bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the cantharidin‐induced skin blister as an in vivo model of inflammation
Authors: Dinh Phong Huy Duc , Corraza Francis , Mestdagh Kristel , Kassengera Zaina , Doyen Virginie , Michel Olivier 
Published: May 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Techniques to create aseptic inflammatory reactions provide information regarding acute inflammatory pathways and may be used to assess the anti‐inflammatory properties of novel drugs.WHAT THIS STUDY ADDS• In this study, we have shown that the cantharidin‐induced blister is a local inflammatory reaction, safe and well tolerated, with a good intra‐subject inter‐day reproducibility. This induced blister is inhibited by specific (anti‐tumour necrosis factor (TNF)) and non specific (corticosteroids) systemic anti‐inflammatory agents. This model could be of interest to evaluate anti‐inflammatory agents in their early phase development.AIM Pharmacological profiling techniques, such as the cantharidin‐induced skin blister, may be used to assess the anti‐inflammatory properties of novel drugs. However, no data are available on the reproducibility of this technique or on the blocking effect of anti‐inflammatory drugs, such as anti‐TNF and corticosteroids.METHODS A group of 30 healthy subjects were randomized into three parallel groups treated with placebo, oral methylprednisolone 20 mg day−1 for 7 days or anti‐tumour necrosis factor (TNF) (adalimumab, Humira®, Abbott) 40 mg s.c. single dose. A first blister was induced at baseline and collected, immediately before the start of treatment and a second blister was obtained 7 days after the start of treatment. The total number of cells, the cell viability and the differential cell count were evaluated by two independent observers, who were blind to treatment. anova was used to compare change from baseline among the three groups before pairwise comparisons.RESULTS Among the placebo group, there was no significant difference in the total cell count, neutrophils, eosinophils and monocytes between day 1 and day 7. Methylprednisolone inhibited the eosinophil influx in mean % (95% CI) (−1.0 (−1.7, −0.3); P < 0.02) and absolute (P < 0.02) values, while anti‐TNF inhibited the neutrophil influx in mean % (95% CI) (−19.3 (−29.5, −9.1); P < 0.01) and absolute (P < 0.05) values.CONCLUSIONS The cantharidin‐induced skin blister is a safe, well tolerated and reproducible procedure. Pre‐treatment with anti‐TNF or methylprednisolone inhibited the neutrophilic or eosinophilic trafficking, respectively. It could be useful in profiling anti‐inflammatory drugs regarding their effects on the cellular inflammatory response.
Long‐term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron‐overloaded patients with sickle cell disease
Authors: Vichinsky Elliott , Bernaudin Françoise , Forni Gian Luca , Gardner Renee , Hassell Kathryn , Heeney Matthew M. , Inusa Baba , Kutlar Abdullah , Lane Peter , Mathias Liesl , Porter John , Tebbi Cameron , Wilson Felicia , Griffel Louis , Deng Wei , Giannone Vanessa , Coates Thomas 
Published: May 2011

SummaryTo date, there is a lack of long‐term safety and efficacy data for iron chelation therapy in transfusion‐dependent patients with sickle cell disease (SCD). To evaluate the long‐term safety and efficacy of deferasirox (a once‐daily oral iron chelator), patients with SCD completing a 1‐year, Phase II, randomized, deferoxamine (DFO)‐controlled study entered a 4‐year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5‐year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow‐up (9·2%) and adverse events (AEs) (7·6%). Investigator‐assessed drug‐related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild‐to‐moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4 years deferasirox exposure significantly decreased by −591 μg/l (95% confidence intervals, −1411, −280 μg/l; P = 0·027; n = 67). Long‐term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years.
Three stories about mother: narratives by women who have lived in care
Authors: Eronen Tuija 
Published: May 2011

ABSTRACTFamilies and social work interventions in their lives are at the core of child welfare. Child welfare practices can shape children's and parents' family memories and narratives of different family relations. However, there is little social work research so far based on the personal narratives of people who have lived in care. The study data consist of the written life stories and biographical interviews of three women who have lived part of their childhood in children's homes. In their narratives, the most central family relation was their relationship to the mother. They used different narrative strategies in their stories while trying to manage both living their childhood in care and presenting their mother morally in the same story. The central moral and emotional stance in the narratives of the mother–daughter relationship was love. Through the analysis, three moral characters of the mother were constructed. The first told about an absent mother, the second a loved and loving mother and in the third, the mother's moral character was continuously negotiated and contested. Constructing a personal story and moral character of oneself and of one's mother can be truly risky in the context of a childhood in care.
A comparison of systems and outcomes for safeguarding children in Australia and Norway
Authors: Kojan Bente Heggem , Lonne Bob 
Published: May 2011

