due to recurrence of obstructive problems, the TE-child and one of the TT-children with adenoidectomy and two of the TT-children with tonsillectomy. Three of the TT-children had tonsil tissue protruding slightly out of the tonsil pouch and twelve TE-children had small tonsil remnants within the tonsil pouches, but with no need for surgery.

Conclusion

Younger children have a small risk of symptom-recurrence requiring re-surgery within two years after TT. For the majority, the positive effect on snoring, infections, behavior and quality of life remain and is similar to TE.
Phosphodiesterase 2A is a major negative regulator of iNOS expression in lipopolysaccharide-treated mouse alveolar macrophages
Authors: Rentsendorj Otgonchimeg , D'Alessio Franco R , Pearse David B
Published: July 2014

PDE2A is a dual-function PDE that is stimulated by cGMP to hydrolyze cAMP preferentially. In a two-hit model of ALI, we found previously that PDE2A decreased lung cAMP, up-regulated lung iNOS, and exacerbated ALI. Recent data suggest that macrophage iNOS expression contributes to ALI but later, promotes lung-injury resolution. However, macrophage iNOS is increased by cAMP, suggesting that PDE2A could negatively regulate macrophage iNOS expression. To test this, we examined the effects of manipulating PDE2A expression and function on LPS-induced iNOS expression in a mouse AM cell line (MH-S) and primary mouse AMs. In MH-S cells, LPS (100 ng/ml) increased PDE2A expression by 15% at 15 min and 50% at 6 h before decreasing at 24 h and 48 h. iNOS expression appeared at 6 h and remained increased 48 h post-LPS. Compared with control Ad, Ad.PDE2A-shRNA enhanced LPS-induced iNOS expression further by fourfold, an effect mimicked by the PDE2A inhibitor BAY 60–7550. Adenoviral PDE2A overexpression or treatment with ANP decreased LPS-induced iNOS expression. ANP-induced inhibition of iNOS was lost by knocking down PDE2A and was not mimicked by 8-pCPT-cGMP, a cGMP analog that does not stimulate PDE2A activity. Finally, we found that in primary AMs from LPS-treated mice, PDE2A knockdown also increased iNOS expression, consistent with the MH-S cell data. We conclude that increased AM PDE2A is an important negative regulator of macrophage iNOS expression.
Bocmodifies the spectrum of holoprosencephaly in the absence ofGas1function
Authors: Seppala Maisa , Xavier Guilherme M. , Fan Chen-Ming , Cobourne Martyn T.
Published: July 2014

Holoprosencephaly is a heterogeneous developmental malformation of the central nervous system characterized by impaired forebrain cleavage, midline facial anomalies and wide phenotypic variation. Indeed, microforms represent the mildest manifestation, associated with facial anomalies but an intact central nervous system. In many cases, perturbations in sonic hedgehog signaling are responsible for holoprosencephaly. Here, we have elucidated the contribution of Gas1 and an additional hedgehog co-receptor, Boc during early development of the craniofacial midline, by generating single and compound mutant mice. Significantly, we find Boc has an essential role in the etiology of a unique form of lobar holoprosencephaly that only occurs in conjunction with combined loss of Gas1. Whilst Gas1−/− mice have microform holoprosencephaly characterized by a single median maxillary central incisor, cleft palate and pituitary anomalies, Boc−/− mice have a normal facial midline. However, Gas1−/−; Boc−/− mutants have lobar holoprosencephaly associated with clefting of the lip, palate and tongue, secondary to reduced sonic hedgehog transduction in the central nervous system and face. Moreover, maxillary incisor development is severely disrupted in these mice, arresting prior to cellular differentiation as a result of apoptosis in the odontogenic epithelium. Thus, Boc and Gas1 retain an essential function in these tooth germs, independent of their role in midline development of the central nervous system and face. Collectively, this phenotype demonstrates both redundancy and individual requirements for Gas1 and Boc during sonic hedgehog transduction in the craniofacial midline and suggests BOC as a potential digenic locus for lobar holoprosencephaly in human populations.
Molecular cloning of ion channels inFelis catusthat are related to periodic paralyses in man: a contribution to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis
Authors: Zapata Marlyn , Kunii Ilda S. , Paninka Rolf M. , Simões Denise M. N. , Castillo Víctor A. , Reche Archivaldo , Maciel Rui M. B. , Dias da Silva Magnus R.
Published: July 2014

Neck ventroflexion in cats has different causes; however, the most common is the hypokalemia associated with flaccid paralysis secondary to chronic renal failure. In humans, the most common causes of acute flaccid paralysis are hypokalemia precipitated by thyrotoxicosis and familial forms linked to mutations in sodium, potassium, and calcium channel genes. Here, we describe the sequencing and analysis of skeletal muscle ion channels in Felis catus that could be related to periodic paralyses in humans, contributing to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis. We studied genomic DNA from eleven cats, including five animals that were hyperthyroid with hypokalemia, although only one presented with muscle weakness, and six healthy control domestic cats. We identified the ion channel ortholog genes KCNJ2, KCNJ12, KCNJ14, CACNA1S and SCN4A in the Felis catus genome, together with several polymorphic variants. Upon comparative alignment with other genomes, we found that Felis catus provides evidence for a high genomic conservation of ion channel sequences. Although we hypothesized that neck ventroflexion in cats could be associated with a thyrotoxic or familial periodic paralysis channel mutation, we did not identify any previously detected human channel mutation in the hyperthyroid cat presenting hypokalemia. However, based on the small number of affected cats in this study, we cannot yet rule out this molecular mechanism. Notwithstanding, hyperthyroidism should still be considered as a differential diagnosis in hypokalemic feline paralysis.
Autocrine signaling is a key regulatory element during osteoclastogenesis
Authors: Kopesky Paul , Tiedemann Kerstin , Alkekhia Dahlia , Zechner Christoph , Millard Bjorn , Schoeberl Birgit , Komarova Svetlana V.
Published: July 2014

