Comparison of prasugrel and clopidogrel-treated patients with acute coronary syndrome undergoing percutaneous coronary intervention: A propensity score-matched analysis of the Acute Myocardial Infarction in Switzerland (AMIS)-Plus Registry

OBJECTIVE The purpose of this study was to investigate outcomes of patients treated with prasugrel or clopidogrel after percutaneous coronary intervention (PCI) in a nationwide acute coronary syndrome (ACS) registry. BACKGROUND Prasugrel was found to be superior to clopidogrel in a randomized trial of ACS patients undergoing PCI. However, little is known about its efficacy in everyday practice. METHODS All ACS patients enrolled in the Acute Myocardial Infarction in Switzerland (AMIS)-Plus registry undergoing PCI and being treated with a thienopyridine P2Y12 inhibitor between January 2010-December 2013 were included in this analysis. Patients were stratified according to treatment with prasugrel or clopidogrel and outcomes were compared using propensity score matching. The primary endpoint was a composite of death, recurrent infarction and stroke at hospital discharge. RESULTS Out of 7621 patients, 2891 received prasugrel (38%) and 4730 received clopidogrel (62%). Independent predictors of in-hospital mortality were age, Killip class >2, STEMI, Charlson comorbidity index >1, and resuscitation prior to admission. After propensity score matching (2301 patients per group), the primary endpoint was significantly lower in prasugrel-treated patients (3.0% vs 4.3%; p=0.022) while bleeding events were more frequent (4.1% vs 3.0%; p=0.048). In-hospital mortality was significantly reduced (1.8% vs 3.1%; p=0.004), but no significant differences were observed in rates of recurrent infarction (0.8% vs 0.7%; p=1.00) or stroke (0.5% vs 0.6%; p=0.85). In a predefined subset of matched patients with one-year follow-up (n=1226), mortality between discharge and one year was not significantly reduced in prasugrel-treated patients (1.3% vs 1.9%, p=0.38). CONCLUSIONS In everyday practice in Switzerland, prasugrel is predominantly used in younger patients with STEMI undergoing primary PCI. A propensity score-matched analysis suggests a mortality benefit from prasugrel compared with clopidogrel in these patients.

Macrofauna abundance and sediment characteristics during R/V Senckenberg cruise west of Sylt in september 2010

The continuously influence of human impacts on the seafloor and benthic habitats demands the knowledge of clearly defined habitats to assess recent conditions and to monitor future changes. In this study, a benthic habitat dominated by sorted bedforms was mapped in 2010 using biological, sedimentological and acoustic data. This approach reveals the first interdisciplinary analysis of macrofauna communities in sorted bedforms in the German Bight. The study area covered 4 km², and was located ca. 3.5 km west of island of Sylt. Sorted bedforms formed as sinuous depressions with an east west orientation. Inside these depressions coarse sand covers the seafloor, while outside predominantly fine to medium sand was found. Based on the hydroacoustic data, two seafloor classes were identified. Acoustic class 1 was linked to coarse sand (type A) found inside these sorted bedforms, whereas acoustic class 2 was related to mainly fine to medium sands (type B). The two acoustic classes and sediment types corresponded with the macrofauna communities 1 and 2. The Aoinides paucibranchiata-Goniadella bobretzkii community on coarse sand and the Spiophanes bombyx - Magelona johnstonii community on fine sand. A transitional community 3 (Scoloplos armiger - Ophelia community), with species found in communities 1 and 2, could not be detected by hydroacoustic methods. This study showed the limits of the used acoustic methods, which were unable to detect insignificant differences in the fauna composition of sandy areas.

