Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia.

Sepsis is a life-threatening state that arises due to a hyperactive inflammatory response stimulated by infection and rarely other insults (e.g., non-infections tissue injury). Although changes in several proinflammatory cytokines and signals are documented in humans and small animal models, far less is known about responses within affected tissues of large animal models. We sought to understand the changes that occur during the initial stages of inflammation by administering intravenous lipopolysaccharide (LPS) to Yorkshire pigs and assessing transcriptomic alterations in the brain, kidney, and whole blood. Robust transcriptional alterations were found in the brain, with upregulated responses enriched in inflammatory pathways and downregulated responses enriched in tight junction and blood vessel functions. Comparison of the inflammatory response in the pig brain to a similar mouse model demonstrated some overlapping changes but also numerous differences, including oppositely dysregulated genes between species. Substantial changes also occurred in the kidneys following LPS with several enriched upregulated pathways (cytokines, lipids, unfolded protein response, etc.) and downregulated gene sets (tube morphogenesis, glomerulus development, GTPase signal transduction, etc.). We also found significant dysregulation of genes in whole blood that fell into several gene ontology categories (cytokines, cell cycle, neutrophil degranulation, etc.). We observed a strong correlation between the brain and kidney responses, with significantly shared upregulated pathways (cytokine signaling, cell death, VEGFA pathways) and downregulated pathways (vasculature and RAC1 GTPases). In summary, we have identified a core set of shared genes and pathways in a pig model of systemic inflammation.

Tonic Serotonin Measurements In Vivo Using N-Shaped Multiple Cyclic Square Wave Voltammetry.

Here, we present the development of a novel voltammetric technique, N-shaped multiple cyclic square wave voltammetry (N-MCSWV) and its application in vivo. It allows quantitative measurements of tonic extracellular levels of serotonin in vivo with mitigated fouling effects. N-MCSWV enriches the electrochemical information by generating high dimensional voltammograms, which enables high sensitivity and selectivity against 5-hydroindoleacetic acid (5-HIAA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), histamine, ascorbic acid, norepinephrine, adenosine, and pH. Using N-MCSWV, in combination with PEDOT:Nafion-coated carbon fiber microelectrodes, a tonic serotonin concentration of 52 ± 5.8 nM (n = 20 rats, ±SEM) was determined in the substantia nigra pars reticulata of urethane-anesthetized rats. Pharmacological challenges with dopaminergic, noradrenergic, and serotonergic synaptic reuptake inhibitors supported the ability of N-MCSWV to selectively detect tonic serotonin levels in vivo. Overall, N-MCSWV is a novel voltammetric technique for analytical quantification of serotonin. It offers continuous monitoring of changes in tonic serotonin concentrations in the brain to further our understanding of the role of serotonin in normal behaviors and psychiatric disorders.

Bubble bilevel ventilation facilitates gas exchange in anesthetized rabbits.

BACKGROUND: Bubble continuous positive airway pressure is an established therapy for infants in respiratory distress. In resource-limited settings, few treatment options exist for infants requiring further respiratory support. A bubble bilevel device has been developed to provide nonelectric, time-cycled, pressure-limited respiratory support. We compared the efficacy of bubble bilevel ventilation with conventional mechanical ventilation in sedated rabbits. METHODS: Six adult rabbits under inhaled isoflurane general anesthesia were ventilated by alternating intervals of conventional and bubble bilevel ventilation for three 10-15-min periods. During each period, interval arterial blood gas (ABG) measurements were obtained after at least 10 min on the respective mode of ventilation. RESULTS: The bubble bilevel system was able to deliver the following pressures: 20/7, 15/5, 12/5, 8/5 cm H2O. The estimated differences in arterial blood gas values on bubble bilevel vs. ventilator were as follows (normalized values): pH 7.41 vs. 7.40, pCO2 37.7 vs. 40, pO2 97.6 vs. 80. In addition, the bubble bilevel ventilation delivered consistent pressure waveforms without interruption for over 60 min on two rabbits. CONCLUSION: This study demonstrates promising in vivo results on the efficacy of a novel bubble bilevel device, which may prove useful for infants in respiratory distress. IMPACT: Given the lack of personnel, funds or infrastructure to provide neonatal mechanical ventilation in resource-limited settings, additional low-cost, low-tech treatments are necessary to save infant lives. Bubble bilevel ventilation reliably delivers two levels of airway pressure to anesthetized rabbits resulting in normalization of blood gases comparable to those achieved on a traditional ventilator. If proven effective, simple technologies like this device have the potential to significantly impact neonatal mortality due to respiratory distress globally.

