Medulloblastoma Down Under 2013 : a report from the third annual meeting of the International Medulloblastoma Working Group.

Medulloblastoma is curable in approximately 70% of patients. Over the past decade, progress in improving survival using conventional therapies has stalled, resulting in reduced quality of life due to treatment-related side effects, which are a major concern in survivors. The vast amount of genomic and molecular data generated over the last 5-10 years encourages optimism that improved risk stratification and new molecular targets will improve outcomes. It is now clear that medulloblastoma is not a single-disease entity, but instead consists of at least four distinct molecular subgroups: WNT/Wingless, Sonic Hedgehog, Group 3, and Group 4. The Medulloblastoma Down Under 2013 meeting, which convened at Bunker Bay, Australia, brought together 50 leading clinicians and scientists. The 2-day agenda included focused sessions on pathology and molecular stratification, genomics and mouse models, high-throughput drug screening, and clinical trial design. The meeting established a global action plan to translate novel biologic insights and drug targeting into treatment regimens to improve outcomes. A consensus was reached in several key areas, with the most important being that a novel classification scheme for medulloblastoma based on the four molecular subgroups, as well as histopathologic features, should be presented for consideration in the upcoming fifth edition of the World Health Organization's classification of tumours of the central nervous system. Three other notable areas of agreement were as follows: (1) to establish a central repository of annotated mouse models that are readily accessible and freely available to the international research community; (2) to institute common eligibility criteria between the Children's Oncology Group and the International Society of Paediatric Oncology Europe and initiate joint or parallel clinical trials; (3) to share preliminary high-throughput screening data across discovery labs to hasten the development of novel therapeutics. Medulloblastoma Down Under 2013 was an effective forum for meaningful discussion, which resulted in enhancing international collaborative clinical and translational research of this rare disease. This template could be applied to other fields to devise global action plans addressing all aspects of a disease, from improved disease classification, treatment stratification, and drug targeting to superior treatment regimens to be assessed in cooperative international clinical trials.

Associação de Rhizoctonia solani Grupo de Anastomose 4 (AG-4 HGI e HGIII) à espécies de plantas invasoras de área de cultivo de batata

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Frequent p53 mutations and occasional loss of chromosome 4 in invasive bladder carcinoma induced by N-butyl-N-(4-hydroxybutil)nitrosamine in B6D2F1 mice

B6D2F1 mice (45/group) were treated with N-butyl-N-(4- hydroxybutyl)nitrosamine (BBN) or uracil as follows: Group 1 received 0.05% BBN in drinking water for the entire experiment, Group 2 received 5 mg of BBN by gastric gavage in 0.1 mL of 20% ethanol twice per week for 10 wk, Group 3 received a 2.5% uracil-containing diet for the entire experiment, and Group 4 was controls (received 0.1 mL of 20% ethanol by gavage twice per week for 10 wk). The surviving mice in Group 1 were killed after week 26 and those in the other groups after week 30. By week 15, three of 11 Group 1 and one of 15 Group 2 mice had bladder carcinoma. By 26 and 30 wk, respectively, invasive carcinomas were observed in 33 of 34 and six of 21 mice in Groups 1 and 2 and renal pelvic carcinomas in 11 of 34 and three of 21 mice in Groups 1 and 2. Four of 19 uracil-treated mice had bladder nodular hyperplasia. By polymerase chain reaction-single-strand conformation polymorphism and sequence analyses, 16 of 20 and two of five bladder carcinomas from Groups 1 and 2, respectively, showed mutations in the p53 gene. Ha-ras mutation was present in one case. Loss of heterozygosity analysis with simple-sequence length polymorphism markers for chromosome 4 showed that 10 of 21, two of 15, and nine of 13 mice in Groups 1-3, respectively, had heterozygous or homozygous deletions. B6D2F1 mice are therefore susceptible to the urothelial carcinogenic effects of BBN and develop frequent p53 mutations and chromosome 4 deletions. Chromosome 4 deletions were also seen with uracil.

