bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical characterization of the fidelity of poliovirus RNA-dependent RNA polymerase
Authors: Freistadt Marion S , Vaccaro Joseph A , Eberle Karen E 
Published: May 2007

Abstract

Background
Putative high mutation rates of RNA viruses are believed to mediate undesirable phenomena, such as emergence of drug resistance. However, very little is known about biochemical fidelity rates for viral RNA-dependent RNA polymerases. Using a recently developed in vitro polymerase assay for poliovirus polymerase 3Dpol [Arnold and Cameron (2000) JBC 275:5329], we measured fidelity for each possible mismatch. Polymerase fidelity, in contrast to sequence error rate, is biochemically defined as k

pol
/K

d
of {(correct plus incorrect) divided by incorrect} incorporations, such that a larger value connotes higher fidelity.

Results
To derive k

pol
/K

d
for correct base incorporation, we performed conventional pre-steady state single turnover measurements, yielding values that range from 0.62 to 9.4 μM-1 sec-1. Pre-steady state measurements for incorrect base incorporation were less straightforward: several anomalous phenomena interfered with data collection. To obtain pre-steady state kinetic data for incorrect base incorporation, three strategies were employed. (1) For some incorrect bases, a conventional approach was feasible, although care was taken to ensure that only single turnovers were being assessed. (2) Heparin or unlabeled RNA traps were used to simulate single turnover conditions. (3) Finally, for some incorrect bases, incorporation was so poor that single datapoints were used to provide kinetic estimates. Overall, we found that fidelity for poliovirus polymerase 3Dpol ranges from 1.2 × 104 to 1.0 × 106 for transition mutations and 3.2 × 105 to 4.3 × 107 for transversion mutations.

Conclusion
These values are unexpectedly high showing that high RNA virus sequence variation is not due to intrinsically low polymerase fidelity. Based on unusual enzyme behavior that we observed, we speculate that RNA mismatches either directly or indirectly cause enzyme RNA dissociation. If so, high sequence variation of RNA viruses may be due to template-switch RNA recombination and/or unknown fitness/selection phenomena. These findings may lead to a mechanistic understanding of RNA virus error catastrophe and improved anti-viral strategies.
Predicting a low cortisol response to adrenocorticotrophic hormone in the critically ill: a retrospective cohort study
Authors: de Jong Margriet FC , Beishuizen Albertus , Spijkstra Jan-Jaap , Girbes Armand RJ , Strack van Schijndel Rob JM , Twisk Jos WR , Groeneveld AB Johan 
Published: May 2007

Abstract
Introduction
Identification of risk factors for diminished cortisol response to adrenocorticotrophic hormone (ACTH) in the critically ill could facilitate recognition of relative adrenal insufficiency in these patients. Therefore, we studied predictors of a low cortisol response to ACTH.

Methods
A retrospective cohort study was conducted in a general intensive care unit of a university hospital over a three year period. The study included 405 critically ill patients, who underwent a 250 μg ACTH stimulation test because of prolonged hypotension or need for vasopressor/inotropic therapy. Plasma cortisol was measured before and 30 and 60 min after ACTH injection. A low adrenal response was defined as an increase in cortisol of less than 250 nmol/l or a peak cortisol level below 500 nmol/l. Various clinical variables were collected at admission and on the test day.

Results
A low ACTH response occurred in 63% of patients. Predictors, in multivariate analysis, included sepsis at admission, low platelets, low pH and bicarbonate, low albumin levels, high Sequential Organ Failure Assessment score and absence of prior cardiac surgery, and these predictors were independent of baseline cortisol and intubation with etomidate. Baseline cortisol/albumin ratios, as an index of free cortisol, were directly related and increases in cortisol/albumin were inversely related to disease severity indicators such as the Simplified Acute Physiology Score II and Sequential Organ Failure Assessment score (Spearman r = -0.21; P < 0.0001).

