bluuebunny/crossref_metadata_2025 huggingface dataset:
Interventions aimed at reducing problems in adult patients discharged from hospital to home: a systematic meta-review
Authors: Mistiaen Patriek , Francke Anneke L , Poot Else
Published: May 2007

Background

Many patients encounter a variety of problems after discharge from hospital and many discharge (planning and support) interventions have been developed and studied. These primary studies have already been synthesized in several literature reviews with conflicting conclusions. We therefore set out a systematic review of the reviews examining discharge interventions. The objective was to synthesize the evidence presented in literature on the effectiveness of interventions aimed to reduce post-discharge problems in adults discharged home from an acute general care hospital.

Methods

A comprehensive search of seventeen literature databases and twenty-five websites was performed for the period 1994–2004 to find relevant reviews. A three-stage inclusion process consisting of initial sifting, checking full-text papers on inclusion criteria, and methodological assessment, was performed independently by two reviewers. Data on effects were synthesized by use of narrative and tabular methods.

Results

Fifteen systematic reviews met our inclusion criteria. All reviews had to deal with considerable heterogeneity in interventions, populations and outcomes, making synthesizing and pooling difficult.

Although a statistical significant effect was occasionally found, most review authors reached no firm conclusions that the discharge interventions they studied were effective.

We found limited evidence that some interventions may improve knowledge of patients, may help in keeping patients at home or may reduce readmissions to hospital. Interventions that combine discharge planning and discharge support tend to lead to the greatest effects. There is little evidence that discharge interventions have an impact on length of stay, discharge destination or dependency at discharge. We found no evidence that discharge interventions have a positive impact on the physical status of patients after discharge, on health care use after discharge, or on costs.

Conclusion

Based on fifteen high quality systematic reviews, there is some evidence that some interventions may have a positive impact, particularly those with educational components and those that combine pre-discharge and post-discharge interventions. However, on the whole there is only limited summarized evidence that discharge planning and discharge support interventions have a positive impact on patient status at hospital discharge, on patient functioning after discharge, on health care use after discharge, or on costs.
Graduates of Lebanese medical schools in the United States: an observational study of international migration of physicians
Authors: Akl Elie A , Maroun Nancy , Major Stella , Chahoud Bechara , Schünemann Holger J
Published: May 2007

Background

As healthcare systems around the world are facing increasing physician shortages, more physicians are migrating from low to high income countries. As an illustrative case of international migration of physicians, we evaluated the current number and historical trends of Lebanese medical graduates (LMG) in the US, and compared their characteristics to those of US medical graduates (USMG) and other international medical graduates (IMG).

Methods

We evaluated the number of LMG using the 2004 the American Medical Association Physicians' Professional Data (AMA-PPD) and then compared it to the number of graduates of other countries. We evaluated the historical trends using the 1978–2004 historical files of the AMA-PPD. We analyzed the characteristics of all LMG and compared them to a random sample of 1000 USMG and a random sample of 1000 IMG using the 2004 AMA-PPD.

Results

In 2004, there were 2,796 LMG in the US, constituting 1.3% of all IMG. Compared to other foreign countries contributing to the US physician workforce, Lebanon ranked 2nd after adjusting for country population size (about 4 million) and 21st overall. About 40% of those who graduated from Lebanese medical schools in the last 25 years are currently active physicians in the US. Since 1978, the number of LMG in the US showed a consistent upward trend at a rate of approximately 71 additional graduates per year. Compared with USMG and IMG, LMG were more likely to work in medical research (OR = 2.31; 95% Confidence Interval (CI) = 1.21; 4.43 and OR = 2.63; 95% CI = 1.34; 5.01, respectively) and to be board certified (OR = 1.43; 95% CI = 1.14; 1.78 and OR = 2.04; 95% CI = 1.65;2.53, respectively) and less likely to be in family practice (OR = 0.14; 95% CI = 0.10; 0.19 and OR = 0.18; 95% CI = 0.12; 0.26, respectively).

Conclusion

Given the magnitude and historical trends of migration of LMG to the US, further exploration of its causes and impact is warranted. High income countries should consider the consequences of their human resources policies on both low income countries' and their own healthcare systems.
Decision-making regarding total knee replacement surgery: A qualitative meta-synthesis
Authors: O'Neill Tracey , Jinks Clare , Ong Bie Nio
Published: May 2007

Background

Knee osteoarthritis is a highly prevalent condition that can result in disability and reduced quality of life. The evidence suggests that total knee replacement surgery (TKR) is an effective intervention for patients with severe knee problems, but there is also an unmet need for this treatment in the UK. To help understand the reason for this unmet need, the aim of this study was to explore the factors that influence the decision-making process of TKR surgery by synthesising the available evidence from qualitative research on this topic.

Methods

A meta-synthesis was undertaken. This involved sevens steps: getting started, deciding what is relevant to the initial interest, reading the studies, determining how the studies are related, translating the studies into one another, synthesising translations, and finally, expressing the synthesis. Second-order and third-order interpretations regarding decision-making in TKR surgery were drawn from the literature.

