bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioavailability of α-tocopherol stereoisomers in rats depends on dietary doses ofall-rac- or RRR-α-tocopheryl acetate
Authors: Jensen Søren K. , Nørgaard Jan V. , Lauridsen Charlotte
Published: February 2006

The biological function of the stereoisomers of α-tocopherol is believed to depend on their bioavailability. Assessment of bioavailability within the body is therefore considered to be a good and easy way to predict biological value. The separation of α-tocopherol methyl ethers by chiral column HPLC is a good and easy tool with which to study the distribution of α-tocopherol stereoisomers. The objective of this investigation was to evaluate the bioavailability and distribution of the stereoisomers of α-tocopherol in the plasma and tissue in growing rats fed 25, 50, 100 or 200mg/kg diet of either RRR- orall-rac-α-tocopheryl acetate for 10d. The ratio between the two vitamin E sources based on their α-tocopherol concentration in plasma and tissues varied in the plasma between 1·04 and 1·74 and in tissues, ratios of 0·84–1·24 for liver, 0·34–1·59 for lung and 0·75–1·50 for spleen were obtained. An increasing dietary level ofall-rac-α-tocopheryl acetate decreased the proportion of RRR-α-tocopherol, whereas the other stereoisomers were not affected. RRS-α-Tocopherol was present in the highest proportion, followed by RSR-, RSS- and RRR-α-tocopherol. In contrast to the other tissues and plasma, the liver contained the highest proportion (29–33%) of the four 2S stereoisomers of total α-tocopherol. Rats fed RRR-α-tocopheryl acetate for 10d showed a significant increase in the plasma and tissue content of RRR-α-tocopherol and a simultaneous decrease in the other three 2R isomers, whereas the absolute content of the 2S isomers was unaffected. In adipose tissue, concentrations of the three synthetic 2R isomers remained constant, whereas there was a steep increase in the content of RRR-α-tocopherol.
Dairy products, calcium and phosphorus intake, and the risk of prostate cancer: results of the French prospective SU.VI.MAX (Supplémentation en Vitamines et Minéraux Antioxydants) study
Authors: Kesse E. , Bertrais S. , Astorg P. , Jaouen A. , Arnault A. , Galan P. , Hercberg S.
Published: February 2006

Although dairy products have been found to be associated with an elevated risk of prostate cancer, studies investigating the potential effect of Ca are limited, and findings are inconsistent. The objective of the present study was to test the relationship between the risk of prostate cancer and consumption of dairy products and Ca. The analysis included 2776 men from the French SU.VI.MAX (Supplementation en Vitamines et Minéraux Antioxydants) prospective study, among whom sixty-nine developed prostate cancer during the follow-up period (median: 7·7 years). Food consumption was assessed at inclusion from repeated 24h records and nutrient intake was calculated using a food composition table. A higher risk of prostate cancer was observed among subjects with higher dairy product (relative risk (RR; 95% CI), 4th quartile V. 1st: 1·35 (1·02, 1·78), P=0·04) and Ca intake (RR (95% CI), 4th quartile P. 1st: 2·43 (1·05, 5·62), P=0·04). Nevertheless, we identified a harmful effect of yoghurt consumption upon the risk of prostate cancer (RR (95% CI), increment 125g/d: 1·61 (1·07, 2·43), P=0·02) independently of the Ca content. Our data support the hypothesis that dairy products have a harmful effect with respect to the risk of prostate cancer, largely related to Ca content. The higher risk of prostate cancer with linear increasing yoghurt consumption seems to be independent of Ca and may be related to some other component.
High-viscosity carboxymethylcellulose reduces carbachol-stimulated intestinal chloride secretion in weaned piglets fed a diet based on skimmed milk powder and maltodextrin
Authors: Lallès Jean-Paul , Boudry Gaëlle , Favier Christine , Sève Bernard
Published: February 2006

High-viscosity carboxymethylcellulose (CMC) promotes gastrointestinal disorders, tissue alterations and bacterial overgrowth in pigs. The impact of CMC on intestinal absorptive and secretory physiology is not known. We hypothesised that CMC consumption alters intestinal Na-dependent glucose absorption and stimulates electrogenic chloride secretion. For testing this hypothesis, twenty-four piglets were weaned at 21d of age and pair-fed for 13d a starter diet based on skimmed milk powder and maltodextrin containing cellulose (control) or CMC. Body weight and faecal total aerobe and coliform counts were measured kinetically. At slaughter, digesta were weighed and characterised for viscosity and pH. Gastrointestinal tissues were weighed and sampled for physiology in Ussing chambers, morphometry and enzymology. Glucose absorption tended to be higher (P=0·08) and carbachol-stimulated chloride secretion was lower (P=0·01) with CMC in the small intestine, without changes in the colon. Aerobes were transiently higher at day 7 (P<0·05) but coliform counts remained unchanged (P=0·78) and β-haemoliticEscherichia coliwere virtually absent. Stomach and small-intestinal segments were heavier, and viscosity higher with CMC (0·001<P<0·05). The pH in the stomach was higher, and in the caecum and proximal colon lower with CMC (0·001<P<0·05). Jejunal villus area was slightly reduced with CMC (P<0·05) without effects on enzyme activities (P>0·10). In conclusion, CMC supplementation had pro-absorptive effects on the small intestine, possibly due to the absence of pathogenicE. coliin the present study.
Effects of fatty acids on skeletal muscle cell differentiationin vitro
Authors: Hurley Matthew S. , Flux Claire , Salter Andrew M. , Brameld John M.
Published: February 2006

