bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐Level Gait Disorder: Associations with Specific White Matter Changes Observed on Advanced Diffusion Imaging
Authors: Kafri Michal , Sasson Efrat , Assaf Yaniv , Balash Yaacov , Aiznstein Orna , Hausdorff Jeffrey M. , Giladi Nir
Published: August 2012

BACKGROUND AND PURPOSE

High‐level gait disorder (HLGD) is a debilitating disorder causing mobility decline in the elderly. Although its clinical characteristics are well described, its anatomical and pathophysiological underpinnings are poorly understood. This study examined the anatomical distribution of white matter (WM) changes in patients with mild to moderate HLGD of the cautious/disequilibrium type, using advanced magnetic resonance imaging (MRI) methods.

METHODS

Thirteen patients with HLGD, 9 elderly and 13 middle‐aged healthy controls were scanned using diffusion tensor imaging, Q‐space imaging, and conventional MRI. The regions of significant differences between the HLGD group and the elderly control group were defined, and the mean fractional anisotropy and displacement values of these areas were extracted.

RESULTS

The HLGD patients had lower fractional anisotropy and higher displacement values in regions related to the motor system, including those along the corticospinal tract and the superior cerebellar peduncles, as well as in cognitive and affective‐related areas, including the anterior limbs of the internal capsule and the genu of the corpus callosum.

CONCLUSIONS

The anatomical distribution associated with HLGD of the cautious/disequilibrium type involves WM pathways that convey motor‐related, cognitive and affective‐related functions. The underlying pathological process leading to these changes most probably includes demyelination.
MRI‐Based Brain Structure Volumes in Temporal Lobe Epilepsy Patients and their Unaffected Siblings: A Preliminary Study
Authors: Scanlon Cathy , Ronan Lisa , Doherty Colin P. , Cavalleri Gianpiero L. , Tirupati Sandya , Alhusaini Saud , Maguire Sinead , Delanty Norman , Iyer Parameswaran M. , Chaila Elijah , Fitzsimons Mary
Published: August 2012

INTRODUCTION

Investigating the heritability of brain structure may be useful in simplifying complicated genetic studies in temporal lobe epilepsy (TLE). A preliminary study is presented to determine if volume deficits of candidate brain structures present at a higher rate in unaffected siblings than controls subjects.

METHODS

T1‐weighted MR images was acquired for 28 TLE patients, a same‐sex unaffected sibling of 12 of these and 28 normal controls. Selected brain structure volumes were measured using an automated whole brain segmentation technique. Candidate brain structure endophenotypes were determined and group differences were investigated between (1) controls and patients and (2) controls and siblings. ICC's were used to measure the quantitative volumetric association within each sibling pair.

RESULTS

TLE patients demonstrated a significantly lower cerebral white matter, bilateral hippocampus, thalamus, and left entorhinal cortex volumes when compared with controls. A significant deficit in cerebral white matter (CWM) was common to patient and nonaffected siblings when compared with controls. Furthermore, a significant correlation was revealed between patients and siblings in CWM and bilateral thalamus.

CONCLUSION

The findings suggest an overlap in the neurodevelopmental genes responsible for both brain structure and the expression of the disease. Further work is ongoing to confirm these findings.
Reversible Splenial Lesion in Postpartum Cerebral Angiopathy: A Case Report
Authors: Takahashi Yoshinobu , Hashimoto Naoya , Tokoroyama Hiroki , Yamauchi Shigeru , Nakasato Matsuyoshi , Kondo Kimito , Nitta Kazumi , Ide Wataru , Hashimoto Ikuo , Kamada Hajime
Published: August 2012

Reversible lesions on magnetic resonance imaging that transiently restrict diffusion in the splenium of the corpus callosum (SCC) without any other accompanying lesions have been reported in various clinical conditions. We offer the first report of postpartum cerebral angiopathy with reversible SCC lesions.
Black Blood MRI in Suspected Large Artery Primary Angiitis of the Central Nervous System
Authors: Pfefferkorn Thomas , Linn Jennifer , Habs Maximilian , Opherk Christina , Cyran Clemens , Ottomeyer Caroline , Straube Andreas , Dichgans Martin , Nikolaou Konstantin , Saam Tobias
Published: August 2012

OBJECTIVES

Single case reports suggest that black blood MRI (T1‐weighted fat and blood suppressed sequences with and without contrast injection; BB‐MRI) may visualize intracranial vessel wall contrast enhancement (CE) in primary angiitis of the central nervous system (PACNS). In this single‐center observational pilot study we prospectively investigated the value of BB‐MRI in the diagnosis of large artery PACNS.

METHODS

Patients with suspected large artery PACNS received a standardized diagnostic program including BB‐MRI. Vessel wall CE was graded (grade 0‐2) by two experienced readers blinded to clinical data and correlated to the final diagnosis.

RESULTS

Four of 12 included patients received a final diagnosis of PACNS. All of them showed moderate (grade 1) to strong (grade 2) vessel wall CE at the sites of stenosis. A moderate (grade 1) vessel wall CE grade was also observed in 6 of the remaining 8 patients in whom alternative diagnoses were made: arteriosclerotic disease (n= 4), intracranial dissection (n= 1), and Moyamoya disease (n= 1).

