bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells
Authors: Borland M Kathleen , Trimmer Patricia A , Rubinstein Jeremy D , Keeney Paula M , Mohanakumar KP , Liu Lei , Bennett James P
Published: December 2008

Background

Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites") in processes of gut enteric and vagal motor neurons. Rostral progression into substantia nigra with death of dopamine neurons produces the motor impairment phenotype that yields a clinical diagnosis. The vast majority of Parkinson's disease occurs sporadically, and current models of sporadic Parkinson's disease (sPD) can utilize directly infused or systemic neurotoxins.

Results

We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells died. Their processes retracted and accumulated ASYN-(+) and UB-(+) aggregates that blocked organelle transport. Mitochondrial movement velocities were reduced by 8 days of rotenone and continued to decline over time. No cytoplasmic inclusions resembling Lewy bodies were observed. Gene microarray analyses showed that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA-encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative expressions revealed small increases in mtDNA-encoded genes and lesser regulation of nDNA-encoded ETC genes.

Conclusion

Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a differentiated human neural cell mimics changes of early Parkinson's disease and may be useful for screening therapeutics for neuroprotection in that disease stage.
Genomic selection of reference genes for real-time PCR in human myocardium
Authors: Pilbrow Anna P , Ellmers Leigh J , Black Michael A , Moravec Christine S , Sweet Wendy E , Troughton Richard W , Richards A Mark , Frampton Chris M , Cameron Vicky A
Published: December 2008

Background

Reliability of real-time PCR (RT-qPCR) data is dependent on the use of appropriate reference gene(s) for normalization. To date, no validated reference genes have been reported for normalizing gene expression in human myocardium. This study aimed to identify validated reference genes for use in gene expression studies of failed and non-failed human myocardium.

Methods

Bioinformatic analysis of published human heart gene expression arrays (195 failed hearts, 16 donor hearts) was used to identify 10 stable and abundant genes for further testing. The expression stability of these genes was investigated in 28 failed and 28 non-failed human myocardium samples by RT-qPCR using geNorm software.

Results

Signal recognition particle 14 kDa (SRP14), tumor protein, translationally-controlled 1 (TPT1) and eukaryotic elongation factor 1A1 (EEF1A1) were ranked the most stable genes. The commonly used reference gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was ranked the least stable of the genes tested. The normalization strategy was tested by comparing RT-qPCR data of both normalized and raw expression levels of brain natriuretic peptide precursor (NPPB), a gene known to be up-regulated in heart failure. Non-normalized levels of NPPB exhibited a marginally significant difference between failed and non-failed samples (p = 0.058). In contrast, normalized NPPB expression levels were significantly higher in heart-failed patients compared with controls (p = 0.023).

Conclusion

This study used publicly available gene array data to identify a strategy for normalization involving two reference genes in combination that may have broad application for accurate and reliable normalization of RT-qPCR data in failed and non-failed human myocardium.
PTEN and rapamycin inhibiting the growth of K562 cells through regulating mTOR signaling pathway
Authors: Cheng Zhi Y , Guo Xiao L , Yang Xiao Y , Niu Zhi Y , Li Shi H , Wang Su Y , Chen Hao , Pan Ling
Published: December 2008

Objective

To investigate, in vitro, the regulatory effects of tumor-suppressing gene PTEN on mTOR (mammalian target of rapamycin) signaling pathway, the effects of transfected PTEN and rapamycin on the growth inhibition, and apoptosis induction for human leukemia cell line K562 cells.

Methods

K562 cells were transfected with recombined adenovirus-PTEN vector containing green fluorescent protein (Ad-PTEN-GFP), followed by the treatment of the cells with or without rapamycin. The proliferation inhibition rate and apoptotic rate of these transfected and/or rapamycin treated K562 cells were measured by MTT assay and flow cytometry (FCM), the expression levels of PTEN-, mTOR-, cyclinD1- and P27kip1- mRNA were measured by real-time fluorescent relative-quantification reverse transcriptional PCR (FQ-PCR), the protein expression levels of PTEN, Akt, p-Akt were detected by western blotting.

Results

The proliferation of K562 cells was inhibited by PTEN gene transfection with/without the treatment of rapamycin. The expression levels of PTEN- and P27kip1- mRNA were up-regulated, and the mTOR- and cyclinD1- mRNA were down-regulated in K562 cells after the cells transfected with wild type PTEN gene and treated with rapamycin.

Conclusion

PTEN and rapamycin inhibited mTOR expression by acting as an upstream regulator of mTOR. Low dose rapamycin in combination with over-expressed PTEN might have synergistic effects on inhibiting the proliferation and promoting apoptosis of K562 cells.
Primary lymphoma of the head and neck: two case reports and review of the literature
Authors: Essadi Ismail , Ismaili Nabil , Tazi Elmehdi , Elmajjaoui Sanaa , Saidi Ammar , Ichou Mohammed , Errihani Hassan
Published: December 2008

Background

The head and neck is the second most common region for the extra-nodal lymphomas after that of gastrointestinal tract. Approximately 2.5% of malignant lymphoma arises in the oral and para-oral region. In this paper we report two cases of early stage head and neck lymphoma which were managed successfully with chemotherapy and a review of the related literature.

