Daily artificial gravity partially mitigates vestibular processing changes associated with head-down tilt bedrest.

Microgravity alters vestibular signaling and reduces body loading, driving sensory reweighting. The unloading effects can be modelled using head-down tilt bedrest (HDT). Artificial gravity (AG) has been hypothesized to serve as an integrated countermeasure for the declines associated with HDT and spaceflight. Here, we examined the efficacy of 30 min of daily AG to counteract brain and behavior changes from 60 days of HDT. Two groups received 30 min of AG delivered via short-arm centrifuge daily (n = 8 per condition), either in one continuous bout, or in 6 bouts of 5 min. To improve statistical power, we combined these groups (AG; n = 16). Another group served as controls in HDT with no AG (CTRL; n = 8). We examined how HDT and AG affect vestibular processing by collecting fMRI scans during vestibular stimulation. We collected these data prior to, during, and post-HDT. We assessed brain activation initially in 12 regions of interest (ROIs) and then conducted an exploratory whole brain analysis. The AG group showed no changes in activation during vestibular stimulation in a cerebellar ROI, whereas the CTRL group showed decreased activation specific to HDT. Those that received AG and showed little pre- to post-HDT changes in left vestibular cortex activation had better post-HDT balance performance. Whole brain analyses identified increased pre- to during-HDT activation in CTRLs in the right precentral gyrus and right inferior frontal gyrus, whereas AG maintained pre-HDT activation levels. These results indicate that AG could mitigate activation changes in vestibular processing that is associated with better balance performance.

Sensory system-specific associations between brain structure and balance.

Nearly 75% of older adults in the US report balance problems. Although it is known that aging results in widespread brain atrophy, less is known about how brain structure relates to balance in aging. We collected T1- and diffusion-weighted MRI scans and measured postural sway of 36 young (18-34 years) and 22 older (66-84 years) adults during eyes open, eyes closed, eyes open-foam, and eyes closed-foam conditions. We calculated summary measures indicating visual, proprioceptive, and vestibular contributions to balance. Across both age groups, thinner cortex in multisensory integration regions was associated with greater reliance on visual inputs for balance. Greater gyrification within sensorimotor and parietal cortices was associated with greater reliance on proprioceptive inputs. Poorer vestibular function was correlated with thinner vestibular cortex, greater gyrification within sensorimotor, parietal, and frontal cortices, and lower free water-corrected axial diffusivity across the corona radiata and corpus callosum. These results expand scientific understanding of how individual differences in brain structure relate to balance and have implications for developing brain stimulation interventions to improve balance.

Brain and Behavioral Evidence for Reweighting of Vestibular Inputs with Long-Duration Spaceflight.

Microgravity alters vestibular signaling. In-flight adaptation to altered vestibular afferents is reflected in post-spaceflight aftereffects, evidenced by declines in vestibularly mediated behaviors (e.g., walking/standing balance), until readaptation to Earth's 1G environment occurs. Here we examine how spaceflight affects neural processing of applied vestibular stimulation. We used fMRI to measure brain activity in response to vestibular stimulation in 15 astronauts pre- and post-spaceflight. We also measured vestibularly-mediated behaviors, including balance, mobility, and rod-and-frame test performance. Data were collected twice preflight and four times postflight. As expected, vestibular stimulation at the preflight sessions elicited activation of the parietal opercular area ("vestibular cortex") and deactivation of somatosensory and visual cortices. Pre- to postflight, we found widespread reductions in this somatosensory and visual cortical deactivation, supporting sensory compensation and reweighting with spaceflight. These pre- to postflight changes in brain activity correlated with changes in eyes closed standing balance, and greater pre- to postflight reductions in deactivation of the visual cortices associated with less postflight balance decline. The observed brain changes recovered to baseline values by 3 months postflight. Together, these findings provide evidence for sensory reweighting and adaptive cortical neuroplasticity with spaceflight. These results have implications for better understanding compensation and adaptation to vestibular functional disruption.

Imaging of lymphatic dysplasia in Noonan syndrome: Case studies and historical atlas.

