bluuebunny/crossref_metadata_2025 huggingface dataset:
Graphical Exploration of Dimensions of Preterm Infant Growth in Weight in Association With Biological, Nutritional, and Energy Expenditure Conditions
Authors: Pridham Karen , Brown Roger , Bamberger Janine M. , Wells Jonathan , Greer Frank , Mounts Kyle
Published: March 2011

The small sample sizes of studies involving preterm infants limit the use of statistics for examination of multivariate conditions contributing to clinically important growth dimensions of weight: rate of weight gain, body composition (fat-free and fat mass), and weight relative to reference infants (z score). The authors used graphical analyses, including multivariate proportional matrix, parallel coordinates, and bivariate plots with regression lines and splines, to explore specific variables derived from a theoretical model of biological, nutritional intake, and energy expenditure conditions influencing growth dimensions. The sample included 28 infants in 4 birth-weight categories: extremely low (<1,000 g), very low/smaller (1,000—1,249 g), very low/larger (1,250—1,499 g), and low (1,500—1,750 g). The authors examined the rate of weight gain before and after nipple feeding initiation. Fat-free mass was estimated with total body water and fetal reference data, and fat mass with skinfold thicknesses. Despite infants achieving the expected rate of weight gain for a fetus of the same postconceptional age, by hospital discharge 13 infants showed growth restriction with weight <10th centile. Infants with respiratory distress syndrome history were highest in negative z-score change from regain of birth weight to discharge, despite higher ordering on protein intake and fat-free mass. Graphical analyses provided visual patterns of distributions and orderings of measures of multiple variables that, taken together, identified potential influencing conditions and raised questions for further study. Other variables, including feeding protocols and practices, infant feeding competence, and health status, may contribute to variability in weight growth dimensions and influence relationships with biologic, nutritional, and energy expenditure conditions.
Differences in healthcare service utilisation in elderly, registered in eight districts of five European countries
Authors: Vadla Raženka , Božikov Jadranka , Åkerström Bengt , Cheung Wai-Yee , Kovačić Luka , Masanovic Maria , Merilainen Satu , Mihel Sandra , Nummelin-Niemi Hanna , Stefanaki Ioanna , Stencrantz BO
Published: March 2011

Aims: The aim of the study was to compare and analyse the differences in self-reported frequencies of visits paid to physicians and hospitalisation rates, as well as their association with socio-demographic factors and health status self-rated by elderly. Methods: A cross-sectional study was performed in eight districts of five European countries (Finland, Sweden, Ireland, Croatia, and Greece). A total of 3540 persons aged 70 or more were interviewed by trained interviewers. Healthcare service utilisation and its association with demographic characteristics and self-rated health were analysed using descriptive statistical methods, chi-square test, and logistic regression. Results: Almost 90% of elderly visited a physician in the past year; 50% visited a specialist, while 24% were hospitalised. A visit to a specialist was paid by 70% of the Greek, 50% to 60% of the Croatian, and around 40% of the Irish, the Finnish, and the Swedish elderly. The highest proportion of hospitalisations (32%) was encountered in Greece and the lowest one (20%) in Sweden. Self-rated poor health appears to be the only common denominator associated with increased healthcare utilisation. Younger age stood out as a statistically significant predictor of the likelihood of specialist consults, while older age, male gender, and the synergy of male gender and current single life were disclosed as the predictors of hospitalisation frequency. Conclusions: Healthcare service utilisation exercised by the elderly across European districts was found to be highly variable and showed a clear distinction between north-western and south-eastern Europe; this is in line with differences in self-rated health.
Through the eyes of young people: Favourite places for physical activity
Authors: Rehrer Nancy J. , Freeman Claire , Cassidy Tania , Waters Debra L. , Barclay Gary E. , Wilson Noela
Published: March 2011

Introduction: A decrease in physical activity amongst adolescents has been observed and it is well documented that low levels of activity are associated with poor health. In an attempt to understand factors that influence physical activity (PA) in young people research was undertaken with high school students in New Zealand to identify preferred places for PA and establish factors that they felt influenced levels of PA. Methods: One hundred males and 73 females in year nine (aged 12—13) in health and physical education classes completed mapping exercises in which they delineated favourite and least favourite places for PA, where they went on a particular Sunday, how they got there and what they did, and chosen after-school activities and how they got there. Results: Open public spaces were the most favoured places for PA with a nearby beach and park most frequently cited. Specific physical activities, having fun, and having friends to do an activity with were the most frequently cited reasons for liking these places. An industrial harbour area, other schools, and cemeteries were the least favoured places. Less than 2% biked somewhere on the Sunday surveyed and only 23% walked somewhere. The majority were driven to activities by car and a similar reliance on cars was observed for after-school activities. Conclusions: A combination of environmental and social factors is important in both encouraging and discouraging PA and should be taken into account when seeking to enhance PA of young people.
The organisation of dementia care by families in Malta: The experiences of family caregivers
Authors: Innes Anthea , Abela Stephen , Scerri Charles
Published: March 2011

