Autism Spectrum Traits in Children with Anxiety Disorders

The aim of this study was to examine ASD traits in children with clinical anxiety in early development, as well as current manifestations. Parents of 42 children with an anxiety disorder (but no known diagnosis of ASD) and 42 typically developing children were interviewed using the Autism Diagnostic Interview (ADI-R). They also completed questionnaires that assessed child anxiety (SCARED-71) and children’s ASD symptoms. Results revealed that children with anxiety disorders had higher scores than typically developing children, for both ASD traits in early development as well as current ASD symptoms. A specific association was found between symptoms of Social Anxiety Disorder and ASD traits early in life. Findings are considered in terms of clinical implications, and limitations are discussed.     

Decoding fMRI events in sensorimotor motor network using sparse paradigm free mapping and activation likelihood estimates

Most functional MRI (fMRI) studies map task‐driven brain activity using a block or event‐related paradigm. Sparse paradigm free mapping (SPFM) can detect the onset and spatial distribution of BOLD events in the brain without prior timing information, but relating the detected events to brain function remains a challenge. In this study, we developed a decoding method for SPFM using a coordinate‐based meta‐analysis method of activation likelihood estimation (ALE). We defined meta‐maps of statistically significant ALE values that correspond to types of events and calculated a summation overlap between the normalized meta‐maps and SPFM maps. As a proof of concept, this framework was applied to relate SPFM‐detected events in the sensorimotor network (SMN) to six motor functions (left/right fingers, left/right toes, swallowing, and eye blinks). We validated the framework using simultaneous electromyography (EMG)–fMRI experiments and motor tasks with short and long duration, and random interstimulus interval. The decoding scores were considerably lower for eye movements relative to other movement types tested. The average successful rate for short and long motor events were 77 ± 13% and 74 ± 16%, respectively, excluding eye movements. We found good agreement between the decoding results and EMG for most events and subjects, with a range in sensitivity between 55% and 100%, excluding eye movements. The proposed method was then used to classify the movement types of spontaneous single‐trial events in the SMN during resting state, which produced an average successful rate of 22 ± 12%. Finally, this article discusses methodological implications and improvements to increase the decoding performance. Hum Brain Mapp 38:5778–5794, 2017. © 2017 Wiley Periodicals, Inc.     

Psychobiological modulation in anxious and depressed patients after a mindfulness meditation programme: a pilot study

Mindfulness meditation is an ancient and simple form of meditation that has been said to induce several important physical and psychological benefits. The present study was designed with the aim of investigating the psychobiological effects of mindfulness meditation practice in a clinical population. Sixteen patients with depression and anxiety symptoms were submitted to a mindfulness meditation programme for the period of 2 months. Psychological well‐being [5‐item Mental Health (MH‐5)] and several endocrine parameters [adrenocorticotropic hormone (ACTH), cortisol, dehydroepiandrosterone‐sulphate (DHEAS), thyroid‐stimulating hormone, triiodothyronine, thyroxine and parathyroid hormone (PTH)] were assessed before and after the meditation programme. At post‐test, the MH‐5 score improved, while the levels of DHEAS and ACTH were raised, and those of PTH decreased. Our results suggest that mindfulness meditation can exert a significant psychobiological modulation by enhancing psychological well‐being, as well as by regulating the levels of several hormonal parameters on different axes. Copyright © 2010 John Wiley & Sons, Ltd.     

Use of Indwelling Pleural Catheter in the Outpatient Management of Recurrent Malignant Pleural Effusion