Conclusion
In critically ill patients, low pH/bicarbonate and platelet count, greater severity of disease and organ failure are predictors of a low adrenocortical response to ACTH, independent of baseline cortisol values and cortisol binding capacity in blood. These findings may help to delineate relative adrenal insufficiency and suggest that adrenocortical suppression occurs as a result of metabolic acidosis and coagulation disturbances.
Musculoskeletal Tuberculosis in Bradford – A 6-Year Review
Authors: Talbot JC , Bismil Q , Saralaya D , Newton DAG , Frizzel RM , Shaw DL 
Published: May 2007

INTRODUCTION Tuberculosis (TB) remains the most common cause of death from infectious disease world-wide. In the UK, the incidence of TB has risen by 25% over the last 10 years; extrapulmonary diagnosis remains challenging and can be delayed. This study evaluates the epidemiology of musculoskeletal tuberculosis in a large multi-ethnic UK city. PATIENTS AND METHODS A review of prospectively recorded data of incidence, anatomical site, ethnic distribution, treatment and drug resistance of musculoskeletal tuberculosis over a 6-year period was performed. RESULTS From January 1999 to December 2004, there were 729 TB notifications; 61 cases (8.4%) had musculoskeletal involvement. Of the patients, 74% were immigrants from the Indian subcontinent; nearly 50% had spinal involvement; 24 patients underwent surgical intervention; 29 were subjected to either diagnostic or therapeutic radiological intervention; and resolution of symptoms was achieved in 59 out of 61 cases. CONCLUSIONS This study highlights the high proportion of musculoskeletal TB in immigrant patients in an area with a relatively large at-risk population, but will also serve to alert physicians, in areas with smaller at-risk populations, of the possibility of musculoskeletal TB.
A Study of the Routine Use of Venous Photoplethysmography in a One-Stop Vascular Surgery Clinic
Authors: Beraldo S , Satpathy A , Dodds SR 
Published: May 2007

INTRODUCTION The decision to offer surgical treatment for varicose veins should be based on objective evidence of venous dysfunction and not only the subjective appearance or the reported symptoms. Special tests are required to identify the sub-group of patients with functional superficial venous reflux accurately. The initial test should be simple, cheap, objective, sensitive and easy to perform by a wide range of staff in order to screen out patients without reflux. The final test should be anatomically specific to identify the appropriate surgical procedure. The aim of this study was to test the feasibility of using photoplethysmography (PPG) as the initial test as part of a one-stop vascular clinic assessment protocol. PATIENTS AND METHODS All patients referred to one consultant over a 68-week period were assessed using standard practice for the first 22 weeks and with an objective assessment protocol based on PPG for the subsequent 46 weeks. RESULTS A total of 347 out-patient appointments for patients with venous disease were booked: 239 (69%) were new referrals. Of the new patients, 59% were CEAP C2/3 and 23% were CEAP C4-6. The introduction of the objective assessment protocol was associated with a reduction in patients offered surgery from 39% to 24% overall and 51% to 28% in new patients with CEAP C2. There was a corresponding increase in the number of patients discharged back to the GP from 19% to 29% overall and 17% to 32%, respectively. The number of patients referred for duplex ultrasound fell slightly from 26% to 22%. Overall, there was a significant change in practice between the two periods (χ2 = 13.3; df = 3; P = 0.004). CONCLUSIONS The introduction of an objective assessment protocol based on PPG as the initial objective test reduces the number of patients offered surgery based on objective evidence of venous dysfunction.
Pre-Operative Oral Iron Supplementation Reduces Blood Transfusion in Colorectal Surgery – A Prospective, Randomised, Controlled Trial
Authors: Lidder PG , Sanders G , Whitehead E , Douie WJ , Mellor N , Lewis SJ , Hosie KB 
Published: May 2007

