bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel superfamily containing the β-grasp fold involved in binding diverse soluble ligands
Authors: Burroughs A Maxwell , Balaji S , Iyer Lakshminarayan M , Aravind L 
Published: January 2007

AbstractBackgroundDomains containing the β-grasp fold are utilized in a great diversity of physiological functions but their role, if any, in soluble or small molecule ligand recognition is poorly studied.ResultsUsing sensitive sequence and structure similarity searches we identify a novel superfamily containing the β-grasp fold. They are found in a diverse set of proteins that include the animal vitamin B12 uptake proteins transcobalamin and intrinsic factor, the bacterial polysaccharide export proteins, the competence DNA receptor ComEA, the cob(I)alamin generating enzyme PduS and the Nqo1 subunit of the respiratory electron transport chain. We present evidence that members of this superfamily are likely to bind a range of soluble ligands, including B12. There are two major clades within this superfamily, namely the transcobalamin-like clade and the Nqo1-like clade. The former clade is typified by an insert of a β-hairpin after the helix of the β-grasp fold, whereas the latter clade is characterized by an insert between strands 4 and 5 of the core fold.ConclusionMembers of both clades within this superfamily are predicted to interact with ligands in a similar spatial location, with their specific inserts playing a role in the process. Both clades are widely represented in bacteria suggesting that this superfamily was derived early in bacterial evolution. The animal lineage appears to have acquired the transcobalamin-like proteins from low GC Gram-positive bacteria, and this might be correlated with the emergence of the ability to utilize B12 produced by gut bacteria.ReviewersThis article was reviewed by Andrei Osterman, Igor Zhulin, and Arcady Mushegian.
Neurotrophin/Trk receptor signaling mediates C/EBPα, -β and NeuroD recruitment to immediate-early gene promoters in neuronal cells and requires C/EBPs to induce immediate-early gene transcription
Authors: Calella Anna Maria , Nerlov Claus , Lopez Rodolphe G , Sciarretta Carla , von Bohlen und Halbach Oliver , Bereshchenko Oksana , Minichiello Liliana 
Published: January 2007

Abstract
Background
Extracellular signaling through receptors for neurotrophins mediates diverse neuronal functions, including survival, migration and differentiation in the central nervous system, but the transcriptional targets and regulators that mediate these diverse neurotrophin functions are not well understood.

Results
We have identified the immediate-early (IE) genes Fos, Egr1 and Egr2 as transcriptional targets of brain derived neurotrophic factor (BDNF)/TrkB signaling in primary cortical neurons, and show that the Fos serum response element area responds to BDNF/TrkB in a manner dependent on a combined C/EBP-Ebox element. The Egr1 and Egr2 promoters contain homologous regulatory elements. We found that C/EBPα/β and NeuroD formed complexes in vitro and in vivo, and were recruited to all three homologous promoter regions. C/EBPα and NeuroD co-operatively activated the Fos promoter in transfection assays. Genetic depletion of Trk receptors led to impaired recruitment of C/EBPs and NeuroD in vivo, and elimination of Cebpa and Cebpb alleles reduced BDNF induction of Fos, Egr1 and Egr2 in primary neurons. Finally, defective differentiation of cortical dendrites, as measured by MAP2 staining, was observed in both compound Cebp and Ntrk knockout mice.

Conclusion
We here identify three IE genes as targets for BDNF/TrkB signaling, show that C/EBPα and -β are recruited along with NeuroD to target promoters, and that C/EBPs are essential mediators of Trk signaling in cortical neurons. We show also that C/EBPs and Trks are required for cortical dendrite differentiation, consistent with Trks regulating dendritic differentiation via a C/EBP-dependent mechanism. Finally, this study indicates that BDNF induction of IE genes important for neuronal function depends on transcription factors (C/EBP, NeuroD) up-regulated during neuronal development, thereby coupling the functional competence of the neuronal cells to their differentiation.
Fibroblast-like synovial cells from normal and inflamed knee joints differently affect the expression of pain-related receptors in sensory neurones: a co-culture study
Authors: von Banchet Gisela Segond , Richter Jonny , Hückel Marion , Rose Christina , Bräuer Rolf , Schaible Hans-Georg 
Published: January 2007