CONCLUSIONS

Our pilot study demonstrates that vessel wall CE is a frequent finding in PACNS and its mimics. Larger trials will be necessary to evaluate the utility of BB‐MRI in the diagnostic workup of PACNS.
Extending Communication for Patients with Disorders of Consciousness
Authors: Liang Xingwen , Kuhlmann Levin , Johnston Leigh A. , Grayden David B. , Vogrin Simon , Crossley Rosemary , Fuller Karen , Lourensz Mark , Cook Mark J.
Published: August 2012

BACKGROUND AND PURPOSE

The difficulty of distinguishing disorders of consciousness from certain disorders of communication leads to the possibility of false diagnosis. Our aim is to communicate with patients with disorders of consciousness through asking them to answer questions with “yes/no” by performing mental imagery tasks using functional magnetic resonance imaging (fMRI).

METHODS

A 1.5 T fMRI study with 5 patients and a control group is presented. Speech comprehension, mental imagery, and question–answer tests were performed.

RESULTS

The imagery task of mental calculation produced equally distinct activation patterns when compared to navigation and motor imagery in controls. For controls, we could infer answers to questions based on imagery activations. Two patients produced activations in similar areas to controls for certain imagery tasks, however, no activations were observed for the question–answer task.

CONCLUSIONS

The results from 2 patients provide independent support of similar work by others with 3 T fMRI, and demonstrate broader clinical utility for these tests at 1.5 T despite lower signal‐to‐noise ratio. Based on the control results, mental calculation adds a robust imagery task for use in future studies of this kind.
BDNF‐mediated migration of cardiac microvascular endothelial cells is impaired during ageing
Authors: Cao Liang , Zhang Liang , Chen Siyun , Yuan Ziqiang , Liu Shaokun , Shen Xiaotao , Zheng Xin , Qi Xufeng , Lee Kenneth K.H. , Chan John Yeuk‐Hon , Cai Dongqing
Published: August 2012

This study indicates that brain‐derived neurotrophic factor (BDNF) can promote young cardiac microvascular endothelial cells (CMECs) to migrate via the activation of the BDNF‐TrkB‐FL‐PI3K/Akt pathway, which may benefit angiogenesis after myocardial infarction (MI). However, the ageing of CMECs led to changes in the expression of receptor Trk isoforms in that among the three isoforms (TrkB‐FL, TrkB‐T1 and TrkB‐T2), only one of its truncated isoforms, TrkB‐T1, continued to be expressed, which leads to the dysfunction of its ligand, a decrease in the migration of CMECs and increased injury in ageing hearts. This shift in receptor isoforms in aged CMECs, together with changes in the ageing microenvironment, might predispose ageing hearts to decreased angiogenic potential and increased cardiac pathology.
Accuracy and reliability of fetal heart rate monitoring using maternal abdominal surface electrodes
Authors: COHEN WAYNE R. , OMMANI SOPHIA , HASSAN SARMINA , MIRZA FADI G. , SOLOMON MOLHAM , BROWN RAYMOND , SCHIFRIN BARRY S. , HIMSWORTH JOHN M. , HAYES‐GILL BARRIE R.
Published: August 2012

Objective. Compare the accuracy and reliability of fetal heart rate identification from maternal abdominal fetal electrocardiogram signals (ECG) and Doppler ultrasound with a fetal scalp electrode. Design. Prospective open method equivalence study. Setting. Three urban teaching hospitals in the Northeast United States. Sample. 75 women with normal pregnancies in labor at >37 weeks of gestation. Methods. Three fetal heart rate detection methods were used simultaneously in 75 parturients. The fetal scalp electrode was the standard against which abdominal fetal ECG and ultrasound were judged. Main outcome measures. The positive percent agreement with the fetal scalp electrode indicated reliability. Bland–Altman analysis determined accuracy. The confusion rate indicated how frequently the devices tracked the maternal heart rate. Results. Positive percent agreement was 81.7 and 73% for the abdominal fetal ECG and ultrasound, respectively (p = 0.002). The abdominal fetal ECG had a lower root mean square error than ultrasound (5.2 vs. 10.6 bpm, p < 0.001). The confusion rate for ultrasound was 20‐fold higher than for abdominal ECG (8.9 vs. 0.4%, respectively, p < 0.001). Conclusion. Compared with the fetal scalp electrode, fetal heart rate detection using abdominal fetal ECG was more reliable and accurate than ultrasound, and abdominal fetal ECG was less likely than ultrasound to display the maternal heart rate in place of the fetal heart rate.
Epstein‐Barr virus frequency in primary central nervous system lymphomas in Turkey
Authors: Saglam Arzu , Akyurek Nalan , Soylemezoglu Figen , Uner Aysegul
Published: August 2012

Primary central nervous system (CNS) lymphomas are rare neoplasms which are usually not associated with Epstein‐Barr virus (EBV) in immunocompetent patients. The aim of this study was to investigate the incidence of EBV in primary CNS lymphomas in the Turkish population. Thirty‐two primary CNS lymphomas diagnosed according to the WHO 2008 criteria were included in this study. The presence of EBV small ribonucleic acids was investigated by in situ hybridization using EBV encoded small RNA oligonucleotides. The expression of CD10, Bcl‐6, MUM‐1/IRF‐4, Bcl‐2, and Ki‐67 were evaluated using immunohistochemistry. The patient cohort included 20 male patients and 12 female patients with a median age of 53.5 years (range 13–75). Seven (22%) of cases were classified as germinal center (GC) and 25 (78%) cases as non‐GC phenotype according to the Hans criteria. Twenty‐six (81%) of the cases showed strong Bcl‐2 expression and the median Ki‐67 index was 78%. EBV expression was observed in four primary CNS lymphoma cases (12.5%). Most primary CNS lymphomas show non‐GC phenotype with high Bcl‐2 expression and high proliferative rate. The incidence of EBV in primary CNS lymphomas from Turkey appears to be higher than that observed in the Western countries.
Coaching communication issues with elite female athletes: Two Norwegian case studies
Authors: Kristiansen E. , Tomten S. E. , Hanstad D. V. , Roberts G. C.
Published: August 2012