Previous studies have shown stimulatory effects of linoleic acid (LA, C18:2) on differentiation of rat muscle cells in culture (Allenet al.1985), but there appears to be little investigation of the effects of other fatty acids. The present study therefore compared the effects of different fatty acids on muscle cell differentiationin vitro. L6 myoblasts were cultured (Dulbecco's Modified Eagles Medium+10% fetal calf serum) in six-well plates until 80% confluent (day 0). Cells were then either harvested or the medium switched to differentiation medium (Dulbecco's Modified Eagles Medium+2% horse serum), supplemented with fatty acid or drug treatments. Cells were harvested on days 0–5 and assayed for creatine kinase (CK), protein and DNA contents, to give a measure of differentiation (CK/DNA). Initial studies indicated a stimulatory effect of thecis9trans11 (c9, t11) isomer of conjugated linoleic acid (CLA) relative to control. By contrast, thetrans10,cis12 (t10, c12) isomer of CLA inhibited differentiation. Further experiments indicated that inhibition of differentiation by the t10, c12 CLA isomer was dose-dependent (up to 200μm) and may be via increased cell proliferation. LA and c9, t11 CLA stimulated differentiation at low concentrations (up to 50μm), but inhibited differentiation at high concentrations (200μm). In contrast, oleic acid stimulated differentiation at all concentrations, whereas the saturated fatty acid, palmitic acid, had no effect. The mechanism appeared not to involve either peroxisome proliferator-activated receptors α or γ. The data suggest that only unsaturated fatty acids have an effect and the presence or absence of acis-9 double bond may be important.
The Mediterranean diet: science and practice
Authors: Willett Walter C
Published: February 2006

Objective

To provide an overview of research relevant to the Mediterranean diet.

Design

Personal perspectives.

Setting

International.

Subject

Populations in Europe, North America, Asia.

Results

Approximately 50 years ago, Keys and colleagues described strikingly low rates of coronary heart disease in the Mediterranean region, where fat intake was relatively high but largely from olive oil. Subsequent controlled feeding studies have shown that compared to carbohydrate, both monounsaturated and polyunsaturated fats reduce LDL and triglycerides and increase HDL cholesterol. Importantly, these beneficial metabolic effects are greater in the presence of underlying insulin resistance. In a detailed analysis within the Nurses' Health Study, trans fat from partially hydrogenated vegetable oils (absent in traditional Mediterranean diets) was most strongly related to risk of heart disease, and both polyunsaturated and monounsaturated fat were inversely associated with risk. Epidemiologic evidence has also supported beneficial effects of higher intakes of fruits and vegetables, whole grains, fish, and daily consumption of moderate amounts of alcohol. Together with regular physical activity and not smoking, our analyses suggest that over 80% of coronary heart disease, 70% of stroke, and 90% of type 2 diabetes can be avoided by healthy food choices that are consistent with the traditional Mediterranean diet.

Conclusion

Both epidemiologic and metabolic studies suggest that individuals can benefit greatly by adopting elements of Mediterranean diets.
The Mediterranean-style diet for the prevention of cardiovascular diseases
Authors: de Lorgeril Michel , Salen Patricia
Published: February 2006

Objectives

To discuss present knowledge about Mediterranean diet and cardiovascular diseases.

Design

Review of existing literature.

Setting and Results

Epidemiological studies as well as randomised dietary trials suggest that Mediterranean diet may be important in relation to the pathogenesis (and prevention) of CHD. For instance, a striking protective effect of an ALA-rich Mediterranean diet was reported in the Lyon Diet Heart Study with a 50 to 70% reduction of the risk of recurrence after 4 years of follow-up in CHD patients. According to our current knowledge, dietary ALA should represent about 0.6 to 1% of total daily energy or about 2 g per day in patients following a Mediterranean diet, whereas the average intake in linoleic acid should not exceed 7 g per day. Supplementation with very-long-chain omega-3 fatty acids (about 1 g per day) in patients following a Mediterranean type of diet was shown to decrease the risk of cardiac death by 30% and of sudden cardiac death by 45% in the GISSI trial.

Conclusions

In the context of a diet rich in oleic acid, poor in saturated fats and low in omega-6 fatty acids (a dietary pattern characterising the traditional Mediterranean diet), even small doses of omega-3 fatty acids (about 1 g EPA + DHA the form of fish oil capsules or 2 g α-linolenic acid in canola oil and margarine) might be very protective. These data underline the importance of the accompanying diet in any dietary strategy using fatty acid complements.
The European Prospective Investigation into Cancer and Nutrition (EPIC)
Authors: Gonzalez Carlos A
Published: February 2006

Objective

To describe the main finding produced so far by the EPIC project, which aims to improve the scientific knowledge of nutritional factors involved in cancer.

