BioMed Central - Latest Articles

Conservation of structure and activity in Plasmodium purine nucleoside phosphorylases

Apirat Chaikuad — 2009-07-03T00:00:00Z

Background: Purine nucleoside phosphorylase (PNP) is central to purine salvage mechanisms in Plasmodium parasites, the causative agents of malaria. Most human malaria results from infection either by Plasmodium falciparum (Pf), the deadliest form of the parasite, or by the widespread Plasmodium vivax (Pv). Whereas the PNP enzyme from Pf has previously been studied in detail, despite the prevalence of Pv little is known about many of the key metabolic enzymes from this parasite, including PvPNP. Results: The crystal structure of PvPNP is described and is seen to have many features in common with the previously reported structure of PfPNP. In particular, the composition and conformations of the active site regions are virtually identical. The crystal structure of a complex of PfPNP co-crystallised with inosine and arsenate is also described, and is found to contain a mixture of products and reactants - hypoxanthine, ribose and arsenate. The ribose C1' in this hybrid complex lies close to the expected point of symmetry along the PNP reaction coordinate, consistent with a conformation between the transition and product states. These two Plasmodium PNP structures confirm the similarity of structure and mechanism of these enzymes, which are also confirmed in enzyme kinetic assays using an array of substrates. These reveal an unusual form of substrate activation by 2' -deoxyinosine of PvPNP, but not PfPNP. Conclusions: The close similarity of the Pf and Pv PNP structures allows characteristic features to be identified that differentiate the Apicomplexa PNPs from the human host enzyme. This similarity also suggests there should be a high level of cross-reactivity for compounds designed to inhibit either of these molecular targets. However, despite these similarities, there are also small differences in the activities of the two Plasmodium enzymes.

A versatile breast reduction technique: Conical plicated central U shaped (COPCUs) mammaplasty

Eray Copcu — 2009-07-03T00:00:00Z

Background: There have been numerous studies on reduction mammaplasty and its modifications in the literature. The multitude of modifications of reduction mammaplasty indicates that the ideal technique has yet to be found. There are four reasons for seeking the ideal technique. One reason is to preserve functional features of the breast: breastfeeding and arousal. Other reasons are to achieve the real geometric and aesthetic shape of the breast with the least scar and are to minimize complications of prior surgical techniques without causing an additional complication. Last reason is the limitation of the techniques described before. To these aims, we developed a new versatile reduction mammaplasty technique, which we called conical plicated central U shaped (COPCUs) mammaplasty. Methods: We performed central plication to achieve a juvenile look in the superior pole of the breast and to prevent postoperative pseudoptosis and used central U shaped flap to achieve maximum NAC safety and to preserve lactation and nipple sensation. The central U flap was 6cm in width and the superior conical plication was performed with 2/0 PDS. Preoperative and postoperative standard measures of the breast including the superior pole fullness were compared. Results: Forty six patients were operated with the above mentioned technique. All of the patients were satisfied with functional and aesthetic results and none of them had major complications. There were no changes in the nipple innervation. Six patients becoming pregnant after surgery did not experience any problems with lactation. None of the patients required scar revision. Conclusion: Our technique is a versatile, safe, reliable technique which creates the least scar, avoids previously described disadvantages, provides maximum preservation of functions, can be employed in all breasts regardless of their sizes.

