A longitudinal VBM study in paediatric obsessive–compulsive disorder at 2-year follow-up after cognitive behavioural therapy

Objectives. To identify neurodevelopmental differences in regional brain volume between medication-free paediatric obsessive–compulsive disorder (OCD) patients and controls at 2-year follow-up after cognitive behavioural therapy. Methods. We assessed 17 medication-free paediatric OCD patients (mean age 13.8 years; SD = 2.8; range 8.2–19.0) and 20 controls, matched on age and gender, with T1-weighted MR scans in a repeated measures design at three time points with intervals of 6 months and 2 years. Voxel based morphometry (VBM) was used to test whole brain voxel-wise for the effects of diagnosis and time on regional grey matter (GM) and white matter volumes. Results. GM volume of the orbitofrontal cortex showed a group × time interaction effect, driven by an increase of GM volume over the whole time period in OCD patients and a decrease in controls. When splitting the groups in two age groups (8–12 and 13–19 years) this interaction effect was only seen in the youngest age group. Conclusions. Neuroimaging findings in paediatric OCD after 6 months of CBT in the GM volume of the orbital frontal cortex are still present at 2-year follow-up.     

How do we process event‐based and time‐based intentions in the brain? an fMRI study of prospective memory in healthy individuals

Prospective memory (PM) refers to the ability to remember to do something in the future, either in response to an event (event‐based) or after a certain amount of time has elapsed (time‐based). While the distinction between event‐ and time‐based PM is widely acknowledged in the literature, little is known about the processes they share and those they do not. This is particularly true concerning their brain substrates, as almost all neuroimaging studies so far have focused on event‐based PM. We proposed a functional magnetic resonance imaging paradigm assessing both event‐based and time‐based PM to 20 healthy young individuals. Analyses revealed that event‐ and time‐based PM both induced activation in the posterior frontal and parietal cortices, and deactivation in the medial rostral prefrontal cortex. In addition, activation more specific to each condition, which may underlie differences in strategic monitoring, was highlighted. Thus, occipital areas were more activated during event‐based PM, probably reflecting target‐checking, while a network comprising the dorsolateral prefrontal cortex, the cuneus/precuneus and, to a lesser extent, the inferior parietal lobule, superior temporal gyrus, and the cerebellum, was more activated in time‐based PM, which may reflect the involvement of time‐estimation processes. These results confirm the allocation of attentional resources to the maintenance of intention for event‐based and time‐based PM, as well as the engagement of distinct mechanisms reflecting the monitoring strategies specific to each condition. Hum Brain Mapp 35:3066–3082, 2014. © 2013 Wiley Periodicals, Inc.     

Vaccinations among medical and nursing students: Coverage and opportunities

Healthcare students are a specific subgroup of healthcare workers as they are often not identified by the occupational medicine systems in healthcare facilities, because of their shared time between hospital wards and universities. Nevertheless, they should comply with the same vaccination recommendations as employed healthcare workers because they are in close and repeated contact with patients. Occupational immunization recommendations may vary between countries, but always include vaccine-preventable diseases that might lead to nosocomial outbeaks and/or fatal outcomes for healthcare workers or patients. Studies conclude that vaccine coverage is too low in healthcare students, and that they are often not aware of their possibility to be vectors of infections to frail patients. Efforts should be made to educate medical and nursing students on vaccines, to convince them of the utility of immunization and to offer them an increased access to occupational vaccinations in hospitals and universities.     

Interleukin-1-Mediated phospholipid breakdown and arachidonic acid release in human synovial cells

Objective. Interleukin-1 (IL-1), an important mediator contributing to joint destruction in rheumatoid arthritis, is known to stimulate the release of arachidonic acid (AA) and prostaglandin E₂ (PGE₂) from adherent synoviocytes. To study the intracellular pathways involved in these functions, we stimulated cultures of human synovial cells with recombinant IL-1β. Methods. AA liberation was measured after labeling synovial cells with ³H-AA, and PGE₂ levels were determined by high performance liquid chromatography or radioimmunoassay. Identification of ³H-AA-labeled phospholipids was performed by thin layer chromatography. Cell-associated phospholipase A₂ (PLA₂) enzymatic activity was determined by an assay with cell-free systems and exogenous substrates. Results. Stimulation of synovial cells with recombinant IL-1β induced a decrease in phosphatidylcholine (PC), phosphatidylinositol (PI), and phosphatidylethanolamine (PE), and a marked increase in cell-associated PLA₂ activity as compared with controls. In the presence of either quinacrine, an inhibitor of PLA₂ pathway activation, or neomycin, which binds to PI mono- and biphosphate thus blocking their degradation by phospholipases, AA and PGE₂ secretion were reduced in a dose-dependent manner. Kinetic studies revealed that quinacrine had little blocking activity on the IL-1-mediated AA release after 1 hour of stimulation but completely abolished it after 5 or 8 hours. In contrast, neomycin exerted a partial but significant inhibitory effect from the first hour of stimulation onward. Addition of quinacrine was also demonstrated to abolish the IL-1-induced hydrolysis of PC and PE but not PI, indicating that PC and PE are the preferred substrates for PLA₂ enzymatic activity in human synovial cells. Conclusion. Our findings strongly suggest that AA and PGE₂ production by IL-1-triggered synoviocytes are largely dependent upon PLA₂-mediated hydrolysis of PC and PE and to a lesser extent upon the earlier degradation of PI.     