The aim of this study was to examine the careers of two successful female elite athletes who later stagnated, and to identify possible factors that might have led to their demotivation. Individual interviews and a focus group interview were conducted. Using a multidisciplinary approach, the stories of April and Hazel raised several issues related to coaching, coach education, and the development of female athletes. Their individual profiles revealed that their perception of the lack of long‐term development was caused by coach miscommunication, having to cope with sudden fame, and injuries provoked by overtraining. The coach–athlete relationship was discussed with a focus on the inexperience of some coaches, the number of coaches the athletes had to deal with, sociolinguistic issues, and the differing criteria of success communicated. Finally, the importance of their national governing bodies to focus on knowledge transfer, the supervision of coaches, and the infrastructure to monitor athletes were discussed.
Subtype specificity interaction of bactridines with mammalian, insect and bacterial sodium channels under voltage clamp conditions
Authors: Peigneur Steve , Sevcik Carlos , Tytgat Jan , Castillo Cecilia , D'Suze Gina
Published: August 2012

The present work demonstrates that bactridines (Bacts) possess different selectivities for neuronal and muscular voltage‐dependent sodium (NaV) channels, with subtle differences on channel isoforms. Bacts 2, 3, 4, 5 and 6 (100 nm) reduced the peak current of several skeletal and neuronal channel isoforms selectively. Bacts 2 and 3 were more potent on NaV1.4, Bacts 4 and 6 on NaV1.3 and Bact 5 on NaV1.7. Bactridines (except Bacts 1 and 5) caused a hyperpolarizing shift in the V1/2 of activation and inactivation of NaV1.3, NaV1.4 and NaV1.6. Voltage shifts of Boltzmann curves fitted to activation and inactivation occurred with a decrease in κ. Since the slope is proportional to κ = RT/zF, changes in κ probably express changes in z, the valence, in a voltage‐dependent manner. Changes in z may express toxin‐induced changes in the channel ionic environment, perhaps due to surface charges of the molecules. Bact 2 induced a NaV1.2 voltage shift of the activation curves but no shift of the mutant NaV1.2 IFM/QQQ; peak INa was reduced in both channel forms, suggesting that channel blockage resulted from toxin binding to a site partially distinct from the α subunit binding site 4. Bactridines emerge as potential research tools to understand sodium channel isoform structure–function relationships and also as pharmacologically interesting peptides.
The carbon footprint of Australian ambulance operations
Authors: Brown Lawrence H , Canyon Deon V , Buettner Petra G , Crawford J Mac , Judd Jenni ,   Australian Ambulance Services Emissions Study Group
Published: August 2012

Objective

To determine the greenhouse gas emissions associated with the energy consumption of Australian ambulance operations, and to identify the predominant energy sources that contribute to those emissions.

Methods

A two‐phase study of operational and financial data from a convenience sample of Australian ambulance operations to inventory their energy consumption and greenhouse gas emissions for 1 year. State‐ and territory‐based ambulance systems serving 58% of Australia's population and performing 59% of Australia's ambulance responses provided data for the study.

Results

Emissions for the participating systems totalled 67 390 metric tons of carbon dioxide equivalents. For ground ambulance operations, emissions averaged 22 kg of carbon dioxide equivalents per ambulance response, 30 kg of carbon dioxide equivalents per patient transport and 3 kg of carbon dioxide equivalents per capita. Vehicle fuels accounted for 58% of the emissions from ground ambulance operations, with the remainder primarily attributable to electricity consumption. Emissions from air ambulance transport were nearly 200 times those for ground ambulance transport.

Conclusion

On a national level, emissions from Australian ambulance operations are estimated to be between 110 000 and 120 000 tons of carbon dioxide equivalents each year. Vehicle fuels are the primary source of emissions for ground ambulance operations. Emissions from air ambulance transport are substantially higher than those for ground ambulance transport.
Earthquake‐related crush fractures and non‐earthquake‐related fractures of the extremities: A comparative radiological study
Authors: Chen Tian‐Wu , Yang Zhi‐Gang , Dong Zhi‐Hui , Tang Si‐Shi , Chu Zhi‐Gang , Shao Heng , Deng Wen , Chen Jing
Published: August 2012

Objective

To determine the features that differentiate earthquake‐related crush extremity fractures from non‐earthquake‐related extremity fractures by using digital radiography (DR) and multidetector row computed tomography (MDCT).

Methods

Six hundred and twenty‐three consecutive victims with crush extremity fractures arising from the 2008 Sichuan earthquake, including 611 undergoing DR and 12 undergoing MDCT, entered the test group, and 316 consecutive victims with non‐earthquake‐related extremity fractures, including 301 undergoing DR and 15 undergoing MDCT, were enrolled in the control group. Image data were reviewed retrospectively and statistically between groups focusing on the anatomic distributions, numbers and types of extremity fractures.

