Inflammatory responses to induced infectious endometritis in mares resistant or susceptible to persistent endometritis

BACKGROUND: The objective of the study was to evaluate the gene expression of inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-α, IL-1 receptor antagonist [ra] and serum amyloid A (SAA) in endometrial tissue and circulating leukocytes in response to uterine inoculation of 105 colony forming units (CFU) Escherichia coli in mares. Before inoculation, mares were classified as resistant or susceptible to persistent endometritis based on their uterine inflammatory response to infusion of 109 killed spermatozoa and histological assessment of the endometrial quality. Endometrial biopsies were obtained 3, 12, 24 and 72 hours (h) after bacterial inoculation and blood samples were obtained during the 7 day period post bacterial inoculation. Expression levels of cytokines and SAA were determined by quantitative real-time reverse transcriptase PCR (qRT-PCR). RESULTS: Compared to levels in a control biopsy (obtained in the subsequent estrous), resistant mares showed an up-regulation of IL-1β, IL-6, IL-8 and TNF-α at 3 h after E. coli inoculation, while susceptible mares showed increased gene expression of IL-6 and IL-1ra. Susceptible mares had a significant lower gene expression of TNF-α,IL-6 and increased expression of IL-1ra 3 h after E. coli inoculation compared to resistant mares. Susceptible mares showed a sustained and prolonged inflammatory response with increased gene expression levels of IL-1β, IL-8, IL-1ra and IL-1β:IL-1ra ratio throughout the entire study period (72 h), whereas levels in resistant mares returned to estrous control levels by 12 hours. Endometrial mRNA transcripts of IL-1β and IL-1ra were significantly higher in mares with heavy uterine bacterial growth compared to mares with no/mild growth.All blood parameters were unaffected by intrauterine E. coli infusion, except for a lower gene expression of IL-10 at 168 h and an increased expression of IL-1ra at 48 h observed in susceptible mares compared to resistant mares. CONCLUSIONS: The current investigation suggests that endometrial mRNA transcripts of pro-inflammatory cytokines in response to endometritis are finely regulated in resistant mares, with initial high expression levels followed by normalization within a short period of time. Susceptible mares had a prolonged expression of pro-inflammatory cytokines, supporting the hypothesis that an unbalanced endometrial gene expression of inflammatory cytokines might play an important role in the pathogenesis of persistent endometritis

Gene Sequencing-Based Analysis of Microbial-Mat Morphotypes, Caicos Platform, British West Indies

Active carbonate platforms provide modern analogs to study microbial-mat development and taphonomy in the sedimentary record. Microbial-mat descriptions and classifications for tropical tidal-flat environments have focused predominantly on morphological observations. This is exemplified by flat and biscuit-shaped mats, where the mat morphotypes are postulated to reflect different Cyanobacteria communities as the main mat-building taxa. To compare the total microbial communities of these two mat types and test this Cyanobacteria hypothesis, we applied optical microscopy and gene sequencing methods using samples from a tidal algal marsh on Little Ambergris Cay, Turks and Caicos, B.W.I. With gene sequencing we find that total diversity and community composition differs significantly between morphotypes; the biscuit mat is more diverse than the flat mat. Microscopy results support that Cyanobacteria populations colonizing the surface layer of these two mat types are responsible for much of the mat's structural elements; however, genetic data find the Cyanobacteria population is indistinguishable between the two mat types. The recovered Cyanobacteria populations fall predominantly into three taxa: Scytonema, Halomicronema, and Crinalium. We propose that the morphology of these two mat types is not controlled by the Cyanobacteria, but instead reflects a time-integrated microbial response to environmental factors, where the microbial community becomes more diverse with time since environmental disturbance

Behavioural responses of non-breeding waterbirds to marine traffic in the near-shore environment

Capsule: Recording of behavioural responses to ferry traffic for 11 target species showed that Red-throated Diver Gavia stellata, Slavonian Grebe Podiceps auratus, and Black-throated Diver Gavia arctica were most likely to react to passing vessels. Aim: To provide information on how responses to marine traffic vary between waterbird species to inform marine spatial planning and environmental impact assessments in the near-shore environment. Methods: We recorded behavioural responses to ferry traffic for 11 target species in near-shore waters: Common Eider Somateria mollissima, Goldeneye Bucephala clangula, Long-tailed Duck Clangula hyemalis, Velvet Scoter Melanitta fusca, Red-breasted Merganser Mergus serrator, Black-throated Diver, Great Northern Diver Gavia immer, Red-throated Diver, European Shag Gulosus aristotelis, Slavonian Grebe and Black Guillemot Cepphus grylle. Responses were analysed using generalized linear models and mixed models. Results: Red-throated Diver, Black-throated Diver and Slavonian Grebe were the most likely species to exhibit a response to passing vessels. While Red-throated Divers and Slavonian Grebes were highly likely to flush, Black-throated Divers and Great Northern Divers rarely took flight, instead favouring swim or dive responses. In rougher sea conditions birds were more likely to take flight, and the propensity to respond declined across the wintering period. Conclusions: This research provides comparative evidence on the behavioural responses of waterbirds to marine traffic. The results support previous studies which highlighted the high sensitivity of diver species to disturbance and provide new evidence that Slavonian Grebe may also be a high sensitivity species

Altered sense of humor in dementia.

