Tollip SNP rs5743899 modulates human airway epithelial responses to rhinovirus infection.

BACKGROUND: Rhinovirus (RV) infection in asthma induces varying degrees of airway inflammation (e.g. neutrophils), but the underlying mechanisms remain unclear. OBJECTIVE: The major goal was to determine the role of genetic variation [e.g. single nucleotide polymorphisms (SNPs)] of Toll-interacting protein (Tollip) in airway epithelial responses to RV in a type 2 cytokine milieu. METHODS: DNA from blood of asthmatic and normal subjects was genotyped for Tollip SNP rs5743899 AA, AG and GG genotypes. Human tracheobronchial epithelial (HTBE) cells from donors without lung disease were cultured to determine pro-inflammatory and antiviral responses to IL-13 and RV16. Tollip knockout and wild-type mice were challenged with house dust mite (HDM) and infected with RV1B to determine lung inflammation and antiviral response. RESULTS: Asthmatic subjects carrying the AG or GG genotype (AG/GG) compared with the AA genotype demonstrated greater airflow limitation. HTBE cells with AG/GG expressed less Tollip. Upon IL-13 and RV16 treatment, cells with AG/GG (vs. AA) produced more IL-8 and expressed less antiviral genes, which was coupled with increased NF-κB activity and decreased expression of LC3, a hallmark of the autophagic pathway. Tollip co-localized and interacted with LC3. Inhibition of autophagy decreased antiviral genes in IL-13- and RV16-treated cells. Upon HDM and RV1B, Tollip knockout (vs. wild-type) mice demonstrated higher levels of lung neutrophilic inflammation and viral load, but lower levels of antiviral gene expression. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest that Tollip SNP rs5743899 may predict varying airway response to RV infection in asthma.

Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels.

During ischemic stroke, neurons at risk are exposed to pathologically high levels of intracellular calcium (Ca++), initiating a fatal biochemical cascade. To protect these neurons, we have developed openers of large-conductance, Ca++-activated (maxi-K or BK) potassium channels, thereby augmenting an endogenous mechanism for regulating Ca++ entry and membrane potential. The novel fluoro-oxindoles BMS-204352 and racemic compound 1 are potent, effective and uniquely Ca++-sensitive openers of maxi-K channels. In rat models of permanent large-vessel stroke, BMS-204352 provided significant levels of cortical neuroprotection when administered two hours after the onset of occlusion, but had no effects on blood pressure or cerebral blood flow. This novel approach may restrict Ca++ entry in neurons at risk while having minimal side effects.

The impact of architectural design upon the environmental sound and light exposure of neonates who require intensive care: an evaluation of the Boekelheide Neonatal Intensive Care Nursery.

OBJECTIVES: To evaluate the differences in environmental sound, illumination and physiological parameters in the Boekelheide Neonatal Intensive Care Unit (BNICU), which was designed to comply with current recommendations and standards, as compared with a conventional neonatal intensive care unit (CNICU). STUDY DESIGN: Prospectively designed observational study. RESULT: Median sound levels in the unoccupied BNICU (37.6 dBA) were lower than the CNICU (42.1 dBA, P<0.001). Median levels of minimum (6.4 vs 48.4 lux, P<0.05) and maximum illumination (357 vs 402 lux, P<0.05) were lower in the BNICU. A group of six neonates delivered at 32 weeks gestation showed significantly less periodic breathing (14 vs 21%) and awake time (17.6 vs 29.3%) in the BNICU as compared to the CNICU. CONCLUSION: Light and sound were both significantly reduced in the BNICU. Care in the BNICU was associated with improved physiological parameters.

Constructing a relevant decision aid for parents of children with bronchopulmonary dysplasia.

BACKGROUND: To develop and test a decision aid for counseling parents of children with bronchopulmonary dysplasia (BPD).Local problem:Parental education about complex conditions is not standardized and communication and understanding may not be adequate. METHODS: Semi-structured interviews were conducted with 33 neonatal clinicians and 12 parents of children with BPD using a qualitative research design. The interviews were used to identify education topics that were felt to be important in BPD education. These topics were then used to create a visual decision aid to be used in counseling sessions with parents. The decision aid was then used in mock counseling sessions with 15 'experienced' participants and 7 'naïve' participants to assess its efficacy. The participants completed a pre and post test to assess change in knowledge as well as an 11-question Likert style acceptability survey. INTERVENTION: Implementation of a decision aid while educating parents about BPD. RESULTS: Topics identified during the interviews were used to create eight educational cards which included pictures, pictographs and statistics. Overall, participants thought the decision aid contained an appropriate amount of information, were easy to understand and improved their knowledge about BPD. Testing demonstrated a significant increase in knowledge in both the 'experienced' (P<0.0001) and 'naïve' group (P=0.0064). CONCLUSION: A decision aid for parents of children with BPD may improve understanding of the condition and help facilitate communication between parents and doctors.