Osteoclasts are responsible for bone destruction in degenerative, inflammatory and metastatic bone disorders. Although osteoclastogenesis has been well-characterized in mouse models, many questions remain regarding the regulation of osteoclast formation in human diseases. We examined the regulation of human precursors induced to differentiate and fuse into multinucleated osteoclasts by receptor activator of nuclear factor kappa-B ligand (RANKL). High-content single cell microscopy enabled the time-resolved quantification of both the population of monocytic precursors and the emerging osteoclasts. We observed that prior to induction of osteoclast fusion, RANKL stimulated precursor proliferation, acting in part through an autocrine mediator. Cytokines secreted during osteoclastogenesis were resolved using multiplexed quantification combined with a Partial Least Squares Regression model to identify the relative importance of specific cytokines for the osteoclastogenesis outcome. Interleukin 8 (IL-8) was identified as one of RANKL-induced cytokines and validated for its role in osteoclast formation using inhibitors of the IL-8 cognate receptors CXCR1 and CXCR2 or an IL-8 blocking antibody. These insights demonstrate that autocrine signaling induced by RANKL represents a key regulatory component of human osteoclastogenesis.
Increased oxidative metabolism and myoglobin expression in zebrafish muscle during chronic hypoxia
Authors: Jaspers Richard T. , Testerink Janwillem , Della Gaspera Bruno , Chanoine Christophe , Bagowski Christophe P. , van der Laarse Willem J.
Published: July 2014

Fish may be extremely hypoxia resistant. We investigated how muscle fibre size and oxidative capacity in zebrafish (Danio rerio) adapt during severe chronic hypoxia. Zebrafish were kept for either 3 or 6 weeks under chronic constant hypoxia (CCH) (10% air/90%N2 saturated water). We analyzed cross-sectional area (CSA), succinate dehydrogenase (SDH) activity, capillarization, myonuclear density, myoglobin (Mb) concentration and Mb mRNA expression of high and low oxidative muscle fibres. After 3 weeks of CCH, CSA, SDH activity, Mb concentration, capillary and myonuclear density of both muscle fibre types were similar as under normoxia. In contrast, staining intensity for Mb mRNA of hypoxic high oxidative muscle fibres was 94% higher than that of normoxic controls (P<0.001). Between 3 and 6 weeks of CCH, CSA of high and low oxidative muscle fibres increased by 25 and 30%, respectively. This was similar to normoxic controls. Capillary and myonuclear density were not changed by CCH. However, in high oxidative muscle fibres of fish maintained under CCH, SDH activity, Mb concentration as well as Mb mRNA content were higher by 86%, 138% and 90%, respectively, than in muscle fibres of fish kept under normoxia (P<0.001). In low oxidative muscle fibres, SDH activity, Mb and Mb mRNA content were not significantly changed. Under normoxia, the calculated interstitial oxygen tension required to prevent anoxic cores in muscle fibres (PO2crit) of high oxidative muscle fibres was between 1.0 and 1.7 mmHg. These values were similar at 3 and 6 weeks CCH. We conclude that high oxidative skeletal muscle fibres of zebrafish continue to grow and increase oxidative capacity during CCH. Oxygen supply to mitochondria in these fibres may be facilitated by an increased Mb concentration, which is regulated by an increase in Mb mRNA content per myonucleus.
Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival
Authors: Toyoda Yusuke , Erkut Cihan , Pan-Montojo Francisco , Boland Sebastian , Stewart Martin P. , Müller Daniel J. , Wurst Wolfgang , Hyman Anthony A. , Kurzchalia Teymuras V.
Published: July 2014

Parkinson's disease is associated with mitochondrial decline in dopaminergic neurons of the substantia nigra. One of the genes linked with the onset of Parkinson's disease, DJ-1/PARK7, belongs to a novel glyoxalase family and influences mitochondrial activity. It has been assumed that glyoxalases fulfill this task by detoxifying aggressive aldehyde by-products of metabolism. Here we show that supplying either D-lactate or glycolate, products of DJ-1, rescues the requirement for the enzyme in maintenance of mitochondrial potential. We further show that glycolic acid and D-lactic acid can elevate lowered mitochondrial membrane potential caused by silencing PINK-1, another Parkinson's related gene, as well as by paraquat, an environmental toxin known to be linked with Parkinson's disease. We propose that DJ-1 and consequently its products are components of a novel pathway that stabilizes mitochondria during cellular stress. We go on to show that survival of cultured mesencephalic dopaminergic neurons, defective in Parkinson's disease, is enhanced by glycolate and D-lactate. Because glycolic and D-lactic acids occur naturally, they are therefore a potential therapeutic route for treatment or prevention of Parkinson's disease.