BioMed Central - Latest articles

Helicobacter pylori and gastroesophageal reflux disease

2008-07-05

Background: The nature of the relationship between Helicobacter pylori and reflux oesophagitis is still not clear. To investigate the correlation between Helicobacter pylori infection and GERD taking into account endoscopic, pH-metric and histopathological data. Methods: Between January 2001 and January 2003 a prospective study was performed in 146 patients with GERD in order to determine the prevalence of Helicobacter pylori infection at gastric mucosa; further the value of the De Meester score endoscopic, manometric and pH-metric parameters, i.e. reflux episodes, pathological reflux episodes and extent of oesophageal acid exposure, of the patients with and without Helicobacter pylori infection were studied and statistically compared. Finally, univariate analysis of the above mentioned data were performed in order to evaluate the statistical correlation with reflux esophagitis. Results: There were no statistically significant differences between the two groups, HP infected and HP negative patients, regarding age, gender and type of symptoms. There was no statistical difference between the two groups regarding severity of symptoms and manometric parameters. The value of the De Meester score and the ph-metric parameters were similar in both groups. On univariate analysis, we observed that hiatal hernia (p=0,01), LES size (p=0,05), oesophageal wave length (p=0,01) and pathological reflux number (p=0,05) were significantly related to the presence of reflux oesophagitis Conclusions: Based on these findings, it seems that there is no significant evidence for an important role for H. pylori infection in the development of GERD and erosive esophagitis. Nevertheless, current data do not provide sufficient evidence to define the relationship between HP and GERD. Further assessments in prospective large studies are warranted.

Coronary artery fistula; coronary computed topography - The diagnostic modality of choice.

Sarah A Early, T B Meaney, Helen M Fenlon and John Hurley — 2008-07-05

Coronary artery fistulae (CAF) are rare anomalies. They are vascular communications between the coronary arteries and other cardiac structures, either cardiac chambers or great vessels. There can be considerable variation in the course of a coronary artery fistula. We report a case of a coronary artery fistula between the left circumflex coronary artery and the right and left atria. CAF are often diagnosed by coronary angiogram, however with the advent of new technologies such as Coronary Computed Tomography Angiography (Coronary CTA) the course and communications of these fistulae can be delineated non-invasively and with greater accuracy.

Adaptive evolution of SCML1 in primates, a gene involved in male reproduction

Haihui Wu and Bing Su — 2008-07-05

Background: Genes involved in male reproduction are often the targets of natural and/or sexual selection. SCML1 is a recently identified X-linked gene with preferential expression in testis. To test whether SCML1 is the target of selection in primates, we sequenced and compared the coding region of SCML1 in major primate lineages, and we observed the signature of positive selection in primates. Results: We analyzed the molecular evolutionary pattern of SCML1 in diverse primate species, and we observed a strong signature of adaptive evolution which is caused by Darwinian positive selection. When compared with the paralogous genes (SCML2 and SCMH1) of the same family, SCML1 evolved rapidly in primates, which is consistent with the proposed adaptive evolution, suggesting functional modification after gene duplication. Gene expression analysis in rhesus macaques shows that during male sexual maturation, there is a significant expression change in testis, implying that SCML1 likely plays a role in testis development and spermatogenesis. The immunohistochemical data indicates that SCML1 is preferentially expressed in germ stem cells of testis, therefore likely involved in spermatogenesis. Conclusions: The adaptive evolution of SCML1 in primates provides a new case in understanding the evolutionary process of genes involved in primate male reproduction.

Role of carotid duplex imaging in carotid screening programmes- an overview

2008-07-04

Background: Stroke is the third most common cause of death in the UK and the largest single cause of severe disability. Each year more than 110,000 people in England suffer from a stroke which costs the National Health Service (NHS) over GBP2.8 billion. Thus, it is imperative that patients at risk be screened for underlying carotid artery atherosclerosis. Aim: To assess the role of carotid ultrasound in different carotid screening programmes. Methods: A literature overview was carried out by using PubMed search engine, to identify different carotid screening programmes that had used ultrasound scan as a screening tool. Results: It appears that the carotid ultrasound is an effective method for screening carotid artery disease in community as it effectively predicts the presence of stenosis with high accuracy. There is a need for primary care to recommend high risk patients for regular screening, to reduce stroke and transient ischemic attack (TIA) related morbidity and mortality. Conclusions: Screening programmes using carotid ultrasonography contribute to public health awareness and promotion which in long term could potentially benefit in disease prevention and essentially promote better standards of healthcare.

Seeded Bayesian Networks: constructing genetic networks from microarray data

Amira Djebbari and John Quackenbush — 2008-07-04

Background: DNA microarrays and other genomics-inspired technologies provide large datasets that often include hidden patterns of correlation between genes reflecting the complex processes that underlie cellular metabolism and physiology. The challenge in analyzing large-scale expression data has been to extract biologically meaningful inferences regarding these processes - often represented as networks - in an environment where the datasets are often imperfect and biological noise can obscure the actual signal. Although many techniques have been developed in an attempt to address these issues, to date their ability to extract meaningful and predictive network relationships has been limited. Here we describe a method that draws on prior information about gene-gene interactions to infer biologically relevant pathways from microarray data. Our approach consists of using preliminary networks derived from the literature and/or protein-protein interaction data as seeds for a Bayesian network analysis of microarray results. Results: Through a bootstrap analysis of gene expression data derived from a number of leukemia studies, we demonstrate that seeded Bayesian Networks have the ability to identify high-confidence gene-gene interactions which can then be validated by comparison to other sources of pathway data. Conclusions: The use of network seeds greatly improves the ability of Bayesian Network analysis to learn gene interaction networks from gene expression data. We demonstrate that the use of seeds derived from the biomedical literature or high-throughput protein-protein interaction data, or the combination, provides improvement over a standard Bayesian Network analysis, allowing networks involving dynamic processes to be deduced from the static snapshots of biological systems that represent the most common source of microarray data. Software implementing these methods has been included in the widely used TM4 microarray analysis package .

