Behavioral disorders as unusual presentation of pediatric extraventricular neurocytoma: report on two cases and review of the literature

Background

Extraventricular neurocytomas (EVNs) are rare parenchymal brain tumors, distinct from central neurocytomas that are typically located within the supratentorial ventricular system. Seizures and headache represent the most common symptoms of extraventricular neurocytomas in the cerebral hemisphere both in adult and pediatric population.

Case presentation

We describe two cases of pediatric EVN with clinical onset characterized by behavioral and attention deficit/ hyperactivity disorders. The association between behavioral/attention disorders in childhood and the presence of a frontal neurocytoma has never been described before. Furthermore, inappropriate levels of inattention, hyperactivity and impulsivity are common among the neurobehavioral and developmental disorders in childhood. We reviewed 43 pediatric cases of extraventricular neurocytoma included in the PubMed database and their clinical presentation, and we never found this unusual relationship.

Conclusion

In childhood, the attention/hyperactivity disorders seem to be often over-diagnosed. When these deficits are more subtle and do not well-fit in a specific neurocognitive disorder, the clinicians should have a suspicion that they might mask the clinical features of a frontal lesion. This paper is focused on the clinical presentation of the extraventricular neurocytoma and the possible organic etiology of an attention and hyperactivity deficit.

     

Cognitive and Kidney Function: Results from a British Birth Cohort Reaching Retirement Age

Background

Previous studies have found associations between cognitive function and chronic kidney disease. We aimed to explore possible explanations for this association in the Medical Research Council National Survey of Health and Development, a prospective birth cohort representative of the general British population.

Methods

Cognitive function at age 60–64 years was quantified using five measures (verbal memory, letter search speed and accuracy, simple and choice reaction times) and glomerular filtration rate (eGFR) at the same age was estimated using cystatin C. The cross-sectional association between cognitive function and eGFR was adjusted for background confounding factors (socioeconomic position, educational attainment), prior cognition, and potential explanations for any remaining association (smoking, diabetes, hypertension, inflammation, obesity).

Results

Data on all the analysis variables were available for 1306–1320 study members (depending on cognitive measure). Verbal memory and simple and choice reaction times were strongly associated with eGFR. For example, the lowest quartile of verbal memory corresponded to a 4.1 (95% confidence interval 2.0, 6.2) ml/min/1.73 m² lower eGFR relative to the highest quartile. Some of this association was explained by confounding due to socioeconomic factors, but very little of it by prior cognition. Smoking, diabetes, hypertension, inflammation and obesity explained some but not all of the remaining association.

Conclusions

These analyses support the notion of a shared pathophysiology of impaired cognitive and kidney function at older age, which precedes clinical disease. The implications of these findings for clinical care and research are important and under-recognised, though further confirmatory studies are required.     

Observational Study Assessing Demographic,Economic and Clinical Factors Associated with Access and Utilization of Health Care Services of Patients with Multiple Sclerosis under Treatment with Interferon Beta-1b (EXTAVIA)

Multiple sclerosis (MS) results in an extensive use of the health care system, even within the first years of diagnosis. The effectiveness and accessibility of the health care system may affect patients'' quality of life. The aim of the present study was to evaluate the health care resource use of MS patients under interferon beta-1b (EXTAVIA) treatment in Greece, the demographic or clinical factors that may affect this use and also patient satisfaction with the health care system. Structured interviews were conducted for data collection. In total, 204 patients (74.02% females, mean age (SD) 43.58 (11.42) years) were enrolled in the study. Analysis of the reported data revealed that during the previous year patients made extensive use of health services in particular neurologists (71.08% visited neurologists in public hospitals, 66.67% in private offices and 48.53% in insurance institutes) and physiotherapists. However, the majority of the patients (52.45%) chose as their treating doctor private practice neurologists, which may reflect accessibility barriers or low quality health services in the public health system. Patients seemed to be generally satisfied with the received health care, support and information on MS (84.81% were satisfied from the information provided to them). Patients'' health status (as denoted by disease duration, disability status and hospitalization needs) and insurance institute were found to influence their visits to neurologists. Good adherence (up to 70.1%) to the study medication was reported. Patients'' feedback on currently provided health services could direct these services towards the patients'' expectations.     

