Pathways with members that have known relevance to a disease are used to support hypotheses generated from analyses of gene expression and proteomic studies. Using cancer as an example, the pitfalls of searching pathways databases as support for genes and proteins that could represent false discoveries are explored.
The frequency with which networks could be generated from 100 instances each of randomly selected five and ten genes sets as input to MetaCore, a commercial pathways database, was measured. A PubMed search enumerated cancer-related literature published for any gene in the networks. Using three, two, and one maximum intervening step between input genes to populate the network, networks were generated with frequencies of 97%, 77%, and 7% using ten gene sets and 73%, 27%, and 1% using five gene sets. PubMed reported an average of 4225 cancer-related articles per network gene.
This can be attributed to the richly populated pathways databases and the interest in the molecular basis of cancer. As information sources become enriched, they are more likely to generate plausible mechanisms for false discoveries.
Databases; Pathways; Genes; Networks; Bioinformatics; Cancer pathways
BMC Research Notes recently published a research article regarding the use of ligated DNA extracted from formalin-fixed paraffin embedded (FFPE) tissue on the Illumina Infinium methylation platform - “Interpretation of genome-wide infinium methylation data from ligated DNA in formalin-fixed, paraffin-embedded paired tumor and normal tissue” Jasmine et al. BMC Research Notes 2012, 5:117. This article repeatedly refers to our previous work and concludes that methylation data obtained from ligated FFPE extracted DNA should be used with great caution. In this Discussion we review the data analysis performed in Jasmine et al’s paper and suggest limitations which subsequently lead the authors to draw what we believe are incorrect conclusions. Moreover, we continue to analyse genome-wide methylation data from DNA extracted from FFPE tissue successfully on both the HumMeth27 and 450 K arrays.
Surveillance of neurotrauma events is necessary to guide the development and evaluation of effective injury prevention initiatives. The aim of this paper is to review potential sources of existing population-based data to inform neurotrauma prevention in Canada, using sources available in Ontario as an example. Data sources, including administrative data holdings from Ontario’s publicly funded health care system and ongoing national surveys, were reviewed to determine the degree of relevance for neurotrauma surveillance, using standards outlined by the World Health Organization as a framework.
Five key data sources were identified for neurotrauma surveillance. Five other sources were considered useful; cause of injury was not identifiable in 5 additional sources; and 4 sources were not relevant for surveillance purposes.
We provide information about which existing data sources are most relevant for neurotrauma surveillance and research, as well as examine the strengths and limitations of these sources. Administrative data can be used to facilitate surveillance of neurotrauma and are considered both useful and cost effective for the development and evaluation of injury prevention programs.
Prevention; Surveillance; Spinal cord injuries; Brain injuries; Data sources
Increasing the scope of an evidence based approach to areas outside healthcare has renewed the importance of a long-standing discussion on randomised versus observational study designs in evaluating the effectiveness of interventions. We investigate statistically if an increasing recognition of the role of certain nonrandomised studies to support or generalize the results of randomised controlled trials has had an impact on the actual inclusion criteria applied in Cochrane reviews.
We conduct an on-line search of the Cochrane Database of Systematic Reviews (CDSR) and divide all Cochrane reviews according to their design inclusion criterion: (A) RCTs only or (B) RCTs and (some subset of) observational studies. We test statistically whether a shift in the proportion of category B reviews has occurred by comparing reviews published before 2008 with reviews published during 2008/09.
We find that the proportion of Cochrane reviews choosing a broader inclusion criterion has increased, although by less than two percentage points. The shift is not statistically significant (P = 0.08).
There is currently not sufficient data to support a hypothesis of a significant shift in favour of including observational studies, neither at the aggregate level nor at the level of individual Review Groups within the Cochrane Collaboration.