Results

Fractures involving multiple extremities were more likely in the test group than the control group (88/623 vs 27/316 victims, P < 0.05). Fractures involving multiple bones (336/623 vs 112/316 victims) and comminuted fractures (324/623 vs 78/316 victims) were seen more frequently in the test group than the control group with both occurring predominantly in the tibia and fibula (all P < 0.05).

Conclusion

Earthquake‐related crush fractures of extremities are more likely than non‐earthquake‐related extremity fractures to involve multiple extremities, multiple bones and to be comminuted. The lower extremities, predominantly the tibia and fibula, are more likely to be involved. This has implications for emergency and disaster planning in earthquake‐prone regions.
Health‐related behaviours and family support and clinical symptoms of BPH: a pilot study from China
Authors: Wang Hongjing , Liang Yuan , Li Yanhua , Cheng Yingsheng , Yin Ping
Published: August 2012

The aim of the current study was to explore the effect of health‐related behaviours and the support of family members on the clinical symptoms of benign prostatic hyperplasia (BPH) patients, and to provide some clues for the symptoms control of BPH. The data were collected in three hospitals in Hubei Province, China, from June to September 2011. The health‐related behaviours included cigarette smoking, alcohol intake, tea and coffee consumption, and drinking water regularly, and the support of family members included the support from spouse, siblings, and offspring in the previous year. The χ2 test and multivariable logistic regression models were used to assess their effects on the International Prostatic Symptom Score (IPSS). With regard to health‐related behaviours, only coffee consumption (OR = 0·33, 95% CI: 0·11–0·96) and drinking water regularly (OR = 0·44, 95% CI: 0·24–0·81) had significant effects on the IPSS. Although the χ2 test suggested that support from offspring of patients with BPH was statistically significant, after adjusting for potential confounding variables the association was not statistically significant. Although there were some limitations, the current study provides preliminary clues and evidences for the role of coffee intake and regularly drinking water played in the Chinese men with BPH. More in‐depth research is needed to enhance the role of health‐related behaviours and social factors in the clinical practice of BPH.
Adjustment of Children and Youth in Military Families: Toward Developmental Understandings
Authors: Maholmes Valerie
Published: August 2012

Nearly, 2 million children in the United States live in military families. Throughout all branches of the U.S. military since September 11, 2001, ca 700,000 children have had or currently have a parent deployed to the combat zones of Iraq or Afghanistan. As a result, researchers are paying increasing attention to the effects of military deployment on children and families. These facts and the changing landscape of military service point to the need to empirically examine the impact of parental military deployment on immediate and longer term child adjustment. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) recently initiated a research program to address these issues. This article draws on attachment and family stress theories as a frame for discussing the effects of parental deployment on child adjustment and family functioning and for outlining the NICHD research priorities. It discusses areas where developmental science can make important contributions as well as challenges for conducting research in military families.
High‐resolution melting analysis: a genotyping tool for population studies on Daphnia
Authors: Kuster C. J. , Von Elert E.
Published: August 2012

Determining genetic variation at the DNA level within and between natural populations is important for understanding the role of natural selection on phenotypic traits, but many techniques of screening for genetic variation are either cost intensive, not sensitive enough or too labour‐ and time‐consuming. Here, we demonstrate high‐resolution melting analysis (HRMA) as a cost‐effective and powerful tool for screening variable target genes in natural populations. HRMA is based on monitoring the melting of PCR amplicons. Owing to saturating concentrations of a dye that binds at high concentrations to double‐stranded DNA, it is possible to genotype high numbers of samples rapidly and accurately. We analysed digestive trypsins of two Daphnia magna populations as an application example for HRMA. One population originated from a pond containing toxic cyanobacteria that possibly produce protease inhibitors and the other from a pond without such cyanobacteria. The hypothesis was that D. magna clones from ponds with cyanobacteria have undergone selection by these inhibitors, which has led to different trypsin alleles. We first sequenced pooled genomic PCR products of trypsins from both populations to identify variable DNA sequences of active trypsins. Second, we screened variable DNA sequences of each D. magna clone from both populations for single nucleotide polymorphisms via HRMA. The HRMA results revealed that both populations exhibited phenotypic differences in the analysed trypsins. Our results indicate that HRMA is a powerful genotyping tool for studying the variation of target genes in response to selection within and between natural Daphnia populations.
Factors associated with early and late failure of dental implants
Authors: Sakka Salah , Baroudi Kusai , Nassani Mohammad Zakaria
Published: August 2012

Osseointegration is a good indication of the clinical success of titanium implants referring to the direct anchorage of such implants to the surrounding host bone. Despite the high success rate of endosseous dental implants, they do fail. A lack of primary stability, surgical trauma, and infection seem to be the most important causes of early implant failure. Early signs of infection may be an indication of a much more critical result than if the same complications occur later, because of disturbance of the primary bone healing process. Occlusal overload and periimplantitis seem to be the most important factors associated with late failure. Suboptimal implant design and improper prosthetic constructions are among those risk factors responsible for implant complications and failure. This concise review highlights the main causes associated with early and late implant failure, as thorough knowledge of this unavoidable clinical fact is essential in the field of oral implantology.
Investigation of the effect of ibuprofen on the healing of osseointegrated oral implants
Authors: Sakka Salah , Hanouneh Salah I.
Published: August 2012

Objective

To investigate the effect of a 1‐week postoperative course of 600 mg of ibuprofen taken four times a day on marginal bone level around oral implants.

