Adaptation changes in dynamic postural control and contingent negative variation during backward disturbance by transient floor translation in the elderly

ABSTRACT: BACKGROUND: We investigated adaptation changes in dynamic postural control and contingent negative variation (CNV) in 13 young and 12 elderly adults. Subjects repeatedly underwent backward postural disturbance by a forward floor translation (S2) 2 s after an auditory warning signal (S1). Initial and second sets were conducted, each set with 20 trials. Posterior peak position of the center of pressure in the anteroposterior direction (CoPy) after S2 was identified. Electroencephalograms from Cz were averaged for each set, and the CNV negative peak was identified. RESULTS: Compared with the first trial, the posterior peak position of CoPy changed significantly forward from the 12th trial in the young and from the 19th trial in the elderly during the initial set. The mean of the posterior peak position was more forward in second set than in the initial set for both groups and was significantly backward in the elderly compared to the young for both sets. These findings indicate that subjects in both groups adapted better to the postural disturbance in the second set than in the initial set, and the adaptation was later in the elderly. Late CNV in the young started to increase negatively from the middle of the S1-S2 period and peaked just before S2. Peak CNV amplitude was larger in the second set than in the initial set. In contrast, late CNV in the elderly exhibited no negative increase as in the young and peaked in the middle of the S1-S2 period, which was followed by gradual decreasing toward S2. No adaptive changes were found in late CNV for the elderly. CONCLUSIONS: It is conceivable that reduced activation of the frontal lobe may be one of the factors contributing to the decrease in postural adaptability in the elderly. The elderly may use various brain regions for the adaptation of dynamic postural control compared with the young.     

Prolonged occupational activity and 6-year changes in postural sway in elderly women

Objectives:

Prolonged occupational work such as farm work has been reported to adversely affect mobility in elderly women. The purpose of this study was to investigate possible relationships between prolonged occupational work and 6-year changes in postural sway in elderly women.

Methods:

Subjects were 392 women aged ≥69 years who participated in a 6-year follow-up examination of the Muramatsu Cohort Study. Handgrip strength and postural sway, measured as gravity-center velocity (cm/s), were evaluated at baseline and 6-year follow-up. Interviews were conducted to determine the time spent on moderate occupational activity (3-5 metabolic equivalents) such as farm work. Activity levels were defined as: 1, no-activity; 2, “short” (>0, ≤17.75 h/wk); and 3, “long” (≥17.75 h/wk).

Results:

At baseline, mean values for age, handgrip strength, and postural sway were 73.3 years (SD 3.7), 20.3 kg (SD 4.1), and 2.0 cm/s (SD 0.8), respectively, and 32.5% of participants engaged in occupational activity. The change in postural sway was significantly greater in the long-activity group (median, 35.0 h/wk) than the no-activity group (0.56 vs. 0.27 cm/s, P=0.021).

Conclusions:

Prolonged occupational work may be detrimental to the control of body balance. Accordingly, elderly individuals are not recommended to engage in prolonged occupational activity.     

Effect of time pressure on attentional shift and anticipatory postural control during unilateral shoulder abduction reactions in an oddball-like paradigm

Background

The effect of time pressure on attentional shift and anticipatory postural control was investigated during unilateral shoulder abduction reactions in an oddball-like paradigm.

Methods

A cue signal (S1) - imperative signal (S2) sequence was repeated with various S2-S1 intervals (1.0, 1.5, and 2.0 s). S2 comprised target and non-target stimuli presented at the position (9° to the left or the right) indicated by S1. Right shoulder abduction was performed only in response to target stimuli, which were presented with a 30% probability. The P1, N1, N2, and P3 components of event-related potentials were analyzed, and onset times of postural muscles (electromyographic activity of erector spinae and gluteus medius) were quantified with respect to middle deltoid activation.

Results

There was no significant effect of S2-S1 interval on the latency or amplitude of P1, N1, or N2. The percentage of subjects with bimodal P3 peaks was significantly smaller and the slope of the P3 waveform in the 100 ms after the first peak was significantly steeper with a 1.0-s S2-S1 interval than with a 1.5- or 2.0-s S2-S1 interval. The onset of postural muscle activity was significantly later in the shorter interval conditions.

Conclusions

These results suggest that with a shorter S2-S1 interval, that is, higher time pressure, attention was allocated to hasten the latter part of cognitive processing that may relate to attentional shift from S2 to next S1, which led to insufficient postural preparation associated with arm movement and anticipatory attention directed to S2.     

Gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo

Purpose

Age-related macular degeneration caused by choroidal neovascularization (CNV) remains difficult to be treated despite the recent advent of several treatment options. In this study, we investigated the in vivo angiogenic control by intravenous injection of polyion complex (PIC) micelle encapsulating plasmid DNA (pDNA) using a mice CNV model.

Methods

The transfection efficiency of the PIC micelle was investigated using the laser-induced CNV in eight-week-old male C57 BJ/6 mice. Firstly, each mouse received intravenous injection of micelle encapsulating pDNA of Yellow Fluorescent Protein (pYFP) on days 1,3 and 5. The expression of YFP was analyzed using fluorescein microscopy and western blotting analysis. In the next experiments, each mouse received intravenous injection of micelle encapsulating pDNA of soluble Fms-like tyrosine kinase-1 (psFlt-1) 1,3 and 5 days after the induction of CNV and the CNV lesion was analyzed by choroidal flatmounts on day 7.

Results

Fluorescein microscopy and western blotting analysis revealed that the expression of YFP was confirmed in the CNV area after injection of the PIC micelle, but the expression was not detected neither in mice that received naked pDNA nor those without CNV. Furthermore, the CNV area in the mice that received intravenous injection of the psFlt-1-encapsulated PIC micelle was significantly reduced by 65% compared to that in control mice (p<0.01).

Conclusions

Transfection of sFlt-1 with the PIC micelle by intravenous injection to mice CNV models showed significant inhibition of CNV. The current results revealed the significant potential of nonviral gene therapy for regulation of CNV using the PIC micelle encapsulating pDNA.     

Utilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization

Purpose

The integrin αvβ3 is differentially expressed on neovascular endothelial cells. We investigated whether a novel intravenously injectable αvβ3 integrin-ligand coupled nanoparticle (NP) can target choroidal neovascular membranes (CNV) for imaging and targeted gene therapy.

Methods

CNV lesions were induced in rats using laser photocoagulation. The utility of NP for in vivo imaging and gene delivery was evaluated by coupling the NP with a green fluorescing protein plasmid (NP-GFPg). Rhodamine labeling (Rd-NP) was used to localize NP in choroidal flatmounts. Rd-NP-GFPg particles were injected intravenously on weeks 1, 2, or 3. In the treatment arm, rats received NP containing a dominant negative Raf mutant gene (NP-ATPμ-Raf) on days 1, 3, and 5. The change in CNV size and leakage, and TUNEL positive cells were quantified.

Results

GFP plasmid expression was seen in vivo up to 3 days after injection of Rd-NP-GFPg. Choroidal flatmounts confirmed the localization of the NP and the expression of GFP plasmid in the CNV. Treating the CNV with NP-ATPμ-Raf decreased the CNV size by 42% (P<0.001). OCT analysis revealed that the reduction of CNV size started on day 5 and reached statistical significance by day 7. Fluorescein angiography grading showed significantly less leakage in the treated CNV (P<0.001). There were significantly more apoptotic (TUNEL-positive) nuclei in the treated CNV.

Conclusion

Systemic administration of αvβ3 targeted NP can be used to label the abnormal blood vessels of CNV for imaging. Targeted gene delivery with NP-ATPμ-Raf leads to a reduction in size and leakage of the CNV by induction of apoptosis in the CNV.     

Effect of empathy trait on attention to various facial expressions: evidence from N170 and late positive potential (LPP)

Background

The present study sought to clarify the relationship between empathy trait and attention responses to happy, angry, surprised, afraid, and sad facial expressions. As indices of attention, we recorded event-related potentials (ERP) and focused on N170 and late positive potential (LPP) components.

Methods

Twenty-two participants (12 males, 10 females) discriminated facial expressions (happy, angry, surprised, afraid, and sad) from emotionally neutral faces under an oddball paradigm. The empathy trait of participants was measured using the Interpersonal Reactivity Index (IRI, J Pers Soc Psychol 44:113–126, 1983).

Results

Participants with higher IRI scores showed: 1) more negative amplitude of N170 (140 to 200 ms) in the right posterior temporal area elicited by happy, angry, surprised, and afraid faces; 2) more positive amplitude of early LPP (300 to 600 ms) in the parietal area elicited in response to angry and afraid faces; and 3) more positive amplitude of late LPP (600 to 800 ms) in the frontal area elicited in response to happy, angry, surprised, afraid, and sad faces, compared to participants with lower IRI scores.

