Augmentation of spelling therapy with transcranial direct current stimulation in primary progressive aphasia: Preliminary results and challenges

Background: Primary progressive aphasia (PPA) is a neurodegenerative disease that primarily affects language functions and often begins in the fifth or sixth decade of life. The devastating effects on work and family life call for the investigation of treatment alternatives. In this article, we present new data indicating that neuromodulatory treatment, using transcranial direct current stimulation (tDCS) combined with a spelling intervention, shows some promise for maintaining or even improving language, at least temporarily, in PPA.

Aims: The main aim of the present article is to determine whether tDCS plus spelling intervention is more effective than spelling intervention alone in treating written language in PPA. We also asked whether the effects of tDCS are sustained longer than the effects of spelling intervention alone.

Methods & Procedures: We present data from six PPA participants who underwent anodal tDCS or sham plus spelling intervention in a within-subject crossover design. Each stimulation condition lasted 3 weeks or a total of 15 sessions with a 2-month interval in between. Participants were evaluated on treatment tasks as well as on other language and cognitive tasks at 2-week and 2-month follow-up intervals after each stimulation condition.

Outcomes & Results: All participants showed improvement in spelling (with sham or tDCS). There was no difference in the treated items between the two conditions. There was, however, consistent and significant improvement for untrained items only in the tDCS plus spelling intervention condition. Furthermore, the improvement lasted longer in the tDCS plus spelling intervention condition compared to sham plus spelling intervention condition.

Conclusions: Neuromodulation with tDCS offers promise as a means of augmenting language therapy to improve written language function at least temporarily in PPA. The consistent finding of generalisation of treatment benefits to untreated items and the superior sustainability of treatment effects with tDCS justifies further investigations. However, the small sample size still requires caution in interpretation. Present interventions need to be optimised, and particular challenges, such as ways to account for the variable effect of degeneration in each individual, are discussed.     

A qualitative study of early childhood educators' beliefs and practices regarding children's socioemotional development

Existing research underscores the significance of early childhood experiences in the childcare context for the development of socioemotional skills and competencies. However, the practices adopted within childcare for the enhancement of children's socioemotional development and the factors mediating these practices are less adequately researched. The present study contributes to this understanding, through studying the perceptions of 34 educators working in childcare centres in Greece with regard to children's socioemotional development and its promotion. Results showed that although they acknowledged the significance of social and emotional competencies for children's adjustment, learning and well-being, they did not report consistent use of practices having as a goal the promotion of such skills. Explanations involve on the one hand the lack of formal policy and the existence of structural barriers and on the other hand a perception that socioemotional development is mostly affected by factors beyond their influence. Results are discussed in relation to prior research and in terms of their implications for designing interventions, curricula and staff training.     

Selective 5HT3 antagonists and sensory processing: a systematic review

Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson’s disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications.Subject terms: Perception, Predictive markers     

Multicentric evaluation of a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas

Objective: To develop a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas (ICC). Patients: Two hundred and one consecutive ICC patients (83 from Essen, Germany, 54 from New York, USA and 64 from Chiba, Japan). The scoring systems were developed utilizing the data set from Essen University and then applied to the data sets from Mount Sinai Medical Center and Chiba University for validation. Eighteen potential prognostic factors were evaluated. Statistical analysis included multivariable regression analyses with the Cox proportional hazard model, power analysis, internal validation with structural equation modelling bootstrapping and external validation. The prognostic scoring model was based mainly in pathological and demographical variables, whereas the clinical scoring model was based mainly in radiological and demographical variables. Results: Gender (P=0.0086), UICC stage (P=0.0140) and R‐class (P=0.0016) were predictive of survival for the prognostic scoring model, while gender (P=0.0023), CA 19‐9 levels (P=0.0153) and macrovascular invasion (P=0.0067) were predictive of survival for the clinical scoring model. Prognostic points were assigned as follows: female:male=1:2 points, UICC (I–II):UICC (III–IV)=1:2 points and R0:R1=1:2 points. Clinical points were allocated as follows: female:male=1:2 points, CA 19‐9 (<100 U/ml):CA 19‐9 (≥100 U/ml)=1:2 points and no macrovascular invasion:macrovascular invasion=1:2 points. Prognostic groups with 3–4, 5 and 6 points (P=0.000001) and clinical groups with 3–4 and 5–6 points (P=0.0103) achieved statistically significant difference. Conclusions: We propose a clinical and prognostic scoring system predictive of long‐term survival after surgical resections for ICC.     