Prognostic factors for lymph node metastasis from advanced squamous cell carcinoma of the skin of the trunk and extremities

2008-07-04

Background: Squamous cell carcinoma (SCC) of the skin of the trunk and extremities may present lymph node metastasis with difficult disease control and poor survival. The purpose of this study was to identify risk factors for lymph node metastasis and outcome. Patients/Methods Retrospective review of 57 patients with locally advanced SCC of the trunk and extremities was performed and several clinical variables including age, gender, ethnicity, previously injured skin (burns, scars, ulcers and others), patient origin (rural or urban), anatomic site and treatment were studied. Results: Fifteen patients presented with previous skin lesions. Thirty-six were classified as T3 tumors and 21 as T4; 46 were N0, and 11, N1. Eleven N0 patients presented lymph node metastasis during follow up. Univariate analysis identified previous skin lesions (ulcers and scars) as risk factor for lymph node metastasis (p=0.047). Better survival was demonstrated for T3 (p=0.018) classification. N0 patients who presented lymph node metastasis during follow up (submitted to lymphadenectomy) had similar survival to patients without lymph node recurrence (p=0.219). Conclusions: Local advanced tumors are at risk of lymph node metastasis. Increased risk is associated to previous lesions at tumor site. T4 classification have worse prognosis. Lymph node recurrences in N0 patients, once treated, did not affect survival. For these patients, we propose close follow up and prompt treatment of lymph node metastasis. These results do not support indication for elective lymphadenectomy or sentinel node mapping. Further prospective studies must address this issue.

Tumor slices as a model to evaluate doxorubicin in vitro treatment and expression of trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 in canine mammary gland cancer

2008-07-04

Background: In women with breast cancer submitted to neoadjuvant chemotherapy based on doxorubicin, tumor expression of groups of three genes (PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2) have classified them as responsive or resistant. We have investigated whether expression of these trios of genes could predict mammary carcinoma response in dogs and whether tumor slices, which maintain epithelial-mesenchymal interactions, could be used to evaluate drug response in vitro. Methods: Tumors from 38 dogs were sliced and cultured with or without doxorubicin 1uM for 24 h. Tumor cells were counted by two observers to establish a percentage variation in cell number, between slices. Based on these results, a reduction in cell number between treated and control samples [greater than or equal to] 21.7%, arbitrarily classified samples, as drug responsive. Tumor expression of PRSS11, MTSS1, CLPTM1 and SMYD2, was evaluated by real time PCR. Relative expression results were then transformed to their natural logarithm values, which were spatially disposed according to the expression of trios of genes, comprising PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. Fisher linear discrimination test was used to generate a separation plane between responsive and non-responsive tumors. Results: Culture of tumor slices for 24 h was feasible. Nine samples were considered responsive and 29 non-responsive to doxorubicin, considering the pre-established cut-off value of cell number reduction [greater than or equal to] 21.7%, between doxorubicin treated and control samples. Relative gene expression was evaluated and tumor samples were then spatially distributed according to the expression of the trios of genes: PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. A separation plane was generated. However, no clear separation between responsive and non-responsive samples could be observed. Conclusion: Three-dimensional distribution of samples according to the expression of the trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 could not predict doxorubicin in vitro responsiveness. Short term culture of mammary gland cancer slices may be an interesting model to evaluate chemotherapy activity.

Idiopathic central precocious puberty in girls: presentation factors

Geraldine Prete, Ana-Claudia Couto-Silva, Christine Trivin and Raja Brauner — 2008-07-04

Background: It is sometimes difficult to distinguish between premature thelarche and precocious puberty in girls who develop breasts before the age of 8 years. We evaluated the frequencies of the signs associated with breast development and the factors influencing the presentation of girls with idiopathic central precocious puberty (CPP). Methods: 353 girls monitored 0.9 +/- 0.7 year after the onset of CPP. Results: The age at CPP was < 3 years in 2%, 3-7 years in 38% and 7-8 years in 60% of cases. Pubic hair was present in 67%, growth rate greater than 2 SDS in 46% and bone age advance greater than 2 years in 33% of cases. Breast development was clinically isolated in 70 (20%) cases. However, only 31 of these (8.8% of the population) had a prepubertal length uterus and gonadotropin responses to gonadotropin releasing hormone and plasma estradiol. The clinical picture of CPP became complete during the year following the initial evaluation. 25% of cases were obese. The increase in weight during the previous year (3.7+/-1.4 kg) and body mass index were positively correlated with the statural growth and bone age advance (P<0.0001). There was no relationship between the clinical-biological presentation and the age at puberty, the interval between the onset of puberty and evaluation, or the presence of familial CPP. Conclusion: The variation in presentation of girls with CPP does not depend on their age, interval between the onset and evaluation, or familial factors. This suggests that there are degrees of hypothalamic-pituitary-ovarian activation that are not explained by these factors.