Conclusions

These results suggest that individuals with high empathy pay attention to various facial expressions more than those with low empathy, from very-early stage (reflected in N170) to late-stage (reflected in LPP) processing of faces.     

Blood Pressure Associates with Standing Balance in Elderly Outpatients

Objectives

Assessment of the association of blood pressure measurements in supine and standing position after a postural change, as a proxy for blood pressure regulation, with standing balance in a clinically relevant cohort of elderly, is of special interest as blood pressure may be important to identify patients at risk of having impaired standing balance in routine geriatric assessment.

Materials and Methods

In a cross-sectional cohort study, 197 community-dwelling elderly referred to a geriatric outpatient clinic of a middle-sized teaching hospital were included. Blood pressure was measured intermittently (n = 197) and continuously (subsample, n = 58) before and after a controlled postural change from supine to standing position. The ability to maintain standing balance was assessed during ten seconds of side-by-side, semi-tandem and tandem stance, with both eyes open and eyes closed. Self-reported impaired standing balance and history of falls were recorded by questionnaires. Logistic regression analyses were used to examine the association between blood pressure and 1) the ability to maintain standing balance; 2) self-reported impaired standing balance; and 3) history of falls, adjusted for age and sex.

Results

Blood pressure decrease after postural change, measured continuously, was associated with reduced ability to maintain standing balance in semi-tandem stance with eyes closed and with increased self-reported impaired standing balance and falls. Presence of orthostatic hypotension was associated with reduced ability to maintain standing balance in semi-tandem stance with eyes closed for both intermittent and continuous measurements and with increased self-reported impaired standing balance for continuous measurements.

Conclusion

Continuous blood pressure measurements are of additional value to identify patients at risk of having impaired standing balance and may therefore be useful in routine geriatric care.     

Harmonization Process and Reliability Assessment of Anthropometric Measurements in the Elderly EXERNET Multi-Centre Study

Background

The elderly EXERNET multi-centre study aims to collect normative anthropometric data for old functionally independent adults living in Spain.

Purpose

To describe the standardization process and reliability of the anthropometric measurements carried out in the pilot study and during the final workshop, examining both intra- and inter-rater errors for measurements.

Materials and Methods

A total of 98 elderly from five different regions participated in the intra-rater error assessment, and 10 different seniors living in the city of Toledo (Spain) participated in the inter-rater assessment. We examined both intra- and inter-rater errors for heights and circumferences.

Results

For height, intra-rater technical errors of measurement (TEMs) were smaller than 0.25 cm. For circumferences and knee height, TEMs were smaller than 1 cm, except for waist circumference in the city of Cáceres. Reliability for heights and circumferences was greater than 98% in all cases. Inter-rater TEMs were 0.61 cm for height, 0.75 cm for knee-height and ranged between 2.70 and 3.09 cm for the circumferences measured. Inter-rater reliabilities for anthropometric measurements were always higher than 90%.

Conclusion

The harmonization process, including the workshop and pilot study, guarantee the quality of the anthropometric measurements in the elderly EXERNET multi-centre study. High reliability and low TEM may be expected when assessing anthropometry in elderly population.     

Evaluation of the London Measure of Unplanned Pregnancy in a United States population of women

Objective

To evaluate the reliability and validity of the London Measure of Unplanned Pregnancy (a U.K.-developed measure of pregnancy intention), in English and Spanish translation, in a U.S. population of women.

Methods

A psychometric evaluation study of the London Measure of Unplanned Pregnancy (LMUP), a six-item, self-completion paper measure was conducted with 346 women aged 15–45 who presented to San Francisco General Hospital for termination of pregnancy or antenatal care. Analyses of the two language versions were carried out separately. Reliability (internal consistency) was assessed using Cronbach''s alpha and item-total correlations. Test-retest reliability (stability) was assessed using weighted Kappa. Construct validity was assessed using principal components analysis and hypothesis testing.

Results

Psychometric testing demonstrated that the LMUP was reliable and valid in both U.S. English (alpha = 0.78, all item-total correlations >0.20, weighted Kappa = 0.72, unidimensionality confirmed, hypotheses met) and Spanish translation (alpha = 0.84, all item-total correlations >0.20, weighted Kappa = 0.77, unidimensionality confirmed, hypotheses met).