Cases presentation

The first case concerns a 48 years male patient having a diffuse large B-Cell lymphoma of the oropharynx at early bulky stage. This patient was managed successfully with 7 of Rituximab 375 mg/m2, Cyclophosphamide 750 mg/m2 d1, Doxorubicine 50 mg/m2 d1, Vincristine 1.4 mg/m2 d1, and prednisone 50 mg/m2 d1-5 (RCHOP) regimen. The second case concerns a 50 years female patient having the nasal natural killer (NK)/T-cell lymphoma of the left nasal pit at early stage. This case was managed successfully with 6 of Cyclophosphamide 750 mg/m2 d1, Doxorubicine 50 mg/m2 d1, Vincristine 1.4 mg/m2 d1, and prednisone 50 mg/m2 d1-5 (CHOP) regimen.

Conclusion

These two cases highlight the important role of CHOP based chemotherapy for achieving successful treatment cure for patients having an early stage head and neck lymphoma.
Baseline left bundle branch block with right bundle branch escape complexes in a patient with coronary artery disease, presents like an alternating bundle branch block: a case report
Authors: Bhimaraj Arvind , Abusin Salaheldin , Margeta Bosko
Published: December 2008

Alternating bundle branch block (ABBB) is a less commonly encountered phenomenon with the advent of re-perfusion therapy for acute myocardial infarction. ECGs simulating the appearance of an ABBB need to be carefully analysed. We present an ECG showing a baseline Left Bundle Branch Block(LBBB) progressing to a high grade AV block with escape complexes having a Right Bundle Branch Block (RBBB) morphology. Such an ECG can be mistaken for an ABBB if not analysed carefully.
Comparative genomics of mutualistic viruses of Glyptapantelesparasitic wasps
Authors: Desjardins Christopher A , Gundersen-Rindal Dawn E , Hostetler Jessica B , Tallon Luke J , Fadrosh Douglas W , Fuester Roger W , Pedroni Monica J , Haas Brian J , Schatz Michael C , Jones Kristine M , Crabtree Jonathan , Forberger Heather , Nene Vishvanath
Published: December 2008

Background

Polydnaviruses, double-stranded DNA viruses with segmented genomes, have evolved as obligate endosymbionts of parasitoid wasps. Virus particles are replication deficient and produced by female wasps from proviral sequences integrated into the wasp genome. These particles are co-injected with eggs into caterpillar hosts, where viral gene expression facilitates parasitoid survival and, thereby, survival of proviral DNA. Here we characterize and compare the encapsidated viral genome sequences of bracoviruses in the family Polydnaviridae associated with Glyptapanteles gypsy moth parasitoids, along with near complete proviral sequences from which both viral genomes are derived.

Results

The encapsidated Glyptapanteles indiensis and Glyptapanteles flavicoxis bracoviral genomes, each composed of 29 different size segments, total approximately 517 and 594 kbp, respectively. They are generated from a minimum of seven distinct loci in the wasp genome. Annotation of these sequences revealed numerous novel features for polydnaviruses, including insect-like sugar transporter genes and transposable elements. Evolutionary analyses suggest that positive selection is widespread among bracoviral genes.

Conclusions

The structure and organization of G. indiensis and G. flavicoxis bracovirus proviral segments as multiple loci containing one to many viral segments, flanked and separated by wasp gene-encoding DNA, is confirmed. Rapid evolution of bracovirus genes supports the hypothesis of bracovirus genes in an 'arms race' between bracovirus and caterpillar. Phylogenetic analyses of the bracoviral genes encoding sugar transporters provides the first robust evidence of a wasp origin for some polydnavirus genes. We hypothesize transposable elements, such as those described here, could facilitate transfer of genes between proviral segments and host DNA.
Evaluation of the MPA Procedure for Estimating Seismic Demands: RC-SMRF Buildings
Authors: Bobadilla Hugo , Chopra Anil K.
Published: December 2008

The modal pushover analysis (MPA) procedure is extended for analysis of reinforced concrete special moment resisting frame (RC-SMRF) buildings, after demonstrating that the theory, assumptions, and approximations underlying this procedure are valid for such systems. The principal extension of the procedure is in the hysteretic model for modal SDF systems, chosen as the peak-oriented model to represent the global monotonic and cyclic behavior of such buildings, characterized by deterioration of stiffness and strength under cyclic deformation. The median seismic demands for 4-, 8-, 12-, and 20-story RC-SMRF buildings—designed to comply with current codes—due to an ensemble of 78 ground motions scaled to four intensity levels were computed by MPA and nonlinear RHA, and compared. It is demonstrated that, even for the most intense ground motions that deform the buildings far into the inelastic range, the MPA procedure demonstrates an adequate degree of accuracy that should make it useful for practical application in estimating seismic demands for RC-SMRF buildings. In contrast the FEMA-356 force distributions are inadequate in estimating seismic demands for the 8-, 12-, and 20-story buildings at all excitation intensities, from the weakest that causes response essentially within the linearly elastic range, to the strongest that drives the buildings far into the inelastic range.
Estimation of Seismic Loss for Spatially Distributed Buildings
Authors: Goda Katsuichiro , Hong H. P.
Published: December 2008