Simultaneous adrenal and extra-adrenal myelolipoma - an uncommon incident: case report and review of the literature

2008-07-04

Background: Extra-adrenal myelolipomas are rare benign tumours. Other soft tissue tumours such as well-differentiated liposarcomas appear morphological almost identical. Preoperative imaging and especially biopsy are important tools to diagnose these lesions. Case presentationWe report a very seldom case of a simultaneous myelolipoma of the adrenal gland in association with an extra-adrenal myelolipoma in an 75-year-old man. With a review of the literature we describe and discuss the aetiology, differential diagnosis and treatment of patients with respect to adrenal and extra-adrenal lesions. Conclusions: The appearance of a simultaneous adrenal and extra-adrenal myelolipoma is a rare incident. We conclude that such lesions should be considered in the differential diagnosis of a fat-containing tumour in the retroperitoneal tissue/compartment.

Relative performance of different exposure modeling approaches for sulfur dioxide concentrations in the air in rural western Canada

Igor Burstyn, Nicola M Cherry, Yutaka Yasui and Hyang-Mi Kim — 2008-07-04

Background: The main objective of this paper is to compare different methods for predicting the levels of SO2 air pollution in oil and gas producing area of rural western Canada. Month-long average air quality measurements were collected over a two-year period (2001-2002) at multiple locations, with some side-by-side measurements, and repeated time-series at selected locations. Methods: We explored how accurately location-specific mean concentrations of SO2 can be predicted for 2002 at 666 locations with multiple measurements. Means of repeated measurements on the 666 locations in 2002 were used as the alloyed gold standard (AGS). First, we considered two approaches: one that uses one measurement from each location of interest; and the other that uses context data on proximity of monitoring sites to putative sources of emission in 2002. Second, we imagined that all of the previous year's (2001's) data were also available to exposure assessors: 9,464 measurements and their context (month, proximity to sources). Exposure prediction approaches we explored with the 2001 data included regression modeling using either mixed or fixed effects models. Third, we used Bayesian methods to combine single measurements from locations in 2002 (not used to calculate AGS) with different priors. Results: The regression method that included both fixed and random effects for prediction (Best Linear Unbiased Predictor) had the best agreement with the AGS (Pearson correlation 0.77) and the smallest mean squared error (MSE: 0.03). The second best method in terms of correlation with AGS (0.74) and MSE (0.09) was the Bayesian method that uses normal mixture prior derived from predictions of the 2001 mixed effects applied in the 2002 context. Conclusions: It is likely that either collecting some measurements from the desired locations and time periods or predictions of a reasonable empirical mixed effects model perhaps is sufficient in most epidemiological applications. The method to be used in any specific investigation will depend on how much uncertainty can be tolerated in exposure assessment and how closely available data matches circumstances for which estimates/predictions are required.

A randomised controlled trial to assess the effectiveness of a single session of nurse administered massage for short term relief of chronic non-malignant pain.

Kate Seers, Nicola Crichton, June Martin, Katrina Coulson and Dawn Carroll — 2008-07-04

Background: Massage is increasingly used to manage chronic pain but its benefit has not been clearly established. The aim of the study is to determine the effectiveness of a single session of nurse admninistered massage for relief of chronic non-malignant pain and anxiety. Methods: A randomised controlled trial design was used, in which the patients were assigned to a massage or control group. The massage group received a 15 minute manual massage and the control group a 15 minute visit to talk about their pain. Adult patients attending a pain relief unit with a diagnosis of chronic pain whose pain was described as moderate or severe were eligible for the study. An observer blind to the patientsa treatment group carried out assessments immediately before (baseline), after treatment and 1, 2, 3 and 4 hours later. Pain was assessed using 100mm visual analogue scale and the McGill Pain Questionnaire. Pain Relief was assessed using a five point verbal rating scale. Anxiety was assessed with the Spielberger short form State-Trait Anxiety Inventory. Results: 101 patients were randomised and evaluated, 50 in the massage and 51 in the control group. There were no statistically significant differences between the groups at baseline interview. Patients in the massage but not the control group had significantly less pain compared to baseline immediately after and one hour post treatment. 95% confidence interval for the difference in mean pain reduction at one hour post treatment between the massage and control groups is 5.47mm to 24.70mm. Patients in the massage but not the control group had statistically significantly less anxiety compared to baseline immediately after and at 1 and 2 hours post treatment. Conclusion: Massage is effective in the short term for chronic pain of moderate to severe intensity.

Use of data mining techniques to investigate disease risk classification as a proxy for compromised biosecurity of cattle herds in Wales