Results

Ten qualitative studies were found and are included in the synthesis. The evidence suggests that social and cultural categories of aging have shaped the expectation of knee osteoarthritis, and this in turn shapes patients' expectations of treatment options. The role of the health care professional was the strongest theme to emerge across all ten studies. Coping strategies and life context determine short and longer-term outcomes of TKR.

Conclusion

The decision-making process regarding TKR surgery is extremely complex, as patients have weigh up numerous considerations before they can make a decision about surgery. By synthesising ten qualitative studies, we have illuminated the importance of the health care professional during this process.
Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE)
Authors: Donnan Peter T , McLernon David , Steinke Douglas , Ryder Stephen , Roderick Paul , Sullivan Frank M , Rosenberg William , Dillon John F
Published: May 2007

Background

Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services.

The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs.

Methods/Design

A population-based retrospective cohort study will follow up all those who have had an incident liver function test (LFT) in primary care to subsequent liver disease or mortality over a period of 15 years (approx. 2.3 million tests in 99,000 people). The study is set in Primary Care in the region of Tayside, Scotland (pop approx. 429,000) between 1989 and 2003. The target population consists of patients with no recorded clinical signs or symptoms of liver disease and registered with a GP. The health technologies being assessed are LFTs, viral and auto-antibody tests, ultrasound, CT, MRI and liver biopsy.

The study will utilise the Epidemiology of Liver Disease In Tayside (ELDIT) database to determine the outcomes of liver disease. These are based on hospital admission data (Scottish Morbidity Record 1), dispensed medication records, death certificates, and examination of medical records from Tayside hospitals. A sample of patients (n = 150) with recent initial ALF tests or invitation to biopsy will complete questionnaires to obtain quality of life data and anxiety measures. Cost-effectiveness and cost utility Markov model analyses will be performed from health service and patient perspectives using standard NHS costs. The findings will also be used to develop a computerised clinical decision support tool.

Discussion

The results of this study will be widely disseminated to primary care, as well as G.I. hospital specialists through publications and presentations at local and national meetings and the project website. This will facilitate optimal decision-making both for the benefit of the patient and the National Health Service.
Translating and validating a Training Needs Assessment tool into Greek
Authors: Markaki Adelais , Antonakis Nikos , Hicks Carolyn M , Lionis Christos
Published: May 2007

Background

The translation and cultural adaptation of widely accepted, psychometrically tested tools is regarded as an essential component of effective human resource management in the primary care arena. The Training Needs Assessment (TNA) is a widely used, valid instrument, designed to measure professional development needs of health care professionals, especially in primary health care. This study aims to describe the translation, adaptation and validation of the TNA questionnaire into Greek language and discuss possibilities of its use in primary care settings.

Methods

A modified version of the English self-administered questionnaire consisting of 30 items was used. Internationally recommended methodology, mandating forward translation, backward translation, reconciliation and pretesting steps, was followed. Tool validation included assessing item internal consistency, using the alpha coefficient of Cronbach. Reproducibility (test – retest reliability) was measured by the kappa correlation coefficient. Criterion validity was calculated for selected parts of the questionnaire by correlating respondents' research experience with relevant research item scores. An exploratory factor analysis highlighted how the items group together, using a Varimax (oblique) rotation and subsequent Cronbach's alpha assessment.

Results

The psychometric properties of the Greek version of the TNA questionnaire for nursing staff employed in primary care were good. Internal consistency of the instrument was very good, Cronbach's alpha was found to be 0.985 (p < 0.001) and Kappa coefficient for reproducibility was found to be 0.928 (p < 0.0001). Significant positive correlations were found between respondents' current performance levels on each of the research items and amount of research involvement, indicating good criterion validity in the areas tested. Factor analysis revealed seven factors with eigenvalues of > 1.0, KMO (Kaiser-Meyer-Olkin) measure of sampling adequacy = 0.680 and Bartlett's test of sphericity, p < 0.001.

Conclusion

The translated and adapted Greek version is comparable with the original English instrument in terms of validity and reliability and it is suitable to assess professional development needs of nursing staff in Greek primary care settings.
Sagittal abdominal diameter as a marker of inflammation and insulin resistance among immigrant women from the Middle East and native Swedish women: a cross-sectional study
Authors: Petersson Helena , Daryani Achraf , Risérus Ulf
Published: May 2007

Background

Immigrant women from the Middle East have elevated risk of cardiovascular disease. Sagittal abdominal diameter (SAD), a simple marker of intra-abdominal fat, predicts insulin resistance and cardiovascular mortality in men. Its usefulness in immigrant women is however unknown. To investigate the predictive role of SAD compared to other anthropometric measures, we examined a random sample of native-Swedes and immigrant women from the Middle East living in Sweden.