Association between TNF-alpha -308G>A polymorphism and the development of acute coronary syndromes in Greek subjects: the CARDIO2000-GENE Study.

PURPOSE: We investigated the association of a polymorphism within the promoter of TauNuF-alpha locus at the position -308 on the likelihood of having acute coronary syndromes (ACS) in Greek adults. METHODS: We studied demographic, lifestyle, and clinical information in 237 hospitalized patients (185 males) with a first event of an ACS and 237 matched by age and sex (controls) without any clinical evidence of coronary heart disease. Genotyping was performed by PCR-RFLP analysis. RESULTS: The genotype frequencies were in patients, 87% (n = 206), 12% (n = 29), and 1% (n = 2) for G/G, G/A, and A/A, and in controls, 96% (n = 227), 4% (n = 10), and 0% (n = 0) for G/G, G/A, and A/A, respectively (P = 0.04). After adjusting for age and sex, as well as various potential confounders, we observed that G/A or A/A genotypes were associated with 1.94-fold higher odds (95% CI 1.06 to 3.68) of ACS compared to G/G homozygotes. No gene to-gender or to-clinical syndrome interactions were observed. Further subgroup analysis showed that the distribution of TNF-alpha -308G>A polymorphism was associated with the presence of family history of CHD in patients, but not in controls. In particular, in G/A and A/A patients 17.2% reported family history of CHD, whereas in G/G patients, 34.5% reported family history (P = 0.036). CONCLUSIONS: Our findings may state a hypothesis of an association between the -308G>A TNF-alpha polymorphism the development of ACS and the presence of family history of CHD, in Greece.     

Body mass index, calcium intake, and physical activity affect calcaneal ultrasound in healthy Greek males in an age-dependent and parameter-specific manner

Quantitative ultrasound (QUS) is a peripheral bone densitometry technique that is rapidly gaining in popularity for the assessment of skeletal status. This study was carried out to examine the effect of anthropometric, dietary, physical activity, and other lifestyle factors on QUS parameters in healthy Greek males of various ages, including children (n = 192), adults (n = 106), and elderly (n = 86) subjects. Calcaneal QUS measurements were performed with the Sahara device (Hologic), which measures broadband ultrasound attenuation (BUA) and speed of sound (SOS) through the os calcis. A composite parameter, the quantitative ultrasound index (QUI), and an estimate of heel bone mineral density (eBMD) were also derived. BUA correlated positively with height, weight, and body mass index, as well as waist and hip circumferences (P < 0.001), but this was not the case for SOS. QUI and eBMD were inconsistently related with anthropometric characteristics. Overweight and obese males had significantly higher BUA than normal-weight subjects (P < 0.05), but similar SOS, QUI, and eBMD; this held true for all age groups. Boys participating in organized physical activities had significantly higher SOS, QUI, and eBMD than those who did not (P < 0.05), although BUA was similar in the two groups; no differences according to organized physical activity were detected in adults and the elderly. On the other hand, adult men devoting at least some time to non-organized physical activities had significantly higher QUS values than their non-exercising peers (P < 0.05); no such effects, however, were seen in children and the elderly. Adult men with calcium intakes above 800mg/day had significantly higher SOS, QUI, and eBMD than those consuming less calcium (P < 0.05), and also tended towards higher BUA (P = 0.079); no such differences were observed among children and elderly men. The effects of physical activity and calcium intake on heel QUS persisted even after controlling for body size. Overall, body weight was the sole significant positive determinant of BUA ( = 0.373; t = 6.589; P < 0.001), explaining approximately 14% of the total variance, while age was the sole significant negative determinant of SOS ( = –0.198; t = –3.321; P = 0.001), albeit explaining only less than 4% of the total variance. In conclusion, body size, dietary calcium intake, and physical activity patterns seem to inconsistently and age-dependently influence heel QUS among healthy Greek males in a parameter-specific manner.