Angel Ortiz-Pelaez and Dirk U. Pfeiffer — 2008-07-04

Background: Biosecurity is at the forefront of the fight against infectious diseases in animal populations. Few research studies have attempted to identify and quantify the effectiveness of biosecurity against disease introduction or presence in cattle farms and, when done, they have relied on the collection of on-farm data. Data on environmental, animal movement, demographic/husbandry systems and density disease determinants can be collated without requiring additional specific on-farm data collection activities, since they have already been collected for some other purposes. The aim of this study was to classify cattle herds according to their risk of disease presence as a proxy for compromised biosecurity in the cattle population of Wales for risk-based surveillance purposes. Results: Three data mining methods have been applied: logistic regression, classification trees and factor analysis. Using the cattle holding population in Wales, a holding was considered positive if at least bovine TB or one of the ten most frequently diagnosed infectious or transmissible non-notifiable diseases in England and Wales, according to the Veterinary Investigation Surveillance Report (VIDA) had been diagnosed in 2004. High-risk holdings can be described as open large cattle herds located in high-density cattle areas with frequent movements off to many locations within Wales. Additional risks are associated with the holding being a dairy enterprise and with a large farming area. Conclusions: This work has demonstrated the potential of mining various livestock-relevant databases to obtain generic criteria for individual cattle herd biosecurity risk classification. Despite the data and analytical constraints the described risk profiles are highly specific and present variable sensitivity depending on the model specifications. Risk profiling of farms provides a tool for designing targeted surveillance activities for endemic or emerging diseases, regardless of the prior amount of information available on biosecurity at farm level. As the delivery of practical evidence-based information and advice is one of the priorities of Defra's new Animal Health and Welfare Strategy (AHWS), data-driven models, derived from existing databases, need to be developed that can then be used to inform activities during outbreaks of endemic diseases and to help design surveillance activities.

Utility of CD4 cell counts for early prediction of virological failure during antiretroviral therapy in a resource-limited setting

Motasim Badri, Stephen D Lawn and Robin Wood — 2008-07-04

Background: Viral load monitoring is not available for the vast majority of patients receiving antiretroviral therapy in resource-limited settings. However, the practical utility of CD4 cell count measurements as an alternative monitoring strategy has not been rigorously assessed. Methods: In this study, we used a novel modelling approach that accounted for all CD4 cell count and VL values measured during follow-up from the first date that VL suppression was achieved. We determined the associations between CD4 counts (absolute values and changes during ART), VL measurements and risk of virological failure (VL>1,000 copies/ml) following initial VL suppression in 330 patients in South Africa. CD4 count changes were modelled both as the difference from baseline (delta CD4 count) and the difference between consecutive values (CD4 count slope) using all 3-monthly CD4 count measurements during follow-up. Results: During 7093.2 patient-months of observation 3756 paired CD4 count and VL measurements were made. In patients who developed virological failure (n=179), VL correlated significantly with absolute CD4 counts (r=-0.08, P =0.003), delta CD4 counts (r=-0.11,P<0.01), and most strongly with CD4 count slopes (r=-0.30,P<0.001). However, the distributions of the absolute CD4 counts, delta CD4 counts and CD4 count slopes at the time of virological failure did not differ significantly from the corresponding distributions in those without virological failure (P=0.99, P=0.92 and P=0.75, respectively). Moreover, in a receiver operating characteristic (ROC) curve, the association between a negative CD4 count slope and virological failure was poor (area under the curve=0.59; sensitivity=53.0%; specificity=63.6%; positive predictive value=10.9%). Conclusions: CD4 count changes correlated significantly with VL at group level but had very limited utility in identifying virological failure in individual patients. CD4 count is an inadequate alternative to VL measurement for early detection of virological failure.

Orthographic familiarity, phonological legality and number of orthographic neighbours affect the onset of ERP lexical effects

Alice M Proverbio and Roberta Adorni — 2008-07-04

Background: It has been suggested that the variability among studies in the onset of lexical effects may be due to a series of methodological differences. In this study we investigated the role of orthographic familiarity, phonological legality and number of orthographic neighbours of words in determining the onset of word/non-word discriminative responses. MethodS ERPs were recorded from 128 sites in 16 Italian University students engaged in a lexical decision task. Stimuli were 400 words, quasi-words (obtained by the replacement of a single letter), pseudo-words (non-derived) and illegal letter strings. All stimuli were balanced for length; words and quasi-words were also balanced for frequency of use, domain of semantic category and imageability. SwLORETA source reconstruction was performed on ERP difference waves of interest. Results: Overall, the data provided evidence that the latency of lexical effects (word/non-word discrimination) varied as a function of the number of a wordas orthographic neighbours, being shorter to non-derived than to derived pseudo-words. This suggests some caveats about the use in lexical decision paradigms of quasi-words obtained by transposing or replacing only 1 or 2 letters. Our findings also showed that the left-occipito/temporal area, reflecting the activity of the left fusiform gyrus (BA37) of the temporal lobe, was affected by the visual familiarity of words, thus explaining its lexical sensitivity (word vs. non-word discrimination). The temporo-parietal area was markedly sensitive to phonological legality exhibiting a clear-cut discriminative response between illegal and legal strings as early as 250 ms of latency. Conclusion: The onset of lexical effects in a lexical decision paradigm depends on a series of factors, including orthographic familiarity, degree of global lexical activity, and phonologic legality of non-words.

