Sources of excessive saturated fat, trans fat and sugar consumption in Brazil: an analysis of the first Brazilian nationwide individual dietary survey.

PubMed

Pereira, Rosangela A; Duffey, Kiyah J; Sichieri, Rosely; Popkin, Barry M

2014-01-01

To examine the patterns of consumption of foods high in solid fats and added sugars (SoFAS) in Brazil. Cross-sectional study; individual dietary intake survey. Food intake was assessed by means of two non-consecutive food records. Foods providing >9·1% of energy from saturated fat, or >1·3% of energy from trans fat, or >13% of energy from added sugars per 100 g were classified as high in SoFAS. Brazilian nationwide survey, 2008-2009. Individuals aged ≥10 years old. Mean daily energy intake was 8037 kJ (1921 kcal), 52% of energy came from SoFAS foods. Contribution of SoFAS foods to total energy intake was higher among women (52%) and adolescents (54%). Participants in rural areas (43%) and in the lowest quartile of per capita family income (43%) reported the smallest contribution of SoFAS foods to total energy intake. SoFAS foods were large contributors to total saturated fat (87%), trans fat (89%), added sugar (98%) and total sugar (96%) consumption. The SoFAS food groups that contributed most to total energy intake were meats and beverages. Top SoFAS foods contributing to saturated fat and trans fat intakes were meats and fats and oils. Most of the added and total sugar in the diet was supplied by SoFAS beverages and sweets and desserts. SoFAS foods play an important role in the Brazilian diet. The study identifies options for improving the Brazilian diet and reducing nutrition-related non-communicable chronic diseases, but also points out some limitations of the nutrient-based criteria.

Flame retardants in UK furniture increase smoke toxicity more than they reduce fire growth rate.

PubMed

McKenna, Sean T; Birtles, Robert; Dickens, Kathryn; Walker, Richard G; Spearpoint, Michael J; Stec, Anna A; Hull, T Richard

2018-04-01

This paper uses fire statistics to show the importance of fire toxicity on fire deaths and injuries, and the importance of upholstered furniture and bedding on fatalities from unwanted fires. The aim was to compare the fire hazards (fire growth and smoke toxicity) using different upholstery materials. Four compositions of sofa-bed were compared: three meeting UK Furniture Flammability Regulations (FFR), and one using materials without flame retardants intended for the mainland European market. Two of the UK sofa-beds relied on chemical flame retardants to meet the FFR, the third used natural materials and a technical weave in order to pass the test. Each composition was tested in the bench-scale cone calorimeter (ISO 5660) and burnt as a whole sofa-bed in a sofa configuration in a 3.4 × 2.25 × 2.4 m 3 test room. All of the sofas were ignited with a No. 7 wood crib; the temperatures and yields of toxic products are reported. The sofa-beds containing flame retardants burnt somewhat more slowly than the non-flame retarded EU sofa-bed, but in doing so produced significantly greater quantities of the main fire toxicants, carbon monoxide and hydrogen cyanide. Assessment of the effluents' potential to incapacitate and kill is provided showing the two UK flame retardant sofa-beds to be the most dangerous, followed by the sofa-bed made with European materials. The UK sofa-bed made only from natural materials (Cottonsafe ® ) burnt very slowly and produced very low concentrations of toxic gases. Including fire toxicity in the FFR would reduce the chemical flame retardants and improve fire safety. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

The sequential organ failure assessment (SOFA) score is an effective triage marker following staggered paracetamol (acetaminophen) overdose.

PubMed

Craig, D G; Zafar, S; Reid, T W D J; Martin, K G; Davidson, J S; Hayes, P C; Simpson, K J

2012-06-01

The sequential organ failure assessment (SOFA) score is an effective triage marker following single time point paracetamol (acetaminophen) overdose, but has not been evaluated following staggered (multiple supratherapeutic doses over >8 h, resulting in cumulative dose of >4 g/day) overdoses. To evaluate the prognostic accuracy of the SOFA score following staggered paracetamol overdose. Time-course analysis of 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Individual timed laboratory samples were correlated with corresponding clinical parameters and the daily SOFA scores were calculated. A total of 39/50 (78%) patients developed hepatic encephalopathy. The area under the SOFA receiver operator characteristic for death/liver transplantation was 87.4 (95% CI 73.2-95.7), 94.3 (95% CI 82.5-99.1), and 98.4 (95% CI 84.3-100.0) at 0, 24 and 48 h, respectively, postadmission. A SOFA score of <6 at tertiary care admission predicted survival with a sensitivity of 100.0% (95% CI 76.8-100.0) and specificity of 58.3% (95% CI 40.8-74.5), compared with 85.7% (95% CI 60.6-97.4) and 75.0% (95% CI 65.2-79.5) , respectively, for the modified Kings College criteria. Only 2/21 patients with an admission SOFA score <6 required renal replacement therapy or intracerebral pressure monitoring. SOFA significantly outperformed the Model for End-stage Liver Disease, but not APACHE II, at 0, 24-and 48-h following admission. A SOFA score <6 at tertiary care admission following a staggered paracetamol overdose, is associated with a good prognosis. Both the SOFA and APACHE II scores could improve triage of high-risk staggered paracetamol overdose patients. © 2012 Blackwell Publishing Ltd.

Sources of excessive saturated fat, trans fat and sugar consumption in Brazil: an analysis of the first Brazilian nationwide individual dietary survey

PubMed Central

Pereira, Rosangela A; Duffey, Kiyah J; Sichieri, Rosely; Popkin, Barry M

2013-01-01

Objective To examine the patterns of consumption of foods high in Solid Fats and Added Sugars (SoFAS) in Brazil. Design Cross-sectional study; individual dietary intake survey. Food intake was assessed by means of two non-consecutive food records. Foods providing >9.1% of energy from SAFA, or >1.3% of energy from TFA, or >13% of energy from added sugars per 100g were classified as high in SoFAS. Setting Brazilian nationwide survey, 2008-09. Subjects ≥10 years old individuals. Results Mean energy intake was 8,037 kJ [1,921kcal], 52% of calories came from SoFAS foods. Contribution of SoFAS foods to total energy intake was higher among women (52%) and adolescents (54%). Subjects in rural areas (43%) and in the lowest quartile of per capita family income (43%) reported the smallest contribution of SoFAS foods to total energy intake. SoFAS foods were large contributors to total SAFA (87%), TFA (89%), added sugar (98%), and total sugar (96%) consumption. The SoFAS food groups that contributed most to total energy intake were the meats and beverages. Top SoFAS foods contributing to SAFA and TFA intakes were meats and fats and oils. Most of the added and total sugar in the diet was supplied by SoFAS beverages and sweets and desserts. Conclusions SoFAS foods play an important role in the Brazilian diet. This study identifies options for improving the Brazilian diet and reducing nutrition-related non communicable chronic diseases, but also points out some limitations of the nutrient-based criteria. PMID:23190560

Distortions in Judged Spatial Relations.

ERIC Educational Resources Information Center

Stevens, Albert

1978-01-01

Distortions in judgments of relative geographical relations were observed, particularly when the locations were in different geographical or political units. Subjects distorted the judged relation to conform with the relation of the superordinate political unit. A model for the hierachical storage of spatial information is presented. (Author/RD)

[Validity of APACHE II, APACHE III, SAPS 2, SAPS 3 and SOFA scales in obstetric patients with sepsis].

PubMed

Zabolotskikh, I B; Musaeva, T S; Denisova, E A

2012-01-01

to estimate efficiency of APACHE II, APACHE III, SAPS II, SAPS III, SOFA scales for obstetric patients with heavy sepsis. 186 medical cards retrospective analysis of pregnant women with pulmonary sepsis, 40 women with urosepsis and puerperas with abdominal sepsis--66 was performed. Middle age of women was 26.7 (22.4-34.5). In population of puerperas with abdominal sepsis APACHE II, APACHE III, SAPS 2, SAPS 3, SOFA scales showed to good calibration, however, high resolution was observed only in APACHE III, SAPS 3 and SOFA (AUROC 0.95; 0.93; 0.92 respectively). APACHE III and SOFA scales provided qualitative prognosis in pregnant women with urosepsis; resolution ratio of these scales considerably exceeds APACHE II, SAPS 2 and SAPS 3 (AUROC 0.73; 0.74; 0.79 respectively). APACHE II scale is inapplicable because of a lack of calibration (X2 = 13.1; p < 0.01), and at other scales (APACHE III, SAPS 2, SAPS 3, SOFA) was observed the insufficient resolution (AUROC < 0.9) in pregnant women with pulmonary sepsis. Prognostic possibilities assessment of score scales showed that APACHE III, SAPS 3 and SOFA scales can be used for a lethality prognosis for puerperas with abdominal sepsis, in population of pregnant women with urosepsis--only APACHE III and SOFA, and with pulmonary sepsis--SAPS 3 and APACHE III only in case of additional clinical information.

The Predictive Prognostic Values of Serum TNF-α in Comparison to SOFA Score Monitoring in Critically Ill Patients

PubMed Central

Yousef, Ayman Abd Al-Maksoud; Suliman, Ghada Abdulmomen

2013-01-01

Background. The use of inflammatory markers to follow up critically ill patients is controversial. The short time frame, the need for frequent and serial measurement of biomarkers, the presence of soluble receptor and their relatively high cost are the major drawbacks. Our study's objective is to compare the prognostic values of serum TNF-α and SOFA score monitoring in critically ill patients. Patients and Methods. A total of ninety patients were included in the study. Forty-five patients developed septic complication (sepsis group). Forty-five patients were critically ill without evidence of infectious organism (SIRS group). Patients' data include clinical status, central venous pressure, and laboratory analysis were measured. A serum level of TNF-α and SOFA score were monitored. Results. Monitoring of TNF-α revealed significant elevation of TNF-α at 3rd and 5th days of ICU admission in both groups. Monitoring of SOFA score revealed significant elevation of SOFA scores in both groups throughout their ICU stay, particularly in nonsurvivors. Positive predictive ability of SOFA score was demonstrated in critically ill patients. Conclusion. Transient significant increase in serum levels of TNF-α were detected in septic patients. Persistent elevation of SOFA score was detected in nonsurvivor septic patients. SOFA score is an independent prognostic value in critically ill patients. PMID:24175285

A comparison of pre ICU admission SIRS, EWS and q SOFA scores for predicting mortality and length of stay in ICU.

PubMed

Siddiqui, Shahla; Chua, Maureen; Kumaresh, Venkatesan; Choo, Robin

2017-10-01

The 2015 sepsis definitions suggest using the quick SOFA score for risk stratification of sepsis patients among other changes in sepsis definition. Our aim was to validate the q sofa score for diagnosing sepsis and comparing it to traditional scores of pre ICU admission sepsis outcome prediction such as EWS and SIRS in our setting in order to predict mortality and length of stay. This was a retrospective cohort study. We retrospectively calculated the q sofa, SIRS and EWS scores of all ICU patients admitted with the diagnosis of sepsis at our center in 2015. This was analysed using STATA 12. Logistic regression and ROC curves were used for analysis in addition to descriptive analysis. 58 patients were included in the study. Based on our one year results we have shown that although q SOFA is more sensitive in predicting LOS in ICU of sepsis patients, the EWS score is more sensitive and specific in predicting mortality in the ICU of such patients when compared to q SOFA and SIRS scores. In conclusion, we find that in our setting, EWS is better than SIRS and q SOFA for predicting mortality and perhaps length of stay as well. The q Sofa score remains validated for diagnosis of sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

Validation of the new Sepsis-3 definitions: proposal for improvement in early risk identification.

PubMed

Giamarellos-Bourboulis, E J; Tsaganos, T; Tsangaris, I; Lada, M; Routsi, C; Sinapidis, D; Koupetori, M; Bristianou, M; Adamis, G; Mandragos, K; Dalekos, G N; Kritselis, I; Giannikopoulos, G; Koutelidakis, I; Pavlaki, M; Antoniadou, E; Vlachogiannis, G; Koulouras, V; Prekates, A; Dimopoulos, G; Koutsoukou, A; Pnevmatikos, I; Ioakeimidou, A; Kotanidou, A; Orfanos, S E; Armaganidis, A; Gogos, C

2017-02-01

Sepsis-3 definitions generated controversies regarding their general applicability. The Sepsis-3 Task Force outlined the need for validation with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score. This was done in a prospective cohort from a different healthcare setting. Patients with infections and at least two signs of systemic inflammatory response syndrome (SIRS) were analysed. Sepsis was defined as total SOFA ≥2 outside the intensive care unit (ICU) or as an increase of ICU admission SOFA ≥2. The primary endpoints were the sensitivity of qSOFA outside the ICU and sepsis definition both outside and within the ICU to predict mortality. In all, 3346 infections outside the ICU and 1058 infections in the ICU were analysed. Outside the ICU, respective mortality with ≥2 SIRS and qSOFA ≥2 was 25.3% and 41.2% (p <0.0001); the sensitivities of qSOFA and of sepsis definition to predict death were 60.8% and 87.2%, respectively. This was 95.9% for sepsis definition in the ICU. The sensitivity of qSOFA and of ≥3 SIRS criteria for organ dysfunction outside the ICU was 48.7% and 72.5%, respectively (p <0.0001). Misclassification outside the ICU with the 1991 and Sepsis-3 definitions into stages of lower severity was 21.4% and 3.7%, respectively (p <0.0001) and 14.9% and 3.7%, respectively, in the ICU (p <0.0001). Adding arterial pH ≤7.30 to qSOFA increased sensitivity for prediction of death to 67.5% (p 0.004). Our analysis positively validated the use of SOFA score to predict unfavourable outcome and to limit misclassification into lower severity. However, qSOFA score had inadequate sensitivity for early risk assessment. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Early detection of nonneurologic organ failure in patients with severe traumatic brain injury: Multiple organ dysfunction score or sequential organ failure assessment?

PubMed

Ramtinfar, Sara; Chabok, Shahrokh Yousefzadeh; Chari, Aliakbar Jafari; Reihanian, Zoheir; Leili, Ehsan Kazemnezhad; Alizadeh, Arsalan

2016-10-01

The aim of this study is to compare the discriminant function of multiple organ dysfunction score (MODS) and sequential organ failure assessment (SOFA) components in predicting the Intensive Care Unit (ICU) mortality and neurologic outcome. A descriptive-analytic study was conducted at a level I trauma center. Data were collected from patients with severe traumatic brain injury admitted to the neurosurgical ICU. Basic demographic data, SOFA and MOD scores were recorded daily for all patients. Odd's ratios (ORs) were calculated to determine the relationship of each component score to mortality, and area under receiver operating characteristic (AUROC) curve was used to compare the discriminative ability of two tools with respect to ICU mortality. The most common organ failure observed was respiratory detected by SOFA of 26% and MODS of 13%, and the second common was cardiovascular detected by SOFA of 18% and MODS of 13%. No hepatic or renal failure occurred, and coagulation failure reported as 2.5% by SOFA and MODS. Cardiovascular failure defined by both tools had a correlation to ICU mortality and it was more significant for SOFA (OR = 6.9, CI = 3.6-13.3, P < 0.05 for SOFA; OR = 5, CI = 3-8.3, P < 0.05 for MODS; AUROC = 0.82 for SOFA; AUROC = 0.73 for MODS). The relationship of cardiovascular failure to dichotomized neurologic outcome was not significant statistically. ICU mortality was not associated with respiratory or coagulation failure. Cardiovascular failure defined by either tool significantly related to ICU mortality. Compared to MODS, SOFA-defined cardiovascular failure was a stronger predictor of death. ICU mortality was not affected by respiratory or coagulation failures.

Surface Design Based on Discrete Conformal Transformations

NASA Astrophysics Data System (ADS)

Duque, Carlos; Santangelo, Christian; Vouga, Etienne

Conformal transformations are angle-preserving maps from one domain to another. Although angles are preserved, the lengths between arbitrary points are not generally conserved. As a consequence there is always a given amount of distortion associated to any conformal map. Different uses of such transformations can be found in various fields, but have been used by us to program non-uniformly swellable gel sheets to buckle into prescribed three dimensional shapes. In this work we apply circle packings as a kind of discrete conformal map in order to find conformal maps from the sphere to the plane that can be used as nearly uniform swelling patterns to program non-Euclidean sheets to buckle into spheres. We explore the possibility of tuning the area distortion to fit the experimental range of minimum and maximum swelling by modifying the boundary of the planar domain through the introduction of different cutting schemes.

Restoring 2D content from distorted documents.

PubMed

Brown, Michael S; Sun, Mingxuan; Yang, Ruigang; Yun, Lin; Seales, W Brent

2007-11-01

This paper presents a framework to restore the 2D content printed on documents in the presence of geometric distortion and non-uniform illumination. Compared with textbased document imaging approaches that correct distortion to a level necessary to obtain sufficiently readable text or to facilitate optical character recognition (OCR), our work targets nontextual documents where the original printed content is desired. To achieve this goal, our framework acquires a 3D scan of the document's surface together with a high-resolution image. Conformal mapping is used to rectify geometric distortion by mapping the 3D surface back to a plane while minimizing angular distortion. This conformal "deskewing" assumes no parametric model of the document's surface and is suitable for arbitrary distortions. Illumination correction is performed by using the 3D shape to distinguish content gradient edges from illumination gradient edges in the high-resolution image. Integration is performed using only the content edges to obtain a reflectance image with significantly less illumination artifacts. This approach makes no assumptions about light sources and their positions. The results from the geometric and photometric correction are combined to produce the final output.

The Relationship between Self-Assembly and Conformal Mappings

NASA Astrophysics Data System (ADS)

Duque, Carlos; Santangelo, Christian

The isotropic growth of a thin sheet has been used as a way to generate programmed shapes through controlled buckling. We discuss how conformal mappings, which are transformations that locally preserve angles, provide a way to quantify the area growth needed to produce a particular shape. A discrete version of the conformal map can be constructed from circle packings, which are maps between packings of circles whose contact network is preserved. This provides a link to the self-assembly of particles on curved surfaces. We performed simulations of attractive particles on a curved surface using molecular dynamics. The resulting particle configurations were used to generate the corresponding discrete conformal map, allowing us to quantify the degree of area distortion required to produce a particular shape by finding particle configurations that minimize the area distortion.

A Comparison of the Quick-SOFA and Systemic Inflammatory Response Syndrome Criteria for the Diagnosis of Sepsis and Prediction of Mortality: A Systematic Review and Meta-Analysis.

PubMed

Serafim, Rodrigo; Gomes, José Andrade; Salluh, Jorge; Póvoa, Pedro

2018-03-01

Several studies were published to validate the quick Sepsis-related Organ Failure Assessment (qSOFA), namely in comparison with the systemic inflammatory response syndrome (SIRS) criteria. We performed a systematic review and meta-analysis with the aim of comparing the qSOFA and SIRS in patients outside the ICU. We searched MEDLINE, CINAHL, and the Web of Science database from February 23, 2016 until June 30, 2017 to identify full-text English-language studies published after the Sepsis-3 publication comparing the qSOFA and SIRS and their sensitivity or specificity in diagnosing sepsis, as well as hospital and ICU length of stay and hospital mortality. Data extraction from the selected studies followed the recommendations of the Meta-analyses of Observational Studies in Epidemiology group and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. From 4,022 citations, 10 studies met the inclusion criteria. Pooling all the studies, a total of 229,480 patients were evaluated. The meta-analysis of sensitivity for the diagnosis of sepsis comparing the qSOFA and SIRS was in favor of SIRS (risk ratio [RR], 1.32; 95% CI, 0.40-2.24; P < .0001; I 2  = 100%). One study described the specificity for the diagnosis of infection comparing SIRS (84.4%; 95% CI, 76.2-90.6) with the qSOFA (97.3%; 95% CI < 92.1-99.4); the qSOFA demonstrated better specificity. The meta-analysis of the area under the receiver operating characteristic curve of six studies comparing the qSOFA and SIRS favored the qSOFA (RR, 0.03; 95% CI, 0.01-0.05; P = .002; I 2  = 48%) as a predictor of inhospital mortality. The SIRS was significantly superior to the qSOFA for sepsis diagnosis, and the qSOFA was slightly better than the SIRS in predicting hospital mortality. The association of both criteria could provide a better model to initiate or escalate therapy in patients with sepsis. PROSPERO CRD42017067645. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Adaptation and Validation of a Pediatric Sequential Organ Failure Assessment Score and Evaluation of the Sepsis-3 Definitions in Critically Ill Children.

PubMed

Matics, Travis J; Sanchez-Pinto, L Nelson

2017-10-02

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) uses the Sequential Organ Failure Assessment (SOFA) score to grade organ dysfunction in adult patients with suspected infection. However, the SOFA score is not adjusted for age and therefore not suitable for children. To adapt and validate a pediatric version of the SOFA score (pSOFA) in critically ill children and to evaluate the Sepsis-3 definitions in patients with confirmed or suspected infection. This retrospective observational cohort study included all critically ill children 21 years or younger admitted to a 20-bed, multidisciplinary, tertiary pediatric intensive care unit between January 1, 2009 and August 1, 2016. Data on these children were obtained from an electronic health record database. The pSOFA score was developed by adapting the original SOFA score with age-adjusted cutoffs for the cardiovascular and renal systems and by expanding the respiratory criteria to include noninvasive surrogates of lung injury. Daily pSOFA scores were calculated from admission until day 28 of hospitalization, discharge, or death (whichever came first). Three additional pediatric organ dysfunction scores were calculated for comparison. Organ dysfunction measured by the pSOFA score, and sepsis and septic shock according to the Sepsis-3 definitions. The primary outcome was in-hospital mortality. The daily pSOFA scores and additional pediatric organ dysfunction scores were compared. Performance was evaluated using the area under the curve. The pSOFA score was then used to assess the Sepsis-3 definitions in the subgroup of children with confirmed or suspected infection. In all, 6303 patients with 8711 encounters met inclusion criteria. Each encounter was treated independently. Of the 8482 survivors of hospital encounters, 4644 (54.7%) were male and the median (interquartile range [IQR]) age was 69 (17-156) months. Among the 229 nonsurvivors, 127 (55.4%) were male with a median (IQR) age of 43 (8-144) months. In-hospital mortality was 2.6%. The maximum pSOFA score had excellent discrimination for in-hospital mortality, with an area under the curve of 0.94 (95% CI, 0.92-0.95). The pSOFA score had a similar or better performance than other pediatric organ dysfunction scores. According to the Sepsis-3 definitions, 1231 patients (14.1%) were classified as having sepsis and had a mortality rate of 12.1%, and 347 (4.0%) had septic shock and a mortality rate of 32.3%. Patients with sepsis were more likely to die than patients with confirmed or suspected infection but no sepsis (odds ratio, 18; 95% CI, 11-28). Of the 229 patients who died during their hospitalization, 149 (65.0%) had sepsis or septic shock during their course. The pSOFA score was adapted and validated with age-adjusted variables in critically ill children. Using the pSOFA score, the Sepsis-3 definitions were assessed in children with confirmed or suspected infection. This study is the first assessment, to date, of the Sepsis-3 definitions in critically ill children. Use of these definitions in children is feasible and shows promising results.

Systemic Inflammatory Response Syndrome, Quick Sequential Organ Function Assessment, and Organ Dysfunction: Insights From a Prospective Database of ED Patients With Infection.

PubMed

Williams, Julian M; Greenslade, Jaimi H; McKenzie, Juliet V; Chu, Kevin; Brown, Anthony F T; Lipman, Jeffrey

2017-03-01

A proposed revision of sepsis definitions has abandoned the systemic inflammatory response syndrome (SIRS), defined organ dysfunction as an increase in total Sequential Organ Function Assessment (SOFA) score of ≥ 2, and conceived "qSOFA" (quick SOFA) as a bedside indicator of organ dysfunction. We aimed to (1) determine the prognostic impact of SIRS, (2) compare the diagnostic accuracy of SIRS and qSOFA for organ dysfunction, and (3) compare standard (Sepsis-2) and revised (Sepsis-3) definitions for organ dysfunction in ED patients with infection. Consecutive ED patients admitted with presumed infection were prospectively enrolled over 3 years. Sufficient observational data were collected to calculate SIRS, qSOFA, SOFA, comorbidity, and mortality. We enrolled 8,871 patients, with SIRS present in 4,176 (47.1%). SIRS was associated with increased risk of organ dysfunction (relative risk [RR] 3.5) and mortality in patients without organ dysfunction (OR 3.2). SIRS and qSOFA showed similar discrimination for organ dysfunction (area under the receiver operating characteristic curve, 0.72 vs 0.73). qSOFA was specific but poorly sensitive for organ dysfunction (96.1% and 29.7%, respectively). Mortality for patients with organ dysfunction was similar for Sepsis-2 and Sepsis-3 (12.5% and 11.4%, respectively), although 29% of patients with Sepsis-3 organ dysfunction did not meet Sepsis-2 criteria. Increasing numbers of Sepsis-2 organ system dysfunctions were associated with greater mortality. SIRS was associated with organ dysfunction and mortality, and abandoning the concept appears premature. A qSOFA score ≥ 2 showed high specificity, but poor sensitivity may limit utility as a bedside screening method. Although mortality for organ dysfunction was comparable between Sepsis-2 and Sepsis-3, more prognostic and clinical information is conveyed using Sepsis-2 regarding number and type of organ dysfunctions. The SOFA score may require recalibration. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

3-(4-Hy­droxy­phen­yl)-7-meth­oxy­chroman-4-one monohydrate

PubMed Central

Xiao, Zhu-Ping; Peng, Zhu-Yun; Luo, Qun; Wu, Ying; Yang, Ye-Ling

2011-01-01

In the title compound, C16H14O4·H2O, the dihedral angle betwen the benzene rings is 71.4 (6)°. The pyran ring is in a sofa conformation. In the crystal, O—H⋯O hydrogen bonds connect the components into a two-dimensional network parallel to (010), incorporating C 2 2(4) and C 2 2(11) chains. In addition, weak C—H⋯O, C—H⋯π and π–π stacking inter­actions [centroid–centroid distance = 3.768 (2) Å] are present. PMID:22199730

76 FR 62894 - Following Procedures When Going Between Rolling Equipment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-11

... Operations Fatality Analysis (SOFA) Working Group. In October 1999, the Working Group issued a report titled ``Findings and Recommendations of the SOFA Working Group.'' The report can be found on FRA's Web site at http... recommendation reads as follows: \\1\\ More recently, in March 2011, the SOFA Working Group issued a report titled...

The Association Between Sequential Organ Failure Assessment Scores and Mortality in Patients With Sepsis During the First Week: The JSEPTIC DIC Study.

PubMed

Nakashima, Tsuyoshi; Miyamoto, Kyohei; Shimokawa, Toshio; Kato, Seiya; Hayakawa, Mineji

2018-01-01

Predicting prognosis is a complex process, particularly in patients with severe sepsis or septic shock. This study aimed to determine the relationship between the Sequential Organ Failure Assessment (SOFA) scores for individual organs during the first week of admission and the in-hospital mortality in patients with sepsis. This study was a post hoc evaluation of the Japan Septic Disseminated Intravascular Coagulation study and included patients admitted to 42 intensive care units in Japan for severe sepsis or septic shock, between January 2011 and December 2013. We assessed the relationship between the organ and total SOFA scores on days 1, 3, and 7 following admission and the in-hospital mortality using logistic regression analysis. We evaluated 2732 patients and found the in-hospital mortality rate was 29.1%. The mean age of the patients (standard deviation) was 70.5 (14.1) years, and the major primary site of infection was the abdomen (33.6%). The central nervous system (CNS) SOFA score exhibited the strongest relationship with mortality on days 1 (adjusted odds ratio [aOR]: 1.49, 95% confidence interval [CI]: 1.40-1.59), 3 (aOR: 1.75, 95% CI: 1.62-1.89), and 7 (aOR: 1.93, 95% CI: 1.77-2.10). The coagulation SOFA scores showed a weak correlation with mortality on day 1, but a strong correlation with mortality on day 7 (aOR: 2.04, 95% CI: 1.87-2.24). The CNS SOFA scores were associated with mortality in patients with severe sepsis on days 1, 3, and 7 following hospitalization. The coagulation SOFA score was associated with mortality on day 7. In clinical situations, the CNS SOFA scores during the acute phase and the CNS SOFA and coagulation SOFA scores during the subsequent phases should be evaluated in order to determine patient prognosis.

Predictive Value of the Sequential Organ Failure Assessment Score for Mortality in a Contemporary Cardiac Intensive Care Unit Population.

PubMed

Jentzer, Jacob C; Bennett, Courtney; Wiley, Brandon M; Murphree, Dennis H; Keegan, Mark T; Gajic, Ognjen; Wright, R Scott; Barsness, Gregory W

2018-03-10

Optimal methods of mortality risk stratification in patients in the cardiac intensive care unit (CICU) remain uncertain. We evaluated the ability of the Sequential Organ Failure Assessment (SOFA) score to predict mortality in a large cohort of unselected patients in the CICU. Adult patients admitted to the CICU from January 1, 2007, to December 31, 2015, at a single tertiary care hospital were retrospectively reviewed. SOFA scores were calculated daily, and Acute Physiology and Chronic Health Evaluation (APACHE)-III and APACHE-IV scores were calculated on CICU day 1. Discrimination of hospital mortality was assessed using area under the receiver-operator characteristic curve values. We included 9961 patients, with a mean age of 67.5±15.2 years; all-cause hospital mortality was 9.0%. Day 1 SOFA score predicted hospital mortality, with an area under the receiver-operator characteristic curve value of 0.83; area under the receiver-operator characteristic curve values were similar for the APACHE-III score, and APACHE-IV predicted mortality ( P >0.05). Mean and maximum SOFA scores over multiple CICU days had greater discrimination for hospital mortality ( P <0.01). Patients with an increasing SOFA score from day 1 and day 2 had higher mortality. Patients with day 1 SOFA score <2 were at low risk of mortality. Increasing tertiles of day 1 SOFA score predicted higher long-term mortality ( P <0.001 by log-rank test). The day 1 SOFA score has good discrimination for short-term mortality in unselected patients in the CICU, which is comparable to APACHE-III and APACHE-IV. Advantages of the SOFA score over APACHE include simplicity, improved discrimination using serial scores, and prediction of long-term mortality. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Sofas and Infant Mortality

PubMed Central

Rechtman, Lauren R.; Colvin, Jeffrey D.; Blair, Peter S.

2014-01-01

OBJECTIVE: Sleeping on sofas increases the risk of sudden infant death syndrome and other sleep-related deaths. We sought to describe factors associated with infant deaths on sofas. METHODS: We analyzed data for infant deaths on sofas from 24 states in 2004 to 2012 in the National Center for the Review and Prevention of Child Deaths Case Reporting System database. Demographic and environmental data for deaths on sofas were compared with data for sleep-related infant deaths in other locations, using bivariate and multivariable, multinomial logistic regression analyses. RESULTS: A total of 1024 deaths on sofas made up 12.9% of sleep-related infant deaths. They were more likely than deaths in other locations to be classified as accidental suffocation or strangulation (adjusted odds ratio [aOR] 1.9; 95% confidence interval [CI], 1.6–2.3) or ill-defined cause of death (aOR 1.2; 95% CI, 1.0–1.5). Infants who died on sofas were less likely to be Hispanic (aOR 0.7; 95% CI, 0.6–0.9) compared with non-Hispanic white infants or to have objects in the environment (aOR 0.6; 95% CI, 0.5–0.7) and more likely to be sharing the surface with another person (aOR 2.4; 95% CI, 1.9–3.0), to be found on the side (aOR 1.9; 95% CI, 1.4–2.4), to be found in a new sleep location (aOR 6.5; 95% CI, 5.2–8.2), and to have had prenatal smoke exposure (aOR 1.4; 95% CI, 1.2–1.6). Data on recent parental alcohol and drug consumption were not available. CONCLUSIONS: The sofa is an extremely hazardous sleep surface for infants. Deaths on sofas are associated with surface sharing, being found on the side, changing sleep location, and experiencing prenatal tobacco exposure, which are all risk factors for sudden infant death syndrome and sleep-related deaths. PMID:25311597

Use of the Sequential Organ Failure Assessment score for evaluating outcome among obstetric patients admitted to the intensive care unit.

PubMed

Jain, Shruti; Guleria, Kiran; Suneja, Amita; Vaid, Neelam B; Ahuja, Sharmila

2016-03-01

To evaluate the prognostic value of the Sequential Organ Failure Assessment (SOFA) score among obstetric patients admitted to the intensive care unit (ICU). A prospective study was conducted among 90 consecutive obstetric patients who were admitted to the ICU of Guru Teg Bahadur Hospital, Delhi, India, between October 6, 2010, and December 25, 2011. Maximum SOFA score was calculated for each of the six organ systems. Receiver operating characteristic curves were used to determine critical cutoff values for total, maximum total, and mean total SOFA scores at various time points. Total SOFA score at admission displayed an area under the curve (AUC) of 0.949, a cutoff value of at least 8.5, sensitivity of 86.7%, and specificity of 90.0%. Maximum total SOFA score had an AUC of 0.980, a cutoff value of at least 10.0, sensitivity of 96.7%, and specificity of 90.0%. Mean total SOFA score had an AUC of 0.997, a cutoff value of at least 9.0, sensitivity of 96.7%, and specificity of 96.7%. In terms of discriminatory power for predicting mortality among obstetric patients admitted to the ICU, total SOFA score at admission was the most relevant, simple, and accurate measure. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Solid fat and added sugar intake among U.S. children: The role of stores, schools, and fast food, 1994-2010.

PubMed

Poti, Jennifer M; Slining, Meghan M; Popkin, Barry M

2013-11-01

Little is known about the role of location in U.S. children's excess intake of energy from solid fat and added sugar, collectively referred to as SoFAS. The goal of this study was to compare the SoFAS content of foods consumed by children from stores, schools, and fast-food restaurants and to determine whether trends from 1994 to 2010 differ across these locations. Children aged 2-18 years (N=22,103) from five nationally representative surveys of dietary intake from 1994 to 2010 were studied. SoFAS content was compared across locations for total intake and key foods. Regression models were used to test and compare linear trends across locations. Data were analyzed in 2012. The mean percentage of total energy intake consumed from each location that was provided by SoFAS remained above recommendations, despite significant improvements between 1994 and 2010 at stores (1994, 38.3%; 2004, 33.2%); schools (1994, 38.7%; 2004, 31.2%); and fast-food restaurants (1994, 34.6%; 2004, 34.6%). For each key food, SoFAS content decreased significantly at stores and schools, yet progress at schools was comparatively slower. Milk was higher in SoFAS at schools compared to stores because of shifts toward flavored milk at schools. Schools provided french fries that were higher in solid fat than store-bought versions and pizza that was not significantly different in SoFAS content than fast-food pizza. However, schools made significantly greater progress for sugar-sweetened beverages, as lower-sugar beverages replaced regular sodas. Key fast foods showed little improvement. These findings can inform future strategies targeted to the specific locations and foods where continued progress is needed to reduce children's SoFAS consumption. © 2013 American Journal of Preventive Medicine.

Comparison of QSOFA score and SIRS criteria as screening mechanisms for emergency department sepsis.

PubMed

Haydar, Samir; Spanier, Matthew; Weems, Patricia; Wood, Samantha; Strout, Tania

2017-11-01

The Quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score has been shown to accurately predict mortality in septic patients and is part of recently proposed diagnostic criteria for sepsis. We sought to ascertain the sensitive of the score in diagnosing sepsis, as well as the diagnostic timeliness of the score when compared to traditional systemic inflammatory response syndrome (SIRS) criteria in a population of emergency department (ED) patients treated in the ED, admitted, and subsequently discharged with a diagnosis of sepsis. Electronic health records of 200 patients who were treated for suspected sepsis in our ED and ultimately discharged from our hospital with a diagnosis of sepsis were randomly selected for review from a population of adult ED patients (N=1880). Data extracted included the presence of SIRS criteria and the qSOFA score as well as time required to meet said criteria. In this cohort, 94.5% met SIRS criteria while in the ED whereas only 58.3% met qSOFA. The mean time from arrival to SIRS documentation was 47.1min (95% CI: 36.5-57.8) compared to 84.0min (95% CI: 62.2-105.8) for qSOFA. The median ED "door" to positive SIRS criteria was 12min and 29min for qSOFA. Although qSOFA may be valuable in predicting sepsis-related mortality, it performed poorly as a screening tool for identifying sepsis in the ED. As the time to meet qSOFA criteria was significantly longer than for SIRS, relying on qSOFA alone may delay initiation of evidence-based interventions known to improve sepsis-related outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Rotational characterization of methyl methacrylate: Internal dynamics and structure determination

NASA Astrophysics Data System (ADS)

Herbers, Sven; Wachsmuth, Dennis; Obenchain, Daniel A.; Grabow, Jens-Uwe

2018-01-01

Rotational constants, Watson's S centrifugal distortion coefficients, and internal rotation parameters of the two most stable conformers of methyl methacrylate were retrieved from the microwave spectrum. Splittings of rotational energy levels were caused by two non equivalent methyl tops. Constraining the centrifugal distortion coefficients and internal rotation parameters to the values of the main isotopologues, the rotational constants of all single substituted 13C and 18O isotopologues were determined. From these rotational constants the substitution structures and semi-empirical zero point structures of both conformers were precisely determined.

Projection lithography with distortion compensation using reticle chuck contouring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tichenor, Daniel A.

2001-01-01

A chuck for holding a reflective reticle where the chuck has an insulator block with a non-planer surface contoured to cause distortion correction of EUV radiation is provided. Upon being placed on the chuck, a thin, pliable reflective reticle will conform to the contour of the chuck's non-planer surface. When employed in a scanning photolithography system, distortion in the scanned direction is corrected.

Poor performance of quick-SOFA (qSOFA) score in predicting severe sepsis and mortality - a prospective study of patients admitted with infection to the emergency department.

PubMed

Askim, Åsa; Moser, Florentin; Gustad, Lise T; Stene, Helga; Gundersen, Maren; Åsvold, Bjørn Olav; Dale, Jostein; Bjørnsen, Lars Petter; Damås, Jan Kristian; Solligård, Erik

2017-06-09

We aimed to evaluate the clinical usefulness of qSOFA as a risk stratification tool for patients admitted with infection compared to traditional SIRS criteria or our triage system; the Rapid Emergency Triage and Treatment System (RETTS). The study was an observational cohort study performed at one Emergency Department (ED) in an urban university teaching hospital in Norway, with approximately 20,000 visits per year. All patients >16 years presenting with symptoms or clinical signs suggesting an infection (n = 1535) were prospectively included in the study from January 1 to December 31, 2012. At arrival in the ED, vital signs were recorded and all patients were triaged according to RETTS vital signs, presenting infection, and sepsis symptoms. These admission data were also used to calculate qSOFA and SIRS. Treatment outcome was later retrieved from the patients' electronic records (EPR) and mortality data from the Norwegian population registry. Of the 1535 admitted patients, 108 (7.0%) fulfilled the Sepsis2 criteria for severe sepsis. The qSOFA score ≥2 identified only 33 (sensitivity 0.32, specificity 0.98) of the patients with severe sepsis, whilst the RETTS-alert ≥ orange identified 92 patients (sensitivity 0.85, specificity 0.55). Twenty-six patients died within 7 days of admission; four (15.4%) of them had a qSOFA ≥2, and 16 (61.5%) had RETTS ≥ orange alert. Of the 68 patients that died within 30 days, only eight (11.9%) scored ≥2 on the qSOFA, and 45 (66.1%) had a RETTS ≥ orange alert. In order to achieve timely treatment for sepsis, a sensitive screening tool is more important than a specific one. Our study is the fourth study were qSOFA finds few of the sepsis cases in prehospital or at arrival to the ED. We add information on the RETTS triage system, the two highest acuity levels together had a high sensitivity (85%) for identifying sepsis at arrival to the ED - and thus, RETTS should not be replaced by qSOFA as a screening and trigger tool for sepsis at arrival. In this observational cohort study, qSOFA failed to identify two thirds of the patients admitted to an ED with severe sepsis. Further, qSOFA failed to be a risk stratification tool as the sensitivity to predict 7-day and 30-day mortality was low. The sensitivity was poorer than the other warning scores already in use at the study site, RETTS-triage and the SIRS criteria.

14-Meth­oxy-4,6-dimethyl-9-phenyl-8,12-dioxa-4,6-di­aza­tetra­cyclo­[8.8.0.02,7.013,18]octa­deca-2(7),13,15,17-tetra­ene-3,5,11-trione

PubMed Central

Jagadeesan, G; Jayashree, S.; Kannan, D.; Bakthadoss, M.; Aravindhan, S.

2013-01-01

The title compound, C23H20N2O6, crystallizes with two mol­ecules in the asymmetric unit in which the dihedral angles between the mean planes of the pyran and phenyl rings are 66.6 (1) and 61.9 (1) °. The fused pyrone and pyran rings each adopts a sofa conformation. In the crystal, C—H⋯O hydrogen bonds link the mol­ecules, forming a two-dimensional network parallel to [001]. PMID:24109298

14-Eth­oxy-4,6-dimethyl-9-phenyl-8,12-dioxa-4,6-diaza­tetra­cyclo­[8.8.0.02,7.013,18]octa­deca-2(7),13,15,17-tetra­ene-3,5,11-trione

PubMed Central

Jagadeesan, G.; Kannan, D.; Bakthadoss, M.; Aravindhan, S.

2013-01-01

In the title compound, C23H20N2O6, the fused pyrone and pyran rings each adopt a sofa conformation. The dihedral angle between the mean planes of the pyran and phenyl rings is 61.9 (1)°. In the crystal, mol­ecules are linked by two pairs of C—H⋯O hydrogen bonds, forming dimers. These dimers are linked via a third C—H⋯O hydrogen bond, forming a two-dimensional network parallel to (10-2). PMID:23476462

Precise CCD positions of Himalia using Gaia DR1 in 2015-2016

NASA Astrophysics Data System (ADS)

Peng, H. W.; Peng, Q. Y.; Wang, N.

2017-05-01

In order to obtain high-precision CCD positions of Himalia, the sixth Jovian satellite, a total of 598 CCD observations have been obtained during the years 2015-2016. The observations were made by using the 2.4 and 1 m telescopes administered by Yunnan Observatories over 27 nights. Several factors that would influence the positional precision of Himalia were analysed, including the reference star catalogue used, the geometric distortion and the phase effect. By taking advantage of its unprecedented positional precision, the recently released catalogue Gaia Data Release 1 was chosen to match reference stars in the CCD frames of both Himalia and open clusters, which were observed for deriving the geometric distortion. The latest version of sofa library was used to calculate the positions of reference stars. The theoretical positions of Himalia were retrieved from the Jet Propulsion Laboratory Horizons System that includes the satellite ephemeris JUP300, while the positions of Jupiter were based on the planetary ephemeris DE431. Our results showed that the means of observed minus computed (O - C) residuals are 0.071 and -0.001 arcsec in right ascension and declination, respectively. Their standard deviations are estimated at about 0.03 arcsec in each direction.

The principle of minimal episteric distortion of the water matrix and its steering role in protein folding

NASA Astrophysics Data System (ADS)

Fernández, Ariel

2013-08-01

A significant episteric ("around a solid") distortion of the hydrogen-bond structure of water is promoted by solutes with nanoscale surface detail and physico-chemical complexity, such as soluble natural proteins. These structural distortions defy analysis because the discrete nature of the solvent at the interface is not upheld by the continuous laws of electrostatics. This work derives and validates an electrostatic equation that governs the episteric distortions of the hydrogen-bond matrix. The equation correlates distortions from bulk-like structural patterns with anomalous polarization components that do not align with the electrostatic field of the solute. The result implies that the interfacial energy stored in the orthogonal polarization correlates with the distortion of the water hydrogen-bond network. The result is validated vis-à-vis experimental data on protein interfacial thermodynamics and is interpreted in terms of the interaction energy between the electrostatic field of the solute and the dipole moment induced by the anomalous polarization of interfacial water. Finally, we consider solutes capable of changing their interface through conformational transitions and introduce a principle of minimal episteric distortion (MED) of the water matrix. We assess the importance of the MED principle in the context of protein folding, concluding that the native fold may be identified topologically with the conformation that minimizes the interfacial tension or disruption of the water matrix.

Accuracy of SOFA score in prediction of 30-day outcome of critically ill patients.

PubMed

Safari, Saeed; Shojaee, Majid; Rahmati, Farhad; Barartloo, Alireza; Hahshemi, Behrooz; Forouzanfar, Mohammad Mehdi; Mohammadi, Elham

2016-12-01

Researchers have attempted to design various scoring systems to determine the severity and predict the outcome of critically ill patients. The present study aimed to evaluate the accuracy of SOFA score in predicting 1-month outcome of these patients in emergency department. The present study is a prospective cross-sectional study of >18 year old non-trauma critically ill patients presented to EDs of 3 hospitals, Tehran, Iran, during October 2014 to October 2015. Baseline characteristics, SOFA score variables, and 1-month outcome of patients were recorded and screening performance characteristics of the score were calculated using STATA 11 software. 140 patients with the mean age of 68.36 ± 18.62 years (18-95) were included (53.5% male). The most common complaints were decrease in level of consciousness (76.43%) and sepsis (60.0%), were the most frequent final diagnoses. Mean SOFA score of the patients was 7.13 ± 2.36 (minimum 2 and maximum 16). 72 (51.43%) patients died during the following 30 days and 16 (11.43%) patients were affected with multiple organ failure. Area under the ROC curve of SOFA score in predicting mortality of studied patients was 0.73 (95%CI: 0.65-0.81) (Fig. 2). Table 2 depicts screening performance characteristics of this scale in prediction of 1-month mortality in the best cut-off point of ≥7. At this cut-off point, sensitivity and specificity of SOFA in predicting 1-month mortality were 75% and 63.23%, respectively. Findings of the present study showed that SOFA scoring system has fair accuracy in predicting 1-month mortality of critically ill patients. However, until a more reliable scoring system is developed, SOFA might be useful for narrative prediction of patient outcome considering its acceptable likelihood ratios.

Prehospital triage of septic patients at the SAMU regulation: Comparison of qSOFA, MRST, MEWS and PRESEP scores.

PubMed

Jouffroy, R; Saade, A; Ellouze, S; Carpentier, A; Michaloux, M; Carli, P; Vivien, B

2018-05-01

A couple of scoring systems have been developed for risk stratification of septic patients. Their performance in the management of out-of-hospital initial care delivery is not documented. This study try to evaluate the predictive ability of Quick Sequential Organ Failure Assessment (qSOFA), Robson Screening Tool (RST), Modified Early Warning Score (MEWS) and Prehospital Early Sepsis Detection (PRESEP) scores on out of-hospital triage of septic patients, to predict intensive care unit (ICU) admission. A retrospective study using call records received by the SAMU 15 regulation call centre including all patients with presumed septic shock was performed. The primary outcome was the admission to the ICU. Among the 47 000 reports received, 37 patients with presumed septic shock were included. Twenty-two patients (59%) were admitted to ICU. AUCs of qSOFA, RST, MEWS and PRESEP scores were respectively 0.40 [0.22-0.59], 0.60 [0.43-0.78], 0.66 [0.47-0.85] and 0.67 [0.51-0.84]. RST outperformed PRESEP, MEWS and qSOFA for sensitivity (1, 0.92, 0.85 and 0.62 respectively). MEWS showed better specificity than PRESEP, MRST and qSOFA (0.33, 0.29, 0.16 and 0.16). MEWS showed comparable positive predictive value than PRESEP and outperformed MRST and qSOFA (0.41, 0.41, 0.39 and 0.29 respectively). Negative predictive value of MRST outperformed PRESEP, MEWS and qSOFA (1, 0.88, 0.80 and 0.44 respectively). Our findings suggest that screening patients at SAMU 15 regulation call centre using qSOFA, MRST, MEWS and PRESEP scores to predict ICU admission is irrelevant. Development of a specific scoring system for out-of-hospital triage of septic patients is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Plasma cell-free DNA and qSOFA score predict 7-day mortality in 481 emergency department bacteraemia patients.

PubMed

Rannikko, Juha; Seiskari, Tapio; Huttunen, Reetta; Tarkiainen, Iina; Jylhävä, Juulia; Hurme, Mikko; Syrjänen, Jaana; Aittoniemi, Janne

2018-04-24

A few studies have shown that both quick Sequential Organ Failure Assessment (qSOFA) score and cell-free DNA (cfDNA) have potential use as a prognostic marker in patients with infection. We studied these two markers alone and in combination to identify those emergency department (ED) patients with the highest risk of death. Plasma cfDNA level was studied on days 0 to 4 after admittance to the ED from 481 culture-positive bloodstream infection cases. The qSOFA score was evaluated retrospectively according to Sepsis-3 definitions. The primary outcome was death by day 7. CfDNA on day 0 was significantly higher in non-survivors than in survivors (2.02 μg/ml vs. 1.35 μg/ml, p<0.001). CfDNA level was high (>1.69 μg/ml) in 134 (28%) out of 481 cases and the qSOFA score was ≥2 in 128 (28%) out of 458 cases. High cfDNA and qSOFA score ≥2 had 70% and 77% sensitivity and 76% and 76% specificity in predicting death by day 7, respectively. High cfDNA alone had odds ratio (OR) of 7.7 (95% CI 3.9-15.3) and qSOFA score ≥2 OR of 11.6 (5.5-24.3), but their combination had OR of 20.3 (10.0-41.4) in predicting death by day 7 when compared with those with low cfDNA and qSOFA score <2. Among the five cases with the highest cfDNA levels, there were three patients with severe disseminated intravascular coagulation. CfDNA and qSOFA score can be used independently to identify those bacteraemia patients at high risk of death, and combining these two markers gives additional advantage. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Organ failure and tight glycemic control in the SPRINT study.

PubMed

Chase, J Geoffrey; Pretty, Christopher G; Pfeifer, Leesa; Shaw, Geoffrey M; Preiser, Jean-Charles; Le Compte, Aaron J; Lin, Jessica; Hewett, Darren; Moorhead, Katherine T; Desaive, Thomas

2010-01-01

Intensive care unit mortality is strongly associated with organ failure rate and severity. The sequential organ failure assessment (SOFA) score is used to evaluate the impact of a successful tight glycemic control (TGC) intervention (SPRINT) on organ failure, morbidity, and thus mortality. A retrospective analysis of 371 patients (3,356 days) on SPRINT (August 2005 - April 2007) and 413 retrospective patients (3,211 days) from two years prior, matched by Acute Physiology and Chronic Health Evaluation (APACHE) III. SOFA is calculated daily for each patient. The effect of the SPRINT TGC intervention is assessed by comparing the percentage of patients with SOFA ≤5 each day and its trends over time and cohort/group. Organ-failure free days (all SOFA components ≤2) and number of organ failures (SOFA components >2) are also compared. Cumulative time in 4.0 to 7.0 mmol/L band (cTIB) was evaluated daily to link tightness and consistency of TGC (cTIB ≥0.5) to SOFA ≤5 using conditional and joint probabilities. Admission and maximum SOFA scores were similar (P = 0.20; P = 0.76), with similar time to maximum (median: one day; IQR: 13 days; P = 0.99). Median length of stay was similar (4.1 days SPRINT and 3.8 days Pre-SPRINT; P = 0.94). The percentage of patients with SOFA ≤5 is different over the first 14 days (P = 0.016), rising to approximately 75% for Pre-SPRINT and approximately 85% for SPRINT, with clear separation after two days. Organ-failure-free days were different (SPRINT = 41.6%; Pre-SPRINT = 36.5%; P < 0.0001) as were the percent of total possible organ failures (SPRINT = 16.0%; Pre-SPRINT = 19.0%; P < 0.0001). By Day 3 over 90% of SPRINT patients had cTIB ≥0.5 (37% Pre-SPRINT) reaching 100% by Day 7 (50% Pre-SPRINT). Conditional and joint probabilities indicate tighter, more consistent TGC under SPRINT (cTIB ≥0.5) increased the likelihood SOFA ≤5. SPRINT TGC resolved organ failure faster, and for more patients, from similar admission and maximum SOFA scores, than conventional control. These reductions mirror the reduced mortality with SPRINT. The cTIB ≥0.5 metric provides a first benchmark linking TGC quality to organ failure. These results support other physiological and clinical results indicating the role tight, consistent TGC can play in reducing organ failure, morbidity and mortality, and should be validated on data from randomised trials.

Organ failure and tight glycemic control in the SPRINT study

PubMed Central

2010-01-01

Introduction Intensive care unit mortality is strongly associated with organ failure rate and severity. The sequential organ failure assessment (SOFA) score is used to evaluate the impact of a successful tight glycemic control (TGC) intervention (SPRINT) on organ failure, morbidity, and thus mortality. Methods A retrospective analysis of 371 patients (3,356 days) on SPRINT (August 2005 - April 2007) and 413 retrospective patients (3,211 days) from two years prior, matched by Acute Physiology and Chronic Health Evaluation (APACHE) III. SOFA is calculated daily for each patient. The effect of the SPRINT TGC intervention is assessed by comparing the percentage of patients with SOFA ≤5 each day and its trends over time and cohort/group. Organ-failure free days (all SOFA components ≤2) and number of organ failures (SOFA components >2) are also compared. Cumulative time in 4.0 to 7.0 mmol/L band (cTIB) was evaluated daily to link tightness and consistency of TGC (cTIB ≥0.5) to SOFA ≤5 using conditional and joint probabilities. Results Admission and maximum SOFA scores were similar (P = 0.20; P = 0.76), with similar time to maximum (median: one day; IQR: [1,3] days; P = 0.99). Median length of stay was similar (4.1 days SPRINT and 3.8 days Pre-SPRINT; P = 0.94). The percentage of patients with SOFA ≤5 is different over the first 14 days (P = 0.016), rising to approximately 75% for Pre-SPRINT and approximately 85% for SPRINT, with clear separation after two days. Organ-failure-free days were different (SPRINT = 41.6%; Pre-SPRINT = 36.5%; P < 0.0001) as were the percent of total possible organ failures (SPRINT = 16.0%; Pre-SPRINT = 19.0%; P < 0.0001). By Day 3 over 90% of SPRINT patients had cTIB ≥0.5 (37% Pre-SPRINT) reaching 100% by Day 7 (50% Pre-SPRINT). Conditional and joint probabilities indicate tighter, more consistent TGC under SPRINT (cTIB ≥0.5) increased the likelihood SOFA ≤5. Conclusions SPRINT TGC resolved organ failure faster, and for more patients, from similar admission and maximum SOFA scores, than conventional control. These reductions mirror the reduced mortality with SPRINT. The cTIB ≥0.5 metric provides a first benchmark linking TGC quality to organ failure. These results support other physiological and clinical results indicating the role tight, consistent TGC can play in reducing organ failure, morbidity and mortality, and should be validated on data from randomised trials. PMID:20704712

Association of the Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) Score With Excess Hospital Mortality in Adults With Suspected Infection in Low- and Middle-Income Countries.

PubMed

Rudd, Kristina E; Seymour, Christopher W; Aluisio, Adam R; Augustin, Marc E; Bagenda, Danstan S; Beane, Abi; Byiringiro, Jean Claude; Chang, Chung-Chou H; Colas, L Nathalie; Day, Nicholas P J; De Silva, A Pubudu; Dondorp, Arjen M; Dünser, Martin W; Faiz, M Abul; Grant, Donald S; Haniffa, Rashan; Van Hao, Nguyen; Kennedy, Jason N; Levine, Adam C; Limmathurotsakul, Direk; Mohanty, Sanjib; Nosten, François; Papali, Alfred; Patterson, Andrew J; Schieffelin, John S; Shaffer, Jeffrey G; Thuy, Duong Bich; Thwaites, C Louise; Urayeneza, Olivier; White, Nicholas J; West, T Eoin; Angus, Derek C

2018-05-20

The quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score has not been well-evaluated in low- and middle-income countries (LMICs). To assess the association of qSOFA with excess hospital death among patients with suspected infection in LMICs and to compare qSOFA with the systemic inflammatory response syndrome (SIRS) criteria. Retrospective secondary analysis of 8 cohort studies and 1 randomized clinical trial from 2003 to 2017. This study included 6569 hospitalized adults with suspected infection in emergency departments, inpatient wards, and intensive care units of 17 hospitals in 10 LMICs across sub-Saharan Africa, Asia, and the Americas. Low (0), moderate (1), or high (≥2) qSOFA score (range, 0 [best] to 3 [worst]) or SIRS criteria (range, 0 [best] to 4 [worst]) within 24 hours of presentation to study hospital. Predictive validity (measured as incremental hospital mortality beyond that predicted by baseline risk factors, as a marker of sepsis or analogous severe infectious course) of the qSOFA score (primary) and SIRS criteria (secondary). The cohorts were diverse in enrollment criteria, demographics (median ages, 29-54 years; males range, 36%-76%), HIV prevalence (range, 2%-43%), cause of infection, and hospital mortality (range, 1%-39%). Among 6218 patients with nonmissing outcome status in the combined cohort, 643 (10%) died. Compared with a low or moderate score, a high qSOFA score was associated with increased risk of death overall (19% vs 6%; difference, 13% [95% CI, 11%-14%]; odds ratio, 3.6 [95% CI, 3.0-4.2]) and across cohorts (P < .05 for 8 of 9 cohorts). Compared with a low qSOFA score, a moderate qSOFA score was also associated with increased risk of death overall (8% vs 3%; difference, 5% [95% CI, 4%-6%]; odds ratio, 2.8 [95% CI, 2.0-3.9]), but not in every cohort (P < .05 in 2 of 7 cohorts). High, vs low or moderate, SIRS criteria were associated with a smaller increase in risk of death overall (13% vs 8%; difference, 5% [95% CI, 3%-6%]; odds ratio, 1.7 [95% CI, 1.4-2.0]) and across cohorts (P < .05 for 4 of 9 cohorts). qSOFA discrimination (area under the receiver operating characteristic curve [AUROC], 0.70 [95% CI, 0.68-0.72]) was superior to that of both the baseline model (AUROC, 0.56 [95% CI, 0.53-0.58; P < .001) and SIRS (AUROC, 0.59 [95% CI, 0.57-0.62]; P < .001). When assessed among hospitalized adults with suspected infection in 9 LMIC cohorts, the qSOFA score identified infected patients at risk of death beyond that explained by baseline factors. However, the predictive validity varied among cohorts and settings, and further research is needed to better understand potential generalizability.

Axial coordination and conformational heterogeneity of nickel(II) tetraphenylprophyrin complexes with nitrogenous bases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jia, S.L.; Song, X.Z.; Ma, J.G.

1998-08-24

Axial ligation of nickel(II) 5,10,15,20-tetraphenylporphyrin (NiTPP) with pyrrolidine or piperidine has been investigated using X-ray crystallography, UV-visible spectroscopy, resonance Raman spectroscopy, and molecular mechanics (MM) calculations. Distinct v{sub 4} Raman lines are found for the 4-, 5-, and 6-coordinate species of NiTPP. The equilibrium constants for addition of the first and second pyrrolidine axial ligands are 1.1 and 3.8 M{sup {minus}1}, respectively. The differences in the calculated energies of the conformers having different ligand rotational angles are small so they may coexist in solution. Because of the similarity in macrocyclic structural parameters of these conformers and the free rotation ofmore » the axial ligands, narrow and symmetric v{sub 2} and v{sub 8} Raman lines are observed. Nonetheless, the normal-coordinate structural-decomposition analysis of the nonplanar distortions of the calculated structures and the crystal structure of the bis(piperidine) complex reveals a relationship between the orientations of axial ligand(s) and the macrocyclic distortions. For the 5-coordinate complex with the plane of the axial ligand bisecting the Ni-N{sub pyrrole} bonds, a primarily ruffled deformation results. With the ligand plane eclipsing the Ni-N{sub pyrrole} bonds, a mainly saddled deformation occurs. With the addition of the second axial ligand, the small doming of the 5-coordinate complexes disappears, and ruffling or saddling deformations change depending on the relative orientation of the two axial ligands. The crystal structure of the NiTPP bis(piperidine) complex shows a macrocycle distortion composed of wav(x) and wav(y) symmetric deformations, but no ruffling, saddling, or doming. The difference in the calculated and observed distortions results partly from the phenyl group orientation imposed by crystal packing forces. MM calculations predict three stable conformers (ruf, sad, and planar) for 4-coordinate NiTPP, and resonance Raman evidence for these conformers was given previously.« less

Assessment of Sepsis-3 criteria and quick SOFA in patients with cirrhosis and bacterial infections.

PubMed

Piano, Salvatore; Bartoletti, Michele; Tonon, Marta; Baldassarre, Maurizio; Chies, Giada; Romano, Antonietta; Viale, Pierluigi; Vettore, Elia; Domenicali, Marco; Stanco, Marialuisa; Pilutti, Chiara; Frigo, Anna Chiara; Brocca, Alessandra; Bernardi, Mauro; Caraceni, Paolo; Angeli, Paolo

2017-08-31

Patients with cirrhosis have a high risk of sepsis, which confers a poor prognosis. The systemic inflammatory response syndrome (SIRS) criteria have several limitations in cirrhosis. Recently, new criteria for sepsis (Sepsis-3) have been suggested in the general population (increase of Sequential Organ Failure Assessment (SOFA) ≥2 points from baseline). Outside the intensive care unit (ICU), the quick SOFA (qSOFA (at least two among alteration in mental status, systolic blood pressure ≤100 mm Hg or respiratory rate ≥22/min)) was suggested to screen for sepsis. These criteria have never been evaluated in patients with cirrhosis. The aim of the study was to assess the ability of Sepsis-3 criteria in predicting in-hospital mortality in patients with cirrhosis and bacterial/fungal infections. 259 consecutive patients with cirrhosis and bacterial/fungal infections were prospectively included. Demographic, laboratory and microbiological data were collected at diagnosis of infection. Baseline SOFA was assessed using preadmission data. Patients were followed up until death, liver transplantation or discharge. Findings were externally validated (197 patients). Sepsis-3 and qSOFA had significantly greater discrimination for in-hospital mortality (area under the receiver operating characteristic (AUROC)=0.784 and 0.732, respectively) than SIRS (AUROC=0.606) (p<0.01 for both). Similar results were observed in the validation cohort. Sepsis-3 (subdistribution HR (sHR)=5.47; p=0.006), qSOFA (sHR=1.99; p=0.020), Chronic Liver Failure Consortium Acute Decompensation score (sHR=1.05; p=0.001) and C reactive protein (sHR=1.01;p=0.034) were found to be independent predictors of in-hospital mortality. Patients with Sepsis-3 had higher incidence of acute-on-chronic liver failure, septic shock and transfer to ICU than those without Sepsis-3. Sepsis-3 criteria are more accurate than SIRS criteria in predicting the severity of infections in patients with cirrhosis. qSOFA is a useful bedside tool to assess risk for worse outcomes in these patients. Patients with Sepsis-3 and positive qSOFA deserve more intensive management and strict surveillance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

qSOFA, SIRS and NEWS for predicting inhospital mortality and ICU admission in emergency admissions treated as sepsis.

PubMed

Goulden, Robert; Hoyle, Marie-Claire; Monis, Jessie; Railton, Darran; Riley, Victoria; Martin, Paul; Martina, Reynaldo; Nsutebu, Emmanuel

2018-06-01

The third international consensus definition for sepsis recommended use of a new prognostic tool, the quick Sequential Organ Failure Assessment (qSOFA), based on its ability to predict inhospital mortality and prolonged intensive care unit (ICU) stay in patients with suspected infection. While several studies have compared the prognostic accuracy of qSOFA to the Systemic Inflammatory Response Syndrome (SIRS) criteria in suspected sepsis, few have compared qSOFA and SIRS to the widely used National Early Warning Score (NEWS). This was a retrospective cohort study carried out in a UK tertiary centre. The study population comprised emergency admissions in whom sepsis was suspected and treated. The accuracy for predicting inhospital mortality and ICU admission was calculated and compared for qSOFA, SIRS and NEWS. Among 1818 patients, 53 were admitted to ICU (3%) and 265 died in hospital (15%). For predicting inhospital mortality, the area under the receiver operating characteristics curve for NEWS (0.65, 95% CI 0.61 to 0.68) was similar to qSOFA (0.62, 95% CI 0.59 to 0.66) (test for difference, P=0.18) and superior to SIRS (P<0.001), which was not predictive. The sensitivity of NEWS≥5 (74%, 95% CI 68% to 79%) was similar to SIRS≥2 (80%, 95% CI 74% to 84%) and higher than qSOFA≥2 (37%, 95% CI 31% to 43%). The specificity of NEWS≥5 (43%, 95% CI 41% to 46%) was higher than SIRS≥2 (21%, 95% CI 19% to 23%) and lower than qSOFA≥2 (79%, 95% CI 77% to 81%). The negative predictive value was 88% (86%-90%) for qSOFA, 86% (82%-89%) for SIRS and 91% (88%-93%) for NEWS. Results were similar for the secondary outcome of ICU admission. NEWS has equivalent or superior value for most test characteristics relative to SIRS and qSOFA, calling into question the rationale of adopting qSOFA in institutions where NEWS is already in use. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Iterative User Interface Design for Automated Sequential Organ Failure Assessment Score Calculator in Sepsis Detection

PubMed Central

Herasevich, Vitaly

2017-01-01

Background The new sepsis definition has increased the need for frequent sequential organ failure assessment (SOFA) score recalculation and the clerical burden of information retrieval makes this score ideal for automated calculation. Objective The aim of this study was to (1) estimate the clerical workload of manual SOFA score calculation through a time-motion analysis and (2) describe a user-centered design process for an electronic medical record (EMR) integrated, automated SOFA score calculator with subsequent usability evaluation study. Methods First, we performed a time-motion analysis by recording time-to-task-completion for the manual calculation of 35 baseline and 35 current SOFA scores by 14 internal medicine residents over a 2-month period. Next, we used an agile development process to create a user interface for a previously developed automated SOFA score calculator. The final user interface usability was evaluated by clinician end users with the Computer Systems Usability Questionnaire. Results The overall mean (standard deviation, SD) time-to-complete manual SOFA score calculation time was 61.6 s (33). Among the 24% (12/50) usability survey respondents, our user-centered user interface design process resulted in >75% favorability of survey items in the domains of system usability, information quality, and interface quality. Conclusions Early stakeholder engagement in our agile design process resulted in a user interface for an automated SOFA score calculator that reduced clinician workload and met clinicians’ needs at the point of care. Emerging interoperable platforms may facilitate dissemination of similarly useful clinical score calculators and decision support algorithms as “apps.” A user-centered design process and usability evaluation should be considered during creation of these tools. PMID:28526675

Using Statistical and Machine Learning Methods to Evaluate the Prognostic Accuracy of SIRS and qSOFA

PubMed Central

Liu, Tieming; Shepherd, Scott; Paiva, William

2018-01-01

Objectives The objective of this study was to compare the performance of two popularly used early sepsis diagnostic criteria, systemic inflammatory response syndrome (SIRS) and quick Sepsis-related Organ Failure Assessment (qSOFA), using statistical and machine learning approaches. Methods This retrospective study examined patient visits in Emergency Department (ED) with sepsis related diagnosis. The outcome was 28-day in-hospital mortality. Using odds ratio (OR) and modeling methods (decision tree [DT], multivariate logistic regression [LR], and naïve Bayes [NB]), the relationships between diagnostic criteria and mortality were examined. Results Of 132,704 eligible patient visits, 14% died within 28 days of ED admission. The association of qSOFA ≥2 with mortality (OR = 3.06; 95% confidence interval [CI], 2.96–3.17) greater than the association of SIRS ≥2 with mortality (OR = 1.22; 95% CI, 1.18–1.26). The area under the ROC curve for qSOFA (AUROC = 0.70) was significantly greater than for SIRS (AUROC = 0.63). For qSOFA, the sensitivity and specificity were DT = 0.39, LR = 0.64, NB = 0.62 and DT = 0.89, LR = 0.63, NB = 0.66, respectively. For SIRS, the sensitivity and specificity were DT = 0.46, LR = 0.62, NB = 0.62 and DT = 0.70, LR = 0.59, NB = 0.58, respectively. Conclusions The evidences suggest that qSOFA is a better diagnostic criteria than SIRS. The low sensitivity of qSOFA can be improved by carefully selecting the threshold to translate the predicted probabilities into labels. These findings can guide healthcare providers in selecting risk-stratification measures for patients presenting to an ED with sepsis. PMID:29770247

Iterative User Interface Design for Automated Sequential Organ Failure Assessment Score Calculator in Sepsis Detection.

PubMed

Aakre, Christopher Ansel; Kitson, Jaben E; Li, Man; Herasevich, Vitaly

2017-05-18

The new sepsis definition has increased the need for frequent sequential organ failure assessment (SOFA) score recalculation and the clerical burden of information retrieval makes this score ideal for automated calculation. The aim of this study was to (1) estimate the clerical workload of manual SOFA score calculation through a time-motion analysis and (2) describe a user-centered design process for an electronic medical record (EMR) integrated, automated SOFA score calculator with subsequent usability evaluation study. First, we performed a time-motion analysis by recording time-to-task-completion for the manual calculation of 35 baseline and 35 current SOFA scores by 14 internal medicine residents over a 2-month period. Next, we used an agile development process to create a user interface for a previously developed automated SOFA score calculator. The final user interface usability was evaluated by clinician end users with the Computer Systems Usability Questionnaire. The overall mean (standard deviation, SD) time-to-complete manual SOFA score calculation time was 61.6 s (33). Among the 24% (12/50) usability survey respondents, our user-centered user interface design process resulted in >75% favorability of survey items in the domains of system usability, information quality, and interface quality. Early stakeholder engagement in our agile design process resulted in a user interface for an automated SOFA score calculator that reduced clinician workload and met clinicians' needs at the point of care. Emerging interoperable platforms may facilitate dissemination of similarly useful clinical score calculators and decision support algorithms as "apps." A user-centered design process and usability evaluation should be considered during creation of these tools. ©Christopher Ansel Aakre, Jaben E Kitson, Man Li, Vitaly Herasevich. Originally published in JMIR Human Factors (http://humanfactors.jmir.org), 18.05.2017.

Assessment of Clinical Criteria for Sepsis

PubMed Central

Seymour, Christopher W.; Liu, Vincent X.; Iwashyna, Theodore J.; Brunkhorst, Frank M.; Rea, Thomas D.; Scherag, André; Rubenfeld, Gordon; Kahn, Jeremy M.; Shankar-Hari, Manu; Singer, Mervyn; Deutschman, Clifford S.; Escobar, Gabriel J.; Angus, Derek C.

2016-01-01

IMPORTANCE The Third International Consensus Definitions Task Force defined sepsis as “life-threatening organ dysfunction due to a dysregulated host response to infection.” The performance of clinical criteria for this sepsis definition is unknown. OBJECTIVE To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. DESIGN, SETTINGS, AND POPULATION Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706 399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. EXPOSURES Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0–3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation). MAIN OUTCOMES AND MEASURES For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). RESULTS In the primary cohort, 148 907 encounters had suspected infection (n = 74 453 derivation; n = 74 454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected infection, of whom 1289 [16%] died), the predictive validity for in-hospital mortality was lower for SIRS (AUROC = 0.64; 95% CI, 0.62–0.66) and qSOFA (AUROC = 0.66; 95% CI, 0.64–0.68) vs SOFA (AUROC = 0.74; 95% CI, 0.73–0.76; P < .001 for both) or LODS (AUROC = 0.75; 95% CI, 0.73–0.76; P < .001 for both). Among non-ICU encounters in the validation cohort (n = 66 522 with suspected infection, of whom 1886 [3%] died), qSOFA had predictive validity (AUROC = 0.81; 95% CI, 0.80–0.82) that was greater than SOFA (AUROC = 0.79; 95% CI, 0.78–0.80; P < .001) and SIRS (AUROC = 0.76; 95% CI, 0.75–0.77; P < .001). Relative to qSOFA scores lower than 2, encounters with qSOFA scores of 2 or higher had a 3- to 14-fold increase in hospital mortality across baseline risk deciles. Findings were similar in external data sets and for the secondary outcome. CONCLUSIONS AND RELEVANCE Among ICU encounters with suspected infection, the predictive validity for in-hospital mortality of SOFA was not significantly different than the more complex LODS but was statistically greater than SIRS and qSOFA, supporting its use in clinical criteria for sepsis. Among encounters with suspected infection outside of the ICU, the predictive validity for in-hospital mortality of qSOFA was statistically greater than SOFA and SIRS, supporting its use as a prompt to consider possible sepsis. PMID:26903335

Investigations of the Binding of [Pt2(DTBPA)Cl2](II) and [Pt2(TPXA)Cl2](II) to DNA via Various Cross-Linking Modes

PubMed Central

Yue, Hongwei; Yang, Bo; Wang, Yan; Chen, Guangju

2013-01-01

We have constructed models for a series of platinum-DNA adducts that represent the binding of two agents, [Pt2(DTBPA)Cl2](II) and [Pt2(TPXA)Cl2](II), to DNA via inter- and intra-strand cross-linking, and carried out molecular dynamics simulations and DNA conformational dynamics calculations. The effects of trans- and cis-configurations of the centers of these di-nuclear platinum agents, and of different bridging linkers, have been investigated on the conformational distortions of platinum-DNA adducts formed via inter- and intra-strand cross-links. The results demonstrate that the DNA conformational distortions for the various platinum-DNA adducts with differing cross-linking modes are greatly influenced by the difference between the platinum-platinum distance for the platinum agent and the platinum-bound N7–N7 distance for the DNA molecule, and by the flexibility of the bridging linkers in the platinum agent. However, the effects of trans/cis-configurations of the platinum-centers on the DNA conformational distortions in the platinum-DNA adducts depend on the inter- and intra-strand cross-linking modes. In addition, we discuss the relevance of DNA base motions, including opening, shift and roll, to the changes in the parameters of the DNA major and minor grooves caused by binding of the platinum agent. PMID:24077126

SOFA & astrometry

NASA Astrophysics Data System (ADS)

Hohenkerk, C.

2015-08-01

The International Astronomical Union's (IAU) Standards of Fundamental Astronomy (SOFA) software library has in the last year introduced a tranche of 32 new routines dealing with the subject area "astrometry". This poster provides a guide to enable users to get to grips easily with the various routines for the transformations between ICRS, ICRS astrometric, GCRS, Celestial Intermediate and observed positions of stars, together with their underlying routines for proper motion, parallax, aberration, light deflection and refraction. A summary of the current status of SOFA is also included.

Ergonomic evaluation of processes and products in the manufacture of upholstery.

PubMed

Fialho, Patrícia Bhering; de Souza, Amaury Paulo; Minette, Luciano José; Silva, José de Castro; de Oliveira, Luciana Aparecida

2012-01-01

This study aimed to perform an ergonomic evaluation of industrial processes and products - upholstered sofas - produced in the furniture cluster of Ubá-MG. The used material was collected from two sofas upholstered industries associated with the union of the furniture industries of Ubá region, located in Minas Gerais estate, Brazil. As for the product were evaluated dimensionally 29 upholstered sofas, with 12 being produced by industry "A" and 17 being produced by industry "B". As for the process, were evaluated: the socioeconomic profile of the worker and environmental factors of lighting and noise. The main results of this study showed that the upholstered sofas produced by industries, in general, fulfilled to the recommendations set out in the work in relation to the backrest height and useful seat depth. All the sofas, however, proved to be inadequate in relation to the seat height to the floor and the dimensions of the armrests Regarding environmental aspects, it was observed that in both industries, the activities in most jobs are performed under adverse conditions to the health and safety of workers and nonconformity with the limits set by Brazilian regulatory standard used in this work.

Prospective validation of a near real-time EHR-integrated automated SOFA score calculator.

PubMed

Aakre, Christopher; Franco, Pablo Moreno; Ferreyra, Micaela; Kitson, Jaben; Li, Man; Herasevich, Vitaly

2017-07-01

We created an algorithm for automated Sequential Organ Failure Assessment (SOFA) score calculation within the Electronic Health Record (EHR) to facilitate detection of sepsis based on the Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) clinical definition. We evaluated the accuracy of near real-time and daily automated SOFA score calculation compared with manual score calculation. Automated SOFA scoring computer programs were developed using available EHR data sources and integrated into a critical care focused patient care dashboard at Mayo Clinic in Rochester, Minnesota. We prospectively compared the accuracy of automated versus manual calculation for a sample of patients admitted to the medical intensive care unit at Mayo Clinic Hospitals in Rochester, Minnesota and Jacksonville, Florida. Agreement was calculated with Cohen's kappa statistic. Reason for discrepancy was tabulated during manual review. Random spot check comparisons were performed 134 times on 27 unique patients, and daily SOFA score comparisons were performed for 215 patients over a total of 1206 patient days. Agreement between automatically scored and manually scored SOFA components for both random spot checks (696 pairs, κ=0.89) and daily calculation (5972 pairs, κ=0.89) was high. The most common discrepancies were in the respiratory component (inaccurate fraction of inspired oxygen retrieval; 200/1206) and creatinine (normal creatinine in patients with no urine output on dialysis; 128/1094). 147 patients were at risk of developing sepsis after intensive care unit admission, 10 later developed sepsis confirmed by chart review. All were identified before onset of sepsis with the ΔSOFA≥2 point criterion and 46 patients were false-positives. Near real-time automated SOFA scoring was found to have strong agreement with manual score calculation and may be useful for the detection of sepsis utilizing the new SEPSIS-3 definition. Copyright © 2017 Elsevier B.V. All rights reserved.

Heme Distortions in Sperm-Whale Carbonmonoxy Myoglobin: Correlations between Rotational Strengths and Heme Distortions in MD-Generated Structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

KIEFL,CHRISTOPH; SCREERAMA,NARASIMHA; LU,YI

2000-07-13

The authors have investigated the effects of heme rotational isomerism in sperm-whale carbonmonoxy myoglobin using computational techniques. Several molecular dynamics simulations have been performed for the two rotational isomers A and B, which are related by a 180{degree} rotation around the {alpha}-{gamma} axis of the heme, of sperm-whale carbonmonoxy myoglobin in water. Both neutron diffraction and NMR structures were used as starting structures. In the absence of an experimental structure, the structure of isomer B was generated by rotating the heme in the structure of isomer A. Distortions of the heme from planarity were characterized by normal coordinate structural decompositionmore » and by the angle of twist of the pyrrole rings from the heme plane. The heme distortions of the neutron diffraction structure were conserved in the MD trajectories, but in the NMR-based trajectories, where the heme distortions are less well defined, they differ from the original heme deformations. The protein matrix induced similar distortions on the heroes in orientations A and B. The results suggest that the binding site prefers a particular macrocycle conformation, and a 180{degree} rotation of the heme does not significantly alter the protein's preference for this conformation. The intrinsic rotational strengths of the two Soret transitions, separated according to their polarization in the heme plane, show strong correlations with the ruf-deformation and the average twist angle of the pyrrole rings. The total rotational strength, which includes contributions from the chromophores in the protein, shows a weaker correlation with heme distortions.« less

Conformational Analysis of Retinoic Acids: Effects of Steric Interactions on Nonplanar Conjugated Polyenes

PubMed Central

Cox, Bryan D.; Muccio, Donald D.; Hamilton, Tracy P.

2013-01-01

Retinoic acids and other vitamin A analogs contain a trimethylcyclohexenyl ring in conjugation with a polyene chain joined at carbon-6 (C6) and carbon-7 (C7). A MP2-SCS/cc-pVDZ// B3LYP/6-31G(d) 2-D potential energy surface was computed for all-trans retinoic acid, which had 6 minima (3 enantiomeric pairs). The global minima were distorted s-gauche enantiomers (6–7 = 53°) with half-chair conformations of the ring. Distorted s-gauche enantiomers (6–7 = 55°) with inverted half-chair ring conformations were 1.7 kJ/mol above the global minima. The s-trans enantiomers (6–7 = 164°) were 11.3 kJ/mol above the global minima. Steric energies were computed by the method of Guo and Karplus to identify key structural elements in retinoic acids which determines their conformation. Small molecule crystal structures in the CCDC database with trimethylcyclohexenyl ring and exocyclic double bonds have ring-chain geometries near to one of the 6 energy minima of retinoic acids, except for retinaldehyde iminium cations. PMID:25798372

Conformational Analysis of Retinoic Acids: Effects of Steric Interactions on Nonplanar Conjugated Polyenes.

PubMed

Cox, Bryan D; Muccio, Donald D; Hamilton, Tracy P

2013-05-01

Retinoic acids and other vitamin A analogs contain a trimethylcyclohexenyl ring in conjugation with a polyene chain joined at carbon-6 (C6) and carbon-7 (C7). A MP2-SCS/cc-pVDZ// B3LYP/6-31G(d) 2-D potential energy surface was computed for all- trans retinoic acid, which had 6 minima (3 enantiomeric pairs). The global minima were distorted s-gauche enantiomers ( 6-7 = 53°) with half-chair conformations of the ring. Distorted s-gauche enantiomers ( 6-7 = 55°) with inverted half-chair ring conformations were 1.7 kJ/mol above the global minima. The s-trans enantiomers ( 6-7 = 164°) were 11.3 kJ/mol above the global minima. Steric energies were computed by the method of Guo and Karplus to identify key structural elements in retinoic acids which determines their conformation. Small molecule crystal structures in the CCDC database with trimethylcyclohexenyl ring and exocyclic double bonds have ring-chain geometries near to one of the 6 energy minima of retinoic acids, except for retinaldehyde iminium cations.

16 CFR 1632.8 - Glossary of terms.

Code of Federal Regulations, 2012 CFR

2012-01-01

... prevent or assist in the healing of decubitus ulcers (bed sores). Flat decubitus pads are covered by the... pressure is exerted on the back of the sofa, it becomes a bed. When the back is lifted, it becomes a sofa...

16 CFR § 1632.8 - Glossary of terms.

Code of Federal Regulations, 2013 CFR

2013-01-01

... pad. Designed to prevent or assist in the healing of decubitus ulcers (bed sores). Flat decubitus pads... sofa. When pressure is exerted on the back of the sofa, it becomes a bed. When the back is lifted, it...

16 CFR 1632.8 - Glossary of terms.

Code of Federal Regulations, 2011 CFR

2011-01-01

... prevent or assist in the healing of decubitus ulcers (bed sores). Flat decubitus pads are covered by the... pressure is exerted on the back of the sofa, it becomes a bed. When the back is lifted, it becomes a sofa...

16 CFR 1632.8 - Glossary of terms.

Code of Federal Regulations, 2014 CFR

2014-01-01

... prevent or assist in the healing of decubitus ulcers (bed sores). Flat decubitus pads are covered by the... pressure is exerted on the back of the sofa, it becomes a bed. When the back is lifted, it becomes a sofa...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rashin, Alexander A., E-mail: alexander-rashin@hotmail.com; Iowa State University, 112 Office and Lab Bldg, Ames, IA 50011-3020; Domagalski, Marcin J.

Conformational differences between myoglobin structures are studied. Most structural differences in whale myoglobin beyond the uncertainty threshold can be correlated with a few specific structural factors. There are always exceptions and a search for additional factors is needed. The results might have serious implications for biological insights from conformational differences. Validation of general ideas about the origins of conformational differences in proteins is critical in order to arrive at meaningful functional insights. Here, principal component analysis (PCA) and distance difference matrices are used to validate some such ideas about the conformational differences between 291 myoglobin structures from sperm whale, horsemore » and pig. Almost all of the horse and pig structures form compact PCA clusters with only minor coordinate differences and outliers that are easily explained. The 222 whale structures form a few dense clusters with multiple outliers. A few whale outliers with a prominent distortion of the GH loop are very similar to the cluster of horse structures, which all have a similar GH-loop distortion apparently owing to intermolecular crystal lattice hydrogen bonds to the GH loop from residues near the distal histidine His64. The variations of the GH-loop coordinates in the whale structures are likely to be owing to the observed alternative intermolecular crystal lattice bond, with the change to the GH loop distorting bonds correlated with the binding of specific ‘unusual’ ligands. Such an alternative intermolecular bond is not observed in horse myoglobins, obliterating any correlation with the ligands. Intermolecular bonds do not usually cause significant coordinate differences and cannot be validated as their universal cause. Most of the native-like whale myoglobin structure outliers can be correlated with a few specific factors. However, these factors do not always lead to coordinate differences beyond the previously determined uncertainty thresholds. The binding of unusual ligands by myoglobin, leading to crystal-induced distortions, suggests that some of the conformational differences between the apo and holo structures might not be ‘functionally important’ but rather artifacts caused by the binding of ‘unusual’ substrate analogs. The causes of P6 symmetry in myoglobin crystals and the relationship between crystal and solution structures are also discussed.« less

[The correlation between procalcitonin, C-reactive protein and severity scores in patients with sepsis and their value in assessment of prognosis].