Methods

157 women participated in the study; 107 immigrants and 50 natives. Anthropometric measurements (SAD, body mass index [BMI], waist circumference [WC] and waist-to-hip ratio [WHR]; all measured in supine position) and cardiovascular risk factors (C-reactive protein [CRP], insulin, glucose, insulin resistance [HOMA-IR], blood pressure and serum lipids) were assessed. The anthropometric measures were compared in their relation to cardiovascular risk factors using linear regression analyses.

Results

Overall, SAD showed a slightly higher correlation with most cardiovascular risk factors, especially insulin resistance, insulin, CRP, apolipoprotein B and triglycerides (all P-values < 0.01) than other anthropometric measures. BMI was however a better predictor of HDL cholesterol. SAD explained a greater proportion of the variation of insulin resistance and CRP levels, even independently of the other anthropometric measures.

Conclusion

SAD identifies insulin resistance, subclinical inflammation or raised serum lipids in a Swedish population with a large proportion of immigrant women from the Middle East. If these results could be confirmed in a larger population, SAD could be a more clinically useful risk marker than other anthropometric measures in women at high risk of cardiovascular disease.
Clinical and medication profiles stratified by household income in patients referred for diabetes care
Authors: Rabi Doreen M , Edwards Alun L , Svenson Lawrence W , Sargious Peter M , Norton Peter , Larsen Erik T , Ghali William A
Published: May 2007

Background

Low income individuals with diabetes are at particularly high risk for poor health outcomes. While specialized diabetes care may help reduce this risk, it is not currently known whether there are significant clinical differences across income groups at the time of referral. The objective of this study is to determine if the clinical profiles and medication use of patients referred for diabetes care differ across income quintiles.

Methods

This cross-sectional study was conducted using a Canadian, urban, Diabetes Education Centre (DEC) database. Clinical information on the 4687 patients referred to the DEC from May 2000 – January 2002 was examined. These data were merged with 2001 Canadian census data on income. Potential differences in continuous clinical parameters across income quintiles were examined using regression models. Differences in medication use were examined using Chi square analyses.

Results

Multivariate regression analysis indicated that income was negatively associated with BMI (p < 0.0005) and age (p = 0.023) at time of referral. The highest income quintiles were found to have lower serum triglycerides (p = 0.011) and higher HDL-c (p = 0.008) at time of referral. No significant differences were found in HBA1C, LDL-c or duration of diabetes. The Chi square analysis of medication use revealed that despite no significant differences in HBA1C, the lowest income quintiles used more metformin (p = 0.001) and sulfonylureas (p < 0.0005) than the wealthy. Use of other therapies were similar across income groups, including lipid lowering medications. High income patients were more likely to be treated with diet alone (p < 0.0005).

Conclusion

Our findings demonstrate that low income patients present to diabetes clinic older, heavier and with a more atherogenic lipid profile than do high income patients. Overall medication use was higher among the lower income group suggesting that differences in clinical profiles are not the result of under-treatment, thus invoking lifestyle factors as potential contributors to these findings.
An improved system for estradiol-dependent regulation of gene expression in yeast
Authors: Quintero María J , Maya Douglas , Arévalo-Rodríguez Miguel , Cebolla Ángel , Chávez Sebastián
Published: May 2007

Background

Saccharomyces cerevisiae is widely utilized in basic research as a model eukaryotic organism and in biotechnology as a host for heterologous protein production. Both activities demand the use of highly regulated systems, able to provide accurate control of gene expression in functional analysis, and timely recombinant protein synthesis during fermentative production. The tightly regulated GAL1-10 promoter is commonly used. However, induction of the GAL system requires the presence of the rather expensive inducer galactose and the absence of glucose in the culture media. An alternative to regulate transcription driven by GAL promoters, free of general metabolic changes, is the incorporation of the hybrid Gal4-ER-VP16 protein developed by D. Picard. This chimeric protein provides galactose-independent activation of transcription from GAL promoters in response to β-estradiol, even in the presence of glucose. However, constitutive expression of this transactivator results in relatively high basal activity of the GAL promoters, therefore limiting the gene expression capacity that is required for a number of applications.

Results

In order to improve this expression tool, we have introduced additional regulatory elements allowing a simultaneous control of both the abundance and the intrinsic activity of the Gal4-ER-VP16 chimeric transactivator. The most efficient combination was obtained by placing the coding sequence of the hybrid activator under the control of the GAL1 promoter. This configuration results in an amplification feedback loop that is triggered by the hormone, and ultimately leads to the enhanced regulation of recombinant genes when these are also driven by a GAL1 promoter. The basal expression level of this system is as low as that of native GAL-driven genes in glucose-containing media.