Incomplete penetrance of familial retinoblastoma linked to germ-line mutations that result in partial loss of RB function

To study the molecular basis for the clinical phenotype of incomplete penetrance of familial retinoblastoma, we have examined the functional properties of three RB mutations identified in the germ line of five different families with low penetrance. RB mutants isolated from common adult cancers and from classic familial retinoblastoma (designated as classic RB mutations) are unstable and generally do not localize to the nucleus, do not undergo cyclin-dependent kinase (cdk)-mediated hyperphosphorylation, show absent protein “pocket” binding activity, and do not suppress colony growth of RB(−) cells. In contrast, two low-penetrant alleles (661W and “deletion of codon 480”) retained the ability to localize to the nucleus, showed normal cdk-mediated hyperphosphorylation in vivo, exhibited a binding pattern to simian virus 40 large T antigen using a quantitative yeast two-hybrid assay that was intermediate between classic mutants (null) and wild-type RB, and had absent E2F1 binding in vitro. A third, low-penetrant allele, “deletion of RB exon 4,” showed minimal hyperphosphorylation in vivo but demonstrated detectable E2F1 binding in vitro. In addition, each low-penetrant RB mutant retained the ability to suppress colony growth of RB(−) tumor cells. These findings suggest two categories of mutant, low-penetrant RB alleles. Class 1 alleles correspond to promoter mutations, which are believed to result in reduced or deregulated levels of wild-type RB protein, whereas class 2 alleles result in mutant proteins that retain partial activity. Characterization of the different subtypes of class 2 low-penetrant genes may help to define more precisely functional domains within the RB product required for tumor suppression.

Two hemoglobin genes in Arabidopsis thaliana: The evolutionary origins of leghemoglobins

We cloned two hemoglobin genes from Arabidopsis thaliana. One gene, AHB1, is related in sequence to the family of nonsymbiotic hemoglobin genes previously identified in a number of plant species (class 1). The second hemoglobin gene, AHB2, represents a class of nonsymbiotic hemoglobin (class 2) related in sequence to the symbiotic hemoglobin genes of legumes and Casuarina. The properties of these two hemoglobins suggest that the two families of nonsymbiotic hemoglobins may differ in function from each other and from the symbiotic hemoglobins. AHB1 is induced, in both roots and rosette leaves, by low oxygen levels. Recombinant AHB1 has an oxygen affinity so high as to make it unlikely to function as an oxygen transporter. AHB2 is expressed at a low level in rosette leaves and is low temperature-inducible. AHB2 protein has a lower affinity for oxygen than AHB1 but is similar to AHB1 in having an unusually low, pH-sensitive oxygen off-rate.

Translocation events in the evolution of aminoacyl-tRNA synthetases.

We have characterized hisS, the gene encoding the histidyl-tRNA synthetase (HisRS) from the tetraodontoid fish Fugu rubripes. The hisS gene is about 3.5 kbp long and contains 13 exons and 12 introns of 172 bp, on average. The Fugu hisS gene encodes a putative protein of 519 amino acids with the three motifs identified as signatures of class 2 aminoacyl-tRNA synthetases. A model for the shifting of intron 8 between Fugu and hamster is proposed based on the successive appearance of a cryptic splicing site followed by an insertion mutation that created a new acceptor site. In addition, sequence comparisons suggest that the hisS gene has undergone a translocation through the first intron. As a result, the Fugu HisRS has an N-terminal sequence markedly different from that in the human and hamster enzymes. We propose that similar events have been responsible for variations at the N-terminal end of other aminoacyl-tRNA synthetases. Our analysis suggests that this involves exchanges through introns of two exons encoding an ancestral 32-amino acid motif.

Fatigue and Co-occurring Symptoms in Women with Irritable Bowel Syndrome

Thesis (Ph.D.)--University of Washington, 2016-06

Migraine With Aura and Migraine Without Aura Are Not Distinct Entities: Further Evidence From a Large Dutch Population Study

It is often debated whether migraine with aura (MA) and migraine without aura (MO) are etiologically distinct disorders. A previous study using latent class analysis (LCA) in Australian twins showed no evidence for separate subtypes of MO and MA. The aim of the present study was to replicate these results in a population of Dutch twins and their parents, siblings and partners (N = 10,144). Latent class analysis of International Headache Society (IHS)-based migraine symptoms resulted in the identification of 4 classes: a class of unaffected subjects (class 0), a mild form of nonmigrainous headache (class 1), a moderately severe type of migraine (class 2), typically without neurological symptoms or aura (8% reporting aura symptoms), and a severe type of migraine (class 3), typically with neurological symptoms, and aura symptoms in approximately half of the cases. Given the overlap of neurological symptoms and nonmutual exclusivity of aura symptoms, these results do not support the MO and MA subtypes as being etiologically distinct. The heritability in female twins of migraine based on LCA classification was estimated at .50 (95% confidence intervals [0CI} .27 -.59), similar to IHS-based migraine diagnosis (h(2) = .49, 95% Cl .19-.57). However, using a dichotomous classification (affected-unaffected) decreased heritability for the IHS-based classification (h(2) = .33, 95% Cl .00-.60), but not the LCA-based classification (h(2) = .51, 95% Cl. 23-.61). Importantly, use of the LCA-based classification increased the number of subjects classified as affected. The heritability of the screening question was similar to more detailed LCA and IHS classifications, suggesting that the screening procedure is an important determining factor in genetic studies of migraine.

