Temporal patterns in principal Salmonella serotypes in the USA; 1996-2014.

Analysing temporal patterns in foodborne illness is important to designing and implementing effective food safety measures. The reported incidence of illness due to Salmonella in the USA. Foodborne Diseases Active Surveillance Network (FoodNet) sites has exhibited no declining trend since 1996; however, there have been significant annual trends among principal Salmonella serotypes, which may exhibit complex seasonal patterns. Data from the original FoodNet sites and penalised cubic B-spline regression are used to estimate temporal patterns in the reported incidence of illness for the top three Salmonella serotypes during 1996-2014. Our results include 95% confidence bands around the estimated annual and monthly curves for each serotype. The results show that Salmonella serotype Typhimurium exhibits a statistically significant declining annual trend and seasonality (P < 0.001) marked by peaks in late summer and early winter. Serotype Enteritidis exhibits a significant annual trend with a higher incidence in later years and seasonality (P < 0.001) marked by a peak in late summer. Serotype Newport exhibits no significant annual trend with significant seasonality (P < 0.001) marked by a peak in late summer.

Rat astrocytic tumour cells are associated with an anti-inflammatory microglial phenotype in an organotypic model.

AIM: Microglia form a high proportion of cells in glial tumours but their role in supporting or inhibiting tumour growth is unclear. Here we describe the establishment of an in vitro model to investigate their role in astrocytomas. METHODS: Rat hippocampal slices were prepared and, after 7 days to allow microglia to become quiescent, rat C6 astrocytic tumour cells were added. Over the following 7 days, infiltration and cell death were studied using fluorescent C6 tumour cells and confocal microscopy; immunophenotyping of microglia was performed using CD68 (phagocytosis), MHCII (antigen-presentation) and Iba1 (microglial marker regardless of functional state). Cell proliferation was assessed using Ki67 and qPCR to detect cytokine expression. Sham and control groups were included. RESULTS: Microscopy showed proliferation of C6 tumour cells with both infiltration of tumour cells into the hippocampal tissue and of microglia among the tumour cells. Confocal experiments confirmed increasing tumour cell infiltration into the hippocampal slice with time (P<0.001), associated with cell death (σ=0.313, P=0.022). Ki67 showed increased proliferation (P<0.001), of both tumour cells and Iba1+ microglia and increased microglial phagocytosis (CD68: P<0.001). Expression of pro-inflammatory cytokines IL1, IL6 and TNFα were downregulated with expression of the anti-inflammatory cytokine TGFß1 maintained. CONCLUSION: This model allows study of the proliferation and infiltration of astrocytic tumour cells in central nervous system tissue and their interaction with microglia. Our data suggest that microglial function is altered in the presence of tumour cells, putatively facilitating tumour progression. Manipulation of the microglial functional state may have therapeutic value for astrocytic tumours.

Readiness of obstetric professionals to inform parents regarding potential outcome of premature infants.

Parents often regard obstetric professionals as an important source of information regarding prematurity. However, there is no information regarding the readiness of these obstetric professionals to inform expectant parents of the potential outcomes of premature infants. Using a self-report questionnaire, we determined the knowledge of obstetric professionals regarding outcomes of premature infants, and gauged their confidence in providing this information to expectant parents. Some 50% of obstetric professionals reported that they 'struggle to answer parental questions' regarding premature infants. The majority of obstetric professionals correctly identified potential morbidities of prematurity, but compared to neonatal professionals, they were less likely to discuss this information with parents. When they do provide information to parents, obstetric professionals were least likely to discuss neurological morbidities. Our study has identified an important barrier to the effective transfer of neonatal outcomes information to expectant parents. This limitation requires further investigation and intervention.

Invited review: gender issues related to spaceflight: a NASA perspective.

This minireview provides an overview of known and potential gender differences in physiological responses to spaceflight. The paper covers cardiovascular and exercise physiology, barophysiology and decompression sickness, renal stone risk, immunology, neurovestibular and sensorimotor function, nutrition, pharmacotherapeutics, and reproduction. Potential health and functional impacts associated with the various physiological changes during spaceflight are discussed, and areas needing additional research are highlighted. Historically, studies of physiological responses to microgravity have not been aimed at examining gender-specific differences in the astronaut population. Insufficient data exist in most of the discipline areas at this time to draw valid conclusions about gender-specific differences in astronauts, in part due to the small ratio of women to men. The only astronaut health issue for which a large enough data set exists to allow valid conclusions to be drawn about gender differences is orthostatic intolerance following shuttle missions, in which women have a significantly higher incidence of presyncope during stand tests than do men. The most common observation across disciplines is that individual differences in physiological responses within genders are usually as large as, or larger than, differences between genders. Individual characteristics usually outweigh gender differences per se.