Conclusion

The feedback regulatory loop that we have engineered allows a 250-fold induction of the regulated gene, without increasing the basal activity of the target promoter, and achieving a 12-fold higher regulation efficiency than the previous configuration.
Evidence for glycosylation on a DNA-binding protein of Salmonella enterica
Authors: Hanna Ebert S , Roque-Barreira Maria-Cristina , Bernardes Emerson S , Panunto-Castelo Ademilson , Sousa Marcelo V , Almeida Igor C , Brocchi Marcelo
Published: May 2007

Background

All organisms living under aerobic atmosphere have powerful mechanisms that confer their macromolecules protection against oxygen reactive species. Microorganisms have developed biomolecule-protecting systems in response to starvation and/or oxidative stress, such as DNA biocrystallization with Dps (DNA-binding protein fromstarved cells). Dps is a protein that is produced in large amounts when the bacterial cell faces harm, which results in DNA protection. In this work, we evaluated the glycosylation in the Dps extracted fromSalmonella entericaserovar Typhimurium. This Dps was purified from the crude extract as an 18-kDa protein, by means of affinity chromatography on an immobilized jacalin column.

Results

TheN-terminal sequencing of the jacalin-bound protein revealed 100% identity with the Dps ofS. entericaserovar Typhimurium. Methyl-alpha-galactopyranoside inhibited the binding of Dps to jacalin in an enzyme-linked lectin assay, suggesting that the carbohydrate recognition domain (CRD) of jacalin is involved in the interaction with Dps. Furthermore, monosaccharide compositional analysis showed that Dps contained mannose, glucose, and an unknown sugar residue. Finally, jacalin-binding Dps was detected in larger amounts during the bacterial earlier growth periods, whereas high detection of total Dps was verified throughout the bacterial growth period.

Conclusion

Taken together, these results indicate that Dps undergoes post-translational modifications in the pre- and early stationary phases of bacterial growth. There is also evidence that a small mannose-containing oligosaccharide is linked to this bacterial protein.
Vanillin production using metabolically engineered Escherichia coli under non-growing conditions
Authors: Barghini Paolo , Di Gioia Diana , Fava Fabio , Ruzzi Maurizio
Published: May 2007

Background

Vanillin is one of the most important aromatic flavour compounds used in the food and cosmetic industries. Natural vanillin is extracted from vanilla beans and is relatively expensive. Moreover, the consumer demand for natural vanillin highly exceeds the amount of vanillin extracted by plant sources. This has led to the investigation of other routes to obtain this flavour such as the biotechnological production from ferulic acid. Studies concerning the use of engineered recombinant Escherichia coli cells as biocatalysts for vanillin production are described in the literature, but yield optimization and biotransformation conditions have not been investigated in details.

Results

Effect of plasmid copy number in metabolic engineering of E. coli for the synthesis of vanillin has been evaluated by the use of genes encoding feruloyl-CoA synthetase and feruloyl hydratase/aldolase from Pseudomonas fluorescens BF13. The higher vanillin production yield was obtained using resting cells of E. coli strain JM109 harbouring a low-copy number vector and a promoter exhibiting a low activity to drive the expression of the catabolic genes. Optimization of the bioconversion of ferulic acid to vanillin was accomplished by a response surface methodology. The experimental conditions that allowed us to obtain high values for response functions were 3.3 mM ferulic acid and 4.5 g/L of biomass, with a yield of 70.6% and specific productivity of 5.9 μmoles/g × min after 3 hours of incubation. The final concentration of vanillin in the medium was increased up to 3.5 mM after a 6-hour incubation by sequential spiking of 1.1 mM ferulic acid. The resting cells could be reused up to four times maintaining the production yield levels over 50%, thus increasing three times the vanillin obtained per gram of biomass.

Conclusion

Ferulic acid can be efficiently converted to vanillin, without accumulation of undesirable vanillin reduction/oxidation products, using E. coli JM109 cells expressing genes from the ferulic acid-degrader Pseudomonas fluorescens BF13. Optimization of culture conditions and bioconversion parameters, together with the reuse of the biomass, leaded to a final production of 2.52 g of vanillin per liter of culture, which is the highest found in the literature for recombinant strains and the highest achieved so far applying such strains under resting cells conditions.
Potential and utilization of thermophiles and thermostable enzymes in biorefining
Authors: Turner Pernilla , Mamo Gashaw , Karlsson Eva Nordberg
Published: May 2007

In today's world, there is an increasing trend towards the use of renewable, cheap and readily available biomass in the production of a wide variety of fine and bulk chemicals in different biorefineries. Biorefineries utilize the activities of microbial cells and their enzymes to convert biomass into target products. Many of these processes require enzymes which are operationally stable at high temperature thus allowing e.g. easy mixing, better substrate solubility, high mass transfer rate, and lowered risk of contamination. Thermophiles have often been proposed as sources of industrially relevant thermostable enzymes. Here we discuss existing and potential applications of thermophiles and thermostable enzymes with focus on conversion of carbohydrate containing raw materials. Their importance in biorefineries is explained using examples of lignocellulose and starch conversions to desired products. Strategies that enhance thermostablity of enzymes both in vivo and in vitro are also assessed. Moreover, this review deals with efforts made on developing vectors for expressing recombinant enzymes in thermophilic hosts.
Pathway interactions between MAPKs, mTOR, PKA, and the glucocorticoid receptor in lymphoid cells
Authors: Miller Aaron L , Garza Anna S , Johnson Betty H , Thompson E Brad
Published: May 2007

