ICF components of corresponding outcome measures in flexor tendon rehabilitation – a systematic review

<p>Abstract</p> <p>Background</p> <p>The International Classification of Functioning, Disability and Health (ICF) delivers a holistic approach to health conditions. The objective of the present study is to provide an overview of flexor tendon rehabilitation outcome measures with respect to ICF components. Furthermore, it aims to investigate to which extent current assessments measure aspects of health according to these components primarily focussing on <it>activity </it>and <it>participation</it>.</p> <p>Methods</p> <p>A systematic literature review was conducted to identify all studies meeting the inclusion criteria. Studies were only included if they assessed more than <it>body function and body structure </it>and referred to the ICF components <it>activity </it>and <it>participation</it>. The outcome measures were analysed and their linkage to the ICF components were investigated to examine to which degree aspects of health outcome as defined by the ICF were considered.</p> <p>Results</p> <p>As anticipated, the application of outcome measures after flexor tendon repair is non conform. In many studies the emphasis still lies on physical impairment neglecting activity limitations and participation restrictions.</p> <p>Aspects of health after flexor tendon repair could be assessed more adequately and cover patients' needs more sufficiently by choosing outcome measures which refer to all aspects of functioning.</p> <p>Conclusion</p> <p>The ICF can help to identify aspects of health which are not being considered. The ICF can help promote further development of adequate outcome measures including activity limitation and participation restrictions by targeting patient centred goals and respecting patients' needs.</p

A study of alternative splicing in the pig

<p>Abstract</p> <p>Background</p> <p>Since at least half of the genes in mammalian genomes are subjected to alternative splicing, alternative pre-mRNA splicing plays an important contribution to the complexity of the mammalian proteome. Expressed sequence tags (ESTs) provide evidence of a great number of possible alternative isoforms. With the EST resource for the domestic pig now containing more than one million porcine ESTs, it is possible to identify alternative splice forms of the individual transcripts in this species from the EST data with some confidence.</p> <p>Results</p> <p>The pig EST data generated by the Sino-Danish Pig Genome project has been assembled with publicly available ESTs and made available in the PigEST database. Using the Distiller package 2,515 EST clusters with candidate alternative isoforms were identified in the EST data with high confidence. In agreement with general observations in human and mouse, we find putative splice variants in about 30% of the contigs with more than 50 ESTs. Based on the criteria that a minimum of two EST sequences confirmed each splice event, a list of 100 genes with the most distinct tissue-specific alternative splice events was generated from the list of candidates. To confirm the tissue specificity of the splice events, 10 genes with functional annotation were randomly selected from which 16 individual splice events were chosen for experimental verification by quantitative PCR (qPCR). Six genes were shown to have tissue specific alternatively spliced transcripts with expression patterns matching those of the EST data. The remaining four genes had tissue-restricted expression of alternative spliced transcripts. Five out of the 16 splice events that were experimentally verified were found to be putative pig specific.</p> <p>Conclusions</p> <p>In accordance with human and rodent studies we estimate that approximately 30% of the porcine genes undergo alternative splicing. We found a good correlation between EST predicted tissue-specificity and experimentally validated splice events in different porcine tissue. This study indicates that a cluster size of around 50 ESTs is optimal for <it>in silico </it>detection of alternative splicing. Although based on a limited number of splice events, the study supports the notion that alternative splicing could have an important impact on species differentiation since 31% of the splice events studied appears to be species specific.</p

Evidence that talin alternative splice variants from Ciona intestinalis have different roles in cell adhesion