Radiological-pathological correlation of negative CT biopsy results enables high negative predictive value for thoracic malignancy.

AIM: To evaluate multidisciplinary team (MDT) practice of radiological-pathological correlation of non-malignant biopsy results to examine the additive effect on the predictive values of computed tomography (CT) biopsy for malignancy and their subsequent management and outcomes. MATERIALS AND METHODS: A service evaluation of the MDT management of non-malignant lung biopsy results (May 2014- May 2017) was undertaken. RESULTS: Sixty patients had a non-malignant diagnosis on initial CT biopsy. Five patients were lost to follow-up leaving 55 in the final cohort. Forty-eight of the 55 patients had biopsy results classified as potentially non-specific, of which 26 were classified as concordant with radiology (e.g., organising pneumonia with compatible CT features), and 22 were classified as discordant (e.g., non-specific inflammation and yet sufficiently suspicious CT features). Patients with concordant negative pathology showed resolution (n=19) or stability (n=6) on imaging follow-up. One lesion demonstrated growth and was proven malignant on surgical resection. Discordant lesions were managed with repeat biopsy (n=8) or surgical resection (n=13), with 12 final benign diagnoses and nine malignancies. The negative predictive value of CT biopsy alone was 44/55 (80%), following repeat biopsy was 44/50 (88%), and following radiological-pathological assessment was 32/33 (97%). No patients underwent a shift in stage from time of biopsy to resection. CONCLUSION: Combining radiological-pathological interpretation of negative biopsy results offers superior negative predictive value for lung malignancy without delayed diagnosis of lung cancer.

Pathology of grey seals Halichoerus grypus in southwest England including pups in early rehabilitation.

Few investigations have examined the pathology of grey seals Halichoerus grypus in southwest England, where it is the most abundant marine mammal. Here, primary pathological findings are presented from 107 post-mortem examinations of grey seals in southwest England between 2013 and 2020. Over three-quarters were pups in their first year of life; the origins of the carcasses reflected the known breeding season and breeding sites of grey seals in the region. Trauma was the most common primary pathological finding (n = 49), followed by infectious disease (n = 36). Traumatic findings included fisheries-related trauma (n = 15), other acute physical traumas (n = 15) and other chronic traumas (n = 19). Infectious disease findings included respiratory infections (n = 21) and gastrointestinal infections (n = 9). There was no difference in the primary pathological findings for seals found dead or that died or were euthanased on the day they were found compared to those dying in early rehabilitation, suggesting that it is appropriate to include findings from seals in early rehabilitation in studies of wild grey seal pathology. Seals that had not been frozen before post-mortem examination were nearly twice as likely to have a primary pathological finding of infectious disease or trauma than those that had been frozen, highlighting the need, wherever possible, to avoid freezing seals prior to post-mortem examination.

Validation of the British Society of Thoracic Imaging guidelines for COVID-19 chest radiograph reporting.

