Achieving sustainable quality in maternity services – using audit of incontinence and dyspareunia to identify shortfalls in meeting standards

BACKGROUND: Some complications of childbirth (for example, faecal incontinence) are a source of social embarrassment for women, and are often under reported. Therefore, it was felt important to determine levels of complications (against established standards) and to consider obstetric measures aimed at reducing them. METHODS: Clinical information was collected on 1036 primiparous women delivering at North and South Staffordshire Acute and Community Trusts over a 5-month period in 1997. A questionnaire was sent to 970 women which included self-assessment of levels of incontinence and dyspareunia prior to pregnancy, at 6 weeks post delivery and 9 to 14 months post delivery. RESULTS: The response rate was 48%(470/970). Relatively high levels of obstetric interventions were found. In addition, the rates of instrumental deliveries differed between the two hospitals. The highest rates of postnatal symptoms had occurred at 6 weeks, but for many women problems were still present at the time of the survey. At 9–14 months high rates of dyspareunia (29%(102/347)) and urinary incontinence (35%(133/382)) were reported. Seventeen women (4%) complained of faecal incontinence at this time. Similar rates of urinary incontinence and dyspareunia were seen regardless of mode of delivery. CONCLUSION: Further work should be undertaken to reduce the obstetric interventions, especially instrumental deliveries. Improvements in a number of areas of care should be undertaken, including improved patient information, improved professional communication and improved professional recognition and management of third degree tears. It is likely that these measures would lead to a reduction in incontinence and dyspareunia after childbirth

MICU2, a Paralog of MICU1, Resides within the Mitochondrial Uniporter Complex to Regulate Calcium Handling

Mitochondrial calcium uptake is present in nearly all vertebrate tissues and is believed to be critical in shaping calcium signaling, regulating ATP synthesis and controlling cell death. Calcium uptake occurs through a channel called the uniporter that resides in the inner mitochondrial membrane. Recently, we used comparative genomics to identify MICU1 and MCU as the key regulatory and putative pore-forming subunits of this channel, respectively. Using bioinformatics, we now report that the human genome encodes two additional paralogs of MICU1, which we call MICU2 and MICU3, each of which likely arose by gene duplication and exhibits distinct patterns of organ expression. We demonstrate that MICU1 and MICU2 are expressed in HeLa and HEK293T cells, and provide multiple lines of biochemical evidence that MCU, MICU1 and MICU2 reside within a complex and cross-stabilize each other's protein expression in a cell-type dependent manner. Using in vivo RNAi technology to silence MICU1, MICU2 or both proteins in mouse liver, we observe an additive impairment in calcium handling without adversely impacting mitochondrial respiration or membrane potential. The results identify MICU2 as a new component of the uniporter complex that may contribute to the tissue-specific regulation of this channel.National Institutes of Health (U.S.) (GM0077465)National Institutes of Health (U.S.) (DK080261

U-Shaped Relation between Plasma Oxytocin Levels and Behavior in the Trust Game

10.1371/journal.pone.0051095PLoS ONE712

Species-Specific Expansion and Molecular Evolution of the 3-hydroxy-3-methylglutaryl Coenzyme A Reductase (HMGR) Gene Family in Plants

Kazakh dandelion (Taraxacum kok-saghyz, Tk) is a rubber-producing plant currently being investigated as a source of natural rubber for industrial applications. Like many other isoprenoids, rubber is a downstream product of the mevalonate pathway. The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme catalyzes the conversion of 3-hydroxy-3-methylglutaryl-CoA to mevalonic acid, a key regulatory step in the MVA pathway. Such regulated steps provide targets for increases in isoprenoid and rubber contents via genetic engineering to increase enzyme activities. In this study, we identify a TkHMGR1 gene that is highly expressed in the roots of Kazakh dandelion, the main tissue where rubber is synthesized and stored. This finding paves the way for further molecular and genetic studies of the TkHMGR1 gene, and its role in rubber biosynthesis in Tk and other rubber-producing plants

Genetic Variation in Jasmonic Acid- and Spider Mite-Induced Plant Volatile Emission of Cucumber Accessions and Attraction of the Predator Phytoseiulus persimilis

Cucumber plants (Cucumis sativus L.) respond to spider–mite (Tetranychus urticae) damage with the release of specific volatiles that are exploited by predatory mites, the natural enemies of the spider mites, to locate their prey. The production of volatiles also can be induced by exposing plants to the plant hormone jasmonic acid. We analyzed volatile emissions from 15 cucumber accessions upon herbivory by spider mites and upon exposure to jasmonic acid using gas chromatography—mass spectrometry. Upon induction, cucumber plants emitted over 24 different compounds, and the blend of induced volatiles consisted predominantly of terpenoids. The total amount of volatiles was higher in plants treated with jasmonic acid than in those infested with spider mites, with (E)-4,8-dimethyl-1,3,7-nonatriene, (E,E)-α-farnesene, and (E)-β-ocimene as the most abundant compounds in all accessions in both treatments. Significant variation among the accessions was found for the 24 major volatile compounds. The accessions differed strongly in total amount of volatiles emitted, and displayed very different odor profiles. Principal component analysis performed on the relative quantities of particular compounds within the blend revealed clusters of highly correlated volatiles, which is suggestive of common metabolic pathways. A number of cucumber accessions also were tested for their attractiveness to Phytoseiulus persimilis, a specialist predator of spider mites. Differences in the attraction of predatory mites by the various accessions correlated to differences in the individual chemical profiles of these accessions. The presence of genetic variation in induced plant volatile emission in cucumber shows that it is possible to breed for cucumber varieties that are more attractive to predatory mites and other biological control agents

