Orienting asymmetries and lateralized processing of sounds in humans

<p>Abstract</p> <p>Background</p> <p>Lateralized processing of speech is a well studied phenomenon in humans. Both anatomical and neurophysiological studies support the view that nonhuman primates and other animal species also reveal hemispheric differences in areas involved in sound processing. In recent years, an increasing number of studies on a range of taxa have employed an orienting paradigm to investigate lateralized acoustic processing. In this paradigm, sounds are played directly from behind and the direction of turn is recorded. This assay rests on the assumption that a hemispheric asymmetry in processing is coupled to an orienting bias towards the contralateral side. To examine this largely untested assumption, speech stimuli as well as artificial sounds were presented to 224 right-handed human subjects shopping in supermarkets in Germany and in the UK. To verify the lateralized processing of the speech stimuli, we additionally assessed the brain activation in response to presentation of the different stimuli using functional magnetic resonance imaging (fMRI).</p> <p>Results</p> <p>In the naturalistic behavioural experiments, there was no difference in orienting behaviour in relation to the stimulus material (speech, artificial sounds). Contrary to our predictions, subjects revealed a significant left bias, irrespective of the sound category. This left bias was slightly but not significantly stronger in German subjects. The fMRI experiments confirmed that the speech stimuli evoked a significant left lateralized activation in BA44 compared to the artificial sounds.</p> <p>Conclusion</p> <p>These findings suggest that in adult humans, orienting biases are not necessarily coupled with lateralized processing of acoustic stimuli. Our results – as well as the inconsistent orienting biases found in different animal species – suggest that the orienting assay should be used with caution. Apparently, attention biases, experience, and experimental conditions may all affect head turning responses. Because of the complexity of the interaction of factors, the use of the orienting assay to determine lateralized processing of sound stimuli is discouraged.</p

What are the beliefs, attitudes and practices of front-line staff in long-term care (LTC) facilities related to osteoporosis awareness, management and fracture prevention?

<p>Abstract</p> <p>Background</p> <p>Compared to the general elderly population, those institutionalized in LTC facilities have the highest prevalence of osteoporosis and subsequently have higher incidences of vertebral and hip fractures. The goal of this study is to determine how well nurses at LTC facilities are educated to properly administer bisphosphonates. A secondary question assessed was the nurse's and PSW's attitudes and beliefs regarding the role and benefits of vitamin D for LTC patients.</p> <p>Methods</p> <p>Eight LTC facilities in Hamilton were surveyed, and all nurses were offered a survey. A total 57 registered nurses were surveyed. A 21 item questionnaire was developed to assess existing management practices and specific osteoporosis knowledge areas.</p> <p>Results</p> <p>The questionnaire assessed the nurse's and personal support worker's (PSWs) education on how to properly administer bisphosphonates by having them select all applicable responses from a list of options. These options included administering the drug before, after or with meals, given with or separate from other medications, given with juice, given with or without water, given with the patient sitting up, or finally given with the patient supine. Only 52% of the nurses and 8.7% of PSWs administered the drug properly, where they selected the options: (given before meals, given with water, given separate from all other medications, and given in a sitting up position). If at least one incorrect option was selected, then it was scored as an inappropriate administration. Bisphosphonates were given before meals by 85% of nurses, given with water by 90%, given separately from other medication by 71%, and was administered in an upright position by 79%. Only 52% of the nurses and 8.7% of PSWs surveyed were administering the drug properly. Regarding the secondary question, of the 57 nurses surveyed, 68% strongly felt their patients should be prescribed vitamin D supplements. Of the 124 PSWs who completed the survey, 44.4% strongly felt their patients should be prescribed vitamin D supplementation.</p> <p>Conclusion</p> <p>Bisphosphonates are quite effective in increasing the bone mineral density of LTC patients, and may reduce fracture rates, but it is only effective if properly administered. In our study, proper administration of bisphosphonate therapy was less than optimal. In summary, although the education of health providers has improved since the mid-1990's, this area still requires further attention and the subject of future quality assurance research.</p

The prognosis for pain, disability, activities of daily living and quality of life after an acute osteoporotic vertebral body fracture: its relation to fracture level, type of fracture and grade of fracture deformation

