bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palliative care: what approaches are suitable in developing countries?
Authors: Ddungu Henry 
Published: June 2011

SummaryThe enormous burden of life‐threatening illnesses, including cancer, human immunodeficiency virus infection, and others, such as sickle cell disease, associated with physical and psychosocial suffering explains the illustrious need for palliative care in developing countries. Despite the demonstrated need, current provision of palliative care in Africa is at best limited, and at worst non‐existent. Access to essential pain medicines, particularly oral morphine, for control of pain is extremely limited and far below the global mean. There is a general lack of government policies that recognize palliative care as an essential component of health care and there is inadequate training for both health care professionals and the general public about palliative care. A public health strategy, as recommended by the World Health Organization (WHO), offers the best approach for translating knowledge and skills into evidence‐based, cost‐effective interventions that can reach everyone in need of palliative care in developing countries.
Chelation treatment in sickle‐cell‐anaemia: much ado about nothing?
Authors: Lucania Gaetano , Vitrano Angela , Filosa Aldo , Maggio Aurelio 
Published: June 2011

SummaryBlood transfusions may prevent and treat serious complications related to sickle‐cell disease (SCD) when performed according to specific guidelines. However, blood transfusion requirements in SCD inevitably lead to increased body iron burden. An adequate chelation treatment may prevent complications and reduce morbidity and mortality. This review evaluates the effectiveness, safety and costs of chelation treatment. The included trials were examined according to the recommendations of the American College of Cardiology (ACC) and the American Heart Association (AHA). Overall, 14 trials and a total of 502 patients with SCD were included in this review. Deferoxamine alone (s.c. or i.v.), deferiprone alone or versus deferoxamine, deferasirox versus deferoxamine and combined treatment with deferoxamine plus deferiprone were included and evaluated in the analysis. Only two randomized clinical trials have been reported. The results of this analysis suggest that use of chelation treatment in SCD to date has been based on little efficacy and safety evidence, although it is widely recommended and practised. The cost/benefit ratio has not been fully explored. Further research with larger randomized clinical trials needs to be performed.
Genetic strategies for the treatment of sickle cell anaemia
Authors: Mansilla‐Soto Jorge , Rivière Isabelle , Sadelain Michel 
Published: June 2011

SummarySickle cell anaemia is a severe inherited blood disorder for which there is presently no curative therapy other than allogeneic haematopoietic stem cell (HSC) transplantation. This therapeutic option, however, is not available to most patients because of the lack of a matched related donor. Different genetic strategies aiming to treat the anaemia and prevent sickling are under investigation. They include strategies to transfer a regulated globin gene in autologous HSCs–the most developed approach, which is about to undergo clinical evaluation–, and strategies to either restore endogenous HBG expression, repair or eliminate HBBS mutant transcripts, or correct the sickle mutation in HSCs or induced pluripotent stem cells. Their common ultimate goals are to afford therapeutic levels of HbA or HbF in the erythroid progeny of autologous HSCs (sufficient to prevent pathological sickling) and engraft the genetically modified HSCs with minimal short‐term toxicity (primarily caused by the conditioning regimen) and long‐term toxicity (primarily caused by genotoxicity). We discuss here the status of application of these technologies, outlining recent advances and the hurdles that lay ahead.
The differential effect of lenalidomide monotherapy in patients with relapsed or refractory transformed non‐Hodgkin lymphoma of distinct histological origin
Authors: Czuczman Myron S. , Vose Julie M. , Witzig Thomas E. , Zinzani Pier L. , Buckstein Rena , Polikoff Jonathan , Li Ju , Pietronigro Dennis , Ervin‐Haynes Annetti , Reeder Craig B. 
Published: June 2011

SummaryTransformed lymphoma (TL) represents a heterogeneous group of lymphomas with an aggressive course and poor prognosis. We assessed the clinical benefit of single‐agent lenalidomide based on histological origin, including transformed follicular lymphoma (tFL) and transformed chronic lymphocytic leukaemia/small lymphocytic lymphoma (tCLL/SLL). Our analysis included 33 patients with TL. Patients received lenalidomide at a median dose of 25 mg/d. The overall response rate (ORR) was 46%, with a median response duration of 12·8 months after a median follow‐up of 5·6 months. Median progression‐free survival was 5·4 months. Among patients with tFL, ORR was 57%, with a median response duration of 12·8 months. None of the patients with tCLL/SLL responded to lenalidomide monotherapy. The most common grade 3/4 adverse events were reversible myelosuppression. Our results suggest that the original lymphoma histology (i.e. FL) in TL patients may potentially be associated with response to salvage lenalidomide monotherapy.
Cross‐border marriage and disparities in early childhood development in a population‐based birth cohort study: the mediation of the home environment
Authors: Wu J. C.‐L. , Bradley R. H. , Chiang T.‐L. 
Published: June 2011

