Subgroup-specific structural variation across 1,000 medulloblastoma genomes

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4 alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kappa B signalling in Group 4, suggest future avenues for rational, targeted therapy.

Hurdles at work: perceptions of hospital food handlers

Abstract Background Food handlers have a very important role in preventing food contamination during its preparation and distribution. This responsibility is even greater in hospitals, since a large number of patients have low immunity and consequently food contamination by pathogenic bacteria could be particularly harmful. Therefore, a good working environment and periodic training should be provided to food handlers by upper management. Methods This study is qualitative research by means of focus group and thematic content analysis methodologies to examine, in detail, the statements by food handlers working in the milk and specific-diet kitchens in a hospital to understand the problems they face in the workplace. Results We found that food handlers are aware of the role they play in restoring patients' health; they consider it important to offer a good-quality diet. However, according to their perceptions, a number of difficulties prevent them from reaching this aim. These include: upper management not prioritizing human and material resources to the dietetic services when making resource allocation decisions; a perception that upper management considers their work to be of lesser importance; delayed overtime payments; lack of periodic training; managers lacking administrative skills; insufficient dietitian staff assistants, leading to overwork, at the same time as there is an excess of dietitians; unhealthy environmental working conditions – high temperature, high humidity, loud and constant noise level, poor ventilation; lack of food, and kitchen utensils and equipment; and relationship conflicts with chief dieticians and co-workers. Conclusion From these findings, improvement in staff motivation could be achieved by considering non-financial incentives, such as improvement in working conditions and showing appreciation and respect through supervision, training and performance appraisal. Management action, such as investments in intermediary management so that managers have the capacity to provide supportive supervision, as well as better use of performance appraisal and access to training, may help overcome the identified problems.

Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic?

Background:The golden retriever muscular dystrophy (GRMD) dogs represent the best available animal model for therapeutic trials aiming at the future treatment of human Duchenne muscular dystrophy (DMD). We have obtained a rare litter of six GRMD dogs (3 males and 3 females) born from an affected male and a carrier female which were submitted to a therapeutic trial with adult human stem cells to investigate their capacity to engraft into dogs muscles by local as compared to systemic injection without any immunosuppression. Methods Human Immature Dental Pulp Stem Cells (hIDPSC) were transplanted into 4 littermate dogs aged 28 to 40 days by either arterial or muscular injections. Two non-injected dogs were kept as controls. Clinical translation effects were analyzed since immune reactions by blood exams and physical scores capacity of each dog. Samples from biopsies were checked by immunohistochemistry (dystrophin markers) and FISH for human probes. Results and Discussion We analyzed the cells' ability in respect to migrate, engraftment, and myogenic potential, and the expression of human dystrophin in affected muscles. Additionally, the efficiency of single and consecutive early transplantation was compared. Chimeric muscle fibers were detected by immunofluorescence and fluorescent in situ hybridisation (FISH) using human antibodies and X and Y DNA probes. No signs of immune rejection were observed and these results suggested that hIDPSC cell transplantation may be done without immunosuppression. We showed that hIDPSC presented significant engraftment in GRMD dog muscles, although human dystrophin expression was modest and limited to several muscle fibers. Better clinical condition was also observed in the dog, which received monthly arterial injections and is still clinically stable at 25 months of age. Conclusion Our data suggested that systemic multiple deliveries seemed more effective than local injections. These findings open important avenues for further researches.