Longitudinal study on the colonisation and transmission of methicillin-resistant Staphylococcus aureus in pig farms.

Knowledge about the dynamics of methicillin-resistant Staphylococcus aureus (MRSA) in pigs lacks detail at the level of individual animal. The aim of our study was therefore to determine the colonisation status of MRSA in individual pigs from birth to slaughter in order to gain a better understanding of substantial factors involved in transmission. Two farrow-to-finish and two grow-to-finish herds were included in the study. A total of 1728 nasal swabs from 390 pigs and 592 environmental wipes were collected at 11 different time points. Intermittent colonisation throughout the entire production cycle was conspicuous in the tracking of MRSA in individual pigs. Almost all pigs from a MRSA-positive herd changed MRSA status several times, which implies that pigs are transiently rather than permanently colonised. We highly recommend the definition of MRSA status at herd level rather that at the level of the individual pig when considering prevention measures against MRSA. Therefore, to avoid the further spread of MRSA in countries with moderate prevalence, such as in Switzerland, defining farms as MRSA positive or MRSA negative and allowing the trade of pigs only within herds of the same status seems feasible. This will also be important for combating the further dissemination of livestock-associated (LA)-MRSA into healthcare facilities and the community via humans who have close contact with animals.

Towards an Earlier Diagnosis of Primary Ciliary Dyskinesia: Which Patients Should Undergo Detailed Diagnostic Testing?

Primary ciliary dyskinesia is a rare heterogeneous recessive genetic disorder of motile cilia, leading to chronic upper and lower respiratory symptoms. Prevalence is estimated at around 1:10,000, but many patients remain undiagnosed, while others receive the label incorrectly. Proper diagnosis is complicated by the fact that the key symptoms such as wet cough, chronic rhinitis and recurrent upper and lower respiratory infection, are common and nonspecific. There is no single gold standard test to diagnose PCD. Presently, the diagnosis is made by augmenting the medical history and physical examination with in patients with a compatible medical history following a demanding combination of tests including nasal nitric oxide, high- speed video microscopy, transmission electron microscopy, genetics, and ciliary culture. These tests are costly and need sophisticated equipment and experienced staff, restricting use to highly specialised centers. Therefore, it would be desirable to have a screening test for identifying those patients who should undergo detailed diagnostic testing. Three recent studies focused on potential screening tools: one paper assessed the validity of nasal nitric oxide for screening, and two studies developed new symptom-based screening tools. These simple tools are welcome, and hopefully remind physicians whom to refer for definitive testing. However, they have been developed in tertiary care settings, where 10 to 50% of tested patients have PCD. Sensitivity and specificity of the tools are reasonable, but positive and negative predictive values may be poor in primary or secondary care settings. While these studies take an important step forward towards an earlier diagnosis of PCD, more remains to be done before we have tools tailored to different health care settings.

The role of reactive astrocytes in the resistance of melanoma brain metastasis to chemotherapy

