Advance Care Planning Documentation at Mad River Family Practice

Advance care planning is a powerful tool that helps to guide clinicians and family members to make care decisions that align with a patients values when that patient is unable to speak for themselves. Advance care planning documents such as advance directives are the primary tool used to put these patient preferences in writing, but there is little information about the true rates of document completion in Vermont. This project was focused on determining how many patients at the Mad River Family Practice had advance care planning documents, developing a tracking tool in the electronic medical record to see trends in document completion among panel patients over time, and identify strategies to increase engagement in advance care planning at the practice.https://scholarworks.uvm.edu/fmclerk/1989/thumbnail.jp

Continuous desalting of refolding solution by ion exchange chromatography

Recombinant proteins expressed in E. coli as insoluble inclusion bodies need to be resolubilized and refolded to obtain its native structure. These steps require certain salts, which lead to buffers with elevated conductivity. When loading such a refolding solution on an ion exchange column for capturing only relatively low binding capacities can be achieved. In order to overcome this problem, an additional process step has to be introduced. The traditional approach is dilution, diafiltration or dialysis. Here we present a novel alternative process for salt removal of protein solutions. We applied anion and cation exchangers of a micro-pore type, where only salts can penetrate into the pores, but no proteins, in order to desalt the solution. The columns were connected together to run in a serial setup. In order to increase operation performance, a continuous process was developed comprising of four columns, two anion and two cation exchangers. Continuous mode was achieved by staggered cycling operation, where one set of columns was loaded while the other set was regenerated. Proof of concept using a scFv as model protein was performed. The refolding solution could be successfully deionized resulting in constantly low conductivity below 0.5 mS/cm. By running the process continuously process time could be reduced by 38.5% and at the same time productivity was increased to 163% compared to batch operation. Desalting of the protein solution resulted in 5-7 fold higher binding capacities in subsequent ion exchange capture step by conventional protein binding resins

Assessment of SNAP Utilization and Accessibility in Vermont

Food insecurity exemplifies one of the many public health crises that the COVID19 pandemic both exposed and amplified. In 2019 an estimated 10.5% of households (13.7 million households) were food insecure as determined by the US Department of Agriculture (USDA) including 5.3 million children. In 2020 this number increased to 15.6% of households, including 17.0 million children as projected by Feeding America. Food insecurity in children, especially in infancy, is associated with the development of obesity and hyperlipidemia, highlighting the necessity of federal and state food assistance programs. We believe that increased funding for SNAP incentive programs and wireless EBT devices for Farmers will result in a longitudinal and sustainable increase in produce consumption among low income individuals in VT. We hypothesize such changes will ultimately result in improved health outcomes and decreased burden on Vermont Medicaid systems.https://scholarworks.uvm.edu/comphp_gallery/1306/thumbnail.jp

Impact of Extrinsic and Intrinsic Hypoxia on Catecholamine Biosynthesis in Absence or Presence of Hif2α in Pheochromocytoma Cells

Pheochromocytomas and paragangliomas (PPGLs) with activated pseudohypoxic pathways are associated with an immature catecholamine phenotype and carry a higher risk for metastasis. For improved understanding of the underlying mechanisms we investigated the impact of hypoxia and pseudohypoxia on catecholamine biosynthesis in pheochromocytoma cells naturally lacking Hif2α (MPC and MTT) or expressing both Hif1α and Hif2α (PC12). Cultivation under extrinsic hypoxia or in spheroid culture (intrinsic hypoxia) increased cellular dopamine and norepinephrine contents in all cell lines. To distinguish further between Hif1α- and Hif2α-driven effects we expressed Hif2α in MTT and MPC-mCherry cells (naturally lacking Hif2α). Presence of Hif2α resulted in similarly increased cellular dopamine and norepinephrine under hypoxia as in the control cells. Furthermore, hypoxia resulted in enhanced phosphorylation of tyrosine hydroxylase (TH). A specific knockdown of Hif1α in PC12 diminished these effects. Pseudohypoxic conditions, simulated by expression of Hif2α under normoxia resulted in increased TH phosphorylation, further stimulated by extrinsic hypoxia. Correlations with PPGL tissue data led us to conclude that catecholamine biosynthesis under hypoxia is mainly mediated through increased phosphorylation of TH, regulated as a short-term response (24-48 h) by HIF1α. Continuous activation of hypoxia-related genes under pseudohypoxia leads to a HIF2α-mediated phosphorylation of TH (permanent status).Funding: This research was funded by the Deutsche Forschungsgemeinschaft (DFG) within the CRC/Transregio205/1 (project number: 314061271-TRR 205), Project No. B12 (N.B. and G.E.), Project No. B10 (S.R., J.P. and M.U.)and Project No. S01 (A.W., C.G. and M.P.) “The Adrenal: Central Relay in Health and Disease“, and by theParadi erence Foundation (N.B., I.P., S.R. and G.E.).S

