bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Lateralization of Emotional Processing: Historical Roots and a Future Incorporating “Dominance”
Authors: Demaree Heath A. , Everhart D. Erik , Youngstrom Eric A. , Harrison David W.
Published: May 2005

This article provides a review of research on the hemispheric specialization in emotional processing during the past 40 years and the theoretical models derived from the conceptual analysis of these results. The publications reviewed here were collected to better appreciate the cortical lateralization of emotional perception (visual and auditory), expression (facial and prosodic), and experience. Four major models of emotional processing are discussed—the Right Hemisphere, Valence, Approach-Withdrawal, and Behavioral Inhibition System–Behavioral Activation System models. Observing the relative merits and limitations of these models, a new direction for exploration is offered. Specifically, to better appreciate the strength and direction (i.e., approach versus withdrawal) of experienced emotions, it is recommended that state “dominance” be evaluated in the context of asymmetrical activation of left-frontal (dominance) versus right-frontal (submission) brain regions.
The Role of Temporal Structure in Human Vision
Authors: Blake Randolph , Lee Sang-Hun
Published: May 2005

Gestalt psychologists identified several stimulus properties thought to underlie visual grouping and figure/ground segmentation, and among those properties was common fate: the tendency to group together individual objects that move together in the same direction at the same speed. Recent years have witnessed an upsurge of interest in visual grouping based on other timedependent sources of visual information, including synchronized changes in luminance, in motion direction, and in figure/ ground relations. These various sources of temporal grouping information can be subsumed under the rubric temporal structure. In this article, the authors review evidence bearing on the effectiveness of temporal structure in visual grouping. They start with an overview of evidence bearing on temporal acuity of human vision, covering studies dealing with temporal integration and temporal differentiation. They then summarize psychophysical studies dealing with figure/ground segregation based on temporal phase differences in deterministic and stochastic events. The authors conclude with a brief discussion of neurophysiological implications of these results.
Persistent expression of factor VIII in vivo following nonprimate lentiviral gene transfer
Authors: Kang Yubin , Xie Litao , Tran Diane Thi , Stein Colleen S. , Hickey Melissa , Davidson Beverly L. , McCray Paul B.
Published: May 2005

Hemophilia A is a clinically important coagulation disorder caused by the lack or abnormality of plasma coagulation factor VIII (FVIII). Gene transfer of the FVIII cDNA to hepatocytes using lentiviral vectors is a potential therapeutic approach. We investigated the efficacy of feline immunodeficiency virus (FIV)–based vectors in targeting hepatocytes and correcting FVIII deficiency in a hemophilia A mouse model. Several viral envelope glycoproteins were screened for efficient FIV vector pseudotyping and hepatocyte transduction. The GP64 glycoprotein from baculovirus Autographa californica multinuclear polyhedrosis virus pseudo-typed FIV efficiently and showed excellent hepatocyte tropism. The GP64-pseudotyped vector was stable in the presence of human or mouse complement. Inclusion of a hybrid liver-specific promoter (murine albumin enhancer/human α1-antitrypsin promoter) further enhanced transgene expression in hepatocytes. We generated a GP64-pseudotyped FIV vector encoding the B domain–deleted human FVIII coding region driven by the liver-specific promoter, with 2 beneficial point mutations in the A1 domain. Intravenous vector administration conferred sustained FVIII expression in hemophilia A mice for several months without the generation of anti–human FVIII antibodies and resulted in partial phenotypic correction. These findings demonstrate the utility of GP64-pseudotyped FIV lentiviral vectors for targeting hepatocytes to correct disorders associated with deficiencies of secreted proteins.
Fractal ventilation enhances respiratory sinus arrhythmia
Authors: Mutch W Alan C , Graham M Ruth , Girling Linda G , Brewster John F
Published: May 2005

Background

Programming a mechanical ventilator with a biologically variable or fractal breathing pattern (an example of 1/f noise) improves gas exchange and respiratory mechanics. Here we show that fractal ventilation increases respiratory sinus arrhythmia (RSA) – a mechanism known to improve ventilation/perfusion matching.

Methods

Pigs were anaesthetised with propofol/ketamine, paralysed with doxacurium, and ventilated in either control mode (CV) or in fractal mode (FV) at baseline and then following infusion of oleic acid to result in lung injury.

Results

Mean RSA and mean positive RSA were nearly double with FV, both at baseline and following oleic acid. At baseline, mean RSA = 18.6 msec with CV and 36.8 msec with FV (n = 10; p = 0.043); post oleic acid, mean RSA = 11.1 msec with CV and 21.8 msec with FV (n = 9, p = 0.028); at baseline, mean positive RSA = 20.8 msec with CV and 38.1 msec with FV (p = 0.047); post oleic acid, mean positive RSA = 13.2 msec with CV and 24.4 msec with FV (p = 0.026). Heart rate variability was also greater with FV. At baseline the coefficient of variation for heart rate was 2.2% during CV and 4.0% during FV. Following oleic acid the variation was 2.1 vs. 5.6% respectively.

