Small clonal B-cell population in the bone marrow as a possible tool in the diagnosis of occult primary parotid lymphoma

Case Description: An 82-years old Hispanic woman with a past medical history significant for pulmonary thromboembolism on oral anticoagulation, rheumatoid arthritis, and hypertension developed a new onset thrombocytopenia. Clinical Findings: Small clonal B-cells populations (SCBP) also known as monoclonal B-cell lymphocytosis was found as part of the workup for an idiopathic thrombocytopenia and lead ultimately to the diagnosis of parotid primary follicular lymphoma coexisting with Warthin tumor involving the bone marrow in a small extent and oncocytic papilloma located in the maxillary sinus. Treatment and Outcome: Patient was treated with Rituximab monotherapy with improvement on her platelet count. Clinical relevance: Although it is unclear the role of this clonal cells, they may work as a possible diagnostic tool for occult lymphomas. Further prospective studies are needed to confirm this possible association.

ANALYSIS OF POPULUS TREMULOIDES CLONAL VARIATION AND DELINEATION IN THE OTTAWA NATIONAL FOREST

The technique of delineating Populus tremuloides (Michx.) clonal colonies based on morphology and phenology has been utilized in many studies and forestry applications since the 1950s. Recently, the availability and robustness of molecular markers has challenged the validity of such approaches for accurate clonal identification. However, genetically sampling an entire stand is largely impractical or impossible. For that reason, it is often necessary to delineate putative genet boundaries for a more selective approach when genetically analyzing a clonal population. Here I re-evaluated the usefulness of phenotypic delineation by: (1) genetically identifying clonal colonies using nuclear microsatellite markers, (2) assessing phenotypic inter- and intraclonal agreement, and (3) determining the accuracy of visible characters to correctly assign ramets to their respective genets. The long-term soil productivity study plot 28 was chosen for analysis and is located in the Ottawa National Forest, MI (46° 37'60.0" N, 89° 12'42.7" W). In total, 32 genets were identified from 181 stems using seven microsatellite markers. The average genet size was 5.5 ramets and six of the largest were selected for phenotypic analyses. Phenotypic analyses included budbreak timing, DBH, bark thickness, bark color or brightness, leaf senescence, leaf serrations, and leaf length ratio. All phenotypic characters, except for DBH, were useful for the analysis of inter- and intraclonal variation and phenotypic delineation. Generally, phenotypic expression was related to genotype with multiple response permutation procedure (MRPP) intraclonal distance values ranging from 0.148 and 0.427 and an observed MRPP delta value=0.221 when the expected delta=0.5. The phenotypic traits, though, overlapped significantly among some clones. When stems were assigned into phenotypic groups, six phenotypic groups were identified with each group containing a dominant genotype or clonal colony. All phenotypic groups contained stems from at least two clonal colonies and no clonal colony was entirely contained within one phenotypic group. These results demonstrate that phenotype varies with genotype and stand clonality can be determined using phenotypic characters, but phenotypic delineation is less precise. I therefore recommend that some genetic identification follow any phenotypic delineation. The amount of genetic identification required for clonal confirmation is likely to vary based on stand and environmental conditions. Further analysis, however, is needed to test these findings in other forest stands and populations.

A Livestock-Associated, Multidrug-Resistant, Methicillin-Resistant Staphylococcus aureus Clonal Complex 97 Lineage Spreading in Dairy Cattle and Pigs in Italy