AbstractBackground Taiwan has experienced a large influx of cross‐border marriage migrants in recent years. The majority have been women in their childbearing ages and have come from countries with lower average standards of living than Taiwan. This trend has changed the ethnic composition of children who live in Taiwan, and it has generated considerable social concern over the future health status of Taiwan's citizens. This study aimed to examine: (1) whether there are disparities in development between children reared in families characterized by cross‐border marriages and children reared in families with two Taiwanese‐born parents; and (2) whether the quality of home environment explains the group differences in early childhood development.Methods Data came from the Taiwan Birth Cohort Study. A total of 19 499 participants who completed 6‐month, 18‐month and 3‐year surveys were included for analysis. Cross‐border marriage status was defined by mother's original nationality and categorized into three broad groups: Taiwanese‐born, Chinese cross‐border and South‐East Asian (SEA) cross‐border. Early childhood development was measured at age 3 years, and covered the domains of gross motor, fine motor, language and socio‐emotional competence. Hierarchical linear regressions were used to examine the mediation effects of the home environment.Results Children of Chinese and SEA cross‐border groups scored lower in fine motor, language and socio‐emotional competence than those of their Taiwanese‐born counterpart at age 3 years. Chinese–Taiwanese group differences in all three developmental domains became insignificant after the addition of home environment, while SEA–Taiwanese group differences in fine motor and language development remained, yet were noticeably reduced. The mediation of home environment was further confirmed using the Sobel test.Conclusions Home environment plays a central role in reducing the disparities in developmental outcomes among children of different marriage groups. Interventions should be directed towards enhancing the quality of early home environment for children reared in families of cross‐border marriages.
Loss of balance between T helper type 17 and regulatory T cells in chronic human immunodeficiency virus infection
Authors: Li D , Chen J , Jia M , Hong K , Ruan Y , Liang H , Liu S , Zhang X , Zhao H , Peng H , Ma P , Shao Y 
Published: June 2011

Summary
The aim of this study is to characterize the changes of CD4+CD25highforkhead box P3 (FoxP3+) regulatory T cells (Treg), interleukin (IL)-17 secreting T helper type 17 (Th17) cell frequencies and the balance of these two subsets in a cohort of chronic human immunodeficiency virus type 1 (HIV-1)-infected patients in China. A total of 115 untreated chronic HIV-infected individuals and 32 healthy donors were recruited in this study. Peripheral blood mononuclear cells were isolated from ethylenediamine tetracetic acid (EDTA) anti-coagulated fresh whole blood and stained to characterize the frequencies of Treg and Th17. Of a total 115 patients, 42 individuals including 10 elite controllers were followed-up for more than 1 year, and changes of Treg and Th17 frequencies were analysed over time. The continuous loss of Th17 cells was accompanied by a concomitant rise in the frequency of Treg cells, resulting in a loss of Th17/Treg balance during the progressive HIV infection. Meanwhile, the Treg levels, Th17 levels and Th17/Treg ratios of the elite controller group were comparable to those of the HIV-1 negative controls in the follow-up study. Additionally, we demonstrated that loss of balance between Th17 and Treg is associated with an earlier CD4 T cell decline during the course of HIV infection. Our results indicate that a loss of immune-balance of Th17 to Treg during HIV-1 disease progression and the persistence of such an immune-balance in the elite controllers may have a critical role in HIV-1 infection and further shed new light into understanding the pathogenesis of HIV-1.
Stimulation of dendritic cells withHelicobacter pylorivacuolating cytotoxin negatively regulates their maturation via the restoration of E2F1
Authors: Kim J M , Kim J S , Yoo D Y , Ko S H , Kim N , Kim H , Kim Y-J 
Published: June 2011