To determine the historical use and utility of various lymphatic imaging modalities in Noonan syndrome (NS) patients, we performed a comprehensive literature review by collecting the published medical imaging of NS lymphatic dysplasias. We correlated imaging findings with clinical phenotypes and treatment. Our analysis of lymphatic imaging modalities provides an algorithmic approach to imaging and patient care across the spectrum of NS developmental defects. A total of 54 NS cases have been published since 1975. Using the observations reported in 15 reviewed publications, an association was made between disruptions in central lymphatic flow and poor clinical presentations/outcomes in NS patients.

Microgravity effects on the human brain and behavior: Dysfunction and adaptive plasticity.

Emerging plans for travel to Mars and other deep space destinations make it critical for us to understand how spaceflight affects the human brain and behavior. Research over the past decade has demonstrated two co-occurring patterns of spaceflight effects on the brain and behavior: dysfunction and adaptive plasticity. Evidence indicates the spaceflight environment induces adverse effects on the brain, including intracranial fluid shifts, gray matter changes, and white matter declines. Past work also suggests that the spaceflight environment induces adaptive neural effects such as sensory reweighting and neural compensation. Here, we introduce a new conceptual framework to synthesize spaceflight effects on the brain, Spaceflight Perturbation Adaptation Coupled with Dysfunction (SPACeD). We review the literature implicating neurobehavioral dysfunction and adaptation in response to spaceflight and microgravity analogues, and we consider pre-, during-, and post-flight factors that may interact with these processes. We draw several instructive parallels with the aging literature which also suggests co-occurring neurobehavioral dysfunction and adaptive processes. We close with recommendations for future spaceflight research, including: 1) increased efforts to distinguish between dysfunctional versus adaptive effects by testing brain-behavioral correlations, and 2) greater focus on tracking recovery time courses.

Thoracic duct stent-graft decompression with 3-month patency: Revisiting a historical treatment option for portal hypertension.

This report introduces the rationale for thoracic duct stent-graft decompression in cirrhotic patients with portal hypertension and provides a case example with 3-month stentgraft patency. Thoracic duct flow and pressure are elevated in cirrhosis. Historically, complications of portal hypertension have been successfully treated with external drainage of the thoracic duct or surgical lymphovenous bypass. A 45-year-old woman with cirrhosis, chronic portosplenomesenteric thrombosis, and acute variceal hemorrhage underwent percutaneous thoracic duct stent-graft placement across the lymphovenous junction. The hemorrhage subsequently resolved and follow up endoscopy demonstrated decompression of the bleeding varices. Venography 40 days later demonstrated a partially patent stent-graft with fibrin sheath formation distally. The stent-graft was extended distally to the right atrium and was fully patent on venography 3 months later. The patient had no further episodes of hemorrhage.

Assessment of the efficacy of an autogenous vaccine against Yersinia pseudotuberculosis in young Merino sheep.

AIMS To assess the efficacy of an autogenous vaccine against Yersinia pseudotuberculosis III in preventing clinical disease and deaths due to yersiniosis in young Merino sheep, and to determine the effect of vaccination on the prevalence of faecal shedding of pathogenic Yersinia spp., daily liveweight gain, and development of antibodies to Yersinia spp. following vaccination and natural exposure. METHODS In six groups (three groups each from two farms) of young Merino sheep, 148-150 animals were systematically allocated to be vaccinated twice with an autogenous, formalin- killed bacterin vaccine containing Y. pseudotuberculosis serotype III or to remain non-vaccinated. All vaccinated and non-vaccinated sheep were run together in their original groups throughout the trial. Faecal and blood samples were collected, and liveweight measured, at the time of vaccination and subsequently over a 6-month period to determine faecal shedding of Y. enterocolitica and Y. pseudotuberculosis, seroprevalence of antibodies to Yersinia outer membrane proteins (YOP) and changes in liveweight. RESULTS None of the six trial groups experienced an outbreak of clinical yersiniosis during the study period. On Farm A, the prevalence of shedding of either or both Yersinia spp. was <40% on all but one sampling occasions. On Farm B the prevalence of shedding of both Yersinia spp. peaked at 98%, 96 days after vaccination. Mean liveweight and daily liveweight gain at the end of the study were similar in vaccinated and non-vaccinated groups on both farms (p>0.1), as was the prevalence of faecal shedding of Yersinia spp. (p>0.2), and the proportion of animals that became seropositive for antibodies to YOP following vaccination (p>0.1). CONCLUSIONS AND CLINICAL RELEVANCE This vaccine had, at most, limited effects on seroconversion and, under the conditions of this study, had no demonstrable impact on liveweight, mean daily liveweight gain or faecal shedding of Yersinia spp. Further studies are needed to determine the efficacy of this vaccine during outbreaks of yersiniosis or following experimental challenge with pathogenic Yersinia spp..