Pandemic methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 97 (CC97) lineages originated from livestock-to-human host jumps. In recent years, CC97 has become one of the major MRSA lineages detected in Italian farmed animals. The aim of this study was to characterize and analyze differences in MRSA and methicillin-susceptible S. aureus (MSSA) mainly of swine and bovine origins. Forty-seven CC97 isolates, 35 MRSA isolates, and 6 MSSA isolates from different Italian pig and cattle holdings; 5 pig MRSA isolates from Germany; and 1 human MSSA isolate from Spain were characterized by macrorestriction pulsed-field gel electrophoresis (PFGE) analysis, multilocus sequence typing (MLST), spa typing, staphylococcal cassette chromosome mec (SCCmec) typing, and antimicrobial resistance pattern analysis. Virulence and resistance genes were investigated by PCR and microarray analysis. Most of the isolates were of SCCmec type V (SCCmec V), except for two German MRSA isolates (SCCmec III). Five main clusters were identified by PFGE, with the German isolates (clusters I and II) showing 60.5% similarity with the Italian isolates, most of which (68.1%) grouped into cluster V. All CC97 isolates were Panton-Valentine leukocidin (PVL) negative, and a few (n = 7) tested positive for sak or scn. All MRSA isolates were multidrug resistant (MDR), and the main features were erm(B)- or erm(C)-mediated (n = 18) macrolide-lincosamide-streptogramin B resistance, vga(A)-mediated (n = 37) pleuromutilin resistance, fluoroquinolone resistance (n = 33), tet(K) in 32/37 tet(M)-positive isolates, and blaZ in almost all MRSA isolates. Few host-associated differences were detected among CC97 MRSA isolates: their extensive MDR nature in both pigs and dairy cattle may be a consequence of a spillback from pigs of a MRSA lineage that originated in cattle as MSSA and needs further investigation. Measures should be implemented at the farm level to prevent spillover to humans in intensive farming areas.

Splitting of a prevalent Mycobacterium bovis spoligotype by variable-number tandem-repeat typing reveals high heterogeneity in an evolving clonal group

Mycobacterium bovis populations in countries with persistent bovine tuberculosis usually show a prevalent spoligotype with a wide geographical distribution. This study applied mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing to a random panel of 115 M. bovis isolates that are representative of the most frequent spoligotype in the Iberian Peninsula, SB0121. VNTR typing targeted nine loci: ETR-A (alias VNTR2165), ETR-B (VNTR2461), ETR-D (MIRU4, VNTR580), ETR-E (MIRU31, VNTR3192), MIRU26 (VNTR2996), QUB11a (VNTR2163a), QUB11b (VNTR2163b), QUB26 (VNTR4052), and QUB3232 (VNTR3232). We found a high degree of diversity among the studied isolates (discriminatory index [D] = 0.9856), which were split into 65 different MIRU-VNTR types. An alternative short-format MIRU-VNTR typing targeting only the four loci with the highest variability values was found to offer an equivalent discriminatory index. Minimum spanning trees using the MIRU-VNTR data showed the hypothetical evolution of an apparent clonal group. MIRU-VNTR analysis was also applied to the isolates of 176 animals from 15 farms infected by M. bovis SB0121; in 10 farms, the analysis revealed the coexistence of two to five different MIRU types differing in one to six loci, which highlights the frequency of undetected heterogeneity.

African 2, a clonal complex of Mycobacterium bovis epidemiologically important in East Africa

We have identified a clonal complex of Mycobacterium bovis isolated at high frequency from cattle in Uganda, Burundi, Tanzania, and Ethiopia. We have named this related group of M. bovis strains the African 2 (Af2) clonal complex of M. bovis. Af2 strains are defined by a specific chromosomal deletion (RDAf2) and can be identified by the absence of spacers 3 to 7 in their spoligotype patterns. Deletion analysis of M. bovis isolates from Algeria, Mali, Chad, Nigeria, Cameroon, South Africa, and Mozambique did not identify any strains of the Af2 clonal complex, suggesting that this clonal complex of M. bovis is localized in East Africa. The specific spoligotype pattern of the Af2 clonal complex was rarely identified among isolates from outside Africa, and the few isolates that were found and tested were intact at the RDAf2 locus. We conclude that the Af2 clonal complex is localized to cattle in East Africa. We found that strains of the Af2 clonal complex of M. bovis have, in general, four or more copies of the insertion sequence IS6110, in contrast to the majority of M. bovis strains isolated from cattle, which are thought to carry only one or a few copies.