Design and setting

Prospective cohort study in 23 centres from 10 European countries. Dietary assessment method varied by countries: in some cases a diet history by personal interview was carried out, while in most countries a self-administered semi-quantitative food-frequency questionnaire was used; in one case the questionnaire was combined with a food record. Information on a wide range of lifestyle factors and anthropometric measurements were also collected for most participants.

Subjects

The cohort includes 521 468 men and women mostly aged between 39 and 69 years, whereas blood samples are available for 387 889 subjects.

Results

To date 24 185 cancer cases have been identified in the follow-up of the cohort. The publications produced by each centre can be consulted on the EPIC website (http://www.iarc.fr/epic/). Among initial findings concerning the associations between cancer and dietary factors, one of the most important results is a protective effect of high fibre intake and fish consumption against colorectal cancer, while high red and processed meat intake increase the risk. Regarding lung cancer the first analyses found a protective effect of fruit intake but no association with vegetable consumption. No association was observed between vegetables and fruit intake and the risk of prostate cancer or breast cancer. Finally, data from Cambridge point to an interesting result regarding breast cancer: no association was observed with saturated fat intake measured by food-frequency questionnaire, but according to the food diary a daily intake of 35 g doubles the risk of breast cancer compared to women with daily intake of 10 g or less.
The SUN cohort study (Seguimiento University of Navarra)
Authors: Ángel Martínez-González Miguel
Published: February 2006

Objective

Cohort study (the SUN project) to identify dietary determinants of hypertension, diabetes, obesity and coronary heart disease (CHD), among other conditions.

Design

The SUN project is a Mediterranean dynamic prospective follow-up (cohort) study assessing participants every 2 years. The recruitment started in 2000 and it is permanently open (this is a dynamic cohort). A preliminary case–control study of myocardial infarction was also conducted, selecting incident cases of myocardial infarction and matched hospital controls.

Setting

The SUN study is conducted in Spain with university graduates, most of them being former students of the University of Navarra. The case–control study was conducted in three tertiary hospitals in the city of Pamplona (Spain).

Subjects

The case–control study included 171 cases and 171 controls. We have currently enrolled more than 17 500 participants in the SUN cohort. Approximately 7500 of them were enrolled less than 2 years ago, and have not received yet the invitation to complete the 2-year follow-up assessment. The follow-up rate for the first 10 000 participants approaches 90%.

Results

The case–control study found inverse associations between olive oil (or adherence to a Mediterranean food pattern) and myocardial infarction. In the SUN cohort, after 28.5 months of follow-up a higher adherence to a Mediterranean food pattern rich in olive oil was associated with a reduced risk of hypertension, though the results were statistically significant only among men.

Conclusions

The SUN study and the accompanying case–control study support the benefits of a Mediterranean diet and olive oil against CHD and hypertension.
The use of indexes evaluating the adherence to the Mediterranean diet in epidemiological studies: a review
Authors: Bach Anna , Serra-Majem Lluís , Carrasco Josep L , Roman Blanca , Ngo Joy , Bertomeu Isabel , Obrador Biel
Published: February 2006

The purpose of this paper is to review some of the methods that several epidemiological studies use to evaluate the adherence of a population to the Mediterranean diet pattern. Among these methods, diet indexes attempt to make a global evaluation of the quality of the diet based on a traditional Mediterranean reference pattern, described as a priori, general and qualitative. The Mediterranean diet indexes, hence, summarise the diet by means of a single score that results from a function of different components, such as food, food groups or a combination of foods and nutrients. The reviewed evaluation methods can be classified into three categories depending on the way they are calculated: (1) those based on a positive or negative scoring of the components, (2) those that add or substract standardised components, and (3) those that are based on a ratio between components.

Dietary scores have been used to explore the multiple associations between the Mediterranean diet, as an integral entity, and health parameters such as life expectancy or the incidence of obesity, cardiovascular diseases and some types of cancers. Moreover, these indexes are also useful tools to measure food consumption trends and to identify the involved factors, as well as to develop comprehensive public health nutrition recommendations.

A more precise and quantitative definition of the Mediterranean diet is required if the adherence to such a dietary pattern is intended to be more accurately measured. Other aspects of the Mediterranean diet indexes should also be taken into account, like the inclusion of typical Mediterranean foods such as nuts and fish and the validation of the dietary pattern approach by using biomarkers.
The primary defect in experimental ileitis originates from a nonhematopoietic source
Authors: Olson Timothy S. , Reuter Brian K. , Scott Kevin G-E. , Morris Margaret A. , Wang Xiao-Ming , Hancock Leslie N. , Burcin Tracy L. , Cohn Steven M. , Ernst Peter B. , Cominelli Fabio , Meddings Jonathan B. , Ley Klaus , Pizarro Theresa T.
Published: February 2006