A simulation-based framework for assessing seismic risk of spatially distributed buildings is developed by taking the spatial correlation of seismic excitations into account. For each of seismic events compiled in a synthetic earthquake catalog, inelastic seismic demand on buildings that are approximated by bilinear single-degree-of-freedom systems is compared with uncertain structural capacity to evaluate seismic damage severity. The proposed framework is employed to investigate the sensitivity of the estimated seismic risk of sets of buildings to the degree of spatially correlated and simultaneously occurring seismic excitations. In particular, four correlation levels—no correlation, full correlation, and partial correlation with/without intra-event components—are considered. The assignment of the partial correlation is based on a recently developed spatial correlation model, and the sets of hypothetical buildings mimic existing building stocks in downtown Vancouver. The analysis results highlight that underestimation or overestimation of correlation of seismic demand could lead to very different probabilistic characteristics of aggregate seismic loss although its mean is unaltered. The sensitivity analysis results suggest that uncertainty in structural capacities as well as average local soil conditions is of relative importance.
Dietary Patterns and Breast Cancer Recurrence and Survival Among Women With Early-Stage Breast Cancer
Authors: Kwan Marilyn L. , Weltzien Erin , Kushi Lawrence H. , Castillo Adrienne , Slattery Martha L. , Caan Bette J.
Published: December 2008

Purpose

To determine the association of dietary patterns with cancer recurrence and mortality of early-stage breast cancer survivors.

Patients and Methods

Patients included 1,901 Life After Cancer Epidemiology Study participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited primarily from the Kaiser Permanente Northern California Cancer Registry. Diet was assessed at cohort entry using a food frequency questionnaire. Two dietary patterns were identified: prudent (high intakes of fruits, vegetables, whole grains, and poultry) and Western (high intakes of red and processed meats and refined grains). Two hundred sixty-eight breast cancer recurrences and 226 all-cause deaths (128 attributable to breast cancer) were ascertained. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs.

Results

Increasing adherence to a prudent dietary pattern was associated with a statistically significant decreasing risk of overall death (P trend = .02; HR for highest quartile = 0.57; 95% CI, 0.36 to 0.90) and death from non–breast cancer causes (P trend = .003; HR for highest quartile = 0.35; 95% CI, 0.17 to 0.73). In contrast, increasing consumption of a Western dietary pattern was related to an increasing risk of overall death (P trend = .05) and death from non–breast cancer causes (P = .02). Neither dietary pattern was associated with risk of breast cancer recurrence or death from breast cancer. These observations were generally not modified by physical activity, being overweight, or smoking.

Conclusion

Women diagnosed with early-stage breast cancer might improve overall prognosis and survival by adopting more healthful dietary patterns.
Highly Active Antiretroviral Therapy and the Incidence of Non–AIDS-Defining Cancers in People With HIV Infection
Authors: Powles Thomas , Robinson David , Stebbing Justin , Shamash Jonathan , Nelson Mark , Gazzard Brian , Mandelia Sundhiya , Møller Henrik , Bower Mark
Published: December 2008

Purpose

The effect of highly active antiretroviral therapy (HAART) on the incidence of non–AIDS-defining cancers (NADCs) is unclear.

Methods

We have investigated the occurrence of NADCs in a prospective cohort of 11,112 HIV-positive individuals, with 71,687 patient-years of follow-up. Standardized incidence ratios (SIRs) were calculated using general population incidence data. We investigated the effect of calendar period, HIV parameters, and immunologic and treatment-related factors on the incidence of these cancers using univariate and multivariate analyses.

Results

The SIR for all NADCs was 1.96 (95% CI, 1.66 to 2.29). There was no significant excess in incidence in the pre-HAART era (1983 to 1995; SIR, 0.95; 95% CI, 0.58 to 1.47). However, the incidence increased in the early HAART period (1996 to 2001) and remains elevated in the most recent established HAART period (2002 to 2007; SIR, 2.05; 95% CI, 1.51 to 2.72, and SIR 2.49; 95% CI, 2.00 to 3.07, respectively). Multivariate analysis showed that use of HAART (hazard ratio [HR] = 1.64; 95% CI, 1.13 to 2.39) and a nadir CD4 count less than 200/μL (HR = 1.67; 95% CI, 1.10 to 2.54) were associated with an increased risk. Only the non-nucleoside reverse transcriptase inhibitors (NNRTIs) were associated with a significantly increased risk of NADCs (HR = 1.45; 95% CI, 1.01 to 2.08). Much of this association was attributable to an increased risk of Hodgkin's lymphoma with NNRTIs (HR = 2.20; 95% CI, 1.03 to 4.69).

Conclusion

Since the introduction of HAART, there has been a significantly increased risk of NADCs, which has now stabilized. A number of factors are associated with this increased risk, including HAART use. There may be an association between the use of NNRTIs and the development of Hodgkin's lymphoma.
A Randomized Phase IIIB Trial of Chemotherapy, Bevacizumab, and Panitumumab Compared With Chemotherapy and Bevacizumab Alone for Metastatic Colorectal Cancer
Authors: Hecht J. Randolph , Mitchell Edith , Chidiac Tarek , Scroggin Carroll , Hagenstad Christopher , Spigel David , Marshall John , Cohn Allen , McCollum David , Stella Philip , Deeter Robert , Shahin Seta , Amado Rafael G.
Published: December 2008

Purpose

Panitumumab, a fully human antibody targeting the epidermal growth factor receptor, is active in patients with metastatic colorectal cancer (mCRC). This trial evaluated panitumumab added to bevacizumab and chemotherapy (oxaliplatin- and irinotecan-based) as first-line treatment for mCRC.