Materials and methods

Twenty‐eight patients were allocated to the ibuprofen group (14 patients) or no‐ibuprofen group (14 patients). Overall, 57 implants were inserted, 31 implants in the ibuprofen group and 26 in the no‐ibuprofen group. The primary outcome measure was the change in marginal bone level around oral implants from baseline (2 weeks postplacement) to the 3‐ and 6‐month radiographic examinations. The paralleling technique and a film holder coupled to a beam‐aiming device were used to take the periapical radiographs. Measurement of changes in bone level was made using a viewing box and ×8 magnifier.

Results

Three subjects were withdrawn from the therapy early as they did not complete the dose of ibuprofen (e.g. because of self‐reported stomach upset). The mean marginal mesial bone loss from the baseline was 0.37 mm at the 3‐month and 0.27 mm at the 6‐month follow up for the ibuprofen group, while the corresponding values for the no‐ibuprofen group were 0.15 mm and 0.08 mm. The mean marginal distal bone loss from the baseline was 0.42 mm at the 3‐month and 0.2 mm at the 6‐month follow up for the ibuprofen group, while the corresponding values for the no‐ibuprofen group were 0.08 mm and 0.15mm. There were no significant differences between the ibuprofen and no‐ibuprofen groups when comparing the bone changes.

Conclusion

Administration of a short course of systemic ibuprofen for postoperative pain management following implant insertion may not have a significant effect on the marginal bone loss around oral implants in the early healing phase.
The association of age at first start with career length in theAustralianThoroughbred racehorse population
Authors: Velie B. D. , Knight P. K. , Thomson P. C. , Wade C. M. , Hamilton N. A.
Published: August 2012

Reasons for performing study

Studies ofThoroughbred racing populations have provided evidence of a positive effect on racing careers for horses that commence racing as 2‐year‐olds. Currently, research investigating the presence of this effect in theAustralianThoroughbred racing population is limited.

Objectives

To investigate the association between age at first start and career length in theAustralianThoroughbred population and estimate the risk of racing retirement for horses racing inAustralia based on age at first start, career earnings, number of starts as a 2‐year‐old and distance raced.

Methods

Data were collected forThoroughbreds, born on or after 1January 1998, that had raced between 1August 2000 and 22February 2011 inAustralia. AKaplan–Meier survival curve, stratified by age group, was produced for career length. ACox proportional hazard model was fitted to assess factors influencing the risk of retirement from racing. The model included sex, age at first start, career earnings, number of starts as a 2‐year‐old, distance raced and appropriate interaction terms.

Results

The study population included 117,088 horses. Geldings had significantly (P<0.001) longer careers than females and intact males, and females had significantly (P<0.001) longer careers than intact males. Risk of retirement from racing decreased with a younger age at first start, a higher number of starts as a 2‐year‐old, and a longer average distance raced. For intact males, the risk of retirement from racing increased as earnings increased, while for females and geldings the risk of retirement from racing decreased as earnings increased.

Conclusions and potential relevance

The introduction of youngThoroughbreds to racing appears to have no apparent adverse effects on these horses racing inAustralia. The impact of some risk factors associated with retirement from racing varied between sexes and should be considered when evaluating career outcomes.
Text‐in‐context: a method for extracting findings in mixed‐methods mixed research synthesis studies
Authors: Sandelowski Margarete , Leeman Jennifer , Knafl Kathleen , Crandell Jamie L.
Published: August 2012

Aim

Our purpose in this paper is to propose a new method for extracting findings from research reports included in mixed‐methods mixed research synthesis studies.

Background

International initiatives in the domains of systematic review and evidence synthesis have been focused on broadening the conceptualization of evidence, increased methodological inclusiveness and the production of evidence syntheses that will be accessible to and usable by a wider range of consumers. Initiatives in the general mixed‐methods research field have been focused on developing truly integrative approaches to data analysis and interpretation.

Data source

The data extraction challenges described here were encountered, and the method proposed for addressing these challenges was developed, in the first year of the ongoing (2011–2016) study: Mixed‐Methods Synthesis of Research on Childhood Chronic Conditions and Family.

Discussion

To preserve the text‐in‐context of findings in research reports, we describe a method whereby findings are transformed into portable statements that anchor results to relevant information about sample, source of information, time, comparative reference point, magnitude and significance and study‐specific conceptions of phenomena.

Implications for nursing

The data extraction method featured here was developed specifically to accommodate mixed‐methods mixed research synthesis studies conducted in nursing and other health sciences, but reviewers might find it useful in other kinds of research synthesis studies.

Conclusion

This data extraction method itself constitutes a type of integration to preserve the methodological context of findings when statements are read individually and in comparison to each other.
Experience of social role strain in Korean women with type 2 diabetes
Authors: Park Hyunjeong , Wenzel Jennifer A.
Published: August 2012

Aim

To expand our understanding of the experience of social role strain in the context of diabetes care among middle‐aged married Korean women with type 2 diabetes.

Background

Diabetes remains an international concern. There are special challenges experienced by middle‐aged married women who may not prioritize self‐care and disease management. These challenges may be heightened in certain cultures due to traditional female and family roles along with other social norms and values.

Design

Descriptive qualitative study.

Methods

This qualitative descriptive study involves in‐depth interviews conducted between January–February 2007 with ten middle‐aged married Korean women purposively selected to represent both higher and lower levels of role strain as measured by the measure of role gratification and strain instrument from the companion study, which was conducted simultaneously.