ABSTRACTUsing aggregated national data, this paper compares outcomes of Australian ‘child protection’ (CP) and Norwegian ‘child welfare services’ (CWS). We highlight each nation's context and key elements of their CP/CWS organizations, with emphasis on policy and programme orientation. System outcomes are examined along with the implications of their different approaches. The main policy focus in Australia is protection and risk, while Norway's systemic approach stresses prevention, early intervention and support. These differences influence practitioner's intervention strategies and how the needs of children and parents are met. In Norway, approximately 80% of the children in the CWS receive some sort of supportive services. In contrast, Australian services for supporting families are narrowly targeted. Both countries share the ‘best interest of the child’ principle and an increased focus on children's rights, and have experienced increased service demands and rates of children in out‐of‐home care. The paper explores the relative merits of these systems.
A prospective study of lymphocyte subpopulations and regulatory T cells in patients with chronic hepatitis C virus infection developing interferon‐induced thyroiditis
Authors: Soldevila Berta , Alonso Núria , Martínez‐Arconada Maria J. , Granada Maria L. , Baía Diogo , Vallejos Virginia , Fraile Manuel , Morillas Rosa M. , Planas Ramon , Pujol‐Borrell Ricardo , Martínez‐Cáceres Eva M. , Sanmartí Anna M. 
Published: May 2011

SummaryObjective  One of the side effects of interferon‐alpha (IFN‐α) therapy is interferon‐induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT remains to be defined. The aim of this study was to assess different peripheral blood lymphocyte subpopulations, mainly CD4+CD25+CD127low/‐FoxP3+ regulatory T cells (Tregs), in patients with chronic hepatitis C virus (HCV) infection who developed IIT.Design, patients and methods  From 120 patients with chronic HCV who started antiviral treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co‐HCV). Peripheral blood mononuclear cells were obtained before treatment (BT), mid‐treatment (MT), end of treatment (ET), 24 weeks post‐treatment (PT) and at appearance of IIT (TT).Results  Eleven patients developed IIT: three Hashimoto’s thyroiditis, one Graves’disease, one positive antithyroidal antibodies, one nonautoimmune hypothyroidism and five destructive thyroiditis. During antiviral treatment, an increase in CD8+ and in Tregs was observed in both groups. A decrease in CD3+, CD19+ and NKT lymphocyte subpopulations was also observed (all P < 0·05). However, no changes were observed in the percentage of CD4+, CD3+γδ+ and iNKT lymphocytes, Th1/Th2 balance and Bcl2 expression on B cells when BT was compared with ET. At the appearance of IIT (TT), IIT patients had a higher Th1 response (CCR5+CCR7−) (P < 0·01) and a higher Tregs percentage (P < 0·05) than Co‐HCV.Conclusions  Our results point to the immunomodulatory effects of IFN‐α on different lymphocyte subpopulations and a possible role of Th1 response and Tregs in patients with HCV who developed IIT.
Added value of CAC in risk stratification for cardiovascular events: a systematic review
Authors: Peters Sanne A. E. , Bakker Marina , den Ruijter Hester M. , Bots Michiel L. 
Published: May 2011

