Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Abstract Introduction Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients. Methods Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO2, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise). Results The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO2 (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study. Conclusion A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients. Trial registration NCT01515163.

Contributions from the systematic review of economic evaluations: the case of childhood hepatitis A vaccination in Brazil

The aim of this study was to present the contributions of the systematic review of economic evaluations to the development of a national study on childhood hepatitis A vaccination. A literature review was performed in EMBASE, MEDLINE, WOPEC, HealthSTAR, SciELO and LILACS from 1995 to 2010. Most of the studies (8 of 10) showed favorable cost-effectiveness results. Sensitivity analysis indicated that the most important parameters for the results were cost of the vaccine, hepatitis A incidence, and medical costs of the disease. Variability was observed in methodological characteristics and estimates of key variables among the 10 studies reviewed. It is not possible to generalize results or transfer epidemiological estimates of resource utilization and costs associated with hepatitis A to the local context. Systematic review of economic evaluation studies of hepatitis A vaccine demonstrated the need for a national analysis and provided input for the development of a new decision-making model for Brazil.

Stigma and higher rates of psychiatric re-hospitalization: São Paulo public mental health system

OBJECTIVE: The aim of this study was to assess re-hospitalization rates of individuals with psychosis and bipolar disorder and to study determinants of readmission. METHODS: Prospective observational study, conducted in São Paulo, Brazil. One hundred-sixty-nine individuals with bipolar and psychotic disorder in need of hospitalization in the public mental health system were followed for 12 months after discharge. Their families were contacted by telephone and interviews were conducted at 1, 2, 6 and 12 months post-discharge to evaluate readmission rates and factors related. RESULTSOne-year re-hospitalization rate was of 42.6%. Physical restraint during hospital stay was a risk factor (OR = 5.4-10.5) for readmission in most models. Not attending consultations after discharge was related to the 12-month point readmission (OR = 8.5, 95%CI 2.3-31.2) and to the survival model (OR = 3.2, 95%CI 1.5-7.2). Number of previous admissions was a risk factor for the survival model (OR = 6.6-11.9). Family's agreement with permanent hospitalization of individuals with mental illness was the predictor associated to readmission in all models (OR = 3.5-10.9) and resulted in shorter survival time to readmission; those readmitted were stereotyped as dangerous and unhealthy. CONCLUSIONS: Family's stigma towards mental illness might contribute to the increase in readmission rates of their relatives with psychiatric disorders. More studies should be conducted to depict mechanisms by which stigma increases re-hospitalization rates.

Comparação dos instrumentos Childhood Autism Rating Scale e Autism Behavior Checklist na identificação e caracterização de indivíduos com distúrbios do espectro autístico

OBJETIVO: Comparar as respostas dos instrumentos Childhood Autism Rating Scale e Autism Behavior Checklist na identificação e caracterização de indivíduos com Distúrbios do Espectro Autístico. MÉTODOS: Participaram 28 indivíduos que estavam em atendimento fonoaudiológico e possuíam diagnósticos inseridos no Espectro do Autismo. Todos foram avaliados por meio dos instrumentos Autism Behavior Checklist e Childhood Autism Rating Scale a partir de informações obtidas, respectivamente, com pais e terapeutas. Os dados foram analisados estatisticamente em relação à concordância das respostas obtidas. Foram considerados concordantes os resultados de alta ou moderada probabilidade para autismo no Autism Behavior Checklist e com autismo leve-moderado ou grave na Childhood Autism Rating Scale, e respostas de baixa probabilidade no Autism Behavior Checklist e sem autismo na Childhood Autism Rating Scale. RESULTADOS: Houve concordância na maior parte das respostas obtidas. Casos em que houve discordância entre os resultados obtidos a partir dos protocolos corroboram dados da literatura, evidenciando que os instrumentos podem não ser suficientes, quando aplicados isoladamente para a definição do diagnóstico. CONCLUSÃO: Enquanto a Childhood Autism Rating Scale pode não diagnosticar crianças efetivamente autistas, o Autism Behavior Checklist pode incluir como autistas, crianças com outros distúrbios. Portanto, recomenda-se o uso complementar dos dois instrumentos.

