bluuebunny/crossref_metadata_2025 huggingface dataset:
AKL1, a botanical mixture for the treatment of asthma: a randomised, double-blind, placebo-controlled, cross-over study
Authors: Thomas Michael , Sheran Jane , Smith Natalie , Fonseca Sofia , Lee Amanda J
Published: May 2007

Background

Despite effective treatments, asthma outcomes remain suboptimal. Interest exists in complementary therapies, particularly in herbal remedies for asthma treatment, currently with inconclusive evidence of efficacy. The encapsulated botanical mixture AKL1 has anecdotal evidence of effectiveness in asthma.

Methods

We performed a randomised controlled cross over study comparing the effectiveness of AKL1 with indistinguishable placebo as add-on therapy in patients uncontrolled on standard asthma treatment. Thirty two adult asthmatics completed a 36 week trial consisting of a 4 week single blind run in period, during which placebo was added to usual treatment, a 12 week double blind active phase in which subjects received AKL1 or placebo, a single blind 8 week washout period receiving placebo and a final 12 week double blind cross-over active treatment phase. Daily diaries were kept of peak expiratory flow and symptoms, and spirometry, validated symptom and health status questionnaire scores and adverse events were monitored at study visits. Paired T tests were used to compare the effects of placebo and AKL1 on outcomes. Changes in outcome measures over treatment phases are presented as means and 95% confidence intervals (CI) of means.

Results

No significant differences in lung function (active-placebo) were found (Forced Expiratory Volume in 1 second: mean difference [95% CI] = 0.01 [-0.12 to 0.14] L, p = 0.9. Peak Expiratory Flow: -4.08 [-35.03 to 26.89]. L/min, p = 0.8).

Trends to clinical improvements favouring active treatment were however consistently seen in the patient-centered outcomes: Asthma Control Questionnaire mean difference (active – placebo) [95% CI] = -0.35 [-0.78 to 0.07], p = 0.10, Asthma Quality of Life Questionnaire mean difference 0.42 [-0.08 to 0.93], p = 0.09, Leicester Cough Questionnaire mean difference 0.49, [-0.18 to 1.16], p = 0.15.

Nine exacerbations occurred during placebo treatment and five whilst on AKL1. No significant adverse events were noted.

Conclusion

AKL1 treatment was well tolerated. No significant improvements in lung function, symptoms, or quality of life were seen, although consistent trends were seen to improvements in patient-centered outcomes. Further studies are needed.
FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension
Authors: Eash John , Olsen Aaron , Breur Gert , Gerrard Dave , Hannon Kevin
Published: May 2007

Background

Skeletal muscle atrophy can occur under many different conditions, including prolonged disuse or immobilization, cachexia, cushingoid conditions, secondary to surgery, or with advanced age. The mechanisms by which unloading of muscle is sensed and translated into signals controlling tissue reduction remains a major question in the field of musculoskeletal research. While the fibroblast growth factors (FGFs) and their receptors are synthesized by, and intimately involved in, embryonic skeletal muscle growth and repair, their role maintaining adult muscle status has not been examined.

Methods

We examined the effects of ectopic expression of FGFR1 during disuse-mediated skeletal muscle atrophy, utilizing hindlimb suspension and DNA electroporation in mice.

Results

We found skeletal muscle FGF4 and FGFR1 mRNA expression to be modified by hind limb suspension,. In addition, we found FGFR1 protein localized in muscle fibers within atrophying mouse muscle which appeared to be resistant to atrophy. Electroporation and ectopic expression of FGFR1 significantly inhibited the decrease in muscle fiber area within skeletal muscles of mice undergoing suspension induced muscle atrophy. Ectopic FGFR1 expression in muscle also significantly stimulated protein synthesis in muscle fibers, and increased protein degradation in weight bearing muscle fibers.

Conclusion

These results support the theory that FGF signaling can play a role in regulation of postnatal skeletal muscle maintenance, and could offer potentially novel and efficient therapeutic options for attenuating muscle atrophy during aging, illness and spaceflight.
Engineering proteinase K using machine learning and synthetic genes
Authors: Liao Jun , Warmuth Manfred K , Govindarajan Sridhar , Ness Jon E , Wang Rebecca P , Gustafsson Claes , Minshull Jeremy
Published: May 2007

Background

Altering a protein's function by changing its sequence allows natural proteins to be converted into useful molecular tools. Current protein engineering methods are limited by a lack of high throughput physical or computational tests that can accurately predict protein activity under conditions relevant to its final application. Here we describe a new synthetic biology approach to protein engineering that avoids these limitations by combining high throughput gene synthesis with machine learning-based design algorithms.

Results

We selected 24 amino acid substitutions to make in proteinase K from alignments of homologous sequences. We then designed and synthesized 59 specific proteinase K variants containing different combinations of the selected substitutions. The 59 variants were tested for their ability to hydrolyze a tetrapeptide substrate after the enzyme was first heated to 68°C for 5 minutes. Sequence and activity data was analyzed using machine learning algorithms. This analysis was used to design a new set of variants predicted to have increased activity over the training set, that were then synthesized and tested. By performing two cycles of machine learning analysis and variant design we obtained 20-fold improved proteinase K variants while only testing a total of 95 variant enzymes.

