Effect of Exercise Training on Circulating Cancer-Associated Immune Cells in Breast Cancer Patients

Breast cancer (BC) is one of the leading causes of cancer deaths among females. It is well known that the presence of a tumor decreases robust anticancer immunity via immune-modulation and enhanced immunosuppression through a process called cancer immunoediting. However, it has yet to be determined if exercise-based rehabilitation can elevate the peripheral anticancer immune profile and reduce myeloid-derived suppressor cell (MDSC) mediated immunosuppression. Purpose: To assess the effects of a 12-week prescribed, individualized, supervised exercise-based rehabilitation program on selected circulating immune cells in BC patients at the University of Northern Colorado Cancer Rehabilitation Institute. Methods: 16 female BC patients currently undergoing treatment were divided into a control group (CON, n=7), engaging in normal activities of daily living, and an exercise group (EX, n=9) that participated in 12-weeks of personalized combined aerobic and resistance training three times a week. Venous blood was collected before and after the intervention period and circulating immune cells will be analyzed for frequency and function using flow cytometry. Results: Early (E-) MDSC levels were significantly lower after the exercise intervention compared to the CON group (CON: 18.2±14.5% vs. EX: 5.3±3.6%, p\u3c0.05). Monocytic (M-) MDSC showed a non-significant change of +48% in the CON group at POST (CON: PRE: 4.5±5.1% vs. POST: iv 6.8±4.5%), while POST M-MDSC levels displayed a non-significant change of -40% in the EX group (EX: PRE 4.9±2.6% vs. POST: 2.9±1.7%). An alternative MDSC phenotype analysis revealed that exercise significantly decreased M-MDSC from PRE to POST in the EX group (0.15±0.13% vs. 0.05± 0.03%, p\u3c0.05), but not in the CON group (0.10±0.11% vs. 0.06±0.05%). There was no effect of exercise on MDSC suppressive activity or type I interferon receptor (IFNAR1) protein expression. The EX group displayed significantly higher levels of circulating Natural Killer (NK) cell frequencies than CON at the POST timepoint (3.5± 6.5 vs. 1.5±3.0 % of CD3- cells, p\u3c0.05), where NK cell level changes were -75% for CON vs. +2% for EX from PRE to POST. There was a significant reduction in CD8+ cytotoxic T lymphocyte (CTLs) and CD4+ T helper (Th) cell frequencies in the EX group when comparing PRE to POST (CTLs: 23.6±10.8 vs. 16.1±10.1 % of CD3+ cells; Th: 41.3±24.3 vs. 27.5±21.1 % of CD3+ cells, p\u3c0.05) Exercise showed no effect on Nur77+ activation status of the these lymphocytes, although percentage changes were +248% vs. -41% and +206% vs. -7% for CTLs and Th cell positive frequency for Nur77, respectively, for CON vs. EX from PRE to POST. Exercise caused a greater increase in Granzyme B (GZB)+ CTLs (+6%) when compared to the control group (+0.5%), and there was a greater yet non-significant percentage change of perforin expressing CTLs and NK cells in the CON group (-16 to -19%) compared to the exercising subjects (-0.5 to -5%). Discussion: Immune modulation remains a major target of interest to fight cancer using novel pharmaceutical and lifestyle interventions such as exercise. This dissertation study suggests that exercise may not be able to fully normalize but rather maintain certain peripheral immune cell frequencies and characteristics, offset the expansion of immunosuppressive cells, and potentially lower systemic inflammation levels. In conclusion, 12-weeks of exercise-based rehabilitation may positively alter some circulating immune cells and at least partially normalize the peripheral anticancer immune profile in BC patients undergoing treatment

Focused multidimensional scaling : interactive visualization for exploration of high-dimensional data

BackgroundVisualization is an important tool for generating meaning from scientific data, but the visualization of structures in high-dimensional data (such as from high-throughput assays) presents unique challenges. Dimension reduction methods are key in solving this challenge, but these methods can be misleading- especially when apparent clustering in the dimension-reducing representation is used as the basis for reasoning about relationships within the data.ResultsWe present two interactive visualization tools, distnet and focusedMDS, that help in assessing the validity of a dimension-reducing plot and in interactively exploring relationships between objects in the data. The distnet tool is used to examine discrepancies between the placement of points in a two dimensional visualization and the points' actual similarities in feature space. The focusedMDS tool is an intuitive, interactive multidimensional scaling tool that is useful for exploring the relationships of one particular data point to the others, that might be useful in a personalized medicine framework.ConclusionsWe introduce here two freely available tools for visually exploring and verifying the validity of dimension-reducing visualizations and biological information gained from these. The use of such tools can confirm that conclusions drawn from dimension-reducing visualizations are not simply artifacts of the visualization method, but are real biological insights.Peer reviewe