Background

Glucocorticoids are frequently used as a primary chemotherapeutic agent in many types of human lymphoid malignancies because they induce apoptosis through activation of the glucocorticoid receptor, with subsequent alteration of a complex network of cellular mechanisms. Despite clinical usage for over fifty years, the complete mechanism responsible for glucocorticoid-related apoptosis or resistance remains elusive. The mitogen-activated protein kinase pathway is a signal transduction network that influences a variety of cellular responses through phosphorylation of specific target substrates, including the glucocorticoid receptor. In this study we have evaluated the pharmaceutical scenarios which converge on the mitogen-activated protein kinase pathway to alter glucocorticoid sensitivity in clones of human acute lymphoblastic CEM cells sensitive and refractory to apoptosis in response to the synthetic glucocorticoid dexamethasone.

Results

The glucocorticoid-resistant clone CEM-C1-15 displays a combination of high constitutive JNK activity and dexamethasone-induced ERK activity with a weak induction of p38 upon glucocorticoid treatment. The cells become sensitive to glucocorticoid-evoked apoptosis after: (1) inhibition of JNK and ERK activity, (2) stimulation of the cAMP/PKA pathway with forskolin, or (3) inhibition of mTOR with rapamycin. Treatments 1–3 in combination with dexamethasone alter the intracellular balance of phospho-MAPKs by lowering JNK phosphorylation and increasing the level of glucocorticoid receptor phosphorylated at serine 211, a modification known to enhance receptor activity.

Conclusion

Our data support the hypothesis that mitogen-activated protein kinases influence the ability of certain malignant lymphoid cells to undergo apoptosis when treated with glucocorticoid. Activated/phosphorylated JNK and ERK appear to counteract corticoid-dependent apoptosis. Inhibiting these MAPKs restores corticoid sensitivity to a resistant clone of CEM cells. Forskolin, which activates the cAMP pathway, and rapamycin, which inhibits mTOR, also inhibit JNK. Further, the sensitizing treatments result in a largely dexamethasone-dependent increase in the total pool of glucocorticoid receptor phosphorylated at serine 211. The phospho-serine 211 receptor is known to be more potent in activating gene transcription and apoptosis. The interactive effects demonstrated here in reverting resistant cells to corticoid sensitivity could provide therapeutic clinical potential in the treatment of lymphoid malignancies.
Bone marrow chimeric mice reveal a dual role for CD36 in Plasmodium berghei ANKA infection
Authors: Cunha-Rodrigues Margarida , Portugal Sílvia , Febbraio Maria , Mota Maria M
Published: May 2007

Background

Adhesion of Plasmodium-infected red blood cells (iRBC) to different host cells, ranging from endothelial to red blood cells, is associated to malaria pathology. In vitro studies have shown the relevance of CD36 for adhesion phenotypes of Plasmodium falciparum iRBC such as sequestration, platelet mediated clumping and non-opsonic uptake of iRBC. Different adhesion phenotypes involve different host cells and are associated with different pathological outcomes of disease. Studies with different human populations with CD36 polymorphisms failed to attribute a clear role to CD36 expression in human malaria. Up to the present, no in vivo model has been available to study the relevance of different CD36 adhesion phenotypes to the pathological course of Plasmodium infection.

Methods

Using CD36-deficient mice and their control littermates, CD36 bone marrow chimeric mice, expressing CD36 exclusively in haematopoietic cells or in non-haematopoietic cells, were generated. Irradiated CD36-/- and wild type mice were also reconstituted with syngeneic cells to control for the effects of irradiation. The reconstituted mice were infected with Plasmodium berghei ANKA and analysed for the development of blood parasitaemia and neurological symptoms.

Results

All mice reconstituted with syngeneic bone marrow cells as well as chimeric mice expressing CD36 exclusively in non-haematopoietic cells died from experimental cerebral malaria between day 6 and 12 after infection. A significant proportion of chimeric mice expressing CD36 only in haematopoietic cells did not die from cerebral malaria.

Conclusion

The analysis of bone marrow chimeric mice reveals a dual role of CD36 in P. berghei ANKA infection. Expression of CD36 in haematopoietic cells, most likely macrophages and dendritic cells, has a beneficial effect that is masked in normal mice by adverse effects of CD36 expression in non-haematopoietic cells, most likely endothelial cells.
Microsatellite polymorphism within pfcrt provides evidence of continuing evolution of chloroquine-resistant alleles in Papua New Guinea
Authors: DaRe Jeana T , Mehlotra Rajeev K , Michon Pascal , Mueller Ivo , Reeder John , Sharma Yagya D , Stoneking Mark , Zimmerman Peter A
Published: May 2007

Background

Polymorphism in the pfcrt gene underlies Plasmodium falciparum chloroquine resistance (CQR), as sensitive strains consistently carry lysine (K), while CQR strains carry threonine (T) at the codon 76. Previous studies have shown that microsatellite (MS) haplotype variation can be used to study the evolution of CQR polymorphism and to characterize intra- and inter-population dispersal of CQR in Papua New Guinea (PNG).