Sense of humor is potentially relevant to social functioning in dementias, but has been little studied in these diseases. We designed a semi-structured informant questionnaire to assess humor behavior and preferences in patients with behavioral variant frontotemporal dementia (bvFTD; n = 15), semantic dementia (SD; n = 7), progressive nonfluent aphasia (PNFA; n = 10), and Alzheimer's disease (AD; n = 16) versus healthy age-matched individuals (n = 21). Altered (including frankly inappropriate) humor responses were significantly more frequent in bvFTD and SD (all patients) than PNFA or AD (around 40% of patients). All patient groups liked satirical and absurdist comedy significantly less than did healthy controls. This pattern was reported premorbidly for satirical comedy in bvFTD, PNFA, and AD. Liking for slapstick comedy did not differ between groups. Altered sense of humor is particularly salient in bvFTD and SD, but also frequent in AD and PNFA. Humor may be a sensitive probe of social cognitive impairment in dementia, with diagnostic, biomarker and social implications

Active Ooid Growth Driven By Sediment Transport in a High-Energy Shoal, Little Ambergris Cay, Turks and Caicos Islands

Ooids are a common component of carbonate successions of all ages and present significant potential as paleoenvironmental proxies, if the mechanisms that control their formation and growth can be understood quantitatively. There are a number of hypotheses about the controls on ooid growth, each offering different ideas on where and how ooids accrete and what role, if any, sediment transport and abrasion might play. These hypotheses have not been well tested in the field, largely due to the inherent challenges of tracking individual grains over long timescales. This study presents a detailed field test of ooid-growth hypotheses on Little Ambergris Cay in the Turks and Caicos Islands, British Overseas Territories. This field site is characterized by westward net sediment transport from waves driven by persistent easterly trade winds. This configuration makes it possible to track changes in ooid properties along their transport path as a proxy for changes in time. Ooid size, shape, and radiocarbon age were compared along this path to determine in which environments ooids are growing or abrading. Ooid surface textures, petrographic fabrics, stable-isotope compositions (δ^(13)C, δ^(18)O, and δ^(34)S), lipid geochemistry, and genetic data were compared to characterize mechanisms of precipitation and degradation and to determine the relative contributions of abiotic (e.g., abiotic precipitation, physical abrasion) and biologically influenced processes (e.g., biologically mediated precipitation, fabric destruction through microbial microboring and micritization) to grain size and character. A convergence of evidence shows that active ooid growth occurs along the transport path in a high-energy shoal environment characterized by frequent suspended-load transport: median ooid size increases by more than 100 μm and bulk radiocarbon ages decrease by 360 yr westward along the ∼ 20 km length of the shoal crest. Lipid and 16S rRNA data highlight a spatial disconnect between the environments with the most extensive biofilm colonization and environments with active ooid growth. Stable-isotope compositions are indistinguishable among samples, and are consistent with abiotic precipitation of aragonite from seawater. Westward increases in ooid sphericity and the abundance of well-polished ooids illustrate that ooids experience subequal amounts of growth and abrasion—in favor of net growth—as they are transported along the shoal crest. Overall, these results demonstrate that, in the Ambergris system, the mechanism of ooid growth is dominantly abiotic and the loci of ooid growth is determined by both carbonate saturation and sediment transport mode. Microbes play a largely destructive, rather than constructive, role in ooid size and fabric

Gene Sequencing-Based Analysis of Microbial-Mat Morphotypes, Caicos Platform, British West Indies

Active carbonate platforms provide modern analogs to study microbial-mat development and taphonomy in the sedimentary record. Microbial-mat descriptions and classifications for tropical tidal-flat environments have focused predominantly on morphological observations. This is exemplified by flat and biscuit-shaped mats, where the mat morphotypes are postulated to reflect different Cyanobacteria communities as the main mat-building taxa. To compare the total microbial communities of these two mat types and test this Cyanobacteria hypothesis, we applied optical microscopy and gene sequencing methods using samples from a tidal algal marsh on Little Ambergris Cay, Turks and Caicos, B.W.I. With gene sequencing we find that total diversity and community composition differs significantly between morphotypes; the biscuit mat is more diverse than the flat mat. Microscopy results support that Cyanobacteria populations colonizing the surface layer of these two mat types are responsible for much of the mat's structural elements; however, genetic data find the Cyanobacteria population is indistinguishable between the two mat types. The recovered Cyanobacteria populations fall predominantly into three taxa: Scytonema, Halomicronema, and Crinalium. We propose that the morphology of these two mat types is not controlled by the Cyanobacteria, but instead reflects a time-integrated microbial response to environmental factors, where the microbial community becomes more diverse with time since environmental disturbance

Design choices for observational studies of the effect of exposure on disease incidence.