Findings

Korean women in this study reported ‘resentment regarding previous role strain’. This psychosocial burden was heightened by a noted pattern of ‘sacrificing self in favour of others’, which complicated both their personal lives and their ability to take care of themselves physically. Added to this were feelings of guilt related to their diabetes and the requirements of day‐to‐day management expressed as, ‘my diabetes makes me a liability’.

Conclusion

The women's role‐strain experience related to their diabetes was intertwined with their past and current daily life. Further explication and interventions to address and manage role strain could potentially improve women's disease management and overall quality of life.
The Role of Scripts in Psychological Maladjustment and Psychotherapy
Authors: Demorest Amy P.
Published: August 2012

This article considers the value of script theory for understanding psychological maladjustment and psychotherapy. Scripts are implicit expectations that individuals develop to understand and deal with emotionally significant life experiences. Script theory provides a way to understand the complex patterns of thinking, feeling, and behavior that characterize personal consistency, as well as a way to address personality development and change. As such it is a vital model for understanding both personality and clinical phenomena. The article begins by describing script theory and noting similar models in personality and clinical psychology. It then outlines both idiographic and nomothetic methods for assessing scripts and discusses the strengths and weaknesses of each. A survey of the author's program of research follows, using a nomothetic method to examine the role of interpersonal scripts in psychological maladjustment and psychotherapy. The article concludes by presenting a promising method for future research synthesizing idiographic and nomothetic approaches and raising important questions for future research on the role of scripts in psychological maladjustment and psychotherapy.
Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte‐derived microRNA‐122
Authors: van der Meer A. J. , Farid W. R. R. , Sonneveld M. J. , de Ruiter P. E. , Boonstra A. , van Vuuren A. J. , Verheij J. , Hansen B. E. , de Knegt R. J. , van der Laan L. J. W. , Janssen H. L. A.
Published: August 2012

As chronic hepatitis C patients with progressive disease can present themselves with normal ALT levels, more sensitive biomarkers are needed. MicroRNAs are newly discovered small noncoding RNAs that are stable and detectable in the circulation. We aimed to investigate the association between hepatocyte‐derived microRNAs in serum and liver injury in patients with chronic hepatitis C. The hepatocyte‐derived miR‐122 and miR‐192 were analysed in sera of 102 chronic HCV‐infected patients and 24 healthy controls. Serum levels of miR‐122 and miR‐192 correlated strongly with ALT (R = 0.67 and R = 0.65, respectively, P < 0.001 for both). Median levels of miR‐122 and miR‐192 in HCV‐infected patients were 23 times and 8 times higher as in healthy controls (P < 0.001 for both). Even within the HCV‐infected patients with a normal ALT (n = 38), the levels of miR‐122 and miR‐192 were 12 times and 4 times higher compared with healthy controls (P < 0.001 for both). Multivariate logistic regression analyses showed that only miR‐122 was a significant predictor of the presence of chronic HCV infection (P = 0.026). Importantly, miR‐122 was also superior in discriminating chronic HCV‐infected patients with a normal ALT from healthy controls compared with the ALT level (AUC = 0.97 vs AUC = 0.78, P = 0.007). In conclusion, our study confirmed that liver injury is associated with high levels of hepatocyte‐derived microRNAs in circulation and demonstrated that in particular miR‐122 is a sensitive marker to distinguish chronic hepatitis C patients from healthy controls. More sensitive blood markers would benefit especially those patients with minor levels of hepatocellular injury, who are not identified by current screening with ALT testing.
Recruitment of Dynamic Endothelial Ca2+ Signals by the TRPA1 Channel Activator AITC in Rat Cerebral Arteries
Authors: Qian Xun , Francis Michael , Solodushko Viktoriya , Earley Scott , Taylor Mark S.
Published: August 2012

Objective

Stimulation of endothelial TRP channels, specifically TRPA1, promotes vasodilation of cerebral arteries through activation of Ca2+‐dependent effectors along the myoendothelial interface. However, presumed TRPA1‐triggered endothelial Ca2+ signals have not been described. We investigated whether TRPA1 activation induces specific spatial and temporal changes in Ca2+ signals along the intima that correlates with incremental vasodilation.

Methods

Confocal imaging, immunofluorescence staining, and custom image analysis were employed.

Results

We found that endothelial cells of rat cerebral arteries exhibit widespread basal Ca2+ dynamics (44 ± 6 events/minute from 26 ± 3 distinct sites in a 3.6 × 104 μm2 field). The TRPA1 activator AITC increased Ca2+ signals in a concentration‐dependent manner, soliciting new events at distinct sites. Origination of these new events corresponded spatially with TRPA1 densities in IEL holes, and the events were prevented by the TRPA1 inhibitor HC‐030031. Concentration‐dependent expansion of Ca2+ events in response to AITC correlated precisely with dilation of pressurized cerebral arteries (p = 0.93 by F‐test). Correspondingly, AITC caused rapid endothelium‐dependent suppression of asynchronous Ca2+ waves in subintimal smooth muscle.

