Exogenous administration of vascular endothelial growth factor prior to human respiratory syncytial virus a2 infection reduces pulmonary pathology in neonatal lambs and alters epithelial innate immune responses

Human respiratory syncytial virus (RSV) affects thousands of children every year. Vascular endothelial growth factor (VEGF) is a regulator of vasculogenesis, pulmonary maturation, and immunity. In order to test the extent to which VEGF may alter RSV infection, 4 groups of lambs received either human recombinant VEGF (rhVEGF) or phosphate-buffered saline (PBS) pretreatment followed by inoculation with human RSV strain A2 or sterile medium. Lambs in each group were sacrificed at 2, 4, and 6 days post infection. Expression of surfactant protein-A (SP-A), surfactant protein-D (SP-D), sheep β-defensin-1 (SBD-1), tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-8, interferon β, and endogenous VEGF were measured to determine effect of rhVEGF pretreatment. RSV lambs pretreated with rhVEGF had reduced viral mRNA and decreased pulmonary pathology at day 6. Pretreatment with rhVEGF increased mRNA expression of SP-A, SBD-1, and TNFα, with alteration of expression in RSV lambs. Endogenous VEGF mRNA levels were increased at day 2 regardless of pretreatment. Pretreatment with rhVEGF increased pulmonary cellular proliferation in RSV lambs at day 4 post infection. Overall, these results suggest that pretreatment with rhVEGF protein may have therapeutic potential to decrease RSV viral load, decrease pulmonary lesion severity, and alter both epithelial innate immune responses and epithelial cell proliferation

Vascular uptake of rehydration fluids in hypohydrated men at rest and exercise

The purpose of this study was to formulate and to evaluate rehydration drinks, which would restore total body water and plasma volume (PV), for astronauts to consume before and during extravehicular activity, a few hours before reentry, and immediately after landing. In the first experiment (rest, sitting), five healthy men (23-41 yr), previously dehydrated for 24 hr., drank six (1a, 2, 4, 5, 6, 7) fluid formulations (one each at weekly intervals) and then sat for 70 min. Pre-test PV were measured with Evans blue dye and changes in PV were calculated with the hematocrit-hemoglobin transformation equation. This rest experiment simulated hypohydrated astronauts preparing for reentry. The second experiment (exercise, supine) followed the same protocol except four healthy men (30-46 yr) worked for 70 min. in the supine position on a cycle ergometer at a mean load of 71+/-1 percent of their peak aerobic work capacity. This exercise experiment simulated conditions for astronauts with reduced total body water engaging in extravehicular activity

'VOR' - an interactive iPad model of the combined angular and linear vestibulo-ocular reflex

The mammalian vestibular system consists of a series of sensory organs located in the labyrinths of the inner ear that are sensitive to angular and linear movements of the head. Afferent inputs from the vestibular end organs contribute to balance, proprioception and vision. The vestibulo-ocular reflex (VOR) driven by these sensory inputs produces oculomotor responses in a direction opposite to head movement which tend to stabilise visual images on the retina. We present a model, in the form of a software application called VOR, which represents a simplified view of this complex system. The basis for our model is the hypothesis that afferent vestibular signals are integrated to maintain a notional internal representation of the head position (RHP). The vestibulo-ocular reflex maintains gaze towards a world-fixed point relative to the RHP, regardless of the actual head position. The RHP will imperfectly match the real head position when end organ input imperfectly reports head movements, such as can occur in cases of organ dysfunction and even in healthy subjects due to adaptation to motion stimuli. We do not claim that any specific observable part of the real vestibulo-ocular system corresponds to the RHP, but it seems reasonable to suggest that it might exist as a literal "neural network", trained through evolution and experience to maintain gaze during head movement. We hypothesise that the real VOR is supported by this internal representation, continually updated by afferent signals from the vestibular end organs, and that VOR eye responses tend to direct the eyes towards a fixed point in the world. Human vestibulo-ocular research typically employs equipment to which a subject is securely attached and allows rotation around, and sometimes linear movement along, one or more axes ("rotating chair") while attempting to maintain gaze on a fixation point, fixed relative to the head or world. A series of consecutive movements are referred to as a "motion profile". Meanwhile eye movements are recorded, using scleral search coils (or, more recently, video cameras and image-processing software) which can detect the horizontal, vertical and torsional components of the direction of each eye. VOR allows the user to define motion profiles and predicts the eye movements that a researcher or clinician might expect to observe in a real subject during such motion profiles. For example, the "on-centre rotation" motion profile specifies that the subject's head is positioned upright and centred around the vertical axis of the rotating chair, with a chair-fixed fixation point 1m in front of the subject. The chair accelerates angularly to 200°/sec over 20 seconds, rotates at a constant 200°/sec for 60 seconds, then decelerates to stationary over 20 seconds. The model accurately predicts the transient nystagmus that would be expected: its direction, duration, phase velocity and even the brief secondary nystagmus which is characteristic of adaptation to constant velocity rotation. VOR also allows the user to define end organ condition configurations, e.g. "normal", "bilateral vestibular loss", "unilateral superior neuritis", which are represented as a series of response gains attached to the sensory inputs from each end organ, relative to a nominal perfect gain of 1, and various other parameters which are derived from the human vestibular system, including the rate of drift of gaze to fixation point in light and dark, the rate at which the end organs adapt to constant stimuli, and quick-phase trigger dependencies. The VOR is not the only source of eye movement while attempting to maintain gaze on a fixation point. In our model, eye position drifts towards the fixation point at a nominal fixed rate. If this slow drift is insufficient to maintain gaze on the fixation point, a saccade or quick phase is triggered. Hence the transduction of mechanical forces at the labyrinths into sensory signals, subject to end organ conditions and adaptation that reduce the strength of the neuronal signals, maintain the RHP. Eye movement is then determined entirely by (a) the direction from RHP to the (world-referenced) fixation point, and (b) the disparity between eye direction and actual fixation point (which may be head-referenced). To validate the model, we prepared 24 motion profile/end organ condition combinations, compared the outputs from our model with real world observations, and found the results to be similar. Similarities include a simple first approximation of the linear and angular VOR; nystagmus caused by a subject's attempts to maintain fixation on a head-referenced target during head movement; decay of nystagmus through adaptation to stimulus, including secondary nystagmus; indefinitely prolonged nystagmus during off-vertical axis rotation (OVAR); rapid decay of nystagmus during the "tilt dump" motion profile, and dynamic cyclovergence during vertical linear acceleration. VOR is programmed in Objective-C using Xcode and runs on the Apple iPad. Its screen displays a 3d graphical representation of the virtual subject's head and eyes, including imaginary lines of sight to clarify eye movements. The user may program an effectively unlimited series of linear and angular motions of the rotating chair, and of the virtual subject's head relative to the chair. They may also program the gain (roughly, the sensitivity) associated with each end organ and other variables relating to the subject. They may select a series of internal variables to chart during the motion profile such as head velocity, eye direction, neuron firing rates, etc., while simultaneously displaying the head and eyes. VOR can record a video screen capture of the virtual head, eyes and lines of sight during the execution of a motion profile, a CSV file containing the internal variables at each time interval, a PNG image of the labelled chart, PDF descriptions of the motion profile and end organ condition configurations, and data files defining the motion profiles and end organ conditions which can then be exchanged between researchers/clinicians. Predefined motion profiles include: lateral, LARP and RALP head impulses; lateral head impulse with close fixation point; sinusoidal yaw, on-centre rotation, linear heave along Y axis, linear oscillation along X, Y and Z axes; linear sled along Y axis; forward- and backward-facing centrifugation; off-vertical axis rotation; tilt dump; and head tilt. Predefined conditions include: normal; left unilateral vestibular loss; bilateral vestibular loss; left superior neuritis; and "perfect" (unrealistic gain of 1 in otoliths, producing perfect linear VOR). All of these motion profiles and conditions may easily be modified, created and shared