INTRODUCTION Allogeneic blood transfusion confers a risk to the recipient. Recent trials in colorectal surgery have shown that the most significant factors predicting blood transfusion are pre-operative haemoglobin, operative blood loss and presence of a transfusion protocol. We report a randomised, controlled trial of oral ferrous sulphate 200 mg TDS for 2 weeks' pre-operatively versus no iron therapy. PATIENTS AND METHODS Patients diagnosed with colorectal cancer were recruited from out-patient clinic and haematological parameters assessed. Randomisation was co-ordinated via a telephone randomisation centre. RESULTS Of the 49 patients recruited, 45 underwent colorectal resection. There were no differences between those patients not receiving iron (n = 23) and the iron-supplemented group (n = 22) for haemoglobin at recruitment, operative blood loss, operation duration or length of hospital stay. At admission to hospital, the iron-supplemented group had a higher haemoglobin than the non-iron treated group (mean haemoglobin concentration 13.1 g/dl [range, 9.6–17 g/dl] versus 11.8 g/dl [range, 7.8–14.7 g/dl]; P = 0.040; 95% CI 0.26–0.97) and were less likely to require operative blood transfusion (mean 0 U [range, 0–4 U] versus 2 U [range, 0–11 U] transfused; P = 0.031; 95% CI 0.13–2.59). This represented a cost reduction of 66% (47 U of blood = £4700 versus oral FeSO4 at £30 + 15 U blood at £1500). At admission, ferritin in the iron-treated group had risen significantly from 40 μg/l (range, 15–222 μg/l) to 73 μg/l (range, 27–386 μg/l; P = 0.0036; 95% CI 46.53–10.57). CONCLUSIONS Oral ferrous sulphate given pre-operatively in patients undergoing colorectal surgery offers a simple, inexpensive method of reducing blood transfusions.
Unplanned General Surgical Re-Admissions – How Many, Which Patients and Why?
Authors: Adeyemo Dayo , Radley Simon 
Published: May 2007

INTRODUCTION The unplanned re-admission rate is a national key performance indicator employed by the UK Department of Health. An adjusted figure, based on admission information data on the hospital electronic Patient Administration System (PAS), but adjusted to take account of case mix is compared with a calculated ‘expected’. While previous studies have investigated unplanned re-admission rates in age-, procedure- or process-specific conditions, ‘all-cause’ general surgical re-admission rate is yet to be studied. The aim of this study was to assess the accuracy of hospital unplanned re-admission data, and identify patterns or possible causes of unplanned general surgical re-admissions. PATIENTS AND METHODS Retrospective audit of case note records of all patients identified from the hospital electronic PAS as unplanned, general surgical re-admissions over a period of 4 consecutive months. RESULTS Of all 161 re-admissions in this study, 46 (29%) were unrelated to the index admission, planned or involved patient self-discharge during the index admission. Of the ‘genuine’, unplanned re-admissions, 80 (78%) followed an emergency index admission, 58 (56%) had chronic or recurrent symptoms, for which 26 (25%) were on waiting lists. Fourteen (14%) were multiple admissions of 4 patients, while 8 (8%) re-admissions required further surgery for significant postoperative complications. CONCLUSIONS Unplanned. general surgical re-admission rates collated from hospital PAS systems may be inaccurate. Nearly half of ‘genuine’, unplanned re-admissions involved patients with chronic and/or recurrent symptoms, which are predictable and may be preventable. Significant postoperative complications accounted for few re-admissions in this study.
AAA Benchmarking by Dr Foster: A Cause for Concern?
Authors: Pandey VA , Kerle MI , Jenkins MP , Wolfe JHN 
Published: May 2007

INTRODUCTION The publication of interpretable performance data for hospitals is an important service. In November 2002, the medical benchmarking company Dr Foster published a league table based on the results of abdominal aortic aneurysm (AAA) repair. The purpose of our study was to establish the validity of the data used in benchmarking. PATIENTS AND METHODS Data on elective infra-renal AAA (IRAAA) repair was obtained from three sources. Data used by Dr Foster was based on the hospital PAS system. The databases for both Dr Foster and PAS were analysed and cross-referenced to the vascular unit database maintained by a separately employed audit co-ordinator. RESULTS Of 395 total aortic aneurysm repairs, 223 (56%) were identified as elective IRAAA repairs on the unit database. Of these, 125 were identified on the PAS database and 115 on the Dr Foster database. The number of deaths was the same in both the unit and Dr Foster databases (n = 11) but the Dr Foster database included deaths in patients who had undergone juxtarenal (n = 1), Type III TAAA (n = 2) and Type IV TAAA (n = 4) repairs and omitted 7 deaths following IRAAA. The sensitivity and specificity for the PAS dataset was 0.51 and 0.93, respectively. For Dr Foster, the results were worse with a sensitivity and specificity of 0.41 and 0.86, respectively. The accuracy of the data was 0.6 and 0.69 for Dr Foster and PAS, respectively. Standardised mortality ratios (SMRs) were used to rank hospitals. Dr Foster's published SMR for elective AAA repair for our unit was 160. The actual SMR was 67. CONCLUSIONS Robust and accurate published league tables should be supported and commended but currently available data appear to be misleading and may cause unnecessary concern to patients.
Testicular Prostheses: Development and Modern Usage
Authors: Bodiwala D , Summerton DJ , Terry TR 
Published: May 2007