Outbreaks of diarrhoea ('winter scours') in weaned Merino sheep in south-eastern Australia.

OBJECTIVE: Identify the cause of outbreaks of diarrhoea during winter that are not attributable to gastrointestinal nematodes in weaned Merino sheep in the high rainfall regions of south-eastern Australia and determine the efficacy of antimicrobials used to treat this syndrome. METHODS: We investigated 45 outbreaks on 24 farms. Faecal samples from affected animals were cultured for Yersinia, Campylobacter and Salmonella spp. Risk factors, including rainfall, temperature and worm egg count (WEC), were assessed. Yersinia spp. were identified with molecular tests and susceptibility to four antimicrobials was determined. RESULTS: Yersinia pseudotuberculosis serotype III and virulent Y. enterocolitica were most frequently isolated. The frequency and severity of disease varied between region, farm and year. Yersinia pseudotuberculosis was detected only during winter, but Y. enterocolitica was present in all seasons. Pathogenic Yersinia species were more often isolated when WECs exceeded 500 eggs/g. A high proportion of Y. enterocolitica and Y. pseudotuberculosis were resistant to sulfafurazole (64% and 86.9%, respectively). CONCLUSIONS: A bacterial enteritis caused by pathogenic Yersinia was the cause of the winter scours syndrome in the 24 flocks investigated. The use of molecular testing increased the sensitivity of detection and identification of Yersinia spp. No clear association between weather, WEC and disease was established, suggesting complex interactions between risk factors are more important than any single factor. Sulfonamides should not be routinely used to treat this syndrome. Rather, during an outbreak the targeted use of an effective antimicrobial, such as oxytetracycline, should be integrated with grazing management strategies, including moving affected mobs onto lower risk pastures and decreasing the stocking rate.

A longitudinal study of faecal shedding of Yersinia enterocolitica and Yersinia pseudotuberculosis by Merino lambs in south-eastern Australia.

A prospective longitudinal study was conducted to investigate potential risk factors for faecal shedding of Yersinia enterocolitica and Y. pseudotuberculosis by Merino lambs in four flocks in south-eastern Australia. The primary aims of the study were to determine the seasonal patterns of shedding of pathogenic Y. enterocolitica and Y. pseudotuberculosis, and to evaluate putative risk factors for faecal shedding of these organisms, including worm egg count, live-weight and growth rate. The risk of shedding varied markedly between Yersinia spp., farms, seasons and years. Shedding of Y. pseudotuberculosis occurred predominately in winter, whereas Y. enterocolitica was commonly isolated from faeces throughout the year. Moderate to high prevalences of shedding of each organism occurred in the absence of outbreaks of yersiniosis. In general, for shedding of Y. pseudotuberculosis, animals with moderate or high worm egg counts were at increased risk of shedding compared with animals with low worm egg counts. Sheep with higher average daily weight gains were at decreased risk of shedding Y. enterocolitica but at increased risk of shedding Y. pseudotuberculosis. Live-weight was not significantly associated with risk of shedding either species. This study highlighted that exposure to determinants of shedding Y. enterocolitica and Y. pseudotuberculosis differ between farms and over time within farms. Shedding is likely influenced by environmental, animal and management factors. Our results indicate that different or additional risk factors are required for yersiniosis over those that cause faecal shedding of Yersinia spp., because moderate to high prevalences of shedding were not always associated with outbreaks of clinical disease.