Mouse model for Chagas disease: immunohistochemical distribution of different stages of Trypanosoma cruzi in tissues throughout infection.

Different stages of Trypanosoma cruzi are seen during mammalian infection. Histologic sections of infected hearts have shown amastigotes and, when using immunohistochemistry (IHC), parasite antigens; however, demonstration of trypomastigotes in these tissues has proven elusive. Using a mouse strain that develops chagasic cardiomyopathy (histologically similar to human infection) 70 days after injecting T. cruzi-Brazil strain, we studied the distribution of parasite stages and the extent of inflammation. All organs had varying amounts of mononuclear inflammation by day 10, which peaked between day 20 and day 30, and decreased by day 50. Amastigotes were detected in myocytes, histiocytes, acinar pancreatic cells, astrocytes and ependymal cells by day 10, and the number of amastigotes peaked on day 30. Immunohistochemistry demonstrated trypomastigotes in sinusoids, vessels and interstitial tissues of several organs between day 15 and 50. Abundant parasite antigens (granular staining) were detected in connective tissues throughout the infection. The burden of amastigotes and trypomastigotes during the acute phase seems to correlate with the degree of inflammation and granular staining in the chronic stage.

Lower body adynamia as a factor to reduce the risk of hypobaric decompression sickness.

BACKGROUND: We define lower body adynamia (LBA) as restricted lower body movement, particularly walking, during both the denitrogenation phase at site pressure and during the exercise phase while at altitude. HYPOTHESIS: Our null hypothesis is that subjects who are adynamic in the lower body but do upper body exercise will be at similar risk of decompression sickness (DCS) and venous gas emboli (VGE) as subjects who randomly walk but do no planned exercise while at altitude. METHODS: We selected a data set that contained 1401 altitude exposures with the following conditions: a) walking was part of the exercise at altitude; or b) there was no planned exercise done at altitude but walking was not restricted; or c) LBA was inforced, but upper body exercise was done at altitude. We used logistic regression (LR) on all 1401 exposures, a log logistic survival analysis (SA) on a subset of data from "a" and "c" (n = 234), and estimated a model for how the incidence of VGE changes through time. RESULTS: The estimated probabilities of DCS and VGE with 95% confidence intervals (Cls) from the LR with a simulation of a 3-h oxygen prebreathe, a 4-h exposure to 4.3 psia in a male, and exercise and LBA conditions as described above are: (see text). CONCLUSION: LBA that includes upper body exercise appears to be as protective against DCS and VGE as random walking by subjects who did no prescribed exercise while at altitude, and is more protective than exercise that included walking. Our conclusions are based on an assumption that we have adequately controlled, through our data selection process and the use of multivariable models, important variables in tests that were not done at the Johnson Space Center.

A mathematical model of diffusion-limited gas bubble dynamics in tissue with varying diffusion region thickness.

The three-region model of gas bubble dynamics consists of a bubble and a well-stirred tissue region with an intervening unperfused diffusion region previously assumed to have constant thickness and uniform gas diffusivity. As a result, the diffusion region gas content remains unchanged as its volume increases with bubble growth, causing dissolved gas in the region to violate Henry's law. Earlier work also neglected the relationship between the varying diffusion region volume and the fixed total tissue volume. The present work corrects these theoretical inconsistencies by postulating a difference in gas diffusivity between an infinitesimally thin layer at the bubble surface and the remainder of the diffusion region, thus allowing both thickness and gas content of the diffusion region to vary during bubble evolution. The corrected model can yield bubble lifetimes considerably longer than those yielded by earlier three-region models, and meets a need for theoretically consistent but relatively simple bubble dynamics models for use in studies of decompression sickness (DCS) in human subjects.

Use of polymerase chain reaction to diagnose the fifth reported US case of autochthonous transmission of Trypanosoma cruzi, in Tennessee, 1998.

