Repeated video head impulse testing in patients is a stable measure of the passive vestibulo-ocular reflex.

OBJECTIVES: The video head impulse test (vHIT) is used as a measure of compensation yet it's stability in patients with vestibular pathology is unknown. METHODS: 144 patients (n = 72 female, mean 54.46 ± 15.8 years) were grouped into one of three primary diagnoses (Peripheral, Central, or Mixed). Subjects were further categorized based on sex (male versus female), ear (left versus right; ipsilesional versus contralesional), age (six groups ranging from 19 to 84 years), and duration between visits (five groups, mean 191.46 ± SE 29.42 days, median 55.5 days). The gain of the VOR during passive head rotation was measured for each semicircular canal (horizontal, anterior, posterior). RESULTS: There was no difference in the VOR gain within any semicircular canal between the two visits (horizontal: p = 0.179; anterior: p = 0.628; posterior: p = 0.613). However, the VOR gain from the horizontal canals was higher than the vertical canals for each visit (p < 0.001). Patients diagnosed with peripheral vestibular pathology had significantly lower (p ≤ 0.001) horizontal semicircular canal gains at each visit. There was no difference in VOR gain between sex (p = 0.215) or age groupings (p = 0.331). Test-retest reliability of vHIT in patient subjects is good (ICC = 0.801) and the VOR gain values across two separate visits were significant and positively correlated (r = 0.67) regardless of sex, ear, age, or duration between visits. CONCLUSION: The vHIT is a stable measure of VOR gain over two different times across a variety of vestibular patients with no influence of age or sex.

Retinal Image Slip Must Pass the Threshold for Human Vestibulo-Ocular Reflex Adaptation.

We sought to determine whether repeated vestibulo-ocular reflex (VOR) adaptation training to increase the VOR gain (eye/head velocity) had a lasting effect in normal subjects and whether there was a retinal image slip tolerance threshold for VOR adaptation. We used the unilateral incremental VOR adaptation technique and horizontal active (self-generated, predictable) head impulses as the vestibular stimulus. Both active and passive (imposed, unpredictable) head impulse VOR gains were measured before and after unilateral incremental VOR adaptation training. The adapting side was pseudo-randomized for left or right. We tested ten normal subjects over one block (10 sessions over 12 days) of VOR adaptation training and testing, immediately followed by a second block (5 sessions over 19 days) of testing only without training. Our findings show robust short-term VOR adaptation of ~ 10 % immediately after each 15-min training session, but that the daily pre-adaptation gain was most different on days 1 and 2, and for subsequent training days before saturating to ~ 5 % greater than the pre-adaptation gain on day 1. This increase was partially retained for 19 days after regular training stopped. The data suggest that stable vision in normal subjects is maintained when there is < 5 % deviation in VOR gain from the original baseline, which corresponds to < 9°/s retinal image slip. Below this threshold, there is poor adaptive drive to return the gain to its original baseline value.

Metabolic maturation in the first 2 years of life in resource-constrained settings and its association with postnatal growths.

Malnutrition continues to affect the growth and development of millions of children worldwide, and chronic undernutrition has proven to be largely refractory to interventions. Improved understanding of metabolic development in infancy and how it differs in growth-constrained children may provide insights to inform more timely, targeted, and effective interventions. Here, the metabolome of healthy infants was compared to that of growth-constrained infants from three continents over the first 2 years of life to identify metabolic signatures of aging. Predictive models demonstrated that growth-constrained children lag in their metabolic maturity relative to their healthier peers and that metabolic maturity can predict growth 6 months into the future. Our results provide a metabolic framework from which future nutritional programs may be more precisely constructed and evaluated.

Human Vestibulo-Ocular Reflex Adaptation Training: Time Beats Quantity.