Brain metastasis is resistant to chemotherapy while the leaky blood-brain-barrier in brain metastasis can not be the underlying reason. Metastatic tumor cells (“seed”) exploit the host microenvironment (“soil”) for survival advantages. Astrocytes which maintain the homeostasis of the brain microenvironment become reactive subsequent to brain damages and protect neurons from various injuries. We observed reactive astrocytes surrounding and infiltrating into brain metastasis in both clinical specimen and experimental animal model, thus raising a possibility that reactive astrocytes may protect tumor cells from cytotoxic chemotherapeutic drugs. ^ To test this hypothesis, we first generated an immortalized astrocyte cell line from H-2Kb-tsA58 mice. The immortal mouse astrocytes expressed specific markers including GFAP. Scanning electron microscopy demonstrated that astrocytes formed direct physical contact with tumor cells. Moreover, the expression of GFAP by astrocytes was up-regulated subsequent to co-culture with tumor cells, indicating that the co-culture of astrocytes and tumor cells may serve as a model to recapitulate the pathophysiological situation of brain metastasis. ^ In co-culture, astrocytes dramatically reduced apoptosis of tumor cells produced by various chemotherapeutic drugs. This protection effect was not because of culturing cells from different species since mouse fibroblasts did not protect tumor cells from chemotherapy. Furthermore, the protection by astrocytes was completely dependent on a physical contact. ^ Gap junctional communication (GJC) served as this physical contact. Tumor cells and astrocytes both expressed the major component of gap junctional channel—connexin 43 and formed functional GJC as evidenced by the “dye transfer” assay. The blockage of GJC between tumor cells and astrocytes by either specific chemical blocker carbenoxolone (CBX) or by genetically knocking down connexin 43 on astrocytes reversed the chemo-protection. ^ Calcium was the signal molecule transmitted through GJC that rescued tumor cells from chemotherapy. Accumulation of cytoplasmic calcium preceded the progress of apoptosis in tumor cells treated with chemotherapeutic drugs. Furthermore, chelation of accumulated cytoplasmic calcium inhibited the apoptosis of tumor cells treated with chemotherapeutic drugs. Most importantly, astrocytes could “shunt” the accumulated cytoplasmic calcium from tumor cells (treated with chemotherapeutic drug) through GJC. We also used gene expression micro-array to investigate global molecular consequence of tumor cells forming GJC with astrocytes. The data demonstrated that astrocytes (but not fibroblasts), through GJC, up-regulated the expressions of several well known survival genes in tumor cells. ^ In summary, this dissertation provides a novel mechanism underlying the resistance of brain metastasis to chemotherapy, which is due to protection by astrocytes through GJC. Interference with the GJC between astrocytes and tumor cells holds great promise in sensitizing brain metastasis to chemotherapy and improving the prognosis for patients with brain metastasis. ^

An exploratory study of screening practices and barriers for postpartum depression in Texas

Purpose. To evaluate the prevalence of Postpartum Depression (PPD) screening among practicing obstetrician-gynecologists in Texas, and to identify factors and barriers associated with routine depression screening practices.^ Subjects. One hundred and eighty-nine fellows and junior fellows of the Texas Association of Obstetricians & Gynecologists (District XI).^ Methods. A survey questionnaire was developed and sent to 2,028 obstetriciangynecologists, asking about their current screening practices related to PPD. The survey questions were related to the physician's demographics, the patient population, screening practices, barriers to screening, and perceptions about resources in the community. Responses were analyzed to determine associations between these factors and the physician's screening practices. ^ Results. The respondents (n=189) constituted 9.3% of the surveyed population, thus the findings cannot be considered representative of all practicing Ob-Gyns in Texas. However, the following trends were observed. Of the respondents, 85.4% reported routinely screening for PPD, while 14.6% did not. However, of those that screened, only 20.2% used the Edinburgh Postnatal Depression Scale and 7.6% screened with the Postpartum Depression Screening Scale, both validated screening tools. The majority (77.2%) reported using an informal patient interview to screen. For those who did not routinely screen, inadequate training and inadequate resources to screen for PPD were the top two barriers. Physician's age was associated with routine screening practice, as older physicians were less likely to screen routinely. Primary insurance coverage of the patient population was also associated with screening practice; physicians with Medicaid and uninsured patients were less likely to screen routinely. Lastly, physicians that believed that adequate resources existed in their communities for the treatment of PPD were more likely to screen than those that did not.^ Conclusions. The present study is the first attempt at assessing Postpartum Depression screening practices and barriers in Texas. Although the response rate was low, the findings related to informal screening methods and inadequate training indicated that education and training with regards to PPD screening and validated screening tools among Ob-Gyns stand to be improved. Connecting physicians to psychiatric resources may also improve screening rates. This first look at screening practices in Texas serves as a platform for future research in order to gain definitive insight into the diagnosis and treatment of PPD, and ultimately design interventions to improve detection rates and treatment.^

Intellectual disability: A quandary for immigration

Current immigration options for individuals with intellectual disabilities do not adequately address their special needs and under existing immigration laws, intellectually disabled adult dependents of United States citizens suffer an excessive burden. This problem causes undue hardship of persons whose families lawfully reside in the United States or have the opportunity to immigrate to the United States. The aim of this review is to examine materials relevant to the issue and answer the question: What are the barriers and pathways for adults with intellectual disability within the family-based preference system under United States immigration law? ^ Adults with intellectual disability are a vulnerable population that often relies upon family members to be their principle caregiver and provide financial support. Under the family-based preference system, the United States has maintained that the reunion of family members with their close relatives promotes the health and welfare of the United States, but a review of the number of findings of inadmissibility due to a mental/physical disorder with associated harmful behavior and the number of waivers granted show otherwise. The lack of reviewability of the decisions made by the Board of Immigration Appeals in addition to the lack of transparency surrounding the immigration process only serve to compound this problem. ^