In July 1998, the mother of an 18-month-old boy in rural Tennessee found a triatomine bug in his crib, which she saved because it resembled a bug shown on a television program about insects that prey on mammals. The gut contents of the Triatoma sanguisuga were found, by light microscopy and polymerase chain reaction (PCR), to be infected with Trypanosoma cruzi; PCR products hybridized with T. cruzi-specific oligonucleotide probes. Whole-blood specimens obtained from the child in July and August were negative by buffy-coat examination and hemoculture but positive by PCR and DNA hybridization, suggesting that he had low-level parasitemia. Specimens obtained after treatment with benznidazole were negative. He did not develop anti-T. cruzi antibody; 19 relatives and neighbors also were seronegative. Two of 3 raccoons trapped in the vicinity had positive hemocultures for T. cruzi. The child's case of T. cruzi infection-the fifth reported US autochthonous case-would have been missed without his mother's attentiveness and the availability of sensitive molecular techniques.

Body schema, gender, and other correlates in nonclinical populations.

The link between body image and eating disorders has been extensively discussed, but investigations using nonclinical populations have not been systematically reviewed. In this article, a model to guide future researchers has been provided, and an attempt has been made to organize and synthesize the existing findings, with special attention to gender differences. Future researchers should more carefully delineate behavioral, emotional, cognitive, motivational, and evaluative components of body schema and should explore the relationship between body schema and outcomes other than eating disturbances. Conclusions in this review include the following: (a) Verbal measures of body schema are more successful than visual assessment tools; (b) measures of body distortion have been less successful than measures of dissatisfaction; (c) gender differences are prevalent; (d) behavioral outcomes can be successfully predicted; and (e) pubertal development plays a critical role in the gender differentiation of body schemas.

Seroprevalence of Trypanosoma cruzi infection in three rural communities in Guatemala.

A systematic, house-based serological survey for Trypanosoma cruzi seroreactivity was conducted in three contiguous communities in Olopa municipality, Chiquimula Department, Guatemala. Blood samples from a total of 292 individuals in 63 households were examined by enzyme-linked immunosorbent assay. The seropositive rate ranged from 0% to 20.8% for the three communities, with a mean of 15.1%. Log-linear models showed that seroprevalence was significantly related to age (P < 0.005) but not to sex. However, when the age group with the lowest prevalence (1-9 years) was excluded from the analysis, age was not a significant factor (P = 0.55). Data from a stratified sample collected at the same time were combined with those of the systematic sample to analyze the relationship between seropositivity and possible explanatory variables. Log-linear models, based on 586 individuals in 129 households from the two surveys, revealed a significant positive association between seropositivity and thatched roofs (P = 0.01).

Mathematical models of diffusion-limited gas bubble dynamics in tissue.

Mathematical models of bubble evolution in tissue have recently been incorporated into risk functions for predicting the incidence of decompression sickness (DCS) in human subjects after diving and/or flying exposures. Bubble dynamics models suitable for these applications assume the bubble to be either contained in an unstirred tissue (two-region model) or surrounded by a boundary layer within a well-stirred tissue (three-region model). The contrasting premises regarding the bubble-tissue system lead to different expressions for bubble dynamics described in terms of ordinary differential equations. However, the expressions are shown to be structurally similar with differences only in the definitions of certain parameters that can be transformed to make the models equivalent at large tissue volumes. It is also shown that the two-region model is applicable only to bubble evolution in tissues of infinite extent and cannot be readily applied to bubble evolution in finite tissue volumes to simulate how such evolution is influenced by interactions among multiple bubbles in a given tissue. Two-region models that are incorrectly applied in such cases yield results that may be reinterpreted in terms of their three-region model equivalents but only if the parameters in the two-region model transform into consistent values in the three-region model. When such transforms yield inconsistent parameter values for the three-region model, results may be qualitatively correct but are in substantial quantitative error. Obviation of these errors through appropriate use of the different models may improve performance of probabilistic models of DCS occurrence that express DCS risk in terms of simulated in vivo gas and bubble dynamics.

Cytokine mRNA levels in the hearts of inbred mice that develop different degrees of cardiomyopathy during infection with Trypanosoma cruzi.