Predictors and correlates for weight changes in patients co-treated with olanzapine and weight mitigating agents; a post-hoc analysis.

BACKGROUND: This study focuses on exploring the relationship between changes in appetite or eating behaviors and subsequent weight change for adult patients with schizophrenia or bipolar disorder treated with olanzapine and adjunctive potential weight mitigating pharmacotherapy. The aim is not to compare different weight mitigating agents, but to evaluate patients' characteristics and changes in their eating behaviors during treatment. Identification of patient subgroups with different degrees of susceptibility to the effect of weight mitigating agents during olanzapine treatment may aid clinicians in treatment decisions. METHODS: Data were obtained from 3 randomized, double-blind, placebo-controlled, 16-week clinical trials. Included were 158 patients with schizophrenia or bipolar disorder and a body mass index (BMI) > or = 25 kg/m2 who had received olanzapine treatment in combination with nizatidine (n = 68), sibutramine (n = 42), or amantadine (n = 48). Individual patients were analyzed for categorical weight loss > or= 2 kg and weight gain > or = 1 kg. Variables that were evaluated as potential predictors of weight outcomes included baseline patient characteristics, factors of the Eating Inventory, individual items of the Eating Behavior Assessment, and the Visual Analog Scale. RESULTS: Predictors/correlates of weight loss > or = 2 kg included: high baseline BMI, low baseline interest in food, and a decrease from baseline to endpoint in appetite, hunger, or cravings for carbohydrates. Reduced cognitive restraint, increase in hunger, and increased overeating were associated with a higher probability of weight gain > or = 1 kg. CONCLUSION: The association between weight gain and lack of cognitive restraint in the presence of increased appetite suggests potential benefit of psychoeducational counseling in conjunction with adjunctive pharmacotherapeutic agents in limiting weight gain during antipsychotic drug therapy. TRIAL REGISTRATION: This analysis was not a clinical trial and did not involve any medical intervention.

Rapid 20th-century increase in coastal upwelling off northwest Africa.

Near-shore waters along the northwest African margin are characterized by coastal upwelling and represent one of the world's major upwelling regions. Sea surface temperature (SST) records from Moroccan sediment cores, extending back 2500 years, reveal anomalous and unprecedented cooling during the 20th century, which is consistent with increased upwelling. Upwelling-driven SSTs also vary out of phase with millennial-scale changes in Northern Hemisphere temperature anomalies (NHTAs) and show relatively warm conditions during the Little Ice Age and relatively cool conditions during the Medieval Warm Period. Together, these results suggest that coastal upwelling varies with NHTAs and that upwelling off northwest Africa may continue to intensify as global warming and atmospheric CO2 levels increase.

A preliminary study of possible genetic influences on the susceptibility of sheep to Johne's disease.

OBJECTIVE: To investigate possible genetic influences on susceptibility or resistance of sheep to Johne's disease. DESIGN: A field and laboratory study of two fine-wool Merino flocks with a high prevalence of disease due to Mycobacterium avium subsp paratuberculosis infection. PROCEDURE: Adult sheep were phenotypically classified as having severe, mild or no disease on the basis of clinical, pathological and cultural tests for paratuberculosis, and as positive or negative in tests for humoral immunity (agar gel immunodiffusion test) or cell mediated immunity (skin test for delayed type hypersensitivity). Correlations with phenotype were sought for polymorphisms at loci within selected immune function genes (NRAMP, MHC complex, IFN-gamma, lysozyme, leukaemia inhibiting factor). RESULTS: Possible associations of particular NRAMP and MHC alleles with susceptibility or resistance to Johne's disease were detected. CONCLUSION: If the results of this preliminary study are confirmed in further work, then the use of rams with "resistant" genotypes may assist in the control of Johne's disease in infected flocks.

