Should C-reactive protein concentration at ICU discharge be used as a prognostic marker?

<p>Abstract</p> <p>Background</p> <p>About one third of hospital mortality in critically ill patients occurs after Intensive Care Unit (ICU) discharge. Some authors have recently hypothesized that unresolved or latent inflammation and sepsis may be an important factor that contributes to death following successful discharge from the ICU.</p> <p>Aim</p> <p>The aim of our study was to determine the ability of the clinical and inflammatory markers at ICU discharge to predict post-ICU mortality.</p> <p>Methods</p> <p>A prospective observational cohort study was conducted during a 14-month period in an 8 bed polyvalent ICU. Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, Therapeutic Intervention Scoring System-28 (TISS-28), C-reactive protein (CRP), white cell count (WCC) and body temperature of the day of ICU discharge were collected from patients who survived their first ICU admission.</p> <p>Results</p> <p>During this period 156 patients were discharged alive from the ICU. A total of 29 patients (18.6%) died after ICU discharge. There were no differences in clinical and demographic characteristics between survivors and nonsurvivors. C-reactive protein levels at ICU discharge were not significantly different between survivors and nonsurvivors. The area under receiver operating characteristics curves of APACHE II, SAPS II, SOFA, TISS-28, CRP, WCC and body temperature at ICU discharge as prognostic markers of hospital death were 0.76 (95% confidence interval (CI) 0.67-0.86); 0.75 (95% CI 0.66-0.85); 0.72 (95% CI 0.62-0.83); 0.64 (95% CI 0.52-0.77); 0.55 (95% CI 0.43-0.67); 0.55 (95% CI 0.42-0.66) and 0.54 (95% CI 0.44-0.67) respectively. The hospital mortality rate of the patients with CRP <5, 5-10, >10 mg/dL was 15.1%, 16.1% and 33.3% respectively (p = NS).</p> <p>Conclusions</p> <p>At ICU discharge serum CRP concentration was a poor marker of post-ICU prognosis. Post-ICU death appears to be unrelated to the persistent inflammatory response.</p

Contribution of microscopy for understanding the mechanism of action against trypanosomatids

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Radio Emission from Ultra-Cool Dwarfs

The 2001 discovery of radio emission from ultra-cool dwarfs (UCDs), the very low-mass stars and brown dwarfs with spectral types of ~M7 and later, revealed that these objects can generate and dissipate powerful magnetic fields. Radio observations provide unparalleled insight into UCD magnetism: detections extend to brown dwarfs with temperatures <1000 K, where no other observational probes are effective. The data reveal that UCDs can generate strong (kG) fields, sometimes with a stable dipolar structure; that they can produce and retain nonthermal plasmas with electron acceleration extending to MeV energies; and that they can drive auroral current systems resulting in significant atmospheric energy deposition and powerful, coherent radio bursts. Still to be understood are the underlying dynamo processes, the precise means by which particles are accelerated around these objects, the observed diversity of magnetic phenomenologies, and how all of these factors change as the mass of the central object approaches that of Jupiter. The answers to these questions are doubly important because UCDs are both potential exoplanet hosts, as in the TRAPPIST-1 system, and analogues of extrasolar giant planets themselves.Comment: 19 pages; submitted chapter to the Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag

Deciphering Heterogeneity in Pig Genome Assembly Sscrofa9 by Isochore and Isochore-Like Region Analyses

Background: The isochore, a large DNA sequence with relatively small GC variance, is one of the most important structures in eukaryotic genomes. Although the isochore has been widely studied in humans and other species, little is known about its distribution in pigs. Principal Findings: In this paper, we construct a map of long homogeneous genome regions (LHGRs), i.e., isochores and isochore-like regions, in pigs to provide an intuitive version of GC heterogeneity in each chromosome. The LHGR pattern study not only quantifies heterogeneities, but also reveals some primary characteristics of the chromatin organization, including the followings: (1) the majority of LHGRs belong to GC-poor families and are in long length; (2) a high gene density tends to occur with the appearance of GC-rich LHGRs; and (3) the density of LINE repeats decreases with an increase in the GC content of LHGRs. Furthermore, a portion of LHGRs with particular GC ranges (50%–51 % and 54%–55%) tend to have abnormally high gene densities, suggesting that biased gene conversion (BGC), as well as time- and energy-saving principles, could be of importance to the formation of genome organization. Conclusion: This study significantly improves our knowledge of chromatin organization in the pig genome. Correlations between the different biological features (e.g., gene density and repeat density) and GC content of LHGRs provide a uniqu

A web-based clinical decision tool to support treatment decision-making in psychiatry: a pilot focus group study with clinicians, patients and carers