Identification and Characterization of the Host Protein DNAJC14 as a Broadly Active Flavivirus Replication Modulator

Viruses in the Flavivirus genus of the Flaviviridae family are arthropod-transmitted and contribute to staggering numbers of human infections and significant deaths annually across the globe. To identify cellular factors with antiviral activity against flaviviruses, we screened a cDNA library using an iterative approach. We identified a mammalian Hsp40 chaperone protein (DNAJC14) that when overexpressed was able to mediate protection from yellow fever virus (YFV)-induced cell death. Further studies revealed that DNAJC14 inhibits YFV at the step of viral RNA replication. Since replication of bovine viral diarrhea virus (BVDV), a member of the related Pestivirus genus, is also known to be modulated by DNAJC14, we tested the effect of this host factor on diverse Flaviviridae family members. Flaviviruses, including the pathogenic Asibi strain of YFV, Kunjin, and tick-borne Langat virus, as well as a Hepacivirus, hepatitis C virus (HCV), all were inhibited by overexpression of DNAJC14. Mutagenesis showed that both the J-domain and the C-terminal domain, which mediates self-interaction, are required for anti-YFV activity. We found that DNAJC14 does not block YFV nor HCV NS2-3 cleavage, and using non-inhibitory mutants demonstrate that DNAJC14 is recruited to YFV replication complexes. Immunofluorescence analysis demonstrated that endogenous DNAJC14 rearranges during infection and is found in replication complexes identified by dsRNA staining. Interestingly, silencing of endogenous DNAJC14 results in impaired YFV replication suggesting a requirement for DNAJC14 in YFV replication complex assembly. Finally, the antiviral activity of overexpressed DNAJC14 occurs in a time- and dose-dependent manner. DNAJC14 overexpression may disrupt the proper stoichiometry resulting in inhibition, which can be overcome upon restoration of the optimal ratios due to the accumulation of viral nonstructural proteins. Our findings, together with previously published work, suggest that the members of the Flaviviridae family have evolved in unique and important ways to interact with this host Hsp40 chaperone molecule

Guidelines for investigating causality of sequence variants in human disease

The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development

Evaluating Effects of Divided Hemispheric Processing on Word Recognition in Foveal and Extrafoveal Displays: The Evidence from Arabic

Background: Previous studies have claimed that a precise split at the vertical midline of each fovea causes all words to the left and right of fixation to project to the opposite, contralateral hemisphere, and this division in hemispheric processing has considerable consequences for foveal word recognition. However, research in this area is dominated by the use of stimuli from Latinate languages, which may induce specific effects on performance. Consequently, we report two experiments using stimuli from a fundamentally different, non-Latinate language (Arabic) that offers an alternative way of revealing effects of split-foveal processing, if they exist. Methods and Findings: Words (and pseudowords) were presented to the left or right of fixation, either close to fixation and entirely within foveal vision, or further from fixation and entirely within extrafoveal vision. Fixation location and stimulus presentations were carefully controlled using an eye-tracker linked to a fixation-contingent display. To assess word recognition, Experiment 1 used the Reicher-Wheeler task and Experiment 2 used the lexical decision task. Results: Performance in both experiments indicated a functional division in hemispheric processing for words in extrafoveal locations (in recognition accuracy in Experiment 1 and in reaction times and error rates in Experiment 2) but no such division for words in foveal locations. Conclusions: These findings from a non-Latinate language provide new evidence that although a functional division i

Biomechanical spinal growth modulation and progressive adolescent scoliosis – a test of the 'vicious cycle' pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr Ian A Stokes. It evaluates the hypothesis that in progressive scoliosis vertebral body wedging during adolescent growth results from asymmetric muscular loading in a "vicious cycle" (vicious cycle hypothesis of pathogenesis) by affecting vertebral body growth plates (endplate physes). A frontal plane mathematical simulation tested whether the calculated loading asymmetry created by muscles in a scoliotic spine could explain the observed rate of scoliosis increase by measuring the vertebral growth modulation by altered compression. The model deals only with vertebral (not disc) wedging. It assumes that a pre-existing scoliosis curve initiates the mechanically-modulated alteration of vertebral body growth that in turn causes worsening of the scoliosis, while everything else is anatomically and physiologically 'normal' The results provide quantitative data consistent with the vicious cycle hypothesis. Dr Stokes' biomechanical research engenders controversy. A new speculative concept is proposed of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. What is not controversial is the need to test this hypothesis using additional factors in his current model and in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. The growth modulation process in the vertebral body can be viewed as one type of the biologic phenomenon of mechanotransduction. In certain connective tissues this involves the effects of mechanical strain on chondrocytic metabolism a possible target for novel therapeutic intervention