PubMed

Wang, Shengyun; Chen, Dechang

2015-02-01

To investigate the correlation between procalcitonin (PCT), C-reactive protein (CRP) and acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score, and to investigate the value in assessment of PCT and CRP in prognosis in patients with sepsis. Clinical data of patients admitted to intensive care unit (ICU) of Changzheng Hospital Affiliated to the Second Military Medical University from January 2011 to June 2014 were retrospectively analyzed. 201 sepsis patients who received PCT and CRP tests, and evaluation of APACHE II score and SOFA score were enrolled. The values of PCT, CRP, APACHE II score and SOFA score between survivals (n = 136) and non-survivals (n = 65) were compared. The values of PCT and CRP among groups with different APACHE II scores and SOFA scores were compared. The relationships between PCT, CRP and APACHE II score and SOFA score were analyzed by Spearman correlation analysis. Receiver operating characteristic (ROC) curve was plotted to assess the prognostic value of PCT and CRP for prognosis of patients with sepsis. Compared with survival group, the values of PCT [μg/L: 11.03 (19.17) vs. 1.39 (2.61), Z = -4.572, P < 0.001], APACHE II score (19.16±5.32 vs. 10.01±3.88, t = -13.807, P < 0.001) and SOFA score (9.66±4.28 vs. 4.27±3.19, t = -9.993, P < 0.001) in non-survival group were significantly increased, but the value of CRP was not significantly different between non-survival group and survival group [mg/L: 75.22 (110.94) vs. 56.93 (100.75), Z = -0.731, P = 0.665]. The values of PCT were significantly correlated with APACHE II score and SOFA score (r1 = 0.373, r2 = 0.392, both P < 0.001), but the values of CRP were not significantly correlated with APACHE II score and SOFA score (r1 = -0.073, P1 = 0.411; r2 = -0.106, P2 = 0.282). The values of PCT rose significantly as the APACHE II score and SOFA score became higher, but the value of CRP was not significantly increased. When APACHE II score was 0-10, 11-20, and > 20, the value of PCT was 1.45 (2.62), 1.96 (9.04), and 7.41 (28.9) μg/L, respectively, and the value of CRP was 57.50 (83.40), 59.00 (119.70), and 77.60 (120.00) mg/L, respectively. When SOFA score was 0-5, 6-10, and > 10, the value of PCT was respectively 1.43 (3.09), 3.41 (9.75), and 5.43 (29.60) μg/L, and the value of CRP was 49.30 (86.20), 76.00 (108.70), and 75.60 (118.10) mg/L, respectively. There was significant difference in PCT between any two groups with different APACHE II and SOFA scores (P < 0.05 or P < 0.01), but no significant differences in CRP were found. The area under the ROC curve (AUC) of PCT for prognosis was significantly greater than that of CRP [0.872 (95% confidence interval 0.811-0.943) vs. 0.512 (95% confidence interval 0.427-0.612), P < 0.001]. When the cut-off value of PCT was 3.36 μg/L, the sensitivity was 66.8%, and the specificity was 45.4%. When the cut-off value of CRP was 44.50 mg/L, the sensitivity was 82.2%, and the specificity was 80.3%. Compared with CRP, PCT was more significantly correlated with APACHE II score and SOFA score. PCT can be a better indicator for evaluation of degree of severity, and also prognosis in sepsis patients.

Switching operations fatality analysis : findings and recommendations of the SOFA working group

DOT National Transportation Integrated Search

1999-10-01

On February 1998, a Switching Operations Fatality Analysis (SOFA) Working Group (WG) was formed at the request of the Federal Railroad Administration (FRA) to review recent fatal incidents and develop recommendations for reducing fatalities in switch...

Better prognostic marker in ICU - APACHE II, SOFA or SAP II!

PubMed

Naqvi, Iftikhar Haider; Mahmood, Khalid; Ziaullaha, Syed; Kashif, Syed Mohammad; Sharif, Asim

2016-01-01

This study was designed to determine the comparative efficacy of different scoring system in assessing the prognosis of critically ill patients. This was a retrospective study conducted in medical intensive care unit (MICU) and high dependency unit (HDU) Medical Unit III, Civil Hospital, from April 2012 to August 2012. All patients over age 16 years old who have fulfilled the criteria for MICU admission were included. Predictive mortality of APACHE II, SAP II and SOFA were calculated. Calibration and discrimination were used for validity of each scoring model. A total of 96 patients with equal gender distribution were enrolled. The average APACHE II score in non-survivors (27.97+8.53) was higher than survivors (15.82+8.79) with statistically significant p value (<0.001). The average SOFA score in non-survivors (9.68+4.88) was higher than survivors (5.63+3.63) with statistically significant p value (<0.001). SAP II average score in non-survivors (53.71+19.05) was higher than survivors (30.18+16.24) with statistically significant p value (<0.001). All three tested scoring models (APACHE II, SAP II and SOFA) would be accurate enough for a general description of our ICU patients. APACHE II has showed better calibration and discrimination power than SAP II and SOFA.

Performance measures for transform data coding.

NASA Technical Reports Server (NTRS)

Pearl, J.; Andrews, H. C.; Pratt, W. K.

1972-01-01

This paper develops performance criteria for evaluating transform data coding schemes under computational constraints. Computational constraints that conform with the proposed basis-restricted model give rise to suboptimal coding efficiency characterized by a rate-distortion relation R(D) similar in form to the theoretical rate-distortion function. Numerical examples of this performance measure are presented for Fourier, Walsh, Haar, and Karhunen-Loeve transforms.

[Evaluation of coagulation disorders with thrombelastography in patients with sepsis].

PubMed

Zhong, Shengjian; Zhang, Chunbao; Hu, Juntao; Tang, Zhanhong

2016-02-01

To compare the results of thrombelastography (TEG) and the conventional coagulability test in patients with sepsis, and to discuss the value of TEG in monitoring blood coagulation dysfunction in patients with sepsis. The clinical data of 92 adult patients with sepsis admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. The patients were divided into sequential organ failure assessment (SOFA) score ≥ 12 group (n = 47) and SOFA < 12 group (n = 45). Thirty-five non-sepsis adult patients with normal coagulation function served as control group. The venous blood was collected for conventional blood coagulation test and routine examination of blood, D-dimer, procalcitonin (PCT), and TEG, and the differences were compared among three groups. Correlations between SOFA and various indexes of patients with sepsis were analyzed by Spearman rank correlation method. As shown in the results of the conventional blood coagulation test, D-dimer was gradually increased with the aggravation of the disease, the values in non-sepsis, SOFA < 12, and SOFA ≥ 12 groups were 0.523 (0.273, 0.928), 0.863 (0.673, 4.221), and 4.118 (2.420, 5.653) mg/L respectively (Z = 25.163, P = 0.000). Platelet count (PLT) in SOFA ≥ 12 group was significantly lower than that of the SOFA < 12 group and non-sepsis group [×10(9)/L: 28.6 (12.8, 48.9) vs. 257.3 (152.6, 339.8), 182.0 (118.0, 229.0), both P < 0.01]. There was no significant difference in prothrombin time (PT) and international normalized ratio (INR) among three groups, and it indicated that the conventional blood coagulation test might not respond quickly to the change in coagulation status of sepsis patients. As shown in the results of TEG, the values of reaction time (R value) and kinetics time (K value) in SOFA < 12 group were lower than those of the non-sepsis group [R value (minutes): 4.4 (3.6, 6.1) vs. 6.3 (6.0, 6.7), P < 0.01; K value (minutes): 1.1 (1.0, 1.5) vs. 1.5 (1.3, 1.8), P < 0.05], while they were higher in SOFA ≥ 12 group than those of the non-sepsis group [R value (minutes): 7.0 (5.7, 8.7) vs. 6.3 (6.0, 6.7), P > 0.05; K value (minutes): 4.2 (3.4, 7.1) vs. 1.5 (1.3, 1.8), P < 0.01]. The α angle, maximum amplitude (MA) and coagulation index (CI) in SOFA < 12 group were higher than those of the non-sepsis group [α angle (degree angle): 73.3 (68.5, 74.7) vs. 66.8 (62.2, 69.0), P < 0.01; MA (mm): 71.7 (61.9, 73.3) vs. 60.3 (58.2, 63.8), P < 0.01; CI: 3.1 (-0.1, 3.9) vs. 0.9 (-0.4, 1.3), P < 0.05], while they were lower in SOFA ≥ 12 group than those of the non-sepsis group [α angle (degree angle): 48.1 (36.6, 53.0) vs. 66.8 (62.2, 69.0), P < 0.01; MA (mm): 37.8 (30.0, 45.7) vs. 60.3 (58.2, 63.8), P < 0.01; CI: -5.6 (-8.4, -3.6) vs. 0.9 (-0.4, 1.3), P < 0.01]. The above results indicated that TEG could distinguish quickly the hypercoagulability and hypocoagulability status in septic patients. PCT in non-sepsis, SOFA < 12, and SOFA ≥ 12 groups were 0.27 (0.05, 1.80), 0.68 (0.10, 10.00), 41.10 (4.24, 100.00) μg/L respectively (Z = 195.475, P = 0.000), which indicate the severity of infectious disease. Correlation analysis results showed that SOFA score was negatively correlated with PLT, α angle, MA, and CI (r value was -0.853, -0.833, -0.881, and -0.859, respectively, all P = 0.000), and it was positively correlated with activated partial thromboplastin time (APTT), D-dimer, R value, K value, and PCT (r value was 0.381, 0.561, 0.587, 0.831, 0.775, respectively, P < 0.05 or P < 0.01), and non correlations was founded with PT, fibrinogen (FBG), and INR (r1 = 0.211, P1 = 0.233; r2 = -0.252, P2 = 0.142; r3 = 0.248, P3 = 0.148). TEG can effectively monitor the change in coagulation in patients with sepsis, and distinguish the hypercoagulable and hypocoagulable state. TEG may be a valuable tool to evaluate degree and risk of sepsis objectively.

Epidemiology and outcome analysis of sepsis and organ dysfunction/failure after burns.

PubMed

Belba, Monika Kristaq; Petrela, Elizana Ylber; Belba, Amy Gjergji

2017-09-01

The aim of this prospective study in adult population is to give frequency data (prevalence, incidence) of burn wound sepsis and its consequences (organ dysfunction/failure); to analyze the evolution of the SOFA cumulative score during the disease and relationship between the SOFA score in the 3rd, 7th, 14th and 21th day after burn with mortality. A prospective cohort study was performed among adult patients (age ≥20 years) admitted in the ICU, with major and moderate burns. Sepsis, organ dysfunction, organ failure and mortality were calculated as Cumulative Incidence (CI) and as Incidence rate (IR). Data from patients with sepsis were compared with those without sepsis. Evaluation of SOFA evolution was done with delta score and the influence of the SOFA score in mortality was calculated with AUC of the ROC curve. Period prevalence of sepsis in our adult burned population was 26%. Incidence proportion as CI was 0.3 or 30 patients per 100 adults. Incidence rate (IR) was 6 patients with sepsis per 100 patient-years. Overall morbidity was 88.1% while overall mortality was 11.9%. Mortality in patients with sepsis was 34.4%. Incidence of MOD was 63% while incidence of MOF was 37%. Respective mortality as CI was 7% and 81% while mortality rate as IR was 1.4 per 100 patient-years in patients with MOD and 16.2 per 100 patient-years in patients with MOF. SOFA-3 should be considered a "reliable indicator" at separating survivors from non survivors and SOFA 7, 14, and 21 should be considered excellent in predicting mortality. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Hyperproteic hypocaloric enteral nutrition in the critically ill patient: A randomized controlled clinical trial

PubMed Central

Rugeles, Saúl-Javier; Rueda, Juan-David; Díaz, Carlos-Eduardo; Rosselli, Diego

2013-01-01

Introduction: Our aim was to evaluate the impact of hyperproteic hypocaloric enteral feeding on clinical outcomes in critically ill patients, particularly on severity of organic failure measured with the Sequential Organ Failure Assessment (SOFA). Materials and Methods: In a double blind clinical trial, 80 critically ill adult patients were randomized to hyperproteic hypocaloric or to isocaloric enteral nutrition; all patients completed follow-up of at least 4 days. Prescribed caloric intake was: Hyperproteic hypocaloric enteral nutrition (15 kcal/kg with 1.7 g/kg of protein) or isocaloric enteral nutrition (25 kcal/kg with 20% of the calories as protein). The main outcome was the differences in delta SOFA at 48 h. Secondary outcomes were intensive care unit (ICU) length of stay, days on ventilator, hyperglycemic events, and insulin requirements. Results: There were no differences in SOFA score at baseline (7.5 (standard deviation (SD) 2.9) vs 6.7 (SD 2.5) P = 0.17). The total amount of calories delivered was similarly low in both groups (12 kcal/kg in intervention group vs 14 kcal/kg in controls), but proteic delivery was significantly different (1.4 vs 0.76 g/kg, respectively P ≤ 0.0001). The intervention group showed an improvement in SOFA score at 48 h (delta SOFA 1.7 (SD 1.9) vs 0.7 (SD 2.8) P = 0.04) and less hyperglycemic episodes per day (1.0 (SD 1.3) vs 1.7 (SD 2.5) P = 0.017). Discussion: Enteral hyperproteic hypocaloric nutrition therapy could be associated with a decrease in multiple organ failure measured with SOFA score. We also found decreased hyperglycemia and a trend towards less mechanical ventilation days and ICU length of stay. PMID:24501485

Prognostic scores in cirrhotic patients admitted to a gastroenterology intensive care unit.

PubMed

Freire, Paulo; Romãozinho, José M; Amaro, Pedro; Ferreira, Manuela; Sofia, Carlos

2011-04-01

prognostic scores have been validated in cirrhotic patients admitted to general Intensive Care Units. No assessment of these scores was performed in cirrhotics admitted to specialized Gastroenterology Intensive Care Units (GICUs). to assess the prognostic accuracy of Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA), Model for End-stage Liver Disease (MELD) and Child-Pugh-Turcotte (CPT) in predicting GICU mortality in cirrhotic patients. the study involved 124 consecutive cirrhotic admissions to a GICU. Clinical data, prognostic scores and mortality were recorded. Discrimination was evaluated with area under receiver operating characteristic curves (AUC). Calibration was assessed with Hosmer-Lemeshow goodness-of-fit test. GICU mortality was 9.7%. Mean APACHE II, SAPS II, SOFA, MELD and CPT scores for survivors (13.6, 25.4, 3.5,18.0 and 8.6, respectively) were found to be significantly lower than those of non-survivors (22.0, 47.5, 10.1, 30.7 and 12.5,respectively) (p < 0.001). All the prognostic systems showed good discrimination, with AUC = 0.860, 0.911, 0.868, 0.897 and 0.914 for APACHE II, SAPS II, SOFA, MELD and CPT, respectively. Similarly, APACHE II, SAPS II, SOFA, MELD and CPT scores achieved good calibration, with p = 0.146, 0.120, 0.686,0.267 and 0.120, respectively. The overall correctness of prediction was 81.9%, 86.1%, 93.3%, 90.7% and 87.7% for the APA-CHE II, SAPS II, SOFA, MELD and CPT scores, respectively. in cirrhotics admitted to a GICU, all the tested scores have good prognostic accuracy, with SOFA and MELD showing the greatest overall correctness of prediction.

Children's memory distortions following social contact with a co-witness: disentangling social and cognitive mechanisms.

PubMed

Bright-Paul, Alexandra; Jarrold, Christopher; Wright, Daniel B; Guillaume, Stephanie

2012-01-01

This study examined whether recalling an event with a co-witness influences children's recall. Individual 3-5-year-olds (n = 48) watched a film with a co-witness. Unbeknown to participants, the co-witness was watching an alternative version of the film. Afterwards both the co-witness and the participant answered questions about the film together (public recall), and the degree to which children conformed to the co-witness's alternative version of events was measured. Subsequently participants were questioned again individually (private recall). Children also completed false belief and inhibitory control tasks. By separating errors made in public and private, the results indicated that both social conformity (32% of errors) and memory distortion (68% of errors) played a role in co-witness influence. Inhibitory control predicted the likelihood of retracting errors in private, but only for children who failed (r = .66) rather than passed false belief tasks (r = -.10). The results suggest that children with a theory of mind conform in the company of the co-witness to avoid social embarrassment, while those a poor theory of mind conform on the basis of an inability to inhibit the co-witness's response. The findings contribute to our understanding of the motivations responsible for co-witness conformity across early childhood.

Quasi-conformal remapping for compensation of human visual field defects - Advances in image remapping for human field defects

NASA Technical Reports Server (NTRS)

Juday, Richard D.; Loshin, David S.

1989-01-01

Image coordinate transformations are investigated for possible use in a low vision aid for human patients. These patients typically have field defects with localized retinal dysfunction predominately central (age related maculopathy) or peripheral (retinitis pigmentosa). Previously simple eccentricity-only remappings which do not maintain conformality were shown. Initial attempts on developing images which hold quasi-conformality after remapping are presented. Although the quasi-conformal images may have less local distortion, there are discontinuities in the image which may counterindicate this type of transformation for the low vision application.

High-protein hypocaloric vs normocaloric enteral nutrition in critically ill patients: A randomized clinical trial.

PubMed

Rugeles, Saúl; Villarraga-Angulo, Luis Gabriel; Ariza-Gutiérrez, Aníbal; Chaverra-Kornerup, Santiago; Lasalvia, Pieralessandro; Rosselli, Diego

2016-10-01

Appropriate caloric intake in critically ill patients receiving enteral nutrition is controversial. This study evaluates the impact of different caloric regimens on severity of organ failure measured with Sequential Organ Failure Assessment (SOFA). We conducted a randomized prospective controlled trial. Study population included adult intensive care unit (ICU) patients expected to require enteral nutrition for more than 96 hours. Goals in the intervention group were hypocaloric (15 kcal/kg per day) enteral nutrition compared to normocaloric (25 kcal/kg per day) enteral nutrition, both with hyperproteic intake (1.7 g of protein/kg per day). Primary end point was change in SOFA score (ΔSOFA) from baseline at 48 hours. Secondary end points were ΔSOFA at 96 hours, insulin requirements, hyperglycemia or hypoglycemic episodes, length of ICU stay, days on ventilator, and 28-day mortality. After screening 443 patients, 120 patients were analyzed. There were no differences between groups in baseline characteristics. We did not find a statistically significant difference in ΔSOFA at 48 hours. Patients in the hypocaloric group showed lower average daily insulin requirements and percentage of patients requiring any insulin. Hyperproteic, hypocaloric nutrition did not show different outcomes compared to normocaloric nutrition, except lower insulin requirements. Hypocaloric nutrition could provide a more physiologic approach with lower need for care and metabolic impact. Copyright © 2016 Elsevier Inc. All rights reserved.

The Structure of the Elusive Simplest Dipeptide Gly-Gly.

PubMed

Cabezas, Carlos; Varela, Marcelino; Alonso, José L

2017-06-01

Among the hundreds of peptide compounds for which conformations have been determined by using different spectroscopic techniques, the structure of the simplest dipeptide glycylglycine (Gly-Gly) is conspicuously absent. Herein, for the first time, solid samples of Gly-Gly have been vaporized by laser ablation and three different structures have been revealed in a supersonic expansion by Fourier transform microwave spectroscopy. The intramolecular hydrogen bonding interactions that stabilize the observed forms have been established based on the 14 N nuclear quadrupole hyperfine structure. We have illustrated how conformer interconversion distorts the equilibrium conformational distribution, giving rise to missing conformers in the conformational landscape. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Muscular contractions in the zebrafish embryo are necessary to reveal thiuram-induced notochord distortions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teraoka, Hiroki; Urakawa, Satsuki; Nanba, Satomi

2006-04-01

Dithiocarbamates form a large group of chemicals that have numerous uses in agriculture and medicine. It has been reported that dithiocarbamates, including thiuram (tetramethylthiuram disulfide), cause wavy distortions of the notochord in zebrafish and other fish embryos. In the present study, we investigated the mechanism underlying the toxicity of thiuram in zebrafish embryos. When embryos were exposed to thiuram (2-1000 nM: 0.48-240 {mu}g/L) from 3 h post fertilization (hpf) (30% epiboly) until 24 hpf (Prim-5), all embryos develop wavy notochords, disorganized somites, and have shortened yolk sac extensions. The thiuram response was specific and did not cause growth retardation ormore » mortality at 24 hpf. The thiuram-dependent responses showed the same concentration dependence with a waterborne EC{sub 5} values of approximately 7 nM. Morphometric measurements revealed that thiuram does not affect the rate of notochord lengthening. However, the rate of overall body lengthening was significantly reduced in thiuram-exposed animals. Other dithiocarbamates, such as ziram, caused similar malformations to thiuram. While expression of genes involved in somitogenesis was not affected, the levels of notochord-specific transcripts were altered after the onset of malformations. Distortion of the notochord started precisely at 18 hpf, which is concomitant with onset of spontaneous rhythmic trunk contractions. Abolishment of spontaneous contractions using tricaine, {alpha}-bungarotoxin, and a paralytic mutant sofa potato, resulted in normal notochord morphology in the presence of thiuram. These results indicate that muscle activity is necessary to reveal the underlying functional deficit and suggest that the developmental target of dithiocarbamates impairs trunk plasticity through an unknown mechanism.« less

Effect of Rap1 binding on DNA distortion and potassium permanganate hypersensitivity.

PubMed

Le Bihan, Yann-Vaï; Matot, Béatrice; Pietrement, Olivier; Giraud-Panis, Marie-Josèphe; Gasparini, Sylvaine; Le Cam, Eric; Gilson, Eric; Sclavi, Bianca; Miron, Simona; Le Du, Marie-Hélène

2013-03-01

Repressor activator protein 1 (Rap1) is an essential factor involved in transcription and telomere stability in the budding yeast Saccharomyces cerevisiae. Its interaction with DNA causes hypersensitivity to potassium permanganate, suggesting local DNA melting and/or distortion. In this study, various Rap1-DNA crystal forms were obtained using specifically designed crystal screens. Analysis of the DNA conformation showed that its distortion was not sufficient to explain the permanganate reactivity. However, anomalous data collected at the Mn edge using a Rap1-DNA crystal soaked in potassium permanganate solution indicated that the DNA conformation in the crystal was compatible with interaction with permanganate ions. Sequence-conservation analysis revealed that double-Myb-containing Rap1 proteins all carry a fully conserved Arg580 at a position that may favour interaction with permanganate ions, although it is not involved in the hypersensitive cytosine distortion. Permanganate reactivity assays with wild-type Rap1 and the Rap1[R580A] mutant demonstrated that Arg580 is essential for hypersensitivity. AFM experiments showed that wild-type Rap1 and the Rap1[R580A] mutant interact with DNA over 16 successive binding sites, leading to local DNA stiffening but not to accumulation of the observed local distortion. Therefore, Rap1 may cause permanganate hypersensitivity of DNA by forming a pocket between the reactive cytosine and Arg580, driving the permanganate ion towards the C5-C6 bond of the cytosine.

75 FR 12730 - Foreign-Trade Zone 158-Vicksburg/Jackson, MS; Amendment to Application for Subzone; Max Home, LLC...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

...-purpose subzone status for the upholstered furniture manufacturing facilities of Max Home, LLC (Max Home... additional manufacturing plant and warehouse (100 employees/ 26 acres/160,000 sq. ft.) are located at 1313... finished upholstered furniture (chairs, seats, sofas, sleep sofas, and sectionals). The additional...

A comparison of three organ dysfunction scores: MODS, SOFA and LOD for predicting ICU mortality in critically ill patients.

PubMed

Khwannimit, Bodin

2007-06-01

To compare the validity of the Multiple Organ Dysfunction Score (MODS), Sequential Organ Failure Assessment (SOFA), and Logistic Organ Dysfunction Score (LOD) for predicting ICU mortality of Thai critically ill patients. A retrospective study was made of prospective data collected between the 1st July 2004 and 31st March 2006 at Songklanagarind Hospital. One thousand seven hundred and eighty two patients were enrolled in the present study. Two hundred and ninety three (16.4%) deaths were recorded in the ICU. The areas under the Receiver Operating Curves (A UC) for the prediction of ICU mortality the results were 0.861 for MODS, 0.879 for SOFA and 0.880 for LOD. The AUC of SOFA and LOD showed a statistical significance higher than the MODS score (p = 0.014 and p = 0.042, respectively). Of all the models, the neurological failure score showed the best correlation with ICU mortality. All three organ dysfunction scores satisfactorily predicted ICU mortality. The LOD and neurological failure had the best correlation with ICU outcome.

Prognostic value of Sequential Organ Failure Assessment and Simplified Acute Physiology II Score compared with trauma scores in the outcome of multiple-trauma patients.

PubMed

Fueglistaler, Philipp; Amsler, Felix; Schüepp, Marcel; Fueglistaler-Montali, Ida; Attenberger, Corinna; Pargger, Hans; Jacob, Augustinus Ludwig; Gross, Thomas

2010-08-01

Prospective data regarding the prognostic value of the Sequential Organ Failure Assessment (SOFA) score in comparison with the Simplified Acute Physiology Score (SAPS II) and trauma scores on the outcome of multiple-trauma patients are lacking. Single-center evaluation (n = 237, Injury Severity Score [ISS] >16; mean ISS = 29). Uni- and multivariate analysis of SAPS II, SOFA, revised trauma, polytrauma, and trauma and ISS scores (TRISS) was performed. The 30-day mortality was 22.8% (n = 54). SOFA day 1 was significantly higher in nonsurvivors compared with survivors (P < .001) and correlated well with the length of intensive care unit stay (r = .50, P < .001). Logistic regression revealed SAPS II to have the best predictive value of 30-day mortality (area under the receiver operating characteristic = .86 +/- .03). The SOFA score significantly added prognostic information with regard to mortality to both SAPS II and TRISS. The combination of critically ill and trauma scores may increase the accuracy of mortality prediction in multiple-trauma patients. 2010 Elsevier Inc. All rights reserved.

Sequential organ failure assessment (SOFA) scores differ between genders in a sepsis cohort: cause or effect?

PubMed

Jacobson, Sofie; Liedgren, Eva; Johansson, Göran; Ferm, Martin; Winsö, Ola

2012-11-01

Controversy exists regarding the influence of gender on sepsis events and outcome. Epidemiological data from other countries may not always apply to local circumstances. The aim of this study was to identify gender differences in patient characteristics, treatment, and outcome related to the occurrence of sepsis at admission to the ICU. A prospective observational cohort study on patients admitted to the ICU over a 3-year period fulfilling sepsis criteria during the first 24 hours. Demographic data, APACHE II score, SOFA score, TISS 76, aetiology, length of stay (LOS), mortality rate, and aspects of treatment were collected and then analysed with respect to gender differences. There were no gender-related differences in mortality or length of stay. Early organ dysfunction assessed as SOFA score at admission was a stronger risk factor for hospital mortality for women than for men. This discrepancy was mainly associated with the coagulation sub-score. CRP levels differed between genders in relation to hospital mortality. Infection from the abdominopelvic region was more common among women, whereas infection from skin or skin structures were more common in men. In this cohort, gender was not associated with increased mortality during a 2-year follow-up period. SOFA score at ICU admission was a stronger risk factor for hospital mortality for women than for men. The discrepancy was mainly related to the coagulation SOFA sub-score. Together with differences in CRP levels this may suggest differences in inflammatory response patterns between genders.

Quasi-Conformal Remapping For Compensation Of Human Visual Field Defects: Advances In Image Remapping For Human Field Defects

NASA Astrophysics Data System (ADS)

Juday, Richard D.; Loshin, David S.

1989-06-01

We are investigating image coordinate transformations possibly to be used in a low vision aid for human patients. These patients typically have field defects with localized retinal dysfunction predominately central (age related maculopathy) or peripheral (retinitis pigmentosa). Previously we have shown simple eccentricity-only remappings which do not maintain conformality. In this report we present our initial attempts on developing images which hold quasi-conformality after remapping. Although the quasi-conformal images may have less local distortion, there are discontinuities in the image which may counterindicate this type of transformation for the low vision application.

Acute Kidney Injury Enhances Outcome Prediction Ability of Sequential Organ Failure Assessment Score in Critically Ill Patients

PubMed Central

Chang, Chih-Hsiang; Fan, Pei-Chun; Chang, Ming-Yang; Tian, Ya-Chung; Hung, Cheng-Chieh; Fang, Ji-Tseng; Yang, Chih-Wei; Chen, Yung-Chang

2014-01-01

Introduction Acute kidney injury (AKI) is a common and serious complication in intensive care unit (ICU) patients and also often part of a multiple organ failure syndrome. The sequential organ failure assessment (SOFA) score is an excellent tool for assessing the extent of organ dysfunction in critically ill patients. This study aimed to evaluate the outcome prediction ability of SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) III score in ICU patients with AKI. Methods A total of 543 critically ill patients were admitted to the medical ICU of a tertiary-care hospital from July 2007 to June 2008. Demographic, clinical and laboratory variables were prospectively recorded for post hoc analysis as predictors of survival on the first day of ICU admission. Results One hundred and eighty-seven (34.4%) patients presented with AKI on the first day of ICU admission based on the risk of renal failure, injury to kidney, failure of kidney function, loss of kidney function, and end-stage renal failure (RIFLE) classification. Major causes of the ICU admissions involved respiratory failure (58%). Overall in-ICU mortality was 37.9% and the hospital mortality was 44.7%. The predictive accuracy for ICU mortality of SOFA (areas under the receiver operating characteristic curves: 0.815±0.032) was as good as APACHE III in the AKI group. However, cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.001) for SOFA score ≤10 vs. ≥11 in these ICU patients with AKI. Conclusions For patients coexisting with AKI admitted to ICU, this work recommends application of SOFA by physicians to assess ICU mortality because of its practicality and low cost. A SOFA score of ≥ “11” on ICU day 1 should be considered an indicator of negative short-term outcome. PMID:25279844

Comparison of PIRO, SOFA, and MEDS scores for predicting mortality in emergency department patients with severe sepsis and septic shock.

PubMed

Macdonald, Stephen P J; Arendts, Glenn; Fatovich, Daniel M; Brown, Simon G A

2014-11-01

The Predisposition Insult Response and Organ failure (PIRO) scoring system has been developed for use in the emergency department (ED) to risk stratify sepsis cases, but has not been well studied among high-risk patients with severe sepsis and septic shock. The PIRO score was compared with the Sequential Organ Failure Assessment (SOFA) and Mortality in ED Sepsis (MEDS) scores to predict mortality in ED patients with features suggesting severe sepsis or septic shock in the ED. This was an analysis of sepsis patients enrolled in a prospective observational ED study of patients presenting with evidence of shock, hypoxemia, or other organ failure. PIRO, MEDS, and SOFA scores were calculated from ED data. Analysis compared areas under the receiver operator characteristic (ROC) curves for 30-day mortality. Of 240 enrolled patients, final diagnoses were septic shock in 128 (53%), severe sepsis without shock in 70 (29%), and infection with no organ dysfunction in 42 (18%). Forty-eight (20%) patients died within 30 days of presentation. Area under the ROC curve (AUC) for mortality was 0.86 (95% confidence interval [CI] = 0.80 to 0.92) for PIRO, 0.81 (95% CI = 0.74 to 0.88) for MEDS, and 0.78 (95% CI = 0.71 to 0.87) for SOFA scores. Pairwise comparisons of the AUC were as follows: PIRO versus SOFA, p = 0.01; PIRO versus MEDS, p = 0.064; and MEDS versus SOFA; p = 0.37. Mortality increased with increasing PIRO scores: PIRO < 5, 0%; PIRO 5 to 9, 5%; PIRO 10 to 14, 5%; PIRO 15 to 19, 37%; and PIRO ≥ 20, 80% (p < 0.001). The MEDS score also showed increasing mortality with higher scores: MEDS < 5, 0%; MEDS 5 to 7, 12%; MEDS 8 to 11, 15%; MEDS 12 to 14, 48%; and MEDS > 15, 65% (p < 0.001). The PIRO model, taking into account comorbidities and septic source as well as physiologic status, performed better than the SOFA score and similarly to the MEDS score for predicting mortality in ED patients with severe sepsis and septic shock. These findings have implications for identifying and managing high-risk patients and for the design of clinical trials in sepsis. © 2014 by the Society for Academic Emergency Medicine.

Associations between flame retardant applications in furniture foam, house dust levels, and residents' serum levels.

PubMed

Hammel, Stephanie C; Hoffman, Kate; Lorenzo, Amelia M; Chen, Albert; Phillips, Allison L; Butt, Craig M; Sosa, Julie Ann; Webster, Thomas F; Stapleton, Heather M

2017-10-01

Polyurethane foam (PUF) in upholstered furniture frequently is treated with flame retardant chemicals (FRs) to reduce its flammability and adhere to rigorous flammability standards. For decades, a commercial mixture of polybrominated diphenyl ethers (PBDEs) called PentaBDE was commonly applied to foam to fulfill these regulations; however, concerns over toxicity, bioaccumulation, and persistence led to a global phase-out in the mid-2000s. Although PentaBDE is still detected in older furniture, other FR compounds such as tris(1,3-dichloroisopropyl) phosphate (TDCIPP) and Firemaster® 550 (FM550) have been increasingly used as replacements. While biomonitoring studies suggest exposure is widespread, the primary sources of exposure are not clearly known. Here, we investigated the relationships between specific FR applications in furniture foam and human exposure. Paired samples of furniture foam, house dust and serum samples were collected from a cohort in North Carolina, USA and analyzed for FRs typically used in PUF. In general, the presence of a specific FR in the sofa of a home was associated with an increase in the concentration of that FR in house dust. For example, the presence of PentaBDE in sofas was associated with significantly higher levels of BDE-47, a major component of PentaBDE, in house dust (10 β =6.4, p<0.001). A similar association was observed with a component of FM550, 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), with levels that were approximately 3 times higher in house dust when FM550 was identified in the sofa foam (p<0.01). These relationships were modified by dust loading rates in the living room and the ratio of sofa size to room size. Interestingly, levels of TDCIPP and tris(1-chloro-2-isopropyl) phosphate (TCIPP) were also higher in dust with detections in sofa foam; however, these associations were not statistically significant and may suggest there are other prominent sources of these compounds in the home. In addition, the presence of PentaBDE in sofa foam was associated with significantly higher levels of BDE-47 in serum (p<0.01). These results suggest that FR applications in sofas are likely major sources of exposure to these compounds in the home. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low sensitivity of qSOFA, SIRS criteria and sepsis definition to identify infected patients at risk of complication in the prehospital setting and at the emergency department triage.

PubMed

Tusgul, Selin; Carron, Pierre-Nicolas; Yersin, Bertrand; Calandra, Thierry; Dami, Fabrice

2017-11-03

Sepsis is defined as life-threatening organ dysfunction caused by a host response to infection. The quick SOFA (qSOFA) score has been recently proposed as a new bedside clinical score to identify patients with suspected infection at risk of complication (intensive care unit (ICU) admission, in-hospital mortality). The aim of this study was to measure the sensitivity of the qSOFA score, SIRS criteria and sepsis definitions to identify the most serious sepsis cases in the prehospital setting and at the emergency department (ED) triage. We performed a retrospective study of all patients transported by emergency medical services (EMS) to the Lausanne University Hospital (CHUV) over twelve months. All patients with a suspected or proven infection after the ED workup were included. We retrospectively analysed the sensitivity of the qSOFA score (≥2 criteria), SIRS criteria (≥2 clinical criteria) and sepsis definition (SIRS criteria + one sign of organ dysfunction or hypoperfusion) in the pre-hospital setting and at the ED triage as predictors of ICU admission, ICU stay of ≥3 days and early (i.e. 48 h) mortality. No direct comparison between the three tools was attempted. Among 11,411 patients transported to the University hospital, 886 (7.8%) were included. In the pre-hospital setting, the sensitivity of qSOFA reached 36.3% for ICU admission, 17.4% for ICU stay of three days or more and 68.0% for 48 h mortality. The sensitivity of SIRS criteria reached 68.8% for ICU admission, 74.6% for ICU stay of three days or more and 64.0% for 48 h mortality. The sensitivity of sepsis definition did not reach 60% for any outcome. At ED triage, the sensitivity of qSOFA reached 31.2% for ICU admission, 30.5% for ICU stay of ≥3 days and 60.0% for mortality at 48 h. The sensitivity of SIRS criteria reached 58.8% for ICU admission, 57.6% for ICU stay of ≥3 days 80.0% for mortality at 48 h. The sensitivity of sepsis definition reached 60.0% for 48 h mortality. Incidence of sepsis in the ED among patients transported by ambulance was 3.8 percent. This rate, associated to the mortality of sepsis, confirms the necessity to dispose of a test to early identify those patients. The sensitivity performance of all three tools was suboptimal. The qSOFA score, SIRS criteria and sepsis definition have low identification sensitivity in selecting septic patients in the pre-hospital setting or upon arrival in the ED at risk of complication.

Gas-phase conformations of 2-methyl-1,3-dithiolane investigated by microwave spectroscopy

NASA Astrophysics Data System (ADS)

Van, Vinh; Stahl, Wolfgang; Schwell, Martin; Nguyen, Ha Vinh Lam

2018-03-01

The conformational analysis of 2-methyl-1,3-dithiolane using quantum chemical calculations at some levels of theory yielded only one stable conformer with envelope geometry. However, other levels of theory indicated two envelope conformers. Analysis of the microwave spectrum recorded using two molecular jet Fourier transform microwave spectrometers covering the frequency range from 2 to 40 GHz confirms that only one conformer exists under jet conditions. The experimental spectrum was reproduced using a rigid-rotor model with centrifugal distortion correction within the measurement accuracy of 1.5 kHz, and molecular parameters were determined with very high accuracy. The gas phase structure of the title molecule is compared with the structures of other related molecules studied under the same experimental conditions.

Real-space visualization of conformation-independent oligothiophene electronic structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taber, Benjamen N.; Kislitsyn, Dmitry A.; Gervasi, Christian F.

2016-05-21

We present scanning tunneling microscopy and spectroscopy (STM/STS) investigations of the electronic structures of different alkyl-substituted oligothiophenes on the Au(111) surface. STM imaging showed that on Au(111), oligothiophenes adopted distinct straight and bent conformations. By combining STS maps with STM images, we visualize, in real space, particle-in-a-box-like oligothiophene molecular orbitals. We demonstrate that different planar conformers with significant geometrical distortions of oligothiophene backbones surprisingly exhibit very similar electronic structures, indicating a low degree of conformation-induced electronic disorder. The agreement of these results with gas-phase density functional theory calculations implies that the oligothiophene interaction with the Au(111) surface is generally insensitivemore » to molecular conformation.« less

Fisheye image rectification using spherical and digital distortion models

NASA Astrophysics Data System (ADS)

Li, Xin; Pi, Yingdong; Jia, Yanling; Yang, Yuhui; Chen, Zhiyong; Hou, Wenguang

2018-02-01

Fisheye cameras have been widely used in many applications including close range visual navigation and observation and cyber city reconstruction because its field of view is much larger than that of a common pinhole camera. This means that a fisheye camera can capture more information than a pinhole camera in the same scenario. However, the fisheye image contains serious distortion, which may cause trouble for human observers in recognizing the objects within. Therefore, in most practical applications, the fisheye image should be rectified to a pinhole perspective projection image to conform to human cognitive habits. The traditional mathematical model-based methods cannot effectively remove the distortion, but the digital distortion model can reduce the image resolution to some extent. Considering these defects, this paper proposes a new method that combines the physical spherical model and the digital distortion model. The distortion of fisheye images can be effectively removed according to the proposed approach. Many experiments validate its feasibility and effectiveness.

Sequential Organ Failure Assessment (SOFA) scores differ between genders in a sepsis cohort: Cause or effect?

PubMed Central

Liedgren, Eva; Johansson, Göran; Ferm, Martin; Winsö, Ola

2012-01-01

Background. Controversy exists regarding the influence of gender on sepsis events and outcome. Epidemiological data from other countries may not always apply to local circumstances. The aim of this study was to identify gender differences in patient characteristics, treatment, and outcome related to the occurrence of sepsis at admission to the ICU. Methods. A prospective observational cohort study on patients admitted to the ICU over a 3-year period fulfilling sepsis criteria during the first 24 hours. Demographic data, APACHE II score, SOFA score, TISS 76, aetiology, length of stay (LOS), mortality rate, and aspects of treatment were collected and then analysed with respect to gender differences. Results. There were no gender-related differences in mortality or length of stay. Early organ dysfunction assessed as SOFA score at admission was a stronger risk factor for hospital mortality for women than for men. This discrepancy was mainly associated with the coagulation sub-score. CRP levels differed between genders in relation to hospital mortality. Infection from the abdominopelvic region was more common among women, whereas infection from skin or skin structures were more common in men. Conclusion. In this cohort, gender was not associated with increased mortality during a 2-year follow-up period. SOFA score at ICU admission was a stronger risk factor for hospital mortality for women than for men. The discrepancy was mainly related to the coagulation SOFA sub-score. Together with differences in CRP levels this may suggest differences in inflammatory response patterns between genders. PMID:22793786

NICE guidance on sepsis is of limited value in postoperative colorectal patients: the scores that cry 'wolf!'

PubMed

Herrod, Pjj; Cox, M; Keevil, H; Smith, Kje; Lund, J N

2018-04-01

Background and aims Late recognition of sepsis and consequent death remains a problem. To address this, the National Institute for Health and Care Excellence has published updated guidance recommending the use of the Quick Sequential Organ Failure Assessment (Q-SOFA) score when assessing patients at risk of sepsis following the publication of the Third International Consensus Definitions for Sepsis and Septic Shock. The trauma from major surgery produces a systemic inflammatory response syndrome (SIRS) postoperatively as part of its natural history, which may falsely trigger scoring systems. We aimed to assess the accuracy of Q-SOFA and SIRS criteria as recommended scores for early detection of sepsis and septic complications in the first 48hrs after colorectal cancer surgery. Methods We reviewed all elective major colorectal operations in a single centre during a 12-month period from prospectively maintained electronic records. Results One hundred and thirty nine patients were included in this study. In all, 29 patients developed postoperative infective complications in hospital. Nineteen patients triggered on SIRS without developing infective complications, while 42 patients triggered on Q-SOFA with no infective complications. The area under the ROC curve was 0.52 for Q-SOFA and 0.67 for SIRS. Discussion Q-SOFA appears to perform little better than a coin toss at identifying postoperative sepsis after colorectal cancer resection and is inferior to the SIRS criteria. More work is required to assess whether a combination of scoring criteria, biochemical markers and automated tools could increase accurate detection of postoperative infection and trigger early intervention.

Counterfactuals in Action: An fMRI Study of Counterfactual Sentences Describing Physical Effort

ERIC Educational Resources Information Center

Urrutia, Mabel; Gennari, Silvia P.; de Vega, Manuel

2012-01-01

Counterfactual statements such as "if Mary had cleaned the room, she would have moved the sofa" convey both actual and hypothetical actions, namely, that Mary did not clean the room or move the sofa, but she would have done so in some possible past situation. Such statements are ubiquitous in daily life and are involved in critical cognitive…

Serial evaluation of the MODS, SOFA and LOD scores to predict ICU mortality in mixed critically ill patients.

PubMed

Khwannimit, Bodin

2008-09-01

To perform a serial assessment and compare ability in predicting the intensive care unit (ICU) mortality of the multiple organ dysfunction score (MODS), sequential organ failure assessment (SOFA) and logistic organ dysfunction (LOD) score. The data were collected prospectively on consecutive ICU admissions over a 24-month period at a tertiary referral university hospital. The MODS, SOFA, and LOD scores were calculated on initial and repeated every 24 hrs. Two thousand fifty four patients were enrolled in the present study. The maximum and delta-scores of all the organ dysfunction scores correlated with ICU mortality. The maximum score of all models had better ability for predicting ICU mortality than initial or delta score. The areas under the receiver operating characteristic curve (AUC) for maximum scores was 0.892 for the MODS, 0.907 for the SOFA, and 0.92for the LOD. No statistical difference existed between all maximum scores and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Serial assessment of organ dysfunction during the ICU stay is reliable with ICU mortality. The maximum scores is the best discrimination comparable with APACHE II score in predicting ICU mortality.

Getting the invite list right: a discussion of sepsis severity scoring systems in severe complicated intra-abdominal sepsis and randomized trial inclusion criteria.

PubMed

Tolonen, Matti; Coccolini, Federico; Ansaloni, Luca; Sartelli, Massimo; Roberts, Derek J; McKee, Jessica L; Leppaniemi, Ari; Doig, Christopher J; Catena, Fausto; Fabian, Timothy; Jenne, Craig N; Chiara, Osvaldo; Kubes, Paul; Kluger, Yoram; Fraga, Gustavo P; Pereira, Bruno M; Diaz, Jose J; Sugrue, Michael; Moore, Ernest E; Ren, Jianan; Ball, Chad G; Coimbra, Raul; Dixon, Elijah; Biffl, Walter; MacLean, Anthony; McBeth, Paul B; Posadas-Calleja, Juan G; Di Saverio, Salomone; Xiao, Jimmy; Kirkpatrick, Andrew W

2018-01-01

Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. Open abdomen management with enhanced clearance of fluid and biomediators from the peritoneum is a potential therapy requiring prospective evaluation. Given the complexity of powering multi-center trials, it is essential to recruit an inception cohort sick enough to benefit from the intervention; otherwise, no effect of a potentially beneficial therapy may be apparent. An evaluation of abilities of recognized predictive systems to recognize SCIAS patients was conducted using an existing intra-abdominal sepsis (IAS) database. All consecutive adult patients with a diffuse secondary peritonitis between 2012 and 2013 were collected from a quaternary care hospital in Finland, excluding appendicitis/cholecystitis. From this retrospectively collected database, a target population (93) of those with either ICU admission or mortality were selected. The performance metrics of the Third Consensus Definitions for Sepsis and Septic Shock based on both SOFA and quick SOFA, the World Society of Emergency Surgery Sepsis Severity Score (WSESSSS), the APACHE II score, Manheim Peritonitis Index (MPI), and the Calgary Predisposition, Infection, Response, and Organ dysfunction (CPIRO) score were all tested for their discriminant ability to identify this subgroup with SCIAS and to predict mortality. Predictive systems with an area under-the-receiving-operating characteristic (AUC) curve > 0.8 included SOFA, Sepsis-3 definitions, APACHE II, WSESSSS, and CPIRO scores with the overall best for CPIRO. The highest identification rates were SOFA score ≥ 2 (78.4%), followed by the WSESSSS score ≥ 8 (73.1%), SOFA ≥ 3 (75.2%), and APACHE II ≥ 14 (68.8%) identification. Combining the Sepsis-3 septic-shock definition and WSESSS ≥ 8 increased detection to 80%. Including CPIRO score ≥ 3 increased this to 82.8% (Sensitivity-SN; 83% Specificity-SP; 74%. Comparatively, SOFA ≥ 4 and WSESSSS ≥ 8 with or without septic-shock had 83.9% detection (SN; 84%, SP; 75%, 25% mortality). No one scoring system behaves perfectly, and all are largely dominated by organ dysfunction. Utilizing combinations of SOFA, CPIRO, and WSESSSS scores in addition to the Sepsis-3 septic shock definition appears to offer the widest "inclusion-criteria" to recognize patients with a high chance of mortality and ICU admission. https://clinicaltrials.gov/ct2/show/NCT03163095; Registered on May 22, 2017.

75 FR 71671 - Draft Report on the Technical Study of the Sofa Super Store Fire-South Carolina, June 18, 2007.

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-24

...-0532-01] Draft Report on the Technical Study of the Sofa Super Store Fire--South Carolina, June 18..., which took place on June 18, 2007. DATES: Comments must be received on or before 12 noon EST, December 2...-6868. SUPPLEMENTARY INFORMATION: Following a fire in Charleston, SC on June 18, 2007, NIST conducted a...

Implications of the new sepsis definition on research and practice.

PubMed

Peach, Brian C

2017-04-01

The Society of Critical-Care Medicine and the European Society of Intensive Care Medicine recently announced a marked change in the sepsis definition. A task force of 19 sepsis clinicians and researchers made the change based on advances in the pathobiological understanding of the septic process. The task force determined that there were numerous justifications for a revision of the sepsis definition, which are outlined in this article. The systemic inflammatory response criteria have been replaced by the Sequential Organ Failure Assessment (SOFA) score in the newly operationalized definition (Singer et al., 2016). In addition to the definition change, the task force recommended using the new quick SOFA (qSOFA) score in non-ICU settings, as a risk stratification tool to identify patients who may be septic or be at risk of developing sepsis. The change in definition will likely have a negative impact on sepsis research in the short-term as hospitals adjust their coding for the new definition, but may result in less misclassification bias and improved research data in the long-term. While the intent of the SCCM/ESICM task force was to better define sepsis for coding and epidemiological research purposes, there is the potential for improved patient outcomes if clinicians are better able to differentiate between sepsis and inflammatory events. The qSOFA tool may also aid clinicians in recognizing sepsis in a quicker manner, leading to more timely treatment, and potentially better outcomes. While the new operationalized Sepsis-3 definition appears on the surface to be an improvement over the previous iterations, it remains to be seen if research data will be more robust using the new criteria. There is the potential for better patient outcomes if clinicians are better able to differentiate sepsis from inflammatory events with the new definition, and if sepsis cases are recognized sooner with qSOFA. Future research on the impact of this definition change on research and practice will be essential, to determine if the Sepsis 3 definition, its associated clinical criteria, and the qSOFA need further revision. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of the SoFAS (solid fats and added sugars) concept: the 2010 Dietary Guidelines for Americans.

PubMed

Nicklas, Theresa A; O'Neil, Carol E

2015-05-01

The diets of most US children and adults are poor, as reflected by low diet quality scores, when compared with the recommendations of the Dietary Guidelines for Americans (DGAs). Contributing to these low scores is that most Americans overconsume solid fats, which may contain saturated fatty acids and added sugars; although alcohol consumption was generally modest, it provided few nutrients. Thus, the 2005 DGAs generated a new recommendation: to reduce intakes of solid fats, alcohol, and added sugars (SoFAAS). What precipitated the emergence of the new SoFAAS terminology was the concept of discretionary calories (a "calorie" is defined as the amount of energy needed to increase the temperature of 1 kg of water by 1°C), which were defined as calories consumed after an individual had met his or her recommended nutrient intakes while consuming fewer calories than the daily recommendation. A limitation with this concept was that additional amounts of nutrient-dense foods consumed beyond the recommended amount were also considered discretionary calories. The rationale for this was that if nutrient-dense foods were consumed beyond recommended amounts, after total energy intake was met then this constituted excess energy intake. In the 2010 DGAs, the terminology was changed to solid fats and added sugars (SoFAS); thus, alcohol was excluded because it made a minor contribution to overall intake and did not apply to children. The SoFAS terminology also negated nutrient-dense foods that were consumed in amounts above the recommendations for the specific food groups in the food patterns. The ambiguous SoFAS terminology was later changed to "empty calories" to reflect only those calories from solid fats and added sugars (and alcohol if consumed beyond moderate amounts). The purpose of this review is to provide an historical perspective on how the dietary recommendations went from SoFAAS to SoFAS and how discretionary calories went to empty calories between the 2005 and 2010 DGAs. This information will provide practitioners, as well as the public, with valuable information to better understand the evolution of SoFAS over time. © 2015 American Society for Nutrition.

Development of the SoFAS (Solid Fats and Added Sugars) Concept: The 2010 Dietary Guidelines for Americans123

PubMed Central

Nicklas, Theresa A; O’Neil, Carol E

2015-01-01

The diets of most US children and adults are poor, as reflected by low diet quality scores, when compared with the recommendations of the Dietary Guidelines for Americans (DGAs). Contributing to these low scores is that most Americans overconsume solid fats, which may contain saturated fatty acids and added sugars; although alcohol consumption was generally modest, it provided few nutrients. Thus, the 2005 DGAs generated a new recommendation: to reduce intakes of solid fats, alcohol, and added sugars (SoFAAS). What precipitated the emergence of the new SoFAAS terminology was the concept of discretionary calories (a “calorie” is defined as the amount of energy needed to increase the temperature of 1 kg of water by 1°C), which were defined as calories consumed after an individual had met his or her recommended nutrient intakes while consuming fewer calories than the daily recommendation. A limitation with this concept was that additional amounts of nutrient-dense foods consumed beyond the recommended amount were also considered discretionary calories. The rationale for this was that if nutrient-dense foods were consumed beyond recommended amounts, after total energy intake was met then this constituted excess energy intake. In the 2010 DGAs, the terminology was changed to solid fats and added sugars (SoFAS); thus, alcohol was excluded because it made a minor contribution to overall intake and did not apply to children. The SoFAS terminology also negated nutrient-dense foods that were consumed in amounts above the recommendations for the specific food groups in the food patterns. The ambiguous SoFAS terminology was later changed to “empty calories” to reflect only those calories from solid fats and added sugars (and alcohol if consumed beyond moderate amounts). The purpose of this review is to provide an historical perspective on how the dietary recommendations went from SoFAAS to SoFAS and how discretionary calories went to empty calories between the 2005 and 2010 DGAs. This information will provide practitioners, as well as the public, with valuable information to better understand the evolution of SoFAS over time. PMID:25979510

Associations among depression severity, painful physical symptoms, and social and occupational functioning impairment in patients with major depressive disorder: a 3-month, prospective, observational study.

PubMed

Harada, Eiji; Satoi, Yoichi; Kuga, Atsushi; Tokuoka, Hirofumi; Kikuchi, Toshiaki; Watanabe, Koichiro; Alev, Levent; Mimura, Masaru

2017-01-01

To investigate associations among depression severity, painful physical symptoms (PPS), and social and occupational functioning impairment in patients with major depressive disorder (MDD) who had achieved complete remission (CR) or partial remission (PR) after acute treatment. This was a 12-week, multicenter, prospective, observational study. Patients with MDD treated with an antidepressant medication for the previous 12 weeks (±3 weeks) who had achieved CR (defined as a 17-item Hamilton Rating Scale for Depression [HAM-D17] score ≤7) or PR (HAM-D17 score ≥8 and ≤18) were enrolled. Depression severity, PPS, and impairment in social and occupational functioning were assessed using the HAM-D17, the Brief Pain Inventory (Short Form) (BPI-SF), and the Social and Occupational Functioning Assessment Scale (SOFAS), respectively, at enrollment (Week 12) and after 12 weeks (Week 24). Overall, 323 Japanese patients with MDD were enrolled (CR n=158, PR n=165) and 288 patients completed the study (CR n=139, PR n=149). HAM-D17 and SOFAS scores were strongly and negatively correlated at enrollment (Week 12; P <0.0001) and Week 24 ( P <0.0001). A weak negative correlation between the BPI-SF and SOFAS was observed at Week 24 ( P =0.0011), but not at enrollment ( P =0.164). Remission status at enrollment (CR or PR) was associated with achieving normal social and occupational functioning (SOFAS score ≥80) at Week 24 in patients who had not achieved normal social and occupational functioning (SOFAS score <80) at enrollment (CR vs PR, OR=0.05 [95% CIs 0.01-0.18], P <0.0001). A greater proportion of patients with CR and no PPS at enrollment achieved SOFAS scores ≥80 at Week 24 than those with CR and PPS. Our results suggest that treating both depressive symptoms and PPS is important for achieving a normal level of functioning on a long-term basis in patients with MDD.

Optimal Mass Transport for Shape Matching and Comparison

PubMed Central

Su, Zhengyu; Wang, Yalin; Shi, Rui; Zeng, Wei; Sun, Jian; Luo, Feng; Gu, Xianfeng

2015-01-01

Surface based 3D shape analysis plays a fundamental role in computer vision and medical imaging. This work proposes to use optimal mass transport map for shape matching and comparison, focusing on two important applications including surface registration and shape space. The computation of the optimal mass transport map is based on Monge-Brenier theory, in comparison to the conventional method based on Monge-Kantorovich theory, this method significantly improves the efficiency by reducing computational complexity from O(n2) to O(n). For surface registration problem, one commonly used approach is to use conformal map to convert the shapes into some canonical space. Although conformal mappings have small angle distortions, they may introduce large area distortions which are likely to cause numerical instability thus resulting failures of shape analysis. This work proposes to compose the conformal map with the optimal mass transport map to get the unique area-preserving map, which is intrinsic to the Riemannian metric, unique, and diffeomorphic. For shape space study, this work introduces a novel Riemannian framework, Conformal Wasserstein Shape Space, by combing conformal geometry and optimal mass transport theory. In our work, all metric surfaces with the disk topology are mapped to the unit planar disk by a conformal mapping, which pushes the area element on the surface to a probability measure on the disk. The optimal mass transport provides a map from the shape space of all topological disks with metrics to the Wasserstein space of the disk and the pullback Wasserstein metric equips the shape space with a Riemannian metric. We validate our work by numerous experiments and comparisons with prior approaches and the experimental results demonstrate the efficiency and efficacy of our proposed approach. PMID:26440265

PAL: A Positional Astronomy Library

NASA Astrophysics Data System (ADS)

Jenness, T.; Berry, D. S.

2013-10-01

PAL is a new positional astronomy library written in C that attempts to retain the SLALIB API but is distributed with an open source GPL license. The library depends on the IAU SOFA library wherever a SOFA routine exists and uses the most recent nutation and precession models. Currently about 100 of the 200 SLALIB routines are available. Interfaces are also available from Perl and Python. PAL is freely available via github.

Validation of Computerized Automatic Calculation of the Sequential Organ Failure Assessment Score

PubMed Central

Harrison, Andrew M.; Pickering, Brian W.; Herasevich, Vitaly

2013-01-01

Purpose. To validate the use of a computer program for the automatic calculation of the sequential organ failure assessment (SOFA) score, as compared to the gold standard of manual chart review. Materials and Methods. Adult admissions (age > 18 years) to the medical ICU with a length of stay greater than 24 hours were studied in the setting of an academic tertiary referral center. A retrospective cross-sectional analysis was performed using a derivation cohort to compare automatic calculation of the SOFA score to the gold standard of manual chart review. After critical appraisal of sources of disagreement, another analysis was performed using an independent validation cohort. Then, a prospective observational analysis was performed using an implementation of this computer program in AWARE Dashboard, which is an existing real-time patient EMR system for use in the ICU. Results. Good agreement between the manual and automatic SOFA calculations was observed for both the derivation (N=94) and validation (N=268) cohorts: 0.02 ± 2.33 and 0.29 ± 1.75 points, respectively. These results were validated in AWARE (N=60). Conclusion. This EMR-based automatic tool accurately calculates SOFA scores and can facilitate ICU decisions without the need for manual data collection. This tool can also be employed in a real-time electronic environment. PMID:23936639

Predictive value of the APACHE II, SAPS II, SOFA and GCS scoring systems in patients with severe purulent bacterial meningitis.

PubMed

Pietraszek-Grzywaczewska, Iwona; Bernas, Szymon; Łojko, Piotr; Piechota, Anna; Piechota, Mariusz

2016-01-01

Scoring systems in critical care patients are essential for predicting of the patient outcome and evaluating the therapy. In this study, we determined the value of the Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Scale (GCS) scoring systems in the prediction of mortality in adult patients admitted to the intensive care unit (ICU) with severe purulent bacterial meningitis. We retrospectively analysed data from 98 adult patients with severe purulent bacterial meningitis who were admitted to the single ICU between March 2006 and September 2015. Univariate logistic regression identified the following risk factors of death in patients with severe purulent bacterial meningitis: APACHE II, SAPS II, SOFA, and GCS scores, and the lengths of ICU stay and hospital stay. The independent risk factors of patient death in multivariate analysis were the SAPS II score, the length of ICU stay and the length of hospital stay. In the prediction of mortality according to the area under the curve, the SAPS II score had the highest accuracy followed by the APACHE II, GCS and SOFA scores. For the prediction of mortality in a patient with severe purulent bacterial meningitis, SAPS II had the highest accuracy.

Memory conformity affects inaccurate memories more than accurate memories.

PubMed

Wright, Daniel B; Villalba, Daniella K

2012-01-01

After controlling for initial confidence, inaccurate memories were shown to be more easily distorted than accurate memories. In two experiments groups of participants viewed 50 stimuli and were then presented with these stimuli plus 50 fillers. During this test phase participants reported their confidence that each stimulus was originally shown. This was followed by computer-generated responses from a bogus participant. After being exposed to this response participants again rated the confidence of their memory. The computer-generated responses systematically distorted participants' responses. Memory distortion depended on initial memory confidence, with uncertain memories being more malleable than confident memories. This effect was moderated by whether the participant's memory was initially accurate or inaccurate. Inaccurate memories were more malleable than accurate memories. The data were consistent with a model describing two types of memory (i.e., recollective and non-recollective memories), which differ in how susceptible these memories are to memory distortion.

Sofa dermatitis.

PubMed

Schad, Karin; Nobbe, Stephan; French, Lars E; Ballmer-Weber, Barbara

2010-11-01

Furniture components can cause contact allergies. In the last years several cases of eczema after sofa contact have been reported. Typically the skin lesions develop on the back, the buttocks, the dorsal aspects of the thighs and arms and are often very resistant to topical corticoid therapy. Dimethylfumarate (DMF) is postulated to be the causative agent for this Type IV hypersensitivity reaction. DMF is an antimicrobial substance, which is used in asian upholstered furniture industry amongst others. We report the case of a 65-year old patient with generalised severely itching maculopapular, partly eczematous skin lesions on the buttocks, back, abdomen and arms. The resistance to therapy, several relapses after discharge from hospital as well as the detailed history lead us to the tentative diagnosis. The sofa dermatitis was proven by positive patch testing with furniture material and dimethylfumarate. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

Association between trends in clinical variables and outcome in intensive care patients with faecal peritonitis: analysis of the GenOSept cohort.

PubMed

Tridente, Ascanio; Clarke, Geraldine M; Walden, Andrew; Gordon, Anthony C; Hutton, Paula; Chiche, Jean-Daniel; Holloway, Paul A H; Mills, Gary H; Bion, Julian; Stüber, Frank; Garrard, Christopher; Hinds, Charles

2015-05-05

Patients admitted to intensive care following surgery for faecal peritonitis present particular challenges in terms of clinical management and risk assessment. Collaborating surgical and intensive care teams need shared perspectives on prognosis. We aimed to determine the relationship between dynamic assessment of trends in selected variables and outcomes. We analysed trends in physiological and laboratory variables during the first week of intensive care unit (ICU) stay in 977 patients at 102 centres across 16 European countries. The primary outcome was 6-month mortality. Secondary endpoints were ICU, hospital and 28-day mortality. For each trend, Cox proportional hazards (PH) regression analyses, adjusted for age and sex, were performed for each endpoint. Trends over the first 7 days of the ICU stay independently associated with 6-month mortality were worsening thrombocytopaenia (mortality: hazard ratio (HR) = 1.02; 95% confidence interval (CI), 1.01 to 1.03; P < 0.001) and renal function (total daily urine output: HR =1.02; 95% CI, 1.01 to 1.03; P < 0.001; Sequential Organ Failure Assessment (SOFA) renal subscore: HR = 0.87; 95% CI, 0.75 to 0.99; P = 0.047), maximum bilirubin level (HR = 0.99; 95% CI, 0.99 to 0.99; P = 0.02) and Glasgow Coma Scale (GCS) SOFA subscore (HR = 0.81; 95% CI, 0.68 to 0.98; P = 0.028). Changes in renal function (total daily urine output and renal component of the SOFA score), GCS component of the SOFA score, total SOFA score and worsening thrombocytopaenia were also independently associated with secondary outcomes (ICU, hospital and 28-day mortality). We detected the same pattern when we analysed trends on days 2, 3 and 5. Dynamic trends in all other measured laboratory and physiological variables, and in radiological findings, changes in respiratory support, renal replacement therapy and inotrope and/or vasopressor requirements failed to be retained as independently associated with outcome in multivariate analysis. Only deterioration in renal function, thrombocytopaenia and SOFA score over the first 2, 3, 5 and 7 days of the ICU stay were consistently associated with mortality at all endpoints. These findings may help to inform clinical decision making in patients with this common cause of critical illness.

A study of the conformational isomerism of 1-iodobutane by high resolution rotational spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arsenault, Eric A.; Obenchain, Daniel A.; Blake, Thomas A.

2017-05-01

The first microwave study of 1-iodobutane, performed by Steinmetz et al.in 1977) led to the determination of the B + C parameter for the anti-anti­and gauche-anti-conformers. Nearly 40 years later, this reinvestigation of 1- iodobutane, by high-resolution microwave spectroscopy, led to the determina­tion of rotational constants, centrifugal distortion constants, nuclear quadrupole coupling constants (NQCCs), and nuclear-sp rotation constants belonging to both of the two previously mentioned conformers, in addition to the gauche­ gauche-conformer, which was observed in this frequency regime for the first time. Comparisons between the three conformers of 1-iodobutanc and other iodo- and bromoalkanes are made, specifically throughmore » an analysis of the nuclear quadrupole coupling constants belonging to the iodine and bromine atoms in the respective chemical environments.« less

A study of the conformational isomerism of 1-iodobutane by high resolution rotational spectroscopy

DOE PAGES

Arsenault, Eric A.; Obenchain, Daniel A.; Blake, Thomas A.; ...

2017-05-01

The first microwave study of 1-iodobutane, performed by Steinmetz et al. in 1977, led to the determination of the B+C parameter for the anti-anti- and gauche-anti-conformers. Nearly 40 years later, in this paper this reinvestigation of 1-iodobutane, by high-resolution microwave spectroscopy, led to the determination of rotational constants, centrifugal distortion constants, nuclear quadrupole coupling constants (NQCCs), and nuclear-spin rotation constants belonging to both of the two previously mentioned conformers, in addition to the gauche-gauche-conformer, which was observed in this frequency regime for the first time. Finally, comparisons between the three conformers of 1-iodobutane and other iodo- and bromoalkanes are made,more » specifically through an analysis of the nuclear quadrupole coupling constants belonging to the iodine and bromine atoms in the respective chemical environments.« less

Comparison of the sequential organ failure assessment score with the King's College Hospital criteria and the model for end-stage liver disease score for the prognosis of acetaminophen-induced acute liver failure.

PubMed

Cholongitas, Evangelos; Theocharidou, Eleni; Vasianopoulou, Panayota; Betrosian, Alex; Shaw, Steve; Patch, David; O'Beirne, James; Agarwal, Banwari; Burroughs, Andrew K

2012-04-01

Acetaminophen-induced acute liver failure (ALF) is a complex multiorgan illness. An assessment of the prognosis is essential for the accurate identification of patients for whom survival without liver transplantation (LT) is unlikely. The aims of this study were the comparison of prognostic models [King's College Hospital (KCH), Model for End-Stage Liver Disease, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II)] and the identification of independent prognostic indicators of outcome. We evaluated consecutive patients with severe acetaminophen-induced ALF who were admitted to the intensive care unit. At admission, demographic, clinical, and laboratory parameters were recorded. The discriminative ability of each prognostic score at the baseline was evaluated with the area under the receiver operating characteristic curve (AUC). In addition, using a multiple logistic regression, we assessed independent factors associated with outcome. In all, 125 consecutive patients with acetaminophen-induced ALF were evaluated: 67 patients (54%) survived with conservative medical management (group 1), and 58 patients (46%) either died without LT (28%) or underwent LT (18%; group 2). Group 1 patients had significantly lower median APACHE II (10 versus 14) and SOFA scores (9 versus 12) than group 2 patients (P < 0.001). The independent indicators associated with death or LT were a longer prothrombin time (P = 0.007), the inspiratory oxygen concentration (P = 0.005), and the lactate level at 12 hours (P < 0.001). The KCH criteria had the highest specificity (83%) but the lowest sensitivity (47%), and the SOFA score had the best discriminative ability (AUC = 0.79). In conclusion, for patients with acetaminophen-induced ALF, the SOFA score performed better than the other prognostic scores, and this reflected the presence of multiorgan dysfunction. A further evaluation of SOFA with the KCH criteria is warranted. Copyright © 2012 American Association for the Study of Liver Diseases.

Low energy intake during the first week in an emergency intensive care unit is associated with reduced duration of mechanical ventilation in critically ill, underweight patients: a single-center retrospective chart review.

PubMed

Ichimaru, Satomi; Fujiwara, Hidetoshi; Amagai, Teruyoshi; Atsumi, Takahiro

2014-06-01

Although nutrition support is essential in intensive care units, optimal energy intake remains unclear. Here, we assessed the influence of energy intake on outcomes of critically ill, underweight patients. A retrospective chart review was conducted in patients with body mass index (BMI) of <20.0 kg/m(2) in an emergency intensive care unit (EICU). Patients were categorized into 4 groups by initial Sequential Organ Failure Assessment score (I-SOFA) and average daily energy intake during the first week: group M-1, I-SOFA ≤8 and <16 kcal/kg/d; group M-2, I-SOFA ≤8 and ≥16 kcal/kg/d; group S-1, I-SOFA >8 and <16 kcal/kg/d; and group S-2, I-SOFA >8 and ≥16 kcal/kg/d. The study included 51 patients with a median age of 69 years. No significant differences were noted in all-cause mortality and length of stay in the EICU and hospital between groups M-1 and M-2 or groups S-1 and S-2. The mechanical ventilation duration (MVD) was significantly shorter in group M-1 than M-2 (2.7 [1.0-5.7] vs 9.2 [4.2-17.4] days; P = .040) and in group S-1 than S-2 (3.1 [0.7-6.0] vs 8.8 [6.1-23.1] days; P = .006). The number of patients who underwent tracheostomy in hospital was significantly lower in group S-1 than in S-2 (20% vs 32%; P = .002). Multivariable analyses to adjust for confounders revealed that average energy intake during the first week in EICU was a significant factor independently associated with MVD but not with the requirement of tracheostomy. Reduced energy intake during the first week in EICU was associated with a reduced MVD in clinically ill patients with BMI <20.0 kg/m(2).

Shear-Induced Amyloid Formation in the Brain: I. Potential Vascular and Parenchymal Processes.

PubMed

Trumbore, Conrad N

2016-09-06

Shear distortion of amyloid-beta (Aβ) solutions accelerates amyloid cascade reactions that may yield different toxic oligomers than those formed in quiescent solutions. Recent experiments indicate that cerebrospinal fluid (CSF) and interstitial fluid (ISF) containing Aβ flow through narrow brain perivascular pathways and brain parenchyma. This paper suggests that such flow causes shear distortion of Aβ molecules involving conformation changes that may be one of the initiating events in the etiology of Alzheimer's disease. Aβ shearing can occur in or around brain arteries and arterioles and is suggested as the origin of cerebral amyloid angiopathy deposits in cerebrovascular walls. Comparatively low flow rates of ISF within the narrow extracellular spaces (ECS) of the brain parenchyma are suggested as a possible initiating factor in both the formation of neurotoxic Aβ42 oligomers and amyloid fibrils. Aβ42 in slow-flowing ISF can gain significant shear energy at or near the walls of tortuous brain ECS flow paths, promoting the formation of a shear-distorted, excited state hydrophobic Aβ42* conformation. This Aβ42* molecule could possibly be involved in one of two paths, one involving rapid adsorption to a brain membrane surface, ultimately forming neurotoxic oligomers on membranes, and the other ultimately forming plaque within the ECS flow pathways. Rising Aβ concentrations combined with shear at or near critical brain membranes are proposed as contributing factors to Alzheimer's disease neurotoxicity. These hypotheses may be applicable in other neurodegenerative diseases, including tauopathies and alpha-synucleinopathies, in which shear-distorted proteins also may form in the brain ECS.

DNA conformations in mismatch repair probed in solution by X-ray scattering from gold nanocrystals

PubMed Central

Hura, Greg L.; Tsai, Chi-Lin; Claridge, Shelley A.; Mendillo, Marc L.; Smith, Jessica M.; Williams, Gareth J.; Mastroianni, Alexander J.; Alivisatos, A. Paul; Putnam, Christopher D.; Kolodner, Richard D.; Tainer, John A.

2013-01-01

DNA metabolism and processing frequently require transient or metastable DNA conformations that are biologically important but challenging to characterize. We use gold nanocrystal labels combined with small angle X-ray scattering to develop, test, and apply a method to follow DNA conformations acting in the Escherichia coli mismatch repair (MMR) system in solution. We developed a neutral PEG linker that allowed gold-labeled DNAs to be flash-cooled and stored without degradation in sample quality. The 1,000-fold increased gold nanocrystal scattering vs. DNA enabled investigations at much lower concentrations than otherwise possible to avoid concentration-dependent tetramerization of the MMR initiation enzyme MutS. We analyzed the correlation scattering functions for the nanocrystals to provide higher resolution interparticle distributions not convoluted by the intraparticle distribution. We determined that mispair-containing DNAs were bent more by MutS than complementary sequence DNA (csDNA), did not promote tetramer formation, and allowed MutS conversion to a sliding clamp conformation that eliminated the DNA bends. Addition of second protein responder MutL did not stabilize the MutS-bent forms of DNA. Thus, DNA distortion is only involved at the earliest mispair recognition steps of MMR: MutL does not trap bent DNA conformations, suggesting migrating MutL or MutS/MutL complexes as a conserved feature of MMR. The results promote a mechanism of mismatch DNA bending followed by straightening in initial MutS and MutL responses in MMR. We demonstrate that small angle X-ray scattering with gold labels is an enabling method to examine protein-induced DNA distortions key to the DNA repair, replication, transcription, and packaging. PMID:24101514

(±)-Pestalachloride D, an antibacterial racemate of chlorinated benzophenone derivative from a soft coral-derived fungus Pestalotiopsis sp.

PubMed

Wei, Mei-Yan; Li, Dan; Shao, Chang-Lun; Deng, Dong-Sheng; Wang, Chang-Yun

2013-03-28

A new antibacterial chlorinated benzophenone derivative, (±)-pestalachloride D (1), along with a related analog, (±)-pestalachloride C (2), was recently isolated from the marine-derived fungus Pestalotiopsis sp. isolated from a soft coral Sarcophyton sp. collected from Yongxing Island in the South China Sea. Both chiral HPLC analysis and single-crystal X-ray data indicated that 1 is a racemic mixture. Interestingly, 1 did not exhibit any effect in the zebrafish embryo teratogenicity assay, while 2 led to abnormal growth. The potential impact on zebrafish embryo growth is discussed based on their crystal structures. The main difference of crystal structures between 1 and 2 is that the six-member non-aromatic ring (O4, C10, C9, C8, C2', and C3') in 1 exhibits a distorted chair conformation, while 2 shows a distorted boat conformation. Moreover, compounds 1 and 2 both exhibited moderate antibacterial activity.

(±)-Pestalachloride D, an Antibacterial Racemate of Chlorinated Benzophenone Derivative from a Soft Coral-Derived Fungus Pestalotiopsis sp

PubMed Central

Wei, Mei-Yan; Li, Dan; Shao, Chang-Lun; Deng, Dong-Sheng; Wang, Chang-Yun

2013-01-01

A new antibacterial chlorinated benzophenone derivative, (±)-pestalachloride D (1), along with a related analog, (±)-pestalachloride C (2), was recently isolated from the marine-derived fungus Pestalotiopsis sp. isolated from a soft coral Sarcophyton sp. collected from Yongxing Island in the South China Sea. Both chiral HPLC analysis and single-crystal X-ray data indicated that 1 is a racemic mixture. Interestingly, 1 did not exhibit any effect in the zebrafish embryo teratogenicity assay, while 2 led to abnormal growth. The potential impact on zebrafish embryo growth is discussed based on their crystal structures. The main difference of crystal structures between 1 and 2 is that the six-member non-aromatic ring (O4, C10, C9, C8, C2′, and C3′) in 1 exhibits a distorted chair conformation, while 2 shows a distorted boat conformation. Moreover, compounds 1 and 2 both exhibited moderate antibacterial activity. PMID:23538869

Ethanol Dimer: Observation of Three New Conformers by Broadband Rotational Spectroscopy

NASA Astrophysics Data System (ADS)

Loru, Donatella; Peña, Isabel; Sanz, M. Eugenia

2017-06-01

The conformational behaviour of the hydrogen-bonded cluster ethanol dimer has been reinvestigated by chirped pulse Fourier transform microwave spectroscopy in the 2-8 GHz frequency region. Three new conformers ({tt}, {tg}+, and {g}-{g}+) have been identified together with the three ({g}+{g}+, {g}-{t}, and {g}+{t}) previously observed by Hearn et al. (J. Chem. Phys. 123, 134324, 2005) and their rotational and centrifugal distortion constants have been determined. By using different carrier gases in the supersonic expansion, the relative abundances of the observed conformers have been estimated. The monosubstituted ^{13}C species and some of the ^{18}O species of the most abundant conformers {g}+{g}+, {g}-{t}, and {tt} have been observed in their natural abundance, which led to the partial determination of their r_{s} structures, and the r_{0} structure for the {tt} conformer. The six observed conformers are stabilized by the delicate interplay of primary O-H...O and secondary C-H...O hydrogen bonds, and dispersion interactions between the methyl groups. Density functional and ab initio methods with different basis sets are benchmarked against the experimental data.

All substituted nickel porphyrins are highly nonplanar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shelnutt, J.A.; Song, X.Z.; Jentzen, W.

1996-12-31

X-ray crystallographic and resonance Raman studies show that only un-substituted Ni porphine is planar in solution; all substituted Ni porphyrin derivatives either are nonplanar or exist as a mixture of planar and nonplanar conformers in solution. Recent modifications in a molecular mechanics force field improve the ability the MM calculations to predict the X-ray structures of porphyrins and also the planar-nonplanar conformational equilibria in many cases. Calculations using the new force field suggests that all geoporphyrins will be highly nonplanar, especially those having meso substituents. The nonplanarity is expected to influence properties such as solubility and metallation/dematallation reactions. Further, amore » method of quantifying these nonplanar structures has been devised; any porphyrin structure can be decomposed into displacements along the out-of-plane normal coordinates. However, usually distortions along only the lowest-frequency normal modes of each symmetry type are required to adequately describe the structure. The lowest-frequency normal coordinates of b{sub lu}, a{sub 2u}, b{sub 2u}, and e{sub g} symmetries correspond to commonly observed symmetric distortions called ruffling (ruf), doming(dom), saddling (sad), and waving (wav(x), wav(y)). The application of this structural decomposition method to several problems including the influences of steric crowding and protein folding on porphyrin conformation will be described.« less

Comparing Quick Sequential Organ Failure Assessment Scores to End-tidal Carbon Dioxide as Mortality Predictors in Prehospital Patients with Suspected Sepsis.

PubMed

Hunter, Christopher L; Silvestri, Salvatore; Ralls, George; Stone, Amanda; Walker, Ayanna; Mangalat, Neal; Papa, Linda

2018-05-01

Early identification of sepsis significantly improves outcomes, suggesting a role for prehospital screening. An end-tidal carbon dioxide (ETCO 2 ) value ≤ 25 mmHg predicts mortality and severe sepsis when used as part of a prehospital screening tool. Recently, the Quick Sequential Organ Failure Assessment (qSOFA) score was also derived as a tool for predicting poor outcomes in potentially septic patients. We conducted a retrospective cohort study among patients transported by emergency medical services to compare the use of ETCO 2 ≤ 25 mmHg with qSOFA score of ≥ 2 as a predictor of mortality or diagnosis of severe sepsis in prehospital patients with suspected sepsis. By comparison of receiver operator characteristic curves, ETCO 2 had a higher discriminatory power to predict mortality, sepsis, and severe sepsis than qSOFA. Both non-invasive measures were easily obtainable by prehospital personnel, with ETCO 2 performing slightly better as an outcome predictor.

Out-of-hospital characteristics and care of patients with severe sepsis: a cohort study

PubMed Central

Seymour, Christopher W.; Band, Roger A.; Cooke, Colin R.; Mikkelsen, Mark E.; Hylton, Julie; Rea, Tom D.; Goss, Christopher H.; Gaieski, David F.

2010-01-01

Purpose Early recognition and treatment in severe sepsis improves outcomes. Yet, out-of-hospital patient characteristics and emergency medical services (EMS) care in severe sepsis is understudied. Our goal was to describe out-of-hospital characteristics and EMS care in patients with severe sepsis, and evaluate associations between out-of-hospital characteristics and severity of organ dysfunction in the emergency department (ED). Materials & Methods We performed a secondary data analysis of existing data from patients with severe sepsis transported by EMS to an academic medical center. We constructed multivariable linear regression models to determine if out-of-hospital factors are associated with serum lactate and SOFA in the ED. Results Two hundred sixteen patients with severe sepsis arrived by EMS. Median serum lactate in the ED was 3.0 mmol/L (IQR:2.0-5.0) and median SOFA score was 4 (IQR:2-6). Sixty-three percent (135) of patients were transported by advanced life support providers and 30% (62) received IV fluid. Lower out-of-hospital Glasgow coma scale (GCS) was independently associated with elevated serum lactate (p<0.01). Out-of-hospital hypotension, greater respiratory rate, and lower GCS were associated with greater SOFA (p<0.01). Conclusions Out-of-hospital fluid resuscitation occurred in less than one-third of patients with severe sepsis, and routinely measured out-of-hospital variables were associated with greater serum lactate and SOFA in the ED. PMID:20381301

Hyperglycemia and glycemic variability are associated with the severity of sepsis in nondiabetic subjects.

PubMed

Preechasuk, Lukana; Suwansaksri, Nattakarn; Ipichart, Nantawan; Vannasaeng, Sathit; Permpikul, Chairat; Sriwijitkamol, Apiradee

2017-04-01

The purpose was to compare glucose variability (GV) obtained via continuous glucose monitoring between nondiabetic sepsis patients and healthy subjects and to seek associations between GV and sepsis severity in nondiabetic sepsis patients. Nondiabetic sepsis inpatients and healthy controls received a 72-hour continuous glucose monitoring (iPro2, Medtronic) postadmission and post-oral glucose tolerance test, respectively. The mean glucose level (MGL) along with GV represented by standard deviation (SD) and the mean amplitude of glycemic excursion (MAGE) were calculated at 24 and 72 hours. Sepsis severity was evaluated with the Sepsis-related Organ Failure Assessment Score (SOFA). MGL and GV in patients with SOFA ≥9 and <9 were compared. Thirty nondiabetic sepsis and 10 healthy subjects were recruited. No differences were found between groups except for higher patient age in sepsis patients. The MGL and MAGE 72h of sepsis patients were significantly higher than those of healthy subjects. MGL and GV 24h were higher in patients with SOFA ≥9 than in patients with SOFA <9 (MGL 24h 195±17 vs 139±27, P<.001; SD 24h 32 [28, 36] vs 19 [5, 58], P=.02; and MAGE 24h 94 [58, 153] vs 54 [16, 179], P=.01). Nondiabetic sepsis patients had higher MGL and GV values than healthy subjects. MGL and GV 24h were associated with sepsis severity. Copyright © 2016 Elsevier Inc. All rights reserved.

Importance of vital signs to the early diagnosis and severity of sepsis: association between vital signs and sequential organ failure assessment score in patients with sepsis.

PubMed

Kenzaka, Tsuneaki; Okayama, Masanobu; Kuroki, Shigehiro; Fukui, Miho; Yahata, Shinsuke; Hayashi, Hiroki; Kitao, Akihito; Sugiyama, Daisuke; Kajii, Eiji; Hashimoto, Masayoshi

2012-01-01

While much attention is given to the fifth vital sign, the utility of the 4 classic vital signs (blood pressure, respiratory rate, body temperature, and heart rate) has been neglected. The aim of this study was to assess a possible association between vital signs and the Sequential Organ Failure Assessment (SOFA) score in patients with sepsis. We performed a prospective, observational study of 206 patients with sepsis. Blood pressure, respiratory rate, body temperature, and heart rate were measured on arrival at the hospital. The SOFA score was also determined on the day of admission. Bivariate correlation analysis showed that all of the vital signs were correlated with the SOFA score. Multiple regression analysis indicated that decreased values of systolic blood pressure (multivariate regression coefficient [Coef] = -0.030, 95% confidence interval [CI] = -0.046 to -0.013) and diastolic blood pressure (Coef = -0.045, 95% CI = -0.070 to -0.019), increased respiratory rate (Coef = 0.176, 95% CI = 0.112 to 0.240), and increased shock index (Coef = 4.232, 95% CI = 2.401 to 6.062) significantly influenced the SOFA score. Increased respiratory rate and shock index were significantly correlated with disease severity in patients with sepsis. Evaluation of these signs may therefore improve early identification of severely ill patients at triage, allowing more aggressive and timely interventions to improve the prognosis of these patients.

Retrospective evaluation of prognostic score performances in cirrhotic patients admitted to an intermediate care unit.