Abstract
Innervation of the joint with thinly myelinated and unmyelinated sensory nerve fibres is crucial for the occurrence of joint pain. During inflammation in the joint, sensory fibres show changes in the expression of receptors that are important for the activation and sensitization of the neurones and the generation of joint pain. We recently reported that both neurokinin 1 receptors and bradykinin 2 receptors are upregulated in dorsal root ganglion (DRG) neurones (the cell bodies of sensory fibres) in the course of acute and chronic antigen-induced arthritis in the rat. In this study, we begin to address mechanisms of the interaction between fibroblast-like synovial (FLS) cells and sensory neurones by establishing a co-culture system of FLS cells and DRG neurones. The proportion of DRG neurones expressing neurokinin 1 receptor-like immunoreactivity was not altered in the co-culture with FLS cells from normal joints but was significantly upregulated using FLS cells from knee joints of rats with antigen-induced arthritis. The proportion of DRG neurones expressing bradykinin 2 receptors was slightly upregulated in the presence of FLS cells from normal joints but upregulation was more pronounced in DRG neurones co-cultured with FLS cells from acutely inflamed joints. In addition, the expression of the transient receptor potential V1 (TRPV1) receptor, which is involved in inflammation-evoked thermal hyperalgesia, was mainly upregulated by co-culturing DRG neurones with FLS cells from chronically inflamed joints. Upregulation of neurokinin 1 receptors but not of bradykinin 2 and TRPV1 receptors was also observed when only the supernatant of FLS cells from acutely inflamed joint was added to DRG neurones. Addition of indomethacin to co-cultures inhibited the effect of FLS cells from acutely inflamed joints on neurokinin 1 receptor expression, suggesting an important role for prostaglandins. Collectively, these data show that FLS cells are able to induce an upregulation of pain-related receptors in sensory neurones and, thus, they could contribute to the generation of joint pain. Importantly, the influence of FLS cells on DRG neurones is dependent on their state of activity, and soluble factors as well as direct cellular contacts are crucial for their interaction with neurones.
Risk of second primary cancer in men with breast cancer
Authors: Satram-Hoang Sacha , Ziogas Argyrios , Anton-Culver Hoda 
Published: January 2007

Abstract
Introduction
A retrospective registry-based cohort study was conducted to examine the risk of second primary cancer following the occurrence of breast cancer in males.

Methods
Data obtained from the California Cancer Registry in the period 1988 to 2003 included 1,926 men aged 85 years and younger diagnosed with a first primary breast cancer. Person-year analysis was applied to determine the risk of second primary cancers after the occurrence of a first primary breast cancer. The effects of age, race, and time since the first breast cancer diagnosis were assessed.

Results
Of the 1,926 male breast cancer cases, 221 (11.5%) developed a second primary cancer. Men with first incidence of breast cancer have a significantly higher risk of second cancer (standardized incidence ratio (SIR) = 1.16, 95% confidence interval (CI) = 1.01–1.32). The risk of a second site-specific cancer is elevated for breast cancer (SIR = 52.12, 95% CI = 31.83–80.49), cutaneous melanoma (SIR = 2.98, 95% CI = 1.63–5.00) and stomach cancer (SIR = 2.11, 95% CI = 1.01–3.88). There is a general tendency towards higher risks of second malignancies among younger men compared to older men and the risk increased with the passage of time.

Conclusion
Male breast cancer patients should be monitored carefully for the occurrence of second primary cancers, especially a second primary breast cancer.
Liver dysfunction associated with artificial nutrition in critically ill patients
Authors: Grau Teodoro , Bonet Alfonso , Rubio Mercedes , Mateo Dolores , Farré Mercé , Acosta José Antonio , Blesa Antonio , Montejo Juan Carlos , de Lorenzo Abelardo García , Mesejo Alfonso ,   the Working Group on Nutrition and Metabolism of the Spanish Society of Critical Care
Published: January 2007

Abstract
Introduction
Liver dysfunction associated with artificial nutrition in critically ill patients is a complication that seems to be frequent, but it has not been assessed previously in a large cohort of critically ill patients.

Methods
We conducted a prospective cohort study of incidence in 40 intensive care units. Different liver dysfunction patterns were defined: (a) cholestasis: alkaline phosphatase of more than 280 IU/l, gamma-glutamyl-transferase of more than 50 IU/l, or bilirubin of more than 1.2 mg/dl; (b) liver necrosis: aspartate aminotransferase of more than 40 IU/l or alanine aminotransferase of more than 42 IU/l, plus bilirubin of more than 1.2 mg/dl or international normalized ratio of more than 1.4; and (c) mixed pattern: alkaline phosphatase of more than 280 IU/l or gamma-glutamyl-transferase of more than 50 IU/l, plus aspartate aminotransferase of more than 40 IU/l or alanine aminotransferase of more than 42 IU/l.