This paper discusses the experiences of dementia family caregivers in Malta. The study design was essentially exploratory as this is the first funded social research on dementia in the island of Malta. In-depth semi-structured interviews were conducted in October 2008 with 17 caregivers. Identification of caregivers was through their relatives’ attendance at a hospital based outpatient memory clinic. Interviews were recorded, transcribed and when required, phrases were translated from Maltese to English. A thematic analysis was guided by the questions; What are the experiences of family caregiving in Malta? And what impact does caregiving have for individual/family life? Three key findings are discussed, namely: the organization of family care in Malta; the use of formal services; and the dislocation of dementia caregiving experiences from wider community life. This paper raises questions about support mechanisms currently available in Malta while presenting cross-national learning opportunities to apply established knowledge to the Maltese context.
Using Photovoice with people with early-stage Alzheimer’s disease: A discussion of methodology
Authors: Wiersma Elaine C.
Published: March 2011

Many scholars and activists have challenged researchers to do research ‘with’ not ‘for’ or ‘on’ people with Alzheimer’s disease and related dementias. Photovoice is a relatively new qualitative methodology that involves giving cameras to participants to record and document their experiences in ways that can create change. In this study, the Photovoice method was used with a group of participants in early stages Alzheimer’s disease to explore the use of Photovoice as a methodology with this population. Specifically, I was hoping to understand how Photovoice could be used as a methodology with this group, and to examine the benefits and challenges of using Photovoice with people with Alzheimer’s disease. This paper discusses some of the practical challenges arising out of using this methodology with people with early stage Alzheimer’s disease as well as some of the issues surrounding research ethics, consent, and capacity.
Successes and challenges of feminist arts-based participatory methodologies with homeless/street-involved women in Victoria
Authors: Clover Darlene
Published: March 2011

This feminist arts-based participatory research project with a group of homeless/street-involved women used group interviews and the creation of collective and individual artworks to explore their personal and political realities and share these with a larger audience. The project built trust and a sense of community, encouraged artistic skills development, and allowed to emerge an artistic identity to combat the stigma of the label ‘homeless’. Individual and collective empowerment came from creating artworks collectively but also, the recognition the women received through publicly sharing their artworks. Tensions and challenges emerged around art as education versus therapy, individual and collective works, the role and place of men, and mental health and the police, two things ever present in the lives of these women.
When the spiral of action research collapses: Using the arts to interpret and continue the process in collective research dialogues
Authors: Tulinius Charlotte , Hølge-Hazelton Bibi
Published: March 2011

In the spiral of action research all participants are expected to work together towards a continuously developing fulfillment of the aims of the project. The data collection is supposed to lead to critical reflection, strategy development, and implementation in cycles, actively involving all participants and researchers. However, communicating processes that go wrong can be difficult. Facing the final communication of an action research project on medical education, we were invited to give a keynote lecture at a workshop with other action researchers. We used this invitation as an opportunity to reframe the researcher—practitioner collaborations as the culturally recognizable stories in the gap between research and practice. This allowed us to continue the action research cycle with a group of research peers that had not been part of the original project. Through the use of photos, music and film clips, and in the frame of a fairy tale, we worked as in a socio-drama, constructing two parallel and illustrated narratives, inviting the peer researchers at the workshop to reflect on our experiences, and to bring in their own experiences. This communication strategy helped us and the research peers to work through the emotional impact of our research. It also developed our understanding of the project process, and supported the peer researchers to tell and share their stories, giving them new insight into their own research processes.
Beneficial Care Approaches in Specialized Daycare Units for Persons With Dementia
Authors: Gústafsdóttir Margrét
Published: March 2011

Background: Daycare services are seen as a valuable means of helping old people to continue living in their own homes. Relatively little is known about care approaches in daycare units and how they benefit the clients themselves. This work attempts to show the way in which the care approaches in daycare units are constituted. Methods: Participant observation that was concluded with individual interviews with the directors of the units. Results: The findings show that beneficial care approaches in these daycare units establish practices and habits that give a particular structure to the course of everyday life of the patient with dementia, enhance the person’s sense of normality, and allow him/her to enjoy being among others, while being appreciated as the person he or she is. Conclusion: Well-organized and knowledgeable daycare service not only provides relief from care for the relatives, but also supports and enriches the lives of the individuals with dementia.
On the Efficacy of Targeted Gang Interventions
Authors: Melde Chris , Gavazzi Stephen , McGarrell Edmund , Bynum Timothy
Published: March 2011

One of the explicit goals of many recent and ongoing criminal justice interventions is to target youth most at risk for involvement in serious, chronic, and violent offending. While targeted programs appear promising at the conceptual level, data limitations have made systematic evaluations of the efficacy of such practices difficult to achieve. The current study helps to fill this void in the literature by examining the relative risk of youth targeted for prevention and intervention services with a comparable sample of youth from the general school population in Cuyahoga County, Ohio. Results suggest that youth targeted by the program under study were significantly less at risk in three of the four risk domains examined, and in seven of the twelve associated subdomains. Further, the nontargeted sample had higher accumulated risk than the targeted sample, which is a robust predictor of gang involvement. Implications for targeted prevention and intervention programs are discussed.
Correlations With Satisfaction Measures in Men Treated With Phosphodiesterase Inhibitors for Erectile Dysfunction
Authors: Mulhall John P. , Kaminetsky Jed C. , Althof Stanley E. , Goldstein Irwin , Creanga Dana L. , Marfatia Aditya , Symonds Tara , Budhwani Meeta
Published: March 2011