The purpose of this paper is to help readers choose an appropriate observational study design for measuring an association between an exposure and disease incidence. We discuss cohort studies, sub-samples from cohorts (case-cohort and nested case-control designs), and population-based or hospital-based case-control studies. Appropriate study design is the foundation of a scientifically valid observational study. Mistakes in design are often irremediable. Key steps are understanding the scientific aims of the study and what is required to achieve them. Some designs will not yield the information required to realise the aims. The choice of design also depends on the availability of source populations and resources. Choosing an appropriate design requires balancing the pros and cons of various designs in view of study aims and practical constraints. We compare various cohort and case-control designs to estimate the effect of an exposure on disease incidence and mention how certain design features can reduce threats to study validity

Mind the Gap: Investigating Toddlers’ Sensitivity to Contact Relations in Predictive Events

Toddlers readily learn predictive relations between events (e.g., that event A predicts event B). However, they intervene on A to try to cause B only in a few contexts: When a dispositional agent initiates the event or when the event is described with causal language. The current studies look at whether toddlers’ failures are due merely to the difficulty of initiating interventions or to more general constraints on the kinds of events they represent as causal. Toddlers saw a block slide towards a base, but an occluder prevented them from seeing whether the block contacted the base; after the block disappeared behind the occluder, a toy connected to the base did or did not activate. We hypothesized that if toddlers construed the events as causal, they would be sensitive to the contact relations between the participants in the predictive event. In Experiment 1, the block either moved spontaneously (no dispositional agent) or emerged already in motion (a dispositional agent was potentially present). Toddlers were sensitive to the contact relations only when a dispositional agent was potentially present. Experiment 2 confirmed that toddlers inferred a hidden agent was present when the block emerged in motion. In Experiment 3, the block moved spontaneously, but the events were described either with non-causal (“here’s my block”) or causal (“the block can make it go”) language. Toddlers were sensitive to the contact relations only when given causal language. These findings suggest that dispositional agency and causal language facilitate toddlers’ ability to represent causal relationships.John Templeton Foundation (#12667)James S. McDonnell Foundation (Causal Learning Collaborative Initiative)National Science Foundation (U.S.) (Career Award (# 0744213

Prediction of Breast Cancer-Related Lymphedema By Dermal Backflow Detected With Near-infrared Fluorescence Lymphatic Imaging

PURPOSE: Mild breast cancer-related lymphedema (BCRL) is clinically diagnosed as a 5%-10% increase in arm volume, typically measured no earlier than 3-6 months after locoregional treatment. Early BCRL treatment is associated with better outcomes, yet amid increasing evidence that lymphedema exists in a latent form, treatment is typically delayed until arm swelling is obvious. In this study, we investigated whether near-infrared fluorescence lymphatic imaging (NIRF-LI) surveillance could characterize early onset of peripheral lymphatic dysfunction as a predictor of BCRL. METHODS: In a prospective, longitudinal cohort/observational study (NCT02949726), subjects with locally advanced breast cancer who received axillary lymph node dissection and regional nodal radiotherapy (RT) were followed serially, between 2016 and 2021, before surgery, 4-8 weeks after surgery, and 6, 12, and 18 months after RT. Arm volume was measured by perometry, and lymphatic (dys) function was assessed by NIRF-LI. RESULTS: By 18 months after RT, 30 of 42 study subjects (71%) developed mild-moderate BCRL (i.e., ≥ 5% arm swelling relative to baseline), all manifested by dermal backflow of lymph into lymphatic capillaries or interstitial spaces. Dermal backflow had an 83% positive predictive value and 86% negative predictive value for BCRL, with a sensitivity of 97%, specificity of 50%, accuracy of 83%, positive likelihood ratio of 1.93, negative likelihood ratio of 0.07, and odds ratio of 29.00. Dermal backflow appeared on average 8.3 months, but up to 23 months, before the onset of mild BCRL. CONCLUSION: BCRL can be predicted by dermal backflow, which often appears months before arm swelling, enabling early treatment before the onset of edema and irreversible tissue changes

The population approach to falls injury prevention in older people: findings of a two community trial

<p>Abstract</p> <p>Background</p> <p>There is a sound rationale for the population-based approach to falls injury prevention but there is currently insufficient evidence to advise governments and communities on how they can use population-based strategies to achieve desired reductions in the burden of falls-related injury. The aim of the study was to quantify the effectiveness of a streamlined (and thus potentially sustainable and cost-effective), population-based, multi-factorial falls injury prevention program for people over 60 years of age.</p> <p>Methods</p> <p>Population-based falls-prevention interventions were conducted at two geographically-defined and separate Australian sites: Wide Bay, Queensland, and Northern Rivers, NSW. Changes in the prevalence of key risk factors and changes in rates of injury outcomes within each community were compared before and after program implementation and changes in rates of injury outcomes in each community were also compared with the rates in their respective States.</p> <p>Results</p> <p>The interventions in neither community substantially decreased the rate of falls-related injury among people aged 60 years or older, although there was some evidence of reductions in occurrence of multiple falls reported by women. In addition, there was some indication of improvements in fall-related risk factors, but the magnitudes were generally modest.</p> <p>Conclusions</p> <p>The evidence suggests that low intensity population-based falls prevention programs may not be as effective as those that are intensively implemented.</p