Profiles of cytokine mRNA expression were examined by semiquantitative RT-PCR in the hearts of DBA/2 (pathopermissive) and B10.D2 (pathoresistant) mice during infection with the Brazil strain of Trypanosoma cruzi. The levels and time-course profiles of IFNgamma, IL-1beta and IL-10 mRNA expression were similar in each strain. TNFalpha, iNOs, and IL-13 mRNA expression peaked at comparable levels and times after infection in each strain, but declined more rapidly in B10.D2 than in DBA/2 mice. Peak IL-2 mRNA levels were also similar between the two strains, but occurred earlier in DBA/2 than in B10.D2 mice. Levels of IL-4, IL-6 and IL-12 mRNA were significantly higher in DBA/2 than in B10.D2 mice from day 10 through day 50 of infection. With the exception of IL-1beta, which was expressed constitutively in both strains, the levels of mRNA of all other cytokines examined reached their peak no later than day 20 and declined significantly by day 50 after infection. The inflammatory infiltrate paralleled the latter cytokines; starting at day 10 in DBA/2 mice and at day 15 in the B10.D2 s, peaking between days 20 and 30 in both strains, decreasing to minimal levels by day 50 in the pathoresistant mice, but maintaining a mild amount through day 70 in the pathopermissive strain. The inflammation was composed mostly of lymphocytes and histiocytes throughout the entire process. These data demonstrate differences in the profiles of cytokine mRNA that may be related to the differential degree of cardiac pathology that develops in these two strains of mice upon infection with T. cruzi.

Cytokine profiles during experimental Chagas' disease.

People infected with Trypanosoma cruzi remain so for life, yet only 30-40% of these individuals develop characteristic chagasic cardiomyopathies. Similarly, when infected with the Brazilian strain of T. cruzi, DBA/2 mice develop severe cardiac damage while B10.D2 mice do not. To better understand the immunological parameters that may be involved in the disease process, we have used this murine model (DBA/2 vs B10.D2) and compared the changes in cytokine production during the course of infection with T cruzi. Concanavalin A (Con A) stimulation of spleen cells harvested during the acute phase (day 30) resulted in similarly high levels of IFN-gamma in both mouse strains. However, the amount of IFN-gamma in supernatants from cultures of B10.D2 spleen cells initiated during the chronic phase (day 72) was at subacute levels, whereas secretion by chronic DBA/2 spleen cells remained high. In addition, Con A-stimulated spleen cells from acute DBA/2 mice produced approximately twice as much IL-10 and significantly more IL-4 than cells from B10.D2 mice. IL-4 secretion remained low by cells from chronic B10.D2 mice, but when using cells from chronic DBA/2 mice, levels continued to increase beyond the already high levels secreted by cells harvested during the acute phase. Proliferative responses to Con A stimulation by spleen cells from DBA/2 mice were significantly higher than those from B10.D2 mice in both the acute and chronic phases. These data suggest that enhanced responses in DBA/2 mice, which may be related to a higher parasite burden, a lack of down-regulation, and/or the onset of autoimmune phenomena, correlate with the more severe cardiomyopathy seen in pathopermissive mice.

Analysis of anti-Trypanosoma cruzi antibody isotype specificities by western blot in sera from patients with different forms of Chagas' disease.

Infection of humans with Trypanosoma cruzi leads to either a lifelong asymptomatic infection or to symptomatic presentations such as cardiomyopathy, mega-syndromes, or both. The reasons for the different clinical manifestations are not understood. We have previously studied a group of chronically infected individuals with different clinical forms of Chagas' disease and found that the levels of some anti-T. cruzi antibody isotypes, analyzed by enzyme-linked immunosorbent assay, differed among patients with different clinical presentations. We have expanded these studies to examine the antigen specificity of these patients' IgG1, 2, 3, IgM, and IgA by western blot. We observed that binding of particular antigens by some antibody isotypes were more prevalent in some clinical groups as compared to others. For example, IgG3 from 13 of 19 (68%) individuals with digestive manifestations bound a 68-kDa antigen, but only 3 of 31 (9%) individuals with cardiac involvement detected this same moiety. We also found that, regardless of the clinical group, the profiles of antigens recognized by each antibody isotype differs dramatically from the profiles recognized by each other isotype. Together with our previous observations demonstrating that the levels of anti-parasite antibody isotypes correlates with the clinical form, these data suggest that overall anti-T. cruzi antibody reactivities may indeed be skewed toward different antigens in individuals with different clinical presentations.