AIM: To validate the British Society of Thoracic Imaging issued guidelines for the categorisation of chest radiographs for coronavirus disease 2019 (COVID-19) reporting regarding reproducibility amongst radiologists and diagnostic performance. MATERIALS AND METHODS: Chest radiographs from 50 patients with COVID-19, and 50 control patients with symptoms consistent with COVID-19 from prior to the emergence of the novel coronavirus were assessed by seven consultant radiologists with regards to the British Society of Thoracic Imaging guidelines. RESULTS: The findings show excellent specificity (100%) and moderate sensitivity (44%) for guideline-defined Classic/Probable COVID-19, and substantial interobserver agreement (Fleiss' k=0.61). Fair agreement was observed for the "Indeterminate for COVID-19" (k=0.23), and "Non-COVID-19" (k=0.37) categories; furthermore, the sensitivity (0.26 and 0.14 respectively) and specificity (0.76, 0.80) of these categories for COVID-19 were not significantly different (McNemar's test p=0.18 and p=0.67). CONCLUSION: An amalgamation of the categories of "Indeterminate for COVID-19" and "Non-COVID-19" into a single "not classic of COVID-19" classification would improve interobserver agreement, encompass patients with a similar probability of COVID-19, and remove the possibility of labelling patients with COVID-19 as "Non-COVID-19", which is the presenting radiographic appearance in a significant minority (14%) of patients.

Modeling gas transport in polymer-grafted nanoparticle membranes.

We use coarse-grained molecular dynamics simulations to study gas diffusion within nanocomposites consisting of matrix-free polymer-grafted nanoparticles. We compare the transport of gas penetrants in systems using polymer models with and without an angle potential and show that gas diffusion enhancement occurs in nanocomposite systems only with the angle potential. This enhancement is related to the free volume in the system, but the cage size experienced by the gas penetrant seems to be a more relevant indicator of gas diffusion enhancement. The enhancement seen in our simulations is smaller than that observed in experiments.

Decreased staging of differentiated thyroid cancer in patients with chronic lymphocytic thyroiditis.

PURPOSE: The biological association between chronic lymphocytic thyroiditis (CLT) and differentiated thyroid cancer (DTC) has not been elucidated yet. The aim of the study was to assess whether the presence of CLT exerts any influence on clinical or histological presentation of DTC. METHODS: Nine hundred and seven consecutive patients with DTC treated in the years 1998-2016 were divided into two groups according to the presence or absence of concomitant CLT. The statistical differences were analysed. RESULTS: Out of 907 patients included in the study, 331 were diagnosed with DTC and CLT (studied group), while 576 patients with DTC but without CLT constituted a control group. The distribution of papillary and follicular thyroid cancer did not differ. In CLT group, the prevalence of pT1 was greater than for pT2-pT4 DTC (P = 0.0003; OR = 1.69, 95% CI 1.27-2.24) compared to controls (68.3 vs. 56.1%, respectively). The presence of multifocal lesions was similar. The thyroid capsule infiltration without extrathyroidal invasion (P < 0.0001; OR = 0.21, 95% CI 0.14-0.31) was more frequent in the studied group, unlike extracapsular invasion, which was significantly more often present in patients with DTC but without CLT (P = 0.004; OR = 1.66; 95% CI 1.17-2.34) as well as nodal involvement (P = 0.048; OR = 0.65, 95% CI 0.42-0.99). CONCLUSIONS: The collected data indicate a protective role of CLT in preventing the spread of the DTC. The presence of CLT might limit tumour growth to the primary site.

Eating out with a food allergy in the UK: Change in the eating out practices of consumers with food allergy following introduction of allergen information legislation.