The vestibulo-ocular reflex (VOR) is the main gaze stabilising system during rapid head movements. The VOR is highly plastic and its gain (eye/head velocity) can be increased via training that induces an incrementally increasing retinal image slip error signal to drive VOR adaptation. Using the unilateral incremental VOR adaptation technique and horizontal active head impulses as the vestibular stimulus, we sought to determine the factors important for VOR adaptation including: the total training time, ratio and number of head impulses to each side (adapting and non-adapting sides; the adapting side was pseudo-randomised left or right) and exposure time to the visual target during each head impulse. We tested 11 normal subjects, each over 5 separate sessions and training protocols. The basic training protocol (protocol one) consisted of unilateral incremental VOR adaptation training lasting 15 min with the ratio of head impulses to each side 1:1. Each protocol varied from the basic. For protocol two, the ratio of impulses were in favour of the adapting side by 2:1. For protocol three, all head impulses were towards the adapting side and the training only lasted 7.5 min. For protocol four, all impulses were towards the adapting side and lasted 15 min. For protocol five, all head impulses were to the adapting side and the exposure time to the visual target during each impulse was doubled. We measured the active and passive VOR gains before and after the training. Albeit with small sample size, our data suggest that the total training time and the visual target exposure time for each head impulse affected adaptation, whereas the total number and repetition rate of head impulses did not. These data have implications for vestibular rehabilitation, suggesting that quality and duration of VOR adaptation exercises are more important than rapid repetition of exercises.

Human Vestibulo-Ocular Reflex Adaptation: Consolidation Time Between Repeated Training Blocks Improves Retention.

We sought to determine if separating vestibulo-ocular reflex (VOR) adaptation training into training blocks with a consolidation (rest) period in between repetitions would result in improved VOR adaptation and retention. Consolidation of motor learning refers to the brain benefitting from a rest period after prior exposure to motor training. The role of consolidation on VOR adaptation is unknown, though clinicians often recommend rest periods as a part of vestibular rehabilitation. The VOR is the main gaze stabilising system during rapid head movements. The VOR is highly plastic and its gain (eye/head velocity) can be increased via training that induces an incrementally increasing retinal image slip error signal to drive VOR adaptation. The unilateral incremental adaptation technique typically consists of one 15-min training block leading to an increase in VOR gain of ~ 10 % towards the training side. We tested nine normal subjects, each over six separate sessions/days. Three training protocols/sessions were 5 min each (1 × 5-min training) and three training protocols/sessions were 55 min each. Each 55-min protocol comprised 5-min training, 20-min rest, 5-min training, 20-min rest, 5-min training (3 × 5-min training). Active and passive VOR gains were measured before and after training. For training with consolidation breaks, VOR gain retention was measured over 1 h. The VOR gain increase after 1 × 5-min training was 3.1 ± 2.1 % (P < 0.01). One might expect that repeating this training three times would result in × 3 total increase of 9.3 %; however, the gain increase after 3 × 5-min training was only 7.1 ± 2.8 % (P < 0.001), suggesting that consolidation did not improve VOR adaptation for our protocols. However, retention was improved by the addition of consolidation breaks, i.e. gains did not decrease over 1 h (P = 0.43). These data suggest that for optimal retention VOR adaptation exercises should be performed over shorter repeated blocks.

Optimal Human Passive Vestibulo-Ocular Reflex Adaptation Does Not Rely on Passive Training.

The vestibulo-ocular reflex (VOR) is the main vision-stabilising system during rapid head movements in humans. A visual-vestibular mismatch stimulus can be used to train or adapt the VOR response because it induces a retinal image slip error signal that drives VOR motor learning. The training context has been shown to affect VOR adaptation. We sought to determine whether active (self-generated) versus passive (externally imposed) head rotation vestibular training would differentially affect adaptation and short-term retention of the active and passive VOR responses. Ten subjects were tested, each over six separate 1.5-h sessions. We compared active versus passive head impulse (transient, rapid head rotations with peak velocity ~ 150 °/s) VOR adaptation training lasting 15 min with the VOR gain challenged to increment, starting at unity, by 0.1 every 90 s towards one side only (this adapting side was randomised to be either left or right). The VOR response was tested/measured in darkness at 10-min intervals, 20-min intervals, and two single 60-min interval sessions for 1 h post-training. The training was active or passive for the 10- and 20-min interval sessions, but only active for the two single 60-min interval sessions. The mean VOR response increase due to training was ~ 10 % towards the adapting side versus ~2 % towards the non-adapting side. There was no difference in VOR adaptation and retention between active and passive VOR training. The only factor to affect retention was exposure to a de-adaptation stimulus. These data suggest that active VOR adaptation training can be used to optimally adapt the passive VOR and that adaptation is completely retained over 1 h as long as there is no visual feedback signal driving de-adaptation.

The Effect of Visual Contrast on Human Vestibulo-Ocular Reflex Adaptation.