Patients and Methods

Patients were randomly assigned within each chemotherapy cohort to bevacizumab and chemotherapy with or without panitumumab 6 mg/kg every 2 weeks. The primary end point was progression-free survival (PFS) within the oxaliplatin cohort. Tumor assessments were performed every 12 weeks and reviewed centrally.

Results

A total of 823 and 230 patients were randomly assigned to the oxaliplatin and irinotecan cohorts, respectively. Panitumumab was discontinued after a planned interim analysis of 812 oxaliplatin patients showed worse efficacy in the panitumumab arm. In the final analysis, median PFS was 10.0 and 11.4 months for the panitumumab and control arms, respectively (HR, 1.27; 95% CI, 1.06 to 1.52); median survival was 19.4 months and 24.5 months for the panitumumab and control arms, respectively. Grade 3/4 adverse events in the oxaliplatin cohort (panitumumab v control) included skin toxicity (36% v 1%), diarrhea (24% v 13%), infections (19% v 10%), and pulmonary embolism (6% v 4%). Increased toxicity without evidence of improved efficacy was observed in the panitumumab arm of the irinotecan cohort. KRAS analyses showed adverse outcomes for the panitumumab arm in both wild-type and mutant groups.

Conclusion

The addition of panitumumab to bevacizumab and oxaliplatin- or irinotecan-based chemotherapy results in increased toxicity and decreased PFS. These combinations are not recommended for the treatment of mCRC in clinical practice.
Comparison of empirical and neural network hot-rolling process models
Authors: Öznergiz E , Özsoy C , Delice I I , Kural A
Published: December 2008

Steel manufacturers are under pressure to improve their productivity levels by optimizing their process parameters to create maximum efficiency and quality levels. One of the keys to achieve this goal is the automation of the steel making process. Automation using artificial intelligence techniques applied to the hot rolling process is a potentially important steel manufacturing technique. The mathematical modelling of the process has been recognized as a desirable approach for designing mill equipment and ensuring productivity and service quality. However, such an analysis is generally very complex and time-consuming. Thus, there is considerable interest in developing simple and effective techniques to obtain accurate rolling force, torque, and slab temperatures. In this paper, a neural network (NN) is used to model the roughing stage of a plate hot rolling process. The NN approach can predict steady-state values of the force, torque, and slab temperature. The proposed NN model is compared with the classical empirical models commonly used in industrial practice. Experimental data obtained from the Ereğli Iron and Steel Factory in Turkey was used in developing the models.
Faculty Development in Small-Group Teaching Skills Associated with a Training Course on Office-Based Treatment of Opioid Dependence
Authors: Wong Jeffrey G. , Holmboe Eric S. , Becker William C. , Fiellin David A. , Jara Gail B. , Martin Judith
Published: December 2008

The Drug Addiction Treatment Act of 2000 (DATA-2000) allows qualified physicians to treat opioid-dependent patients with schedule III-V medications, such as buprenorphine, in practices separate from licensed, accredited opioid treatment programs. Physicians may attain this qualification by completing 8-hours of training in treating opioid dependence. This paper describes the evaluation of a faculty development workshop designed to enhance teaching skills of small-group facilitators involved with DATA-2000 training sessions. This workshop coached the facilitators on their teaching roles in the DATA-2000 session through experiential practice of patient-case discussions related to treatment of opioid-dependence. Descriptive questionnaires evaluated the value of the workshop. Twenty-six facilitators participated in the workshops. Paired mean score responses for specific teaching skill abilities demonstrated statistically significant improvement in all categories. Evaluation of the DATA-2000 training session small-group facilitators was uniformly positive. This faculty development workshop was successful in improving teaching skills for our small-group faculty facilitators.
An Adolescent with a Different Substance Abuse
Authors: Hocaoglu Cicek
Published: December 2008

From the beginning of history, it is a well known fact that some people admire to substances making them tipsy and stories about them were told and heard in everywhere and in every time. As shown in several studies, psychiatric disorders related to substance abuse especially in adolescents are becoming more prevalent in all countries including Turkey every year and this is another well-known reality of our time. There are many known psychoactive substances affecting the mental well being of young people and disturbing their social adaptation skills. Inhalants are the preferred psychoactive substances between the young people because of the factors making their abuse become widespread such as cheapness, ease of availability and frequent use in daily life. Here we report an adolescent with a different substance abuse.
Urgent Cholecystectomy for Acute Cholecystitis in a District General Hospital – Is it Feasible?
Authors: Khan MN , Nordon I , Ghauri Ask , Ranaboldo C , Carty N
Published: December 2008

INTRODUCTION

Laparoscopic cholecystectomy has become the gold standard for treatment of symptomatic gall stone disease. However, its place remains controversial in the management of acute cholecystitis due to a high reported incidence of bile leaks and conversion rate. Tertiary referral centres have reported good results. We present a series of cases after the introduction of an urgent cholecystectomy pathway in a district general hospital.