The Variety of Leibniz Algebras Defined by the Identity x(y(zt)) ≡ 0

2000 Mathematics Subject Classification: Primary: 17A32; Secondary: 16R10, 16P99, 17B01, 17B30, 20C30

A preceptoria na estratégia saúde da família: o olhar dos profissionais de saúde

The proposal of teaching-service integration from work experience brings a challenge to the professionals involved in health services: to combine their healthcare practice to the preparation of new professionals in accordance with the national health model. In Recife, the assistance network is known as school network, since it provides all its health equipment for Higher Education Institutions, in special for professionals who work as preceptors, making this activity an important component of the services network. The objective of the present study was to analyze preceptorship experience herein Multidisciplinary Residences in Health in the look of health professionals. This is a qualitative descriptive study, involving physicians, dentists, and nurses that have worked as preceptors for at least two years in multidisciplinary residency linked to two Higher Education Institutions. A semistructured interview was used as research instrument and data were processed by using the software Alceste 4.9. Results indicated four semantic classes which were divided into two axis. Axis 1, composed of class 4, and Axis 2, composed of classes 3, 2 and 1. Categorization considered the relation between classes. It was observed that in class 4 work overload is a dilemma for professional participation in preceptorship. This is noted by the words manage, time, patient, give, and complicated. However, it is also observed that the preceptorship involves positive learning and teaching actions, reinforced by the words say, explain, and discuss. Class 2 shows the preceptorship as an experience exchange, a positive moment that provides theoretical upgrade to the preceptor, associated to the professional practices performed by the binominal preceptor-student in health services and communities. In this perspective, everyone is benefited since preceptorship is structured according to dynamic aspects of knowledge, experienced in settings permeated by people´s health necessities. In class 3, potentialities of this practice are shown, and personal compromise is the main reason of acting as a preceptor in this network of education/attention, demonstrated in the words reason, formation, to like and professionals. Last, but not the least, class 1 suggests the importance of preceptorship and one of the strategies to create the National Politics of Humanization, from the teachingservice-community integration, observed in the words: arrives, university, fundamental, manner, partnership, service, and student. Besides, it rates perspectives and challenges for the improvement of the preceptorship in health services. Integrating teaching and service can enhance the proposals of changes concerning the healthcare model practiced in services, but this relation is still superficial. The preceptor is an actor in action, playing real life roles, and that is when he becomes essential to seek training with the profile defended in the proposed training of a professional who is capable of learning to learn

The clinical significance of medicines reconciliation in children admitted to hospital