Role of metabolic gases in bubble formation during hypobaric exposures.

Our hypothesis is that metabolic gases play a role in the initial explosive growth phase of bubble formation during hypobaric exposures. Models that account for optimal internal tensions of dissolved gases to predict the probability of occurrence of venous gas emboli were statistically fitted to 426 hypobaric exposures from National Aeronautics and Space Administration tests. The presence of venous gas emboli in the pulmonary artery was detected with an ultrasound Doppler detector. The model fit and parameter estimation were done by using the statistical method of maximum likelihood. The analysis results were as follows. 1) For the model without an input of noninert dissolved gas tissue tension, the log likelihood (in absolute value) was 255.01. 2) When an additional parameter was added to the model to account for the dissolved noninert gas tissue tension, the log likelihood was 251.70. The significance of the additional parameter was established based on the likelihood ratio test (P < 0.012). 3) The parameter estimate for the dissolved noninert gas tissue tension participating in bubble formation was 19. 1 kPa (143 mmHg). 4) The additional gas tissue tension, supposedly due to noninert gases, did not show an exponential decay as a function of time during denitrogenation, but it remained constant. 5) The positive sign for this parameter term in the model is characteristic of an outward radial pressure of gases in the bubble. This analysis suggests that dissolved gases other than N2 in tissues may facilitate the initial explosive bubble-growth phase.

Evolved gas, pain, the power law, and probability of hypobaric decompression sickness.

The intensity of a pain-only decompression sickness (DCS) symptom with respect to time at altitude increases, peaks, and then declines in some cases. A similar pattern is also seen in a graph of the probability density function [f(t)] for DCS. The f(t) is the proportion of DCS per unit time with respect to time at altitude. The integration of f(t) with respect to time provides the cumulative probability of DCS [P(DCS)]. We suspect that the perceived intensity of pain with a given stimulus intensity is related to the P(DCS); it may be related to the intensity of the stimulus to a power (alpha). Our stimuli are defined as pressure ratio [PR = (phi P1N2/ P2)-11] or pressure difference [delta P = phi P1N2-P2], where phi P1N2 is the N2 partial pressure calculated in the 360 min half-time (t1/2) compartment or t1/2 is estimated with other parameters and P2 is ambient pressure after the ascent. Both stimuli represent a potential released volume of gas. We tested the null hypothesis that alpha > 1 was no better than alpha = 1 in PR alpha and delta P alpha in a log logistic survival analysis of 1085 exposures in hypobaric chambers. The log likelihood number increased from -1198 for alpha = 0 for the null model to -724 for PR alpha when alpha = 3.52 with a 42 min t1/2 and -714 for delta P alpha when alpha = 8.44 with a 91 min t1/2. We conclude that the improvement in our expressions for decompression dose with alpha > 1 is not by random chance and that alpha may link the physics of gas evolution to the biology of pain perception. Because of our empirical approach, we do not exclude other possible interpretations.

Information about venous gas emboli improves prediction of hypobaric decompression sickness.

HYPOTHESIS: Information about venous gas emboli (VGE) detected in the pulmonary artery such as the occurrence of VGE, Grade of VGE, the time when VGE first appear, and the time course of the Grade or occurrence of VGE, could be used to better assess the probability of decompression sickness [P(DCS)] in any hypobaric decompression. We hypothesized that these data would improve the estimate of P(DCS) since objective measurements of the decompression stress are available for the individual. METHODS: A binary correlation and survival analysis approach were used on information from 1,322 hypobaric chamber exposures to establish the relationships between VGE and DCS. RESULTS: Based on the correlation analysis, the absence of VGE is highly correlated with the absence of a DCS symptom, as evident from a negative predictive value of 0.98. However, the presence of VGE in the pulmonary artery is not highly correlated with a subsequent DCS symptom, as evident from a positive predictive value of 0.39 for Grades III and IV VGE. The correlation results suggest the presence of VGE in the pulmonary artery is a necessary, but not sufficient, condition for DCS. Based on the survival analysis, the log logistic survival model, a one-variable model with two parameters gave a log likelihood (LL) of -757. This model was expanded to include seven additional variables, including four about VGE, and the nine-parameter model gave a better LL of -481. CONCLUSION: Information about VGE plus other variables known to influence DCS is useful to better assess the P(DCS) for hypobaric decompressions.