Results
Seven hundred and twenty-five of 3,409 patients received artificial nutrition: 303 received total parenteral nutrition (TPN) and 422 received enteral nutrition (EN). Twenty-three percent of patients developed liver dysfunction: 30% in the TPN group and 18% in the EN group. The univariate analysis showed an association between liver dysfunction and TPN (p < 0.001), Multiple Organ Dysfunction Score on admission (p < 0.001), sepsis (p < 0.001), early use of artificial nutrition (p < 0.03), and malnutrition (p < 0.01). In the multivariate analysis, liver dysfunction was associated with TPN (p < 0.001), sepsis (p < 0.02), early use of artificial nutrition (p < 0.03), and calculated energy requirements of more than 25 kcal/kg per day (p < 0.05).

Conclusion
TPN, sepsis, and excessive calculated energy requirements appear as risk factors for developing liver dysfunction. Septic critically ill patients should not be fed with excessive caloric amounts, particularly when TPN is employed. Administering artificial nutrition in the first 24 hours after admission seems to have a protective effect.
The struggle for iron: gastrointestinal microbes modulate the host immune response during infection
Authors: Markel Troy A , Crisostomo Paul R , Wang Meijing , Herring Christine M , Meldrum Kirstan K , Lillemoe Keith D , Meldrum Daniel R 
Published: January 2007

AbstractThe gastrointestinal track is one source of potential bacterial entry into the host, and the local immune system at the mucosal border is paramount in establishing host immune tolerance and the immune response to invading organisms. Macrophages use iron for production of hydroxy-radical and superoxide reactions, which are necessary for microbial killing. Presumably, as a survival strategy, bacteria, which also require iron for survival, have adapted the ability to sequester iron from the host, thereby limiting the availability to macrophages. As current modes of antimicrobial therapy are evolving, examination of nontraditional therapies is emerging. One such potential therapy involves altering the bacterial micronutrient iron concentration. Necrotizing enterocolitis is a clinical condition where such a strategy makes intuitive sense. This review will describe the immune response to gastrointestinal infection, the mechanisms that the gastrointestinal system uses to absorb intraluminal iron, and the critical role iron plays in the infectious process.
Effect of Atorvastatin on Cognitive Function in Patients from the Lipid Lowering and Onset of Renal Disease (LORD) Trial
Authors: Summers Mathew J. , Oliver Kate R. , Coombes Jeff S. , Fassett Robert G. 
Published: January 2007

Study Objective. To examine the effect of atorvastatin on cognitive function by testing two hypotheses: that atorvastatin 10 mg/day would impair cognitive function, and that other biochemical and demographic measures would better predict cognitive performance than atorvastatin alone.Design. Randomized, double‐blind, placebo‐controlled study.Setting. Two primary acute care settings in the north and northwest of Tasmania, Australia.Patients. Fifty‐seven patients from the Lipid Lowering and Onset of Renal Disease (LORD) trial.Intervention. Participants were randomly assigned to receive either atorvastatin 10 mg/day or matching placebo. Cognitive testing was performed in two sessions occurring 12 weeks apart and involved three repeated measures of attention and concentration.Measurements and Main Results. Performance was measured using three standard neuropsychological tests: Digit Symbol Coding subtest, Trail Making Test, and Stroop Color‐Word Reading Test. Patients received atorvastatin for a mean of 72.93 weeks and placebo for a mean of 68.85 weeks. Repeated‐measures multivariate analysis of variance failed to identify any significant differences between the two groups on any of the three cognitive measures. Multiple regression analyses identified no single factor or combination of plasma cholesterol levels, renal function, liver function, or age that predicted cognitive performance in either the atorvastatin or placebo group on the three measures at either testing session.Conclusion. Atorvastatin 10 mg/day did not produce decrements to cognitive performance. In addition, biochemical and demographic measures and the receipt of atorvastatin versus placebo did not individually or in combination predict cognitive performance on measures of attention and concentration.
Predictors of In‐Hospital Mortality for Bloodstream Infections Caused by Enterobacter Species or Citrobacter freundii
Authors: Deal Eli N. , Micek Scott T. , Ritchie David J. , Reichley Richard M. , Dunne W. Michael , Kollef Marin H. 
Published: January 2007