Aims and Objectives: The NICE/NPSA guidance on Medicines Reconciliation in adults upon hospital admission excludes children under the age of 16.1 Hence the primary aim and objective of this study was to use medicines reconciliation to primarily identify if discrepancies occur upon hospital admission. Secondary objectives were to clinically assess for harm discrepancies that were identified in paediatric patients on long term medications at four hospitals across the UK. Method: Medicines reconciliation is a procedure where the current medication history of a patient prior to hospital admission would be taken and verifying the medication orders made at hospital admission against this history, addressing any discrepancies identified. Medicines reconciliation was carried out prospectively for 244 paediatric patients on chronic medication across four UK hospitals (Birmingham, London, Leeds and North Staffordshire) between January – May 2011. Medicines reconciliation was conducted by a clinical pharmacist using the following sources of information: 1) the patient's Pre-Admission Medication (PAM) from the patient's general practitioner 2) examination of the Patient's Own Medications brought into hospital, 3) a semi-structured interview with the parent-carers and 4) identification of admission medication orders written on the drug chart prior to clinical pharmacy input (Drug Chart). Discrepancies between the PAM and Drug Chart were documented and classified as intentional or unintentional. Intentional discrepancies were defined as changes that were made knowingly by the prescriber and confirmed. Unintentional discrepancies were assessed for clinical significance by an expert panel and assigned a significance score based on the likelihood of causing potential discomfort or clinical deterioration: class 1 unlikely, class 2 moderate and class 3 severe.2 Results: 1004 medication regimens were included from the 244 patients across the four sites. 588 of the 1004 (59%) medicines, had discrepancies between the PAM and Drug Chart; of these 36% (n = 209) were unintentional and included for clinically assessment. 189 drug discrepancies 30% were classified as class 1, 47% were class 2 and 23% were class 3 discrepancies. The remaining 20 discrepancies were cases where deviating from the PAM would have been the right thing to do, which might suggest that an intentional but undocumented discrepancy by the prescriber writing up the admission order may have occurred. Conclusion: The results suggest that medication discrepancies in paediatric patients do occur upon hospital admission, which do have a potential to cause harm and that medicines reconciliation is a potential solution to preventing such discrepancies. References: 1. National Institute for Health and Clinical Excellence. National Patient Safety Agency. PSG001. Technical patient safety solutions for medicines reconciliation on admission of adults to hospital. London: NICE; 2007. 2. Cornish, P. L., Knowles, S. R., Marchesano, et al. Unintended Medication Discrepancies at the Time of Hospital Admission. Archives of Internal Medicine 2005; 165:424–429

Unraveling the function of bacterial-type phosphoenolpyruvate carboxylase in vascular plants

Two distinct phosphoenolpyruvate carboxylase (PEPC) isozymes occur in vascular plants and green algae: plant-type PEPC (PTPC) and bacterial-type PEPC (BTPC). PTPC polypeptides typically form a tightly regulated cytosolic Class-1 PEPC homotetramer. BTPCs, however, appear to be less widely expressed and to exist only as catalytic and regulatory subunits that physically interact with co-expressed PTPC subunits to form hetero-octameric Class-2 PEPC complexes that are highly desensitized to Class-1 PEPC allosteric effectors. Yeast two-hybrid studies indicated that castor plant BTPC (RcPPC4) interacts with all three Arabidopsis thaliana PTPC isozymes, and that it forms stronger interactions with AtPPC2 and AtPPC3, suggesting that specific PTPCs are preferred for Class-2 PEPC formation. In contrast, Arabidopsis BTPC (AtPPC4) appeared to interact very weakly with AtPPC2 and AtPPC3, suggesting that BTPCs from different species may have different physical properties, hypothesized to be due to sequence dissimilarities within their ~10 kDa intrinsically disordered region. Recent RNA-seq and microarray data were analyzed to obtain a better understanding of BTPC expression patterns in different tissues of various monocot and dicot species. High levels of BTPC transcripts, polypeptides and Class-2 PEPC complexes were originally discovered in developing castor seeds, but the analysis revealed a broad range of diverse tissues where abundant BTPC transcripts are also expressed, such as the developing fruits of cucumber, grape, and tomato. Marked BTPC expression correlated well with the presence of ~116 kDa immunoreactive BTPC polypeptides, as well as Class-2 PEPC complexes in the immature fruit of cucumbers and tomatoes. It is therefore hypothesized that in vascular plants BTPC and thus Class-2 PEPC complexes maintain anaplerotic PEP flux in tissues with elevated malate levels that would potently inhibit ‘housekeeping’ Class-1 PEPCs. Elevated levels of malate can be used by biosynthetically active sink tissues such as immature tomatoes and cucumbers for rapid cell expansion, drought or salt stressed roots for osmoregulation, and developing seeds and pollen as a precursor for storage lipid and protein biosynthesis.