PATIENTS AND METHODS

A practice of urgent cholecystectomy for acute cholecystitis was introduced by three consultant general surgeons. All prospective patients having an urgent laparoscopic cholecystectomy for acute cholecystitis, over an 8-month period were entered into a database. A dedicated ultrasound service was instituted to provide prompt diagnosis in these patients. Their demographic details, operative findings, laboratory results were recorded in a prospective database. Timing of ERCP, postoperative complications and conversion rate and hospital stay were also noted.

RESULTS

There were 64 patients in the study with a median age of 51 years (range, 21–84 years). There were 21 males and 43 females. All patients underwent laparoscopic cholecystectomy during the index admission. Eleven patients had pre-operative ERCP and 12 patients had on-table cholangiogram. There were no conversions. Postoperative ERCP was required in six patients. The median time interval between admission and operation was 3 days (range, 2–7 days). There were two bile leaks but no common bile duct injury. There were two cases of superficial wound infection. One patient required re-operation for smail bowel obstruction secondary to a port site hernia.

CONCLUSIONS

Urgent laparoscopic cholecystectomy for acute cholecystitis is a feasible treatment option in a district general hospital. A safe practice can be ensured by adherence to a care pathway and a multidisciplinary, consultant-delivered service. Urgent cholecystectomy service can be provided safely in a district general hospital with outcomes comparable to previously published literature.
No incentives, no innovation
Authors: Hackett Jon
Published: December 2008

While the NHS has expressed a commitment to innovation with a succession of dedicated 'arms length bodies,' there are numerous high-profile cases in which advances on the ground have not received as much support as they might. In his recent Next Stage Review report, Lord Darzi has emphasised a commitment to clinical decision-making at all levels of the NHS but whether this will involve embracing best practice from the bottom up remains to be seen. For this article I spoke to two surgeons, whose sometimes controversial innovations were admired by many, about the obstacles they faced.
Aspiring surgeons vie for College prize
Authors: Ludvigsen Anna
Published: December 2008

The second annual Harold Ellis Medical Student Prize was awarded on 21 October 2008. The event was set up by the Opportunities in Surgery committee (OiS) to give medical students the opportunity to demonstrate their interest in surgery.
C-Reactive Protein and Coronary Heart Disease: Predictive Test or Therapeutic Target?
Authors: Hingorani Aroon D , Shah Tina , Casas Juan P , Humphries Steve E , Talmud Philippa J
Published: December 2008

Background: The hepatocyte-derived acute-phase reactant C-reactive protein (CRP) has been the subject of intense research over the last 2 decades for its possible role in the pathogenesis of cardiovascular diseases. This research has spawned interest in the use of the blood concentration of CRP for predicting a first coronary heart disease (CHD) event, which has been made possible with the development of high-sensitivity CRP (hsCRP) assays that can measure the typically low concentrations of CRP that circulate in the absence of an overt infective or inflammatory episode, and as a potential causal factor that might be targeted therapeutically. The research has encompassed observational and genetic epidemiology, basic science studies with cells and tissues, experiments with animal models and humans, and randomized trials (although not of specific CRP-lowering therapies as yet).

Content: We focus on investigations of the potential role of small differences in basal hsCRP concentration seen in healthy individuals and the relationship of such differences to the long-term risk of a first CHD event, rather than on research devoted to the high acute-phase CRP concentrations, which occur after acute atherothrombotic events and can influence the severity of ischemic tissue damage and the subsequent prognosis. We concentrate mainly on research findings at the translational interface and draw on evidence from human observational and genetic epidemiology, as well as from randomized trials.

Conclusions: As the field matures from one of discovery to an evaluative science, the development of possible clinical applications requires a sharpening of focus on and a critical appraisal of the strengths and deficiencies of the accumulated evidence. Such assessments require attention to both the current state of affairs and the design of future research, so that the existing uncertainties about the utility of CRP in predicting CHD and its role in causing this disease can be resolved.
Status of the U.S. EPA's Sediment Quality Criteria Development Effort
Authors: Zarba CS
Published: December 2008

In July, 1984, under the authority of the Clean Water Act, the Environmental Protection Agency (EPA) initiated an effort to develop sediment quality criteria. This effort was initiated with a workshop, in which a variety of experts worked to identify an approach by which the Agency could develop numerical sediment quality criteria. Efforts are under way to evaluate, modify, and verify the approach selected by the workshop through literature reviews, bioassays, data analysis, and field verification studies. The near-term goal of this effort is to present the findings of this effort to the EPA's Science Advisory Board for review and eventual approval.
Distribution of Heavy Metals in Sewage Sludge: The Effect of Particle Size
Authors: Campbell JA , Towner JV , Vallurupalli R
Published: December 2008