The Role of the Arched Helicases in Exosome-Mediated Function

RNA processing and degradation are two important functions that control gene expression and promote RNA fidelity in the cell. A major ribonuclease complex, called the exosome, is involved in both of these processes. The exosome is composed of ten essential proteins with only one catalytically active subunit, called Rrp44. While the same ten essential subunits make up both the nuclear and cytoplasmic exosome, there are nuclear and cytoplasmic exosome cofactors that promote specific exosome functions in each of the cell compartments. To date, it is unclear how the exosome distinguishes between RNA substrates. We hypothesize that compartment specific cofactors may promote the substrate specificity of the exosome. In this work, I characterize several cofactors of the exosome, both nuclear and cytoplasmic. First, I describe the arch domain, which is a unique domain in a nuclear and a cytoplasmic cofactor of the exosome. Specifically, I show that the arch domain of the nuclear exosome cofactor, Mtr4, is required for specific exosome-mediated activities and overlaps functionally with the exosome-associated exonuclease, Rrp6. Further, I show that the arch domain of Ski2 is required for the degradation of normal and aberrant mRNAs. Additionally, this work describes in detail the Mtr4 domains involved in the physical association with other RNA processing proteins. Further, I characterize the minimal Mtr4-binding region in a third exosome cofactor, Trf5. Understanding how exosome cofactors synergistically promote exosome function will provide us a better understanding of how the exosome complex precisely regulates its catalytic activities. As described here, cofactors play a major role in determining the substrate specificity of the nuclear and cytoplasmic exosome. Moreover, specific accessory domains, which are not involved in the catalytic function of the cofactor, are required for substrate targeting of the eukaryotic RNA exosome.

The Shc adaptor protein and its role on Her -2 /neu oncogenesis

Shc proteins are implicated in coupling receptor tyrosine kinases to the mitogen-activated protein kinase (MAPK) pathway by recruiting Grb2/SOS to the plasma membrane. To better understand the role of Shc in oncogenesis brought about by point mutation activated neu (p185*), we transfected a Shc mutant (ShcΔCH1), which lacks the Grb2 binding site Y317 by deletion of collagen-homology domain 1, into p185*-transformed NIH3T3 cells. The cellular transformation phenotypes were found to be largely suppressed by expression of ShcΔCH1. This study indicates that Shc plays a critical role in mediating the oncogenical signals of p185*. Although ShcΔCH1 still retained another Grb2 binding site (Y239/240), we did not detect its physical association with Grb2. We also found that ShcΔCH1 could associate with p185*; however, this association did not interfere with the endogenous Shc-p185* interaction or the Shc-Grb2 interaction. In addition, p185*-mediated MAPK/Elk activation, PI3-K activation and Src activation likewise was not inhibited by ShcΔCH1 expression. Taken together, our current study clearly indicates that ShcΔCH1 suppresses the p185*-induced transformation, and that this suppression is mediated through a MAPK-independent and possibly PI3-K, Src-independent pathway. These results suggest that Shc may be involved in other unidentified signal pathways which are critical for p185*-induced cellular transformation besides the three pathways that we have studied. ^

Ice and snow measurements during Nathaniel B. Palmer cruise NBP0709 (SIMBA experiment)