Efficacy, safety and tolerability of terbinafine for Tinea capitis in children: Brazilian multicentric study with daily oral tablets for 1, 2 and 4 weeks

Background: Tinea capitis is a common skin disease seen predominantly in children. The standard therapies for this disease are griseofulvin and ketoconazole. Nevertheless, these drugs have drawbacks in that they are only fungistatic and require treatment for at least 6 weeks. Previous studies with oral terbinafine for the treatment of Tinea capitis have shown that this agent is effective when given for 4 weeks, comparable to an 8-week regimen with griseofulvin. To date there is no data on the use of oral terbinafine in Brazilian children. Objectives: To assess the efficacy, safety and tolerability of oral terbinafine in short-term treatments (1-, 2- and 4-week treatment) of Tinea capitis in children. Patients and methods: One hundred and thirty-two children aged 1-14 years were enrolled in this study, but only 107 were considered for the final efficacy analysis. Diagnosis included clinical assessment and examination by Wood's light. Confirmation was obtained by direct microscopy and culture for fungus. Terbinafine dosage (125 or 250 mg/day) was adjusted according to patient weight. Efficacy was evaluated both by clinical and mycological assessment. Safety and tolerability variables included data on adverse reaction and clinical laboratory evaluations. Results: Mycological evaluation in the follow-up visit at week 12 showed negative direct microscopy and culture results in 48.6, 60.5 and 69.7% patients in groups 1-, 2- and 4-week, respectively (n.s.). At week 12, 84.8% patients in group 4-week achieved clinical cure with a significant difference compared to groups 1- and 2-week, 54.3 and 60.5%, respectively (P < 0.01). Adverse reactions were present in 4.8, 6.8 and 10.9% of patients in groups 1-, 2- and 4-week, respectively. Terbinafine was not associated with clinically relevant increases in liver function tests. Conclusions: Terbinafine is an effective, well tolerated and safe antifungal agent for the treatment of Tinea capitis m children. The shorter duration of treatment resulted in lower cure rates. However, it is important to note that depending on the severity of the disease, a 1-week-only treatment can also be effective in this indication.

Glycogen storage and muscle glucose transporters (GLUT-4) of mice selectively bred for high voluntary wheel running

To examine the evolution of endurance-exercise behaviour, we have selectively bred four replicate lines of laboratory mice (Mus domesticus) for high voluntary wheel running ('high runner' or HR lines), while also maintaining four non-selected control (C) lines. By generation 16, HR mice ran ∼2.7-fold more than C mice, mainly by running faster (especially in females), a differential maintained through subsequent generations, suggesting an evolutionary limit of unknown origin. We hypothesized that HR mice would have higher glycogen levels before nightly running, show greater depletion of those depots during their more intense wheel running, and have increased glycogen synthase activity and GLUT-4 protein in skeletal muscle. We sampled females from generation 35 at three times (photophase 07:00 h-19:00 h) during days 5-6 of wheel access, as in the routine selection protocol: Group 1, day 5, 16:00 h-17:30 h, wheels blocked from 13:00 h; Group 2, day 6, 02:00 h-03:30 h (immediately after peak running); and Group 3, day 6, 07:00 h-08:30 h. An additional Group 4, sampled 16:00 h-17:30 h, never had wheels. HR individuals with the mini-muscle phenotype (50% reduced hindlimb muscle mass) were distinguished for statistical analyses comparing C, HR normal, and HR mini. HR mini ran more than HR normal, and at higher speeds, which might explain why they have been favored by the selective-breeding protocol. Plasma glucose was higher in Group 1 than in Group 4, indicating a training effect (phenotypic plasticity). Without wheels, no differences in gastrocnemius GLUT-4 were observed. After 5 days with wheels, all mice showed elevated GLUT-4, but HR normal and mini were 2.5-fold higher than C. At all times and irrespective of wheel access, HR mini showed approximately three-fold higher [glycogen] in gastrocnemius and altered glycogen synthase activity. HR mini also showed elevated glycogen in soleus when sampled during peak running. All mice showed some glycogen depletion during nightly wheel running, in muscles and/or liver, but the magnitude of this depletion was not large and hence does not seem to be limiting to the evolution of even-higher wheel running.

Chemopreventive activity of apple extract following medium-term oral carcinogenesis assay induced by 4-nitroquinoline-1-oxide

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Antioxidant activity of apple extract protects against rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide

Several studies have shown that apple (Malus sp.) has many components able to exert chemopreventive activity. The aim of this study was to evaluate the chemopreventive potential of apple extract following medium-term oral carcinogenesis assay induced by 4-nitroquinoline 1-oxide (4NQO) by means of histopathological analysis and gene expression of antioxidant enzymes, such as CuZnSOD, MnSOD and catalase. A total of 30 male Wistar rats were distributed into five groups, as follows (n = 6 per group): Group 1 - negative control group (non-treated group); Group 2 - received 4NQO during 8 weeks in drinking water and treated with apple extract by gavage between the 1st and 4th weeks daily (initiation phase); Group 3 - received 4NQO for 8 weeks in drinking water and treated with apple extract by gavage between the 5th and 8th weeks daily (promotion phase); Group 4 - received apple extract by gavage for eight consecutive weeks only; and Group 5 - received 4NQO for 8 weeks in drinking water daily. Histopathological analysis revealed that apple extract protect oral lesions induced by 4NQO at initiation or promotion phase. Higher gene expression of CuZnSOD and MnSOD enzymes were noticed in groups treated with apple extract as well. Taken together, our results demonstrate that the apple extract is able to modulate medium-term oral carcinogenesis assay as a result of antioxidant activity.