PubMed

Dupont, Benoît; Delvincourt, Maxime; Koné, Mamadou; du Cheyron, Damien; Ollivier-Hourmand, Isabelle; Piquet, Marie-Astrid; Terzi, Nicolas; Dao, Thông

2015-08-01

The prognosis of cirrhotic patients in the Intensive Care Unit requires the development of predictive tools for mortality. We aimed to evaluate the ability of different prognostic scores to predict hospital mortality in these patients. A single-centre retrospective analysis was conducted of 281 hospital stays of cirrhotic patients at an Intermediate Care Unit between June 2009 and December 2010. The performance of the Simplified Acute Physiology Score (SOFA), the Simplified Acute Physiology Score (SAPS) II or III, Child-Pugh, Model for End-Stage Liver Disease (MELD), MELD-Na and the Chronic Liver Failure-Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF) in predicting hospital mortality were compared. Mean age was 58.2±12.1 years; 77% were male. The main cause of admission was acute gastrointestinal bleeding (47%). The in-hospital mortality rate was 25.3%. Receiver operating characteristic curve analyses demonstrated that SOFA (0.82) MELD-Na (0.82) or MELD (0.81) scores at admission predicted in-hospital mortality better than Child-Pugh (0.76), SAPS II (0.77), SAPS III (0.75) or CLIF-C ACLF (0.75). We then developed the cirrhosis prognostic score (Ci-Pro), which performed better (0.89) than SOFA. SOFA, MELD and especially the Ci-Pro score show the best performance in predicting hospital mortality of cirrhotic patients admitted to an Intermediate Care Unit. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Review article: scoring systems for assessing prognosis in critically ill adult cirrhotics.

PubMed

Cholongitas, E; Senzolo, M; Patch, D; Shaw, S; Hui, C; Burroughs, A K

2006-08-01

Cirrhotic patients admitted to intensive care units (ICU) still have poor outcomes. Some current ICU prognostic models [Acute Physiology and Chronic Health Evaluation (APACHE), Organ System Failure (OSF) and Sequential Organ Failure Assessment (SOFA)] were used to stratify cirrhotics into risk categories, but few cirrhotics were included in the original model development. Liver-specific scores [Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD)] could be useful in this setting. To evaluate whether ICU prognostic models perform better compared with liver-disease specific ones in cirrhotics admitted to ICU. We performed a structured literature review identifying clinical studies focusing on prognosis and risk factors for mortality in adult cirrhotics admitted to ICU. We found 21 studies (five solely dealing with gastrointestinal bleeding) published during the last 20 years (54-420 patients in each). APACHE II and III, SOFA and OSF had better discrimination for correctly predicting death compared with the CTP score. The MELD score was evaluated only in one study and had good predictive accuracy [receiver operator characteristic (ROC) curve: 0.81). Organ dysfunction models (OSF, SOFA) were superior compared with APACHE II and III (ROC curve: range 0.83-0.94 vs. 0.66-0.88 respectively). Cardiovascular, liver and renal system dysfunction were more frequently independently associated with mortality. General-ICU models had better performance in cirrhotic populations compared with CTP score; OSF and SOFA had the best predictive ability. Further prospective and validation studies are needed.

Metric Calibration of a Focused Plenoptic Camera Based on a 3d Calibration Target

NASA Astrophysics Data System (ADS)

Zeller, N.; Noury, C. A.; Quint, F.; Teulière, C.; Stilla, U.; Dhome, M.

2016-06-01

In this paper we present a new calibration approach for focused plenoptic cameras. We derive a new mathematical projection model of a focused plenoptic camera which considers lateral as well as depth distortion. Therefore, we derive a new depth distortion model directly from the theory of depth estimation in a focused plenoptic camera. In total the model consists of five intrinsic parameters, the parameters for radial and tangential distortion in the image plane and two new depth distortion parameters. In the proposed calibration we perform a complete bundle adjustment based on a 3D calibration target. The residual of our optimization approach is three dimensional, where the depth residual is defined by a scaled version of the inverse virtual depth difference and thus conforms well to the measured data. Our method is evaluated based on different camera setups and shows good accuracy. For a better characterization of our approach we evaluate the accuracy of virtual image points projected back to 3D space.

Predictors of outcome in myxoedema coma: a study from a tertiary care centre.

PubMed

Dutta, Pinaki; Bhansali, Anil; Masoodi, Shriq Rashid; Bhadada, Sanjay; Sharma, Navneet; Rajput, Rajesh

2008-01-01

With the easy availability of thyroid hormone assays, thyroid disorders are now recognised even in a subclinical state. However, patients are still seen with advanced manifestations of the disease, particularly in developing countries. This observational study analysed the predictors of outcome in patients with myxoedema coma and tested the validity of different modules to define morbidity and mortality in these patients. Twenty-three consecutive patients with myxoedema coma who presented from January 1999 to August 2006 were studied. The thyroid function test and random serum cortisol were measured in all patients at the time of admission. Patients were given oral or intravenous (i.v.) thyroxine with intention to treat with the latter according to availability. Various modules that predict outcome, including Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score, were analysed. SOFA score was repeated every 2 days until the time of discharge or demise. Twenty-three patients (20 women; 87%) of 59.5 +/- 14.4 years of age (range, 30 to 89 years) were seen during the study period. Nine (39%) patients were diagnosed with hypothyroidism for the first time at the time of presentation of myxoedema coma, whereas 14 (70%) were diagnosed with hypothyroidism previously. However, the treatment defaulters presented early to the hospital and had more severe manifestations than de novo subjects. Nineteen (82%) had thyroprivic (primary) and 4 (17%) had trophoprivic (secondary) hypothyroidism. Fifteen (65%) patients presented in the winter and in 17 (74%) sepsis was the major accompanying comorbidity. Twelve (52%) had a history of diuretic use, thereby delaying the initial diagnosis. Patients who received oral L-thyroxine had no difference in outcome from those receiving i.v. thyroxine. Twelve (52%) subjects died and sepsis was the predominant cause of death. Various predictors of mortality included hypotension (p = 0.01) and bradycardia (p = 0.03) at presentation, need for mechanical ventilation (p = 0.00), hypothermia unresponsive to treatment (p = 0.01), sepsis (p = 0.01), intake of sedative drugs (p = 0.02), lower GCS (p = 0.03), high APACHE II score (p = 0.04), and high SOFA score (p = 0.00). However, SOFA score was more effective than other predictive models as baseline and day 3 SOFA scores of more than 6 were highly predictive of poor outcome. L-Thyroxine treatment defaulters had more severe manifestations compared with de novo subjects. Outcome was not influenced by either aetiology or route of administration of L-thyroxine, and SOFA score was the best outcome predictor model.

[Prediction of mortality in patients with acute hepatic failure].

PubMed

Eremeeva, L F; Berdnikov, A P; Musaeva, T S; Zabolotskikh, I B

2013-01-01

The article deals with a study of 243 patients (from 18 to 65 years old) with acute hepatic failure. Purpose of the study was to evaluate the predictive capability of severity scales APACHE III, SOFA, MODS, Child-Pugh and to identify mortality predictors in patients with acute hepatic failure. Results; The best predictive ability in patients with acute hepatic failure and multiple organ failure had APACHE III and SOFA scales. The strongest mortality predictors were: serum creatinine > 132 mmol/L, fibrinogen < 1.4 g/L, Na < 129 mmol/L.

pH-Dependent DNA Distortion and Repression of Gene Expression by Pectobacterium atrosepticum PecS.

PubMed

Deochand, Dinesh K; Meariman, Jacob K; Grove, Anne

2016-07-15

Transcriptional activity is exquisitely sensitive to changes in promoter DNA topology. Transcription factors may therefore control gene activity by modulating the relative positioning of -10 and -35 promoter elements. The plant pathogen Pectobacterium atrosepticum, which causes soft rot in potatoes, must alter gene expression patterns to ensure growth in planta. In the related soft-rot enterobacterium Dickeya dadantii, PecS functions as a master regulator of virulence gene expression. Here, we report that P. atrosepticum PecS controls gene activity by altering promoter DNA topology in response to pH. While PecS binds the pecS promoter with high affinity regardless of pH, it induces significant DNA distortion only at neutral pH, the pH at which the pecS promoter is repressed in vivo. At pH ∼8, DNA distortions are attenuated, and PecS no longer represses the pecS promoter. A specific histidine (H142) located in a crevice between the dimerization- and DNA-binding regions is required for pH-dependent changes in DNA distortion and repression of gene activity, and mutation of this histidine renders the mutant protein incapable of repressing the pecS promoter. We propose that protonated PecS induces a DNA conformation at neutral pH in which -10 and -35 promoter elements are suboptimally positioned for RNA polymerase binding; on deprotonation of PecS, binding is no longer associated with significant changes in DNA conformation, allowing gene expression. We suggest that this mode of gene regulation leads to differential expression of the PecS regulon in response to alkalinization of the plant apoplast.

Evidence for conformational capture mechanism for damage recognition by NER protein XPC/Rad4.

NASA Astrophysics Data System (ADS)

Chakraborty, Sagnik; Steinbach, Peter J.; Paul, Debamita; Min, Jung-Hyun; Ansari, Anjum

Altered flexibility of damaged DNA sites is considered to play an important role in damage recognition by DNA repair proteins. Characterizing lesion-induced DNA dynamics has remained a challenge. We have combined ps-resolved fluorescence lifetime measurements with cytosine analog FRET pair uniquely sensitive to local unwinding/twisting to analyze DNA conformational distributions. This innovative approach maps out with unprecedented sensitivity the alternative conformations accessible to a series of DNA constructs containing 3-base-pair mismatch, suitable model lesions for the DNA repair protein xeroderma pigmentosum C (XPC) complex. XPC initiates eukaryotic nucleotide excision repair by recognizing various DNA lesions primarily through DNA deformability. Structural studies show that Rad4 (yeast ortholog of XPC) unwinds DNA at the lesion site and flips out two nucleotide pairs. Our results elucidate a broad range of conformations accessible to mismatched DNA even in the absence of the protein. Notably, the most severely distorted conformations share remarkable resemblance to the deformed conformation seen in the crystal structure of the Rad4-bound ``recognition'' complex supporting for the first time a possible ``conformational capture'' mechanism for damage recognition by XPC/Rad4. NSF Univ of Illinois-Chicago.

Development and evaluation of an influenza pandemic intensive care unit triage protocol.

PubMed

Cheung, Winston; Myburgh, John; Seppelt, Ian M; Parr, Michael J; Blackwell, Nikki; Demonte, Shannon; Gandhi, Kalpesh; Hoyling, Larissa; Nair, Priya; Passer, Melissa; Reynolds, Claire; Saunders, Nicholas M; Saxena, Manoj K; Thanakrishnan, Govindasamy

2012-09-01

To develop an influenza pandemic ICU triage (iPIT) protocol that excludes patients with the highest and lowest predicted mortality rates, and to determine the increase in ICU bed availability that would result. Post-hoc analysis of a study evaluating two triage protocols, designed to determine which patients should be excluded from access to ICU resources during an influenza pandemic. ICU mortality rates were determined for the individual triage criteria in the protocols and included criteria based on the Sequential Organ Failure Assessment (SOFA) score. Criteria resulting in mortality rates outside the 25th and 75th percentiles were used as exclusion criteria in a new iPIT-1 protocol. The SOFA threshold component was modified further and reported as iPIT-2 and iPIT-3. Increase in ICU bed availability. The 25th and 75th percentiles for ICU mortality were 8.3% and 35.2%, respectively. Applying the iPIT-1 protocol resulted in an increase in ICU bed availability at admission of 71.7% ± 0.6%. Decreasing the lower SOFA score exclusion criteria to ≤6 (iPIT-2) and ≤4 (iPIT-3) resulted in an increase in ICU bed availability at admission of 66.9% ± 0.6% and 59.4 ± 0.7%, respectively (P < 0.001). The iPIT protocol excludes patients with the lowest and highest ICU mortality, and provides increases in ICU bed availability. Adjusting the lower SOFA score exclusion limit provides a method of escalation or de- escalation to cope with demand.

Risk factors, sequential organ failure assessment and model for end-stage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit.

PubMed

Cholongitas, E; Senzolo, M; Patch, D; Kwong, K; Nikolopoulou, V; Leandro, G; Shaw, S; Burroughs, A K

2006-04-01

Prognostic scores in an intensive care unit (ICU) evaluate outcomes, but derive from cohorts containing few cirrhotic patients. To evaluate 6-week mortality in cirrhotic patients admitted to an ICU, and to compare general and liver-specific prognostic scores. A total of 312 consecutive cirrhotic patients (65% alcoholic; mean age 49.6 years). Multivariable logistic regression to evaluate admission factors associated with survival. Child-Pugh, Model for End-stage Liver Disease (MELD), Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were compared by receiver operating characteristic curves. Major indication for admission was respiratory failure (35.6%). Median (range) Child-Pugh, APACHE II, MELD and SOFA scores were 11 (5-15), 18 (0-44), 24 (6-40) and 11 (0-21), respectively; 65% (n = 203) died. Survival improved over time (P = 0.005). Multivariate model factors: more organs failing (FOS) (<3 = 49.5%, > or =3 = 90%), higher FiO(2), lactate, urea and bilirubin; resulting in good discrimination [area under receiver operating characteristic curve (AUC) = 0.83], similar to SOFA and MELD (AUC = 0.83 and 0.81, respectively) and superior to APACHE II and Child-Pugh (AUC = 0.78 and 0.72, respectively). Cirrhotics admitted to ICU with > or =3 failing organ systems have 90% mortality. The Royal Free model discriminated well and contained key variables of organ function. SOFA and MELD were better predictors than APACHE II or Child-Pugh scores.

Examination of the Positive and Negative Syndrome Scale factor structure and longitudinal relationships with functioning in early psychosis.

PubMed

Best, Michael W; Grossman, Michael; Oyewumi, L Kola; Bowie, Christopher R

2016-04-01

We examined the factor structure of the Positive and Negative Syndrome Scale (PANSS) in early-episode psychosis and its relationships with functioning at baseline and follow-up. A total of 240 consecutive admissions to an early intervention in psychosis clinic were assessed at intake to the program with the PANSS, Global Assessment of Functioning (GAF) and Social and Occupational Functioning Assessment Scale (SOFAS). Seventy individuals were reassessed at follow-up. A maximum likelihood factor analysis was conducted on baseline PANSS scores and the ability of each factor to predict baseline and follow-up GAF and SOFAS was examined. A five-factor model with varimax rotation was the best fit to our data and was largely congruent with factors found previously. The negative symptom factor was the best predictor of GAF and SOFAS at baseline and follow-up. Negative symptoms are the best symptomatic predictor of functioning in individuals with early psychosis and are an important treatment target to improve recovery. © 2014 Wiley Publishing Asia Pty Ltd.

The non-contact heart rate measurement system for monitoring HRV.

PubMed

Huang, Ji-Jer; Yu, Sheng-I; Syu, Hao-Yi; See, Aaron Raymond

2013-01-01

A noncontact ECG monitoring and analysis system was developed using capacitive-coupled device integrated to a home sofa. Electrodes were placed on the backrest of a sofa separated from the body with only the chair covering and the user's clothing. The study also incorporates measurements using different fabric materials, and a pure cotton material was chosen to cover the chair's backrest. The material was chosen to improve the signal to noise ratio. The system is initially implemented on a home sofa and is able to measure non-contact ECG through thin cotton clothing and perform heart rate analysis to calculate the heart rate variability (HRV) parameters. It was also tested under different conditions and results from reading and sleeping exhibited a stable ECG. Subsequently, results from our calculated HRV were found to be identical to those of a commercially available HRV analyzer. However, HRV parameters are easily affected by motion artifacts generated during drinking or eating with the latter producing a more severe disturbance. Lastly, parameters measured are saved on a cloud database, providing users with a long-term monitoring and recording for physiological information.

Opposing influences by subsite -1 and subsite +1 residues on relative xylopyranosidase/arabinofuranosidase activities of bifunctional beta-D-xylosidase/alpha-L-arabinofuranosidase

USDA-ARS?s Scientific Manuscript database

Conformational inversion occurs 7-8 kcal/mol more readily in furanoses than pyranoses. This difference is exploited here to disclose active-site residues involved in distorting substrate towards reactivity. Spontaneous glycoside hydrolysis rates are ordered 4-nitrophenyl-alpha-L-arabinofuranoside (4...

How amide hydrogens exchange in native proteins.

PubMed

Persson, Filip; Halle, Bertil

2015-08-18

Amide hydrogen exchange (HX) is widely used in protein biophysics even though our ignorance about the HX mechanism makes data interpretation imprecise. Notably, the open exchange-competent conformational state has not been identified. Based on analysis of an ultralong molecular dynamics trajectory of the protein BPTI, we propose that the open (O) states for amides that exchange by subglobal fluctuations are locally distorted conformations with two water molecules directly coordinated to the N-H group. The HX protection factors computed from the relative O-state populations agree well with experiment. The O states of different amides show little or no temporal correlation, even if adjacent residues unfold cooperatively. The mean residence time of the O state is ∼100 ps for all examined amides, so the large variation in measured HX rate must be attributed to the opening frequency. A few amides gain solvent access via tunnels or pores penetrated by water chains including native internal water molecules, but most amides access solvent by more local structural distortions. In either case, we argue that an overcoordinated N-H group is necessary for efficient proton transfer by Grotthuss-type structural diffusion.

How amide hydrogens exchange in native proteins

PubMed Central

Persson, Filip; Halle, Bertil

2015-01-01

Amide hydrogen exchange (HX) is widely used in protein biophysics even though our ignorance about the HX mechanism makes data interpretation imprecise. Notably, the open exchange-competent conformational state has not been identified. Based on analysis of an ultralong molecular dynamics trajectory of the protein BPTI, we propose that the open (O) states for amides that exchange by subglobal fluctuations are locally distorted conformations with two water molecules directly coordinated to the N–H group. The HX protection factors computed from the relative O-state populations agree well with experiment. The O states of different amides show little or no temporal correlation, even if adjacent residues unfold cooperatively. The mean residence time of the O state is ∼100 ps for all examined amides, so the large variation in measured HX rate must be attributed to the opening frequency. A few amides gain solvent access via tunnels or pores penetrated by water chains including native internal water molecules, but most amides access solvent by more local structural distortions. In either case, we argue that an overcoordinated N–H group is necessary for efficient proton transfer by Grotthuss-type structural diffusion. PMID:26195754

The role of enzyme distortion in the single displacement mechanism of family 19 chitinases

PubMed Central

Brameld, Ken A.; Goddard, William A.

1998-01-01

By using molecular dynamics simulations, we have examined the binding of a hexaNAG substrate and two potential hydrolysis intermediates (an oxazoline ion and an oxocarbenium ion) to a family 19 barley chitinase. We find the hexaNAG substrate binds with all sugars in a chair conformation, unlike the family 18 chitinase which causes substrate distortion. Glu 67 is in a position to protonate the anomeric oxygen linking sugar residues D and E whereas Asn 199 serves to hydrogen bond with the C2′ N-acetyl group of sugar D, thus preventing the formation of an oxazoline ion intermediate. In addition, Glu 89 is part of a flexible loop region allowing a conformational change to occur within the active site to bring the oxocarbenium ion intermediate and Glu 89 closer by 4–5 Å. A hydrolysis product with inversion of the anomeric configuration occurs because of nucleophilic attack by a water molecule that is coordinated by Glu 89 and Ser 120. Issues important for the design of inhibitors specific to family 19 chitinases over family 18 chitinases also are discussed. PMID:9539727

Discriminating the structure of exo-2-aminonorbornane using nuclear quadrupole coupling interactions.

PubMed

Écija, Patricia; Cocinero, Emilio J; Lesarri, Alberto; Millán, Judith; Basterretxea, Francisco; Fernández, José A; Castaño, Fernando

2011-04-28

The intrinsic conformational and structural properties of the bicycle exo-2-aminonorbornane have been probed in a supersonic jet expansion using Fourier-transform microwave (FT-MW) spectroscopy and quantum chemical calculations. The rotational spectrum revealed two different conformers arising from the internal rotation of the amino group, exhibiting small (MHz) hyperfine patterns originated by the (14)N nuclear quadrupole coupling interaction. Complementary ab initio (MP2) and DFT (B3LYP and M05-2X) calculations provided comparative predictions for the structural properties, rotational and centrifugal distortion data, hyperfine parameters, and isomerization barriers. Due to the similarity of the rotational constants, the structural assignment of the observed rotamers and the calculation of the torsion angles of the amino group were based on the conformational dependence of the (14)N nuclear quadrupole coupling hyperfine tensor. In the most stable conformation (ss), the two amino N-H bonds are staggered with respect to the adjacent C-H bond. In the second conformer (st), only one of the N-H bonds is staggered and the other is trans. A third predicted conformer (ts) was not detected, consistent with a predicted conformational relaxation to conformer ss through a low barrier of 5.2 kJ mol(-1).

Crystal structure of an Okazaki fragment at 2-A resolution

NASA Technical Reports Server (NTRS)

Egli, M.; Usman, N.; Zhang, S. G.; Rich, A.

1992-01-01

In DNA replication, Okazaki fragments are formed as double-stranded intermediates during synthesis of the lagging strand. They are composed of the growing DNA strand primed by RNA and the template strand. The DNA oligonucleotide d(GGGTATACGC) and the chimeric RNA-DNA oligonucleotide r(GCG)d(TATACCC) were combined to form a synthetic Okazaki fragment and its three-dimensional structure was determined by x-ray crystallography. The fragment adopts an overall A-type conformation with 11 residues per turn. Although the base-pair geometry, particularly in the central TATA part, is distorted, there is no evidence for a transition from the A- to the B-type conformation at the junction between RNA.DNA hybrid and DNA duplex. The RNA trimer may, therefore, lock the complete fragment in an A-type conformation.

Predictors of outcome in myxoedema coma: a study from a tertiary care centre

PubMed Central

Dutta, Pinaki; Bhansali, Anil; Masoodi, Shriq Rashid; Bhadada, Sanjay; Sharma, Navneet; Rajput, Rajesh

2008-01-01

Background With the easy availability of thyroid hormone assays, thyroid disorders are now recognised even in a subclinical state. However, patients are still seen with advanced manifestations of the disease, particularly in developing countries. This observational study analysed the predictors of outcome in patients with myxoedema coma and tested the validity of different modules to define morbidity and mortality in these patients. Methods Twenty-three consecutive patients with myxoedema coma who presented from January 1999 to August 2006 were studied. The thyroid function test and random serum cortisol were measured in all patients at the time of admission. Patients were given oral or intravenous (IV) thyroxine with intention to treat with the latter according to availability. Various modules that predict outcome, including Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score, were analysed. SOFA score was repeated every 2 days until the time of discharge or demise. Results Twenty-three patients (20 women; 87%) of 59.5 ± 14.4 years of age (range, 30 to 89 years) were seen during the study period. Nine (39%) patients were diagnosed with hypothyroidism for the first time at the time of presentation of myxoedema coma, whereas 14 (70%) were diagnosed with hypothyroidism previously. However, the treatment defaulters presented early to the hospital and had more severe manifestations than de novo subjects. Nineteen (82%) had thyroprivic (primary) and 4 (17%) had trophoprivic (secondary) hypothyroidism. Fifteen (65%) patients presented in the winter and in 17 (74%) sepsis was the major accompanying comorbidity. Twelve (52%) had a history of diuretic use, thereby delaying the initial diagnosis. Patients who received oral L-thyroxine had no difference in outcome from those receiving IV thyroxine. Twelve (52%) subjects died and sepsis was the predominant cause of death. Various predictors of mortality included hypotension (p = 0.01) and bradycardia (p = 0.03) at presentation, need for mechanical ventilation (p = 0.00), hypothermia unresponsive to treatment (p = 0.01), sepsis (p = 0.01), intake of sedative drugs (p = 0.02), lower GCS (p = 0.03), high APACHE II score (p = 0.04), and high SOFA score (p = 0.00). However, SOFA score was more effective than other predictive models as baseline and day 3 SOFA scores of more than 6 were highly predictive of poor outcome. Conclusion L-Thyroxine treatment defaulters had more severe manifestations compared with de novo subjects. Outcome was not influenced by either aetiology or route of administration of L-thyroxine, and SOFA score was the best outcome predictor model. PMID:18173846

Disturbance of DNA conformation by the binding of testosterone-based platinum drugs via groove-face and intercalative interactions: a molecular dynamics simulation study

PubMed Central

2013-01-01

Background To explore novel platinum-based anticancer agents that are distinct from the structure and interaction mode of the traditional cisplatin by forming the bifunctional intrastrand 1,2 GpG adduct, the monofunctional platinum + DNA adducts with extensive non-covalent interactions had been studied. It was reported that the monofunctional testosterone-based platinum(II) agents present the high anticancer activity. Moreover, it was also found that the testosterone-based platinum agents could cause the DNA helix to undergo significant unwinding and bending over the non-testosterone-based platinum agents. However, the interaction mechanisms of these platinum agents with DNA at the atomic level are not yet clear so far. Results In the present work, we used molecular dynamics (MD) simulations and DNA conformational dynamics calculations to study the DNA distortion properties of the testosterone-based platinum + DNA, the improved testosterone-based platinum + DNA and the non-testosterone-based platinum + DNA adducts. The results show that the intercalative interaction of the improved flexible testosterone-based platinum agent with DNA molecule could cause larger DNA conformational distortion than the groove-face interaction of the rigid testosterone-based platinum agent with DNA molecule. Further investigations for the non-testosterone-based platinum agent reveal the occurrence of insignificant change of DNA conformation due to the absence of testosterone ligand in such agent. Based on the DNA dynamics analysis, the DNA base motions relating to DNA groove parameter changes and hydrogen bond destruction of DNA base pairs were also discussed in this work. Conclusions The flexible linker in the improved testosterone-based platinum agent causes an intercalative interaction with DNA in the improved testosterone-based platinum + DNA adduct, which is different from the groove-face interaction caused by a rigid linker in the testosterone-based platinum agent. The present investigations provide useful information of DNA conformation affected by a testosterone-based platinum complex at the atomic level. PMID:23517640

Pediatric CLIF-SOFA score is the best predictor of 28-day mortality in children with decompensated chronic liver disease.

PubMed

Bolia, Rishi; Srivastava, Anshu; Yachha, Surender Kumar; Poddar, Ujjal

2018-03-01

Early identification of children with decompensated chronic liver disease (DCLD) at risk of short-term mortality helps improve outcome. We aimed to evaluate the predictors of outcome and role of Child-Pugh, pediatric end-stage liver disease (PELD) and pediatric chronic liver failure sequential organ failure assessment (pCLIF-SOFA) score for prognosticating 28-day mortality in children with DCLD. DCLD children were prospectively evaluated with a clinico-laboratory proforma and followed for 28 days to determine outcome. Child-Pugh, PELD and pCLIF-SOFA were calculated at admission. Univariate and multivariate analysis was performed to identify the best predictors of outcome. A total of 110 children (74 boys, 96 [4-204] months) were enrolled and 37 (33.6%) died at 28 days. Significant risk factors for mortality were a higher international normalized ratio (hazard ratio [HR] 1.17; 95% CI 1.04-1.31; p <0.001) and bilirubin (HR 1.04; 95% CI 1.01-1.08; p <0.001), lower albumin (HR 0.46; 95% CI 0.27-0.77; p = 0.03) and sodium (HR 0.93; 95% CI 0.89-0.98; p = 0.01), absence of treatable etiology (HR 2.00; 95% CI 1.40-2.87; p = 0.001) and presence of organ failure (HR 3.22; 95% CI 1.98-10.58; p <0.001). Organ failure and serum sodium were independent predictors of poor outcome on multivariate analysis. pCLIF-SOFA (16 [9-22] vs. 9 [5-15]), Child-Pugh (11 [9-15] vs. 10 [8-14]) and PELD (22.2 [7.5-45.3] vs. 15.3 [4.5-23.9]) scores were significantly higher in non-survivors. The area under the curve was 0.977 for pCLIF-SOFA, 0.815 for Child-Pugh score, and 0.741 for PELD score. A pCLIF-SOFA score of ≥11 identified 28-day mortality with a sensitivity and specificity of 94.9% and 91.5%, respectively. Thirty-four percent of children with DCLD have a poor short-term outcome. Organ failure and low serum sodium are independent predictors of outcome. pCLIF-SOFA performs better than Child-Pugh and PELD in prognostication of 28-day mortality. Our study supports the use of scores based on organ failure in prognosticating children with DCLD. The ability to predict the course of a disease is an important part of the assessment, enabling timely interventions that improve outcomes. We evaluated the outcome (death vs. survival) and compared three different scoring systems for their ability to predict mortality within 28 days in children with decompensated chronic liver disease (DCLD). One-third of children with DCLD died within 28 days and the pediatric chronic liver failure sequential organ failure assessment score, which considers the main organ systems of the body (lungs, liver, brain, kidney, blood and cardiac) fared better for identification of children with a poor outcome than the Child-Pugh and pediatric end-stage liver disease score which comprise of only liver-related parameters. Our study supports the use of scores based on organ failure in prognosticating children with DCLD. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Building a Sustainable Global Surgery Nonprofit Organization at an Academic Institution.

PubMed

Frisella, Margaret M

Surgical Outreach for the Americas is a 501(c)3 nonprofit organization providing surgical care to those in need in developing countries of the Western Hemisphere. Every year since its inception in 2008, teams of surgeons, nurses, and allied health professionals have traveled to areas of need and performed primarily hernia repair surgeries for those without access to affordable health care. Surgical Outreach for the Americas (SOfA) began as a general concept based on World Health Organization statistics claiming that 11% of the global burden of disease can be resolved via surgery. Armed with this information, a group of compassionate and selfless health care professionals planned the first trip, to the Dominican Republic, in January 2009. Building on what was first just an ambition to help others, we now also train surgeons, surgery residents, and nurses in the countries we serve. To date, SOfA has successfully treated 734 patients, with 899 total surgical procedures performed (693 of these under general anesthesia). These procedures include inguinal hernia, umbilical hernia, testicular masses, orchiectomies, and various general surgical procedures. Through the efforts of a great many talented individuals and robust fundraising efforts, the SOfA message continues to gain momentum. SOfA not only considers the health and well-being of the disadvantaged through capacity-building efforts but strives to educate and improve the skills of health care professionals in the countries we visit. Our goal is to increase the number of missions each year and begin a 2-fold educational program that (a) provides surgical resident education through participation in mission work and (b) provides local surgeon education in the areas served. Copyright © 2016. Published by Elsevier Inc.

Survival predictor in patients with acute respiratory distress syndrome and diffuse alveolar damage undergoing open lung biopsy

PubMed Central

Chang, Chih-Hao; Hung, Chen-Yiu; Chiu, Li-Chung; Huang, Chung-Chi; Hu, Han-Chung

2017-01-01

Background Diffuse alveolar damage (DAD) is a typical pathological finding of open lung biopsies in patients with acute respiratory distress syndrome (ARDS). Patients with ARDS and DAD have been reported to have a poorer prognosis than those without DAD. The aim of this study was to investigate the survival predictors in patients with ARDS and DAD. Methods We retrospectively reviewed all ARDS patients who underwent an open lung biopsy which showed evidence of DAD from January 2006 to June 2015 at Chang Gung Memorial Hospital. Clinical data including baseline characteristics, medication, and survival outcomes were analyzed. Results A total of 64 ARDS patients with DAD were eligible for analysis and divided into known etiology (n = 17, 26.6%) and unknown etiology groups (n = 47, 73.4%). There was no significant difference in hospital mortality rate between the two groups (71.9% vs. 70.6%, p = 0.890). Univariate logistic regression analysis revealed that sequential organ failure assessment (SOFA) score at the time of a diagnosis of ARDS, and SOFA score, PaO2/FiO2 ratio, and positive end expiratory pressure level when the biopsy was performed were associated with hospital mortality. Multivariate analysis showed that the SOFA score on the day of the biopsy was an independent predictor of hospital mortality (odds ratio 1.413, 95% confidence interval 1.127–1.772; p = 0.03). There were no significant differences in the use, dose, duration and timing from ARDS to glucocorticoid therapy between the survivors and nonsurvivors. Conclusion For selected ARDS patients who underwent an open lung biopsy with pathological DAD, SOFA score was an independent predictor of hospital mortality. PMID:28678876

Outcome and prognostic factors of malaria-associated acute kidney injury requiring hemodialysis: A single center experience

PubMed Central

Kute, V. B.; Shah, P. R.; Munjappa, B. C.; Gumber, M. R.; Patel, H. V.; Jain, S. H.; Engineer, D. P.; Naresh, V. V. Sai; Vanikar, A. V.; Trivedi, H. L.

2012-01-01

Acute kidney injury (AKI) is one of the most dreaded complications of severe malaria. We carried out prospective study in 2010, to describe clinical characteristics, laboratory parameters, prognostic factors, and outcome in 59 (44 males, 15 females) smear-positive malaria patients with AKI. The severity of illness was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA) score, Multiple Organ Dysfunction Score (MODS), and Glasgow Coma Scale (GCS) scores. All patients received artesunate and hemodialysis (HD). Mean age of patients was 33.63 ± 14 years. Plasmodium falciparum malaria was seen in 76.3% (n = 45), Plasmodium vivax in 16.9% (n = 10), and mixed infection in 6.8% (n = 4) patients. Presenting clinical features were fever (100%), nausea-vomiting (85%), oliguria (61%), abdominal pain/tenderness (50.8%), and jaundice (74.5%). Mean APACHE II, SOFA, MODS, and GCS scores were 18.1 ± 3, 10.16 ± 3.09, 9.71 ± 2.69, and 14.15 ± 1.67, respectively, all were higher among patients who died than among those who survived. APACHE II ≥20, SOFA and MODS scores ≥12 were associated with higher mortality (P < 0.05). 34% patients received blood component transfusion and exchange transfusion was done in 15%. Mean number of HD sessions required was 4.59 ± 3.03. Renal biopsies were performed in five patients (three with patchy cortical necrosis and two with acute tubular necrosis). 81.3% of patients had complete renal recovery and 11.8% succumbed to malaria. Prompt diagnosis, timely HD, and supportive therapy were associated with improved survival and recovery of kidney functions in malarial with AKI. Mortality was associated with higher APACHE II, SOFA, MODS, GCS scores, requirement of inotrope, and ventilator support. PMID:22279340

Lactate clearance in septic shock is not a surrogate for improved microcirculatory flow

PubMed Central

Puskarich, Michael A.; Shapiro, Nathan I.; Massey, Michael J.; Kline, Jeffrey A.; Jones, Alan E.

2016-01-01

Introduction Failure to normalize lactate is associated with poor outcomes in septic shock. It has been suggested that persistently elevated lactate may result from regional ischemia due to disturbed and/or heterogenous microcirculatory blood flow. Objectives The goal of this study was to determine if lactate clearance may serve as a surrogate marker for changes in microcirculatory blood flow in patients with septic shock. Methods This was a prospective observational study performed within a previously published clinical trial of L-carnitine for the treatment of vasopressor-dependent septic shock. Intravital video microscopy was performed at enrollment and 12 hours later, and microcirculatory flow index (MFI) was assessed. Associations between enrollment MFI, lactate, and SOFA score were determined, in addition to associations between ΔMFI, lactate clearance, and ΔSOFA. A preplanned subgroup analysis of only patients with an elevated initial lactate was performed. Results We enrolled a total of 31 patients, 23 with survival to and sufficient quality videos both at enrollment and 12 hours. ΔMFI, lactate clearance, and ΔSOFA were 0.1 (IQR 0, 0.3), 18% (IQR −10%, 46%), and −2 (IQR −4, 0). Both ΔMFI and lactate clearance were associated with ΔSOFA (β = −5.3, p = 0.01 and β = −3.5, 0.047), but not with each other, even in the subgroup of patients with an initially elevated lactate. Conclusion We observed no association between degree of lactate clearance and change in microcirculatory blood flow in patients with septic shock. These data suggest against the hypothesis that lactate clearance may be used as a surrogate marker of microcirculatory blood flow. PMID:26825368

Single-centre validation of the EASL-CLIF consortium definition of acute-on-chronic liver failure and CLIF-SOFA for prediction of mortality in cirrhosis.

PubMed

Silva, Pedro E Soares E; Fayad, Leonardo; Lazzarotto, César; Ronsoni, Marcelo F; Bazzo, Maria L; Colombo, Bruno S; Dantas-Correa, Esther B; Narciso-Schiavon, Janaína L; Schiavon, Leonardo L

2015-05-01

The idea of acute-on-chronic liver failure (ACLF) has emerged to identify those subjects with organ failure and high mortality rates. However, the absence of a precise definition has limited the clinical application and research related to the ACLF concept. We sought to validate the ACLF definition and the CLIF-SOFA Score recently proposed by the EASL-CLIF Consortium in a cohort of patients admitted for acute decompensation (AD) of cirrhosis. In this prospective cohort study, patients were followed during their hospital stay and thirty and 90-day mortality was evaluated by phone call, in case of hospital discharge. All subjects underwent laboratory evaluation at admission. Between December 2010 and November 2013, 192 cirrhotic patients were included. At enrollment, 46 patients (24%) met the criteria for ACLF (Grades 1, 2 and 3 in 18%, 4% and 2% respectively). The 30-day mortality was 65% in ACLF group and 12% in the remaining subjects (P < 0.001). Logistic regression analysis showed that 30-day mortality was independently associated with ascites and ACLF at admission. The Kaplan-Meier survival probability at 90-day was 92% in patients without ascites or ACLF and only 22% for patients with both ascites and ACLF. The AUROC of CLIF-SOFA in predicting 30-day mortality was 0.847 ± 0.034, with sensitivity of 64%, specificity of 90% and positive likelihood ratio of 6.61 for values ≥9. In our single-centre experience the CLIF-SOFA and the EASL-CLIF Consortium definition of ACLF proved to be strong predictors of short-term mortality in cirrhotic patients admitted for AD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of a prognostic nomogram for cirrhotic patients with upper gastrointestinal bleeding.

PubMed

Zhou, Yu-Jie; Zheng, Ji-Na; Zhou, Yi-Fan; Han, Yi-Jing; Zou, Tian-Tian; Liu, Wen-Yue; Braddock, Martin; Shi, Ke-Qing; Wang, Xiao-Dong; Zheng, Ming-Hua

2017-10-01

Upper gastrointestinal bleeding (UGIB) is a complication with a high mortality rate in critically ill patients presenting with cirrhosis. Today, there exist few accurate scoring models specifically designed for mortality risk assessment in critically ill cirrhotic patients with upper gastrointestinal bleeding (CICGIB). Our aim was to develop and evaluate a novel nomogram-based model specific for CICGIB. Overall, 540 consecutive CICGIB patients were enrolled. On the basis of Cox regression analyses, the nomogram was constructed to estimate the probability of 30-day, 90-day, 270-day, and 1-year survival. An upper gastrointestinal bleeding-chronic liver failure-sequential organ failure assessment (UGIB-CLIF-SOFA) score was derived from the nomogram. Performance assessment and internal validation of the model were performed using Harrell's concordance index (C-index), calibration plot, and bootstrap sample procedures. UGIB-CLIF-SOFA was also compared with other prognostic models, such as CLIF-SOFA and model for end-stage liver disease, using C-indices. Eight independent factors derived from Cox analysis (including bilirubin, creatinine, international normalized ratio, sodium, albumin, mean artery pressure, vasopressin used, and hematocrit decrease>10%) were assembled into the nomogram and the UGIB-CLIF-SOFA score. The calibration plots showed optimal agreement between nomogram prediction and actual observation. The C-index of the nomogram using bootstrap (0.729; 95% confidence interval: 0.689-0.766) was higher than that of the other models for predicting survival of CICGIB. We have developed and internally validated a novel nomogram and an easy-to-use scoring system that accurately predicts the mortality probability of CICGIB on the basis of eight easy-to-obtain parameters. External validation is now warranted in future clinical studies.

Speaking out on safe sleep: evidence-based infant sleep recommendations.

PubMed

Bartick, Melissa; Smith, Linda J

2014-11-01

The American Academy of Pediatrics (AAP) issued recommendations in 2005 and 2011 to reduce sleep-related infant death, which advise against all bedsharing for sleep. These recommendations overemphasize the risks of bedsharing, and this overemphasis has serious unintended consequences. It may result in increased deaths on sofas as tired parents try to avoid feeding their infants in bed. Current evidence shows that other risks are far more potent, such as smoking, shared sleep on sofas, sleeping next to impaired caregivers, and formula feeding. The emphasis on separate sleep is diverting resources away from addressing these critical risk factors. Recommendations to avoid bedsharing may also interfere with breastfeeding. We examine both the evidence behind the AAP recommendations and the evidence omitted from those recommendations. We conclude that the only evidence-based universal advice to date is that sofas are hazardous places for adults to sleep with infants; that exposure to smoke, both prenatal and postnatal, increases the risk of death; and that sleeping next to an impaired caregiver increases the risk of death. No sleep environment is completely safe. Public health efforts must address the reality that tired parents must feed their infants at night somewhere and that sofas are highly risky places for parents to fall asleep with their infants, especially if parents are smokers or under the influence of alcohol or drugs. All messaging must be crafted and reevaluated to avoid unintended negative consequences, including impact on breastfeeding rates, or falling asleep in more dangerous situations than parental beds. We must realign our resources to focus on the greater risk factors, and that may include greater investment in smoking cessation and doing away with aggressive formula marketing. This includes eliminating conflicts of interest between formula marketing companies and organizations dedicated to the health of children.

Perceptions of Chemistry: Why Is the Common Perception of Chemistry, the Most Visual of Sciences, So Distorted?

ERIC Educational Resources Information Center

Habraken, Clarisse L.

1996-01-01

Highlights the need to reinvigorate chemistry education by means of the visual-spatial approach, an approach wholly in conformance with the way modern chemistry is thought about and practiced. Discusses the changing world, multiple intelligences, imagery, chemistry's pictorial language, and perceptions in chemistry. Presents suggestions on how to…

Ethyl 3-[1-(4-methoxy-phen-yl)-4-oxo-3-phenylazetidin-2-yl]-2-nitro-1-phenyl-2,3,10,10a-tetra-hydro-1H,5H-pyrrolo[1,2-b]isoquinoline-10a-carboxyl-ate.

PubMed

Sundaresan, S S; Ramesh, P; Arumugam, N; Raghunathan, R; Ponnuswamy, M N

2010-02-17

In the title mol-ecule, C(37)H(35)N(3)O(6), the pyrrolidine ring adopts a twist conformation and the piperidine ring is in a distorted boat conformation. One of the phenyl rings is disordered over two positions with occupancies of 0.54 (2) and 0.46 (2) and the ethyl carboxyl-ate group is also disordered over two orientations with occupancies of 0.75 (1) and 0.25 (1).

Does the achievement of an intermediate glycemic target reduce organ failure and mortality? A post hoc analysis of the Glucontrol trial.

PubMed

Penning, Sophie; Chase, J Geoffrey; Preiser, Jean-Charles; Pretty, Christopher G; Signal, Matthew; Mélot, Christian; Desaive, Thomas

2014-06-01

This research evaluates the impact of the achievement of an intermediate target glycemic band on the severity of organ failure and mortality. Daily Sequential Organ Failure Assessment (SOFA) score and the cumulative time in a 4.0 to 7.0 mmol/L band (cTIB) were evaluated daily up to 14 days in 704 participants of the multicentre Glucontrol trial (16 centers) that randomized patients to intensive group A (blood glucose [BG] target: 4.4-6.1 mmol/L) or conventional group B (BG target: 7.8-10.0 mmol/L). Sequential Organ Failure Assessment evolution was measured by percentage of patients with SOFA less than or equal to 5 on each day, percentage of individual organ failures, and percentage of organ failure-free days. Conditional and joint probability analysis of SOFA and cTIB 0.5 or more assessed the impact of achieving 4.0 to 7.0 mmol/L target glycemic range on organ failure. Odds ratios (OR) compare the odds risk of death for cTIB 0.5 or more vs cTIB less than 0.5, where a ratio greater than 1.0 indicates an improvement for achieving cTIB 0.5 or more independent of SOFA or glycemic target. Groups A and B were matched for demographic and severity of illness data. Blood glucose differed between groups A and B (P<.05), as expected. There was no difference in the percentage of patients with SOFA less than or equal to 5, individual organ failures, and organ failure-free days between groups A and B over days 1 to 14. However, 20% to 30% of group A patients failed to achieve cTIB 0.5 or more for all days, and significant crossover confounds interpretation. Mortality OR was greater than 1.0 for patients with cTIB 0.5 or more in both groups but much higher for group A on all days. There was no difference in organ failure in the Glucontrol study based on intention to treat to different glycemic targets. Actual outcomes and significant crossover indicate that this result may not be due to the difference in target or treatment. Odds ratios-associated achieving an intermediate 4.0 to 7.0 mmol/L range improved outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

Sepsis patients in the emergency department: stratification using the Clinical Impression Score, Predisposition, Infection, Response and Organ dysfunction score or quick Sequential Organ Failure Assessment score?

PubMed

Quinten, Vincent M; van Meurs, Matijs; Wolffensperger, Anna E; Ter Maaten, Jan C; Ligtenberg, Jack J M

2017-05-08

The aim of this study was to compare the stratification of sepsis patients in the emergency department (ED) for ICU admission and mortality using the Predisposition, Infection, Response and Organ dysfunction (PIRO) and quick Sequential Organ Failure Assessment (qSOFA) scores with clinical judgement assessed by the ED staff. This was a prospective observational study in the ED of a tertiary care teaching hospital. Adult nontrauma patients with suspected infection and at least two Systemic Inflammatory Response Syndrome criteria were included. The primary outcome was direct ED to ICU admission. The secondary outcomes were in-hospital, 28-day and 6-month mortality, indirect ICU admission and length of stay. Clinical judgement was recorded using the Clinical Impression Scores (CIS), appraised by a nurse and the attending physician. The PIRO and qSOFA scores were calculated from medical records. We included 193 patients: 103 presented with sepsis, 81 with severe sepsis and nine with septic shock. Fifteen patients required direct ICU admission. The CIS scores of nurse [area under the curve (AUC)=0.896] and the attending physician (AUC=0.861), in conjunction with PIRO (AUC=0.876) and qSOFA scores (AUC=0.849), predicted direct ICU admission. The CIS scores did not predict any of the mortality endpoints. The PIRO predicted in-hospital (AUC=0.764), 28-day (AUC=0.784) and 6-month mortality (AUC=0.695). The qSOFA score also predicted in-hospital (AUC=0.823), 28-day (AUC=0.848) and 6-month mortality (AUC=0.620). Clinical judgement is a fast and reliable method to stratify between ICU and general ward admission in ED patients with sepsis. The PIRO and qSOFA scores do not add value to this stratification, but perform better on the prediction of mortality. In sepsis patients, therefore, the principle of 'treat first what kills first' can be supplemented with 'judge first and calculate later'.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

The conformational free-energy landscape of β-D-mannopyranose: evidence for a (1)S(5) → B(2,5) → (O)S(2) catalytic itinerary in β-mannosidases.

PubMed

Ardèvol, Albert; Biarnés, Xevi; Planas, Antoni; Rovira, Carme

2010-11-17

The mechanism of glycosidic bond cleavage by glycosidases involves substrate ring distortions in the Michaelis complex that favor catalysis. Retaining β-mannosidases bind the substrate in a (1)S(5) conformation, and recent experiments have proposed an unusual substrate conformational pathway ((1)S(5) → B(2,5) → (O)S(2)) for the hydrolysis reaction. By means of Car-Parrinello metadynamics simulations, we have obtained the conformational free-energy surface (FES) of a β-d-mannopyranose molecule associated with the ideal Stoddart conformational diagram. We have found that (1)S(5) is among the most stable conformers and simultaneously is the most preactivated conformation in terms of elongation/shortening of the C1-O1/C1-O5 bonds, C1-O1 orientation, and charge development at the anomeric carbon. Analysis of the computed FES gives support to the proposed (1)S(5) → B(2,5) → (O)S(2) catalytic itinerary, showing that the degree of preactivation of the substrate in glycoside hydrolases (GHs) is related to the properties of an isolated sugar ring. We introduce a simple preactivation index integrating several structural, electronic, and energetic properties that can be used to predict the conformation of the substrate in the Michaelis complex of any GH.

Gender and Sex Role as Factors in Person Perception.

ERIC Educational Resources Information Center

Leggett, Delia C.

Role theory predicts that when expectations are disconfirmed, the perception of persons who do not conform to the stereotypes may be distorted. To investigate the evaluation of sex-typed behavior in males and females, male and female college students (N=120) read about one of four persons described as either a man or woman in either a masculine or…

Computer-assisted map projection research

USGS Publications Warehouse

Snyder, John Parr

1985-01-01

Computers have opened up areas of map projection research which were previously too complicated to utilize, for example, using a least-squares fit to a very large number of points. One application has been in the efficient transfer of data between maps on different projections. While the transfer of moderate amounts of data is satisfactorily accomplished using the analytical map projection formulas, polynomials are more efficient for massive transfers. Suitable coefficients for the polynomials may be determined more easily for general cases using least squares instead of Taylor series. A second area of research is in the determination of a map projection fitting an unlabeled map, so that accurate data transfer can take place. The computer can test one projection after another, and include iteration where required. A third area is in the use of least squares to fit a map projection with optimum parameters to the region being mapped, so that distortion is minimized. This can be accomplished for standard conformal, equalarea, or other types of projections. Even less distortion can result if complex transformations of conformal projections are utilized. This bulletin describes several recent applications of these principles, as well as historical usage and background.

Crystal structure of the mutant D52S hen egg white lysozyme with an oligosaccharide product.

PubMed

Hadfield, A T; Harvey, D J; Archer, D B; MacKenzie, D A; Jeenes, D J; Radford, S E; Lowe, G; Dobson, C M; Johnson, L N

1994-11-11

The crystal structure of a mutant hen egg white lysozyme, in which the key catalytic residue aspartic acid 52 has been changed to a serine residue (D52S HEWL), has been determined and refined to a crystallographic R value of 0.173 for all data F > 0 between 8 and 1.9 A resolution. The D52S HEWL structure is very similar to the native HEWL structure (r.m.s. deviation of main-chain atoms 0.20 A). Small shifts that result from the change in hydrogen bonding pattern on substitution of Asp by Ser were observed in the loop between beta-strands in the region of residues 46 to 49. D52S HEWL exhibits less than 1% activity against the bacterial cell wall substrate. Cocrystallisation experiments with the hexasaccharide substrate beta(1-4) polymer of N-acetyl-D-glucosamine (GlcNAc6) resulted in crystals between 5 days and 14 days after the initial mixing of enzyme and substrate. Analysis by laser absorption mass spectrometry of the oligosaccharides present after incubation with native and D52S HEWL under conditions similar to those used for crystal growth showed that after 14 days with native HEWL complete catalysis to GlcNAc3. GlcNAc2 and GlcNac had occurred but with D52S HEWL only partial catalysis to the major products GlcNAc4 and GlcNAc2 had occurred and at least 50% of the GlcNAc6 remained intact. X-ray analysis of the D52S-oligosaccharide complex crystals showed that they contained the product GlcNAc4. The structure of the D52S HEWL-GlcNAc4 complex has been determined and refined to an R value of 0.160 for data between 8 and 2 A resolution. GlcNAc4 occupies sites A to D in the active site cleft. Careful refinement and examination of 2Fo-Fc electron density maps showed that the sugar in site D has the sofa conformation, a conformation previously observed with the HEWL complex with tetra-N-acetylglucosamine lactone transition state analogue, the HEWL complex with the cell wall trisaccharide and the phage T4 lysozyme complex with a cell wall product. The semi-axial C(5)-C(6) geometry of the sofa is stabilised by hydrogen bonds from the O-6 hydroxyl group to the main-chain N of Val109 and main-chain O of Ala107. The sugar in site D adopts the alpha configuration, seemingly in conflict with the observation that the hydrolysis of beta (1-4) glycosidie linkage by HEWL proceeds with 99.9% retention of beta-configuration.(ABSTRACT TRUNCATED AT 400 WORDS)

Understanding textbook quality in the USA: How governments distort the market

NASA Astrophysics Data System (ADS)

Oliveira, João Batista

1995-11-01

Textbooks deliver education and shape the daily routines of classrooms. Even in countries where schools enjoy ample and various instructional resources, text-books are the single most important support for teachers and students. It is not surprising, then, that textbooks are a major concern of states, schools, teachers, parents, publishers, and the research community. But textbooks often become a scapegoat for educational evils. In the USA, government regulation, special interest groups, and publishers exert pressure on textbook policies and state and local adoption processes. The result: textbooks are published to conform to a market distorted by government regulation. This paper discusses how their quality is constrained by government and special interest groups that interfere with the natural course of regulations and markets.

Cell Adhesion Molecule L1 in Folded (Horseshoe) and Extended Conformations

PubMed Central

Schürmann, Gregor; Haspel, Jeffrey; Grumet, Martin; Erickson, Harold P.

2001-01-01

We have investigated the structure of the cell adhesion molecule L1 by electron microscopy. We were particularly interested in the conformation of the four N-terminal immunoglobulin domains, because x-ray diffraction showed that these domains are bent into a horseshoe shape in the related molecules hemolin and axonin-1. Surprisingly, rotary-shadowed specimens showed the molecules to be elongated, with no indication of the horseshoe shape. However, sedimentation data suggested that these domains of L1 were folded into a compact shape in solution; therefore, this prompted us to look at the molecules by an alternative technique, negative stain. The negative stain images showed a compact shape consistent with the expected horseshoe conformation. We speculate that in rotary shadowing the contact with the mica caused a distortion of the protein, weakening the bonds forming the horseshoe and permitting the molecule to extend. We have thus confirmed that the L1 molecule is primarily in the horseshoe conformation in solution, and we have visualized for the first time its opening into an extended conformation. Our study resolves conflicting interpretations from previous electron microscopy studies of L1. PMID:11408583

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, G.D.; Bharadwaj, R.K.

The molecular geometries and conformational energies of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) and 1,3-dimethyl-1,3-dinitro methyldiamine (DDMD) and have been determined from high-level quantum chemistry calculations and have been used in parametrizing a classical potential function for simulations of HMX. Geometry optimizations for HMX and DDMD and rotational energy barrier searches for DDMD were performed at the B3LYP/6-311G** level, with subsequent single-point energy calculations at the MP2/6-311G** level. Four unique low-energy conformers were found for HMX, two whose conformational geometries correspond closely to those found in HMX polymorphs from crystallographic studies and two additional, lower energy conformers that are not seen in the crystallinemore » phases. For DDMD, three unique low-energy conformers, and the rotational energy barriers between them, were located. In parametrizing the classical potential function for HMX, nonbonded repulsion/dispersion parameters, valence parameters, and parameters describing nitro group rotation and out-of-plane distortion at the amine nitrogen were taken from the previous studies of dimethylnitramine. Polar effects in HMX and DDMD were represented by sets of partial atomic charges that reproduce the electrostatic potential and dipole moments for the low-energy conformers of these molecules as determined from the quantum chemistry wave functions. Parameters describing conformational energetics for the C-N-C-N dihedrals were determined by fitting the classical potential function to reproduce relative conformational energies in HMX as found from quantum chemistry. The resulting potential was found to give a good representation of the conformer geometries and relative conformer energies in HMX and a reasonable description of the low-energy conformers and rotational energy barriers in DDMD.« less

[Prevalence of severe sepsis in intensive care units. A national multicentric study].

PubMed

Dougnac, Alberto L; Mercado, Marcelo F; Cornejo, Rodrigo R; Cariaga, Mario V; Hernández, Glenn P; Andresen, Max H; Bugedo, Guillermo T; Castillo, Luis F

2007-05-01

Severe sepsis (SS) is the leading cause of death in the Intensive Care Units (ICU). To study the prevalence of SS in Chilean ICUs. An observational, cross-sectional study using a predesigned written survey was done in all ICUs of Chile on April 21st, 2004. General hospital and ICU data and the number of hospitalized patients in the hospital and in the ICU at the survey day, were recorded. Patients were followed for 28 days. Ninety four percent of ICUs participated in the survey. The ICU occupation index was 66%. Mean age of patients was 57.7+/-18 years and 59% were male, APACHE II score was 15+/-7.5 and SOFA score was 6+/-4. SS was the admission diagnosis of 94 of the 283 patients (33%) and 38 patients presented SS after admission. On the survey day, 112 patients fulfilled SS criteria (40%). APACHE II and SOFA scores were significantly higher in SS patients than in non SS patients. Global case-fatality ratio at 28 days was 15.9% (45/283). Case-fatality ratio in patients with or without SS at the moment of the survey was 26.7% (30/112) and 8.7% (17/171), respectively p <0.05. Thirteen percent of patients who developed SS after admission, died. Case-fatality ratios for patients with SS from Santiago and the other cities were similar, but APACHE II score was significantly higher in patients from Santiago. In SS patients, the independent predictors of mortality were SS as cause of hospital admission, APACHE II and SOFA scores. Ninety nine percent of SS patients had a known sepsis focus (48% respiratory and 30% abdominal). Eighty five patients that presented SS after admission, had a respiratory focus. SS is highly prevalent in Chilean ICUs and represents the leading diagnosis at admission. SS as cause of hospitalization, APACHE II and SOFA scores were independent predictors of mortality.

Predictive relevance of clinical scores and inflammatory parameters in secondary peritonitis.

PubMed

Zügel, Nikolaus P; Kox, Martin; Lichtwark-Aschoff, Michael; Gippner-Steppert, Cornelia; Jochum, Marianne

2011-01-01

To measure and evaluate clinical scores and various inflammation parameters for providing a better outcome assessment of patients with secondary peritonitis. Prospective study. ICU of a university and a university affiliated hospital. Fifty-six patients with severe secondary peritonitis were enrolled in this study executed within 4 years. Blood samples were taken preoperatively and 2, 6, 8, 12, 18, 24, 30, 36, 42 and 48 hours post operation, thereafter every 12th hour until day 5 respectively once daily until day 14. Etiology of peritonitis, clinical score systems (APACHE II, MOF and SOFA), and 27 mainly with activity tests or enzyme-immunoassays measurable inflammation parameters were simultaneously analyzed and stratified into lethal outcome (n = 11) or survival (n = 45), respectively. The etiological distribution of peritonitis was identical among both groups. Proportion of intraperitoneal fungi, E. coli, and bacteroids was substantially higher during the primary operation in the group with lethal outcome. With increasing significance initial and follow-up APACHE II, MOF and SOFA scores provided higher values in this group. Various plasma/serum parameters of hemostasis, leukocyte proteolytic system, acute phase reaction, cytokine system, cell adhesion, opsonization, and main organ functions showed significantly different values between both groups at the preoperative stage and/or during observation period I (day 0-4). Logistic regression analysis revealed the SOFA score and neopterin concentration as the combination with the best sensitivity (63.6%) and specificity (93.2%) for predicting the patients' survival even at the preoperative stage. For the observation period I, the combination of SOFA score and TNF receptor II showed the highest predictive sensitivity (72.7%) and specificity (95.6%). Evaluation of the severity of secondary peritonitis using a scoring system with high prognostic relevance could conceivably result in an earlier and adequate application of intensive care such as hemofiltration, administration of immunoglobulins and serial abdominal lavage to improve successful outcome.

Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis

PubMed Central

2012-01-01

Background Community-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome. Method We evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards. Severity assessment scores (CURB-65, PSI, APACHE II, SOFA) and serologic markers (HMGB-1, RAGE, sRAGE) were evaluated on admission. Results Thirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission. Fourteen (46.6%) had pandemic (H1N1) influenza A virus, 2 (6.6%) had seasonal influenza A and 14 other diagnoses. Of the patients in the study group, 16 (53.3%) had a fatal outcome. ARDS was observed in 17 (56.6%) and a total of 22 patients had severe sepsis on admission (73%). The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003) with similar results in ARDS patients (P = .005). sRAGE levels tended to be higher in non-surviving (P = .058) and ARDS patients (P = .058). Logistic regression modeling demonstrated that SOFA (P = .013) and sRAGE (P = .05) were the only variables that modified the probability of a fatal outcome. Conclusion The association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP. SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients. PMID:22264245

Validation of prognostic scores to predict short-term mortality in patients with acute-on-chronic liver failure.

PubMed

Song, Do Seon; Kim, Tae Yeob; Kim, Dong Joon; Kim, Hee Yeon; Sinn, Dong Hyun; Yoon, Eileen L; Kim, Chang Wook; Jung, Young Kul; Suk, Ki Tae; Lee, Sang Soo; Lee, Chang Hyeong; Kim, Tae Hun; Choe, Won Hyeok; Yim, Hyung Joon; Kim, Sung Eun; Baik, Soon Koo; Jang, Jae Young; Kim, Hyoung Su; Kim, Sang Gyune; Yang, Jin Mo; Sohn, Joo Hyun; Choi, Eun Hee; Cho, Hyun Chin; Jeong, Soung Won; Kim, Moon Young

2018-04-01

The aim of this study was to validate the chronic liver failure-sequential organ failure assessment score (CLIF-SOFAs), CLIF consortium organ failure score (CLIF-C OFs), CLIF-C acute-on-chronic liver failure score (CLIF-C ACLFs), and CLIF-C acute decompensation score in Korean chronic liver disease patients with acute deterioration. Acute-on-chronic liver failure was defined by either the Asian Pacific Association for the study of the Liver ACLF Research Consortium (AARC) or CLIF-C criteria. The diagnostic performances for short-term mortality were compared by the area under the receiver operating characteristic curve. Among a total of 1470 patients, 252 patients were diagnosed with ACLF according to the CLIF-C (197 patients) or AARC definition (95 patients). As the ACLF grades increased, the survival rates became significantly lower. The areas under the receiver operating characteristic of the CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs were significantly higher than those of the Child-Pugh, model for end-stage liver disease, and model for end-stage liver disease-Na scores in ACLF patients according to the CLIF-C definition (all P < 0.05), but there were no significant differences in patients without ACLF or in patients with ACLF according to the AARC definition. The CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs had higher specificities with a fixed sensitivity than liver specific scores in ACLF patients according to the CLIF-C definition, but not in ACLF patients according to the AARC definition. The CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs are useful scoring systems that provide accurate information on prognosis in patients with ACLF according to the CLIF-C definition, but not the AARC definition. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Are prognostic scores and biomarkers such as procalcitonin the appropriate prognostic precursors for elderly patients with sepsis in the emergency department?

PubMed

Lee, Woon Jeong; Woo, Seon Hee; Kim, Dae Hee; Seol, Seung Hwan; Park, Si Kyung; Choi, Seung Pill; Jekarl, Dong Wook; Lee, Seung Ok

2016-10-01

The mortality of patients with severe sepsis and septic shock is still high, and the prognosis of elderly patients tends to be particularly poor. Therefore, this study sought to conduct a comparative analysis of the abbreviated mortality in emergency department sepsis (abbMEDS) score, sequential organ failure assessment (SOFA) score, infection probability score (IPS), initial procalcitonin (PCT), and cytokine levels to investigate the effectiveness of each index in predicting the prognosis of elderly patients with sepsis in the emergency department (ED). This was a single-center prospective study, and classified 55 patients (≥65 years of age) with systemic inflammatory response syndrome (SIRS) from January 2013 to December 2013 in the ED. A total of 36 elderly patients were diagnosed with sepsis. The prediction of prognosis using the prognostic scores (abbMEDS, SOFA, IPS) was analyzed. An early blood examination (WBC count, C-reactive protein, PCT, and cytokines) was conducted within the first 2 h of the patient's arrival at the ED. The median (IQR) age of subjects was 76.5 (70.5-81.5). After 28 days, 27 subjects (75 %) had survived, and 9 (25 %) had died. Fifteen (41.7 %) were sent to intensive care units (ICUs). The SOFA score and abbMEDS showed higher median (IQR) values of 9.5 (7.0-11.0) and 13.5 (12.0-15.0), respectively, in the ICU group than in the general ward group (p < 0.001). Analysis of the levels of PCT, IL-10, IL-6, and IL-5 had a significantly better ability to predict ICU admission (p = 0.001, p = 0.023, p = 0.030, p = 0.001). The prediction of mortality in the first 28 days via SOFA and the abbMEDS resulted in scores of 11.0 (8.0-11.0) and 14.0 (12.5-15.5) (p = 0.004, p = 0.003), respectively. However, levels of IPS, PCT, and cytokines did not show significant differences. In predicting ICU admission and the death of elderly sepsis patients in ED, SOFA and abbMEDS scores were effective. Of the various biomarkers, PCT, IL-10, IL-6, and IL-5 were effective in predicting ICU admission, but were not effective in predicting the death of elderly sepsis patients.

Conformational Space and Stability of ETD Charge Reduction Products of Ubiquitin

NASA Astrophysics Data System (ADS)

Lermyte, Frederik; Łącki, Mateusz Krzysztof; Valkenborg, Dirk; Gambin, Anna; Sobott, Frank

2017-01-01

Owing to its versatility, electron transfer dissociation (ETD) has become one of the most commonly utilized fragmentation techniques in both native and non-native top-down mass spectrometry. However, several competing reactions—primarily different forms of charge reduction—occur under ETD conditions, as evidenced by the distorted isotope patterns usually observed. In this work, we analyze these isotope patterns to compare the stability of nondissociative electron transfer (ETnoD) products, specifically noncovalent c/ z fragment complexes, across a range of ubiquitin conformational states. Using ion mobility, we find that more extended states are more prone to fragment release. We obtain evidence that for a given charge state, populations of ubiquitin ions formed either directly by electrospray ionization or through collapse of more extended states upon charge reduction, span a similar range of collision cross-sections. Products of gas-phase collapse are, however, less stabilized towards unfolding than the native conformation, indicating that the ions retain a memory of previous conformational states. Furthermore, this collapse of charge-reduced ions is promoted if the ions are `preheated' using collisional activation, with possible implications for the kinetics of gas-phase compaction.

Structural distortions due to missense mutations in human formylglycine-generating enzyme leading to multiple sulfatase deficiency.

PubMed

Meshach Paul, D; Chadah, Tania; Senthilkumar, B; Sethumadhavan, Rao; Rajasekaran, R

2017-11-03

The major candidate for multiple sulfatase deficiency is a defective formylglycine-generating enzyme (FGE). Though adequately produced, mutations in FGE stall the activation of sulfatases and prevent their activity. Missense mutations, viz. E130D, S155P, A177P, W179S, C218Y, R224W, N259I, P266L, A279V, C336R, R345C, A348P, R349Q and R349W associated with multiple sulfatase deficiency are yet to be computationally studied. Aforementioned mutants were initially screened through ws-SNPs&GO 3D program. Mutant R345C acquired the highest score, and hence was studied in detail. Discrete molecular dynamics explored structural distortions due to amino acid substitution. Therein, comparative analyses of wild type and mutant were carried out. Changes in structural contours were observed between wild type and mutant. Mutant had low conformational fluctuation, high atomic mobility and more compactness than wild type. Moreover, free energy landscape showed mutant to vary in terms of its conformational space as compared to wild type. Subsequently, wild type and mutant were subjected to single-model analyses. Mutant had lesser intra molecular interactions than wild type suggesting variations pertaining to its secondary structure. Furthermore, simulated thermal denaturation showed dissimilar pattern of hydrogen bond dilution. Effects of these variations were observed as changes in elements of secondary structure. Docking studies of mutant revealed less favourable binding energy towards its substrate as compared to wild type. Therefore, theoretical explanations for structural distortions of mutant R345C leading to multiple sulfatase deficiency were revealed. The protocol of the study could be useful to examine the effectiveness of pharmacological chaperones prior to experimental studies.

Hemispherical map for the human brain cortex

NASA Astrophysics Data System (ADS)

Tosun, Duygu; Prince, Jerry L.

2001-07-01

Understanding the function of the human brain cortex is a primary goal in human brain mapping. Methods to unfold and flatten the cortical surface for visualization and measurement have been described in previous literature; but comparison across multiple subjects is still difficult because of the lack of a standard mapping technique. We describe a new approach that maps each hemisphere of the cortex to a portion of a sphere in a standard way, making comparison of anatomy and function across different subjects possible. Starting with a three-dimensional magnetic resonance image of the brain, the cortex is segmented and represented as a triangle mesh. Defining a cut around the corpus collosum identifies the left and right hemispheres. Together, the two hemispheres are mapped to the complex plane using a conformal mapping technique. A Mobius transformation, which is conformal, is used to transform the points on the complex plane so that a projective transformation maps each brain hemisphere onto a spherical segment comprising a sphere with a cap removed. We determined the best size of the spherical cap by minimizing the relative area distortion between hemispherical maps and original cortical surfaces. The relative area distortion between the hemispherical maps and the original cortical surfaces for fifteen human brains is analyzed.

1′-Methyl-4′-(1-naphth­yl)-3′′-(1-naphthyl­methyl­ene)acenaphthene-1-spiro-2′-pyrrolidine-3′-spiro-1′′-cyclo­hexane-2,2′′-dione

PubMed Central

Athimoolam, S.; Radha, V. Anu; Bahadur, S. Asath; Kumar, R. Ranjith; Perumal, S.

2008-01-01

In the title compound, C42H33NO2, the six-membered cyclo­hexa­none ring adopts a slightly distorted chair conformation and the five-membered pyrrolidine ring is in an envelope conformation. The mol­ecular structure features four intra­molecular C—H⋯O inter­actions and an intra­molecular C—H⋯π inter­action. Furthermore, the crystal packing is stabilized by an inter­molecular C—H⋯O and three inter­molecular C—H⋯π inter­actions. PMID:21200972

The Molecular Structure of Phenetole Studied by Microwave Spectroscopy and Quantum Chemical Calculations

NASA Astrophysics Data System (ADS)

Ferres, Lynn; Stahl, Wolfgang; Nguyen, Ha Vinh Lam

2016-06-01

A pulsed molecular beam Fourier transform microwave spectrometer operating in the frequency range 2 - 26.5 GHz was used to measure the spectrum of phenetole (ethyl phenyl ether or ethoxybenzene, C6H5OC2H5). The conformational landscape is completely determined by the orientations of the phenyl ring and the ethyl group. A two-dimensional potential energy surface was calculated at the MP2/6-311++G(d,p) level of theory. Two conformers were found: The trans conformer has a Cs symmetry, and the gauche conformer has the ethyl group tilted out of the phenyl plane by about 70°. Totally 186 rotational transitions were assigned to the more stable planar trans conformer, and fitted using a semi-rigid rotor model to measurement accuracy of 2 kHz. Highly accurate rotational and centrifugal distortion constants were determined. Several method and basis set combinations were applied to check for convergence and to compare with the experimentally deduced molecular parameters. The inertial defect of the observed conformer Δc = (Ic - Ia - Ib) = -6.718 uÅ2 confirms that the heavy atom skeleton is planar with two pairs of hydrogen atoms out of plane. All lines in the spectrum could be assigned to the trans conformer, which confirms that the gauche conformer cannot be observed under our measurement conditions. In agreement with the rather high torsional barrier of the methyl group (V3 = 1168 wn) calculated by quantum chemical methods, all assigned lines appeared sharp and no signs of splittings were observed for the methyl internal rotation.

In search of a new class of stable nitroxide: synthesis and reactivity of a peri-substituted N,N-bissulfonylhydroxylamine.

PubMed

Patel, Bhaven; Carlisle, Julie; Bottle, Steven E; Hanson, Graeme R; Kariuki, Benson M; Male, Louise; McMurtrie, John C; Spencer, Neil; Grainger, Richard S

2011-04-07

Acyclic bissulfonylnitroxides have never been isolated, and degrade through fragmentation. In an approach to stabilising a bissulfonylnitroxide radical, the cyclic, peri-substituted N,N-bissulfonylhydroxylamine, 2-hydroxynaphtho[1,8-de][1,3,2]dithiazine 1,1,3,3-tetraoxide (1), has been prepared by formal nitrogen insertion into the sulfur-sulfur bond of a sulfinylsulfone, naphtho[1,8-cd][1,2]dithiole 1,1,2-trioxide. The heterocyclic ring of 1 is shown to adopt a sofa conformation by X-ray crystallography, with a pseudo-axial hydroxyl group. N,N-Bissulfonylhydroxylamine 1 displays high thermal, photochemical and hydrolytic stability compared to acyclic systems. EPR analysis reveals formation of the corresponding bissulfonylnitroxide 2 upon oxidation of 1 with the Ce(IV) salts CAN and CTAN. Although 2 does not undergo fragmentation, it cannot be isolated, since hydrogen atom abstraction to reform 1 occurs in situ. The stability and reactivity of 1 and 2 are compared with the known cyclic benzo-fused N,N-bissulfonylhydroxylamine, N-hydroxy-O-benzenedisulfonimide (6), for which the X-ray data, and EPR of the corresponding nitroxide 10, are also reported for the first time.

[Volatile organic compounds (VOCs) emitted from furniture and electrical appliances].

PubMed

Tanaka-Kagawa, Toshiko; Jinno, Hideto; Furukawa, Yoko; Nishimura, Tetsuji

2010-01-01

Organic chemicals are widely used as ingredients in household products. Therefore, furniture and other household products as well as building products may influence the indoor air quality. This study was performed to estimate quantitatively influence of household products on indoor air quality. Volatile organic compound (VOC) emissions were investigated for 10 products including furniture (chest, desk, dining table, sofa, cupboard) and electrical appliances (refrigerator, electric heater, desktop personal computer, liquid crystal display television and audio) by the large chamber test method (JIS A 1912) under the standard conditions of 28 degrees C, 50% relative humidity and 0.5 times/h ventilation. Emission rate of total VOC (TVOC) from the sofa showed the highest; over 7900 microg toluene-equivalent/unit/h. Relatively high TVOC emissions were observed also from desk and chest. Based on the emission rates, the impacts on the indoor TVOC were estimated by the simple model with a volume of 17.4 m3 and ventilation frequency of 0.5 times/h. The estimated TVOC increment for the sofa was 911 microg/m3, accounting for almost 230% of the provisional target value, 400 microg/m3. The values of estimated increment of toluene emitted from cupboard and styrene emitted from refrigerator were 10% and 16% of guideline values, respectively. These results revealed that VOC emissions from household products may influence significantly indoor air quality.

Rumen microbial response in production of CLA and methane to safflower oil in association with fish oil or/and fumarate.

PubMed

Li, Xiang Z; Long, Rui J; Yan, Chang G; Lee, Hong G; Kim, Young J; Song, Man K

2011-06-01

Supplementation effect of fish oil and/or fumarate on production of conjugated linoleic acid (CLA) and methane by rumen microbes was examined when incubated with safflower oil. One hundred and twenty milligrams of safflower oil (SO), safflower oil with 24 mg fish oil (SOFO), safflower oil with 24 mmol/L fumarate (SOFA), or safflower oil with 24 mg fish oil and 24 mmol/L fumarate (SOFOFA) were added to the 90 mL culture solution. The culture solution was also made without any supplements (control). The SOFA and SOFOFA increased pH and propionate (C3) compared to other treatments from 3 h incubation time. An accumulated amount of total methane (CH(4) ) for 12 h incubation was decreased by all the supplements compared to control. The concentrations of c9,t11CLA for all the incubation times were increased in the treatments of SOFO, SOFA and SOFOFA compared to SO. The highest concentration of c9,t11CLA was observed from SOFOFA among all the treatments at all incubation times. Overall data indicate that supplementation of combined fumarate and/or fish oil when incubated with safflower oil could depress CH(4) generation and increase production of C(3) and CLA under the condition of current in vitro study. © 2011 The Authors; Animal Science Journal © 2011 Japanese Society of Animal Science.

Modeling protein conformational changes by iterative fitting of distance constraints using reoriented normal modes.

PubMed

Zheng, Wenjun; Brooks, Bernard R

2006-06-15

Recently we have developed a normal-modes-based algorithm that predicts the direction of protein conformational changes given the initial state crystal structure together with a small number of pairwise distance constraints for the end state. Here we significantly extend this method to accurately model both the direction and amplitude of protein conformational changes. The new protocol implements a multisteps search in the conformational space that is driven by iteratively minimizing the error of fitting the given distance constraints and simultaneously enforcing the restraint of low elastic energy. At each step, an incremental structural displacement is computed as a linear combination of the lowest 10 normal modes derived from an elastic network model, whose eigenvectors are reorientated to correct for the distortions caused by the structural displacements in the previous steps. We test this method on a list of 16 pairs of protein structures for which relatively large conformational changes are observed (root mean square deviation >3 angstroms), using up to 10 pairwise distance constraints selected by a fluctuation analysis of the initial state structures. This method has achieved a near-optimal performance in almost all cases, and in many cases the final structural models lie within root mean square deviation of 1 approximately 2 angstroms from the native end state structures.

Studies on the Conformational Landscape of Tert-Butyl Acetate Using Microwave Spectroscopy and Quantum Chemical Calculations

NASA Astrophysics Data System (ADS)

Zhao, YueYue; Mouhib, Halima; Li, Guohua; Stahl, Wolfgang; Kleiner, Isabelle

2014-06-01

The tert-Butyl acetate molecule was studied using a combination of quantum chemical calculations and molecular beam Fourier transform microwave spectroscopy in the 9 to 14 GHz range. Due to its rather rigid frame, the molecule possesses only two different conformers: one of Cs and one of C1 symmetry. According to ab initio calculations, the Cs conformer is 46 kJ/mol lower in energy and is the one observed in the supersonic jet. We report on the structure and dynamics of the most abundant conformer of tert-butyl acetate, with accurate rotational and centrifugal distortion constants. Additionally, the barrier to internal rotation of the acetyl methyl group was determined. Splittings due to the internal rotation of the methyl group of up to 1.3 GHz were observed in the spectrum. Using the programs XIAM and BELGI-Cs, we determine the barrier height to be about 113 cm-1 and compare the molecular parameters obtained from these two codes. Additionally, the experimental rotational constants were used to validate numerous quantum chemical calculations. This study is part of a larger project which aims at determining the lowest energy conformers of organic esters and ketones which are of interest for flavor or perfume synthetic applications Project partly supported by the PHC PROCOPE 25059YB.

14N Quadrupole Coupling in the Microwave Spectra of N-Vinylformamide

NASA Astrophysics Data System (ADS)

Kannengießer, Raphaela; Stahl, Wolfgang; Nguyen, Ha Vinh Lam; Bailey, William C.

2016-06-01

The microwave spectra of two conformers, trans and cis, of the title compound were recorded using two molecular beam Fourier transform microwave spectrometers operating in the frequency range 2 GHz to 40 GHz, and aimed at analysis of their 14N quadrupole hyperfine structures. Rotational constants, centrifugal distortion constants, and nuclear quadrupole coupling constants (NQCCs) χaa and χbb - χcc, were all determined with very high accuracy. Two fits including 176 and 117 hyperfine transitions were performed for the trans and cis conformers, respectively. Standard deviations of both fits are close to the measurement accuracy of 2 kHz. The NQCCs of the two conformers are almost exactly the same, and are compared with values found for other saturated and unsaturated formamides. Complementary quantum chemical calculations - MP2/6-311++G(d,p) rotational constants, MP2/cc-pVTZ centrifugal distortion constants, and B3PW91/6-311+G(d,p)//MP2/6-311++G(d,p) nuclear quadrupole coupling constants - give spectroscopic parameters in excellent agreement with the experimental parameters. B3PW91/6-311+G(d,p) calculated electric field gradients, in conjunction with eQ/h = 4.599(12) MHz/a.u., yields more reliable NQCCs for formamides possessing conjugated π-electron systems than does the B3PW91/6-311+G(df,pd) model recommended in Ref., whereas this latter performs better for aliphatic formamides. We conclude from this that f-polarization functions on heavy atoms hinder rather than help with modeling of conjugated π-electron systems. W. C. Bailey, Chem. Phys., 2000, 252, 57 W. C. Bailey, Calculation of Nuclear Quadrupole Coupling Constants in Gaseous State Molecules, http://nqcc.wcbailey.net/index.html.

Quantitative Assessment of Molecular Dynamics Sampling for Flexible Systems.

PubMed

Nemec, Mike; Hoffmann, Daniel

2017-02-14

Molecular dynamics (MD) simulation is a natural method for the study of flexible molecules but at the same time is limited by the large size of the conformational space of these molecules. We ask by how much the MD sampling quality for flexible molecules can be improved by two means: the use of diverse sets of trajectories starting from different initial conformations to detect deviations between samples and sampling with enhanced methods such as accelerated MD (aMD) or scaled MD (sMD) that distort the energy landscape in controlled ways. To this end, we test the effects of these approaches on MD simulations of two flexible biomolecules in aqueous solution, Met-Enkephalin (5 amino acids) and HIV-1 gp120 V3 (a cycle of 35 amino acids). We assess the convergence of the sampling quantitatively with known, extensive measures of cluster number N c and cluster distribution entropy S c and with two new quantities, conformational overlap O conf and density overlap O dens , both conveniently ranging from 0 to 1. These new overlap measures quantify self-consistency of sampling in multitrajectory MD experiments, a necessary condition for converged sampling. A comprehensive assessment of sampling quality of MD experiments identifies the combination of diverse trajectory sets and aMD as the most efficient approach among those tested. However, analysis of O dens between conventional and aMD trajectories also reveals that we have not completely corrected aMD sampling for the distorted energy landscape. Moreover, for V3, the courses of N c and O dens indicate that much higher resources than those generally invested today will probably be needed to achieve convergence. The comparative analysis also shows that conventional MD simulations with insufficient sampling can be easily misinterpreted as being converged.

Adolescent girls' most common source of junk food away from home.

PubMed

Cohen, Deborah A; Ghosh-Dastidar, Bonnie; Beckman, Robin; Lytle, Leslie; Elder, John; Pereira, Mark A; Veblen Mortenson, Sara; Pickrel, Julie; Conway, Terry L

2012-09-01

Contextual factors associated with adolescent girls' dietary behaviors could inform future interventions to improve diet. High school girls completed a 7-day diary, recording all trips made. In places other than home or school they recorded the food eaten. Girls made an average of 11.4 trips per week other than to home or school. Snacks high in solid oils, fats and added sugars (SOFAS) were frequently consumed. Girls reported eating an average of 3.5 servings per week of snacks high in SOFAS at someone else's house compared to 3.0 servings per week at retail food outlets. Findings demonstrate that low nutrient foods are ubiquitous and efforts should be made to reduce their availability in multiple settings. Copyright © 2012 Elsevier Ltd. All rights reserved.

Theoretical study of the Hoogsteen-Watson-Crick junctions in DNA.

PubMed

Cubero, Elena; Luque, F Javier; Orozco, Modesto

2006-02-01

A series of d (AT)(n) oligonucleotides containing mixtures of normal B-type Watson-Crick and antiparallel Hoogsteen helices have been studied using molecular dynamics simulation techniques to analyze the structural and thermodynamic impact of the junction between Watson-Crick and antiparallel Hoogsteen structures. Analysis of molecular dynamics simulations strongly suggests that for all oligonucleotides studied the antiparallel Hoogsteen appears as a reasonable conformation, only slightly less stable than the canonical B-type Watson-Crick one. The junctions between the Watson-Crick and Hoogsteen structures introduces a priori a sharp discontinuity in the helix, because the properties of each type of conformation are very well preserved in the corresponding fragments. However, and quite counterintuitively, junctions do not largely distort the duplex in structural, dynamics or energetic terms. Our results strongly support the possibility that small fragments of antiparallel Hoogsteen duplex might be embedded into large fragments of B-type Watson-Crick helices, making possible protein-DNA interactions that are specific of the antiparallel Hoogsteen conformation.

Theoretical Study of the Hoogsteen–Watson-Crick Junctions in DNA

PubMed Central

Cubero, Elena; Luque, F. Javier; Orozco, Modesto

2006-01-01

A series of d (AT)n oligonucleotides containing mixtures of normal B-type Watson-Crick and antiparallel Hoogsteen helices have been studied using molecular dynamics simulation techniques to analyze the structural and thermodynamic impact of the junction between Watson-Crick and antiparallel Hoogsteen structures. Analysis of molecular dynamics simulations strongly suggests that for all oligonucleotides studied the antiparallel Hoogsteen appears as a reasonable conformation, only slightly less stable than the canonical B-type Watson-Crick one. The junctions between the Watson-Crick and Hoogsteen structures introduces a priori a sharp discontinuity in the helix, because the properties of each type of conformation are very well preserved in the corresponding fragments. However, and quite counterintuitively, junctions do not largely distort the duplex in structural, dynamics or energetic terms. Our results strongly support the possibility that small fragments of antiparallel Hoogsteen duplex might be embedded into large fragments of B-type Watson-Crick helices, making possible protein-DNA interactions that are specific of the antiparallel Hoogsteen conformation. PMID:16287814

Dystonia: Physical Therapy

MedlinePlus

... straight. Soft, sunken chairs and sofas do not foster proper alignment and may affect the position of ... dystonia, one should consider modifying the task to foster posture and muscle control. A person with trouble ...

MRI-Related Geometric Distortions in Stereotactic Radiotherapy Treatment Planning: Evaluation and Dosimetric Impact.