The vestibulo-ocular reflex (VOR) is the main retinal image stabilising mechanism during rapid head movement. When the VOR does not stabilise the world or target image on the retina, retinal image slip occurs generating an error signal that drives the VOR response to increase or decrease until image slip is minimised, i.e. VOR adaptation occurs. Visual target contrast affects the human smooth pursuit and optokinetic reflex responses. We sought to determine if contrast also affected VOR adaptation. We tested 12 normal subjects, each over 16 separate sessions. For sessions 1-14, the ambient light level (lx) during adaptation training was as follows: dark, 0.1, 0.2, 0.3, 0.5, 0.7, 1, 2, 8, 16, 32, 64, 128 and 255 lx (light level for a typical room). For sessions 15-16, the laser target power (related to brightness) was halved with ambient light at 0 and 0.1 lx. The adaptation training lasted 15 min and consisted of left/right active head impulses. The VOR gain was challenged to increment, starting at unity, by 0.1 every 90 s for rotations to the designated adapting side and fixed at unity towards the non-adapting side. We measured active and passive VOR gains before and after adaptation training. We found that for both the active and passive VOR, there was a significant increase in gain only towards the adapting side due to training at contrast level 1.5 k and above (2 lx and below). At contrast level 261 and below (16 lx and above), adaptation training resulted in no difference between adapting and non-adapting side gains. Our modelling suggests that a contrast threshold of ~ 1000, which is 60 times higher than that provided by typical room lighting, must be surpassed for robust active and passive VOR adaptation. Our findings suggest contrast is an important factor for adaptation, which has implication for rehabilitation programs.

Association between serum vitamin D, retinol and zinc status, and acute respiratory infections in underweight and normal-weight children aged 6-24 months living in an urban slum in Bangladesh.

We conducted a longitudinal assessment in 466 underweight and 446 normal-weight children aged 6-24 months living in the urban slum of Dhaka, Bangladesh to determine the association between vitamin D and other micronutrient status with upper respiratory tract infection (URI) and acute lower respiratory infection (ALRI). Incidence rate ratios of URI and ALRI were estimated using multivariable generalized estimating equations. Our results indicate that underweight children with insufficient and deficient vitamin D status were associated with 20% and 23-25% reduced risk of URI, respectively, compared to children with sufficient status. Underweight children, those with serum retinol deficiency were at 1·8 [95% confidence interval (CI) 1·4-2·4] times higher risk of ALRI than those with retinol sufficiency. In normal-weight children there were no significant differences between different vitamin D status and the incidence of URI and ALRI. However, normal-weight children with zinc insufficiency and those that were serum retinol deficient had 1·2 (95% CI 1·0-1·5) times higher risk of URI and 1·9 (95% CI 1·4-2·6) times higher risk of ALRI, respectively. Thus, our results should encourage efforts to increase the intake of retinol-enriched food or supplementation in this population. However, the mechanisms through which vitamin D exerts beneficial effects on the incidence of childhood respiratory tract infection still needs further research.

Association of vitamin D status with incidence of enterotoxigenic, enteropathogenic and enteroaggregative Escherichia coli diarrhoea in children of urban Bangladesh.

OBJECTIVE: To evaluate the association between vitamin D status and diarrhoeal episodes by enterotoxigenic (ETEC), enteropathogenic (EPEC) and enteroaggregative (EAEC) E. coli in underweight and normal-weight children aged 6-24 months in urban Bangladesh. METHODS: Cohorts of 446 normal-weight and 466 underweight children were tested separately for ETEC, EPEC and EAEC from diarrhoeal stool samples collected during 5 months of follow-up while considering vitamin D status at enrolment as the exposure. Cox proportional hazards models with unordered failure events of the same type were used to determine diarrhoeal risk factors after adjusting for sociodemographic and concurrent micronutrient status. RESULTS: Vitamin D status was not independently associated with the risk of incidence of ETEC, EPEC and EAEC diarrhoea in underweight children, but moderate-to-severe retinol deficiency was associated with reduced risk for EPEC diarrhoea upon adjustment. Among normal-weight children, insufficient vitamin D status and moderate-to-severe retinol deficiency were independently associated with 44% and 38% reduced risk of incidence of EAEC diarrhoea, respectively. These children were at higher risk of ETEC diarrhoea with vitamin D deficiency status when adjusted for micronutrient status only. CONCLUSION: This study demonstrates for the first time that normal-weight children with insufficient vitamin D status have a reduced risk of EAEC diarrhoea than children with sufficient status. Moderate-to-severe deficiency of serum retinol is associated with reduced risk of EPEC and EAEC diarrhoea in underweight and normal-weight children.