Methods

Here, following identification of new polymorphic MS in introns 2 and 3 within the pfcrt gene (msint2 and msint3, respectively), locus-by-locus and haplotype heterozygosity (H) analyses were performed to determine the distribution of this intronic polymorphism among pfcrt chloroquine-sensitive and CQR alleles.

Results

For MS flanking the pfcrt CQR allele, H ranged from 0.07 (B5M77, -18 kb) to 0.094 (9B12, +2 kb) suggesting that CQ selection pressure was responsible for strong homogenisation of this gene locus. In a survey of 206 pfcrt-SVMNT allele-containing field samples from malaria-endemic regions of PNG, H for msint2 was 0.201. This observation suggests that pfcrt msint2 exhibits a higher level of diversity than what is expected from the analyses of pfcrt flanking MS. Further analyses showed that one of the three haplotypes present in the early 1980's samples has become the predominant haplotype (frequency = 0.901) in CQR parasite populations collected after 1995 from three PNG sites, when CQR had spread throughout malaria-endemic regions of PNG. Apparent localized diversification of pfcrt haplotypes at each site was also observed among samples collected after 1995, where minor CQR-associated haplotypes were found to be unique to each site.

Conclusion

In this study, a higher level of diversity at MS loci within the pfcrt gene was observed when compared with the level of diversity at pfcrt flanking MS. While pfcrt (K76T) and its immediate flanking region indicate homogenisation in PNG CQR parasite populations, pfcrt intronic MS variation provides evidence that the locus is still evolving. Further studies are needed to determine whether these intronic MS introduce the underlying genetic mechanisms that may generate pfcrt allelic diversity.
Rapid detection of Pfcrt and Pfmdr1 mutations in Plasmodium falciparum isolates by FRET and in vivo response to chloroquine among children from Osogbo, Nigeria
Authors: Ojurongbe Olusola , Ogungbamigbe Titus O , Fagbenro-Beyioku Adetayo F , Fendel Rolf , Kremsner Peter G , Kun Jürgen FJ
Published: May 2007

Background

Chloroquine (CQ) has been in use in Africa for a long time. Because of misuse, this drug has now lost its efficacy due to the emergence of resistance strains in most parts of Africa. Recently, it was shown that after chloroquine has been withdrawn from the market, chloroquine-sensitive Plasmodium falciparum re-emerged and chloroquine could again be used successfully as an antimalarial. Surveillance of parasite populations is, therefore, important to decide whether chloroquine could be re-introduced.

Methods

To estimate the prevalence of the most pivotal polymorphisms, including Pfcrt K76T, Pfmdr1 N86Y and Pfmdr1 Y184F mutations, and their contributions to the outcome of CQ treatment, isolates from Osogbo Western Nigeria were tested using the Fluorescence Resonance Energy Transfer (FRET) method on a real-time PCR instrument.

Results

116 children with acute uncomplicated P. falciparum malaria infections were treated with the standard dosage of CQ and followed-up for 28 days. Blood samples were collected on filter paper at enrollment and during follow-up for identification of parasite carrying the chloroquine resistant transporter (pfcrt) and P. falciparum-multi drug resistance (pfmdr1) gene mutations. Parasitological assessment of response to treatment showed that 62% of the patients were cured and 38% failed the CQ treatment. The presence of single mutant pfcrt (T76) alleles (P = 0.003) and in combination with mutant pfmdr1 Y86 (P = 0.028) was significantly associated with in vivo CQR. No other mutation on its own or in combinations was significantly associated with treatment outcome. Mutant pfcrt was more prevalent in both pre- and post-treatment isolates. No association was observed between age or initial level of parasitaemia and chloroquine treatment outcome.

Conclusion

The result established the usefulness and accuracy of real time PCR in pfcrt and pfmdr1 mutation detection and also give further evidence to the reliability of the pfcrt T76 point mutation as a molecular marker for CQ resistance.
Severe sepsis due to severe falciparum malaria and leptospirosis co-infection treated with activated protein C
Authors: Srinivas Rajagopala , Agarwal Ritesh , Gupta Dheeraj
Published: May 2007

Co-infection with falciparum malaria and leptospirosis is uncommon. The aim of this study is to report a case of severe sepsis secondary to dual infection with falciparum malaria and leptospirosis. The literature is also reviewed on the clinical course of such co-infections, and the possible mechanisms and treatment of patients with life-threatening malaria and leptospirosis with activated protein C. The patient was a 25-year old male admitted in the Respiratory Intensive Care Unit (RICU) with fever, haemolysis, acute renal failure, hepatitis, acute lung injury (ALI) and altered sensorium. A syndromic evaluation was done and investigations revealed falciparum parasitaemia. He was treated with parenteral artesunate, ceftriaxone and doxycycline, and adjunctive therapies as for severe sepsis. Infusion of activated protein C was started 20 hours after onset of organ dysfunction, and intensive haemodialysis was instituted. Over the next four days the patient became afebrile with progressive resolution of ALI, renal failure and hepatitis. HisLeptospiraserology (requested as part of the evaluation) was reported positive on day 5. Dual infections are common and under-recognized in the tropics. Failure to treat potential co-infections may lead to poor outcomes. Acute lung injury in falciparum malaria has high mortality rates and therapy as for severe sepsis may improve survival. Adjunctive therapies, including activated protein C, cannot replace source eradication.
Malaria vector control by indoor residual insecticide spraying on the tropical island of Bioko, Equatorial Guinea
Authors: Sharp Brian L , Ridl Frances C , Govender Dayanandan , Kuklinski Jaime , Kleinschmidt Immo
Published: May 2007