BACKGROUND: Strict allergen avoidance is important in day-to-day management of food allergy and avoidance when eating outside the home can present particular difficulties. EU legislation (EU FIC) introduced in December 2014 aimed to improve food allergen information provision for customers by requiring retailers of non-prepacked foods to provide information related to the content of one or more of 14 specified food allergens within their foods. OBJECTIVES: To investigate the impact of EU FIC on the behaviours, experiences and attitudes of consumers with food allergy when eating out. METHODS: As part of longitudinal research, participants with food allergy from across the UK took part in either (A) pre and post legislation in-depth interviews, or (B) pre and post legislation surveys. In-depth interviews were carried out with 28 participants pre and post legislation and analysed using the framework approach. Self-report surveys were completed by 129 participants pre and post legislation, and responses were subject to quantitative analyses. RESULTS: Improvements in allergen information provision and raised awareness of food allergy in eating out venues were reported following introduction of EU FIC. Whilst participants favoured written allergen information, they expressed greater confidence in communicating with eating out staff and in trusting the allergen information that they provided. Improvements were judged to be gradual, sporadic or inconsistent in implementation. CONCLUSION & CLINICAL RELEVANCE: For many participants, the "ideal" eating out experience was one in which a range of information resources were available and where written allergen information was complemented by proactive and accommodating staff within an allergy-aware environment. Whilst the onus is on legislators and food providers to ensure that adequate allergen information is provided, clinicians play an important role in encouraging patients with food allergy to pursue their legal right to make allergen enquiries to avoid accidental allergen ingestion when eating out.

Cognitive profiles in childhood and adolescence differ between adult psychotic and affective symptoms: a prospective birth cohort study.

BACKGROUND: Differences between verbal and non-verbal cognitive development from childhood to adulthood may differentiate between those with and without psychotic symptoms and affective symptoms in later life. However, there has been no study exploring this in a population-based cohort. METHOD: The sample was drawn from the MRC National Survey of Health and Development, and consisted of 2384 study members with self-reported psychotic experiences and affective symptoms at the age of 53 years, and with complete cognitive data at the ages of 8 and 15 years. The association between verbal and non-verbal cognition at age 8 years and relative developmental lag from age 8 to 15 years, and both adult outcomes were tested with the covariates adjusted, and mutually adjusted for verbal and non-verbal cognition. RESULTS: Those with psychotic experiences [thought interference (n = 433), strange experience (n = 296), hallucination (n = 88)] had lower cognition at both the ages of 8 and 15 years in both verbal and non-verbal domains. After mutual adjustment, lower verbal cognition at age 8 years and greater verbal developmental lag were associated with higher likelihood of psychotic experiences within individuals, whereas there was no association between non-verbal cognition and any psychotic experience. In contrast, those with case-level affective symptoms (n = 453) had lower non-verbal cognition at age 15 years, and greater developmental lag in the non-verbal domain. After adjustment, lower non-verbal cognition at age 8 years and greater non-verbal developmental lag were associated with higher risk of case-level affective symptoms within individuals. CONCLUSIONS: These results suggest that cognitive profiles in childhood and adolescence differentiate psychiatric disease spectra.

Is children's weight a public health or a private family issue? A qualitative analysis of online discussion about National Child Measurement Programme feedback in England.

BACKGROUND: The National Child Measurement Programme (NCMP) is a child weight monitoring system in England, taking place in the first and final years of primary school. Many local authorities consider it important to inform parents if their child is overweight, and do so by letter alongside the offer of support and advice. Such letters have been met with mixed reactions from parents, but research seeking to better understand parents' responses is often limited by reliance on survey data and low participation rates. This study aimed to collect a broad variety of perspectives on the programme by analyzing views expressed in parent-to-parent discussions posted online. METHODS: UK-based online parenting fora were used to identify discussion threads based around the NCMP between 2010 and 2017. Thirty-one discussion threads from two parent fora were identified. Thematic analysis was used to identify themes in these data. RESULTS: The primary themes identified related to (1) the legitimacy of feedback and judgement from health professionals, (2) the relative importance of collecting population level data above individual preferences, and (3) risks versus benefits of having conversations with children about weight. Most threads adopted an 'argument, counter-argument' format, providing two sides to each issue raised. Information and opinions consistent with public health messages were frequently provided, such as how data are used, that feedback is intended to be helpful, and the importance of collecting national data. There was little evidence of individual parents shifting their views in response to others' arguments. CONCLUSIONS: This study provides novel insight into peer-to-peer debates about the NCMP, including the arguments parents find convincing and acceptable for and against a national programme to weigh children and provide feedback to parents about their weight. Online fora were used as an opportunity to express criticism or distress, but also to seek advice from peers regarding concerns about whether or not to opt-out. Thus, both general issues related to the legitimacy of population screening and outcomes for individual children were of concern to parents.