Clinical and Organizational Issues in the Management of Surviving Breast and Colorectal Cancer Patients: Attitudes and Feelings of Medical Oncologists

Background

The fast growing demand and the shortage of resources are pushing toward more efficient models of survivorship care delivery. The Associazione Italiana di Oncologia Medica (AIOM) established an interdisciplinary working group with the purpose of promoting organizational improvements at the national level. A survey aimed at assessing attitudes and feelings of oncologists was considered preliminary to further initiatives.

Methods

A 25-item questionnaire, sent to the mailing list of the Society, explored the following issues on the practice of breast and colorectal cancer patients'' follow up: 1) organization; 2) clinical features; 3) feelings about the different meanings of follow-up.

Results

Ninety-one oncologists of 160 institutions (57%) answered to the questionnaire. Although follow up is considered a distinct oncological activity in 68%, a fully shared organization between specialists is not common and communications with Primary Care Physicians are not structured in the majority of the cases. Fifty-five and 30% of the oncologists follow breast and colorectal cancer patients indefinitely. In case of discharge a survivorship care plan is delivered in only 9%. The majority of respondents do not hold a role of follow up in mortality reduction.

Conclusions

Although survivorship care represents a significant part of the oncologists'' workload, an “oncology-centered” model is largely adopted and established care pathways are still incomplete. Survivorship care needs to be put at the center of an educational policy and of a widespread organizational effort, directed at improving appropriateness and quality.     

Quantitative phosphoproteomics reveals novel roles of cAMP in plants

3′,5′-cyclic adenosine monophosphate (cAMP) is finally recognized as an essential signaling molecule in plants where cAMP-dependent processes include responses to hormones and environmental stimuli. To better understand the role of 3′,5′-cAMP at the systems level, we have undertaken a phosphoproteomic analysis to elucidate the cAMP-dependent response of tobacco BY-2 cells. These cells overexpress a molecular “sponge” that buffers free intracellular cAMP level. The results show that, firstly, in vivo cAMP dampening profoundly affects the plant kinome and notably mitogen-activated protein kinases, receptor-like kinases, and calcium-dependent protein kinases, thereby modulating the cellular responses at the systems level. Secondly, buffering cAMP levels also affects mRNA processing through the modulation of the phosphorylation status of several RNA-binding proteins with roles in splicing, including many serine and arginine-rich proteins. Thirdly, cAMP-dependent phosphorylation targets appear to be conserved among plant species. Taken together, these findings are consistent with an ancient role of cAMP in mRNA processing and cellular programming and suggest that unperturbed cellular cAMP levels are essential for cellular homeostasis and signaling in plant cells.     

Interaction between sexual steroids and immune response in affecting oxidative status of birds

One hypothesis explaining the honesty of secondary sexual traits regulated by testosterone (T) is that T can impair the balance between pro-oxidant compounds and antioxidant defences, favouring a status of oxidative stress that only good quality individuals can sustain (oxidative handicap hypothesis). In the present study, we evaluated for the first time the effects of sexual steroids, T and its metabolites 5-α-dihydrotestosterone (DHT) and estradiol (E2) on oxidative damage and plasma non-enzymatic antioxidant capacity, while birds are faced by an oxidative challenge induced by an immune stimulation with sheep red blood cells. We used male and female diamond doves Geopelia cuneata, a species that shows an orange-red periorbital ring, whose size and color are strongly affected by androgens, but not by estrogens. Immunization increased oxidative damage in all groups, regardless of hormone treatment. It also decreased anti-oxidant capacity in all groups, except for testosterone treated birds. The ratio of oxidative damage over anti-oxidant capacity (oxidative stress) was increased in both immunological challenged controls and E2 birds, while challenged birds treated with androgens did not differ from non-challenged birds. The response of males and females to our treatments never differed. Our results undermine the idea that T can induce honest signalling through a pro-oxidant activity.     