Vitamin-D status is not a confounder of the relationship between zinc and diarrhoea: a study in 6-24-month-old underweight and normal-weight children of urban Bangladesh.

BACKGROUND/OBJECTIVE: The role of micronutrients particularly zinc in childhood diarrhoea is well established. Immunomodulatory functions of vitamin-D in diarrhoea and its role in the effect of other micronutrients are not well understood. This study aimed to investigate whether vitamin-D directly associated or confounded the association between other micronutrient status and diarrhoeal incidence and severity in 6-24-month underweight and normal-weight children in urban Bangladesh. SUBJECTS/METHODS: Multivariable generalised estimating equations were used to estimate incidence rate ratios for incidence (Poisson) and severity (binomial) of diarrhoea on cohorts of 446 normal-weight and 466 underweight children. Outcomes of interest included incidence and severity of diarrhoea, measured daily during a follow-up period of 5 months. The exposure of interest was vitamin-D status at enrolment. RESULTS: Normal-weight and underweight children contributed 62 117 and 62 967 day observation, with 14.2 and 12.8 days/child/year of diarrhoea, respectively. None of the models showed significant associations of vitamin-D status with diarrhoeal morbidity. In the final model, zinc-insufficient normal-weight children had 1.3 times more days of diarrhoea than sufficient children (P<0.05). Again zinc insufficiency and mother's education (1-5 and >5 years) had 1.8 and 2.3 times more risk of severe diarrhoea. In underweight children, older age and female had 24-63 and 17% fewer days of diarrhoea and 52-54 and 31% fewer chances of severe diarrhoea. CONCLUSION: Vitamin-D status was not associated with incidence and severity of diarrhoea in study children. Role of zinc in diarrhoea was only evident in normal-weight children. Our findings demonstrate that vitamin-D is not a confounder of the relationship between zinc and diarrhoea.

Evaluation of a new enzyme immunoassay for the detection of Helicobacter pylori in stool specimens.

H. pylori infects the gastric mucosa and causes many digestive disorders such as peptic ulcer, chronic gastritis and gastric cancer. H. pylori infection relates neither to functional health status, nor to intensity of dyspepsia. There is evidence that in most patients with H. pylori positive functional dyspepsia do not improve with eradication of the organism.This study evaluated the diagnostic accuracy of HpSA by determining the sensitivity and specificity of the stool antigen test in predicting successful eradication during and after anti microbial therapy. The work was conducted on patients who underwent upper gastrointestinal endoscopy at Al-Azhar University hospitals. Fifty patients (34 male & 16 female) with dyspepsia were selected, the exclusion criteria included use of antibiotics and proton pump inhibitors up to one month before the study. All cases were submitted to, full history, general and local examination and upper gastrointestinal endoscopy. Biopsies were taken from the antrum and body of the stomach for rapid urease test and histopathology. Stool samples were taken to detect H. pylori stool antigen. Positive patients received eradication treatment for one month and H. pylori status was re-determined by rapid urease test, histological examination and HpSA test one month later. H. pylori was detected by rapid urease test in 29 (58%) dyspeptic patient by histology in 26(52%) dyspeptic patient, while H. pylori was detected by HpSA immunoassay in 16 (32%) dyspeptic patient. The sensitivity and specificity of HpSA were 57.7% and 95.8% respectively. After successful eradication of H. pylori, reassessment by rapid urease test and histology revealed curative rate of 86.2% and 84.6% respectively, while HpSA immunoassay revealed curative rate 75%. Based on these results, the HpSA immunoassay gave sensitivity (75%) and specificity (100%). The H. pylori stool test represents an accurate and novel non-invasive concept for diagnosis of infection and can be used for daily routine in clinical practice. HpSA is a promising non-invasive test for diagnosis of H. pylori infection but may be hampered by low patient acceptability. So, HpSA is a valuable test in the pre-and post eradication assessment of infection. HpSA can be profitably employed in the primary diagnosis of H. pylori infection. This non invasive test could be very useful in investigating dyspeptic young patients. Also, it could be used profitably in epidemiological studies to determine the prevalence of H. pylori infection in the asymptomatic subjects in different communities.