PubMed

Pappas, Eleftherios P; Alshanqity, Mukhtar; Moutsatsos, Argyris; Lababidi, Hani; Alsafi, Khalid; Georgiou, Konstantinos; Karaiskos, Pantelis; Georgiou, Evangelos

2017-12-01

In view of their superior soft tissue contrast compared to computed tomography, magnetic resonance images are commonly involved in stereotactic radiosurgery/radiotherapy applications for target delineation purposes. It is known, however, that magnetic resonance images are geometrically distorted, thus deteriorating dose delivery accuracy. The present work focuses on the assessment of geometric distortion inherent in magnetic resonance images used in stereotactic radiosurgery/radiotherapy treatment planning and attempts to quantitively evaluate the consequent impact on dose delivery. The geometric distortions for 3 clinical magnetic resonance protocols (at both 1.5 and 3.0 T) used for stereotactic radiosurgery/radiotherapy treatment planning were evaluated using a recently proposed phantom and methodology. Areas of increased distortion were identified at the edges of the imaged volume which was comparable to a brain scan. Although mean absolute distortion did not exceed 0.5 mm on any spatial axis, maximum detected control point disposition reached 2 mm. In an effort to establish what could be considered as acceptable geometric uncertainty, highly conformal plans were utilized to irradiate targets of different diameters (5-50 mm). The targets were mispositioned by 0.5 up to 3 mm, and dose-volume histograms and plan quality indices clinically used for plan evaluation and acceptance were derived and used to investigate the effect of geometrical uncertainty (distortion) on dose delivery accuracy and plan quality. The latter was found to be strongly dependent on target size. For targets less than 20 mm in diameter, a spatial disposition of the order of 1 mm could significantly affect (>5%) plan acceptance/quality indices. For targets with diameter greater than 2 cm, the corresponding disposition was found greater than 1.5 mm. Overall results of this work suggest that efficacy of stereotactic radiosurgery/radiotherapy applications could be compromised in case of very small targets lying distant from the scanner's isocenter (eg, the periphery of the brain).

Can Sepsis Be Detected in the Nursing Home Prior to the Need for Hospital Transfer?

PubMed

Sloane, Philip D; Ward, Kimberly; Weber, David J; Kistler, Christine E; Brown, Benjamin; Davis, Katherine; Zimmerman, Sheryl

2018-06-01

To determine whether and to what extent simple screening tools might identify nursing home (NH) residents who are at high risk of becoming septic. Retrospective chart audit of all residents who had been hospitalized and returned to participating NHs during the study period. A total of 236 NH residents, 59 of whom returned from hospitals with a diagnosis of sepsis and 177 who had nonsepsis discharge diagnoses, from 31 community NHs that are typical of US nursing homes overall. NH documentation of vital signs, mental status change, and medical provider visits 0-12 and 13-72 hours prior to the hospitalization. The specificity and sensitivity of 5 screening tools were evaluated for their ability to detect residents with incipient sepsis during 0-12 and 13-72 hours prior to hospitalization: The Systemic Inflammatory Response Syndrome criteria, the quick Sequential Organ Failure Assessment (SOFA), the 100-100-100 Early Detection Tool, and temperature thresholds of 99.0°F and 100.2°F. In addition, to validate the hospital diagnosis of sepsis, hospital discharge records in the NHs were audited to calculate SOFA scores. Documentation of 1 or more vital signs was absent in 26%-34% of cases. Among persons with complete vital sign documentation, during the 12 hours prior to hospitalization, the most sensitive screening tools were the 100-100-100 Criteria (79%) and an oral temperature >99.0°F (51%); and the most specific tools being a temperature >100.2°F (93%), the quick SOFA (88%), the Systemic Inflammatory Response Syndrome criteria (86%), and a temperature >99.0°F (85%). Many SOFA data points were missing from the record; in spite of this, 65% of cases met criteria for sepsis. NHs need better systems to monitor NH residents whose status is changing, and to present that information to medical providers in real time, either through rapid medical response programs or telemetry. Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Increased B-type natriuretic peptide and decreased proteinuria might reflect decreased capillary leakage and is associated with a better outcome in patients with severe burns

PubMed Central

2011-01-01

Introduction It is difficult to adjust fluid balance adequately in patients with severe burns due to various physical changes. B-type natriuretic peptide (BNP) is emerging as a potential marker of hydration state. Proteinuria is used as a predictor of outcome in severe illness and might correlate to systemic capillary leakage. This study investigates whether combining BNP and proteinuria can be used as a guide for individualized resuscitation and as a predictor of outcome in patients with severe burns. Methods From 2006 to 2009, 38 consecutive patients (age 47 ± 15 years, 74% male) with severe burns were included and followed for 20 days. All had normal kidney function at admission. BNP and proteinuria were routinely measured. Ordered and actually administered fluid resuscitation volumes were recorded. The Sequential Organ Failure Assessment (SOFA) score was used as the measure of outcome. Results BNP increased during follow-up, reaching a plateau level at Day 3. Based on median BNP levels at Day 3, patients were divided into those with low BNP and those with high BNP levels. Both groups had comparable initial SOFA scores. Patients with high BNP received less fluid from Days 3 to 10. Furthermore, patients with a high BNP at Day 3 had less morbidity, reflected by lower SOFA scores on the following days. To minimize effects of biological variability, proteinuria on Days 1 and 2 was averaged. By dividing the patients based on median BNP at Day 3 and median proteinuria, patients with high BNP and low proteinuria had significantly lower SOFA scores during the entire follow-up period compared to those patients with low BNP and high proteinuria. Conclusions Patients with higher BNP levels received less fluid. This might be explained by a lower capillary leakage in these patients, resulting in more intravascular fluid and consequently an increase in BNP. In combination with low proteinuria, possibly reflecting minimal systemic capillary leakage, a high BNP level was associated with a better outcome. BNP and proteinuria have prognostic potential in severely burned patients and may be used to adjust individual resuscitation. PMID:21722363

Following the crowd: Brain Substrates of Long-Term Memory Conformity

PubMed Central

Edelson, Micah; Sharot, Tali; Dolan, Raymond J; Dudai, Yadin

2012-01-01

Human memory is strikingly susceptible to social influences, yet we know little about the underlying mechanisms. We examined how socially induced memory errors are generated in the brain by studying the memory of individuals exposed to recollections of others. Participants exhibited a strong tendency to conform to erroneous recollections of the group, producing both long-lasting and temporary errors, even when their initial memory was strong and accurate. Functional brain imaging revealed that social influence modified the neuronal representation of memory. Specifically, a particular brain signature of enhanced amygdala activity and enhanced amygdala-hippocampus connectivity predicted long-lasting, but not temporary memory alterations. Our findings reveal how social manipulation can alter memory and extend the known functions of the amygdala to encompass socially-mediated memory distortions. PMID:21719681

Molecular mechanics approach for design and conformational studies of macrocyclic ligands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rohini,; Akbar, Rifat; Kanungo, B. K., E-mail: b.kanungo@gmail.com

2015-08-28

Computational Chemistry has revolutionized way of viewing molecules at the quantum mechanical scale by allowing simulating various chemical scenarios that are not possible to study in a laboratory. The remarkable applications of computational chemistry have promoted to design and test of the effectiveness of various methods for searching the conformational space of highly flexible molecules. In this context, we conducted a series of optimization and conformational searches on macrocyclic based ligands, 9N3Me5Ox, (1,4,7-tris(5-methyl-8-hydroxyquinoline)-1,4,7-triazacyclononane) and 12N3Me5Ox, (1,5,9-tris(5-methyl-8-hydroxyquinoline)-1,5,9-triazacyclododecane) and studied their selectivity and coordination behavior with some lanthanide metal ions in molecular mechanics and semiempirical methods. The methods include both systematic andmore » random conformational searches for dihedral angles, torsion angles and Cartesian coordinates. Structural studies were carried out by using geometry optimization, coordination scans and electronic properties were evaluated. The results clearly show that chair-boat conformational isomer of 9N3Me5Ox ligand is more stable due to lower eclipsing ethane interaction and form stronger adduct complexes with lanthanide metal ion. This is because of the fact that, in a central unit of 9N3 of the ligand form six endo type bonds out of nine. The rest of bonds have trans conformation. In contrast, for the adduct of 12N3Me5Ox, two C-C bonds have on eclipsed conformation, and others have synclinal and antiperiplanar confirmations. The distortion of the two eclipsed conformations may affect the yields and the stability of the complexes.« less

Femtosecond Heterodyne Transient Grating Detection of Conformational Dynamics in the S0 (11Ag-) State of Carotenoids After Nonradiative Decay of the S2 (11Bu+) State

NASA Astrophysics Data System (ADS)

Roscioli, Jerome D.; Ghosh, Soumen; Bishop, Michael M.; Lafountain, Amy M.; Frank, Harry A.; Beck, Warren F.

Transient grating spectroscopy was used to study the dynamics of nonradiative decay of the S1 (21Ag-) state in ß-carotene and peridinin after optical preparation of the S2) state. The kinetics of the recovery of the absorption and dispersion components of the third-order signal exhibit significantly different time constants. For β-carotene in benzonitrile, the absorption and dispersion recovery time constants are 11.6 and 10.2 ps. For peridinin in methanol, the time constants are 9.9 and 7.4 ps. These results indicate that the initial product of the decay of the S1 state is a conformationally displaced structure. The decay rate for the S1 state and the conformational relaxation rate are both slowed in peridinin as the polarity of the solvent decreases; in ethyl acetate, the conformational relaxation time constant is 45 ps, which rules out a dominant contribution from vibrational cooling. These results indicate that the S1 state develops intramolecular charge transfer character owing to distortions along torsional and out-of-plane coordinates, with a pyramidal structure favored as the most stable conformation. Recovery of the photoselected ground state conformation involves a reverse charge-transfer event followed by relaxation to a planar structure. Work supported by Photosynthetic Systems Program of the U.S. Department of Energy under Grant DE-SC0010847.

46 CFR 72.05-55 - Furniture and furnishings.

Code of Federal Regulations, 2013 CFR

2013-10-01

... be used on the top surface of such articles. (2) All free standing furniture such as chairs, sofas... incombustible materials with solid sides and bottoms. (c) Passageways and stairway enclosures shall contain only...

46 CFR 72.05-55 - Furniture and furnishings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... be used on the top surface of such articles. (2) All free standing furniture such as chairs, sofas... incombustible materials with solid sides and bottoms. (c) Passageways and stairway enclosures shall contain only...

46 CFR 72.05-55 - Furniture and furnishings.

Code of Federal Regulations, 2014 CFR

2014-10-01

... be used on the top surface of such articles. (2) All free standing furniture such as chairs, sofas... incombustible materials with solid sides and bottoms. (c) Passageways and stairway enclosures shall contain only...

46 CFR 72.05-55 - Furniture and furnishings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... be used on the top surface of such articles. (2) All free standing furniture such as chairs, sofas... incombustible materials with solid sides and bottoms. (c) Passageways and stairway enclosures shall contain only...

Correlation between the severity of critically ill patients and clinical predictors of bronchial aspiration

PubMed Central

de Medeiros, Gisele Chagas; Sassi, Fernanda Chiarion; Zambom, Lucas Santos; de Andrade, Claudia Regina Furquim

2016-01-01

Objective: To determine whether the severity of non-neurological critically ill patients correlates with clinical predictors of bronchial aspiration. Methods: We evaluated adults undergoing prolonged orotracheal intubation (> 48 h) and bedside swallowing assessment within the first 48 h after extubation. We collected data regarding the risk of bronchial aspiration performed by a speech-language pathologist, whereas data regarding the functional level of swallowing were collected with the American Speech-Language-Hearing Association National Outcome Measurement System (ASHA NOMS) scale and those regarding health status were collected with the Sequential Organ Failure Assessment (SOFA). Results: The study sample comprised 150 patients. For statistical analyses, the patients were grouped by ASHA NOMS score: ASHA1 (levels 1 and 2), ASHA2 (levels 3 to 5); and ASHA3 (levels 6 and 7). In comparison with the other patients, those in the ASHA3 group were significantly younger, remained intubated for fewer days, and less severe overall clinical health status (SOFA score). The clinical predictors of bronchial aspiration that best characterized the groups were abnormal cervical auscultation findings and cough after swallowing. None of the patients in the ASHA 3 group presented with either of those signs. Conclusions: Critically ill patients 55 years of age or older who undergo prolonged orotracheal intubation (≥ 6 days), have a SOFA score ≥ 5, have a Glasgow Coma Scale score ≤ 14, and present with abnormal cervical auscultation findings or cough after swallowing should be prioritized for a full speech pathology assessment. PMID:27167432

Is 'gut feeling' by medical staff better than validated scores in estimation of mortality in a medical intensive care unit? - The prospective FEELING-ON-ICU study.

PubMed

Radtke, Anne; Pfister, Roman; Kuhr, Kathrin; Kochanek, Matthias; Michels, Guido

2017-10-01

The aim of the FEELING-ON-ICU study was to compare mortality estimations of critically ill patients based on 'gut feeling' of medical staff and by Acute Physiology And Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II and Sequential Organ Failure Assessment (SOFA). Medical staff estimated patients' mortality risks via questionnaires. APACHE II, SAPS II and SOFA were calculated retrospectively from records. Estimations were compared with actual in-hospital mortality using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). 66 critically ill patients (60.6% male, mean age 63±15years (range 30-86)) were evaluated each by a nurse (n=66, male 32.4%) and a physician (n=66, male 67.6%). 15 (22.7%) patients died on the intensive care unit. AUC was largest for estimations by physicians (AUC 0.814 (95% CI 0.705-0.923)), followed by SOFA (AUC 0.749 (95% CI 0.629-0.868)), SAPS II (AUC 0.723 (95% CI 0.597-0.849)), APACHE II (AUC 0.721 (95% CI 0.595-0.847)) and nursing staff (AUC 0.669 (95% CI 0.529-0.810)) (p<0.05 for all results). The concept of physicians' 'gut feeling' was comparable to classical objective scores in mortality estimations of critically ill patients. Concerning practicability physicians' evaluations were advantageous to complex score calculation. Copyright © 2017 Elsevier Inc. All rights reserved.

The predictive value of resting heart rate following osmotherapy in brain injury: back to basics.

PubMed

Hasanpour Mir, Mahsa; Yousefshahi, Fardin; Abdollahi, Mohammad; Ahmadi, Arezoo; Nadjafi, Atabak; Mojtahedzadeh, Mojtaba

2012-12-30

The importance of resting heart rate as a prognostic factor was described in several studies. An elevated heart rate is an independent risk factor for adverse cardiovascular events and total mortality in patients with coronary artery disease, chronic heart failure, and the general population. Also heart rate is elevated in the Multi Organ Dysfunction Syndrome (MODS) and the mortality due to MODS is highly correlated with inadequate sinus tachycardia.To evaluate the value of resting heart rate in predicting mortality in patients with traumatic brain injury along scoring systems like Acute Physiology and Chronic Health Evaluation(APACHE II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Score (GCS). By analyzing data which was collected from an open labeled randomized clinical trial that compared the different means of osmotherapy (mannitol vs bolus or infusion hypertonic saline), heart rate, GCS, APACHE II and SOFA score were measured at baseline and daily for 7 days up to 60 days and the relationship between elevated heart rate and mortality during the first 7 days and 60th day were assessed. After adjustments for confounding factors, although there was no difference in mean heart rate between either groups of alive and expired patients, however, we have found a relative correlation between 60th day mortality rate and resting heart rate (P=0.07). Heart rate can be a prognostic factor for estimating mortality rate in brain injury patients along with APACHE II and SOFA scores in patients with brain injury.

Risk Factors for Mortality in Patients with Serratia marcescens Bacteremia

PubMed Central

Kim, Sun Bean; Jeon, Yong Duk; Kim, Jung Ho; Kim, Jae Kyoung; Ann, Hea Won; Choi, Heun; Kim, Min Hyung; Song, Je Eun; Ahn, Jin Young; Jeong, Su Jin; Han, Sang Hoon; Choi, Jun Yong; Song, Young Goo; Kim, June Myung

2015-01-01

Purpose Over the last 30 years, Serratia marcescens (S. marcescens) has emerged as an important pathogen, and a common cause of nosocomial infections. The aim of this study was to identify risk factors associated with mortality in patients with S. marcescens bacteremia. Materials and Methods We performed a retrospective cohort study of 98 patients who had one or more blood cultures positive for S. marcescens between January 2006 and December 2012 in a tertiary care hospital in Seoul, South Korea. Multiple risk factors were compared with association with 28-day all-cause mortality. Results The 28-day mortality was 22.4% (22/98 episodes). In a univariate analysis, the onset of bacteremia during the intensive care unit stay (p=0.020), serum albumin level (p=0.011), serum C-reactive protein level (p=0.041), presence of indwelling urinary catheter (p=0.023), and Sequential Oran Failure Assessment (SOFA) score at the onset of bacteremia (p<0.001) were significantly different between patients in the fatal and non-fatal groups. In a multivariate analysis, lower serum albumin level and an elevated SOFA score were independently associated with 28-day mortality [adjusted odds ratio (OR) 0.206, 95% confidential interval (CI) 0.044-0.960, p=0.040, and adjusted OR 1.474, 95% CI 1.200-1.810, p<0.001, respectively]. Conclusion Lower serum albumin level and an elevated SOFA score were significantly associated with adverse outcomes in patients with S. marcescens bacteremia. PMID:25683980

Risk factors for mortality in patients with Serratia marcescens bacteremia.

PubMed

Kim, Sun Bean; Jeon, Yong Duk; Kim, Jung Ho; Kim, Jae Kyoung; Ann, Hea Won; Choi, Heun; Kim, Min Hyung; Song, Je Eun; Ahn, Jin Young; Jeong, Su Jin; Ku, Nam Su; Han, Sang Hoon; Choi, Jun Yong; Song, Young Goo; Kim, June Myung

2015-03-01

Over the last 30 years, Serratia marcescens (S. marcescens) has emerged as an important pathogen, and a common cause of nosocomial infections. The aim of this study was to identify risk factors associated with mortality in patients with S. marcescens bacteremia. We performed a retrospective cohort study of 98 patients who had one or more blood cultures positive for S. marcescens between January 2006 and December 2012 in a tertiary care hospital in Seoul, South Korea. Multiple risk factors were compared with association with 28-day all-cause mortality. The 28-day mortality was 22.4% (22/98 episodes). In a univariate analysis, the onset of bacteremia during the intensive care unit stay (p=0.020), serum albumin level (p=0.011), serum C-reactive protein level (p=0.041), presence of indwelling urinary catheter (p=0.023), and Sequential Oran Failure Assessment (SOFA) score at the onset of bacteremia (p<0.001) were significantly different between patients in the fatal and non-fatal groups. In a multivariate analysis, lower serum albumin level and an elevated SOFA score were independently associated with 28-day mortality [adjusted odds ratio (OR) 0.206, 95% confidential interval (CI) 0.044-0.960, p=0.040, and adjusted OR 1.474, 95% CI 1.200-1.810, p<0.001, respectively]. Lower serum albumin level and an elevated SOFA score were significantly associated with adverse outcomes in patients with S. marcescens bacteremia.

Use of beta-methylphenylalanine (beta MeF) residues to probe the nature of the interaction of substance P with its receptor: effects of beta MeF-containing substance P analogs on rabbit iris smooth muscle contraction.

PubMed

Birney, D M; Cole, D C; Crosson, C E; Kahl, B F; Neff, B W; Reid, T W; Ren, K; Walkup, R D

1995-06-23

The effects of substituting (2S,3S)-beta-methylphenylalanine (S-beta MeF) or (2S,3R)-beta-methylphenylalanine (R-beta MeF) for the Phe7 and/or Phe8 residues of the tachykinin substance P (SP, RPKPQQFFGLM-NH2) upon the ability of SP to stimulate contraction of the rabbit iris smooth muscle were investigated. The eight beta MeF-containing SP analogs (four monosubstituted analogs, four disubstituted analogs) 1-8 were synthesized and found to be agonsts of SP in the smooth muscle contraction assay, having EC50 values ranging from 0.15 to 10.0 nM. Three analogs are significantly more active than SP [8R-(beta MeF)SP (4), 7S,8S-(beta MeF)2SP (5), and 7R,8S-(beta MeF)2SP (6)], three analogs are approximately equipotent with SP [7S-(beta MeF)SP (1), 7R-(beta MeF)SP (2), and 7S,8R-(beta MeF)2SP (8)], and two analogs are significantly less active than SP [8S-(beta MeF)SP (3) and 7R,8R-(beta MeF)2SP (7)]. The effects of the beta MeF substitutions upon the activity of SP are not additive and cannot be explained using simple conformational models which focus only on the side chain conformations of the beta MeF residues. It is postulated that the beta MeF residues induce minor distortions in the peptide backbone with resultant consequences upon peptide-receptor binding which are not dictated soley by the side chain conformations. This idea is consistent with 1H-NMR data for the monosubstituted analogs 1-4, which imply that the beta MeF substitutions cause slight distortions in the peptide backbone and that the beta MeF side chains are assuming trans or gauche(-) conformations.

NMR structure of the DNA decamer duplex containing double T*G mismatches of cis-syn cyclobutane pyrimidine dimer: implications for DNA damage recognition by the XPC-hHR23B complex.

PubMed

Lee, Joon-Hwa; Park, Chin-Ju; Shin, Jae-Sun; Ikegami, Takahisa; Akutsu, Hideo; Choi, Byong-Seok

2004-01-01

The cis-syn cyclobutane pyrimidine dimer (CPD) is a cytotoxic, mutagenic and carcinogenic DNA photoproduct and is repaired by the nucleotide excision repair (NER) pathway in mammalian cells. The XPC-hHR23B complex as the initiator of global genomic NER binds to sites of certain kinds of DNA damage. Although CPDs are rarely recognized by the XPC-hHR23B complex, the presence of mismatched bases opposite a CPD significantly increased the binding affinity of the XPC-hHR23B complex to the CPD. In order to decipher the properties of the DNA structures that determine the binding affinity for XPC-hHR23B to DNA, we carried out structural analyses of the various types of CPDs by NMR spectroscopy. The DNA duplex which contains a single 3' T*G wobble pair in a CPD (CPD/GA duplex) induces little conformational distortion. However, severe distortion of the helical conformation occurs when a CPD contains double T*G wobble pairs (CPD/GG duplex) even though the T residues of the CPD form stable hydrogen bonds with the opposite G residues. The helical bending angle of the CPD/GG duplex was larger than those of the CPD/GA duplex and properly matched CPD/AA duplex. The fluctuation of the backbone conformation and significant changes in the widths of the major and minor grooves at the double T*G wobble paired site were also observed in the CPD/GG duplex. These structural features were also found in a duplex that contains the (6-4) adduct, which is efficiently recognized by the XPC-hHR23B complex. Thus, we suggest that the unique structural features of the DNA double helix (that is, helical bending, flexible backbone conformation, and significant changes of the major and/or minor grooves) might be important factors in determining the binding affinity of the XPC-hHR23B complex to DNA.

Jet formation at the interaction of localized waves on the free surface of dielectric liquid in a tangential electric field

NASA Astrophysics Data System (ADS)

Kochurin, E. A.; Zubarev, N. M.

2018-01-01

Nonlinear dynamics of the free surface of finite depth non-conducting fluid with high dielectric constant subjected to a strong horizontal electric field is considered. Using the conformal transformation of the region occupied by the fluid into a strip, the process of interaction of counter-propagating waves is numerically simulated. The nonlinear solitary waves on the surface can separately propagate along or against the direction of electric field without distortion. At the same time, the shape of the oppositely traveling waves can be distorted as the result of their interaction. In the problem under study, the nonlinearity leads to increasing the wave amplitudes and the duration of their interaction. This effect is inversely proportional to the fluid depth. In the shallow water limit, the tendency to the formation of a vertical liquid jet is observed.

Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of d-Glucose Conformers.

PubMed

Satoh, Hiroko; Oda, Tomohiro; Nakakoji, Kumiyo; Uno, Takeaki; Tanaka, Hiroaki; Iwata, Satoru; Ohno, Koichi

2016-11-08

This paper describes our approach that is built upon the potential energy surface (PES)-based conformational analysis. This approach automatically deduces a conformational transition network, called a conformational reaction route map (r-map), by using the Scaled Hypersphere Search of the Anharmonic Downward Distortion Following method (SHS-ADDF). The PES-based conformational search has been achieved by using large ADDF, which makes it possible to trace only low transition state (TS) barriers while restraining bond lengths and structures with high free energy. It automatically performs sampling the minima and TS structures by simply taking into account the mathematical feature of PES without requiring any a priori specification of variable internal coordinates. An obtained r-map is composed of equilibrium (EQ) conformers connected by reaction routes via TS conformers, where all of the reaction routes are already confirmed during the process of the deduction using the intrinsic reaction coordinate (IRC) method. The postcalculation analysis of the deduced r-map is interactively carried out using the RMapViewer software we have developed. This paper presents computational details of the PES-based conformational analysis and its application to d-glucose. The calculations have been performed for an isolated glucose molecule in the gas phase at the RHF/6-31G level. The obtained conformational r-map for α-d-glucose is composed of 201 EQ and 435 TS conformers and that for β-d-glucose is composed of 202 EQ and 371 TS conformers. For the postcalculation analysis of the conformational r-maps by using the RMapViewer software program we have found multiple minimum energy paths (MEPs) between global minima of 1 C 4 and 4 C 1 chair conformations. The analysis using RMapViewer allows us to confirm the thermodynamic and kinetic predominance of 4 C 1 conformations; that is, the potential energy of the global minimum of 4 C 1 is lower than that of 1 C 4 (thermodynamic predominance) and that the highest energy of those of all the TS structures along a route from 4 C 1 to 1 C 4 is lower than that of 1 C 4 to 4 C 1 (kinetic predominance).

Bis[bis­(diphenyl­thio­phosphin­yl)amido-κ2 S,S′]platinum(II)

PubMed Central

Güzelsoylu, Cemal; Irişli, Sevil; Büyükgüngör, Orhan

2011-01-01

In the title compound, [Pt(C24H20NP2S2)2], the Pt atom is in a distorted square-planar environment and contains two six-membered carbon-free chelate rings, one in twist-boat and the other in a half-chair conformation. Two phenyl groups are disordered over two set of sites in ratios of 0.721 (13):0.279 (13) and 0.71 (7):0.29 (7). PMID:21753991

Single-molecule analysis of a molecular disassemblase reveals the mechanism of Hsc70-driven clathrin uncoating

PubMed Central

Böcking, Till; Aguet, François; Harrison, Stephen C.; Kirchhausen, Tomas

2010-01-01

Heat shock cognate protein 70 (Hsc70) supports remodeling of protein complexes -- for example, disassembly of clathrin coats on endocytic coated vesicles. To understand how a simple ATP driven molecular clamp catalyzes a large-scale disassembly reaction, we have used single-particle fluorescence imaging to track the dynamics of Hsc70 and its clathrin substrate in real time. Hsc70 accumulates to a critical level, determined by kinetic modeling to be one Hsc70 for every two functional attachment sites; rapid, all-or-none uncoating then ensues. We propose that Hsc70 traps conformational distortions, seen previously by electron cryomicroscopy, in the vicinity of each occupied site and that accumulation of local strains destabilises the clathrin lattice. Capture of conformational fluctuations may be a general mechanism for chaperone-driven disassembly of protein complexes. PMID:21278753

Piperidinium bis­(2-oxidobenzoato-κ2 O 1,O 2)borate

PubMed Central

Tang, Zhi-Hua; Huang, Chaojun

2009-01-01

The asymmetric unit of the title compound, C5H12N+·C14H8BO6 − or [C5H12N][BO4(C7H4O)2], contains two piperidinium cations and two bis­(salicylato)borate anions. The coordination geometries around the B atoms are distorted tetra­hedral. In the two mol­ecules, the aromatic rings are oriented at dihedral angles of 76.27 (3) and 83.86 (3)°. The rings containing B atoms have twist-boat conformations, while the two cations adopt chair conformations. In the crystal, the component species are linked by N—H⋯O hydrogen bonds. In the crystal structure, intra- and inter­molecular N—H⋯O hydrogen bonds link the mol­ecules. PMID:21581628

Apply 3D model on the customized product color combination for the interior decoration

NASA Astrophysics Data System (ADS)

Chen, Cheih-Ying

2013-03-01

The customized product color interface for the interior decoration is designed to simulate the display of various color combination sofas in the interior of the room. There are 144 color combinations of the spatial image resulted from four the interior rooms and 36 popular color sofas. The image compositing technique is adopted to appear the 144 color combinations of the spatial image on computer screen. This study tests the experience of using the interface by the questionnaire for User Interface Satisfaction (QUIS). The results show that the high grade of evaluation items including wonderful, easy, satisfying, stimulating and flexible for the experience of users. Therefore, the entrepreneur who wants to display the color primarily commodity could using the customized color combination interface with 3D models for consumers to take opportunity to find the appropriate products to meet with the interior room, so as to shorten communication time between entrepreneurs and consumers.

Matching of electron beams for conformal therapy of target volumes at moderate depths.

PubMed

Zackrisson, B; Karlsson, M

1996-06-01

The basic requirements for conformal electron therapy are an accelerator with a wide range of energies and field shapes. The beams should be well characterised in a full 3-D dose planning system which has been verified for the geometries of the current application. Differences in the basic design of treatment units have been shown to have a large influence on beam quality and dosimetry. Modern equipment can deliver electron beams of good quality with a high degree of accuracy. A race-track microtron with minimised electron scattering and a multi-leaf collimator (MLC) for electron collimating will facilitate the isocentric technique as a general treatment technique for electrons. This will improve the possibility of performing combined electron field techniques in order to conform the dose distribution with no or minimal use of a bolus. Furthermore, the isocentric technique will facilitate multiple field arrangements that decrease the problems with distortion of the dose distribution due to inhomogeneities, etc. These situations are demonstrated by clinical examples where isocentric, matched electron fields for treatment of the nose, thyroid and thoracic wall have been used.

Synthesis and structural and conformational study of some esters derived from 8-β-hydroxy-3-phenethyl-3- azabicyclico [3.2.11] octan-8-α-carboxylic acid

NASA Astrophysics Data System (ADS)

Diez, M.; Izquierdo, M. L.; Arias, M. S.; Galvez, E.; Matesanz, E.; Martinez-Ripoll, M.

1991-09-01

A series of 8-β-hydroxy-8-α-alkoxycarbonyl- N-phenethyl-3-azabicyclo [3.2.1.]octane derivatives have been synthesized and studied by IR, 1H and 13C NMR spectroscopy, and the crystal structure of ethyl-8-β-hydroxy-3-phenethyl-3-azabicyclo [3.2.1] octan-8-α-carboxylate ( Va) has been determined by X-ray diffraction. In deuterochloroform and deuterobenzene the cyclopentane and piperidine rings of the title compounds show an envelope conformation flattened at C8 and a distorted chair conformation puckered at C8 and flattened at N3, respectively, with the N-substituent in an equatorial position. These results are in close agreement with that found for compound Va in the crystalline state. By comparing the NMR and X-ray parameters of the title compounds with those of the corresponding 8-α-hydroxy-8β-alkoxycarbonyl- N-phenethyl-3- azabicyclo [3.2.1] octane epimers and 3-phenethyl-3-azabicyclo [3.2.1] octan-8-α-(andβ)ol, several stereoelectronic effects have been deduced.

Design, synthesis, characterisation, conformation and biological investigation of N-acyl r-2,c-6-bis (4-methoxyphenyl)-c-3,t-3-dimethylpiperidin-4-ones

NASA Astrophysics Data System (ADS)

Mohanraj, V.; Ponnuswamy, S.

2017-09-01

In a wide research programme towards the study of piperidin-4-ones with efficient pharmacological effect, a new series of N-acyl r-2,c-6-bis(4-methoxyphenyl)-c-3,t-3-dimethylpiperidin-4-ones 2-5 are synthesized and characterized by IR spectra, 1H, 13C, DEPT - 135 and 2D (COSY and HSQC) NMR and mass spectra. The parent compound 1 prefers to exist in a chair conformation whereas the extracted coupling constant, chemical shifts and estimated dihedral angles show that the N-acyl piperdine-4-ones 2-5 prefer to exist in a distorted boat conformation B1 (with C2 and C5 in prow and stern positions) with coplanar orientation of Nsbnd Cdbnd O moiety. The existence of a fast Nsbnd CO rotational equilibrium between the boat conformations B (I) and B (II) has also been observed. Anti bacterial activity of the above test compounds 1-5 is determined against pseudomonas sp. and salmonella sp. The antioxidant activities are determined by the ABTS, DPPH and superoxide assays. Furthermore, molecular docking studies have been carried out for the compounds 1-5 with target protein CHK1.

Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection

PubMed Central

Maciag, Joseph J.; Mackenzie, Sarah H.; Tucker, Matthew B.; Schipper, Joshua L.; Swartz, Paul; Clark, A. Clay

2016-01-01

The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly formed, but distorted, active sites. To examine the interconversion of active and inactive states in the ensemble, we used detection of related solvent positions to analyze 4,995 waters in 15 high-resolution (<2.0 Å) structures of wild-type caspase-3, resulting in 450 clusters with the most highly conserved set containing 145 water molecules. The data show that regions of the protein that contact the conserved waters also correspond to sites of posttranslational modifications, suggesting that the conserved waters are an integral part of allosteric mechanisms. To test this hypothesis, we created a library of 19 caspase-3 variants through saturation mutagenesis in a single position of the allosteric site of the dimer interface, and we show that the enzyme activity varies by more than four orders of magnitude. Altogether, our database consists of 37 high-resolution structures of caspase-3 variants, and we demonstrate that the decrease in activity correlates with a loss of conserved water molecules. The data show that the activity of caspase-3 can be fine-tuned through globally desolvating the active conformation within the native ensemble, providing a mechanism for cells to repartition the ensemble and thus fine-tune activity through conformational selection. PMID:27681633

Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection.

PubMed

Maciag, Joseph J; Mackenzie, Sarah H; Tucker, Matthew B; Schipper, Joshua L; Swartz, Paul; Clark, A Clay

2016-10-11

The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly formed, but distorted, active sites. To examine the interconversion of active and inactive states in the ensemble, we used detection of related solvent positions to analyze 4,995 waters in 15 high-resolution (<2.0 Å) structures of wild-type caspase-3, resulting in 450 clusters with the most highly conserved set containing 145 water molecules. The data show that regions of the protein that contact the conserved waters also correspond to sites of posttranslational modifications, suggesting that the conserved waters are an integral part of allosteric mechanisms. To test this hypothesis, we created a library of 19 caspase-3 variants through saturation mutagenesis in a single position of the allosteric site of the dimer interface, and we show that the enzyme activity varies by more than four orders of magnitude. Altogether, our database consists of 37 high-resolution structures of caspase-3 variants, and we demonstrate that the decrease in activity correlates with a loss of conserved water molecules. The data show that the activity of caspase-3 can be fine-tuned through globally desolvating the active conformation within the native ensemble, providing a mechanism for cells to repartition the ensemble and thus fine-tune activity through conformational selection.

Automating the selection of standard parallels for conic map projections

NASA Astrophysics Data System (ADS)

Šavriǒ, Bojan; Jenny, Bernhard

2016-05-01

Conic map projections are appropriate for mapping regions at medium and large scales with east-west extents at intermediate latitudes. Conic projections are appropriate for these cases because they show the mapped area with less distortion than other projections. In order to minimize the distortion of the mapped area, the two standard parallels of conic projections need to be selected carefully. Rules of thumb exist for placing the standard parallels based on the width-to-height ratio of the map. These rules of thumb are simple to apply, but do not result in maps with minimum distortion. There also exist more sophisticated methods that determine standard parallels such that distortion in the mapped area is minimized. These methods are computationally expensive and cannot be used for real-time web mapping and GIS applications where the projection is adjusted automatically to the displayed area. This article presents a polynomial model that quickly provides the standard parallels for the three most common conic map projections: the Albers equal-area, the Lambert conformal, and the equidistant conic projection. The model defines the standard parallels with polynomial expressions based on the spatial extent of the mapped area. The spatial extent is defined by the length of the mapped central meridian segment, the central latitude of the displayed area, and the width-to-height ratio of the map. The polynomial model was derived from 3825 maps-each with a different spatial extent and computationally determined standard parallels that minimize the mean scale distortion index. The resulting model is computationally simple and can be used for the automatic selection of the standard parallels of conic map projections in GIS software and web mapping applications.

Chemical probes of the conformation of DNA modified by cis-diamminedichloroplatinum(II)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marrot, L.; Leng, M.

The purpose of this work was to analyze at the nucleotide level the distortions induced by the binding of cis-diamminedichloroplatinum(II) (cis-DDP) to DNA by means of chemical probes. In order to test the chemical probes, experiments were first carried out on two platinated oligonucleotides. It has been verified by circular dichroism and gel electrophoresis that the binding of cis-DDP to an AG or to a GTG site within a double-stranded oligonucleotide distorts the double helix. The reactivity of the oligonucleotide platinated at the GTG site with chloroacetaldehyde, diethyl pyrocarbonate, and osmium tetraoxide, respectively, suggests a local denaturation of the doublemore » helix. The 5'G residue and the T residue within the adduct are no longer paired, while the 3'G residue is paired. The double helix is more distorted (but not denatured) at the 5' side of the adduct than at the 3' side. The reactivities of the chemical probes with six platinated DNA restriction fragments show that even at a relatively high level of platination only a few base pairs are unpaired but the double helix is largely distorted. No local denaturation has been detected at the GG sites separated from the nearest GG or AG sites by at least three base pairs. The AG sites separated from the nearest AG or GG sites by at least three base pairs do not denature the double helix locally when they are in the sequences puAG/pyTC. It is suggested that the distortion within these sequences is induced by adducts located further away along the DNA fragments, these sequences not being the major sites for the binding of cis-DDP.« less

Cadmium-1,4-cyclohexanedicarboxylato coordination polymers bearing different di-alkyl-2,2'-bipyridines: syntheses, crystal structures and photoluminescence studies.

PubMed

Rosales-Vázquez, Luis D; Sánchez-Mendieta, Víctor; Dorazco-González, Alejandro; Martínez-Otero, Diego; García-Orozco, Iván; Morales-Luckie, Raúl A; Jaramillo-Garcia, Jonathan; Téllez-López, Antonio

2017-09-26

Four coordination polymers have been synthesized using self-assembly solution reactions under ambient conditions, reacting Cd(ii) ions with 1,4-cyclohexanedicarboxylic acid in the presence of different 2,2'-bipyridine co-ligands: {[Cd(H 2 O)(e,a-cis-1,4-chdc)(2,2'-bpy)]·H 2 O} n (1); [Cd 2 (H 2 O) 2 (e,a-cis-1,4-chdc) 2 (4,4'-dmb) 2 ] n (2); {[Cd(e,a-cis-1,4-chdc)(5,5'-dmb)]·H 2 O·CH 3 OH} n (3) and {[Cd(e,e-trans-1,4-chdc)(4,4'-dtbb)]·CH 3 OH} n (4), where 1,4-chdc = 1,4-cyclohexanedicarboxylato, 2,2'-bpy = 2,2'-bipyridine, 4,4'-dmb = 4,4'-dimethyl-2,2'-bipyridine, 5,5'-dmb = 5,5'-dimethyl-2,2'-bipyridine and 4,4'-dtbb = 4,4'-di-tert-butyl-2,2'-bipyridine. Crystallographic studies show that compound 1 has a 1D structure propagating along the crystallographic b-axis; the Cd ion in 1 is six-coordinated with a distorted-octahedral coordination sphere. Compound 2 has two crystallographic different Cd ions and both are six-coordinated with a distorted-octahedral coordination sphere. Compound 3 exhibits a seven-coordinated Cd ion having a distinctive distorted-monocapped trigonal prismatic geometry. In compound 4, the Cd ion is also seven-coordinated in a distorted monocapped octahedral geometry. Compounds 2, 3 and 4 possess rhombic-shaped dinuclear units (Cd 2 O 2 ) as nodes to generate larger cycles made up of four dinuclear units, a Cd 4 motif, bridged by four 1,4-chdc ligands, accomplishing, thus, 2D structures. Remarkably, in compound 4 the 1,4-chdc ligand conformation changes to the equatorial, equatorial trans, unlike the other compounds where the bridging ligand conformation is the more typical equatorial, axial cis. The solid state luminescence properties of 1-4 were investigated; polymers 3 and 4 exhibited a strong blue emission (λ em = 410-414 nm) compared to 1 and 2; structure-related photoluminescence is attributed to the degree of hydration of the compounds. Furthermore, Cd-polymer 3 suspended in acetone allows the fluorescence selective sensing of acetonitrile over common organic solvents such as alcohols and DMF, based on turn-on fluorescence intensity with a limit of 53 μmol L -1 .

Nuclear Magnetic Resonance Studies of an N2-Guanine Adduct Derived from the Tumorigen Dibenzo[a,l]pyrene in DNA: Impact of Adduct Stereochemistry, Size, and Local DNA Sequence on Solution Conformations

PubMed Central

2015-01-01

The dimensions and arrangements of aromatic rings (topology) in adducts derived from the reactions of polycyclic aromatic hydrocarbon (PAH) diol epoxide metabolites with DNA influence the distortions and stabilities of double-stranded DNA, and hence their recognition and processing by the human nucleotide excision repair (NER) system. Dibenzo[a,l]pyrene (DB[a,l]P) is a highly tumorigenic six-ring PAH, which contains a nonplanar and aromatic fjord region that is absent in the structurally related bay region five-ring PAH benzo[a]pyrene (B[a]P). The PAH diol epoxide–DNA adducts formed include the stereoisomeric 14S and 14Rtrans-anti-DB[a,l]P-N2-dG and the stereochemically analogous 10S- and 10R-B[a]P-N2-dG (B[a]P-dG) guanine adducts. However, nuclear magnetic resonance (NMR) solution studies of the 14S-DB[a,l]P-N2-dG adduct in DNA have not yet been presented. Here we have investigated the 14S-DB[a,l]P-N2-dG adduct in two different sequence contexts using NMR methods with distance-restrained molecular dynamics simulations. In duplexes with dC opposite the adduct deleted, a well-resolved base-displaced intercalative adduct conformation can be observed. In full duplexes, in contrast to the intercalated 14R stereoisomeric adduct, the bulky DB[a,l]P residue in the 14S adduct is positioned in a greatly widened and distorted minor groove, with significant disruptions and distortions of base pairing at the lesion site and two 5′-side adjacent base pairs. These unique structural features are significantly different from those of the stereochemically analogous but smaller B[a]P-dG adduct. The greater size and different topology of the DB[a,l]P aromatic ring system lead to greater structurally destabilizing DNA distortions that are partially compensated by stabilizing DB[a,l]P-DNA van der Waals interactions, whose combined effects impact the NER response to the adduct. These structural results broaden our understanding of the structure–function relationship in NER. PMID:24617538

Contemporary Patterns of Multiple Organ Dysfunction in Trauma.

PubMed

Shepherd, Joanna M; Cole, Elaine; Brohi, Karim

2017-04-01

Multiple organ dysfunction syndrome (MODS) is associated with poor outcomes for trauma patients. Different forms of MODS may exist and have different consequences. The ability to distinguish them clinically may have implications for prognosis and treatment. We wished to study whether prolonged MODS (PRMODS) could be observed as a distinct clinical entity to early resolving MODS (ERMODS) in critically injured patients. Adult major trauma patients recruited to a prospective observational study at a single major trauma center were eligible for inclusion. MODS was defined as Sequential Organ Failure Assessment (SOFA) score >5; and PRMODS as lasting >7 days. Time to recovery (TTR) was calculated as the number of days before the SOFA fell below the MODS threshold (≤5). Five hundred ninety-five patients were enrolled of whom 285 developed ERMODS (48%) and 184 (31%) PRMODS. Organ dysfunction was more severe and protracted in PRMODS, especially in patients without brain injury (mean SOFA 11 vs. 6, Day 2, P < 0.001; TTR 17 vs. 3 days, P < 0.001). PRMODS exhibited higher rates of hepatic and renal dysfunction (84% vs. 56%; and 78% vs. 47%, P≤0.001). Patterns of recovery were distinct in hepatic, renal, and neurological systems (TTR 15 vs. 4; 20 vs. 3; and 28 vs. 7 days, P < 0.01). PRMODS was associated with higher infection and mortality rates (91% vs. 41%; and 22% vs. 7%, P < 0.001). PRMODS appears common, a distinct clinical entity, and associated with worse patient outcomes. PRMODS may represent an important endpoint for studies evaluating outcomes following trauma.

Robust expertise effects in right FFA

PubMed Central

McGugin, Rankin Williams; Newton, Allen T; Gore, John C; Gauthier, Isabel

2015-01-01

The fusiform face area (FFA) is one of several areas in occipito-temporal cortex whose activity is correlated with perceptual expertise for objects. Here, we investigate the robustness of expertise effects in FFA and other areas to a strong task manipulation that increases both perceptual and attentional demands. With high-resolution fMRI at 7Telsa, we measured responses to images of cars, faces and a category globally visually similar to cars (sofas) in 26 subjects who varied in expertise with cars, in (a) a low load 1-back task with a single object category and (b) a high load task in which objects from two categories rapidly alternated and attention was required to both categories. The low load condition revealed several areas more active as a function of expertise, including both posterior and anterior portions of FFA bilaterally (FFA1/FFA2 respectively). Under high load, fewer areas were positively correlated with expertise and several areas were even negatively correlated, but the expertise effect in face-selective voxels in the anterior portion of FFA (FFA2) remained robust. Finally, we found that behavioral car expertise also predicted increased responses to sofa images but no behavioral advantages in sofa discrimination, suggesting that global shape similarity to a category of expertise is enough to elicit a response in FFA and other areas sensitive to experience, even when the category itself is not of special interest. The robustness of expertise effects in right FFA2 and the expertise effects driven by visual similarity both argue against attention being the sole determinant of expertise effects in extrastriate areas. PMID:25192631

Prognosis Biomarkers of Severe Sepsis and Septic Shock by 1H NMR Urine Metabolomics in the Intensive Care Unit

PubMed Central

Modesto-Alapont, Vicente; Gonzalez-Marrachelli, Vannina; Vento-Rehues, Rosa; Jorda-Miñana, Angela; Blanquer-Olivas, Jose; Monleon, Daniel

2015-01-01

Early diagnosis and patient stratification may improve sepsis outcome by a timely start of the proper specific treatment. We aimed to identify metabolomic biomarkers of sepsis in urine by 1H-NMR spectroscopy to assess the severity and to predict outcomes. Urine samples were collected from 64 patients with severe sepsis or septic shock in the ICU for a 1H NMR spectra acquisition. A supervised analysis was performed on the processed spectra, and a predictive model for prognosis (30-days mortality/survival) of sepsis was constructed using partial least-squares discriminant analysis (PLS-DA). In addition, we compared the prediction power of metabolomics data respect the Sequential Organ Failure Assessment (SOFA) score. Supervised multivariate analysis afforded a good predictive model to distinguish the patient groups and detect specific metabolic patterns. Negative prognosis patients presented higher values of ethanol, glucose and hippurate, and on the contrary, lower levels of methionine, glutamine, arginine and phenylalanine. These metabolites could be part of a composite biopattern of the human metabolic response to sepsis shock and its mortality in ICU patients. The internal cross-validation showed robustness of the metabolic predictive model obtained and a better predictive ability in comparison with SOFA values. Our results indicate that NMR metabolic profiling might be helpful for determining the metabolomic phenotype of worst-prognosis septic patients in an early stage. A predictive model for the evolution of septic patients using these metabolites was able to classify cases with more sensitivity and specificity than the well-established organ dysfunction score SOFA. PMID:26565633

The predictive value of resting heart rate following osmotherapy in brain injury: back to basics

PubMed Central

2012-01-01

Background The importance of resting heart rate as a prognostic factor was described in several studies. An elevated heart rate is an independent risk factor for adverse cardiovascular events and total mortality in patients with coronary artery disease, chronic heart failure, and the general population. Also heart rate is elevated in the Multi Organ Dysfunction Syndrome (MODS) and the mortality due to MODS is highly correlated with inadequate sinus tachycardia. To evaluate the value of resting heart rate in predicting mortality in patients with traumatic brain injury along scoring systems like Acute Physiology and Chronic Health Evaluation(APACHE II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Score (GCS). Method By analyzing data which was collected from an open labeled randomized clinical trial that compared the different means of osmotherapy (mannitol vs bolus or infusion hypertonic saline), heart rate, GCS, APACHE II and SOFA score were measured at baseline and daily for 7 days up to 60 days and the relationship between elevated heart rate and mortality during the first 7 days and 60th day were assessed. Results After adjustments for confounding factors, although there was no difference in mean heart rate between either groups of alive and expired patients, however, we have found a relative correlation between 60th day mortality rate and resting heart rate (P=0.07). Conclusion Heart rate can be a prognostic factor for estimating mortality rate in brain injury patients along with APACHE II and SOFA scores in patients with brain injury. PMID:23351393

Variceal bleeding in cirrhotic patients: What is the best prognostic score?

PubMed

Mohammad, Asmaa N; Morsy, Khairy H; Ali, Moustafa A

2016-09-01

To find the most accurate, suitable, and applicable scoring system for the prediction of outcome in cirrhotic patients with bleeding varices. A prospective study was conducted comprising 120 cirrhotic patients with acute variceal bleeding who were admitted to Tropical Medicine and Gastroenterology Department in Sohag University Hospital, over a 1-year period (1/2015 to 1/2016). The clinical, laboratory, and endoscopic parameters were studied. Child-Turcotte-Pugh (CTP) classification score, Model for end-stage liver disease (MELD) score, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, and AIMS65 score were calculated for all patients. Univariate and multivariate analyses were performed for all the measured parameters and scores. Of the 120 patients (92 male) admitted during the study period, eight patients (6.67%) died in the hospital. Advanced age, the presence of encephalopathy, rebleeding, and higher serum bilirubin were independent factors associated with higher hospital mortality. The largest area under the receiver operator curve (AUROC) was obtained for the AIMS65 score and SOFA score, followed by the MELD score and APACHEII score, then CTP score, all of which achieved very good performance (AUROC>0.8). AIMS65 score showed the best sensitivity, specificity, and negative and positive predictive values. Although the AIMS65 score was not significantly different from the MELD, SOFA, and APACHEII scores, it was the optimum among them in terms of the prediction of mortality. AIMS65 score is the best simple and applicable scoring system for independently predicting mortality in cirrhotic patients with acute variceal bleeding.

Fluid overload and survival in critically ill patients with acute kidney injury receiving continuous renal replacement therapy

PubMed Central

Kim, Il Young; Kim, Joo Hui; Lee, Dong Won; Lee, Soo Bong; Rhee, Harin; Seong, Eun Young; Kwak, Ihm Soo

2017-01-01

Background Fluid overload is known to be associated with increased mortality in patients with acute kidney injury (AKI) who are critically ill. In this study, we intended to uncover whether the adverse effect of fluid overload on survival could be applied to all of the patients with AKI who received continuous renal replacement therapy (CRRT). Methods We analyzed 341 patients with AKI who received CRRT in our intensive care units. The presence of fluid overload was defined as a minimum 10% increase in body weight from the baseline. Demographics, comorbid diseases, clinical data, severity of illness [the sequential organ failure assessment (SOFA) score, number of vasopressors, diagnosis of sepsis, use of ventilator] upon ICU admission, fluid overload status, and time elapsed from AKI diagnosis until CRRT initiation were reviewed from the medical charts. Results Patients with total fluid overload from 3 days before CRRT initiation to ICU discharge had a significantly lower survival rate after ICU admission, as compared to patients with no fluid overload (P < 0.001). Among patients with sepsis (P < 0.001) or with high SOFA scores (P < 0.001), there was a significant difference in survival of the patients with and without fluid overload. In patients without sepsis or with low SOFA score, there was no significant difference in survival of patients irrespective of fluid overload. Conclusion Our study demonstrates that the adverse effect of fluid overload on survival is more evident in patients with sepsis or with more severe illness, and that it might not apply to patients without sepsis or with less severe illness. PMID:28196107

32 CFR 651.54 - Introduction.

Code of Federal Regulations, 2012 CFR

2012-07-01

... for Significant Impacts Outside the United States) provide guidance for analyzing the environmental impacts of Army actions abroad and in the global commons. Army components will, consistent with diplomatic factors (including applicable Status of Forces Agreements (SOFAs) and stationing agreements), national...

32 CFR 651.54 - Introduction.

Code of Federal Regulations, 2014 CFR

2014-07-01

... for Significant Impacts Outside the United States) provide guidance for analyzing the environmental impacts of Army actions abroad and in the global commons. Army components will, consistent with diplomatic factors (including applicable Status of Forces Agreements (SOFAs) and stationing agreements), national...

32 CFR 651.54 - Introduction.

Code of Federal Regulations, 2013 CFR

2013-07-01

... for Significant Impacts Outside the United States) provide guidance for analyzing the environmental impacts of Army actions abroad and in the global commons. Army components will, consistent with diplomatic factors (including applicable Status of Forces Agreements (SOFAs) and stationing agreements), national...

32 CFR 651.54 - Introduction.

Code of Federal Regulations, 2011 CFR

2011-07-01

... for Significant Impacts Outside the United States) provide guidance for analyzing the environmental impacts of Army actions abroad and in the global commons. Army components will, consistent with diplomatic factors (including applicable Status of Forces Agreements (SOFAs) and stationing agreements), national...

Albumin supplementation for hypoalbuminemia following burns: unnecessary and costly!

PubMed

Melinyshyn, Alex; Callum, Jeannie; Jeschke, Marc C; Cartotto, Robert

2013-01-01

Following fluid resuscitation, patients with major burns frequently develop prolonged hypoalbuminemia. It is not known whether this should be corrected by albumin supplementation. The purpose of this study was to determine whether there are any benefits associated with albumin supplementation to correct hypoalbuminemia in burned adults. We conducted a retrospective comparison of patients with burns ≥ 20% TBSA admitted to an adult regional American Burn Association-verified burn center, from May 1, 2009, to September 30, 2010, where we did not routinely supplement albumin (control group), with patients admitted from October 1, 2010, to May 30, 2011, where we had instituted a protocol in which 5% human albumin was provided to maintain serum albumin levels >20 g/L (albumin group). Comparisons were made from postburn (PB) day 2 to day 30 inclusive. There were no significant differences between control (n = 26) and albumin (n = 17) in age (48 ± 15 vs 45 ± 21 years; P = .56), burn size (33 ± 13 vs 34 ± 13 %TBSA; P = .831), or full thickness burn size (19 ± 19 vs 23 ± 19 %TBSA; P = .581). Inhalation injury was significantly more frequent in the albumin group than in controls (71% vs 31%; P = .01). The groups did not differ significantly in need for admission escharotomy, admission Sequential Organ Failure Assessment (SOFA) score, number of surgical procedures/first 30 days, or 24 and 48 hours fluid resuscitation volume requirements. The overall mean daily serum albumin level from PB day 2 to 30 in the albumin group (26.9 ± 3.0 g/L) was significantly greater than in controls (21.9 ± 4.4 g/L; P < .001). There were no significant differences between the groups in daily SOFA score/first 30 days, peak SOFA score, ΔSOFA, hospital length of stay, time to wound healing, duration of mechanical ventilation, or 30-day and in-hospital mortality. The cost of routinely supplementing 5% albumin between PB day 2 to 30 in the albumin group was more than four times that for the controls where we did not routinely provide albumin (Can $65.50 vs Can $16.57 per patient per day). We conclude that routine supplementation of 5% human albumin to maintain a serum albumin level ≥ 20 g/L in burn patients is expensive and provides no benefit.

Quantum chemical studies on hypothetical Fischer type Mo(CO)5[C(OEt)Me] and Mo(CO)5[C(OMe)Et] carbene complexes

NASA Astrophysics Data System (ADS)

Gövdeli, Nezafet; Karakaş, Duran

2018-07-01

Quantum chemical calculations at B3LYP/LANL2DZ/6-31G(d) level were made on anti-eclipsed, anti-staggered, syn-eclipsed, syn-staggered conformers of hypothetical Fischer type Mo(CO)5[C(OEt)Me] and Mo(CO)5[C(OMe)Et] carbene complexes in the gas phase. The most stable conformer of the complexes was found to be anti-staggered according to the total energy values calculated at given level. Structural parameters, vibration spectra, charge distributions, molecular orbital energy diagrams, contour diagrams of frontier orbitals, molecular electrostatic potential maps and some electronic structure descriptors were obtained for the most stable conformers. NMR spectra of the most stable conformers were calculated at GIAO/B3LYP/LANL2DZ level. The most stable conformer geometry was found to be distorted octahedral. IR and NMR spectra of the complexes are consistent with their geometry. HOMOs of the complexes were found to be center-atomic character and LUMOs were carbene-carbon character. From the calculated charge analysis and molecular electrostatic potential maps, it is found that carbene-carbon acts as electrofil and metal center nucleophile. It is suggested that the catalytic properties of the carbene complexes may be due to the fact that the carbene-carbon behave as electrophile and metal center nucleophile. Some electronic structure descriptors of the complexes were calculated and the molecular properties were estimated.

NMR and computational studies of stereoisomeric equine estrogen-derived DNA cytidine adducts in oligonucleotide duplexes: opposite orientations of diastereomeric forms.

PubMed

Zhang, Na; Ding, Shuang; Kolbanovskiy, Alexander; Shastry, Anant; Kuzmin, Vladimir A; Bolton, Judy L; Patel, Dinshaw J; Broyde, Suse; Geacintov, Nicholas E

2009-08-04

The equine estrogens equilin (EQ) and equilenin (EN) are the active components in the widely prescribed hormone replacement therapy formulation Premarin. Metabolic activation of EQ and EN generates the catechol 4-hydroxyequilenin (4-OHEN) that autoxidizes to the reactive o-quinone form in aerated aqueous solutions. The o-quinones react predominantly with C, and to a lesser extent with A and G, to form premutagenic cyclic covalent DNA adducts in vitro and in vivo. To obtain insights into the structural properties of these biologically important DNA lesions, we have synthesized site-specifically modified oligonucleotides containing the stereoisomeric 1'S,2'R,3'R-4-OHEN-C3 and 1'R,2'S,3'S-4-OHEN-C4 adducts derived from the reaction of 4-OHEN with the C in the oligonucleotide 5'-GGTAGCGATGG in aqueous solution. A combined NMR and computational approach was utilized to determine the conformational characteristics of the two major 4-OHEN-C3 and 4-OHEN-C4 stereoisomeric adducts formed in this oligonucleotide hybridized with its complementary strand. In both cases, the modified C adopts an anti glycosidic bond conformation; the equilenin distal ring protrudes into the minor groove while its two proximal hydroxyl groups are exposed on the major groove side of the DNA duplex. The bulky 4-OHEN-C adduct distorts the duplex within the central GC*G portion, but Watson-Crick pairing is maintained adjacent to C* in both stereoisomeric adducts. For the 4-OHEN-C3 adduct, the equilenin rings are oriented toward the 5'-end of the modified strand, while in 4-OHEN-C4 the equilenin is 3'-directed. Correspondingly, the distortions of the double-helical structures are more pronounced on the 5'- or the 3'-side of the lesion, respectively. These differences in stereoisomeric adduct conformations may play a role in the processing of these lesions in cellular environments.

Image remapping strategies applied as protheses for the visually impaired

NASA Technical Reports Server (NTRS)

Johnson, Curtis D.

1993-01-01

Maculopathy and retinitis pigmentosa (rp) are two vision defects which render the afflicted person with impaired ability to read and recognize visual patterns. For some time there has been interest and work on the use of image remapping techniques to provide a visual aid for individuals with these impairments. The basic concept is to remap an image according to some mathematical transformation such that the image is warped around a maculopathic defect (scotoma) or within the rp foveal region of retinal sensitivity. NASA/JSC has been pursuing this research using angle invariant transformations with testing of the resulting remapping using subjects and facilities of the University of Houston, College of Optometry. Testing is facilitated by use of a hardware device, the Programmable Remapper, to provide the remapping of video images. This report presents the results of studies of alternative remapping transformations with the objective of improving subject reading rates and pattern recognition. In particular a form of conformal transformation was developed which provides for a smooth warping of an image around a scotoma. In such a case it is shown that distortion of characters and lines of characters is minimized which should lead to enhanced character recognition. In addition studies were made of alternative transformations which, although not conformal, provide for similar low character distortion remapping. A second, non-conformal transformation was studied for remapping of images to aid rp impairments. In this case a transformation was investigated which allows remapping of a vision field into a circular area representing the foveal retina region. The size and spatial representation of the image are selectable. It is shown that parametric adjustments allow for a wide variation of how a visual field is presented to the sensitive retina. This study also presents some preliminary considerations of how a prosthetic device could be implemented in a practical sense, vis-a-vis, size, weight and portability.

The CC/DFT Route towards Accurate Structures and Spectroscopic Features for Observed and Elusive Conformers of Flexible Molecules: Pyruvic Acid as Case Study

PubMed Central

Barone, Vincenzo; Biczysko, Malgorzata; Bloino, Julien; Cimino, Paola; Penocchio, Emanuele; Puzzarini, Cristina

2018-01-01

The structures, relative stabilities as well as the rotational and vibrational spectra of the three low-energy conformers of Pyruvic acid (PA) have been characterized using a state-of-the-art quantum-mechanical approach designed for flexible molecules. By making use of the available experimental rotational constants for several isotopologues of the most stable PA conformer, Tc-PA, the semi-experimental equilibrium structure has been derived. The latter provides a reference for the pure theoretical determination of the equilibrium geometries for all conformers, thus confirming for these structures an accuracy of 0.001 Å and 0.1 deg. for bond lengths and angles, respectively. Highly accurate relative energies of all conformers (Tc-, Tt- and Ct-PA) and of the transition states connecting them are provided along with the thermodynamic properties at low and high temperatures, thus leading to conformational enthalpies accurate to 1 kJ mol−1. Concerning microwave spectroscopy, rotational constants accurate to about 20 MHz are provided for the Tt- and Ct-PA conformers, together with the computed centrifugal-distortion constants and dipole moments required to simulate their rotational spectra. For Ct-PA, vibrational frequencies in the mid-infrared region accurate to 10 cm−1 are reported along with theoretical estimates for the transitions in the near-infrared range, and the corresponding infrared spectrum including fundamental transitions, overtones and combination bands has been simulated. In addition to the new data described above, theoretical results for the Tc- and Tt-PA conformers are compared with all available experimental data to further confirm the accuracy of the hybrid coupled-cluster/density functional theory (CC/DFT) protocol applied in the present study. Finally, we discuss in detail the accuracy of computational models fully based on double-hybrid DFT functionals (mainly at the B2PLYP/aug-cc-pVTZ level) that avoid the use of very expensive CC calculations. PMID:26575928

A Study of 2-Iodobutane by Rotational Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arsenault, Eric A.; Obenchain, Daniel A.; Choi, Yoon Jeong

2016-09-15

The rotational transitions belonging to 2-iodobutane (sec-butyl-iodide, CH3CHICH2CH3) have been measured over the frequency range 5.5-16.5 GHz via jet-pulsed Fourier transform microwave (FTMW) spectroscopy. The complete nuclear quadrupole coupling tensor of iodine, ¬, has been obtained for the gauche (g)-, anti (a)-, and gauche0 (g0)-conformers, as well as the four 13C isotopologues of the gauche species. Rotational constants, centrifugal distortion constants, quadrupole coupling constants, and nuclear spin-rotation constants were determined for each species. Changes in the ¬ of the iodine nucleus, resulting from conformational and isotopic dierences, will be discussed. Isotopic substitution of g-2-iodobutane allowed for a rs structure tomore » be determined for the carbon backbone. Additionally, isotopic substitution, in conjunction with an ab initio structure, allowed for a t of various r0 structural parameters belonging to g-2-iodobutane.« less

Intramolecular structure and dynamics of mequinol and guaiacol in the gas phase: Rotationally resolved electronic spectra of their S1 states

NASA Astrophysics Data System (ADS)

Ruiz-Santoyo, José Arturo; Rodríguez-Matus, Marcela; Cabellos, José Luis; Yi, John T.; Pratt, David W.; Schmitt, Michael; Merino, Gabriel; Álvarez-Valtierra, Leonardo

2015-09-01

The molecular structures of guaiacol (2-methoxyphenol) and mequinol (4-methoxyphenol) have been studied using high resolution electronic spectroscopy in a molecular beam and contrasted with ab initio computations. Mequinol exhibits two low frequency bands that have been assigned to electronic origins of two possible conformers of the molecule, trans and cis. Guaiacol also shows low frequency bands, but in this case, the bands have been assigned to the electronic origin and vibrational modes of a single conformer of the isolated molecule. A detailed study of these bands indicates that guaiacol has a vibrationally averaged planar structure in the ground state, but it is distorted along both in-plane and out-of-plane coordinates in the first electronically excited state. An intramolecular hydrogen bond involving the adjacent -OH and -OCH3 groups plays a major role in these dynamics.

Intramolecular structure and dynamics of mequinol and guaiacol in the gas phase: Rotationally resolved electronic spectra of their S1 states.

PubMed

Ruiz-Santoyo, José Arturo; Rodríguez-Matus, Marcela; Cabellos, José Luis; Yi, John T; Pratt, David W; Schmitt, Michael; Merino, Gabriel; Álvarez-Valtierra, Leonardo

2015-09-07

The molecular structures of guaiacol (2-methoxyphenol) and mequinol (4-methoxyphenol) have been studied using high resolution electronic spectroscopy in a molecular beam and contrasted with ab initio computations. Mequinol exhibits two low frequency bands that have been assigned to electronic origins of two possible conformers of the molecule, trans and cis. Guaiacol also shows low frequency bands, but in this case, the bands have been assigned to the electronic origin and vibrational modes of a single conformer of the isolated molecule. A detailed study of these bands indicates that guaiacol has a vibrationally averaged planar structure in the ground state, but it is distorted along both in-plane and out-of-plane coordinates in the first electronically excited state. An intramolecular hydrogen bond involving the adjacent   -OH and   -OCH3 groups plays a major role in these dynamics.

Isolation and characterisation of an unexpected byproduct in the regioselective butane diacetal protection of α-methyl galactopyranoside.

PubMed

Fontenelle, Clément Q; Kuppala, Ramakrishna; Light, Mark; Linclau, Bruno

2018-01-02

The regioselective protection of both methyl galactopyranoside anomers at the 2 and 3-positions as the butane diacetal (BDA) is well known. Here we describe the formation of an unexpected byproduct, which mainly occurs when α-methyl galactopyranoside is reacted with 2,3-butanedione under BF 3 •OEt 2 catalysis. The structure of the byproduct, which did not arise from anomerisation to the β-anomer or from BDA formation at the galactopyranoside 3,4-positions, was elucidated by NMR and X-ray crystallographic analysis, and proved to be the expected BDA protected galactopyranoside, but in which the stereochemistry of both its BDA acetal centres are inverted. Interestingly, the conformation of the resulting six-membered BDA ring was distorted to a skew boat conformation in order to maintain anomeric stabilisation. Copyright © 2017. Published by Elsevier Ltd.

Metalloregulatory Proteins: Metal Selectivity and Allosteric Switching

PubMed Central

Caballero, Hermes Reyes; Campanello, Gregory C.; Giedroc, David P.

2011-01-01

Prokaryotic organisms have evolved an impressive capacity to quickly adapt to a changing and challenging microenvironment in which the availability of both biologically required and non-essential transition metal ions can vary dramatically. In all bacteria, a panel of metalloregulatory proteins control the expression of genes encoding membrane transporters and metal trafficking proteins, that collectively manage metal homeostasis and resistance. These “metal sensors” are specialized allosteric proteins, in which the direct binding of a specific or small number of “cognate” metal ion(s) drives a conformational change in the regulator that allosterically activates or inhibits operator DNA binding, or alternatively, distorts the promoter structure thereby converting a poor promoter to a strong one. In this review, we discuss our current understanding of the features that control metal specificity of the allosteric response in these systems, and the role that structure, thermodynamics and conformational dynamics play in mediating allosteric activation or inhibition of DNA binding. PMID:21511390

An Independent Evaluation of the Switching Operations Facility Analysis 2010 Working Group's Processes

DOT National Transportation Integrated Search

2009-12-01

The Switching Operations Fatality Analysis (SOFA) Working Group was formed to analyze the factors contributing to fatalities in switching operations. The 2010 Working Group invited an independent team of evaluators to assess the thoroughness of the S...

Anisotropic crystal structure distortion of the monoclinic polymorph of acetaminophen at high hydrostatic pressures.

PubMed

Boldyreva, E V; Shakhtshneider, T P; Vasilchenko, M A; Ahsbahs, H; Uchtmann, H

2000-04-01

The anisotropy of structural distortion of the monoclinic polymorph of acetaminophen induced by hydrostatic pressure up to 4.0 GPa was studied by single-crystal X-ray diffraction in a Merrill-Bassett diamond anvil cell (DAC). The space group (P2(1)/n) and the general structural pattern remained unchanged with pressure. Despite the overall decrease in the molar volume with pressure, the structure expanded in particular crystallographic directions. One of the linear cell parameters (c) passed through a minimum as the pressure increased. The intramolecular bond lengths changed only slightly with pressure, but the changes in the dihedral and torsion angles were very large. The compressibility of the intermolecular hydrogen bonds NH...O and OH...O was measured. NH...O bonds were shown to be slightly more compressible than OH...O bonds. The anisotropy of structural distortion was analysed in detail in relation to the pressure-induced changes in the molecular conformations, to the compression of the hydrogen-bond network, and to the changes in the orientation of molecules with respect to each other in the pleated sheets in the structure. Dirichlet domains were calculated in order to analyse the relative shifts of the centroids of the hydrogen-bonded cycles and of the centroids of the benzene rings with pressure.

Gas Phase Conformations and Methyl Internal Rotation for 2-PHENYLETHYL Methyl Ether and its Argon Van Der Waals Complex from Fourier Transform Microwave Spectroscopy

NASA Astrophysics Data System (ADS)

Gurusinghe, Ranil M.; Tubergen, Michael

2015-06-01

A mini-cavity microwave spectrometer was used to record the rotational spectra arising from 2-phenylethyl methyl ether and its weakly bonded argon complex in the frequency range of 10.5 - 22 GHz. Rotational spectra were found for two stable conformations of the monomer: anti-anti and gauche-anti, which are 1.4 kJ mol-1 apart in energy at wB97XD/6-311++G(d,p) level. Doubled rotational transitions, arising from internal motion of the methyl group, were observed for both conformers. The program XIAM was used to fit the rotational constants, centrifugal distortion constants, and barrier to internal rotation to the measured transition frequencies of the A and E internal rotation states. The best global fit values of the rotational constants for the anti-anti conformer are A= 3799.066(3) MHz, B= 577.95180(17) MHz, C= 544.7325(3) MHz and the A state rotational constants of the gauche-anti conformer are A= 2676.1202(7) MHz, B= 760.77250(2) MHz, C= 684.78901(2) MHz. The rotational spectrum of 2-phenylethyl methyl ether - argon complex is consistent with the geometry where argon atom lies above the plane of the benzene moiety of gauche-anti conformer. Tunneling splittings were too small to resolve within experimental accuracy, likely due to an increase in three fold potential barrier when the argon complex is formed. Fitted rotational constants are A= 1061.23373(16) MHz, B= 699.81754(7) MHz, C= 518.33553(7) MHz. The lowest energy solvated ether - water complex with strong intermolecular hydrogen bonding has been identified theoretically. Progress on the assignment of the water complex will also be presented.

Early prediction of norepinephrine dependency and refractory septic shock with a multimodal approach of vascular failure.

PubMed

Conrad, Marie; Perez, Pierre; Thivilier, Carine; Levy, Bruno

2015-08-01

The purpose of the study is to improve our ability to detect catecholamine dependency and refractory septic shock. Fifty-one patients with septic shock were studied within the first 4 hours of norepinephrine administration. Patients were divided into 2 groups according to their evolution in the intensive care unit, namely, group A, shock reversal, and group B, no shock reversal. Reversal of shock was defined as the maintenance of a systolic blood pressure greater than or equal to 90 mm Hg without vasopressor support for 24 hours or more. Vascular reactivity was tested using incremental doses of phenylephrine. Muscle tissue oxygen saturation and its changes during a vascular occlusion test were measured. Group B patients had a higher Sequential Organ Failure Assessment (SOFA) score and lactate level and more frequently received norepinephrine and renal replacement. Overall mortality was 100% in group B (16/16) and 20% (7/35) in group A. Phenylephrine increased mean arterial pressure in a dose-dependent manner more significantly in group A patients than in group B (P = .0004). Basal tissue oxygen saturation and the recovery slope after vascular occlusion test were lower in group B. In multivariate analysis, 4 parameters remained independently associated with mortality: the increase in mean arterial pressure at phenylephrine 6 μg/kg per minute, the recovery slope, SOFA score, and norepinephrine doses at H0. The intensity of septic shock-induced vascular hyporesponsiveness to vasopressor is tightly linked to septic shock severity and evolution and may potentially be identified early with simple to obtain parameters such as near-infrared spectroscopy value, SOFA score, or norepinephrine dose. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical features, complications and mortality in critically ill patients with 2009 influenza A(H1N1) in Sfax,Tunisia.

PubMed

Damak, Hassen; Chtara, Kamilia; Bahloul, Mabrouk; Kallel, Hatem; Chaari, Anis; Ksibi, Hichem; Chaari, Adel; Chelly, Hedi; Rekik, Noureddine; Ben Hamida, Chokri; Bouaziz, Mounir

2011-07-01

Africa, as the rest of the world, was touched by the 2009 pandemic influenza A(H1N1). In the literature, a few publications covering this subject emerged from this continent. We prospectively describe baseline characteristics, treatment and outcomes of consecutive critically ill patients with confirmed 2009 influenza A(H1N1) in the intensive care unit (ICU) of Sfax hospital. From 29 November 2009 through 21 January 2010, 32 patients with confirmed 2009 influenza A(H1N1) were admitted to our ICU. We prospectively analysed data and outcomes of these patients and compared survivors and dead patients to identify any predictors of death. Patients were young (mean, 36·1 [SD], 20·7 years) and 21 (65·6%) of whom had co-morbidities. During ICU care, 29 (90·6%) patients had respiratory failure; among these, 15 (46·9%) patients required invasive ventilation with a median duration of 9 (IQR 3-12) days. In our experience, respiratory dysfunction can remain isolated but may also be associated with other dysfunctions or complications, such as, septic shock, seizures, myasthenia gravis exacerbation, Guillan-Barre syndrome, acute renal failure, nosocomial infections and biological disturbances. The nine patients (28·1%) who died had greater initial severity of illness (SAPS II and sequential organ failure assessment (SOFA) scores) but also a higher SOFA score and increasing severity of organ dysfunction during their ICU evolution. Critical illness from the 2009 influenza A(H1N1) in Sfax occurred in young individuals and was associated with severe acute respiratory and additional organ system failure. SAPS II and SOFA scores at ICU admission, and also during evolution, constitute a good predictor of death. © 2011 Blackwell Publishing Ltd.

Hypophosphatemia after nontraumatic intracranial hemorrhage.

PubMed

Junttila, E; Koskenkari, J; Ala-Kokko, T

2017-07-01

The aim of this study was to assess the incidence and contributing factors of hypophosphatemia and the association with poor long-term outcome after nontraumatic intracranial hemorrhage. This was a prospective, observational study of patients with nontraumatic intracranial hemorrhage (i.e., aneurysmal or perimesencephalic subarachnoid hemorrhage, or spontaneous intracerebral or intraventricular hemorrhage) treated in the intensive care unit (ICU) at our university hospital. Plasma phosphate concentrations were measured serially in 2-day sections during the 6 day study period. The ICU mortality was recorded, 3-month and 1-year outcomes were assessed using the Glasgow Outcome Scale. One hundred patients were enrolled. The frequency of hypophosphatemia (Pi ≤ 0.65 mmol/l) was 70%. Chronic hypertension, acute hydrocephalus, and diffuse brain edema were more common in patients with hypophosphatemia compared with normophosphatemics (44% vs. 21%, P = 0.021; 59% vs. 33%, P = 0.021; and 43% vs. 13%, P = 0.004, respectively). Hypophosphatemic patients had higher maximum SOFA scores [10 (7-11) vs. 7.5 (5.75-10), P = 0.024]. Initial phosphate concentration correlated inversely with APACHE II score on admission (ρ = -0.304, P = 0.002) and SOFA score on the first ICU day (ρ = -0.269, P = 0.008). There was no difference in outcome between hypophosphatemic and normophosphatemic patients. In all five patients with severe hypophosphatemia (Pi < 0.32 mmol/l) the functional outcome was good. Hypophosphatemia was common in this patient population. The outcome was similar between hypophosphatemic and normophosphatemic patients. Chronic hypertension, acute hydrocephalus, diffuse brain edema and higher SOFA scores were more common in patients with hypophosphatemia. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial.

PubMed

de Azevedo, Rodrigo Palacio; Freitas, Flávio Geraldo Resende; Ferreira, Elaine Maria; Pontes de Azevedo, Luciano Cesar; Machado, Flávia Ribeiro

2015-09-16

Constipation is a common problem in intensive care units. We assessed the efficacy and safety of laxative therapy aiming to promote daily defecation in reducing organ dysfunction in mechanically ventilated patients. We conducted a prospective, randomized, controlled, nonblinded phase II clinical trial at two general intensive care units. Patients expected to remain ventilated for over 3 days were randomly assigned to daily defecation or control groups. The intervention group received lactulose and enemas to produce 1-2 defecations per day. In the control group, absence of defecation was tolerated up to 5 days. Primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score between the date of enrollment and intensive care unit discharge, death or day 14. We included 88 patients. Patients in the treatment group had a higher number of defecations per day (1.3 ± 0.42 versus 0.7 ± 0.56, p < 0.0001) and lower percentage of days without defecation (33.1 ± 15.7% versus 62.3 ± 24.5%, p < 0.0001). Patients in the intervention group had a greater reduction in SOFA score (-4.0 (-6.0 to 0) versus -1.0 (-4.0 to 1.0), p = 0.036) with no difference in mortality rates or in survival time. Adverse events were more frequent in the treatment group (4.5 (3.0-8.0) versus 3.0 (1.0-5.7), p = 0.016), including more days with diarrhea (2.0 (1.0-4.0) versus 1.0 (0-2.0) days, p < 0.0001). Serious adverse events were rare and did not significantly differ between groups. Laxative therapy improved daily defecation in ventilated patients and was associated with a greater reduction in SOFA score. Clinical Trials.gov NCT01607060, registered 24 May 2012.

Evolution and prognosis of long intensive care unit stay patients suffering a deterioration: A multicenter study.

PubMed

Hernández-Tejedor, Alberto; Cabré-Pericas, Lluís; Martín-Delgado, María Cruz; Leal-Micharet, Ana María; Algora-Weber, Alejandro

2015-06-01

The prognosis of a patient who deteriorates during a prolonged intensive care unit (ICU) stay is difficult to predict. We analyze the prognostic value of the serialized Sequential Organ Failure Assessment (SOFA) score and other variables in the early days after a complication and to build a new predictive score. EPIPUSE (Evolución y pronóstico de los pacientes con ingreso prolongado en UCI que sufren un empeoramiento, Evolution and prognosis of long intensive care unit stay patients suffering a deterioration) study is a prospective, observational study during a 3-month recruitment period in 75 Spanish ICUs. We focused on patients admitted in the ICU for 7 days or more with complications of adverse events that involve organ dysfunction impairment. Demographics, clinical variables, and serialized SOFA after a supervening clinical deterioration were recorded. Univariate and multivariate analyses were performed, and a predictive model was created with the most discriminating variables. We included 589 patients who experienced 777 cases of severe complication or adverse event. The entire sample was randomly divided into 2 subsamples, one for development purposes (528 cases) and the other for validation (249 cases). The predictive model maximizing specificity is calculated by minimum SOFA + 2 * cardiovascular risk factors + 2 * history of any oncologic disease or immunosuppressive treatment + 3 * dependence for basic activities of daily living. The area under the receiver operating characteristic curve is 0.82. A 14-point cutoff has a positive predictive value of 100% (92.7%-100%) and negative predictive value of 51% (46.4%-55.5%) for death. EPIPUSE model can predict mortality with a specificity and positive predictive value of 99% in some groups of patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Mortality of adult intensive care units in Turkey using the APACHE II and SOFA systems (outcome assessment in Turkish intensive care units).

PubMed

Kaymak, Cetin; Sencan, Irfan; Izdes, Seval; Sari, Aydin; Yagmurdur, Hatice; Karadas, Derya; Oztuna, Derya

2018-04-01

The aim of this study was to evaluate intensive care unit (ICU) performance using risk-adjusted ICU mortality rates nationally, assessing patients who died or had been discharged from the ICU. For this purpose, this study analyzed the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) databases, containing detailed clinical and physiological information and mortality of mixed critically ill patients in a medical ICU at secondary and tertiary referral ICUs in Turkey. A total of 690 adult intensive care units in Turkey were included in the study. Among 690 ICUs evaluated, 39.7% were secondary and 60.3% were tertiary ICUs. A total of 4188 patients were enrolled in this study. Intensive care units of ministry, university, and private hospitals were evaluated all over Turkey. During the study period, clinical data that were collected concurrently for each patient contained demographic details and the diagnostic category leading to ICU admission. APACHE II and SOFA scores following ICU admission were calculated and recorded. Patients were followed up for outcome data until death or ICU discharge. The mean age of patients was 68.8 ±19 and 54% of them were male. The mean APACHE II score was 20 ±8.7. The ICUs' mortality rate was 46.3%, and mean predicted mortality was 37.2% for APACHE II. The standardized mortality ratio was 1.28 (95% confidence interval: 1.21-1.31). There was a wide difference in outcome for patients admitted to different ICUs and severity of illness using risk adjustment methods. The high mortality rate in patients could be related to comorbid diseases, high mechanical ventilation rates and older ages.

Early thrombomodulin-α administration outcome for acute disseminated intravascular coagulopathy in gastrointestinal surgery.

PubMed

Konishi, Hirotaka; Okamoto, Kazuma; Shoda, Katsutoshi; Arita, Tomohiro; Kosuga, Toshiyuki; Morimura, Ryo; Komatsu, Shuhei; Murayama, Yasutoshi; Shiozaki, Atsushi; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Fujiwara, Hitoshi; Otsuji, Eigo

2017-02-07

To investigate the efficacy of thrombomodulin (TM)-α for treatment of disseminated intravascular coagulopathy (DIC) in the field of gastrointestinal surgery. Thirty-six peri-operative DIC patients in the field of gastrointestinal surgery who were treated with TM-α were retrospectively investigated. The relationships between patient demographics and the efficacy of TM-α were examined. Analysis of survival at 28 d was also performed on some parameters by means of the Kaplan-Meier method. Relationships between the initiation of TM-α and patient demographics were also evaluated. Abscess formation or bacteremia was the most frequent cause of DIC (33%), followed by digestive tract perforation (31%). Twenty-six patients developed DIC after surgery, frequently within 1 wk (81%). TM-α was most often administered within 1 d of the DIC diagnosis (72%) and was continued for more than 3 d (64%). Although bleeding tendency was observed in 7 patients (19%), a hemostatic procedure was not needed. DIC scores, systemic inflammatory response syndrome (SIRS) scores, quick-sequential organ failure assessment (qSOFA) scores, platelet counts, and prothrombin time ratios significantly improved after 1 wk ( P < 0.05, for all). The overall survival rate at 28 d was 71%. The duration of TM-α administration (≥ 4 , ≤ 6) and improvements in DIC-associated scores (DIC, SIRS and qSOFA) at 1 wk were significantly better prognostic factors for 28-d survival ( P < 0.05, for all). TM-α was administered significantly earlier to patients with severe clinical symptoms, such as high qSOFA scores, sepsis, shock or high lactate values ( P < 0.05, for all). Early administration of TM-α and improvements in each parameter were essential for treatment of DIC. The diagnosis of patients with mild symptoms requires further study.

Two-thirds of foods consumed on myplate contain SoFAS

USDA-ARS?s Scientific Manuscript database

Background: Public health efforts focus upon improving diet quality to prevent chronic disease. MyPlate, which represents the 2010 Dietary Guidelines for Americans, encourages limiting the consumption of solid fats (SoF) and added sugars (AS). We examined nationally representative consumption data t...

Software Products - Naval Oceanography Portal

Science.gov Websites

section Advanced Search... Sections Home Time Earth Orientation Astronomy Meteorology Oceanography Ice You astronomy. Available as Fortran, C, or Python source code. Current version: 3.1 Software Products by Our computer or programmable calculator. Standards Of Fundamental Astronomy (SOFA) Libraries The International

PAL: Positional Astronomy Library

NASA Astrophysics Data System (ADS)

Jenness, T.; Berry, D. S.

2016-06-01

The PAL library is a partial re-implementation of Pat Wallace's popular SLALIB library written in C using a Gnu GPL license and layered on top of the IAU's SOFA library (or the BSD-licensed ERFA) where appropriate. PAL attempts to stick to the SLA C API where possible.

16 CFR 1633.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... confirmation test on the mattress set it manufactures. (r) Confirmation test means a pre-market test conducted... included; examples are convertible sofa bed mattresses, corner group mattresses, day bed mattresses, roll...) This term includes any one, or any combination of the following: replacing the ticking or batting...

16 CFR 1633.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... confirmation test on the mattress set it manufactures. (r) Confirmation test means a pre-market test conducted... included; examples are convertible sofa bed mattresses, corner group mattresses, day bed mattresses, roll...) This term includes any one, or any combination of the following: replacing the ticking or batting...