Systematic reviews; Observational study; Randomized controlled trial
Scientific progress is driven by the availability of information, which makes it essential that data be broadly, easily and rapidly accessible to researchers in every field. In addition to being good scientific practice, provision of supporting data in a convenient way increases experimental transparency and improves research efficiency by reducing unnecessary duplication of experiments. There are, however, serious constraints that limit extensive data dissemination. One such constraint is that, despite providing a major foundation of data to the advantage of entire community, data producers rarely receive the credit they deserve for the substantial amount of time and effort they spend creating these resources. In this regard, a formal system that provides recognition for data producers would serve to incentivize them to share more of their data.
The process of data citation, in which the data themselves are cited and referenced in journal articles as persistently identifiable bibliographic entities, is a potential way to properly acknowledge data output. The recent publication of several sorghum genomes in Genome Biology is a notable first example of good data citation practice in the field of genomics and demonstrates the practicalities and formatting required for doing so. It also illustrates how effective use of persistent identifiers can augment the submission of data to the current standard scientific repositories.
A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted.
We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently.
There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff.
Current Controlled Trials ISRCTN62323832
The proliferating cell nuclear antigen (PCNA) is a key protein in the eukaryotic DNA replication and cell proliferation. Following the cloning and characterisation of the human PCNA gene, the question of the existence of pseudogenes in the human genome was raised.
In this short communication we summarise the existing information about the PCNA pseudogenes and critically assess their status.
We propose the existence of at least four valid PCNA pseudogenes, PCNAP1, PCNAP2, LOC392454 and LOC390102. We would like to recommend assignment of a name for LOC392454 as "proliferating cell nuclear antigen pseudogene 3" (alias PCNAP3) and a name for LOC390102 as "proliferating cell nuclear antigen pseudogene 4" (alias PCNAP4). We prompt for more critical evaluation of the existence of a PCNA pseudogene, designated as PCNAP.
The goal of this Geographic Information System (GIS) study was to obtain accurate information on the locations of study subjects, road network and services for research purposes so that the clinical outcomes of interest (e.g., vaccine efficacy, burden of disease, nasopharyngeal colonization and its reduction) could be linked and analyzed at a distance from health centers, hospitals, doctors and other important services. The information on locations can be used to investigate more accurate crowdedness, herd immunity and/or transmission patterns.
A randomized, placebo-controlled, double-blind trial of an 11-valent pneumococcal conjugate vaccine (11PCV) was conducted in Bohol Province in central Philippines, from July 2000 to December 2004. We collected the information on the geographic location of the households (N = 13,208) of study subjects. We also collected a total of 1982 locations of health and other services in the six municipalities and a comprehensive GIS data over the road network in the area.
We calculated the numbers of other study subjects (vaccine and placebo recipients, respectively) within the neighborhood of each study subject. We calculated distances to different services and identified the subjects sharing the same services (calculated by distance). This article shows how to collect a complete GIS data set for human to human transmitted vaccine study in developing country settings in an efficient and economical way.
The collection of geographic locations in intervention trials should become a routine task. The results of public health research may highly depend on spatial relationships among the study subjects and between the study subjects and the environment, both natural and infrastructural.
Trial registration number
This article aims to offer, on the basis of Coherence theory, the epistemological proposition that mutually supportive evidence from multiple systematic reviews may successfully refute radical, philosophical scepticism.
A case study including seven systematic reviews is presented with the objective of refuting radical philosophical scepticism towards the belief that glass-ionomer cements (GIC) are beneficial in tooth caries therapy. The case study illustrates how principles of logical and empirical coherence may be applied as evidence in support of specific beliefs in healthcare.
The results show that radical scepticism may epistemologically be refuted on the basis of logical and empirical coherence. For success, several systematic reviews covering interconnected beliefs are needed. In praxis, these systematic reviews would also need to be of high quality and its conclusions based on reviewed high quality trials.
A refutation of radical philosophical scepticism to clinical evidence may be achieved, if and only if such evidence is based on the logical and empirical coherence of multiple systematic review results. Practical application also requires focus on the quality of the systematic reviews and reviewed trials.
