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.
This manuscript presents the concerns around the increasingly common problem of not having readily available or useful “gold standard” measurements. This issue is particularly important in critical care where many measurements used in decision making are surrogates of what we would truly wish to use. However, the question is broad, important and applicable in many other areas.
In particular, a gold standard measurement often exists, but is not clinically (or ethically in some cases) feasible. The question is how does one even begin to develop new measurements or surrogates if one has no gold standard to compare with?
We raise this issue concisely with a specific example from mechanical ventilation, a core bread and butter therapy in critical care that is also a leading cause of length of stay and cost of care. Our proposed solution centers around a hierarchical validation approach that we believe would ameliorate ethics issues around radiation exposure that make current gold standard measures clinically infeasible, and thus provide a pathway to create a (new) gold standard.
Gold standard; Mechanical ventilation; Research methodology; Validation; Clinical trials; Animal trials
Dynamin is a super-family of large GTPase proteins that polymerise during their biological activity. Dynamin polymers form around lipid tubes and contribute to the membrane fission and scission of nascent vesicles from parent membranes. Here we used the NCBI Gene Expression Omnibus (GEO) database and the BioGPS gene expression portal to study differential dynamin gene expression in normal human organs or tissues. From the GDS1096 and GDS596 dataset, we downloaded the relative expression levels of dynamin-related genes (presented as percentages), with respect to all of the other genes on the array (platform Affymetrix GPL96), which includes the best characterised human genes. The expression profiles of dynamin in the central nervous system (CNS) are clearly distinct from the expression profiles in the other organs or tissues studied. We found that the classical dynamin DNM1 and DNM3 genes reach their maximum expression levels (100% of maximal expression) in all normal human CNS tissues studied. This is in contrast to the expression profile in the other normal human organs or tissues studied, in which both dynamin DNM1 and DNM3 genes showed approximately 50% maximal expression. This data mining analysis supports the concept that there is a relationship between the synapse and the molecular function of dynamin, suggesting a new field of work in the study of neurodegenerative diseases.
Dynamin; Central nervous system; Gene expression; Data mining
A recent article in Circulation Research suggests that the protein ABCC6, which when defective is responsible for pseudoxanthoma elasticum, an inherited condition with skin, eye and cardiovascular manifestations, is associated with dysfunction in mitochondria – Martin et al.: ABCC6 Localizes to the Mitochondria-Associated Membrane.Circ Res 2012, 111:516–520. We present complementary information based on a bioinformatics analysis, which was not performed in the article cited, to examine the suggestion that ABCC6 is localized to mitochondria.
All the computational strategies and integrative approaches that constitute references in the field indicate that ABCC6 is localized outside of mitochondria.
Our computational and integrative results, including both experimental and predictive data, show that there is no support in favor of the localization of ABCC6 in mitochondria.
Mitochondria; ABCC6/MRP6; Pseudoxanthoma elasticum (PXE); Mitochondria-associated membrane (MAM)
Currently there is an ongoing debate and limited evidence on the use of masks and respirators for the prevention of respiratory infections in health care workers (HCWs). This study aimed to examine available policies and guidelines around the use of masks and respirators in HCWs and to describe areas of consistency between guidelines, as well as gaps in the recommendations, with reference to the WHO and the CDC guidelines.
Policies and guidelines related to mask and respirator use for the prevention of influenza, SARS and TB were examined. Guidelines from the World Health Organization (WHO), the Center for Disease Control and Prevention (CDC), three high-income countries and six low/middle-income countries were selected.
Uniform recommendations are made by the WHO and the CDC in regards to protecting HCWs against seasonal influenza (a mask for low risk situations and a respirator for high risk situations) and TB (use of a respirator). However, for pandemic influenza and SARS, the WHO recommends mask use in low risk and respirators in high risk situations, whereas, the CDC recommends respirators in both low and high risk situations. Amongst the nine countries reviewed, there are variations in the recommendations for all three diseases. While, some countries align with the WHO recommendations, others align with those made by the CDC. The choice of respirator and the level of filtering ability vary amongst the guidelines and the different diseases. Lastly, none of the policies discuss reuse, extended use or the use of cloth masks.
Currently, there are significant variations in the policies and recommendations around mask and respirator use for protection against influenza, SARS and TB. These differences may reflect the scarcity of level-one evidence available to inform policy development. The lack of any guidelines on the use of cloth masks, despite widespread use in many low and middle-income countries, remains a policy gap. Health organizations and countries should jointly evaluate the available evidence, prioritize research to inform evidence gaps, and develop consistent policy on masks and respirator use in the health care setting.