Conclusion

The number of protein variants that must be tested to obtain significant functional improvements determines the type of tests that can be performed. Protein engineers wishing to modify the property of a protein to shrink tumours or catalyze chemical reactions under industrial conditions have until now been forced to accept high throughput surrogate screens to measure protein properties that they hope will correlate with the functionalities that they intend to modify. By reducing the number of variants that must be tested to fewer than 100, machine learning algorithms make it possible to use more complex and expensive tests so that only protein properties that are directly relevant to the desired application need to be measured. Protein design algorithms that only require the testing of a small number of variants represent a significant step towards a generic, resource-optimized protein engineering process.
Development of a one-step embryonic stem cell-based assay for the screening of sprouting angiogenesis
Authors: Hermant Bastien , Desroches-Castan Agnès , Dubessay Marie-Laure , Prandini Marie-Hélène , Huber Philippe , Vittet Daniel
Published: May 2007

Background

Angiogenesis assays are important tools for the identification of regulatory molecules and the potential development of therapeutic strategies to modulate neovascularization. Although numerous in vitro angiogenesis models have been developed in the past, they exhibit limitations since they do not recapitulate the entire angiogenic process or correspond to multi-step procedures that are not easy to use. Convenient, reliable, easily quantifiable and physiologically relevant assays are still needed for pharmacological screenings of angiogenesis.

Results

Here, we have optimized an angiogenesis model based on ES cell differentiation for screening experiments. We have established conditions leading to angiogenic sprouting of embryoid bodies during ES cell differentiation in type I three-dimensional collagen gels. Immunostaining experiments carried out during these cultures showed the formation of numerous buds comprising CD31 positive cells, after 11 days of culture of ES cells. Moreover, this one-step model has been validated in response to activators and inhibitors of angiogenesis. Sprouting was specifically stimulated in the presence of VEGF and FGF2. Alternatively, endothelial sprouting induced by angiogenic activators was inhibited by angiogenesis inhibitors such as angiostatin, TGFβ and PF4. Sprouting angiogenesis can be easily quantified by image analysis after immunostaining of endothelial cells with CD31 pan-endothelial marker.

Conclusion

Taken together, these data clearly validate that this one-step ES differentiation model constitutes a simple and versatile angiogenesis system that should facilitate, in future investigations, the screening of both activators and inhibitors of angiogenesis.
Tyr66 acts as a conformational switch in the closed-to-open transition of the SHP-2 N-SH2-domain phosphotyrosine-peptide binding cleft
Authors: Guvench Olgun , Qu Cheng-Kui , MacKerell Alexander D
Published: May 2007

Background

The N-terminal SH2 domain (N-SH2) of the non-receptor tyrosine phosphatase SHP-2 is involved both in localization of SHP-2 by recognition of phosphotyrosine (pY) peptides and self-inhibition of SHP-2 phosphatase activity through the formation of a protein – protein interface with the phosphatase domain. Mutations that disrupt this interface break the coupling between pY-peptide binding cleft conformation and self-inhibition, thereby increasing both SHP-2 phosphatase activity and pY-peptide binding affinity, and are associated with the congenital condition Noonan syndrome and various pediatric leukemias. To better characterize the molecular process involved in N-SH2 pY-dependent binding, we have applied explicit-solvent molecular dynamics simulations to study the closed-to-open transition of the N-SH2 pY-peptide binding cleft.

Results

The existence of stable conformations in the left-handed helical and the extended regions of Tyr66 φ/ψ space prevent rapid interconversion of the backbone and create a conformational switch such that Tyr66 in a left-handed helical backbone conformation results in an open cleft and in an extended backbone conformation results in a closed cleft. The stable conformations arise from deep, well-localized free-energy minima in the left-handed helical and extended regions of the Tyr66 φ/ψ map. Changing the Tyr66 backbone conformation from extended to left-handed helical induces a closed-to-open transition in the cleft, and the reverse change in backbone conformation induces the reverse, open-to-closed transition. In the open-cleft state, weak solvent-exposed interactions involving the sidechains of Tyr66, Asp40, Lys55, and Gln57 serve to anchor the Tyr66 sidechain to the surface of the protein and away from the binding cleft entrance, thereby facilitating pY-peptide access to the binding cleft.

Conclusion

The simulations point to a regulatory role for Tyr66 and surrounding residues in SHP-2 function: mutations at Tyr66, Asp40, Lys55, and/or Gln57 are predicted to break the switching mechanism and negatively impact pY-peptide binding. This in turn would interfere with cellular localization and the coupled SHP-2 phosphatase activity. The structurally well-defined binding cleft conformations resulting from the switch-like transition suggest the possibility of applying structure-based methods to develop inhibitors of N-SH2 pY-peptide binding to serve as research tools for signal transduction and precursors to therapeutics for SHP-2-related diseases.
Binding of Sudan II and IV to lecithin liposomes and E. coli membranes: insights into the toxicity of hydrophobic azo dyes
Authors: Li Lu , Gao Hong-Wen , Ren Jiao-Rong , Chen Ling , Li Yu-Cheng , Zhao Jian-Fu , Zhao He-Ping , Yuan Yuan
Published: May 2007

