2,247 research outputs found

    Recainam, A potent new antiarrhythmic agent: Effects on complex ventricular arrhythmias

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    The antiarrhythmic efficacy and safety of intravenous recainam, a newly synthesized compound displaying potent class I antiarrhythmic activity, were tested in 10 hospitalized patients with frequent (>30/h) complex ventricular ectopic beats. There were seven men and three women of average age 57 years (range 21 to 74); five had ischemic heart disease, three had cardiomyopathy and two had valvular heart disease. Recainam was given as a 3.0 mg/kg per 40 min loading infusion followed by a 0.9 mg/kg per h maintenance infusion over a 24 hour observation period. Arrhythmia response was assessed both in the short term (comparing 2 hours before and 1 hour after drug loading) and in the long term (comparing 48 hours before drug loading and 23 hours of maintenance infusion).The median frequency of total premature ventricular complexes decreased in the short term by 99.6% (from 392.5 to 1.5/h, p < 0.005) and in the long term by 99.7% (from 435 to 1.3/h, p < 0.01). Repetitive beats were suppressed by a median of 100% both in the short term (p < 0.006) and during 24 hour infusion (from 80.9 to 0/h, p < 0.003). More than 90% suppression of repetitive beats occurred in all 10 patients (100%) and more than 90% suppression of total arrhythmias occurred in 9 patients (90%) during the maintenance period. Electrocardiographic PR and QRS intervals increased by 19% (p < 0.001) and 24% (p < 0.003), respectively, during therapy, but the JTc interval decreased (p < 0.001). Plasma recainam concentrations averaged 5.2 ± 0.9 μg/ml after loading and 3.0 ± 0.5 μg/ml during maintenance therapy. No adverse symptoms occurred.In summary, recainam is a promising, highly efficacious and well tolerated agent when administered intravenously for short-term and maintenance suppression of complex ventricular arrhythmias. The efficacy of oral and intravenous recainam for arrhythmia management deserves further evaluation

    Transmission of foot-and-mouth disease SAT2 viruses at the wildlife-livestock interface of two major transfrontier conservation areas in Southern Africa

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    Over a decade ago, foot-and-mouth disease (FMD) re-emerged in Southern Africa specifically in beef exporting countries that had successfully maintained disease-free areas in the past. FMD virus (FMDV) serotype SAT2 has been responsible for a majority of these outbreaks. Epidemiological studies have revealed the importance of the African buffalo as the major wildlife FMD reservoir in the region. We used phylogeographic analysis to study dynamics of FMD transmission between buffalo and domestic cattle at the interface of the major wildlife protected areas in the region currently encompassing two largest Transfrontier conservation areas: Kavango–Zambezi (KAZA) and Great Limpopo (GL). Results of this study showed restricted local occurrence of each FMDV SAT2 topotypes I, II, and III, with occasional virus migration from KAZA to GL. Origins of outbreaks in livestock are frequently attributed to wild buffalo, but our results suggest that transmission from cattle to buffalo also occurs. We used coalescent Bayesian skyline analysis to study the genetic variation of the virus in cattle and buffalo, and discussed the association of these genetic changes in the virus and relevant epidemiological events that occurred in this area. Our results show that the genetic diversity of FMDV SAT2 has decreased in buffalo and cattle population during the last decade. This study contributes to understand the major dynamics of transmission and genetic variation of FMDV SAT2 in Southern Africa, which will could ultimately help in designing efficient strategies for the control of FMD at a local and regional levelThis project was funded in part by grants from the USDA/ARS and CORUS (French Ministry of Foreign Affairs). The FMD virus database was compiled with funds from the SADC FMD Project.http://www.frontiersin.orgam2016Zoology and Entomolog

    Transmission of foot-and-mouth disease SAT2 viruses at the wildlife-livestock interface of two major transfrontier conservation areas in Southern Africa

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    Over a decade ago, foot-and-mouth disease (FMD) re-emerged in Southern Africa specifically in beef exporting countries that had successfully maintained disease-free areas in the past. FMD virus (FMDV) serotype SAT2 has been responsible for a majority of these outbreaks. Epidemiological studies have revealed the importance of the African buffalo as the major wildlife FMD reservoir in the region. We used phylogeographic analysis to study dynamics of FMD transmission between buffalo and domestic cattle at the interface of the major wildlife protected areas in the region currently encompassing two largest Transfrontier conservation areas: Kavango–Zambezi (KAZA) and Great Limpopo (GL). Results of this study showed restricted local occurrence of each FMDV SAT2 topotypes I, II, and III, with occasional virus migration from KAZA to GL. Origins of outbreaks in livestock are frequently attributed to wild buffalo, but our results suggest that transmission from cattle to buffalo also occurs. We used coalescent Bayesian skyline analysis to study the genetic variation of the virus in cattle and buffalo, and discussed the association of these genetic changes in the virus and relevant epidemiological events that occurred in this area. Our results show that the genetic diversity of FMDV SAT2 has decreased in buffalo and cattle population during the last decade. This study contributes to understand the major dynamics of transmission and genetic variation of FMDV SAT2 in Southern Africa, which will could ultimately help in designing efficient strategies for the control of FMD at a local and regional levelThis project was funded in part by grants from the USDA/ARS and CORUS (French Ministry of Foreign Affairs). The FMD virus database was compiled with funds from the SADC FMD Project.http://www.frontiersin.orgam2016Zoology and Entomolog

