Conversational artificial intelligence: the interface with the patient concerns inventory.

The patient concerns inventory (PCI) allows patients to highlight the issues they would like to discuss at their outpatient consultation. It improves patient-clinician communication and has proven benefits. While the PCI is effective, patient experiences could be improved with better access to it and the ability to more easily and frequently express their concerns. This, of course, is in the context of ever-increasing healthcare challenges and limited resources. Use of conversational artificial intelligence (CAI) represents an opportunity to improve information flow between patients and professionals remote from the consultation. This paper highlights the potential for CAI to provide an 'always-on' platform, using natural language interface technology and based on the PCI, which patients can access via their mobile devices. We also discuss potential pitfalls and concerns, along with outlining a current clinical trial assessing, in the first instance, usability of this technology.

Non-Invasive Prenatal Testing (NIPT) - We Need a National Programme.

Aims The provision of non-invasive prenatal testing (NIPT), a blood test screening for aneuploidy during pregnancy, varies widely internationally. In Ireland, NIPT is available privately, costing over €400. Gobal research on the patient perspective on NIPT shows a strong desire for the test to be provided for free. Attitudes towards NIPT amongst pregnant women in Ireland have not previously been studied. We assessed this in women attending maternity services in our unit. Methods This was a cross-sectional observational study involving a telephone survey. Women were asked about their prior knowledge of NIPT. Women with no prior knowledge were given information about NIPT and asked about their opinion of the test. Results One hundred and twelve (n=112) women participated. Of these, 60% (n=67) had not heard of NIPT, 86% (n=96) believe it should be freely available, and 80% (n=90) said they would avail of the test if it were free. Cost was the main prohibitive factor for those choosing not to have the test. All women wished to be more informed about NIPT. Conclusion Awareness of NIPT amongst women attending maternity services in Ireland may be low, but there is a desire for more information and a more equitable provision of the test.

A qualitative analysis of online misinformation and conspiracy theories in psoriasis.

Psoriasis is a chronic, hereditary disease with a complex immunopathogenesis, rendering it susceptible to misinformation. Misinformation related to psoriasis can have negative effects both on the public perception of psoriasis and on patients' knowledge of psoriasis. To characterize misinformation related to psoriasis available online, we performed a formal literature review via PubMed and a thematic review via Google. Key themes of misinformation included 'victim-blaming' (hygiene), 'vector' (contagion), 'vaccination', 'vilification' of conventional therapy, 'validation' of natural treatment and diet, 'veneration' of cures and 'vocalization' from celebrities. Misinformation related to psoriasis is pervasive on social media and other websites. Dermatologists, as patient advocates, should be aware of the content of misinformation available online and combat misleading health information to optimize health outcomes for patients with psoriasis.

Alcohol, tobacco, and marijuana consumption is associated with increased odds of same-day substance co- and tri-use.

BACKGROUND: Little is known about event-level patterns of marijuana co- or tri-use with alcohol and tobacco. Thus, the study goal was to examine patterns of same-day alcohol, cigarette, and marijuana co- and tri-use at the individual level in non-treatment-seeking alcohol users. METHODS: Participants (N = 551) completed an in-person interview for alcohol, cigarette, and marijuana use over the previous 30 days, and the event-level substance use patterns of n = 179 participants who reported using each of these substances at least once per month were analyzed. RESULTS: The use of alcohol, marijuana, or cigarettes independently increased the probability of subsequent, simultaneous co-use of one of the two remaining substances. The co-use of alcohol with cigarettes and marijuana with cigarettes produced generally additive effects on the odds of same day tri-use of marijuana and alcohol, respectively. Conversely, the co-use of alcohol and marijuana produced sub-additive effects on likelihood of cigarette use. Sex moderated several of the observed patterns of co- and tri-use: the relationship between alcohol or cigarette use predicting marijuana co-use was stronger in men, whereas the observed additive relationships between drug co-use leading to tri-use was stronger in women. CONCLUSIONS: The presented results may aid in the understanding of how simultaneous co-use of marijuana with alcohol and/or tobacco relates to the etiology, maintenance, and treatment of comorbid and trimorbid substance use disorder. Replication and extension of the results in treatment seeking populations using more fine-grained analysis approaches, e.g. ecological momentary assessment, is needed.

The Odyssey of the Ancestral Escherich Strain through Culture Collections: an Example of Allopatric Diversification.

