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1.
Occup Ther Health Care ; 37(3): 426-443, 2023.
Article in English | MEDLINE | ID: mdl-34971349

ABSTRACT

This pilot study was designed to investigate the effects of a holistic lighting intervention on the quality of life for individuals with low vision. Sixty participants (44 women; median age 69 years) with visual impairment received lighting interventions, including a home visit and consultation in a lighting lab. Assisted by low vision consultants, participants evaluated their performance using the Canadian Occupational Performance Measure (COPM) before and after the intervention. Improvements in visual functioning and quality of life were evaluated using the 39-item National Eye Institute Visual Function Questionnaire (NEI VFQ-39), the Groffman Visual Tracing Test, and the Farnsworth Dichotomous Test (D15). Following the lighting intervention, scores improved for all activities in the COPM (p < 0.01), for near activities and vision-specific role difficulties in the VFQ-39 (p < 0.05), and overall in the D15 test (p < 0.05). These results suggest the intervention provided an effective method for improving the participants' quality of life and performance.


Subject(s)
Occupational Therapy , Vision, Low , Humans , Female , Aged , Quality of Life , Lighting , Pilot Projects , Visual Acuity , Canada , Vision Disorders , Surveys and Questionnaires , Sickness Impact Profile
2.
Br J Pharmacol ; 167(1): 164-82, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22506660

ABSTRACT

BACKGROUND AND PURPOSE: Positive allosteric modulation of α4ß2 nicotinic acetylcholine (nACh) receptors could add a new dimension to the pharmacology and therapeutic approach to these receptors. The novel modulator NS9283 was therefore tested extensively. EXPERIMENTAL APPROACH: Effects of NS9283 were evaluated in vitro using fluorescence-based Ca(2+) imaging and electrophysiological voltage clamp experiments in Xenopus oocytes, mammalian cells and thalamocortical neurons. In vivo the compound was tested in models covering a range of cognitive domains in mice and rats. KEY RESULTS: NS9283 was shown to increase agonist-evoked response amplitude of (α4)(3) (ß2)(2) nACh receptors in electrophysiology paradigms. (α2)(3) (ß2)(2) , (α2)(3) (ß4)(2) and (α4)(3) (ß4)(2) were modulated to comparable extents, but no effects were detected at α3-containing or any 2α : 3ß stoichiometry nACh receptors. Native nACh receptors in thalamocortical neurons similarly displayed DHßE-sensitive currents that were receptive to modulation. NS9283 had favourable effects on sensory information processing, as shown by reversal of PCP-disrupted pre-pulse inhibition. NS9283 further improved performance in a rat model of episodic memory (social recognition), a rat model of sustained attention (five-choice serial reaction time task) and a rat model of reference memory (Morris water maze). Importantly, the effects in the Morris water maze could be fully reversed with mecamylamine, a blocker of nACh receptors. CONCLUSIONS AND IMPLICATIONS: These results provide compelling evidence that positive allosteric modulators acting at the (α4)(3) (ß2)(2) nACh receptors can augment activity across a broad range of cognitive domains, and that α4ß2 nACh receptor allosteric modulation therefore constitutes a promising therapeutic approach to symptomatic treatment of cognitive impairment.


Subject(s)
Nicotinic Agonists/pharmacology , Oxadiazoles/pharmacology , Protein Subunits/physiology , Pyridines/pharmacology , Receptors, Nicotinic/physiology , Allosteric Regulation/drug effects , Animals , Cell Line , Cell Line, Tumor , Cognition/drug effects , Female , HEK293 Cells , Humans , Male , Maze Learning/drug effects , Mice , Motor Activity/drug effects , Nicotine/pharmacology , Nicotinic Agonists/pharmacokinetics , Oocytes/drug effects , Oocytes/physiology , Oxadiazoles/pharmacokinetics , Pyridines/pharmacokinetics , Rats , Rats, Sprague-Dawley , Rats, Wistar , Recognition, Psychology/drug effects , Xenopus laevis
3.
Neuroscience ; 136(3): 715-28, 2005.
Article in English | MEDLINE | ID: mdl-16344146

ABSTRACT

In this study we explored whether a postnatal doubling of the total number of neurons occurs in the human Brodmann areas 44 and 45 (Broca's area). We describe the most recent error prediction formulae and their application for the modern stereological estimators for volume and number of neurons. We estimated the number of neurons in 3D optical disector probes systematically random sampled throughout the entire Brodmann areas (BA) 44 and 45 in developing and young adult cases. In the relatively small number of male and female cases studied no substantial postnatal increase in total number of neurons occurred in areas 44 and 45; the volume of these areas reached adult values around 7 years. In addition, we did find indications that a shift from a right-over-left to a left-over-right asymmetry may occur in the volume of BA 45 during postnatal development. No major asymmetry in total number of neurons in BA 44 and 45 was detected.


Subject(s)
Frontal Lobe/cytology , Neurons/physiology , Stereotaxic Techniques , Adult , Age Factors , Cell Count/methods , Child , Female , Frontal Lobe/growth & development , Functional Laterality , Humans , Infant , Infant, Newborn , Male , Postmortem Changes , Sex Factors
4.
Eur Respir J ; 10(2): 404-8, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9042640

ABSTRACT

In many but not all cases, malignant mesothelioma is associated with an elevated content of hyaluronan in pleural fluid. The hyaluronan-producing mesothelioma has not yet been immunohistochemically characterized; therefore, the purpose of this study was to compare the immunohistochemical reactivity patterns in relation to the ability of this tumour to produce hyaluronan. Pleural fluid samples from 33 patients with malignant mesothelioma were analysed for content hyaluronan using a quantitative high performance liquid chromatographic method. Biopsy specimens from the patients were studied immunohistochemically, using monoclonal antibodies against carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), a low molecular weight cytokeratin antigen (CAM 5.2) and vimentin. An elevated hyaluronan content, i.e. > 100 mg.L-1, was noted in 23 patients (70%). There was no reactivity to the monoclonal antibody raised against CEA in any case. There was a significantly higher reactivity to EMA (p = 0.026), a higher reactivity to CAM 5.2 (p = 0.053) and a lower reactivity to vimentin (p = 0.057) in the hyaluronan-producing mesotheliomas as compared to those with normal levels of hyaluronan. Mesotheliomas that produced hyaluronan differed immunohistochemically from those that did not. The connection between the ability to produce different antigens and hyaluronan may relate to the degree of differentiation of the tumour. Both of these characteristics (immunophenotype and ability to produce hyaluronan) may, therefore, be of importance in studies concerning the prognosis and treatment of the malignant mesothelioma.


Subject(s)
Hyaluronic Acid/biosynthesis , Mesothelioma/metabolism , Pleural Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Carcinoembryonic Antigen/analysis , Chromatography, High Pressure Liquid , Humans , Immunohistochemistry , Keratins/analysis , Male , Middle Aged , Mucin-1/analysis , Pleural Effusion, Malignant/metabolism , Vimentin/analysis
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