Novel swing-assist un-motorized exoskeletons for gait training

Kalyan Mankala — 2009-07-03T00:00:00Z

Robotics is emerging as a promising tool for functional training of human movement. Much of the research in this area over the last decade has focused on upper extremity orthotic devices. Some recent commercial designs proposed for the lower extremity are powered and expensive - hence, these are unaffordable by most clinics. In this paper, we present a novel un-motorized bilateral exoskeleton that can be used to assist in treadmill training of motor-impaired patients, such as with motor-incomplete spinal cord injury. The exoskeleton is designed such that the human leg will have a desirable swing motion, once it is strapped to the exoskeleton. Since this exoskeleton is un-motorized, it can be produced cheaply and also will have the potential to reduce the physical demand on therapists during treadmill training.The salient features of this swing-assist exoskeleton are: (i) The design uses torsional springs at the hip and the knee joints to assist the swing motion. The springs get charged by the treadmill during stance phase of the leg and provide propulsion forces to the leg during swing. (ii) The design of the exoskeleton uses simple dynamic models of sagittal plane walking, which are used to optimize the parameters of the springs so that the foot can clear the ground and have a desirable forward motion during walking. (iii) This design approach was used to construct a bilateral exoskeleton and was tested during treadmill walking for a range of walking speeds between 1.0 mph and 4.0 mph. Joint encoders and interface force-torque sensors mounted on the exoskeleton were used to evaluate the effectiveness of the exoskeleton in terms of the hip and knee joint torques applied by the human during treadmill walking.

Improved breast cancer survival following introduction of an organized mammography screening program among both screened and unscreened women: a population-based cohort study

Mette Kalager — 2009-07-03T00:00:00Z

IntroductionMammography screening reduces breast cancer mortality through earlier diagnosis but may convey further benefit if screening is associated with optimized treatment through multidisciplinary medical care. In Norway, a national mammography screening program was introduced among women aged 50 to 69 years during 1995/6 to 2004. Also during this time, multidisciplinary breast cancer care units were implemented. Methods: We constructed three cohorts of breast cancer patients: 1) the pre-program group comprising women diagnosed and treated before mammography screening began in their county of residence, 2) the post-program group comprising women diagnosed and treated through multidisciplinary breast cancer care units in their county but before they had been invited to mammography screening; and 3) the screening group comprising women diagnosed and treated after invitation to screening. We calculated Kaplan-Meier plots and multivariable Cox proportional hazard models. Results: We studied 41,833 women with breast cancer. The nine-year breast cancer-specific survival rate was 0.66 (95%CI: 0.65 to 0.67) in the pre-program group; 0.72 (95%CI: 0.70 to 0.74) in the post-program group; and 0.84 (95%CI: 0.80 to 0.88) in the screening group. In multivariable analyses, the risk of death from breast cancer was 14% lower in the post-program group than in the pre-program group (hazard ratio 0.86; (95%CI: 0.78 to 0.95, P=0.003)). Conclusions: After 9 years follow-up, at least 33% of the improved survival is attributable to improved breast cancer management through multidisciplinary medical care.

The association between Colombian medical students' healthy personal habits and a positive attitude toward preventive counseling: cross-sectional analyses

John Duperly — 2009-07-03T00:00:00Z

Background: Physician-delivered preventive counseling is important for the prevention and management of chronic diseases. Data from the U.S. indicates that medical students with healthy personal habits have a better attitude towards preventive counseling. However, this association and its correlates have not been addressed in rapidly urbanized settings where chronic disease prevention strategies constitute a top public health priority. This study examines the association between personal health practices and attitudes toward preventive counseling among first- and fifth-year students from 8 medical schools in Bogota, Colombia. Methods: During 2006, a total of 661 first- and fifth-year medical students completed a culturally adapted Spanish version of the "Healthy Doctor = Healthy Patient" survey (response rate=78%). Logistic regression analyses were used to assess the association between overall personal practices on physical activity, nutrition, weight control, smoking, alcohol use (main exposure variable) and student attitudes toward preventive counseling on these issues (main outcome variable), stratified by year of training and adjusting by gender and medical training-related factors (basic knowledge, perceived adequacy of training and perception of the school's promotion on each healthy habit). Results: The median age and percentage of females for the first- and fifth-year students were 21 years and 59.5% and 25 years and 65%, respectively. After controlling for gender and medical training-related factors, consumption of [greater than or equal to]5 daily servings of fruits and/or vegetables, not being a smoker or binge drinker were associated with a positive attitude toward counseling on nutrition (OR = 4.71; CI= 1.6-14.1; p = 0.006 smoking (OR = 2.62; CI= 1.1-5.9; p = 0.022), and alcohol consumption (OR = 2.61; CI= 1.3-5.4; p = 0.009), respectively. Conclusion: As for U.S. physician and medical students, a positive association was found between the personal health habits of Colombian medical students and their corresponding attitudes toward preventive counseling, independent of gender and medial training-related factors. Our findings, the first relating to this association in medical students in developing regions, also suggest that within the medical school context, interventions focused on promoting healthy student lifestyles can potentially improve future physician's attitudes toward preventive counseling.