Eur J Clin Invest 2012; 42 (1): 110–116AbstractBackground  Identification of individuals at high risk for cardiovascular disease (CVD) is important to initiate adequate treatment and to prevent future events. Moreover, identification of low‐risk individuals is important to refrain from unneeded therapy. Current risk prediction models do not accurately predict the risk of CVD in individuals, and new markers have been sought to improve the risk assessment in individuals. Coronary artery calcification (CAC) is a marker of atherosclerosis that might improve current risk assessment when added to traditional risk factors.Materials and methods  We performed a systematic review on PubMed search (1 February 2011) on studies reporting on the added value of CAC in risk prediction in asymptomatic individuals.Results  Of 39 publications on CAC and CVD, nine studies were carried out in asymptomatic individuals. All studies showed an increase in area under the curve ranging from 0·05 to 0·20 when CAC was added to the risk model. Four studies reported on improvements of individuals in low‐, intermediate‐, and high‐risk categories. Addition of CAC to the risk model resulted in a net reclassification improvement ranging from 14% to 30%, meaning that CAC measurement reclassified a substantial proportion of individuals into correct risk categories. This improvement was most pronounced in those at intermediate Framingham risk.Conclusions  The available studies consistently showed that CAC scoring improves risk stratification in CVD risk categories when added to traditional risk factors only, especially among individuals at intermediate risk for CVD. Cost‐effectiveness analyses together with a randomized controlled trial are needed before widespread introduction of CAC in clinical care.
Phospholipase Cγ2 is required for basal but not oestrogen deficiency–induced bone resorption
Authors: Kertész Zsuzsanna , Győri Dávid , Körmendi Szandra , Fekete Tünde , Kis‐Tóth Katalin , Jakus Zoltán , Schett Georg , Rajnavölgyi Éva , Dobó‐Nagy Csaba , Mócsai Attila 
Published: May 2011

Eur J Clin Invest 2012; 42 (1): 49–60AbstractBackground  Osteoclasts play a critical role in bone resorption under basal conditions, but they also contribute to pathological bone loss during diseases including postmenopausal osteoporosis. Phospholipase Cγ2 (PLCγ2) is an important signalling molecule in diverse haematopoietic lineages. Here, we tested the role of PLCγ2 in basal and ovariectomy‐induced bone resorption, as well as in in vitro osteoclast cultures using PLCγ2‐deficient (PLCγ2−/−) mice.Materials and methods  The trabecular architecture of long bone metaphyses was tested by micro‐CT and histomorphometric analyses. Postmenopausal osteoporosis was modelled by surgical ovariectomy. Osteoclast development and function, gene expression and PLCγ2 phosphorylation were tested on in vitro osteoclast and macrophage cultures.Results  PLCγ2−/− mice had significantly higher trabecular bone mass under basal conditions than wild‐type mice. PLCγ2 was required for in vitro development and resorptive function of osteoclasts, but not for upregulation of osteoclast‐specific gene expression. PLCγ2 was phosphorylated in a Src‐family‐dependent manner upon macrophage adhesion but not upon stimulation by M‐CSF or RANKL. Surprisingly, ovariectomy‐induced bone resorption in PLCγ2−/− mice was similar to, or even more robust than, that in wild‐type animals.Conclusions  Our results indicate that PLCγ2 participates in bone resorption under basal conditions, likely because of its role in adhesion receptor signalling during osteoclast development. In contrast, PLCγ2 does not appear to play a major role in ovariectomy‐induced bone loss. These results suggest that basal and oestrogen deficiency–induced bone resorption utilizes different signalling pathways and that PLCγ2 may not be a suitable therapeutic target in postmenopausal osteoporosis.
Improving the effectiveness of wood‐ash fertilization in mixed mountain pastures
Authors: Ferreiro A. , Merino A. , Díaz N. , Piñeiro J. 
Published: May 2011

AbstractMountain pastures can be improved by the application of wood ash, but its effectiveness as a source of N, P and other elements requires improved management practices. Two application rates of wood ash (6 and 12 t ha−1) were tested in a 4‐year trial on a low‐input fertilized pasture. Ash was complemented with mineral P, and N fixation was encouraged by sowing white clover. Wood‐ash application led to increased pasture yield (by 100%) and to increased proportions of white clover and ryegrass (60%), thus improving pasture feed value. N fixation by white clover, and possibly increased mineralization because of higher pH, may have compensated for lack of N in the wood ash. Addition of mineral fertilizer improved the supply of P, although incorporation of the wood ash into the soil may also have enhanced release of P from non‐extractable components. High amounts of compounds containing Ca and Mg contributed to the long‐term maintenance of soil reserves of these elements. Despite high inputs of K (175–350 mg kg−1) from wood ash, annual additions of K are required to counteract depletion via plant uptake and leaching. Increased Mn availability after the treatment (up to 400 mg kg−1) may limit repeated applications of wood ash, at least on poorly aerated soils.
Predictors of pain in nursing home residents with dementia: a cross‐sectional study
Authors: Lin Pei‐Chao , Lin Li‐Chan , Shyu Yea‐Ing L , Hua Mau‐Sun 
Published: May 2011