Conclusion

These findings suggest FV enhances physiological entrainment between respiratory, brain stem and cardiac nonlinear oscillators, further supporting the concept that RSA itself reflects cardiorespiratory interaction. In addition, these results provide another mechanism whereby FV may be superior to conventional CV.
Common polymorphism in H19 associated with birthweight and cord blood IGF-II levels in humans
Authors: Petry Clive J , Ong Ken K , Barratt Bryan J , Wingate Diane , Cordell Heather J , Ring Susan M , Pembrey Marcus E ,   The ALSPAC Study Team, Reik Wolf , Todd John A , Dunger David B
Published: May 2005

Background

Common genetic variation at genes that are imprinted and exclusively maternally expressed could explain the apparent maternal-specific inheritance of low birthweight reported in large family pedigrees. We identified ten single nucleotide polymorphisms (SNPs) in H19, and we genotyped three of these SNPs in families from the contemporary ALSPAC UK birth cohort (1,696 children, 822 mothers and 661 fathers) in order to explore associations with size at birth and cord blood IGF-II levels.

Results

Both offspring's and mother's H19 2992C>T SNP genotypes showed associations with offspring birthweight (P = 0.03 to P = 0.003) and mother's genotype was also associated with cord blood IGF-II levels (P = 0.0003 to P = 0.0001). The offspring genotype association with birthweight was independent of mother's genotype (P = 0.01 to P = 0.007). However, mother's untransmitted H19 2992T allele was also associated with larger birthweight (P = 0.04) and higher cord blood IGF-II levels (P = 0.002), suggesting a direct effect of mother's genotype on placental IGF-II expression and fetal growth. The association between mother's untransmitted allele and cord blood IGF-II levels was more apparent in offspring of first pregnancies than subsequent pregnancies (P-interaction = 0.03). Study of the independent Cambridge birth cohort with available DNA in mothers (N = 646) provided additional support for mother's H19 2992 genotype associations with birthweight (P = 0.04) and with mother's glucose levels (P = 0.01) in first pregnancies.

Conclusion

The common H19 2992T allele, in the mother or offspring or both, may confer reduced fetal growth restraint, as indicated by associations with larger offspring birth size, higher cord blood IGF-II levels, and lower compensatory early postnatal catch-up weight gain, that are more evident among mother's smaller first-born infants.
Comparison of array-based comparative genomic hybridization with gene expression-based regional expression biases to identify genetic abnormalities in hepatocellular carcinoma
Authors: Furge Kyle A , Dykema Karl J , Ho Coral , Chen Xin
Published: May 2005

Background

Regional expression biases (REBs) are genetic intervals where gene expression is coordinately changed. For example, if a region of the genome is amplified, often the majority of genes that map within the amplified region show increased expression when compared to genes located in cytogenetically normal regions. As such, REBs have the potential to act as surrogates for cytogenetic data traditionally obtained using molecular technologies such as comparative genomic hybridization. However as REBs are identified using transcriptional information, detection of REBs may also identify local transcriptional abnormalities produced by both genetic and epigenetic mechanisms.

Results

REBs were identified from a set of hepatocellular carcinoma (HCC) gene expression profiles using a multiple span moving binomial test and compared to genetic abnormalities identified using array-based comparative genomic hybridization (aCGH). In the majority of cases, REBs overlapped genetic abnormalities as determined by aCGH. For example, both methods identified narrow regions of frequent amplification on chromosome 1p and narrow regions of frequent deletion on 17q. In a minority of cases, REBs were identified in regions not determined to be abnormal via other cytogenetic technologies. Specifically, expression biases reflective of cell proliferation were frequently identified on chromosome 6p21-23.

Conclusion

Identification of REBs using a multiple span moving binomial test produced reasonable approximations of underlying cytogenetic abnormalities. However, caution should be used when attributing REBs identified on chromosome 6p to cytogenetic events in rapidly proliferating cells.
Predictive screening for regulators of conserved functional gene modules (gene batteries) in mammals
Authors: Nelander Sven , Larsson Erik , Kristiansson Erik , Månsson Robert , Nerman Olle , Sigvardsson Mikael , Mostad Petter , Lindahl Per
Published: May 2005

Background

The expression of gene batteries, genomic units of functionally linked genes which are activated by similar sets of cis- and trans-acting regulators, has been proposed as a major determinant of cell specialization in metazoans. We developed a predictive procedure to screen the mouse and human genomes and transcriptomes for cases of gene-battery-like regulation.

Results

In a screen that covered ~40 per cent of all annotated protein-coding genes, we identified 21 co-expressed gene clusters with statistically supported sharing of cis-regulatory sequence elements. 66 predicted cases of over-represented transcription factor binding motifs were validated against the literature and fell into three categories: (i) previously described cases of gene battery-like regulation, (ii) previously unreported cases of gene battery-like regulation with some support in a limited number of genes, and (iii) predicted cases that currently lack experimental support. The novel predictions include for example Sox 17 and RFX transcription factor binding sites that were detected in ~10% of all testis specific genes, and HNF-1 and 4 binding sites that were detected in ~30% of all kidney specific genes respectively. The results are publicly available at http://www.wlab.gu.se/lindahl/genebatteries.