This literature review examined the relationship of erectile function to patient satisfaction. Published correlation coefficients ( r values) were sought between patient-reported outcomes (PROs; i.e., instruments/questionnaires) assessing erection or erectile function and PROs assessing individual sexual satisfaction, satisfaction in the context of the couple or relationship, or satisfaction with erection. The U.S. National Library of Medicine’s PubMed database was searched for English-language, randomized, double-blind, placebo-controlled trials of treatment with a phosphodiesterase type 5 inhibitor in men with erectile dysfunction (ED) who were not selected for any concomitant disease. Trials that reported correlations between an ED-specific and psychometrically validated PRO for an erection/erectile function concept and for a selected satisfaction concept were included. All correlations were positive, with almost all r values >" xbd="285" xhg="262" ybd="1530" yhg="1502"/>.50. The positive relationship between results on erection/erectile function PROs and results on satisfaction PROs is probably reinforced bidirectionally such that improved erection/erectile function improves satisfaction, which further improves erection and/or erectile function.
Investigation of Effect on Glycosylated Hemoglobin, Blood Pressure, and Body Mass Index of Diabetes Intensive Education Program in Patients With Type 2 Diabetes Mellitus
Authors: Beyazıt Emel , Mollaoğlu Mukadder
Published: March 2011

This study investigated the effects of a diabetes intensive education program (DIEP) on glycosylated hemoglobin (HbA1c), body mass index (BMI), and arterial blood pressure (BP). An 8-week randomized-controlled trial was conducted in Cumhuriyet University Hospital. Diabetes patients were randomized to control group (CG; n = 25) and intervention group (IG; n = 25) who received DIEP, including the factors affecting metabolic control and implementation of diabetes guidelines. Primary outcomes included HbA1c, BP, and BMI. After the 8 weeks, there was a significant decrease in HbA1c mean values for the intervention group. Also, BP significantly decreased from 143/87 to 130/80 mmHg in the IG as compared with an increase from 137/82 to 137/86 mmHg in the CG. In addition, the results demonstrated that DIEP improved the number of patients at goal for BP (130/80 mmHg). Baseline BMI did not change significantly in either group during the course of the study. These findings show that the DIEP may be effective in decreasing HbA1c levels and improving adherence to BP control.
Using a Syndemics Theory Approach to Study HIV Risk Taking in a Population of Men Who Use the Internet to Find Partners for Unprotected Sex
Authors: Klein Hugh
Published: March 2011

This study examines the value of using syndemics theory as a model for understanding HIV risk taking in a population of men who are at great risk for acquiring and/or transmitting HIV. The principal aim is to provide an empirical test of the applicability of the theory to sexual risk behaviors in this particular research population. The study was based on a national random sample of 332 men who have sex with men, or MSM, who use the Internet to seek men with whom they can engage in unprotected sex. Data collection was conducted via telephone interviews between January 2008 and May 2009. As hypothesized in the syndemics theory model, attitudes toward condom use were central to understanding men’s involvement in risky sex. As hypothesized, these attitudes depended on various demographic, psychological/psychosocial functioning, and sex-related preference measures. Also as hypothesized, psychological and psychosocial functioning were found to be very important to the overall model, and as expected, these factors were shaped greatly by factors such as demographic characteristics and childhood maltreatment experiences. The structural equation assessing the fit of the overall model indicated solid support for the syndemics theory approach. Overall, syndemics theory seems to apply fairly well to understanding the complexity of the factors that underlie men’s risk-taking practices. The complicated interplay among factors such as attitudes toward condom use, childhood maltreatment experiences, psychological and psychosocial functioning, and substance use and abuse—all of which are central to a syndemics theory approach to studying risk—was demonstrated.
Hand injuries from tools in domestic and leisure settings: relative incidence and patterns of initial management
Authors: Williams S. T. B. , Power D.
Published: March 2011

A search of the UK Department of Trade and Industry’s Home and Leisure Accident database found 16,003 emergency hospital attendances in 2000–2002 following accidents with tools. The hand was the site of injury in 9535 cases (60%). The tool most commonly involved was a Stanley knife, causing as many hand injuries (21%) as all power tools combined. The power tools most frequently causing hand injury were circular saws (28% of power tool injuries), hedge trimmers (21%) and electric drills (17%). Compared to injuries from manual tools, power tool hand injuries were more than twice as likely to be referred to specialists and three times more likely to be admitted to hospital. Specialist referral/admission most commonly occurred following hand injury from mowers (51% admitted/referred), routers (50%) and circular saws (48%). The rate for manual blade injuries was 14%. Missed diagnoses following manual blade injuries may stem from comparatively low rates of specialist assessment.
Usability of an Atrial Fibrillation Anticoagulation Decision-Support Tool
Authors: Wess Mark L. , Saleem Jason J. , Tsevat Joel , Luckhaupt Sara E. , Johnston Joseph A. , Wise Ruth E. , Kopke Jonathan E. , Eckman Mark H.
Published: March 2011