Conclusion

The LMUP was reliable and valid in U.S. English and Spanish translation and therefore may now be used with U.S. women.     

Obesity impact on the attentional cost for controlling posture

Background

This study investigated the effects of obesity on attentional resources allocated to postural control in seating and unipedal standing.

Methods

Ten non obese adults (BMI = 22.4±1.3, age = 42.4±15.1) and 10 obese adult patients (BMI = 35.2±2.8, age = 46.2±19.6) maintained postural stability on a force platform in two postural tasks (seated and unipedal). The two postural tasks were performed (1) alone and (2) in a dual-task paradigm in combination with an auditory reaction time task (RT). Performing the RT task together with the postural one was supposed to require some attentional resources that allowed estimating the attentional cost of postural control. 4 trials were performed in each condition for a total of 16 trials.

Findings

(1) Whereas seated non obese and obese patients exhibited similar centre of foot pressure oscillations (CoP), in the unipedal stance only obese patients strongly increased their CoP sway in comparison to controls. (2) Whatever the postural task, the additional RT task did not affect postural stability. (3) Seated, RT did not differ between the two groups. (4) RT strongly increased between the two postural conditions in the obese patients only, suggesting that body schema and the use of internal models was altered with obesity.

Interpretation

Obese patients needed more attentional resources to control postural stability during unipedal stance than non obese participants. This was not the case in a more simple posture such as seating. To reduce the risk of fall as indicated by the critical values of CoP displacement, obese patients must dedicate a strong large part of their attentional resources to postural control, to the detriment of non-postural events. Obese patients were not able to easily perform multitasking as healthy adults do, reflecting weakened psycho-motor abilities.     

Proprioceptive Changes Impair Balance Control in Individuals with Chronic Obstructive Pulmonary Disease

Introduction

Balance deficits are identified as important risk factors for falling in individuals with chronic obstructive pulmonary disease (COPD). However, the specific use of proprioception, which is of primary importance during balance control, has not been studied in individuals with COPD. The objective was to determine the specific proprioceptive control strategy during postural balance in individuals with COPD and healthy controls, and to assess whether this was related to inspiratory muscle weakness.

Methods

Center of pressure displacement was determined in 20 individuals with COPD and 20 age/gender-matched controls during upright stance on an unstable support surface without vision. Ankle and back muscle vibration were applied to evaluate the relative contribution of different proprioceptive signals used in postural control.

Results

Individuals with COPD showed an increased anterior-posterior body sway during upright stance (p = 0.037). Compared to controls, individuals with COPD showed an increased posterior body sway during ankle muscle vibration (p = 0.047), decreased anterior body sway during back muscle vibration (p = 0.025), and increased posterior body sway during simultaneous ankle-muscle vibration (p = 0.002). Individuals with COPD with the weakest inspiratory muscles showed the greatest reliance on ankle muscle input when compared to the stronger individuals with COPD (p = 0.037).

Conclusions

Individuals with COPD, especially those with inspiratory muscle weakness, increased their reliance on ankle muscle proprioceptive signals and decreased their reliance on back muscle proprioceptive signals during balance control, resulting in a decreased postural stability compared to healthy controls. These proprioceptive changes may be due to an impaired postural contribution of the inspiratory muscles to trunk stability. Further research is required to determine whether interventions such as proprioceptive training and inspiratory muscle training improve postural balance and reduce the fall risk in individuals with COPD.     

Global copy number analyses by next generation sequencing provide insight into pig genome variation

Background

Copy number variations (CNVs) confer significant effects on genetic innovation and phenotypic variation. Previous CNV studies in swine seldom focused on in-depth characterization of global CNVs.

Results

Using whole-genome assembly comparison (WGAC) and whole-genome shotgun sequence detection (WSSD) approaches by next generation sequencing (NGS), we probed formation signatures of both segmental duplications (SDs) and individualized CNVs in an integrated fashion, building the finest resolution CNV and SD maps of pigs so far. We obtained copy number estimates of all protein-coding genes with copy number variation carried by individuals, and further confirmed two genes with high copy numbers in Meishan pigs through an enlarged population. We determined genome-wide CNV hotspots, which were significantly enriched in SD regions, suggesting evolution of CNV hotspots may be affected by ancestral SDs. Through systematically enrichment analyses based on simulations and bioinformatics analyses, we revealed CNV-related genes undergo a different selective constraint from those CNV-unrelated regions, and CNVs may be associated with or affect pig health and production performance under recent selection.

