Learning and switching between stimulus-saccade associations in Parkinson’s disease

Making flexible associations between what we see and what we do is important for many everyday tasks. Previous work in patients with focal lesions has shown that the control of saccadic eye movements in such contexts relies on a network of areas in the frontal cerebral cortex. These regions are reciprocally connected with structures in the basal ganglia although the contribution of these sub-cortical structures to oculomotor control in complex tasks is not well understood. We report the performance of patients with idiopathic Parkinsons disease (PDs) in a test which required learning and switching between arbitrary cue-saccade rules. In Experiment 1 feedback was given following each response which reliably indicated which of the two possible rules was correct. PDs were slower to learn the first cue-saccade association presented, but did not show increased error or reaction time switch costs when switching between two rules within blocks. In a follow up experiment the feedback given by the computer was adjusted to be probabilistic such that executing a response based upon the “correct” rule only resulted in positive feedback on 80% of trials. Under these conditions patients were impaired in terms of response latencies and number of errors. In all conditions PDs showed multi-stepping/hypometria of saccades consistent with a motoric deficit in executing actions based on cognitive cues. The findings are consistent with a role for the nigrostriatal dopamine system in the reinforcement of saccade-response-outcome associations. Intact performance of PDs when associations are not stochastically reinforced suggests that striatal learning systems are complemented by cognitive representations of task rules which are unaffected in the early stages of PD.     

Alexithymia and Emotional Intelligence in Patients with Panic Disorder, Generalized Anxiety Disorder and Major Depressive Disorder

Emotional Intelligence (EI) is a broad personality construct signifying the ability to perceive and to regulate affects within oneself. Alexithymia is another personality construct denoting difficulty in identifying and expressing emotions, with an externally oriented thinking style. Although previously considered to be independent, some studies have shown that these constructs overlap. The aim of this study was to evaluate and compare the levels of EI and alexithymia in patients with panic disorder, major depressive disorder (MDD), and generalized anxiety disorder (GAD). The subjects included 171 psychiatric patients and 56 non-clinical controls. Psychiatric diagnoses were based on DSM-IV criteria. The Emotional Intelligence Scale-34 (EIS-34) and the Toronto Alexithymia Scale (TAS-20) were used to assess EI and alexithymia. All three patient groups scored statistically significantly higher than the non-clinical controls on TAS-20 total score and the TAS-20 subfactors of difficulty identifying feelings and difficulty describing feelings. EIS-34 scores were lower in patient groups than in the non-clinical controls, but only the EIS-34 intrapersonal subscale was significant difference. Total TAS-20 and EIS-34 scores in the patient cohort were inversely and significantly correlated These results reaffirm an overlap between EI and alexithymia with the intrapersonal factor of EI to be more dependent on the difficulty identifying feelings dimension of alexithymia in subjects with MDD and GAD.     

Stigma,public awareness about intellectual disability and attitudes to inclusion among different ethnic groups

Background Attitudes to the inclusion of people with intellectual disabilities (IDs) have been studied extensively, yet evidence on public awareness about ID and stigma is limited. The relationship between attitudes, knowledge and stigma associated with ID is poorly understood. The present study examined these factors and the relationships between them in the context of a multicultural society. Method UK residents of working age (n = 1002) were presented with a diagnostically unlabelled vignette of someone with a mild ID. They were asked to label the difficulties presented and to complete measures of social distance and attitudes to the inclusion of people with IDs. Results While attitudes to the inclusion of people with IDs were relatively positive overall, social contact was viewed with ambivalence. Inclusion attitudes and social distance were only moderately correlated. Across the whole sample 28% recognised typical symptoms of mild ID. Recognition of ID was associated with lower stigma and more positive attitudes than attribution of the difficulties presented to other causes. White Westerners showed increased knowledge, lower stigma and favoured inclusion more than participants from ethnic minorities. Among the latter group, Asians showed lower stigma and attitudes more in line with inclusion policies than participants of Black African/Caribbean backgrounds. Once a host of contextual factors were considered jointly, only contact was consistently associated with the variables measured. Conclusions Stigma associated with ID is of concern across all ethnic groups, although it appears to be increased among the public from ethnic minorities. Given that contact and awareness are associated with reduced stigma, they should be considered as prime foci for efforts to tackle ID stigma. The current findings serve as baseline for attempts to increase public awareness and tackle stigma.     

The Functional Assessment Test: A Method of Evaluating Improvement in Function After Knee Arthroplasty

Questionnaires are marginally useful for objectively measuring function after knee arthroplasty. The Functional Assessment (FA) test is an easily administered, timed test of a person’s ability to stand, walk and ascend/descend stairs that would be useful for quantifying a patient’s function after knee arthroplasty. Four hundred forty-five individuals were included in the study: 313 without lower extremity arthritis or neurologic disease and 132 with advanced degenerative arthritis prior to knee arthroplasty. As expected, the test times were longer for individuals afflicted with knee arthritis. Arthroplasty patients were tested pre- and postoperatively to determine if their FA test time improved. The FA test takes less than a minute and is practical for use in the clinical setting as a simple means of quantifying function before and after knee arthroplasty.     

A case of slipped capital femoral epiphysis results from hypophosphatemic rickets： treatment and midterm follow-up

In this case, a male patient presented with a clinically and radiographieally unstable slipped capital femoral epiphysis （SCFE） as well as slipped calcaneal epiphysis years. Subsequent thorough at the age of 23 work-up revealed that he had some features of rickets and labo- ratory test demonstrated he had hypophos- phatemia （2.3mg/dl）, normocalcemia, normal vi- tamin D metabolite levels, and secondary hy- perparathyroidism.     

Neuronal Nitric Oxide Synthase (NOS1) Polymorphisms Interact with Financial Hardship to Affect Depression Risk

There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual''s susceptibility to depression.     

A chemical compound that stimulates the human homologous recombination protein RAD51

RAD51 and other members of the RecA family of strand exchange proteins assemble on ssDNA to form presynaptic filaments, which carry out the central steps of homologous recombination. A microplate-based assay was developed for high-throughput measurement of hRAD51 filament formation on ssDNA. With this method, a 10,000 compound library was screened, leading to the identification of a small molecule (RS-1) that enhances hRAD51 binding in a wide range of biochemical conditions. Salt titration experiments showed that RS-1 can enhance filament stability. Ultrastructural analysis of filaments formed on ssDNA showed that RS-1 can increase both protein–DNA complex lengths and the pitch of helical filament turns. RS-1 stimulated hRAD51-mediated homologous strand assimilation (D-loop) activity by at least 5- to 11-fold, depending on the condition. This D-loop stimulation occurred even in the presence of Ca²⁺ or adenylyl-imidodiphosphate, indicating that the mechanism of stimulation was distinct from that conferred by Ca²⁺ and/or inhibition of ATPase. No D-loop activity was observed in the absence of a nucleotide triphosphate cofactor, indicating that the compound does not substitute for this requirement. These results indicate that RS-1 enhances the homologous recombination activity of hRAD51 by promoting the formation of active presynaptic filaments. Cell survival assays in normal neonatal human dermal fibroblasts demonstrated that RS-1 promotes a dose-dependent resistance to the cross-linking chemotherapeutic drug cisplatin. Given that RAD51-dependent recombination is a major determinant of cisplatin resistance, RS-1 seems to function in vivo to stimulate homologous recombination repair proficiency. RS-1 has many potential applications in both research and medical settings.