Quantitative and time-resolved miRNA pattern of early human T cell activation

T cells are central to the immune response against various pathogens and cancer cells. Complex networks of transcriptional and post-transcriptional regulators, including microRNAs (miRNAs), coordinate the T cell activation process. Available miRNA datasets, however, do not sufficiently dissolve the dynamic changes of miRNA controlled networks upon T cell activation. Here, we established a quantitative and time-resolved expression pattern for the entire miRNome over a period of 24 h upon human Tcell activation. Based on our time-resolved datasets, we identified central miRNAs and specified common miRNA expression profiles. We found the most prominent quantitative expression changes for miR155-5p with a range from initially 40 molecules/cell to 1600 molecules/cell upon T-cell activation. We established a comprehensive dynamic regulatory network of both the up- and downstream regulation of miR155. Upstream, we highlight IRF4 and its complexes with SPI1 and BATF as central for the transcriptional regulation of miR-155. Downstream of miR-155-5p, we verified 17 of its target genes by the time-resolved data recorded after T cell activation. Our data provide comprehensive insights into the range of stimulus induced miRNA abundance changes and lay the ground to identify efficient points of intervention for modifying the T cell response

Chemoradiotherapy-induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse

Cervical cancer therapy is still a major clinical challenge, as patients substantially differ in their response to standard treatments, including chemoradiotherapy (CRT). During cervical carcinogenesis, T-helper (Th)-17 cells accumulate in the peripheral blood and tumor tissues of cancer patients and are associated with poor prognosis. In this prospective study, we find increased Th17 frequencies in the blood of patients after chemoradiotherapy and a post-therapeutic ratio of Th17/CD4+ T cells > 8% was associated with early recurrence. Furthermore, Th17 cells promote resistance of cervical cancer cells toward CRT, which was dependent on the AKT signaling pathway. Consistently, patients with high Th17 frequencies in pretherapeutic biopsies exhibit lower response to primary CRT. This work reveals a key role of Th17 cells in CRT resistance and elevated Th17 frequencies in the blood after CRT correspond with early recurrence. Our results may help to explain individual treatment responses of cervical cancer patients and suggest evaluation of Th17 cells as a novel predictive biomarker for chemoradiotherapy responses and as a potential target for immunotherapy in cervical cancer

Eine tugendethische Perspektive auf unsere Mensch-Tier-Beziehung

Eine gute Mensch-Tier-Beziehung trägt einerseits zum glücklichen Leben der Menschen bei, andererseits wird dadurch Tierleid vermieden. In der aristotelischen Tugendethik ist das höchste Strebensziel das glückliche Leben und alle Handlungen werden danach ausgerichtet. Obwohl es zwischen Mensch und Tier gewisse Merkmals-unterschiede gibt, wie etwa die Sprache, gelten beide, in einem holistischen Sinne einer Gesamtheit alles Seienden, als gleichermaßen zoa (Lebewesen). Es liegt in der menschlichen Natur, dass wir nach dem Glück streben und das Unglück vermeiden. Tugenden führen zu unserem Glück und eine gute Mensch-Tier-Beziehung kann den Tugenderwerb fördern. Dagegen begünstigt eine schlechte Beziehung den Erwerb von Anti-Tugenden, die uns unglücklich machen. Tugenden sind Haltungen, die erworben werden, indem die moralisch richtige Handlungsweise in einer bestimmten Situation ausgeübt wird. Freundschaft trägt zum glücklichen Leben bei und diese ist auch zwischen Menschen und Hunden möglich. Es gibt verschiedene Freundschaftsformen. Als die höchste gilt die vollkommene Freundschaft. Sie findet zwischen zwei tugendhaften Personen statt. Der Tugenderwerb erfordert eine hohe kognitive und moralische Leistungsfähigkeit. Wir können nicht in den Hund hinein blicken, daher wissen wir nicht, ob Hunde in der Lage sind Tugenden zu erwerben, aber dies wäre die Voraussetzung für eine vollkommene Freundschaft. Trotzdem zählt der Hund zu unserer Familie und trägt zu unserem Glück bei.On the one hand, a good human-animal-relationship can lead to a happy human life, on the other hand it helps to avoid animal suffering. In Aristotles virtue ethics, the highest aim is a happy life and all actions are aligned with it. Although there are differences in attributes between human beings and animals, such as language, both are considered in a holistic sense of the entirety of all beings equally as zoa (living beings). It lies in the human nature that we strive for happiness and try to avoid unhappiness. Virtual behaviour leads to our happiness and good human-animal-relations can promote virtues. In contrast a bad relationship can cause the acquisition of anti-virtues which make us unhappy. Virtues are dispositions acquired by exercising the morally correct action in a particular case. Friendship contributes to the happy life and is also possible between humans and dogs. There are different forms of friendship; the highest form of friendship takes place between two virtuous persons. The acquisition of virtue requires a high cognitive and moral capacity. We cant read a dogs mind, so we do not know, if dogs are able to acquire virtues, but that is the precondition for a virtuous friendship. Nevertheless, the dog is a family member and contributes to our happiness.vorgelegt von Nicole WalchZusammenfassungen in Deutsch und EnglischAbweichender Titel laut Übersetzung des Verfassers/der VerfasserinKarl-Franzens-Universität Graz, Diplomarbeit, 2018(VLID)258173