Impact of mitral regurgitation on left ventricular remodeling and function in children with rheumatic heart disease.

The impact of mitral regurgitation (MR) from pediatric rheumatic heart disease (RHD) and its effect on left ventricular (LV) remodeling and function following surgical intervention is uncertain. The objective is to explore the impact of mitral valve (MV) surgeries on myocardial mechanics, remodeling and function and identify pre-operative predictors of post-operative dysfunction which may contribute to the optimal timing of intervention. A retrospective review of echocardiographic data was performed of eighteen pediatric patients with RHD (median 9yrs, IQR 6-12) who underwent MV surgery. Echocardiograms pre-operatively and a median of 13.5 months (IQR 10.2-15) following intervention were compared to controls. Pre-operative LV end-diastolic indexed volumes (LVEDVi) were significantly increased compared to controls and remained persistently larger post-operatively. LV ejection fraction (LVEF) (pre 62.6% ± 6.1, post 51.7% ± 9.7, p = 0.002), and global longitudinal strain (GLS) (pre - 24.3 ± 4.1, post - 18.2 ± 2.6, p < 0.001) decreased post-operatively at mid-term follow-up. Pre-operative LVEDVi was a significant predictor of post-operative LVEF, with a cut-off of ≥ 102 ml/m2 associated with LV dysfunction (LVEF < 55%; sensitivity 70%, specificity 75%). Pre-operative LVEDVi also negatively correlated with GLS (r = - 0.58, p = 0.01). LV dimensions and volumes remain persistently larger than controls while LV function decreases post-surgical alleviation of MR in paediatric RHD. Pre-operative LVEDVi predicted post-operative LV dysfunction and utilising LV indexed volumes in directing timing of surgical planning should be considered. Further studies are required to investigate whether timely alleviation of MR before significant LV dilatation and remodeling occur may substantially prevent LV dysfunction and improve outcomes.

An investigation into the perceived value of the College of Radiographers voluntary accreditation scheme for advanced and consultant practitioners in breast imaging.

INTRODUCTION: A voluntary accreditation scheme has been introduced, requiring advanced (AdP) and consultant practitioners (CP) to submit several pieces of work to the College of Radiographers (CoR). However, few individuals have opted to become voluntary accredited. This study investigated the reasons behind becoming voluntary accredited, the value that was gained and why there appears to be a lack of support for the scheme. METHODS: An online electronic survey was conducted using a mixed methods approach. Open questions enabled individual opinions and thoughts to be expressed, Likert scale style questions allowed further understanding of the level of agreement and closed questions identified the support for and against the scheme. RESULTS: A total of 55 respondents participated, including 18 AdPs, 25 CPs, 1 consultant trainee practitioner, 5 practitioners and 6 listed as 'other'. Forty-four participants were non-accredited, citing too much clinical work; no recognition from employers and too much effort for little reward. Motivations for joining the scheme were to improve the profession; help create a new consultant post and protect the non-clinical element of the consultant role. CONCLUSION: The CoR voluntary accreditation scheme has a small perceived value but overall, the majority of respondents believed the scheme did not warrant the work needed to apply. Concern was raised about the risk of creating a two-tier profession by the scheme's instigation. The results of this study suggest that the CoR's voluntary accreditation scheme would need to address these barriers before more practitioners would apply.

Effect of anti-heart failure therapy on diastolic function in children with single-ventricle circulations.