The Sea Ice Mass Balance in the Antarctic (SIMBA) experiment was conducted from the RVIB N.B. Palmer in September and October 2007 in the Bellingshausen Sea in an area recently experiencing considerable changes in both climate and sea ice cover. Snow and ice properties were observed at 3 short-term stations and a 27-day drift station (Ice Station Belgica, ISB) during the winter-spring transition. Repeat measurements were performed on sea ice and snow cover at 5 ISB sites, each having different physical characteristics, with mean ice (snow) thicknesses varying from 0.6 m (0.1 m) to 2.3 m (0.7 m). Ice cores retrieved every five days from 2 sites and measured for physical, biological, and chemical properties. Three ice mass-balance buoys (IMBs) provided continuous records of snow and ice thickness and temperature. Meteorological conditions changed from warm fronts with high winds and precipitation followed by cold and calm periods through four cycles during ISB. The snow cover regulated temperature flux and controlled the physical regime in which sea ice morphology changed. Level thin ice areas had little snow accumulation and experienced greater thermal fluctuations resulting in brine salinity and volume changes, and winter maximum thermodynamic growth of ~0.6 m in this region. Flooding and snow-ice formation occurred during cold spells in ice and snow of intermediate thickness. In contrast, little snow-ice formed in flooded areas with thicker ice and snow cover, instead nearly isothermal, highly permeable ice persisted. In spring, short-lived cold air episodes did not effectively penetrate the sea ice nor overcome the effect of ocean heat flux, thus favoring net ice thinning from bottom melt over ice thickening from snow-ice growth, in all cases. These warm ice conditions were consistent with regional remote sensing observations of earlier ice breakup and a shorter sea ice season, more recently observed in the Bellingshausen Sea.

Estado, Justicia y Sociedad : la Administración de Justicia en la provincia de Buenos Aires, 1853-1881

Esta ponencia es la presentación del proyecto de tesis, que tiene por objetivo estudiar el proceso de constitución y consolidación del poder judicial, responsable de la administración de justicia, como integrante del Estado provincial, legitimador de su accionar político y mediador con la sociedad civil. La investigación se ubica en la provincia de Buenos Aires, entre 1853 y 1881, que sancionó su propia Constitución en 1854, en la que declaraba en su artículo 118 que el poder judicial sería independiente de todo otro en el ejercicio de sus funciones. Es decir que en esta provincia la consagración de la teoría de los poderes del Estado y la ley como definidora de lo que era justo, requirieron de la organización del poder judicial. El sistema judicial de la provincia de Buenos Aires comenzó su formación como poder del Estado a partir de la reforma rivadaviana y el proceso alcanzó su madurez entre 1853 y 1881, como parte fundamental del proyecto liberal, asentado sobre la autoridad de la ley. El poder judicial garantizaba la legitimidad del sistema político republicano de matriz liberal, pero la dependencia con el poder ejecutivo se mantuvo en parte, representada en el presupuesto, los nombramientos y los jurys. La organización judicial en formación incluyó al ámbito rural con una fisonomía institucional que tendía a consolidar la relación entre Estado y sociedad civil; ésta manifestaba sus necesidades a través de la opinión pública y el poder las interpretaba con el fin de legitimar su acción política. En este proceso de legitimación, el poder judicial era funcional al Estado, lo que se consolidó con el tiempo. La Constitución de 1873, a pesar de ser ideal en algunas de sus propuestas, dio protagonismo y efectividad a las instituciones judiciales que se formaron y pusieron en funcionamiento con una nueva concepción de justicia, que sin dejar de lado el derecho natural se consolidaba en una función más positiva, atenta a los derechos individuales y de propiedad. Para comprender el rol que jugó el sistema de justicia en la formación del Estado es necesario desenmarañar la compleja trama de relaciones entre el poder político y los magistrados, y a su vez entre ellos y la sociedad. Pero esto no se puede realizar sin conocer y comprender que entendían por justicia, y definir de qué forma organizaron su administración. En la realización de esta investigación atenderé a las soluciones que el ordenamiento jurídico debía brindar a una determinada sociedad, las instituciones que lo formaron y las ideas de quienes lo gestaron. El uso de la fuente judicial será fundamental para observar si la letra de la ley fue cumplida en la administración de justicia y de qué manera. Pero esa fuente judicial confirmará o no la aplicación de las leyes dictadas por el poder legislativo y los decretos emanados del ejecutivo, por ello será necesario reconstruir los organigramas del Poder Judicial a partir del estudio de los Registros Oficiales y los debates legislativos de la provincia.