Conclusions

Our findings indicate that factors that stimulate TRPA1 channels expand Ca2+ signal‐effector coupling at discrete sites along the endothelium to evoke graded cerebral artery vasodilation.
Stoking the drug target pipeline for human African trypanosomiasis
Authors: Phillips Margaret A.
Published: August 2012

Trypanosoma brucei is the causative agent of African sleeping sickness, putting at risk up to 50 million people in sub‐Saharan Africa. Current drug therapies are limited by toxicity and difficult treatment regimes and as the development of vaccines remains unlikely, the identification of better drugs to control this deadly disease is needed. Strategies for the identification of new lead compounds include phenotypic screening or target‐based approaches. Implementation of the latter has been hampered by the lack of defined targets that are both essential and druggable. In this issue of Molecular Microbiology, Jones et al. () report on the characterization of T. brucei pyridoxal kinase (PdxK), an enzyme required for the salvage of vitamin B6, an essential enzymatic cofactor. Genetic knock‐down and small molecule inhibitor studies were used to demonstrate that PdxK is essential for parasite growth both in vitro and in a mouse model, providing both genetic and chemical validation of the target. An enzyme assay compatible with high‐throughput screening (HTS) was developed and the X‐ray crystal structure solved, showing the potential for species selective inhibition. These studies add a greatly needed additional target into the drug discovery pipeline for this deadly parasitic infection.
Science Signaling
Podcast: 28 August 2012
Authors: Wang Guanghui , VanHook Annalisa M.
Published: August 2012

A protease can help protect against neurodegeneration by preventing inflammation in microglia.
Keep On Neurexin
Authors: Hurtley Stella M.
Published: August 2012

Two synaptic adhesion molecules that have been implicated in psychiatric diseases affect the kinetics of synaptic events.
Mutually Exclusive Transcription
Authors: VanHook Annalisa M.
Published: August 2012

Cis-regulatory elements ensure that the expression domains of two patterning signals do not overlap.
Activation of the Unfolded Protein Response by 2-Deoxy-
d
-Glucose Inhibits Kaposi's Sarcoma-Associated Herpesvirus Replication and Gene Expression
Authors: Leung Howard J. , Duran Elda M. , Kurtoglu Metin , Andreansky Samita , Lampidis Theodore J. , Mesri Enrique A.
Published: August 2012

Lytic replication of the Kaposi's sarcoma-associated herpesvirus (KSHV) is essential for the maintenance of both the infected state and characteristic angiogenic phenotype of Kaposi's sarcoma and thus represents a desirable therapeutic target. During the peak of herpesvirus lytic replication, viral glycoproteins are mass produced in the endoplasmic reticulum (ER). Normally, this leads to ER stress which, through an unfolded protein response (UPR), triggers phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α), resulting in inhibition of protein synthesis to maintain ER and cellular homeostasis. However, in order to replicate, herpesviruses have acquired the ability to prevent eIF2α phosphorylation. Here we show that clinically achievable nontoxic doses of the glucose analog 2-deoxy-
d
-glucose (2-DG) stimulate ER stress, thereby shutting down eIF2α and inhibiting KSHV and murine herpesvirus 68 replication and KSHV reactivation from latency. Viral cascade genes that are involved in reactivation, including the master transactivator (RTA) gene, glycoprotein B, K8.1, and angiogenesis-regulating genes are markedly decreased with 2-DG treatment. Overall, our data suggest that activation of UPR by 2-DG elicits an early antiviral response via eIF2α inactivation, which impairs protein synthesis required to drive viral replication and oncogenesis. Thus, induction of ER stress by 2-DG provides a new antiherpesviral strategy that may be applicable to other viruses.
Proteomic Response of Bacillus subtilis to Lantibiotics Reflects Differences in Interaction with the Cytoplasmic Membrane
Authors: Wenzel Michaela , Kohl Bastian , Münch Daniela , Raatschen Nadja , Albada H. Bauke , Hamoen Leendert , Metzler-Nolte Nils , Sahl Hans-Georg , Bandow Julia E.
Published: August 2012

Mersacidin, gallidermin, and nisin are lantibiotics, antimicrobial peptides containing lanthionine. They show potent antibacterial activity. All three interfere with cell wall biosynthesis by binding lipid II, but they display different levels of interaction with the cytoplasmic membrane. On one end of the spectrum, mersacidin interferes with cell wall biosynthesis by binding lipid II without integrating into bacterial membranes. On the other end of the spectrum, nisin readily integrates into membranes, where it forms large pores. It destroys the membrane potential and causes leakage of nutrients and ions. Gallidermin, in an intermediate position, also readily integrates into membranes. However, pore formation occurs only in some bacteria and depends on membrane composition. In this study, we investigated the impact of nisin, gallidermin, and mersacidin on cell wall integrity, membrane pore formation, and membrane depolarization in
Bacillus subtilis
. The impact of the lantibiotics on the cell envelope was correlated to the proteomic response they elicit in
B. subtilis
. By drawing on a proteomic response library, including other envelope-targeting antibiotics such as bacitracin, vancomycin, gramicidin S, or valinomycin, YtrE could be identified as the most reliable marker protein for interfering with membrane-bound steps of cell wall biosynthesis. NadE and PspA were identified as markers for antibiotics interacting with the cytoplasmic membrane.
Influence of Vehicles Used for Oral Dosing of Test Molecules on the Progression of Mycobacterium tuberculosis Infection in Mice
Authors: Singh Shubhra , Dwivedi Richa , Chaturvedi Vinita
Published: August 2012

Preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. We studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate-80 on the progression of
Mycobacterium tuberculosis
infection in mice. Infection was monitored by physical (survival time and body weight) and bacteriological (viable counts in lungs) parameters. Compared with water, corn oil significantly improved both sets of parameters, whereas the other vehicles affected only physical parameters.
Leptospira interrogans Catalase Is Required for Resistance to H
2
O
2
and for Virulence
Authors: Eshghi Azad , Lourdault Kristel , Murray Gerald L. , Bartpho Thanatchaporn , Sermswan Rasana W. , Picardeau Mathieu , Adler Ben , Snarr Brendan , Zuerner Richard L. , Cameron Caroline E.
Published: August 2012