Introduction: In individuals with nonvalvular atrial fibrillation, anticoagulant therapy with warfarin reduces the rate of thromboembolic events but increases the risk of bleeding. Treatment decisions frequently are inconsistent with guidelines. A new web-based atrial fibrillation decision-support tool (AF-DST) provides patient-specific information on the risk-benefit tradeoff of anticoagulation. Methods: The authors performed a pilot usability testing study of the AF-DST with 4 medical house officers and 4 attending physicians by simulating 9 outpatient clinical encounters involving tradeoffs between risks and benefits of anticoagulation. They recorded positive and negative critical incidents in the simulations and assessed satisfaction with use of the AF-DST by the Computer System Usability Questionnaire (CSUQ; score range on each item: 1 = strongly disagree to 7 = strongly agree). Results: Users found the AF-DST to be helpful and had high CSUQ scores (mean item score, 6.3). Usability testing identified 6 positive and 14 negative critical incidents. Participants felt that the AF-DST guided them toward the correct decision. Nevertheless, they desired more information on the “black box” calculations and ignored alerts. Training level appeared to affect how the AF-DST was used, in particular, how users interacted with the AF-DST. Conclusions: Overall satisfaction with the AF-DST was high and the tool effectively communicated recommendations and uncertainty. Usability testing identified design issues and potential errors caused by decision-support tool use; these gaps should be addressed prior to clinical implementation.
The SIMARD Screening Tool to Identify Unfit Drivers
Authors: Bédard Michel , Weaver Bruce , Man-Son-Hing Malcolm , Classen Sherrilene , Porter Michelle ,   for the Candrive investigators
Published: March 2011

Dobbs and Schopflocher published an article in which they introduced a tool to identify people who are unfit to drive because of cognitive impairment. In our view, their conclusion that this tool has “. . . a high degree of accuracy that can be used for immediate decisions in the clinical setting”1(p119) is too strongly stated, particularly given that the cut-points they used yield false positive (FP) and false negative (FN) percentages in the 6% to 11% range. We believe the reason for using dual cut-points is to ensure that FP and FN fractions are both controlled very stringently, and that it would be more appropriate to set cut-offs that maintain both of them closer to 1%. Using our own data, we constructed two pairs of dual cut-points—one pair that yielded FP and FN percentages similar to those from the Dobbs and Schopflocher article and another pair that yielded FP and FN percentages no greater than 1%. For the first pair of cut-points, 53% of test results were indeterminate (compared to 50% for Dobbs and Schopflocher). For the second pair of cut-points, 86% of test results were indeterminate. Presumably, the same pattern would be observed in Dobbs and Schopflocher’s data if their current dual cut-points were replaced with cut-points that controlled the FP and FN percentages at more appropriate levels. We also plotted receiver operating characteristic curves, and calculated the area under the curve (AUC) for the Screen for the Identification of Cognitively Impaired Medically At-Risk Drivers, A Modification of the DemTect (SIMARD-MD) and for the combination of the Mini-Mental State Examination and Trail-Making Test A (using our data for the latter). The difference between them was trivial (AUC = 0.75 and 0.72, respectively). Taken together, the results of the two analytic approaches suggest that other tools currently in use by physicians perform at least as well as the SIMARD-MD, and that it does not represent a significant breakthrough.
Aberrant DNA methylation characterizes juvenile myelomonocytic leukemia with poor outcome
Authors: Olk-Batz Christiane , Poetsch Anna R. , Nöllke Peter , Claus Rainer , Zucknick Manuela , Sandrock Inga , Witte Tania , Strahm Brigitte , Hasle Henrik , Zecca Marco , Starý Jan , Bergstraesser Eva , De Moerloose Barbara , Trebo Monika , van den Heuvel-Eibrink Marry M. , Wojcik Dorota , Locatelli Franco , Plass Christoph , Niemeyer Charlotte M. , Flotho Christian ,   the European Working Group of Myelodysplastic Syndromes in Childhood (EWOG-MDS)
Published: March 2011

Aberrant DNA methylation contributes to the malignant phenotype in virtually all types of cancer, including myeloid leukemia. We hypothesized that CpG island hypermethylation also occurs in juvenile myelomonocytic leukemia (JMML) and investigated whether it is associated with clinical, hematologic, or prognostic features. Based on quantitative measurements of DNA methylation in 127 JMML cases using mass spectrometry (MassARRAY), we identified 4 gene CpG islands with frequent hypermethylation: BMP4 (36% of patients), CALCA (54%), CDKN2B (22%), and RARB (13%). Hypermethylation was significantly associated with poor prognosis: when the methylation data were transformed into prognostic scores using a LASSO Cox regression model, the 5-year overall survival was 0.41 for patients in the top tertile of scores versus 0.72 in the lowest score tertile (P = .002). Among patients given allogeneic hematopoietic stem cell transplantation, the 5-year cumulative incidence of relapse was 0.52 in the highest versus 0.10 in the lowest score tertile (P = .007). In multivariate models, DNA methylation retained prognostic value independently of other clinical risk factors. Longitudinal analyses indicated that some cases acquired a more extensively methylated phenotype at relapse. In conclusion, our data suggest that a high-methylation phenotype characterizes an aggressive biologic variant of JMML and is an important molecular predictor of outcome.
A20 (TNFAIP3) genetic alterations in EBV-associated AIDS-related lymphoma
Authors: Giulino Lisa , Mathew Susan , Ballon Gianna , Chadburn Amy , Barouk Sharon , Antonicelli Giuseppina , Leoncini Lorenzo , Liu Yi Fang , Gogineni Swarna , Tam Wayne , Cesarman Ethel
Published: March 2011