Sequence diversity in three tomato species: SNPs, markers, and molecular evolution

Jose Jimenez-Gomez — 2009-07-03T00:00:00Z

Background: Tomato species are of significant agricultural and ecological interest, with cultivated tomato being among the most common vegetable crops grown. Wild tomato species are native to diverse habitats in South America and show great morphological and ecological diversity that has proven useful in breeding programs. However, relatively little is known about nucleotide diversity between tomato species. Until recently limited sequence information was available for tomato, preventing genome-wide evolutionary analyses. Now, an extensive collection of tomato expressed sequence tags (ESTs) is available at the SOL Genomics Network (SGN). This database holds sequences from several species, annotated with quality values, assembled into unigenes, and tested for homology against other genomes. Despite the importance of polymorphism detection for breeding and natural variation studies, such analyses in tomato have mostly been restricted to cultivated accessions. Importantly, previous polymorphisms surveys mostly ignored the linked meta-information, limiting functional and evolutionary analyses. The current data in SGN is thus an under-exploited resource. Here we describe a cross-species analysis taking full-advantage of available information. Results: We mined 20,000 interspecific polymorphisms between Solanum lycopersicum and S. habrochaites or S. pennellii and 28,800 intraspecific polymorphisms within S. lycopersicum. Using the available meta-information we classified genes into functional categories and obtained estimations of single nucleotide polymorphisms (SNP) quality, position in the gene, and effect on the encoded proteins, allowing us to perform evolutionary analyses. Finally, we developed a set of more than 10,000 between-species molecular markers optimized by sequence quality and predicted intron position. Experimental validation of 491 of these molecular markers resulted in confirmation of 413 polymorphisms. Conclusions: We present a new analysis of the extensive tomato EST sequences available that represents the most comprehensive survey of sequence diversity across Solanum species to date. These SNPs, plus thousands of molecular makers designed to detect the polymorphisms are available to the community via a website. Evolutionary analyses on these polymorphism uncovered sets of genes potentially important for the evolution and domestication of tomato; interestingly these sets were enriched for genes involved in response to the environment.

Nuclear accumulation of polyglutamine disease proteins and neuropathology

Lauren Havel — 2009-07-03T00:00:00Z

There are nine inherited neurodegenerative disorders caused by polyglutamine (polyQ) expansion in various disease proteins. Although these polyglutamine proteins have different functions and are localized in different subcellular regions, all the polyQ diseases share a common pathological feature: the nuclear accumulation of polyQ disease proteins and the formation of inclusions. The nuclear accumulation of polyQ proteins in turn leads to gene transcriptional dysregulation and neuropathology. Here we will discuss potential mechanisms behind the nuclear accumulation of mutant polyQ proteins, since an understanding of how polyQ proteins accumulate in the nucleus could help elucidate the pathogenesis of these diseases and develop their treatment.

Expression of HNF4alpha in the human and rat choroid plexus - Implications for drug transport across the blood-cerebrospinal-fluid (CSF) barrier