Nordic Walking, modalidad terapéutica contra la fatiga relativa al cáncer

Existe evidencia de que el ejercicio físico puede mejorar los síntomas de los pacientes y supervivientes de cáncer y en especial la fatiga relativa al cáncer (FRC). El Nordic Walking (NW) es una novedosa forma de ejercicio físico que presenta ventajas fisiológicas y psicológicas significativas respecto de la marcha normal. Este artículo propone el NW como tratamiento terapéutico alternativo contra la FRC

Nordic Walking, modalidad terapéutica contra la fatiga relativa al cáncer

Existe evidencia de que el ejercicio físico puede mejorar los síntomas de los pacientes y supervivientes de cáncer y en especial la fatiga relativa al cáncer (FRC). El Nordic Walking (NW) es una novedosa forma de ejercicio físico que presenta ventajas fisiológicas y psicológicas significativas respecto de la marcha normal. Este artículo propone el NW como tratamiento terapéutico alternativo contra la FRC

Estado, Justicia y Sociedad : la Administración de Justicia en la provincia de Buenos Aires, 1853-1881

Esta ponencia es la presentación del proyecto de tesis, que tiene por objetivo estudiar el proceso de constitución y consolidación del poder judicial, responsable de la administración de justicia, como integrante del Estado provincial, legitimador de su accionar político y mediador con la sociedad civil. La investigación se ubica en la provincia de Buenos Aires, entre 1853 y 1881, que sancionó su propia Constitución en 1854, en la que declaraba en su artículo 118 que el poder judicial sería independiente de todo otro en el ejercicio de sus funciones. Es decir que en esta provincia la consagración de la teoría de los poderes del Estado y la ley como definidora de lo que era justo, requirieron de la organización del poder judicial. El sistema judicial de la provincia de Buenos Aires comenzó su formación como poder del Estado a partir de la reforma rivadaviana y el proceso alcanzó su madurez entre 1853 y 1881, como parte fundamental del proyecto liberal, asentado sobre la autoridad de la ley. El poder judicial garantizaba la legitimidad del sistema político republicano de matriz liberal, pero la dependencia con el poder ejecutivo se mantuvo en parte, representada en el presupuesto, los nombramientos y los jurys. La organización judicial en formación incluyó al ámbito rural con una fisonomía institucional que tendía a consolidar la relación entre Estado y sociedad civil; ésta manifestaba sus necesidades a través de la opinión pública y el poder las interpretaba con el fin de legitimar su acción política. En este proceso de legitimación, el poder judicial era funcional al Estado, lo que se consolidó con el tiempo. La Constitución de 1873, a pesar de ser ideal en algunas de sus propuestas, dio protagonismo y efectividad a las instituciones judiciales que se formaron y pusieron en funcionamiento con una nueva concepción de justicia, que sin dejar de lado el derecho natural se consolidaba en una función más positiva, atenta a los derechos individuales y de propiedad. Para comprender el rol que jugó el sistema de justicia en la formación del Estado es necesario desenmarañar la compleja trama de relaciones entre el poder político y los magistrados, y a su vez entre ellos y la sociedad. Pero esto no se puede realizar sin conocer y comprender que entendían por justicia, y definir de qué forma organizaron su administración. En la realización de esta investigación atenderé a las soluciones que el ordenamiento jurídico debía brindar a una determinada sociedad, las instituciones que lo formaron y las ideas de quienes lo gestaron. El uso de la fuente judicial será fundamental para observar si la letra de la ley fue cumplida en la administración de justicia y de qué manera. Pero esa fuente judicial confirmará o no la aplicación de las leyes dictadas por el poder legislativo y los decretos emanados del ejecutivo, por ello será necesario reconstruir los organigramas del Poder Judicial a partir del estudio de los Registros Oficiales y los debates legislativos de la provincia.

Estado, Justicia y Sociedad : la Administración de Justicia en la provincia de Buenos Aires, 1853-1881