Communication: Stiffening of dilute alcohol and alkane mixtures with water.

We probe the anomalous compressibilities of dilute mixtures of alcohols and alkane gases in water using molecular simulations. The response to increasing solute concentration depends sensitively on temperature, with the compressibility decreasing upon solute addition at low temperatures and increasing at elevated temperatures. The thermodynamic origin of stiffening is directly tied to the solute's partial compressibility, which is negative at low temperatures and rises above water's compressibility with increasing temperature. Hydration shell waters concurrently tilt towards clathrate-like structures at low temperatures that fade with heating. Kirkwood-Buff theory traces the solute's partial compressibility to changes in the solute-water association volume upon heating and incongruous packing of waters at the boundary between the more structured hydration shell and bulk water.

Temperature and pressure dependence of the interfacial free energy against a hard surface in contact with water and decane.

Theoretical descriptions of molecular-scale solvation frequently invoke contributions proportional to the solvent exposed area, under the tacit expectation that those contributions are tied to a surface tension for macroscopic surfaces. Here we examine the application of revised scaled-particle theory (RSPT) to extrapolate molecular simulation results for the wetting of molecular-to-meso-scale repulsive solutes in liquid water and decane to determine the interfacial free energies of hard, flat surfaces. We show that the RSPT yields interfacial free energies at ambient pressures that are consistently greater than that obtained from the liquid-vapor surface tensions of water and decane by ∼4%. Nevertheless, the hard surface and liquid-vapor interfacial free energies are parallel over a broad temperature range at 1 bar indicating similar entropic contributions. With increasing pressure, the hard, flat interfacial free energies exhibit a maximum in the vicinity of ∼1000 bars. This non-monotonic behavior in both water and decane reflects solvent dewetting at low pressures, followed by wetting at higher pressures as the solvents are pushed onto the solute. By comparing the results of RSPT against classic scaled-particle theory (CSPT), we show that CSPT systematically predicts greater entropic penalties for interface formation and makes inconsistent predictions between the pressure dependence of the interfacial free energy and solvent contact density with the solute surface.

Lifetime affect and midlife cognitive function: prospective birth cohort study.

BACKGROUND: Recurrent affective problems are predictive of cognitive impairment, but the timing and directionality, and the nature of the cognitive impairment, are unclear. AIMS: To test prospective associations between life-course affective symptoms and cognitive function in late middle age. METHOD: A total of 1668 men and women were drawn from the Medical Research Council National Survey of Health and Development (the British 1946 birth cohort). Longitudinal affective symptoms spanning age 13-53 years served as predictors; outcomes consisted of self-reported memory problems at 60-64 years and decline in memory and information processing from age 53 to 60-64 years. RESULTS: Regression analyses revealed no clear pattern of association between longitudinal affective symptoms and decline in cognitive test scores, after adjusting for gender, childhood cognitive ability, education and midlife socioeconomic status. In contrast, affective symptoms were strongly, diffusely and independently associated with self-reported memory problems. CONCLUSIONS: Affective symptoms are more clearly associated with self-reported memory problems in late midlife than with objectively measured cognitive performance.

Does convenience matter in health care delivery? A systematic review of convenience-based aspects of process utility.

OBJECTIVES: To systematically review the existing literature on the value associated with convenience in health care delivery, independent of health outcomes, and to try to estimate the likely magnitude of any value found. METHODS: A systematic search was conducted for previously published studies that reported preferences for convenience-related aspects of health care delivery in a manner that was consistent with either cost-utility analysis or cost-benefit analysis. Data were analyzed in terms of the methodologies used, the aspects of convenience considered, and the values reported. RESULTS: Literature searches generated 4715 records. Following a review of abstracts or full-text articles, 27 were selected for inclusion. Twenty-six studies reported some evidence of convenience-related process utility, in the form of either a positive utility or a positive willingness to pay. The aspects of convenience valued most often were mode of administration (n = 11) and location of treatment (n = 6). The most common valuation methodology was a discrete-choice experiment containing a cost component (n = 15). CONCLUSIONS: A preference for convenience-related process utility exists, independent of health outcomes. Given the diverse methodologies used to calculate it, and the range of aspects being valued, however, it is difficult to assess how large such a preference might be, or how it may be effectively incorporated into an economic evaluation. Increased consistency in reporting these preferences is required to assess these issues more accurately.