Conclusions

Our studies lay out one way for characterization of CNVs in the pig genome, provide insight into the pig genome variation and prompt CNV mechanisms studies when using pigs as biomedical models for human diseases.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-593) contains supplementary material, which is available to authorized users.     

The Role of Copy Number Variation in Susceptibility to Amyotrophic Lateral Sclerosis: Genome-Wide Association Study and Comparison with Published Loci

Background

The genetic contribution to sporadic amyotrophic lateral sclerosis (ALS) has not been fully elucidated. There are increasing efforts to characterise the role of copy number variants (CNVs) in human diseases; two previous studies concluded that CNVs may influence risk of sporadic ALS, with multiple rare CNVs more important than common CNVs. A little-explored issue surrounding genome-wide CNV association studies is that of post-calling filtering and merging of raw CNV calls. We undertook simulations to define filter thresholds and considered optimal ways of merging overlapping CNV calls for association testing, taking into consideration possibly overlapping or nested, but distinct, CNVs and boundary estimation uncertainty.

Methodology and Principal Findings

In this study we screened Illumina 300K SNP genotyping data from 730 ALS cases and 789 controls for copy number variation. Following quality control filters using thresholds defined by simulation, a total of 11321 CNV calls were made across 575 cases and 621 controls. Using region-based and gene-based association analyses, we identified several loci showing nominally significant association. However, the choice of criteria for combining calls for association testing has an impact on the ranking of the results by their significance. Several loci which were previously reported as being associated with ALS were identified here. However, of another 15 genes previously reported as exhibiting ALS-specific copy number variation, only four exhibited copy number variation in this study. Potentially interesting novel loci, including EEF1D, a translation elongation factor involved in the delivery of aminoacyl tRNAs to the ribosome (a process which has previously been implicated in genetic studies of spinal muscular atrophy) were identified but must be treated with caution due to concerns surrounding genomic location and platform suitability.

Conclusions and Significance

Interpretation of CNV association findings must take into account the effects of filtering and combining CNV calls when based on early genome-wide genotyping platforms and modest study sizes.     

Saccades Improve Postural Control: A Developmental Study in Normal Children

Introduction

Dual-task performance is known to affect postural stability in children. This study focused on the effect of oculomotor tasks like saccadic eye movements on postural stability, studied in a large population of children by recording simultaneously their eye movements and posture.

Materials and Methods

Ninety-five healthy children from 5.8 to 17.6 years old were examined. All children were free of any vestibular, neurological, ophtalmologic and orthoptic abnormalities. Postural control was measured with a force platform TechnoConcept®, and eye movements with video oculography (MobilEBT®). Children performed two oculomotor tasks: fixation of a stable central target and horizontal saccades. We measured the saccade latency and the number of saccades during fixation as well as the surface, length and mean velocity of the center of pressure.

Results

During postural measurement, we observed a correlation between the age on the one hand and a decrease in saccade latency as well as an improvement in the quality of fixation on the other. Postural sway decreases with age and is reduced in the dual task (saccades) in comparison with a simple task of fixation.

Discussion - Conclusion

These results suggest a maturation of neural circuits controlling posture and eye movements during childhood. This study also shows the presence of an interaction between the oculomotor system and the postural system. Engaging in oculomotor tasks results in a reduction of postural sway.     

Electrical activation in the coronary sinus branches as a guide to cardiac resynchronisation therapy: rationale for a coordinate system

Background

For successful cardiac resynchronisation therapy (CRT) a spatial and electrical separation of right and left ventricular electrodes is essential. The spatial distribution of electrical delays within the coronary sinus (CS) tributaries has not yet been identified.

Objective

Electrical delays within the CS are described during sinus rhythm (SR) and right ventricular pacing (RVP). A coordinate system grading the mitral ring from 0° to 360° and three vertical segments is proposed to define the lead positions irrespective of individual CS branch orientation.

Methods

In 13 patients undergoing implantation of a CRT device 6±2.5, (median 5) lead positions within the CS were mapped during SR and RVP. The delay to the onset and the peak of the local signal was measured from the earliest QRS activation or the pacing spike. Fluoroscopic positions were compared to localizations on a nonfluoroscopic electrode imaging system.