Interest in community-based interventions (CBIs) for health promotion is increasing, with a lot of recent activity in the field. This paper aims, from a state government perspective, to examine the experience of funding and managing six obesity prevention CBIs, to identify lessons learned and to consider the implications for future investment. Specifically, we focus on the planning, government support, evaluation, research and workforce development required.
The lessons presented in this paper come from analysis of key project documents, the experience of the authors in managing the projects and from feedback obtained from key program stakeholders.
CBIs require careful management, including sufficient planning time and clear governance structures. Selection of interventions should be based on evidence and tailored to local needs to ensure adequate penetration in the community. Workforce and community capacity must be assessed and addressed when selecting communities. Supporting the health promotion workforce to become adequately skilled and experienced in evaluation and research is also necessary before implementation.
Comprehensive evaluation of future projects is challenging on both technical and affordability grounds. Greater emphasis may be needed on process evaluation complemented by organisation-level measures of impact and monitoring of nutrition and physical activity behaviours.
CBIs offer potential as one of a mix of approaches to obesity prevention. If successful approaches are to be expanded, care must be taken to incorporate lessons from existing and past projects. To do this, government must show strong leadership and work in partnership with the research community and local practitioners.
The pancreas has dual functions as a digestive organ and as an endocrine organ, by secreting digestive enzymes and endocrine hormones. Some early studies have revealed that serum amylase levels are lower in individuals with chronic pancreatitis, severe long-term type 2 diabetes or type 1 diabetes. Regarding this issue, we recently reported that low serum amylase levels were associated with metabolic syndrome and diabetes in asymptomatic adults. In the light of this, we further investigated the fundamental relationship between serum amylase and cardiometabolic aspects by reanalyzing previous data which comprised subjects without diabetes treatment with oral hypoglycemic drugs or insulin (n = 2,344).
Serum amylase was inversely correlated with body mass index independently of age. Higher serum amylase levels were noted in older subjects aged 55 years old or more (n = 1,114) than in younger subjects (P < 0.0001, ANOVA), probably due to lower kidney function. It was likely that serum amylase may act similarly to other cardiometabolic protective factors such as high-density lipoprotein cholesterol. However, serum amylase levels were significantly lower in drinkers, particularly daily drinkers (n = 746, P < 0.0001, ANOVA). Meanwhile, despite of consistent inverse relationship between serum amylase and fasting plasma glucose, the relationship between serum amylase and HbA1c may be rather complicated in individuals with normal or mildly impaired glucose metabolism (up to HbA1c 6.0% (NGSP)).
Revisiting the cardiometabolic relevance of serum amylase may yield novel insight not only into glucose homeostasis and metabolic abnormalities related to obesity, but also possibly carbohydrate absorption in the gut.
The controversies surrounding transgenic crops, often called Genetically Modified Organisms (GMOs), call for a need to raise the level of public awareness of Genetic Modification (GM) technology in Africa. This should be accomplished by educating the public about the potential benefits and risks that may be associated with this new technology. In the last 15 years, GM crop producing countries have benefited from adoption of this new technology in the form of improved crop productivity, food security, and quality of life. The increased income to resource-poor farmers is a key benefit at the individual level especially as most countries using this technology are in the developing world, including three African countries (South Africa, Burkina Faso and Egypt). Despite clear benefits to countries and farmers who grow GMOs, many people are concerned about suspected potential risks associated with GMOs. This sparks debate as to whether GM technology should be adopted or not. Given the concerns regarding the safety of GMO products, thorough scientific investigation of safe application of GMOs is required. The objective of this paper is to respond to the issues of GM agriculture in Africa and some of the issues surrounding the adoption of GM crops between developed and developing countries. In this article, I analyse relevant papers relating to the adoption of GM technology particularly in developing countries including the few African countries that have adopted GM crops. The issues discussed span a wide range including: safety; potential benefits and risks; disputes between the United States of America (USA) and the European Union (EU) over adoption of GM crops with a focus on Africa continent. This article is concluded by summarising the issues raised and how GM technology can be adopted for agricultural development in Africa.