Conclusion

21 co-expressed gene clusters were enriched for a total of 66 shared cis-regulatory sequence elements. A majority of these predictions represent novel cases of potential co-regulation of functionally coupled proteins. Critical technical parameters were evaluated, and the results and the methods provide a valuable resource for future experimental design.
BMP-6 inhibits growth of mature human B cells; induction of Smad phosphorylation and upregulation of Id1
Authors: Kersten Christian , Sivertsen Einar A , Hystad Marit E , Forfang Lise , Smeland Erlend B , Myklebust June H
Published: May 2005

Background

Bone morphogenetic proteins (BMPs) belong to the TGF-β superfamily and are secreted proteins with pleiotropic roles in many different cell types. A potential role of BMP-6 in the immune system has been implied by various studies of malignant and rheumatoid diseases. In the present study, we explored the role of BMP-6 in normal human peripheral blood B cells.

Results

The B cells were found to express BMP type I and type II receptors and BMP-6 rapidly induced phosphorylation of Smad1/5/8. Furthermore, Smad-phosphorylation was followed by upregulation of Id1 mRNA and Id1 protein, whereas Id2 and Id3 expression was not affected. Furthermore, we found that BMP-6 had an antiproliferative effect both in naïve (CD19+CD27-) and memory B cells (CD19+CD27+) stimulated with anti-IgM alone or the combined action of anti-IgM and CD40L. Additionally, BMP-6 induced cell death in activated memory B cells. Importantly, the antiproliferative effect of BMP-6 in B-cells was completely neutralized by the natural antagonist, noggin. Furthermore, B cells were demonstrated to upregulate BMP-6 mRNA upon stimulation with anti-IgM.

Conclusion

In mature human B cells, BMP-6 inhibited cell growth, and rapidly induced phosphorylation of Smad1/5/8 followed by an upregulation of Id1.
Serotypes, intimin variants and other virulence factors of eae positive Escherichia coli strains isolated from healthy cattle in Switzerland. Identification of a new intimin variant gene (eae-η2)
Authors: Blanco Miguel , Schumacher Sandra , Tasara Taurai , Zweifel Claudio , Blanco Jesús E , Dahbi Ghizlane , Blanco Jorge , Stephan Roger
Published: May 2005

Background

Enteropathogenic Escherichia coli (EPEC) and Shigatoxin-producing Escherichia coli (STEC) share the ability to introduce attaching-and-effacing (A/E) lesions on intestinal cells. The genetic determinants for the production of A/E lesions are located on the locus of enterocyte effacement (LEE), a pathogenicity island that also contains the genes encoding intimin (eae). This study reports information on the occurrence of eae positive E. coli carried by healthy cattle at the point of slaughter, and on serotypes, intimin variants, and further virulence factors of isolated EPEC and STEC strains.

Results

Of 51 eae positive bovine E. coli strains, 59% were classified as EPEC and 41% as STEC. EPEC strains belonged to 18 O:H serotypes, six strains to typical EPEC serogroups. EPEC strains harbored a variety of intimin variants with eae-β1 being most frequently found. Moreover, nine EPEC strains harbored ast A (EAST1), seven bfpA (bundlin), and only one strain was positive for the EAF plasmid. We have identified a new intimin gene (η2) in three bovine bfpA and astA-positive EPEC strains of serotype ONT:H45. STEC strains belonged to seven O:H serotypes with one serotype (O103:H2) accounting for 48% of the strains. The majority of bovine STEC strains (90%) belonged to five serotypes previously reported in association with hemolytic uremic syndrom (HUS), including one O157:H7 STEC strain. STEC strains harbored four intimin variants with eae-ε1 and eae-γ1 being most frequently found. Moreover, the majority of STEC strains carried only stx 1 genes (13 strains), and was positive for ehxA (18 strains) encoding for Enterohemolysin. Four STEC strains showed a virulence pattern characteristic of highly virulent human strains (stx 2 and eae positive).

Conclusion

Our data confirm that ruminants are an important source of serologically and genetically diverse intimin-harboring E. coli strains. Moreover, cattle have not only to be considered as important asymptomatic carriers of O157 STEC but can also be a reservoir of EPEC and eae positive non-O157 STEC, which are described in association with human diseases.
Use of re-randomized data in meta-analysis
Authors: Hozo Iztok , Djulbegovic Benjamin , Clark Otavio , Lyman Gary H
Published: May 2005

Background

Outcomes collected in randomized clinical trials are observations of random variables that should be independent and identically distributed. However, in some trials, the patients are randomized more than once thus violating both of these assumptions. The probability of an event is not always the same when a patient is re-randomized; there is probably a non-zero covariance coming from observations on the same patient. This is of particular importance to the meta-analysts.

Methods

We developed a method to estimate the relative error in the risk differences with and without re-randomization of the patients. The relative error can be estimated by an expression depending on the percentage of the patients who were re-randomized, multipliers (how many times more likely it is to repeat an event) for the probability of reoccurrences, and the ratio of the total events reported and the initial number of patients entering the trial.