Biophysical Characterisation of Neuroglobin of the Icefish, a Natural Knockout for Hemoglobin and Myoglobin. Comparison with Human Neuroglobin

The Antarctic icefish Chaenocephalus aceratus lacks the globins common to most vertebrates, hemoglobin and myoglobin, but has retained neuroglobin in the brain. This conserved globin has been cloned, over-expressed and purified. To highlight similarities and differences, the structural features of the neuroglobin of this colourless-blooded fish were compared with those of the well characterised human neuroglobin as well as with the neuroglobin from the retina of the red blooded, hemoglobin and myoglobin-containing, closely related Antarctic notothenioid Dissostichus mawsoni. A detailed structural and functional analysis of the two Antarctic fish neuroglobins was carried out by UV-visible and Resonance Raman spectroscopies, molecular dynamics simulations and laser-flash photolysis. Similar to the human protein, Antarctic fish neuroglobins can reversibly bind oxygen and CO in the Fe²⁺ form, and show six-coordination by distal His in the absence of exogenous ligands. A very large and structured internal cavity, with discrete docking sites, was identified in the modelled three-dimensional structures of the Antarctic neuroglobins. Estimate of the free-energy barriers from laser-flash photolysis and Implicit Ligand Sampling showed that the cavities are accessible from the solvent in both proteins.Comparison of structural and functional properties suggests that the two Antarctic fish neuroglobins most likely preserved and possibly improved the function recently proposed for human neuroglobin in ligand multichemistry. Despite subtle differences, the adaptation of Antarctic fish neuroglobins does not seem to parallel the dramatic adaptation of the oxygen carrying globins, hemoglobin and myoglobin, in the same organisms.     

Using liposomes as carriers for polyphenolic compounds: the case of trans-resveratrol

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol found in various plants, especially in the skin of red grapes. The effect of resveratrol on human health is the topic of numerous studies. In fact this molecule has shown anti-cancer, anti-inflammatory, blood-sugar-lowering ability and beneficial cardiovascular effects. However, for many polyphenol compounds of natural origin bioavailability is limited by low solubility in biological fluids, as well as by rapid metabolization in vivo. Therefore, appropriate carriers are required to obtain efficient therapeutics along with low administration doses.Liposomes are excellent candidates for drug delivery purposes, due to their biocompatibility, wide choice of physico-chemical properties and easy preparation.In this paper liposome formulations made by a saturated phosphatidyl-choline (DPPC) and cholesterol (or its positively charged derivative DC-CHOL) were chosen to optimize the loading of a rigid hydrophobic molecule such as resveratrol.Plain and resveratrol loaded liposomes were characterized for size, surface charge and structural details by complementary techniques, i.e. Dynamic Light Scattering (DLS), Zeta potential and Small Angle X-ray Scattering (SAXS). Nuclear and Electron Spin magnetic resonances (NMR and ESR, respectively) were also used to gain information at the molecular scale.The obtained results allowed to give an account of loaded liposomes in which resveratrol interacted with the bilayer, being more deeply inserted in cationic liposomes than in zwitterionic liposomes. Relevant properties such as the mean size and the presence of oligolamellar structures were influenced by the loading of RESV guest molecules.The toxicity of all these systems was tested on stabilized cell lines (mouse fibroblast NIH-3T3 and human astrocytes U373-MG), showing that cell viability was not affected by the administration of liposomial resveratrol.     

Subtle effects of biological invasions: cellular and physiological responses of fish eating the exotic pest Caulerpa racemosa

The green alga Caulerpa racemosa var. cylindracea has invaded Mediterranean seabed including marine reserves, modifying the structure of habitats and altering the distributional patterns of associated organisms. However, the understanding of how such invasion can potentially affect functional properties of Mediterranean subtidal systems is yet to be determined. In this study, we show that C. racemosa changes foraging habit of the native white seabream, Diplodus sargus. In invaded areas, we found a high frequency of occurrence of C. racemosa in the stomach contents of this omnivorous fish (72.7 and 85.7%), while the alga was not detected in fish from a control area. We also found a significant accumulation of caulerpin, one of the main secondary metabolites of C. racemosa, in fish tissues. The level of caulerpin in fish tissues was used here as an indicator of the trophic exposure to the invasive pest and related with observed cellular and physiological alterations. Such effects included activation of some enzymatic pathways (catalase, glutathione peroxidases, glutathione S-transferases, total glutathione and the total oxyradical scavenging capacity, 7-ethoxy resorufin O-deethylase), the inhibition of others (acetylcholinesterase and acylCoA oxidase), an increase of hepatosomatic index and decrease of gonadosomatic index. The observed alterations might lead to a detrimental health status and altered behaviours, potentially preventing the reproductive success of fish populations. Results of this study revealed that the entering of alien species in subtidal systems can alter trophic webs and can represent an important, indirect mechanism which might contribute to influence fluctuations of fish stocks and, also, the effectiveness of protection regimes.