The host immune response contributes to Haemophilus influenzae virulence

SummaryBackgroundThere is compelling evidence that infections with non-typeable Haemophilus influenzae (NTHi) are associated with exacerbations in COPD patients. However, NTHi has also been isolated frequently during clinically stable disease. In this study we tested the hypothesis that genetically distinct NTHi isolates obtained from COPD patients differ in virulence which could account for dissimilarities in the final outcome of an infection (stable vs. exacerbation).ResultsNTHi isolates (n = 32) were obtained from stable COPD patients, or during exacerbations. Genetically divergent NTHi isolates were selected and induction of inflammation was assessed as an indicator of virulence using different in vitro models. Despite marked genomic differences among NTHi isolates, in vitro studies could not distinguish between NTHi isolates based on their inflammatory capacities. Alternatively, when using a whole blood assay results demonstrated marked inter-, but not intra-individual differences in cytokine release between healthy volunteers irrespective of the origin of the NTHi isolate used.ConclusionResults suggest that the individual immune reactivity might be an important predictor for the clinical outcome (exacerbation vs. no exacerbation) following NTHi infection

Bias in protein and potassium intake collected with 24-h recalls (EPIC-Soft) is rather comparable across European populations

Purpose: We investigated whether group-level bias of a 24-h recall estimate of protein and potassium intake, as compared to biomarkers, varied across European centers and whether this was influenced by characteristics of individuals or centers. Methods: The combined data from EFCOVAL and EPIC studies included 14 centers from 9 countries (n = 1,841). Dietary data were collected using a computerized 24-h recall (EPIC-Soft). Nitrogen and potassium in 24-h urine collections were used as reference method. Multilevel linear regression analysis was performed, including individual-level (e.g., BMI) and center-level (e.g., food pattern index) variables. Results: For protein intake, no between-center variation in bias was observed in men while it was 5.7% in women. For potassium intake, the between-center variation in bias was 8.9% in men and null in women. BMI was an important factor influencing the biases across centers (p <0.01 in all analyses). In addition, mode of administration (p = 0.06 in women) and day of the week (p = 0.03 in men and p = 0.06 in women) may have influenced the bias in protein intake across centers. After inclusion of these individual variables, between-center variation in bias in protein intake disappeared for women, whereas for potassium, it increased slightly in men (to 9.5%). Center-level variables did not influence the results. Conclusion: The results suggest that group-level bias in protein and potassium (for women) collected with 24-h recalls does not vary across centers and to a certain extent varies for potassium in men. BMI and study design aspects, rather than center-level characteristics, affected the biases across center

Packing and covering immersion models of planar subcubic graphs

A graph $H$ is an immersion of a graph $G$ if $H$ can be obtained by some sugraph $G$ after lifting incident edges. We prove that there is a polynomial function $f:\Bbb{N}\times\Bbb{N}\rightarrow\Bbb{N}$, such that if $H$ is a connected planar subcubic graph on $h>0$ edges, $G$ is a graph, and $k$ is a non-negative integer, then either $G$ contains $k$ vertex/edge-disjoint subgraphs, each containing $H$ as an immersion, or $G$ contains a set $F$ of $f(k,h)$ vertices/edges such that $G\setminus F$ does not contain $H$ as an immersion