Outpatient rehabilitative treatment of chronic fatigue syndrome (CFS/ME)

Aims: To assess the outcome of outpatient multidisciplinary rehabilitative treatment (graded activities/exercise programme, family sessions, and supportive care) compared with supportive care alone for children and adolescents with chronic fatigue syndrome (CFS/ME). Methods: Fifty six young people (aged 9–17 years) with CFS/ME by standard criteria were followed up for 3–24 months. All subjects received supportive care. Families additionally opted to either enter the rehabilitation programme (supportive care plus graded activities/exercise programme and family sessions) or have no additional treatment. Results: Twenty two (39%) subjects had supportive care alone and 26 (46%) entered the programme. Treatment groups were comparable at baseline in terms of age, severity and duration of illness, Wellness score, and school attendance. At end of follow up, those in the programme group had significantly higher Wellness score and school attendance than those having supportive care alone. The programme significantly reduced the overall severity of illness: after the programme, 43% had complete resolution of CFS/ME compared to only 4.5% of those having supportive care alone. The presence of depressed mood and family beliefs about the aetiology of CFS/ME were not significantly associated with outcomes. Conclusions: Outpatient rehabilitative treatment offers significant potential to improve the prognosis of CFS/ME in childhood and adolescence.     

Trimethyltin-induced neurogenesis in the murine hippocampus

Neurogenesis continues to occur in the mature rodent brain with one of the most prominent sources for new neurons being the subgranular layer (SGL) of the dentate gyrus (DG) in the hippocampus. A number of factors can stimulate this process including synaptic activity and injury. To determine if this process would occur upon a direct injury to the dentate region, we exposed young, 21 day old male CD-1 mice to the hippocampal toxicant, trimethyltin (TMT). An acute i.p. injection of TMT (2 mg/kg) produced extensive damage and loss of dentate granule neurons within 72 h. This active period of degeneration was accompanied by an increase in the generation of progenitor cells within the SGL as identified by BrdU uptake and Ki-67 immunostaining. As additional markers for neurogenesis, both nestin and doublecortin showed increased staining patterns within the blades of the dentate. In these young weanling mice, the level of proliferation was sufficient to significantly repopulate the dentate region by 4 weeks post-TMT, suggesting a high level of regenerative potential. Our data indicate a significant level of neurogenesis occurring during the active process of degeneration and in an environment of microglia activation. The TMT-induced injury offers a model system for further examination of the process of neurogenesis, neural adaptation, and the influence of inflammatory factors and glia interactions.     

Evolving small neurocontrollers with self-organized compact encoding

This article presents a novel method for the evolution of artificial autonomous agents with small neurocontrollers. It is based on adaptive, self-organized compact genotypic encoding (SOCE) generating the phenotypic synaptic weights of the agent's neurocontroller. SOCE implements a parallel evolutionary search for neurocontroller solutions in a dynamically varying and reduced subspace of the original synaptic space. It leads to the emergence of compact successful neurocontrollers starting from large networks. The method can serve to estimate the network size needed to perform a given task, and to delineate the relative importance of the neurons composing the agent's controller network.     

The cognitive-orientation theory of anorexia nervosa

The major goal was to explore the cognitive-motivational dynamics of anorexia in terms of the cognitive-orientation (CO) theory (Kreitler & Kreitler, 1982). CO is a comprehensive theory of behavior that assumes that behavior is a function of a cognitively shaped motivational disposition and performance. The study deals with the motivational disposition for anorexia. It focused on examining whether beliefs of four types (about self, goals, norms, and reality) concerning themes relevant for anorexia (defined in pretests) identify correctly anorectics. All participants were women 15 to 18 years old: 58 anorectics (35 restricting, 23 binge eating/purging) and 59 matched healthy controls. All were administered a background-information questionnaire and the CO-Anorexia questionnaire assessing beliefs about 30 themes. The results showed that the themes formed 5 clusters defined by foci, such as dissociation from reality, the body, drives or emotionality, and identified significantly the anorectics of each type and the healthy controls. A brief CO questionnaire was developed. Discussion centered on the similarity of the identified themes to some of those discussed by others, on the pathogeneity of the CO of anorexia, and on outlining a blueprint of a theory of anorexia.     

Classification of human astrocytic gliomas on the basis of gene expression: a correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes

The development of targeted treatment strategies adapted to individual patients requires identification of the different tumor classes according to their biology and prognosis. We focus here on the molecular aspects underlying these differences, in terms of sets of genes that control pathogenesis of the different subtypes of astrocytic glioma. By performing cDNA-array analysis of 53 patient biopsies, comprising low-grade astrocytoma, secondary glioblastoma (respective recurrent high-grade tumors), and newly diagnosed primary glioblastoma, we demonstrate that human gliomas can be differentiated according to their gene expression. We found that low-grade astrocytoma have the most specific and similar expression profiles, whereas primary glioblastoma exhibit much larger variation between tumors. Secondary glioblastoma display features of both other groups. We identified several sets of genes with relatively highly correlated expression within groups that: (a). can be associated with specific biological functions; and (b). effectively differentiate tumor class. One prominent gene cluster discriminating primary versus nonprimary glioblastoma comprises mostly genes involved in angiogenesis, including VEGF fms-related tyrosine kinase 1 but also IGFBP2, that has not yet been directly linked to angiogenesis. In situ hybridization demonstrating coexpression of IGFBP2 and VEGF in pseudopalisading cells surrounding tumor necrosis provided further evidence for a possible involvement of IGFBP2 in angiogenesis. The separating groups of genes were found by the unsupervised coupled two-way clustering method, and their classification power was validated by a supervised construction of a nearly perfect glioma classifier.     

A phase II,double-blind,randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies

tgAAVCF, an adeno-associated cystic fibrosis transmembrane conductance regulator (CFTR) viral vector/gene construct, was administered to 23 patients in a Phase II, double-blind, randomized, placebo-controlled clinical trial. For each patient, a dose of 100,000 replication units of tgAAVCF was administered to one maxillary sinus, while the contralateral maxillary sinus received a placebo treatment, thereby establishing an inpatient control. Neither the primary efficacy endpoint, defined as the rate of relapse of clinically defined, endoscopically diagnosed recurrent sinusitis, nor several secondary endpoints (sinus transepithelial potential difference [TEPD], histopathology, sinus fluid interleukin [IL]-8 measurements) achieved statistical significance when comparing treated to control sinuses within patients. One secondary endpoint, measurements of the anti-inflammatory cytokine IL-10 in sinus fluid, was significantly (p < 0.03) increased in the tgAAVCF-treated sinus relative to the placebo-treated sinus at day 90 after vector instillation. The tgAAVCF administration was well tolerated, without adverse respiratory events, and there was no evidence of enhanced inflammation in sinus histopathology or alterations in serum-neutralizing antibody titer to adeno-associated virus (AAV) capsid protein after vector administration. In summary, this Phase II trial confirms the safety of tgAAVCF but provides little support of its efficacy in the within-patient controlled sinus study. Various potentially confounding factors are discussed.