Results

We illustrate our methods using two randomized trials testing growth factors in febrile neutropenia. We showed that under some circumstances the relative error of taking into account re-randomized patients was sufficiently small to allow using the results in the meta-analysis. Our findings indicate that if the study in question is of similar size to other studies included in the meta-analysis, the error introduced by re-randomization will only minimally affect meta-analytic summary point estimate.

We also show that in our model the risk ratio remains constant during the re-randomization, and therefore, if a meta-analyst is concerned about the effect of re-randomization on the meta-analysis, one way to sidestep the issue and still obtain reliable results is to use risk ratio as the measure of interest.

Conclusion

Our method should be helpful in the understanding of the results of clinical trials and particularly helpful to the meta-analysts to assess if re-randomized patient data can be used in their analyses.
Prevalence of oropharyngeal beta-lactamase-producing Capnocytophagaspp. in pediatric oncology patients over a ten-year period
Authors: Jolivet-Gougeon Anne , Tamanai-Shacoori Zohreh , Desbordes Laurent , Gandemer Virginie , Sixou Jean-Louis , Morvan-Graveline Nolwenn , Cormier Michel , Bonnaure-Mallet Martine
Published: May 2005

Background

The aim of this study was to evaluate the prevalence of beta-lactamase-producing Capnocytophaga isolates in young children hospitalized in the Pediatric Oncology Department of Hôpital Sud (Rennes, France) over a ten-year period (1993–2002).

Methods

In neutropenic children, a periodic survey of the oral cavity allows a predictive evaluation of the risk of systemic infections by Capnocytophaga spp. In 449 children with cancer, 3,053 samples were collected by oral swabbing and plated on TBBP agar. The susceptibility of Capnocytophaga isolates to five beta-lactams was determined.

Results

A total of 440 strains of Capnocytophaga spp. were isolated, 309 (70%) of which were beta-lactamase producers. The beta-lactamase-producing strains were all resistant to cefazolin, 86% to amoxicillin, and 63% to ceftazidime. The proportion of strains resistant to third-generation cephalosporins remained high throughout the ten-year study, while susceptibility to imipenem and amoxicillin combined with clavulanic acid was always conserved.

Conclusion

These results highlight the risk of antibiotic failure in Capnocytophaga infections and the importance of monitoring immunosuppressed patients and testing for antibiotic susceptibility and beta-lactamase production.
Technology-dependency among patients discharged from a children's hospital: a retrospective cohort study
Authors: Feudtner Chris , Villareale Nanci Larter , Morray Barbara , Sharp Virginia , Hays Ross M , Neff John M
Published: May 2005

Background

Advances in medical technology may be increasing the population of children who are technology-dependent (TD). We assessed the proportion of children discharged from a children's hospital who are judged to be TD, and determined the most common devices and number of prescription medications at the time of discharge.

Methods

Chart review of 100 randomly selected patients from all services discharged from a children's hospital during the year 2000. Data were reviewed independently by 4 investigators who classified the cases as TD if the failure or withdrawal of the technology would likely have adverse health consequences sufficient to require hospitalization. Only those cases where 3 or 4 raters agreed were classified as TD.

Results

Among the 100 randomly sampled patients, the median age was 7 years (range: 1 day to 24 years old), 52% were male, 86% primarily spoke English, and 54% were privately insured. The median length of stay was 3 days (range: 1 to 103 days). No diagnosis accounted for more than 5% of cases. 41% were deemed to be technology dependent, with 20% dependent upon devices, 32% dependent upon medications, and 11% dependent upon both devices and medications. Devices at the time of discharge included gastrostomy and jejeunostomy tubes (10%), central venous catheters (7%), and tracheotomies (1%). The median number of prescription medications was 2 (range: 0–13), with 12% of cases having 5 or more medications. Home care services were planned for 7% of cases.

Conclusion

Technology-dependency is common among children discharged from a children's hospital.
Atypical microbial infections of digestive tract may contribute to diarrhea in mucopolysaccharidosis patients: a MPS I case study
Authors: Węgrzyn Grzegorz , Kurlenda Julianna , Liberek Anna , Tylki-Szymańska Anna , Czartoryska Barbara , Piotrowska Ewa , Jakóbkiewicz-Banecka Joanna , Węgrzyn Alicja
Published: May 2005

Background

Mucopolysaccharidoses are heritable, metabolic diseases caused by deficiency in an activity of one of specific lysosomal enzymes involved in degradation of mucoplysaccharides (glycosaminoglycans). Among many medical problems of patients with mucopolysaccharidoses, there are frequent episodes of diarrhea of unknown etiology.

Case presentation

A girl, diagnosed enzymatically for mucopolysaccharidosis type I (deficiency of α-L-iduronidase) at the age of 3 years and 9 months, was investigated until the age of 5 years and 4 months. Frequent loose stools and episodes of diarrhea, often accompanied by vomiting, were encountered. Detailed microbiological analyses were performed and atypical microbial infections (most often enetropathogenic Escherichia coli, but also other species, like Pseudomonas aeruginosa or Staphylococcus aureus, as well as adenoviruses) of the digestive tract were found in most severe diarrhea episodes. Often, isolations of pathogenic bacterial strains from stools of the investigated patient suffering from diarrhea were not obvious during the first screening, and only detailed microbiological studies, including re-isolation of colonies, gave the results of isolation of particular pathogenic strains (especially in the case of enetropathogenic E. coli).