Roles of the Immune Cytokine Environment on Clonal Growth of Murine and Human Tet2 Mutant Bone Marrow Progenitors: Implications for Myelodysplastic Syndromes

TET2 is a tumor suppressor gene that has been implicated in the epigenetic regulation of gene expression. Inactivating TET2 mutations are common in MDS. These mutations may contribute to early clonal dominance and myeloid transformation, although the exact mechanisms remain to be elucidated. Common to the environment of MDS are elevations in cytokines, such as TNFα and IFN-γ. It was hypothesized that inflammatory cytokines TNF-α and IFN-γ may promote clonal expansion of TET2 mutant progenitors. Adult (10-14 weeks-old) Tet2 wild type (+/+) and Tet2 mutant (-/-) C57BL/6 mice strains were chosen as a model system. Lineage negative cells (Lin-), enriched for hematopoietic stem and progenitor cells, were isolated from Tet2 +/+ and -/- bone marrow and cultured in the absence or presence of varying concentrations of TNFα or IFN-γ in methylcellulose colony formation assays and long term cell culture assays, over a period of 12 and 30 days respectively, and their colony growth, cell count, immunophenotype and resistance to apoptosis were examined. Where indicated, serial re-plating was performed. Expression of apoptotic regulators was assessed by qRT-PCR. In the triplicate experiments, starting with equal densities of Tet2 +/+ and -/- Lin- cells, Tet2 -/- Lin- cells displayed increased resistance to cytokine-induced growth suppression and superior colony forming ability over +/+ in the serial re-plating assays under stress of increasing TNFα or IFN γ. Tet2 -/- progenitors also displayed a lower apoptotic index compared to +/+ under stress of increasing TNFα, suggesting increased resistance to TNFα induced apoptosis. Transcriptional data showed low expression of Tnfr1, Fas and caspase 8, as well as a high expression of Bcl-2 and Iap1 in Tet2 -/- compared to +/+ under stress of TNFα. Tet2-/- also showed increased basal expression of endogenous TNFα mRNA compared to +/+. In the human colony growth assay, the clonal growth of TET2 mutant CFU-GM progenitors was enhanced at low TNFα concentrations. Conclusion: Mutations that promote resistance to environmental stem cell stressors are a known mechanism of clonal selection in aplastic anaemia and JAK2-mutant MPN and our findings suggest that this mechanism may be critical to clonal selection and dominance in MDS.

Uso de estimulación eléctrica medular en el manejo de síndrome doloroso regional complejo: revisión sistemática

La estimulación eléctrica medular (EEM), es una técnica mínimamente invasiva, segura, con pocos efectos secundarios y resultados favorables en patologías crónicas asociadas a dolor severo de difícil manejo, tal como es el caso del Síndrome Doloroso Regional Complejo (SDRC). La evidencia actual señala beneficios en esta patología particular, motivo por el cuál es de interés hacer una revisión actualizada sobre la EEM en SDRC.

Mejoras en el complejo deportivo provincial de Cáceres para alcanzar un rendimiento eficiente

INTRODUCCIÓN: Si observamos los cambios experimentales durante los últimos afios en el ámbito deportivo, en concreto desde los afios 70 hasta hoy, apreciamos sin lugar a dudas que éstos han sido enormes tanto cualitativa como cuantitativamente. Algunos de los cambios más importantes y significativos los encontramos en el gran aumento de instalaciones deportivas y equipamientos, así como en el incremento de personas que se han sumado a la práctica de alguna modalidad deportiva. Hoy nos encontramos con personas o colectivos que han accedido a la práctica de de actividades físico - deportivas y que tradicionalmente siempre o la mayoría de las veces permanecían al margen, mujeres, adultos, discapacitados, etc. Otro de los cambios que se ponen de manifiesto, es el mayor volumen económico del negocio deportivo o el incremento de personas ocupadas en el sector deportivo dentro de sus múltiples ámbitos. Es durante este período, coincidiendo con el desarrollo de la Constitución, cuando el deporte pasa a ser considerado como un derecho de los ciudadanos que los poderes públicos deben garantizar. Durante los primeros afios de la democracia los ayuntamientos comienzan con la creación de equipamientos deportivos abiertos a todos los ciudadanos, esto trae consigo una inversión económica muy importante para establecer una red de equipamientos e instalaciones deportivas que de alguna manera suple en un primer momento la falta de infraestructuras tan deficiente. Culminada la fase de construcción de instalaciones básicas, surgió la necesidad de establecer unos objetivos para rentabilizar las redes de equipamientos. De este modo la construcción de las instalaciones se hizo a partir de las necesidades y de los recursos existentes, bajo la orientación de planes directores, para secuenciar de la manera más adecuada posible la dotación deportiva de las comarcas y las provincias, comienzan a aparecer los primeros censos de instalaciones deportivas. El punto de inflexión más importantes, sin lugar a dudas, es la organización y desarrollo de los Juegos Olímpicos de Barcelona 92, significa además el punto culminante en la creación de nuevos equipamientos, caracterizándose principalmente por el intento de profesionalizar la gestión y exigencias de criterios de rentabilidad, no sólo social, sino también económica. En la actualidad la perspectiva en el ámbito dei deporte y la actividad fisica, parece enfocar hacia la preocupación por el cliente, la calidad dei servicio, y los criterios de eficacia y rentabilidad económica. Considerándose la actividad deportiva como una mejora dei estilo de vida. No obstante en los últimos afíos las instalaciones deportivas de ámbito público, parecen haber insertado entre sus objetivos, el de rentabilidad económica con el fin de poder competir con cualquier entidad, y poder incrementar la calidad de sus servidos. Analizando la Ley dei Deporte de 1990 en cuanto a instalaciones deportivas de ámbito público se refiere, nos encontramos con una serie de requisitos que deben cumplir…