Monika Niehof — 2009-07-03T00:00:00Z

Background: The choroid plexus consists of highly differentiated epithelium and functions as a barrier at the interface of the blood-cerebrospinal-fluid (CSF). This tissue may therefore determine the bioavailability and transport of drugs to the brain. Little is known about the expression of drug and xenobiotic metabolizing enzymes (DME) and of drug transporters in the human choroid plexus. Notably, the transcription factor and zinc finger protein HNF4alpha is a master regulator of DMEs and of drug transporters. As of today its activity in the blood-CSF barrier is unknown. Here we report our efforts in determining HNF4alpha activity in the regulation of ABC transporters in the human and rat choroid plexus. Results: We report expression of HNF4alpha by qRT-PCR and by immunohistochemistry and evidence transcript expression of the ATP-binding cassette transporters ABCB1, ABCB4, ABCC1-6 in choroid plexus. Additionally, HNF4alpha DNA binding activity at regulatory sequences of ABCB4 and ABCC1 was determined by EMSA bandshift assays with a specific antibody. We then performed siRNA mediated functional knock down of HNF4alpha in Caco-2 cells and found ABCC1 gene expression to be repressed in cell culture experiments. Conclusions: Our study evidences activity of HNF4alpha in human and rat choroid plexus. This transcription factor targets DMEs and drug transporters and may well determine availability of drugs at the blood-CSF barrier.

Folksong based appraisal of bio-eco-cultural heritage of sorghum (Sorghum bicolor (L.) Moench): A new approach in ethnobiology

Firew Mekbib — 2009-07-03T00:00:00Z

Background: sorghum is one of the main staple crops for the world's poorest and most food insecure people. As Ethiopia is the centre of origin and diversity for sorghum, the crop has been cultivated for many thousand years and hence the heritage of the crop is expected to be rich. Folksong based appraisal of bioecocultural heritage has not been done before. Methods: In order to assess the bioecocultural heritage of sorghum by folk songs various research methods were employed. These included focus group discussions with 360 farmers, direct on farm participatory monitoring and observation with 120 farmers, and key informant interviews with 60 farmers and development agents. Relevant secondary data was also collected from the museum curators and historians. Results: It has been found out that the crop is intimately associated with the life of the farmers. The association of sorghum with the farmers from seed selection to utilization is presented using folk songs. Folksong includes both tune and textual (ballad stories or poems) types. Folksongs described that farmers maintain a number of varieties on farm for many biological, socio-economic, ecological, ethnological and cultural reasons. Farmers describe sorghum as follows: Leaf number is less than twenty; Panicle holds thousand seeds; a clever farmer holds of it. Besides, they described the various farmers' varieties ethnobotanically by songs. The relative importance of sorghum vis-a-vis others crops is similarly explained in folksong terms. Conclusions: The qualitative description of farmers' characterisation of crop system based on folksongs is a new system of appraising farmers' bioecocultural heritages. Hence, researchers in addition to formal and quantitative descriptions, have to use the folksong system for enhanced characterisation and utilization of bioecocultural heritages. In general, the vital characteristics of the folksongs used in describing the bioecocultural heritages are their oral traditions, varied function, communal or individual recreation and message transmissions.

Quality of life in Brazilian obese adolescents: effects of a long-term multidisciplinary lifestyle therapy

Mara Cristina Lofrano-Prado — 2009-07-03T00:00:00Z

Background: Obesity has adverse physical, social, and economic consequences that can negatively affect quality of life (QOL). Thus the aim of this study was to verify the effects of a long-term multidisciplinary lifestyle intervention on QOL, body image, anxiety, depression and binge eating in obese adolescents. Methods: Sixty-six obese adolescents (41 girls and 25 boys; BMI: 35.62+/-4.18kg/m2) were recruited from the Multidisciplinary Obesity Intervention Program outpatient clinic, and were submitted to a multidisciplinary lifestyle therapy (short-term = 12 weeks and long-term = 24 weeks), composed of medical, dietary, exercise and psychological programs. Validated self-report questionnaires were used to assess symptoms of anxiety Trait/State (STAI); depression (BDI); binge eating (BES), body image dissatisfaction (BSQ) and QOL (SF-36). Data were analyzed by means of scores; comparisons were made by ANOVA for repeated measures, and Tukey's test as post-hoc and Students T test. Results: Long-term therapy decreased depression and binge eating symptoms, body image dissatisfaction, and improved QOL in girls, whereas, for boys, 24 weeks, were effective to reduce anxiety trait/state and symptoms of binge eating, and to improve means of dimensions of QOL (p<.05). Conclusions: A long-term multidisciplinary lifestyle therapy is effective to control psychological aspects and to improve QOL in obese adolescents.