Background

Sudan red compounds are hydrophobic azo dyes, still used as food additives in some countries. However, they have been shown to be unsafe, causing tumors in the liver and urinary bladder in rats. They have been classified as category 3 human carcinogens by the International Agency for Research on Cancer. A number of hypotheses that could explain the mechanism of carcinogenesis have been proposed for dyes similar to the Sudan red compounds. Traditionally, investigations of the membrane toxicity of organic substances have focused on hydrocarbons, e.g. polycyclic aromatic hydrocarbons (PAHs), and DDT. In contrast to hydrocarbons, Sudan red compounds contain azo and hydroxy groups, which can form hydrogen bonds with the polar head groups of membrane phospholipids. Thus, entry may be impeded. They could have different toxicities from other lipophilic hydrocarbons. The available data show that because these compounds are lipophilic, interactions with hydrophobic parts of the cell are important for their toxicity. Lipophilic compounds accumulate in the membrane, causing expansion of the membrane surface area, inhibition of primary ion pumps and increased proton permeability.

Results

This work investigated the interactions of the amphiphilic compounds Sudan II and IV with lecithin liposomes and live Escherichia coli (E. coli). Sudan II and IV binding to lecithin liposomes and live E. coli corresponds to the Langmuir adsorption isotherm. In the Sudan red compounds – lecithin liposome solutions, the binding ratio of Sudan II to lecithin is 1/31 and that of Sudan IV to 1/314. The binding constant of the Sudan II-lecithin complex is 1.75 × 104 and that of the Sudan IV-lecithin complex 2.92 × 105. Besides, the influences of pH, electrolyte and temperature were investigated and analyzed quantitatively. In the Sudan red compounds – E.coli mixture, the binding ratios of Sudan II and Sudan IV to E.coli membrane phospholipid are 1/29 and 1/114. The binding constants of the Sudan II – and Sudan IV- E.coli membrane phospholipid complexes are 1.86 × 104 and 6.02 × 104. Over 60% of Sudan II and 75% of Sudan IV penetrated into E.coli, in which 90% of them remained in the E.coli membrane.

Conclusion

Experiments of Sudan II and IV binding to lecithin liposomes and live E. coli indicates that amphiphilic compounds may besequestered in thelecithin liposomes and membrane phospholipid bilayer according to the Langmuir adsorption law. Penetration into the cytosol was impeded and inhibited for Sudan red compounds. It is possible for such compounds themselves (excluding their metabolites and by-products)not result directly in terminal toxicity. Therefore, membrane toxicity could be manifested as membrane blocking and membrane expansion. The method established here may be useful for evaluating the interaction of toxins with membranes.
On the origin of the histone fold
Authors: Alva Vikram , Ammelburg Moritz , Söding Johannes , Lupas Andrei N
Published: May 2007

Background

Histones organize the genomic DNA of eukaryotes into chromatin. The four core histone subunits consist of two consecutive helix-strand-helix motifs and are interleaved into heterodimers with a unique fold. We have searched for the evolutionary origin of this fold using sequence and structure comparisons, based on the hypothesis that folded proteins evolved by combination of an ancestral set of peptides, the antecedent domain segments.

Results

Our results suggest that an antecedent domain segment, corresponding to one helix-strand-helix motif, gave rise divergently to the N-terminal substrate recognition domain of Clp/Hsp100 proteins and to the helical part of the extended ATPase domain found in AAA+ proteins. The histone fold arose subsequently from the latter through a 3D domain-swapping event. To our knowledge, this is the first example of a genetically fixed 3D domain swap that led to the emergence of a protein family with novel properties, establishing domain swapping as a mechanism for protein evolution.

Conclusion

The helix-strand-helix motif common to these three folds provides support for our theory of an 'ancient peptide world' by demonstrating how an ancestral fragment can give rise to 3 different folds.
Structure, substrate recognition and reactivity of Leishmania major mevalonate kinase
Authors: Sgraja Tanja , Smith Terry K , Hunter William N
Published: May 2007

Background

Isoprenoid precursor synthesis via the mevalonate route in humans and pathogenic trypanosomatids is an important metabolic pathway. There is however, only limited information available on the structure and reactivity of the component enzymes in trypanosomatids. Since isoprenoid biosynthesis is essential for trypanosomatid viability and may provide new targets for therapeutic intervention it is important to characterize the pathway components.

Results

Putative mevalonate kinase encoding genes from Leishmania major (Lm MK) and Trypanosoma brucei (Tb MK) have been cloned, over-expressed in and proteins isolated from procyclic-form T. brucei. A highly sensitive radioactive assay was developed and shows ATP-dependent phosphorylation of mevalonate. Apo and (R)-mevalonate bound crystal structures of Lm MK, from a bacterial expression system, have been determined to high resolution providing, for the first time, information concerning binding of mevalonate to an MK. The mevalonate binds in a deep cavity lined by highly conserved residues. His25 is key for binding and for discrimination of (R)- over (S)-mevalonate, with the main chain amide interacting with the C3 hydroxyl group of (R)-mevalonate, and the side chain contributing, together with Val202 and Thr283, to the construction of a hydrophobic binding site for the C3 methyl substituent. The C5 hydroxyl, where phosphorylation occurs, points towards catalytic residues, Lys18 and Asp155. The activity of Lm MK was significantly reduced compared to MK from other species and we were unable to obtain ATP-binding data. Comparisons with the rat MK:ATP complex were used to investigate how this substrate might bind. In Lm MK, helix α2 and the preceding polypeptide adopt a conformation, not seen in related kinase structures, impeding access to the nucleotide triphosphate binding site suggesting that a conformational rearrangement is required to allow ATP binding.