Little is known about interactions between filamentous heterotrophs and filamentous cyanobacteria. Here, interactions between the filamentous heterotrophic bacteria Fibrella aestuarina (strain BUZ 2) and Fibrisoma limi (BUZ 3) with an axenic strain of the autotrophic filamentous cyanobacterium Nostoc muscorum (SAG 25.82) were studied in mixed cultures under nutrient rich (carbon source present in medium) and poor (carbon source absent in medium) conditions.
F. aestuarina BUZ 2 significantly reduced the cyanobacterial population whereas F. limi BUZ 3 did not. Physical contact between heterotrophs and autotroph was observed and the cyanobacterial cells showed some level of damage and lysis. Therefore, either contact lysis or entrapment with production of extracellular compounds in close vicinity of host cells could be considered as potential modes of action.
The supernatants from pure heterotrophic cultures did not have an effect on Nostoc cultures. However, supernatant from mixed cultures of BUZ 2 and Nostoc had a negative effect on cyanobacterial growth, indicating that the lytic compounds were only produced in the presence of Nostoc.
The growth and survival of tested heterotrophs was enhanced by the presence of Nostoc or its metabolites, suggesting that the heterotrophs could utilize the autotrophs and its products as a nutrient source. However, the autotroph could withstand and out-compete the heterotrophs under nutrient poor conditions.
Our results suggest that the nutrients in cultivation media, which boost or reduce the number of heterotrophs, were the important factor influencing the outcome of the interplay between filamentous heterotrophs and autotrophs. For better understanding of these interactions, additional research is needed. In particular, it is necessary to elucidate the mode of action for lysis by heterotrophs, and the possible defense mechanisms of the autotrophs.
In Arabidopsis, non-expressor of pathogenesis related genes-1, NPR1 has been shown to be a positive regulator of the salicylic acid controlled systemic acquired resistance pathway and modulates the cross talk between SA and JA signaling. Transgenic plants expressing AtNPR1 constitutively exhibited resistance against pathogens as well as herbivory. In the present study, tobacco transgenic plants expressing AtNPR1 were studied further for their response to infection by the sedentary endoparasitic root knot nematode, Meloidogyne incognita. Transgenic plants showed enhanced resistance against the root-knot nematode infection. Prominent differences in the shoot and root weights of wild type and transgenic plants were observed post-inoculation with M. incognita. This was associated with a decrease in the number of root galls and egg masses in transgenic plants compared to WT. The transgenic plants also showed constitutive and induced expression of some PR protein genes, when challenged with M. incognita.
Transgenic tobacco; AtNPR1; constitutive expression of PR proteins; nematode resistance; Meloidogyne incognita
Difficult airway especially failed intubation has been associated with a high incidence of mortality and morbidity. Most of mortalities occur when an anaesthesiologist encounters an unanticipated difficult airway.
In 1999, a 23 yr. old, 65 kg weight and 170 cm height female patient had been scheduled for arthroscopy. Despite totally normal airway assessment (thyromental distance, mouth opening, jaw and neck movement ...) I was astonished by encountering a grade IV Cormack - Lehane laryngoscopic view. Tracheal intubation was impossible and ventilation was very difficult.
On attempt to attain a better laryngoscopic view, while manipulating submandibular region I encountered a bulky noncompliant submental space (Submental Sign). This event made me more alert regarding this finding. Thereafter I noted for this sign throughout the past years and I found it very helpful.
These findings encouraged me to write this report, and suggest a routine examination of submental space in order to keep the safety of the patient at the heart of the care we provide.
Evaluation of the submental space is suggested as an alternative predictor of difficult airway and routine examination of the submental space is of value in airway assessment.
The transcription factor Hypoxia-Inducible Factor-1α is a master regulator of the cellular response to low oxygen concentration. Compound C, an inhibitor of AMP-activated kinase, has been reported to inhibit hypoxia dependent Hypoxia-Inducible Factor-1α activation via a mechanism that is independent of AMP-activated kinase but dependent on its interaction with the mitochondrial electron transport chain. The objective of this study is to characterize the interaction of Compound C with the mitochondrial electron transport chain and to determine the mechanism through which the drug influences the stability of the Hypoxia-Inducible Factor-1α protein.