Complexity of N-Myc transcriptional function in childhood neuroblastoma

Myc is a transcription factor that can activate transcription of several hundreds genes by direct binding to their promoters at specific DNA sequences (E-box). However, recent studies have also shown that it can exert its biological role by repressing transcription. Such studies collectively support a model in which c-Myc-mediated repression occurs through interactions with transcription factors bound to promoter DNA regions but not through direct recognition of typical E-box sequences. Here, we investigated whether N-Myc can also repress gene transcription, and how this is mechanistically achieved. We used human neuroblastoma cells as a model system in that N-MYC amplification/over-expression represents a key prognostic marker of this tumour. By means of transcription profile analyses we could identify at least 5 genes (TRKA, p75NTR, ABCC3, TG2, p21) that are specifically repressed by N-Myc. Through a dual-step-ChIP assay and genetic dissection of gene promoters, we found that N-Myc is physically associated with gene promoters in vivo, in proximity of the transcription start site. N-Myc association with promoters requires interaction with other proteins, such as Sp1 and Miz1 transcription factors. Furthermore, we found that N-Myc may repress gene expression by interfering directly with Sp1 and/or with Miz1 activity (i.e. TRKA, p75NTR, ABCC3, p21) or by recruiting Histone Deacetylase 1 (Hdac1) (i.e. TG2). In vitro analyses show that distinct N-Myc domains can interact with Sp1, Miz1 and Hdac1, supporting the idea that Myc may participate in distinct repression complexes by interacting specifically with diverse proteins. Finally, results show that N-Myc, through repressed genes, affects important cellular functions, such as apoptosis, growth, differentiation and motility. Overall, our results support a model in which N-Myc, like c-Myc, can repress gene transcription by direct interaction with Sp1 and/or Miz1, and provide further lines of evidence on the importance of transcriptional repression by Myc factors in tumour biology.

Reconceptualising professional development in early childhood education. A study on teachers' professionalism carried out in Bologna province.

The research undertaken for this doctoral thesis explores the issue of teachers professionalism within pre-school institutions. The issue of early childhood professionalism has become increasingly important in the academic debate over the last decade as it is documented by a growing body of research published on the topic both nationally (Contini & Manini, 2007; Bondioli & Ferrari, 2004) and internationally (Peeters, 2008; Urban & Dalli, 2008; Urban, 2010). The study presented in this thesis aims at investigating teachers’ conceptualisations of professionalism by focusing on their understandings of educational work. The idea standing at the core of this research is that exploring the concept of professionalism from a ground-up perspective could lead to important reflections for a re-conceptualisation of professional development as a space for change directed from within institutions. The study is framed within a broadly sociological concern that inform the data analysis by contextualising the issue of early childhood professionalism in the contemporary socio-political arena. The research involves sixty teachers operating in state, municipal and private pre-school institutions located in Bologna province that took part to focus groups and interviews. The empirical materials, consisting of oral and written statements, are interpreted through phenomenographical analysis that gives account of how features of professionalism vary across the different institutional settings in which they are played out. This thesis, written in English and informed by an European research background, offers a contribution to the furthering of systemic approaches to the investigation of early childhood education professionalism in the context of the national and international academic debate.

Lateralization of cognitive functions after stroke in childhood

A child's brain shows a remarkable ability to recover from adverse events such as stroke. Language functions recover particularly well, while visuo-spatial skills are more affected by brain damage, regardless of its localization. This study investigated the lateralization of language and visual search after childhood stroke.

Chronic impact of topiramate on acid-base balance and potassium in childhood

Topiramate, which is commonly prescribed for seizure disorders and migraine prophylaxis, sometimes causes metabolic acidosis and hypokalemia. Since the effects of topiramate on acid-base balance and potassium levels have not been well explored in children, acid-base balance, anion gap and potassium were assessed in 24 patients (8 females and 16 males) aged between 4.6 and 19 years on topiramate for more than 12 months and in an age-matched control group. Plasma bicarbonate (21.7 versus 23.4 mmol/L; P<0.03), carbon dioxide pressure (39.7 versus 43.2mm Hg; P<0.05), and potassium (3.7 versus 4.0 mmol/L; P<0.03) were on the average lower and chloride (109 versus 107 mmol/L; P<0.03) higher in patients treated with topiramate than in controls. Blood pH, plasma sodium and the anion gap were similar in patients on topiramate and in controls. In patients on topiramate no significant correlation was observed between the dosage of this agent and plasma bicarbonate or potassium as well as between topiramate blood level and the mentioned electrolytes. In conclusion long-term topiramate treatment is associated with a mild, statistically significant tendency towards compensated normal anion gap metabolic acidosis and hypokalemia.

Neuroimaging in childhood arterial ischaemic stroke: evaluation of imaging modalities and aetiologies