A20, a negative regulator of NF-κB, has been implicated as a tumor suppressor gene in multiple types of B-cell lymphoma. AIDS-related lymphomas (ARLs) are high-grade B-cell lymphomas that are frequently associated with EBV infection. We examined a panel of ARLs for A20 alterations. FISH showed A20 deletion in 6 of 33 cases (18%). A20 mutations were found in 3 of 19 cases (16%), including 2 cases with deletions of the comple-mentary allele. Immunohistochemistry showed the absence of A20 protein in 7 of 55 samples (13%). In contrast to reports in Hodgkin lymphoma in which EBV infection and A20 alteration are mutually exclusive, A20 inactivation was observed in both EBV+ and EBV− cases. The EBV latent membrane protein 1, which activates NF-κB, was not expressed in 12 of 13 cases with A20 loss. In ARLs loss of A20 may be an alternative mechanism of NF-κB activation in the absence of latent membrane protein 1 expression.
How I treat acute chest syndrome in children with sickle cell disease
Authors: Miller Scott T.
Published: March 2011

Acute chest syndrome describes new respiratory symptoms and findings, often severe and progressive, in a child with sickle cell disease and a new pulmonary infiltrate. It may be community-acquired or arise in children hospitalized for pain or other complications. Recognized etiologies include infection, most commonly with atypical bacteria, and pulmonary fat embolism (PFE); the cause is often obscure and may be multifactorial. Initiation of therapy should be based on clinical findings. Management includes macrolide antibiotics, supplemental oxygen, modest hydration and often simple transfusion. Partial exchange transfusion should be reserved for children with only mild anemia (Hb > 9 g/dL) but deteriorating respiratory status. Therapy with corticosteroids may be of value; safety, efficacy and optimal dosing strategy need prospective appraisal in a clinical trial. On recovery, treatment with hydroxyurea should be discussed to reduce the likelihood of recurrent episodes.
Autologous stem cell transplantation as a first-line treatment strategy for chronic lymphocytic leukemia: a multicenter, randomized, controlled trial from the SFGM-TC and GFLLC
Authors: Sutton Laurent , Chevret Sylvie , Tournilhac Olivier , Diviné Marine , Leblond Véronique , Corront Bernadette , Leprêtre Stéphane , Eghbali Houchingue , Van Den Neste Eric , Michallet Mauricette , Maloisel Frédéric , Bouabdallah Krimo , Decaudin Didier , Berthou Christian , Brice Pauline , Gonzalez Hugo , Chapiro Elise , Radford-Weiss Isabelle , Leporrier Nathalie , Maloum Karim , Nguyen-Khac Florence , Davi Frédéric , Lejeune Julie , Merle-Béral Hélène , Leporrier Michel ,   for the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) and Groupe Français d'étude de la Leucémie Lymphoïde Chronique (GFLLC)
Published: March 2011

Long-term responses have been reported after autologous stem cell transplantation (ASCT) for chronic lymphocytic leukemia (CLL). We conducted a prospective, randomized trial of ASCT in previously untreated CLL patients. We enrolled 241 patients < 66 years of age with Binet stage B or C CLL. They received 3 courses of mini-CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone/prednisolone) and then 3 courses of fludarabine. Patients in complete response (CR) were then randomized to ASCT or observation, whereas the other patients were randomized to dexamethasone, high-dose aracytin, cisplatin (DHAP) salvage followed by either ASCT or 3 courses of fludarabine plus cyclophosphamide (FC). The primary end point was event-free survival (EFS). After up-front treatment, 105 patients entered CR and were randomized between ASCT (n = 52) and observation (n = 53); their respective 3-year EFS rates were 79.8% and 35.5%; the adjusted hazard ratio was 0.3 (95% CI: 0.1-0.7; P = .003). Ninety-four patients who did not enter CR were randomized between ASCT (n = 46) and FC (n = 48); their respective 3-year EFS rates were 48.9% and 44.4%, respectively; the adjusted hazard ratio was 1.7 (95% CI: 0.9-3.2; P = .13). No difference in overall survival was found between the 2 response subgroups. In young CLL patients in CR, ASCT consolidation markedly delayed disease progression. No difference was observed between ASCT and FC in patients requiring DHAP salvage.
Characterization of the mononuclear phagocyte system in zebrafish
Authors: Wittamer Valerie , Bertrand Julien Y. , Gutschow Patrick W. , Traver David
Published: March 2011