    Assessing the cost of global biodiversity and conservation knowledge

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    Knowledge products comprise assessments of authoritative information supported by stan-dards, governance, quality control, data, tools, and capacity building mechanisms. Considerable resources are dedicated to developing and maintaining knowledge productsfor biodiversity conservation, and they are widely used to inform policy and advise decisionmakers and practitioners. However, the financial cost of delivering this information is largelyundocumented. We evaluated the costs and funding sources for developing and maintain-ing four global biodiversity and conservation knowledge products: The IUCN Red List ofThreatened Species, the IUCN Red List of Ecosystems, Protected Planet, and the WorldDatabase of Key Biodiversity Areas. These are secondary data sets, built on primary datacollected by extensive networks of expert contributors worldwide. We estimate that US160million(range:US160million (range: US116–204 million), plus 293 person-years of volunteer time (range: 278–308 person-years) valued at US14million(rangeUS 14 million (range US12–16 million), were invested inthese four knowledge products between 1979 and 2013. More than half of this financingwas provided through philanthropy, and nearly three-quarters was spent on personnelcosts. The estimated annual cost of maintaining data and platforms for three of these knowl-edge products (excluding the IUCN Red List of Ecosystems for which annual costs were notpossible to estimate for 2013) is US6.5millionintotal(range:US6.5 million in total (range: US6.2–6.7 million). We esti-mated that an additional US114millionwillbeneededtoreachpredefinedbaselinesofdatacoverageforallthefourknowledgeproducts,andthatonceachieved,annualmaintenancecostswillbeapproximatelyUS114 million will be needed to reach pre-defined baselines ofdata coverage for all the four knowledge products, and that once achieved, annual mainte-nance costs will be approximately US12 million. These costs are much lower than those tomaintain many other, similarly important, global knowledge products. Ensuring that biodi-versity and conservation knowledge products are sufficiently up to date, comprehensiveand accurate is fundamental to inform decision-making for biodiversity conservation andsustainable development. Thus, the development and implementation of plans for sustain-able long-term financing for them is critical

    Recommendations From the International Consortium on Professional Nursing Practice in Long-Term Care Homes

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    AbstractIn response to the International Association of Gerontology and Geriatrics' global agenda for clinical research and quality of care in long-term care homes (LTCHs), the International Consortium on Professional Nursing Practice in Long Term Care Homes (the Consortium) was formed to develop nursing leadership capacity and address the concerns regarding the current state of professional nursing practice in LTCHs. At its invitational, 2-day inaugural meeting, the Consortium brought together international nurse experts to explore the potential of registered nurses (RNs) who work as supervisors or charge nurses within the LTCHs and the value of their contribution in nursing homes, consider what RN competencies might be needed, discuss effective educational (curriculum and practice) experiences, health care policy, and human resources planning requirements, and to identify what sustainable nurse leadership strategies and models might enhance the effectiveness of RNs in improving resident, family, and staff outcomes. The Consortium made recommendations about the following priority issues for action: (1) define the competencies of RNs required to care for older adults in LTCHs; (2) create an LTCH environment in which the RN role is differentiated from other team members and RNs can practice to their full scope; and (3) prepare RN leaders to operate effectively in person-centered care LTCH environments. In addition to clear recommendations for practice, the Consortium identified several areas in which further research is needed. The Consortium advocated for a research agenda that emphasizes an international coordination of research efforts to explore similar issues, the pursuit of examining the impact of nursing and organizational models, and the showcasing of excellence in nursing practice in care homes, so that others might learn from what works. Several studies already under way are also described

    Congenital syndactyly in cattle: four novel mutations in the low density lipoprotein receptor-related protein 4 gene (LRP4)

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    BACKGROUND: Isolated syndactyly in cattle, also known as mulefoot, is inherited as an autosomal recessive trait with variable penetrance in different cattle breeds. Recently, two independent mutations in the bovine LRP4 gene have been reported as the primary cause of syndactyly in the Holstein and Angus cattle breeds. RESULTS: We confirmed the previously described LRP4 exon 33 two nucleotide substitution in most of the affected Holstein calves and revealed additional evidence for allelic heterogeneity by the identification of four new LRP4 non-synonymous point mutations co-segregating in Holstein, German Simmental and Simmental-Charolais families. CONCLUSION: We confirmed a significant role of LRP4 mutations in the pathogenesis of congenital syndactyly in cattle. The newly detected missense mutations in the LRP4 gene represent independent mutations affecting different conserved protein domains. However, the four newly described LRP4 mutations do still not explain all analyzed cases of syndactyly

    New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

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    Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

    Hundreds of variants clustered in genomic loci and biological pathways affect human height

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    Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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