Conclusion

We conclude that atypical microbial infections of digestive tract may contribute significantly to diarrhea in mucopolysaccaridosis patients. Since isolated strains were not typical and their isolation was often possible only after detailed investigation (not during a standard screening), such atypical microbial infections of digestive tract of mucopolysaccharidosis patients could be usually overlooked to date. Importantly, these atypical infections could be effectively treated with antimicrobial agents.
Mental health literacy in an educational elite – an online survey among university students
Authors: Lauber Christoph , Ajdacic-Gross Vladeta , Fritschi Nadja , Stulz Niklaus , Rössler Wulf
Published: May 2005

Background

Mental health literacy is a prerequisite for early recognition and intervention in mental disorders. The aims of this paper are to determine whether a sample of university students recognise different symptoms of depression and schizophrenia and to reveal factors influencing correct recognition.

Methods

Bivariate and correspondence analyses of the results from an online survey among university students (n = 225).

Results

Most participants recognised the specific symptoms of depression. The symptoms of schizophrenia were acknowledged to a lower extent. Delusions of control and hallucinations of taste were not identified as symptoms of schizophrenia. Repeated revival of a trauma for depression and split personality for schizophrenia were frequently mistaken as symptoms of the respective disorders. Bivariate analyses demonstrated that previous interest in and a side job related to mental disorders, as well as previous personal treatment experience had a positive influence on symptom recognition. The correspondence analysis showed that male students of natural science, economics and philosophy are illiterate in recognising the symptoms depression and schizophrenia.

Conclusion

Among the educational elite, a wide variability in mental health literacy was found. Therefore, it's important for public mental health interventions to focus on the different recognition rates in depression and schizophrenia. Possibilities for contact must be arranged according to interest and activity (e.g., at work). In order to improve mental health literacy, finally, education and/or internship should be integrated in high school or apprenticeship curricula. Special emphasis must be given towards the effects of gender and stereotypes held about mental illnesses.
Overweight and obesity at school entry among migrant and German children: a cross-sectional study
Authors: Will Beata , Zeeb Hajo , Baune Bernhard T
Published: May 2005

Background

Overweight and obesity have become a global epidemic and are increasing rapidly in both childhood and adolescence. Obesity is linked both to socioeconomic status and to ethnicity among adults. It is unclear whether similar associations exist in childhood. The aim of the present study was to assess differences in overweight and obesity in migrant and German children at school entry.

Methods

The body mass index (BMI) was calculated for 525 children attending the 2002 compulsory pre-school medical examinations in 12 schools in Bielefeld, Germany. We applied international BMI cut off points for overweight and obesity by sex and age. The migration status of children was based on sociodemographic data obtained from parents who were interviewed separately.

Results

The overall prevalence of overweight in children aged 6–7 was 11.9% (overweight incl. obesity), the obesity prevalence was 2.5%. The prevalence of overweight and obesity was higher for migrant children (14.7% and 3.1%) than for German children (9.1% and 1.9%). When stratified by parental social status, migrant children had a significantly higher prevalence of overweight than German children in the highest social class. (27.6% vs. 10.0%, p = 0.032) Regression models including country/region and socioeconomic status as independent variables indicated similar results. The patterns of overweight among migrant children differed only slightly depending on duration of stay of their family in Germany.

Conclusion

Our data indicate that children from ethnic minorities in Germany are more frequently overweight or obese than German children. Social class as well as family duration of stay after immigration influence the pattern of overweight and obesity in children at school entry.
Liposome retention in size exclusion chromatography
Authors: Ruysschaert Tristan , Marque Audrey , Duteyrat Jean-Luc , Lesieur Sylviane , Winterhalter Mathias , Fournier Didier
Published: May 2005

Background

Size exclusion chromatography is the method of choice for separating free from liposome-encapsulated molecules. However, if the column is not presaturated with lipids this type of chromatography causes a significant loss of lipid material. To date, the mechanism of lipid retention is poorly understood. It has been speculated that lipid binds to the column material or the entire liposome is entrapped inside the void.

Results

Here we show that intact liposomes and their contents are retained in the exclusion gel. Retention depends on the pore size, the smaller the pores, the higher the retention. Retained liposomes are not tightly fixed to the beads and are slowly released from the gels upon direct or inverted eluent flow, long washing steps or column repacking. Further addition of free liposomes leads to the elution of part of the gel-trapped liposomes, showing that the retention is transitory. Trapping reversibility should be related to a mechanism of partitioning of the liposomes between the stationary phase, water-swelled polymeric gel, and the mobile aqueous phase.

Conclusion

Retention of liposomes by size exclusion gels is a dynamic and reversible process, which should be accounted for to control lipid loss and sample contamination during chromatography.
A simple technique for quantifying apoptosis in 96-well plates
Authors: Ribble Deborah , Goldstein Nathaniel B , Norris David A , Shellman Yiqun G
Published: May 2005

Background

Analyzing apoptosis has been an integral component of many biological studies. However, currently available methods for quantifying apoptosis have various limitations including multiple, sometimes cell-damaging steps, the inability to quantify live, necrotic and apoptotic cells at the same time, and non-specific detection (i.e. "false positive"). To overcome the shortcomings of current methods that quantify apoptosisin vitroand to take advantage of the 96-well plate format, we present here a modified ethidium bromide and acridine orange (EB/AO) staining assay, which may be performed entirely in a 96-well plate. Our method combines the advantages of the 96-well format and the conventional EB/AO method for apoptotic quantification.