The evolutionarily conserved immune system of the zebrafish (Danio rerio), in combination with its genetic tractability, position it as an excellent model system in which to elucidate the origin and function of vertebrate immune cells. We recently reported the existence of antigen-presenting mononuclear phagocytes in zebrafish, namely macrophages and dendritic cells (DCs), but have been impaired in further characterizing the biology of these cells by the lack of a specific transgenic reporter line. Using regulatory elements of a class II major histocompatibility gene, we generated a zebrafish reporter line expressing green fluorescent protein (GFP) in all APCs, macrophages, DCs, and B lymphocytes. Examination of mhc2dab:GFP; cd45:DsRed double-transgenic animals demonstrated that kidney mhc2dab:GFPhi; cd45:DsRedhi cells were exclusively mature monocytes/macrophages and DCs, as revealed by morphologic and molecular analyses. Mononuclear phagocytes were found in all hematolymphoid organs, but were most abundant in the intestine and spleen, where they up-regulate the expression of inflammatory cytokines upon bacterial challenge. Finally, mhc2dab:GFP and cd45:DsRed transgenes mark mutually exclusive cell subsets in the lymphoid fraction, enabling the delineation of the major hematopoietic lineages in the adult zebrafish. These findings suggest that mhc2dab:GFP and cd45:DsRed transgenic lines will be instrumental in elucidating the immune response in the zebrafish.
Non-CPAP therapies in obstructive sleep apnoea
Authors: Randerath W.J. , Verbraecken J. , Andreas S. , Bettega G. , Boudewyns A. , Hamans E. , Jalbert F. , Paoli J.R. , Sanner B. , Smith I. , Stuck B.A. , Lacassagne L. , Marklund M. , Maurer J.T. , Pepin J.L. , Valipour A. , Verse T. , Fietze I.
Published: March 2011

In view of the high prevalence and the relevant impairment of patients with obstructive sleep apnoea syndrome (OSAS) lots of methods are offered which promise definitive cures for or relevant improvement of OSAS.

This report summarises the efficacy of alternative treatment options in OSAS.

An interdisciplinary European Respiratory Society task force evaluated the scientific literature according to the standards of evidence-based medicine.

Evidence supports the use of mandibular advancement devices in mild to moderate OSAS. Maxillomandibular osteotomy seems to be as efficient as continuous positive airway pressure (CPAP) in patients who refuse conservative treatment. Distraction osteogenesis is usefully applied in congenital micrognathia or midface hypoplasia. There is a trend towards improvment after weight reduction. Positional therapy is clearly inferior to CPAP and long-term compliance is poor. Drugs, nasal dilators and apnoea triggered muscle stimulation cannot be recommended as effective treatments of OSAS at the moment. Nasal surgery, radiofrequency tonsil reduction, tongue base surgery, uvulopalatal flap, laser midline glossectomy, tongue suspension and genioglossus advancement cannot be recommended as single interventions. Uvulopalatopharyngoplasty, pillar implants and hyoid suspension should only be considered in selected patients and potential benefits should be weighed against the risk of long-term side-effects. Multilevel surgery is only a salvage procedure for OSA patients.
Effect of different asthma treatments on risk of cold-related exacerbations
Authors: Reddel H.K. , Jenkins C. , Quirce S. , Sears M.R. , Bateman E.D. , O’Byrne P.M. , Humbert M. , Buhl R. , Harrison T. , Brusselle G.G. , Thorén A. , Sjöbring U. , Peterson S. , Östlund O. , Eriksson G.S.
Published: March 2011

Common colds often trigger asthma exacerbations. The present study compared cold-related severe exacerbations during budesonide/formoterol maintenance and reliever therapy, and different regimens of maintenance inhaled corticosteroids (ICS), with or without long-acting β2-agonists (LABA), and with as-needed short-acting β2-agonists (SABA) or LABA.

Reported colds and severe exacerbations (defined by oral corticosteroid use and/or hospitalisation/emergency room visit) were assessed for 12,507 patients during 6–12 months of double-blind treatment. Exacerbations occurring ≤14 days after onset of reported colds were analysed by a Poisson model.

The incidence of colds was similar across treatments. Asthma symptoms and reliever use increased during colds. Budesonide/formoterol maintenance and reliever therapy reduced severe cold-related exacerbations by 36%versuspooled comparators plus SABA (rate ratio (RR) 0.64; p=0.002), and for individual treatment comparisons, by 52%versusthe same maintenance dose of ICS/LABA (RR 0.48; p<0.001); there were nonsignificant reductionsversushigher maintenance doses of ICS or ICS/LABA (RR 0.83 and 0.72, respectively). As-needed LABA did not reduce cold-related exacerbationsversusas-needed SABA (RR 0.96).