Disclosing intimate partner violence to health care clinicians- what a difference the setting makes: a qualitative study

Jane Liebschutz, Tracy Battaglia, Erin Finley and Tali Averbuch — 2008-07-04

Background: Despite endorsement by national organizations, the impact of screening for intimate partner violence (IPV) is understudied, particularly as it occurs in different clinical settings. We analyzed interviews of IPV survivors to understand the risks and benefits of disclosing IPV to clinicians across specialties. Methods: Participants were English-speaking female IPV survivors recruited through IPV programs in Massachusetts. In-depth interviews describing medical encounters related to abuse were analyzed for common themes using Grounded Theory qualitative research methods. Encounters with health care clinicians were categorized by outcome (IPV disclosure by patient, discovery evidenced by discussion of IPV by clinician without patient disclosure, or non-disclosure), attribute (beneficial, unhelpful, harmful), and specialty (emergency department (ED), primary care (PC), obstetrics/gynecology (OB/GYN)). Results: Of 27 participants aged 18-56, 5 were white, 10 Latina, and 12 black. Of 59 relevant health care encounters, 23 were in ED, 17 in OB/GYN, and 19 in PC. Seven of 9 ED disclosures were characterized as unhelpful; the majority of disclosures in PC and OB/GYN were characterized as beneficial. There were no harmful disclosures in any setting. Unhelpful disclosures resulted in emotional distress and alienation from health care. Regardless of whether disclosure occurred, beneficial encounters were characterized by familiarity with the clinician, acknowledgement of the abuse, respect and relevant referrals. Conclusion: While no harms resulted from IPV disclosure, survivor satisfaction with disclosure is shaped by the setting of the encounter. Clinicians should aim to build a therapeutic relationship with IPV survivors that empowers and educates patients and does not demand disclosure.

Molecular Epidemiology and pathogenic Potential of underdiagnosed human Papillomavirus Types

2008-07-04

Background: Human papillomavirus (HPV) tests are crucial diagnostic tools for the prevention of neoplastic lesions of the uterine cervix. However most commercial methods are designed to detect high-risk (HR) HPV types and a limited selection of low-risk ones, thus missing a fair number of intermediate/low-risk types. As a result, many HPV infections remain undiagnosed, generating distrust in virological diagnosis among gynaecologists, who continue to rely preferentially on cytological and colposcopic findings. Results: In this study, we tested 6,335 consecutive clinical samples, most of them from Italian patients with cytological abnormalities. The samples, collected in 2000-2007, were analyzed using PCR amplification of a 173-206 bp (depending on HPV type) conserved region in the L1 open reading frame, restriction endonuclease analysis and, where required, sequence analysis for type determination. Analysis of a smaller male sample and long term follow-up of a few female subjects was also performed. A total of 2,004 samples tested positive for HPV DNA (32.1%); 21.3% of them were mixed infections. Overall, 59 known and 2 unknown HPV types were detected. Their relative prevalence was calculated; notably, types not clearly identifiable using the most common commercial method accounted for 36% of infections. Clinical findings associated with the underdiagnosed types ranged from H-SIL to low-grade abnormalities, although none of these infections resulted in invasive cancer. Conclusions: Given the high prevalence of some underdiagnosed HPV types in the population (principally HPV53, HPV66, HPV84, and HPV87) and their frequent association with cytological abnormalities, techniques capable of detecting and typing them would prove extremely useful.

Muscle performance and ankle joint mobility in long-term patients with diabetes

2008-07-04

Background: Long-term patients with diabetes and peripheral neuropathy show altered foot biomechanics and abnormal foot loading. This study aimed at assessing muscle performance and ankle mobility in such patients under controlled conditions. Methods: Forty six long-term diabetes patients with (DN) and without (D) peripheral neuropathy, and 21 controls (C) were examined. Lower leg muscle performance and ankle mobility were assessed by means of a dedicated equipment, with the patient seated and the examined limb unloaded. 3D active ranges of motion and moments of force were recorded, the latter during maximal isometric contractions, with the foot blocked in different positions. Results: All patients showed reduced ankle mobility. In the sagittal and transversal planes reduction vs C was 11% and 20% for D, 20% and 21% for DN, respectively. Dorsal-flexing moments were significantly reduced in all patients and foot positions, the highest reduction being 28% for D and 37% for DN. Reductions of plantar-flexing moments were in the range 12-15% for D (only with the foot blocked in neutral and in dorsal-flexed position), and in the range 10-24% for DN. In all patients, reductions in the frontal and transversal planes ranged 14-41%. Conclusions: The investigation revealed ankle functional impairments in patients with diabetes, with or without neuropathy, thus suggesting that other mechanisms besides neuropathy might contribute to alter foot-ankle biomechanics. Such impairments may then play a role in the development of abnormal gait and in the onset of plantar ulcers.

Timing and deciphering mitochondrial DNA macro-haplogroup R0 variability in Central Europe and Middle East

2008-07-04

Background: Nearly half of the West Eurasian assemblage of human mitochondrial DNA (mtDNA) is fractioned into numerous sub-lineages of the predominant haplogroup (hg) R0. Several hypotheses have been proposed on the origin and the expansion times of some R0 sub-lineages, which were partially inconsistent with each other. Here we describe the phylogenetic structure and genetic variety of hg R0 in five European populations and one population from the Middle East. Results: Our analysis of 1,350 mtDNA haplotypes belonging to R0, including entire control region sequences and 45 single nucleotide polymorphisms from the coding region, revealed significant differences in the distribution of different sub-hgs even between geographically closely located regions. Estimates of coalescence times that were derived using diverse algorithmic approaches consistently affirmed that the major expansions of the different R0 hgs occurred in the terminal Pleistocene and early Holocene. Conclusions: Given an estimated coalescence time of the distinct lineages of 10 - 18 kya, the differences in the distributions could hint to either limited maternal gene flow after the last glacial maximum due to the alpine nature of the regions involved or to a stochastic loss of diversity due to environmental events and/or disease episodes occurred at different times and in distinctive regions. Our comparison of two different ways of obtaining the timing of the most recent common ancestor confirms that the time of a sudden expansion can be adequately recovered from control region data with valid confidence intervals. For reliable estimates, both procedures should be applied in order to cross-check the results for validity and soundness.