Conclusion

Our new structural information, consistent with data on homologous enzymes allows a detailed description of how mevalonate is recognized and positioned for catalysis in MK. The mevalonate-binding site is highly conserved yet the ATP-binding site is structurally distinct in Lm MK. We are unable to provide a definitive explanation for the low activity of recombinant protein isolated from a bacterial expression system compared to material isolated from procyclic-form Trypanosoma brucei.
Accuracy of self-reported height measurements in parents and its effect on mid-parental target height calculation
Authors: Braziuniene Ieva , Wilson Thomas A , Lane Andrew H
Published: May 2007

Background

Clinical determination of mid-parental height is an important part of the assessment of a child's growth, however our clinical impression has been that parents cannot be relied upon to accurately report their own heights. Therefore, we conducted this study to assess the accuracy of parental height self-reporting and its effect on calculated mid-parental target height for children presenting to a pediatric endocrinology office.

Methods

All parents bringing their children for an initial evaluation to a pediatric endocrinology clinic over a period of nine months were questioned and then measured by a pediatric endocrinologist. Parents were blinded to the study. Mid-parental target heights, based on reported and actual height were compared.

Results

There were 241 families: 98 fathers and 217 mothers in our study. Mean measured paternal height was 173.2 cm, self reported 174.9 cm (p < 0.0001), partner reported 177 cm (p = 0.0004). Only 50% of fathers and 58% of mothers reported their height within ± 2 cm of their measured height, while 15% of fathers and 12% of mothers were inaccurate by more than 4 cm. Mean measured maternal height was 160.6 cm, self-reported 161.1 cm (NS), partner reported 161.7 cm (NS). Inaccuracy of height self-report had a small but significant effect on the mean MPTH (0.4 cm, p = 0.045). Analysis showed that only 70% of MPTH calculated by reported heights fell within ± 2 cm of MPTH calculated using measured heights, 24% being in ± 2–4 cm range, and 6% were inaccurate by more than 4 cm.

Conclusion

There is a significant difference in paternal measured versus reported heights with an overall trend for fathers to overestimate their own height. A large subset of parents makes a substantial error in their height self-report, which leads to erroneous MPTH. Inaccuracy is even greater when one parent reports the other parent's height. When a child's growth is in question, measured rather than reported parental heights should be obtained.
DNA microarray data integration by ortholog gene analysis reveals potential molecular mechanisms of estrogen-dependent growth of human uterine fibroids
Authors: Wei Tao , Geiser Andrew G , Qian Hui-Rong , Su Chen , Helvering Leah M , Kulkarini Nalini H , Shou Jianyong , N'Cho Mathias , Bryant Henry U , Onyia Jude E
Published: May 2007

Background

Uterine fibroids or leiomyoma are a common benign smooth muscle tumor. The tumor growth is well known to be estrogen-dependent. However, the molecular mechanisms of its estrogen-dependency is not well understood.

Methods

Differentially expressed genes in human uterine fibroids were either retrieved from published papers or from our own statistical analysis of downloaded array data. Probes for the same genes on different Affymetrix chips were mapped based on probe comparison information provided by Affymetrix. Genes identified by two or three array studies were submitted for ortholog analysis. Human and rat ortholog genes were identified by using ortholog gene databases, HomoloGene and TOGA and were confirmed by synteny analysis with MultiContigView tool in the Ensembl genome browser.

Results

By integrated analysis of three recently published DNA microarray studies with human tissue, thirty-eight genes were found to be differentially expressed in the same direction in fibroid compared to adjacent uterine myometrium by at least two research groups. Among these genes, twelve with rat orthologs were identified as estrogen-regulated from our array study investigating uterine expression in ovariectomized rats treated with estrogen. Functional and pathway analyses of the twelve genes suggested multiple molecular mechanisms for estrogen-dependent cell survival and tumor growth. Firstly, estrogen increased expression of the anti-apoptotic PCP4 gene and suppressed the expression of growth inhibitory receptors PTGER3 and TGFBR2. Secondly, estrogen may antagonize PPARγ signaling, thought to inhibit fibroid growth and survival, at two points in the PPAR pathway: 1) through increased ANXA1 gene expression which can inhibit phospholipase A2 activity and in turn decrease arachidonic acid synthesis, and 2) by decreasing L-PGDS expression which would reduce synthesis of PGJ2, an endogenous ligand for PPARγ. Lastly, estrogen affects retinoic acid (RA) synthesis and mobilization by regulating expression of CRABP2 and ALDH1A1. RA has been shown to play a significant role in the development of uterine fibroids in an animal model.