Conceptualization of an Anthropomorphic Replacement Hand with a Sensory Feedback System

In this paper, a concept for an anthropomorphic replacement hand cast with silicone with an integrated sensory feedback system is presented. In order to construct the personalized replacement hand, a 3D scan of a healthy hand was used to create a 3D-printed mold using computer-aided design (CAD). To allow for movement of the index and middle fingers, a motorized orthosis was used. Information about the applied force for grasping and the degree of flexion of the fingers is registered using two pressure sensors and one bending sensor in each movable finger. To integrate the sensors and additional cavities for increased flexibility, the fingers were cast in three parts, separately from the rest of the hand. A silicone adhesive (Silpuran 4200) was examined to combine the individual parts afterwards. For this, tests with different geometries were carried out. Furthermore, different test series for the secure integration of the sensors were performed, including measurements of the registered information of the sensors. Based on these findings, skin-toned individual fingers and a replacement hand with integrated sensors were created. Using Silpuran 4200, it was possible to integrate the needed cavities and to place the sensors securely into the hand while retaining full flexion using a motorized orthosis. The measurements during different loadings and while grasping various objects proved that it is possible to realize such a sensory feedback system in a replacement hand. As a result, it can be stated that the cost-effective realization of a personalized, anthropomorphic replacement hand with an integrated sensory feedback system is possible using 3D scanning and 3D printing. By integrating smaller sensors, the risk of damaging the sensors through movement could be decreased

„Und es geht nicht nur um den festlichen Abend – sondern ums Grundsätzliche“: Klassische Komponistinnen und Komponisten in den Kibbuzim der 1940er bis 1980er Jahre

Wenn von Musikern in Erez Israel, der hebräischen Eigenbezeichnung für das Palästina der Mandatszeit, die Rede ist, so sind meist die vielen gut ausgebildeten Musikerinnen und Musiker aus Mitteleuropa in Tel Aviv und Jerusalem gemeint, die in den 1930er Jahren sowohl das städtische Musikleben aktiv gestalteten als auch Teil eines anspruchsvollen Publikums wurden. Kaum bekannt ist, dass einige Musiker freiwillig aufs Land in Gemeinschaftssiedlungen zogen und dort mithilfe vieler – auch musikalisch nicht vorgebildeter - Akteurinnen und Akteure ein vielfältiges Musikleben in ihren eigenen Kibbuzim, der Region und der ganzen Kibbuzbewegung schufen. Unter den Musikakteurinnen und -akteuren in Kibbuzim gab es auch solche, die klassische Musik komponierten. Dabei handelte es sich überwiegend um Personen, die in den 1920er Jahren in Mitteleuropa geboren wurden und insbesondere nach 1948 aktiv waren. Diese Komponisten, darunter auch eine Komponistin, gründeten und unterhielten regionale sowie auch überregionale Chöre und Orchester. Neben der Ensembleleitung erfüllten die Komponisten eine wichtige Funktion im Kibbuzbildungssystem etwa durch den Auf- und Ausbau des Fachbereichs Musik an Oberschulen. Eine weitere musikpädagogische Aufgabe in Kibbuzim war das Erteilen von individuellem Instrumentalunterricht. Neben den musikpädagogischen Tätigkeiten konnten sich einige Musiker im Kibbuz tatsächlich als Komponisten betätigen, und zwar im Rahmen der Chagim, der kibbuzeigenen Feiertage. Außerdem gelang es Kibbuzkomponisten eigene Werke von Chören und Orchestern aufführen zu lassen, allerdings war dies keine Selbstverständlichkeit und musste immer wieder – auch mithilfe eines Interessensverbands - dem Verband der Kibbuzkomponisten- erkämpft werden. Eine besondere Möglichkeit ergab sich einzig für Theodor Holdheim, dem es gelang eine Kibbuzoper zu komponieren und zur Aufführung zu bringen. Für einige Komponisten ergab sich die Möglichkeit außerhalb von Israel tätig zu werden, etwa zu Fortbildungszwecken zu reisen oder bei Aufführung oder Aufnahme ihrer Werke mitzuwirken. Außerdem gelang es einigen Komponisten einzelne Werke im Ausland im Konzert oder Radio aufführen zu lassen, ohne, dass die Komponisten dorthin mitreisten.When referring to musicians in Erez Israel, the Hebrew term for Mandate-era Palestine, we usually mean the many well-educated musicians from Central Europe in Tel Aviv and Jerusalem who, in the 1930s, both actively shaped urban musical life and also became part of a sophisticated audience. It is hardly known that some musicians voluntarily moved to the countryside to communal settlements and created a diverse musical life in their own kibbutzim, the region and the entire kibbutz movement with the help of many - also musically untrained - protagonists. Among the musical protagonists in the kibbutzim there were also some who composed classical music. These were mostly people who were born in Central Europe in the 1920s and were especially active after 1948. These composers, including one female composer, founded and maintained regional as well as national choirs and orchestras. In addition to leading ensembles, the composers fulfilled an important function in the kibbutz education system, for example by establishing and expanding the music departments in high schools. Another music educational task in kibbutzim was the teaching of individual instrumental lessons. In addition to music educational activities, some musicians on the kibbutz were actually able to work as composers, contributing to the chagim, the kibbutz's own holidays. In addition, with the help of their interest group, the Association of Kibbutz Composers, they succeeded in having their own works performed by choirs and orchestras, although this was by no means a matter of course and had to be fought for again and again. Only Theodor Holdheim had the unique opportunity to compose and stage a kibbutz opera. Some kibbutz composers had the opportunity to work outside of Israel, for example, to travel for educational purposes or to participate in the performance or recording of their works. In addition, some composers succeeded in having individual works performed abroad in concerts or on the radio, without the composers traveling there themselves