Fc receptor-defined T-lymphocyte subpopulations in patients with cutaneous T-cell lymphoma.

The distribution of peripheral blood T cells bearing Fc receptors for IgG (T gamma) and IgM (T mu) was determined in 18 patients with cutaneous T-cell lymphoma (Sézary syndrome, mycosis fungoides) and 15 normal controls. The mean percent of T mu and T gamma cells in the patients with morphologically normal lymphocytes was similar to that of the control subjects. In 13 patients with circulating malignant cells representing 30-100% of their peripheral blood lymphocytes, the mean percentages of T mu and T gamma were low. In 9 patients the majority of the malignant T cells did not exhibit Fc receptors for IgG or IgM. In some patients, however, high blood lymphocyte counts resulted in normal or high concentrations of all the T-cell subsets. Further, in 4 patients, lymphocytes with the characteristic nuclear abnormalities of "Sézary/mycosis" cells were found in both the T mu and T gamma, as well as the Tnon gamma non mu, subpopulations. The heterogeneity of the Fc receptors on cutaneous T-cell lymphoma lymphocytes suggests that these receptors are not useful as clonal markers in these disorders.

Reduced bicuculline response and GABAA agonist binding in aged rat hippocampus.

Extracellular field recordings from CA1 pyramidal cells in the rat hippocampal slice preparation were used to examine the effects of age on gamma-aminobutyric acid (GABA)-mediated recurrent inhibition. The actions of bicuculline (1-100 microM), a GABAA antagonist, were assessed in slices from young (1-3 months) and aged (26 months) Fischer 344 rats. Pre-drug population spike amplitudes were smaller in slices from aged rats. Bicuculline increased population spike amplitudes in slices from both age groups, but slices from young rats were more sensitive to the antagonist. Bicuculline also produced multiple population spikes in slices from both age groups, however the increase in population spike burst durations was much greater in slices from young rats than in slices from aged rats. Agonist radiolabeled GABAA binding site density was significantly decreased in hippocampal tissue from aged rats. Our results suggest there is a reduction in GABAergic inhibition in hippocampal slices from aged rats, possibly mediated by a decrease in GABAA receptors.

State reporting of live births of newborns weighing less than 500 grams: impact on neonatal mortality rates.

The National Center for Health Statistics reports that in 1983 65% of all infant deaths in the United States occurred in the neonatal period. Of these reported neonatal deaths, 17% were of infants weighing less than 500 g at birth. There was, however, variation in state-reported incidence of live births of newborns in this weight cohort (0.2 to 2.2 per 1,000 live births). The states with the lowest neonatal mortality rate have the lowest incidence of birth weights less than 500 g (rho = .77). If it is assumed that mortality for this weight category is nearly 100%, there is marked variation (5% to 32%) in the contribution of this weight cohort to a state's total neonatal mortality rate. Contributing to this variation may be definitions of live birth used by states. The World Health Organization defines a live birth as the product of conception showing signs of life "irrespective of the duration of pregnancy" and this definition is used by 33 states. Only one state (Ohio) includes the gestational criteria of "at least 20 weeks" in its definition of live birth. There is evidence to suggest that definitions are not uniformly used within individual states. For example, in 1983, 20 states did not report any live births with weights less than 500 g among their "other" populations of nonwhite, nonblack residents. Half of these states, however, use the World Health Organization definition of live birth. Despite the exclusionary wording in Ohio's definition of liver birth, 16% of newborns who died in that state had birth weights less than 500 g.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of antenatal administration of Betamethasone on hospital costs and survival of premature infants.

Prenatal administration of glucocorticoids has been shown to decrease in incidence and severity of respiratory distress syndrome in premature infants, but little is known regarding the immediate economic impact of this reduction in respiratory morbidity. This study retrospectively examined 342 infants born during 1978 and 1979 and hospitalized in the University of Minnesota Hospitals. Comparison of survival and the hospital charges for infants whose mothers had not received prenatal glucocorticoid therapy showed that administration of glucocorticoids has a significant effect in lowering mortality in infants with birth weights between 750 and 1,249 gm (27 to 29 weeks' gestation). Glucocorticoid therapy was also effective in decreasing morbidity as reflected by hospital charges of surviving infants with birth weights between 1,250 and 1,749 gm (30 to 32 weeks' gestation). In both steroid-treated and nontreated mothers, prolongation of gestation decreases hospital charges in a linear fashion. The noted decrease in hospital costs should not justify prenatal glucocorticoid administration but should stimulate examination of long-term effects of the drug on surviving infants.

Management of esophageal and pharyngeal perforation in the newborn infant.