More than a century ago, Theodor Escherich isolated the bacterium that was to become Escherichia coli, one of the most studied organisms. Not long after, the strain began an odyssey and landed in many laboratories across the world. As laboratory culture conditions could be responsible for major changes in bacterial strains, we conducted a genome analysis of isolates of this emblematic strain from different culture collections (England, France, the United States, Germany). Strikingly, many discrepancies between the isolates were observed, as revealed by multilocus sequence typing (MLST), the presence of virulence-associated genes, core genome MLST, and single nucleotide polymorphism/indel analyses. These differences are correlated with the phylogeographic history of the strain and were due to an unprecedented number of mutations in coding DNA repair functions such as mismatch repair (MutL) and oxidized guanine nucleotide pool cleaning (MutT), conferring a specific mutational spectrum and leading to a mutator phenotype. The mutator phenotype was probably acquired during subculturing and corresponded to second-order selection. Furthermore, all of the isolates exhibited hypersusceptibility to antibiotics due to mutations in efflux pump- and porin-encoding genes, as well as a specific mutation in the sigma factor-encoding gene rpoS. These defects reflect a self-preservation and nutritional competence tradeoff allowing survival under the starvation conditions imposed by storage. From a clinical point of view, dealing with such mutator strains can lead microbiologists to draw false conclusions about isolate relatedness and may impact therapeutic effectiveness. IMPORTANCE Mutator phenotypes have been described in laboratory-evolved bacteria, as well as in natural isolates. Several genes can be impacted, each of them being associated with a typical mutational spectrum. By studying one of the oldest strains available, the ancestral Escherich strain, we were able to identify its mutator status leading to tremendous genetic diversity among the isolates from various collections and allowing us to reconstruct the phylogeographic history of the strain. This mutator phenotype was probably acquired during the storage of the strain, promoting adaptation to a specific environment. Other mutations in rpoS and efflux pump- and porin-encoding genes highlight the acclimatization of the strain through self-preservation and nutritional competence regulation. This strain history can be viewed as unintentional experimental evolution in culture collections all over the word since 1885, mimicking the long-term experimental evolution of E. coli of Lenski et al. (O. Tenaillon, J. E. Barrick, N. Ribeck, D. E. Deatherage, J. L. Blanchard, A. Dasgupta, G. C. Wu, S. Wielgoss, S. Cruveiller, C. Médigue, D. Schneider, and R. E. Lenski, Nature 536:165-170, 2016, https://doi.org/10.1038/nature18959) that shares numerous molecular features.

Synthesis of sp(3)-rich scaffolds for molecular libraries through complexity-generating cascade reactions.

An efficient strategy for the synthesis of complex small molecules from simple building blocks is presented. Key steps of the strategy include tandem Petasis and Diels-Alder reactions, and divergent complexity-generating cyclization cascades from a key dialdehyde intermediate. The methodology is validated through the synthesis of a representative compound set, which has been used in the production of 1617 molecules for the European Lead Factory.

Elevated CDCP1 predicts poor patient outcome and mediates ovarian clear cell carcinoma by promoting tumor spheroid formation, cell migration and chemoresistance.

Hematogenous metastases are rarely present at diagnosis of ovarian clear cell carcinoma (OCC). Instead dissemination of these tumors is characteristically via direct extension of the primary tumor into nearby organs and the spread of exfoliated tumor cells throughout the peritoneum, initially via the peritoneal fluid, and later via ascites that accumulates as a result of disruption of the lymphatic system. The molecular mechanisms orchestrating these processes are uncertain. In particular, the signaling pathways used by malignant cells to survive the stresses of anchorage-free growth in peritoneal fluid and ascites, and to colonize remote sites, are poorly defined. We demonstrate that the transmembrane glycoprotein CUB-domain-containing protein 1 (CDCP1) has important and inhibitable roles in these processes. In vitro assays indicate that CDCP1 mediates formation and survival of OCC spheroids, as well as cell migration and chemoresistance. Disruption of CDCP1 via silencing and antibody-mediated inhibition markedly reduce the ability of TOV21G OCC cells to form intraperitoneal tumors and induce accumulation of ascites in mice. Mechanistically our data suggest that CDCP1 effects are mediated via a novel mechanism of protein kinase B (Akt) activation. Immunohistochemical analysis also suggested that CDCP1 is functionally important in OCC, with its expression elevated in 90% of 198 OCC tumors and increased CDCP1 expression correlating with poor patient disease-free and overall survival. This analysis also showed that CDCP1 is largely restricted to the surface of malignant cells where it is accessible to therapeutic antibodies. Importantly, antibody-mediated blockade of CDCP1 in vivo significantly increased the anti-tumor efficacy of carboplatin, the chemotherapy most commonly used to treat OCC. In summary, our data indicate that CDCP1 is important in the progression of OCC and that targeting pathways mediated by this protein may be useful for the management of OCC, potentially in combination with chemotherapies and agents targeting the Akt pathway.

Dual function of the hemagglutinin H5 fused to chicken CD154 in a potential strategy of DIVA against avian influenza disease: preliminary study.