Results

During SR, electrical delays in the CS were inhomogenous in patients with or without left bundle branch block (LBBB). During RVP, the delays increased by 44±32 ms (signal onset from 36±33 ms to 95±30 ms; p<0.001, signal peak from 105±44 ms to 156±30 ms; p<0.001). The activation pattern during RVP was homogeneous and predictable by taking the grading on the CS ring into account: (% QRS) = 78−0.002 (grade−162)², p<0.0001. This indicates that 78% of the QRS duration can be expected as a maximum peak delay at 162° on the CS ring.

Conclusion

Electrical delays within the CS vary during SR, but prolong and become predictable during RVP. A coordinate system helps predicting the local delays and facilitates interindividual comparison of lead positions irrespective of CS branch anatomy.     

Suppression and regression of choroidal neovascularization in mice by a novel CCR2 antagonist, INCB3344

Purpose

To investigate the effect of an intravitreally administered CCR2 antagonist, INCB3344, on a mouse model of choroidal neovascularization (CNV).

Methods

CNV was induced by laser photocoagulation on Day 0 in wild type mice. INCB3344 or vehicle was administered intravitreally immediately after laser application. On Day 14, CNV areas were measured on retinal pigment epithelium (RPE)-choroid flat mounts and histopathologic examination was performed on 7 µm-thick sections. Macrophage infiltration was evaluated by immunohistochemistry on RPE-choroid flat mounts and quantified by flow cytometry on Day 3. Expression of vascular endothelial growth factor (VEGF) protein in RPE-choroid tissue was examined by immunohistochemistry and ELISA, VEGF mRNA in sorted macrophages in RPE-choroid tissue was examine by real-time PCR and expression of phosphorylated extracellular signal-regulated kinase (p-ERK 1/2) in RPE-choroid tissue was measured by Western blot analysis on Day 3. We also evaluated the efficacy of intravitreal INCB3344 to spontaneous CNV detected in Cu, Zn-superoxide dismutase (SOD1) deficient mice. Changes in CNV size were assessed between pre- and 1week post-INCB3344 or vehicle administration in fundus photography and fluorescence angiography (FA).

Results

The mean CNV area in INCB3344-treated mice decreased by 42.4% compared with the vehicle-treated control mice (p<0.001). INCB3344 treatment significantly inhibited macrophage infiltration into the laser-irradiated area (p<0.001), and suppressed the expression of VEGF protein (p = 0.012), VEGF mRNA in infiltrating macrophages (p<0.001) and the phosphorylation of ERK1/2 (p<0.001). The area of spontaneous CNV in Sod1 ^−/− mice regressed by 70.35% in INCB3344-treated animals while no change was detected in vehicle-treated control mice (p<0.001).

Conclusions

INCB3344 both inhibits newly forming CNV and regresses established CNV. Controlling inflammation by suppressing macrophage infiltration and angiogenic ability via the CCR-2/MCP-1 signal may be a useful therapeutic strategy for treating CNV associated with age-related macular degeneration.     

The characterisation of three types of genes that overlie copy number variable regions

Background

Due to the increased accuracy of Copy Number Variable region (CNV) break point mapping, it is now possible to say with a reasonable degree of confidence whether a gene (i) falls entirely within a CNV; (ii) overlaps the CNV or (iii) actually contains the CNV. We classify these as type I, II and III CNV genes respectively.

Principal Findings

Here we show that although type I genes vary in copy number along with the CNV, most of these type I genes have the same expression levels as wild type copy numbers of the gene. These genes must, therefore, be under homeostatic dosage compensation control. Looking into possible mechanisms for the regulation of gene expression we found that type I genes have a significant paucity of genes regulated by miRNAs and are not significantly enriched for monoallelically expressed genes. Type III genes, on the other hand, have a significant excess of genes regulated by miRNAs and are enriched for genes that are monoallelically expressed.

Significance

Many diseases and genomic disorders are associated with CNVs so a better understanding of the different ways genes are associated with normal CNVs will help focus on candidate genes in genome wide association studies.     

Differential changes in QTc duration during in-hospital haloperidol use

Aims

To evaluate changes in QT duration during low-dose haloperidol use, and determine associations between clinical variables and potentially dangerous QT prolongation.