Torf und Torfersatzprodukte im Vergleich : Eigenschaften, Verfügbarkeit, ökologische Nachhaltigkeit und soziale Auswirkungen

Im Auftrag der Branchenverbände JardinSuisse Unternehmerverband Gärtner Schweiz und VSGP Verband Schweizer Gemüseproduzenten als Träger der Stiftung GartenbauDer Abbau von Torf ist mit relevanten Treibhausgasmissionen verbunden und führt zur Zerstörung sensibler Ökosysteme. Aus diesem Grund bestehen in den Garten- und Gemüsebau-Branchen Bestrebungen, den Torfverbrauch zu reduzieren. Der Verzicht auf Torf bedingt die Verfügbarkeit von alternativen Substraten, welche den pflanzenbaulichen Anforderungen genügen. Gleichzeitig sollen die Alternativsubstrate auch tatsächlich zu einer Reduktion – und nicht zu einer Verlagerung – der Umweltbelastung führen. Um die Umweltwirkungen von Torf und Torfalternativprodukten umfassend zu beurteilen, werden in dieser Studie Ökobilanzen für zehn Substratkomponenten und sieben beispielhafte Substratmischungen erstellt. Zusätzlich zu den Umweltauswirkungen werden für die einzelnen Substratkomponenten die pflanzenbaulichen Eigenschaften, die zukünftige Verfügbarkeit sowie die sozialen Auswirkungen der Produktion beurteilt. Von den untersuchten Substratkomponenten zeichnen sich insbesondere Landerde, Rindenkompost, TEFA-Maisfasern, Holzfasern und Holzhäcksel sowohl durch geringe Umweltauswirkungen als auch durch eine positive Beurteilung der sozialen Aspekte und der zukünftigen Verfügbarkeit aus. Die Gewinnung und Nutzung von Torf sind mit hohen Treibhausgasemissionen verbunden (siehe Bild). Der grösste Teil dieser Emissionen entsteht dabei nicht während des Abbaus und des Transports in die Schweiz, sondern wenn die organische Substanz im Torf während und nach der Nutzung im Gartenbau zersetzt wird. Deshalb gilt auch für Substratmischungen: je weniger Torf, desto ökologischer. Mischungen aus lokalen Substratkomponenten stellen somit die Basis für eine nachhaltige Entwicklung im Gartenbau dar

Similar Risks – Different Results

Analyzing the Inconsistent Application of the Precautionary Principle in European GMO Authorizatio

Mechanisms of toxicity mediated by neutrophil and eosinophil granule proteins.

Neutrophils and eosinophils are granulocytes which are characterized by the presence of granules in the cytoplasm. Granules provide a safe storage site for granule proteins that play important roles in the immune function of granulocytes. Upon granulocytes activation, diverse proteins are released from the granules into the extracellular space and contribute to the fight against infections. In this article, we describe granule proteins of both neutrophils and eosinophils able to kill pathogens and review their anticipated mechanism of antimicrobial toxicity. It should be noted that an excess of granules protein release can lead to tissue damage of the host resulting in chronic inflammation and organ dysfunction