BACKGROUND: Children with functionally univentricular circulations have chronic volume loading of the systemic ventricle, potentially affecting ventricular function. Medications including angiotensin-converting enzyme inhibitors and ß-blockers are used to treat ventricular dysfunction, despite limited evidence of their efficacy in this population. OBJECTIVE: To determine the effects of angiotensin-converting enzyme inhibitors on elevated filling pressures in children with single ventricle physiology. METHODS: We performed a single-centre, retrospective review of patients with single ventricle physiology who underwent multiple cardiac catheterisations between 1991 and 2013. Study population comprised of patients who commenced or had optimised dosing of angiotensin-converting enzyme inhibitors between assessments in response to high ventricular filling pressures. Patients undergoing interventions influencing loading conditions between assessments were excluded. RESULTS: A total of 17 patients were identified, with dominant morphologic right ventricle in eight patients (47.1%). Among them, 11 (64.7%) were pre-Fontan and six (35.3%) were post-Fontan completion. Median inter-assessment interval was 9.4 months (range 7.3-19.1). There was a reduction in end-diastolic pressure from 13 to 10 mmHg (p=0.002), mean pulmonary artery pressure from 16 to 13 mmHg (p=0.049), and mean atrial pressure from 12 to 9 mmHg (p=0.001). There was one cardiac transplant, and there were no patient deaths at median follow-up after 31 months. CONCLUSIONS: We observed a reduction in ventricular end-diastolic pressure, pulmonary artery pressure, and mean atrial pressure following treatment with angiotensin-converting enzyme inhibitors in patients with single ventricle physiology. Our study provides insights into the potential impact of anti-heart failure therapy in single ventricle circulations and calls for larger, controlled studies to assess for a therapeutic response.

Use of alpha-, beta-Estrogen Receptor as a "new tool" for detection of specific small molecule activity.

Cell-based screening methods for nuclear receptor ligands that use transgenic plant cells expressing a single human NR may have advantages over other eukaryotic systems which express multiple NRs. For example, signal-to-noise ratio might be improved because ligands would be less likely to bind to other NRs and/or less likely to cause confounding functional changes in plant cells. As a first step toward this aim we have expressed in plants truncated human estrogen receptor (ER) constructs linked to reporters, or selective markers such as luciferase, green fluorescent protein (GFP) and hygromycin. A variety of ligands for the ER (including estradiol and known phytoestrogens) have then been tested for their ability to over-express the linked marker gene(s) which could be measured (luciferase activity), visualized under fluorescent microscopy (GFP activity), or selected on antibiotic-containing media (Hygromycin B). Our results show a close association between the effects of ER ligands in the transgenic plant roots and their effects on native ERs in mammalian cells. With the stable expression of an ERalpha-GFP ligand detection system in A. thaliana, the estradiol- mediated response in transgenic roots is inhibited by an ER partial agonist (tamoxifen) and an antagonist (fulvestrant) at concentrations relevant to their use in breast cancer. We conclude that it is possible to express human NRs in plants in a form that can report on exogenous or endogenous ER ligands and that these constructs have a pharmacology which is relevant to ligands for the native NRs in human cells.

Imaging and percutaneous occlusion of a large aneurysm of the ductus arteriosus in an infant with Loeys-Dietz syndrome.

Loeys-Dietz is a multisystem congenital syndrome that comprises craniofacial and cutaneous abnormalities as well as structural cardiac defects. One of its key pathological features is an aggressive widespread vasculopathy that can manifest as aortic or cerebral aneurysms, which is prone to dissection and rupture. We report a case of a large aneurysm of the ductus arteriosus in a patient with Loeys-Dietz syndrome, successfully occluded by interventional catheterization.

Poroqueratosis: Revisión / Porokeratosis: A review

La poroqueratosis es un trastorno hereditario de la queratinización, descrita por Mibelli. Se describen mútiples variantes clínicas; todas representadas por una lesión primaria común: la pápula hiperqueratósica. El diagnóstico se confirma con la histopatología, donde se aprecia la laminilla cornoide, el hallazgo más representativo de la dermatosis. La escasa respuesta a la terapéutica, la frecuente recurrencia y su potencial carácter pre-neoplásico, hacen de esta patología un problema complejo para el dermatólogo. El objetivo de este artículo, es reconocer las distintas formas de poroqueratosis, arribar a su diagnostico y orientar un tratamiento.