Study Objective. To identify predictors of in‐hospital mortality among patients with bacteremia caused by Enterobacter cloacae, Enterobacter aerogenes, or Citrobacter freundii.Design. Retrospective cohort study.Setting. 1300‐bed tertiary academic medical center.Patients. One hundred twenty‐four patients who had bloodstream infections caused by E. cloacae (3), E. aerogenes (71), or C. freundii (50) between 1998 and 2004.Measurements and Main Results. Data from patients with bloodstream infections caused by Enterobacter sp or C. freundii were retrospectively segregated according to hospital survival (98 survivors, 26 nonsurvivors). Multiple patient characteristics and processes of care were evaluated to identify factors contributing to in‐hospital mortality. Multiple logistic regression was performed based on univariate comparisons to determine independent risk factors for in‐hospital mortality. Among the 124 cases of bacteremia, the crude in‐hospital mortality rate was 21% (26 cases). Univariate analysis revealed that survivors were more likely to receive an aminoglycoside as part of their empiric antimicrobial regimen (40% [39/98]) compared with nonsurvivors (19% [5/26], p=0.05). Other factors related to antimicrobial therapy including choice and number of agents used did not differ between survivors and nonsurvivors (p>0.05). Vasopressor use (31% [30/98] vs 62% [16/26]), care in an intensive care unit (19% [19/98] vs 54% [14/26]), and acute renal failure (13% [13/98] vs 31% [8/26]) occurred more frequently in nonsurvivors (p<0.05). Multiple logistic regression identified resistance to second‐ or third‐generation cephalosporins (adjusted odds ratio [OR] 5.16, 95% confidence interval [CI] 2.66–10.0, p=0.013), trimethoprim‐sulfamethoxazole resistance (adjusted OR 5.44, 95% CI 2.53–11.7, p=0.027), and mechanical ventilation (adjusted OR 12.2, 95% CI 5.99–24.5, p<0.001) as independent determinants of mortality.Conclusion. Among patients with Enterobacter sp or C. freundii bloodstream infections, those with trimethoprim‐sulfamethoxazole‐resistant or secondor third‐generation cephalosporin‐resistant strains or those who required mechanical ventilation had an increased risk of mortality.
The Contraceptive Patch in Relation to Ischemic Stroke and Acute Myocardial Infarction
Authors: Jick Susan S. , Jick Hershel 
Published: January 2007

Study Objective. To compare rates of stroke and acute myocardial infarction in users of the Ortho EVRA contraceptive patch with these rates in users of norgestimate‐containing oral contraceptives (OCs) with 35 μg of ethinyl estradiol.Design. Retrospective, population‐based, epidemiologic study.Data Source. PharMetrics database.Subjects. Females aged 15–45 years in the PharMetrics database who had filled at least one prescription for the Ortho EVRA contraceptive patch or a norgestimate OC between April 1, 2002, and March 31, 2005.Measurements and Main Results. Incidence rates and 95% confidence intervals (CI) were estimated for the outcomes of ischemic stroke and acute myocardial infarction by exposure. Crude incidence rates of ischemic stroke among users of the patch and users of norgestimate OCs were 13.6/100,000 woman‐years (95% CI 5.9–26.8) and 11.3/100,000 woman‐years (95% CI 5.4–20.8), respectively. The crude incidence rate of acute myocardial infarction was 1.7/100,000 woman‐years (95% CI 0.04–9.5) in current patch users and 7.9/100,000 woman‐years (95% CI 3.2–16.3) in current users of norgestimate OCs. Incidence rate ratios (IRRs) were estimated for the outcomes by comparing data for users of the patch and users of a norgestimate OC. The IRR for stroke was 1.2 (95% CI 0.41–3.4) and for acute myocardial infarction was 0.2 (95% CI 0.004–1.7).Conclusion. Ischemic stroke and acute myocardial infarction are rare among young women who use hormonal contraceptives, and the current data provide no suggestion of an increased risk of either ischemic stroke or acute myocardial infarction in users of the Ortho EVRA contraceptive patch compared with users of norgestimate OCs.
Error Rates Among Clinical Pharmacists in Calculating the APACHE II Score
Authors: Greenwood Bonnie , Szumita Paul M. , Levy Howard , Lilly Craig M. 
Published: January 2007