BACKGROUND: Talins are large, modular cytoskeletal proteins found in animals and amoebozoans such as Dictyostelium discoideum. Since the identification of a second talin gene in vertebrates, it has become increasingly clear that vertebrate Talin1 and Talin2 have non-redundant roles as essential links between integrins and the actin cytoskeleton in distinct plasma membrane-associated adhesion complexes. The conserved C-terminal I/LWEQ module is important for talin function. This structural element mediates the interaction of talins with F-actin. The I/LWEQ module also targets mammalian Talin1 to focal adhesion complexes, which are dynamic multicomponent assemblies required for cell adhesion and cell motility. Although Talin1 is essential for focal adhesion function, Talin2 is not targeted to focal adhesions. The nonvertebrate chordate Ciona intestinalis has only one talin gene, but alternative splicing of the talin mRNA produces two proteins with different C-terminal I/LWEQ modules. Thus, C. intestinalis contains two talins, Talin-a and Talin-b, with potentially different activities, despite having only one talin gene. RESULTS: We show here that, based on their distribution in cDNA libraries, Talin-a and Talin-b are differentially expressed during C. intestinalis development. The I/LWEQ modules of the two proteins also have different affinities for F-actin. Consistent with the hypothesis that Talin-a and Talin-b have different roles in cell adhesion, the distinct I/LWEQ modules of Talin-a and Talin-b possess different subcellular targeting determinants. The I/LWEQ module of Talin-a is targeted to focal adhesions, where it most likely serves as the link between integrin and the actin cytoskeleton. The Talin-b I/LWEQ module is not targeted to focal adhesions, but instead preferentially labels F-actin stress fibers. These different properties of C. intestinalis the Talin-a and Talin-b I/LWEQ modules mimic the differences between mammalian Talin1 and Talin2. CONCLUSION: Vertebrates and D. discoideum contain two talin genes that encode proteins with different functions. The urochordate C. intestinalis has a single talin gene but produces two separate talins by alternative splicing that vary in a domain crucial for talin function. This suggests that multicellular organisms require multiple talins as components of adhesion complexes. In C. intestinalis, alternative splicing, rather than gene duplication followed by neo-functionalization, accounts for the presence of multiple talins with different properties. Given that C. intestinalis is an excellent model system for chordate biology, the study of Talin-a and Talin-b will lead to a deeper understanding of cell adhesion in the chordate lineage and how talin functions have been parceled out to multiple proteins during metazoan evolution

Improved ability of biological and previous caries multimarkers to predict caries disease as revealed by multivariate PLS modelling

<p>Abstract</p> <p>Background</p> <p>Dental caries is a chronic disease with plaque bacteria, diet and saliva modifying disease activity. Here we have used the PLS method to evaluate a multiplicity of such biological variables (n = 88) for ability to predict caries in a cross-sectional (baseline caries) and prospective (2-year caries development) setting.</p> <p>Methods</p> <p>Multivariate PLS modelling was used to associate the many biological variables with caries recorded in thirty 14-year-old children by measuring the numbers of incipient and manifest caries lesions at all surfaces.</p> <p>Results</p> <p>A wide but shallow gliding scale of one fifth caries promoting or protecting, and four fifths non-influential, variables occurred. The influential markers behaved in the order of plaque bacteria > diet > saliva, with previously known plaque bacteria/diet markers and a set of new protective diet markers. A differential variable patterning appeared for new versus progressing lesions. The influential biological multimarkers (n = 18) predicted baseline caries better (ROC area 0.96) than five markers (0.92) and a single lactobacilli marker (0.7) with sensitivity/specificity of 1.87, 1.78 and 1.13 at 1/3 of the subjects diagnosed sick, respectively. Moreover, biological multimarkers (n = 18) explained 2-year caries increment slightly better than reported before but predicted it poorly (ROC area 0.76). By contrast, multimarkers based on previous caries predicted alone (ROC area 0.88), or together with biological multimarkers (0.94), increment well with a sensitivity/specificity of 1.74 at 1/3 of the subjects diagnosed sick.</p> <p>Conclusion</p> <p>Multimarkers behave better than single-to-five markers but future multimarker strategies will require systematic searches for improved saliva and plaque bacteria markers.</p

Genital Herpes Has Played a More Important Role than Any Other Sexually Transmitted Infection in Driving HIV Prevalence in Africa