Porokeratosis is an inherited disorder of keratinization, described by Mibelli. Mutiple clinical variants have been reported, all represented by a common primary lesion: the hyperkeratotic papule. The diagnosis is confirmed by the histopathological study, which shows the cornoid lamella, the most representative finding of these dermatoses. It's a complex pathology due to the poor response to therapy, the frequent recurrence and pre-neoplasic potencial. The goal of this article is the recognition of different porokeratosis forms, and review the issue in order to reach the correct diagnosis and treatment.

Improved growth and stress tolerance in the Arabidopsis oxt1 mutant triggered by altered adenine metabolism.

Plants perceive and respond to environmental stresses with complex mechanisms that are often associated with the activation of antioxidant defenses. A genetic screen aimed at isolating oxidative stress-tolerant lines of Arabidopsis thaliana has identified oxt1, a line that exhibits improved tolerance to oxidative stress and elevated temperature but displays no apparent deleterious growth effects under non-stress conditions. Oxt1 harbors a mutation that arises from the altered expression of a gene encoding adenine phosphoribosyltransferase (APT1), an enzyme that converts adenine to adenosine monophosphate (AMP), indicating a link between purine metabolism, whole-plant growth responses, and stress acclimation. The oxt1 mutation results in decreased APT1 expression that leads to reduced enzymatic activity. Correspondingly, oxt1 plants possess elevated levels of adenine. Decreased APT enzyme activity directly correlates with stress resistance in transgenic lines that ectopically express APT1. The metabolic alteration in oxt1 plants also alters the expression of several antioxidant defense genes and the response of these genes to oxidative challenge. Finally, it is shown that manipulation of adenine levels can induce stress tolerance to wild-type plants. Collectively, these results show that alterations in cellular adenine levels can trigger stress tolerance and improve growth, leading to increases in plant biomass. The results also suggest that adenine might play a part in the signals that modulate responses to abiotic stress and plant growth.

The sinister course of an intramural right coronary artery.

We report the case of an adolescent who was presented with long-standing exertional symptoms, and was diagnosed with an anomalous right coronary arterial origin arising above the commissural junction between the left and right aortic sinus, with inter-arterial and intramural compression. The precise origin of this lesion outside the aortic sinuses is unusual, and multi-detector computed tomography gave excellent definition and spatial resolution of the anomalous origin and course. It is crucial to have a high index of suspicion of exertional symptoms, as sudden death may be the first manifestation of an anomalous coronary artery.

Reprint of: Psychosomatic medicine and consultation-liaison psychiatry: scope of practice, processes, and competencies for psychiatrists working in the field of CL psychiatry or psychosomatics. A consensus statement of the European Association of Consultation-Liaison Psychiatry and Psychosomatics (EACLPP) and the Academy of Psychosomatic Medicine (APM).

OBJECTIVE: In 2008, the Board of the European Association of Consultation-Liaison Psychiatry and Psychosomatics (EACLPP) and the Academy of Psychosomatic Medicine (APM) Council commissioned the creation of a task force to study consensus-based summaries of core roles, scope of clinical practice, and basic competencies for psychiatrists working in the field of Psychosomatic Medicine (PM) and/or Consultation-Liaison Psychiatry (CLP). METHOD: The task force used existing statements of competencies and feedback from EACLPP and APM symposia and workshops to develop a draft document. After review by the EACLPP and APM committees, and the EACLPP Board and APM Council, a period of comment from the field preceded a final draft resubmitted for consideration of the EACLPP Board and APM Council in February 2010. RESULTS: The two organizations completed approval of final publication of the consensus statement on June 11, 2010. This consensus statement is a summary of clinical competencies, scope of clinical effort, and roles considered by the sponsoring organizations to be fundamental to the practice of this subspecialty or special area of expertise, anywhere, of PM or CLP. CONCLUSION: This consensus statement delineates a set of basic competencies and roles of a PM/CLP psychiatrist to serve as an internationally recognized base that may be used by national societies and institutions to formulate their own competencies, scope of practice, and roles or help with guideline formulation.

Reactive oxygen species regulate alkaloid metabolism in undifferentiated N. tabacum cells.