Perforation of the esophagus or pharynx may occur during placement of endotracheal or nasogastric tubes in the newborn infant. Controversy exists, however, whether medical or surgical therapy is better in the management of these perforations. Nine patients who had esophageal or pharyngeal perforation in the neonatal period and were treated medically with antibiotics, nutritional support, and closed chest-tube drainage of pneumothoraces are described. All perforations healed without surgical repair. No mortality or morbidity occurred secondary to these perforations. This study, together with a review of the 73 patients described in the literature, indicate that perforations of the pharynx and esophagus can be satisfactorily managed medically. There is no apparent advantage to routine early surgical exploration. Only complications such as mediastinitis and mediastinal mass formation seem to require surgical treatment. Medical therapy with close observation for signs of sepsis and/or mediastinal changes will enable most newborn infants to avoid an operation and will identify those infants for whom surgery is definitely indicated.

Tomographic imaging of foam.

The morphology of three-dimensional foams is of interest to physicists, engineers, and mathematicians. It is desired to image the 3-dimensional structure of the foam. Many different techniques have been used to image the foam, including magnetic resonance imaging, and short-focal length lenses. We use a camera and apply tomographic algorithms to accurately image a set of bubbles. We correct for the distortion of a curved plexiglas container using ray-tracing.

Androgen inhibits, while oestrogen enhances, restraint-induced activation of neuropeptide neurones in the paraventricular nucleus of the hypothalamus.

The hormonal response to stress is enhanced by oestrogen but inhibited by androgens. To determine underlying changes in activity of neuropeptide neurones in the paraventricular nucleus of the hypothalamus (PVN), we examined the effect of oestrogen and androgen treatment on restraint-induced c-fos mRNA, corticotropin-releasing hormone (CRH) heteronuclear RNA, and arginine vasopressin hnRNA expression in the PVN. Male rats were gonadectomized and injected with oestradiol benzoate (EB) or dihydrotestosterone propionate (DHTP; s.c., daily for 4 days). Rats were stressed by restraint for 10 min or 30 min before killing. Other rats were stressed for 30 min and then returned to their home cage for 20 min before killing. Corticosterone and adrenocorticotropic hormone responses to restraint stress were significantly greater in EB-treated rats and lower in DHTP-treated rats at the 30-min timepoint compared to controls. c-fos mRNA increases following stress were augmented by EB but inhibited by DHTP. CRH hnRNA expression increased significantly in the PVN in response to restraint stress, and this increase was augmented by EB treatment, but decreased by DHTP treatment. Vasopressin hnRNA expression was also increased in response to stress, and this increase was attenuated by DHTP. These findings indicate that gonadal hormones influence the reactivity of the hypothalamic-pituitary adrenal axis to stress.

A Hankel transform approach to tomographic image reconstruction.

A relatively unexplored algorithm is developed for reconstructing a two-dimensional image from a finite set of its sampled projections. The algorithm, referred to as the Hankel-transform-reconstruction (HTR) algorithm, is polar-coordinate based. The algorithm expands the polar-form Fourier transform F(r,theta) of an image into a Fourier series in theta calculates the appropriately ordered Hankel transform of the coefficients of this series, giving the coefficients for the Fourier series of the polar-form image f(p,phi); resolves this series, giving a polar-form reconstruction; and interpolates this reconstruction to a rectilinear grid. The HTR algorithm is outlined, and it is shown that its performance compares favorably to the popular convolution-backprojection algorithm.

The 'tubulin-like' S1 protein of Spirochaeta is a member of the hsp65 stress protein family.

A 65-kDa protein (called S1) from Spirochaeta bajacaliforniensis was identified as 'tubulin-like' because it cross-reacted with at least four different antisera raised against tubulin and was isolated, with a co-polymerizing 45-kDa protein, by warm-cold cycling procedures used to purify tubulin from mammalian brain. Furthermore, at least three genera of non-cultivable symbiotic spirochetes (Pillotina, Diplocalyx, and Hollandina) that contain conspicuous 24-nm cytoplasmic tubules displayed a strong fluorescence in situ when treated with polyclonal antisera raised against tubulin. Here we summarize results that lead to the conclusion that this 65-kDa protein has no homology to tubulin. S1 is an hsp65 stress protein homologue. Hsp65 is a highly immunogenic family of hsp60 proteins which includes the 65-kDa antigens of Mycobacterium tuberculosis (an active component of Freund's complete adjuvant), Borrelia, Treponema, Chlamydia, Legionella, and Salmonella. The hsp60s, also known as chaperonins, include E. coli GroEL, mitochondrial and chloroplast chaperonins, the pea aphid 'symbionin' and many other proteins involved in protein folding and the stress response.

The effect of median filtering on edge estimation and detection.