Prospecção clonal em variedades viníferas na região da Serra Gaúcha.

A seleção clonal supõe que o cultivo prolongado de uma determinada variedade origina variabilidade nos indivíduos daquela população. O presente trabalho teve por objetivo prospectar e identificar plantas de variedades viníferas com base em suas características morfológicas, fenológicas e fitossanitárias em vinhedos antigos.

Procedencia de los esclavos negros analizada a través del complejo de distribución, desarrollado desde Cartagena.

Introducción Cartagena de Indias fue el puerto de mayor importancia en el comercio de esclavos en la América Hispana  Colonial. Fue el mayor centro de  recepción y dispersión de los mismos al eje del Pacifico utilizando el paso de  Panamá y el mar del sur va a cubrir la demanda desde Chile hasta Acapulco.

Fundamentos teóricos del Pensamiento complejo de Edgar Morin

In face of what he considered as the crisis of the Western paradigm of simplification and disjunction, based on the reduction and separation of knowledge, Edgar Morin posited the emergence of a new paradigm of complexity that would attempt to articulate and contextualize scientific, humanistic, and artistic cultures. To accomplish such purpose, Morin argued for an integration of ideas, concepts and notions drawing on different theoretical sources. Approaching complexity has required a dialectic and creative resignification of the legacy of such theories through a new synthesis that both integrates and surpasses them qualitatively.

Consideraciones básicas del pensamiento complejo de Edgar Morin, en la educación

This essay consists of a brief description and analysis of Edgar Morin´s complex thinking. For that reason, it focuses on the systematic approach that refers to the interconnection and interactions of objects, people, and environment as a whole, which serve as the basis of the educational proposal, where knowledge must be regarded as an integrated fashion and not as something fragmented. Thus, human knowledge should raise awareness that we are just a component of a more general system (complex and in constant interaction), where education can be an effective source for students to develop the capacity of understanding other complex systems, besides living organisms, where also there is a big influence from “new sciences” and humanities. Therefore, the purpose of this work is to develop those ideas proposed by Edgar Morin.

DISFUNCIONALIDAD AMBIENTAL MARPLATENSE . EL CASO DEL COMPLEJO HABITACIONAL CENTENARIO. MAR DEL PLATA. ARGENTINA.

El fenómeno de la fragmentación socio territorial es tomado como base en el presente análisis. El que está guiado  por el siguiente objetivo general: Analizar las posibles conexiones en el comportamiento de los indicadores de oferta ambiental y de demanda social puestos en relieve en un barrio de viviendas sociales ubicado en el noroeste del ejido  de la ciudad de Mar del Plata, Argentina. Se trata de un complejo habitacional de 1600 viviendas que alberga aproximadamente a 20000 habitantes.  Con alta proporción de jefes de hogar desocupados, subocupados e informales. Y que presenta en la actualidad deficiencias de mantenimiento edilicio. El trabajo pretende aportar al  conocimiento de la  problemática de vivienda en la ciudad así como dar cuenta de la importancia de la planificación que contemplara cuestiones de salubridad  asociada  a la producción de desechos  acumulados en áreas dispuestas a tal fin con capacidad y mantenimiento deficientes, así como la previsión de vías de acceso y circulación interna acorde con el número de habitantes. También se incluyen los problemas generados por la eliminación de espacios verdes.