SummaryHelicobacter pylori induces an infiltration of dendritic cells (DCs) into the infected gastric mucosa. Although DCs play an important role in the regulation of inflammation, the effects of H. pylori vacuolating cytotoxin (VacA) on DC maturation process have not yet been elucidated. The role of VacA in DC maturation following co-exposure to Escherichia coli lipopolysaccharide (LPS) was investigated. The treatment of immature DCs with LPS up-regulated the expression of surface molecules [e.g. CD40, CD80, CD86 and major histocompatibility complex (MHC) class II], as well as the production of cytokines [e.g. interleukin (IL)-1β, IL-12p70 and tumour necrosis gactor (TNF)-α] compared with those of unstimulated controls. Co-stimulation with H. pylori VacA significantly reduced the up-regulated DC maturation markers induced by LPS. In addition, VacA sustained the immature state of DCs with high endocytosis and low migratory capacity. The LPS-induced down-regulation of E2F1 expression in DCs was recovered by co-stimulation with VacA. Moreover, suppression of E2F1 by small interfering RNA resulted in a significant recovery of the inhibited DC maturation by VacA. In contrast, VacA did not affect nuclear factor (NF)-κB responses to LPS and the NF-κB signal was not associated with VacA-induced inhibition of DC maturation. These results suggest that the exposure of DCs to H. pylori VacA negatively regulates DC maturation via the restoration of E2F1. The immunomodulatory action of VacA on DCs may contribute to the ability of VacA-producing H. pylori to establish a persistent infection in the gastric mucosa.
Iron administration reduces airway hyperreactivity and eosinophilia in a mouse model of allergic asthma
Authors: Maazi H , Shirinbak S , Bloksma N , Nawijn M C , van Oosterhout A J M 
Published: June 2011

Summary
The prevalence of allergic diseases has increased dramatically during the last four decades and is paralleled by a striking increase in iron intake by infants in affluent societies. Several studies have suggested a link between increased iron intake and the marked increase in prevalence of allergic diseases. We hypothesized that the increased iron intake by infants offers an explanation for the increased prevalence of allergic disease in industrialized societies during the past four decades. A well-established mouse model of ovalbumin (OVA)-driven allergic asthma was used to test the effects of differences in iron intake and systemic iron levels on the manifestations of allergic asthma. Surprisingly, iron supplementation resulted in a significant decrease in airway eosinophilia, while systemic iron injections lead to a significant suppression of both allergen-induced airway eosinophilia and hyperreactivity compared to placebo. In contrast, mice fed on an iron-deprived diet did not show any difference in developing experimentally induced allergic asthma when compared to those fed on an iron-sufficient control diet. In contrast to our hypothesis, airway manifestations of allergic asthma are suppressed by both increased levels of iron intake and systemic iron administrations in the mouse model.
The relationship between fat depot‐specific preadipocyte differentiation and metabolic syndrome in obese women
Authors: Park Hyun Tae , Lee Eun Sil , Cheon Yong‐Pil , Lee Dong Ryul , Yang Kyung‐Sook , Kim Young Tae , Hur Jun Young , Kim Sun Haeng , Lee Kyu Wan , Kim Tak 
Published: June 2011

SummaryObjective  Obesity is strongly associated with metabolic syndrome, but not all obese individuals display a clustering of metabolic risk factors. Recent studies have shown that in vitro subcutaneous (SC)‐preadipocyte differentiation is negatively associated with obesity. These results suggest that impaired adipogenesis is an important factor linking obesity to metabolic disorders. We examined whether in vitro preadipocyte differentiation is associated with metabolic syndrome, independent of obesity.Design/patients/measurements  Paired adipose tissue samples were obtained from the 13 nonobese women and the 65 obese women. The CD34+/CD31− cells were isolated from the stromal‐vascular fraction of both SC and omental (OM) fat depots by immune magnetic separation, and the subset was cultured with a differentiation cocktail. Then, we analysed the relationship between the degree of preadipocyte differentiation and metabolic factors.Results  Obese women without metabolic syndrome (n = 37) had significantly higher SC‐preadipocyte differentiation than equally obese women with metabolic syndrome (n = 28); however, OM‐preadipocyte differentiation was similar in both groups. SC‐preadipocyte differentiation was strongly correlated with triglycerides, HDL cholesterol, homoeostasis model assessment of insulin resistance and OM‐adipocyte size. However, OM‐preadipocyte differentiation was not correlated with any of these parameters.Conclusions  This study identified that SC‐preadipocyte differentiation is associated with metabolic syndrome independent of obesity, whereas OM‐preadipocyte differentiation is not. These findings suggest that, in the setting of obesity, an enhanced adipogenic capacity of SC depots could be protective for metabolic syndrome. Our data underscores an interaction between adipose tissue homoeostasis and metabolic disorder.
Multiple forms of hypogonadism of central, peripheral or combined origin in males with Prader–Willi syndrome
Authors: Radicioni A. F. , Di Giorgio G. , Grugni G. , Cuttini M. , Losacco V. , Anzuini A. , Spera S. , Marzano C. , Lenzi A. , Cappa M. , Crinò A. 
Published: June 2011