Severe cold-related exacerbations were reduced by budesonide/formoterol maintenance and reliever therapy compared with ICS with or without LABA and with as-needed SABA. Subanalyses suggested the importance of the ICS component in reducing cold-related exacerbations. Future studies should document the cause of exacerbations, in order to allow identification of different treatment effects.
TGFβ1 enhances MAD1 expression and stimulates promoter-bound Pol II phosphorylation: basic functions of C/EBP, SP and SMAD3 transcription factors
Authors: Hein Nadine , Jiang Kan , Cornelissen Christian , Lüscher Bernhard
Published: March 2011

Background

The MAD1 protein, a member of the MYC/MAX/MAD network of transcriptional regulators, controls cell proliferation, differentiation and apoptosis. MAD1 functions as a transcriptional repressor, one direct target gene being the tumor suppressor PTEN. Repression of this gene is critical to mediate the anti-apoptotic function of MAD1. Under certain conditions it also antagonizes the functions of the oncoprotein MYC. Previous studies have demonstrated that MAD1 expression is controlled by different cytokines and growth factors. Moreover we have recently demonstrated that the MAD1 promoter is controlled by the cytokine granulocyte colony-stimulating factor (G-CSF) through the activation of STAT3, MAP kinases and C/EBP transcription factors.

Results

We observed that in addition to G-CSF, the cytokine transforming growth factor β (TGFβ1) rapidly induced the expression of MAD1 mRNA and protein in promyelocytic tumor cells. Moreover we found that C/EBP and SP transcription factors cooperated in regulating the expression of MAD1. This cooperativity was dependent on the respective binding sites in the proximal promoter, with the CCAAT boxes being bound by C/EBPα/β heterodimers. Both C/EBP and SP transcription factors bound constitutively to DNA without obvious changes in response to TGFβ1. In addition SMAD3 stimulated the MAD1 reporter, cooperated with C/EBPα and was bound to the core promoter region. Thus SMAD3 appears to be a potential link between TGFβ1 signaling and C/EBP regulated promoter activity. Moreover TGFβ1 stimulated the phosphorylation of polymerase II at serine 2 and its progression into the gene body, consistent with enhanced processivity.

Conclusions

Our findings suggest that C/EBP and SP factors provide a platform of transcription factors near the core promoter of the MAD1 gene that participate in mediating signal transduction events emanating from different cytokine receptors. SMAD3, a target of TGFβ1 signaling, appears to be functionally relevant. We suggest that a key event induced by TGFβ1 at the MAD1 promoter is the recruitment or activation of cofactors, possibly in complex with C/EBP, SP, and SMAD3 transcriptional regulators, that control polymerase activity.
Introgression potential between safflower (Carthamus tinctorius) and wild relatives of the genus Carthamus
Authors: Mayerhofer Marion , Mayerhofer Reinhold , Topinka Deborah , Christianson Jed , Good Allen G
Published: March 2011

Background

Safflower, Carthamus tinctorius, is a thistle that is grown commercially for the production of oil and birdseed and recently, as a host for the production of transgenic pharmaceutical proteins. C. tinctorius can cross with a number of its wild relatives, creating the possibility of gene flow from safflower to weedy species. In this study we looked at the introgression potential between different members of the genus Carthamus, measured the fitness of the parents versus the F1 hybrids, followed the segregation of a specific transgene in the progeny and tried to identify traits important for adaptation to different environments.

Results

Safflower hybridized and produced viable offspring with members of the section Carthamus and species with chromosome numbers of n = 10 and n = 22, but not with n = 32. The T-DNA construct of a transgenic C. tinctorius line was passed on to the F1 progeny in a Mendelian fashion, except in one specific cross, where it was deleted at a frequency of approximately 21%. Analyzing fitness and key morphological traits like colored seeds, shattering seed heads and the presence of a pappus, we found no evidence of hybrid vigour or increased weediness in the F1 hybrids of commercial safflower and its wild relatives.

Conclusion

Our results suggest that hybridization between commercial safflower and its wild relatives, while feasible in most cases we studied, does not generate progeny with higher propensity for weediness.
Anal infections with concomitant Chlamydia trachomatisgenotypes among men who have sex with men in Amsterdam, the Netherlands
Authors: Quint Koen D , Bom Reinier JM , Quint Wim GV , Bruisten Sylvia M , van der Loeff Maarten F Schim , Morré Servaas A , de Vries Henry JC
Published: March 2011

Background

Lymphogranuloma venereum (LGV) proctitis is caused by Chlamydia trachomatis (Ct) genotype L and is endemic among men who have sex with men (MSM) in western society. Genotype L infections need to be distinguished from non-LGV (genotypes A-K) Ct infections since they require prolonged antibiotic treatment. For this purpose, an in-house developed pmpH based LGV polymerase chain reaction (PCR) test is used at the Amsterdam STI outpatient clinic. We investigated retrospectively the anal Ct genotype distribution, and the frequency of concomitant genotype infections in MSM infected with LGV and non-LGV Ct infections. To detect concomitant Ct genotype infections, the pmpH LGV PCR and genoTyping Reverse Hybridization Assay (Ct-DT RHA) were used.

Methods

A total of 201 Ct positive rectal swabs from MSM were selected, which were previously diagnosed as either LGV (n = 99) or non-LGV Ct infection (n = 102) according to the algorithm of Ct detection by the commercially available Aptima Combo 2 assay followed by an in-house pmpH LGV PCR. The samples were retested with the commercially available Ct-DT RHA, which differentiates between 14 major genotypes and is able to detect concomitant Ct genotypes.