In this study we demonstrated that the vaccine candidate against avian influenza virus H5N1 based on the hemagglutinin H5 (HA) fused to the chicken CD154 (HACD) can also be used for differentiating infected from vaccinated animals (DIVA). As the strategy of DIVA requires at least two proteins, we obtained a variant of the nucleoprotein (NP49-375) in E. coli. After its purification by IMAC, the competence of the proteins NP49-375 and HACD as coating antigens in indirect ELISA assays were tested by using the sera of chickens immunized with the proteins HA and HACD and the reference sera from several avian influenza subtypes. Together with these sera, the sera from different species of birds and the sera of chickens infected with other avian viral diseases were analyzed by competition ELISA assays coated with the proteins NP49-375 and HACD. The results showed that the segment CD154 in the chimeric protein HACD did not interfere with the recognition of the molecule HA by its specific antibodies. Also, we observed variable detection levels when the reference sera were analyzed in the ELISA plates coated with the protein NP49-375. Moreover, only the antibodies of the reference serum subtype H5 were detected in the ELISA plates coated with the protein HACD. The competition ELISA assays showed percentages of inhibition of 88-91% for the positives sera and less than 20% for the negative sera. We fixed the cut-off value of these assays at 25%. No antibody detection was observed in the sera from different species of birds or the sera of chickens infected with other avian viral diseases. This study supported the fact that the ELISA assays using the proteins NP49-375 and HACD could be valuable tools for avian influenza surveillance and as a strategy of DIVA for counteracting the highly pathogenic avian influenza virus H5N1 outbreaks.

Regional and global left ventricular function following a simulated 5 km race in sports-trained adolescents.

The effects of a short, high-intensity bout of exercise on cardiac systolic and diastolic function are not well understood in adolescent athletes. Consequently, the aims of the study were to evaluate global left ventricular (LV) systolic and diastolic function, as well as segmental wall motion responses (cardiac strain), prior to as well as 45 and 225 min following a simulated 5 km cross-country race. Twenty trained, adolescent males (age: 15.2 ± 0.7 years) volunteered for exercise testing. LV fractional shortening and the ratio of early (E) and late (A) peak flow velocities reflected global systolic and diastolic function, respectively. Peak longitudinal mitral annular septal tissue velocities were also determined during systole and diastole. Longitudinal strain (ε) and strain rates were determined across the LV. LV fractional shortening was significantly (P < 0.05) higher at 225 min post-race (37.6 ± 5.8%) compared to pre-race (34.5 ± 4.7%) and 45 min post-race (34.9 ± 5.4 %). This difference was abolished after adjusting for post-race heart rates. There was a significant (P < 0.05) decrease in the E:A ratio at both 45 min (2.04 ± 0.57) and 225 min post-race (2.20 ± 0.66) compared to the pre-race value (2.80 ± 0.68). When these data were adjusted for post-race heart rates, these pre-post-race differences in E:A ratio were abolished. There were no significant alterations in either tissue Doppler velocities or longitudinal ε. The evidence suggests that a 5 km race does not lead to any significant post-exercise attenuation in global or regional LV systolic and diastolic function in trained adolescents.

Unsteady flow affects swimming energetics in a labriform fish (Cymatogaster aggregata).

Unsteady water flows are common in nature, yet the swimming performance of fishes is typically evaluated at constant, steady speeds in the laboratory. We examined how cyclic changes in water flow velocity affect the swimming performance and energetics of a labriform swimmer, the shiner surfperch, Cymatogaster aggregata, during station holding. Using intermittent-flow respirometry, we measured critical swimming speed (Ucrit), oxygen consumption rates (O2) and pectoral fin use in steady flow versus unsteady flows with either low- [0.5 body lengths (BL) s(-1)] or high-amplitude (1.0 BL s(-1)) velocity fluctuations, with a 5 s period. Individuals in low-amplitude unsteady flow performed as well as fish in steady flow. However, swimming costs in high-amplitude unsteady flow were on average 25.3% higher than in steady flow and 14.2% higher than estimated values obtained from simulations based on the non-linear relationship between swimming speed and oxygen consumption rate in steady flow. Time-averaged pectoral fin use (fin-beat frequency measured over 300 s) was similar among treatments. However, measures of instantaneous fin use (fin-beat period) and body movement in high-amplitude unsteady flow indicate that individuals with greater variation in the duration of their fin beats were better at holding station and consumed less oxygen than fish with low variation in fin-beat period. These results suggest that the costs of swimming in unsteady flows are context dependent in labriform swimmers, and may be influenced by individual differences in the ability of fishes to adjust their fin beats to the flow environment.

An intestinal epithelial defect conferring ER stress results in inflammation involving both innate and adaptive immunity.