SummaryBackground  Hypogonadism in Prader–Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect, but pathophysiology is still unclear.Objectives  To investigate the aetiology of hypothalamic–pituitary–gonadal axis dysfunction in PWS males.Methods  Clinical examination and blood sampling for luteinizing hormone (LH), follicle‐stimulating hormone (FSH), testosterone, inhibin B and sexhormone–binding globulin (SHBG) were performed in 34 PWS patients, age 5·1–42·7 years, and in 125 healthy males of same age range. All participants were divided into two groups : < or ≥13·5 years.Results  Pubertal PWS patients showed an arrest of pubertal development. Patients <13·5 years had normal LH, FSH, testosterone and 7/10 had low inhibin B. Among those ≥13·5 years, 8/24 patients had normal LH and testosterone, high FSH and low inhibin B. 5/24 had low FSH, LH, testosterone and inhibin B; one showed normal LH and FSH despite low testosterone and inhibin B; 4/24 had low testosterone and LH but normal FSH despite low inhibin B; 6/24 showed high FSH, low inhibin B and normal LH despite low testosterone. Compared with controls, patients <13·5 years had lower LH, inhibin B, similar FSH, testosterone, SHBG levels and testicular volume; those ≥13·5 years had smaller testicular volume, near‐significantly lower LH, testosterone, SHBG, inhibin B and higher FSH.Conclusion  PWS patients display heterogeneity of hypogonadism: (i) hypogonadotropic hypogonadism of central origin for LH and/or FSH; (ii) early primary testicular dysfunction (Sertoli cells damage); and (iii) a combined hypogonadism (testicular origin for FSH‐inhibin B axis and central origin for LH‐T axis).
Polymorphisms of the UCP2 gene are associated with body fat distribution and risk of abdominal obesity in Spanish population
Authors: Martinez‐Hervas Sergio , Mansego Maria L. , de Marco Griselda , Martinez Fernando , Alonso Mónica P. , Morcillo Sonsoles , Rojo‐Martinez Gemma , Real Jose T. , Ascaso Juan F. , Redon Josep , Martin Escudero Juan C. , Soriguer Federico , Chaves Felipe J. 
Published: June 2011

Eur J Clin Invest 2011AbstractBackground  Increased accumulation of fat results from an imbalance between energy expenditure and intake, being modulated by different environmental and genetic factors. Uncoupling proteins (UCPs) are mitochondrial carrier proteins able to spend energy generating heat. Therefore, variations in these genes are good candidates as potential modulators of body fat accumulation. Our aim was to investigate the possible association of genetic variations of the gene codifying the UCP2 protein with obesity and fat distribution.Design  We performed a cross‐sectional study in 2367 individuals from two population‐based studies from different regions of Spain. The Hortega Study included 1436 individuals (693 women) 21–85 years old, and the Pizarra Study included 931 individuals (584 women) 18–65 years old. We evaluated three polymorphisms of the UCP2 gene.Results  The TT genotype of the rs660339 polymorphism and the AA genotype of the rs659366 polymorphism of the UCP2 gene were significantly associated with higher waist circumference in the Hortega Study. Furthermore, subjects carrying both genotypes (TT+AA) also showed higher central adiposity compared with other genotypes. This association was also present in the Pizarra Study. Moreover, in the pooled population, we found a stronger association with waist circumference. Even, we found association with BMI. Furthermore, rs659366 polymorphism was associated with the risk of abdominal obesity (P = 0·04: OR = 1·3; CI = 1·01–1·67).Conclusions  Polymorphisms of the UCP2 gene (rs660339 and rs659366) were associated with central obesity. This study shows association between the UCP2 gene and the susceptibility to obesity and body fat distribution in a south European population.
Liver dysfunction in chronic heart failure: prevalence, characteristics and prognostic significance
Authors: Poelzl Gerhard , Ess Michael , Mussner‐Seeber Christine , Pachinger Otmar , Frick Matthias , Ulmer Hanno 
Published: June 2011

