High throughput protein expression screening in the nervous system – needs and limitations

The cellular complexity of the brain (some estimate that there are up to 10³ different cell types) is exceeded by the synaptic complexity, with each of the ∼10¹¹ neurons in the brain having around 10³–10⁴ synapses. Proteomic studies of the synapse have revealed that the postsynaptic density is the most complex multiprotein structure yet identified, with ∼10³ different proteins. Such studies, however, use brain tissue with many different regions and therefore different cell types, and there is clear potential for heterogeneity of protein content at different synapses within and between brain regions. Although large-scale mRNA-based assays are in progress to map this sort of complexity at the cellular level, and indeed all brain-expressed genes, analysis of protein distribution (at synapses and other structures) is still in the very early stages. We review existing large-scale protein expression studies and the specific technical obstacles that need to be overcome before applying the scaling used in nucleic acid based approaches.     

Risperidone and falls in ambulatory nursing home residents with dementia and psychosis or agitation: secondary analysis of a double-blind, placebo-controlled trial.

OBJECTIVE: Authors evaluated the association between use/dosage of risperidone (RIS) and falls in a residential-care dementia population. METHODS: Authors performed secondary analysis of data from ambulatory patients in a randomized, double-blind, placebo-controlled, 12-week trial of three RIS dosages (0.5 mg/day, 1 mg/day, 2 mg/day). Outcomes included number of fallers, rate of falls, and time until the first fall after randomization. Additional analyses evaluated wandering as a potential moderating or mediating variable. RESULTS: The ambulatory sample included 537 subjects. Of those, 22.3% on placebo, 18.0% on RIS 0.5 mg/day, 12.7% on 1 mg/day, and 27.3% on 2 mg/day, respectively, fell during the trial. The difference between the RIS 1 mg/day group and placebo was significant, with a significantly lower hazard ratio in the RIS 1-mg/day group than placebo. Wandering was associated with an increased risk of falls. Among 205 patients with the highest levels of wandering at baseline, RIS 1 mg/day was associated with approximately a 70% reduction in risk for falls versus placebo condition. However, in those with the lowest levels of wandering at baseline, RIS 2 mg/day may have increased the risk of falls. CONCLUSIONS: Evaluating the benefits versus risks of risperidone in patients with dementia is complex and must consider multiple outcomes as a function of dose. At 1 mg/day, RIS was associated with decreased falls, especially in patients who exhibit wandering. However, at 2 mg/day, it may increase the risk of falls in ambulatory individuals with low levels of wandering.     

Structural white matter abnormalities in patients with idiopathic dystonia

We investigated whether structural white matter abnormalities, in the form of disruption of axonal coherence and integrity as measured with diffusion tensor imaging (DTI), constitute an underlying pathological mechanism of idiopathic dystonia (ID), independent of genotype status. We studied seven subjects with ID: all had cervical dystonia as their main symptom (one patient also had spasmodic dysphonia and two patients had concurrent generalized dystonia, both DYT1‐negative). We compared DTI MR images of patients with 10 controls, evaluating differences in mean diffusivity (MD) and fractional anisotropy (FA). ID was associated with increased FA values in the thalamus and adjacent white matter, and in the white matter underlying the middle frontal gyrus. ID was also associated with increase in MD in adjacent white matter to the pallidum and putamen bilaterally, left caudate, and in subcortical hemispheric regions, including the postcentral gyrus. Abnormal FA and MD in patients with ID indicate that abnormal axonal coherence and integrity contribute to the pathophysiology of dystonia. These findings suggest that ID is not only a functional disorder, but also associated with structural brain changes. Impaired connectivity and disrupted flow of information may contribute to the impairment of motor planning and regulation in dystonia. © 2006 Movement Disorder Society     

Effect of bite tray impression technique on relocation accuracy in frameless stereotactic radiotherapy.