Extensive evidence from observational studies suggests a role for genital herpes in the HIV epidemic. A number of herpes vaccines are under development and several trials of the efficacy of HSV-2 treatment with acyclovir in reducing HIV acquisition, transmission, and disease progression have just reported their results or will report their results in the next year. The potential impact of these interventions requires a quantitative assessment of the magnitude of the synergy between HIV and HSV-2 at the population level.A deterministic compartmental model of HIV and HSV-2 dynamics and interactions was constructed. The nature of the epidemiologic synergy was explored qualitatively and quantitatively and compared to other sexually transmitted infections (STIs). The results suggest a more substantial role for HSV-2 in fueling HIV spread in sub-Saharan Africa than other STIs. We estimate that in settings of high HSV-2 prevalence, such as Kisumu, Kenya, more than a quarter of incident HIV infections may have been attributed directly to HSV-2. HSV-2 has also contributed considerably to the onward transmission of HIV by increasing the pool of HIV positive persons in the population and may explain one-third of the differential HIV prevalence among the cities of the Four City study. Conversely, we estimate that HIV had only a small net impact on HSV-2 prevalence.HSV-2 role as a biological cofactor in HIV acquisition and transmission may have contributed substantially to HIV particularly by facilitating HIV spread among the low-risk population with stable long-term sexual partnerships. This finding suggests that prevention of HSV-2 infection through a prophylactic vaccine may be an effective intervention both in nascent epidemics with high HIV incidence in the high risk groups, and in established epidemics where a large portion of HIV transmission occurs in stable partnerships

Indole is an essential herbivore-induced volatile priming signal in maize

Herbivore-induced volatile organic compounds prime non-attacked plant tissues to respond more strongly to subsequent attacks. However, the key volatiles that trigger this primed state remain largely unidentified. In maize, the release of the aromatic compound indole is herbivore-specific and occurs earlier than other induced responses. We therefore hypothesized that indole may be involved in airborne priming. Using indole-deficient mutants and synthetic indole dispensers, we show that herbivore-induced indole enhances the induction of defensive volatiles in neighbouring maize plants in a species-specific manner. Furthermore, the release of indole is essential for priming of mono- and homoterpenes in systemic leaves of attacked plants. Indole exposure markedly increases the herbivore-induced production of the stress hormones jasmonate-isoleucine conjugate and abscisic acid, which represents a likely mechanism for indole-dependent priming. These results demonstrate that indole functions as a rapid and potent aerial priming agent that prepares systemic tissues and neighbouring plants for incoming attacks

Changes in Brain MicroRNAs Contribute to Cholinergic Stress Reactions

Mental stress modifies both cholinergic neurotransmission and alternative splicing in the brain, via incompletely understood mechanisms. Here, we report that stress changes brain microRNA (miR) expression and that some of these stress-regulated miRs regulate alternative splicing. Acute and chronic immobilization stress differentially altered the expression of numerous miRs in two stress-responsive regions of the rat brain, the hippocampal CA1 region and the central nucleus of the amygdala. miR-134 and miR-183 levels both increased in the amygdala following acute stress, compared to unstressed controls. Chronic stress decreased miR-134 levels, whereas miR-183 remained unchanged in both the amygdala and CA1. Importantly, miR-134 and miR-183 share a common predicted mRNA target, encoding the splicing factor SC35. Stress was previously shown to upregulate SC35, which promotes the alternative splicing of acetylcholinesterase (AChE) from the synapse-associated isoform AChE-S to the, normally rare, soluble AChE-R protein. Knockdown of miR-183 expression increased SC35 protein levels in vitro, whereas overexpression of miR-183 reduced SC35 protein levels, suggesting a physiological role for miR-183 regulation under stress. We show stress-induced changes in miR-183 and miR-134 and suggest that, by regulating splicing factors and their targets, these changes modify both alternative splicing and cholinergic neurotransmission in the stressed brain