IntroductionTo analyse the effectiveness and safety of the indwelling pleural catheter in the management of recurrent malignant pleural effusion.Patients and methodsA prospective multicentre study was performed in 63 consecutive outpatients from four Spanish hospitals. A total of 43 men and 20 women were included, with a median age of 67 years. In seven of the cases treatment with pleurodesis had failed; in five other cases their lung was trapped; in another five cases after repeat therapeutic thoracocentesis, and the rest of them as a preference choice to pleurodesis. All patients had an indwelling pleural catheter inserted (PleurX^®, Denver Biomedical).ResultsMost of patients (94.5%) reported an improvement in their respiratory symptoms (cough and dyspnoea) and their ability to function independently. Average length of the catheterisation was 45 days (6-222). Average amount of drained pleural effusion was 75 ml, with a frequency of drainage of between 3 and 4 times per week and once fortnightly. Spontaneous pleurodesis was achieved following 34.9% of procedures. No complications occurred during the insertion of the catheter. The post-catheterisation complications were empyema (3 cases), chest pain (2 cases), and tumour metastasis (3 cases).ConclusionsThe use of an indwelling pleural catheter is an effective palliative treatment in the outpatient management for patients suffering malignant pleural effusion. It is also a simple treatment that can be easily applied, does not require hospitalisation and can be easily managed by the patient at home, with a low rate of complications.     

A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN

The PI 3-phosphatase PTEN (phosphatase and tensin homologue deleted on chromosome 10), one of the most important tumor suppressors, must associate with the plasma membrane to maintain appropriate steady-state levels of phosphatidylinositol 3,4,5-triphosphate. Yet the mechanism of membrane binding has received little attention and the key determinants that regulate localization, a phosphatidylinositol 4,5-bisphosphate (PIP₂) binding motif and a cluster of phosphorylated C-terminal residues, were not included in the crystal structure. We report that membrane binding requires PIP₂ and show that phosphorylation regulates an intramolecular interaction. A truncated version of the enzyme, PTEN_1–351, bound strongly to the membrane, an effect that was reversed by co-expression of the remainder of the molecule, PTEN_352–403. The separate fragments associated in vitro, an interaction dependent on phosphorylation of the C-terminal cluster, a portion of the PIP₂ binding motif, integrity of the phosphatase domain, and the CBR3 loop. Our investigation provides direct evidence for a model in which PTEN switches between open and closed states and phosphorylation favors the closed conformation, thereby regulating localization and function. Small molecules targeting these interactions could potentially serve as therapeutic agents in antagonizing Ras or PI3K-driven tumors. The study also stresses the importance of determining the structure of the native enzyme.     

Control of food intake by MC4-R signaling in the lateral hypothalamus, nucleus accumbens shell and ventral tegmental area: interactions with ethanol

The melanocortin system is involved in animal models of obesity and anorexia-cachexia and MC4 receptors (MC4-R) are currently a target system for the development of drugs aimed to treat obesity and eating disorders in humans. Previous evidence suggest that feeding peptides might lack their orexigenic activity while stimulate ethanol intake. The present study comparatively evaluated food intake (4-h interval) in Sprague-Dawley (SD) rats drinking ethanol (6% w/v, 2 bottle choice paradigm) (EE group) and ethanol-na?ve (EN) rats in response to bilateral infusion of the selective MC4-R antagonist HS014 (0, 0.02 or 0.05 μg/0.5 μl/site) or the selective MC4-R agonist cyclo(NH-CH(2)-CH(2)-CO-His-d-Phe-Arg-Trp-Glu)-NH(2) (0, 0.75 or 1.5 μg/0.5 μl/site), into the lateral hypothalamus (LH), the nucleus accumbens (NAc), or the ventral tegmental area (VTA). The main findings in the study are: (1) LH-infusions of the MC4-R antagonist increased and the agonist reduced feeding and total calories consumed, while ethanol intake remained unaltered. (2) NAc- and VTA-infusions of the selective agonist reduced food, ethanol and total calories intake. (3) NAc- and VTA-infusions of the MC4-R antagonist increased feeding in EN rats, but not in EE animals which showed a mild increase in ethanol intake, while total calories consumed remained unaltered. Present data show that having ethanol available reduces feeding elicited by NAc and VTA-MC4-R blockade. Additionally, while MC4-R signaling in the LH appears to modulate homeostatic aspects of feeding, it may contribute to non-homeostatic aspects of ingestive behaviors in the VTA and the NAc.     