The particle size distribution in two anaerobically digested sludges from contrasting United Kingdom catchments has been estimated by a manual sieving technique. Seven particle size fractions were isolated: <20, 20 to 35, 35 to 45, 45 to 64, 64 to 85, 85 to 125, and > 125 µm. In both samples, the less than 20-µm fraction was the largest fraction, accounting for almost 50% of the total. Particles recovered in the coarsest (>125 µm) fraction were readily distinguished as plant remains and cellulose fibers. The distribution of eight metals, chromium, iron, manganese, nickel, copper, zinc, cadmium, and lead, were controlled by the particle size distribution with the finest fraction dominating. However, the distributions of chromium, copper, zinc, cadmium, and lead differed from those of iron, manganese, and nickel in that there was a much wider span of concentration (on a dry weight basis) between coarsest and finest particles. We attribute the wide concentration range of the former group to the repartitioning of these contaminants in sewage from predominantly solution phases to solids, by a sorption process, governed at least to an extent by surface area. On the other hand, iron, manganese, and nickel, if predominantly associated with solid phases in raw sewage, would be little influenced by alteration during treatment.
Development of New Jersey State Approved Methods for the Analysis of Sludge
Authors: Dengler SH
Published: December 2008

New Jersey, the most densely populated state, produces approximately 2 300 000 dry lb/day (10 432 800 kg/day) of sewage sludge. Half of the sludge is disposed of in the ocean, the rest is managed through land-based alternatives consisting of agricultural land application, composting, and incineration. Land-based options for sludge management have effects on air, ground, and surface water quality. The New Jersey Sludge Quality Assurance Regulations (SQAR), promulgated 18 Oct. 1979, require wastewater facilities to periodically sample and analyze the sludge for certain parameters based on total sewage flow. It was the intent of these regulations to supply the necessary data to determine the quantity, chemical and physical nature, and management mode of the sludge being generated. When the SQARs were promulgated, there were no standardized analytical methods for sludge analysis. A Sludge Methods Task Force, consisting of representatives from academia, major treatment works, industry, and the state and federal government, was created to establish the testing methods. The general procedure adopted by the task force consists of literature and in-house laboratory methods review, and conducting intra-and interlaboratory method validation studies. Once finalized as acceptable methods, the task force recommended their incorporation into the State's laboratory certification program as “approved” methods for the analysis of sludge.
Analysis for Diesel Oil Components in Drilling Fluids
Authors: Tompkins DF , Handel ED , Telliard W
Published: December 2008

Three methods of isolating No. 2 diesel oil from a bentonite-based drilling fluid were evaluated: soxhlet extraction, ultrasonic extraction, and retort distillation. The efficiency of each method was demonstrated by either gas chromatographic analysis or by a determination of the weight or volume of the residue recovered. Of the methods evaluated, only retort distillation demonstrated recoveries greater than 90%.
Thermal Inactivation of Human Enteric Viruses in Sewage Sludge and Virus Detection by Nitrose Cellulose-Enzyme Immunoassay
Authors: Loh PC , Fujioka RS , Hirano WM
Published: December 2008

The Zimpro Thermal Sludge Treatment Process installed at the Sand Island Wastewater Treatment Plant, Honolulu, HI, was evaluated for its reliability in disinfecting human enteric viruses and fecal bacteria in the treated sludge. The principle of this process involves grinding the sludge particles to a small size (< 4.8 mm) and heating the ground sludge to 193°C under 330 psi pressure for 30 min. Such thermally treated sludge yielded no human enteric viruses and little or no fecal bacteria (< 2 to 24 MPN/100 g), thus rendering the sludge safe for reuse. In corollary studies, the nitrocellulose-enzyme immunoassay was evaluated as an alternate cost-effective method to augment infectivity assays for the detection of human enteric viruses. The method was found to be rapid, highly sensitive (it can detect picogram quantities), and specific for the detection of human enteric viruses.
Marine Sediment Toxicity Tests
Authors: Chapman PM
Published: December 2008

Sediments are a major repository for persistent aquatic contaminants, the availability of which cannot be determined by chemical analyses or field surveys alone. Sediment bioassays provide information on the toxicity of contaminated sediments by measuring the level of their effect on test organisms. Testing involves laboratory exposure of test species to field-collected sediments and can range from the use of whole organisms to individual cells. Exposure routes involve the use of whole sediments, sediment elutriates, or sediment extracts. Except in the case of extracts, sediments cannot be stored and must be tested shortly after collection. Testing methodologies developed to date include most major trophic levels. Measured test responses include acute lethal, sublethal, genotoxic/cytotoxic, and microbial activity measurements. Quality assurance/quality control procedures for collection, handling, and testing have been developed, and an interlaboratory calibration exercise has been successfully completed. Comparative testing of different techniques and routes of exposure indicates a high degree of robustness in the techniques tested to date.
Toxicity of U.S. Waterway Sediments with Particular Reference to the New York Harbor Area
Authors: Jones RA , Lee GF
Published: December 2008

A study was conducted in the mid- to late-1970s on the toxicity of elutriate test mixtures of water and sediment from U.S. harbors and waterways to grass shrimp or daphnia. While for many waterway sediments, 20 to 30% mortality was found after 96-h exposure, those of the New York harbor area showed somewhat greater toxicity. The specific cause of the mortalities was not investigated at that time. It is known that the sediments contained a wide variety of chemical contaminants which, if available to the organisms, could be toxic to them. More than 30 chemical parameters, including heavy metals and chlorinated hydrocarbon pesticides, were measured in the sediments; of the parameters measured, only ammonia was released in sufficient amounts to potentially cause acute lethality in the test waters associated with the sediments. Recent review of the data showed that there is a relationship between the concentration of ammonia in the sediment/water mixtures (elutriates) and the mortality of grass shrimp in the tests. Furthermore, the concentrations that appeared to cause about 50% mortality of the grass shrimp in the 96-h exposure were about the level of 96-h LC50 to grass shrimp for ammonia.
Assessment of Risks Associated with Enteric Viruses in Contaminated Drinking Water
Authors: Gerba CP , Haas CN
Published: December 2008