We recently characterized Winnie mice carrying a missense mutation in Muc2, leading to severe endoplasmic reticulum stress in intestinal goblet cells and spontaneous colitis. In this study, we characterized the immune responses due to this intestinal epithelial dysfunction. In Winnie, there was a fourfold increase in activated dendritic cells (DCs; CD11c(+) major histocompatibility complex (MHC) class II(hi)) in the colonic lamina propria accompanied by decreased colonic secretion of an inhibitor of DC activation, thymic stromal lymphopoietin (TSLP). Winnie also displayed a significant increase in mRNA expression of the mucosal T(H)17 signature genes Il17a, IL17f, Tgfb, and Ccr6, particularly in the distal colon. Winnie mesenteric lymph node leukocytes secreted multiple T(H)1, T(H)2, and T(H)17 cytokines on activation, with a large increase in interleukin-17A (IL-17A) progressively with age. A major source of mucosal IL-17A in Winnie was CD4(+) T lymphocytes. Loss of T and B lymphocytes in Rag1(-/-) × Winnie (RaW) crosses did not prevent spontaneous inflammation but did prevent progression with age in the colon but not the cecum. Adoptive transfer of naive T cells into RaW mice caused more rapid and severe colitis than in Rag1(-/-), indicating that the epithelial defect results in an intestinal microenvironment conducive to T-cell activation. Thus, the Winnie primary epithelial defect results in complex multicytokine-mediated colitis involving both innate and adaptive immune components with a prominent IL-23/T(H)17 response, similar to that of human ulcerative colitis.

Cluster of Legionnaires' disease associated with a public whirlpool spa, France, April-May 2010.

In May 2010, a cluster of three cases of Legionnaires' disease was identified in France. The results of the epidemiological, environmental and microbiological investigations allowed the rapid identification of a public whirlpool spa as the most probable source of contamination and the implementation of appropriate control measures. This investigation has stressed the need for good cooperation between partners and the importance of the molecular analysis of Legionella strains.

Using multimedia technology to help combat the negative effects of protective isolation on patients: the Open Window project--an engineering challenge.

The Open Window project was established with the aim of creating a "virtual window" for each patient who is confined to protective isolation due to treatment for illness. This virtual window as developed provides a range of media or experiences. This paper describes the approach taken to the system design and discusses initial experiences with implementing such a system in a critical care setting. The system design was predicated on two guiding principles. Firstly it should be intuitive to use and the technology used to create the virtual window hidden from patient view. Secondly the system must be able to be installed at the point of care in a way that delivers the experience under the patient's control, without compromising the function or safety of the clinical environment. Patient acceptance of the system is being measured as part of an on-going trial and at this interim phase of data analysis 100% (n=55) of participants in the intervention group have reported that the technology was easy to use. We conclude that the system as designed and installed is an effective, robust and reliable system upon which to base a multimedia interventions in a critical care room.

Prospective study of early bereavement on psychological and behavioural cardiac risk factors.

BACKGROUND: Increasing evidence supports the role of emotional stress in the onset of cardiovascular disease. Although bereavement is a major emotional stress with both acute and more long-term features, the mechanism of its association with cardiovascular risk is not well understood, in particular because of limited studies of acute bereavement. The aim of the study was to identify psychological and behavioural changes in acute bereavement and potential modifiers of these changes. METHODS: Bereaved (n= 62) and non-bereaved individuals (n= 50) were evaluated within 2 weeks and at 6 months following loss using the Centre for Epidemiologic Studies -- Depression, Spielberger State Anxiety and Anger, Social Support Questionnaire and changes in appetite, cigarette and alcohol consumption, cortisol and lipids. RESULTS: Compared with non-bereaved, acutely bereaved had increased symptoms of depression (26.7 +/- 1.7 vs 5.9 +/- 0.7, P < 0.001), anxiety (47.4 +/- 2.0 vs 28.2 +/- 1.4, P < 0.001) and anger (median 16.0 vs 15.0, P < 0.001). Greater depressive symptoms were associated with being unprepared for the death, decreased sleep duration and younger age. Acutely, bereaved slept less than non-bereaved (5.8 +/- 0.2 vs 7.2 +/- 0.2 h, P < 0.001). Reduced sleep time was associated with increased anger and depression and decreased satisfaction with social support. Compared with the non-bereaved, the acutely bereaved had higher cortisol (median 306 vs 266, P= 0.003), reduced appetite (P < 0.001) and lower total cholesterol (median 4.9 vs 5.4, P= 0.006) and low-density lipoprotein (median 2.4 vs 2.9, P < 0.001). CONCLUSION: These results offer insight into the psychological, behavioural and physical changes that may contribute to cardiovascular risk in bereavement.