Eur J Clin Invest 2011AbstractBackground  Although abnormal liver morphology and function have long been recognized, characterization and importance of liver dysfunction in heart failure are poorly defined. This study sought to investigate the relevance of circulating liver function tests (LFTs) in an unselected chronic heart failure (CHF) cohort.Materials and methods  A total of 1032 consecutive ambulatory patients with CHF were enrolled from 2000 to 2008. Clinical and laboratory variables including LFTs were collected at study entry. Follow‐up (median 36 months) was available in 1002 (97·1%) patients. The endpoint was defined as death from any cause or heart transplantation. Hazard ratios (HR) for transplant‐free survival were estimated per log unit using Cox proportional hazard regression models for sex‐stratified data.Results  Sex‐specific prevalence of cholestatic enzyme elevation was 19·2% as opposed to elevated transaminases in 8·3%. Cholestatic enzymes, but not transaminases, were significantly associated with severity of heart failure syndrome and backward failure. The endpoint was recorded in 339 patients (33·8%). T‐Bil, γ‐glutamyltransferase (GGT) and alkaline phosphatase (ALP) were associated with adverse outcome in bivariate models. Of these, GGT [HR 1·22 (1·06, 1·41); P = 0·006] and ALP [HR 1·52 (1·09, 2·12); P = 0·014] were independently associated with the endpoint after adjustment for a wide array of clinical and laboratory predictors.Conclusions  Liver dysfunction is frequent in CHF and characterized by a predominantly cholestatic enzyme profile that is associated with disease severity and prognosis. Thus, we propose a cardio‐hepatic syndrome in CHF. Future studies are needed to clarify the exact mechanisms of organ interaction.
Silicon concentration and leaf longevity: is silicon a player in the leaf dry mass spectrum?
Authors: Cooke Julia , Leishman Michelle R. 
Published: June 2011

Summary1. Multiple functions of plant silicon are known from agricultural species where silicon fertilizer alleviates biotic and abiotic stress impacts. In contrast, the function of plant silicon in natural ecosystems is often overlooked and is relatively poorly understood.2. We investigated a potential integration of silicon with the leaf dry mass economics framework. We examined the relationship between leaf longevity, a trait considered to optimize leaf carbon use, and leaf silicon concentration across plant functional types and phylogenetic groups, testing the hypothesis that short‐lived leaves have higher silicon content to maximize carbon allocation to growth. We considered leaf longevity a continuous trait (months, n = 155 species) and a binary trait (annual vs. perennial, n = 602 species).3. A significant negative correlation was found across all species between leaf longevity (months) and relative silicon concentration, indicating that across functional types and plant families, leaves with shorter life spans contain higher concentrations of silicon. A similar significant relationship was also found within deciduous angiosperm leaves. Silicon concentration was significantly higher in annual vs. perennial species across most plant functional types. Within order and family, no significant difference in silicon concentration was found between annual and perennial leaves except in the Poales and the Poaceae, where annual leaves had higher silicon concentration. Relative leaf/shoot silicon concentration varied much more than leaf longevity across the phylogeny, and there was a stronger phylogenetic signal from silicon concentration than from leaf longevity. Evolutionary divergence analysis showed that divergences between relative silicon concentration and leaf life span (months) were not significantly correlated; however, using a larger data set, leaf life span (as an annual/perennial binary trait) and relative silicon concentration were significantly correlated, implying that across a larger data set, shifts to higher relative leaf/shoot silicon concentration are consistently associated with shifts to annual foliage.4. We suggest that in shorter‐lived leaves, silicon could be a metabolically cheaper alternative to carbon, allowing a more favourable leaf carbon balance over short periods. Silicon could be a less versatile, but more disposable resource, with the potential to function in structural, stress alleviation and defensive roles by substituting for carbon that could be allocated to further growth and reproduction.