The level of the acute osteoporotic vertebral fracture, fracture type and grade of fracture deformation were determined in 107 consecutive patients and related to pain, disability, activities of daily living (ADL) and quality of life (QoL) after 3 weeks, 3, 6 and 12 months. Two-thirds of the fractured patients were women and with a similar average age, around 75 years, as the men. Fifty-eight of the acute fractures were located in the thoracic spine and 49 in the lumbar spine and predominantly at the Th12 and L1 levels. Sixty-nine percent of the fractures were wedge, 19% concave and 12% crush fractures. There were 22 mildly, 50 moderately and 35 severely deformed vertebrae. The grade of fracture deformation was not related to gender, age or fracture location. Severely deformed vertebrae predominantly (92%) occurred among the crush fracture type. One year after the fracture, irrespective of fracture level, fracture type or grade of fracture deformation, 4/5 still had pronounced pain and deteriorated QoL. Initial severe fracture deformation by far was the worst prognostic factor for severe lasting pain and disability, and deterioration of ADL and QoL. Factors like fracture level, lumbar fractures tended to improve steadily while thoracic deteriorated, type of fracture, the wedge and concave resulting in less pain and better QoL than the crush fracture type and gender influenced to a lesser extent the outcomes during the year after the acute fracture

Structural Insights into the Inhibition of Cytosolic 5′-Nucleotidase II (cN-II) by Ribonucleoside 5′-Monophosphate Analogues

Cytosolic 5′-nucleotidase II (cN-II) regulates the intracellular nucleotide pools within the cell by catalyzing the dephosphorylation of 6-hydroxypurine nucleoside 5′-monophosphates. Beside this physiological function, high level of cN-II expression is correlated with abnormal patient outcome when treated with cytotoxic nucleoside analogues. To identify its specific role in the resistance phenomenon observed during cancer therapy, we screened a particular class of chemical compounds, namely ribonucleoside phosphonates to predict them as potential cN-II inhibitors. These compounds incorporate a chemically and enzymatically stable phosphorus-carbon linkage instead of a regular phosphoester bond. Amongst them, six compounds were predicted as better ligands than the natural substrate of cN-II, inosine 5′-monophosphate (IMP). The study of purine and pyrimidine containing analogues and the introduction of chemical modifications within the phosphonate chain has allowed us to define general rules governing the theoretical affinity of such ligands. The binding strength of these compounds was scrutinized in silico and explained by an impressive number of van der Waals contacts, highlighting the decisive role of three cN-II residues that are Phe 157, His 209 and Tyr 210. Docking predictions were confirmed by experimental measurements of the nucleotidase activity in the presence of the three best available phosphonate analogues. These compounds were shown to induce a total inhibition of the cN-II activity at 2 mM. Altogether, this study emphasizes the importance of the non-hydrolysable phosphonate bond in the design of new competitive cN-II inhibitors and the crucial hydrophobic stacking promoted by three protein residues

A stable pattern of EEG spectral coherence distinguishes children with autism from neuro-typical controls - a large case control study

<p>Abstract</p> <p>Background</p> <p>The autism rate has recently increased to 1 in 100 children. Genetic studies demonstrate poorly understood complexity. Environmental factors apparently also play a role. Magnetic resonance imaging (MRI) studies demonstrate increased brain sizes and altered connectivity. Electroencephalogram (EEG) coherence studies confirm connectivity changes. However, genetic-, MRI- and/or EEG-based diagnostic tests are not yet available. The varied study results likely reflect methodological and population differences, small samples and, for EEG, lack of attention to group-specific artifact.</p> <p>Methods</p> <p>Of the 1,304 subjects who participated in this study, with ages ranging from 1 to 18 years old and assessed with comparable EEG studies, 463 children were diagnosed with autism spectrum disorder (ASD); 571 children were neuro-typical controls (C). After artifact management, principal components analysis (PCA) identified EEG spectral coherence factors with corresponding loading patterns. The 2- to 12-year-old subsample consisted of 430 ASD- and 554 C-group subjects (n = 984). Discriminant function analysis (DFA) determined the spectral coherence factors' discrimination success for the two groups. Loading patterns on the DFA-selected coherence factors described ASD-specific coherence differences when compared to controls.</p> <p>Results</p> <p>Total sample PCA of coherence data identified 40 factors which explained 50.8% of the total population variance. For the 2- to 12-year-olds, the 40 factors showed highly significant group differences (<it>P </it>< 0.0001). Ten randomly generated split half replications demonstrated high-average classification success (C, 88.5%; ASD, 86.0%). Still higher success was obtained in the more restricted age sub-samples using the jackknifing technique: 2- to 4-year-olds (C, 90.6%; ASD, 98.1%); 4- to 6-year-olds (C, 90.9%; ASD 99.1%); and 6- to 12-year-olds (C, 98.7%; ASD, 93.9%). Coherence loadings demonstrated reduced short-distance and reduced, as well as increased, long-distance coherences for the ASD-groups, when compared to the controls. Average spectral loading per factor was wide (10.1 Hz).</p> <p>Conclusions</p> <p>Classification success suggests a stable coherence loading pattern that differentiates ASD- from C-group subjects. This might constitute an EEG coherence-based phenotype of childhood autism. The predominantly reduced short-distance coherences may indicate poor local network function. The increased long-distance coherences may represent compensatory processes or reduced neural pruning. The wide average spectral range of factor loadings may suggest over-damped neural networks.</p