Background

A comprehensive malaria control intervention was initiated in February 2004 on Bioko Island, Equatorial Guinea. This manuscript reports on the continuous entomological monitoring of the indoor residual spray (IRS) programme during the first two years of its implementation.

Methods

Mosquitoes were captured daily using window traps at 16 sentinel sites and analysed for species identification, sporozoite rates and knockdown resistance (kdr) using polymerase chain reaction (PCR) to assess the efficacy of the vector control initiative from December 2003 to December 2005.

Results

A total of 2,807 and 10,293 Anopheles funestus and Anopheles gambiae s.l. respectively were captured throughout the study period. Both M and S molecular forms of An. gambiae s.s. and Anopheles melas were identified. Prior to the first round of IRS, sporozoite rates were 6.0, 8.3 and 4.0 for An. gambiae s.s., An. melas and An. funestus respectively showing An. melas to be an important vector in areas in which it occurred. After the third spray round, no infective mosquitoes were identified. After the first spray round using a pyrethroid spray the number of An. gambiae s.s. were not reduced due to the presence of the kdr gene but An funestus and An. melas populations declined from 23.5 to 3.1 and 5.3 to 0.8 per trap per 100 nights respectively. After the introduction of a carbamate insecticide in the second round, An. gambiae s.s. reduced from 25.5 to 1.9 per trap per 100 nights and An. funestus and An. melas remained at very low levels. Kdr was found only in the M-form of An. gambiae s.s. with the highest frequency at Punta Europa (85%).

Conclusion

All three vectors that were responsible for malaria transmission before the start of the intervention were successfully controlled once an effective insecticide was used.

Continuous entomological surveillance including resistance monitoring is of critical importance in any IRS based malaria vector control programme. This paper demonstrates that sufficient resources for such monitoring should be included in any proposal in order to avoid programme failures.
Sparing effects of selenium and ascorbic acid on vitamin C and E in guinea pig tissues
Authors: Bertinato Jesse , Hidiroglou Nick , Peace Robert , Cockell Kevin A , Trick Keith D , Jee Penny , Giroux Alex , Madère Réné , Bonacci Giuseppe , Iskandar Monica , Hayward Stephen , Giles Nicholas , L'Abbé Mary R
Published: May 2007

Background

Selenium (Se), vitamin C and vitamin E function as antioxidants within the body. In this study, we investigated the effects of reduced dietary Se and L-ascorbic acid (AA) on vitamin C and α-tocopherol (AT) status in guinea pig tissues.

Methods

Male Hartley guinea pigs were orally dosed with a marginal amount of AA and fed a diet deficient (Se-D/MC), marginal (Se-M/MC) or normal (Se-N/MC) in Se. An additional diet group (Se-N/NC) was fed normal Se and dosed with a normal amount of AA. Guinea pigs were killed after 5 or 12 weeks on the experimental diets at 24 and 48 hours post AA dosing.

Results

Liver Se-dependent glutathione peroxidase activity was decreased (P < 0.05) in guinea pigs fed Se or AA restricted diets. Plasma total glutathione concentrations were unaffected (P > 0.05) by reduction in dietary Se or AA. All tissues examined showed a decrease (P < 0.05) in AA content in Se-N/MC compared to Se-N/NC guinea pigs. Kidney, testis, muscle and spleen showed a decreasing trend (P < 0.05) in AA content with decreasing Se in the diet. Dehydroascorbic acid concentrations were decreased (P < 0.05) in several tissues with reduction in dietary Se (heart and spleen) or AA (liver, heart, kidney, muscle and spleen). At week 12, combined dietary restriction of Se and AA decreased AT concentrations in most tissues. In addition, restriction of Se (liver, heart and spleen) and AA (liver, kidney and spleen) separately also reduced AT in tissues.

Conclusion

Together, these data demonstrate sparing effects of Se and AA on vitamin C and AT in guinea pig tissues.
Monitoring and analysis of dynamic growth of human embryonic stem cells: comparison of automated instrumentation and conventional culturing methods
Authors: Narkilahti Susanna , Rajala Kristiina , Pihlajamäki Harri , Suuronen Riitta , Hovatta Outi , Skottman Heli
Published: May 2007

Background

Human embryonic stem cells (hESCs) are a potential source of cells for use in regenerative medicine. Automation of culturing, monitoring and analysis is crucial for fast and reliable optimization of hESC culturing methods. Continuous monitoring of living cell cultures can reveal more information and is faster than using laborious traditional methods such as microscopic evaluation, immunohistochemistry and flow cytometry.