Background. The Food and Drug Administration recently advocated the use of acuity scoring to determine those patients whose mortality benefits outweigh risks of adverse effects from drotrecogin alfa (activated). Many institutions have adopted an Acute Physiology and Chronic Health Evaluation (APACHE) II cutoff score of 25 (i.e., if > 25, administer the agent) as a component in determining eligibility for treatment with this agent. Concern is increasing that errors in the acquisition of APACHE scores can lead to prescribing errors with drotrecogin alfa (activated).Objective. To determine the ability of clinical pharmacists in ascertaining APACHE II scores.Methods. Fifteen clinical pharmacists calculated APACHE II scores for the clinical scenarios of three patients. End points were the pharmacists' APACHE II score calculation, decision to start drotrecogin alfa (activated) treatment, and evaluation of individual components of the APACHE II scores.Results. Of the 15 pharmacists, correct APACHE II scores were derived by nine (60%) pharmacists for patient no. 1 (APACHE score 44), by two (13%) pharmacists for patient no. 2 (APACHE score 22), and by two (13%) pharmacists for patient no. 3 (APACHE score 19). Scoring errors occurred in 32 of the 45 (71%) derivations. The pharmacists were significantly more likely to correctly prescribe drotrecogin alfa for the two patients with true APACHE scores of 19 and 44 than for the patient whose score was 22, which was closer to the prescribing cutoff score of 25 (both p<0.001, patient no. 1 vs no. 2, and patient no. 2 vs no. 3, Fisher exact test) All individual components of the score were correctly evaluated at least 80% of the time, except for mean arterial pressure, respiratory rate, and Glasgow Coma Scale score.Conclusion. Caution must be used in applying results of APACHE II scores estimated by only one trained individual when deciding to administer or withhold drotrecogin alfa (activated).
Access to and Satisfaction with Care Comparing Patients with and without Serious Mental Illness
Authors: Kilbourne Amy M. , McCarthy John F. , Post Edward P. , Welsh Deborah , Pincus Harold Alan , Bauer Mark S. , Blow Frederic C. 
Published: January 2007

Objectives: We compared perceived access to and satisfaction with health care between patients diagnosed with serious mental illness (SMI: schizophrenia or bipolar disorder) and among those with no SMI diagnosis. Method: We conducted a national, cross-sectional study of VA patients in Fiscal Year (FY) 1999 (N=7,187) who completed the VA's Large Health Survey of Veteran Enrollees (LHSV) section on access and satisfaction and either received a diagnosis of schizophrenia or bipolar disorder, or did not and were randomly selected from the general non-SMI VA patient population (non-SMI group). We compared the probability of perceived poor access and dissatisfaction using multivariable logistic regression adjusting for patient covariates. Results: Compared to non-SMI patients, patients diagnosed with bipolar disorder were more likely to report difficulty in receiving care they needed (adjusted OR =1.36, p < .05) or seeing a specialist (adjusted OR=1.44, p < .001). Patients diagnosed with schizophrenia were more likely to report dissatisfaction, including thoroughness by their provider (adjusted OR=1.37, p < .001) and the provider's explanation of problems (adjusted OR=1.54, p < .001) compared to non-SMI patients. Conclusions: Patients diagnosed with bipolar disorder reported greater problems with access to health care, while those diagnosed with schizophrenia were less satisfied with the process of care.
Correlates of Quality of Life in Primary Care Patients with Hypertension
Authors: Ayalon Liat , Gross Revital , Tabenkin Hava , Porath Avi , Heymann Anthony , Porter Boaz 
Published: January 2007

Background: Hypertension has been associated with lower levels of quality of life (QoL). However, the specific correlates of lower QoL in this patient population have remained largely unclear. Methods: A cross-sectional design of 1,125 primary care patients with hypertension. We evaluated demographics, health status, subjective health and mental health, health behaviors, health beliefs, knowledge of hypertension treatment, satisfaction with medical care, and quality of medical care as potential predictors of QoL and perceived QoL in the hypothetical absence of hypertension. Results: Worse financial status, poorer blood pressure control, worse subjective health, mental distress, lack of hypertension diet, and irregular hypertension care were all associated with worse QoL. Worse financial status, poorer blood pressure control, higher body mass index, mental distress, and following a hypertension diet were associated with better QoL in the hypothetical absence of hypertension. Conclusions: In addition to taking into consideration well known determinants of QoL, such as financial status, health status, and mental health, physicians need to be aware of the potential tradeoff between following medical recommendations that advocate for a strict diet and the impact these have on patients' QoL. Physicians also need to be aware of the effect of imparting information regarding imbalanced blood pressure on perceived QoL.