Methods

In a retrospective cohort study in a tertiary university teaching hospital in The Netherlands, all 1788 patients receiving haloperidol between 2005 and 2007 were studied; ninety-seven were suitable for final analysis. Rate-corrected QT duration (QTc) was measured before, during and after haloperidol use. Clinical variables before haloperidol use and at the time of each ECG recording were retrieved from hospital charts. Mixed model analysis was used to estimate changes in QT duration. Risk factors for potentially dangerous QT prolongation were estimated by logistic regression analysis.

Results

Patients with normal before-haloperidol QTc duration (male ≤430 ms, female ≤450 ms) had a significant increase in QTc duration of 23 ms during haloperidol use; twenty-three percent of patients rose to abnormal levels (male ≥450 ms, female ≥470 ms). In contrast, a significant decrease occurred in patients with borderline (male 430–450 ms, female 450–470 ms) or abnormal before-haloperidol QTc duration (15 ms and 46 ms, respectively); twenty-three percent of patients in the borderline group, and only 9% of patients in the abnormal group obtained abnormal levels. Potentially dangerous QTc prolongation was independently associated with surgery before haloperidol use (OR_adj 34.9, p = 0.009) and before-haloperidol QTc duration (OR_adj 0.94, p = 0.004).

Conclusion

QTc duration during haloperidol use changes differentially, increasing in patients with normal before-haloperidol QTc duration, but decreasing in patients with prolonged before-haloperidol QTc duration. Shorter before-haloperidol QTc duration and surgery before haloperidol use predict potentially dangerous QTc prolongation.     

Distribution,functional impact,and origin mechanisms of copy number variation in the barley genome

Background

There is growing evidence for the prevalence of copy number variation (CNV) and its role in phenotypic variation in many eukaryotic species. Here we use array comparative genomic hybridization to explore the extent of this type of structural variation in domesticated barley cultivars and wild barleys.

Results

A collection of 14 barley genotypes including eight cultivars and six wild barleys were used for comparative genomic hybridization. CNV affects 14.9% of all the sequences that were assessed. Higher levels of CNV diversity are present in the wild accessions relative to cultivated barley. CNVs are enriched near the ends of all chromosomes except 4H, which exhibits the lowest frequency of CNVs. CNV affects 9.5% of the coding sequences represented on the array and the genes affected by CNV are enriched for sequences annotated as disease-resistance proteins and protein kinases. Sequence-based comparisons of CNV between cultivars Barke and Morex provided evidence that DNA repair mechanisms of double-strand breaks via single-stranded annealing and synthesis-dependent strand annealing play an important role in the origin of CNV in barley.

Conclusions

We present the first catalog of CNVs in a diploid Triticeae species, which opens the door for future genome diversity research in a tribe that comprises the economically important cereal species wheat, barley, and rye. Our findings constitute a valuable resource for the identification of CNV affecting genes of agronomic importance. We also identify potential mechanisms that can generate variation in copy number in plant genomes.     

Ocular Surface Displacement with and without Contact Lenses during Non-Contact Tonometry

Purpose

To evaluate the displacement of the central ocular surface during non-contact tonometry with and without soft contact lenses and determine the factors associated with the displacement of the central ocular surface and intraocular pressure (IOP) reading changes caused by wearing soft contact lenses (CLs).

Methods

One eye each in 21 subjects was studied. The cornea was photographed using a high-speed camera at 5,000 frames/sec during non-contact tonometry without contact lenses (NCL), with -5.0 diopters (D), -0.5 D and +5.0 D CL. The displacement of the ocular surface and the factors affecting displacement at the IOP reading and maximum displacement time were investigated.

Results

The IOP readings while wearing +5 D CL were significantly higher than those obtained while wearing -5 D CL. The ocular surface displacement between +5 D CL and other groups were significantly different. A significant positive correlation was found between the ocular surface displacement of subjects at the IOP reading time and the IOP obtained with the non-contact tonometer. A significant negative correlation was found between the ocular surface curvature and the IOP obtained using the non-contact tonometer. The radius of curvature of the ocular surface affected the displacement during the IOP reading and maximum displacement time.

Conclusions

Our results indicate that soft contact lens use changes the ocular surface behavior and IOP readings during non-contact tonometry. The radius of curvature of the eye affects the ocular surface displacement and IOP readings in this situation.