Response initiation in young adults at risk for psychosis in the Northern Finland 1986 Birth Cohort.

INTRODUCTION: This is one of the very few studies to investigate the specific executive function/processing speed component of response initiation in subjects at familial risk (FR) for psychosis, and the first such study in subjects at clinical risk (CR) for psychosis. METHODS: Participants (N = 177) were members of the general population-based Northern Finland 1986 Birth Cohort in the following four groups: FR for psychosis (n = 62), CR for psychosis (n = 21), psychosis (n = 25) and control subjects (n = 69). The response initiation of these groups was compared in three different tests: Semantic fluency, Stockings of Cambridge and Spatial working memory. RESULTS: The two risk groups did not differ significantly from control group, but differed from, and outperformed the psychosis group in semantic fluency response initiation. CONCLUSIONS: Response initiation deficits were not evident in a non-help seeking psychosis high-risk sample.

AntigenMap 3D: an online antigenic cartography resource.

SUMMARY: Antigenic cartography is a useful technique to visualize and minimize errors in immunological data by projecting antigens to 2D or 3D cartography. However, a 2D cartography may not be sufficient to capture the antigenic relationship from high-dimensional immunological data. AntigenMap 3D presents an online, interactive, and robust 3D antigenic cartography construction and visualization resource. AntigenMap 3D can be applied to identify antigenic variants and vaccine strain candidates for pathogens with rapid antigenic variations, such as influenza A virus. AVAILABILITY AND IMPLEMENTATION: http://sysbio.cvm.msstate.edu/AntigenMap3D

Detection of African swine fever virus-like sequences in ponds in the Mississippi Delta through metagenomic sequencing.

Metagenomic characterization of water virome was performed in four Mississippi catfish ponds. Although differing considerably from African swine fever virus (ASFV), 48 of 446,100 sequences from 12 samples were similar enough to indicate that they represent new members in the family Asfarviridae. At present, ASFV is the only member of Asfarviridae, and this study presents the first indication of a similar virus in North America. At this point, there is no indication that the identified virus(es) pose a threat to human or animal health, and further study is needed to characterize their potential risks to both public health and agricultural development.

Meeting the health information needs of prostate cancer patients using personal health records.

BACKGROUND: There is interest in the use of health information technology in the form of personal health record (phr) systems to support patient needs for health information, care, and decision-making, particularly for patients with distressing, chronic diseases such as prostate cancer (pca). We sought feedback from pca patients who used a phr. METHODS: For 6 months, 22 pca patients in various phases of care at the BC Cancer Agency (bcca) were given access to a secure Web-based phr called provider, which they could use to view their medical records and use a set of support tools. Feedback was obtained using an end-of-study survey on usability, satisfaction, and concerns with provider. Site activity was recorded to assess usage patterns. RESULTS: Of the 17 patients who completed the study, 29% encountered some minor difficulties using provider. No security breaches were known to have occurred. The two most commonly accessed medical records were laboratory test results and transcribed doctor's notes. Of survey respondents, 94% were satisfied with the access to their medical records, 65% said that provider helped to answer their questions, 77% felt that their privacy and confidentiality were preserved, 65% felt that using provider helped them to communicate better with their physicians, 83% found new and useful information that they would not have received by talking to their health care providers, and 88% said that they would continue to use provider. CONCLUSIONS: Our results support the notion that phrs can provide cancer patients with timely access to their medical records and health information, and can assist in communication with health care providers, in knowledge generation, and in patient empowerment.