INTRODUCTION Testicular prostheses produced from various materials have been in use since 1941. The absence of a testicle has been shown to be a psychologically traumatic experience for males of all ages. The indications for insertion of a prosthesis include absence or following orchidectomy from a number of causes such as malignancy, torsion and orchitis. The most common substance used around the world in the manufacture of these implants is silicone; however, in the US, this material is currently banned because of theoretical health risks. This has led to the development of saline-filled prostheses as an alternative. PATIENTS AND METHODS A Medline search was carried out on all articles on testicular prosthesis between 1966 and 2006. CONCLUSIONS This review highlights the controversies regarding prosthetic materials, the complications of insertion and the potential benefits of this commonly performed procedure.
Enhanced Unique Pattern of Hematopoietic Cell Mobilization Induced by the CXCR4 Antagonist 4F-Benzoyl-TN14003
Authors: Abraham Michal , Biyder Katia , Begin Michal , Wald Hanna , Weiss Ido D. , Galun Eithan , Nagler Arnon , Peled Amnon 
Published: May 2007

Abstract
An increase in the number of stem cells in blood following mobilization is required to enhance engraftment after high-dose chemotherapy and improve transplantation outcome. Therefore, an approach that improves stem cell mobilization is essential. The interaction between CXCL12 and its receptor, CXCR4, is involved in the retention of stem cells in the bone marrow. Therefore, blocking CXCR4 may result in mobilization of hematopoietic progenitor and stem cells. We have found that the CXCR4 antagonist known as 4F-benzoyl-TN14003 (T-140) can induce mobilization of hematopoietic stem cells and progenitors within a few hours post-treatment in a dose-dependent manner. Furthermore, although T-140 can also increase the number of white blood cells (WBC) in blood, including monocytes, B cells, and T cells, it had no effect on mobilizing natural killer cells. T-140 was found to efficiently synergize with granulocyte colony-stimulating factor (G-CSF) in its ability to mobilize WBC and progenitors, as well as to induce a 660-fold increase in the number of erythroblasts in peripheral blood. Comparison between the CXCR4 antagonists T-140 and AMD3100 showed that T-140 with or without G-CSF was significantly more potent in its ability to mobilize hematopoietic stem cells and progenitors into blood. These results demonstrate that different CXCR4 antagonists may have different therapeutic potentials.
Disclosure of potential conflicts of interest is found at the end of this article.
Chemotaxis and Differentiation of Human Adipose Tissue CD34+/CD31− Progenitor Cells: Role of Stromal Derived Factor-1 Released by Adipose Tissue Capillary Endothelial Cells
Authors: Sengenès Coralie , Miranville Alexandra , Maumus Marie , de Barros Sandra , Busse Rudi , Bouloumié Anne 
Published: May 2007

AbstractThe native CD34+/CD31− cell population present in the stroma-vascular fraction of human adipose tissue (hAT) displays progenitor cell properties since they exhibit adipocyte- and endothelial cell-like phenotypes under appropriate stimuli. To analyze the signals within hAT regulating their phenotypes, the influence of hAT-derived capillary endothelial cells (CECs) was studied on the chemotaxis and differentiation of the hAT-CD34+/CD31− cells. Conditioned medium from hAT-CECs led to a strong chemotaxis of the hAT-CD34+/CD31− cells that was inhibited with pretreatments with pertussis toxin, CXCR-4 antagonist, or neutralizing antibodies. Furthermore, hAT-CECs produced and secreted the CXCR-4 ligand, that is, the stromal derived factor-1 (SDF-1). Finally, hAT-CECs induced the differentiation of hAT-CD34+/CD31− cells toward an endothelial cell (EC) phenotype. Indeed, hAT-CECs and -CD34+/CD31− cell coculture stimulated in a two-dimensional system the expression of the EC CD31 marker by the hAT-progenitor cells and, in a three-dimensional approach, the formation of capillary-like structures via a SDF-1/CXCR-4 dependent pathway. Thus, the migration and differentiation of hAT progenitor cells are modulated by hAT-CEC-derived factors. SDF-1, which is secreted by hAT-derived CECs, and its receptor CXCR-4, expressed by hAT-derived progenitor cells, may promote chemotaxis and differentiation of hAT-derived progenitor cells and thus contribute to the formation of the vascular network during the development of hAT.Disclosure of potential conflicts of interest is found at the end of this article.
High Histone Acetylation and Decreased Polycomb Repressive Complex 2 Member Levels Regulate Gene Specific Transcriptional Changes During Early Embryonic Stem Cell Differentiation Induced by Retinoic Acid
Authors: Lee Elliot R. , Murdoch Fern E. , Fritsch Michael K. 
Published: May 2007