The initiating etiologic factor in Crohn's disease (CD) remains unclear. SAMP1/YitFc (SAMP) mice develop chronic ileitis similar to human CD. We used bone marrow chimeras to determine if SAMP ileitis results from a primary immunological defect or from dysregulated mucosal immunity secondary to intrinsic, nonhematopoietic (e.g., epithelial) dysfunction. SAMP mice receiving wild-type (AKR) BM developed severe ileitis, whereas SAMP BM did not confer ileitis to WT recipients. WT lymphocytes from reconstituted SAMP mice resembled native SAMP populations in regard to surface phenotype and cytokine production. Ilea from native SAMP mice and SAMP recipients of wild-type BM displayed decreased epithelial barrier resistance ex vivo and increased epithelial permeability in vivo compared to native WT mice and AKR recipients of SAMP BM. This permeability defect preceded the development of ileal inflammation, was present in the absence of commensal bacteria, and was accompanied by altered ileal mRNA expression of the tight junction proteins claudin-2 and occludin. Our results provide evidence that the primary defect conferring ileitis in SAMP mice originates from a nonhematopoietic source. Generation of pathogenic lymphocytes is a consequence of this defect and does not reflect intrinsic proinflammatory leukocyte properties. Decreased barrier function suggests that defects in the epithelium may represent the primary source of SAMP ileitis susceptibility.
Natural killer cell behavior in lymph nodes revealed by static and real-time imaging
Authors: Bajénoff Marc , Breart Béatrice , Huang Alex Y.C. , Qi Hai , Cazareth Julie , Braud Veronique M. , Germain Ronald N. , Glaichenhaus Nicolas
Published: February 2006

Natural killer (NK) cells promote dendritic cell (DC) maturation and influence T cell differentiation in vitro. To better understand the nature of the putative interactions among these cells in vivo during the early phases of an adaptive immune response, we have used immunohistochemical analysis and dynamic intravital imaging to study NK cell localization and behavior in lymph nodes (LNs) in the steady state and shortly after infection with Leishmania major. In the LNs of naive mice, NK cells reside in the medulla and the paracortex, where they closely associate with DCs. In contrast to T cells, intravital microscopy revealed that NK cells in the superficial regions of LNs were slowly motile and maintained their interactions with DCs over extended times in the presence or absence of immune-activating signals. L. major induced NK cells to secrete interferon-γ and to be recruited to the paracortex, where concomitant CD4 T cell activation occurred. Therefore, NK cells form a reactive but low mobile network in a strategic area of the LN where they can receive inflammatory signals, interact with DCs, and regulate colocalized T cell responses.
Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses
Authors: Boscardin Silvia B. , Hafalla Julius C.R. , Masilamani Revati F. , Kamphorst Alice O. , Zebroski Henry A. , Rai Urvashi , Morrot Alexandre , Zavala Fidel , Steinman Ralph M. , Nussenzweig Ruth S. , Nussenzweig Michel C.
Published: February 2006

Resistance to several prevalent infectious diseases requires both cellular and humoral immune responses. T cell immunity is initiated by mature dendritic cells (DCs) in lymphoid organs, whereas humoral responses to most antigens require further collaboration between primed, antigen-specific helper T cells and naive or memory B cells. To determine whether antigens delivered to DCs in lymphoid organs induce T cell help for antibody responses, we targeted a carrier protein, ovalbumin (OVA), to DCs in the presence of a maturation stimulus and assayed for antibodies to a hapten, (4-hydroxy-3-nitrophenyl) acetyl (NP), after boosting with OVA-NP. A single DC-targeted immunization elicited long-lived T cell helper responses to the carrier protein, leading to large numbers of antibody-secreting cells and high titers of high-affinity antihapten immunoglobulin Gs. Small doses of DC-targeted OVA induced higher titers and a broader spectrum of anti-NP antibody isotypes than large doses of OVA in alum adjuvant. Similar results were obtained when the circumsporozoite protein of Plasmodium yoelii was delivered to DCs. We conclude that antigen targeting to DCs combined with a maturation stimulus produces broad-based and long-lived T cell help for humoral immune responses.
A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition
Authors: Kjer-Nielsen Lars , Borg Natalie A. , Pellicci Daniel G. , Beddoe Travis , Kostenko Lyudmila , Clements Craig S. , Williamson Nicholas A. , Smyth Mark J. , Besra Gurdyal S. , Reid Hugh H. , Bharadwaj Mandvi , Godfrey Dale I. , Rossjohn Jamie , McCluskey James
Published: February 2006

Little is known regarding the basis for selection of the semi-invariant αβ T cell receptor (TCR) expressed by natural killer T (NKT) cells or how this mediates recognition of CD1d–glycolipid complexes. We have determined the structures of two human NKT TCRs that differ in their CDR3β composition and length. Both TCRs contain a conserved, positively charged pocket at the ligand interface that is lined by residues from the invariant TCR α- and semi-invariant β-chains. The cavity is centrally located and ideally suited to interact with the exposed glycosyl head group of glycolipid antigens. Sequences common to mouse and human invariant NKT TCRs reveal a contiguous conserved “hot spot” that provides a basis for the reactivity of NKT cells across species. Structural and functional data suggest that the CDR3β loop provides a plasticity mechanism that accommodates recognition of a variety of glycolipid antigens presented by CD1d. We propose a model of NKT TCR–CD1d–glycolipid interaction in which the invariant CDR3α loop is predicted to play a major role in determining the inherent bias toward CD1d. The findings define a structural basis for the selection of the semi-invariant αβ TCR and the unique antigen specificity of NKT cells.
Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine
Authors: Trumpfheller Christine , Finke Jennifer S. , López Carolina B. , Moran Thomas M. , Moltedo Bruno , Soares Helena , Huang Yaoxing , Schlesinger Sarah J. , Park Chae Gyu , Nussenzweig Michel C. , Granelli-Piperno Angela , Steinman Ralph M.
Published: February 2006

Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to maturing dendritic cells in lymphoid tissue by engineering protein antigen into an antibody to DEC-205, a receptor for antigen presentation. Here we characterize the CD4+ T cell immune response to HIV gag and compare efficacy with other vaccine strategies in a single dose. DEC-205–targeted HIV gag p24 or p41 induces stronger CD4+ T cell immunity relative to high doses of gag protein, HIV gag plasmid DNA, or recombinant adenovirus-gag. High frequencies of interferon (IFN)-γ– and interleukin 2–producing CD4+ T cells are elicited, including double cytokine-producing cells. In addition, the response is broad because the primed mice respond to an array of peptides in different major histocompatibility complex haplotypes. Long-lived T cell memory is observed. After subcutaneous vaccination, CD4+ and IFN-γ–dependent protection develops to a challenge with recombinant vaccinia-gag virus at a mucosal surface, the airway. We suggest that a DEC-targeted vaccine, in part because of an unusually strong and protective CD4+ T cell response, will improve vaccine efficacy as a stand-alone approach or with other modalities.
In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules
Authors: Yan Jingbo , Parekh Vrajesh V. , Mendez-Fernandez Yanice , Olivares-Villagómez Danyvid , Dragovic Srdjan , Hill Timothy , Roopenian Derry C. , Joyce Sebastian , Van Kaer Luc
Published: February 2006

Endoplasmic reticulum (ER)-associated aminopeptidase (ERAP)1 has been implicated in the final proteolytic processing of peptides presented by major histocompatibility complex (MHC) class I molecules. To evaluate the in vivo role of ERAP1, we have generated ERAP1-deficient mice. Cell surface expression of the class Ia molecules H-2Kb and H-2Db and of the class Ib molecule Qa-2 was significantly reduced in these animals. Although cells from mutant animals exhibited reduced capacity to present several self- and foreign antigens to Kb-, Db-, or Qa-1b–restricted CD8+ cytotoxic T cells, presentation of some antigens was unaffected or significantly enhanced. Consistent with these findings, mice generated defective CD8+ T cell responses against class I–presented antigens. These findings reveal an important in vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules.
Microbial Aerosol Contamination of Dental Healthcare Workers' Faces and Other Surfaces in Dental Practice
Authors: Prospero Emilia , Savini Sandra , Annino Isidoro
Published: March 2006

The purpose of this study was to focus attention on the need to adopt infection control procedures in dentistry. The quantitative and qualitative bacterial contamination of dental healthcare workers' faces and other surfaces in dental practice was determined. Oral fluids become aerosolized during dentistry and oral microbes have been used as the markers of their spread that may carry blood-borne pathogens.
Infection Control Practices in Clinical Laboratories in Pakistan
Authors: Mujeeb Syed Abdul , Adil Malik Mohummad , Altaf Arshad , Shah Sharaf Ali , Luby Stephen
Published: March 2006

Clinical laboratories in Karachi, Pakistan, were evaluated for adherence to standard precautions using an observational checklist. Among 44 laboratories, gloves were used in 2, protective gowns in 12, disinfectant in 7, and an incinerator in 7. Standard worker safety precautions are not followed at major clinical laboratories in Karachi.
Detection of Hepatitis C Virus Antibody and RNA in Hemostatic Gauze Used for Dentistry
Authors: Hasegawa Hiromasa , Yamada Tetsuo , Esumi Mariko
Published: March 2006

We investigated whether the presence of hepatitis C virus (HCV) infection can be detected in hemostatic gauze used during oral treatments. We were able to detect both antibody to HCV and HCV RNA in samples from patients serologically proven to have HCV and also in gauze used for these patients that was left at room temperature even for as long as 24 hours. Thus, this method is useful for the screening of HCV infection in situations in which blood sampling is not feasible.
Contamination of Trypan Blue With Burkholderia cepacia in a Cornea Bank
Authors: Morel Pascal C. , Roubi Nora , Talon Daniel R. , Bertrand Xavier
Published: March 2006

Objective:

To describe Burkholderia cepacia contamination of a cornea bank and the measures taken to identify and eliminate the source of infection.

Methods:

Cultures were performed to assess the extent and source of contamination, and pulsed-fleld gel electrophoresis was used for molecular typing.

Results:

Routine surveillance cultures identified 5 contaminated corneas during a 10-day period. Additional cultures showed that 28 of 88 samples were positive for this organism. Environmental investigation showed that an open bottle of trypan blue used to assess corneal morphology was contaminated with the epidemic strain.