Antibody responses to the merozoite surface protein-1 complex in cerebral malaria patients in India

2008-07-04

Background: Plasmodium falciparum infection causes cerebral malaria (CM) in a subset of patients with anti-malarial treatment protecting only about 70% to 80% of patients. Why a subset of malaria patients develops CM complications, including neurological sequelae or death, is still not well understood. It is believed that host immune factors may modulate CM outcomes and there is substantial evidence that cellular immune factors, such as cytokines, play an important role in this process. In this study, the potential relationship between the antibody responses to the merozoite surface protein (MSP)-1 complex (which consists of four fragments namely: MSP-183, MSP-130, MSP-138 and MSP-142), MSP-636 and MSP-722 and CM was investigated. Methods: Peripheral blood antibody responses to recombinant antigens of the two major allelic forms of MSP-1 complex, MSP-636 and MSP-722 were compared between healthy subjects, mild malaria patients (MM) and CM patients residing in a malaria endemic region of central India. Total IgG and IgG subclass antibody responses were determined using ELISA method. Results: The prevalence and levels of IgG and its subclasses in the plasma varied for each antigen. In general, the prevalence of total IgG, IgG1 and IgG3 was higher in the MM patients and lower in CM patients compared to healthy controls. Significantly lower levels of total IgG antibodies to the MSP-1f38, IgG1 levels to MSP-1d83, MSP-119 and MSP-636 and IgG3 levels to MSP-1f42 and MSP-722 were observed in CM patients as compared to MM patients. Conclusion: These results suggest that there may be some dysregulation in the generation of antibody responses to some MSP antigens in CM patients and it is worth investigating further whether perturbations of antibody responses in CM patients contribute to pathogenesis.

Peri-operative Data on the Nuss procedure in children with pectus excavatum: Independent survey of the first 20 years' data

Aristotle D Protopapas and Thanos Athanasiou — 2008-07-04

ObjectiveTo review the literature and assess the cumulative data on the Nuss operation in children on its twenty years' anniversary: The Nuss procedure corrects the pectus excavatum by minimal access semi-permanent insertion of metal bars in order to reduce the deformity and refashion the contour of the growing thorax. The advantage over previous techniques is avoidance of osteochondrotomies and thence allowance for normal growth of the thorax. Study design PubMed search was performed. Primary outcomes were mortality, morbidity and individual complications. Secondary outcomes were procedure time and hospital stay. Results: We merged the data from 19 reports comprising 1949 children of mean age 10.6 years. No mortality was observed and the procedure was associated with morbidity of 15.4%. The commonest complications are bar-related adverse events (5.7%) and pneumothorax (3.5%).The average procedure time and the average hospital stay were 68 minutes and 5.5 days respectively. Conclusion: 20 years of initial evidence suggests that the Nuss group of procedures is a safe minimal access option for correction of pectus excavatum in childhood.

Between-groups within-gene heterogeneity of residual variances in microarray gene expression data

Joaquim Casellas and Luis Varona — 2008-07-04

Background: The analysis of microarray gene expression data typically tries to identify differential gene expression patterns in terms of differences of the mathematical expectation between groups of arrays (e.g. treatments or biological conditions). Nevertheless, the differential expression pattern could also be characterized by group-specific dispersion patterns, although little is known about this phenomenon in microarray data. Commonly, a homogeneous gene-specific residual variance is assumed in hierarchical mixed models for gene expression data, although it could result in substantial biases if this assumption is not true. Results: In this manuscript, a hierarchical mixed model with within-gene heterogeneous residual variances is proposed to analyze gene expression data from non-competitive hybridized microarrays. Moreover, a straightforward Bayes factor is adapted to easily check within-gene (between groups) heterogeneity of residual variances when samples are grouped in two different treatments. This Bayes factor only requires the analysis of the complex model (hierarchical mixed model with between-groups heterogeneous residual variances for all analyzed genes) and gene-specific Bayes factors are provided from the output of a simple Markov chain Monte Carlo sampling. Conclusions: This statistical development opens new research possibilities within the gene expression framework, where heterogeneity in residual variability could be viewed as an alternative and plausible characterization of differential expression patterns.

Chronic disease risk factors, healthy days and medical claims in South African employees presenting for health risk screening

2008-07-04

Background: South Africa (SA) has a dual burden of disease with non-communicable diseases (NCD) accounting for more than a third (37%) of all deaths. The aim of this study was determine the health and risk profile of South African employees presenting for health risk assessments, and to measure the association with readiness to change and health-related expenditure. Methods: Employees (n=1954) from 18 companies were invited to take part in a wellness day, which included a health-risk assessment. Self-reported health behaviour and health status was recorded. Clinical measures included cholesterol finger-prick test, blood pressure and Body Mass Index (BMI). Health-related age was calculated using an algorithm incorporating the relative risk for all case mortality associated with smoking, physical activity, fruit and vegetable intake, BMI and cholesterol. Medical claims data were obtained from the health insurer. Results: The mean percentage of participation was 26% (n = 1954) and ranged from 4% in transport to 81% in the consulting sector. Health-related age (38.5 +/- 12.9 years) was significantly higher than chronological age (34.9 +/- 10.3 yrs) (p<0.001). Both chronological and risk-related age were significantly different between the sectors (P< 0.001), with the manufacturing sector being the oldest and finance having the youngest employees. Health-related age was significantly associated with number of days adversely affected by mental and physical health, days away from work and total annual medical costs (p<0.001). Employees had higher rates of overweight, smoking among men, and physical inactivity (total sample) when compared the general SA population. Increased health-related expenditure was associated with increased number of risk factors, absenteeism and reduced physical activity. Conclusion: SA employees' health and lifestyle habits are placing them at increased risk for NCD's, suggesting that they may develop NCD's earlier than expected. Inter-sectoral differences for health-related age might provide insight into those companies which have the greatest need for interventions, and may also assist in predicting future medical expenditure. This study underscores the importance of determining the health and risk status of employees which could assist in identifying the appropriate interventions to reduce the risk of NCD's among employees.