Background. Treatment decision tools have been developed in many fields of medicine, including psychiatry, however benefits for patients have not been sustained once the support is withdrawn. We have developed a web-based computerised clinical decision support tool (CDST), which can provide patients and clinicians with continuous, up-to-date, personalised information about the efficacy and tolerability of competing interventions. To test the feasibility and acceptability of the CDST we conducted a focus group study, aimed to explore the views of clinicians, patients and carers. Methods. The CDST was developed in Oxford. To tailor treatments at an individual level, the CDST combines the best available evidence from the scientific literature with patient preferences and values, and with patient medical profile to generate personalised clinical recommendations. We conducted three focus groups comprising of three different participant types: consultant psychiatrists, participants with mental health diagnosis and/or experience of caring for someone with a mental health diagnosis, and primary care practitioners and nurses. Each 1-hour focus group started with a short visual demonstration of the CDST. To standardise the discussion during the focus groups, we used the same topic guide that covered themes relating to the acceptability and usability of the CDST. Focus groups were recorded and any identifying participant details were anonymised. Data were analysed thematically and managed using the Framework method and the constant comparative method. Results. The focus groups took place in Oxford between October 2016 and January 2017. Overall 31 participants attended (12 consultants, 11 primary care practitioners and 8 patients or carers). The main themes that emerged related to CDST applications in clinical practice, communication, conflicting priorities and record keeping. CDST was considered a useful clinical decision support, with recognised value in promoting clinician-patient collaboration and contributing to the development of personalised medicine. One major benefit of the CDST was perceived to be the open discussion about the possible side-effects of medications. Participants from all the three groups, however, universally commented that the terminology and language presented on the CDST were too medicalised, potentially leading to ethical issues around consent to treatment. Conclusions. The CDST can improve communication pathways between patients, carers and clinicians, identifying care priorities and providing an up-to-date platform for implementing evidence-based practice, with regard to prescribing practices

Increase in immune cell infiltration with progression of oral epithelium from hyperkeratosis to dysplasia and carcinoma

In the present study, epithelium derived lesions of various pathological manifestations were examined histologically and immunohistochemically for mononuclear cell infiltration. The infiltrate under the transformed epithelium of oral lesions, was examined for differences in the composition of immune mononuclear cells as the epithelium moves from hyperkeratosis through various degrees of dysplasia to squamous cell carcinoma. The study was performed on 53 human tongue tissues diagnosed as hyperkeratosis (11 cases), mild dysplasia (nine cases), moderate and severe dysplasia (14 cases) and squamous cell carcinoma (19 cases). A similar analysis was performed on 30 parotid gland tissues diagnosed as pleomorphic adenoma (14 cases) and carcinoma ex-pleomorphic adenoma (16 cases). Immunohistochemical analysis of various surface markers of the tumour infiltrating immune cells was performed and correlated with the transformation level as defined by morphology and the expression of p53 in the epithelium. The results revealed that, in the tongue lesions, the changes in the epithelium from normal appearance to transformed were accompanied by a corresponding increase in the infiltration of CD4, CD8, CD14, CD19+20, and HLA/DR positive cells. The most significant change was an increase in B lymphocytes in tongue lesions, that was in accordance with the transformation level (P<0.001). In the salivary gland, a significant number of cases did not show an infiltrate. In cases where an infiltrate was present, a similar pattern was observed and the more malignant tissues exhibited a higher degree of immune cell infiltration

A Meta-Analysis of Microarray Gene Expression in Mouse Stem Cells: Redefining Stemness

While much progress has been made in understanding stem cell (SC) function, a complete description of the molecular mechanisms regulating SCs is not yet established. This lack of knowledge is a major barrier holding back the discovery of therapeutic uses of SCs. We investigated the value of a novel meta-analysis of microarray gene expression in mouse SCs to aid the elucidation of regulatory mechanisms common to SCs and particular SC types.We added value to previously published microarray gene expression data by characterizing the promoter type likely to regulate transcription. Promoters of up-regulated genes in SCs were characterized in terms of alternative promoter (AP) usage and CpG-richness, with the aim of correlating features known to affect transcriptional control with SC function. We found that SCs have a higher proportion of up-regulated genes using CpG-rich promoters compared with the negative controls. Comparing subsets of SC type with the controls a slightly different story unfolds. The differences between the proliferating adult SCs and the embryonic SCs versus the negative controls are statistically significant. Whilst the difference between the quiescent adult SCs compared with the negative controls is not. On examination of AP usage, no difference was observed between SCs and the controls. However, comparing the subsets of SC type with the controls, the quiescent adult SCs are found to up-regulate a larger proportion of genes that have APs compared to the controls and the converse is true for the proliferating adult SCs and the embryonic SCs.These findings suggest that looking at features associated with control of transcription is a promising future approach for characterizing “stemness” and that further investigations of stemness could benefit from separate considerations of different SC states. For example, “proliferating-stemness” is shown here, in terms of promoter usage, to be distinct from “quiescent-stemness”

Factor structure and measurement invariance across various demographic groups and over time for the phq-9 in primary care patients in spain

The Patient Health Questionnaire (PHQ-9) is a widely-used screening tool for depression in primary care settings. The purpose of the present study is to identify the factor structure of the PHQ-9 and to examine the measurement invariance of this instrument across different sociodemographic groups and over time in a sample of primary care patients in Spain. Data came from 836 primary care patients enrolled in a randomized controlled trial (PsicAP study) and a subsample of 218 patients who participated in a follow-up assessment at 3 months. Confirmatory factor analysis (CFA) was used to test one- and two-factor structures identified in previous studies. Analyses of multiple-group invariance were conducted to determine the extent to which the factor structure is comparable across various demo- graphic groups (i.e., gender, age, marital status, level of education, and employment situa- tion) and over time. Both one-factor and two-factor re-specified models met all the pre- established fit criteria. However, because the factors identified in the two-factor model were highly correlated (r = .86), the one-factor model was preferred for its parsimony. Multi-group CFA indicated measurement invariance across different demographic groups and across time. The present findings suggest that physicians in Spain can use the PHQ-9 to obtain a global score for depression severity in different demographic groups and to reliably monitor changes over time in the primary care setting