Conclusion:

Trypan blue played a major role in this contamination of corneas. This episode shows that microbial contamination can affect transplanted corneas despite ongoing culture surveillance and suggests that new methods may be needed to avoid this risk.
Use of an Alcohol-Based Hand Rub and Quality Improvement Interventions to Improve Hand Hygiene in a Russian Neonatal Intensive Care Unit
Authors: Brown Samuel M. , Lubimova Anna V. , Khrustalyeva Natalya M. , Shulaeva Svetlana V. , Tekhova Iya , Zueva Ludmila P. , Goldmann Donald , O'Rourke Edward J.
Published: March 2006

Background:

Hand hygiene (HH) is critical to infection control, but compliance is low. Alcohol-based antiseptics may improve HH. HH practices in Russia are not well described, and facilities are often inadequate.

Setting:

Four 6-bed units in a neonatal intensive care unit in St. Petersburg, Russia.

Methods:

Prospective surveillance of HH compliance, nosocomial colonization, and antibiotic administration was performed from January until June 2000. In February 2000, alcohol-based hand rub was provided for routine HH use. Eight weeks later, a quality improvement intervention was implemented, consisting of review of interim data, identification of opinion leaders, posting of colonization incidence rates, and regular feedback. Means of compliance, colonization, and antibiotic use were compared for periods before and after each intervention.

Results:

A total of 1,027 events requiring HH were observed. Compliance was 44.2% before the first intervention, 42.3% between interventions, and 48% after the second intervention. Use of alcohol rose from 15.2% of HH indications to 25.2% between interventions and 41.5% after the second intervention. The incidence of nosocomial colonization (per 1,000 patient-days) with Klebsiella pneumoniae was initially 21.5, decreased to 4.7, and then was 3.2 in the final period. Rates of antibiotic and device use also decreased.

Conclusions:

HH may have increased slightly, but the largest effect was a switch from soap and water to alcohol, which may have been associated with decreased cross-transmission of Klebsiella, although this may have been confounded by lower device use. Alcohol-based antiseptic may be an improvement over current practices, but further research is required.
Pseudo-Outbreak ofPseudomonas aeruginosaandSerratia marcescensRelated to Bronchoscopes
Authors: Silva Cláudia V. , Magalhães Vanda D. , Pereira Crésio R. , Kawagoe Julia Y. , Ikura Chizue , Ganc Arnaldo J.
Published: March 2006

Objective:

To investigate an apparent outbreak involving simultaneous isolation ofPseudomonas aeruginosaandSerratia marcescensfrom bronchoalveolar lavage (BAL) samples.

Design:

Retrospective and prospective cohort studies using chart review, environmental sampling, and ribotyping of all available isolates. Cleaning and disinfection procedures for the bronchoscopes were also evaluated.

Setting:

A 380-bed private hospital in Sao Paulo, Brazil.

Patients:

Forty-one patients who underwent bronchoscopic procedures between December 1994 and October 1996 and from whomP. aeruginosaandS. marcescenswere concomitantly isolated. Bronchoscopes and related items were microbiologically assessed.

Results:

P. aeruginosaand S.marcescenswere simultaneously isolated from BAL samples 12.6% of the time (41 of 324) during the epidemic period versus 1.8% of the time (1 of 54) in the pre-epidemic period (P= .035). Ribotyping revealed two strains ofP. aeruginosaand one of S.marcescensthat were isolated from BAL samples of patients with no signs of respiratory tract infection, suggesting a pseudo-outbreak. Evaluation of bronchoscope disinfection revealed that inappropriate methods were being used. Implementation of simple control measures resulted in a significant decrease in simultaneous isolation of these species.

Conclusion:

Prevention of pseudo-outbreaks requires meticulous use of preventive measures for infection-prone medical procedures.
Planning optimal measurements of isotopomer distributions for estimation of metabolic fluxes
Authors: Rantanen Ari , Mielikäinen Taneli , Rousu Juho , Maaheimo Hannu , Ukkonen Esko
Published: February 2006

Motivation: Flux estimation using isotopomer information of metabolites is currently the most reliable method to obtain quantitative estimates of the activity of metabolic pathways. However, the development of isotopomer measurement techniques for intermediate metabolites is a demanding task. Careful planning of isotopomer measurements is thus needed to maximize the available flux information while minimizing the experimental effort.

Results: In this paper we study the question of finding the smallest subset of metabolites to measure that ensure the same level of isotopomer information as the measurement of every metabolite in the metabolic network. We study the computational complexity of this optimization problem in the case of the so-called positional enrichment data, give methods for obtaining exact and fast approximate solutions, and evaluate empirically the efficacy of the proposed methods by analyzing a metabolic network that models the central carbon metabolism of Saccharomyces cerevisiae.

Contact:  ajrantan@cs.helsinki.fi
Prediction of HLA-DQ3.2β Ligands: evidence of multiple registers in class II binding peptides
Authors: Tong Joo Chuan , Zhang Guang Lan , Tan Tin Wee , August J. Thomas , Brusic Vladimir , Ranganathan Shoba
Published: March 2006

Motivation: While processing of MHC class II antigens for presentation to helper T-cells is essential for normal immune response, it is also implicated in the pathogenesis of autoimmune disorders and hypersensitivity reactions. Sequence-based computational techniques for predicting HLA-DQ binding peptides have encountered limited success, with few prediction techniques developed using three-dimensional models.

