Control of human cytomegalovirus replication by liver resident natural killer cells

Natural killer cells are considered to be important for control of human cytomegalovirus– a major pathogen in immune suppressed transplant patients. Viral infection promotes the development of an adaptive phenotype in circulating natural killer cells that changes their anti-viral function. In contrast, less is understood how natural killer cells that reside in tissue respond to viral infection. Here we show natural killer cells resident in the liver have an altered phenotype in cytomegalovirus infected individuals and display increased anti-viral activity against multiple viruses in vitro and identify and characterise a subset of natural killer cells responsible for control. Crucially, livers containing natural killer cells with better capacity to control cytomegalovirus replication in vitro are less likely to experience viraemia post-transplant. Taken together, these data suggest that virally induced expansion of tissue resident natural killer cells in the donor organ can reduce the chance of viraemia post-transplant

Ex Vivo Perfusion of Porcine Pancreas and Liver Sourced from Commercial Abattoirs after Circulatory Death as a Research Resource: A Methodological Study

Background: Machine perfusion (MP) is increasingly used for human transplant organ preservation. The use of MP for research purposes is another opportunity for this technology. The porcine pancreas and liver are similar in anatomical size and function to their human counterparts, making them an excellent resource for research, but they have some important differences from human organs which can influence their research use. In this paper, we describe a technique developed and tested for the retrieval of porcine organs for use in research on perfused viable organs. Methods: Whole-organ porcine pancreata and livers were harvested at a commercial abattoir, following standard slaughterhouse processes. The standard slaughterhouse process involved a thoracotomy and mid-line laparotomy, and all the thoracoabdominal organs were removed. The pancreas, fixed in the retroperitoneum, was carefully dissected from its attachments to the surrounding structures, and tissue planes between the pancreas, spleen, duodenum, and colon were meticulously identified and dissected. Vessel exposure and division: The aorta, portal vein (PV), hepatic vein (HV), and hepatic artery (HA) were dissected and isolated, preserving the input and output channels for the liver and pancreas. A distal 3 cm of the aorta was preserved and divided and served as the input for the pancreas perfusions. The liver, PV, HV, and HA were preserved and divided to preserve the physiological channels of the input (PV and HA) and output (HV) for the liver perfusions. The porcine hepatic and pancreas anatomy shares significant resemblance with the gross anatomy found in humans, and this was taken into consideration when designing the perfusion circuitry. The porcine pancreas and spleen shared a common blood supply, with branches arising from the splenic artery. The organs were flushed with cold, heparinised normal saline and transported in a temperature-regulated receptacle maintained at a core temperature between 4 and 8 °C, in line with the standards of static cold storage (SCS), to a dedicated perfusion lab and perfused using our novel perfusion machine with autologous, heparinised porcine blood, also collected at the abattoir

Whole-Sample Mapping of Cancerous and Benign Tissue Properties

Structural and mechanical differences between cancerous and healthy tissue give rise to variations in macroscopic properties such as visual appearance and elastic modulus that show promise as signatures for early cancer detection. Atomic force microscopy (AFM) has been used to measure significant differences in stiffness between cancerous and healthy cells owing to its high force sensitivity and spatial resolution, however due to absorption and scattering of light, it is often challenging to accurately locate where AFM measurements have been made on a bulk tissue sample. In this paper we describe an image registration method that localizes AFM elastic stiffness measurements with high-resolution images of haematoxylin and eosin (H\&E)-stained tissue to within 1.5 microns. Color RGB images are segmented into three structure types (lumen, cells and stroma) by a neural network classifier trained on ground-truth pixel data obtained through k-means clustering in HSV color space. Using the localized stiffness maps and corresponding structural information, a whole-sample stiffness map is generated with a region matching and interpolation algorithm that associates similar structures with measured stiffness values. We present results showing significant differences in stiffness between healthy and cancerous liver tissue and discuss potential applications of this technique.Comment: Accepted at MICCAI201

IL-2(high) tissue-resident T cells in the human liver: Sentinels for hepatotropic infection

The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+)). These tissue-resident memory T cells (TRM) are preferentially expanded in patients with partial immune control of HBV infection and can remain in the liver after the resolution of infection, including compartmentalized responses against epitopes within all major HBV proteins. Sequential IL-15 or antigen exposure followed by TGFβ induces liver-adapted TRM, including their signature high expression of exhaustion markers PD-1 and CD39. We suggest that these inhibitory molecules, together with paradoxically robust, rapid, cell-autonomous IL-2 and IFNγ production, equip liver CD8 TRM to survive while exerting local noncytolytic hepatic immunosurveillance

A comparison of early reading outcomes and program costs in four primary reading programs for improved decision-making

xiii, 189 p. A print copy of this title is available through the UO Libraries under the call numbers: KNIGHT LB1573 .G238 2007This study uses cost-effectiveness tools to support school site decision-makers. It looks at four reading protocols for first and second graders using common outcomes of early reading proficiency. Similar outcome measures are a requirement of cost-effectiveness analysis but are a common shortcoming of program evaluations as presented in the literature. The comparison of Success For All, a Reading First protocol, and two locally designed instructional protocols gives the reader an opportunity to review the reading alternatives. The review is undertaken to highlight program costs ranging from difficult to discern indirect costs to readily accessible budget expenditures. The qualities of good reading programs are characterized and the essential elements of cost-effectiveness tools delineated before applying their theoretical principles to four schools in a large Northwest city.Adviser: Gerald Tinda

sj-docx-1-fac-10.1177_27325016231217153 – Supplemental material for Nerve Blocks Utilized in The Face: A Comprehensive Review

Supplemental material, sj-docx-1-fac-10.1177_27325016231217153 for Nerve Blocks Utilized in The Face: A Comprehensive Review by Joshua Kohan, Armin Edalatpour, Allison J. Seitz, Daniel Y. Cho and Brian H. Gander in FACE</p

sj-jpg-3-fac-10.1177_27325016231217153 – Supplemental material for Nerve Blocks Utilized in The Face: A Comprehensive Review

Supplemental material, sj-jpg-3-fac-10.1177_27325016231217153 for Nerve Blocks Utilized in The Face: A Comprehensive Review by Joshua Kohan, Armin Edalatpour, Allison J. Seitz, Daniel Y. Cho and Brian H. Gander in FACE</p

sj-docx-2-fac-10.1177_27325016231217153 – Supplemental material for Nerve Blocks Utilized in The Face: A Comprehensive Review

Supplemental material, sj-docx-2-fac-10.1177_27325016231217153 for Nerve Blocks Utilized in The Face: A Comprehensive Review by Joshua Kohan, Armin Edalatpour, Allison J. Seitz, Daniel Y. Cho and Brian H. Gander in FACE</p