Conclusion

Integrated analysis of multiple array datasets revealed twelve human and rat ortholog genes that were differentially expressed in human uterine fibroids and transcriptionally responsive to estrogen in the rat uterus. Functional and pathway analysis of these genes suggest multiple potential molecular mechanisms for the poorly understood estrogen-dependent growth of uterine fibroids. Fully understanding the exact molecular interactions among these gene products requires further study to validate their roles in uterine fibroids. This work provides new avenues of study which could influence the future direction of therapeutic intervention for the disease.
Indian community health insurance schemes provide partial protection against catastrophic health expenditure
Authors: Devadasan Narayanan , Criel Bart , Van Damme Wim , Ranson Kent , Van der Stuyft Patrick
Published: May 2007

Background

More than 72% of health expenditure in India is financed by individual households at the time of illness through out-of-pocket payments. This is a highly regressive way of financing health care and sometimes leads to impoverishment. Health insurance is recommended as a measure to protect households from such catastrophic health expenditure (CHE). We studied two Indian community health insurance (CHI) schemes, ACCORD and SEWA, to determine whether insured households are protected from CHE.

Methods

ACCORD provides health insurance cover for the indigenous population, living in Gudalur, Tamil Nadu. SEWA provides insurance cover for self employed women in the state of Gujarat. Both cover hospitalisation expenses, but only upto a maximum limit of US$23 and US$45, respectively.

We reviewed the insurance claims registers in both schemes and identified patients who were hospitalised during the period 01/04/2003 to 31/03/2004. Details of their diagnoses, places and costs of treatment and self-reported annual incomes were obtained. There is no single definition of CHE and none of these have been validated. For this research, we used the following definition; "annual hospital expenditure greater than 10% of annual income," to identify those who experienced CHE.

Results

There were a total of 683 and 3152 hospital admissions at ACCORD and SEWA, respectively. In the absence of the CHI scheme, all of the patients at ACCORD and SEWA would have had to pay OOP for their hospitalisation. With the CHI scheme, 67% and 34% of patients did not have to make any out-of-pocket (OOP) payment for their hospital expenses at ACCORD and SEWA, respectively. Both CHI schemes halved the number of households that would have experienced CHE by covering hospital costs. However, despite this, 4% and 23% of households with admissions still experienced CHE at ACCORD and SEWA, respectively. This was related to the following conditions: low annual income, benefit packages with low maximum limits, exclusion of some conditions from the benefit package, and use of the private sector for admissions.

Conclusion

CHI appears to be effective at halving the incidence of CHE among hospitalised patients. This protection could be further enhanced by improving the design of the CHI schemes, especially by increasing the upper limits of benefit packages, minimising exclusions and controlling costs.
Food safety in hospital: knowledge, attitudes and practices of nursing staff of two hospitals in Sicily, Italy
Authors: Buccheri Cecilia , Casuccio Alessandra , Giammanco Santo , Giammanco Marco , La Guardia Maurizio , Mammina Caterina
Published: May 2007

Background

Food hygiene in hospital poses peculiar problems, particularly given the presence of patients who could be more vulnerable than healthy subjects to microbiological and nutritional risks. Moreover, in nosocomial outbreaks of infectious intestinal disease, the mortality risk has been proved to be significantly higher than the community outbreaks and highest for foodborne outbreaks. On the other hand, the common involvement in the role of food handlers of nurses or domestic staff, not specifically trained about food hygiene and HACCP, may represent a further cause of concern.

The purpose of this study was to evaluate knowledge, attitudes, and practices concerning food safety of the nursing staff of two hospitals in Palermo, Italy. Association with some demographic and work-related determinants was also investigated.

Methods

The survey was conducted, by using a semi-structured questionnaire, in March-November 2005 in an acute general hospital and a paediatric hospital, where nursing staff is routinely involved in food service functions.

Results

Overall, 401 nurses (279, 37.1%, of the General Hospital and 122, 53.5%, of the Paediatric Hospital, respectively) answered. Among the respondents there was a generalized lack of knowledge about etiologic agents and food vehicles associated to foodborne diseases and proper temperatures of storage of hot and cold ready to eat foods. A general positive attitude towards temperature control and using clothing and gloves, when handling food, was shared by the respondents nurses, but questions about cross-contamination, refreezing and handling unwrapped food with cuts or abrasions on hands were frequently answered incorrectly. The practice section performed better, though sharing of utensils for raw and uncooked foods and thawing of frozen foods at room temperatures proved to be widely frequent among the respondents. Age, gender, educational level and length of service were inconsistently associated with the answer pattern.

More than 80% of the respondent nurses did not attend any educational course on food hygiene. Those who attended at least one training course fared significantly better about some knowledge issues, but no difference was detected in both the attitude and practice sections.