Abstract
Histone modifications play a crucial role during embryonic stem (ES) cell differentiation. During differentiation, binding of polycomb repressive complex 2 (PRC2), which mediates trimethylation of lysine 27 on histone H3 (K27me3), is lost on developmental genes that are transcriptionally induced. We observed a global decrease in K27me3 in as little as 3 days after differentiation of mouse ES cells induced by retinoic acid (RA) treatment. The global levels of the histone K27 methyltransferase EZH2 also decreased with RA treatment. A loss of EZH2 binding and K27me3 was observed locally on PRC2 target genes induced after 3 days of RA, including Nestin. In contrast, direct RA-responsive genes that are rapidly induced, such as Hoxa1, showed a loss of EZH2 binding and K27me3 after only a few hours of RA treatment. Following differentiation induced by leukemia inhibitor factor (LIF) withdrawal without RA, Hoxa1 was not transcriptionally activated. Small interfering RNA-mediated knockdown of EZH2 resulted in loss of K27me3 during LIF withdrawal, but the Hoxa1 gene remained transcriptionally silent after loss of this repressive mark. Induction of histone hyperacetylation overrode the repressive K27me3 modification and resulted in Hoxa1 gene expression. Together, these data show that there are multiple temporal phases of derepression of PRC2 target genes during ES cell differentiation and that other epigenetic marks (specifically, increased acetylation of histones H3 and H4), in addition to derepression, are important for gene-specific transcriptional activation. This report demonstrates the temporal interplay of various epigenetic changes in regulating gene expression during early ES cell differentiation.
Disclosure of potential conflicts of interest is found at the end of this article.
Prediction of Severe Hypoglycemia
Authors: Cox Daniel J. , Gonder-Frederick Linda , Ritterband Lee , Clarke William , Kovatchev Boris P. 
Published: May 2007

OBJECTIVE—Prevention of severe hypoglycemia (SH) is premised partially on the ability to accurately anticipate its occurrence. This study prospectively tests methods for predicting SH using blood glucose meter readings.
RESEARCH DESIGN AND METHODS—One hundred adults with type 1 diabetes were followed for 6 months, and 79 insulin-using adults with type 2 diabetes were followed for 4 months. During this time, subjects’ routine self-monitored blood glucose (SMBG) readings were stored on and retrieved from memory meters, and participants were queried biweekly about occurrence of SH. Respective demographics for the two groups were age 40.7 and 50.2 years, duration of diabetes 20.0 and 12.2 years, A1C 7.6 and 8.8%, and male sex 43 and 39%, respectively.
RESULTS—Relative risk for SH, quantified by the ratio of an individual's low blood glucose index (LBGI) based on the previous 150 SMBG readings to the LBGI based on recent SMBG readings, increased significantly in the 24 h before SH episodes in individuals with type 1 and type 2 diabetes (t = 10.3, P &lt; 0.0001, and t = 4.2, P &lt; 0.001, respectively). A sliding algorithm detected 58% of imminent (within 24 h) SH episodes in the type 1 diabetic group and 60% of those in the type 2 diabetic group when three SMBG readings were available in the 24 h before an episode. Detection increased to 63 and 75%, respectively, if five SMBG readings were available in the 24 h before an episode.
CONCLUSIONS—SH often follows a specific blood glucose fluctuation pattern that is identifiable from SMBG. Thus, partial prediction of imminent SH is possible, providing a potential tool to trigger self-regulatory prevention of significant hypoglycemia.