Results

We compared our method and the conventional EB/AO method for quantifying apoptosis of suspension cells (Jurkat) and adherent cells (A375) under normal growth and apoptosis-inducing conditions. We found that our new EB/AO method achieved quantification results comparable to those produced using the conventional EB/AO method for both suspension and adherent cells.

Conclusion

By eliminating the detaching and washing steps, our method drastically reduces the time needed to perform the test, minimizes damage to adherent cells, and decreases the possibility of losing floating cells. Overall, our method is an improvement over the currently available techniques especially for adherent cells.
Clinical undergraduate training and assessment in primary health care: Experiences gained from Crete, Greece
Authors: Belos George , Lionis Christos , Fioretos Michael , Vlachonicolis John , Philalithis Anastas
Published: May 2005

Background

Primary Health Care (PHC) is increasingly being introduced into undergraduate medical education. In Greece, the Faculty of Medicine of the University of Crete was the first to introduce a 4-week long training in primary health care. This paper presents the experiences gained from the initial implementation of the teaching of practice-based primary care in rural Crete and reports on the assessment scale that was developed.

Methods

284 students' case write-ups from the 6 primary care units (PCUs) where they were allocated for the period 1990 to 1994 were analysed. The demographic data of the students and patients and the number of home visits were studied. Content analysis of the students' write-ups was carried out, using an assessment scale consisting of 10 dichotomous variables, in order to quantify eight (8) primary qualitative criteria.

Results

Internal reliability was estimated by the index KR20 = 0.67. Face and content validity was found to conform to the standards set for the course, while logistic linear regression analysis showed that the quality criteria could be used as an assessment scale.

The number of home visits carried out varied between the various different PCUs (p < 0.001) and more were reported in the write-ups that fulfilled criteria related to the biopsychosocial approach (p < 0.05). Nine quantitative criteria were fulfilled in more than 90% of case reports, but laboratory investigations were reported only in 69.0% of case reports. Statistically significant differences between the PCUs were observed in the fulfilment of criteria related to the community approach, patient assessment and information related to the patient's perception of the illness, but not to those related to aspects of clinical patient management. Differences in reporting laboratory investigations (p < 0.001) are explained by the lack of such facilities in some PCUs. Demographic characteristics of the patients or the students' do not affect the criteria.

Conclusion

The primary health care course achieved the objectives of introducing students to comprehensive, community oriented care, although there was variation between the PCUs. The assessment scale that was developed to analyse the case-write ups of the students provided data that can be used to evaluate the course.
Cardiac auscultation training of medical students: a comparison of electronic sensor-based and acoustic stethoscopes
Authors: Høyte Henning , Jensen Torstein , Gjesdal Knut
Published: May 2005

Background

To determine whether the use of an electronic, sensor based stethoscope affects the cardiac auscultation skills of undergraduate medical students.

Methods

Forty eight third year medical students were randomized to use either an electronic stethoscope, or a conventional acoustic stethoscope during clinical auscultation training. After a training period of four months, cardiac auscultation skills were evaluated using four patients with different cardiac murmurs. Two experienced cardiologists determined correct answers. The students completed a questionnaire for each patient. The thirteen questions were weighted according to their relative importance, and a correct answer was credited from one to six points.

Results

No difference in mean score was found between the two groups (p = 0.65). Grading and characterisation of murmurs and, if present, report of non existing murmurs were also rated. None of these yielded any significant differences between the groups.

Conclusion

Whether an electronic or a conventional stethoscope was used during training and testing did not affect the students' performance on a cardiac auscultation test.
Play dough as an educational tool for visualization of complicated cerebral aneurysm anatomy
Authors: Eftekhar Behzad , Ghodsi Mohammad , Ketabchi Ebrahim , Ghazvini Arman Rakan
Published: May 2005

Background

Imagination of the three-dimensional (3D) structure of cerebral vascular lesions using two-dimensional (2D) angiograms is one of the skills that neurosurgical residents should achieve during their training. Although ongoing progress in computer software and digital imaging systems has facilitated viewing and interpretation of cerebral angiograms enormously, these facilities are not always available.

Methods

We have presented the use of play dough as an adjunct to the teaching armamentarium for training in visualization of cerebral aneurysms in some cases.

Results

The advantages of play dough are low cost, availability and simplicity of use, being more efficient and realistic in training the less experienced resident in comparison with the simple drawings and even angiographic views from different angles without the need for computers and similar equipment. The disadvantages include the psychological resistance of residents to the use of something in surgical training that usually is considered to be a toy, and not being as clean as drawings or computerized images.