We found that Compound C functions as an inhibitor of complex I of the mitochondrial electron transport chain as demonstrated by its effect on mitochondrial respiration. It also prevents hypoxia-induced Hypoxia-Inducible Factor-1α stabilization in a dose dependent manner. In addition, Compound C does not have significant effects on reactive oxygen species production from complex I via both forward and reverse electron flux.
This study provides evidence that similar to other mitochondrial electron transport chain inhibitors, Compound C regulates Hypoxia-Inducible Factor-1α stability by controlling the cellular oxygen concentration.
This article aims to update the existing systematic review evidence elicited by Mickenautsch et al. up to 18 January 2008 (published in the European Journal of Paediatric Dentistry in 2009) and addressing the review question of whether, in the same dentition and same cavity class, glass-ionomer cement (GIC) restored cavities show less recurrent carious lesions on cavity margins than cavities restored with amalgam.
The systematic literature search was extended beyond the original search date and a further hand-search and reference check was done. The quality of accepted trials was assessed, using updated quality criteria, and the risk of bias was investigated in more depth than previously reported. In addition, the focus of quantitative synthesis was shifted to single datasets extracted from the accepted trials.
The database search (up to 10 August 2010) identified 1 new trial, in addition to the 9 included in the original systematic review, and 11 further trials were included after a hand-search and reference check. Of these 21 trials, 11 were excluded and 10 were accepted for data extraction and quality assessment. Thirteen dichotomous datasets of primary outcomes and 4 datasets with secondary outcomes were extracted. Meta-analysis and cumulative meta-analysis were used in combining clinically homogenous datasets. The overall results of the computed datasets suggest that GIC has a higher caries-preventive effect than amalgam for restorations in permanent teeth. No difference was found for restorations in the primary dentition.
This outcome is in agreement with the conclusions of the original systematic review. Although the findings of the trials identified in this update may be considered to be less affected by attrition- and publication bias, their risk of selection- and detection/performance bias is high. Thus, verification of the currently available results requires further high-quality randomised control trials.
This article constitutes a partial update of the original systematic review evidence by Yengopal et al. from 15 January 2008 (published in the Journal of Oral Science in 2009) with primary focus on research quality in regard to bias risk in trials. Its aim is to update the existing systematic review evidence from the English literature as to whether caries occurrence on pits and fissures of teeth sealed with either GIC or resin is the same.
In addition to the 12 trials included during the original systematic review, 5 new trials were identified during the database search (up to 26 August 2010) and 2 further trials were included from a hand search and reference check. Of these, 3 trials were excluded and 16 were accepted for data extraction and quality assessment. The quality of accepted trials was assessed, using updated quality criteria, and the risk of bias was investigated in more depth than previously reported. In addition, the focus of quantitative synthesis was shifted to single datasets that were extracted from the accepted trials.
Twenty-six dichotomous and 4 continuous datasets were extracted. Meta-analysis and cumulative meta-analysis were used in combining clinically homogenous datasets. The overall outcome of the computed datasets suggest no difference between the caries-preventive effects of GIC- and resin-based fissure sealants.
This overall outcome is in agreement with the conclusions of the original systematic review. Although the findings of the trials identified in this update may be considered to be less affected by attrition- and publication bias, their risk of selection- and detection-/performance bias is high. Thus, verification of the currently available results requires further high quality randomised control trials.
Although many strain typing methods exist for pathogenic Escherichia coli, most have drawbacks in terms of resolving power, interpretability, or scalability. For this reason, multilocus sequence typing (MLST) is an appealing alternative especially when applied to the typing of temporal and spatially separated isolates. This method relies on an unambiguous DNA sequence analysis of nucleotide polymorphisms in housekeeping genes and has shown a high degree of intraspecies discriminatory power for bacterial and fungal pathogens.