It is now well established that enteric viruses, such as hepatitis A, Norwalk, rotavirus, and so forth, can be transmitted by sewage-contaminated water and food. Standards for viruses in water have been suggested by the World Health Organization and several other organizations. Few attempts have been made to assess the risks associated with exposure to low numbers of enteric viruses in the environment.

To determine the risks that may be associated with exposure to human enteric viruses, the literature on minimum infectious dose, incidence of clinical illness, and mortality was reviewed. This information was then used to assess the probability of infection, illness, and mortality for individuals consuming drinking water containing various concentrations of enteric viruses. Risks were determined on a daily, annual, and lifetime basis. This analysis suggested that significant risks of illness (>1:10 000) and mortality (>1:1 000 000) may arise from the exposure to low levels of the enteric virus.
Decrease of brachial-ankle pulse wave velocity in female subclinical hypothyroid patients during normalization of thyroid function: a double-blind, placebo-controlled study
Authors: Nagasaki Toshiki , Inaba Masaaki , Yamada Shinsuke , Shirakawa Kumi , Nagata Yuki , Kumeda Yasuro , Hiura Yoshikazu , Tahara Hideki , Ishimura Eiji , Nishizawa Yoshiki
Published: December 2008

Objective

Subclinical hypothyroidism affects 5–15% of the general population, is especially prevalent in females, and may be associated with increased morbidity from cardiovascular disease, although it remains controversial. We recently reported a significant increase in the brachial-ankle pulse wave velocity (baPWV), a parameter of arterial stiffening and an independent predictor of cardiovascular events, in subclinical hypothyroidism without thyroiditis. The current study was performed to assess changes in baPWV in female subclinical hypothyroidism with autoimmune chronic thyroiditis (Hashimoto's disease) after restoration of normal thyroid function.

Methods

In a randomized placebo-controlled study, 95 female subclinical hypothyroid patients were monitored for changes in baPWV before and after levothyroxine (l-T4) replacement therapy. Changes in baPWV were also measured in 42 age-matched normal female subjects.

Results

The baseline baPWV values in patients with subclinical hypothyroidism were significantly higher than in normal subjects. With attainment of euthyroidism, baPWV showed a significant decrease from 1776.7±86.0 to 1674.3±79.2 cm/s (P=0.006) in patients treated withl-T4, but the changes in baPWV and TSH were not correlated. The change in baPWV was significantly and negatively correlated with age and baseline pulse pressure, but multiple regression analysis revealed that these parameters failed to be associated with the change in baPWV.

Conclusions

Sustained normalization of thyroid function duringl-T4replacement therapy significantly decreases baPWV in female subclinical hypothyroid patients with autoimmune chronic thyroiditis, suggesting the improvement of arterial stiffening and, consequently, possible prevention of cardiovascular disease.
A Mutant Plasma Membrane Protein Is Stabilized Upon Loss of Yvh1, a Novel Ribosome Assembly Factor
Authors: Liu Yu , Chang Amy
Published: December 2008

Pma1-10 is a mutant plasma membrane ATPase defective at the restrictive temperature in stability at the cell surface. At 37°, Pma1-10 is ubiquitinated and internalized from the plasma membrane for degradation in the vacuole. YVH1, encoding a tyrosine phosphatase, is a mutant suppressor of pma1-10; in the absence of Yvh1, Pma1-10 remains stable at the plasma membrane, thereby permitting cells to grow. The RING finger domain of Yvh1, but not its phosphatase domain, is required for removal of mutant Pma1-10 from the plasma membrane. Yvh1 is a novel ribosome assembly factor: in yvh1Δ cells, free 60S and 80S ribosomal subunits are decreased, free 40S subunits are increased, and half-mer polysomes are accumulated. Pma1-10 is also stabilized by deletion of 60S ribosomal proteins Rpl19a and Rpl35a. We propose that changes in ribosome biogenesis caused by loss of Yvh1 or specific ribosomal proteins have effects on the plasma membrane, perhaps by producing specific translational changes.
Characterization of a Local Renin‐Angiotensin System in Rat Gingival Tissue
Authors: Santos C.F. , Akashi A.E. , Dionísio T.J. , Sipert C.R. , Didier D.N. , Greene A.S. , Oliveira S.H.P. , Pereira H.J.V. , Becari C. , Oliveira E.B. , Salgado M.C.O.
Published: December 2008

Background: The systemic renin‐angiotensin system (RAS) promotes the plasmatic production of angiotensin (Ang) II, which acts through interaction with specific receptors. There is growing evidence that local systems in various tissues and organs are capable of generating angiotensins independently of circulating RAS. The aims of this study were to investigate the expression and localization of RAS components in rat gingival tissue and evaluate the in vitro production of Ang II and other peptides catalyzed by rat gingival tissue homogenates incubated with different Ang II precursors.