Esta ponencia es la presentación del proyecto de tesis, que tiene por objetivo estudiar el proceso de constitución y consolidación del poder judicial, responsable de la administración de justicia, como integrante del Estado provincial, legitimador de su accionar político y mediador con la sociedad civil. La investigación se ubica en la provincia de Buenos Aires, entre 1853 y 1881, que sancionó su propia Constitución en 1854, en la que declaraba en su artículo 118 que el poder judicial sería independiente de todo otro en el ejercicio de sus funciones. Es decir que en esta provincia la consagración de la teoría de los poderes del Estado y la ley como definidora de lo que era justo, requirieron de la organización del poder judicial. El sistema judicial de la provincia de Buenos Aires comenzó su formación como poder del Estado a partir de la reforma rivadaviana y el proceso alcanzó su madurez entre 1853 y 1881, como parte fundamental del proyecto liberal, asentado sobre la autoridad de la ley. El poder judicial garantizaba la legitimidad del sistema político republicano de matriz liberal, pero la dependencia con el poder ejecutivo se mantuvo en parte, representada en el presupuesto, los nombramientos y los jurys. La organización judicial en formación incluyó al ámbito rural con una fisonomía institucional que tendía a consolidar la relación entre Estado y sociedad civil; ésta manifestaba sus necesidades a través de la opinión pública y el poder las interpretaba con el fin de legitimar su acción política. En este proceso de legitimación, el poder judicial era funcional al Estado, lo que se consolidó con el tiempo. La Constitución de 1873, a pesar de ser ideal en algunas de sus propuestas, dio protagonismo y efectividad a las instituciones judiciales que se formaron y pusieron en funcionamiento con una nueva concepción de justicia, que sin dejar de lado el derecho natural se consolidaba en una función más positiva, atenta a los derechos individuales y de propiedad. Para comprender el rol que jugó el sistema de justicia en la formación del Estado es necesario desenmarañar la compleja trama de relaciones entre el poder político y los magistrados, y a su vez entre ellos y la sociedad. Pero esto no se puede realizar sin conocer y comprender que entendían por justicia, y definir de qué forma organizaron su administración. En la realización de esta investigación atenderé a las soluciones que el ordenamiento jurídico debía brindar a una determinada sociedad, las instituciones que lo formaron y las ideas de quienes lo gestaron. El uso de la fuente judicial será fundamental para observar si la letra de la ley fue cumplida en la administración de justicia y de qué manera. Pero esa fuente judicial confirmará o no la aplicación de las leyes dictadas por el poder legislativo y los decretos emanados del ejecutivo, por ello será necesario reconstruir los organigramas del Poder Judicial a partir del estudio de los Registros Oficiales y los debates legislativos de la provincia.

Nordic Walking, modalidad terapéutica contra la fatiga relativa al cáncer

Existe evidencia de que el ejercicio físico puede mejorar los síntomas de los pacientes y supervivientes de cáncer y en especial la fatiga relativa al cáncer (FRC). El Nordic Walking (NW) es una novedosa forma de ejercicio físico que presenta ventajas fisiológicas y psicológicas significativas respecto de la marcha normal. Este artículo propone el NW como tratamiento terapéutico alternativo contra la FRC

Climate sensitivity across marine domains of life: limits to evolutionary adaptation shape species interactions, supplementary material

Organisms in all domains, Archaea, Bacteria, and Eukarya will respond to climate change with differential vulnerabilities resulting in shifts in species distribution, coexistence, and interactions. The identification of unifying principles of organism functioning across all domains would facilitate a cause and effect understanding of such changes and their implications for ecosystem shifts. For example, the functional specialization of all organisms in limited temperature ranges leads us to ask for unifying functional reasons. Organisms also specialize in either anoxic or various oxygen ranges, with animals and plants depending on high oxygen levels. Here, we identify thermal ranges, heat limits of growth, and critically low (hypoxic) oxygen concentrations as proxies of tolerance in a meta-analysis of data available for marine organisms, with special reference to domain-specific limits. For an explanation of the patterns and differences observed, we define and quantify a proxy for organismic complexity across species from all domains. Rising complexity causes heat (and hypoxia) tolerances to decrease from Archaea to Bacteria to uni- and then multicellular Eukarya. Within and across domains, taxon-specific tolerance limits likely reflect ultimate evolutionary limits of its species to acclimatization and adaptation. We hypothesize that rising taxon-specific complexities in structure and function constrain organisms to narrower environmental ranges. Low complexity as in Archaea and some Bacteria provide life options in extreme environments. In the warmest oceans, temperature maxima reach and will surpass the permanent limits to the existence of multicellular animals, plants and unicellular phytoplankter. Smaller, less complex unicellular Eukarya, Bacteria, and Archaea will thus benefit and predominate even more in a future, warmer, and hypoxic ocean.