Methods: We describe a structure-based prediction model for modeling peptide-DQ3.2β complexes. We have developed a rapid and accurate protocol for docking candidate peptides into the DQ3.2β receptor and a scoring function to discriminate binders from the background. The scoring function was rigorously trained, tested and validated using experimentally verified DQ3.2β binding and non-binding peptides obtained from biochemical and functional studies.

Results: Our model predicts DQ3.2β binding peptides with high accuracy [area under the receiver operating characteristic (ROC) curve AROC > 0.90], compared with experimental data. We investigated the binding patterns of DQ3.2β peptides and illustrate that several registers exist within a candidate binding peptide. Further analysis reveals that peptides with multiple registers occur predominantly for high-affinity binders.

Contact:  shoba@els.mq.edu.au

Supplementary information: Supplementary data is available at Bioinformatics online.
Family specific rates of protein evolution
Authors: Luz Hannes , Vingron Martin
Published: March 2006

Motivation: Amino acid changing mutations in proteins are contstrained by purifying selection and accumulate at different rates. We estimate evolutionary rates on multiple alignments of eukaryotic protein families in a maximum likelihood framework and spot sets of slow and fast evolving proteins.

Results: We find that the evolution of indispensable proteins is constrained by selection and that protein secretion is coupled to an increased evolutionary rate.

Contact:  luz@molgen.mpg.de

Supplementary information:
Stochastic models of receptor oligomerization by bivalent ligand
Authors: Alarcón Tomás , Page Karen M
Published: February 2006

In this paper, we develop stochastic models of receptor binding by a bivalent ligand. A detailed kinetic study allows us to analyse the role of cross-linking in cell activation by receptor oligomerization. We show how oligomer formation could act to buffer intracellular signalling against stochastic fluctuations. In addition, we put forward the hypothesis that formation of long linear oligomers increases the range of ligand concentration to which the cell is responsive, whereas formation of closed oligomers increases ligand concentration specificity. Thus, different physiological functions requiring different degrees of specificity to ligand concentration would favour formation of oligomers with different lengths and geometries. Furthermore, provided that ligand concentration specificity is taken as a design principle, our model enables us to estimate parameters, such as the minimum proportion of receptors, that must engage in oligomer formation in order to trigger a cellular response.
The number of zeros of a sum of fractional powers
Authors: Jameson G.J.O
Published: February 2006

We consider functions of the form, where. A version of Descartes's rule of signs applies. Further, ifand, then the number of zeros offis bounded by the number of sign changes of. The estimate is reduced by 1 for each relation of the form.
Existence and regularity for mixtures of micromagnetic materials
Authors: Acerbi Emilio , Fonseca Irene , Mingione Giuseppe
Published: February 2006

A new model for the energy of a mixture of micromagnetic materials is introduced within the context of functions with special bounded variation. Existence and regularity for the solution of an optimal design problem in micromagnetics are obtained.
Explicit equations of motion for constrained mechanical systems with singular mass matrices and applications to multi-body dynamics
Authors: Udwadia Firdaus E , Phohomsiri Phailaung
Published: February 2006

We present the new, general, explicit form of the equations of motion for constrained mechanical systems applicable to systems with singular mass matrices. The systems may have holonomic and/or non-holonomic constraints, which may or may not satisfy D'Alembert's principle at each instant of time. The equation provides new insights into the behaviour of constrained motion and opens up new ways of modelling complex multi-body systems. Examples are provided and applications of the equation to such systems are illustrated.
Transfer matrix analysis of the elastostatics of one-dimensional repetitive structures
Authors: Stephen N.G
Published: February 2006

Transfer matrices are used widely for the dynamic analysis of engineering structures, increasingly so for static analysis, and are particularly useful in the treatment of repetitive structures for which, in general, the behaviour of a complete structure can be determined through the analysis of a single repeating cell, together with boundary conditions if the structure is not of infinite extent. For elastostatic analyses, non-unity eigenvalues of the transfer matrix of a repeating cell are the rates of decay of self-equilibrated loading, as anticipated by Saint-Venant's principle. Multiple unity eigenvalues pertain to the transmission of load, e.g. tension, or bending moment, and equivalent (homogenized) continuum properties, such as cross-sectional area, second moment of area and Poisson's ratio, can be determined from the associated eigen- and principal vectors. Various disparate results, the majority new, others drawn from diverse sources, are presented. These include calculation of principal vectors using the Moore–Penrose inverse, bi- and symplectic orthogonality and relationship with the reciprocal theorem, restrictions on complex unity eigenvalues, effect of cell left-to-right symmetry on both the stiffness and transfer matrices, eigenvalue veering in the absence of translational symmetry and limitations on possible Jordan canonical forms. It is shown that only a repeating unity eigenvalue can lead to a non-trivial Jordan block form, so degenerate decay modes cannot exist. The present elastostatic analysis complements Langley's (Langley 1996
Proc. R. Soc. A
452
, 1631–1648) transfer matrix analysis of wave motion energetics.
An empirical approach for delayed oscillator stability and parametric identification
Authors: Mann Brian P , Young Keith A
Published: February 2006