Pathogenic
Leptospira
spp. are likely to encounter higher concentrations of reactive oxygen species induced by the host innate immune response. In this study, we characterized
Leptospira interrogans
catalase (KatE), the only annotated catalase found within pathogenic
Leptospira
species, by assessing its role in resistance to H
2
O
2
-induced oxidative stress and during infection in hamsters. Pathogenic
L. interrogans
bacteria had a 50-fold-higher survival rate under H
2
O
2
-induced oxidative stress than did saprophytic
L. biflexa
bacteria, and this was predominantly catalase dependent. We also characterized KatE, the only annotated catalase found within pathogenic
Leptospira
species. Catalase assays performed with recombinant KatE confirmed specific catalase activity, while protein fractionation experiments localized KatE to the bacterial periplasmic space. The insertional inactivation of
katE
in pathogenic
Leptospira
bacteria drastically diminished leptospiral viability in the presence of extracellular H
2
O
2
and reduced virulence in an acute-infection model. Combined, these results suggest that
L. interrogans
KatE confers
in vivo
resistance to reactive oxygen species induced by the host innate immune response.
Cathelicidin Antimicrobial Peptide Expression Is Not Induced or Required for Bacterial Clearance during Salmonella enterica Infection of Human Monocyte-Derived Macrophages
Authors: Strandberg Kristi L. , Richards Susan M. , Gunn John S.
Published: August 2012

Salmonella enterica
serovar Typhimurium is able to resist antimicrobial peptide killing by induction of the PhoP-PhoQ and PmrA-PmrB two-component systems and the lipopolysaccharide (LPS) modifications they mediate. Murine cathelin-related antimicrobial peptide (CRAMP) has been reported to inhibit
S
. Typhimurium growth
in vitro
and
in vivo
. We hypothesize that infection of human monocyte-derived macrophages (MDMs) with
Salmonella enterica
serovar Typhi and
S
. Typhimurium will induce human cathelicidin antimicrobial peptide (CAMP) production, and exposure to LL-37 (processed, active form of CAMP/hCAP18) will lead to upregulation of PmrAB-mediated LPS modifications and increased survival
in vivo
. Unlike in mouse macrophages, in which CRAMP is upregulated during infection,
camp
gene expression was not induced in human MDMs infected with
S
. Typhi or
S
. Typhimurium. Upon infection, intracellular levels of Δ
phoPQ
, Δ
pmrAB
, and PhoP
c
S
. Typhi decreased over time but were not further inhibited by the vitamin D
3
-induced increase in
camp
expression. MDMs infected with wild-type (WT)
S
. Typhi or
S
. Typhimurium released similar levels of proinflammatory cytokines; however, the LPS modification mutant strains dramatically differed in MDM-elicited cytokine levels. Overall, these findings indicate that
camp
is not induced during
Salmonella
infection of MDMs nor is key to
Salmonella
intracellular clearance. However, the cytokine responses from MDMs infected with WT or LPS modification mutant strains differ significantly, indicating a role for LPS modifications in altering the host inflammatory response. Our findings also suggest that
S
. Typhi and
S
. Typhimurium elicit different proinflammatory responses from MDMs, despite being capable of adding similar modifications to their LPS structures.
The Alveolar Epithelial Cell Chemokine Response to Pneumocystis Requires Adaptor Molecule MyD88 and Interleukin-1 Receptor but Not Toll-Like Receptor 2 or 4
Authors: Bello-Irizarry Sheila N. , Wang Jing , Olsen Keith , Gigliotti Francis , Wright Terry W.
Published: August 2012

Pneumocystis
is an opportunistic fungal pathogen that causes pneumonia in a variety of clinical settings. An early step in
Pneumocystis
infection involves the attachment of organisms to alveolar epithelial cells (AECs). AECs produce chemokines in response to
Pneumocystis
stimulation, but the upstream host-pathogen interactions that activate AEC signaling cascades are not well-defined. MyD88 is an adaptor molecule required for activation of proinflammatory signaling cascades following Toll-like receptor (TLR)-dependent recognition of conserved molecular patterns on pathogens. To determine whether the TLR/MyD88 pathway is required for the AEC chemokine response to
Pneumocystis
, wild-type (WT) and MyD88-deficient AECs were incubated with
Pneumocystis
. As expected, WT AECs produced CCL2 and CXCL2 following
Pneumocystis
stimulation. In contrast, MyD88-deficient AECs were severely impaired in their ability to respond to
Pneumocystis
. MyD88-deficient AECs did not display
Pneumocystis
-induced Jun N-terminal protein kinase activation and produced much less chemokine than
Pneumocystis
-stimulated WT AECs. Using a panel of TLR agonists, primary murine AECs were found to respond vigorously to TLR2 and TLR4 agonists. However, the AEC chemokine response to
Pneumocystis
did not require TLR2 or TLR4. Surprisingly, the interleukin-1 receptor (IL-1R) was required for an AEC chemokine response to
Pneumocystis
. The role of MyD88 in early responses during
Pneumocystis
infection was supported by
in vivo
studies demonstrating that MyD88-deficient mice showed impaired
Pneumocystis
-stimulated chemokine production and impaired inflammatory cell recruitment. These data indicate an important role for MyD88 in the AEC inflammatory response to
Pneumocystis
.