Aim The aim of this study was to describe neuroimaging patterns associated with arterial ischaemic stroke (AIS) in childhood and to differentiate them according to stroke aetiology. Method Clinical and neuroimaging (acute and follow-up) findings were analysed prospectively in 79 children (48 males, 31 females) aged 2 months to 15 years 8 months (median 5y 3mo) at the time of stroke by the Swiss Neuropaediatric Stroke Registry from 2000 to 2006. Results Stroke was confirmed in the acute period in 36 out of 41 children who underwent computed tomography, in 53 of 57 who underwent T2-weighted magnetic resonance imaging (MRI) and in all 48 children who underwent diffusion-weighted MRI. AIS occurred in the anterior cerebral artery (ACA) in 63 participants and in all cases was associated with lesions of the middle cerebral artery (MCA). The lesion was cortical-subcortical in 30 out of 63 children, cortical in 25 out of 63, and subcortical in 8 of 63 children. Among participants with AIS in the posterior circulation territory, the stroke was cortical-subcortical in 8 out of 16, cortical in 5 of 16, and thalamic in 3 out of 16 children. Interpretation AIS mainly involves the anterior circulation territory, with both the ACA and the MCA being affected. The classification of Ganesan is an appropriate population-based classification for our Swiss cohort, but the neuroimaging pattern alone is insufficient to determine the aetiology of stroke in a paediatric population. The results show a poor correlation between lesion pattern and aetiology.

Mitochondrial tRNA(Leu(UUR)) mutation m.3302A > G presenting as childhood-onset severe myopathy: threshold determination through segregation study

Mitochondrial tRNA(Leu(UUR)) mutation m.3302A > G is associated with respiratory chain complex I deficiency and has been described as a rare cause of mostly adult-onset slowly progressive myopathy. Five families with 11 patients have been described so far; 5 of them died young due to cardiorespiratory failure. Here, we report on a segregation study in a family with an index patient who already presented at the age of 18 months with proximal muscular hypotonia, abnormal fatigability, and lactic acidosis. This early-onset myopathy was rapidly progressive. At 8 years, the patient is wheel-chair bound, requires nocturnal assisted ventilation, and suffers from recurrent respiratory infections. Severe complex I deficiency and nearly homoplasmy for m.3302A > G were found in muscle. We collected blood, hair, buccal swabs and muscle biopsies from asymptomatic adults in this pedigree and determined heteroplasmy levels in these tissues as well as OXPHOS activities in muscle. All participating asymptomatic adults had normal OXPHOS activities. In contrast to earlier reports, we found surprisingly little variation of heteroplasmy levels in different tissues of the same individual. Up to 45% mutation load in muscle and up to 38% mutation load in other tissues were found in non-affected adults. The phenotypic spectrum of tRNA(Leu(UUR)) m.3302A > G mutation seems to be wider than previously described. A threshold of more than 45% heteroplasmy in muscle seems to be necessary to alter complex I activity leading to clinical manifestation. The presented data may be helpful for prognostic considerations and counseling in affected families.

Vascular hospitalization rates and costs in patients with peripheral artery disease in the United States

BACKGROUND: Peripheral artery disease (PAD) is common and imposes a high risk of major systemic and limb ischemic events. The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international prospective registry of patients at risk of atherothrombosis caused by established arterial disease or the presence of 3 atherothrombotic risk factors. METHODS AND RESULTS: We compared the 2-year rates of vascular-related hospitalizations and associated costs in US patients with established PAD across patient subgroups. Symptomatic PAD at enrollment was identified on the basis of current intermittent claudication with an ankle-brachial index (ABI) <0.90 or a history of lower-limb revascularization or amputation. Asymptomatic PAD was diagnosed on the basis of an enrollment ABI <0.90 in the absence of symptoms. Overall, 25 763 of the total 68 236-patient REACH cohort were enrolled from US sites; 2396 (9.3%) had symptomatic and 213 (0.8%) had asymptomatic PAD at baseline. One- and cumulative 2-year follow-up data were available for 2137 (82%) and 1677 (64%) of US REACH patients with either symptomatic or asymptomatic PAD, respectively. At 2 years, mean cumulative hospitalization costs, per patient, were $7445, $7000, $10 430, and $11 693 for patients with asymptomatic PAD, a history of claudication, lower-limb amputation, and revascularization, respectively (P=0.007). A history of peripheral intervention (lower-limb revascularization or amputation) was associated with higher rates of subsequent procedures at both 1 and 2 years. CONCLUSIONS: The economic burden of PAD is high. Recurring hospitalizations and repeat revascularization procedures suggest that neither patients, physicians, nor healthcare systems should assume that a first admission for a lower-extremity PAD procedure serves as a permanent resolution of this costly and debilitating condition.

Successful treatment of childhood high-risk hepatoblastoma with dose-intensive multiagent chemotherapy and surgery: final results of the SIOPEL-3HR study

The primary objective was to determine the efficacy of a newly designed preoperative chemotherapy regimen in an attempt to improve the cure rate of children with high-risk hepatoblastoma.

Family characteristics as risk factors for childhood acute lymphoblastic leukemia: a population-based case-control study

To date, few risk factors for childhood acute lymphoblastic leukemia (ALL) have been confirmed and the scientific literature is full of controversial "evidence." We examined if family characteristics, particularly maternal and paternal age and number of older siblings, were risk factors for childhood acute lymphoblastic leukemia (ALL).