The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants

Multiple independent genomic profiling efforts have recently identified clinically and molecularly distinct subgroups of ependymoma arising from all three anatomic compartments of the central nervous system (supratentorial brain, posterior fossa, and spinal cord). These advances motivated a consensus meeting to discuss: (1) the utility of current histologic grading criteria, (2) the integration of molecular-based stratification schemes in future clinical trials for patients with ependymoma and (3) current therapy in the context of molecular subgroups. Discussion at the meeting generated a series of consensus statements and recommendations from the attendees, which comment on the prognostic evaluation and treatment decisions of patients with intracranial ependymoma (WHO Grade II/III) based on the knowledge of its molecular subgroups. The major consensus among attendees was reached that treatment decisions for ependymoma (outside of clinical trials) should not be based on grading (II vs III). Supratentorial and posterior fossa ependymomas are distinct diseases, although the impact on therapy is still evolving. Molecular subgrouping should be part of all clinical trials henceforth

The Experience in Nicaragua: Childhood Leukemia in Low Income Countries—The Main Cause of Late Diagnosis May Be “Medical Delay”

Background. The event-free survival for pediatric leukemia in low-income Countries is much lower than in high-income countries. Late diagnosis, which is regarded as a contributing factor, may be due to “parental” or “medical” delay. Procedures. The present study analyses determinants of lag time from first symptoms to diagnosis of leukemia, comparing pediatric (0–16 years old) patients in two referral centers, one in Nicaragua and one in Italy. An observational retrospective study was conducted to assess factors influencing the time to diagnosis. Results. 81 charts of children diagnosed with acute myeloid leukemia or lymphoblastic leukemia were analyzed from each centre. Median lag time to diagnosis was higher in Nicaragua than in Italy (29 versus 14 days, P < 0.001) and it was mainly due to “physician delay” (16.5 versus 7 days, P < 0.001), whereas “patient delay” from symptoms to first medical assessment was similar in the two centers (7 versus 5 days, P = 0.27). Moreover, median lag time from symptoms to diagnosis was decreased in Nicaraguan districts were a specific training program upon childhood oncological diseases was carried out (20.5 versus 40 days, P = 0.0019). Conclusions. Our study shows that delay in diagnosis of childhood leukemia is mainly associated with “physician delay” and it may be overcome by programs of continuous medical education

Evolutionarily conserved BON1 regulates the basal cytosolic Ca2+ level by calmodulin-independent activation of Ca2+ pumps in Arabidopsis

Plasma membrane-localized autoinhibited Ca2+ pumps are essential for maintaining basal cytosolic Ca2+ levels for regulating growth processes and environmental responses. These pumps are known to be activated by calmodulins to maintain Ca2+ homeostasis in plants and animals. Here, we demonstrate that the evolutionarily conserved copine protein BON1 is critical for maintaining low cytosolic Ca2+ concentrations by directly regulating two plasma membrane-localized Ca2+ pumps ACA8 and ACA10 inArabidopsis. BON1 interacts with a region within the N-terminal domain of ACA8 and ACA10, preceding the calmodulin binding sites, and stimulates ACA8 activity. This activation can occur without calmodulin binding, indicating that BON1 and calmodulin independently regulate the Ca2+ pump. Loss of BON1 function results in elevated basal cytosolic Ca2+ concentrations, which can be partially rescued by overexpressing hyperactive ACA8 or ACA10. Furthermore, we show that BON1 has one high-affinity Ca2+ binding in the VWA domain that is critical for activation of ACA8 as well as for BON1 function, suggesting a feedback mechanism for Ca2+ homeostasis at resting concentrations. Our findings suggest that this Ca2+ responsive regulatory mechanism extends beyond Arabidopsis, as we show interactions between ACA and BON proteins from algae flowering plants, pointing to an ancient regulatory mechanism for maintaining basal cytosolic Ca2+. Notably, a human plasma membrane-localized autoinhibited Ca2+ pump can also be activated by a human BON protein in a yeast functional assay system, suggesting evolutionary conservation in Ca2+ regulation across species

Family history of cancer and the risk of childhood brain tumors: a pooled analysis of the ESCALE and ESTELLE studies (SFCE)

PURPOSE: Although some specific genetic syndromes such as neurofibromatosis (NF) have been identified as risk factor of childhood brain tumors (CBT), the potential role of inherited susceptibility in CBT has yet to be elucidated. METHODS: To further investigate this, we conducted a pooled analysis of two nationwide case-control studies ESCALE and ESTELLE. The mothers of 509 CBT cases and 3,102 controls aged under 15 years who resided in France at diagnosis/interview, frequency-matched by age and gender, responded to a telephone interview conducted by trained interviewers. Pooled odds ratio (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. RESULTS: CBT was significantly associated with the family history of cancer in relatives (OR 1.2, 95% CI 1.0-1.5). The OR was slightly higher for maternal relatives than for paternal relatives, and when at least two relatives had a history of cancer. CBT was significantly associated with a family history of brain tumor (OR 2.1, 95% CI 1.3-3.7). This association seemed stronger for first-degree relatives (mother, father, and siblings), for whom, by contrast, no association was seen for cancers other than CBT. No specificity by CBT subtypes or by age of the children were found for any of these findings. CONCLUSION: Our findings support the hypothesis of a familial susceptibility of CBT, not due to being a known NF carrier

THE MANAGEMENT OF THE DOMESTIC REFRIGERATION: HYGIENIC AND SANITARY CHARACTERISTICS OF REFRIGERATORS FROM NORTHEN AND CENTRAL ITALY

This study aimed to provide information on the consumer management of refrigerated food. N&deg; 469 interviews were carried out and the results obtained were subjected to descriptive statistical analysis and further processed with the Multiple Correspondence Analysis and Cluster Analysis. Five homogeneous groups were obtained. In each of them a significant number of refrigerators (60) were tested to assess the temperature and the microbiological status (TVC, Enterobacteriaceae, Salmonella spp. and Listeria spp.). Listeria monocytogenes and Salmonella spp. were not recovered; Listeria innocua was recovered (3.3%). Regarding the TVC values, the 30% of the tested refrigerators was classified as not appropriate (28.3%) or not acceptable (1.7%). Consumer education should be focused in order to reduce foodborne disease. Only safety-conscious consumers can become active partners within the food safety chain