Methods: Reverse transcription‐polymerase chain reaction assessed mRNA expression. Immunohistochemical analysis aimed to detect and localize renin. A standardized fluorimetric method with tripeptide hippuryl‐histidyl‐leucine was used to measure tissue angiotensin‐converting enzyme (ACE) activity, whereas high performance liquid chromatography showed products formed after the incubation of tissue homogenates with Ang I or tetradecapeptide renin substrate (TDP).

Results: mRNA for renin, angiotensinogen, ACE, and Ang II receptors (AT1a, AT1b, and AT2) was detected in gingival tissue; cultured gingival fibroblasts expressed renin, angiotensinogen, and AT1a receptor. Renin was present in the vascular endothelium and was intensely expressed in the epithelial basal layer of periodontally affected gingival tissue. ACE activity was detected (4.95 ± 0.89 nmol histidyl‐leucine/g/minute). When Ang I was used as substrate, Ang 1‐9 (0.576 ± 0.128 nmol/mg/minute), Ang II (0.066 ± 0.008 nmol/mg/minute), and Ang 1‐7 (0.111 ± 0.017 nmol/mg/minute) were formed, whereas these same peptides (0.139 ± 0.031, 0.206 ± 0.046, and 0.039 ± 0.007 nmol/mg/minute, respectively) and Ang I (0.973 ± 0.139 nmol/mg/minute) were formed when TDP was the substrate.

Conclusion: Local RAS exists in rat gingival tissue and is capable of generating Ang II and other vasoactive peptides in vitro.
In Vivo Validation of a Three‐Dimensional Optical Method to Document Volumetric Soft Tissue Changes of the Interdental Papilla
Authors: Strebel Jan , Ender Andreas , Paqué Frank , Krähenmann Michael , Attin Thomas , Schmidlin Patrick R.
Published: December 2008

Background: Non‐surgical and surgical periodontal treatment may cause volumetric changes in the gingival contour. Many techniques have been suggested to minimize soft tissue shrinkage; however, there is a lack of three‐dimensional (3D) quantitative data comparing different treatment approaches. The aim of the present study was to clinically validate an easy‐to‐use chair‐side procedure to document volumetric changes in the interdental papilla region.

Methods: Nine volunteers participated in the study. A thin layer of a flowable composite resin material was applied on a papilla and volumetrically analyzed using the clinical chair‐side computer‐aided design/computer‐aided machining (CAD/CAM) 3D method. To accurately measure the applied volumes, the composite resin volume was also determined using microcomputed tomography (μ‐CT) and weight measurements. In addition, inter‐ and intraexaminer differences were evaluated in the same manner using a dental training unit (phantom head) to simulate clinical conditions.

Results: No statistically significant difference was found between the results obtained by μ‐CT and the weight measurements. The CAD/CAM 3D method showed a significant underestimation of the composite resin volume (P = 0.0047) compared to μ‐CT, although the two methods correlated well (R2 = 0.991). High accuracy was found when inter‐ and intraexaminer differences were evaluated, showing a concordance correlation coefficient of 0.99.

Conclusion: CAD/CAM 3D device and software are an easy‐to‐use chair‐side method to document changes in soft tissues.
Prevalence of Halitosis in Young Male Adults: A Study in Swiss Army Recruits Comparing Self‐Reported and Clinical Data
Authors: Bornstein Michael M. , Stocker Bruce L. , Seemann Rainer , Bürgin Walter B. , Lussi Adrian
Published: December 2008

Background: Sound epidemiologic data on halitosis are rare. We evaluated the prevalence of halitosis in a young male adult population in Switzerland using a standardized questionnaire and clinical examination.

Methods: Six hundred twenty‐six Swiss Army recruits aged 18 to 25 years (mean: 20.3 years) were selected as study subjects. First, a standardized questionnaire focusing on dental hygiene, self‐reported halitosis, smoking, and alcohol consumption was filled out by all participants. In the clinical examination, objective values for the presence of halitosis were gathered through an organoleptic assessment of the breath odor and the measurement of volatile sulfur compounds (VSCs). Additionally, tongue coating, plaque index, and probing depths were evaluated for each recruit.

Results: The questionnaire revealed that only 17% of all included recruits had never experienced halitosis. The organoleptic evaluation (grades 0 to 3) identified eight persons with grade 3, 148 persons with grade 2, and 424 persons with grade 1 or 0. The calculation of the Pearson correlation coefficient to evaluate the relationship among the three methods of assessing halitosis revealed little to no correlation. The organoleptic score showed high reproducibility (kappa = 0.79). Tongue coating was the only influencing factor found to contribute to higher organoleptic scores and higher VSC values.

Conclusions: Oral malodor seemed to pose an oral health problem for about one‐fifth of 20‐year‐old Swiss males questioned. No correlation between self‐reported halitosis and organoleptic or VSC measurements could be detected. Although the organoleptic method described here offers a high reproducibility, the lack of correlation between VSC values and organoleptic scores has to be critically addressed. For further studies assessing new organoleptic scores, a validated index should always be included as a direct control.