Gestão da Informação e Gestão do Conhecimento: análise das publicações do grupo de trabalho 4 no Encontro Nacional de Pesquisa em Ciência da Informação 2005-2014

Este estudo se baseia em duas áreas afins, a área da Gestão da Informação (GI) que busca gerir a informação registrada e a Gestão do Conhecimento (GC) que procura formas de gerir o capital intelectual dos indivíduos. Na busca por compreender sobre as duas áreas do conhecimento, procurou-se analisar os trabalhos presentes no Grupo de Trabalho 4 do Encontro Nacional de Pesquisa em Pós-Graduação em Ciência da Informação (ENANCIB). Devido a este fato, o presente trabalho tem por objetivo principal investigar como a Gestão da Informação e Gestão do Conhecimento são abordadas nos trabalhos apresentados no ENANCIB, tendo por objetivos específicos identificar os trabalhos sobre GI e GC do GT4, a análise de autoria e co-autoria presente nos mesmo, realizar a averiguação das palavras-chave utilizadas, e a investigação de aspectos de abordagem da GI e GC. Para a consecução dos objetivos foi utilizado o método exploratório-descritivo, pois foi realizada a descrições dos contextos dos trabalhos para descobrir as relações existentes entre seus componentes. Como resultado, conclui-se que embora a GI e a GC sejam abordadas em muitos trabalhos, há muitos trabalhos no qual não se é possível ter uma identificação sobre a abordagem de ambas as áreas. Quanto à autoria dos trabalhos, Marta L. P. Valentim é a autora com maior número de apresentações por evento, no que tange a co-autoria há a predominância de dois autores por trabalho. No que se relaciona as palavras-chave encontradas nos trabalhos, observou que a palavra mais comum é GI. E os aspectos em que GI e GC são abordadas são variados, salientando a sua forte presença em organizações.

Patient education to prevent falls among older hospital inpatients : a randomized controlled trial

Background Falls are a common adverse event during hospitalization of older adults, and few interventions have been shown to prevent then. Methods This study was a 3-group randomized trial to evaluate the efficacy of 2 forms of multimedia patient education compared with usual care for the prevention of in-hospital falls. Older hospital patients (n = 1206) admitted to a mixture of acute (orthopedic, respiratory, and medical) and subacute (geriatric and neurorehabilitation) hospital wards at 2 Australian hospitals were recruited between January 2008 and April 2009. The interventions were a multimedia patient education program based on the health-belief model combined with trained health professional follow-up (complete program), multi-media patient education materials alone (materials only), and usual care (control). Falls data were collected by blinded research assistants by reviewing hospital incident reports, hand searching medical records, and conducting weekly patient interviews. Results Rates of falls per 1000 patient-days did not differ significantly between groups (control, 9.27; materials only, 8.61; and complete program, 7.63). However, there was a significant interaction between the intervention and presence of cognitive impairment. Falls were less frequent among cognitively intact patients in the complete program group (4.01 per 1000 patient-days) than among cognitively intact patients in the materials-only group (8.18 per 1000 patient-days) (adjusted hazard ratio, 0.51; 95% confidence interval, 0.28-0.93]) and control group (8.72 per 1000 patient-days) (adjusted hazard ratio, 0.43; 95% confidence interval, 0.24-0.78). Conclusion Multimedia patient education with trained health professional follow-up reduced falls among patients with intact cognitive function admitted to a range of hospital wards.

The influence of culture on safety : culture, organisational culture and safety culture

Transport and Storage Sector - Identified as one of 4 primary targets in the National Occupational Health and Safety Strategy 2002-2012 (NOHSS) The Heavy Vehicle Industry -80% of the freight task -29% of the employees in Transport and Storage 5 years on: -Transport and Storage - 22% reduction -Heavy Vehicle Industry - only an 11% reduction Intervention strategies that aren’t targeted to a specific audience may have differing levels of success due to cultural beliefs and values (McLeroy et al., 1994) Research Goal: - To explore the influence of culture on safety in the heavy vehicle industry

Long-term persistence of tissue-engineered adipose flaps in a murine model to 1 year : an update