Plants produce an immense number of natural products and undifferentiated cells from various plant tissues have long been considered an ideal source for their synthesis. However, undifferentiated plant cells often either lose their biosynthetic capacity over time or exhibit immediate repression of the required pathways once dedifferentiated. In this study, freshly prepared callus tissue was employed to further investigate the regulation of a natural product pathway in undifferentiated tobacco cells. Putrescine N-methyltransferase (PMT) is a pathway-specific enzyme required in nicotinic alkaloid production in Nicotiana species. Callus derived from transgenic Nicotiana tabacum plants harboring PMT promoter-GUS fusions were used to study factors that influence PMT expression. Under normal callus growth conditions in the presence of light and auxin, PMT promoter activity was strongly repressed. Conversely, dark conditions and the absence of auxin were found to upregulate PMT promoter activity, with light being dominant to the repressive effects of auxin. Since reactive oxygen species (ROS) are known by-products of photosynthesis and have been implicated in signaling, their involvement was investigated in transgenic callus by treatment with the ROS scavenger, dimethylthiourea, or catalase. Under highly repressive conditions for alkaloid synthesis, including normal culture conditions in the light, both ROS scavengers resulted in significant induction of PMT promoter activity. Moreover, treatment of callus with catalase resulted in the upregulation of PMT promoter activity and alkaloid accumulation in this tissue. These results suggest that ROS impact the regulation of the alkaloid pathway in undifferentiated cells and have implications for regulation of the pathway in other plant tissues.

The A312L 5'-UTR of Chlorella virus PBCV-1 is a translational enhancer in Arabidopsis thaliana.

PBCV-1 (Paramecium bursaria Chlorella virus) is a large double stranded DNA virus that replicates in certain eukaryotic chlorella like green algae. The PBCV-1 A312L gene encodes a 33-kDa protein whose function currently is unknown. The 5'-UTR of the A312L mRNA is 153 nucleotides, longer than the 5'-UTR in any other PBCV-1 gene. The sequence 5'-AAAC was repeated 17 times within 156bp 5' to the A312L gene start codon and this sequence was repeated 13 times continuously in the 5'-UTR of the mRNA. Recombinant genes were constructed in vector pBI121 that contained the A312L 5'-UTR, in both the forward and inverse-complement orientations, fused to the GUS gene under the control of the CaMV 35S promoter. These constructs were introduced into Arabidopsis thaliana and the results indicated that the A312L 5'-UTR functions as a translational enhancer only in the forward orientation. Overall, the ratio of GUS enzyme activity to GUS mRNA was 15-fold higher in constructs derived from the A312L 5'-UTR in the forward orientation as compared to constructs containing the 5'-UTR in the inverse-complement orientation or those lacking the A312L 5'-UTR.

A polyadenylation factor subunit implicated in regulating oxidative signaling in Arabidopsis thaliana.

BACKGROUND: Plants respond to many unfavorable environmental conditions via signaling mediated by altered levels of various reactive oxygen species (ROS). To gain additional insight into oxidative signaling responses, Arabidopsis mutants that exhibited tolerance to oxidative stress were isolated. We describe herein the isolation and characterization of one such mutant, oxt6. METHODOLOGY/PRINCIPAL FINDINGS: The oxt6 mutation is due to the disruption of a complex gene (At1g30460) that encodes the Arabidopsis ortholog of the 30-kD subunit of the cleavage and polyadenylation specificity factor (CPSF30) as well as a larger, related 65-kD protein. Expression of mRNAs encoding Arabidopsis CPSF30 alone was able to restore wild-type growth and stress susceptibility to the oxt6 mutant. Transcriptional profiling and single gene expression studies show elevated constitutive expression of a subset of genes that encode proteins containing thioredoxin- and glutaredoxin-related domains in the oxt6 mutant, suggesting that stress can be ameliorated by these gene classes. Bulk poly(A) tail length was not seemingly affected in the oxt6 mutant, but poly(A) site selection was different, indicating a subtle effect on polyadenylation in the mutant. CONCLUSIONS/SIGNIFICANCE: These results implicate the Arabidopsis CPSF30 protein in the posttranscriptional control of the responses of plants to stress, and in particular to the expression of a set of genes that suffices to confer tolerance to oxidative stress.