16 CFR 1633.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... confirmation test on the mattress set it manufactures. (r) Confirmation test means a pre-market test conducted... included; examples are convertible sofa bed mattresses, corner group mattresses, day bed mattresses, roll...) This term includes any one, or any combination of the following: replacing the ticking or batting...

16 CFR 1633.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... confirmation test on the mattress set it manufactures. (r) Confirmation test means a pre-market test conducted... included; examples are convertible sofa bed mattresses, corner group mattresses, day bed mattresses, roll...) This term includes any one, or any combination of the following: replacing the ticking or batting...

16 CFR § 1633.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... confirmation test on the mattress set it manufactures. (r) Confirmation test means a pre-market test conducted... included; examples are convertible sofa bed mattresses, corner group mattresses, day bed mattresses, roll...) This term includes any one, or any combination of the following: replacing the ticking or batting...

The structural analysis and modelling of ring substituent effect for the ortho-derivatives of 1-hydroxynaphthalene-2-carboxanilides and 2-hydroxynaphthalene-1-carboxanilides

NASA Astrophysics Data System (ADS)

Škorňa, Peter; Michalík, Martin; Lukeš, Vladimír; Klein, Erik

2017-09-01

The quantum chemical DFT study of 1-hydroxynaphthalene-2-carboxanilide (A-H) and 2-hydroxynaphthalene-1-carboxanilide (B-H) and their selected ortho-derivatives (A-R, B-R) is presented. The structural analysis showed that the energetically preferred conformation is stabilized via the intramolecular hydrogen bonds occurring between the Cdbnd O⋯H-O1 of A-H molecule and Cdbnd O⋯H-O2 groups of B-H molecule. The A-R derivatives are practically planar, while the B-R derivatives are slightly distorted due to the spatial repulsion of hydrogen atoms. The conformation analysis of molecules with deprotonated hydroxyl group supports the concept of existence of two conformer types with respect to the sbnd NHsbnd COsbnd bridge orientation. Stabilization of the naphtholate moiety by a hydrogen bond to the amide sbnd NHsbnd group may allow the compound to cross the membrane to the extracellular space. The ortho substitution effect on the selected calculated properties was analyzed and the theoretical data were correlated with the substituent constants. For the B-R derivatives, the antitubercular activity concentrations were correlated and predicted by the calculated quantities.

The distorted tropane of scopoline.

PubMed

Écija, Patricia; Cocinero, Emilio J; Lesarri, Alberto; Basterretxea, Francisco J; Fernández, José A; Castaño, Fernando

2013-06-24

The structural isomerization of scopine into scopoline (oscine) has been observed in a supersonic jet expansion using microwave spectroscopy. The rotational spectrum evidences a single structure in the gas phase, providing a first description of the (three-ring) structurally distorted tropane in scopoline. The absence of rotational signatures of any scopine conformation suggests a practically quantitative isomerization at the vaporization temperatures of the experiment (ca. 90 °C). The determined rotational parameters of scopoline reveal the structural consequences of the intramolecular cyclation of scopine, which breaks the original epoxy group and creates a new ether bridge and a 7β-hydroxytropane configuration. The hydroxy group further stabilizes the molecule by an O-H⋅⋅⋅N intramolecular hydrogen bond, which, in turn, forces the N-methyl group to the less stable axial form. Supporting ab initio (MP2) and DFT (B3LYP, M06-2X) calculations are included. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design, fabrication, and test of a graphite/epoxy metering truss. [as applied to the LST

NASA Technical Reports Server (NTRS)

Oken, S.; Skoumal, D. E.

1975-01-01

A graphite/epoxy metering truss as applied to the large space telescope was investigated. A full-scale truss was designed, fabricated and tested. Tests included static limit loadings, a modal survey and thermal-vacuum distortion evaluation. The most critical requirement was the demonstration of the dimensional stability provided by the graphite/epoxy truss concept. Crucial to the attainment of this objective was the ability to make very sophisticated thermal growth measurements which was provided by a seven beam laser interferometer. The design of the basic truss elements were tuned to provide the high degree of dimensional stability and stiffness required by the truss. The struts and spider assembly were fabricated with Fiberite's AS/934 and HMS/934 broadgoods. The rings utilized T300 graphite fabricate with the same materials. The predicted performance of the truss was developed using the NASTRAN program. These results showed conformance with the critical stiffness and thermal distortion requirements and correlated well with the test results.

Multi-drug resistance profile of PR20 HIV-1 protease is attributed to distorted conformational and drug binding landscape: molecular dynamics insights.

PubMed

Chetty, Sarentha; Bhakat, Soumendranath; Martin, Alberto J M; Soliman, Mahmoud E S

2016-01-01

The PR20 HIV-1 protease, a variant with 20 mutations, exhibits high levels of multi-drug resistance; however, to date, there has been no report detailing the impact of these 20 mutations on the conformational and drug binding landscape at a molecular level. In this report, we demonstrate the first account of a comprehensive study designed to elaborate on the impact of these mutations on the dynamic features as well as drug binding and resistance profile, using extensive molecular dynamics analyses. Comparative MD simulations for the wild-type and PR20 HIV proteases, starting from bound and unbound conformations in each case, were performed. Results showed that the apo conformation of the PR20 variant of the HIV protease displayed a tendency to remain in the open conformation for a longer period of time when compared to the wild type. This led to a phenomena in which the inhibitor seated at the active site of PR20 tends to diffuse away from the binding site leading to a significant change in inhibitor-protein association. Calculating the per-residue fluctuation (RMSF) and radius of gyration, further validated these findings. MM/GBSA showed that the occurrence of 20 mutations led to a drop in the calculated binding free energies (ΔGbind) by ~25.17 kcal/mol and ~5 kcal/mol for p2-NC, a natural peptide substrate, and darunavir, respectively, when compared to wild type. Furthermore, the residue interaction network showed a diminished inter-residue hydrogen bond network and changes in inter-residue connections as a result of these mutations. The increased conformational flexibility in PR20 as a result of loss of intra- and inter-molecular hydrogen bond interactions and other prominent binding forces led to a loss of protease grip on ligand. It is interesting to note that the difference in conformational flexibility between PR20 and WT conformations was much higher in the case of substrate-bound conformation as compared to DRV. Thus, developing analogues of DRV by retaining its key pharmacophore features will be the way forward in the search for novel protease inhibitors against multi-drug resistant strains.

41 CFR 301-11.15 - What expenses may be considered part of the daily lodging cost when I rent on a long-term basis?

Code of Federal Regulations, 2010 CFR

2010-07-01

...., stove, refrigerator, chairs, tables, bed, sofa, television, or vacuum cleaner); (b) Cost of connecting/disconnecting and using utilities; (c) Cost of reasonable maid fees and cleaning charges; (d) Monthly telephone...

Conformation and hydrogen bonding in 4-Aminobutanol

NASA Astrophysics Data System (ADS)

Khalil, Andrew S.; Duguay, Taylor M.; Lavrich, Richard J.

2017-06-01

Rotational spectra of the most abundant and four 13C isotopomers of 4-aminobutanol have been recorded in natural abundance using a Fourier-transform microwave spectrometer. For the most abundant isotopomer, 56 hyperfine components from the fifteen a- and b-type transitions measured were fit to the quadupole coupling constants, χaa = -3.843(3) MHz, χbb = 1.971(3) MHz. Rotational and centrifugal distortion constants determined from fits of the resulting unsplit line centers to the Watson A-reduction Hamiltonian are A = 4484.893(3) MHz, B = 2830.721(1) MHz, C = 1942.9710(3) MHz, ΔJ = 0.98(3) kHz, ΔJK = 1.4(1) kHz, ΔK = - 2.6(5) kHz, δJ = 0.27(1) kHz, and δK = 1.7(1) kHz. Between nine and eleven rotational transitions were measured for the 13C isotopes and rotational constants were determined by fixing the distortion constants to the values found for the normal isotope. The five sets of moments of inertia were used to determine the 4-aminobutanol substitution structure as well to perform a least-squares fit of the lowest energy ab initio structure. The heavy atom coordinates determined from these two methods are in excellent agreement. The conformation of 4-aminobutanol is stabilized by an intramolecular hydrogen bond from the alcohol proton to amino nitrogen with a resulting hydrogen bond distance of 1.891 Å. The experimental structure is consistent with the lowest energy ab initio [MP2/6-311++G(d,p)] structure.

Conformational studies of lithium phenyl stearate

NASA Astrophysics Data System (ADS)

Barron, Christopher

The structure and conformation of lithium phenyl stearate (and to a lesser extent, for comparative purposes, cadmium stearate) was investigated using Fourier transform infrared spectroscopy, and various modelling techniques. The infrared results for LiPS show that the aliphatic portion of the soap molecule is much more ordered at room temperature than had been expected, having only 0.62 and 0.60 gtg and gg defects per molecule respectively, where an isotropic chain would have 1.35 and 1.21 gtg and gg defects per chain respectively. As the temperature is increased the number of conformational defects increases continuously, until at <130°C the chain reaches an isotropic degree of disorder. At this point the phase transition begins, so the chain reaches liquid like disorder before the phase transition begins.Modelling of the phenyl stearic acid showed that the phenyl group was restricted to certain angle of rotation values, and that the bonds close to the phenyl group were prevented from attaining true rotational isomeric state conformations, gtg defects near the phenyl group were distorted only slightly from their usual angular position, and an additional band in the infrared spectrum of LiPS at 1363 cm-1 has been assigned to this distorted gtg/gtg' defect. The gg defects near the phenyl group have a much greater distortion (and energy) resulting in a much reduced probability of occurrence. The number of gg defects present at the phase transition (<130°C) was only 75% of that expected for an isotropic n-alkane of equivalent chain length, indicating that the four bonds nearest to the phenyl group have a reduced probability of forming a gg defect.The modelling of the ionic core of LiPS gives a reasonable estimate of between 5.6 to 7.1 A for the core radius. When this is used to calculate the hexagonal cylinder diameter, at room temperature, along with the average chain extension, it gives a value for the cylinder diameter of between 33.9 to 36.8A. The hexagonal lattice parameter determined by X-ray diffraction has a value 35.9A. Also after the LiPS sample has gone through the phase transition beginning at >130°C, the hexagonal lattice parameter is 31.4A while the cylinder diameter lies between 30.2 and 33.2A.Crystalline cadmium stearate was found to contain two crystal forms, orthorhombic which has lattice dimensions of a0=5.05A, b0=7.35A and c0=48.6A and the other eithermonoclinic or triclinic. In the reverse hexagonal phase, the cadmium stearate molecule behaves like an isotropic n-alkane of equivalent chain length. The model used to predict the core radius of divalent metal soaps gives rise to some inconsistencies: the cylinder diameter thus determined gives a result between 28.8A to 31.7A, while the lattice parameter determined by X-ray diffraction gives a value of 36.9A. The assumption that the n-carboxylate ions in a divalent metal soap behave like two independent monovalent metal ion soaps appears to be incorrect.

46 CFR 116.423 - Furniture and furnishings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ARRANGEMENT Fire Protection § 116.423 Furniture and furnishings. (a) For the purpose of this subpart, rooms containing “fire resistant furnishings” are considered to be those in which: (1) Furniture such as chairs, sofas, and similar items are tested and meet the requirements in UL 1056 “Fire Test of Upholstered...

46 CFR 116.423 - Furniture and furnishings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ARRANGEMENT Fire Protection § 116.423 Furniture and furnishings. (a) For the purpose of this subpart, rooms containing “fire resistant furnishings” are considered to be those in which: (1) Furniture such as chairs, sofas, and similar items are tested and meet the requirements in UL 1056 “Fire Test of Upholstered...

Replacing the Sofa with the Spotlight: Interrogating the Therapeutic Value of Personal Testimony within Community-Based Theatre

ERIC Educational Resources Information Center

Leffler, Elliot

2012-01-01

Julie Salverson, a Canadian scholar-practitioner, has long challenged the assumption that personal storytelling within Community-Based Theatre is necessarily therapeutic. Salverson critiques an "aesthetic of injury," arguing that theatre practitioners have foregrounded personal narratives in a way that reinscribes a "victim…

46 CFR 72.05-55 - Furniture and furnishings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... shall be of approved fire resistant fabrics. (4) All rugs and carpets shall be of wool or other material... subpart, rooms containing “fire resistant furnishings” will be considered to be those in which: (1) All... fire resistant furnishings. In addition, all upholstery and padding of chairs, sofas, etc., in these...

Assembly and analysis of eukaryotic Argonaute–RNA complexes in microRNA-target recognition

PubMed Central

Gan, Hin Hark; Gunsalus, Kristin C.

2015-01-01

Experimental studies have uncovered a variety of microRNA (miRNA)–target duplex structures that include perfect, imperfect and seedless duplexes. However, non-canonical binding modes from imperfect/seedless duplexes are not well predicted by computational approaches, which rely primarily on sequence and secondary structural features, nor have their tertiary structures been characterized because solved structures to date are limited to near perfect, straight duplexes in Argonautes (Agos). Here, we use structural modeling to examine the role of Ago dynamics in assembling viable eukaryotic miRNA-induced silencing complexes (miRISCs). We show that combinations of low-frequency, global modes of motion of Ago domains are required to accommodate RNA duplexes in model human and C. elegans Ago structures. Models of viable miRISCs imply that Ago adopts variable conformations at distinct target sites that generate distorted, imperfect miRNA-target duplexes. Ago's ability to accommodate a duplex is dependent on the region where structural distortions occur: distortions in solvent-exposed seed and 3′-end regions are less likely to produce steric clashes than those in the central duplex region. Energetic analyses of assembled miRISCs indicate that target recognition is also driven by favorable Ago-duplex interactions. Such structural insights into Ago loading and target recognition mechanisms may provide a more accurate assessment of miRNA function. PMID:26432829

Spaces of differential forms and maps with controlled distortion

NASA Astrophysics Data System (ADS)

Vodop'yanov, Sergei K.

2010-09-01

We study necessary and sufficient conditions for an approximately differentiable map f\\colon M\\to M' between Riemannian manifolds to induce a bounded transfer operator of differential forms with respect to the norms of Lebesgue spaces. As a corollary, we see that every homeomorphism f\\colon M\\to M' of class \\operatorname{ACL}(M) whose transfer operator of differential forms with norm in L_p is an isomorphism must necessarily be either quasi-conformal or quasi-isometric. We give some applications of our results to the study of the functoriality of cohomology in Lebesgue spaces.

The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix.

PubMed

Gundogdu, Mehmet; Llabrés, Salomé; Gorelik, Andrii; Ferenbach, Andrew T; Zachariae, Ulrich; van Aalten, Daan M F

2018-05-17

O-linked β-N-acetyl- D -glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain. Recently, OGT mutations have been associated with intellectual disability, although it is not understood how they affect OGT structure and function. Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Influence of molecular distortion on the exciton quenching for quaterthiophene-terminated self-assembled monolayers on Au(111)

NASA Astrophysics Data System (ADS)

Kato, Hiroyuki S.; Murakami, Yoshinari; Saitoh, Riyo; Osumi, Yuji; Okaue, Daijiro; Kiriyama, Yoshiaki; Ueba, Takahiro; Yamada, Takashi; Ie, Yutaka; Aso, Yoshio; Munakata, Toshiaki

2018-03-01

We have studied the dynamics of photoexcited electronic states for structure-specific alkanethiolate-based self-assembled monolayers (SAMs) on Au(111). At the even numbers of methylene units (n) in the alkylene chain, a molecular distortion due to strong interference between the end substituents is expected. Focused on this geometrical perturbation, here, we examine the influence of the molecular distortion on the quenching process of photoexcited quaterthiophene (4T)-terminated alkanethiolate SAMs (4TCnS-SAMs) for even n (= 6 and 8). The occupied and unoccupied electronic levels of 4TCnS-SAMs are specified by ultraviolet photoelectron spectroscopy (UPS) and two-photon photoemission (2PPE) spectroscopy, respectively. The quenching rate, i.e., lifetime (τn), of the photoexcited state for 4TCnS-SAMs is evaluated by the time-resolved 2PPE measurements. In comparison to the previously reported results for odd n [J. Phys. Chem. C 119 (2015) 7400-7407], we find that τn for even n is not in the middle of those for n ± 1 but close to that for n - 1, i.e., τ6 ≈ τ5 and τ8 ≈ τ7, in contrast to the negligible difference in the electronic levels for all n. By the examination of molecular configurations using scanning tunneling microscopy (STM) and infrared reflection absorption spectroscopy (IRAS), we elucidate the weak n dependence of the 4T group orientation and the n-parity-dependent conformation change of alkylene chain. We conclude that the n parity dependence of τn results from a structural distortion of the aliphatic alkylene chain, in which a skewed alkylene chain appears for even n, rather than the electronic modification of the aromatic 4T groups.

Intramolecular structure and dynamics of mequinol and guaiacol in the gas phase: Rotationally resolved electronic spectra of their S{sub 1} states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruiz-Santoyo, José Arturo; Rodríguez-Matus, Marcela; Álvarez-Valtierra, Leonardo, E-mail: leoav@fisica.ugto.mx, E-mail: gmerino@mda.cinvestav.mx

2015-09-07

The molecular structures of guaiacol (2-methoxyphenol) and mequinol (4-methoxyphenol) have been studied using high resolution electronic spectroscopy in a molecular beam and contrasted with ab initio computations. Mequinol exhibits two low frequency bands that have been assigned to electronic origins of two possible conformers of the molecule, trans and cis. Guaiacol also shows low frequency bands, but in this case, the bands have been assigned to the electronic origin and vibrational modes of a single conformer of the isolated molecule. A detailed study of these bands indicates that guaiacol has a vibrationally averaged planar structure in the ground state, butmore » it is distorted along both in-plane and out-of-plane coordinates in the first electronically excited state. An intramolecular hydrogen bond involving the adjacent   –OH and   –OCH{sub 3} groups plays a major role in these dynamics.« less

Experimental investigation of a 0.15 scale model of a conformal variable-ramp inlet for the F-16 airplane

NASA Technical Reports Server (NTRS)

Hawkins, J. E.

1980-01-01

A 0.15 scale model of a proposed conformal variable-ramp inlet for the Multirole Fighter was tested from Mach 0.8 to 2.2 at a wide range of angles of attack and sideslip. Inlet ramp angle was varied to optimize ramp angle as a function of engine airflow, Mach number, angle of attack, and angle of sideslip. Several inlet configuration options were investigated to study their effects on inlet operation and to establish the final flight configuration. These variations were cowl sidewall cutback, cowl lip bluntness, boundary layer bleed, and first-ramp leading edge shape. Diagnostic and engine face instrumentation were used to evaluate inlet operation at various inlet stations and at the inlet/engine interface. Pressure recovery and stability of the inlet were satisfactory for the proposed application. On the basis of an engine stability audit of the worst-case instantaneous distortion patterns, no inlet/engine compatibility problems are expected for normal operations.

Synthesis, spectroscopic characterization and theoretical calculations of ClF2CC(O)NPCl3 ([chloro(difluor)acetyl]phosphorimidic trichloride).

PubMed

Iriarte, Ana G; Cutin, Edgardo H; Argüello, Gustavo A

2014-01-01

The synthesis of [chloro(difluor)acetyl]phosphorimidic trichloride (ClF2CC(O)NPCl3), together with a tentative assignment of the vibrational, NMR and mass spectra, are reported. Quantum chemical calculations (MP2 and B3LYP methods with 6-311+G(d) and 6-311+G(2df,p) basis sets) predict three stable conformers in the gas phase (syn, gauche and anti, defined according to the rotation around both the ClCCN and the CCNP dihedral angles). However, only a single C1 symmetry conformer is observed in the liquid phase, possessing the CO double bond in synperiplanar orientation with respect to the PN double bond, and the ClC bond distorted from the plane defined by the CC(O)NP entity. A Natural Bond Orbital (NBO) analysis was carried out for the title compound and related molecules in order to provide an explanation about the electronic properties. Copyright © 2013 Elsevier B.V. All rights reserved.

Toward accurate prediction of pKa values for internal protein residues: the importance of conformational relaxation and desolvation energy.

PubMed

Wallace, Jason A; Wang, Yuhang; Shi, Chuanyin; Pastoor, Kevin J; Nguyen, Bao-Linh; Xia, Kai; Shen, Jana K

2011-12-01

Proton uptake or release controls many important biological processes, such as energy transduction, virus replication, and catalysis. Accurate pK(a) prediction informs about proton pathways, thereby revealing detailed acid-base mechanisms. Physics-based methods in the framework of molecular dynamics simulations not only offer pK(a) predictions but also inform about the physical origins of pK(a) shifts and provide details of ionization-induced conformational relaxation and large-scale transitions. One such method is the recently developed continuous constant pH molecular dynamics (CPHMD) method, which has been shown to be an accurate and robust pK(a) prediction tool for naturally occurring titratable residues. To further examine the accuracy and limitations of CPHMD, we blindly predicted the pK(a) values for 87 titratable residues introduced in various hydrophobic regions of staphylococcal nuclease and variants. The predictions gave a root-mean-square deviation of 1.69 pK units from experiment, and there were only two pK(a)'s with errors greater than 3.5 pK units. Analysis of the conformational fluctuation of titrating side-chains in the context of the errors of calculated pK(a) values indicate that explicit treatment of conformational flexibility and the associated dielectric relaxation gives CPHMD a distinct advantage. Analysis of the sources of errors suggests that more accurate pK(a) predictions can be obtained for the most deeply buried residues by improving the accuracy in calculating desolvation energies. Furthermore, it is found that the generalized Born implicit-solvent model underlying the current CPHMD implementation slightly distorts the local conformational environment such that the inclusion of an explicit-solvent representation may offer improvement of accuracy. Copyright © 2011 Wiley-Liss, Inc.

16 CFR 1632.8 - Glossary of terms.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... The seat slopes, in the sitting position, for added comfort (see fig. 5). (w) Push-back sofa. When... lounge. An upholstered couch chair or a couch with a chair back. It has a permanent back rest, no arms... positions for a chaise lounge effect or a single sleeper. The vertical back support always remains upright...

32 CFR 536.17 - Single-service claims responsibility (DODD 5515.8 and DODD 5515.9).

Code of Federal Regulations, 2011 CFR

2011-07-01

... U.S.C. 2734); (2) MCA (10 U.S.C. 2733); (3) Status of Forces Agreements (10 U.S.C. 2734a and 2734b); (4) NATO SOFA (4 U.S.T. 1792, Treaties and International Acts Series (T.I.A.S.) 2846) and other...

32 CFR 536.17 - Single-service claims responsibility (DODD 5515.8 and DODD 5515.9).

Code of Federal Regulations, 2010 CFR

2010-07-01

... U.S.C. 2734); (2) MCA (10 U.S.C. 2733); (3) Status of Forces Agreements (10 U.S.C. 2734a and 2734b); (4) NATO SOFA (4 U.S.T. 1792, Treaties and International Acts Series (T.I.A.S.) 2846) and other...

Release of volatile and semi-volatile toxicants during house fires.

PubMed

Hewitt, Fiona; Christou, Antonis; Dickens, Kathryn; Walker, Richard; Stec, Anna A

2017-04-01

Qualitative results are presented from analysis of volatile and semi-volatile organic compounds (VOCs/SVOCs) obtained through sampling of gaseous effluent and condensed particulates during a series of experimental house fires conducted in a real house. Particular emphasis is given to the 16 polycyclic aromatic hydrocarbons (PAHs) listed by the Environmental Protection Agency due to their potentially carcinogenic effects. The initial fuel packages were either cooking oil or a single sofa; these were burned both alone, and in furnished surroundings. Experiments were performed at different ventilation conditions. Qualitative Gas Chromatography-Mass Spectrometry (GC-MS) analysis found VOC/SVOC releases in the developing stages of the fires, and benzo(a)pyrene - the most carcinogenic PAH - was found in at least one sampling interval in the majority of fires. A number of phosphorus fire retardants were detected, in both the gaseous effluent and particulates, from fires where the initial fuel source was a sofa. Their release during the fire is significant as they pose toxicological concerns separate from those presented by the PAHs. Copyright © 2016. Published by Elsevier Ltd.

Simulations of absorption spectra of conjugated oligomers: role of planar conformation and aggregation in condensed phase

NASA Astrophysics Data System (ADS)

Yuan, Xiang-Ai; Wen, Jin; Zheng, Dong; Ma, Jing

2018-04-01

This Review highlights the structure/property relationship underlying the morphology modulation through various factors towards the exploration of light-absorbing materials for efficient utilisation of solar power. Theoretical study using a combination of molecular dynamics imulations and the time-dependent density functional theory demonstrated that the planarity plays an important role in tuning spectral properties of oligomer aggregates. The aggregation-induced blue-shift in absorption spectra of oligothiophenes and the red-shift for oligofluorenols were rationalised in a unified way from the reduced (and increased) content of planar conformations in molecular aggregates. The planarity versus non-planarity of oligomers can be modulated by introduction of alkyl side chain or steric bulky substituents. The substitution with various groups in the ortho-position of azobenzene leads to the distorted backbone, breaking symmetry, and hence the red-shift in spectra, expanding the application in biological systems with visible light absorption. The donor-acceptor substituent groups in conjugated oligomers can increase the degree of planarity, electron delocalisation and polarisation, and charge separation, giving rise to the red-shift in spectra and enhancement in polarisability and charge mobility for device applications. The solvent dependent and pH-sensitive properties and intramolecular hydrogen bonds also caused the shift of absorption spectra with the appearance of planar conformers.

Conformational preferences for some 3-(4‧-substituted phenylsulfonyl)-1-methyl-2-piperidones through spectroscopic and theoretical studies

NASA Astrophysics Data System (ADS)

Olivato, Paulo R.; Santos, Jean M. M.; Cerqueira, Carlos R.; Vinhato, Elisângela; Zukerman-Schpector, Julio; Ng, Seik Weng; Tiekink, Edward R. T.; Colle, Maurizio Dal

2012-11-01

The analysis of the infrared (IR) carbonyl band of some 3-(4'-substituted phenylsulfonyl)-1-methyl-2-piperidones 1-5 bearing as substituents: OMe 1, Me 2, H 3, Cl 4 and NO25, supported by B3LYP/6-31G(d,p) calculations along with NBO analysis (for 1, 3 and 5) and X-ray diffraction (for 5), indicated the existence of three stable conformations i.e. quasi-axial (q-ax), syn-clinal (s-cl) and quasi-equatorial (q-eq). In the gas phase, the q-ax conformer is calculated as the most stable (ca. 88%) and the least polar, the s-cl conformer is less stable (ca. 12%) but more polar, and the q-eq conformer is the least stable (ca. 1%) and the most polar of the three conformers evaluated. The sum of the most important orbital interactions from NBO analysis and the trend of the electrostatic interactions accounts for the relative populations as well as for the νCO frequencies of the q-ax, s-cl and q-eq conformers calculated in the gas phase. The unique IR νCO band in CCl4 may be ascribed to the most stable q-ax conformer. The more intense (60%) high frequency doublet component in CHCl3 may be assigned to the summing up of the least stable q-eq and the less stable s-cl conformers, as their frequencies are almost coincident. The occurrence of only a single νCO band in both CH2Cl2 and CH3CN supports the fact that the νCO band of the two more polar conformers appear as a single band. Additional support to this rationalization is given by the single point PCM method, which showed a progressive increase of the q-eq + s-cl/q-ax population ratio going from the gas phase to CCl4, to CHCl3, to CH2Cl2 and to CH3CN. X-ray single crystal analysis of 5 indicates that this compound displays a quasi-axial geometry with respect to the [Odbnd Csbnd CHsbnd S] moiety, and that the 2-piperidone ring assumes a slightly distorted half-chair conformation. In the crystal packing, molecules of 5 are arranged into supramolecular layers linked through Csbnd H⋯O interactions along with π⋯π interactions between adjacent benzene rings.

SURFACE FLUID REGISTRATION OF CONFORMAL REPRESENTATION: APPLICATION TO DETECT DISEASE BURDEN AND GENETIC INFLUENCE ON HIPPOCAMPUS

PubMed Central

Shi, Jie; Thompson, Paul M.; Gutman, Boris; Wang, Yalin

2013-01-01

In this paper, we develop a new automated surface registration system based on surface conformal parameterization by holomorphic 1-forms, inverse consistentsurface fluid registration, and multivariate tensor-based morphometry (mTBM). First, we conformally map a surface onto a planar rectangle space with holomorphic 1-forms. Second, we compute surface conformal representation by combining its local conformal factor and mean curvature and linearly scale the dynamic range of the conformal representation to form the feature image of the surface. Third, we align the feature image with a chosen template image via the fluid image registration algorithm, which has been extended into the curvilinear coordinates to adjust for the distortion introduced by surface parameterization. The inverse consistent image registration algorithm is also incorporated in the system to jointly estimate the forward and inverse transformations between the study and template images. This alignment induces a corresponding deformation on the surface. We tested the system on Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset to study AD symptoms on hippocampus. In our system, by modeling a hippocampus as a 3D parametric surface, we nonlinearly registered each surface with a selected template surface. Then we used mTBM to analyze the morphometrydifference between diagnostic groups. Experimental results show that the new system has better performance than two publically available subcortical surface registration tools: FIRST and SPHARM. We also analyzed the genetic influence of the Apolipoprotein E ε4 allele (ApoE4),which is considered as the most prevalent risk factor for AD.Our work successfully detected statistically significant difference between ApoE4 carriers and non-carriers in both patients of mild cognitive impairment (MCI) and healthy control subjects. The results show evidence that the ApoE genotype may be associated with accelerated brain atrophy so that our workprovides a new MRI analysis tool that may help presymptomatic AD research. PMID:23587689

Induced chirality of cage metal complexes switched by their supramolecular and covalent binding.

PubMed

Kovalska, Vladyslava B; Vakarov, Serhii V; Kuperman, Marina V; Losytskyy, Mykhaylo Y; Gumienna-Kontecka, Elzbieta; Voloshin, Yan Z; Varzatskii, Oleg A

2018-01-23

An ability of the ribbed-functionalized iron(ii) clathrochelates to induce a CD output in interactions with a protein, covalent bonding or supramolecular interactions with a low-molecular-weight chiral inductor, was discovered. The interactions of CD inactive, carboxyl-terminated iron(ii) clathrochelates with serum albumin induced their molecular asymmetry, causing an appearance of strong CD signals in the range of 350-600 nm, whereas methyl ester and amide clathrochelate derivatives remained almost CD inactive. The CD spectra of carboxyl-terminated clathrochelates on supramolecular interactions or covalent bonding with (R)-(+)-1-phenylethylamine gave a substantially lower CD output than with albumin, affected by both the solvent polarity and the isomerism of clathrochelate's ribbed substituents. In supramolecular assemblies, the bands were most intensive for ortho-substituted carboxyl-terminated clathrochelates. The ortho- and meta-phenylethylamide cage complexes in tetrachloromethane inverted the signs of their CD bands compared with those in acetonitrile. It was suggested that the tris-dioximate metal clathrochelates possess a Russian doll-like molecular system. Because of the distorted TP-TAP geometry, their coordination polyhedron had no inversion centre and possessed an inherent chirality together with the equiprobability of its left(Λ)- and right(Δ)-handle twists. The selective fixation of one of these C 3 -distorted conformations resulted in the appearance of the CD signal in the range of their visible metal-to-ligand charge transfer bands. Calculations by DFT methods were used to illustrate the possible conformations of the macrobicyclic molecules, as well as the intramolecular interactions between the cage framework and optically active distal substituents responsible for the chirality induction of the metal-centred coordination polyhedra.

Mw Systematic Study of Alkaloids: the Distorted Tropane of Scopoline

NASA Astrophysics Data System (ADS)

Ecija, Patricia; Cocinero, Emilio J.; Basterretxea, Francisco J.; Fernandez, Jose A.; Castano, Fernando; Lesarri, Alberto

2013-06-01

Tropane alkaloids have diverse pharmacological uses and are well-known for their neurostimulant activity. Previous structure-activity-relationship established correlations between bioactivity and several aspects of ligand conformation and stereochemistry, including delicate intramolecular effects like nitrogen inversion^{a}. We have initiated a series of structural studies on tropane alkaloids^{b}, aimed to discerning their intrinsic stereochemical properties using rotational spectroscopy in supersonic jets^{c}. Here we extend these studies to the epoxytropanes, initially motivated to interrogate the influence of the epoxy group on nitrogen inversion and ring conformation. The rotational spectrum evidences a single structure in the gas phase, providing a first description of the (three ring) structurally-distorted tropane in scopoline. The determined rotational parameters of scopoline reveal the structural consequences of the intramolecular cyclation of scopine, which breaks the original epoxy group and creates a new ether bridge and a 7β-hydroxytropane configuration. The hydroxyl group further stabilizes the molecule by an O-H \\cdots N intramolecular hydrogen bond, which, in turn, forces the N-methyl group to the less stable axial form^{b}. The experimental work was supported by ab initio and DFT calculations. ^{a} i) S.Singh, Chem. Rev. 100, 925 (2000); ii) A. Krunic, D. Pan, W.J. Dunn III, S.V.S. Miariappan, Bioorg. & Med. Chem. 17, 811 (2009). ^{b} E.J. Cocinero, A. Lesarri, P. écija, J.-U. Grabow, J.A. Fernández, F. Castaño, Phys. Chem. Chem. Phys. 12, 6076 (2010). ^{c} E.J. Cocinero, A. Lesarri, P. écija, J.-U. Grabow, J.A. Fernández, F. Castaño, Phys. Chem. Chem. Phys. 12, 12486 (2010).

Fever, thrombocytopenia, and AKI-A profile of malaria, dengue, and leptospirosis with renal failure in a South Indian tertiary-care hospital.

PubMed

Prabhu, Mayoor V; S, Arun; Ramesh, Venkat

In the tropics, the triad of fever, thrombocytopenia, and AKI portends a grim prognosis with high mortality and a severe strain on already-stretched resources. Malaria, dengue, and leptospirosis account for most cases. We undertook a review of cases to determine factors accounting for adverse prognosis. All patients presenting to the emergency room (ER) with a history of fever, thrombocytopenia, and renal failure were included in the study. Patients were followed until discharge or death, and end points looked at were 1-week and 30-day mortality, and renal function upon discharge. Parameters like liver function test (LFT), renal function, and platelet count upon discharge were also documented. A total of 43 patients was included in the study. Mean age was 42.5 years with 86% males. Mean APACHE and SOFA scores on admission were 23.89 and 15.42, respectively. Mean admission platelet counts were 41,000. Mean serum creatinine was 4.1, and bilirubin was 9.94. A platelet count of < 34,000, serum creatinine of > 4, albumin of > 2.3, SOFA score of > 20, and APACHE score of > 32.2 were significantly predictive of 1 week mortality. Need for mechanical ventilation, oliguria on admission, and need for dialysis all were highly predictive of 30-day mortality. In addition, a serum bicarbonate of < 12, INR of > 1.5, hemoglobin of < 9.5 were highly predictive of higher 30 day mortality. Overall, 1-week mortality was 16.3%, of which 48% was accounted for by patients with leptospirosis. Factors like low platelet count, oliguria, need for dialysis, high APACHE and SOFA scores on admission, need for mechanical ventilation, and low serum albumin portend a grave prognosis. There is need for randomized control trials (RCT) to further determine adverse prognostic factors in this subsect of patients.

[Prolonged mechanical ventilation probability model].

PubMed

Añón, J M; Gómez-Tello, V; González-Higueras, E; Oñoro, J J; Córcoles, V; Quintana, M; López-Martínez, J; Marina, L; Choperena, G; García-Fernández, A M; Martín-Delgado, C; Gordo, F; Díaz-Alersi, R; Montejo, J C; Lorenzo, A García de; Pérez-Arriaga, M; Madero, R

2012-10-01

To design a probability model for prolonged mechanical ventilation (PMV) using variables obtained during the first 24 hours of the start of MV. An observational, prospective, multicenter cohort study. Thirteen Spanish medical-surgical intensive care units. Adult patients requiring mechanical ventilation for more than 24 hours. None. APACHE II, SOFA, demographic data, clinical data, reason for mechanical ventilation, comorbidity, and functional condition. A multivariate risk model was constructed. The model contemplated a dependent variable with three possible conditions: 1. Early mortality; 2. Early extubation; and 3. PMV. Of the 1661 included patients, 67.9% (n=1127) were men. Age: 62.1±16.2 years. APACHE II: 20.3±7.5. Total SOFA: 8.4±3.5. The APACHE II and SOFA scores were higher in patients ventilated for 7 or more days (p=0.04 and p=0.0001, respectively). Noninvasive ventilation failure was related to PMV (p=0.005). A multivariate model for the three above exposed outcomes was generated. The overall accuracy of the model in the training and validation sample was 0.763 (95%IC: 0.729-0.804) and 0.751 (95%IC: 0.672-0.816), respectively. The likelihood ratios (LRs) for early extubation, involving a cutoff point of 0.65, in the training sample were LR (+): 2.37 (95%CI: 1.77-3.19) and LR (-): 0.47 (95%CI: 0.41-0.55). The LRs for the early mortality model, for a cutoff point of 0.73, in the training sample, were LR (+): 2.64 (95%CI: 2.01-3.4) and LR (-): 0.39 (95%CI: 0.30-0.51). The proposed model could be a helpful tool in decision making. However, because of its moderate accuracy, it should be considered as a first approach, and the results should be corroborated by further studies involving larger samples and the use of standardized criteria. Copyright © 2011 Elsevier España, S.L. y SEMICYUC. All rights reserved.

Defining sepsis on the wards: results of a multi-centre point-prevalence study comparing two sepsis definitions.

PubMed

Szakmany, T; Pugh, R; Kopczynska, M; Lundin, R M; Sharif, B; Morgan, P; Ellis, G; Abreu, J; Kulikouskaya, S; Bashir, K; Galloway, L; Al-Hassan, H; Grother, T; McNulty, P; Seal, S T; Cains, A; Vreugdenhil, M; Abdimalik, M; Dennehey, N; Evans, G; Whitaker, J; Beasant, E; Hall, C; Lazarou, M; Vanderpump, C V; Harding, K; Duffy, L; Guerrier Sadler, A; Keeling, R; Banks, C; Ng, S W Y; Heng, S Y; Thomas, D; Puw, E W; Otahal, I; Battle, C; Minik, O; Lyons, R A; Hall, J E

2018-02-01

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54-75%) and specificity of 47% (41-53%); SEPSIS-3 criteria had a sensitivity of 86% (76-92%) and specificity of 32% (27-38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5-5.6) and 1.6 (1.3-2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63-0.76)), followed by NEWS (0.58 (0.51-0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49-0.61)) and quickSOFA score (0.56 (0.49-0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

[Epidemiology of acute kidney failure in Spanish ICU. Multicenter prospective study FRAMI].

PubMed

Herrera-Gutiérrez, M E; Seller-Pérez, G; Maynar-Moliner, J; Sánchez-Izquierdo-Riera, J A

2006-01-01

Multicenter study oriented at establishing the incidence and prognosis of acute kidney failure (AKF) in the ICU of our country. Prospective study of adult patients admitted over 8 months in 43 Spanish ICUs to detect AKF defined as creatinine>or=2 mg/dl or diuresis<400 ml/24 hours (in chronic patients 100% increase of creatinine, excluding those with baseline creatinine>or=4 mg/dl). 901 episodes of AKF (AKF episodes (incidence 5.7%), 55% of which occurred on admission. A total of 38.4% of the episodes were due to acute tubular necrosis (ATN), 36.6% to prerenal, and 21.2% to mixed. Renal depuration (RC) was required in 38%. Mortality was 42.3% during the AKF episode (34.1% in those who were admitted with AKF versus 50.9% in those who developed it after admission), 80% in patients with Hepatorenal Syndrome, 51.6% in ATN and 29.9% in prerenal. We detect an independent relationship with mortality for age (OR 1.03), background of diabetes (OR 2.06), development of AKF in the ICU (OR 2.51), oliguria (OR 5.76) and RC (OR 2.32). Recovery of the kidney function occurred in 85.6% of the survivors and RC was maintained in only 1.1% on discharge from the ICU. We calculated the area under the curve of APACHE II on admission (0.62), SOFA on onset of AKF (0.68), Liaño index (0.7) and maximum SOFA (0.79). AKF in ICU patients does not show an elevated incidence but does have high mortality, presenting greater seriousness when it appears after admission. However, recovery is elevated in patients who survive. The usual prognostic indexes are not exact in this patient group, the ISA and maximum SOFA being those which shows a closer relationship with mortality.

Early non-invasive ventilation treatment for severe influenza pneumonia.

PubMed

Masclans, J R; Pérez, M; Almirall, J; Lorente, L; Marqués, A; Socias, L; Vidaur, L; Rello, J

2013-03-01

The role of non-invasive ventilation (NIV) in acute respiratory failure caused by viral pneumonia remains controversial. Our objective was to evaluate the use of NIV in a cohort of (H1N1)v pneumonia. Usefulness and success of NIV were assessed in a prospective, observational registry of patients with influenza A (H1N1) virus pneumonia in 148 Spanish intensive care units (ICUs) in 2009-10. Significant variables for NIV success were included in a multivariate analysis. In all, 685 patients with confirmed influenza A (H1N1)v viral pneumonia were admitted to participating ICUs; 489 were ventilated, 177 with NIV. The NIV was successful in 72 patients (40.7%), the rest required intubation. Low Acute Physiology and Chronic Health Evaluation (APACHE) II, low Sequential Organ Failure Assessment (SOFA) and absence of renal failure were associated with NIV success. Success of NIV was independently associated with fewer than two chest X-ray quadrant opacities (OR 3.5) and no vasopressor requirement (OR 8.1). However, among patients with two or more quadrant opacities, a SOFA score ≤7 presented a higher success rate than those with SOFA score >7 (OR 10.7). Patients in whom NIV was successful required shorter ventilation time, shorter ICU stay and hospital stay than NIV failure. In patients in whom NIV failed, the delay in intubation did not increase mortality (26.5% versus 24.2%). Clinicians used NIV in 25.8% of influenza A (H1N1)v viral pneumonia admitted to ICU, and treatment was effective in 40.6% of them. NIV success was associated with shorter hospital stay and mortality similar to non-ventilated patients. NIV failure was associated with a mortality similar to those who were intubated from the start. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Coronary flow reserve is associated with tissue ischemia and is an additive predictor of intensive care unit mortality to traditional risk scores in septic shock.

PubMed

Ikonomidis, Ignatios; Makavos, George; Nikitas, Nikitas; Paraskevaidis, Ioannis; Diamantakis, Argyris; Kopterides, Petros; Theodorakopoulou, Maria; Parissis, John; Lekakis, John; Armaganidis, Apostolos; Dimopoulou, Ioanna

2014-03-01

Reduced coronary velocity flow reserve (CFR) is associated with poor outcome in patients with cardiovascular disease. We investigated whether CFR is associated with tissue ischemia and acidosis, impaired myocardial deformation and adverse outcome in patients with septic shock. In 70 mechanically-ventilated patients with septic shock, we examined: a) S' and E' mitral annular velocities using tissue Doppler imaging (TDI), b) CFR of the left anterior descending artery after adenosine infusion using transesophageal Doppler echocardiography and c) lactate, pyruvate and glycerol in tissue by means of a microdialysis (MD) catheter inserted into the subcutaneous adipose tissue as markers of tissue ischemia and acidosis. SOFA and APACHE II prognostic scores and mortality in the intensive care unit (ICU) were recorded. Reduced CFR, S' and E' as well as increased E/E' correlated with increased SOFA, APACHE II and MD lactate to pyruvate ratio (p<0.05 for all correlations). Impaired TDI markers also correlated with increased MD glycerol (p<0.05). Reduced CFR correlated with decreased E' (p<0.05). CFR was 1.8 ± 0.42 in non-survivors (n=34) versus 2.08 ± 0.44 in survivors (p=0.007). A CFR<1.90 predicted mortality with sensitivity of 70% and specificity of 69% (area under the curve 77%; p=0.003). CFR had an additive value to APACHE (chi-square change: 4.358, p=0.03) and SOFA (chi-square change: 3.692, p=0.04) for the prediction of mortality. Tissue ischemia and acidosis is a common pathophysiological link between decreased CFR and impaired LV myocardial deformation in septic shock. CFR is an additive predictor of ICU mortality to traditional risk scores in septic shock. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Prevalence of upper limb work-related musculoskeletal disorders (UL-WMSDs) in workers of the upholstered furniture industry].

PubMed

Nicoletti, S; Carino, M; Di Leone, G; Trani, G; Carella, F; Rubino, G; Leone, E; Popolizio, R; Colafiglio, S; Ambrosi, L

2008-01-01

The upholstered furniture industry, the so-called "triangle of the sofa industry", is a geographic area of national and strategic economic importance in southern Italy. The single tasks are carried out mostly manually, with the characteristics of a handicraft approach. The aim of the survey was to assess the prevalence of upper limb work-related musculoskeletal disorders (UL-WMSDs) in 30 factories of the sofa industry located in a large geographic area of the Puglia and Basilicata Regions. In the period 1 January-31 December 2003 a network of occupational physicians investigated a population of 5.477 subjects (exposed n=3481, controls n=1996, M=3865, F=1612) in 30 different factories of the area. More than 60 percent of the total workforce studied was employed in large-sized companies (>500 employees). The following work tasks were considered: filling preparation workers, leather-cutting operators, sewing and upholstery-assembly workers. Case-definition was assessed through standardized procedures: symptoms by questionnaire plus physical and laboratory/imaging findings. Cumulative prevalence rates of UL-WMSDs as at 31 December 2003 reached values of up to 30% in high risk groups. Prevalence rates showed good correlation with the concise OCRA index used for assessment of exposure to repetitive strain and movements of the upper limb. The most frequently occurring disorders were tendon-related cysts and wrist tendonitis. Shoulder disorders were more frequent in male and female leather-cutting operators. This survey showed a significantly high prevalence of UL-WMSDs in sofa industry workers. It did not seem to be confirmed in this study that there was a greater female susceptibility to UL-WMSDs with the exception of carpal tunnel syndrome: gender difference seems to be less relevant at increasing levels of occupational exposure to repetitive movements and exertion of the upper limbs.

Comparison of the Performance Between Sepsis-1 and Sepsis-3 in ICUs in China: A Retrospective Multicenter Study.

PubMed

Cheng, Baoli; Li, Zhongwang; Wang, Jingya; Xie, Guohao; Liu, Xu; Xu, Zhipeng; Chu, Lihua; Zhao, Jialian; Yao, Yongming; Fang, Xiangming

2017-09-01

The definition of sepsis was updated to sepsis-3 in February 2016. However, the performance of the previous and new definition of sepsis remains unclear in China. This was a retrospective multicenter study in six intensive care unit (ICUs) from five university-affiliated hospitals to compare the performance between sepsis-1 and sepsis-3 in China. From May 1, 2016 to June 1, 2016, 496 patients were enrolled consecutively. Data were extracted from the electronic clinical records. We evaluated the performance of sepsis-1 and sepsis-3 by measuring the area under the receiver operating characteristic curves (AUROC) to predict 28-day mortality rates. Of 496 enrolled patients, 186 (37.5%) were diagnosed with sepsis according to sepsis-1, while 175 (35.3%) fulfilled the criteria of sepsis-3. The AUROC of systemic inflammatory response syndrome (SIRS) is significantly smaller than that of sequential organ failure assessment (SOFA) (0.55 [95% confidence interval, 0.46-0.64] vs. 0.69 (95% confidence interval, 0.61-0.77], P = 0.008) to predict 28-day mortality rates of infected patients. Moreover, 5.9% infected patients (11 patients) were diagnosed as sepsis according to sepsis-1 but not to sepsis-3. The APACHE II, SOFA scores, and mortality rate of the 11 patients were significantly lower than of patients whose sepsis was defined by both the previous and new criteria (8.6±3.5 vs. 16.3±6.2, P =  < 0.001; 1 (0-1) vs. 6 (4-8), P = <0.001; 0.0 vs. 33.1%, P = 0.019). In addition, the APACHE II, length of stay in ICU, and 28-day mortality rate of septic patients rose gradually corresponding with the raise in SOFA score (but not the SIRS score). Sepsis-3 performed better than sepsis-1 in the study samples in ICUs in China.

Diagnostic and prognostic value of presepsin vs. established biomarkers in critically ill patients with sepsis or systemic inflammatory response syndrome.

PubMed

Brodska, Helena; Valenta, Jiri; Pelinkova, Kveta; Stach, Zdenek; Sachl, Robert; Balik, Martin; Zima, Tomas; Drabek, Tomas

2018-03-28

Inflammatory biomarkers may aid to distinguish between systemic inflammatory response syndrome (SIRS) vs. sepsis. We tested the hypotheses that (1) presepsin, a novel biomarker, can distinguish between SIRS and sepsis, and (2) higher presepsin levels will be associated with increased severity of illness and (3) with 28-day mortality, outperforming traditional biomarkers. Procalcitonin (PCT), C-reactive protein (CRP), presepsin, and lactate were analyzed in 60 consecutive patients (sepsis and SIRS, n=30 per group) on day 1 (D1) to D3 (onset sepsis, or after cardiac surgery). The systemic organ failure assessment (SOFA) score was determined daily. There was no difference in mortality in sepsis vs. SIRS (12/30 vs. 8/30). Patients with sepsis had higher SOFA score vs. patients with SIRS (11±4 vs. 8±5; p=0.023), higher presepsin (AUC=0.674; p<0.021), PCT (AUC=0.791; p<0.001), CRP (AUC=0.903; p<0.0001), but not lactate (AUC=0.506; p=0.941). Unlike other biomarkers, presepsin did not correlate with SOFA on D1. All biomarkers were associated with mortality on D1: presepsin (AUC=0.734; p=0.0006; best cutoff=1843 pg/mL), PCT (AUC=0.844; p<0.0001), CRP (AUC=0.701; p=0.0048), and lactate (AUC=0.778; p<0.0001). Multiple regression analyses showed independent associations of CRP with diagnosis of sepsis, and CRP and lactate with mortality. Increased neutrophils (p=0.002) and decreased lymphocytes (p=0.007) and monocytes (p=0.046) were also associated with mortality. Presepsin did not outperform traditional sepsis biomarkers in diagnosing sepsis from SIRS and in prognostication of mortality in critically ill patients. Presepsin may have a limited adjunct value for both diagnosis and an early risk stratification, performing independently of clinical illness severity.

Outcome scoring systems for short-term prognosis in critically ill cirrhotic patients.

PubMed

Tu, Kun-Hua; Jenq, Chang-Chyi; Tsai, Ming-Hung; Hsu, Hsiang-Hao; Chang, Ming-Yang; Tian, Ya-Chung; Hung, Cheng-Chieh; Fang, Ji-Tseng; Yang, Chih-Wei; Chen, Yung-Chang

2011-11-01

Cirrhotic patients admitted to intensive care units (ICUs) have high mortality rates. This study evaluated specific predictors and scoring systems for hospital and 6-month mortality in critically ill cirrhotic patients. This investigation is a prospective clinical study performed in a 10-bed specialized hepatogastroenterology ICU in a tertiary care university hospital in Taiwan. Two hundred two consecutive cirrhotic patients admitted to the ICU during a 2-year period were enrolled in this study. Demographic, clinical, and laboratory variables recorded on the first day of ICU admission and scoring systems applied were prospectively recorded for post hoc analysis for predicting survival. The overall hospital mortality was 59.9%, and the 6-month mortality rate was 70.8%. The main causes of cirrhosis were hepatitis B (29%), hepatitis C (22%), and alcoholism (20%). The major cause of ICU admission was upper gastrointestinal bleeding (36%). Multiple logistic regression analysis revealed that the Acute Kidney Injury Network (AKIN) score at the 48th hour of ICU admission and the Sequential Organ Failure Assessment (SOFA) as well as the Model for End-Stage Liver Disease scores on the first day of ICU admission were independent risk factors for hospital mortality. The SOFA score had the best discriminatory power (0.872 ± 0.036), whereas the AKIN had the best Youden index (0.57) and the highest correctness of prediction (79%). Cumulative survival rates at the 6-month follow-up after hospital discharge differed significantly (P < 0.05) for AKIN stage 0 vs. stages 1, 2, and 3, and for AKIN stage 1 vs. stage 3. The AKIN, SOFA, and Model for End-stage Liver Disease (MELD) scores showed well discriminative power in predicting hospital mortality in this group of patients. The AKIN scoring system proved to be a reproducible evaluation tool with excellent prognostic abilities for these patients.

Comparison of scoring systems and outcome of patients admitted to a liver intensive care unit of a tertiary referral centre with severe variceal bleeding.

PubMed

Al-Freah, M A B; Gera, A; Martini, S; McPhail, M J W; Devlin, J; Harrison, P M; Shawcross, D; Abeles, R D; Taylor, N J; Auzinger, G; Bernal, W; Heneghan, M A; Wendon, J A

2014-06-01

Acute variceal haemorrhage (AVH) is associated with significant mortality. To determine outcome and factors associated with hospital mortality (HM) in patients with AVH admitted to intensive care unit (ICU) and to compare outcomes of patients requiring transfer to a tertiary ICU (transfer group, TG) to a local in-patient group (LG). A retrospective study of all adult patients (N = 177) admitted to ICU with AVH from 2000-2008 was performed. Median age was 48 years (16-80). Male represented 58%. Median MELD score was 16 (6-39), SOFA score was 8 (6-11). HM was higher in patients who had severe liver disease or critical illness measured by MELD, SOFA, APACHE II scores and number of failed organs (NFO), P < 0.05. Patients with day-1 lactate ≥ 2 mmol/L had increased HM (P < 0.001). MELD score performed as well as APACHE II, SOFA and NFO (P < 0.001) in predicting HM (AUROC = 0.84, 0.81, 0.79 and 0.82, respectively P > 0.05 for pair wise comparisons). Re-bleeding was associated with increased HM (56.9% vs. 31.6%, P = 0.002). The TG (n = 124) had less severe liver disease and critical illness and consequently had lower HM than local patients (32% vs. 57%, P = 0.002). TG patients with ≥2 endoscopies prior to transfer had increased 6-week mortality (P = 0.03). Time from bleeding to transfer ≥3 days was associated with re-bleeding (OR = 2.290, P = 0.043). MELD score was comparable to ICU prognostic models in predicting mortality. Blood lactate was also predictive of hospital mortality. Delays in referrals and repeated endoscopy were associated with increased re-bleeding and mortality in this group. © 2014 John Wiley & Sons Ltd.

Resonance Raman spectra of bacteriorhodopsin's primary photoproduct: evidence for a distorted 13-cis retinal chromophore.

PubMed Central

Braiman, M; Mathies, R

1982-01-01

We have obtained the resonance Raman spectrum of bacteriorhodopsin's primary photoproduct K with a novel low-temperature spinning sample technique. Purple membrane at 77 K is illuminated with spatially separated actinic (pump) and probe laser beams. The 514-nm pump beam produces a photostationary steady-state mixture of bacteriorhodopsin and K. This mixture is then rotated through the red (676 nm) probe beam, which selectively enhances the Raman scattering from K. The essential advantage of our successive pump-and-probe technique is that it prevents the fluorescence excited by the pump beam from masking the red probe Raman scattering. K exhibits strong Raman lines at 1516, 1294, 1194, 1012, 957, and 811 cm-1. The effects of C15 deuteration on K's fingerprint lines correlate well with those seen in 13-cis model compounds, indicating that K has a 13-cis chromophore. However, the presence of unusually strong "low-wavenumber" lines at 811 and 957 cm-1, attributable to hydrogen out-of-plane wags, indicates that the protein holds the chromophore in a distorted conformation after trans leads to cis isomerization. PMID:6281770

Single-molecule FRET unveils induced-fit mechanism for substrate selectivity in flap endonuclease 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rashid, Fahad; Harris, Paul D.; Zaher, Manal S.

Human flap endonuclease 1 (FEN1) and related structure-specific 5’nucleases precisely identify and incise aberrant DNA structures during replication, repair and recombination to avoid genomic instability. Yet, it is unclear how the 5’nuclease mechanisms of DNA distortion and protein ordering robustly mediate efficient and accurate substrate recognition and catalytic selectivity. Here, single-molecule sub-millisecond and millisecond analyses of FEN1 reveal a protein-DNA induced-fit mechanism that efficiently verifies substrate and suppresses off-target cleavage. FEN1 sculpts DNA with diffusion-limited kinetics to test DNA substrate. This DNA distortion mutually ‘locks’ protein and DNA conformation and enables substrate verification with extreme precision. Strikingly, FEN1 never missesmore » cleavage of its cognate substrate while blocking probable formation of catalytically competent interactions with noncognate substrates and fostering their pre-incision dissociation. These findings establish FEN1 has practically perfect precision and that separate control of induced-fit substrate recognition sets up the catalytic selectivity of the nuclease active site for genome stability.« less

Single-molecule FRET unveils induced-fit mechanism for substrate selectivity in flap endonuclease 1

DOE PAGES

Rashid, Fahad; Harris, Paul D.; Zaher, Manal S.; ...

2017-02-23

Human flap endonuclease 1 (FEN1) and related structure-specific 5’nucleases precisely identify and incise aberrant DNA structures during replication, repair and recombination to avoid genomic instability. Yet, it is unclear how the 5’nuclease mechanisms of DNA distortion and protein ordering robustly mediate efficient and accurate substrate recognition and catalytic selectivity. Here, single-molecule sub-millisecond and millisecond analyses of FEN1 reveal a protein-DNA induced-fit mechanism that efficiently verifies substrate and suppresses off-target cleavage. FEN1 sculpts DNA with diffusion-limited kinetics to test DNA substrate. This DNA distortion mutually ‘locks’ protein and DNA conformation and enables substrate verification with extreme precision. Strikingly, FEN1 never missesmore » cleavage of its cognate substrate while blocking probable formation of catalytically competent interactions with noncognate substrates and fostering their pre-incision dissociation. These findings establish FEN1 has practically perfect precision and that separate control of induced-fit substrate recognition sets up the catalytic selectivity of the nuclease active site for genome stability.« less

Single-molecule FRET unveils induced-fit mechanism for substrate selectivity in flap endonuclease 1

PubMed Central

Rashid, Fahad; Harris, Paul D; Zaher, Manal S; Sobhy, Mohamed A; Joudeh, Luay I; Yan, Chunli; Piwonski, Hubert; Tsutakawa, Susan E; Ivanov, Ivaylo; Tainer, John A; Habuchi, Satoshi; Hamdan, Samir M

2017-01-01

Human flap endonuclease 1 (FEN1) and related structure-specific 5’nucleases precisely identify and incise aberrant DNA structures during replication, repair and recombination to avoid genomic instability. Yet, it is unclear how the 5’nuclease mechanisms of DNA distortion and protein ordering robustly mediate efficient and accurate substrate recognition and catalytic selectivity. Here, single-molecule sub-millisecond and millisecond analyses of FEN1 reveal a protein-DNA induced-fit mechanism that efficiently verifies substrate and suppresses off-target cleavage. FEN1 sculpts DNA with diffusion-limited kinetics to test DNA substrate. This DNA distortion mutually ‘locks’ protein and DNA conformation and enables substrate verification with extreme precision. Strikingly, FEN1 never misses cleavage of its cognate substrate while blocking probable formation of catalytically competent interactions with noncognate substrates and fostering their pre-incision dissociation. These findings establish FEN1 has practically perfect precision and that separate control of induced-fit substrate recognition sets up the catalytic selectivity of the nuclease active site for genome stability. DOI: http://dx.doi.org/10.7554/eLife.21884.001 PMID:28230529

Clinical Significance of Soluble Hemoglobin Scavenger Receptor CD163 (sCD163) in Sepsis, a Prospective Study

PubMed Central

Feng, Lin; Zhou, Xin; Su, Long-Xiang; Feng, Dan; Jia, Yan-Hong; Xie, Li-Xin

2012-01-01

Objective We investigated serum soluble CD163 (sCD163) levels for use in the diagnosis, severity assessment, and prognosis of sepsis in the critical ill patients and compared sCD163 with other infection-related variables. Methods During july 2010 and April 2011, serum was obtained from 102 sepsis patients (days 1, 3, 5, 7, and 10 after admission to an ICU) and 30 systemic inflammatory response syndrome (SIRS) patients with no sepsis diagnosed. Serum levels of sCD163, procalcitonon (PCT), and C reactive protein (CRP) were determined respectively. Sequential organ failure assessment (SOFA) scores for sepsis patients were also recorded. Then evaluated their roles in sepsis. Results The sCD163 levels were 0.88(0.78–1.00)ug/mL for SIRS patients, 1.50(0.92–2.00)ug/mL for moderate sepsis patients, and 2.95(2.18–5.57)ug/mL for severe sepsis patients on day1. The areas under the ROC curves for sCD163, CRP, and PCT for the diagnosis of sepsis were, respectively, 0.856(95%CI: 0.791–0.921), 0.696(95%CI: 0.595–0.797), and 0.629(95%CI: 0.495–0.763), At the recommended cut-off 1.49 ug/mL for sCD163, the sensitivity is 74.0% with 93.3% specificity. Based on 28-day survivals, sCD163 levels in the surviving group stay constant, while they tended to gradually increase in the non-surviving group.The area under the ROC curve for sCD163 for sepsis prognosis was 0.706(95%CI 0.558–0.804). Levels of sCD163 with cut-off point >2.84 ug/mL have sensitivity of 55.8.0%, specificity 80.4%.Common risk factors for death and sCD163 were included in multivariate logistic regression analysis; the odds ratios (OR) for sCD163 and SOFA scores for sepsis prognosis were 1.173 and 1.396, respectively (P<0.05). Spearman rank correlation analysis showed that sCD163 was weakly, but positively correlated with CRP, PCT, and SOFA scores (0.2< r <0.4, P<0.0001), but not with leukocyte counts (r <0.2, P = 0.450). Conclusion Serum sCD163 is superior to PCT and CRP for the diagnosis of sepsis and differentiate the severity of sepsis. sCD163 levels were more sensitive for dynamic evaluations of sepsis prognosis. Serum sCD163 and SOFA scores are prognostic factors for sepsis. Trial Registration www.chictr.org ChiCTR-ONC-10000812 PMID:22911680

An Integrated approach (thermodynamic, structural, and computational) to the study of complexation of alkali-metal cations by a lower-rim calix[4]arene amide derivative in acetonitrile.

PubMed

Horvat, Gordan; Stilinović, Vladimir; Hrenar, Tomica; Kaitner, Branko; Frkanec, Leo; Tomišić, Vladislav

2012-06-04

The calix[4]arene secondary-amide derivative L was synthesized, and its complexation with alkali-metal cations in acetonitrile (MeCN) was studied by means of spectrophotometric, NMR, conductometric, and microcalorimetric titrations at 25 °C. The stability constants of the 1:1 (metal/ligand) complexes determined by different methods were in excellent agreement. For the complexation of M(+) (M = Li, Na, K) with L, both enthalpic and entropic contributions were favorable, with their values and mutual relations being quite strongly dependent on the cation. The enthalpic and overall stability was the largest in the case of the sodium complex. Molecular and crystal structures of free L, its methanol and MeCN solvates, the sodium complex, and its MeCN solvate were determined by single-crystal X-ray diffraction. The inclusion of a MeCN molecule in the calixarene hydrophobic cavity was observed both in solution and in the solid state. This specific interaction was found to be stronger in the case of metal complexes compared to the free ligand because of the better preorganization of the hydrophobic cone to accept the solvent molecule. Density functional theory calculations showed that the flattened cone conformation (C(2) point group) of L was generally more favorable than the square cone conformation (C(4) point group). In the complex with Na(+), L was in square cone conformation, whereas in its adduct with MeCN, the conformation was slightly distorted from the full symmetry. These conformations were in agreement with those observed in the solid state. The classical molecular dynamics simulations indicated that the MeCN molecule enters the L hydrophobic cavity of both the free ligand and its alkali-metal complexes. The inclusion of MeCN in the cone of free L was accompanied by the conformational change from C(2) to C(4) symmetry. As in solution studies, in the case of ML(+) complexes, an allosteric effect was observed: the ligand was already in the appropriate square cone conformation to bind the solvent molecule, allowing it to more easily and faster enter the calixarene cavity.

Good Buy! Buying Home Furnishings.

ERIC Educational Resources Information Center

Thypin, Marilyn; Glasner, Lynne

A short fictional work for limited English speakers relates a young couple's experience in learning about buying home furnishings. The newly married couple need a comfortable place to sit in their living room but cannot afford to buy a sofa in one payment, and they do not qualify for credit cards. They consider the prices and credit arrangement at…

Noisy Preferences in Risky Choice: A Cautionary Note

PubMed Central

2017-01-01

We examine the effects of multiple sources of noise in risky decision making. Noise in the parameters that characterize an individual’s preferences can combine with noise in the response process to distort observed choice proportions. Thus, underlying preferences that conform to expected value maximization can appear to show systematic risk aversion or risk seeking. Similarly, core preferences that are consistent with expected utility theory, when perturbed by such noise, can appear to display nonlinear probability weighting. For this reason, modal choices cannot be used simplistically to infer underlying preferences. Quantitative model fits that do not allow for both sorts of noise can lead to wrong conclusions. PMID:28569526

N-(3,4-Dimethyl-phen-yl)-4-hydr-oxy-2-methyl-2H-1,2-benzothia-zine-3-carboxamide 1,1-dioxide.

PubMed

Siddiqui, Waseeq Ahmad; Ali, Muhammad; Zia-Ur-Rehman, Muhammad; Sharif, Saima; Tizzard, Graham John

2009-03-28

1,2-Benzothia-zines similar to the title compound, C(18)H(18)N(2)O(4)S, are well known in the literature for their biological activities and are used as medicines in the treatment of inflammation and rheumatoid arthritis. The thia-zine ring adopts a distorted half-chair conformation. The enolic H atom is involved in an intra-molecular O-H⋯O hydrogen bond, forming a six-membered ring. In the crystal, mol-ecules arrange themselves into centrosymmetric dimers by means of pairs of weak inter-molecular N-H⋯O hydrogen bonds.

Gas-Phase Structures of Linalool and Coumarin Studied by Microwave Spectroscopy

NASA Astrophysics Data System (ADS)

Nguyen, H. V. L.; Stahl, W.; Grabow, J.-U.

2013-06-01

The microwave spectra of two natural substances, linalool and coumarin, were recorded in the microwave range from 9 to 16 GHz and 8.5 to 10.5 GHz, respectively.Linalool is an acyclic monoterpene and the main component of lavender oil. It has a structure with many possible conformations. The geometry of the lowest energy conformer has been determined by a combination of microwave spectroscopy and quantum chemical calculations. Surprisingly, a globular rather than a prolate shape was found. This structure is probably stabilized by a π interaction between two double bonds which are arranged in two stacked layers of atoms within the molecule. A-E splittings due to the internal rotation of one methyl group could be resolved and the barrier to internal rotation was determined to be 400.20(64) cm^{-1}. The standard deviation of the fit was close to experimental accuracy. For an identification of the observed conformer not only the rotational constants but also the internal rotation parameters of one of the methyl groups were needed. Coumarin is a widely used flavor in perfumery as sweet woodruff scent. The aromatic structure allows solely for one planar conformer, which was found under molecular beam conditions and compared to other molecules with similar structures. Here, the rotational spectrum could be described by a set of parameters including the rotational constants and the centrifugal distortion constants using a semi-rigid molecule Hamiltonian. Furthermore, the rotational transitions of all nine ^{13}C isotopologues were measured in natural abundance. As a consequence, the microwave structure of coumarin could be almost completely determined.

Electronic structure of the metal center in the Cd(2+), Zn(2+), and Cu(2+) substituted forms of KDO8P synthase: implications for catalysis.

PubMed

Kona, Fathima; Tao, Peng; Martin, Philip; Xu, Xingjue; Gatti, Domenico L

2009-04-28

Aquifex aeolicus 3-deoxy-d-manno-octulosonate 8-phosphate synthase (KDO8PS) is active with a variety of different divalent metal ions bound in the active site. The Cd(2+), Zn(2+), and Cu(2+) substituted enzymes display similar values of k(cat) and similar dependence of K(m)(PEP) and K(m)(A5P) on both substrate and product concentrations. However, the flux-control coefficients for some of the catalytically relevant reaction steps are different in the presence of Zn(2+) or Cu(2+), suggesting that the type of metal bound in the active site affects the behavior of the enzyme in vivo. The type of metal also affects the rate of product release in the crystal environment. For example, the crystal structure of the Cu(2+) enzyme incubated with phosphoenolpyruvate (PEP) and arabinose 5-phosphate (A5P) shows the formed product, 3-deoxy-d-manno-octulosonate 8-phosphate (KDO8P), still bound in the active site in its linear conformation. This observation completes our structural studies of the condensation reaction, which altogether have provided high-resolution structures for the reactants, the intermediate, and the product bound forms of KDO8PS. The crystal structures of the Cd(2+), Zn(2+), and Cu(2+) substituted enzymes show four residues (Cys-11, His-185, Glu-222, and Asp-233) and a water molecule as possible metal ligands. Combined quantum mechanics/molecular mechanics (QM/MM) geometry optimizations reveal that the metal centers have a delocalized electronic structure, and that their true geometry is square pyramidal for Cd(2+) and Zn(2+) and distorted octahedral or distorted tetrahedral for Cu(2+). These geometries are different from those obtained by QM optimization in the gas phase (tetrahedral for Cd(2+) and Zn(2+), distorted tetrahedral for Cu(2+)) and may represent conformations of the metal center that minimize the reorganization energy between the substrate-bound and product-bound states. The QM/MM calculations also show that when only PEP is bound to the enzyme the electronic structure of the metal center is optimized to prevent a wasteful reaction of PEP with water.

Molecular dynamics simulation of the opposite-base preference and interactions in the active site of formamidopyrimidine-DNA glycosylase.

PubMed

Popov, Alexander V; Endutkin, Anton V; Vorobjev, Yuri N; Zharkov, Dmitry O

2017-05-08

Formamidopyrimidine-DNA glycosylase (Fpg) removes abundant pre-mutagenic 8-oxoguanine (oxoG) bases from DNA through nucleophilic attack of its N-terminal proline at C1' of the damaged nucleotide. Since oxoG efficiently pairs with both C and A, Fpg must excise oxoG from pairs with C but not with A, otherwise a mutation occurs. The crystal structures of several Fpg-DNA complexes have been solved, yet no structure with A opposite the lesion is available. Here we use molecular dynamic simulation to model interactions in the pre-catalytic complex of Lactococcus lactis Fpg with DNA containing oxoG opposite C or A, the latter in either syn or anti conformation. The catalytic dyad, Pro1-Glu2, was modeled in all four possible protonation states. Only one transition was observed in the experimental reaction rate pH dependence plots, and Glu2 kept the same set of interactions regardless of its protonation state, suggesting that it does not limit the reaction rate. The adenine base opposite oxoG was highly distorting for the adjacent nucleotides: in the more stable syn models it formed non-canonical bonds with out-of-register nucleotides in both the damaged and the complementary strand, whereas in the anti models the adenine either formed non-canonical bonds or was expelled into the major groove. The side chains of Arg109 and Phe111 that Fpg inserts into DNA to maintain its kinked conformation tended to withdraw from their positions if A was opposite to the lesion. The region showing the largest differences in the dynamics between oxoG:C and oxoG:A substrates was unexpectedly remote from the active site, located near the linker joining the two domains of Fpg. This region was also highly conserved among 124 analyzed Fpg sequences. Three sites trapping water molecules through multiple bonds were identified on the protein-DNA interface, apparently helping to maintain enzyme-induced DNA distortion and participating in oxoG recognition. Overall, the discrimination against A opposite to the lesion seems to be due to incorrect DNA distortion around the lesion-containing base pair and, possibly, to gross movement of protein domains connected by the linker.

Multipolar electrostatics based on the Kriging machine learning method: an application to serine.

PubMed

Yuan, Yongna; Mills, Matthew J L; Popelier, Paul L A

2014-04-01

A multipolar, polarizable electrostatic method for future use in a novel force field is described. Quantum Chemical Topology (QCT) is used to partition the electron density of a chemical system into atoms, then the machine learning method Kriging is used to build models that relate the multipole moments of the atoms to the positions of their surrounding nuclei. The pilot system serine is used to study both the influence of the level of theory and the set of data generator methods used. The latter consists of: (i) sampling of protein structures deposited in the Protein Data Bank (PDB), or (ii) normal mode distortion along either (a) Cartesian coordinates, or (b) redundant internal coordinates. Wavefunctions for the sampled geometries were obtained at the HF/6-31G(d,p), B3LYP/apc-1, and MP2/cc-pVDZ levels of theory, prior to calculation of the atomic multipole moments by volume integration. The average absolute error (over an independent test set of conformations) in the total atom-atom electrostatic interaction energy of serine, using Kriging models built with the three data generator methods is 11.3 kJ mol⁻¹ (PDB), 8.2 kJ mol⁻¹ (Cartesian distortion), and 10.1 kJ mol⁻¹ (redundant internal distortion) at the HF/6-31G(d,p) level. At the B3LYP/apc-1 level, the respective errors are 7.7 kJ mol⁻¹, 6.7 kJ mol⁻¹, and 4.9 kJ mol⁻¹, while at the MP2/cc-pVDZ level they are 6.5 kJ mol⁻¹, 5.3 kJ mol⁻¹, and 4.0 kJ mol⁻¹. The ranges of geometries generated by the redundant internal coordinate distortion and by extraction from the PDB are much wider than the range generated by Cartesian distortion. The atomic multipole moment and electrostatic interaction energy predictions for the B3LYP/apc-1 and MP2/cc-pVDZ levels are similar, and both are better than the corresponding predictions at the HF/6-31G(d,p) level.

Nominal group technique-elicited barriers and facilitators to following the Dietary Guidelines for solid fats and added sugars in children: The HEALTH Study

USDA-ARS?s Scientific Manuscript database

The US population has a high intake of discretionary solid fats and added sugars (SoFAS) which currently exceeds federal dietary recommendations. The goal of this study was to identify barriers and facilitators to following the DGA. Thirty-eight 5th grade children across six Human Nutrition Resear...

Developmental Changes in Mother-Infant Face-to-Face Communication: Birth to 3 Months.

ERIC Educational Resources Information Center

Lavelli, Manuela; Fogel, Alan

2002-01-01

Investigated development of face-to-face communication in infants between 1 and 14 weeks old and their mothers. Found a curvilinear development of early face-to-face communication, with increases occurring between weeks 4 and 9. When placed on a sofa, infants' face-to-face communication was longer than when they were held. Girls spent a longer…

Commonly used severity scores are not good predictors of mortality in sepsis from severe leptospirosis: a series of ten patients.

PubMed

Velissaris, Dimitrios; Karanikolas, Menelaos; Flaris, Nikolaos; Fligou, Fotini; Marangos, Markos; Filos, Kriton S

2012-01-01

Introduction. Severe leptospirosis, also known as Weil's disease, can cause multiorgan failure with high mortality. Scoring systems for disease severity have not been validated for leptospirosis, and there is no documented method to predict mortality. Methods. This is a case series on 10 patients admitted to ICU for multiorgan failure from severe leptospirosis. Data were collected retrospectively, with approval from the Institution Ethics Committee. Results. Ten patients with severe leptospirosis were admitted in the Patras University Hospital ICU in a four-year period. Although, based on SOFA scores, predicted mortality was over 80%, seven of 10 patients survived and were discharged from the hospital in good condition. There was no association between SAPS II or SOFA scores and mortality, but survivors had significantly lower APACHE II scores compared to nonsurvivors. Conclusion. Commonly used severity scores do not seem to be useful in predicting mortality in severe leptospirosis. Early ICU admission and resuscitation based on a goal-directed therapy protocol are recommended and may reduce mortality. However, this study is limited by retrospective data collection and small sample size. Data from large prospective studies are needed to validate our findings.

About the structural role of disulfide bridges in serum albumins: evidence from protein simulated unfolding.

PubMed

Paris, Guillaume; Kraszewski, Sebastian; Ramseyer, Christophe; Enescu, Mironel

2012-11-01

The role of the 17 disulfide (S-S) bridges in preserving the native conformation of human serum albumin (HSA) is investigated by performing classical molecular dynamics (MD) simulations on protein structures with intact and, respectively, reduced S-S bridges. The thermal unfolding simulations predict a clear destabilization of the protein secondary structure upon reduction of the S-S bridges as well as a significant distortion of the tertiary structure that is revealed by the changes in the protein native contacts fraction. The effect of the S-S bridges reduction on the protein compactness was tested by calculating Gibbs free energy profiles with respect to the protein gyration radius. The theoretical results obtained using the OPLS-AA and the AMBER ff03 force fields are in agreement with the available experimental data. Beyond the validation of the simulation method, the results here reported provide new insights into the mechanism of the protein reductive/oxidative unfolding/folding processes. It is predicted that in the native conformation of the protein, the thiol (-SH) groups belonging to the same reduced S-S bridge are located in potential wells that maintain them in contact. The -SH pairs can be dispatched by specific conformational transitions of the peptide chain located in the neighborhood of the cysteine residues. Copyright © 2012 Wiley Periodicals, Inc.

Conformational Characteristics of Poly(tetrafluoroethylene) (PTFE) Based Upon Ab Initio Electronic Structure Calculations on Model Molecules

NASA Technical Reports Server (NTRS)

Smith, Grant D.; Jaffe, R. L.; Yoon, D. Y.; Arnold, James O. (Technical Monitor)

1994-01-01

Conformational energy contours of perfluoroalkanes, determined from ab initio calculations, confirm the well-known spitting of trans states into two minima at plus or minus 17 degrees but also show that the gauche states split as well, with minima at plus or minus 124 degrees and plus or minus 84 in order to relieve steric crowding. The directions of such split distortions from the perfectly staggered states are strongly coupled for adjacent pairs of bonds in a manner identical to the intradyad pair for poly (isobutylene) chains. These conformational characteristics are fully represented by a six-state rotational isomeric state (RIS) model for PTFE comprised of t(+), t(-), g(sup +)+, g(sup +)-, g(sup -) + and g(sup -)-states, located at the split energy minima. The resultant 6 x 6 statistical weight matrix is described by first-order interaction parameters for the g+(+) (ca. 0.6 kcal/mol) and g+- (ca. 2.0 kcal/mol) states, and second order parameters for the g(sup +)+g(sup +)+ (ca 0.6 kcal/mol) and g(sup +)+g(sup -)+ (ca. 1.0 kcal/mol) states. This six-state RIS model, without adjustment of the geometric or energy parameters as determined from the ab initio calculations, predicts the unperturbed chain dimensions and the fraction of gauche bonds as a function of temperature for PTFE in good agreement with available experimental values.

Experimental Raman and IR spectral and theoretical studies of vibrational spectrum and molecular structure of Pantothenic acid (vitamin B5)

NASA Astrophysics Data System (ADS)

Srivastava, Mayuri; Singh, N. P.; Yadav, R. A.

2014-08-01

Vibrational spectrum of Pantothenic acid has been investigated using experimental IR and Raman spectroscopies and density functional theory methods available with the Gaussian 09 software. Vibrational assignments of the observed IR and Raman bands have been proposed in light of the results obtained from computations. In order to assign the observed IR and Raman frequencies the potential energy distributions (PEDs) have also been computed using GAR2PED software. Optimized geometrical parameters suggest that the overall symmetry of the molecule is C1. The molecule is found to possess eight conformations. Conformational analysis was carried out to obtain the most stable configuration of the molecule. In the present paper the vibrational features of the lowest energy conformer C-I have been studied. The two methyl groups have slightly distorted symmetries from C3V. The acidic Osbnd H bond is found to be the smallest one. To investigate molecular stability and bond strength we have used natural bond orbital analysis (NBO). Charge transfer occurs in the molecule have been shown by the calculated highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energies. The mapping of electron density iso-surface with electrostatic potential (ESP), has been carried out to get the information about the size, shape, charge density distribution and site of chemical reactivity of the molecule.

A human transcription factor in search mode.

PubMed

Hauser, Kevin; Essuman, Bernard; He, Yiqing; Coutsias, Evangelos; Garcia-Diaz, Miguel; Simmerling, Carlos

2016-01-08

Transcription factors (TF) can change shape to bind and recognize DNA, shifting the energy landscape from a weak binding, rapid search mode to a higher affinity recognition mode. However, the mechanism(s) driving this conformational change remains unresolved and in most cases high-resolution structures of the non-specific complexes are unavailable. Here, we investigate the conformational switch of the human mitochondrial transcription termination factor MTERF1, which has a modular, superhelical topology complementary to DNA. Our goal was to characterize the details of the non-specific search mode to complement the crystal structure of the specific binding complex, providing a basis for understanding the recognition mechanism. In the specific complex, MTERF1 binds a significantly distorted and unwound DNA structure, exhibiting a protein conformation incompatible with binding to B-form DNA. In contrast, our simulations of apo MTERF1 revealed significant flexibility, sampling structures with superhelical pitch and radius complementary to the major groove of B-DNA. Docking these structures to B-DNA followed by unrestrained MD simulations led to a stable complex in which MTERF1 was observed to undergo spontaneous diffusion on the DNA. Overall, the data support an MTERF1-DNA binding and recognition mechanism driven by intrinsic dynamics of the MTERF1 superhelical topology. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

High resolution spectroscopy of 1,2-difluoroethane in a molecular beam: A case study of vibrational mode-coupling

NASA Astrophysics Data System (ADS)

Mork, Steven W.; Miller, C. Cameron; Philips, Laura A.

1992-09-01

The high resolution infrared spectrum of 1,2-difluoroethane (DFE) in a molecular beam has been obtained over the 2978-2996 cm-1 spectral region. This region corresponds to the symmetric combination of asymmetric C-H stretches in DFE. Observed rotational fine structure indicates that this C-H stretch is undergoing vibrational mode coupling to a single dark mode. The dark mode is split by approximately 19 cm-1 due to tunneling between the two identical gauche conformers. The mechanism of the coupling is largely anharmonic with a minor component of B/C plane Coriolis coupling. Effects of centrifugal distortion along the molecular A-axis are also observed. Analysis of the fine structure identifies the dark state as being composed of C-C torsion, CCF bend, and CH2 rock. Coupling between the C-H stretches and the C-C torsion is of particular interest because DFE has been observed to undergo vibrationally induced isomerization from the gauche to trans conformer upon excitation of the C-H stretch.

Synthon preference in the cocrystal of 3,4,5-trifluorophenylboronic acid with urea.

PubMed

Kopczyńska, Karolina; Marek, Paulina H; Banaś, Bartłomiej; Madura, Izabela D

2017-11-01

The comprehensive description of the crystal structure of a novel 1:1 cocrystal of 3,4,5-trifluorophenylboronic acid with urea, C 6 H 4 BF 3 O 2 ·CH 4 N 2 O, is presented. Both components are good candidates for crystal engineering as they can create a variety of supramolecular synthons. The preference for the formation of different hetrosynthons is verified based on theoretical calculations. The syn-anti conformation of boronic acid has been found to be the most favourable in the formation of intermolecular interactions with urea. Moreover, the distortions present in the boron coordination sphere have been described quantitatively based on experimental data according to bond-valence vector model calculations. The results revealed that the deformation of the sphere is typical for a syn-anti conformation of boronic acids. The supramolecular structure of the cocrystal is composed of large synthons in the form of layers made up of O-H...O and N-H...O hydrogen bonds. The layers are joined via N-H...F hydrogen bonds which are unusual for urea cocrystal structures.

Structures of RNA Polymerase Closed and Intermediate Complexes Reveal Mechanisms of DNA Opening and Transcription Initiation.

PubMed

Glyde, Robert; Ye, Fuzhou; Darbari, Vidya Chandran; Zhang, Nan; Buck, Martin; Zhang, Xiaodong

2017-07-06

Gene transcription is carried out by RNA polymerases (RNAPs). For transcription to occur, the closed promoter complex (RPc), where DNA is double stranded, must isomerize into an open promoter complex (RPo), where the DNA is melted out into a transcription bubble and the single-stranded template DNA is delivered to the RNAP active site. Using a bacterial RNAP containing the alternative σ 54 factor and cryoelectron microscopy, we determined structures of RPc and the activator-bound intermediate complex en route to RPo at 3.8 and 5.8 Å. Our structures show how RNAP-σ 54 interacts with promoter DNA to initiate the DNA distortions required for transcription bubble formation, and how the activator interacts with RPc, leading to significant conformational changes in RNAP and σ 54 that promote RPo formation. We propose that DNA melting is an active process initiated in RPc and that the RNAP conformations of intermediates are significantly different from that of RPc and RPo. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Ring-to-chain conformation may be a determining factor in the ability of xanthophylls to bind to the bulk light-harvesting complex of plants

NASA Astrophysics Data System (ADS)

Young, Andrew J.; Phillip, Denise M.; Hashimoto, Hideki

2002-12-01

The binding of xanthophylls to the main light-harvesting complex (LHC) of higher plants has been studied using the technique of in vitro reconstitution. This demonstrated that the carotenoid diol lactucaxanthin (native to many LHC) would not support the assembly of LHC whilst other diols, notably zeaxanthin and lutein would. Analysis of the most stable forms of the carotenoid end-groups found in xanthophylls native to higher plant LHC (as determined by theoretical calculations) revealed profound differences in the adiabatic potential energy curves for the C5-C6-C7-C8-torsion angle for the ɛ end-groups in lactucaxanthin (6-s- trans), in comparison to carotenoids possessing a 3-hydroxy β end-group (zeaxanthin; 6-s- cis), 3-hydroxy-4-keto β end-group (astaxanthin, 6-s- cis) or a 3-hydroxy-5,6-epoxy end-group (violaxanthin, distorted 6-s- cis). The (ɛ end-groups of other carotenoids studied were 6-s- trans. We examine the possible relationship between carotenoid ring-to-chain conformation and binding to LHC.