This paper investigates a semi-empirical approach for determining the stability of systems that can be modelled by ordinary differential equations with a time delay. This type of model is relevant to biological oscillators, machining processes, feedback control systems and models for wave propagation and reflection, where the motion of the waves themselves is considered to be outside the system model. A primary aim is to investigate the extension of empirical Floquet theory to experimental or numerical data obtained from time-delayed oscillators. More specifically, the reconstructed time series from a numerical example and an experimental milling system are examined to obtain a finite number of characteristic multipliers from the reduced order dynamics. A secondary goal of this work is to demonstrate a benefit of empirical characteristic multiplier estimation by performing system identification on a delayed oscillator. The principal results from this study are the accurate estimation of delayed oscillator characteristic multipliers and the utilization the empirical results for parametric identification of model parameters. Combining these results with previous research on an experimental milling system provides a particularly relevant result—the first approach for identifying all model parameters for stability prediction directly from the cutting process vibration history.
Enumerating the bent diagonal squares of Dr Benjamin Franklin FRS
Authors: Schindel Daniel , Rempel Matthew , Loly Peter
Published: February 2006

All 8th order Franklin bent diagonal squares with distinct elements 1, …, 64 have been constructed by an exact backtracking method. Our count of 1, 105, 920 dramatically increases the handful of known examples, and is some eight orders of magnitude less than a recent upper bound. Exactly one-third of these squares are pandiagonal, and therefore magic. Moreover, these pandiagonal Franklin squares have the same population count as the eighth order ‘complete’, or ‘most-perfect pandiagonal magic’, squares. However, while distinct, both types of squares are related by a simple transformation. The situation for other orders is also discussed.
MHC genes and oxidative stress in sticklebacks: an immuno-ecological approach
Authors: Kurtz Joachim , Wegner K. Mathias , Kalbe Martin , Reusch Thorsten B.H , Schaschl Helmut , Hasselquist Dennis , Milinski Manfred
Published: February 2006

Individual variation in the susceptibility to infection may result from the varying ability of hosts to specifically recognize different parasite strains. Alternatively, there could be individual host differences in fitness costs of immune defence. Although, these two explanations are not mutually exclusive, they have so far been treated in separate experimental approaches. To analyse potential relationships, we studied body condition and oxidative stress, which may reflect costs of immunity, in three-spined sticklebacks that had been experimentally exposed to three species of naturally occurring parasite. These sticklebacks differed in a trait, which is crucial to specific parasite defence, i.e. individual genetic diversity at major histocompatibility complex (MHC) class IIB loci. Oxidative stress was quantified as tissue acrolein, a technique that has been applied to questions of immuno-ecology for the first time. We measured gene expression at the MHC and other estimates of immune activation. We found that fish with high levels of MHC expression had poor condition and elevated oxidative stress. These results indicate that MHC-based specific immunity is connected with oxidative stress. They could, thus, also be relevant in the broader context of the evolution of sexually selected signals that are based on carotenoids and are, thus supposed to reflect oxidative stress resistance.
Testing game theory models: fighting ability and decision rules in chameleon contests
Authors: Stuart-Fox Devi
Published: February 2006

Game theory models of animal contests make many non-mutually exclusive predictions, complicating empirical tests. These predictions regard the relationship between contest parameters and fighting ability, for which body size is usually used as a proxy. However, in many systems, body size may be a limited proxy since multiple traits and contextual factors such as experience influence fighting ability. Using contests between male Cape dwarf chameleons,Bradypodion pumilum, I test alternative game theory models of extended contests. I show how the most likely candidate model can be identified through a process of elimination, based on tests of key predictions. In addition, I present a measure of fighting ability based on multiple traits that allows ability to change as experience changes. In dwarf chameleons, persistence is based on loser thresholds rather than assessment of relative ability, ruling out the sequential assessment model. Winners and losers do not match behaviours in early parts of the contest, arguing against all types of war of attrition models. Although the cumulative assessment model remained as the most likely candidate model, not all specific predictions of this model were upheld.
Genetic rescue of an insular population of large mammals
Authors: Hogg John T , Forbes Stephen H , Steele Brian M , Luikart Gordon
Published: February 2006

Natural populations worldwide are increasingly fragmented by habitat loss. Isolation at small population size is thought to reduce individual and population fitness via inbreeding depression. However, little is known about the time-scale over which adverse genetic effects may develop in natural populations or the number and types of traits likely to be affected. The benefits of restoring gene flow to isolates are therefore also largely unknown. In contrast, the potential costs of migration (e.g. disease spread) are readily apparent. Management for ecological connectivity has therefore been controversial and sometimes avoided. Using pedigree and life-history data collected during 25 years of study, we evaluated genetic decline and rescue in a population of bighorn sheep founded by 12 individuals in 1922 and isolated at an average size of 42 animals for 10–12 generations. Immigration was restored experimentally, beginning in 1985. We detected marked improvements in reproduction, survival and five fitness-related traits among descendants of the 15 recent migrants. Trait values were increased by 23–257% in maximally outbred individuals. This is the first demonstration, to our knowledge, of increased male and female fitness attributable to outbreeding realized in a fully competitive natural setting. Our findings suggest that genetic principles deserve broader recognition as practical management tools with near-term consequences for large-mammal conservation.