Calmodulin interacts with and regulates the RNA-binding activity of an Arabidopsis polyadenylation factor subunit.

The Arabidopsis (Arabidopsis thaliana) gene that encodes the probable ortholog of the 30-kD subunit of the mammalian cleavage and polyadenylation specificity factor (CPSF) is a complex one, encoding small (approximately 28 kD) and large (approximately 68 kD) polypeptides. The small polypeptide (AtCPSF30) corresponds to CPSF30 and is the focus of this study. Recombinant AtCPSF30 was purified from Escherichia coli and found to possess RNA-binding activity. Mutational analysis indicated that an evolutionarily conserved central core of AtCPSF30 is involved in RNA binding, but that RNA binding also requires a short sequence adjacent to the N terminus of the central core. AtCPSF30 was found to bind calmodulin, and calmodulin inhibited the RNA-binding activity of the protein in a calcium-dependent manner. Mutational analysis showed that a small part of the protein, again adjacent to the N terminus of the conserved core, is responsible for calmodulin binding; point mutations in this region abolished both binding to and inhibition of RNA binding by calmodulin. Interestingly, AtCPSF30 was capable of self-interactions. This property also mapped to the central conserved core of the protein. However, calmodulin had no discernible effect on the self-association. These results show that the central portion of AtCPSF30 is involved in a number of important functions, and they raise interesting possibilities for both the interplay between splicing and polyadenylation and the regulation of these processes by stimuli that act through calmodulin.

Comparison of mechanical properties of four large, wave-exposed seaweeds.

Seaweeds have a simple structural design compared to most terrestrial plants. Nonetheless, some species have adapted to the severe mechanical conditions of the surf zone. The material properties of either tissue sections or the whole stipe of four wave-exposed seaweeds, Durvillaea antarctica, D. willana, Laminaria digitata, and L. hyperborea, were tested in tension, bending, and torsion. Durvillaea has a very low modulus of elasticity in tension (E(tension) = 3-7 MN·m(-2)) and in bending (E(bending) = 9-12 MN · m(-2)), torsion modulus (G = 0.3 MN · m(-2)) and strength (σ(b)rk = 1-2 MN · m(-2)), combining a compliable and twistable stipe "material" with a comparatively high breaking strain (ε(brk) = 0.4-0.6). In comparison, the smaller stipes of Laminaria have a higher modulus of elasticity in tension (E(tension) = 6-28 MN·m(-2)) and in bending (E(bending) = 84-109 MN·m(-2)), similar strength (σ(brk) = 1-3 MN·m(-2)), and a higher torsion modulus (G = 0.7-10 MN·m(-2)), combined with a lower breaking strain (ε(brk) = 0.2-0.3) than Durvillaea. Time-dependent, viscoelastic reactions were investigated with cycling tests. The tested species dissipated 42-52% of the loading energy in tension through plastic-viscoelastic processes, a finding that bears important ecological implications. Overall, there seems to be no correlation between single material properties and the size or habitat position of the tested seaweed species.

Regulation of membrane fatty acid composition by temperature in mutants of Arabidopsis with alterations in membrane lipid composition.