Synthesis, X-ray crystallography, and computational analysis of 1-azafenestranes.

PubMed

Denmark, Scott E; Montgomery, Justin I; Kramps, Laurenz A

2006-09-06

The tandem [4+2]/[3+2] cycloaddition of nitroalkenes has been employed in the synthesis of 1-azafenestranes, molecules of theoretical interest because of planarizing distortion of their central carbon atoms. The synthesis of c,c,c,c-[5.5.5.5]-1-azafenestrane was completed in good yield from a substituted nitrocyclopentene, and its borane adduct was analyzed through X-ray crystallography, which showed a moderate distortion from ideal tetrahedral geometry. The syntheses of two members of the [4.5.5.5] family of 1-azafenestranes are also reported, including one with a trans fusion at a bicyclic ring junction which brings about considerable planarization of one of the central angles (16.8 degrees deviation from tetrahedral geometry). While investigating the [4.5.5.5]-1-azafenestranes, a novel dyotropic rearrangement that converts nitroso acetals into tetracyclic aminals was discovered. Through conformational analysis, a means to prevent this molecular reorganization was formulated and realized experimentally with the use of a bulky vinyl ether in the key [4+2] cycloaddition reaction. Finally, DFT calculations on relative strain energy for the 1-azafenestranes, as well as their predicted central angles, are disclosed.

Theoretical and experimental investigations of coincidences in Poisson distributed pulse trains and spectral distortion caused by pulse pileup

NASA Astrophysics Data System (ADS)

Bristow, Quentin

1990-03-01

The occurrence rates of pulse strings, or sequences of pulses with interarrival times less than the resolving time of the pulse-height analysis system used to acquire spectra, are derived from theoretical considerations. Logic circuits were devised to make experimental measurements of multiple pulse string occurrence rates in the output from a scintillation detector over a wide range of count rates. Markov process theory was used to predict state transition rates in the logic circuits, enabling the experimental data to be checked rigorously for conformity with those predicted for a Poisson distribution. No fundamental discrepancies were observed. Monte Carlo simulations, incorporating criteria for pulse pileup inherent in the operation of modern analog to digital converters, were used to generate pileup spectra due to coincidences between two pulses (first order pileup) and three pulses (second order pileup) for different semi-Gaussian pulse shapes. Coincidences between pulses in a single channel produced a basic probability density function spectrum. The use of a flat spectrum showed the first order pileup distorted the spectrum to a linear ramp with a pileup tail. A correction algorithm was successfully applied to correct entire spectra (simulated and real) for first and second order pileups.

Distortions induced in double-stranded oligonucleotides by the binding of cis- or trans-diammine-dichloroplatinum(II) to the d(GTG) sequence.

PubMed Central

Anin, M F; Leng, M

1990-01-01

Conformational changes induced in double-stranded oligonucleotides by the binding of trans- or cis-diamminedichloro platinum(II) to the d(GTG) sequence have been characterized by means of melting temperatures, electrophoretic migrations in non-denaturing polyacrylamide gels, reactivities with the artificial nuclease Phenanthroline-copper and with chemical probes. The cis-platinum adduct behaves more as a centre of directed bend than as a hinge joint, the induced bend angle being of the order of 25-30 degrees. The double helix is locally denatured over 2 base pairs (corresponding to the platinated 5'G residue and the central T residue) and is distorted over 4-5 base pairs. The trans-platinum adduct behaves also more as a centre of directed bend than as a hinge joint, the induced bend angle being of the order of 60 degrees. The double helix is locally denatured over 4 base pairs (corresponding to the immediately 5'T residue adjacent to the adduct and to the three base residues of the adduct). Both the cis- and trans-platinum adducts decrease the thermal stability of the double helix. Images PMID:2388824

Crystal structure of bis-[tetra-kis-(tetra-hydro-furan-κO)lithium] bis[μ-2,2',2''-methanetriyltris(4,6-di-tert-butylphenolato)-κ4O,O':O',O'']-dimagnesiate.

PubMed

Zhou, Hongyan; Wang, Lei

2017-07-01

The title ion-association metal complex, [Li(C 4 H 8 O) 4 ] 2 [Mg 2 (C 43 H 61 O 3 ) 2 ], has been synthesized from the tridentate phenolic ligand tris-(3,5-di- tert -butyl-2-hy-droxy-phen-yl)methane in tetra-hydro-furan (THF). The aryl-oxo magnesiate complex anion is binuclear with each Mg 2 O 4 complex unit inversion-related and bridged through the two tridentate chelating phenolate O-donors of the ligand. The complex centres have a distorted tetra-hedral stereochemistry [Mg-O range 1.8796 (17)-2.0005 (16) Å] and an Mg⋯Mg separation of 2.9430 (14) Å]. The LiO 4 coodination sphere of the cation comprises four THF O-donor atoms and has a slightly distorted tetra-hedral conformation [Li-O range 1.899 (5)- 1.953 (5) Å]. In the crystal, a number of stabilizing intra-anion C-H⋯O hydrogen-bonding inter-actions are present but no inter-species associations are found.

A proposal for the molecular basis of μ and δ opiate receptor differentiation based on modeling of two types of cyclic enkephalins and a narcotic alkaloid

NASA Astrophysics Data System (ADS)

Michel, André; Villeneuve, Gérald; DiMaio, John

1991-12-01

The molecular basis underlying the divergent receptor selectivity of two cyclic opioid peptides Tyr-c[ N δ- d-Orn2-Gly-Phe-Leu-] (c-ORN) and [ d-Pen2, l-Cys5]-enkephalinamide (c-PEN) was investigated using a molecular modeling approach. Ring closure and conformational searching procedures were used to determine low-energy cyclic backbone conformers. Following reinsertion of amino acid side chains, the narcotic alkaloid 7α-[(1R)-1-methyl-1-hydroxy-3-phenylpropyl]-6,14-endoethenotetrahydro oripavine (PEO) was used as a flexible template for bimolecular superpositions with each of the determined peptide ring conformers using the coplanarity and cocentricity of the phenolic rings as the minimum constraint. A vector space of PEO, accounting for all possible orientations for the C21-aromatic ring of PEO served as a geometrical locus for the aromatic ring of the Phe4 residue in the opioid peptides. Although a vast number of polypeptide conformations satisfied the criteria of the opiate pharmacophore, they could be grouped into three classes differing in magnitude and sign of the torsional angle values of the tyrosyl side chain. Only class III conformers for both c-ORN and c-PEN, having tyramine dihedral angles χ1 =-150° ± 30° and χ2=-155° ± 20°, had significant structural and conformational properties that were mutually compatible while respecting the PEO vector space. Comparison of these properties in the context of the divergent receptor selectivity of the studied opioid peptides suggests that the increased distortion of the peptide backbone in the closure region of c-PEN together with the pendant β,β-dimethyl group, combine to generate a steric volume which is absent in c-ORN and that may be incompatible with a restrictive topography of the μ receptor. The nature and stereo-chemistry of substituents adjacent to the closure region of the peptides could also modulate receptor selection by interacting with a charged (δ) or neutral (μ) subsite.

MCCE2: improving protein pKa calculations with extensive side chain rotamer sampling.

PubMed

Song, Yifan; Mao, Junjun; Gunner, M R

2009-11-15

Multiconformation continuum electrostatics (MCCE) explores different conformational degrees of freedom in Monte Carlo calculations of protein residue and ligand pK(a)s. Explicit changes in side chain conformations throughout a titration create a position dependent, heterogeneous dielectric response giving a more accurate picture of coupled ionization and position changes. The MCCE2 methods for choosing a group of input heavy atom and proton positions are described. The pK(a)s calculated with different isosteric conformers, heavy atom rotamers and proton positions, with different degrees of optimization are tested against a curated group of 305 experimental pK(a)s in 33 proteins. QUICK calculations, with rotation around Asn and Gln termini, sampling His tautomers and torsion minimum hydroxyls yield an RMSD of 1.34 with 84% of the errors being <1.5 pH units. FULL calculations adding heavy atom rotamers and side chain optimization yield an RMSD of 0.90 with 90% of the errors <1.5 pH unit. Good results are also found for pK(a)s in the membrane protein bacteriorhodopsin. The inclusion of extra side chain positions distorts the dielectric boundary and also biases the calculated pK(a)s by creating more neutral than ionized conformers. Methods for correcting these errors are introduced. Calculations are compared with multiple X-ray and NMR derived structures in 36 soluble proteins. Calculations with X-ray structures give significantly better pK(a)s. Results with the default protein dielectric constant of 4 are as good as those using a value of 8. The MCCE2 program can be downloaded from http://www.sci.ccny.cuny.edu/~mcce. 2009 Wiley Periodicals, Inc.

Local Anesthetics in the Gas-Phase the Rotational Spectrum of Butamben and Isobutamben

NASA Astrophysics Data System (ADS)

Vallejo-López, Montserrat; Ecija, Patricia; Caminati, Walther; Grabow, Jens-Uwe; Lesarri, Alberto; Cocinero, Emilio J.

2016-06-01

Benzocaine (BZ), butamben (BTN) and isobutamben (BTI) are local anesthetics characterized by a hydrophilic head and a lipophilic aliphatic tail linked by an aminobenzoate group. Previous rotational work on BZ (H2N-C6H4-COO-Et) showed that its ethyl aliphatic tail may adopt either in-plane (trans) or out of plane (gauche) conformations, with a low interconversion barrier below 50 cm-1. Here we extend the rotational study to BTN and BTI, isolated in a supersonic jet expansion and vaporized either by heating or UV ps-laser ablation methods. Both molecules share a 14 heavy-atoms skeleton, differing in their butyl (-(CH2)3-CH3) or isobutyl (-CH2-CH(CH3)2) four-carbon tail. We detected a single conformer for BTN and two conformers for BTI. The two molecules do not adopt an all-trans carbon skeleton. Conversely, the β-ethyl carbon in BTN is gauche. For BTI the β-carbon may be either trans or gauche. The microwave spectrum covered the cm- (BTN, BTI, 6-18 GHz) and mm-wave (BTW, 50-75 GHz) frequency ranges.In all the cases, rotational and centrifugal distortion constants as well as the diagonal elements of the 14N nuclear quadrupole coupling tensor were accurate determined and compared to the theoretical results (ab initio and DFT). No transitions belonging to configurations predicted as higher minima of the PES were found, pointing out that conformational interconversions may take place in the jet. A. Lesarri, S. T. Shipman, G. G. Brown, L. Alvarez-Valtierra, R. D. Suenram, B. H. Pate, Int. Symp. Mol. Spectrosc., 2008, Comm. RH07. E. Aguado, A. Longarte, E. Alejandro, J. A. Fernández, F. Castaño, J. Phys. Chem. A, 2006, 110, 6010.

Twisting a β-Carotene, an Adaptive Trick from Nature for Dissipating Energy during Photoprotection*

PubMed Central

Sobotka, Roman; Kish, Elizabeth; Shukla, Mahendra Kumar; Pascal, Andrew A.; Polívka, Tomáš; Robert, Bruno

2017-01-01

Cyanobacteria possess a family of one-helix high light-inducible proteins (Hlips) that are homologous to light-harvesting antenna of plants and algae. An Hlip protein, high light-inducible protein D (HliD) purified as a small complex with the Ycf39 protein is evaluated using resonance Raman spectroscopy. We show that the HliD binds two different β-carotenes, each present in two non-equivalent binding pockets with different conformations, having their (0,0) absorption maxima at 489 and 522 nm, respectively. Both populations of β-carotene molecules were in all-trans configuration and the absorption position of the farthest blue-shifted β-carotene was attributed entirely to the polarizability of the environment in its binding pocket. In contrast, the absorption maximum of the red-shifted β-carotene was attributed to two different factors: the polarizability of the environment in its binding pocket and, more importantly, to the conformation of its β-rings. This second β-carotene has highly twisted β-rings adopting a flat conformation, which implies that the effective conjugation length N is extended up to 10.5 modifying the energetic levels. This increase in N will also result in a lower S1 energy state, which may provide a permanent energy dissipation channel. Analysis of the carbonyl stretching region for chlorophyll a excitations indicates that the HliD binds six chlorophyll a molecules in five non-equivalent binding sites, with at least one chlorophyll a presenting a slight distortion to its macrocycle. The binding modes and conformations of HliD-bound pigments are discussed with respect to the known structures of LHCII and CP29. PMID:27994060

Interplay between membrane curvature and protein conformational equilibrium investigated by solid-state NMR.

PubMed

Liao, Shu Y; Lee, Myungwoon; Hong, Mei

2018-03-01

Many membrane proteins sense and induce membrane curvature for function, but structural information about how proteins modulate their structures to cause membrane curvature is sparse. We review our recent solid-state NMR studies of two virus membrane proteins whose conformational equilibrium is tightly coupled to membrane curvature. The influenza M2 proton channel has a drug-binding site in the transmembrane (TM) pore. Previous chemical shift data indicated that this pore-binding site is lost in an M2 construct that contains the TM domain and a curvature-inducing amphipathic helix. We have now obtained chemical shift perturbation, protein-drug proximity, and drug orientation data that indicate that the pore-binding site is restored when the full cytoplasmic domain is present. This finding indicates that the curvature-inducing amphipathic helix distorts the TM structure to interfere with drug binding, while the cytoplasmic tail attenuates this effect. In the second example, we review our studies of a parainfluenza virus fusion protein that merges the cell membrane and the virus envelope during virus entry. Chemical shifts of two hydrophobic domains of the protein indicate that both domains have membrane-dependent backbone conformations, with the β-strand structure dominating in negative-curvature phosphatidylethanolamine (PE) membranes. 31 P NMR spectra and 1 H- 31 P correlation spectra indicate that the β-strand-rich conformation induces saddle-splay curvature to PE membranes and dehydrates them, thus stabilizing the hemifusion state. These results highlight the indispensable role of solid-state NMR to simultaneously determine membrane protein structures and characterize the membrane curvature in which these protein structures exist. Copyright © 2018 Elsevier Inc. All rights reserved.

N-(2,3-Dimethyl-phen-yl)-4-hydr-oxy-2-methyl-2H-1,2-benzothia-zine-3-carboxamide 1,1-dioxide.

PubMed

Siddiqui, Waseeq Ahmad; Bukahari, Iftikhar Hussain; Zia-Ur-Rehman, Muhammad; Khan, Islam Ullah; Tizzard, Graham John

2009-02-28

In the crystal structure of the title compound, C(18)H(18)N(2)O(4)S, the thia-zine ring adopts a distorted half-chair conformation. 1,2-Benzothia-zines of this kind have a wide range of biological activities and are mainly used as medicines in the treatment of inflammation and rheumatoid arthritis. The enolic H atom is involved in an intra-molecular O-H⋯O hydrogen bond, forming a six-membered ring. The mol-ecules arrange themselves into centrosymmetric dimers by means of inter-molecular N-H⋯O hydrogen bonds. A weak inter-molcular C-H⋯O inter-action is also present.

N-(3,4-Dimethyl­phen­yl)-4-hydr­oxy-2-methyl-2H-1,2-benzothia­zine-3-carboxamide 1,1-dioxide

PubMed Central

Siddiqui, Waseeq Ahmad; Ali, Muhammad; Zia-ur-Rehman, Muhammad; Sharif, Saima; Tizzard, Graham John

2009-01-01

1,2-Benzothia­zines similar to the title compound, C18H18N2O4S, are well known in the literature for their biological activities and are used as medicines in the treatment of inflammation and rheumatoid arthritis. The thia­zine ring adopts a distorted half-chair conformation. The enolic H atom is involved in an intra­molecular O—H⋯O hydrogen bond, forming a six-membered ring. In the crystal, mol­ecules arrange themselves into centrosymmetric dimers by means of pairs of weak inter­molecular N—H⋯O hydrogen bonds. PMID:21582605

Diethylpyrocarbonate and permanganate provide evidence for an unusual DNA conformation induced by binding of the antitumour antibiotics bleomycin and phleomycin.

PubMed Central

Fox, K R; Grigg, G W

1988-01-01

DNA structural changes induced by bleomycin have been investigated using diethylpyrocarbonate and permanganate as probes under conditions in which the antibiotic binds to, but does not cut the DNA. Diethyl-pyrocarbonate shows an enhanced reaction with adenines in the presence of the antibiotic in the sequences GTA greater than GCA greater than GAA, on the 3' side of the drug cutting site (GPy). Permanganate ions display an enhanced reactivity at the second pyrimidine of the sequence GPyPy. The results are consistent with a model in which bleomycin distorts the structure of the base pair on the 3' side of its binding site. Images PMID:2451809

Noisy preferences in risky choice: A cautionary note.

PubMed

Bhatia, Sudeep; Loomes, Graham

2017-10-01

We examine the effects of multiple sources of noise in risky decision making. Noise in the parameters that characterize an individual's preferences can combine with noise in the response process to distort observed choice proportions. Thus, underlying preferences that conform to expected value maximization can appear to show systematic risk aversion or risk seeking. Similarly, core preferences that are consistent with expected utility theory, when perturbed by such noise, can appear to display nonlinear probability weighting. For this reason, modal choices cannot be used simplistically to infer underlying preferences. Quantitative model fits that do not allow for both sorts of noise can lead to wrong conclusions. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Where Should Infants Sleep? A Comparison of Risk for Suffocation of Infants Sleeping in Cribs, Adult Beds, and Other Sleeping Locations

ERIC Educational Resources Information Center

Maloney, Michael J.

2004-01-01

Objectives: To ascertain whether the number of sudden infant deaths as a result of suffocation in cribs, in adult beds, on sofas or chairs, and on other sleep surfaces was increasing whether attributable to increased reporting, diagnostic shift, or an actual increase in suffocation deaths and to compare the risk of reported accidental suffocation…

Arterial to end-tidal carbon dioxide tension difference (CO2 gap) as a prognostic marker for adverse outcomes in emergency department patients presenting with suspected sepsis.

PubMed

Shetty, Amith; Sparenberg, Sebastian; Adams, Kristian; Selvedran, Selwyn; Tang, Benjamin; Hanna, Kim; Iredell, Jonathan

2018-05-13

The arterial to end-tidal carbon dioxide tension difference (CO 2 gap) correlates with physiologic dead space. The prognostic value of increased CO 2 gap in trauma and respiratory distress patients is documented. Transpulmonary arteriovenous shunting is identified as a predictor of mortality in non-pulmonary sepsis. We set out to investigate the prognostic value of the CO 2 gap in a pilot study of patients with suspected sepsis from non-respiratory causes. Patients presenting to tertiary Australian ED with suspected sepsis (n = 215) underwent near-simultaneous end-tidal carbon dioxide and partial pressure of carbon dioxide measurements. We investigated the correlation of CO 2 gap levels with the primary outcome of in-hospital mortality (IHM) and secondary outcomes of sepsis (ΔSOFA ≥2) and IHM and/or intensive care unit stay ≥72 h (IHM/ICU72h) in patients with sepsis because of non-respiratory causes. Among patients included in the analysis (n = 165), the CO 2 gap showed modest positive correlation with qSOFA (ρ = 0.39) and weak positive correlation with SOFA scores (ρ = 0.29) (both P < 0.01). The CO 2 gap had modest predictive value for primary outcome (IHM), area under receiver operating curve (AUROC 0.85, 95% confidence interval [CI] 0.78-0.90) and IHM/ICU72h outcome (AUROC 0.80, 95% CI 0.73-0.86), but lower predictive value for sepsis outcome (AUROC 0.64, 95% CI 0.55-0.71) (all P < 0.001). We report modest test performance for primary outcome at CO 2 gap ≥5 and ≥10 mmHg cut-offs. In this pilot study of patients with suspected sepsis from non-respiratory causes, an increased CO 2 gap demonstrates value in risk stratification and needs to be further evaluated and compared to other existent biomarkers. © 2018 Australasian College for Emergency Medicine & Australasian Society for Emergency Medicine.

Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

PubMed Central

Galeiras, Rita; Mourelo, Mónica; Pértega, Sonia; Lista, Amanda; Ferreiro, Mª Elena; Salvador, Sebastián; Montoto, Antonio; Rodríguez, Antonio

2016-01-01

Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study Design and Setting: This was an observational, retrospective study. Patient Sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome Measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and Methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006–2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%–58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%–65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients with acute traumatic SCI admitted to the ICU, and renal dysfunction occurs in half of the cases. Creatinine values should be requested starting at the admission while neither the peak CPK values nor the hemodynamic SOFA scores could be used to properly discriminate between patients with and without renal dysfunction. PMID:27688625

An Evaluation of the Usefulness of Extracorporeal Liver Support Techniques in Patients Hospitalized in the ICU for Severe Liver Dysfunction Secondary to Alcoholic Liver Disease

PubMed Central

Piechota, Mariusz; Piechota, Anna

2016-01-01

Background The mortality rate in patients with severe liver dysfunction secondary to alcoholic liver disease (ALD) who do not respond to the standard treatment is exceptionally high. Objectives The main aim of this study was to evaluate the usefulness of applying extracorporeal liver support techniques to treat this group of patients. Patients and Methods The data from 23 hospital admissions of 21 patients with ALD who were admitted to the department of anesthesiology and intensive therapy (A&IT) at the Dr Wł. Biegański Regional Specialist Hospital in Łódź between March 2013 and July 2015 were retrospectively analyzed. Results A total of 111 liver dialysis procedures were performed during the 23 hospitalizations, including 13 dialyses using fractionated plasma separation and adsorption (FPSA) with the Prometheus® system, and 98 procedures using the single pass albumin dialysis (SPAD) system. Upon admission to the intensive care unit (ICU), the median (interquartile range [IQR]) Glasgow coma scale (GCS), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation (APACHE) II, and simplified acute physiology score (SAPS) II scores were 15 (14 - 15), 9 (7 - 13), 17 (14 - 24), and 32 (22 - 50), respectively. The ICU, 30-day, and three-month mortality rates were 43.48%, 39.13%, and 73.91%, respectively. As determined by the receiver operative characteristic (ROC) analysis for single-factor models, the significant predictors of death in the ICU included the patients’ SOFA, APACHE II, SAPS II, and model of end-stage liver disease modified by the united network for organ sharing (MELD UNOS Modification) scores; the duration of stay (in days) in the A&IT Department; and bile acid, creatinine and albumin levels upon ICU admission. The ROC analysis indicated the significant discriminating power of the SOFA, APACHE II, SAPS II, and MELD UNOS modification scores on the three-month mortality rate. Conclusions The application of extracorporeal liver support techniques in patients with severe liver dysfunction secondary to ALD appears justified in the subset of patients with MELD UNOS Modification scores of 18 - 30. PMID:27642344

Clinical course of sepsis, severe sepsis, and septic shock in a cohort of infected patients from ten Colombian hospitals

PubMed Central

2013-01-01

Background Sepsis has several clinical stages, and mortality rates are different for each stage. Our goal was to establish the evolution and the determinants of the progression of clinical stages, from infection to septic shock, over the first week, as well as their relationship to 7-day and 28-day mortality. Methods This is a secondary analysis of a multicenter cohort of inpatients hospitalized in general wards or intensive care units (ICUs). The general estimating equations (GEE) model was used to estimate the risk of progression and the determinants of stages of infection over the first week. Cox regression with time-dependent covariates and fixed covariates was used to determine the factors related with 7-day and 28-day mortality, respectively. Results In 2681 patients we show that progression to severe sepsis and septic shock increases with intraabdominal and respiratory sources of infection [OR = 1,32; 95%IC = 1,20-1,46 and OR = 1.21, 95%CI = 1,11-1,33 respectively], as well as according to Acute Physiology and Chronic Health Evaluation II (APACHE II) [OR = 1,03; 95%CI = 1,02-1,03] and Sequential Organ Failure Assessment (SOFA) [OR = 1,16; 95%CI = 1,14-1,17] scores. The variables related with first-week mortality were progression to severe sepsis [HR = 2,13; 95%CI = 1,13-4,03] and septic shock [HR = 3,00; 95%CI = 1,50-5.98], respiratory source of infection [HR = 1,76; 95%IC = 1,12-2,77], APACHE II [HR = 1,07; 95% CI = 1,04-1,10] and SOFA [HR = 1,09; 95%IC = 1,04-1,15] scores. Conclusions Intraabdominal and respiratory sources of infection, independently of SOFA and APACHE II scores, increase the risk of clinical progression to more severe stages of sepsis; and these factors, together with progression of the infection itself, are the main determinants of 7-day and 28-day mortality. PMID:23883312

Biomarkers of Endothelial Activation Are Associated with Poor Outcome in Critical Illness.

PubMed

Mikacenic, Carmen; Hahn, William O; Price, Brenda L; Harju-Baker, Susanna; Katz, Ronit; Kain, Kevin C; Himmelfarb, Jonathan; Liles, W Conrad; Wurfel, Mark M

2015-01-01

Endothelial activation plays a role in organ dysfunction in the systemic inflammatory response syndrome (SIRS). Angiopoietin-1 (Ang-1) promotes vascular quiescence while angiopoietin-2 (Ang-2) mediates microvascular leak. Circulating levels of Ang-1 and Ang-2 in patients with SIRS could provide insight on risks for organ dysfunction and death distinct from inflammatory proteins. In this study, we determined if biomarkers of endothelial activation and inflammation exhibit independent associations with poor outcomes in SIRS. We studied 943 critically ill patients with SIRS admitted to an Intensive Care Unit (ICU) of an academic medical center. We measured plasma levels of endothelial markers (Ang-1, Ang-2, soluble vascular cell adhesion molecule-1 (sVCAM-1)) and inflammatory markers (interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-colony stimulating factor (G-CSF), soluble tumor necrosis factor receptor-1 (sTNFR-1)) within 24 hours of enrollment. We tested for associations between each marker and 28 day mortality, shock, and day 3 sequential organ failure assessment (SOFA) score. For 28 day mortality, we performed sensitivity analysis for those subjects with sepsis and those with sterile inflammation. We used multivariate models to adjust for clinical covariates and determine if associations identified with endothelial activation markers were independent of those observed with inflammatory markers. Higher levels of all biomarkers were associated with increased 28 day mortality except levels of Ang-1 which were associated with lower mortality. After adjustment for comorbidities and sTNFR-1 concentration, a doubling of Ang-1 concentration was associated with lower 28 day mortality (Odds ratio (OR) = 0.81; p<0.01), shock (OR = 0.82; p<0.001), and SOFA score (β = -0.50; p<0.001), while Ang-2 concentration was associated with increased mortality (OR = 1.55; p<0.001), shock (OR = 1.51; p<0.001), and SOFA score (β = +0.63; p<0.001). sVCAM-1 was not independently associated with SIRS outcomes. In critically ill patients with SIRS, early measurements of Ang-1 and Ang-2 are associated with death and organ dysfunction independently of simultaneously-measured markers of inflammation.

Risk Factors for Noninvasive Ventilation Failure in Critically Ill Subjects With Confirmed Influenza Infection.

PubMed

Rodríguez, Alejandro; Ferri, Cristina; Martin-Loeches, Ignacio; Díaz, Emili; Masclans, Joan R; Gordo, Federico; Sole-Violán, Jordi; Bodí, María; Avilés-Jurado, Francesc X; Trefler, Sandra; Magret, Monica; Moreno, Gerard; Reyes, Luis F; Marin-Corral, Judith; Yebenes, Juan C; Esteban, Andres; Anzueto, Antonio; Aliberti, Stefano; Restrepo, Marcos I

2017-10-01

Despite wide use of noninvasive ventilation (NIV) in several clinical settings, the beneficial effects of NIV in patients with hypoxemic acute respiratory failure (ARF) due to influenza infection remain controversial. The aim of this study was to identify the profile of patients with risk factors for NIV failure using chi-square automatic interaction detection (CHAID) analysis and to determine whether NIV failure is associated with ICU mortality. This work was a secondary analysis from prospective and observational multi-center analysis in critically ill subjects admitted to the ICU with ARF due to influenza infection requiring mechanical ventilation. Three groups of subjects were compared: (1) subjects who received NIV immediately after ICU admission for ARF and then failed (NIV failure group); (2) subjects who received NIV immediately after ICU admission for ARF and then succeeded (NIV success group); and (3) subjects who received invasive mechanical ventilation immediately after ICU admission for ARF (invasive mechanical ventilation group). Profiles of subjects with risk factors for NIV failure were obtained using CHAID analysis. Of 1,898 subjects, 806 underwent NIV, and 56.8% of them failed. Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, infiltrates in chest radiograph, and ICU mortality (38.4% vs 6.3%) were higher ( P < .001) in the NIV failure than in the NIV success group. SOFA score was the variable most associated with NIV failure, and 2 cutoffs were determined. Subjects with SOFA ≥ 5 had a higher risk of NIV failure (odds ratio = 3.3, 95% CI 2.4-4.5). ICU mortality was higher in subjects with NIV failure (38.4%) compared with invasive mechanical ventilation subjects (31.3%, P = .018), and NIV failure was associated with increased ICU mortality (odds ratio = 11.4, 95% CI 6.5-20.1). An automatic and non-subjective algorithm based on CHAID decision-tree analysis can help to define the profile of patients with different risks of NIV failure, which might be a promising tool to assist in clinical decision making to avoid the possible complications associated with NIV failure. Copyright © 2017 by Daedalus Enterprises.

Biophotonics of skin: method for correction of deep Raman spectra distorted by elastic scattering

NASA Astrophysics Data System (ADS)

Roig, Blandine; Koenig, Anne; Perraut, François; Piot, Olivier; Gobinet, Cyril; Manfait, Michel; Dinten, Jean-Marc

2015-03-01

Confocal Raman microspectroscopy allows in-depth molecular and conformational characterization of biological tissues non-invasively. Unfortunately, spectral distortions occur due to elastic scattering. Our objective is to correct the attenuation of in-depth Raman peaks intensity by considering this phenomenon, enabling thus quantitative diagnosis. In this purpose, we developed PDMS phantoms mimicking skin optical properties used as tools for instrument calibration and data processing method validation. An optical system based on a fibers bundle has been previously developed for in vivo skin characterization with Diffuse Reflectance Spectroscopy (DRS). Used on our phantoms, this technique allows checking their optical properties: the targeted ones were retrieved. Raman microspectroscopy was performed using a commercial confocal microscope. Depth profiles were constructed from integrated intensity of some specific PDMS Raman vibrations. Acquired on monolayer phantoms, they display a decline which is increasing with the scattering coefficient. Furthermore, when acquiring Raman spectra on multilayered phantoms, the signal attenuation through each single layer is directly dependent on its own scattering property. Therefore, determining the optical properties of any biological sample, obtained with DRS for example, is crucial to correct properly Raman depth profiles. A model, inspired from S.L. Jacques's expression for Confocal Reflectance Microscopy and modified at some points, is proposed and tested to fit the depth profiles obtained on the phantoms as function of the reduced scattering coefficient. Consequently, once the optical properties of a biological sample are known, the intensity of deep Raman spectra distorted by elastic scattering can be corrected with our reliable model, permitting thus to consider quantitative studies for purposes of characterization or diagnosis.

Conformational stability, structural parameters and vibrational assignment from variable temperature infrared spectra of krypton solutions and ab initio calculations of ethylisothiocyanate.

PubMed

Durig, James R; Zheng, Chao

2007-11-01

Variable temperature (-105 to -150 degrees C) studies of the infrared spectra (3500-400 cm(-1)) of ethylisothiocyanate, CH(3)CH(2)NCS, dissolved in liquid krypton have been recorded. Additionally the infrared spectra of the gas and solid have been re-investigated. These spectroscopic data indicate a single conformer in all physical states with a large number of molecules in the gas phase at ambient temperature in excited states of the CN torsional mode which has a very low barrier to conformational interchange. To aid in the analyses of the vibrational and rotational spectra, ab initio calculations have been carried out by the perturbation method to the second order (MP2) with valence and core electron correlation using a variety of basis sets up to 6-311+G(2df,2pd). With the smaller basis sets up to 6-311+G(d,p) and cc-PVDZ, the cis conformer is indicated as a transition state with all larger basis sets the cis conformer is the only stable form. The predicted energy difference from these calculations between the cis form and the higher energy trans conformer is about 125 cm(-1) which represents essentially the barrier to internal rotation of the NCS group (rotation around NC axis). Density functional theory calculation by the B3LYP method with the same basis sets predicts this barrier to be about 25 cm(-1). By utilizing the previously reported microwave rotational constants with the structural parameters predicted by the ab initio MP2(full)/6-311+G(d,p) calculations, adjusted r(0) structural parameters have been obtained for the cis form. The determined heavy atom parameters are: r(NC)=1.196(5), r(CS)=1.579(5), r(CN)=1.439(5), r(CC)=1.519(5)A for the distances and angles of angleCCN=112.1(5), angleCNC=146.2(5), angleNCS=174.0(5) degrees . The centrifugal distortion constants, dipole moments, conformational stability, vibrational frequencies, infrared intensities and Raman activities have been predicted from ab initio calculations and compared to experimental quantities when available. These results are compared to the corresponding quantities of some similar molecules.

Crystal structure of trans-diammine(1,4,8,11-tetra­aza­cyclo­tetra­decane-κ4 N)chromium(III) tetra­chlorido­zincate chloride monohydrate from synchrotron data

PubMed Central

Moon, Dohyun; Choi, Jong-Ha

2016-01-01

The asymmetric unit of the title complex salt, [Cr(C10H24N4)(NH3)2][ZnCl4]Cl·H2O, is comprised of four halves of the CrIII complex cations (the counterparts being generated by application of inversion symmetry), two tetra­chlorido­zincate anions, two chloride anions and two water mol­ecules. Each CrIII ion is coordinated by the four N atoms of the cyclam (1,4,8,11-tetra­aza­cyclo­tetra­deca­ne) ligand in the equatorial plane and by two N atoms of ammine ligands in axial positions, displaying an overall distorted octa­hedral coordination environment. The Cr—N(cyclam) bond lengths range from 2.0501 (15) to 2.0615 (15) Å, while the Cr—(NH3) bond lengths range from 2.0976 (13) to 2.1062 (13) Å. The macrocyclic cyclam moieties adopt the trans-III conformation with six- and five-membered chelate rings in chair and gauche conformations. The [ZnCl4]2− anions have a slightly distorted tetra­hedral shape. In the crystal, the Cl− anions link the complex cations, as well as the solvent water mol­ecules, through N—H⋯Cl and O—H⋯Cl hydrogen-bonding inter­actions. The supra­molecular set-up also includes N—H⋯Cl, C—H⋯Cl, N—H⋯O and O—H⋯Cl hydrogen bonding between N—H or C—H groups of cyclam, ammine N—H and water O—H donor groups, and O atoms of the water mol­ecules, Cl− anions or Cl atoms of the [ZnCl4]2− anions as acceptors, leading to a three-dimensional network structure. PMID:27375863

High proportions of foods recommended for consumption by United States Dietary Guidance contain solid fats and added sugar: Results from the National Health and Nutrition Examination Survey (2007-2008)

USDA-ARS?s Scientific Manuscript database

The 2010 Dietary Guidelines for Americans (DGA) recommend that individuals older than one year reduce intakes of solid fats (SoF) and added sugars (AS; together SoFAS). MyPlate, illustrates the proportions of five major food groups to promote healthy eating (Vegetables, Grains, Protein Foods, Fruit...

High Resolution Diffusion Tensor Imaging of Cortical-Subcortical White Matter Tracts in TBI

DTIC Science & Technology

2010-10-01

by the individual (e.g., car full of lettuce ) or words that share phonemic qualities (e.g., chair/cat; sofa/soup). The observed bidirectional...subjective clustering score minus the expected subjective clustering score. An example is if the word pair car/ lettuce (subjective observed score of 1) is...adjusted subjective clustering formula of observed subjective clustering (car/ lettuce , subjective observed score of 1) minus expected subjective

Solvent induced conformational fluctuation of alanine dipeptide studied by using vibrational probes

NASA Astrophysics Data System (ADS)

Cai, Kaicong; Du, Fenfen; Liu, Jia; Su, Tingting

2015-02-01

The solvation effect on the three dimensional structure and the vibrational feature of alanine dipeptide (ALAD) was evaluated by applying the implicit solvents from polarizable continuum solvent model (PCM) through ab initio calculations, by using molecular dynamic (MD) simulations with explicit solvents, and by combining these two approaches. The implicit solvent induced potential energy fluctuations of ALAD in CHCl3, DMSO and H2O are revealed by means of ab initio calculations, and a global view of conformational and solvation environmental dependence of amide I frequencies is achieved. The results from MD simulations with explicit solvents show that ALAD trends to form PPII, αL, αR, and C5 in water, PPII and C5 in DMSO, and C5 in CHCl3, ordered by population, and the demonstration of the solvated structure, the solute-solvent interaction and hydrogen bonding is therefore enhanced. Representative ALAD-solvent clusters were sampled from MD trajectories and undergone ab initio calculations. The explicit solvents reveal the hydrogen bonding between ALAD and solvents, and the correlation between amide I frequencies and the Cdbnd O bond length is built. The implicit solvents applied to the ALAD-solvent clusters further compensate the solvation effect from the bulk, and thus enlarge the degree of structural distortion and the amide I frequency red shift. The combination of explicit solvent in the first hydration shell and implicit solvent in the bulk is helpful for our understanding about the conformational fluctuation of solvated polypeptides through vibrational probes.

HbA1c is outcome predictor in diabetic patients with sepsis.

PubMed

Gornik, Ivan; Gornik, Olga; Gasparović, Vladimir

2007-07-01

We have investigated predictive value of HbA1c for hospital mortality and length of stay (LOS) in patients with type 2 diabetes admitted because of sepsis. A prospective observational study was implemented in a university hospital, 286 patients with type 2 diabetes admitted with sepsis were included. Leukocyte count, CRP, admission plasma glucose, APACHE II and SOFA score were noted at admission, HbA1c was measured on the first day following admission. Hospital mortality and hospital length of stay (LOS) were the outcome measures. Admission HbA1c was significantly lower in surviving patients than in non-survivors (median 8.2% versus 9.75%, respectively; P<0.001). There was a significant correlation between admission HbA1c and hospital LOS of surviving patients (r=0.29; P<0.001). Logistic regression showed that HbA1c is an independent predictor of hospital mortality (odds ratio 1.36), together with female sex (OR 2.24), APACHE II score (OR 1.08) and SOFA score (OR 1.28). Multiple regression showed that HbA1c and APACHE II score are independently related to hospital LOS. According to our results, HbA1c is an independent predictive factor for hospital mortality and hospital LOS of diabetic patients with sepsis.

Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach.

PubMed

Ferrario, Manuela; Cambiaghi, Alice; Brunelli, Laura; Giordano, Silvia; Caironi, Pietro; Guatteri, Luca; Raimondi, Ferdinando; Gattinoni, Luciano; Latini, Roberto; Masson, Serge; Ristagno, Giuseppe; Pastorelli, Roberta

2016-02-05

Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy.

Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach

PubMed Central

Ferrario, Manuela; Cambiaghi, Alice; Brunelli, Laura; Giordano, Silvia; Caironi, Pietro; Guatteri, Luca; Raimondi, Ferdinando; Gattinoni, Luciano; Latini, Roberto; Masson, Serge; Ristagno, Giuseppe; Pastorelli, Roberta

2016-01-01

Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy. PMID:26847922

Identifying the adaptive mechanism in globular proteins: Fluctuations in densely packed regions manipulate flexible parts

NASA Astrophysics Data System (ADS)

Yilmaz, Lutfu Safak; Atilgan, Ali Rana

2000-09-01

A low-resolution structural model based on the packing geometry of α-carbons is utilized to establish a connection between the flexible and rigid parts of a folded protein. The former commonly recognizes a complementing molecule for making a complex, while the latter manipulates the necessary conformational change for binding. We attempt analytically to distinguish this control architecture that intrinsically exists in globular proteins. First with two-dimensional simple models, then for a native protein, bovine pancreatic trypsin inhibitor, we explicitly demonstrate that inserting fluctuations in tertiary contacts supported by the stable core, one can regulate the displacement of residues on loop regions. The positional fluctuations of the flexible regions are annihilated by the rest of the protein in conformity with the Le Chatelier-Braun principle. The results indicate that the distortion of the principal nonbonded contacts between highly packed residues is accompanied by that of the slavery fluctuations that are widely distributed over the native structure. These positional arrangements do not appear in a reciprocal relation between a perturbation and the associated response; the effect of a movement of residue i on residue j is not equal to that of the same movement of residue j on residue i.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rycyna, R.E.; Wallace, J.C.; Sharma, M.

Acetone-photosensitized UV irradiation of three thymine oligomers, d(TpT), d(TpTpT), and d(TpTpTpT), forms predominantly cis-syn cyclobutyl photodimers. C-18 reverse-phase high-performance liquid chromatography is used to purify the following positional isomers: d(TpT(p)T), d(T(p)TpT), d-(TpTpT(p)T), d(TpT(p)TpT), d(T(p)TpTpT), and d(T(p)TpT(p)T), where T(p)T represents the cis-syn photodimer. Conformational properties of the cis-syn dimers and adjacent thymine nucleotides have been investigated in solution by using /sup 1/H, /sup 13/C, and /sup 31/P NMR spectroscopy. These studies show that (1) the photodimer conformation in longer oligothymidylates is similar to that in the dinucleoside monophosphate and (2) the cis-syn dimer induces alterations to a greater degree on themore » 5' side than on the 3' side of the photodimer. Specifically, the photodimer distorts the exocyclic bonds epsilon (C3'-O3') in Tp- and ..gamma..(C5'-C4') in -pT(p)- on the 5' side and slightly alters the furanose equilibrium of the -pT nucleotide on the 3' side of the dimer.« less

Deciphering hierarchical features in the energy landscape of adenylate kinase folding/unfolding

NASA Astrophysics Data System (ADS)

Taylor, J. Nicholas; Pirchi, Menahem; Haran, Gilad; Komatsuzaki, Tamiki

2018-03-01

Hierarchical features of the energy landscape of the folding/unfolding behavior of adenylate kinase, including its dependence on denaturant concentration, are elucidated in terms of single-molecule fluorescence resonance energy transfer (smFRET) measurements in which the proteins are encapsulated in a lipid vesicle. The core in constructing the energy landscape from single-molecule time-series across different denaturant concentrations is the application of rate-distortion theory (RDT), which naturally considers the effects of measurement noise and sampling error, in combination with change-point detection and the quantification of the FRET efficiency-dependent photobleaching behavior. Energy landscapes are constructed as a function of observation time scale, revealing multiple partially folded conformations at small time scales that are situated in a superbasin. As the time scale increases, these denatured states merge into a single basin, demonstrating the coarse-graining of the energy landscape as observation time increases. Because the photobleaching time scale is dependent on the conformational state of the protein, possible nonequilibrium features are discussed, and a statistical test for violation of the detailed balance condition is developed based on the state sequences arising from the RDT framework.

Large area nanoimprint by substrate conformal imprint lithography (SCIL)

NASA Astrophysics Data System (ADS)

Verschuuren, Marc A.; Megens, Mischa; Ni, Yongfeng; van Sprang, Hans; Polman, Albert

2017-06-01

Releasing the potential of advanced material properties by controlled structuring materials on sub-100-nm length scales for applications such as integrated circuits, nano-photonics, (bio-)sensors, lasers, optical security, etc. requires new technology to fabricate nano-patterns on large areas (from cm2 to 200 mm up to display sizes) in a cost-effective manner. Conventional high-end optical lithography such as stepper/scanners is highly capital intensive and not flexible towards substrate types. Nanoimprint has had the potential for over 20 years to bring a cost-effective, flexible method for large area nano-patterning. Over the last 3-4 years, nanoimprint has made great progress towards volume production. The main accelerator has been the switch from rigid- to wafer-scale soft stamps and tool improvements for step and repeat patterning. In this paper, we discuss substrate conformal imprint lithography (SCIL), which combines nanometer resolution, low patterns distortion, and overlay alignment, traditionally reserved for rigid stamps, with the flexibility and robustness of soft stamps. This was made possible by a combination of a new soft stamp material, an inorganic resist, combined with an innovative imprint method. Finally, a volume production solution will be presented, which can pattern up to 60 wafers per hour.

Synthesis, spectral characterization, crystal structure and molecular docking study of 2,7-diaryl-1,4-diazepan-5-ones

NASA Astrophysics Data System (ADS)

Sethuvasan, S.; Sugumar, P.; Maheshwaran, V.; Ponnuswamy, M. N.; Ponnuswamy, S.

2016-07-01

In this study, a series of variously substituted r-2,c-7-diaryl-1,4-diazepan-5-ones 9-16 have been synthesized using Schmidt rearrangement and are characterized by IR, mass and 1D & 2D NMR spectral data. The proton NMR coupling constant and estimated dihedral angles reveal that the compounds 9-16 prefer a chair conformation with equatorial orientation of alkyl and aryl groups. Single crystal X-ray structure has been solved for compounds 9 and 11 which also indicates the preference for distorted chair conformation with equatorial orientation of substituents. The compounds 9-16 have been docked with the structure of Methicillin-resistant Staphylococcus aureus (MRSA) and the results demonstrate that compound 10 is having better docking score and glide energy than others and it is comparable to co-crystal ligand. Furthermore, all the compounds have been evaluated for their antibacterial and antioxidant activities. All the compounds show moderate antibacterial activity and only 11 exhibits better activity against S. aures and Escherichia coli. The compounds 11, 13 and 14 exhibit half of the antioxidant power when compared to the BHT and the remaining compounds show moderate activity.

Rotational Spectra of Hydrogen Bonded Networks of Amino Alcohols

NASA Astrophysics Data System (ADS)

Zhang, Di; Zwier, Timothy S.

2014-06-01

The rotational spectra of several different amino alcohols including D/L-allo-threoninol, 2-amino-1,3-propanediol and 1,3-diamino-2-propanol over the 6.5-18.5 GHz range have been investigated under jet-cooled conditions using chirped-pulsed Fourier transform microwave spectroscopy. Despite the small size of these molecules, a great variety of conformations have been observed in the molecular expansion. While the NH2 group is typically thought of as a H-bond acceptor, it often acts both as acceptor and donor in forming H-bonded networks. With three adjacent H-bonding substituents (a combination of OH and NH2 groups), many different hydrogen bonding patterns are possible, including H-bonded chains and H-bonded cycles. Since many of these structures differ primarily by the relative orientation of the H-atoms, the analysis of these rotational spectra are challenging. Only through an exhaustive conformational search and the comparison with the experimental rotational constants, nuclear quadrupolar splittings, and line strengths are we able to understand the complex nature of these interactions. The ways in which the presence and number of NH2 groups affects the relative energies, and distorts the structures will be explored.

Conformability of balloon-expandable stents to the carotid siphon: an in vitro study.

PubMed

du Mesnil de Rochemont, R; Yan, B; Zanella, F E; Rüfenacht, D A; Berkefeld, J

2006-02-01

Endovascular placement of coronary balloon-expandable stents in patients with recurrent cerebral ischemia has emerged as a treatment option for intracranial arterial occlusive disease. We have developed an in vitro model matching the tortuous curve of the carotid siphon that allows the assessment of apposition of stents to a curved vessel wall. Six types of balloon-expandable coronary stents were implanted in a silicone model of the carotid siphon. Digital radiographs and 3D rotational angiograms were obtained. Stent morphology was evaluated and the degree of apposition between stent and wall of the model was measured on a digital workstation. All 6 stents showed lack of apposition between stent and the wall at the convexity of the anterior segment of the carotid siphon and the wall at the concavity at both extremities of the stent. In and around the curve, the modules of the stents did not expand completely to their nominal diameter and were distorted to an oval shape. The tested coronary balloon-expandable stents did not completely conform to the vessel wall of the model of the carotid siphon and further development is needed to approach the goal of an "ideal intracranial stent."

Structure-based Analysis to Hu-DNA Binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swinger,K.; Rice, P.

2007-01-01

HU and IHF are prokaryotic proteins that induce very large bends in DNA. They are present in high concentrations in the bacterial nucleoid and aid in chromosomal compaction. They also function as regulatory cofactors in many processes, such as site-specific recombination and the initiation of replication and transcription. HU and IHF have become paradigms for understanding DNA bending and indirect readout of sequence. While IHF shows significant sequence specificity, HU binds preferentially to certain damaged or distorted DNAs. However, none of the structurally diverse HU substrates previously studied in vitro is identical with the distorted substrates in the recently publishedmore » Anabaena HU(AHU)-DNA cocrystal structures. Here, we report binding affinities for AHU and the DNA in the cocrystal structures. The binding free energies for formation of these AHU-DNA complexes range from 10-14.5 kcal/mol, representing K{sub d} values in the nanomolar to low picomolar range, and a maximum stabilization of at least 6.3 kcal/mol relative to complexes with undistorted, non-specific DNA. We investigated IHF binding and found that appropriate structural distortions can greatly enhance its affinity. On the basis of the coupling of structural and relevant binding data, we estimate the amount of conformational strain in an IHF-mediated DNA kink that is relieved by a nick (at least 0.76 kcal/mol) and pinpoint the location of the strain. We show that AHU has a sequence preference for an A+T-rich region in the center of its DNA-binding site, correlating with an unusually narrow minor groove. This is similar to sequence preferences shown by the eukaryotic nucleosome.« less

DNA interactions of antitumor cisplatin analogs containing enantiomeric amine ligands.

PubMed Central

Malina, J; Hofr, C; Maresca, L; Natile, G; Brabec, V

2000-01-01

Modifications of natural DNA and synthetic oligodeoxyribonucleotide duplexes in a cell-free medium by analogs of antitumor cisplatin containing enantiomeric amine ligands, such as cis-[PtCl(2)(RR-DAB)] and cis-[PtCl(2)(SS-DAB)] (DAB = 2,3-diaminobutane), were studied by various methods of molecular biophysics and biophysical chemistry. These methods include DNA binding studies by pulse polarography and atomic absorption spectrophotometry, mapping of DNA adducts using transcription assay, interstrand cross-linking assay using gel electrophoresis under denaturing conditions, differential scanning calorimetry, chemical probing, and bending and unwinding studies of the duplexes containing single, site-specific cross-link. The major differences resulting from the modification of DNA by the two enantiomers are the thermodynamical destabilization and conformational distortions induced in DNA by the 1,2-d(GpG) intrastrand cross-link. It has been suggested that these differences are associated with a different biological activity of the two enantiomers observed previously. In addition, the results of the present work are also consistent with the view that formation of hydrogen bonds between the carbonyl oxygen of the guanine residues and the "quasi equatorial" hydrogen of the cis amine in the 1, 2-d(GpG) intrastrand cross-link plays an important role in determining the character of the distortion induced in DNA by this lesion. PMID:10733979

Marvels of enzyme catalysis at true atomic resolution: distortions, bond elongations, hidden flips, protonation states and atom identities.

PubMed

Neumann, Piotr; Tittmann, Kai

2014-12-01

Although general principles of enzyme catalysis are fairly well understood nowadays, many important details of how exactly the substrate is bound and processed in an enzyme remain often invisible and as such elusive. In fortunate cases, structural analysis of enzymes can be accomplished at true atomic resolution thus making possible to shed light on otherwise concealed fine-structural traits of bound substrates, intermediates, cofactors and protein groups. We highlight recent structural studies of enzymes using ultrahigh-resolution X-ray protein crystallography showcasing its enormous potential as a tool in the elucidation of enzymatic mechanisms and in unveiling fundamental principles of enzyme catalysis. We discuss the observation of seemingly hyper-reactive, physically distorted cofactors and intermediates with elongated scissile substrate bonds, the detection of 'hidden' conformational and chemical equilibria and the analysis of protonation states with surprising findings. In delicate cases, atomic resolution is required to unambiguously disclose the identity of atoms as demonstrated for the metal cluster in nitrogenase. In addition to the pivotal structural findings and the implications for our understanding of enzyme catalysis, we further provide a practical framework for resolution enhancement through optimized data acquisition and processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Selective binding of meiosis-specific yeast Hop1 protein to the holliday junctions distorts the DNA structure and its implications for junction migration and resolution.

PubMed

Tripathi, Pankaj; Anuradha, S; Ghosal, Gargi; Muniyappa, K

2006-12-08

Saccharomyces cerevisiae HOP1, which encodes a component of synaptonemal complex (SC), plays an important role in both gene conversion and crossing over between homologs, as well as enforces meiotic recombination checkpoint control over the progression of recombination intermediates. In hop1Delta mutants, meiosis-specific double-strand breaks (DSBs) are reduced to 10% of the wild-type level, and at aberrantly late times, these DSBs are processed into inter-sister recombination intermediates. However, the underlying mechanism by which Hop1 protein regulates these nuclear events remains obscure. Here we show that Hop1 protein interacts selectively with the Holliday junction, changes its global conformation and blocks the dissolution of the junction by a RecQ helicase. The Holliday junction-Hop1 protein complexes are significantly more stable at higher ionic strengths and molar excess of unlabeled competitor DNA than complexes containing other recombination intermediates. Structural analysis of the Holliday junction using 2-aminopurine fluorescence emission, DNase I footprinting and KMnO4 probing provide compelling evidence that Hop1 protein binding induces significant distortion at the center of the Holliday junction. We propose that Hop1 protein might coordinate the physical monitoring of meiotic recombination intermediates with the process of branch migration of Holliday junction.

Prescription Patterns for Tigecycline in Severely Ill Patients for Non-FDA Approved Indications in a Developing Country: A Compromised Outcome

PubMed Central

Moghnieh, Rima A.; Abdallah, Dania I.; Fawaz, Ismail A.; Hamandi, Tarek; Kassem, Mohammad; El-Rajab, Nabila; Jisr, Tamima; Mugharbil, Anas; Droubi, Nabila; Al Tabah, Samaa; Sinno, Loubna; Ziade, Fouad; Daoud, Ziad; Ibrahim, Ahmad

2017-01-01

Introduction: With the rise in antibiotic resistance, tigecycline has been used frequently in off-label indications, based on its in-vitro activity against multidrug-resistant organisms. In this study, our aim was to assess its use in approved and unapproved indications. Materials and Methods: This is a retrospective chart review evaluating a 2-year experience of tigecycline use for > 72 h in 153 adult patients inside and outside critical care unit from January 2012 to December 2013 in a Lebanese tertiary-care hospital. Results: Tigecycline was mostly used in off-label indications (81%) and prescribed inside the critical care area, where the number of tigecycline cycles was 16/1,000 patient days. Clinical success was achieved in 43.4% of the patients. In the critically ill group, it was significantly higher in patients with a SOFA score <7 using multivariate analysis (Odds Ratio (OR) = 12.51 [4.29–36.51], P < 0.0001). Microbiological success was achieved in 43.3% of patients. Yet, the univariate and adjusted multivariate models failed to show a significant difference in this outcome between patients inside vs. outside critical care area, those with SOFA score <7 vs. ≥ 7, and in FDA-approved vs. off-label indications. Total mortality reached ~45%. It was significantly higher in critically ill patients with SOFA score ≥7 (OR = 5.17 [2.43–11.01], P < 0.0001) and in off-label indications (OR = 4.00 [1.30–12.31], P = 0.01) using an adjusted multivariate model. Gram-negative bacteria represented the majority of the clinical isolates (81%) and Acinetobacter baumannii predominated (28%). Carbapenem resistance was present in 85% of the recovered Acinetobacter, yet, more than two third of the carbapenem-resistant Acinetobacter species were still susceptible to tigecycline. Conclusion: In our series, tigecycline has been mostly used in off-label indications, specifically in severely ill patients. The outcome of such infections was not inferior to that of FDA-approved indications, especially inside critical care area. The use of this last resort antibiotic in complicated clinical scenarios with baseline microbiological epidemiology predominated by extensively-drug resistant pathogens ought to be organized. PMID:28396656

Liver Cirrhosis is Independently Associated With 90-Day Mortality in ARDS Patients.

PubMed

Gacouin, Arnaud; Locufier, Maxime; Uhel, Fabrice; Letheulle, Julien; Bouju, Pierre; Fillatre, Pierre; Le Tulzo, Yves; Tadié, Jean Marc

2016-01-01

In a few studies, cirrhosis has been associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). These studies were, however, conducted mostly before 2000. Over the last 15 years, the prognosis of cirrhotic patients admitted to the intensive care unit (ICU) seems to have improved and major changes in the management of mechanical ventilation (MV) of ARDS have appeared. The aim of this study was to determine whether cirrhosis remains a factor for poor prognosis despite improvements in MV techniques and supportive therapies for ARDS. Retrospective analysis of data recorded from 232 patients (42 with cirrhosis and 290 without cirrhosis) who received lung-protective ventilation for ARDS defined according to American-European Consensus Conference criteria and admitted from 2006 to 2013. Alcohol was the most common aetiology of the cirrhosis. The end point was mortality at day-90 from the diagnosis of ARDS, survival was calculated using the Kaplan-Meier method, and we used a Cox-proportional hazard model to determine whether cirrhosis remained independently associated with mortality after adjustment for other prognostic variables for ARDS described previously. Organ dysfunctions were assessed based on the Sequential Organ Failure Assessment (SOFA) criteria, pulmonary and nonpulmonary dysfunctions were distinguished and compared between cirrhotic and non-cirrhotic patients on the first 3 days of VM. Comparison of survival curves showed that cirrhotic patients had a poorer 90-day prognosis than non-cirrhotic patients (P = 0.03 by the log-rank test). After adjusted analysis, cirrhosis remained independently associated with mortality at day 90 (adjusted hazard ratio 2.09, 95% CI, 1.27-3.45, P = 0.004). Non-pulmonary SOFA scores were significantly higher in cirrhotic patients than in non-cirrhotic patients on day 1 (P < 0.001), day 2 (P = 0.003), and day 3 (P = 0.002) of MV for ARDS whereas pulmonary SOFA scores did not differ significantly. Despite improvements in the management of cirrhotic patients admitted to the ICU and in the management of MV for the treatment of ARDS, cirrhosis remained associated with a poorer prognosis in ARDS patients. The prognosis of cirrhotic patients with ARDS appears related to extrapulmonary organ dysfunctions rather than pulmonary dysfunction.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoff, M; Rane-Levandovsky, S; Andre, J

Purpose: Traditional arterial spin labeling (ASL) acquisitions with echo planar imaging (EPI) readouts suffer from image distortion due to susceptibility effects, compromising ASL’s ability to accurately quantify cerebral blood flow (CBF) and assess disease-specific patterns associated with CBF abnormalities. Phase labeling for additional coordinate encoding (PLACE) can remove image distortion; our goal is to apply PLACE to improve the quantitative accuracy of ASL CBF in humans. Methods: Four subjects were imaged on a 3T Philips Ingenia scanner using a 16-channel receive coil with a 21/21/10cm (frequency/phase/slice direction) field-of-view. An ASL sequence with a pseudo-continuous ASL (pCASL) labeling scheme was employedmore » to acquire thirty dynamics of single-shot EPI data, with control and label datasets for all dynamics, and PLACE gradients applied on odd dynamics. Parameters included a post-labeling delay = 2s, label duration = 1.8s, flip angle = 90°, TR/TE = 5000/23.5ms, and 2.9/2.9/5.0mm (frequency/phase/slice direction) voxel size. “M0” EPI-reference images and T1-weighted spin-echo images with 0.8/1.0/3.3mm (frequency/phase/slice directions) voxel size were also acquired. Complex conjugate image products of pCASL odd and even dynamics were formed, a linear phase ramp applied, and data expanded and smoothed. Data phase was extracted to map control, label, and M0 magnitude image pixels to their undistorted locations, and images were rebinned to original size. All images were corrected for motion artifacts in FSL 5.0. pCASL images were registered to M0 images, and control and label images were subtracted to compute quantitative CBF maps. Results: pCASL image and CBF map distortions were removed by PLACE in all subjects. Corrected images conformed well to the anatomical T1-weighted reference image, and deviations in corrected CBF maps were evident. Conclusion: Eliminating pCASL distortion with PLACE can improve CBF quantification accuracy using minimal pulse sequence modifications and no additional scan time, improving ASL’s clinical applicability.« less

A principal component analysis of the dynamics of subdomains and binding sites in human serum albumin.

PubMed

Paris, Guillaume; Ramseyer, Christophe; Enescu, Mironel

2014-05-01

The conformational dynamics of human serum albumin (HSA) was investigated by principal component analysis (PCA) applied to three molecular dynamics trajectories of 200 ns each. The overlap of the essential subspaces spanned by the first 10 principal components (PC) of different trajectories was about 0.3 showing that the PCA based on a trajectory length of 200 ns is not completely convergent for this protein. The contributions of the relative motion of subdomains and of the subdomains (internal) distortion to the first 10 PCs were found to be comparable. Based on the distribution of the first 3 PC, 10 protein conformers are identified showing relative root mean square deviations (RMSD) between 2.3 and 4.6 Å. The main PCs are found to be delocalized over the whole protein structure indicating that the motions of different protein subdomains are coupled. This coupling is considered as being related to the allosteric effects observed upon ligand binding to HSA. On the other hand, the first PC of one of the three trajectories describes a conformational transition of the protein domain I that is close to that experimentally observed upon myristate binding. This is a theoretical support for the older hypothesis stating that changes of the protein onformation favorable to binding can precede the ligand complexation. A detailed all atoms PCA performed on the primary Sites 1 and 2 confirms the multiconformational character of the HSA binding sites as well as the significant coupling of their motions. Copyright © 2013 Wiley Periodicals, Inc.

THE CM-, MM-, AND SUB-MM-WAVE SPECTRUM OF ALLYL ISOCYANIDE AND RADIOASTRONOMICAL OBSERVATIONS IN ORION KL AND THE SgrB2 LINE SURVEYS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haykal, I.; Margulès, L.; Huet, T. R.

2013-11-10

Organic isocyanides have an interesting astrochemistry and some of these molecules have been detected in the interstellar medium (ISM). However, rotational spectral data for this class of compounds are still scarce. We provide laboratory spectra of the four-carbon allyl isocyanide covering the full microwave region, thus allowing a potential astrophysical identification in the ISM. We assigned the rotational spectrum of the two cis (synperiplanar) and gauche (anticlinal) conformations of allyl isocyanide in the centimeter-wave region (4-18 GHz), resolved its {sup 14}N nuclear quadrupole coupling (NQC) hyperfine structure, and extended the measurements into the millimeter and submillimeter-wave (150-900 GHz) ranges formore » the title compound. Rotational constants for all the monosubstituted {sup 13}C and {sup 15}N isotopologues are additionally provided. Laboratory observations are supplemented with initial radioastronomical observations. Following analysis of an extensive dataset (>11000 rotational transitions), accurate ground-state molecular parameters are reported for the cis and gauche conformations of the molecule, including rotational constants, NQC parameters, and centrifugal distortion terms up to octic contributions. Molecular parameters have also been obtained for the two first excited states of the cis conformation, with a dataset of more than 3300 lines. The isotopic data allowed determining substitution and effective structures for the title compound. We did not detect allyl isocyanide either in the IRAM 30 m line survey of Orion KL or in the PRIMOS survey toward SgrB2. Nevertheless, we provided an upper limit to its column density in Orion KL.« less

Base pairing and base mis-pairing in nucleic acids

NASA Technical Reports Server (NTRS)

Wang, A. H. J.; Rich, A.

1986-01-01

In recent years we have learned that DNA is conformationally active. It can exist in a number of different stable conformations including both right-handed and left-handed forms. Using single crystal X-ray diffraction analysis we are able to discover not only additional conformations of the nucleic acids but also different types of hydrogen bonded base-base interactions. Although Watson-Crick base pairings are the predominant type of interaction in double helical DNA, they are not the only types. Recently, we have been able to examine mismatching of guanine-thymine base pairs in left-handed Z-DNA at atomic resolution (1A). A minimum amount of distortion of the sugar phosphate backbone is found in the G x T pairing in which the bases are held together by two hydrogen bonds in the wobble pairing interaction. Because of the high resolution of the analysis we can visualize water molecules which fill in to accommodate the other hydrogen bonding positions in the bases which are not used in the base-base interactions. Studies on other DNA oligomers have revealed that other types of non-Watson-Crick hydrogen bonding interactions can occur. In the structure of a DNA octamer with the sequence d(GCGTACGC) complexed to an antibiotic triostin A, it was found that the two central AT base pairs are held together by Hoogsteen rather than Watson-Crick base pairs. Similarly, the G x C base pairs at the ends are also Hoogsteen rather than Watson-Crick pairing. Hoogsteen base pairs make a modified helix which is distinct from the Watson-Crick double helix.

Policy Options and the U.S. Withdrawal from Iraq: An Analysis of the Way Ahead

DTIC Science & Technology

2009-08-01

Our specialists combine in-country experience, language skills, and the use of local primary-source data to produce empirically based work. All of...President Obama takes over, due to the supposed certitudes of the recently signed Status of Forces Agreement (SOFA); however, there are crucial decisions to...was ratified by the Iraqi parliament on November 27, 2008, and signed by the leaders of the two countries on December 14, 2008. This agreement

High veno-arterial carbon dioxide gradient is not predictive of worst outcome after an elective cardiac surgery: a retrospective cohort study.

PubMed

Morel, Jerome; Grand, Nathalie; Axiotis, Gregory; Bouchet, Jean Baptiste; Faure, Michael; Auboyer, Christian; Vola, Marco; Molliex, Serge

2016-12-01

Alteration of tissue perfusion is a main contributor of organ dysfunction. In cardiac surgery, the importance of organ dysfunction is associated with worse outcome. Central venous-arterial difference in CO 2 tension (ΔCO 2 ) has been proposed as a global marker of the adequacy of tissue perfusion in shock states. We hypothesized that ΔCO 2 could be increased in case of postoperative organ failure or worse outcome. In this monocentric retrospective cohort study, we retrieved, from our database, 220 consecutive patients admitted in intensive care after an elective cardiac surgery. Four time points were formed: ICU admission, and 6, 24 and 48 h after. A ΔCO 2 below 6 mmHg defined the normal range values. The SOFA score, intensive care unit and hospital length of stay, hospital and 6-month mortality rate were recorded. We compared patient with low ΔCO 2 (<6 mmHg) and high ΔCO 2 (≥6 mmHg). We included 55 (25 %) and 165 patients in low and high ΔCO 2 groups, respectively. The SOFA score, the hospital and 6 months mortality rate were higher in patients with low ΔCO 2 . Surprisingly, we did not find results previously published in other surgical settings. In cardiac surgery, ΔCO 2 has a low predictive value of outcome.

Early Stage Blood Purification for Paraquat Poisoning: A Multicenter Retrospective Study.

PubMed

Li, An; Li, Wenxiong; Hao, Fengtong; Wang, Haishi

2016-01-01

To evaluate the efficacy of conservative treatment vs. hemoperfusion (HP) vs. HP + continuous veno-venous hemofiltration (CVVH) for acute Paraquat (PQ) poisoning. This was a multicenter retrospective study of patients with PQ poisoning between January 2013 and June 2014. Clinical data and PQ serum levels were collected at baseline and after 24, 48, and 72 h of treatment. Seventy-five, 65, and 43 underwent conservative treatment only (conservative treatment group), conservative treatment + HP (HP group), and conservative treatment + HP + CVVH (HP + CVVH group), respectively. PQ serum levels decreased in all groups after 72 h of treatment (p < 0.001); meanwhile, these values decreased faster in the HP and HP + CVVH groups compared with the conservative treatment group. More importantly, PQ blood levels were significantly lower in the HP + CVVH group compared with the HP group at 24 h (p < 0.05). Sequential organ failure assessment (ΔSOFA) values in the HP and HP + CVVH groups were significantly lower compared with that obtained for the conservative treatment group (p < 0.05). The 60-day survival rates were 21.3, 43.1 and 46.5%, respectively. Multivariate analysis indicated that age, PQ dose, admission PQ levels, and admission SOFA score were independently associated with mortality. HP and HP + CVVH were protective factors. Early HP or HP + CVVH after PQ poisoning could decrease PQ blood levels, alleviate organ damage, and increase survival. © 2016 S. Karger AG, Basel.

Reducing NOx Emissions for a 600 MWe Down-Fired Pulverized-Coal Utility Boiler by Applying a Novel Combustion System.

PubMed

Ma, Lun; Fang, Qingyan; Lv, Dangzhen; Zhang, Cheng; Chen, Yiping; Chen, Gang; Duan, Xuenong; Wang, Xihuan

2015-11-03

A novel combustion system was applied to a 600 MWe Foster Wheeler (FW) down-fired pulverized-coal utility boiler to solve high NOx emissions, without causing an obvious increase in the carbon content of fly ash. The unit included moving fuel-lean nozzles from the arches to the front/rear walls and rearranging staged air as well as introducing separated overfire air (SOFA). Numerical simulations were carried out under the original and novel combustion systems to evaluate the performance of combustion and NOx emissions in the furnace. The simulated results were found to be in good agreement with the in situ measurements. The novel combustion system enlarged the recirculation zones below the arches, thereby strengthening the combustion stability considerably. The coal/air downward penetration depth was markedly extended, and the pulverized-coal travel path in the lower furnace significantly increased, which contributed to the burnout degree. The introduction of SOFA resulted in a low-oxygen and strong-reducing atmosphere in the lower furnace region to reduce NOx emissions evidently. The industrial measurements showed that NOx emissions at full load decreased significantly by 50%, from 1501 mg/m3 (O2 at 6%) to 751 mg/m3 (O2 at 6%). The carbon content in the fly ash increased only slightly, from 4.13 to 4.30%.

Prognostic factors and scoring system for survival in colonic perforation.

PubMed

Komatsu, Shuhei; Shimomatsuya, Takumi; Nakajima, Masayuki; Amaya, Hirokazu; Kobuchi, Taketsune; Shiraishi, Susumu; Konishi, Sayuri; Ono, Susumu; Maruhashi, Kazuhiro

2005-01-01

No ideal and generally accepted prognostic factors and scoring systems exist to determine the prognosis of peritonitis associated with colonic perforation. This study was designed to investigate prognostic factors and evaluate the various scoring systems to allow identification of high-risk patients. Between 1996 and 2003, excluding iatrogenic and trauma cases, 26 consecutive patients underwent emergency operations for colorectal perforation and were selected for this retrospective study. Several clinical factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI, and MOF scores were calculated. The overall mortality was 26.9%. Compared with the survivors, non-survivors were found more frequently in Hinchey's stage III-IV, a low preoperative marker of pH, base excess (BE), and a low postoperative marker of white blood cell count, PaO2/FiO2 ratio, and renal output (24h). According to the logistic regression model, BE was a significant independent variable. Concerning the prognostic scoring systems, an APACHE II score of 19, a SOFA score of 8, an MPI score of 30, and an MOF score of 7 or more were significantly related to poor prognosis. Preoperative BE and postoperative white blood cell count were reliable prognostic factors and early classification using prognostic scoring systems at specific points in the disease process are useful to improve our understanding of the problems involved.

Multidrug Resistance Acinetobacter Bacteremia Secondary to Ventilator-Associated Pneumonia: Risk Factors and Outcome.

PubMed

Brotfain, Evgeni; Borer, Abraham; Koyfman, Leonid; Saidel-Odes, Lisa; Frenkel, Amit; Gruenbaum, Shaun E; Rosenzweig, Vsevolod; Zlotnik, Alexander; Klein, Moti

2017-10-01

Acinetobacter baumannii is a multidrug resistant (MDR), gram-negative bacterium commonly implicated in ventilator-associated pneumonia (VAP) in critically ill patients. Patients in the intensive care unit (ICU) with VAP often subsequently develop A baumannii bacteremia, which may significantly worsen outcomes. In this study, we retrospectively reviewed the clinical and laboratory records of 129 ICU patients spanning 6 years with MDR A baumannii VAP; 46 (35%) of these patients had concomitant MDR A baumannii bacteremia. The ICU mortality rate was higher in patients with VAP having A baumannii bacteremia compared to nonbacteremic patients (32.4% vs 9.6% respectively, P < .005). Age >65 years, an Acute Physiology and Chronic Health Evaluation II (APACHE-II) score higher than 20, a Sequential Organ Failure Assessment (SOFA) score higher than 7 on the day of bacteremia, and the presence of comorbid disease (chronic obstructive pulmonary disease [COPD] and chronic renal failure) were found to be independent risk factors for in-hospital mortality in this population. Multidrug resistant A baumannii was not an independent risk factor for mortality. Although the presence of comorbid diseases (COPD and chronic renal failure) and severity of disease (APACHE > 20 and SOFA >7) were found to be independent risk factors for ICU mortality, MDR A baumannii bacteremia was not an independent risk factor for mortality in our critically ill population.

Rethinking the concept of sepsis and septic shock.

PubMed

A Cabrita, Joana; Pinheiro, Isabel; Menezes Falcão, L

2018-06-16

Sepsis is a major global health problem and represents a challenge for physicians all over the world. The knowledge of sepsis and septic shock is a topic of interest among the scientific community and society in general. New guidelines for management of sepsis and septic shock were developed in 2016, providing an update on this area. In Sepsis-3 new definitions for sepsis and septic shock were published. The purpose of this narrative review is to discuss and compare the new criteria of 2016 with the old criteria, purposing at the same time an alternative approach for this topic. SOFA criteria (Sequential Organ Failure Assessment Score) are more complete, but too extensive and usually difficult to apply outside the intensive care units, therefore inducing potentially delay in the proper treatment. We purpose combined criteria for the selection of sepsis patients. Initially, we could apply qSOFA (quick Sepsis Related Organ Failure Assessment) criteria, due to its easy application, associated with the SIRS (systemic inflammatory response syndrome) criteria, allowing to select the patients who are infected and need faster treatment. In that way we would use the best of old and newest criteria, allowing the early selection of patients who are infected and require faster treatment, while the search for a better and faster tool continues. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Early prediction of intensive care unit-acquired weakness using easily available parameters: a prospective observational study.

PubMed

Wieske, Luuk; Witteveen, Esther; Verhamme, Camiel; Dettling-Ihnenfeldt, Daniela S; van der Schaaf, Marike; Schultz, Marcus J; van Schaik, Ivo N; Horn, Janneke

2014-01-01

An early diagnosis of Intensive Care Unit-acquired weakness (ICU-AW) using muscle strength assessment is not possible in most critically ill patients. We hypothesized that development of ICU-AW can be predicted reliably two days after ICU admission, using patient characteristics, early available clinical parameters, laboratory results and use of medication as parameters. Newly admitted ICU patients mechanically ventilated ≥2 days were included in this prospective observational cohort study. Manual muscle strength was measured according to the Medical Research Council (MRC) scale, when patients were awake and attentive. ICU-AW was defined as an average MRC score <4. A prediction model was developed by selecting predictors from an a-priori defined set of candidate predictors, based on known risk factors. Discriminative performance of the prediction model was evaluated, validated internally and compared to the APACHE IV and SOFA score. Of 212 included patients, 103 developed ICU-AW. Highest lactate levels, treatment with any aminoglycoside in the first two days after admission and age were selected as predictors. The area under the receiver operating characteristic curve of the prediction model was 0.71 after internal validation. The new prediction model improved discrimination compared to the APACHE IV and the SOFA score. The new early prediction model for ICU-AW using a set of 3 easily available parameters has fair discriminative performance. This model needs external validation.

New comparison of psychological meaning of colors in samples and objects with semantic ratings

NASA Astrophysics Data System (ADS)

Lee, Tien-Rein

2002-06-01

In color preference and color-meaning research, color chips are widely used as stimuli. Are meanings of isolated color chips generalizeable to contextualized colors? According to Taft (1996), few significant differences exist between chip and object ratings for the same color. A similar survey was performed on 192 college students. This article reports the results of the study comparing semantic rating of color applied to a variety of familiar objects. The objects were a cup, T-shirt, sofa, car, notebook, and MP3 player, all images that represent daily life familiar objects. Subjects rated a set of 16 color chips, against 6 bipolar, 7-step semantic differential scales. The scales consisted of beautiful-ugly, soft-hard, warm-cool, elegant-vulgar, loud- discreet, and masculine-feminine. Analyses performed on the data indicated that unlike Taft's findings on 1996, significant differences existed between chip and object rating for the same color in every scale. The results of the study have implications for the use of color chips in color planning which suggest they are not compatible with the generality of results of the earlier color meaning research. Generally, a color judged to be beautiful, elegant and warm when presented as a chip does not equal beautiful, elegant, and warm when applied to the surface of an object such as a cup, T-shirt, sofa, car.

Conformational Rearrangement Within the Soluble Domains of the CD4 Receptor is Ligand-Specific

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashish,F.; Juncadella, I.; Garg, R.

2008-01-01

Ligand binding induces shape changes within the four modular ectodomains (D1-D4) of the CD4 receptor, an important receptor in immune signaling. Small angle x-ray scattering (SAXS) on both a two-domain and a four-domain construct of the soluble CD4 (sCD4) is consistent with known crystal structures demonstrating a bilobal and a semi-extended tetralobal Z conformation in solution, respectively. Detection of conformational changes within sCD4 as a result of ligand binding was followed by SAXS on sCD4 bound to two different glycoprotein ligands: the tick saliva immunosuppressor Salp15 and the HIV-1 envelope protein gp120. Ab initio modeling of these data showed thatmore » both Salp15 and gp120 bind to the D1 domain of sCD4 and yet induce drastically different structural rearrangements. Upon binding, Salp15 primarily distorts the characteristic lobal architecture of the sCD4 without significantly altering the semi-extended shape of the sCD4 receptor. In sharp contrast, the interaction of gp120 with sCD4 induces a shape change within sCD4 that can be described as a Z-to-U bi-fold closure of the four domains across its flexible D2-D3 linker. Placement of known crystal structures within the boundaries of the SAXS-derived models suggests that the ligand-induced shape changes could be a result of conformational changes within this D2-D3 linker. Functionally, the observed shape changes in CD4 receptor causes dissociation of lymphocyte kinase from the cytoplasmic domain of Salp15-bound CD4 and facilitates an interaction between the exposed V3 loops of CD4-bound gp120 molecule to the extracellular loops of its co-receptor, a step essential for HIV-1 viral entry.« less

SEA domain autoproteolysis accelerated by conformational strain: mechanistic aspects.

PubMed

Johansson, Denny G A; Macao, Bertil; Sandberg, Anders; Härd, Torleif

2008-04-04

A subclass of SEA (sea urchin sperm protein, enterokinase, and agrin) domain proteins undergoes autoproteolysis between glycine and serine in a conserved G(-1)S+1VVV motif to generate stable heterodimers. Autoproteolysis has been suggested to involve only the intramolecular catalytic action of the conserved serine hydroxyl in combination with conformational strain of the glycine-serine peptide bond. We conducted a number of experiments and simulations on the SEA domain from the MUC1 mucin to test this mechanism. Alanine-scanning mutagenesis of polar residues in the vicinity of the cleavage site demonstrates that only the nucleophile at position +1 is required for efficient proteolysis. Molecular modeling shows that an uncleaved trans peptide is incompatible with the native heterodimeric structure, resulting in disruption of secondary structure elements and distortion of the scissile peptide bond. Insertion of glycine residues (to obtain G(n)G(-1)S+1VVV motifs) appears to relieve strain, and autoproteolysis is 100 times slower in a 1G (n=1) mutant and not measurable in 2G and 4G mutants. Removal of the catalytic serine hydroxyl hampers cleavage considerably, but measurable autoproteolysis of this S1098A mutant still proceeds in the presence of strain alone. The uncleaved SEA precursor populates interconverting partially folded conformations, and autoproteolysis coincides with adoption of proper beta-sheet secondary structure and completed folding. Molecular dynamics simulations of the precursor show that the serine hydroxyl and the preceding glycine carbonyl carbon can be in van der Waals contact at the same time as the scissile peptide bond becomes strained. These observations are all consistent with autoproteolysis accelerated by N-->O acyl shift and conformational strain imposed upon protein folding in a reaction for which the free-energy barrier is decreased by substrate destabilization rather than by transition-state stabilization. The energetics of this coupled folding and autoproteolysis mechanism is accounted for in an accompanying article.

Conformational Changes during Pore Formation by the Perforin-Related Protein Pleurotolysin

PubMed Central

Lukoyanova, Natalya; Kondos, Stephanie C.; Farabella, Irene; Law, Ruby H. P.; Reboul, Cyril F.; Caradoc-Davies, Tom T.; Spicer, Bradley A.; Kleifeld, Oded; Traore, Daouda A. K.; Ekkel, Susan M.; Voskoboinik, Ilia; Trapani, Joseph A.; Hatfaludi, Tamas; Oliver, Katherine; Hotze, Eileen M.; Tweten, Rodney K.; Whisstock, James C.; Topf, Maya; Saibil, Helen R.; Dunstone, Michelle A.

2015-01-01

Membrane attack complex/perforin-like (MACPF) proteins comprise the largest superfamily of pore-forming proteins, playing crucial roles in immunity and pathogenesis. Soluble monomers assemble into large transmembrane pores via conformational transitions that remain to be structurally and mechanistically characterised. Here we present an 11 Å resolution cryo-electron microscopy (cryo-EM) structure of the two-part, fungal toxin Pleurotolysin (Ply), together with crystal structures of both components (the lipid binding PlyA protein and the pore-forming MACPF component PlyB). These data reveal a 13-fold pore 80 Å in diameter and 100 Å in height, with each subunit comprised of a PlyB molecule atop a membrane bound dimer of PlyA. The resolution of the EM map, together with biophysical and computational experiments, allowed confident assignment of subdomains in a MACPF pore assembly. The major conformational changes in PlyB are a ∼70° opening of the bent and distorted central β-sheet of the MACPF domain, accompanied by extrusion and refolding of two α-helical regions into transmembrane β-hairpins (TMH1 and TMH2). We determined the structures of three different disulphide bond-trapped prepore intermediates. Analysis of these data by molecular modelling and flexible fitting allows us to generate a potential trajectory of β-sheet unbending. The results suggest that MACPF conformational change is triggered through disruption of the interface between a conserved helix-turn-helix motif and the top of TMH2. Following their release we propose that the transmembrane regions assemble into β-hairpins via top down zippering of backbone hydrogen bonds to form the membrane-inserted β-barrel. The intermediate structures of the MACPF domain during refolding into the β-barrel pore establish a structural paradigm for the transition from soluble monomer to pore, which may be conserved across the whole superfamily. The TMH2 region is critical for the release of both TMH clusters, suggesting why this region is targeted by endogenous inhibitors of MACPF function. PMID:25654333

Rotational spectrum and conformational composition of cyanoacetaldehyde, a compound of potential prebiotic and astrochemical interest.

PubMed

Møllendal, Harald; Margulès, Laurent; Motiyenko, Roman A; Larsen, Niels Wessel; Guillemin, Jean-Claude

2012-04-26

The rotational spectrum of cyanoacetaldehyde (NCCH(2)CHO) has been investigated in the 19.5-80.5 and 150-500 GHz spectral regions. It is found that cyanoacetaldehyde is strongly preferred over its tautomer cyanovinylalcohol (NCCH═CHOH) in the gas phase. The spectra of two rotameric forms of cyanoacetaldehyde produced by rotation about the central C-C bond have been assigned. The C-C-C-O dihedral angle has an unusual value of 151(3)° from the synperiplanar (0°) position in one of the conformers denoted I, while this dihedral angle is exactly synperiplanar in the second rotamer called II, which therefore has C(s) symmetry. Conformer I is found to be preferred over II by 2.9(8) kJ/mol from relative intensity measurements. A double minimum potential for rotation about the central C-C bond with a small barrier maximum at the exact antiperiplanar (180°) position leads to Coriolis perturbations in the rotational spectrum of conformer I. Selected transitions of I were fitted to a Hamiltonian allowing for this sort of interaction, and the separation between the two lowest vibrational states was determined to be 58794(14) MHz [1.96112(5) cm(-1)]. Attempts to include additional transitions in the fits using this Hamiltonian failed, and it is concluded that it lacks interaction terms to account satisfactorily for all the observed transitions. The situation was different for II. More than 2000 transitions were assigned and fitted to the usual Watson Hamiltonian, which allowed very accurate values to be determined not only for the rotational constants, but for many centrifugal distortion constants as well. Two vibrationally excited states were also assigned for this form. Theoretical calculations were performed at the B3LYP, MP2, and CCSD levels of theory using large basis sets to augment the experimental work. The predictions of these calculations turned out to be in good agreement with most experimental results.

eIF1 Loop 2 interactions with Met-tRNAi control the accuracy of start codon selection by the scanning preinitiation complex.