Conclusion

Although technology and computerized software using the patients' own imaging data seems likely to become more advanced in the future, use of play dough in some complicated cerebral aneurysm cases may be helpful in 3D reconstruction of the real situation.
Hospital service areas – a new tool for health care planning in Switzerland
Authors: Klauss Gunnar , Staub Lukas , Widmer Marcel , Busato André
Published: May 2005

Background

The description of patient travel patterns and variations in health care utilization may guide a sound health care planning process. In order to accurately describe these differences across regions with homogeneous populations, small area analysis (SAA) has proved as a valuable tool to create appropriate area models. This paper presents the methodology to create and characterize population-based hospital service areas (HSAs) for Switzerland.

Methods

We employed federal hospital discharge data to perform a patient origin study using small area analysis. Each of 605 residential regions was assigned to one of 215 hospital provider regions where the most frequent number of discharges took place. HSAs were characterized geographically, demographically, and through health utilization indices and rates that describe hospital use. We introduced novel planning variables extracted from the patient origin study and investigated relationships among health utilization indices and rates to understand patient travel patterns for hospital use. Results were visualized as maps in a geographic information system (GIS).

Results

We obtained 100 HSAs using a patient origin matrix containing over four million discharges. HSAs had diverse demographic and geographic characteristics. Urban HSAs had above average population sizes, while mountainous HSAs were scarcely populated but larger in size. We found higher localization of care in urban HSAs and in mountainous HSAs. Half of the Swiss population lives in service areas where 65% of hospital care is provided by local hospitals.

Conclusion

Health utilization indices and rates demonstrated patient travel patterns that merit more detailed analyses in light of political, infrastructural and developmental determinants. HSAs and health utilization indices provide valuable information for health care planning. They will be used to study variation phenomena in Swiss health care.
Trends in provision of photodynamic therapy and clinician attitudes: a tracker survey of a new health technology
Authors: Foy Robbie C , Foot Barny , Francis Jill , Chakravarthy Usha , Wormald Richard PL
Published: May 2005

Background

There has been debate about the cost-effectiveness of photodynamic therapy (PDT), a treatment for neovascular age-related macular degeneration. We have been monitoring trends for the provision of PDT in the UK National Health Service. The fourth annual 'tracker' survey took place as definitive National Institute for Clinical Excellence (NICE) guidance was issued. We assessed trends in PDT provision up to the point of release of the NICE guidance and identified likely sources of pressure on ophthalmologists to provide PDT.

Methods

National postal questionnaire survey of clinicians with potential responsibility for PDT provision. The survey explored reported local provision, beliefs about the effectiveness of PDT and what sources of opinion might influence attitudes towards providing PDT.

Results

The response rate was 73% (111/150). Almost half of the surveyed ophthalmology units routinely provided PDT, as part of a trend of steady growth in provision. The proportion of respondents who believed that further proof of effectiveness was required has also declined despite the absence of any new substantial evidence. Attitudes towards providing PDT were positive, on average, and were more strongly associated with perceived social pressure from local colleagues than from other sources. Local colleagues were seen as being most approving of PDT.

Conclusion

Those responsible for implementing the NICE guidance need to address ophthalmologists' beliefs about the evidence of effectiveness for PDT and draw upon supportive local individuals or networks to enhance the credibility of the guidance.
Cost-effectiveness of recommended nurse staffing levels for short-stay skilled nursing facility patients
Authors: Ganz David A , Simmons Sandra F , Schnelle John F
Published: May 2005

Background

Among patients in skilled nursing facilities for post-acute care, increased registered nurse, total licensed staff, and nurse assistant staffing is associated with a decreased rate of hospital transfer for selected diagnoses. However, the cost-effectiveness of increasing staffing to recommended levels is unknown.

Methods

Using a Markov cohort simulation, we estimated the incremental cost-effectiveness of recommended staffing versus median staffing in patients admitted to skilled nursing facilities for post-acute care. The outcomes of interest were life expectancy, quality-adjusted life expectancy, and incremental cost-effectiveness.

Results

The incremental cost-effectiveness of recommended staffing versus median staffing was $321,000 per discounted quality-adjusted life year gained. One-way sensitivity analyses demonstrated that the cost-effectiveness ratio was most sensitive to the likelihood of acute hospitalization from the nursing home. The cost-effectiveness ratio was also sensitive to the rapidity with which patients in the recommended staffing scenario recovered health-related quality of life as compared to the median staffing scenario. The cost-effectiveness ratio was not sensitive to other parameters.

Conclusion

Adopting recommended nurse staffing for short-stay nursing home patients cannot be justified on the basis of decreased hospital transfer rates alone, except in facilities with high baseline hospital transfer rates. Increasing nurse staffing would be justified if health-related quality of life of nursing home patients improved substantially from greater nurse and nurse assistant presence.
The costs and effects of a nationwide insecticide-treated net programme: the case of Malawi
Authors: Stevens Warren , Wiseman Virginia , Ortiz Juan , Chavasse Desmond
Published: May 2005

Background

Insecticide-treated nets (ITNs) are a proven intervention to reduce the burden of malaria, yet there remains a debate as to the best method of ensuring they are universally utilized. This study is a cost-effectiveness analysis of an intervention in Malawi that started in 1998, in Blantyre district, before expanding nationwide. Over the 5-year period, 1.5 million ITNs were sold.