Establishment of tissue-specific tolerance is driven by regulatory T cells selected by thymic epithelium

Grafts of thymic epithelium (TE) rudiments restore T cell development and function in allogeneic athymic mice. These TE chimeras are specifically tolerant to grafts of peripheral tissues (e.g. skin and heart) from the TE donor strain, although they harbor peripheral immunocompetent T cells capable of rejecting those grafts. Initial analysis has shown that TE chimeras also harbor TE-selected CD4 T lymphocytes that inhibit graft rejection by tissue-reactive T cells in immunocompetent recipients. Peripheral tolerance in TE chimeras is thus maintained by dominant mechanisms dependent on regulatory CD4 T lymphocytes. Here we show that TE-selected regulatory T cells recruit nontolerant tissue-reactive CD4 and CD8 T cells to express similar regulatory functions. Only recent thymic emigrants, but not peripheral resident mature T cells are susceptible to this process of functional education, which also requires exposure to specific antigens and occurs entirely in the periphery. We propose that these mechanisms play a major role in establishing and maintaining natural self tolerance to tissue-specific antigens.     

Autonomic failure in Parkinson’s disease is associated with striatal dopamine deficiencies

Journal of Neurology - Autonomic dysfunction is a common non-motor symptom in Parkinson’s disease (PD). Dopamine and serotonin are known to play a role in autonomic regulation, and,...     

Prevalence,severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes

The primary objective of this study was to investigate factors associated with fatigue severity in newly diagnosed patients with higher‐risk myelodysplastic syndromes (MDS). The secondary objectives were to assess symptom prevalence and to examine the relationships between fatigue, quality of life (QoL) and overall symptom burden in these patients. The analyses were conducted in 280 higher‐risk MDS patients. Pre‐treatment patient‐reported fatigue was evaluated with the Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue scale and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30). Female gender (P = 0·018), poor performance status (i.e., ECOG of 2–4) (P < 0·001) and lower levels of haemoglobin (Hb) (P = 0·026) were independently associated with higher fatigue severity. The three most prevalent symptoms were as follows: fatigue (92%), dyspnoea (63%) and pain (55%). Patients with higher levels of fatigue also had greater overall symptom burdens. The mean global QoL scores of patients with the highest versus those with the lowest levels of fatigue were 29·2 [standard deviation (SD), 18·3] and 69·0 (SD, 18·8), respectively and this difference was four times the magnitude of a clinically meaningful difference. Patient‐reported fatigue severity revealed the effects of disease burden on overall QoL more accurately than did degree of anaemia. Special attention should be given to the female patients in the management of fatigue.     

CDK13-related disorder: Report of a series of 18 previously unpublished individuals and description of an epigenetic signature

PurposeRare genetic variants in CDK13 are responsible for CDK13-related disorder (CDK13-RD), with main clinical features being developmental delay or intellectual disability, facial features, behavioral problems, congenital heart defect, and seizures. In this paper, we report 18 novel individuals with CDK13-RD and provide characterization of genome-wide DNA methylation.MethodsWe obtained clinical phenotype and neuropsychological data for 18 and 10 individuals, respectively, and compared this series with the literature. We also compared peripheral blood DNA methylation profiles in individuals with CDK13-RD, controls, and other neurodevelopmental disorders episignatures. Finally, we developed a support vector machine–based classifier distinguishing CDK13-RD and non–CDK13-RD samples.ResultsWe reported health and developmental parameters, clinical data, and neuropsychological profile of individuals with CDK13-RD. Genome-wide differential methylation analysis revealed a global hypomethylated profile in individuals with CDK13-RD in a highly sensitive and specific model that could aid in reclassifying variants of uncertain significance.ConclusionWe describe the novel features such as anxiety disorder, cryptorchidism, and disrupted sleep in CDK13-RD. We define a CDK13-RD DNA methylation episignature as a diagnostic tool and a defining functional feature of the evolving clinical presentation of this disorder. We also show overlap of the CDK13 DNA methylation profile in an individual with a functionally and clinically related CCNK-related disorder.     

Structural characterization and cytotoxic properties of a 4-O-methylglucuronoxylan from castanea sativa. 2. Evidence of a structure-activity relationship

Xylans were purified from delignified holocellulose alkaline extracts of Castanea sativa (Spanish chestnut) and Argania spinosa (Argan tree) and their structures analyzed by means of GC of their per-trimethylsilylated methylglycoside derivatives and (1)H NMR spectroscopy. The structures deduced were characteristic of a 4-O-methylglucuronoxylan (MGX) and a homoxylan (HX), respectively, with degrees of polymerization ranging from 182 to 360. In the case of MGX, the regular or random distribution of 4-O-methylglucuronic acid along the xylosyl backbone--determined by MALDI mass spectrometry after autohydrolysis of the polysaccharide--varied and depended both on the botanical source from which they were extracted and on the xylan extraction procedure. The MGX also inhibited in different ways the proliferation as well as the migration and invasion capability of A431 human epidermoid carcinoma cells. These biological properties could be correlated with structural features including values of the degree of polymerization, 4-O-MeGlcA to xylose ratios, and distribution of 4-O-MeGlcA along the xylosyl backbone, giving evidence of a defined structure-activity relationship.