PubMed

Thakur, Anil; Hinnebusch, Alan G

2018-05-01

The eukaryotic 43S preinitiation complex (PIC), bearing initiator methionyl transfer RNA (Met-tRNA i ) in a ternary complex (TC) with eukaryotic initiation factor 2 (eIF2)-GTP, scans the mRNA leader for an AUG codon in favorable context. AUG recognition evokes rearrangement from an open PIC conformation with TC in a "P OUT " state to a closed conformation with TC more tightly bound in a "P IN " state. eIF1 binds to the 40S subunit and exerts a dual role of enhancing TC binding to the open PIC conformation while antagonizing the P IN state, necessitating eIF1 dissociation for start codon selection. Structures of reconstituted PICs reveal juxtaposition of eIF1 Loop 2 with the Met-tRNA i D loop in the P IN state and predict a distortion of Loop 2 from its conformation in the open complex to avoid a clash with Met-tRNA i We show that Ala substitutions in Loop 2 increase initiation at both near-cognate UUG codons and AUG codons in poor context. Consistently, the D71A-M74A double substitution stabilizes TC binding to 48S PICs reconstituted with mRNA harboring a UUG start codon, without affecting eIF1 affinity for 40S subunits. Relatively stronger effects were conferred by arginine substitutions; and no Loop 2 substitutions perturbed the rate of TC loading on scanning 40S subunits in vivo. Thus, Loop 2-D loop interactions specifically impede Met-tRNA i accommodation in the P IN state without influencing the P OUT mode of TC binding; and Arg substitutions convert the Loop 2-tRNA i clash to an electrostatic attraction that stabilizes P IN and enhances selection of poor start codons in vivo.

Ultra-wideband, omni-directional, low distortion coaxial antenna

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eubanks, Travis Wayne; Gibson, Christopher Lawrence

An antenna for producing an omni-directional pattern, and using all frequencies of a frequency range simultaneously, is provided with first and second electrically conductive elements disposed coaxially relative to a central axis. The first element has a first surface of revolution about the axis, the first surface of revolution tapering radially outwardly while extending axially away from the second element to terminate at a first axial end of the first element. The second element has a second surface of revolution about the axis, the second surface of revolution tapering radially outwardly while extending axially toward the first element to terminatemore » at a first axial end of the second element. The first and second surfaces of revolution overlap one another radially and axially, and are mutually non-conformal.« less

Jehovah's Witnesses' refusal of blood: obedience to scripture and religious conscience.

PubMed Central

Ridley, D T

1999-01-01

Jehovah's Witnesses are students of the Bible. They refuse transfusions out of obedience to the scriptural directive to abstain and keep from blood. Dr Muramoto disagrees with the Witnesses' religious beliefs in this regard. Despite this basic disagreement over the meaning of Biblical texts, Muramoto flouts the religious basis for the Witnesses' position. His proposed policy change about accepting transfusions in private not only conflicts with the Witnesses' fundamental beliefs but it promotes hypocrisy. In addition, Muramoto's arguments about pressure to conform and coerced disclosure of private information misrepresent the beliefs and practices of Jehovah's Witnesses and ignore the element of individual conscience. In short, Muramoto resorts to distortion and uncorroborated assertions in his effort to portray a matter of religious faith as a matter of medical ethical debate. PMID:10635500

N-(2,3-Dimethyl­phen­yl)-4-hydr­oxy-2-methyl-2H-1,2-benzothia­zine-3-carboxamide 1,1-dioxide

PubMed Central

Siddiqui, Waseeq Ahmad; Bukahari, Iftikhar Hussain; Zia-ur-Rehman, Muhammad; Khan, Islam Ullah; Tizzard, Graham John

2009-01-01

In the crystal structure of the title compound, C18H18N2O4S, the thia­zine ring adopts a distorted half-chair conformation. 1,2-Benzothia­zines of this kind have a wide range of biological activities and are mainly used as medicines in the treatment of inflammation and rheumatoid arthritis. The enolic H atom is involved in an intra­molecular O—H⋯O hydrogen bond, forming a six-membered ring. The mol­ecules arrange themselves into centrosymmetric dimers by means of inter­molecular N—H⋯O hydrogen bonds. A weak inter­molcular C—H⋯O inter­action is also present. PMID:21582293

Methyl 2-methyl-4-(oxiran-2-ylmeth-oxy)-2H-1,2-benzothia-zine-3-carboxyl-ate 1,1-dioxide.

PubMed

Ahmad, Matloob; Siddiqui, Hamid Latif; Zia-Ur-Rehman, Muhammad; Elsegood, Mark R J; Weaver, George W

2010-01-09

In the title compound, C(14)H(15)NO(6)S, the thia-zine ring adopts a distorted half-chair conformation. The structure displays several cooperative weak inter-molecular C-H⋯O hydrogen-bonding inter-actions, giving rise to a two-dimensional sheet packing motif. The CH(2) group in the meth-oxy linker to the oxirane ring, and the CH group in that ring, exhibit twofold positional disorder. The three-membered oxirane ring is twisted approximately perpendicular with respect to thia-zine ring (dihedral angle = 60/86° for the major/minor disorder components). 1,2-Benzothia-zines of this kind have a wide range of biological activities and are mainly used as medicines in the treatment of inflammation and rheumatoid arthritis.

Design and Simulation Test of an Open D-Dot Voltage Sensor

PubMed Central

Bai, Yunjie; Wang, Jingang; Wei, Gang; Yang, Yongming

2015-01-01

Nowadays, sensor development focuses on miniaturization and non-contact measurement. According to the D-dot principle, a D-dot voltage sensor with a new structure was designed based on the differential D-dot sensor with a symmetrical structure, called an asymmetric open D-dot voltage sensor. It is easier to install. The electric field distribution of the sensor was analyzed through Ansoft Maxwell and an open D-dot voltage sensor was designed. This open D-voltage sensor is characteristic of accessible insulating strength and small electric field distortion. The steady and transient performance test under 10 kV-voltage reported satisfying performances of the designed open D-dot voltage sensor. It conforms to requirements for a smart grid measuring sensor in intelligence, miniaturization and facilitation. PMID:26393590

Phase transitions, optical and electronic properties of the layered perovskite hybrid [NH3(CH2)2COOH ]2CdCl4 of Y-aminobutyric acid (GABA)

NASA Astrophysics Data System (ADS)

AlShammari, Mohammed B.; Kaiba, A.; Guionneau, P.; Geesi, Mohammed H.; Aljohani, Talal; Riadi, Yassine

2018-06-01

A new organic-inorganic hybrid with the formula (NH3C3H6CO2H)2CdCl4 has been crystallized and investigated by X-ray diffraction. Structural investigations highlight a first-order reversible structural phase transition occurring within the range (290-370 K) between a chiral (phase II) and non-centrosymmetric (Phase I) crystal packing. This strong structural reorganization is the result of conformational changes in the organic chains accompanied by a decrease in octahedral distortion. The accurate crystallographic analysis illustrates the crucial role of organic moieties. The experimental energy gap value (3.65 eV) is in good agreement with the theoretical value obtained by density functional theory.

Synthesis, characterization stereochemistry and anti-bacterial evaluation of certain N-acyl-c-3,t-3-dimethyl-r-2,c-6-diphenylpiperidin-4-ones

NASA Astrophysics Data System (ADS)

Ponnuswamy, S.; Kayalvizhi, R.; Jamesh, M.; Uma Maheswari, J.; Thenmozhi, M.; Ponnuswamy, M. N.

2016-09-01

A new series of N-acyl-c-3,t-3-dimethyl-r-2,c-6-diphenylpiperidin-4-ones 2-6 has been synthesized and characterized using IR, mass, 1H, 13C, DEPT and 2D (COSY and HSQC) NMR spectral techniques. The NMR spectral data indicate that the N-acylpiperidin-4-ones 2-6 prefer to exist in a distorted boat conformation B1 with coplanar orientation of N-C=O moiety. The stereodynamics of these systems have been studied by recording the dynamic 1H NMR spectra of compound 4, and the energy barrier for N-CO rotation is determined to be 52.75 kJ/mol. Furthermore the compounds 1-5 show significant antibacterial activity.

Crystal structure of [(2R,3R,4S)-3,4-bis(acet-yloxy)-5-iodo-3,4-di-hydro-2H-pyran-2-yl]methyl acetate.

PubMed

Zukerman-Schpector, Julio; Caracelli, Ignez; Stefani, Hélio A; Shamim, Anwar; Tiekink, Edward R T

2015-01-01

In the title compound, C12H15IO7, the 3,4-di-hydro-2H-pyran ring is in a distorted half-boat conformation with the atom bearing the acet-yloxy group adjacent to the C atom bearing the methyl-acetate group lying 0.633 (6) Å above the plane of the remaining ring atoms (r.m.s. deviation = 0.0907 Å). In the crystal, mol-ecules are linked into a supra-molecular chain along the a axis through two C-H⋯O inter-actions to the same acceptor carbonyl O atom; these chains pack with no specific inter-molecular inter-actions between them.

Comparison of the conformation of an oligonucleotide containing a central G-T base pair with the non-mismatch sequence by proton NMR.

PubMed Central

Quignard, E; Fazakerley, G V; van der Marel, G; van Boom, J H; Guschlbauer, W

1987-01-01

We have recorded NOESY spectra of two non-selfcomplementary undecanucleotide duplexes. From the observed NOEs we do not detect any significant distortion of the helix when a G-C pair is replaced by a G-T pair and the normal interresidue connectivities can be followed through the mismatch site. We conclude that the 2D spectra of the non-exchangeable protons do not allow differentiation between a wobble or rare tautomer form for the mismatch. NOE measurements in H2O, however, clearly show that the mismatch adopts a wobble structure and give information on the hydration in the minor groove for the G-T base pair which is embedded between two A-T base pairs in the sequence. PMID:3033602

[Formulation of combined predictive indicators using logistic regression model in predicting sepsis and prognosis].

PubMed

Duan, Liwei; Zhang, Sheng; Lin, Zhaofen

2017-02-01

To explore the method and performance of using multiple indices to diagnose sepsis and to predict the prognosis of severe ill patients. Critically ill patients at first admission to intensive care unit (ICU) of Changzheng Hospital, Second Military Medical University, from January 2014 to September 2015 were enrolled if the following conditions were satisfied: (1) patients were 18-75 years old; (2) the length of ICU stay was more than 24 hours; (3) All records of the patients were available. Data of the patients was collected by searching the electronic medical record system. Logistic regression model was formulated to create the new combined predictive indicator and the receiver operating characteristic (ROC) curve for the new predictive indicator was built. The area under the ROC curve (AUC) for both the new indicator and original ones were compared. The optimal cut-off point was obtained where the Youden index reached the maximum value. Diagnostic parameters such as sensitivity, specificity and predictive accuracy were also calculated for comparison. Finally, individual values were substituted into the equation to test the performance in predicting clinical outcomes. A total of 362 patients (218 males and 144 females) were enrolled in our study and 66 patients died. The average age was (48.3±19.3) years old. (1) For the predictive model only containing categorical covariants [including procalcitonin (PCT), lipopolysaccharide (LPS), infection, white blood cells count (WBC) and fever], increased PCT, increased WBC and fever were demonstrated to be independent risk factors for sepsis in the logistic equation. The AUC for the new combined predictive indicator was higher than that of any other indictor, including PCT, LPS, infection, WBC and fever (0.930 vs. 0.661, 0.503, 0.570, 0.837, 0.800). The optimal cut-off value for the new combined predictive indicator was 0.518. Using the new indicator to diagnose sepsis, the sensitivity, specificity and diagnostic accuracy rate were 78.00%, 93.36% and 87.47%, respectively. One patient was randomly selected, and the clinical data was substituted into the probability equation for prediction. The calculated value was 0.015, which was less than the cut-off value (0.518), indicating that the prognosis was non-sepsis at an accuracy of 87.47%. (2) For the predictive model only containing continuous covariants, the logistic model which combined acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score to predict in-hospital death events, both APACHE II score and SOFA score were independent risk factors for death. The AUC for the new predictive indicator was higher than that of APACHE II score and SOFA score (0.834 vs. 0.812, 0.813). The optimal cut-off value for the new combined predictive indicator in predicting in-hospital death events was 0.236, and the corresponding sensitivity, specificity and diagnostic accuracy for the combined predictive indicator were 73.12%, 76.51% and 75.70%, respectively. One patient was randomly selected, and the APACHE II score and SOFA score was substituted into the probability equation for prediction. The calculated value was 0.570, which was higher than the cut-off value (0.236), indicating that the death prognosis at an accuracy of 75.70%. The combined predictive indicator, which is formulated by logistic regression models, is superior to any single indicator in predicting sepsis or in-hospital death events.

An Overview of Major Terrestrial, Celestial, and Temporal Coordinate Systems for Target Tracking

DTIC Science & Technology

2016-08-10

interp and Subroutines) http://hpiers.obspm.fr/eop-pc/index.php?index=models General Software for Astronomy and Time Conversions The IAU’s Standards...of Fundamental Astronomy Software [146] http://www.iausofa.org Software for Optimal 2D Assignment An overview of 2D assignment algorithms; the... Astronomy (SOFA) library were used to change the epoch of the data. The points in red are at the epoch of the Hipparcos catalog (1994.25 TT), and 20

Twenty-Fifth Annual Conference on the Physics and Chemistry of Semiconductor Interfaces. Volume 16, Number 4

DTIC Science & Technology

1998-08-01

Shigefusa Chichibu, Takayuki Sofa, Kazumi Wada, and Shuji Nakamura Dynamics of localized excitons in InGaN/GaN quantum wells ,. 0 _ _ . w 7onn...Electron. Electron Phys. 11, 413 (1959). 2E. G. Bylander, J. Appl. Phys. 49, 1188 (1978). 3M. Hiraki et al., J. Lumin. 12/13, 941 (1976). 4A. O...University of Tokyo, Noda, Chiba 278-8510, Japan Takayuki Sotab) TT . . . Department of Electrical, Electronics, and Computer Engineering, Waseda

Policy Options and the U.S. Withdrawal from Iraq: An Analysis of the Way Ahead

DTIC Science & Technology

2009-02-01

specialists combine in-country experience, language skills, and the use of local primary-source data to produce empirically based work. All of our...due to the supposed certitudes of the recently signed Status of Forces Agreement (SOFA); however, there are crucial decisions to be made, and made...Iraqi parliament on November 27, 2008, and signed by the leaders of the two countries on December 14, 2008. This agreement replaces the UN mandate on

Policy Options and the U.S. Withdrawal from Iraq: An Analysis of the Way Ahead

DTIC Science & Technology

2009-07-01

country experience, language skills, and the use of local primary-source data to produce empirically based work. All of our analysts have advanced...the supposed certitudes of the recently signed Status of Forces Agreement (SOFA); however, there are crucial decisions to be made, and made quickly...parliament on November 27, 2008, and signed by the leaders of the two countries on December 14, 2008. This agreement replaces the UN mandate on the first

Interplay between Peptide Bond Geometrical Parameters in Nonglobular Structural Contexts

PubMed Central

Esposito, Luciana; De Simone, Alfonso; Vitagliano, Luigi

2013-01-01

Several investigations performed in the last two decades have unveiled that geometrical parameters of protein backbone show a remarkable variability. Although these studies have provided interesting insights into one of the basic aspects of protein structure, they have been conducted on globular and water-soluble proteins. We report here a detailed analysis of backbone geometrical parameters in nonglobular proteins/peptides. We considered membrane proteins and two distinct fibrous systems (amyloid-forming and collagen-like peptides). Present data show that in these systems the local conformation plays a major role in dictating the amplitude of the bond angle N-Cα-C and the propensity of the peptide bond to adopt planar/nonplanar states. Since the trends detected here are in line with the concept of the mutual influence of local geometry and conformation previously established for globular and water-soluble proteins, our analysis demonstrates that the interplay of backbone geometrical parameters is an intrinsic and general property of protein/peptide structures that is preserved also in nonglobular contexts. For amyloid-forming peptides significant distortions of the N-Cα-C bond angle, indicative of sterical hidden strain, may occur in correspondence with side chain interdigitation. The correlation between the dihedral angles Δω/ψ in collagen-like models may have interesting implications for triple helix stability. PMID:24455689

Interplay between peptide bond geometrical parameters in nonglobular structural contexts.

PubMed

Esposito, Luciana; Balasco, Nicole; De Simone, Alfonso; Berisio, Rita; Vitagliano, Luigi

2013-01-01

Several investigations performed in the last two decades have unveiled that geometrical parameters of protein backbone show a remarkable variability. Although these studies have provided interesting insights into one of the basic aspects of protein structure, they have been conducted on globular and water-soluble proteins. We report here a detailed analysis of backbone geometrical parameters in nonglobular proteins/peptides. We considered membrane proteins and two distinct fibrous systems (amyloid-forming and collagen-like peptides). Present data show that in these systems the local conformation plays a major role in dictating the amplitude of the bond angle N-C(α)-C and the propensity of the peptide bond to adopt planar/nonplanar states. Since the trends detected here are in line with the concept of the mutual influence of local geometry and conformation previously established for globular and water-soluble proteins, our analysis demonstrates that the interplay of backbone geometrical parameters is an intrinsic and general property of protein/peptide structures that is preserved also in nonglobular contexts. For amyloid-forming peptides significant distortions of the N-C(α)-C bond angle, indicative of sterical hidden strain, may occur in correspondence with side chain interdigitation. The correlation between the dihedral angles Δω/ψ in collagen-like models may have interesting implications for triple helix stability.

Molecular dynamics study of some non-hydrogen-bonding base pair DNA strands

NASA Astrophysics Data System (ADS)

Tiwari, Rakesh K.; Ojha, Rajendra P.; Tiwari, Gargi; Pandey, Vishnudatt; Mall, Vijaysree

2018-05-01

In order to elucidate the structural activity of hydrophobic modified DNA, the DMMO2-D5SICS, base pair is introduced as a constituent in different set of 12-mer and 14-mer DNA sequences for the molecular dynamics (MD) simulation in explicit water solvent. AMBER 14 force field was employed for each set of duplex during the 200ns production-dynamics simulation in orthogonal-box-water solvent by the Particle-Mesh-Ewald (PME) method in infinite periodic boundary conditions (PBC) to determine conformational parameters of the complex. The force-field parameters of modified base-pair were calculated by Gaussian-code using Hartree-Fock /ab-initio methodology. RMSD Results reveal that the conformation of the duplex is sequence dependent and the binding energy of the complex depends on the position of the modified base-pair in the nucleic acid strand. We found that non-bonding energy had a significant contribution to stabilising such type of duplex in comparison to electrostatic energy. The distortion produced within strands by such type of base-pair was local and destabilised the duplex integrity near to substitution, moreover the binding energy of duplex depends on the position of substitution of hydrophobic base-pair and the DNA sequence and strongly supports the corresponding experimental study.

Localized DNA melting and structural pertubations in the origin of replication, oriC, of Escherichia coli in vitro and in vivo.

PubMed Central

Gille, H; Messer, W

1991-01-01

The leftmost region of the Escherichia coli origin of DNA replication (oriC) contains three tandemly repeated AT-rich 13mers which have been shown to become single-stranded during the early stages of initiation in vitro. Melting is induced by the ATP form of DnaA, the initiator protein of DNA replication. KMnO4 was used to probe for single-stranded regions and altered DNA conformation during the initiation of DNA replication at oriC in vitro and in vivo. Unpairing in the AT-rich 13mer region is thermodynamically stable even in the absence of DnaA protein, but only when divalent cations are omitted from the reaction. In the presence of Mg2+, oriC melting is strictly DnaA dependent. The sensitive region is distinct from that detected in the absence of DnaA as it is located further to the left within the minimal origin. In addition, the DNA is severely distorted between the three 13mers and the IHF binding site in oriC. A change of conformation can also be observed during the initiation of DNA replication in vivo. This is the first in vivo evidence for a structural change at the 13mers during initiation complex formation. Images PMID:2026151

Metric Optimization for Surface Analysis in the Laplace-Beltrami Embedding Space

PubMed Central

Lai, Rongjie; Wang, Danny J.J.; Pelletier, Daniel; Mohr, David; Sicotte, Nancy; Toga, Arthur W.

2014-01-01

In this paper we present a novel approach for the intrinsic mapping of anatomical surfaces and its application in brain mapping research. Using the Laplace-Beltrami eigen-system, we represent each surface with an isometry invariant embedding in a high dimensional space. The key idea in our system is that we realize surface deformation in the embedding space via the iterative optimization of a conformal metric without explicitly perturbing the surface or its embedding. By minimizing a distance measure in the embedding space with metric optimization, our method generates a conformal map directly between surfaces with highly uniform metric distortion and the ability of aligning salient geometric features. Besides pairwise surface maps, we also extend the metric optimization approach for group-wise atlas construction and multi-atlas cortical label fusion. In experimental results, we demonstrate the robustness and generality of our method by applying it to map both cortical and hippocampal surfaces in population studies. For cortical labeling, our method achieves excellent performance in a cross-validation experiment with 40 manually labeled surfaces, and successfully models localized brain development in a pediatric study of 80 subjects. For hippocampal mapping, our method produces much more significant results than two popular tools on a multiple sclerosis study of 109 subjects. PMID:24686245

Syntheses, structures, and properties of imidazolate-bridged Cu(II)-Cu(II) and Cu(II)-Zn(II) dinuclear complexes of a single macrocyclic ligand with two hydroxyethyl pendants.

PubMed

Li, Dongfeng; Li, Shuan; Yang, Dexi; Yu, Jiuhong; Huang, Jin; Li, Yizhi; Tang, Wenxia

2003-09-22

The imidazolate-bridged homodinuclear Cu(II)-Cu(II) complex, [(CuimCu)L]ClO(4).0.5H(2)O (1), and heterodinuclear Cu(II)-Zn(II) complex, [(CuimZnL(-)(2H))(CuimZnL(-)(H))](ClO(4))(3) (2), of a single macrocyclic ligand with two hydroxyethyl pendants, L (L = 3,6,9,16,19,22-hexaaza-6,19-bis(2-hydroxyethyl)tricyclo[22,2,2,2(11,14)]triaconta-1,11,13,24,27,29-hexaene), have been synthesized as possible models for copper-zinc superoxide dismutase (Cu(2),Zn(2)-SOD). Their crystal structures analyzed by X-ray diffraction methods have shown that the structures of the two complexes are markedly different. Complex 1 crystallizes in the orthorhombic system, containing an imidazolate-bridged dicopper(II) [Cu-im-Cu](3+) core, in which the two copper(II) ions are pentacoordinated by virtue of an N4O environment with a Cu.Cu distance of 5.999(2) A, adopting the geometry of distorted trigonal bipyramid and tetragonal pyramid, respectively. Complex 2 crystallizes in the triclinic system, containing two similar Cu-im-Zn cores in the asymmetric unit, in which both the Cu(II) and Zn(II) ions are pentacoordinated in a distorted trigonal bipyramid geometry, with the Cu.Zn distance of 5.950(1)/5.939(1) A, respectively. Interestingly, the macrocyclic ligand with two arms possesses a chairlike (anti) conformation in complex 1, but a boatlike (syn) conformation in complex 2. Magnetic measurements and ESR spectroscopy of complex 1 have revealed the presence of an antiferromagnetic exchange interaction between the two Cu(II) ions. The ESR spectrum of the Cu(II)-Zn(II) heterodinuclear complex 2 displayed a typical signal for mononuclear trigonal bipyramidal Cu(II) complexes. From pH-dependent ESR and electronic spectroscopic studies, the imidazolate bridges in the two complexes have been found to be stable over broad pH ranges. The cyclic voltammograms of the two complexes have been investigated. Both of the two complexes can catalyze the dismutation of superoxide and show rather high activity.

Shape Classification Using Wasserstein Distance for Brain Morphometry Analysis.

PubMed

Su, Zhengyu; Zeng, Wei; Wang, Yalin; Lu, Zhong-Lin; Gu, Xianfeng

2015-01-01

Brain morphometry study plays a fundamental role in medical imaging analysis and diagnosis. This work proposes a novel framework for brain cortical surface classification using Wasserstein distance, based on uniformization theory and Riemannian optimal mass transport theory. By Poincare uniformization theorem, all shapes can be conformally deformed to one of the three canonical spaces: the unit sphere, the Euclidean plane or the hyperbolic plane. The uniformization map will distort the surface area elements. The area-distortion factor gives a probability measure on the canonical uniformization space. All the probability measures on a Riemannian manifold form the Wasserstein space. Given any 2 probability measures, there is a unique optimal mass transport map between them, the transportation cost defines the Wasserstein distance between them. Wasserstein distance gives a Riemannian metric for the Wasserstein space. It intrinsically measures the dissimilarities between shapes and thus has the potential for shape classification. To the best of our knowledge, this is the first. work to introduce the optimal mass transport map to general Riemannian manifolds. The method is based on geodesic power Voronoi diagram. Comparing to the conventional methods, our approach solely depends on Riemannian metrics and is invariant under rigid motions and scalings, thus it intrinsically measures shape distance. Experimental results on classifying brain cortical surfaces with different intelligence quotients demonstrated the efficiency and efficacy of our method.

DNA wrapping and distortion by an oligomeric homeodomain protein.

PubMed

Williams, Hannah; Jayaraman, Padma-Sheela; Gaston, Kevin

2008-10-31

Many transcription factors alter DNA or chromatin structure. Changes in chromatin structure are often brought about by the recruitment of chromatin-binding proteins, chromatin-modifying proteins, or other transcription co-activator or co-repressor proteins. However, some transcription factors form oligomeric assemblies that may themselves induce changes in DNA conformation and chromatin structure. The proline-rich homeodomain (PRH/Hex) protein is a transcription factor that regulates cell differentiation and cell proliferation, and has multiple roles in embryonic development. Earlier, we showed that PRH can repress transcription by multiple mechanisms, including the recruitment of co-repressor proteins belonging to the TLE family of chromatin-binding proteins. Our in vivo crosslinking studies have shown that PRH forms oligomeric complexes in cells and a variety of biophysical techniques suggest that the protein forms octamers. However, as yet we have little knowledge of the role played by PRH oligomerisation in the regulation of promoter activity or of the architecture of promoters that are regulated directly by PRH in cells. Here, we compare the binding of PRH and the isolated PRH homeodomain to DNA fragments with single and multiple PRH sites, using gel retardation assays and DNase I and chemical footprinting. We show that the PRH oligomer binds to multiple sites within the human Goosecoid promoter with high affinity and that the binding of PRH brings about DNA distortion. We suggest that PRH octamers wrap DNA in order to bring about transcriptional repression.

A Bridge to Coordination Isomer Selection in Lanthanide(III) DOTA-tetraamide Complexes

PubMed Central

Vipond, Jeff; Woods, Mark; Zhao, Piyu; Tircso, Gyula; Ren, Jimin; Bott, Simon G.; Ogrin, Doug; Kiefer, Garry E.; Kovacs, Zoltan; Sherry, A.Dean

2008-01-01

Interest in macrocyclic lanthanide complexes such as DOTA is driven largely through interest in their use as contrast agents for MRI. The lanthanide tetraamide derivatives of DOTA have shown considerable promise as PARACEST agents, taking advantage of the slow water exchange kinetics of this class of complex. We postulated that water exchange in these tetraamide complexes could be slowed even further by introducing a group to sterically encumber the space above the water coordination site, thereby hindering the departure and approach of water molecules to the complex. The ligand 8O2-bridged-DOTAM was synthesized in a 34% yield from cyclen. It was found that the lanthanide complexes of this ligand did not possess a water molecule in the inner coordination sphere of the bound lanthanide. The crystal structure of the ytterbium complex revealed that distortions to the coordination sphere were induced by the steric constraints imposed on the complex by the bridging unit. The extent of the distortion was found to increase with increasing ionic radius of the lanthanide ion, eventually resulting in a complete loss of symmetry in the complex. Because this ligand system is bicyclic, the conformation of each ring in the system is constrained by that of the other, in consequence inclusion of the bridging unit in the complexes means only a twisted square antiprismatic coordination geometry is observed for complexes of 8O2-bridged-DOTAM. PMID:17295475

Shape Classification Using Wasserstein Distance for Brain Morphometry Analysis

PubMed Central

Su, Zhengyu; Zeng, Wei; Wang, Yalin; Lu, Zhong-Lin; Gu, Xianfeng

2015-01-01

Brain morphometry study plays a fundamental role in medical imaging analysis and diagnosis. This work proposes a novel framework for brain cortical surface classification using Wasserstein distance, based on uniformization theory and Riemannian optimal mass transport theory. By Poincare uniformization theorem, all shapes can be conformally deformed to one of the three canonical spaces: the unit sphere, the Euclidean plane or the hyperbolic plane. The uniformization map will distort the surface area elements. The area-distortion factor gives a probability measure on the canonical uniformization space. All the probability measures on a Riemannian manifold form the Wasserstein space. Given any 2 probability measures, there is a unique optimal mass transport map between them, the transportation cost defines the Wasserstein distance between them. Wasserstein distance gives a Riemannian metric for the Wasserstein space. It intrinsically measures the dissimilarities between shapes and thus has the potential for shape classification. To the best of our knowledge, this is the first work to introduce the optimal mass transport map to general Riemannian manifolds. The method is based on geodesic power Voronoi diagram. Comparing to the conventional methods, our approach solely depends on Riemannian metrics and is invariant under rigid motions and scalings, thus it intrinsically measures shape distance. Experimental results on classifying brain cortical surfaces with different intelligence quotients demonstrated the efficiency and efficacy of our method. PMID:26221691

Optimal self-cleavage activity of the hepatitis delta virus RNA is dependent on a homopurine base pair in the ribozyme core.

PubMed Central

Been, M D; Perrotta, A T

1995-01-01

A non-Watson-Crick G.G interaction within the core region of the hepatitis delta virus (HDV) antigenomic ribozyme is required for optimal rates of self-cleavage activity. Base substitutions for either one or both G's revealed that full activity was obtained only when both G's were replaced with A's. At those positions, substitutions that generate potential Watson-Crick, G.U, heteropurine, or homopyrimidine combinations resulted in dramatically lower cleavage activity. A homopurine symmetric base pair, of the same type identified in the high-affinity binding site of the HIV RRE, is most consistent with this data. Additional features shared between the antigenomic ribozyme and the Rev binding site in the vicinity of the homopurine pairs suggest some structural similarity for this region of the two RNAs and a possible motif associated with this homopurine interaction. Evidence for a homopurine pair at the equivalent position in a modified form of the HDV genomic ribozyme was also found. With the postulated symmetric pairing scheme, large distortions in the nucleotide conformation, the sugar-phosphate backbone, or both would be necessary to accommodate this interaction at the end of a helix; we hypothesize that this distortion is critical to the structure of the active site of the ribozyme and it is stabilized by the homopurine base pair. PMID:8595561

Relationship between the nonlinear ferroelectric and liquid crystal models for microtubules

NASA Astrophysics Data System (ADS)

Satarić, M. V.; Tuszyński, J. A.

2003-01-01

Microtubules (MTs), which are the main components of the cytoskeleton, are important in a variety of cellular activities, but some physical properties underlying the most important features of their behavior are still lacking satisfactory explanation. One of the essential enigmas regarding the energy balance in MTs is the hydrolysis of the exchangable guanosine 5'-triphosphate bound to the β monomer of the molecule. The energy released in the hydrolysis process amounts to 6.25×10-20 J and has been the subject of many attempts to answer the questions of its utilization. Earlier, we put forward a hypothesis that this energy can cause a local conformational distortion of the dimer. This distortion should have nonlinear character and could lead to the formation of a traveling kink soliton. In this paper we use the formalism of the liquid crystal theory to consider the nonlinear dynamics of MTs. We demonstrate that this new model is formally equivalent to our earlier ferroelectric model which was widely exploited in an attempt to elucidate some important dynamical activities in MTs. We also study the stability of kink solitons against small perturbations and their unusual mutual interactions as well as the interactions with structural inhomogenities of MTs. Our new approach based on liquid crystal properties of microtubules has been recently corroborated by new insights gained from the electrostatic properties of tubulin and microtubules.

Crystal structures of two cross-bridged chromium(III) tetra­aza­macrocycles

PubMed Central

Prior, Timothy J.; Maples, Danny L.; Maples, Randall D.; Hoffert, Wesley A.; Parsell, Trenton H.; Silversides, Jon D.; Archibald, Stephen J.; Hubin, Timothy J.

2014-01-01

The crystal structure of di­chlorido­(4,10-dimethyl-1,4,7,10-tetra­aza­bicyclo­[5.5.2]tetra­deca­ne)chromium(III) hexa­fluorido­phosphate, [CrCl2(C12H26N4)]PF6, (I), has monoclinic symmetry (space group P21/n) at 150 K. The structure of the related di­chlorido­(4,11-dimethyl-1,4,8,11-tetra­aza­bicyclo­[6.6.2]hexa­deca­ne)chromium(III) hexa­fluorido­phosphate, [CrCl2(C14H30N4)]PF6, (II), also displays monoclinic symmetry (space group P21/c) at 150 K. In each case, the CrIII ion is hexa­coordinate with two cis chloride ions and two non-adjacent N atoms bound cis equatorially and the other two non-adjacent N atoms bound trans axially in a cis-V conformation of the macrocycle. The extent of the distortion from the preferred octa­hedral coordination geometry of the CrIII ion is determined by the parent macrocycle ring size, with the larger cross-bridged cyclam ring in (II) better able to accommodate this preference and the smaller cross-bridged cyclen ring in (I) requiring more distortion away from octa­hedral geometry. PMID:25309165

Crystal structure of bis­[trans-(ethane-1,2-di­amine-κ2 N,N′)bis­(thio­cyanato-κN)chromium(III)] tetra­chlorido­zincate from synchrotron data

PubMed Central

Moon, Dohyun; Choi, Jong-Ha

2015-01-01

The structure of the title compound, [Cr(NCS)2(C2H8N2)2]2[ZnCl4], has been determined from synchrotron data. In the asymmetric unit, there are four independent halves of the CrIII complex cations, each of which lies on an inversion centre, and one tetra­chlorido­zincate anion in a general position. The CrIII atoms are coordinated by the four N atoms of two ethane-1,2-di­amine (en) ligands in the equatorial plane and two N-bound NCS− anions in a trans arrangement, displaying a slightly distorted octa­hedral geometry with crystallographic inversion symmetry. The Cr—N(en) and Cr—N(NCS) bond lengths range from 2.0653 (10) to 2.0837 (10) Å and from 1.9811 (10) to 1.9890 (10) Å, respectively. The five-membered metalla-rings are in stable gauche conformations. The [ZnCl4]2− anion has a distorted tetra­hedral geometry. The crystal structure is stabilized by inter­molecular hydrogen bonds involving the en NH2 or CH2 groups as donors and chloride ligands of the anion and S atoms of NCS− ligands as acceptors. PMID:25705463

Structural Mechanism of Replication Stalling on a Bulky Amino-Polycyclic Aromatic Hydrocarbon DNA Adduct by a Y Family DNA Polymerase

PubMed Central

Kirouac, Kevin N.; Basu, Ashis K.; Ling, Hong

2013-01-01

Polycyclic aromatic hydrocarbons and their nitro derivatives are culprits of the detrimental health effects of environmental pollution. These hydrophobic compounds metabolize to reactive species and attach to DNA producing bulky lesions, such as N-[deoxyguanosine-8-yl]-1-aminopyrene (APG), in genomic DNA. The bulky adducts block DNA replication by high-fidelity polymerases and compromise replication fidelities and efficiencies by specialized lesion bypass polymerases. Here we present three crystal structures of the DNA polymerase Dpo4, a model translesion DNA polymerase of the Y family, in complex with APG-lesion-containing DNA in pre-insertion and extension stages. APG is captured in two conformations in the pre-insertion complex; one is highly exposed to the solvent, whereas the other is harbored in a shallow cleft between the finger and unique Y family little finger domain. In contrast, APG is in a single conformation at the extension stage, in which the pyrene ring is sandwiched between the little finger domain and a base from the turning back single-stranded template strand. Strikingly, a nucleotide intercalates the DNA helix to form a quaternary complex with Dpo4, DNA, and an incoming nucleotide, which stabilizes the distorted DNA structure at the extension stage. The unique APG DNA conformations in Dpo4 inhibit DNA translocation through the polymerase active site for APG bypass. We also modeled an insertion complex that illustrates a solvent-exposed pyrene ring contributing to an unstable insertion state. The structural work combined with our lesion replication assays provides a novel structural mechanism on bypass of DNA adducts containing polycyclic aromatic hydrocarbon moieties. PMID:23876706

Structural mechanism of replication stalling on a bulky amino-polycyclic aromatic hydrocarbon DNA adduct by a y family DNA polymerase.

PubMed

Kirouac, Kevin N; Basu, Ashis K; Ling, Hong

2013-11-15

Polycyclic aromatic hydrocarbons and their nitro derivatives are culprits of the detrimental health effects of environmental pollution. These hydrophobic compounds metabolize to reactive species and attach to DNA producing bulky lesions, such as N-[deoxyguanosine-8-yl]-1-aminopyrene (APG), in genomic DNA. The bulky adducts block DNA replication by high-fidelity polymerases and compromise replication fidelities and efficiencies by specialized lesion bypass polymerases. Here we present three crystal structures of the DNA polymerase Dpo4, a model translesion DNA polymerase of the Y family, in complex with APG-lesion-containing DNA in pre-insertion and extension stages. APG is captured in two conformations in the pre-insertion complex; one is highly exposed to the solvent, whereas the other is harbored in a shallow cleft between the finger and unique Y family little finger domain. In contrast, APG is in a single conformation at the extension stage, in which the pyrene ring is sandwiched between the little finger domain and a base from the turning back single-stranded template strand. Strikingly, a nucleotide intercalates the DNA helix to form a quaternary complex with Dpo4, DNA, and an incoming nucleotide, which stabilizes the distorted DNA structure at the extension stage. The unique APG DNA conformations in Dpo4 inhibit DNA translocation through the polymerase active site for APG bypass. We also modeled an insertion complex that illustrates a solvent-exposed pyrene ring contributing to an unstable insertion state. The structural work combined with our lesion replication assays provides a novel structural mechanism on bypass of DNA adducts containing polycyclic aromatic hydrocarbon moieties. © 2013.

Conformational dynamics of abasic DNA upon interactions with AP endonuclease 1 revealed by stopped-flow fluorescence analysis.

PubMed

Kanazhevskaya, Lyubov Yu; Koval, Vladimir V; Vorobjev, Yury N; Fedorova, Olga S

2012-02-14

Apurinic/apyrimidinic (AP) sites are abundant DNA lesions arising from exposure to UV light, ionizing radiation, alkylating agents, and oxygen radicals. In human cells, AP endonuclease 1 (APE1) recognizes this mutagenic lesion and initiates its repair via a specific incision of the phosphodiester backbone 5' to the AP site. We have investigated a detailed mechanism of APE1 functioning using fluorescently labeled DNA substrates. A fluorescent adenine analogue, 2-aminopurine, was introduced into DNA substrates adjacent to the abasic site to serve as an on-site reporter of conformational transitions in DNA during the catalytic cycle. Application of a pre-steady-state stopped-flow technique allows us to observe changes in the fluorescence intensity corresponding to different stages of the process in real time. We also detected an intrinsic Trp fluorescence of the enzyme during interactions with 2-aPu-containing substrates. Our data have revealed a conformational flexibility of the abasic DNA being processed by APE1. Quantitative analysis of fluorescent traces has yielded a minimal kinetic scheme and appropriate rate constants consisting of four steps. The results obtained from stopped-flow data have shown a substantial influence of the 2-aPu base location on completion of certain reaction steps. Using detailed molecular dynamics simulations of the DNA substrates, we have attributed structural distortions of AP-DNA to realization of specific binding, effective locking, and incision of the damaged DNA. The findings allowed us to accurately discern the step that corresponds to insertion of specific APE1 amino acid residues into the abasic DNA void in the course of stabilization of the precatalytic complex.

Gas-Phase Molecular Structure of Nopinone and its Water Complexes Studied by Microwave Fourier Transform Spectroscopy and Quantum Chemical Calculations

NASA Astrophysics Data System (ADS)

Neeman, Elias M.; Aviles Moreno, Juan-Ramon; Huet, T. R.

2016-06-01

Several monoterpenes and terpenoids are biogenic volatile organic compounds which are emitted in the atmosphere, where they react with OH, O_3 and NO_x etc. to give rise to several oxidation and degradation products. Their decomposition products are a major source of secondray organic aerosol (SOA). Spectroscopic information on these atmospheric species is still very scarce. The rotational spectrum of nopinone (C_9H14O) one of the major oxidation products of β-pinene, and of its water complexes were recorded in a supersonic jet expansion with a Fourier transform microwave spectrometer over the range 2-20 GHz. The structure of the unique stable conformer of the nopinone was optimized using density functional theory and ab initio calculations. Signals from the parent species and from the 13C and 18O isotopomers were observed in natural abundance. A magnetic hyperfine structure associated with the pairs of hydrogen nuclei in the methylene groups was observed and modeled. The structures of several conformers of the nopinone-water complexes with up to three molecules of water were optimized using density functional theory and ab initio calculations. The energetically most stable of calculated conformers were observed and anlyzed. The rotational and centrifugal distortion parameters were fitted to a Watson's Hamiltonian in the A-reduction. The present work provides the first spectroscopic characterization of nopinone and its water complexes in the gas phase. A. Calogirou, B.R. Larsen, and D. Kotzias, Atmospheric Environment, 33, 1423-1439, (1999) P. Paasonen et al., Nat. Geosci., 6, 438-442 (2013) D. Zhang and R. Zhang The Journal of Chemical Physics, 122, 114308, (2005) R. Winterhalter et al. Journal of Atmospheric Chemistry, 35, 165-197, (2000)

Protein structural dynamics at the gas/water interface examined by hydrogen exchange mass spectrometry.

PubMed

Xiao, Yiming; Konermann, Lars

2015-08-01

Gas/water interfaces (such as air bubbles or foam) are detrimental to the stability of proteins, often causing aggregation. This represents a potential problem for industrial processes, for example, the production and handling of protein drugs. Proteins possess surfactant-like properties, resulting in a high affinity for gas/water interfaces. The tendency of previously buried nonpolar residues to maximize contact with the gas phase can cause significant structural distortion. Most earlier studies in this area employed spectroscopic tools that could only provide limited information. Here we use hydrogen/deuterium exchange (HDX) mass spectrometry (MS) for probing the conformational dynamics of the model protein myoglobin (Mb) in the presence of N(2) bubbles. HDX/MS relies on the principle that unfolded and/or highly dynamic regions undergo faster deuteration than tightly folded segments. In bubble-free solution Mb displays EX2 behavior, reflecting the occurrence of short-lived excursions to partially unfolded conformers. A dramatically different behavior is seen in the presence of N(2) bubbles; EX2 dynamics still take place, but in addition the protein shows EX1 behavior. The latter results from interconversion of the native state with conformers that are globally unfolded and long-lived. These unfolded species likely correspond to Mb that is adsorbed to the surface of gas bubbles. N(2) sparging also induces aggregation. To explain the observed behavior we propose a simple model, that is, "semi-unfolded" ↔ "native" ↔ "globally unfolded" → "aggregated". This model quantitatively reproduces the experimentally observed kinetics. To the best of our knowledge, the current study marks the first exploration of surface denaturation phenomena by HDX/MS. © 2015 The Protein Society.

Changing Definitions of Sepsis

PubMed Central

Gül, Fethi; Arslantaş, Mustafa Kemal; Cinel, İsmail; Kumar, Anand

2017-01-01

Sepsis is one of the main causes of morbidity and mortality in critically ill patients despite the use of modern antibiotics and resuscitation therapies. Outcomes in sepsis have improved overall, probably because of an enhanced focus on early diagnosis and other improvements in supportive care, but mortality rates still remain unacceptably high. The diagnosis and definition of sepsis is a critical problem due to the heterogeneity of this disease process. Although it is apparent that much more needs to be done to advance our understanding, sepsis and related terms remain difficult to define. A 1991 consensus conference developed initial definitions that systemic inflammatory response syndrome (SIRS) to infection would be called sepsis. Definitions of sepsis and septic shock were revised in 2001 to incorporate the threshold values for organ damage. In early 2016, the new definitions of sepsis and septic shock have changed dramatically. Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The consensus document describes organ dysfunction as an acute increase in total Sequential Organ Failure Assessment (SOFA) score two points consequently to the infection. A significant change in the new definitions is the elimination of any mention of SIRS. The Sepsis-3 Task Force also introduced a new bedside index, called the qSOFA, to identify outside of critical care units patients with suspected infection who are likely to develop sepsis. Recently updated the consensus definitions improved specificity compared with the previous descriptions. PMID:28752002

Prognostic value of the reactive oxygen species in severe sepsis and septic shock patients: a pilot study.

PubMed

Montini, Luca; DE Sole, Pasquale; Pennisi, Mariano A; Rossi, Cristina; Scatena, Roberto; DE Pascale, Gennaro; Bello, Giuseppe; Cutuli, Salvatore L; Antonelli, Massimo

2016-12-01

Reactive oxygen species (ROS) have been shown to play a role in the pathophysiology of sepsis. The aim of this study was to investigate ROS production over time in critically ill with sepsis patients and its correlation with outcome. This was a pilot single-centre prospective, observational study of patients consecutively admitted to our 18-general ICU. Over a period of 6 months all the consecutive patients with recent-onset of severe sepsis or septic shock were enrolled. Clinical and demographic characteristics of all patients were recorded. ROMs (ROS metabolites), reduced sulfhydryl groups (SH) and plasmatic lactate levels were collected at enrollment in the study and then every 5-7 days over 28 days or until sepsis resolution or death during sepsis. ROMs were analysed spectrophotometrically by the d-ROMs test (Diacron-Italia). SH were assayed in plasma by Ellman's reaction by spectrophotometric method. Septic shock-related mortality was defined as death that occurred during the follow up period, when the signs of shock remained, and death could not be attributed to causes other than septic shock by the attending physician. Twenty-five patients were studied. The SOFA score and the plasmatic lactate levels significantly correlated with the ROMs plasmatic levels. The mortality rate was higher in patients whose ROMs plasmatic levels decreased during septic shock evolution. Serial measurements of the ROMs plasmatic levels together with the SOFA score and lactate levels could help to identify septic shock patients with a very high probability of death.

Epidemiology, clinical characteristics, and risk factors for mortality of early- and late-onset invasive candidiasis in intensive care units in China

PubMed Central

Yang, Yi; Guo, Fengmei; Kang, Yan; Zang, Bin; Cui, Wei; Qin, Bingyu; Qin, Yingzhi; Fang, Qiang; Qin, Tiehe; Jiang, Dongpo; Cai, Bojing; Li, Ruoyu; Qiu, Haibo

2017-01-01

Abstract To identify the epidemiology, treatments, outcomes, and risk factors for patients with early- or late-onset invasive candidiasis (EOIC or LOIC) in intensive care units in China. Patients were classified as EOIC (≤10 days) or LOIC (>10 days) according to the time from hospital admission to IC onset to identify distinct clinical characteristics. There were 105 EOIC cases and 201 LOIC cases in this study. EOIC was related to more severe clinical conditions at ICU admission or prior to IC. Significantly, more cases of Candida parapsilosis infection were found in patients with LOIC than in those with EOIC. The mortality of EOIC was significantly lower than that for LOIC. Sequential Organ Failure Assessment (SOFA) score at ICI diagnosis in the EOIC group and the interval from ICU admission to ICI occurrence in the LOIC group were identified as risk factors for mortality. Susceptibility to the first-line agent was associated with a lower risk of mortality in the LOIC group. The mortality rate was significantly lower in the EOIC group, and there were more cases of non-albicans infection in the LOIC group. Susceptibility to the first-line agent was an important predictor of mortality in the LOIC group. SOFA score at ICI diagnosis in the EOIC group and interval from ICU admission to ICI occurrence in the LOIC group were identified as risk factors for mortality. PMID:29049184

[Manufacture of upholstered furniture and work-related upper limb musculoskeletal disorders: an industrial sector prevention project].

PubMed

Di Leone, G; Carino, M; Nicoletti, S; Trani, G; Ambrosi, L

2008-01-01

In cooperation with the IRCCS Fondazione Maugeri and the IRCCS Fondazione Ospedale Maggiore Policlinico - EPM-CEMOC, of Milan, the Local Health Unit in Bari, Italy carried out a research project, sponsored partly by the Italian Ministry of Health, on upper limb work-related musculoskeletal disorders (UL-WMSDs) in a specific manufacturing sector, the upholstered furniture industry. This "sofa district" is widely represented with approximately 14,000 workers and 500 factories over a wide geographic area of southern Italy. Advanced technology in the manufacturing process is combined with workers performing intensive arm-hand tasks. The aim of the study included: a) assessment of exposure to repetitive strain and movements of the upper limb in a representative sample of the factories using the OCRA method, b) analysis of the annual prevalence and incidence rates, c) definition of possible improvement via ergonomic solutions in the various factories. Via a network of occupational physicians a total of more than 6000 subjects were examined over a 5-year period. Case-definition was assessed through standardized procedures. A detailed description of the manufacturing process of the upholstered furniture industry and of the characteristics of the working population is provided Exposed groups at risk were:filling preparation workers, leather-cutting operators, sewing and upholstery-assembly workers. Data collected in private companies of different size in this extensive industrial "sofa area" emphasize the importance of prevention through adequate ergonomic solutions and the need to improve training programmes covering the whole area.

Subjective time runs faster under the influence of bright rather than dim light conditions during the forenoon.

PubMed

Morita, Takeshi; Fukui, Tomoe; Morofushi, Masayo; Tokura, Hiromi

2007-05-16

The study investigated if 6 h morning bright light exposure, compared with dim light exposure, could influence time sense (range: 5-15 s). Eight women served as participants. The participant entered a bioclimatic chamber at 10:00 h on the day before the test day, where an ambient temperature and relative humidity were controlled at 25 degrees C and 60%RH. She sat quietly in a sofa in 50 lx until 22:00 h, retired at 22:00 h and then slept in total darkness. She rose at 07:00 h the following morning and again sat quietly in a sofa till 13:00 h, either in bright (2500 lx) or dim light (50 lx), the order of light intensities between the two occasions being randomized. The time-estimation test was performed from 13:00 to 13:10 h in 200 lx. The participant estimated the time that had elapsed between two buzzers, ranging over 5-15 s, and inputting the estimate into a computer. The test was carried out separately upon each individual. Results showed that the participants estimated higher durations of the given time intervals after previous exposure to 6 h of bright rather than dim light. The finding is discussed in terms of different load errors (difference between the actual core temperature and its thermoregulatory set-point) following 6-h exposure to bright or dim light in the morning.

Predisposing factors for critical illness polyneuromyopathy in a multidisciplinary intensive care unit.

PubMed

Nanas, S; Kritikos, K; Angelopoulos, E; Siafaka, A; Tsikriki, S; Poriazi, M; Kanaloupiti, D; Kontogeorgi, M; Pratikaki, M; Zervakis, D; Routsi, C; Roussos, C

2008-09-01

To investigate risk factors of critical illness polyneuromyopathy (CIPM) in a general multidisciplinary intensive care unit (ICU). Prospective observational study in a 28-bed university multidisciplinary ICU. Four hundred and seventy-four (323 M/151 F, age 55 +/- 19) consecutive patients were prospectively evaluated. All patients were assigned admission Acute Physiology and Chronic Health Evaluation (APACHE II; 15 +/- 7) and Sequential Organ Failure Assessment (SOFA; 6 +/- 3) scores and were subsequently evaluated for newly developed neuromuscular weakness. Other potential causes of new-onset weakness after ICU admission were excluded before CIPM was diagnosed. Forty-four (23.8%) of 185 patients developed generalized weakness that met the criteria for CIPM. Patients with CIPM had higher APACHE II (18.9 +/- 6.6 vs 15.6 +/- 6.4, P = 0.004) and SOFA scores (8.4 +/- 2.9 vs 7.1 +/- 2.9, P = 0.013). According to multivariate logistic regression analysis, the following risk factors were independently associated with the development of CIPM: severity of illness at the time of ICU admission, administration of aminoglycoside antibiotics and high blood glucose levels. Analysis according to severity of illness stratification revealed the emergence of Gram (-) bacteremia as the most important independent predisposing factor for CIPM development in less severely ill patients. CIPM has a high incidence in the ICU setting. Our study revealed the association of aminoglycosides, hyperglycemia and illness severity with CIPM development, as well as the association between Gram (-) bacteremia and development of CIPM in less severely ill patient population.

Recombinant human erythropoietin reduces plasminogen activator inhibitor and ameliorates pro-inflammatory responses following trauma

PubMed Central

Shiehmorteza, M.; Ahmadi, A.; Abdollahi, M.; Nayebpour, M.; Mohammadi, M.; Hamishehkar, H.; Najafi, A.; Pazoki, M.; Mojtahedzadeh, M.

2011-01-01

Background and the purpose of the study sBesides its hematopoietic effects, erythropoietin (EPO) by mobilization of iron and modulation of some inflammatory cytokines has antioxidant and anti-inflammatory properties. The purpose of this study was to evaluate these effects of erythropoietin and its impact on organ function in traumatized patients. Methods Twenty-six ICU-admitted traumatized patients within 24 hrs after trauma were randomly assigned to the EPO (received EPO, 300 units/Kg/day) and Control (not received EPO) groups. The inflammatory biomarkers including Tumor Necrosis Factor alpha (TNF-α), Interleukin 1 (IL-1), Plasminogen Activator Inhibitor 1 (PAI-1) and Nitrotyrosine were recorded at the admission, 3, 6 and 9 days thereafter. Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores were also recorded. Results Among 12 patients (EPO group) TNF-α level at the day of 9 (P=0.046), and within EPO group at the days of 3 (P=0.026 ameliorate), 6 (P=0.016), and 9 (P=0.052) were significantly lowered. Level of IL-1 and PAI-1 decreased significantly at days of 3, 6 and 9 post intervention. Also there were significant differences between two groups in the SOFA score during three measured time intervals (the first, third and seventh days). Conclusion From the results of this study it seems that injection of erythrocyte stimulating agent is well tolerated and inhibits the inflammatory response and oxidative stress following trauma. PMID:22615653

Density functional theory and Raman spectroscopy applied to structure and vibrational mode analysis of 1,1',3,3'-tetraethyl-5,5',6,6'-tetrachloro- benzimidazolocarbocyanine iodide and its aggregate.

PubMed

Aydin, Metin; Dede, Özge; Akins, Daniel L

2011-02-14

We have measured electronic and Raman scattering spectra of 1,1',3,3'-tetraethyl-5,5',6,6'-tetrachloro-benzimidazolocarbocyanine iodide (TTBC) in various environments, and we have calculated the ground state geometric and spectroscopic properties of the TTBC cation in the gas and solution phases (e.g., bond distances, bond angles, charge distributions, and Raman vibrational frequencies) using density functional theory. Our structure calculations have shown that the ground state equilibrium structure of a cis-conformer lies ∼200 cm(-1) above that of a trans-conformer and both conformers have C(2) symmetry. Calculated electronic transitions indicate that the difference between the first transitions of the two conformers is about 130 cm(-1). Raman spectral assignments of monomeric- and aggregated-TTBC cations have been aided by density functional calculations at the same level of the theory. Vibrational mode analyses of the calculated Raman spectra reveal that the observed Raman bands above 700 cm(-1) are mainly associated with the in-plane deformation of the benzimidazolo moieties, while bands below 700 cm(-1) are associated with out-of-plane deformations of the benzimidazolo moieties. We have also found that for the nonresonance excited experimental Raman spectrum of aggregated-TTBC cation, the Raman bands in the higher-frequency region are enhanced compared with those in the nonresonance spectrum of the monomeric cation. For the experimental Raman spectrum of the aggregate under resonance excitation, however, we find new Raman features below 600 cm(-1), in addition to a significantly enhanced Raman peak at 671 cm(-1) that are associated with out-of-plane distortions. Also, time-dependent density functional theory calculations suggest that the experimentally observed electronic transition at ∼515 nm (i.e., 2.41 eV) in the absorption spectrum of the monomeric-TTBC cation predominantly results from the π → π∗ transition. Calculations are further interpreted as indicating that the observed shoulder in the absorption spectrum of TTBC in methanol at 494 nm (i.e., 2.51 eV) likely results from the ν(") = 0 → ν' = 1 transition and is not due to another electronic transition of the trans-conformer-despite the fact that measured and calculated NMR results (not provided here) support the prospect that the shoulder might be attributable to the 0-0 band of the cis-conformer.

Ethyl 4-anilino-2,6-bis­(4-chloro­phen­yl)-1-phenyl-1,2,5,6-tetra­hydro­pyridine-3-carboxyl­ate

PubMed Central

Yu, Jianfeng; Tang, Shiming; Zeng, Jingbin; Yan, Zifeng

2013-01-01

The title compound, C32H28Cl2N2O2, was synthesized by a multicomponent reaction of 4-chloro­benzaldehyde, aniline and ethyl aceto­acetate. The central 1,2,5,6-tetra­hydro­pyridine ring exhibits a distorted boat conformation and the two chloro­phenyl rings attached to the central ring at positions 2 and 6 are oriented in opposite directions. The two O atoms of the eth­oxy­carbonyl group are involved in intra­molecular N—H⋯O and C—H⋯O hydrogen bonds. In the crystal, weak C—H⋯O hydrogen bonds link mol­ecules related by translation along the b axis into chains. PMID:23795109

Linking Well-Tempered Metadynamics Simulations with Experiments

PubMed Central

Barducci, Alessandro; Bonomi, Massimiliano; Parrinello, Michele

2010-01-01

Abstract Linking experiments with the atomistic resolution provided by molecular dynamics simulations can shed light on the structure and dynamics of protein-disordered states. The sampling limitations of classical molecular dynamics can be overcome using metadynamics, which is based on the introduction of a history-dependent bias on a small number of suitably chosen collective variables. Even if such bias distorts the probability distribution of the other degrees of freedom, the equilibrium Boltzmann distribution can be reconstructed using a recently developed reweighting algorithm. Quantitative comparison with experimental data is thus possible. Here we show the potential of this combined approach by characterizing the conformational ensemble explored by a 13-residue helix-forming peptide by means of a well-tempered metadynamics/parallel tempering approach and comparing the reconstructed nuclear magnetic resonance scalar couplings with experimental data. PMID:20441734

APCAP--activated protein C in acute pancreatitis: a double-blind randomized human pilot trial.

PubMed

Pettilä, Ville; Kyhälä, Lea; Kylänpää, Marja-Leena; Leppäniemi, Ari; Tallgren, Minna; Markkola, Antti; Puolakkainen, Pauli; Repo, Heikki; Kemppainen, Esko

2010-01-01

Previous human studies have shown low activity of protein C (APC) in severe acute pancreatitis (SAP). This, together with the findings in animal models, suggests that activated protein C (APC) may protect against pancreatic injury and ameliorate the disease. We, therefore, evaluated its effect on multiple organ dysfunction (MOD) measured by the SOFA (Sequential Organ Failure Assessment) and on organ-failure-free days, and the safety of APC in SAP. A prospective double blind randomized pilot study was use. The study occurred in one university hospital tertiary intensive care unit (ICU) with eight beds. The patients were chosen according to the following inclusion criteria: 1) Those admitted to the hospital < 96 h from the onset of pain, 2) Those who had a three-fold increase in serum amylase over normal upper range or/and in whom computed tomography (CT) verification of SAP was noted, 3) Those who had one or more organ dysfunction (OD), and 4) Those in whom less than 48 hours had passed since their first OD. Of a total of 215 adult patients with SAP screened between June 2003 and August 2007, 158 fulfilled the study inclusion criteria. After exclusions 32 patients were randomized to the study. The intervention consisted of APC (N = 16) administered intravenously for 96 hours with a dose of 24 μg/kg/hour or placebo (N = 16) with a similar infusion rate. The sample size for the study was calculated according to the primary end-point: the change in SOFA during study drug infusion (Days 0 and 5). Comparisons between the study groups were performed using patient-related changes and calculation of difference in means (DIM, 95% CIs) and regarding categorical variables with Fisher's exact test. For all comparisons P < 0.05 was considered significant. No serious bleeding was detected clinically or by CT scans in either group. No significant difference in SOFA score change between the APC and placebo groups was found (difference in means (DIM) +2.3, 95% CI -0.7 to +5.3). Treatment with APC was associated with an increase in serum levels of both total and conjugated bilirubin. No differences in ventilator-free days, in renal replacement therapy-free days, in vasopressor-free days, or in days alive outside the hospital were detected. No serious bleeding or differences in the evolution of MOD were detected between APC and the placebo. Instead we found an increase in serum bilirubin in the APC group compared to the placebo group in patients with SAP. ClinicalTrials.gov NCT01017107.

Mortality prediction in patients with acute kidney injury requiring renal replacement therapy after cardiac surgery.

PubMed

Skarupskienė, Inga; Adukauskienė, Dalia; Kuzminskienė, Jurgita; Rimkutė, Laima; Balčiuvienė, Vilma; Žiginskienė, Edita; Kuzminskis, Vytautas; Adukauskaitė, Agnė; Pentiokinienė, Daiva; Bumblytė, Inga Arūnė

2017-01-01

Acute kidney injury (AKI) is a common and potentially serious postoperative complication after cardiac surgery, and it remains a cause of major morbidity and mortality. The aim of our study was to assess the prognostic illness severity score and to estimate the significant risk factors for poor outcome of patients with AKI requiring renal replacement therapy (RRT) after cardiac surgery. We retrospectively analyzed data of adult (>18 years) patients (n=111) who underwent open heart surgery and had developed AKI with need for RRT. Prognostic illness severity scores were calculated and perioperative risk factors of lethal outcome were assessed at the RRT initiation time. We defined three illness severity scores: Acute Physiology and Chronic Health Evaluation (APACHE II) as a general score, Sequential Organ Failure Assessment (SOFA) as an organ failure score, and Liano score as a kidney-specific disease severity score. Logistic regression was also used for the multivariate analysis of mortality risk factors. Hospital mortality was 76.5%. More than 7% of patients remained dialysis-dependent after their discharge from the hospital. The prognostic abilities of the scores were assessed for their discriminatory power. The area under the receiver-operating characteristic (ROC) curve of SOFA score was 0.719 (95% CI, 0.598-0.841), of Liano was 0.661 (95% CI, 0.535-0.787) and 0.668 (95% CI, 0.550-0.785) of APACHE II scores. From 16 variables analyzed for model selection, we reached a final logistic regression model, which demonstrated four variables significantly associated with patients' mortality. Glasgow coma score<14 points (OR=3.304; 95% CI, 1.130-9.662; P=0.003), mean arterial blood pressure (MAP)<63.5mmHg (OR=3.872; 95% CI, 1.011-13.616; P=0.035), serum creatinine>108.5μmol/L (OR=0.347; 95% CI, 0.123-0.998; P=0.046) and platelet count<115×10 9 /L (OR=3.731; 95% CI, 1.259-11.054; P=0.018) were independent risk factors for poor patient outcome. Our study demonstrated that SOFA score estimation is the most accurate to predict the fatal outcome in patients with AKI requiring RRT after cardiac surgery. Lethal patient outcome is related to Glasgow coma score, mean arterial blood pressure, preoperative serum creatinine and postoperative platelet count. Copyright © 2017 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Sp. z o.o. All rights reserved.

Relationship Between Beta Cell Dysfunction and Severity of Disease Among Critically Ill Children: A STROBE-Compliant Prospective Observational Study.

PubMed

Liu, Ping-Ping; Lu, Xiu-Lan; Xiao, Zheng-Hui; Qiu, Jun; Zhu, Yi-Min

2016-05-01

Although beta cell dysfunction has been proved to predict prognosis among humans and animals, its prediction on severity of disease remains unclear among children. The present study was aimed to examine the relationship between beta cell dysfunction and severity of disease among critically ill children.This prospective study included 1146 critically ill children, who were admitted to Pediatric Intensive Care Unit (PICU) of Hunan Children's Hospital from November 2011 to August 2013. Information on characteristics, laboratory tests, and prognostic outcomes was collected. Homeostasis model assessment (HOMA)-β, evaluating beta cell function, was used to divide all participants into 4 groups: HOMA-β = 100% (group I, n = 339), 80% ≤ HOMA-β < 100% (group II, n = 71), 40% ≤ HOMA-β < 80% (group III, n = 293), and HOMA-β < 40% (group IV, n = 443). Severity of disease was assessed using the worst Sequential Organ Failure Assessment (SOFA) score, Pediatric Risk of Mortality (PRISM) III score, incidence of organ damage, septic shock, multiple organ dysfunction syndrome (MODS), mechanical ventilation (MV) and mortality. Logistic regression analysis was used to evaluate the risk of developing poor outcomes among patients in different HOMA-β groups, with group I as the reference group.Among 1146 children, incidence of HOMA-β < 100% was 70.41%. C-peptide and insulin declined with the decrement of HOMA-β (P < 0.01). C-reactive protein and procalcitonin levels, rather than white blood cell, were significantly different among 4 groups (P < 0.01). In addition, the worst SOFA score and the worst PRISMIII score increased with declined HOMA-β. For example, the worst SOFA score in group I, II, III, and IV was 1.55 ± 1.85, 1.71 ± 1.93, 1.92 ± 1.63, and 2.18 ± 1.77, respectively. Furthermore, patients with declined HOMA-β had higher risk of developing septic shock, MODS, MV, and mortality, even after adjusting age, gender, myocardial injury, and lung injury. For instance, compared with group I, the multivariate-adjusted odds ratio (95% confidence interval) for developing septic shock was 2.17 (0.59, 8.02), 2.94 (2.18, 6.46), and 2.76 (1.18, 6.46) among patients in group II, III, and IV, respectively.Beta cell dysfunction reflected the severity of disease among critically ill children. Therefore, assessment of beta cell function is critically important to reduce incidence of adverse events in PICU.

The validity and reliability of the Arabic version of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU): A prospective cohort study.

PubMed

Selim, Abeer; Kandeel, Nahed; Elokl, Mohamed; Khater, Mohamed Shawky; Saleh, Ashraf Nabil; Bustami, Rami; Ely, E Wesley

2018-04-01

Accurate diagnosis for Arabic speaking critically ill patients suffering from delirium is limited by the need for a valid/reliable translation of a standardized delirium instrument such as the Confusion Assessment Method for the ICU (CAM-ICU). To determine the validity and reliability of the Arabic version of the CAM-ICU. A prospective cohort study design was used to conduct the current study. Data collection took place in Geriatric, Emergency and Surgical intensive care units. Fifty-eight adult patients met the inclusion criteria and participated in the study. Among the participants 22(38%) patients were on mechanical ventilation. After translating the CAM-ICU into Arabic language, the Arabic CAM-ICU was administered by two well-trained critical care nurses and compared with reference standard assessments by delirium experts using the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM -IV-TR), along with assessment of severity of illness using Sequential Organ Failure Assessment (SOFA). Concurrent validity was assessed by calculating sensitivity, specificity and positive and negative predictive value (PPV and NPV) for the two Arabic CAM-ICU raters, where calculations were based on considering the DSM-IV-TR criterion as the reference standard. The convergent validity of the Arabic CAM-ICU was explored by comparing the Arabic CAM-ICU ratings and the total score of SOFA (severity of illness) and MMSE (cognitive impairment). A total of 58 ICU patients were included, of whom 27 (47%) were diagnosed with delirium during their ICU stay via DSM-IV criteria. Interrater reliability for the Arabic CAM-ICU, overall and for mechanically ventilated patients assessed using Cohen's kappa (κ) were 0.82 and 1, respectively, p < 0.001. The sensitivities (95% CI) for the two critical care nurses when using the Arabic CAM-ICU compared with the reference standard were 81% (60%-93%) and 85% (65%-95%), respectively, whereas specificity (95% CI) was 81%(62%-92%) for both nurses. High sensitivity and specificity measures were also observed across subgroups; 100% for mechanically ventilated patients, 88% (60%-98%) and 79% (49%-94%) for those aged 65 years or older and 82% (56%-95%) and 75% (43%-93%) for those with SOFA scores at or above the median value. The Arabic CAM-ICU appeared to be valid and reliable tool for diagnosing delirium. Future investigations may lead to a better understanding of the prevalence, predictors, and consequences of delirium among critically ill Arabic speaking patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Usefulness of midregional pro-adrenomedullin as a marker of organ damage and predictor of mortality in patients with sepsis.

PubMed

Bernal-Morell, Enrique; García-Villalba, Eva; Vera, Maria Del Carmen; Medina, Blanca; Martinez, Monica; Callejo, Victoria; Valero, Salvador; Cinesi, Cesar; Piñera, Pascual; Alcaraz, Antonia; Marin, Irene; Muñoz, Angeles; Cano, Alfredo

2018-03-01

Midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP) and sepsis. In this paper, we examined the ability of MR-proADM to predict organ damage and long-term mortality in sepsis patients, compared to that of procalcitonin, C-reactive protein and lactate. This was a prospective observational cohort, enrolling severe sepsis or septic shock patients admitted to internal service department. The association between biomarkers and 90-day mortality was assessed by Cox regression analysis and Kaplan-Meier curves. The accuracy of biomarkers for mortality was determined by area under the receiver operating characteristic curve (AUROC) analysis. A total of 148 patients with severe sepsis, according to the criteria of the campaign to survive sepsis, were enrolled. Eighty-five (57.4%) had sepsis according to the new criteria of Sepsis-3. MR-proADM showed the best AUROC to predict sepsis as defined by the Sepsis-3 criteria (AUROC of 0.771, 95% CI 0.692-0.850, p <0.001) and was the only marker independently associated with Sepsis-3 criteria (OR = 4.78, 95% CI 2.25-10.14; p < 0.001) in multivariate analysis. MR-proADM was the biomarker with the best AUROC to predict mortality in 90 days (AUROC of 0.731, CI 95% 0.612-0.850, p <0.001) and was the only marker that kept its independence [hazard ratio (HR) of 1.4, 95% CI 1.2-1.64, p <0.001] in multivariate analysis. The cut-off point of MR-proADM of 1.8 nmol/L (HR of 4.65, 95% CI 6.79-10.1, p < 0.001) was the one that had greater discriminative capacity to predict 90 days mortality. All patients with MR-proADM concentrations ≤0.60 nmol/L survived up to 90 days. In patients with SOFA ≤ 6, the addition of MR-proADM to SOFA score increased the ability of SOFA to identify non-survivors, AUROC of 0.65 (CI 95% 0.537-0.764) and AUROC of 0.700 (CI 95% 0.594-0.800), respectively (p < 0.05 for both). MR-proADM is a good biomarker in the early identification of high risk septic patients and may contribute to improve the predictive capacity of SOFA scale, especially when scores are low. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

The architecture of metal coordination groups in proteins.

PubMed

Harding, Marjorie M

2004-05-01

A set of tables is presented and a survey given of the architecture of metal coordination groups in a representative set of protein structures from the Protein Data Bank [Bernstein et al. (1977), J. Mol. Biol. 112, 535-542; Berman et al. (2000), Nucleic Acids Res. 28, 235-242]. The structures have been determined to a resolution of 2.5 A or better; the metals considered are Ca, Mg, Mn, Fe, Cu, Zn, Na and K, with particular emphasis on Ca and Zn and the exclusion of haem groups and Fe/S clusters; the proteins are a representative set in which none has more than 30% sequence identity with any other. In them the metal is coordinated by several donor groups from different amino-acid residues in the protein chain and often also by water or other small molecules. The tables, for approximately 600 metal coordination groups, include information on the conformations of the protein chain in the region around the metal and reliability indicators. They illustrate the wide variety of coordination numbers, chelate-loop sizes and other properties and the different characteristics of different metals. They show that glycine has a particular significance in the position adjacent to a donor residue, especially in Ca coordination groups. They also show that metal coordination does not appear to lead to significant distortions of the torsion angles phi, psi from their normally allowed values. Very few metal coordination groups occur more than once in the representative set and when they do they are usually related in fold and function; they have similar but not necessarily identical conformations. However, individual chelate loops, for example Zn(-C-X-X'-C-), in which both cysteines are coordinated to Zn through S, and X and X' are any amino acids, are repeated frequently in many different and unrelated proteins. Not all chelate loops with the same composition have the same conformation, but for smaller loops there are usually one or two strongly preferred and well defined conformations. Quite frequently more than one metal coordination group is associated with one protein chain; these proteins are identified.

Role of conserved nucleotides in building the 16S rRNA binding site of E. coli ribosomal protein S8.

PubMed Central

Allmang, C; Mougel, M; Westhof, E; Ehresmann, B; Ehresmann, C

1994-01-01

Ribosomal protein S8 specifically recognizes a helical and irregular region of 16S rRNA that is highly evolutionary constrained. Despite its restricted size, the precise conformation of this region remains a question of debate. Here, we used chemical probing to analyze the structural consequences of mutations in this RNA region. These data, combined with computer modelling and previously published data on protein binding were used to investigate the conformation of the RNA binding site. The experimental data confirm the model in which adenines A595, A640 and A642 bulge out in the deep groove. In addition to the already proposed non canonical U598-U641 interaction, the structure is stabilized by stacking interactions (between A595 and A640) and an array of hydrogen bonds involving bases and the sugar phosphate backbone. Mutations that alter the ability to form these interdependent interactions result in a local destabilization or reorganization. The specificity of recognition by protein S8 is provided by the irregular and distorted backbone and the two bulged adenines 640 and 642 in the deep groove. The third adenine (A595) is not a direct recognition site but must adopt a bulged position. The U598-U641 pair should not be directly in contact with the protein. Images PMID:7937081

Mg2+ in the Major Groove Modulates B-DNA Structure and Dynamics

PubMed Central

Guéroult, Marc; Boittin, Olivier; Mauffret, Oliver; Etchebest, Catherine; Hartmann, Brigitte

2012-01-01

This study investigates the effect of Mg2+ bound to the DNA major groove on DNA structure and dynamics. The analysis of a comprehensive dataset of B-DNA crystallographic structures shows that divalent cations are preferentially located in the DNA major groove where they interact with successive bases of (A/G)pG and the phosphate group of 5′-CpA or TpG. Based on this knowledge, molecular dynamics simulations were carried out on a DNA oligomer without or with Mg2+ close to an ApG step. These simulations showed that the hydrated Mg2+ forms a stable intra-strand cross-link between the two purines in solution. ApG generates an electrostatic potential in the major groove that is particularly attractive for cations; its intrinsic conformation is well-adapted to the formation of water-mediated hydrogen bonds with Mg2+. The binding of Mg2+ modulates the behavior of the 5′-neighboring step by increasing the BII (ε-ζ>0°) population of its phosphate group. Additional electrostatic interactions between the 5′-phosphate group and Mg2+ strengthen both the DNA-cation binding and the BII character of the 5′-step. Cation binding in the major groove may therefore locally influence the DNA conformational landscape, suggesting a possible avenue for better understanding how strong DNA distortions can be stabilized in protein-DNA complexes. PMID:22844516

Single hydration of the peptide bond: the case of the Vince lactam.

PubMed

Écija, Patricia; Basterretxea, Francisco J; Lesarri, Alberto; Millán, Judith; Castaño, Fernando; Cocinero, Emilio J

2012-10-18

2-Azabicyclo[2.2.1]hept-5-en-3-one (ABH or Vince lactam) and its monohydrated complex (ABH···H(2)O) have been observed in a supersonic jet by Fourier transform microwave spectroscopy. ABH is broadly used in the synthesis of therapeutic drugs, whereas the ABH···H(2)O system offers a simple model to explain the conformational preferences of water linked to a constrained peptidic bond. A single predominant form of the Vince lactam and its singly hydrated complex have been detected, determining the rotational constants, centrifugal distortion constants, and nuclear quadrupole coupling tensor. The monohydrated complex is stabilized by two hydrogen bonds (C═O···H-O and N-H···O) closing a six-membered ring. The complexation energy has been estimated to be ∼10 kJ mol(-1) from experimental results. In addition, the observed structure in the gas phase has been compared with solid-phase diffraction data. The structural parameters and binding energies of ABH···H(2)O have also been compared with similar molecules containing peptide bonds. Ab initio (MP2) and density functional (M06-2X and B3LYP) methods have supported the experimental work, describing the rotational parameters and conformational landscape of the title compound and its singly hydrated complex.

Functional and conformational transitions of mevalonate diphosphate decarboxylase from Bacopa monniera.

PubMed

Abbassi, Shakeel; Patel, Krunal; Khan, Bashir; Bhosale, Siddharth; Gaikwad, Sushama

2016-02-01

Functional and conformational transitions of mevalonate diphosphate decarboxylase (MDD), a key enzyme of mevalonate pathway in isoprenoid biosynthesis, from Bacopa monniera (BmMDD), cloned and overexpressed in Escherichia coli were studied under thermal, chemical and pH-mediated denaturation conditions using fluorescence and Circular dichroism spectroscopy. Native BmMDD is a helix dominant structure with 45% helix and 11% sheets and possesses seven tryptophan residues with two residues exposed on surface, three residues partially exposed and two situated in the interior of the protein. Thermal denaturation of BmMDD causes rapid structural transitions at and above 40°C and transient exposure of hydrophobic residues at 50°C, leading to aggregation of the protein. An acid induced molten globule like structure was observed at pH 4, exhibiting altered but compact secondary structure, distorted tertiary structure and exposed hydrophobic residues. The molten globule displayed different response at higher temperature and similar response to chemical denaturation as compared to the native protein. The surface tryptophans have predominantly positively charged amino acids around them, as indicated by higher KSV for KI as compared to that for CsCl. The native enzyme displayed two different lifetimes, τ1 (1.203±0.036 ns) and τ2 (3.473±0.12 ns) indicating two populations of tryptophan. Copyright © 2015 Elsevier B.V. All rights reserved.

Crystal structure of bis­[trans-di­chlorido­bis(propane-1,3-di­amine-κ2 N,N′)chromium(III)] dichromate from synchrotron data

PubMed Central

Moon, Dohyun; Ryoo, Keon Sang; Choi, Jong-Ha

2016-01-01

The structure of the title compound, [CrCl2(tn)2]2[Cr2O7] (tn = propane-1,3-di­amine; C3H10N2), has been determined from synchrotron data. The asymmetric unit contains one CrIII complex cation and half a [Cr2O7]2− anion. In the complex cation, the CrIII ion is coordinated by the four N atoms of two propane-1,3-di­amine (tn) ligands in the equatorial plane and by two Cl atoms in a trans configuration, displaying a distorted octa­hedral coordination sphere. The two six-membered rings in the complex cation have an anti chair–chair conformation with respect to each other. The mean Cr—N(tn) and Cr—Cl bond lengths are 2.09 (1) and 2.320 (2) Å, respectively. The slightly bent dichromate anion is disordered over two sets of sites (occupancy ratio = 0.7:0.3) and has a staggered conformation. The crystal structure is stabilized by inter­molecular hydrogen bonds involving the NH2 groups of the tn ligands as donors and the O atoms of the [Cr2O7]2− anion and chlorido ligands as acceptors. PMID:27920920

Label-free liquid crystal biosensor based on specific oligonucleotide probes for heavy metal ions.

PubMed

Yang, Shengyuan; Wu, Chao; Tan, Hui; Wu, Yan; Liao, Shuzhen; Wu, Zhaoyang; Shen, Guoli; Yu, Ruqin

2013-01-02

In this study, to enhance the capability of metal ions disturbing the orientation of liquid crystals (LCs), we designed a new label-free LC biosensor for the highly selective and sensitive detection of heavy metal ions. This strategy makes use of the target-induced DNA conformational change to enhance the disruption of target molecules for the orientation of LC leading to an amplified optical signal. The Hg(2+) ion, which possesses a unique property to bind specifically to two DNA thymine (T) bases, is used as a model heavy metal ion. In the presence of Hg(2+), the specific oligonucleotide probes form a conformational reorganization of the oligonucleotide probes from hairpin structure to duplex-like complexes. The duplex-like complexes are then bound on the triethoxysilylbutyraldehyde/N,N-dimethyl-N-octadecyl (3-aminopropyl) trimethoxysilyl chloride (TEA/DMOAP)-coated substrate modified with capture probes, which can greatly distort the orientational profile of LC, making the optical image of LC cell birefringent as a result. The optical signal of LC sensor has a visible change at the Hg(2+) concentration of low to 0.1 nM, showing good detection sensitivity. The cost-effective LC sensing method can translate the concentration signal of heavy metal ions in solution into the presence of DNA duplexes and is expected to be a sensitive detection platform for heavy metal ions and other small molecule monitors.

Skip residues modulate the structural properties of the myosin rod and guide thick filament assembly

DOE PAGES

Taylor, Keenan C.; Buvoli, Massimo; Korkmaz, Elif Nihal; ...

2015-07-06

The rod of sarcomeric myosins directs thick filament assembly and is characterized by the insertion of four skip residues that introduce discontinuities in the coiled-coil heptad repeats. We report in this paper that the regions surrounding the first three skip residues share high structural similarity despite their low sequence homology. Near each of these skip residues, the coiled-coil transitions to a nonclose-packed structure inducing local relaxation of the superhelical pitch. Moreover, molecular dynamics suggest that these distorted regions can assume different conformationally stable states. In contrast, the last skip residue region constitutes a true molecular hinge, providing C-terminal rod flexibility.more » Assembly of myosin with mutated skip residues in cardiomyocytes shows that the functional importance of each skip residue is associated with rod position and reveals the unique role of the molecular hinge in promoting myosin antiparallel packing. By defining the biophysical properties of the rod, the structures and molecular dynamic calculations presented here provide insight into thick filament formation, and highlight the structural differences occurring between the coiled-coils of myosin and the stereotypical tropomyosin. Finally, in addition to extending our knowledge into the conformational and biological properties of coiled-coil discontinuities, the molecular characterization of the four myosin skip residues also provides a guide to modeling the effects of rod mutations causing cardiac and skeletal myopathies.« less

Economic decision-making compared with an equivalent motor task.

PubMed

Wu, Shih-Wei; Delgado, Mauricio R; Maloney, Laurence T

2009-04-14

There is considerable evidence that human economic decision-making deviates from the predictions of expected utility theory (EUT) and that human performance conforms to EUT in many perceptual and motor decision tasks. It is possible that these results reflect a real difference in decision-making in the 2 domains but it is also possible that the observed discrepancy simply reflects typical differences in experimental design. We developed a motor task that is mathematically equivalent to choosing between lotteries and used it to compare how the same subject chose between classical economic lotteries and the same lotteries presented in equivalent motor form. In experiment 1, we found that subjects are more risk seeking in deciding between motor lotteries. In experiment 2, we used cumulative prospect theory to model choice and separately estimated the probability weighting functions and the value functions for each subject carrying out each task. We found no patterned differences in how subjects represented outcome value in the motor and the classical tasks. However, the probability weighting functions for motor and classical tasks were markedly and significantly different. Those for the classical task showed a typical tendency to overweight small probabilities and underweight large probabilities, and those for the motor task showed the opposite pattern of probability distortion. This outcome also accounts for the increased risk-seeking observed in the motor tasks of experiment 1. We conclude that the same subject distorts probability, but not value, differently in making identical decisions in motor and classical form.

The role of amino acid electron-donor/acceptor atoms in host-cell binding peptides is associated with their 3D structure and HLA-binding capacity in sterile malarial immunity induction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patarroyo, Manuel E., E-mail: mepatarr@mail.com; Universidad Nacional de Colombia, Bogota; Almonacid, Hannia

Highlights: Black-Right-Pointing-Pointer Fundamental residues located in some HABPs are associated with their 3D structure. Black-Right-Pointing-Pointer Electron-donor atoms present in {beta}-turn, random, distorted {alpha}-helix structures. Black-Right-Pointing-Pointer Electron-donor atoms bound to HLA-DR53. Black-Right-Pointing-Pointer Electron-acceptor atoms present in regular {alpha}-helix structure bound to HLA-DR52. -- Abstract: Plasmodium falciparum malaria continues being one of the parasitic diseases causing the highest worldwide mortality due to the parasite's multiple evasion mechanisms, such as immunological silence. Membrane and organelle proteins are used during invasion for interactions mediated by high binding ability peptides (HABPs); these have amino acids which establish hydrogen bonds between them in some of theirmore » critical binding residues. Immunisation assays in the Aotus model using HABPs whose critical residues had been modified have revealed a conformational change thereby enabling a protection-inducing response. This has improved fitting within HLA-DR{beta}1{sup Asterisk-Operator} molecules where amino acid electron-donor atoms present in {beta}-turn, random or distorted {alpha}-helix structures preferentially bound to HLA-DR53 molecules, whilst HABPs having amino acid electron-acceptor atoms present in regular {alpha}-helix structure bound to HLA-DR52. This data has great implications for vaccine development.« less

Structure of a peptide adsorbed on graphene and graphite.