Here we used the MLST method to study the genetic diversity among E. coli O157 isolates collected from humans from two different locations of USA over a period of several years (2000-2008). MLST analysis of 33 E. coli O157 patient isolates using the eBurst algorithm distinguished 26 different sequence types (STs), which were clustered into two clonal groups and 11 singletons. The predominant ST was ST2, which consisted of 5 isolates (14.28%) followed by ST1 (11.42%). All the isolates under clonal group I exhibited a virtually similar virulence profile except for two strains, which tested negative for the presence of stx genes. The isolates that were assigned to clonal group II in addition to the 11 singletons were found to be phylogenetically distant from clonal group I. Furthermore, we observed a positive correlation between the virulence profile of the isolates and their clonal origin.
Our data suggests the presence of genetic diversity among E. coli O157 isolates from humans shows no measurable correlation to the geographic origin of the isolates.
Cognitive tests have been used in population surveys as first stage screens for dementia but are biased by education. However functional ability scales are less biased by education than the cognitive scale and thus can be used in screening for dementia.
To validate Activities of Daily Living (ADL) scale appropriate for use in assessing the presence of dementia in an elderly population living in care homes in Sri Lanka.
Sinhalese version of the modified Bristol and Blessed scale was administered to subjects aged 55 years and above residing in 14 randomly selected elders' homes. Receiver Operating Characteristic (ROC) was used to determine the cut-off scores of both the scales.
Based on the ROC analysis, optimal cut off score of the modified Bristol scale was 20 with a sensitivity of 100%, specificity of 74.2% and the area under the curve 0.933(95% CI: 0.871-0.995) while the optimal cut off score of the modified Blessed scale was 10.5 with a sensitivity of 100%, specificity of 71% and the area under the curve 0.892 (95% CI: 0.816-0.967).
The findings confirm that both the scales can be used in screening for dementia in the elderly living in care homes in Sri Lanka.
Stable isotope probing (SIP) technique was developed to link function, structure and activity of microbial cultures metabolizing carbon and nitrogen containing substrates to synthesize their biomass. Currently, available methods are restricted solely to the estimation of fully saturated heavy stable isotope incorporation and convenient methods with sufficient accuracy are still missing. However in order to track carbon fluxes in microbial communities new methods are required that allow the calculation of partial incorporation into biomolecules.
In this study, we use the characteristics of the so-called 'half decimal place rule' (HDPR) in order to accurately calculate the partial13C incorporation in peptides from enzymatic digested proteins. Due to the clade-crossing universality of proteins within bacteria, any available high-resolution mass spectrometry generated dataset consisting of tryptically-digested peptides can be used as reference.
We used a freely available peptide mass dataset from Mycobacterium tuberculosis consisting of 315,579 entries. From this the error of estimated versus known heavy stable isotope incorporation from an increasing number of randomly drawn peptide sub-samples (100 times each; no repetition) was calculated. To acquire an estimated incorporation error of less than 5 atom %, about 100 peptide masses were needed. Finally, for testing the general applicability of our method, peptide masses of tryptically digested proteins from Pseudomonas putida ML2 grown on labeled substrate of various known concentrations were used and13C isotopic incorporation was successfully predicted. An easy-to-use script  was further developed to guide users through the calculation procedure for their own data series.
Our method is valuable for estimating13C incorporation into peptides/proteins accurately and with high sensitivity. Generally, our method holds promise for wider applications in qualitative and especially quantitative proteomics.
It was showed that stomatognathic functions correlate with alterations in locomotion, that are detectable through the analysis of loading during walking. For example, subjects with symptoms of Temporomandibular disorders (TMDs) showed a significant higher load pressure on the two feet, respect to health subjects, when cotton rolls were inserted. This previous study appeared to suggest that the alteration of postural loads associated to a particular alteration of stomatognathic condition (in this case, the cotton rolls inserted between the two dental arches) is detectable only in TMD's subjects, while it resulted not detectable in health subjects, because in that study, health subjects did not show any significant alteration of postural loads related to the different stomatognathic tested conditions. In other words, in that previous study, in the group of health subjects, no significant difference in postural loads was observed among the different test conditions; while TMD subjects showed a significant higher load pressure on the two feet when cotton rolls were inserted, respect to all the other tested conditions. Thus, the aim of this study was to better investigate these correlations in health subjects without TMD's symptoms, testing other different intra-oral conditions, and to verifywhether an experimentally induced imbalance of occlusion, obtained putting an unilateral cotton roll, could cause an alteration of postural loading on feet during walking.