A photograph-based study of the incidence of fatal truck underride crashes in Indiana.

Photographs were used to estimate the incidence of fatal crashes in which passenger vehicles underrode the fronts, sides and rears of large trucks in Indiana during 1993. The photographs were obtained for 98 of the 107 eligible fatal crashes between large trucks and passenger vehicles in 1993. A protocol was developed to judge the presence and extent of underride, the presence of intrusion into the passenger vehicle compartment, and the likelihood of death or serious injury if underride had been prevented. The incidence of fatal underride was compared with the incidence reported in the Fatality Analysis Reporting System (FARS), a census of fatal crashes on public roads in the U.S.A. For the same 107 fatal large truck-passenger vehicle crashes, the incidence of underride reported in FARS was much lower than in the photograph-based study: 6 versus 63%. Photographs contain details absent from police reports, the primary data source for FARS, and thus enable more complete identification of underride crashes. Preventing underride would have substantially reduced the likelihood of death or serious injury in ca 20% of the underride crashes.

Cytokine profiles during experimental Chagas' disease

People infected with Trypanosoma cruzi remain so for life, yet only 30-40 percent of these individuals develop characteristic chagasic cardiomyopathies. Similarly, when infected with the Brazilian strain of T. cruzi, DBA/2 mice develop severe cardiac damage while B10.D2 mice do not. To better understand the immunological parameters that may be involved in the disease process, we have used this murine model (DBA/2 vs B10.D2) and compared to changes in cytokine production during the course of infection with T. cruzi. Concanavalin A (Con A) stimulation of spleen cells harvested during the acute phase (day 30) resulted in similarly high levels of IFN-gamma in both mouse strains. However, the amount of IFN-gamma in supernatants from cultures of B10.D2 spleen cells initiated during the chronic phase (day 72) was at subacute levels, whereas secretion by chronic DBA/2 spleen cells remained high. In addition, Con A-stimulated spleen cells from acute DBA/2 mice produced approximately twice as much IL-10 and significantly more IL-4 than cells from B10.D2 mice. IL-4 secretion remained low by cells from chronic B10.D2 mice, but when using cells from chronic DBA/2 mice, levels continued to increase beyond the already high levels secreted by cells harvested during the acute phase. Proliferative responses to Con A stimulation by spleen cells from DBA/2 mice were significantly higher than those from B10.D2 mice in both the acute and chronic phases. These data suggest that enhanced responses in DBA/2 mice, which may be related to a higher parasite burden, a lack of down-regulation, and/or the onset of autoimmune phenomena, correlate with the more severe cardiomyopathy seen in pathopermissive mice.

Mice deficient for 5-lipoxygenase, but not leukocyte-type 12-lipoxygenase, display altered immune responses during infection with Schistosoma mansoni.

Periovular granuloma formation during Schistosoma mansoni infection is a complex, multifaceted immunologic response. Products of arachidonic acid metabolism have been shown to contribute to this response through studies in which general inhibitors of lipoxygenase function reduce granulomatous inflammation. To determine which lipoxygenases are important for granuloma development in schistosomiasis, wild type mice or mice deficient for 5-lipoxygenase (5-LO) or "leukocyte-type" 12-lipoxygenase (12-LO) were infected with S. mansoni and studied for responses to schistosome eggs and egg antigens. At the acute stage of infection, when granuloma formation is usually maximal, 5-LO deficient mice developed smaller granulomas around liver-deposited schistosome eggs compared with wild type or 12-LO deficient mice. 5-LO mice also displayed less antibody-mediated (5 h) and cell-mediated, delayed-type (24 h) hypersensitivity to schistosome egg antigens than did the other two infection groups. In an attempt to determine possible mechanisms for the reduced inflammatory responses, we also measured hepatic mRNA levels of cytokines that have been shown to influence granuloma size (IL-4, IL-10, and IFN-gamma). The mRNA levels for IL-10 were significantly lower in 5-LO-deficient mice, but SEA-stimulated spleen cells did not demonstrate a significant difference in IL-10 production between wild type and 5-LO mice. These data suggest that 5-LO plays a role in host responses to schistosomiasis via a mechanism that cannot be explained solely by changes in expression of these cytokines.