External Validation of the ProACS Score for Risk Stratification of Patients with Acute Coronary Syndromes

INTRODUCTION: The ProACS risk score is an early and simple risk stratification score developed for all-cause in-hospital mortality in acute coronary syndromes (ACS) from a Portuguese nationwide ACS registry. Our center only recently participated in the registry and was not included in the cohort used for developing the score. Our objective was to perform an external validation of this risk score for short- and long-term follow-up. METHODS: Consecutive patients admitted to our center with ACS were included. Demographic and admission characteristics, as well as treatment and outcome data were collected. The ProACS risk score variables are age (≥72 years), systolic blood pressure (≤116 mmHg), Killip class (2/3 or 4) and ST-segment elevation. We calculated ProACS, Global Registry of Acute Coronary Events (GRACE) and Canada Acute Coronary Syndrome risk score (C-ACS) risk scores for each patient. RESULTS: A total of 3170 patients were included, with a mean age of 64±13 years, 62% with ST-segment elevation myocardial infarction. All-cause in-hospital mortality was 5.7% and 10.3% at one-year follow-up. The ProACS risk score showed good discriminative ability for all considered outcomes (area under the receiver operating characteristic curve >0.75) and a good fit, similar to C-ACS, but lower than the GRACE risk score and slightly lower than in the original development cohort. The ProACS risk score provided good differentiation between patients at low, intermediate and high mortality risk in both short- and long-term follow-up (p<0.001 for all comparisons). CONCLUSIONS: The ProACS score is valid in external cohorts for risk stratification for ACS. It can be applied very early, at the first medical contact, but should subsequently be complemented by the GRACE risk score.

DINÂMICA DA REGENERAÇÃO NATURAL NO SUB-BOSQUE DE Pinus caribaea Morelet. var. caribaea NA RESERVA BIOLÓGICA DE SALTINHO, TAMANDARÉ - PE

O estudo da estrutura e dinâmica da regeneração natural em sub-bosque de plantios com espécies exóticas, como as do gênero Pinus , possibilita dar informações para manejo, conservação e reestabelecimento das espécies nativas de uma comunidade vegetal. O objetivo deste trabalho foi identificar e quantificar a dinâmica da regeneração natural das espécies arbustivo-arbóreas ocorrentes no sub-bosque do povoamento de Pinus caribaea , na Rebio de Saltinho, em Pernambuco. Foram medidas as espécies regenerantes de 10 parcelas permanentes, de 1 x 50 m, e incluídos os indivíduos com circunferência na base a 30 cm do solo (CAB 0,30m) ≤ 15 cm e altura superior a um metro. A altura foi classificada em: Classe 1, indivíduos arbustivoarbóreos, com altura 1 ≤ H ≤ 2; Classe 2 com altura 2 < H ≤ 3; e Classe 3, com altura > 3 m e CAP ≤ 15 cm. Calcularam-se os parâmetros fitossociológicos, a dinâmica da regeneração e os índices de Shannon (H’) e a equabilidade (J’) por Pielou. Protium heptaphyllum teve maior número de indivíduos e valor de importância (VI), e Miconia prasina a melhor frequência nos dois levantamentos. Quanto ao índice H’ de 3,32 nats.ind-1 (2007) passou a 3,07 nats.ind-1 (2012), e a equabilidade de J’ de 0,85 a 0,62, havendo decréscimo tanto para a diversidade, quanto para a distribuição. O levantamento de 2012 registrou aumento de 12,5% do número de indivíduos, e os regenerantes de 2007 tiveram 48,31% de mortalidade. Com relação ao número de indivíduos e área basal, os percentuais de ganhos foram superiores ao das perdas. Conclui-se que a sucessão ecológica da regeneração do sub-bosque do povoamento estudado, encontra-se em modificação positiva, e o povoamento de Pinus caribaea, não está impedindo o surgimento de novos indivíduos e espécies.

Unraveling the function of bacterial-type phosphoenolpyruvate carboxylase in vascular plants

Thesis (Master, Biology) -- Queen's University, 2016-09-29 20:09:46.997

Waste Disposal Requirements for Commercial Deer-Processing Facilities

Waste from a deer-processing facility is required by law to be disposed of in any permitted municipal solid waste (Class 3) landfill or a permitted construction and demolition debris (Class 2) landfill that has specific approval to accept animal carcasses. Disposal of deer-processing waste on the property of the processing facility or at any other unpermitted site IS NOT ALLOWED. Waste from commercial deer processing facilities must be disposed of per the requirements of the S.C. Solid Waste Policy and Management Act of 1991.