Conclusion

Results strongly emphasize the need for a safer management of catering in the hospitals, where non professional food handlers, like nursing or domestic staff, are involved in food service functions.
Doctor and practice characteristics associated with differences in patient evaluations of general practice
Authors: Heje Hanne N , Vedsted Peter , Sokolowski Ineta , Olesen Frede
Published: May 2007

Background

Variation in patients' evaluation due to general practitioner (GP) and practice factors may provide information useful in a quality improvement context. However, the extent to which differences in patients' evaluation of the GPs are associated with differences in GP and practice characteristics must also be ascertained in order to facilitate comparison of adjusted patient evaluations between GPs. The aim of this study was to determine such associations in a setting where GPs serve a list of patients and act as gatekeepers.

Methods

We carried out a patient evaluation survey among voluntarily participating GPs using the EUROPEP questionnaire, which produced 28,260 patient evaluations (response rate 77.3%) of 365 GPs. In our analyses we compared the prevalence of positive evaluations in groups of GPs.

Results

Our principal finding was a negative association between the GP's age and the evaluation of all aspects, except accessibility. We also found an association between the way the practice was organised and the patients' evaluation of accessibility, with GPs in single-handed practices getting far the most positive evaluations. Long weekly working hours were associated with more positive evaluations of all dimensions except accessibility, whereas more than 0.5 full-time employees per GP, a higher number of listed patients per GP and working in a training practice were associated with negative evaluation of accessibility.

Conclusion

GP characteristics are mainly associated with patients' experience of interpersonal aspects of care, while practice characteristics are associated with evaluation of accessibility. These differences need to be accounted for when comparing patient evaluations of different practices.
Jack-of-all-trades, master of none: Postgraduate perspectives on interdisciplinary health research in Australia
Authors: Carey Gemma E , Smith James A
Published: May 2007

Background

Interdisciplinary health research is increasingly perceived as an expectation of research institutions and funding bodies within Australia. However, little consideration has been given to the extent to which this re-orientation has produced a new type of researcher – an interdisciplinary health researcher.

Discussion

As cross-enrolled postgraduate research students, we assert that we do not have an intellectual home. Rather, we must forge a virtual intellectual home through the process of bridging disciplines. In this paper we explain that this virtual home affords us the role of 'interlockers' in future health research. The interlocker role privileges a breadth of understandings across disciplines, rather than a depth in one.

We conclude by reiterating that there is an undeniable need for interdisciplinary health research, and that the roles and actions of interdisciplinary health researchers need to be better understood and catered for. We therefore call for increased consideration and discussion concerning the future roles and capacities of interdisciplinary health researchers such as ourselves.
Functional mapping of hospitals by diagnosis-dominant case-mix analysis
Authors: Fushimi Kiyohide , Hashimoto Hideki , Imanaka Yuichi , Kuwabara Kazuaki , Horiguchi Hiromasa , Ishikawa Kohichi B , Matsuda Shinya
Published: May 2007

Background

Principles and methods for the allocation of healthcare resources among healthcare providers have long been health policy research issues in many countries. Healthcare reforms including the development of a new case-mix system, Diagnosis Procedure Combination (DPC), and the introduction of a DPC-based payment system are currently underway in Japan, and a methodology for adequately assessing the functions of healthcare providers is needed to determine healthcare resource allocations.

Methods

By two-dimensional mapping of the rarity and complexity of diagnoses for patients receiving treatment, we were able to quantitatively demonstrate differences in the functions of different healthcare service provider groups.

Results

On average, inpatients had diseases that were 3.6-times rarer than those seen in outpatients, while major teaching hospitals treated inpatients with diseases 3.0-times rarer on average than those seen at small hospitals.

Conclusion

We created and evaluated a new indicator for DPC, the diagnosis-dominant case-mix system developed in Japan, whereby the system was used to assess the functions of healthcare service providers. The results suggest that it is possible to apply the case-mix system to the integrated evaluation of outpatient and inpatient healthcare services and to the appropriate allocation of healthcare resources among health service providers.
Time-trend and variations in the proportion of second-eye cataract surgery
Authors: Hoffmeister Lorena , Román Rubén , Comas Mercè , Cots Francesc , Bernal-Delgado Enrique , Castells Xavier
Published: May 2007

Background

Despite recommendations for greater use of second-eye cataract surgery and the bilateral progression of the disease, there is a substantial proportion of unmet need for this treatment. Few studies have explored the factors associated with second-eye cataract surgery utilisation. The objective of our study was to estimate the proportion of second-eye cataract surgery, evaluate its time-trend, and explore differences in utilisation by patients' gender, age, and region of residence.

Methods

All senile cataract surgeries performed between 1999 and 2002 in the public health system of Catalonia (Spain) were obtained from the Minimum Data Set. The proportion of second-eye surgery from November 2000 to December 2002 was calculated. The time-trend of this proportion was characterised through linear regression models with the logarithmic transformation of time.

Results

The proportion of second-eye surgery was 30.0% and showed an increasing trend from 24.8% (95% Confidence Interval [CI] 21.6; 26.1) in November 2000 to 31.8% (95% CI 31.4; 33.6) in December 2002. This proportion was 1.9% (95% CI 0.9; 2.9) higher in women (p < 0.001) and held constant across time. Male patients aged less than 60 had the lowest proportion (22.6%; 95% CI 22.4; 22.9) and females between 70 and 79 had the highest proportion (27.4%; 95% CI 26.9; 27.9). The time-trend for the proportion of second-eye surgery in those aged over 80 years was greater than for younger ages, showing an increase of 9% at the end of the period for both males and females. Variations between regions decreased over time because regions with the lowest initial proportions of second-eye surgery (approximately 17%) showed a greater increase over the study period.