Results

Excellent genotyping agreement was observed between the Ct-DT RHA and the pmpH LGV PCR (Kappa = 0.900, 95%CI = 0.845-0.955, McNemar's p = 1.000). A concomitant non-LGV genotype was detected in 6/99 (6.1%) LGV samples. No additional LGV infections were observed with the Ct-DT RHA among the non-LGV Ct group. In the non-LGV group genotype G/Ga (34.3%) was seen most frequent, followed by genotype D/Da (22.5%) and genotype J (13.7%). All LGV infections were caused by genotype L2.

Conclusions

Concomitant non-LGV genotypes do not lead to missed LGV proctitis diagnosis. The pmpH LGV PCR displayed excellent agreement with the commercially available Ct-DT genotyping RHA test. The genotypes G/Ga, D/Da and J were the most frequent non-LGV Ct strains in MSM.
Inhibin B and anti-Müllerian hormone as markers of gonadal function after hematopoietic cell transplantation during childhood
Authors: Laporte Sylvie , Couto-Silva Ana-Claudia , Trabado Séverine , Lemaire Pierre , Brailly-Tabard Sylvie , Espérou Hélène , Michon Jean , Baruchel André , Fischer Alain , Trivin Christine , Brauner Raja
Published: March 2011

Background

It is difficult to predict the reproductive capacity of children given hematopoietic cell transplantation (HCT) before pubertal age because the plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are not informative and no spermogram can be done.

Methods

We classified the gonadal function of 38 boys and 34 girls given HCT during childhood who had reached pubertal age according to their pubertal development and FSH and LH and compared this to their plasma inhibin B and anti-Müllerian hormone (AMH).

Results

Ten (26%) boys had normal testicular function, 16 (42%) had isolated tubular failure and 12 (32%) also had Leydig cell failure. All 16 boys given melphalan had tubular failure. AMH were normal in 25 patients and decreased in 6, all of whom had increased FSH and low inhibin B.

Seven (21%) girls had normal ovarian function, 11 (32%) had partial and 16 (47%) complete ovarian failure. 7/8 girls given busulfan had increased FSH and LH and 7/8 had low inhibin B. AMH indicated that ovarian function was impaired in all girls.

FSH and inhibin B were negatively correlated in boys (P < 0.0001) and girls (P = 0.0006). Neither the age at HCT nor the interval between HCT and evaluation influenced gonadal function.

Conclusion

The concordance between FSH and inhibin B suggests that inhibin B may help in counselling at pubertal age. In boys, AMH were difficult to use as they normally decrease when testosterone increases at puberty. In girls, low AMH suggest that there is major loss of primordial follicles.
Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin
Authors: Bak Rasmus O , Stenderup Karin , Rosada Cecilia , Petersen Line B , Moldt Brian , Dagnæs-Hansen Frederik , Jakobsen Maria , Kamp Søren , Jensen Thomas G , Dam Tomas N , Mikkelsen Jacob Giehm
Published: March 2011

Background

Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα), interleukin-12 (IL-12), and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs) delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B) of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs.

Methods

Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels.

Results

Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by immunohistological examination.

Conclusions

Our studies consolidate the properties of lentiviral vectors as a tool for potent gene delivery and for evaluation of mRNA targets for anti-inflammatory therapy. However, in contrast to local anti-TNFα treatment, the therapeutic potential of targeting IL-12B at the RNA level in psoriasis is questioned.
Oxaliplatin long-circulating liposomes improved therapeutic index of colorectal carcinoma
Authors: Yang Chuang , Liu Hai Z , Fu Zhong X , Lu Wei D
Published: March 2011

Background

Cytotoxic drugs are non-selective between normal and pathological tissue, and this poses a challenge regarding the strategy for treatment of tumors. To achieve sufficient antitumor activity for colorectal carcinoma, optimization of the therapeutic regimen is of great importance. We investigated the ability of oxaliplatin long-circulating liposomes (PEG-liposomal L-oHP) to provide an improved therapeutic index of colorectal carcinoma.

Results

We determined that PEG- liposomes conjugated with cells at 2 h, with a mean fluorescence intensity that was enhanced upon extended induction time. The PEG-liposomal L-oHP induced a significant apoptotic response as compared with free L-oHP, 23.21% ± 3.38% vs. 16.85% ± 0.98%, respectively. Fluorescence imaging with In-Vivo Imaging demonstrated that PEG- liposomes specifically targeted tumour tissue. After intravenous injections of PEG-liposomal L-oHP or free L-oHP, the tumour volume suppression ratio was 26.08% ± 12.43% and 18.19% ± 7.09%, respectively, the percentage increased life span (ILS%) was 45.36% and 76.19%, respectively, and Bcl-2, Bax mRNA and protein expression in tumour tissue was 0.27-fold vs. 0.88-fold and 1.32-fold vs. 1.61-fold compared with free L-oHP, respectively.

Conclusion

The PEG-liposomal L-oHP exhibited a tendency to target tumour tissue and demonstrated a significantly greater impact on apoptosis compared to free oxaliplatin.