Intrauterine and transmammary transmission of Mycobacterium avium subsp paratuberculosis in sheep.

OBJECTIVE: To investigate intrauterine infection of foetuses with Mycobacterium avium subsp paratuberculosis and the presence of infection in mammary secretions of sheep. DESIGN: A study of 142 late-pregnant ewes and their foetuses from two heavily infected flocks. PROCEDURE: Infection of ewes was determined at necropsy by histopathology and culture of tissues and mammary secretions. Antemortem tests (clinical assessment, faecal culture and serology) were also applied. Foetuses from 59 infected ewes and 47 apparently uninfected ewes were examined by culture and histopathology. RESULTS: Five of five ewes with clinical ovine Johne's disease had infected foetuses. Only one of 54 subclinically affected ewes, and none of 47 uninfected ewes had an infected foetus. M a paratuberculosis was cultured from mammary secretions or mammary glands of only two of 76 ewes, both of which were clinical cases and had infected foetuses. CONCLUSION: Although intrauterine or transmammary transmission of Mycobacterium avium subsp paratuberculosis may occur frequently in clinically affected sheep, these are less common in subclinically infected ewes. Therefore these modes of transmission are unlikely to compromise existing control programs for ovine Johne's disease on most farms, especially if programs include the immediate culling of clinically affected sheep.

Field evaluation of tracer sheep for the detection of early natural infection with Mycobacterium avium subsp paratuberculosis.

OBJECTIVE: To determine whether tracer sheep could be used to detect S strain Mycobacterium avium subsp paratuberculosis on pasture, and to provide further insight into the early stages of infection. DESIGN: A field study on two farms in an endemic area for ovine Johne's disease in New South Wales. Procedure Lambs, weaners and adult ewes were introduced to pasture with varying amounts of M. a. paratuberculosis contamination and monitored using skin tests, gamma interferon assay, faecal culture and serial necropsy of small groups for up to 15 months after first exposure. RESULTS: Culture from tissues was the most sensitive method for detecting early infection in sheep after natural exposure to S strain M. a. paratuberculosis. The organism was detected in at least one introduced sheep from every exposed group, 6 to 12 months after first exposure. Histopathological lesions were detected in only 17% of culture-positive sheep, and only after at least 8 months of exposure. Similarly, antemortem diagnostic tests had low sensitivity during the early stages of naturally acquired infection. There was no evidence of any differences in infection rate between sheep first exposed as neonates, as weaners or as adults. A higher proportion of lambs born to ewes from an infected flock were infected than lambs suckling uninfected ewes introduced to the same infected environment, and infection was detected earlier in these 'resident' lambs. CONCLUSION: These findings indicate that groups of unexposed 'tracer' sheep, tested by culture of tissues at slaughter 6 to 12 months after first exposure, might be a useful way to assess pasture infectivity in control programs for ovine Johne's disease.

A 2 X 2 achievement goal framework.

A 2 x 2 achievement goal framework comprising mastery-approach, mastery-avoidance, performance-approach, and performance-avoidance goals was proposed and tested in 3 studies. Factor analytic results supported the independence of the 4 achievement goal constructs. The goals were examined with respect to several important antecedents (e.g., motive dispositions, implicit theories, socialization histories) and consequences (e.g., anticipatory test anxiety, exam performance, health center visits), with particular attention allocated to the new mastery-avoidance goal construct. The results revealed distinct empirical profiles for each of the achievement goals; the pattern for mastery-avoidance goals was, as anticipated, more negative than that for mastery-approach goals and more positive than that for performance-avoidance goals. Implications of the present work for future theoretical development in the achievement goal literature are discussed.

Postmenopausal bleeding: a practical approach.

PURPOSE: To provide nurse practitioners (NPs) with a practical approach for the management of postmenopausal bleeding in office settings. DATA SOURCES: Selected scientific literature and the author's own experience. CONCLUSIONS: Postmenopausal bleeding should be considered cancer until proven otherwise, despite the fact that abnormal pathology is found in only 15% of endometrial biopsies. IMPLICATIONS FOR PRACTICE: Post menopausal bleeding can be safely evaluated and managed by NPs using aspiration endometrial biopsies and/or transvaginal ultrasound. Hospitalization for dilation and curettage under anaesthesia can often be avoided.