Compression of cognitive morbidity by higher education in individuals aged 75+ living in Germany

Background

Previous studies have shown that higher education may reduce dementia risk and promote a better cognitive functioning in older age.

Objective

The study investigated to what extent higher education leads to compression of cognitive morbidity, and thus a shorter lifetime affected by cognitive impairment and dementia, in individuals aged 75 years and older living in Germany.

Methods

Our sample included n = 742 individuals of the population‐based Leipzig Longitudinal Study of the Aged (LEILA75+; 1998‐2013), who were free of dementia at baseline. The impact of higher education on compression of cognitive morbidity was studied by analyzing the association between education and (1) cognitive functioning over the study period and age at dementia onset, (2) age at death, and (3) the cumulative lifetime cognitive morbidity.

Results

Individuals with more years of education had a higher cumulative cognitive functioning over the lifetime period 75 to 100 years (weighted for survival probability), but not a later age of dementia onset nor a later age at death.

Conclusion

Our results suggest, in individuals aged 75 years and older, higher education only compresses cognitive morbidity prior to dementia onset. Findings may be specific to countries where education is not a necessary requirement for access to good quality health care services.     

A placebo-controlled double-blind randomized study of venlafaxine in the treatment of depression in dementia

BACKGROUND/AIMS: To evaluate the efficacy and safety of venlafaxine in the treatment of major depression in dementia. METHODS: Thirty-one outpatients who had dementia and major depression participated in this randomized, double-blind, placebo-controlled, 6-week, flexible dose clinical trial. The screening measures were Cornell Scale for depression in dementia, DSM-IV for depression and dementia and Mini-Mental State Examination. The outcome measures were response rate, Montgomery-Asberg Depression Rating scale and Clinical Global Impressions. RESULTS: The percentage of patients defined as Montgomery-Asberg Depression Rating scale responders was approximately the same in the placebo and in the venlafaxine groups. Clinical Global Impressions showed no significant difference between the groups. The reasons for dropouts show borderline significance between the two groups. There was no statistically significant difference in the incidence of adverse events between the venlafaxine and placebo-treated groups. CONCLUSIONS: Our data do not support the hypothesis that venlafaxine improves mood in elderly demented patients.     

Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays

Tumoral cells in Hodgkin lymphoma (HL) display an increased growth fraction and diminished apoptosis, implying a profound disturbance of the cell cycle and apoptosis regulation. However, limitations of molecular techniques have prevented the analysis of the tumor suppressor pathways and cell-cycle checkpoints. Tissue microarray (TMA) is a powerful tool for analyzing a large number of molecular variables in a large series of tumors, although the feasibility of this technique has not yet been demonstrated in heterogeneous tumors. The expression of 29 genes regulating the cell cycle and apoptosis were analyzed by immunohistochemistry and in situ hybridization in 288 HL biopsies using TMA. The sensitivity of the technique was validated by comparing the results with those obtained in standard tissue sections. The results revealed multiple alterations in different pathways and checkpoints, including G1/S and G2/M transition and apoptosis. Striking findings were the overexpression of cyclin E, CDK2, CDK6, STAT3, Hdm2, Bcl2, Bcl-X(L), survivin, and NF-kappaB proteins. A multiparametric analysis identified proteins associated with increased growth fraction (Hdm2, p53, p21, Rb, cyclins A, B1, D3, and E, CDK2, CDK6, SKP2, Bcl-X(L), survivin, STAT1, and STAT3), and proteins associated with apoptosis (NF-kappaB, STAT1, and RB). The analysis also demonstrated that Epstein-Barr virus (EBV)-positive cases displayed a characteristic profile, confirming the pathogenic role of EBV in HL. Survival probability depends on multiple biologic factors, including overexpression of Bcl2, p53, Bax, Bcl-X(L), MIB1, and apoptotic index. In conclusion, Hodgkin and Reed-Sternberg cells harbor concurrent and overlapping alterations in the major tumor suppressor pathways and cell-cycle checkpoints. This appears to determine the viability of the tumoral cells and the clinical outcome.