Aim.  The aim of this study was to investigate the association between care activities and pain and restraint and pain in residents with dementia.Background.  If pain in people with dementia is not identified or alleviated in a timely manner, it could lead to an adverse effect on their physical, mental, social health and quality of life. Care activities and restraint might cause pain, but little is known as to whether they are true risk‐factors of pain in people with dementia.Design.  A cross‐sectional research design was employed.Methods.  One hundred and twelve people with dementia were chosen from two nursing homes located in northern Taiwan. The demographic and clinical data collected included diagnoses, analgesics, restraints, recent falls, etc. The severity of dementia was assessed using the Clinical Dementia Rating Scale. The researchers observed every participant immediately following instances of routine care and then recorded the level of pain using the Chinese version of the Pain Assessment in Advanced Dementia scale.Results.  About 36·6% of the participants had a Chinese version of the Pain Assessment in Advanced Dementia scale score above two points and an overall mean score of 1·50 (SD 1·81) with a range from 0–8. Only one resident with dementia received regular analgesic. Pain level in residents with dementia that needed assisted care was higher than in residents who were able to move about freely. It showed a positive correlation between level of pain and the severity of dementia among residents. The major predictors for pain in residents with dementia included restraint, assisted bathing and assisted transfer.Conclusion.  The findings confirm the association between care activities and pain and between restraint and pain in residents with dementia.Relevance to clinical practice.  Formal caregivers need to minimise the triggering of pain when they assist residents’ daily activities and avoid unnecessary restraints, while offering personalised, conventional nursing care to residents with late‐stage dementia.
Polysomnography and actigraphy concordance in juvenile idiopathic arthritis, asthma and healthy children
Authors: WARD TERESA M. , LENTZ MARTHA , KIECKHEFER GAIL M. , LANDIS CAROL A. 
Published: May 2011

SummaryThe aims of this study were to evaluate sensitivity, specificity and accuracy with an epoch‐by‐epoch comparison of polysomnography (PSG) and actigraphy with activity counts scored at low, medium and high thresholds, and to compare PSG‐derived total sleep time (TST), sleep efficiency (SE) and wake after sleep onset (WASO) to the same variables derived from actigraphy at low, medium and high thresholds in 9‐ to 11‐year‐old children with juvenile idiopathic arthritis (JIA), asthma and healthy control children. One night of PSG and actigraphy were recorded. Pairwise group comparisons for sensitivity showed significant differences at the low [Tukey’s honest significant difference (HSD)P < 0.002], medium (P < 0.001) and high thresholds (P < 0.001) between JIA and asthma groups, and at the high threshold between JIA and controls (P < 0.009). Significant differences were found for specificity at the low (P < 0.001), medium (P < 0.001) and high thresholds (P < 0.001) between JIA and asthma groups, and between JIA and controls (low,P < 0.002: medium,P < 0.002: high,P < 0.008 threshold). PSG TST, WASO and SE were not significantly different among the groups, but significant group differences were found for actigraphy TST, WASO and SE at all three thresholds. Actigraphy showed the least overestimation or underestimation of sleep or wakefulness at the medium threshold for TST and WASO for all three groups. Compared to PSG, actigraphy was most accurate in the identification of sleep from wakefulness in 9‐ to 11‐year‐old healthy children, and less accurate in children with JIA and asthma.
Genomics and population biology of Cryptosporidium species
Authors: WIDMER G. , SULLIVAN S. 
Published: May 2011

SummaryWe describe recent advances in the genomics and population biology of Cryptosporidium parvum and C. hominis, the causative agents of cryptosporidiosis in humans and animals. Many basic aspects of the biology of Cryptosporidium species remain to be investigated and effective drugs to control cryptosporidiosis are not available. Sequencing and annotation of the genome of C. parvum and C. hominis has uncovered unique features of the metabolism of these species. The recently sequenced genome of the gastric species C. muris is providing new insights into the evolution of the genus. Cryptosporidian sequence information has facilitated the identification of polymorphic genetic markers. Genotyping of oocysts excreted by human and animal hosts using such markers has revealed many new species and genotypes, and is leading to a better understanding of the epidemiology of cryptosporidiosis.
Glatiramer Acetate Treatment Directly Targets CD11b+Ly6G− Monocytes and Enhances the Suppression of Autoreactive T cells in Experimental Autoimmune Encephalomyelitis
Authors: Toker A. , Slaney C. Y. , Bäckström B. T. , Harper J. L. 
Published: May 2011

