Residual vein thrombosis and onset of post-thrombotic syndrome: Influence of the 4G/5G polymorphism of plasminogen activator inhibitor-1 gene

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of plasminogen activator. The functional 4G/5G polymorphism of the gene coding for PAI-1 may affect PAI-1 plasmatic activity, influencing the imbalance between coagulation and fibrinolysis cascades. In this prospective cohort analytic study, we investigated the role of this single nucleotide polymorphism in the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. PATIENTS/METHODS: In a group of 168 patients with post-surgical deep vein thrombosis of the legs, we analyzed the 4G/5G polymorphism in the promoter of PAI-1 gene and plasmatic PAI-1 activity. Enrolled patients were divided in two groups: patients with 4G/5G polymorphism and increased PAI-1 activity (n=85) and patients without 4G/5G polymorphism and normal PAI-1 activity (n=83). All patients were treated according to current protocols and re-examined after 3, 12 and 36months in order to evaluate the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. RESULTS: We found a significantly increased PAI activity in carrier of the 4G allele, who experienced much more frequently a persistence of thrombosis after 3, 12 and 36months and/or the development of post-thrombosis syndrome, in spite of the anticoagulant treatment. CONCLUSIONS: These data not only confirm the role played by PAI-1 activity and by the 4G/5G SNP of the PAI-1 gene, but also suggest that current therapeutic protocols, recommending the administration of low weight molecular heparin and oral anticoagulant for the treatment of deep vein thrombosis, could be non sufficient for patients genetically predisposed to a less efficient clot lysis

Disease-modifying therapies alter gut microbial composition in MS.

Objective:To determine the effects of the disease-modifying therapies, glatiramer acetate (GA) and dimethyl fumarate (DMF), on the gut microbiota in patients with MS. Methods:Participants with relapsing MS who were either treatment-naive or treated with GA or DMF were recruited. Peripheral blood mononuclear cells were immunophenotyped. Bacterial DNA was extracted from stool, and amplicons targeting the V4 region of the bacterial/archaeal 16S rRNA gene were sequenced (Illumina MiSeq). Raw reads were clustered into Operational Taxonomic Units using the GreenGenes database. Differential abundance analysis was performed using linear discriminant analysis effect size. Phylogenetic investigation of communities by reconstruction of unobserved states was used to investigate changes to functional pathways resulting from differential taxon abundance. Results:One hundred sixty-eight participants were included (treatment-naive n = 75, DMF n = 33, and GA n = 60). Disease-modifying therapies were associated with changes in the fecal microbiota composition. Both therapies were associated with decreased relative abundance of the Lachnospiraceae and Veillonellaceae families. In addition, DMF was associated with decreased relative abundance of the phyla Firmicutes and Fusobacteria and the order Clostridiales and an increase in the phylum Bacteroidetes. Despite the different changes in bacterial taxa, there was an overlap between functional pathways affected by both therapies. Interpretation:Administration of GA or DMF is associated with differences in gut microbial composition in patients with MS. Because those changes affect critical metabolic pathways, we hypothesize that our findings may highlight mechanisms of pathophysiology and potential therapeutic intervention requiring further investigation

Soluble CD40L and cardiovascular risk in asymptomatic low-grade carotid stenosis

Background and Purpose-We investigated whether soluble CD40L (sCD40L) may predict the risk of cardiovascular (CV) events in patients with asymptomatic carotid plaques. Methods-Forty-two patients with asymptomatic low-grade carotid stenosis (ALCS) and 21 controls without any carotid stenosis were enrolled. All subjects had at least a major cardiovascular risk factor (CRF). Plasma levels of C-reactive protein (CRP), IL-6, and sCD40L were measured. Subjects were reviewed every 12 months (median follow-up, 8 years). Results-ALCS patients had higher (P<0.0001) CRP, IL-6, and sCD40L than controls. Fourteen patients experienced a CV event. Cox regression analysis showed that only high sCD40L levels (P=0.003) independently predicted cardiovascular risk. Conclusions-High levels of sCD40L may predict the risk of CV events in ALCS