Conclusion

We predict greater utilization of second-eye surgery in patients aged 70 to 79 years and in women. A greater increase in the utilisation rates of second-eye surgery is expected in the regions with lower proportions and in older patients. The observed trend suggests that there will be a substantial proportion of unmet need for bilateral surgery.
Patient adherence to medical treatment: a review of reviews
Authors: van Dulmen Sandra , Sluijs Emmy , van Dijk Liset , de Ridder Denise , Heerdink Rob , Bensing Jozien
Published: May 2007

Background

Patients' non-adherence to medical treatment remains a persistent problem. Many interventions to improve patient adherence are unsuccessful and sound theoretical foundations are lacking. Innovations in theory and practice are badly needed. A new and promising way could be to review the existing reviews of adherence to interventions and identify the underlying theories for effective interventions. That is the aim of our study.

Methods

The study is a review of 38 systematic reviews of the effectiveness of adherence interventions published between 1990 and 2005. Electronic literature searches were conducted in Medline, Psychinfo, Embase and the Cochrane Library. Explicit inclusion and exclusion criteria were applied. The scope of the study is patient adherence to medical treatment in the cure and care sector.

Results

Significant differences in the effectiveness of adherence interventions were found in 23 of the 38 systematic reviews. Effective interventions were found in each of four theoretical approaches to adherence interventions: technical, behavioural, educational and multi-faceted or complex interventions. Technical solutions, such as a simplification of the regimen, were often found to be effective, although that does not count for every therapeutic regimen.

Overall, our results show that, firstly, there are effective adherence interventions without an explicit theoretical explanation of the operating mechanisms, for example technical solutions. Secondly, there are effective adherence interventions, which clearly stem from the behavioural theories, for example incentives and reminders. Thirdly, there are other theoretical models that seem plausible for explaining non-adherence, but not very effective in improving adherence behaviour. Fourthly, effective components within promising theories could not be identified because of the complexity of many adherence interventions and the lack of studies that explicitly compare theoretical components.

Conclusion

There is a scarcity of comparative studies explicitly contrasting theoretical models or their components. The relative weight of these theories and the effective components in the interventions designed to improve adherence, need to be assessed in future studies.
Utilization and expenditures of veterans obtaining primary care in community clinics and VA medical centers: an observational cohort study
Authors: Maciejewski Matthew L , Perkins Mark , Li Yu-Fang , Chapko Michael , Fortney John C , Liu Chuan-Fen
Published: May 2007

Background

To compare VA inpatient and outpatient utilization and expenditures of veterans seeking primary care in community-based outpatient clinics (CBOCs) and VA medical centers (VAMCs) in fiscal years 2000 (FY00) and 2001.

Methods

The sample included 25,092 patients who obtained primary care exclusively from 108 CBOCs in FY00, 26,936 patients who obtained primary care exclusively from 72 affiliated VAMCs in FY00, and 11,450 "crossover" patients who obtained primary care in CBOCs and VAMCs in FY00. VA utilization and expenditure data were drawn from the VA's system-wide cost accounting system. Veteran demographic characteristics and a 1999 Diagnostic Cost Group risk score were obtained from VA administrative files. Outpatient utilization (primary care, specialty care, mental health, pharmacy, radiology and laboratory) and inpatient utilization were estimated using count data models and expenditures were estimated using one-part or two-part models. The second part of two-part models was estimated using generalized linear regressions.

Results

CBOC patients had a slightly more primary care visits per year than VAMC patients (p < 0.0001), but lower primary care costs (-$71, p < 0.0001). CBOC patients had lower odds of one or more specialty, mental health, ancillary visits and hospital stays per year, and fewer numbers of visits and stays if they had any and lower specialty, mental health, ancillary and inpatient expenditures (all, p < 0.0001). As a result, CBOC patients had lower total outpatient and overall expenditures than VAMC patients (p < 0.0001).

Conclusion

CBOCs provided veterans improved access to primary care and other services, but expenditures were contained because CBOC patients who sought health care had fewer visits and hospital stays than comparable VAMC patients. These results suggest a more complex pattern of health care utilization and expenditures by CBOC patients than has been found in prior studies. This study also illustrates that CBOCs continue to be a critical primary care and mental health access point for veterans.
Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio
Authors: Sharifah Sakinah SA , Tri Handayani S , Azimahtol Hawariah LP
Published: May 2007

Background

Zerumbone is a cytotoxic component isolated from Zingiber zerumbet Smith, a herbal plant which is also known as lempoyang. This new anticancer bioactive compound from Z. zerumbet was investigated for its activity and mechanism in human liver cancer cell lines.