Population structure of the malaria vector Anopheles moucheti in the equatorial forest region of Africa

2008-07-04

Background: Anopheles moucheti is a major malaria vector in forested areas of Africa. However, despite its important epidemiological role, it remains poorly known and insufficiently studied. Here, levels of genetic differentiation were estimated between different A. moucheti populations sampled throughout its distribution range in Central Africa. Methods: Polymorphism at ten microsatellite markers was compared in mosquitoes sampled in Cameroon, the Democratic Republic of Congo and an island on Lake Victoria in Uganda. Microsatellite data were used to estimate genetic diversity within populations, their relative long-term effective population size, and the level of genetic differentiation between them. Results: All specimens collected in Tsakalakuku (Democratic Republic of Congo) were identified as A. m. bervoetsi while other samples consisted of A. m. moucheti. Successful amplification was obtained at all microsatellite loci within all A. m. moucheti samples while only six loci amplified in A. m. bervoetsi. Allelic richness and heterozygosity were high for all populations except the island population of Uganda and A. m. bervoetsi. High levels of genetic differentiation were recorded between A. m. bervoetsi and each A. m. moucheti sample as well as between the island population of A. m. moucheti and mainland populations. Significant isolation by distance was evidenced between mainland populations. Conclusion: High levels of genetic differentiation supports complete speciation of A. m. bervoetsi which should henceforth be recognized as a full species and named A. bervoetsi. Isolation by distance is the main force driving differentiation between mainland populations of A. m. moucheti. Genetically and geographically isolated populations exist on Lake Victoria islands, which might serve as relevant field sites for evaluation of innovative vector control strategies.

Prevalence of depressive disorders in Rasht, Iran: a community based study

2008-07-04

IntroductionDepression is a well known health problem worldwide. Prevalence of depressive disorders varies in different societies. Aim: to determine the prevalence of depressive disorders and some associated factors in Rasht City (Northern part of Iran). Materials & Methods: 4020 subjects were selected among 394925 residents of Rasht aged between 18 -70 during 2003 - 2004. In the first phase, subjects were screened by Beck's Depression Inventory. In the second phase, those who scored more than 15 were assessed through semi-structured psychiatric interview (DSMIV).Socio-demographic data including age, gender, marital status, educational level, and socio-economical class was recorded as well. Results: 9.5% of samples (63% female and 37% male) were diagnosed by depressive disorders. The prevalence of minor depressive disorder, dysthymia and major depressive disorder was 5%, 2/5%, and 1% respectively. Socio-economic class was significantly associated with both depressive symptoms based on BDI score (p <0.001) and depressive disorders based on clinical interview (p <0.001). Conclusion: Comparing to other studies, this study revealed that prevalence of dysthymic and minor depressive disorder was more than major depressive disorder, and low socioeconomical class was the most significant risk factor associated with depression. Regarding our study limitations, researchers and policy makers should not consider our findings as conclusive results. Results of this study could be applied by researchers using analytical methodology to assess relationship between depressive disorders and associated factors.

Opposing effects of D-aspartic acid and nitric oxide on tuning of testosterone production in mallard testis during the reproductive cycle

Maria M Di Fiore, Claudia Lamanna, Loredana Assisi and Virgilio Botte — 2008-07-04

Background: D-Aspartic acid (D-Asp) and nitric oxide (NO) play an important role in tuning testosterone production in the gonads of male vertebrates. In particular, D-Asp promotes either the synthesis or the release of testosterone, whereas NO inhibits it. In this study, we have investigated for the first time in birds the putative effects of D-Asp and NO on testicular testosterone production in relation to two phases of the reproductive cycle of the adult captive wild-strain mallard (Anas platyrhynchos) drake. It is a typical seasonal breeder and its cycle consists of a short reproductive period (RP) in the spring (April-May) and a non reproductive period (NRP) in the summer (July), a time when the gonads are quiescent. The presence and the localization of D-Asp and NO in the testis and the trends of D-Asp, NO and testosterone levels were assessed during the main phases of the bird's reproductive cycle. Furthermore, in vitro experiments revealed the direct effect of exogenously administered D-Asp and NO on testosterone steroidogenesis. Methods: By using immunohistochemical (IHC) techniques, we studied the presence and the distributional pattern of D-Asp and NO in the testes of RP and NRP drakes. D-Asp levels were evaluated by an enzymatic method, whereas NO content, via nitrite, was assessed using biochemical measurements. Finally, immunoenzymatic techniques determined testicular testosterone levels. Results: IHC analyses revealed the presence of D-Asp and NO in Leydig cells. The distributional pattern of both molecules was in some way correlated to the steroidogenic pathway, which is involved in autocrine testosterone production. Indeed, whereas NO was present only during the NRP, D-Asp was almost exclusively present during the RP. Consistently, the high testosterone testicular content occurring during RP was coupled to a high D-Asp level and a low NO content in the gonad. By contrast, in sexually inactive drakes (NRP), the low testosterone content in the gonad was coupled to a low D-Asp content and to a relatively high NO level. Consequently, to determine the exogenous effects of the two amino acids on testosterone synthesis, we carried out in vitro experiments using testis sections deriving from both the RP and NRP. When testis slices were incubated for 60 or 120 min with D-Asp, testosterone was enhanced, whereas in the presence of L-Arg, a precursor of NO, it was inhibited. Conclusions: Our results provide new insights into the involvement of D-Asp and NO in testicular testosterone production in the adult captive wild-strain mallard drake. The localization of these two molecules in the Leydig cells in different periods of the reproductive cycle demonstrates that they play a potential role in regulating local testosterone production.