AbstractGlatiramer acetate (GA) is used for the treatment of relapsing‐remitting multiple sclerosis (MS) and can suppress experimental autoimmune encephalomyelitis in animals. Effective GA treatment is associated with the induction of anti‐inflammatory TH2 responses and antigen‐specific expansion of CD25+/Foxp3+ Tregs through the modulation of antigen‐presenting cells. Here, we show that intravenous injection of fluorochrome‐labelled GA resulted in rapid and specific binding of GA to CD11b+ F4/80lo Ly6G− blood monocytes via an MHC class II–independent mechanism. Intravenous GA treatment enhanced the intrinsic capability of these monocytes to directly suppress T cell proliferation in vitro. The suppressive function correlated with reduced proliferation of myelin‐specific T cells in vivo after intravenous GA treatment. In contrast, subcutaneous treatment with GA inhibited the pro‐inflammatory IFNγ‐producing T cell phenotype rather than suppressing T cell proliferation. These data indicate that (1) GA engages directly with circulating monocytes to induce type II monocyte suppressor function; and (2) the therapeutic efficacy of GA may be expanded by employing different routes of GA administration to engage alternative mechanisms of suppression of autoreactive T cells in MS.
Differential Binding and Internalization of Clostridium difficile Toxin A by Human Peripheral Blood Monocytes, Neutrophils and Lymphocytes
Authors: Modi N. , Gulati N. , Solomon K. , Monaghan T. , Robins A. , Sewell H. F. , Mahida Y. R. 
Published: May 2011

AbstractColitis due to Clostridium difficile infection is mediated by secreted toxins A and B and is characterized by infiltration by cells from the systemic circulation. The aim of our study was to investigate interactions between fluorescently labelled toxin A and peripheral blood monocytes, neutrophils and lymphocytes. Purified toxin A was labelled with Alexa Fluor® 488 (toxin A488) and incubated with isolated human peripheral blood mononuclear cells or washed whole blood cells for varying time intervals at either 37 or 4 °C/ice. The ability of trypan blue to quench cell surface–associated (but not cytoplasmic) fluorescence was also investigated. At 37 °C, toxin A488‐associated fluorescence in monocytes peaked at 1 h (majority internalized), with subsequent loss associated with cell death. In contrast to monocytes, binding of toxin A488 in neutrophils was greater on ice than at 37 °C. Studies using trypan blue suggested that over 3 h at 37 °C, most of the toxin A488‐associated fluorescence in neutrophils remained at the cell surface. Over 48 h (37 °C and ice/4 °C), there was minimal toxin A488‐associated fluorescence in lymphocytes. These studies suggest major differences in interactions between toxin A and circulating cells that infiltrate the mucosa during colonic inflammation in C. difficile infection.
The characteristics of aeolian sediment flux profiles in the south‐eastern Tengger Desert
Authors: ZHANG ZHENGCAI , DONG ZHIBAO , ZHAO AIGUO 
Published: May 2011

AbstractDeserts are one of the most important dust sources in the world. Because dust content changes as a function of height at low levels in the atmosphere, this affects long‐term dust transport. In this paper, field data measured above shifting sands in the south‐eastern Tengger Desert were used to analyse the vertical distribution of sediment fluxes in the near‐surface layer (0 to 48 m). It was possible to express horizontal sediment flux as a power function, but aeolian deposition as a function of height could be expressed as an exponential function. There are two curve types for the particle size distributions in the horizontal sediment flux and aeolian deposition: bimodal and unimodal curves. For the horizontal sediment flux and aeolian deposition, heights of 24 m and 32 m, respectively, were the key heights in the size distribution curve; below these heights, the curve was bimodal, whereas above these heights, it was unimodal. At heights of 4 to 16 m, and especially between 8 m and 12 m, the data were particularly interesting because the sediment size, transport mode, degree of sorting, and the skewness and kurtosis change. For the horizontal sediment flux, wind turbulence moved saltating particles higher than expected.