Results

Zerumbone significantly showed an antiproliferative activity upon HepG2 cells with an IC50 of 3.45 ± 0.026 μg/ml. Zerumbone was also found to inhibit the proliferation of non-malignant Chang Liver and MDBK cell lines. However the IC50 obtained was higher compared to the IC50 for HepG2 cells (> 10 μg/ml). The extent of DNA fragmentation was evaluated by the Tdt-mediated dUTP nick end labelling assay which showed that, zerumbone significantly increased apoptosis in HepG2 cells in a time-course manner. In detail, the apoptotic process triggered by zerumbone involved the up-regulation of pro-apoptotic Bax protein and the suppression of anti-apoptotic Bcl-2 protein expression. The changes that occurred in the levels of this antagonistic proteins Bax/Bcl-2, was independent of p53 since zerumbone did not affect the levels of p53 although this protein exists in a functional form. Western blotting analysis for Bax protein was further confirmed qualitatively with an immunoassay that showed the distribution of Bax protein in zerumbone-treated cells.

Conclusion

Therefore, zerumbone was found to induce the apoptotic process in HepG2 cells through the up and down regulation of Bax/Bcl-2 protein independently of functional p53 activity.
Indoor collections of the Anopheles funestus group (Diptera: Culicidae) in sprayed houses in northern KwaZulu-Natal, South Africa
Authors: Mouatcho Joel C , Hargreaves Keith , Koekemoer Lizette L , Brooke Basil D , Oliver Shüne V , Hunt Richard H , Coetzee Maureen
Published: May 2007

Background

Insecticide resistance in malaria vector mosquitoes presents a serious problem for those involved in control of this disease. South Africa experienced a severe malaria epidemic during 1999/2000 due to pyrethroid resistance in the major vector Anopheles funestus. Subsequent monitoring and surveillance of mosquito populations were conducted as part of the malaria vector control programme.

Methods

A sample of 269 Anopheles funestus s.l. was collected in Mamfene, northern KwaZulu-Natal, using exit window traps in pyrethroid sprayed houses between May and June 2005. Mosquitoes were identified to species level, assayed for insecticide susceptibility, analysed for Plasmodium falciparum infectivity and blood meal source.

Results

Of the 220 mosquitoes identified using the rDNA PCR method, two (0.9%) were An. funestus s.s. and 218 (99.1%) Anopheles parensis. Standard WHO insecticide susceptibility tests were performed on F1 progeny from wild caught An. parensis females and a significant survival 24 h post exposure was detected in 40% of families exposed to 0.05% deltamethrin. Biochemical analysis of F1 An. parensis showed no elevation in levels/activity of the detoxifying enzyme systems when compared with an insecticide susceptible An. funestus laboratory strain. Among the 149 female An. parensis tested for P. falciparum circumsporozoite infections, 13.4% were positive. All ELISA positive specimens (n = 20) were re-examined for P. falciparum infections using a PCR assay and none were found to be positive. Direct ELISA analysis of 169 blood meal positive specimens showed > 75% of blood meals were taken from animals. All blood fed, false positive mosquito samples for the detection of sporozoites of P. falciparum were zoophilic.

Conclusion

The combination of pyrethroid resistance and P. falciparum false-positivity in An. parensis poses a problem for vector control. If accurate species identification had not been carried out, scarce resources would have been wasted in the unnecessary changing of control strategies to combat a non-vector species.
Large-scale malaria survey in Cambodia: Novel insights on species distribution and risk factors
Authors: Incardona Sandra , Vong Sirenda , Chiv Lim , Lim Pharath , Nhem Sina , Sem Rithy , Khim Nimol , Doung Socheat , Mercereau-Puijalon Odile , Fandeur Thierry
Published: May 2007

Background

In Cambodia, estimates of the malaria burden rely on a public health information system that does not record cases occurring among remote populations, neither malaria cases treated in the private sector nor asymptomatic carriers. A global estimate of the current malaria situation and associated risk factors is, therefore, still lacking.

Methods

A large cross-sectional survey was carried out in three areas of multidrug resistant malaria in Cambodia, enrolling 11,652 individuals. Fever and splenomegaly were recorded. Malaria prevalence, parasite densities and spatial distribution of infection were determined to identify parasitological profiles and the associated risk factors useful for improving malaria control programmes in the country.

Results

Malaria prevalence was 3.0%, 7.0% and 12.3% in Sampovloun, Koh Kong and Preah Vihear areas. Prevalences and Plasmodium species were heterogeneously distributed, with higher Plasmodium vivax rates in areas of low transmission. Malaria-attributable fevers accounted only for 10–33% of malaria cases, and 23–33% of parasite carriers were febrile. Multivariate multilevel regression analysis identified adults and males, mostly involved in forest activities, as high risk groups in Sampovloun, with additional risks for children in forest-fringe villages in the other areas along with an increased risk with distance from health facilities.

Conclusion

These observations point to a more complex malaria situation than suspected from official reports. A large asymptomatic reservoir was observed. The rates of P. vivax infections were higher than recorded in several areas. In remote areas, malaria prevalence was high. This indicates that additional health facilities should be implemented in areas at higher risk, such as remote rural and forested parts of the country, which are not adequately served by health services. Precise malaria risk mapping all over the country is needed to assess the extensive geographical heterogeneity of malaria endemicity and risk populations, so that current malaria control measures can be reinforced accordingly.