A previously developed method for achieving patient relocation in fractionated stereotactic radiotherapy (attachment of an infrared fiducial system to a bite tray) relies on the integrity of a bite tray system that incorporates moulding to the patient's upper dentition. Reproducible and accurate patient positioning requires stability of the bite tray and mould during the full treatment process, both during the time the bite tray is inserted in the patient's mouth, and between separate bite tray insertions. The optimum construction method for a stable reproducible tray has not been sufficiently investigated. We undertook a study to identify factors which might influence the integrity of the hard palate bite tray system. Reprosil Fast Set Putty was used to construct 3 impression conditions; teeth only; teeth and alveolar sulcus; and teeth, alveolar sulcus, and the hard palate. Reproducibility was assessed by volunteers inserting the impressions multiple times and recording the locations of 8 standard reference points. Our results showed the optimal impression technique (i.e., the one that led to the smallest ranges in positional and rotational errors) was that which incorporated the teeth, alveolar sulcus, and hard palate.     

Use of the SADP for measurement of attitudes of Chinese dental students and dental surgery assistants toward disabled persons

The purpose of this study was to determine the attitudes of Chinese dental students and dental surgery assistants toward disabled persons using the Scale to Determine Attitudes Toward Disabled Persons, the SADP. A group of 99 Hong Kong University psychology students, 50 male and 49 female, was used as the control and to determine the internal consistency and reliability of the Chinese version of the scale. A group of 4th year (n = 25) and a group of 3rd year (n = 46) dental students and a group of in-house dental surgery assistants (n = 86) at the Prince Philip Dental Hospital, Hong Kong, were asked to complete a Chinese translation of the SADP. Results showed that there was no significant difference between attitude scores of 3rd and 4th year dental students (p = 0.06). There was a significant difference in attitude scores between dental students and the dental surgery assistants (p < O.OOl), with those of dental students being lower. In the control group, there was no significant difference between female control and dental surgery assistant scores (p = 0.289). There was a significant difference between dental students and male control scores (p < 10⁶). Not only did the dental students score lower than the dental surgery assistants, but they also scored significantly lower than a group of non-dental students of the same University.     

Children: Rights, education and equal opportunity

The point of departure in this paper is the concept of RIGHTS. Whereas most countries accept that children have rights as is evidenced in the UNO Declaration of Rights of the Child (1959), such rights are statements, not laws. Statements advocating benefits, care, love, education etc. are goals or beliefs. Few countries have legalised rights; consequently, children may be at risk. In countries where there is discrimination of some degree in respect of race, colour, sex, religion, national or social origin, financial standing in society, level of education and so on, the right to “rights” as stated in the UNO Declaration is further jeopardised. The implications for educational provision from early childhood and onwards in countries where “rights” are not entrenched in statutes or where child advocacy is not forceful enough for all people are examined in this paper. Consequently, the chances for equal opportunity in life are reduced in situations where the child did not receive the benefit of education. Such a child may not perish as he might as a result of being deprived of food, but “the deprivation and injustice, the degradation of an individual and the setting of his vital interests at naught would at least approach in gravity the act of allowing him to die for the want of food” (1981, Wringe). In this paper, the author argues for the Rights of the Child, particularly where discrimination and inequalities exist and where provision for early education has to contend with excessive population growth.     

The Results of Water Fluoridation in Ireland

The visit of Dr. Trendley Dean to Dublin in the mid-1950s helped accelerate the decision to introduce water fluoridation as a public health measure in the prevention of caries in the Republic of Ireland. A challenge to the constitutional validity of the Health (Fluoridation of Water Supplies) Act 1960 failed and in 1964 the water supplies of Dublin city were fluoridated. Over the next seven to eight years all the major urban communities in the Republic of Ireland were fluoridated. Currently, 67 percent of the 3.5 million people in the country reside in fluoridated communities. Studies conducted over the last 20 years show that residents of fluoridated communities have better dental health than those in nonfluoridated communities—the mean dmft is lower in children and the number of natural teeth present in adults is higher.