Methods

The costs were calculated retrospectively through analysis of expenditure data. Costs and effects were measured as cost per treated-net year (cost/TNY) and cost per net distributed.

Results

The mean cost/TNY was calculated at $4.41, and the mean cost/ITN distributed at $2.63. It also shows evidence of economies of scale, with the cost/TNY falling from $7.69 in year one (72,196 ITN) to $3.44 in year five (720,577 ITN). Cost/ITN distributed dropped from $5.04 to $1.92.

Conclusion

Combining targeting and social marketing has the potential of being both cost-effective and capable of achieving high levels of coverage, and it is possible that increasing returns to scale can be achieved.
The Bhopal disaster and its aftermath: a review
Authors: Broughton Edward
Published: May 2005

On December 3 1984, more than 40 tons of methyl isocyanate gas leaked from a pesticide plant in Bhopal, India, immediately killing at least 3,800 people and causing significant morbidity and premature death for many thousands more. The company involved in what became the worst industrial accident in history immediately tried to dissociate itself from legal responsibility. Eventually it reached a settlement with the Indian Government through mediation of that country's Supreme Court and accepted moral responsibility. It paid $470 million in compensation, a relatively small amount of based on significant underestimations of the long-term health consequences of exposure and the number of people exposed. The disaster indicated a need for enforceable international standards for environmental safety, preventative strategies to avoid similar accidents and industrial disaster preparedness.

Since the disaster, India has experienced rapid industrialization. While some positive changes in government policy and behavior of a few industries have taken place, major threats to the environment from rapid and poorly regulated industrial growth remain. Widespread environmental degradation with significant adverse human health consequences continues to occur throughout India.
Discovery of a new human T-cell lymphotropic virus (HTLV-3) in Central Africa
Authors: Calattini Sara , Chevalier Sébastien Alain , Duprez Renan , Bassot Sylviane , Froment Alain , Mahieux Renaud , Gessain Antoine
Published: May 2005

Human T-cell Leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are pathogenic retroviruses that infect humans and cause severe hematological and neurological diseases. Both viruses have simian counterparts (STLV-1 and STLV-2). STLV-3 belongs to a third group of lymphotropic viruses which infect numerous African monkeys species. Among 240 Cameroonian plasma tested for the presence of HTLV-1 and/or HTLV-2 antibodies, 48 scored positive by immunofluorescence. Among those, 27 had indeterminate western-blot pattern. PCR amplification ofpolandtaxregions, using HTLV-1, -2 and STLV-3 highly conserved primers, demonstrated the presence of a new human retrovirus in one DNA sample.tax(180 bp) andpol(318 bp) phylogenetic analyses demonstrated the strong relationships between the novel human strain (Pyl43) and STLV-3 isolates from Cameroon. The virus, that we tentatively named HTLV-3, originated from a 62 years old Bakola Pygmy living in a remote settlement in the rain forest of Southern Cameroon. The plasma was reactive on MT2 cells but was negative on C19 cells. The HTLV 2.4 western-blot exhibited a strong reactivity to p19 and a faint one to MTA-1. On the INNO-LIA strip, it reacted faintly with the generic p19 (I/II), but strongly to the generic gp46 (I/II) and to the specific HTLV-2 gp46. The molecular relationships between Pyl43 and STLV-3 are thus not paralleled by the serological results, as most of the STLV-3 infected monkeys have an "HTLV-2 like" WB pattern. In the context of the multiple interspecies transmissions which occurred in the past, and led to the present-day distribution of the PTLV-1, it is thus very tempting to speculate that this newly discovered human retrovirus HTLV-3 might be widespread, at least in the African continent.
Genetic polymorphisms in the matrix metalloproteinase 12 gene (MMP12) and breast cancer risk and survival: the Shanghai Breast Cancer Study
Authors: Shin Aesun , Cai Qiuyin , Shu Xiao-Ou , Gao Yu-Tang , Zheng Wei
Published: May 2005

Introduction

Matrix metalloproteinase 12 (MMP12) is a proteolytic enzyme responsible for cleavage of plasminogen to angiotensin, which has an angiostatic effect. Using data from a population-based case–control study conducted among Chinese women in Shanghai, we evaluated the association of breast cancer risk and survival with two common polymorphisms in the MMP12 gene: A-82G in the promoter region and A1082G in exon, resulting in an amino acid change of asparagine to serine.

Methods

Included in the study were 1,129 cases and 1,229 age-frequency-matched population controls. Breast cancer patients were followed up to determine the intervals of overall survival and disease-free survival.

Results

The frequencies of the G allele in the A-82G and A1082G polymorphism among controls were 0.029 and 0.107, respectively. There were no associations between MMP12 polymorphisms and breast cancer risk. Patients with the AG or GG genotype of the A1082G polymorphism showed poorer overall survival (though the difference was not statistically significant) than patients with the AA genotype (hazard ratio 1.36, 95% CI 0.92 to 2.00).

Conclusion

This result suggests that MMP12 A1082G polymorphism may be related to prognosis in breast cancer patients. Additional studies with larger sample sizes are warranted.