Outcomes of global coagulation assays in patients with Philadelphia-negative myeloproliferative neoplasms with respect to genetic determinants of clonal progression

Classical myeloproliferative neoplasms (MPNs) are hematopoietic stem cell disorders that manifest with inflammation, promotion of atherosclerosis, hypercoagulability, fibrosis, and clonal evolution. The complex biological background lends itself to multi-omics studies. We have previously shown that reduced platelet fibrinogen receptor (PFR) expression may follow hyperactivation of plasma-dependent mechanisms, such as tissue factor (TF) release, unbalanced thrombin generation, involvement of protease-activated receptors (PARs). Acetylsalicylic acid (ASA) helped to restore the expression of PFRs. In this study, we enrolled 53 MPN patients, subjecting them to advanced genetic testing (panel of 30 genes in NGS), global coagulation testing (Rotational Thromboelastometry - ROTEM) and cytofluorometric determination of PFRs. ROTEM parameters appear to differ considerably depending on the type of pathology under investigation, cell count, and selected mutations. Essential thrombocythemia (ET) and CALR mutation appear to correlate with increased efficiency of both classical coagulation pathways, with significantly more contracted clot formation times (CFTs). In contrast, primary myelofibrosis (PMF) and polycythemia vera (PV) show greater imbalances in the hemostatic system. PV, probably due to its peculiar hematological features, shows a lengthening of the CFT and, at the same time, a selective contraction of parameters in INTEM with the increase of platelets and white blood cells. PMF - in contrast - seems to exploit the extrinsic pathway more to increase cell numbers. The presence of DNMT3A mutations is associated with reduced clotting time (CT) in EXTEM, while ASXL1 causes reduced maximal lysis (ML). EZH2 could be responsible for the elongation of CFT in INTEM assay. In addition, increased PFR expression is associated with history of hemorrhage and sustained CT time in FIBTEM under ASA prophylaxis. Our findings corroborate the existing models on the connection between fibrosis, genetic complexity, clonal progression, and hypercoagulability. Global coagulation assays and PFR expression are potentially useful tools for dynamic evaluation of treatments’ outcomes.

Overlapped Sequence Types (sts) And Serogroups Of Avian Pathogenic (apec) And Human Extra-intestinal Pathogenic (expec) Escherichia Coli Isolated In Brazil.

Avian pathogenic Escherichia coli (APEC) strains belong to a category that is associated with colibacillosis, a serious illness in the poultry industry worldwide. Additionally, some APEC groups have recently been described as potential zoonotic agents. In this work, we compared APEC strains with extraintestinal pathogenic E. coli (ExPEC) strains isolated from clinical cases of humans with extra-intestinal diseases such as urinary tract infections (UTI) and bacteremia. PCR results showed that genes usually found in the ColV plasmid (tsh, iucA, iss, and hlyF) were associated with APEC strains while fyuA, irp-2, fepC sitDchrom, fimH, crl, csgA, afa, iha, sat, hlyA, hra, cnf1, kpsMTII, clpVSakai and malX were associated with human ExPEC. Both categories shared nine serogroups (O2, O6, O7, O8, O11, O19, O25, O73 and O153) and seven sequence types (ST10, ST88, ST93, ST117, ST131, ST155, ST359, ST648 and ST1011). Interestingly, ST95, which is associated with the zoonotic potential of APEC and is spread in avian E. coli of North America and Europe, was not detected among 76 APEC strains. When the strains were clustered based on the presence of virulence genes, most ExPEC strains (71.7%) were contained in one cluster while most APEC strains (63.2%) segregated to another. In general, the strains showed distinct genetic and fingerprint patterns, but avian and human strains of ST359, or ST23 clonal complex (CC), presented more than 70% of similarity by PFGE. The results demonstrate that some zoonotic-related STs (ST117, ST131, ST10CC, ST23CC) are present in Brazil. Also, the presence of moderate fingerprint similarities between ST359 E. coli of avian and human origin indicates that strains of this ST are candidates for having zoonotic potential.