Strain-encoding cardiovascular magnetic resonance for assessment of right-ventricular regional function

2008-07-04

Background: Tissue tagging by cardiovascular magnetic resonance (CMR) is a comprehensive method for assessment of cardiac regional function. However, imaging the right ventricle (RV) using this technique is problematic due to the thin wall of the RV relative to tag spacing which limits assessment of regional function using conventional in-plane tagging. Hypothesis: We hypothesize that the use of through-plane tags in the strain-encoding (SENC) CMR technique would result in reproducible measurements of the RV regional function due to high image quality and spatial resolution possible with SENC. Aim: To test the intra- and inter-observer variabilities of RV peak systolic strain measurements with SENC CMR for assessment of RV regional function (systolic strain) in healthy volunteers. Methods: Healthy volunteers (n = 21) were imaged using SENC. A four-chamber view was acquired in a single breath-hold. Circumferential strain was measured during systole at six equidistant points along the RV free wall. Peak contraction is defined as the maximum value of circumferential strain averaged from the six points, and regional function is defined as the strain value at each point at the time of peak contraction. Results: Mean values for peak circumferential strain (+/- standard deviation) of the basal, mid, and apical regions of the RV free wall were -20.4+/-2.9%, -18.8+/-3.9%, and -16.5+/-5.7%, Altman plots showed good intra- and inter-observer agreements with mean difference of 0.11% and 0.32% and limits of agreement of -4.038 to 4.174 and -4.903 to 5.836, respectively. Conclusion: SENC CMR allows for rapid quantification of RV regional function with low intra- and inter-observer variabilities, which could permit accurate quantification of regional strain in patients with RV dysfunction.

Estrogen level monitoring in artificial frozen-thawed embryo transfer cycles using step-up regime without pituitary suppression: is it necessary?

Zhihong Niu, Yun Feng, Yijuan Sun, Aijun Zhang and Huiqin Zhang — 2008-07-04

Background: To discuss the meaning of serum oestradiol monitoring in frozen embryo transfer cycle using hormone replacement without pretreatment with gonadotropin hormone (GnRH) agonist.MethodThe data from two hundred twelve women undergoing two hundred seventy-four frozen-thawed embryo transfer (FET) cycles was included in this retrospective cohort study. They ware detected of serum oestradiol levels and endometrium thicknesses during hormone supplement FET cycles and compared their pregnancy outcomes according to their oestradiol level on progesterone initiation day. Results: Patients with different levels of serum oestradiol (percentile 0-25th, 25th-75th and 75th-100th) on progesterone initiation day yielded the endometrium thickness of 9.3+/-0.12, 8.9+/-0.07 and 9.1+/-0.11 mm( P>0.05) and the pregnancy rate of 32.2%, 38.4% and 36.3% (P>0.05) respectively. Conclusions: The serum estradiol level did not predict pregnancy success in hormone replacement FET cycles, suggesting that oestradiol monitoring in this method of endometrial preparation is unnecessary.

Synchrony between orientation-selective neurons is modulated during adaptation-induced plasticity in cat visual cortex

2008-07-03

Background: Visual neurons respond essentially to luminance variations occurring within their receptive fields. In primary visual cortex, each neuron is a filter for stimulus features such as orientation, motion direction and velocity, with the appropriate combination of features eliciting maximal firing rate. Temporal correlation of spike trains was proposed as a potential code for linking the neuronal responses evoked by various features of a same object. In the present study, synchrony strength was measured between cells following an adaptation protocol (prolonged exposure to a non-preferred stimulus) which induce plasticity of neurons' orientation preference. Results: Multi-unit activity from area 17 of anesthetized adult cats was recorded. Single cells were sorted out and (1) orientation tuning curves were measured before and following 12 min adaptation and 60 min after adaptation (2) pairwise synchrony was measured by an index that was normalized in relation to the cells' firing rate. We first observed that the prolonged presentation of a non-preferred stimulus produces attractive (58%) and repulsive (42%) shifts of cells' tuning curves. It follows that the adaptation-induced plasticity leads to changes in preferred orientation difference, i.e. increase or decrease in tuning properties between neurons. We report here that, after adaptation, the neuron pairs that shared closer tuning properties display a significant increase of synchronization. Recovery from adaptation was accompanied by a return to the initial synchrony level. Conclusion: We conclude that synchrony reflects the similarity in neurons' response properties, and varies accordingly when these properties change.