BACKGROUND: A wide range of cellular responses occur when plants are exposed to elevated temperature, including adjustments in the unsaturation level of membrane fatty acids. Although membrane bound desaturase enzymes mediate these adjustments, it is unknown how they are regulated to achieve these specific membrane compositions. Furthermore, the precise roles that different membrane fatty acid compositions play in photosynthesis are only beginning to be understood. To explore the regulation of the membrane composition and photosynthetic function in response to temperature, we examined the effect of temperature in a collection of mutants with altered membrane lipid fatty acid composition. RESULTS: In agreement with previous studies in other species, the level of unsaturation of membrane fatty acids in Arabidopsis was inversely correlated with growth temperature. The time required for the membrane fatty acids to attain the composition observed at elevated temperature was consistent with the timing required for the synthesis of new fatty acids. Comparisons of temperature-induced fatty acid alterations in membranes were made among several Arabidopsis lines including wild-type Columbia, and the compositional mutants, fad5, fad6, act1 and double mutants, fad7 fad8 and act1 fad6. The results revealed key changes that occur in response to elevated temperature regardless of the specific mutations in the glycerolipid pathway, including marked decreases in trienoic fatty acids and consistent increases in unsaturated 16:0 and in dienoic 18:2 levels. Fluorescence measurements of various mutants indicated that photosynthetic stability as well as whole plant growth at elevated temperature is influenced by certain membrane fatty acid compositions. CONCLUSIONS: The results of this study support the premise that defined proportions of saturated and unsaturated fatty acids in membrane lipids are required for photosynthetic thermostability and acclimation to elevated temperature. The results also suggest that changes in the membrane fatty acid composition brought about in response to temperature are regulated in such a way so as to achieve highly similar unsaturation levels despite mutations that alter the membrane composition prior to a high-temperature exposure. The results from examination of the mutant lines also suggest that interorganellar transfer of fatty acids are involved in mediating temperature-induced membrane alterations, and reveal steps in the fatty acid unsaturation pathway that appear to have key roles in the acclimatization of membranes to high temperature.

Wound-induced gene expression of putrescine N-methyltransferase in leaves of Nicotiana tabacum.

Putrescine N-methyltransferase (PMT) catalyzes the first committed step in the biosynthesis of pyrrolinium ring-containing alkaloids. Earlier studies have indicated that PMT gene expression is restricted to root tissue in Solanaceus plant species. During the analysis to further elucidate factors that govern the regulation of alkaloid synthesis, evidence was found for a novel expression pattern dictated by the 5'-flanking region of at least two members of the PMT-gene family. A 627-bp DNA fragment upstream of the NtPMT3 gene was fused to the beta-glucuronidase (GUS) reporter gene and used to produce stable transgenic lines of Nicotiana tabacum. Fluorometric and histochemical assays conducted on transgenic plants indicated high expression levels in root tissue and, in agreement with previous studies, no expression was detected in leaves. However, expression was observed in leaves when they were mechanically wounded. This expression was highly localized around the wound site and showed little evidence of long distance signaling, including lack of responsiveness to jasmonic acid. Expression was transient, with maximum levels immediately after wounding and diminishing after approximately 2-4 h. RT-PCR analysis of mRNA isolated from wild-type plants also indicated upregulation of PMT expression in leaves upon wounding as well as very low transcript levels in unwounded leaves. Low levels of PMT activity were detected in leaf tissue, which did not increase significantly upon wounding.

Simian malaria at two sites in the Brazilian Amazon. I--The infection rates of Plasmodium brasilianum in non-human primates.

The parasite that causes simian malaria in the Brazilian Amazon, Plasmodium brasilianum, is infective to man. In this region, where humans live within and in close proximity to the forest, it was suspected that this parasite could be the cause of a zoonosis. A study was performed in the areas surrounding two hydroelectric plants in the Amazon, Balbina and Samuel, aiming at determining the zoonotic potential of this parasite. P. brasilianum was detected in, respectively, 15.8% and 9.9% of 126 and 252 primates belonging to seven and eight species examined from Balbina and Samuel. The highest malaria infection rates were found among the red-howler monkey Alouatta seniculus straminea (32.3%), the bearded-saki Chiropotes satanas chiropotes (50%) and the spider-monkey Ateles paniscus paniscus (2[1+]) from Balbina and in the squirrel-monkey Saimiri ustus (21%) and the black-faced-spider-monkey Ateles paniscus chamek (28.6%) from Samuel.