Threshold J/ψ−J/\psi- production in nucleon-nucleon collisions

We analyze $J/\psi-$ production in nucleon-nucleon collisions near threshold in the framework of a general model independent formalism, which can be applied to any reaction $N+N\to N+N+V^0$, where $V^0=\omega$, $\phi$, or $J/\psi$. Such reactions show large isotopic effects: a large difference for $pp$- and $pn$-collisions, which is due to the different spin structure of the corresponding matrix elements. The analysis of the spin structure and of the polarization observables is based on symmetry properties of the strong interaction. Using existing experimental data on the different decays of $J/\psi-$meson, we suggest a model for $N+N\to N+N+J/\psi$, based on $t-$channel $\eta+\pi$-exchanges. We predict polarization phenomena for the $n+p\to n+p+J/\psi$-reaction and the ratio of cross sections for $np$ and $pp$-collisions. For the processes $\eta(\pi)+N\to N+J/\psi$ we apply two different approaches: vector meson exchange and local four-particle interaction. In both cases we find larger $J/\psi$-production in $np$-collisions, with respect to $pp$-collisions.Comment: 17 pages, 6 figure

Comparación de frecuencias alélicas y genotípicas de los polimorfismos CAPN1-316 Y CAPN1-4751 del gen de la Calpaina en tres poblaciones de ganado criollo boliviano

La terneza de la carne está en parte determinada por el sistema proteico calpaína (CAPN1) / calpastatina (CAST). Bolivia posee en los llanos tres biotipos de ganado Criollo: los Yacumeños, los Chaqueños y los Saavedreños. El objetivo del presente trabajo fue determinar la frecuencia alélica y genotípica del gen de la CAPN1 en tres poblaciones de ganado Criollo de Bolivia. Se obtuvieron muestras de sangre de 28 Criollos del Chaco (CCH), 85 Criollos Yacumeños (CYA) y 30 Criollos Saavedreños (CSV). El ADN se extrajo utilizando el kit comercial Wizard® Genomic Purification, y posteriormente se tipificaron dos polimorfismos (CAPN1-316 y CAPN1-4751) del gen CAPN1 mediante el método ARMS-PCR. La frecuencias alélicas y genotípicas, las heterocigosidades esperadas y observadas, así como, el índice FIS y el desequilibrio de ligamiento (LD) fueron calculadas mediante los programas MS-Tools y Genepop. Las frecuencias de los alelos asociados a mayor terneza para las poblaciones de CCH, CYA y CSV fueron: 23%, 22% y 33 % para el alelo C del SNP CAPN1-316 y 75%, 76% y 60% para el alelo C del CAPN1-4751. La heterocigocidad observada en las tres poblaciones se hallan en un rango de 0,30 a 0,46 para el marcador CAPN1-316 y de 0,21 a 0,60 para el polimorfismo CAPN1-4751. Los resultados demuestran que los bovinos criollos en las poblaciones analizadas poseen altas frecuencias alélicas para las variantes asociadas a mayor terneza de la carne. Por otra parte, no se observaron valores significativos de LD (P>0,01) entre los dos polimorfismos tipificados en las poblaciones estudiadas. Sería necesario tipificar ambos polimorfismos en futuros programas de selección asistida por marcadores genéticos.Meat tenderness is in part determined by the calpain (CAPN1) / calpastatin (CAST) genes. In the lowlands of Bolivia, three well differentiated Creole cattle populations can be distinguished: the Yacumeños, Chaqueños and Saavedreños. The main objective of this research was to determine the allelic and genotypic frequencies of two polymorphisms of the calpain gene in three Creole cattle populations in Bolivia. Blood samples of 28 Creole cattle from Chaqueño cattle (CCH), 85 from Yacumeño cattle (CYA) and 30 from Saavadreño cattle (CSV) were collected. Total DNA was extracted using the commercial kit Wizard® Genomic Purification and subsequently two polymorphisms (CAPN1-316 and CAPN1- 4751) of the CAPN1 gene were genotyped by the amplification refractory mutation system (ARMS-PCR) method. Allelic and genotypic frequencies, expected and observed heterozygosities, the FIS index and the magnitude of linkage disequilibrium (LD) were calculated using the software MS-Tools and Genepop. The allelic frequencies of variants associated with tenderness in the three populations CCH, CYA and CSV were 23%, 22% and 23% for the CAPN1- 316 and 75%, 76% and 60% for the CAPN1-4751. The observed heterozygosities in the three populations fluctuated between 0.30 and 0.46 for the CAPN1-316 marker and between 0.21 and 0.60 for the CAPN1-4751 marker. The results showed that the analysed populations of Creole cattle presented high frequencies of the alleles previously associated with tenderness in meat. The analysis of LD, however, did not show evidence of linkage between the two markers. It is necessary to perform a genetic analysis for both polymorphisms if included in future selection programs.Fil: Pereira, J. A. C.. Universidad Autónoma Gabriel René Moreno; BoliviaFil: Falomir Lockhart, Agustin Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Loza, A.. Universidad Autónoma Gabriel René Moreno; BoliviaFil: Villegas Castagnasso, Egle Etel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Rojas, P.. Universidad Autónoma Gabriel René Moreno; BoliviaFil: Carino, M. . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Ripoli, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Giovambattista, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentin

Brazilian Buffalo Genetic Variability by Cross-Specific Microsatellite Set

Buffaloes (Bubalus bubalis) are widely distributed and were introduced to Brazil in 1895. Most of the molecular genetic characterization of buffaloes has been done with cross-specific (cattle) markers, but few of them include Brazilian populations. Nineteen commonly used cattle microsatellites were tested to develop a multiplexed set of microsatellites and characterize Brazilian buffalo. Three PCR mixes were finally developed with the 11 markers that succeed in amplify and were polymorphic (58%). The average number of alleles was 5.42, with an average observed and expected heterocigozity of 0.441 and 0.695, respectively. As it was expected, Brazilian buffalo variability was lower than the previously reported from the domestication centres (China and India), but higher than the seriously selected European populations. The exclusion power calculated for the eleven markers in Brazilian buffalo was 0.9999999996, this allows its use in DNA based traceability.Instituto de Genética Veterinari

Pennsylvania Folklife Vol. 18, No. 4

• Discord in the Garden • The Folk Festival Seminars: Crafts and Customs of the Year • What to Read on the Amish • Soup\u27s On! • Festival Highlights • Folk Festival Program • Folk Festival Geisinger • Four Interviews with Powwowers • The First Historian of the Pennsylvania Germans • The Public Sale Sixty Years Ago • The Long Shingle • Quilts and Quilting: Folk-Cultural Questionnaire No. 12https://digitalcommons.ursinus.edu/pafolklifemag/1036/thumbnail.jp

Swiss Recommendations for Cutaneous Basal Cell Carcinoma

Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer in Switzerland and worldwide. Most BCCs can be treated in a curative setting. However, patients can develop locally destructive and, rarely, metastatic tumors that require a different treatment approach. The clinical subtype of individual lesions provides prognostic information and influences management decisions. Surgical excision, topical therapies, and radiotherapy are highly effective in the majority of subtypes as well as in low- and high-risk diseases. For patients with low-risk diseases and superficial tumors not amenable to surgery, several nonsurgical alternatives are available. Systemic therapy is indicated for high-risk BCCs, which are not amenable to either surgery or radiotherapy. Hedgehog pathway inhibitors (HHI) are currently approved. Other therapeutic options such as immune checkpoint inhibitors show promising results in clinical trials. This first version of Swiss recommendations for diagnosis and management of BCC was prepared through extensive literature review and an advisory board consensus of expert dermatologists and oncologists in Switzerland. The present guidelines recommend therapies based on a multidisciplinary team approach and rate of recurrence for individual lesions. Based on the risk of recurrence, two distinct groups have been identified: low-risk (easy-to-treat) and high-risk (difficult-to-treat) tumors. Based on these classifications, evidence-based recommendations of available therapies are presented herein