Methods

We analyzed the growth dynamics of two hESC lines HS237 and HS293 in a conventional culture medium containing serum replacement and a xeno-free X-vivo 10 medium. We used a new automated culture platform utilizing machine vision technology, which enables automatic observation, recording and analysis of intact living cells. We validated the results using flow cytometry for cell counting and characterization.

Results

In our analyses, hESC colony growth could be continuously monitored and the proportion of undifferentiated cells automatically analyzed. No labeling was needed and we could, for the first time, perform detailed follow up of live, undisturbed cell colonies, and record all the events in the culture. The growth rate of the hESCs cultured in X-vivo 10 medium was significantly lower and a larger proportion of the cells were differentiated.

Conclusion

The new automated system enables rapid and reliable analysis of undifferentiated growth dynamics of hESCs. We demonstrate the effectiveness of the system by comparing hESC growth in different culture conditions.
3D active workspace of human hand anatomical model
Authors: Dragulescu Doina , Perdereau Véronique , Drouin Michel , Ungureanu Loredana , Menyhardt Karoly
Published: May 2007

Background

If the model of the human hand is created with accuracy by respecting the type of motion provided by each articulation and the dimensions of articulated bones, it can function as the real organ providing the same motions. Unfortunately, the human hand is hard to model due to its kinematical chains submitted to motion constraints. On the other hand, if an application does not impose a fine manipulation it is not necessary to create a model as complex as the human hand is. But always the hand model has to perform a certain space of motions in imposed workspace architecture no matter what the practical application does.

Methods

Based on Denavit-Hartenberg convention, we conceived the kinematical model of the human hand, having in mind the structure and the behavior of the natural model. We obtained the kinematical equations describing the motion of every fingertip with respect to the general coordinate system, placed on the wrist. For every joint variable, a range of motion was established. Dividing these joint variables to an appropriate number of intervals and connecting them, the complex surface bordering the active hand model workspace was obtained.

Results

Using MATLAB 7.0, the complex surface described by fingertips, when hand articulations are all simultaneously moving, was obtained. It can be seen that any point on surface has its own coordinates smaller than the maximum length of the middle finger in static position. Therefore, a sphere having the centre in the origin of the general coordinate system and the radius which equals this length covers the represented complex surface.

Conclusion

We propose a human hand model that represents a new solution compared to the existing ones. This model is capable to make special movements like power grip and dexterous manipulations. During them, the fingertips do not exceed the active workspace encapsulated by determined surfaces. The proposed kinematical model can help to choose which model joints could be eliminated in order to preserve only the motions important for a certain application. The study shows that all models, simplified or not, exhibit a pronounced similitude with the real hand motion, validated by the fingertips' computed trajectories. The results were used to design an artificial hand capable to make some of the hand's functions with a reduced set of degrees of freedom.
Etiology and antibiotic resistance patterns of community-acquired urinary tract infections in J N M C Hospital Aligarh, India
Authors: Akram Mohammed , Shahid Mohammed , Khan Asad U
Published: May 2007

Background

Urinary tract infections (UTIs) remain the common infections diagnosed in outpatients as well as hospitalized patients. Current knowledge on antimicrobial susceptibility pattern is essential for appropriate therapy. Extended-Spectrum beta-Lactamase (ESBL) producing bacteria may not be detected by routine disk diffusion susceptibility test, leading to inappropriate use of antibiotics and treatment failure. The aim of this study was to determine the distribution and antibiotic susceptibility patterns of bacterial strains isolated from patients with community acquired urinary tract infections (UTIs) at Aligarh hospital in India as well as identification of ESBL producers in the population of different uropathogens.

Methods

Urinary isolates from symptomatic UTI cases attending to the JN Medical College and hospital at Aligarh were identified by conventional methods. Antimicrobial susceptibility testing was performed by Kirby Bauer's disc diffusion method. Isolates resistant to third generation cephalosporin were tested for ESBL production by double disk synergy test method.

Results

Of the 920 tested sample 100 samples showed growth of pathogens among which the most prevalent wereE. coli(61%) followed byKlebsiellaspp (22%). The majority (66.66%) of the isolates were from female while the remaining were from male. Among the gram-negative enteric bacilli high prevalence of resistance was observed against ampicillin and co-trimoxazole. Most of the isolates were resistant to 4 or more number of antibiotics. Forty two percent of isolates were detected to produce ESBL among which 34.42 % wereE. coliisolates.

Conclusion

This study revealed thatE. coliwas the predominant bacterial pathogen of community acquired UTIs in Aligarh, India. It also demonstrated an increasing resistance to Co-trimoxazole and production of extended spectrum β-lactamase among UTI pathogens in the community. This study is useful for clinician in order to improve the empiric treatment.