Infectious diseases; Seasonal influenza; Pandemic influenza; Sever Acute Respiratory Syndrome (SARS); Tuberculosis (TB); Masks; Respirators
The aim of this paper was to provide an overview of the current knowledge and understanding of the potential beneficial physiological effects of glucosamine (GlcN) on joint health. The objective was to reach a consensus on four critical questions and to provide recommendations for future research priorities. To this end, nine scientists from Europe and the United States were selected according to their expertise in this particular field and were invited to participate in the Hohenheim conference held in August 2011. Each expert was asked to address a question that had previously been posed by the chairman of the conference. Based on a systematic review of the literature and the collection of recent data, the experts documented the effects of GlcN on cartilage ageing, metabolic/kinetic and maintenance of joint health as well as reduction of risk of OA development. After extensive debate and discussion the expert panel addressed each question and a general consensus statement was developed, agreeing on the current state-of-the-art and future areas for basic and clinical studies. This paper summarizes the available evidence for beneficial effects of GlcN on joint health and proposes new insight into the design of future clinical trials aimed at identifying beneficial physiological effect of GlcN on joint tissues.
Glucosamine; Osteoarthritis; Treatment; Prevention
The Cameroon health system is divided into central, intermediate and peripheral levels. Of the 43 health districts with a measles outbreak in Cameroon in 2011, only the Nylon Health District organized a documented outbreak response immunization. We present the methods and results of the response campaign solely shouldered by the district and intermediate level. The risk group, targets and neighborhoods to be vaccinated were identified after a detailed analysis of initial cases. The intermediate level defined strategies, provided logistics, capacity building and 41% of the operational budget while 59% was completed by the peripheral level. Microsoft Office Excel 2007 was used to estimate coverage rates and to draw an epidemic curve. The response immunization campaign was organized on the 14th epidemiological week, 10 weeks after the onset of the outbreak which ended 11 weeks thereafter. A total of 15867(108.5%) children aged 9-59 months were vaccinated in five health areas at a direct cost (vaccines excluded) of 71.34FCFA ($0.143) per vaccinated child. An additional 824 children aged 9-59 months were vaccinated around the residence of notified cases in neighborhoods which were not involved in the response campaign. The number of cases after the response campaign was lower than before. Once vaccines are available, prompt outbreak response campaigns can be organized at operational level to obtain commendable results instead of depending solely on international organizations or central levels. Decision makers at the intermediate and operational levels should redeploy available funds during emergencies to prevent the development of extreme public health conditions.
Measles; Outbreak; Response immunization campaign; Nylon health district
Fragile X Syndrome (FXS) and its associated disorders are caused by the expansion of the CGG repeat in the 5’ untranslated region of the fragile X mental retardation 1 (FMR1) gene, with disease classification based on the number of CGG repeats. The mechanisms of repeat expansion are dependent on the presence of cis elements and the absence of trans factors both of which are not mutually exclusive and contribute to repeat instability. Expansions associated with trans factors are due to the haploinsuffient or reduced expression of several DNA repair/metabolizing proteins. The reduction of expression in trans factors has been primarily conducted in animal models without substantial examination of many of these expansion mechanisms and trans factors in humans.
To understand the trans factors and pathways associated with trinucleotide repeat expansion we have analyzed two microarray datasets which characterized the transcript expression in patients with FXS and in controls.
We observed significant down regulation of DNA damage/repair pathway transcripts. This observation was consistent in both datasets, which used different populations. Within these datasets, several transcripts overlapped in the direction of association and fold change. Further characterization of these genes will be critical to understand their role in trinucleotide repeat instability in FXS.
Haploinsufficiency; FMR1; DNA repair/replication proteins
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
Image registration is one of the most important and universally useful computational tasks in biomedical image analysis. A recent article by Xing & Qiu (IEEE Transactions on Pattern Analysis and Machine Intelligence, 33(10):2081–2092, 2011) is based on an inappropriately narrow conceptualization of the image registration problem as the task of making two images look alike, which disregards whether the established spatial correspondence is plausible. The authors propose a new algorithm, Nonparametric Local Smoothing (NLS) for image registration, but use image similarities alone as a measure of registration performance, although these measures do not relate reliably to the realism of the correspondence map.
Using data obtained from its authors, we show experimentally that the method proposed by Xing & Qiu is not an effective registration algorithm. While it optimizes image similarity, it does not compute accurate, interpretable transformations. Even judged by image similarity alone, the proposed method is consistently outperformed by a simple pixel permutation algorithm, which is known by design not to compute valid registrations.
This study has demonstrated that the NLS algorithm proposed recently for image registration, and published in one of the most respected journals in computer science, is not, in fact, an effective registration method at all. Our results also emphasize the general need to apply registration evaluation criteria that are sensitive to whether correspondences are accurate and mappings between images are physically interpretable. These goals cannot be achieved by simply reporting image similarities.
Image registration; Correspondence; Accuracy
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.