Extrinsic value orientation and "the tragedy of the commons".

Two studies examined the effect of Extrinsic Value Orientation (Kasser & Ryan, 1993, 1996) upon harvesting strategies and personal profit within commons dilemmas, in which individual and group interests can be at odds. At an individual or within-group level of analysis, extrinsically oriented persons (who value money, fame, and popularity) harvested more than intrinsically oriented persons (who value self-acceptance, intimacy, and community). However, a counteracting group-level effect was found such that groups with a greater number of extrinsic members harvested less on average than did groups with more intrinsic members, because their commons did not last as long. As a result, even excessive harvesters within extrinsic groups did no better than did self-restrained harvesters within intrinsic groups. Supplementary analyses indicate that extrinsic values are associated with acquisitiveness regarding resources, more so than apprehension regarding others' acquisitiveness.

Chronic prenatal exposure to carbon monoxide results in a reduction in tyrosine hydroxylase-immunoreactivity and an increase in choline acetyltransferase-immunoreactivity in the fetal medulla: implications for Sudden Infant Death Syndrome.

Maternal cigarette smoking during pregnancy is associated with a significantly increased risk of Sudden Infant Death Syndrome (SIDS). This study investigated the effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, on the neuroglial and neurochemical development of the medulla in the fetal guinea pig. Pregnant guinea pigs were exposed to 200 p.p.m CO for 10 h per day from day 23-25 of gestation (term = 68 days) until day 61-63, at which time fetuses were removed and brains collected for analysis. Using immunohistochemistry and quantitative image analysis, examination of the medulla of CO-exposed fetuses revealed a significant decrease in tyrosine hydroxylase-immunoreactivity (TH-IR) in the nucleus tractus solitarius, dorsal motor nucleus of the vagus (DMV), area postrema, intermediate reticular nucleus, and the ventrolateral medulla (VLM), and a significant increase in choline acetyltransferase-immunoreactivity (ChAT-IR) in the DMV and hypoglossal nucleus compared with controls. There was no difference between groups in immunoreactivity for the m2 muscarinic acetylcholine receptor, substance P- or met-enkephalin in any of the medullary nuclei examined, nor was there evidence of reactive astrogliosis. The results show that prenatal exposure to CO affects cholinergic and catecholaminergic pathways in the medulla of the guinea pig fetus, particularly in cardiorespiratory centers, regions thought to be compromised in SIDS.

Exposure to prenatal carbon monoxide and postnatal hyperthermia: short and long-term effects on neurochemicals and neuroglia in the developing brain.

The effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, was studied alone or in combination with postnatal hyperthermia, on the structural and neurochemical development of the postnatal brain at 1 and 8 weeks. Pregnant guinea pigs (n = 11) were exposed to 200 p.p.m CO for 10 h/day from midgestation until term (68 days), whereas control mothers (n = 10) breathed room air. On postnatal day 4, neonates from the control and CO-exposed pregnancies were exposed to hyperthermia (35 degrees C) for 75 min or remained at ambient (23 degrees C) temperature. Using semiquantitative immunohistochemical techniques the following neurotransmitter alterations were found in the medulla at 1 week: a decrease in met-enkephalin-immunoreactivity (IR) following postnatal hyperthermia and an increase in 5-hydroxytryptamine-IR following a combination of CO and hyperthermia. No alterations were observed in substance P- or tyrosine-hydroxylase-IR in any paradigm. At 8 weeks of age the combination of prenatal CO exposure followed by a brief hyperthermic stress postnatally resulted in lesions throughout the brain and an increase in glial fibrillary acidic protein-IR in the medulla. Such effects on brain development could be of relevance in cardiorespiratory control in the neonate and could have implications for the etiology of Sudden Infant Death Syndrome, where smoking and hyperthermia are major risk factors.