In this paper we consider the effect of median prefiltering on the subsequent estimation and detection of edges in digital images. Where possible, a quantitative statistical comparison is made for a number of filters defined with two-dimensional geometries; in some cases one-dimensional analyses are required to illustrate certain points. Noise images prefiltered by median filters defined with a variety of windowing geometries are used to support the analysis, and it is found that median prefiltering improves the performance of both thresholding and zero-crossing based edge detectors.

Spatially variant apodization for image reconstruction from partial Fourier data.

Sidelobe artifacts are a common problem in image reconstruction from finite-extent Fourier data. Conventional shift-invariant windows reduce sidelobe artifacts only at the expense of worsened mainlobe resolution. Spatially variant apodization (SVA) was previously introduced as a means of reducing sidelobe artifacts, while preserving mainlobe resolution. Although the algorithm has been shown to be effective in synthetic aperture radar (SAR), it is heuristically motivated and it has received somewhat limited analysis. In this paper, we show that SVA is a version of minimum-variance spectral estimation (MVSE). We then present a complete development of the four types of two-dimensional SVA for image reconstruction from partial Fourier data. We provide simulation results for various real-valued and complex-valued targets and point out some of the limitations of SVA. Performance measures are presented to help further evaluate the effectiveness of SVA.

Partial Radon transforms.

This article formally defines partial Radon transforms for functions of more than two dimensions. It shows that a generalized projection-slice theorem exists which connects planar and hyperplanar projections of a function to its Fourier transform. In addition, a general theoretical framework is provided for carrying out n-dimensional backprojection reconstruction in a multistage fashion through the use of the partial Radon transform.

High-resolution planetary imaging via spotlight-mode synthetic aperture radar.

We consider the application of a spotlight-mode synthetic aperture radar (SAR) imaging technique to the problem of high-resolution lunar imaging and other related radar astronomy problems. This approach offers improved image quality, compared with conventional processing, at the expense of slightly increased computational effort. Results of the processing of lunar data acquired with the 12.6 cm wavelength radar system at Arecibo Observatory are presented, and compared with the best available published result, by Stacy (1993), which uses focusing techniques from stripmap SAR.

Mothers and their children look at baby pictures: the NICU experience in retrospect.

Photographs of Neonatal Intensive Care Unit (NICU) patients are frequently given to parents to promote bonding, but little attention has been paid to how families respond years later to viewing these special baby pictures. This study examines how 71 mothers of 3 to 7-year-old developmentally normal (DQ greater than or equal to 80) children who weighed less than 1,500 g at birth describe this experience. Compared to a group of mothers whose children were full term at birth, the NICU mothers described personally feeling and perceiving their children as more fearful (p less than .05), inquisitive (p less than .0001), worried (p less than .01), thoughtful (p less than .0001), and tearful (p less than .05). The responses of NICU mothers were significantly more highly correlated with their perceptions of their children's responses than were the mother-child correlations observed in a comparison group. The NICU children were reported by their mothers to ask about the NICU equipment, pain, being alone, their physical scars, and if their being "bad" caused their need for intensive neonatal care. Recommendations are provided on how pediatric care providers can assist NICU parents anticipate questions and respond to their children's concerns as they view these potentially distressing photographs.

Trends in volunteerism. A new way of managing volunteers furthers providers' goals.

Today's volunteers come from many walks of life--professionals, children, people with disabilities, and skilled tradespeople. Each has a special skill to offer in the spirit of volunteerism. To take advantage of the increasing number of volunteers, hospitals must begin to form more meaningful alliances with their communities. Healthcare volunteerism creates opportunities for renewed linkages between the community and the hospital. Hospitals should also look even closer to home--their own neighborhoods. Often staff fail to see their neighbors' failing conditions as services for the disadvantaged have declined. This creates ill will. But some hospitals are avoiding this by recruiting volunteers to help improve the lives of their yards, fixing up their houses, and fulfilling other needs. Another area where volunteers can be beneficial to the hospital is in political activism. Healthcare leaders, however, must discuss political issues with volunteers, and not keep them in the dark on issues of importance. Many volunteers are active politically and can give healthcare a voice in crucial matters.

A comparison of the direct cost of care in an open-bay and single-family room NICU.

OBJECTIVE: This research examined the proposition that the direct costs of care were no different in an open-bay (OPBY) as compared with a single-family room (SFR) neonatal intensive care (NICU) environment. STUDY DESIGN: This was a sequential cohort study. RESULT: General linear models were implemented using clinical and cost data for all neonates admitted to the two cohorts studied. Costs were adjusted to year 2007 U.S. dollars. Models were constructed for the unadjusted regression and subsequently by adding demographic variables, treatment variables, length of respiratory support and length of stay. With the exception of the last, none were found to achieve significance. The full model had R(2)=0.799 with P=0.0095 and predicted direct costs of care less in the SFR NICU. CONCLUSION: For the time, location and administrative practices in place, this study demonstrates that care can be provided in the SFR NICU at no additional cost as compared with OPBY NICU.