PubMed

Katoch, Jyoti; Kim, Sang Nyon; Kuang, Zhifeng; Farmer, Barry L; Naik, Rajesh R; Tatulian, Suren A; Ishigami, Masa

2012-05-09

Noncovalent functionalization of graphene using peptides is a promising method for producing novel sensors with high sensitivity and selectivity. Here we perform atomic force microscopy, Raman spectroscopy, infrared spectroscopy, and molecular dynamics simulations to investigate peptide-binding behavior to graphene and graphite. We studied a dodecamer peptide identified with phage display to possess affinity for graphite. Optical spectroscopy reveals that the peptide forms secondary structures both in powder form and in an aqueous medium. The dominant structure in the powder form is α-helix, which undergoes a transition to a distorted helical structure in aqueous solution. The peptide forms a complex reticular structure upon adsorption on graphene and graphite, having a helical conformation different from α-helix due to its interaction with the surface. Our observation is consistent with our molecular dynamics calculations, and our study paves the way for rational functionalization of graphene using biomolecules with defined structures and, therefore, functionalities.

Investigation of a van der Waals complex with C 1 symmetry: the free-jet rotational spectrum of 1,2-difluoroethane-Ar

NASA Astrophysics Data System (ADS)

Melandri, Sonia; Velino, Biagio; Favero, Paolo G.; Dell'Erba, Adele; Caminati, Walther

2000-04-01

The van der Waals complex between Ar and 1,2-difluoroethane has been investigated by free-jet absorption millimeter-wave spectroscopy in the frequency range 60-78 GHz. The analysis of the spectroscopic constants derived from the rotational spectrum allowed the determination of the dimer's structure. 1,2-Difluoroethane is in the gauche conformation and the Ar atom is in a position stabilized by the interaction with one fluorine and the two carbon atoms. The distance between Ar and the center of mass (CM) of the monomer is 3.968 Å, the angle between the Ar-CM line and the C-C bond is 65° and the dihedral angle Ar-CM-C-C is 99°. From centrifugal distortion effects the dissociation energy of the complex has been estimated to be 2.1 kJ/mol.

Addiction surplus: the add-on margin that makes addictive consumptions difficult to contain.

PubMed

Adams, Peter J; Livingstone, Charles

2015-01-01

Addictive consumptions generate financial surpluses over-and-above non-addictive consumptions because of the excessive consumption of addicted consumers. This add-on margin or 'addiction surplus' provides a powerful incentive for beneficiaries to protect their income by ensuring addicted consumers keep consuming. Not only that, addiction surplus provides the financial base that enables producers to sponsor activities which aim to prevent public health initiatives from reducing consumption. This paper examines the potency of addiction surplus to engage industry, governments and communities in an on-going reliance on addiction surplus. It then explores how neo-liberal constructions of a rational consumer disguise the ethical and exploitative dynamics of addiction surplus by examining ways in which addictive consumptions fail to conform to notions of autonomy and rationality. Four measures are identified to contain the distorting effects of addiction surplus. Copyright © 2014 Elsevier B.V. All rights reserved.

An optical system with aberrations on diffraction integrals written in terms of a generalized ABCD matrix

NASA Astrophysics Data System (ADS)

Zhao, Chaoying; Tan, Weihan

2008-12-01

: In this paper, we consider the transformation of a ray beam as it passes through an optical system containing a glass plate with parallel surfaces inclined to the optical axis at the Brewster’s angle, by investigating the effects of the optical system on amplitude and phase distributions. By applying generalized matrix optics and diffraction integrals and considering the influence of a quarter of a wavelength of aberration on the transmitted amplitude and phase distributions at the focus of a de-collimating lens, we find that the central peak amplitude descends from 1.0 to 0.8 and the phase distortion is less than π/2. The general feature of the amplitude distribution shows an elongation along the y-axis perpendicular to the optical axis in the direction of tilt of the inclined plate, and conforms to the inclination direction of the glass plate.

KEY INTERACTIONS FOR CLATHRIN COAT STABILITY

PubMed Central

Böcking, Till; Aguet, Francois; Rapoport, Iris; Banzhaf, Manuel; Yu, Anan; Zeeh, Jean Christophe; Kirchhausen, Tom

2014-01-01

SUMMARY Clathrin-coated vesicles are major carriers of vesicular traffic in eukaryotic cells. This endocytic pathway relies on cycles of clathrin coat assembly and Hsc70-mediated disassembly. Here we identify histidine residues as major determinants of lattice assembly and stability. They are located at the invariant interface between the proximal and distal segments of clathrin heavy chains, in triskelions centered on two adjacent vertices of the coated-vesicle lattice. Mutation of these histidine to glutamine alters the pH dependence of coat stability. We then describe single-particle fluorescence imaging experiments in which we follow the effect of these histidine mutations on susceptibility to Hsc70-dependent uncoating. Coats destabilized by these mutations require fewer Hsc70 molecules to initiate disassembly as predicted by a model in which Hsc70 traps conformational distortions during the auxilin- and Hsc70:ATP-mediated uncoating reaction. PMID:24815030

Linking well-tempered metadynamics simulations with experiments.

PubMed

Barducci, Alessandro; Bonomi, Massimiliano; Parrinello, Michele

2010-05-19

Linking experiments with the atomistic resolution provided by molecular dynamics simulations can shed light on the structure and dynamics of protein-disordered states. The sampling limitations of classical molecular dynamics can be overcome using metadynamics, which is based on the introduction of a history-dependent bias on a small number of suitably chosen collective variables. Even if such bias distorts the probability distribution of the other degrees of freedom, the equilibrium Boltzmann distribution can be reconstructed using a recently developed reweighting algorithm. Quantitative comparison with experimental data is thus possible. Here we show the potential of this combined approach by characterizing the conformational ensemble explored by a 13-residue helix-forming peptide by means of a well-tempered metadynamics/parallel tempering approach and comparing the reconstructed nuclear magnetic resonance scalar couplings with experimental data. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Synthesis and Characterization of Mononuclear, Pseudotetrahedral Cobalt(III) Compounds

PubMed Central

2015-01-01

The preparation and characterization of two mononuclear cobalt(III) tropocoronand complexes, [Co(TC-5,5)](BF4) and [Co(TC-6,6)](BPh4), are reported. The cobalt(III) centers exist in rare pseudotetrahedral conformations, with twist angles of 65° and 74° for the [Co(TC-5,5]+ and [Co(TC-6,6)]+ species, respectively. Structural and electrochemical characteristics are compared with those of newly synthesized [Ga(TC-5,5)](GaCl4) and [Ga(TC-6,6)](GaCl4) analogues. The spin state of the pseudotetrahedral [Co(TC-6,6)](BPh4) compound was determined to be S = 2, a change in spin state from the value of S = 1 that occurs in the square-planar and distorted square-planar complexes, [Co(TC-3,3)](X) (X = BPh4, BAr′4) and [Co(TC-4,4)](BPh4), respectively. PMID:25531129

Methyl 2-methyl-4-(oxiran-2-ylmeth­oxy)-2H-1,2-benzothia­zine-3-carboxyl­ate 1,1-dioxide

PubMed Central

Ahmad, Matloob; Siddiqui, Hamid Latif; Zia-ur-Rehman, Muhammad; Elsegood, Mark R. J.; Weaver, George W.

2010-01-01

In the title compound, C14H15NO6S, the thia­zine ring adopts a distorted half-chair conformation. The structure displays several cooperative weak inter­molecular C—H⋯O hydrogen-bonding inter­actions, giving rise to a two-dimensional sheet packing motif. The CH2 group in the meth­oxy linker to the oxirane ring, and the CH group in that ring, exhibit twofold positional disorder. The three-membered oxirane ring is twisted approximately perpendicular with respect to thia­zine ring (dihedral angle = 60/86° for the major/minor disorder components). 1,2-Benzothia­zines of this kind have a wide range of biological activities and are mainly used as medicines in the treatment of inflammation and rheumatoid arthritis. PMID:21579762

Response to article titled "US-funded measurements of cervical cancer death rates in India: scientific and ethical concerns" by Eric J Suba.

PubMed

Sankaranarayanan, Rengaswamy; Nene, Bhagwan M; Shastri, Surendra; Esmy, Pullikotil Ekkuru; Rajkumar, Rajamanickam; Muwonge, Richard; Swaminathan, Rajaraman; Malvi, Sylla G; Kane, Shubada; Desai, Sangeeta; Kelkar, Rohini; Hingmire, Sanjay; Jayant, Kasturi

2014-01-01

Dr Eric Suba has been distorting facts and persistently disseminating biased and misleading views and statements regarding our studies over the past several years. His article in the Indian Journal of Medical Ethics fails to mention the facts that seem unfavourable to his arguments, and the ethical concerns are unsubstantiated by the evidence. In this context, we present the following clarifications for the attention of your readers, notably with regard to: (i) the study design and inclusion of a control group; (ii) the informed consent of the women participating in the study; (iii) the conformity with international ethical standards and guidelines, and (iv) the provision of screening to women in the control arm of the studies. We also highlight the benefits that are flowing from this research and the risk that misinformation may further delay access for women to life-saving cervical cancer screening.

An X-ray absorption spectroscopy study of the interactions of Ni2+ with yeast enolase.

PubMed

Wang, S; Scott, R A; Lebioda, L; Zhou, Z H; Brewer, J M

1995-05-15

An x-ray absorption spectroscopy (XAS) study was carried out at pH 7.6 on solutions of Ni2+ and yeast enolase depleted of its physiological cofactor (Mg2+) in the presence or absence of substrate/product, the very strongly bound competitive inhibitor 2-phosphonoacetohydroxamate and Mg2+. Both "conformational" and "catalytic" Ni2+ are distorted octahedral in coordination, in agreement with several spectroscopic studies but in contrast to the coordination in the crystal at pH 6.0. The data are consistent with direct coordination of what must be the catalytic Ni2+ to the phosphate of the substrate, in agreement with some previous data but in disagreement with recent interpretations by other workers. The ligands around the metal ions obtained from the x-ray structure give simulated XAS spectra in good agreement with the observed spectra.

Crystal structure of 3-benzamido-1-(4-nitro-benz-yl)quinolinium tri-fluoro-methane-sulfonate.

PubMed

Nicolas-Gomez, Mariana; Bazany-Rodríguez, Iván J; Plata-Vargas, Eduardo; Hernández-Ortega, Simón; Dorazco-González, Alejandro

2016-05-01

In the title compound, C23H18N3O3 (+)·CF3SO3 (-), the asymmetric unit contains two crystallographically independent organic cations with similar conformations. Each cation shows a moderate distortion between the planes of the amide groups and the quinolinium rings with dihedral angles of 14.90 (2) and 31.66 (2)°. The quinolinium and phenyl rings are slightly twisted with respect to each other at dihedral angles of 6.99 (4) and 8.54 (4)°. The tri-fluoro-methane-sulfonate anions are linked to the organic cations via N-H⋯O hydrogen-bonding inter-actions involving the NH amide groups. In the crystal, the organic cations are linked by weak C-H⋯O(nitro group) inter-actions into supramol-ecular chains propagating along the b-axis direction.

Synthesis and Structural Characterization of a Novel Indium Mercapto Derivative [clln(sch2(co)o)2]2-[(4-mepyh)2]2+

NASA Technical Reports Server (NTRS)

Banger, Kulbinder K.; Duraj, Stan A.; Fanwick, Philip E.; Hepp, Aloysius F.; Martock, Robert A.

2004-01-01

The synthesis and structural characterization of a novel In(III) complex is described. The reaction between InCl3 with sodium mercapto-acetic acid, (NaSCH2(CO)OH) in 4-methylpyridine, (CH3(C5H5N), (4-Mepy)) at 25 C affords [ClIn(SCH2(CO)O)2]2- [(4-MepyH)2]2+. X-ray diffraction studies show it to have a distorted square pyramidal geometry, with the [(-SCH2(CO)CO-)] ligands in a trans conformation. The compound crystallizes in the P(raised dash) 1 (No. 2) space group with a = 7.8624 Angstrom, b = 9.950 Angstrom, c = 13.793 Angstrom, alpha = 107.60 degrees, beta= 90.336 degrees, gamma = 98.983 degrees, V = 1014.3 Angstroms (sup 3), R(F(raised circle)) = 0.037, and R(sub w) = 0.048.

Acenaphthenequinone thiosemicarbazone and its transition metal complexes: synthesis, structure, and biological activity.

PubMed

Rodriguez-Argüelles, M C; Belicchi Ferrari, M; Gasparri Fava, G; Pelizzi, C; Pelosi, G; Albertini, R; Bonati, A; Dall'Aglio, P P; Lunghi, P; Pinelli, S

1997-04-01

The reaction of iron, nickel, copper, and zinc chlorides or acetates with acenaphthenequinone thiosemicarbazone, Haqtsc leads to the formation of novel complexes that have been characterized by spectroscopic studies (NMR, IR) and biological properties. The crystal structures of the free ligand Haqtsc 1 and of the compound [Ni(aqtsc)2].DMF 2, have also been determined by X-ray methods from diffractometer data. In 1, the conformation of the two nonequivalent molecules is governed by intramolecular hydrogen bonds, while an intermolecular hydrogen bond is responsible for dimer-like groups formation. In 2, the coordination geometry about nickel is distorted octahedral, and the two ligand molecules are terdentate monodeprotonated. Biological studies have shown that, for the first time at least up the used doses, a free ligand is active both in the inhibition of cell proliferation and in the induced differentiation on Friend erythroleukemia cells (FLC).

(Cryptand-222)potassium(+) (hydrogensulfido)[5,10,15,20-tetra-kis(2-pival-amido-phen-yl)porphyrinato]ferrate(II).

PubMed

Dhifet, Mondher; Belkhiria, Mohamed Salah; Daran, Jean-Claude; Nasri, Habib

2009-07-22

As part of a systematic investigation for a number of Fe(II) porphyrin complexes used as biomimetic models for cytochrome P450, crystals of the title compound, [K(C(18)H(36)N(2)O(6))][Fe(II)(C(64)H(64)N(8)O(4))(HS)], were prepared. The compound exhibits a non-planar conformation with major ruffling and saddling distortions. The average equatorial iron-pyrrole N atom [Fe-N(p) = 2.102 (2) Å] bond length and the distance between the Fe(II) atom and the 24-atom core of the porphyrin ring (Fe-P(C)= 0.558 Å) are typical for high-spin iron(II) penta-coordinate porphyrinates. One of the tert-butyl groups in the structure is disordered over two sets with occupancies of 0.84 and 0.16.

(Cryptand-222)potassium(+) (hydrogensulfido)[5,10,15,20-tetra­kis(2-pival­amido­phen­yl)porphyrinato]ferrate(II)

PubMed Central

Dhifet, Mondher; Belkhiria, Mohamed Salah; Daran, Jean-Claude; Nasri, Habib

2009-01-01

As part of a systematic investigation for a number of FeII porphyrin complexes used as biomimetic models for cytochrome P450, crystals of the title compound, [K(C18H36N2O6)][FeII(C64H64N8O4)(HS)], were prepared. The compound exhibits a non-planar conformation with major ruffling and saddling distortions. The average equatorial iron–pyrrole N atom [Fe—Np = 2.102 (2) Å] bond length and the distance between the FeII atom and the 24-atom core of the porphyrin ring (Fe—PC= 0.558 Å) are typical for high-spin iron(II) penta­coordinate porphyrinates. One of the tert-butyl groups in the structure is disordered over two sets with occupancies of 0.84 and 0.16. PMID:21583412

Trends in intakes and sources of solid fats and added sugars among US children and adolescents: 1994-2010

PubMed Central

Slining, Meghan M.; Popkin, Barry M.

2013-01-01

Objective There are increasing global concerns about improving the dietary intakes of children and adolescents. In the United States (U.S.) the focus is on reducing energy from foods and beverages that provide empty calories from solid fats and added sugars (SoFAS). We examine trends in intakes and sources of solid fat and added sugars among U.S. 2- to 18- year olds from 1994-2010. Methods Data from five nationally representative surveys, the Continuing Survey of Food Intakes by Individuals Surveys (1994-1996) and the What We Eat In America, National Health and Nutrition Examination Surveys (2003-2004, 2005-2006, 2007-2008 and 2009-2010) were used to examine key food sources and energy from solid fats and added sugars. Sample sizes ranged from 2,594 to 8,259 per survey period, for a total of 17,268 observations across the five surveys. Food files were linked over time to create comparable food groups and nutrient values. Differences were examined by age, race/ethnicity and family income. Results Daily intake of energy from SoFAS among U.S. 2-18 year olds decreased from 1994-2010, with declines primarily detected in the recent time periods. Solid fats accounted for a greater proportion of total energy intake than did added sugars. Conclusions Although the consumption of solid fats and added sugars among children and adolescents in the United States decreased between 1994–1998 and 2009–2010, mean intakes continue to exceed recommended limits. PMID:23554397

Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study.

PubMed

Friesecke, Sigrun; Stecher, Stephanie-Susanne; Gross, Stefan; Felix, Stephan B; Nierhaus, Axel

2017-09-01

Sepsis is the most common cause of death in medical intensive care units (ICU). If sepsis progresses to refractory septic shock, mortality may reach 90-100% despite optimum current therapy. Extracorporeal cytokine adsorption in addition to regular therapy was studied prospectively in refractory septic shock patients on a medical ICU. Refractory shock was defined as increasing vasopressor dose required to maintain mean arterial blood pressure above 65 mmHg or increasing lactate levels despite protocol-guided shock therapy for 6 h. We analysed noradrenaline requirements after 6 and 12 h (primary endpoint), lactate clearance after 6 and 12 h, SOFA-scores in the first days and achievement of shock reversal (i.e., normalization of lactate concentrations and sustained discontinuation of vasopressors; secondary endpoints). Twenty consecutive patients with refractory septic shock were included; CytoSorb ® treatment was started after 7.8 ± 3.7 h of shock therapy. Following the initiation of adsorption therapy, noradrenaline dose could be significantly reduced after 6 (-0.4 µg/kg/min; p = 0.03) and 12 h (-0.6 µg/kg/min; p = 0.001). Lactate clearance improved significantly. SOFA-scores on day 0, 1 and 2 remained unchanged. Shock reversal was achieved in 13 (65%) patients; 28-day survival was 45%. In severe septic shock unresponsive to standard treatment, haemodynamic stabilization was achieved using cytokine adsorption therapy, resulting in shock reversal in two-thirds of these patients. The study was registered in the German Register for Clinical Trials (DRKS) No. 00005149.

Ventilator-associated pneumonia in surgical emergency intensive care unit.

PubMed

Ertugrul, Bulent M; Yildirim, Ayse; Ay, Pinar; Oncu, Serkan; Cagatay, Atahan; Cakar, Nahit; Ertekin, Cemalettin; Ozsut, Halit; Eraksoy, Haluk; Calangu, Semra

2006-01-01

To investigate the incidence, risk factors and the etiology of ventilator-associated pneumonia (VAP) in surgical emergency intensive care unit (ICU) patients. We conducted this prospective cohort study in the surgical emergency ICU of Istanbul Medical Faculty between December 1999 and May 2001. We included 100 mechanically ventilated patients in this study. We diagnosed VAP according to the current diagnostic criteria. We identified the etiology of VAP cases by both quantitative cultures of endotracheal aspiration and blood cultures. To analyze the predisposing factors for the development of VAP, we recorded the following variables: age, gender, acute physiology and chronic health evaluation (APACHE) II score, Glasgow coma scale (GCS), sequential organ failure assessment (SOFA) score, serum albumin level, duration of mechanical ventilation (MV) prior to the development of VAP, and underlying diseases. We determined the VAP incidence rate as 28%. We found the APACHE II score and the duration of MV to be statistically significant variables for the development of VAP. There were no significant differences regarding age, gender, GCS, SOFA score, albumin level, or underlying diseases for the development of VAP. The isolated bacteria among VAP cases were as follows: Staphylococcus aureus (n=12, 43%), Acinetobacter spp. (n=6, 21%), coagulase-negative Staphylococci (n=4, 15%), Pseudomonas aeruginosa (n=3, 10.7%) and Klebsiella pneumoniae (n=3, 10.7%). Ventilator-associated pneumonia is a common infection, and certain interventions might affect the incidence of VAP. The ICU clinicians should be aware of the risk factors for VAP, which could prove useful in identifying patients at high risk for VAP, and modifying patient care to minimize the risk of VAP.

[Evolution in muscle strength in critical patients with invasive mechanical ventilation].

PubMed

Via Clavero, G; Sanjuán Naváis, M; Menéndez Albuixech, M; Corral Ansa, L; Martínez Estalella, G; Díaz-Prieto-Huidobro, A

2013-01-01

To assess the evolution of muscle strength in critically ill patients with mechanical ventilation (MV) from withdrawal of sedatives to hospital discharge. A cohort study was conducted in two intensive care units in the Hospital Universitari de Bellvitge from November 2011 to March 2012. Consecutive patients with MV > 72h. Dependent outcome: Muscle strength measured with the Medical Research Council (MRC) scale beginning on the first day the patient was able to answer 3 out of 5 simple orders (day 1), every week, at ICU discharge and at hospital discharge or at day 60 Independent outcomes: factors associated with muscle strength loss, ventilator-free days, ICU length of stay and hospital length of stay. The patients were distributed into two groups (MRC< 48, MRC ≥ 48) after the first measurement. Thirty-four patients were assessed. Independent outcomes associated with muscle strength weakness were: days with cardiovascular SOFA >2 (P<.001) and days with costicosteroids (P<.001). Initial MRC in MRC<48 group was 38 (27-43), and 52 (50-54) in MRC ≥ 48. The largest muscle strength gain was obtained the first week (31% versus 52%). A MRC < 48 value was associated with more MV days (P<.007) and a longer ICU stay. (P<.003). The greatest muscle strength gain after withdrawing of the sedatives was achieved in the first week. Muscle strength loss was associated with a cardiovascular SOFA > 2 and costicosteroids. Patients with a MRC < 48 required more days with MV and a longer ICU stay. Copyright © 2013 Elsevier España, S.L. y SEEIUC. All rights reserved.

[Contraindications to succinylcholine in the intensive care unit. A prevalence study].

PubMed

Muñoz-Martínez, T; Garrido-Santos, I; Arévalo-Cerón, R; Rojas-Viguera, L; Cantera-Fernández, T; Pérez-González, R; Díaz-Garmendia, E

2015-03-01

To determine the prevalence of contraindications to succinylcholine in patients admitted to the ICU. An observational study was carried out, describing the frequency of succinylcholine contraindication by stays, and associating the contraindications to population variables. The adult general ICU of a reference hospital. Clinical-surgical critically ill patients. Thirty consecutive days were analyzed. None. Population variables: age, sex, APACHE II and SOFA scores, illness, days of hospitalization, mechanical ventilation and renal replacement therapy. hyperkalemia, bedridden patients, rhabdomyolysis, muscle trauma, burns, infusion of neuromuscular blocking agents, acute renal failure, chronic renal failure, intraocular hypertension, intracranial hypertension, statin use, malignant hyperthermia, neuromuscular disease, spinal cord sectioning, bradycardia < 50 bpm, succinylcholine allergy, and pseudo-cholinesterase deficiency. A total of 102 patients were admitted, aged 60 ± 16 years (56.9% males), with the generation of 657 stays. Main diseases: elective heart surgery (33%), respiratory failure (22%) and sepsis (14%). We documented 466 stays (70.9%) with contraindications, particularly bedridden patients (n=140), neuromuscular blocking agents (n=101), acute renal failure (n=126), statin use (n=167), neuromuscular disease (n=159) and bradycardia (n=76). We recorded 74 stays (11.3%) at high risk of complications, secondary to hyperkalemic risk associated to receptor dysregulation. A high risk of complications was associated to advanced age, prolonged hospitalization, prolonged length of stay in the ICU, higher APACHE II and SOFA scores, mechanical ventilation and renal replacement therapy. Given the high prevalence of contraindications to succinylcholine observed, we discourage its use in patients admitted to the ICU. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

An initial investigation of abnormal bodily phenomena in subjects at ultra high risk for psychosis: Their prevalence and clinical implications.

PubMed

Madeira, Luis; Bonoldi, Ilaria; Rocchetti, Matteo; Samson, Carly; Azis, Matilda; Queen, Beverly; Bossong, Matthijs; Perez, Jesus; Stone, James; Allen, Paul; Howes, Oliver D; McGuire, Philip; Raballo, Andrea; Fusar-Poli, Paolo; Ballerini, Massimo; Stanghellini, Giovanni

2016-04-01

Contemporary phenomenological research has considered abnormal bodily phenomena (ABP) to be a phenotypic trait of subjects with schizophrenia in their first psychotic episode. Yet the prevalence of ABP and their clinical significance in subjects at Ultra High Risk (UHR) of psychosis remain unidentified. This study is an exploratory investigation of ABP in UHR subjects and matched healthy controls (HCs) examining their relation to clinical features and basic self-disturbances. A sample of 26 UHR and 14 HC subjects from three prodromal and early intervention clinics in South London, West London and Cambridge was assessed with the Abnormal Bodily Phenomena questionnaire (ABPq), Comprehensive Assessment of At-Risk Mental States (CAARMS), the Positive and Negative Syndrome Scale (PANSS), the Social and Occupational Functioning Assessment Scale (SOFAS) and the Examination of Anomalous Self Experiences (EASE) checklist. In our sample ABP occurred in 73.1% of UHR subjects and prominent ABP (proABP) were referred in 53.8% of them. No HC subject reported ABP. The UHR group with proABP had lower CAARMS total score (t=-9.265, p=0.006). There were no differences in PANSS total score (t=-1.235, p=0.277), SOFAS score (H(2) 22.27, p=0.666) and EASE total scores (z=8.565, adjusted p=0.185) in the UHR subjects with prominent ABP versus those that did not. This initial investigation suggests that ABP could be a prevalent phenotypic feature of UHR subjects. Copyright © 2015 Elsevier Inc. All rights reserved.

PROTEIN NEEDS OF CRITICALLY ILL PATIENTS RECEIVING PARENTERAL NUTRITION.

PubMed

Germano Borges de Oliveira Nascimento Freitas, Renata; Negrão Nogueira, Roberto José; Hessel, Gabriel

2015-07-01

assess whether the current protein intake recommendations may improve the biochemical parameters of critical patients receiving parenteral nutrition. longitudinal study with three evaluations made (during the first 72 hours, on the 7th and the 14th days of PN). The following tests were applied: albumin, C-reactive protein, prealbumin, total cholesterol, HDL, triglycerides, lymphocytes, and glutathione peroxidase. The severity was determined by SOFA. The statistical analysis included the Spearman and Mann-Whitney tests, as well as ANOVA (analysis of variance). among the 53 patients evaluated, 20 (37.74%) died. The mean calorie was 24.68 ± 9.78 kcal/kg (beginning of PN), 26.49 ± 8.89 kcal/kg (3rd to 7th days of PN), and 30.9 ± 12.19 kcal/kg (7th to 14th days of PN). The mean protein was 1.19 ± 0.44 g/kcal/kg (first 72 hours of PN), 1.29 ± 0.44 g/kcal/kg (3rd to 7th days of PN) and 1.49 ± 0.69 g/kcal/kg (7th to 14th days of PN). Prealbumin, albumin, total cholesterol and HDL were below the reference values, while the CRP levels were high. Throughout the three evaluation times, there was no a significant improvement on the levels of laboratory examinations. A strong and negative correlation was found between SOFA and prealbumin (r = -0.64, p = 0.05). the protein offer, according to the traditional recommendations, was not enough to improve the biochemical parameters of critical patients undergoing parenteral nutrition. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Trends in intakes and sources of solid fats and added sugars among U.S. children and adolescents: 1994-2010.

PubMed

Slining, M M; Popkin, B M

2013-08-01

There are increasing global concerns about improving the dietary intakes of children and adolescents. In the United States (U.S.), the focus is on reducing energy from foods and beverages that provide empty calories from solid fats and added sugars (SoFAS). We examine trends in intakes and sources of solid fat and added sugars among U.S. 2-18 year olds from 1994 to 2010. Data from five nationally representative surveys, the Continuing Survey of Food Intakes by Individuals Surveys (1994-1996) and the What We Eat In America, National Health and Nutrition Examination Surveys (2003-2004, 2005-2006, 2007-2008 and 2009-2010) were used to examine key food sources and energy from solid fats and added sugars. Sample sizes ranged from 2594 to 8259 per survey period, for a total of 17 268 observations across the five surveys. Food files were linked over time to create comparable food groups and nutrient values. Differences were examined by age, race/ethnicity and family income. Daily intake of energy from SoFAS among U.S. 2-18 year olds decreased from 1994 to 2010, with declines primarily detected in the recent time periods. Solid fats accounted for a greater proportion of total energy intake than did added sugars. Although the consumption of solid fats and added sugars among children and adolescents in the U.S. decreased between 1994-1998 and 2009-2010, mean intakes continue to exceed recommended limits. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

Insight as a social identity process in the evolution of psychosocial functioning in the early phase of psychosis.

PubMed

Klaas, H S; Clémence, A; Marion-Veyron, R; Antonietti, J-P; Alameda, L; Golay, P; Conus, P

2017-03-01

Awareness of illness (insight) has been found to have contradictory effects for different functional outcomes after the early course of psychosis. Whereas it is related to psychotic symptom reduction and medication adherence, it is also associated with increased depressive symptoms. In this line, the specific effects of insight on the evolution of functioning over time have not been identified, and social indicators, such as socio-occupational functioning have barely been considered. Drawing from social identity theory we investigated the impact of insight on the development of psychosocial outcomes and the interactions of these variables over time. The participants, 240 patients in early phase of psychosis from the Treatment and Early Intervention in Psychosis Program (TIPP) of the University Hospital of Lausanne, Switzerland, were assessed at eight time points over 3 years. Cross-lagged panel analyses and multilevel analyses were conducted on socio-occupational and general functioning [Social and Occupational Functioning Assessment Scale (SOFAS) and Global Assessment of Functioning (GAF)] with insight, time and depressive symptoms as independent variables. Results from multilevel analyses point to an overall positive impact of insight on psychosocial functioning, which increases over time. Yet the cross-lagged panel analysis did not reveal a systematic positive and causal effect of insight on SOFAS and GAF scores. Depressive symptoms seem only to be relevant in the beginning of the treatment process. Our results point to a complex process in which the positive impact of insight on psychosocial functioning increases over time, even when considering depressive symptoms. Future studies and treatment approaches should consider the procedural aspect of insight.

An investigation of a possible relationship between olfactory identification deficits at first episode and four-year outcomes in patients with psychosis.

PubMed

Good, Kimberley P; Tibbo, Philip; Milliken, Heather; Whitehorn, David; Alexiadis, Maria; Robertson, Nancy; Kopala, Lili C

2010-12-01

Olfactory identification deficits are found in a significant proportion of patients with schizophrenia spectrum psychotic disorders and appear to be predictive of incomplete remission of negative and cognitive symptoms. In the current study, we examined whether patients with first episode psychosis who have olfactory identification deficits (microsmic) have poorer functional outcome than those whose olfactory status is normal (normosmic). Sixty-six (66) first episode psychosis patients (46 M and 20 F) were assessed with the University of Pennsylvania Smell Identification Test (UPSIT) at baseline. UPSIT scores served to classify patients into subgroups. The patients' psychiatrists completed the Social and Occupational Functioning Assessment Scale (SOFAS) and the Levels of Functioning Scale (LOFS) after at least 6 months of treatment. The Premorbid Assessment Scale (PAS) was rated by a parent at baseline. Thirty-eight percent (38%) of the sample was identified as 'microsmic'. LOFS and SOFAS scores were significantly lower in the microsmic group than in the normosmic group. Symptoms were significantly worse in the microsmic group in comparison to the normosmic group. PAS scores did not differ between groups. First episode patients identified as microsmic at baseline assessment went on to demonstrate poorer functional outcome compared to normosmic patients despite no differences in premorbid adjustment. Olfactory identification deficits at first episode may provide a marker for poorer outcome. Testing olfaction is simple and inexpensive, and could provide clinically valuable information at first episode to identify those patients who might benefit from more intensive interventions promoting functional recovery. Copyright © 2010 Elsevier B.V. All rights reserved.

High Resolution Millimeter Wave Absorption Spectroscopy of Flexi- Ble Complex Organic Molecules: Laboratory Spectrum of 1, 2-Butanediol

NASA Astrophysics Data System (ADS)

Maris, Assimo

2017-11-01

The enhancing sensibility of radioastronomical observations allows for detec- tion of complex organic molecules (COMs) with increasing size. Observations performed by the Atacama Large Millimeter Array (ALMA) open up new oppor- tunities to reveal the COMs, at the same time, the huge amount of data collected and the extremely rich surveys represent a challenge for the astrochemistry community. Among all the detected molecules, the diols are object of chemical interest, because of their similarity with important biological building block molecules such as sugar alcohols. The simplest of them, ethylene glycol (EG), is one of the largest COMs detected in space thus far. Lines attributable to the most stable conformer of EG were detected in different environments and recently also the higher energy conformer has been observed both towards IRAS 16293-2422 and the Orion KL. Observations of 1, 2- and 1, 3-propanediol toward Sgr B2 (N-LMH) were attempted as part of the GBT Prebiotic Interstellar Molecule Sur- vey Legacy Project, but no transitions were detected. Although up to now, due the fact that the column densities of molecules tend to decrease with increasing molecular weight, no large diols have been observed in interstellar space, owing to the raising sensitivity of the radioastronomy observations, their future detection can not be excluded. In this context we report, for the first time, the laboratory millimeter spectrum of 1, 2-butanediol (BD) recorded in the 59.6-103.6 GHz frequency region (5.03-2.89 mm). BD (the ethylated form of EG) is a flexible molecule characterized by a great conformational complexity, thus at room condi- tions the population is distributed in a large number of species, leading to a very congested spectrum. This problem has been overcome exploiting the rotational and conformational cooling produced by the supersonic expansion technique. Six conformers of BD, including the global minimum, have been assigned yielding the rotational constants and centrifugal distortion constants up to the forth- or sixth-order. The experimental spectroscopic constants and theoretical electric dipole moment components were used to predict the rotational spectrum of each of the observed conformers up to 163 GHz. Making use of the training received by the ALMA Regional Center in Bologna, selected lines of the most stable conformer of BD were searched toward the IRAS 16293-2422 A source exploiting Band 3 observations performed during the ALMA-project 2012.1.00712.S. No match was found, however further observations, aimed specifically to its search, could be more successful. Moreover considering that the maximum spectral signal of heavy molecules is predicted at higher frequencies, additional laboratory measurements at sub-millimeter wavelengths can be performed, starting from the present assignments. The new data could be used to attempt new observations in COMs-reach sources.

The conformations of 13-vertex ML2C2B10 metallacarboranes: experimental and computational studies.

PubMed

Dalby, Kelly J; Ellis, David; Erhardt, Stefan; McIntosh, Ruaraidh D; Macgregor, Stuart A; Rae, Karen; Rosair, Georgina M; Settels, Volker; Welch, Alan J; Hodson, Bruce E; McGrath, Thomas D; Stone, F Gordon A

2007-03-21

The docosahedral metallacarboranes 4,4-(PMe(2)Ph)2-4,1,6-closo-PtC(2)B(10)H(12), 4,4-(PMe(2)Ph)2-4,1,10-closo-PtC(2)B(10)H(12), and [N(PPh(3))2][4,4-cod-4,1,10-closo-RhC(2)B(10)H(12)] were prepared by reduction/metalation of either 1,2-closo-C(2)B(10)H(12) or 1,12-closo-C(2)B(10)H(12). All three species were fully characterized, with a particular point of interest of the latter being the conformation of the {ML2} fragment relative to the carborane ligand face. Comparison with conformations previously established for six other ML(2)C(2)B(10) species of varying heteroatom patterns (4,1,2-MC(2)B(10), 4,1,6-MC(2)B(10), 4,1,10-MC(2)B(10), and 4,1,12-MC(2)B(10)) reveals clear preferences. In all cases a qualitative understanding of these was afforded by simple MO arguments applied to the model heteroarene complexes [(PH3)2PtC(2)B(4)H(6)]2- and [(PH3)2PtCB(5)H(6)]3-. Moreover, DFT calculations on [(PH3)2PtC(2)B(4)H(6)]2- in its various isomeric forms approximately reproduced the observed conformations in the 4,1,2-, 4,1,6-, and 4,1,10-MC(2)B(10) species, although analogous calculations on [(PH3)2PtCB(5)H(6)]3- did not reproduce the conformation observed in the 4,1,12-MC(2)B(10) metallacarborane. DFT calculations on (PH3)2PtC(2)B(10)H(12) yielded good agreement with experimental conformations in all four isomeric cases. Apparent discrepancies between observed and computed Pt-C distances were probed by further refinement of the 4,1,2- model to 1,2-(CH2)3-4,4-(PMe3)2-4,1,2-closo-PtC(2)B(10)H(10). This still has a more distorted structure than measured experimentally for 1,2-(CH2)3-4,4-(PMe(2)Ph)2-4,1,2-closo-PtC(2)B(10)H(10), but the structural differences lie on a very shallow potential energy surface. For the model compound a henicosahedral transition state was located 8.3 kcal mol(-1) above the ground-state structure, consistent with the fluxionality of 1,2-(CH2)3-4,4-(PMe(2)Ph)2-4,1,2-closo-PtC(2)B(10)H(10) in solution.

Inference Control Mechanism for Statistical Database: Frequency-Imposed Data Distortions.

ERIC Educational Resources Information Center

Liew, Chong K.; And Others

1985-01-01

Introduces two data distortion methods (Frequency-Imposed Distortion, Frequency-Imposed Probability Distortion) and uses a Monte Carlo study to compare their performance with that of other distortion methods (Point Distortion, Probability Distortion). Indications that data generated by these two methods produce accurate statistics and protect…

AST: World Coordinate Systems in Astronomy

NASA Astrophysics Data System (ADS)

Berry, David S.; Warren-Smith, Rodney F.

2014-04-01

The AST library provides a comprehensive range of facilities for attaching world coordinate systems to astronomical data, for retrieving and interpreting that information in a variety of formats, including FITS-WCS, and for generating graphical output based on it. Core projection algorithms are provided by WCSLIB (ascl:1108.003) and astrometry is provided by the PAL (ascl:1606.002) and SOFA (ascl:1403.026) libraries. AST bindings are available in Python (pyast), Java (JNIAST) and Perl (Starlink::AST). AST is used as the plotting and astrometry library in DS9 and GAIA, and is distributed separately and as part of the Starlink software collection.

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

PubMed Central

Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

2016-01-01

IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. CONCLUSIONS AND RELEVANCE These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis. PMID:26903338

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

PubMed

Singer, Mervyn; Deutschman, Clifford S; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig M; Hotchkiss, Richard S; Levy, Mitchell M; Marshall, John C; Martin, Greg S; Opal, Steven M; Rubenfeld, Gordon D; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C

2016-02-23

Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. To evaluate and, as needed, update definitions for sepsis and septic shock. A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

A simple scoring system based on neutrophil count in sepsis patients.

PubMed

Ueda, Takahiro; Aoyama-Ishikawa, Michiko; Nakao, Atsunori; Yamada, Taihei; Usami, Makoto; Kotani, Joji

2014-03-01

The assessment of critically ill patients is often a challenge for clinicians. There are a number of scoring systems such as Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) and C-reactive protein test (CRP), which have been shown to correlate with outcome in a variety of Intensive Care Unit (ICU) patients. Therefore, use of repeated measures of these preexisting scores over time is a reasonable attempt to assess the severity of organ dysfunction and predict outcome in critically ill patients. Several reports suggest that the neutrophil is a useful marker of sepsis. However, since both a large number and a small number of neutrophils indicate a severe situation, neutrophil count is difficult to use to directly predict patients'. We proposed a novel scoring system identify predictive factors using a simple blood cell count that may be associated with mortality in ICU patients. Our novel scoring system (n-score) was calculated as follows: ranges of neutrophils of 0-4999 cells/mm(3) and 5000-9999 cells/mm(3) were defined as 3 and 1 points, respectively. When the neutrophil count was over 10,000 cells/mm(3), the score was calculated by dividing the number of cells by 10,000. Then, 1 or 2 points were added when patients were female or male, respectively. We hypothesize that n-score may be a simple and easy scoring system to estimate mortality of the patients with sepsis and severe sepsis/septic shock without requirement of special methods or special measuring equipment, and may be as reliable as the APACHE II score or SOFA score. The retrospective evaluation was conducted at the Department of Emergency, Disaster and Critical Care Medicine at the Hyogo College of Medicine. Seventy-seven patients who were admitted to the emergency center and diagnosed sepsis or severe sepsis/septic shock between June 2007 and December 2012 and gave informed consent were enrolled. The n-score was significantly higher in non-survivors of sepsis and severe sepsis/septic shock (p<0.01, t-test) than in survivors. The ROC curve showed a sensitivity of 61.5% and a specificity of 80.4% at an n-score of 3.8 points; the area under the curve was 0.736. In addition, n-score correlated with APACHE II score (p<0.01, R=0.378) and SOFA score (p<0.05, R=0.256) on admission. Based on these preliminary evaluations, we hypothesize that n-score may be a useful scoring system to detect risk of death in sepsis and severe sepsis/septic shock. Copyright © 2014 Elsevier Ltd. All rights reserved.

Using continuous renal replacement therapy to manage patients of shock and acute renal failure

PubMed Central

Soni, Sachin S; Nagarik, Amit P; Adikey, Gopal Kishan; Raman, Anuradha

2009-01-01

Background: The incidence of acute renal failure (ARF) in the hospital setting is increasing. It portends excessive morbidity and mortality and a considerable burden on hospital resources. Extracorporeal therapies show promise in the management of patients with shock and ARF. It is said that the potential of such therapy goes beyond just providing renal support. The aim of our study was to analyze the clinical setting and outcomes of critically ill ARF patients managed with continuous renal replacement therapy (CRRT). Patients and Methods: Ours was a retrospective study of 50 patients treated between January 2004 and November 2005. These 50 patients were in clinical shock and had concomitant ARF. All of these patients underwent CVVHDF (continuous veno-venous hemodiafiltration) in the intensive care unit. For the purpose of this study, shock was defined as systolic BP < 100 mm Hg in spite of administration of one or more inotropic agents. SOFA (Sequential Organ Failure Assessment) score before initiation of dialysis support was recorded in all cases. CVVHDF was performed using the Diapact® (Braun) CRRT machine. The vascular access used was as follows: femoral in 32, internal jugular in 8, arteriovenous fistula (AVF) in 4, and subclavian in 6 patients. We used 0.9% or 0.45% (half-normal) saline as a prefilter replacement, with addition of 10% calcium gluconate, magnesium sulphate, sodium bicarbonate, and potassium chloride in separate units, while maintaining careful monitoring of electrolytes. Anticoagulation of the extracorporeal circuit was achieved with systemic heparin in 26 patients; frequent saline flushes were used in the other 24 patients. Results: Of the 50 patients studied, 29 were males and 21 females (1.4:1). The average age was 52.88 years (range: 20–75 years). Causes of ARF included sepsis in 24 (48%), hemodynamically mediated renal failure (HMRF) in 18 (36%), and acute over chronic kidney disease in 8 (16%) patients. The overall mortality was 74%. The average SOFA score was 14.31. The variables influencing mortality on multivariate analysis were: age [odds ratio (OR):1.65; 95% CI: 1.35 to 1.92; P = 0.04], serum creatinine (OR:1.68; 95% CI: 1.44 to 1.86; P = 0.03), and serum bicarbonate (OR: 0.76; 95% CI: 0.55 to 0.94; P = 0.01). On univariate analysis the SOFA score was found to be a useful predictor of mortality. Conclusions: Despite advances in treating critically ill patients with newer extracorporeal therapies, mortality is dismally high. Multiorgan dysfunction adversely affects outcome of CRRT. Older age, level of azotemia, and severity of metabolic acidosis are important predictors of adverse outcome. PMID:19561951

Cell Free DNA and Procalcitonin as Early Markers of Complications in ICU Patients with Multiple Trauma and Major Surgery.

PubMed

Ahmed, Asmaa I; Soliman, Randa A; Samir, Shereif

2016-12-01

Cell free DNA (cfDNA) was recently suggested as a new marker of sepsis and poor outcome in ICU patients. Procalcitonin has also been the focus of attention as an early marker for systemic inflammation and sepsis. cfDNA, procalcitonin (PCT), C-reactive protein (CRP), and lactate levels were measured in 30 ICU patients with multiple trauma or after major surgery on the first day of admission and on 5th and 7th days for PCT, CRP, and lactate. cfDNA was measured by real-time PCR, PCT by ELISA, CRP immunoturbidimetrically, and lactate spectrophotometrically. SOFA score and Injury Severity Score (ISS) for trauma patients were calculated. Significantly higher levels of cfDNA were observed in non-survivor patients in comparison to survivors and in patients with sepsis in comparison to those without sepsis (p = 0.002 and p = 0.02, respectively). The ROC curve was calculated for cfDNA as a predictor of outcome, the area under the curve (AUC) was 0.847 (95% CI: 0.669 - 0.952), at a cutoff value of 15500 ng/µL, sensitivity = 83.3%, specificity = 77.8% (p < 0.0001). As a prognostic marker of sepsis, the AUC for cfDNA was 0.788 (95% CI: 0.601 - 0.915), sensitivity = 56.25%, specificity = 100% (p = 0.0007). Day 5 PCT levels significantly correlated with SOFA scores on day 5, ISS on admission (p < 0.001 and p = 0.028, respectively), and a significant elevation of its levels was observed in non-survivor patients compared to survivors (p = 0.001). As a predictor of sepsis, PCT showed a sensitivity of 81.3%, specificity of 100% on day 5, (AUC: 0.987, 95% CI: 0.955 - 1.00); at a cutoff value of 202.90 pg/mL (p = 0.001). As a predictor of outcome, PCT on day 5 showed a sensitivity of 94.0% and a specificity of 78.0% at a cutoff value of 194.40 pg/mL (p = 0.001). Day 1 CRP correlated with ISS on admission, and on day 5 it correlated with SOFA score 5, while lactate correlated with length of stay on days 1, 5, and 7, and its levels were significantly higher in non-survivors on days 5 and 7. cfDNA is a good predictor of patient outcome in ICU and to a lesser extent as a marker of sepsis. PCT is another promising marker that can complement cfDNA to reach better patient management. Other markers can help in less severe cases.

Generic distortion model for metrology under optical microscopes

NASA Astrophysics Data System (ADS)

Liu, Xingjian; Li, Zhongwei; Zhong, Kai; Chao, YuhJin; Miraldo, Pedro; Shi, Yusheng

2018-04-01

For metrology under optical microscopes, lens distortion is the dominant source of error. Previous distortion models and correction methods mostly rely on the assumption that parametric distortion models require a priori knowledge of the microscopes' lens systems. However, because of the numerous optical elements in a microscope, distortions can be hardly represented by a simple parametric model. In this paper, a generic distortion model considering both symmetric and asymmetric distortions is developed. Such a model is obtained by using radial basis functions (RBFs) to interpolate the radius and distortion values of symmetric distortions (image coordinates and distortion rays for asymmetric distortions). An accurate and easy to implement distortion correction method is presented. With the proposed approach, quantitative measurement with better accuracy can be achieved, such as in Digital Image Correlation for deformation measurement when used with an optical microscope. The proposed technique is verified by both synthetic and real data experiments.

Distortion and Residual Stress Control in Integrally Stiffened Structure Produced by Direct Metal Deposition

NASA Technical Reports Server (NTRS)

Lin, Shih-Yung; Hoffman, Eric K.; Domack, Marcia S.

2007-01-01

2-D thermo-mechanical model developed to characterize distortion and residual stresses in integral structure produced by DMD. Demonstrated as a tool to guide experimental development of DMD fabrication process for aero structures. Distortion and residual stresses are local to deposit. Most distortion develops during deposition of the first few layers; Little change in distortion or residual stresses after fifth deposit layer Most of distortion is localized just beneath the build. Thicker build plates and the use of build lands results in greatest decrease in levels of distortion. Pre-straining shown to reduce distortion. Difficult to implement, particularly for complex stiffener arrays. Clamp position has complex effect on distortion and stresses. Overall distortion reduced with decreasing clamp clearance. Larger clamp clearances induce bending. Use of pre-heat and active cooling show minor influence on panel distortion. Generate changes in thermal gradients in the build plate.

Computational Analysis of a Zn-Bound Tris(imidazolyl) Calix[6]arene Aqua Complex: Toward Incorporating Second-Coordination Sphere Effects into Carbonic Anhydrase Biomimetics.

PubMed

Koziol, Lucas; Essiz, Sebnem G; Wong, Sergio E; Lau, Edmond Y; Valdez, Carlos A; Satcher, Joe H; Aines, Roger D; Lightstone, Felice C

2013-03-12

Molecular dynamics simulations and quantum-mechanical calculations were performed to characterize a supramolecular tris(imidazolyl) calix[6]arene Zn(2+) aqua complex, as a biomimetic model for the catalyzed hydration of carbon dioxide to bicarbonate, H2O + CO2 → H(+) + HCO3(-). On the basis of potential-of-mean-force (PMF) calculations, stable conformations had distorted 3-fold symmetry and supported either one or zero encapsulated water molecules. The conformation with an encapsulated water molecule is calculated to be lower in free energy than the conformation with an empty cavity (ΔG = 1.2 kcal/mol) and is the calculated free-energy minimum in solution. CO2 molecule partitioning into the cavity is shown to be very facile, proceeding with a barrier of 1.6 kcal/mol from a weak encounter complex which stabilizes the species by about 1.0 kcal/mol. The stabilization energy of CO2 is calculated to be larger than that of H2O (ΔΔG = 1.4 kcal/mol), suggesting that the complex will preferentially encapsulate CO2 in solution. In contrast, the PMF for a bicarbonate anion entering the cavity is calculated to be repulsive in all nonbonding regions of the cavity, due to the diameter of the calix[6]arene walls. Geometry optimization of the Zn-bound hydroxide complex with an encapsulated CO2 molecule showed that multiple noncovalent interactions direct the reactants into optimal position for nucleophilic addition to occur. The calixarene complex is a structural mimic of the hydrophilic/hydrophobic divide in the enzyme, providing a functional effect for CO2 addition in the catalytic cycle. The results show that Zn-binding calix[6]arene scaffolds can be potential synthetic biomimetics for CO2 hydration catalysis, both in terms of preferentially encapsulating CO2 from solution and by spatially fixing the reactive species inside the cavity.

Detection and Rectification of Distorted Fingerprints.

PubMed

Si, Xuanbin; Feng, Jianjiang; Zhou, Jie; Luo, Yuxuan

2015-03-01

Elastic distortion of fingerprints is one of the major causes for false non-match. While this problem affects all fingerprint recognition applications, it is especially dangerous in negative recognition applications, such as watchlist and deduplication applications. In such applications, malicious users may purposely distort their fingerprints to evade identification. In this paper, we proposed novel algorithms to detect and rectify skin distortion based on a single fingerprint image. Distortion detection is viewed as a two-class classification problem, for which the registered ridge orientation map and period map of a fingerprint are used as the feature vector and a SVM classifier is trained to perform the classification task. Distortion rectification (or equivalently distortion field estimation) is viewed as a regression problem, where the input is a distorted fingerprint and the output is the distortion field. To solve this problem, a database (called reference database) of various distorted reference fingerprints and corresponding distortion fields is built in the offline stage, and then in the online stage, the nearest neighbor of the input fingerprint is found in the reference database and the corresponding distortion field is used to transform the input fingerprint into a normal one. Promising results have been obtained on three databases containing many distorted fingerprints, namely FVC2004 DB1, Tsinghua Distorted Fingerprint database, and the NIST SD27 latent fingerprint database.

Pathogens and outcomes in pediatric septic shock patients supported by extracorporeal membrane oxygenation.

PubMed

Chang, Tu-Hsuan; Wu, En-Ting; Lu, Chun-Yi; Huang, Shu-Chien; Yang, Tzu-I; Wang, Ching-Chia; Chen, Jong-Min; Lee, Ping-Ing; Huang, Li-Min; Chang, Luan-Yin

2017-08-04

Refractory septic shock is the leading cause of mortality in children. There is limited evidence to support extracorporeal membrane oxygenation (ECMO) use in pediatric septic shock. We described the etiology and outcomes of septic patients in our institution and attempted to find predictive factors. We retrospectively reviewed 55 pediatric patients with septic shock who required ECMO support in a tertiary medical center from 2008 to 2015. Septic shock was defined as culture proved or clinical suspected sepsis with hypotension or end-organ hypoperfusion. ECMO would be applied when pediatric advanced life support steps were performed thoroughly without clinical response. Patient's demographics, laboratory parameters before and after ECMO, and outcomes were analyzed. Among 55 children with ECMO support, 31% of them survived on discharge. For 25 immunocompromised patients, causal pathogens were found in 17 patients: 7 due to bacteremia, 9 with preexisting virus infections and one with invasive fungal infection. Among 30 previously healthy patients, causal pathogens were found in 18 patients: 10 due to bacteremia (the most common was pneumococcus), 7 with preexisting virus infections including influenza (n = 4), adenovirus (n = 2), RSV, and 1 patient had mixed virus and bacterial infections. Predictive factors associated with death were arterial blood gas pH, CO 2 and Glasgow Coma Scale (p < 0.05). SOFA score was a valuable predictive scoring system for outcome prediction (p < 0.05). Pediatric patients with refractory septic shock had high mortality rate and ECMO could be used as a rescue modality, and SOFA score could be applied to predict outcomes. Copyright © 2017. Published by Elsevier B.V.

Comparison of the Nosocomial Pneumonia Mortality Prediction (NPMP) model with standard mortality prediction tools.

PubMed

Srinivasan, M; Shetty, N; Gadekari, S; Thunga, G; Rao, K; Kunhikatta, V

2017-07-01

Severity or mortality prediction of nosocomial pneumonia could aid in the effective triage of patients and assisting physicians. To compare various severity assessment scoring systems for predicting intensive care unit (ICU) mortality in nosocomial pneumonia patients. A prospective cohort study was conducted in a tertiary care university-affiliated hospital in Manipal, India. One hundred patients with nosocomial pneumonia, admitted in the ICUs who developed pneumonia after >48h of admission, were included. The Nosocomial Pneumonia Mortality Prediction (NPMP) model, developed in our hospital, was compared with Acute Physiology and Chronic Health Evaluation II (APACHE II), Mortality Probability Model II (MPM 72  II), Simplified Acute Physiology Score II (SAPS II), Multiple Organ Dysfunction Score (MODS), Sequential Organ Failure Assessment (SOFA), Clinical Pulmonary Infection Score (CPIS), Ventilator-Associated Pneumonia Predisposition, Insult, Response, Organ dysfunction (VAP-PIRO). Data and clinical variables were collected on the day of pneumonia diagnosis. The outcome for the study was ICU mortality. The sensitivity and specificity of the various scoring systems was analysed by plotting receiver operating characteristic (ROC) curves and computing the area under the curve for each of the mortality predicting tools. NPMP, APACHE II, SAPS II, MPM 72  II, SOFA, and VAP-PIRO were found to have similar and acceptable discrimination power as assessed by the area under the ROC curve. The AUC values for the above scores ranged from 0.735 to 0.762. CPIS and MODS showed least discrimination. NPMP is a specific tool to predict mortality in nosocomial pneumonia and is comparable to other standard scores. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Withholding or withdrawing of life-sustaining therapy in older adults (≥ 80 years) admitted to the intensive care unit.

PubMed

Guidet, Bertrand; Flaatten, Hans; Boumendil, Ariane; Morandi, Alessandro; Andersen, Finn H; Artigas, Antonio; Bertolini, Guido; Cecconi, Maurizio; Christensen, Steffen; Faraldi, Loredana; Fjølner, Jesper; Jung, Christian; Marsh, Brian; Moreno, Rui; Oeyen, Sandra; Öhman, Christina Agwald; Pinto, Bernardo Bollen; Soliman, Ivo W; Szczeklik, Wojciech; Valentin, Andreas; Watson, Ximena; Zafeiridis, Tilemachos; De Lange, Dylan W

2018-05-17

To document and analyse the decision to withhold or withdraw life-sustaining treatment (LST) in a population of very old patients admitted to the ICU. This prospective study included intensive care patients aged ≥ 80 years in 309 ICUs from 21 European countries with 30-day mortality follow-up. LST limitation was identified in 1356/5021 (27.2%) of patients: 15% had a withholding decision and 12.2% a withdrawal decision (including those with a previous withholding decision). Patients with LST limitation were older, more frail, more severely ill and less frequently electively admitted. Patients with withdrawal of LST were more frequently male and had a longer ICU length of stay. The ICU and 30-day mortality were, respectively, 29.1 and 53.1% in the withholding group and 82.2% and 93.1% in the withdrawal group. LST was less frequently limited in eastern and southern European countries than in northern Europe. The patient-independent factors associated with LST limitation were: acute ICU admission (OR 5.77, 95% CI 4.32-7.7), Clinical Frailty Scale (CFS) score (OR 2.08, 95% CI 1.78-2.42), increased age (each 5 years of increase in age had a OR of 1.22 (95% CI 1.12-1.34) and SOFA score [OR of 1.07 (95% CI 1.05-1.09 per point)]. The frequency of LST limitation was higher in countries with high GDP and was lower in religious countries. The most important patient variables associated with the instigation of LST limitation were acute admission, frailty, age, admission SOFA score and country. ClinicalTrials.gov (ID: NTC03134807).

Escitalopram treatment for depressive disorder following acute coronary syndrome: a 24-week double-blind, placebo-controlled trial.

PubMed

Kim, Jae-Min; Bae, Kyung-Yeol; Stewart, Robert; Jung, Bo-Ok; Kang, Hee-Ju; Kim, Sung-Wan; Shin, Il-Seon; Hong, Young Joon; Kim, Ju Han; Shin, Hee-Young; Kang, Gaeun; Ahn, Youngkeun; Kim, Jong-Keun; Jeong, Myung Ho; Yoon, Jin-Sang

2015-01-01

Depression is common after acute coronary syndrome (ACS) and has adverse effects on prognosis. There are few evidence-based interventions for treating depression in ACS. This study investigated the efficacy and safety of escitalopram in treating depressive disorders identified 2-14 weeks after a confirmed ACS episode. A total of 217 patients with DSM-IV depressive disorders (121 major and 96 minor) and ACS were randomly assigned to receive escitalopram in flexible doses of 5-20 mg/d (n = 108) or placebo (n = 109) for 24 weeks. The study was conducted from 2007 to 2013. The primary outcome measure was the Hamilton Depression Rating Scale (HDRS). Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), Clinical Global Impressions-Severity of Illness scale (CGI-S), Social and Occupational Functioning Assessment Scale (SOFAS), and World Health Organization Disability Assessment Schedule-12. Cardiovascular safety outcomes included echocardiography, electrocardiography, laboratory test, body weight, and blood pressure results. Escitalopram was superior to placebo in reducing HDRS scores (mean difference = 2.3, P = .016, effect size = 0.38). Escitalopram was also superior to placebo in decreasing depressive symptoms evaluated by the MADRS, BDI, and CGI-S and in improving SOFAS functioning level. Escitalopram was not associated with any harmful changes in cardiovascular safety measures. Dizziness was significantly more frequently reported in the escitalopram group (P = .018), but there were no significant differences in any other adverse events. These results indicate that escitalopram has clinically meaningful antidepressant effects with no evidence of reduced cardiovascular safety in depressive disorder following ACS. ClinicalTrials.gov identifier: NCT00419471. © Copyright 2015 Physicians Postgraduate Press, Inc.

An analysis of the predictors of mortality and morbidity in patients admitted after suicidal hanging to an Indian multidisciplinary Intensive Care Unit

PubMed Central

Renuka, MK; Kalaiselvan, MS; Arunkumar, AS

2017-01-01

Background and Aims: Hanging is a frequently used method to attempt suicide in India. There is a lack of data in the Indian population regarding clinical features and outcomes of suicidal hanging. The purpose of this study was to evaluate the factors affecting mortality and morbidity in patients admitted with suicidal hanging to the Intensive Care Unit (ICU). Methods: A 6-year retrospective study of adult patients admitted to the ICU with suicidal hanging was analysed for demographics, mode of hanging, lead time to emergency room (ER) admission, clinical presentation, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, admission Glasgow coma scale (GCS) and neurological outcomes. The primary outcome was in-hospital mortality rate. Secondary outcomes were hospital length of stay (LOS), ICU-LOS, time for neurological recovery, organ support and duration of mechanical ventilation. Statistical analysis was performed using the Student's t-test for continuous variables and Chi-square test for categorical variables. Results: We analysed data of 106 patients. The median age was 27 years [Interquartile Range (IQR) (22–34)]. The median lead time to ER admission was 1 h [IQR (0.5–1.4)] with median ICU stay of 3 days [IQR (2–4)]. Vasopressors were administered to 27.4% patients. GCS was ≤7 in 65% patients, and 84.9% patients received mechanical ventilation. Mortality rate was 10.3%. Survivors recovered with normal organ function. Conclusion: Suicidal hanging is associated with significant mortality. Admission GCS, APACHE II and 48 h SOFA score were predictors of poor outcome. PMID:28794524

Variants in LTA, TNF, IL1B and IL10 genes associated with the clinical course of sepsis.

PubMed

Montoya-Ruiz, Carolina; Jaimes, Fabián A; Rugeles, Maria T; López, Juan Álvaro; Bedoya, Gabriel; Velilla, Paula A

2016-12-01

The aim of this study was to explore the association between some SNPs of the TNF, LTA, IL1B and IL10 genes with cytokine concentrations and clinical course in Colombian septic patients. We conducted a cross-sectional study to genotype 415 septic patients and 205 patients without sepsis for the SNPs -308(G/A) rs1800629 of TNF; +252 (G/A) rs909253 of LTA; -511(A/G) rs16944 and +3953(C/T) rs1143634 of IL1B; and -1082(A/G) rs1800896, -819(C/T) rs1800871 and -592(C/A) rs1800872 of IL10. The association of theses SNPs with the following parameters was evaluated: (1) the presence of sepsis; (2) severity and clinical outcomes; (3) APACHE II and SOFA scores; and (4) procalcitonin, C-reactive protein, tumor necrosis factor, lymphotoxin alpha, interleukin 1 beta and interleukin 10 plasma concentrations. We found an association between the SNP LTA +252 with the development of sepsis [OR 1.29 (1.00-1.68)]; the SNP IL10 -1082 with sepsis severity [OR 0.53 (0.29-0.97)]; the TNF -308 with mortality [OR 0.33 (0.12-0.95)]; and the IL10 -592 and IL10 -1082 with admission to the intensive care unit (ICU) [OR 3.36 (1.57-7.18)] and [OR 0.18 (0.04-0.86)], respectively. None of the SNPs were associated with cytokine levels, procalcitonin and C-reactive protein serum concentrations, nor with APACHE II and SOFA scores. Our results suggest that these genetic variants play an important role in the development of sepsis and its clinical course.

Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition.

PubMed

Harris, P N A; McNamara, J F; Lye, D C; Davis, J S; Bernard, L; Cheng, A C; Doi, Y; Fowler, V G; Kaye, K S; Leibovici, L; Lipman, J; Llewelyn, M J; Munoz-Price, S; Paul, M; Peleg, A Y; Rodríguez-Baño, J; Rogers, B A; Seifert, H; Thamlikitkul, V; Thwaites, G; Tong, S Y C; Turnidge, J; Utili, R; Webb, S A R; Paterson, D L

2017-08-01

To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI). Prospective studies, randomized trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process. Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed. These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.

Intensive Care in India: The Indian Intensive Care Case Mix and Practice Patterns Study.

PubMed

Divatia, Jigeeshu V; Amin, Pravin R; Ramakrishnan, Nagarajan; Kapadia, Farhad N; Todi, Subhash; Sahu, Samir; Govil, Deepak; Chawla, Rajesh; Kulkarni, Atul P; Samavedam, Srinivas; Jani, Charu K; Rungta, Narendra; Samaddar, Devi Prasad; Mehta, Sujata; Venkataraman, Ramesh; Hegde, Ashit; Bande, B D; Dhanuka, Sanjay; Singh, Virendra; Tewari, Reshma; Zirpe, Kapil; Sathe, Prachee

2016-04-01

To obtain information on organizational aspects, case mix and practices in Indian Intensive Care Units (ICUs). An observational, 4-day point prevalence study was performed between 2010 and 2011 in 4209 patients from 124 ICUs. ICU and patient characteristics, and interventions were recorded for 24 h of the study day, and outcomes till 30 days after the study day. Data were analyzed for 4038 adult patients from 120 ICUs. On the study day, mean age, Acute Physiology and Chronic Health Evaluation (APACHE II) and sequential organ failure assessment (SOFA) scores were 54.1 ± 17.1 years, 17.4 ± 9.2 and 3.8 ± 3.6, respectively. About 46.4% patients had ≥1 organ failure. Nearly, 37% and 22.2% patients received mechanical ventilation (MV) and vasopressors or inotropes, respectively. Nearly, 12.2% patients developed an infection in the ICU. About 28.3% patients had severe sepsis or septic shock (SvSpSS) during their ICU stay. About 60.7% patients without infection received antibiotics. There were 546 deaths and 183 terminal discharges (TDs) from ICU (including left against medical advice or discharged on request), with ICU mortality 729/4038 (18.1%). In 1627 patients admitted within 24 h of the study day, the standardized mortality ratio was 0.67. The APACHE II and SOFA scores, public hospital ICUs, medical ICUs, inadequately equipped ICUs, medical admission, self-paying patient, presence of SvSpSS, acute respiratory failure or cancer, need for a fluid bolus, and MV were independent predictors of mortality. The high proportion of TDs and the association of public hospitals, self-paying patients, and inadequately equipped hospitals with mortality has important implications for critical care in India.

Effect of SeptimebTM as a new natural extract on severe sepsis: A randomized clinical trial.

PubMed

Pourdast, Alieh; Sanaei, Maryam; Jafari, Sirous; Mohammadi, Mostafa; Khalili, Hossein; Shafiee, Gita; Ahadi, Zeinab; Rostami, Mahsa; Alizad, Saba; Heshmat, Ramin; Mohraz, Minoo

2017-01-01

Septimeb as a herbal medicine has regulatory effects on inflammation. This study set to evaluate the effects of Septimeb among patients with sepsis on inflammatory biomarkers and survival rate. In this randomized clinical trial, 51 patients with sepsis from the ICU and medical ward of Imam Khomeini Hospital were divided into two groups: Septimeb (n=25) and control group (n=26). In the control group, the patients received a standard treatment only for 7 days, while Septimeb group received Septimeb (6cc vial with 500cc serum glucose infusion 5% daily for one to two hours) plus standard treatment of sepsis for 7 days. Then, blood samples were analyzed. APACHE (Acute Physiologic and Chronic Health Evaluation), SOFA (Sequential Organ Failure Assessment), and GCS (Glasgow Coma Score) values were calculated daily. Treatment with Septimeb showed a significant decrease in SOFA value (1.54±0.83) compared to the control group (2.39±0.88) (P<0.001) and a significant increase in GCS value (14.46±0.88) compared to the control group (12.86±1.78) (P<0.001). Improvements of these values can confirm the potential of Septimeb in the reduction of severity of sepsis (P<0.05). There were significant decreases in lactate and blood sugar and WBC levels. In addition, inflammatory factors such as ESR (Septimeb group: 52.07±34.80, control group: 51.75±42.10, P=0.98) and CRP (Septimeb group: 48.86±23.21, control group: 49.93±36.22, P=0.92) decreased, but did not show a significant reduction. Septimeb has positive effects on reduction of the severity of sepsis which leads to reduction of patients' mortality rates.

The association between hyperoxia and patient outcomes after cardiac arrest: Analysis of a high-resolution database

PubMed Central

Elmer, Jonathan; Scutella, Michael; Pullalarevu, Raghevesh; Wang, Bo; Vaghasia, Nishit; Trzeciak, Stephen; Rosario-Rivera, Bedda L.; Guyette, Francis X.; Rittenberger, Jon C.; Dezfulian, Cameron

2014-01-01

Purpose Previous observational studies have inconsistently associated early hyperoxia with worse outcomes after cardiac arrest and have methodological limitations. We tested this association using a high-resolution database controlling for multiple disease-specific markers of severity of illness and care processes. Methods This was a retrospective analysis of a single-center, prospective registry of consecutive cardiac arrest patients. We included patients who survived and were mechanically ventilated ≥24h after arrest. Our main exposure was arterial oxygen tension (PaO2), which we categorized hourly for 24 hours as severe hyperoxia (>300mmHg), moderate or probable hyperoxia (101-299mmHg), normoxia (60-100mmHg) or hypoxia (<60mmHg). We controlled for Utstein-style covariates, markers of disease severity and markers of care responsiveness. We performed unadjusted and multiple logistic regression to test the association between oxygen exposure and survival to discharge, and used ordered logistic regression to test the association of oxygen exposure with neurological outcome and Sequential Organ Failure Assessment (SOFA) score at 24h. Results Of 184 patients, 36% were exposed to severe hyperoxia and overall mortality was 54%. Severe hyperoxia, but not moderate or probable hyperoxia, was associated with decreased survival in both unadjusted and adjusted analysis (adjusted odds ratio (OR) for survival 0.83 per hour exposure, P=0.04). Moderate or probable hyperoxia was not associated with survival but was associated with improved SOFA score 24h (OR 0.92, P<0.01). Conclusion Severe hyperoxia was independently associated with decreased survival to hospital discharge. Moderate or probable hyperoxia was not associated with decreased survival and was associated with improved organ function at 24h. PMID:25472570

Effect of SeptimebTM as a new natural extract on severe sepsis: A randomized clinical trial

PubMed Central

Pourdast, Alieh; Sanaei, Maryam; Jafari, Sirous; Mohammadi, Mostafa; Khalili, Hossein; Shafiee, Gita; Ahadi, Zeinab; Rostami, Mahsa; Alizad, Saba; Heshmat, Ramin; Mohraz, Minoo

2017-01-01

Background: Septimeb as a herbal medicine has regulatory effects on inflammation. This study set to evaluate the effects of Septimeb among patients with sepsis on inflammatory biomarkers and survival rate. Methods: In this randomized clinical trial, 51 patients with sepsis from the ICU and medical ward of Imam Khomeini Hospital were divided into two groups: Septimeb (n=25) and control group (n=26). In the control group, the patients received a standard treatment only for 7 days, while Septimeb group received Septimeb (6cc vial with 500cc serum glucose infusion 5% daily for one to two hours) plus standard treatment of sepsis for 7 days. Then, blood samples were analyzed. APACHE (Acute Physiologic and Chronic Health Evaluation), SOFA (Sequential Organ Failure Assessment), and GCS (Glasgow Coma Score) values were calculated daily. Results: Treatment with Septimeb showed a significant decrease in SOFA value (1.54±0.83) compared to the control group (2.39±0.88) (P<0.001) and a significant increase in GCS value (14.46±0.88) compared to the control group (12.86±1.78) (P<0.001). Improvements of these values can confirm the potential of Septimeb in the reduction of severity of sepsis (P<0.05). There were significant decreases in lactate and blood sugar and WBC levels. In addition, inflammatory factors such as ESR (Septimeb group: 52.07±34.80, control group: 51.75±42.10, P=0.98) and CRP (Septimeb group: 48.86±23.21, control group: 49.93±36.22, P=0.92) decreased, but did not show a significant reduction. Conclusion: Septimeb has positive effects on reduction of the severity of sepsis which leads to reduction of patients’ mortality rates. PMID:28503281

Pitfalls in gastrointestinal permeability measurement in ICU patients with multiple organ failure using differential sugar absorption.

PubMed

Oudemans-van Straaten, Heleen M; van der Voort, Peter J; Hoek, Frans J; Bosman, Rob J; van der Spoel, Johan I; Zandstra, Durk F

2002-02-01

To assess whether gastrointestinal permeability (GIP) at intensive care unit (ICU) admission, measured by differential sugar absorption, is related to severity of disease and multiple organ failure (MOF). Post hoc, to analyse the relation between the urinary sugar recovery and renal function. Prospective observational cohort study. Eighteen-bed general ICU of a teaching hospital. Sixty-four ventilated patients admitted with MOF. GIP was assessed within 24 h using cellobiose (C), sucrose (S) and mannitol (M) absorption. Severity of disease: APACHE II and III, SAPS II and MPM II systems. Organ failure: SOFA, MODS and Goris score. The median urinary recovery of C was 0.147% (range 0.004-2.145%), of S 0.249% (0.001-3.656%) and of M 10.7% (0.6-270%). In 16 patients, M recovery was over 100% of the oral dose. They received red blood cell transfusion (RBC). In the non-transfused, the median cellobiose/mannitol (CM) ratio was 0.015 (0.0004-0.550). CM ratio was not related to severity of disease and inversely related to the SOFA score ( r=-0.30, p=0.04). Post hoc regression analysis showed that recoveries of C, S and M were positively related to urinary volume. Recoveries of C and S, but not of M, were positively related to creatinine clearance. The CM ratio corrected for diuresis, but was inversely related to creatinine clearance. Differential C, S and M absorption testing is unreliable after RBC transfusion, since bank blood contains mannitol. The excretion of C and S, but not of M, is limited by renal dysfunction. Differential sugar absorption is not reliable to test GIP in MOF patients, since non-permeability related factors act as confounders.

Endotoxin Elimination in Patients with Septic Shock: An Observation Study.

PubMed

Adamik, Barbara; Zielinski, Stanislaw; Smiechowicz, Jakub; Kübler, Andrzej

2015-12-01

To evaluate the effectiveness of endotoxin elimination with an adsorption column in patients with septic shock and endotoxemia. The elimination therapy was guided by a new bedside method of measuring endotoxin activity (EA). Intensive care unit (ICU) patients with septic shock and suspected Gram-negative infection were consecutively added to the study group within the first 24 h. Endotoxin elimination was performed using hemoperfusion with the Alteco LPS Adsorber. The primary endpoint was improvement in organ function within the first 24 h of treatment. A secondary objective was to assess the usefulness of a new method of measuring EA to help guide endotoxin elimination therapy. Out of 64 patients 18 had a high baseline EA [0.70 EA units (0.66-0.77)]. Those patients had endotoxin elimination treatment in addition to conventional medical therapy. At 24 h after endotoxin elimination, the EA had decreased to 0.56 EA units (0.43-0.77), (p = 0.005); MAP increased from 69 (62-80) to 80 mm Hg (68-88), (p = 0.002), and noradrenaline use decreased from 0.28 (0.15-0.80) to 0.1 μg/kg/min (0.00-0.70) at the same time (p = 0.04). The SOFA score had decreased from 11 (9-15) to 9 (7-14) points 24 h after endotoxin elimination (p = 0.01) with a median delta SOFA -2 points. Endotoxin elimination did not have a significant effect on the ICU length of stay or ICU mortality. Effective endotoxin elimination resulted in a significant improvement in hemodynamic parameters and of organ function. The application of the EA assay was useful for the bedside monitoring of endotoxemia in critically ill ICU patients.

Clinical Significance of Tissue Factor and CD13 Double-Positive Microparticles in Sirs Patients with Trauma and Severe Sepsis.

PubMed

Matsumoto, Hisatake; Yamakawa, Kazuma; Ogura, Hiroshi; Koh, Taichin; Matsumoto, Naoya; Shimazu, Takeshi

2017-04-01

Activated immune cells such as monocytes are key factors in systemic inflammatory response syndrome (SIRS) following trauma and sepsis. Activated monocytes induce almost all tissue factor (TF) expression contributing to inflammation and coagulation. TF and CD13 double-positive microparticles (TF/CD13MPs) are predominantly released from these activated monocytes. This study aimed to evaluate TF/CD13MPs and assess their usefulness as a biomarker of pathogenesis in early SIRS following trauma and sepsis. This prospective study comprising 24 trauma patients, 25 severe sepsis patients, and 23 healthy controls was conducted from November 2012 to February 2015. Blood samples were collected from patients within 24 h after injury and diagnosis of severe sepsis and from healthy controls. Numbers of TF/CD13MPs were measured by flow cytometry immediately thereafter. Injury Severity Score (ISS) and Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were calculated at patient enrollment. APACHE II and SOFA scores and International Society of Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) diagnostic criteria algorithm were calculated at the time of enrollment of severe sepsis patients. Numbers of TF/CD13MPs were significantly increased in both trauma and severe sepsis patients versus controls and correlated significantly with ISS and APACHE II score in trauma patients and with APACHE II and ISTH DIC scores in severe sepsis patients. Increased numbers of TF/CD13MPs correlated significantly with severities in the acute phase in trauma and severe sepsis patients, suggesting that TF/CD13MPs are important in the pathogenesis of early SIRS following trauma and sepsis.

Plasma suPAR as a prognostic biological marker for ICU mortality in ARDS patients.

PubMed

Geboers, Diederik G P J; de Beer, Friso M; Tuip-de Boer, Anita M; van der Poll, Tom; Horn, Janneke; Cremer, Olaf L; Bonten, Marc J M; Ong, David S Y; Schultz, Marcus J; Bos, Lieuwe D J

2015-07-01

We investigated the prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) on day 1 in patients with the acute respiratory distress syndrome (ARDS) for intensive care unit (ICU) mortality and compared it with established disease severity scores on day 1. suPAR was determined batchwise in plasma obtained within 24 h after admission. 632 ARDS patients were included. Significantly (P = 0.02) higher median levels of suPAR were found with increasing severity of ARDS: 5.9 ng/ml [IQR 3.1-12.8] in mild ARDS (n = 82), 8.4 ng/ml [IQR 4.1-15.0] in moderate ARDS (n = 333), and 9.0 ng/ml [IQR 4.5-16.0] in severe ARDS (n = 217). Non-survivors had higher median levels of suPAR [12.5 ng/ml (IQR 5.1-19.5) vs. 7.4 ng/ml (3.9-13.6), P < 0.001]. The area under the receiver operator characteristic curve (ROC-AUC) for mortality of suPAR (0.62) was lower than the ROC-AUC of the APACHE IV score (0.72, P = 0.007), higher than that of the ARDS definition classification (0.53, P = 0.005), and did not differ from that of the SOFA score (0.68, P = 0.07) and the oxygenation index (OI) (0.58, P = 0.29). Plasma suPAR did not improve the discrimination of the established disease severity scores, but did improve net reclassification of the APACHE score (29%), SOFA score (23%), OI (38%), and Berlin definition classification (39%). As a single biological marker, the prognostic value for death of plasma suPAR in ARDS patients is low. Plasma suPAR, however, improves the net reclassification, suggesting a potential role for suPAR in ICU mortality prediction models.

Prospective evaluation of the prognostic scores for cirrhotic patients admitted to an intensive care unit.

PubMed

Levesque, Eric; Hoti, Emir; Azoulay, Daniel; Ichaï, Philippe; Habouchi, Houssam; Castaing, Denis; Samuel, Didier; Saliba, Faouzi

2012-01-01

Cirrhotic patients admitted to an Intensive Care Unit (ICU) have a poor prognosis. Identifying patients in whom ICU care will be useful can be challenging. The aim of this study was to assess the predictive value of prognostic scores with respect to mortality and to identify mortality risk factors. Three hundred and seventy-seven cirrhotic patients admitted to a Liver ICU between May 2005 and March 2009 were enrolled in this study. Their average age was 55.5±11.4 years. The etiology of cirrhosis was alcohol (68%), virus hepatitis (18%), or mixed (5.5%). The main causes of hospitalization were gastrointestinal hemorrhage (43%), sepsis (19%), and hepatic encephalopathy (12%). ICU and in-hospital mortality rates were 34.7% and 43.0%, respectively. Infection was the major cause of death (81.6%). ROC curve analysis demonstrated that SOFA (0.92) and SAPS II (0.89) scores calculated within 24h of admission predicted ICU mortality better than the Child-Pugh score (0.79) or MELD scores with (0.79-0.82) or without the incorporation of serum sodium levels (0.82). Statistical analysis showed that the prognostic severity scores, organ replacement therapy, and infection were accurate predictors of mortality. On multivariate analysis, mechanical ventilation, vasopressor therapy, bilirubin level at admission, and infection were independently associated with ICU mortality. For cirrhotic patients admitted to the ICU, SAPS II, and SOFA scores predicted ICU mortality better than liver-specific scores. Mechanical ventilation or vasopressor therapy, bilirubin levels at admission and infection in patients with advanced cirrhosis were associated with a poor outcome. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Application of a modified sequential organ failure assessment score to critically ill patients

PubMed Central

Ñamendys-Silva, S.A.; Silva-Medina, M.A.; Vásquez-Barahona, G.M.; Baltazar-Torres, J.A.; Rivero-Sigarroa, E.; Fonseca-Lazcano, J.A.; Domínguez-Cherit, G.

2013-01-01

The purpose of the present study was to explore the usefulness of the Mexican sequential organ failure assessment (MEXSOFA) score for assessing the risk of mortality for critically ill patients in the ICU. A total of 232 consecutive patients admitted to an ICU were included in the study. The MEXSOFA was calculated using the original SOFA scoring system with two modifications: the PaO2/FiO2 ratio was replaced with the SpO2/FiO2 ratio, and the evaluation of neurologic dysfunction was excluded. The ICU mortality rate was 20.2%. Patients with an initial MEXSOFA score of 9 points or less calculated during the first 24 h after admission to the ICU had a mortality rate of 14.8%, while those with an initial MEXSOFA score of 10 points or more had a mortality rate of 40%. The MEXSOFA score at 48 h was also associated with mortality: patients with a score of 9 points or less had a mortality rate of 14.1%, while those with a score of 10 points or more had a mortality rate of 50%. In a multivariate analysis, only the MEXSOFA score at 48 h was an independent predictor for in-ICU death with an OR = 1.35 (95%CI = 1.14-1.59, P < 0.001). The SOFA and MEXSOFA scores calculated 24 h after admission to the ICU demonstrated a good level of discrimination for predicting the in-ICU mortality risk in critically ill patients. The MEXSOFA score at 48 h was an independent predictor of death; with each 1-point increase, the odds of death increased by 35%. PMID:23369978

A dimensional comparison between embedded 3D-printed and silicon microchannels

NASA Astrophysics Data System (ADS)

O'Connor, J.; Punch, J.; Jeffers, N.; Stafford, J.

2014-07-01

The subject of this paper is the dimensional characterization of embedded microchannel arrays created using contemporary 3D-printing fabrication techniques. Conventional microchannel arrays, fabricated using deep reactive ion etching techniques (DRIE) and wet-etching (KOH), are used as a benchmark for comparison. Rectangular and trapezoidal cross-sectional shapes were investigated. The channel arrays were 3D-printed in vertical and horizontal directions, to examine the influence of print orientation on channel characteristics. The 3D-printed channels were benchmarked against Silicon channels in terms of the following dimensional characteristics: cross-sectional area (CSA), perimeter, and surface profiles. The 3D-printed microchannel arrays demonstrated variances in CSA of 6.6-20% with the vertical printing approach yielding greater dimensional conformity than the horizontal approach. The measured CSA and perimeter of the vertical channels were smaller than the nominal dimensions, while the horizontal channels were larger in both CSA and perimeter due to additional side-wall roughness present throughout the channel length. This side-wall roughness caused significant shape distortion. Surface profile measurements revealed that the base wall roughness was approximately the resolution of current 3D-printers. A spatial periodicity was found along the channel length which appeared at different frequencies for each channel array. This paper concludes that vertical 3D-printing is superior to the horizontal printing approach, in terms of both dimensional fidelity and shape conformity and can be applied in microfluidic device applications.

Microwave spectrum of 2,6-dimethylcyclohexanone

NASA Astrophysics Data System (ADS)

Jang, Heesu; Shim, Jae-Seol; Oh, Jung Jin

2017-07-01

The rotational spectrum of 2,6-dimethylcyclohexanone (DMCHO) was measured in the frequency region from 6 to 12 GHz. Among three possible conformational isomers, two conformers were identified where two methyl groups are aligned in the equatorial/equatorial (ee) and the equatorial/axial (ea) positions. Both b-type and c-type transitions for (e,e)-2,6-DMCHO, and a-type, b-type, and c-type transitions for (e,a)-2,6-DMCHO were assigned to determine the rotational constants and quartic centrifugal distortion constants based on the Watson-A reduction Hamiltonian: (ee) A = 2150.95789(48) MHz, B = 1578.76212(40) MHz, C = 990.19141(45) MHz, ΔJ = 0.086(11) kHz, ΔJK = -0.134(20) kHz, ΔK = 0.298(15) kHz, δJ = 23.4(24) Hz, and δK = 101.4(77) Hz; and (ea) A = 2082.62538(83) MHz, B = 1566.59564(59) MHz, C = 1113.90153(75) MHz, ΔJ = 0.066(23) kHz. In addition, dipole moment components of the two isomers were determined by Stark effect measurements: (ee) μb = 2.6673(12) D, μc = 1.0379(11) D, μtotal = 2.8621(12) D; and (ea) μa = 1.385(253) D, μb = 2.358(104) D, μc = 1.172(21) D, μtotal = 2.975(144) D. Ab initio calculations for all three isomers were compared with each other and with experimental results.