BACKGROUND Tissue engineering of patient-specific adipose tissue has the potential to revolutionize reconstructive surgery. Numerous models have been described for the production of adipose tissue with success in the short term, but little has been reported on the stability of this tissue-engineered fat beyond 4 months. METHODS A murine model of de novo adipogenesis producing a potentially transplantable adipose tissue flap within 4 to 6 weeks was developed in the authors' laboratory. In this study, the authors assess the ability of three-chamber (44-μl volume) configurations shown to be adipogenic in previous short-term studies (autograft, n = 8; open, n = 6; fat flap, n = 11) to maintain their tissue volume for up to 12 months in vivo, to determine the most adipogenic configuration in the long term. RESULTS Those chambers having the most contact with existing vascularized adipose tissue (open and fat flap groups) showed increased mean adipose tissue percentage (77 ± 5.6 percent and 81 ± 6.9 percent, respectively; p < 0.0007) and volume (12 ± 6.8 μl and 30 ± 14 μl, respectively; p < 0.025) when compared with short-term controls and greater adipose tissue volume than the autograft (sealed) chamber group (4.9 ± 5.8 μl; p = 0.0001) at 1 year. Inclusion of a vascularized fat flap within the chamber produced the best results, with new fat completely filling the chamber by 1 year. CONCLUSIONS These findings demonstrate that fat produced by tissue engineering is capable of maintaining its volume when the appropriate microenvironment is provided. This has important implications for the application of tissue-engineering techniques in humans.

Clinical trials in pediatrics

“Children are not little adults.” Almost all aspects of children's health including clinical trials and drug development are poor cousins of adult health. Over the years, pediatricians worldwide caution against blind extrapolation of adult data to children as it may result in considerable harm [1,2]. Also, it is increasingly recognized that the roots of many chronic diseases in adulthood stem from childhood and tackling health issues in children lead to improved health in adults [3,4]. Furthermore, investment in early childhood has long-term benefits in adults not only in health but also in other aspects of life such as education and crime reduction [4,5]. Arguably, health at birth is the single most important predictor of health in adulthood as the inequality of an infant at birth has intergenerational effects [5]. The Carolina Abecedarian Project showed that early childhood programs that are of high quality result in substantial societal benefits (e.g., reduction of crime, increased earnings, better education) [4,5]. A recent publication from this project found that this benefit also translated into improved adult health outcomes [4]. In a randomized trial, Campbell and colleagues described that disadvantaged children who were randomized to the intervention group (early education, health screenings and nutrition program) had significantly lower rates of metabolic syndrome, obesity and hypertension, when aged in their mid-30s, compared with the control group [4]...

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

This study aimed to investigate whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer. TransPORTEC, an international consortium related to the PORTEC3 trial, was established for translational research in high-risk endometrial cancer. In this explorative study, routine molecular analyses were used to detect prognostic subgroups: p53 immunohistochemistry, microsatellite instability and POLE proofreading mutation. Furthermore, DNA was analyzed for hotspot mutations in 13 additional genes (BRAF, CDKNA2, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, and PTEN) and protein expression of ER, PR, PTEN, and ARID1a was analyzed. Rates of distant metastasis, recurrence-free, and overall survival were calculated using the Kaplan-Meier method and log-rank test. In total, samples of 116 high-risk endometrial cancer patients were included: 86 endometrioid; 12 serous; and 18 clear cell. For endometrioid, serous, and clear cell cancers, 5-year recurrence-free survival rates were 68%, 27%, and 50% (P=0.014) and distant metastasis rates 23%, 64%, and 50% (P=0.001), respectively. Four prognostic subgroups were identified: (1) a group of p53-mutant tumors; (2) microsatellite instable tumors; (3) POLE proofreading-mutant tumors; and (4) a group with no specific molecular profile (NSMP). In group 3 (POLE-mutant; n=14) and group 2 (microsatellite instable; n=19) patients, no distant metastasis occurred, compared with 50% distant metastasis rate in group 1 (p53-mutant; n=36) and 39% in group 4 (NSMP; P<0.001). Five-year recurrence-free survival was 93% and 95% for group 3 (POLE-mutant) and group 2 (microsatellite instable) vs 42% (group 1, p53-mutant) and 52% (group 4, NSMP; P<0.001). Targetable FBXW7 and FGFR2 mutations (6%), alterations in the PI3K-AKT pathway (60%) and hormone receptor positivity (45%) were frequently found. In conclusion, molecular analysis of high-risk endometrial cancer identifies four distinct prognostic subgroups, with potential therapeutic implications. High frequencies of targetable alterations were identified and may serve as targets for individualized treatment