In a sample of thirty Caucasian adult females (mean age 28.5 ± 4.5), asymptomatic for TMDs, when a cotton roll was positioned on the left or the right sides of dental arches, so causing a lateral shift of the mandible, the percentage of loading and the loading surface of the ipsi-lateral foot, left or right, were found to be significantly lower than in habitual occlusion (p < 0.05). Males were not included because of their different postural attitude respect to females. Further studies in a sample of males will be presented.
This study showed that in health subjects without TMD's symptoms, an experimentally induced imbalance of the occlusion, obtained through an unilateral cotton roll, is associated to detectable alterations in the distribution of loading on feet surface, during walking.
Recently, the promise of a new universal long-term flu vaccine has become more tangible than ever before. Such a vaccine would protect against very many seasonal and pandemic flu strains for many years, making annual vaccination unnecessary. However, due to complacency behavior, it remains unclear whether the introduction of such vaccines would maintain high and stable levels of vaccination coverage year after year.
To predict the impact of universal long-term flu vaccines on influenza epidemics we developed a mathematical model that linked human cognition and memory with the transmission dynamics of influenza. Our modeling shows that universal vaccines that provide short-term protection are likely to result in small frequent epidemics, whereas universal vaccines that provide long-term protection are likely to result in severe infrequent epidemics.
Influenza vaccines that provide short-term protection maintain risk awareness regarding influenza in the population and result in stable vaccination coverage. Vaccines that provide long-term protection could lead to substantial drops in vaccination coverage and should therefore include an annual epidemic risk awareness programs in order to minimize the risk of severe epidemics.
The basis for understanding the characteristics of gene functional categories in chicken has been enhanced by the ongoing sequencing of the zebra finch genome, the second bird species to be extensively sequenced. This sequence provides an avian context for examining how variation in chicken has evolved since its divergence from its common ancestor with zebra finch as well as well as a calibrating point for studying intraspecific diversity within chicken. Immune genes have been subject to many selective processes during their evolutionary history: this gene class was investigated here in a set of orthologous chicken and zebra finch genes with functions assigned from the human ortholog. Tests demonstrated that nonsynonymous sites at immune genes were highly conserved both in chicken and on the avian lineage. McDonald-Kreitman tests provided evidence of adaptive evolution and a higher rate of selection on fixation of nonsynonymous substitutions at immune genes compared to that at non-immune genes. Further analyses showed that GC content was much higher in chicken than in zebra finch genes, and was significantly elevated in both species' immune genes. Pathogen challenges are likely to have driven the selective forces that have shaped variation at chicken immune genes, and continue to restrict diversity in this functional class.
Fragile × syndrome is caused by loss of expression of the FMRP protein involved in the control of a large number of mRNA targets. The Drosophila ortholog dFXR interacts with a protein complex that includes Argonaute2, an essential component of the RNA-induced silencing complex (RISC). Furthermore dFXR associates with Dicer, another essential processing enzyme of the RNAi pathway. Both microRNA and microRNA precursors can co-immunoprecipitate with dFXR. Consequently it has been suggested that the Fragile × syndrome may be due to a defect in an RNAi-related apparatus.
We have investigated the RNAi response in Fragile × patient cells lacking FMRP compared with normal controls. RNAi responses were successfully detected, but no statistically significant difference between the response in normal cells compared to patients cells was found - neither one nor two days after transfection.
Our data show that in human fibroblasts from Fragile × patients lacking FMRP the RNAi response is not significantly impaired.