Grafting Technologies for Use in Liver Cell Therapies of Human Hepatic Stem Cells

While the healthy liver is capable of rapidly regenerating after acute injury, patients with severe liver disease can undergo acute liver failure. The only widely used treatment for severe damage and failure is liver transplantation, but the paucity of available donor organs and the overwhelming number of patients waiting for transplants prompts a need for the development of alternative therapeutic strategies. Current therapies primarily introduce mature donor cells into hosts via cell suspension delivered through a vascular route; this results in inefficient engraftment, the engraftment of cells at ectopic sites, and can lead to complications with emboli formation and the need for immunosuppression. Sourcing of the cells to be transplanted is difficult, due mostly to the scarcity of available normal human tissue, in addition to poor cryopreservation methods, forcing one to obtain and utilize freshly isolated cells whenever available. Key problems associated with liver regeneration can be solved using tissue engineering themes which take advantage of the proliferative capacity of the stem cell population, along with its associated matrix. These strategies have been applied to three key facets needed for clinical programs in liver cell therapies: cryopreservation, 3-dimensional (3-D) cultures, and grafting technologies for transplantation of the cells. The optimization of cryopreservation methods for stem cell banking was first achieved through the use of hyaluronan (HA) hydrogels. Isotonic medium supplemented with small amounts of HA (0.05 or 0.10%) improved cell attachment and colony formation due at least in part to increased expression of key cell adhesion factors in the stem and progenitor cell populations. The culturing and expansion of hHpSCs in an ex vivo three-dimensional (3-D) environment was achieved using hyaluronan hydrogels mixed with other matrix components found in the liver's stem cell niche, in combination with a tailored serum-free medium. Cell aggregates formed within the HA hydrogels, remained viable, and demonstrated a stable stem cell phenotype after weeks of culture. Finally, culturing conditions were utilized in vivo to improve methods of cell transplantation through the incorporation of grafting strategies after hepatic injury. These strategies were compared with current methods for transplantation of liver cells, which resulted in scattered aggregates within the liver and loss of significant numbers of cells to other locations. By contrast, grafting strategies provided a suitable scaffold which allowed all transplanted cells to remain within the liver and dramatically improved engraftment and expansion without evidence of emboli formation. The techniques developed here have improved current alternative methods available for the treatment of liver failure and are preclinical, but are expected to rapidly translate to therapeutic uses

Giardia lamblia Reactive Arthritis Mimicking Acute Periprosthetic Knee Infection: A Case Report

Background: The difficulty in diagnosing Periprosthetic joint infection (PJI) is exacerbated by the more varied presentation of PJI and the lower synovial fluid WBC count thresholds applied when a prosthesis is present. Multiple reports have described pseudosepsis after total knee arthroplasty (TKA) due to gout or pseudogout. Further confusing the picture, periprosthetic infection also frequently coexists with crystalline arthropathy. Our review of the literature revealed no reports describing reactive arthritis (ReA) mimicking acute infection in the setting of previous TKA. In this case report, we describe a pseudo-periprosthetic infection of a well-functioning TKA secondary to ReA in the setting of Giardia lamblia gastroenteritis. Case: A healthy 49-year-old man with a well-functioning total knee replacement developed a painful swollen knee. The erythrocyte sedimentation rate was 12 mm/hour, and C-reactive protein was 20.3 mg/L. Aspiration revealed 24,440 white blood cells and 5% neutrophils. His 2018 International Consensus Meeting (ICM) definition score of 5 met criteria for “possibly infected.” He was diagnosed with ReA secondary to Giardia lamblia, mimicking acute periprosthetic infection. He was successfully treated with a 10-week course of multiple oral antiparasitic medications. Conclusion: Systemic parasitic infectious ReA can mimic acute infection in the presence of total knee arthroplasty. Careful application of the 2018 ICM criteria can be critical for workup and the treatment of suspected periprosthetic infection

Non-Syndromic Multi Focal Non-Ossifying Fibroma: A Diagnostic Challenge of Giant-Cell Rich Lesions

Background: Diagnosing GCL can be extremely difficult due to the rarity of these lesions. Histologically many benign GCL mimic each other and can further be mistaken for a malignant GCL. Additionally confusing the diagnosis, many benign GCL have significant morphological overlap. However, it is of utmost importance to arrive at an accurate diagnosis as treatment varies significantly based on the pathology. Our patient presentation highlights that differentiating GCLs can be a diagnostic challenge as illustrated. Our review of the literature found scarce reports of multifocal non-ossifying fibroma. In this case report, we describe a non-syndromic multifocal non-ossifying fibroma successfully treated with biopsy curettage and grafting. This patient was informed that her case would be submitted for publication and she agreed. Case: A 14 year-old-girl complained of left knee pain for 3 months and radiographic imaging showed a destructive bone lesion at her distal femoral metaphysis, the tibial tubercle, and proximal fibula. The patient had no history of trauma and reported no infectious, inflammatory, or syndromic symptoms. Core biopsy of the left thigh lesion showed findings most consistent with giant cell tumor. Bone scintigraphy revealed new lesions at the distal femur and proximal tibia on the contralateral (right) side. Patient was treated with biopsy curettage and grafting. Intra-operative frozen section permanent reads showed giant-cell rich non-ossifying fibroma. Due to discrepancy in core biopsy and intra-operative biopsy a independent pathology consult was requested on surgical specimens. Histologically, the differential diagnosis included non-ossifying fibroma, giant cell tumor of bone, and ossifying fibroma. Radiographic imaging combined with histology gave a final pathological diagnosis most consistent with non-ossifying fibroma. Conclusion: Differentiating non-syndromic multifocal non-ossifying fibroma from other giant cell rich lesions can be a diagnostic challenge. A combined approach using histology, clinical presentation, and radiology is imperative in reaching the correct diagnosis

Recurrent Hemarthrosis Secondary to Erosive Patellofemoral Arthritis Treated with Arthroplasty: A Report of 3 Cases

Background: Spontaneous hemarthrosis of the knee joint in the elderly population is a rare phenomenon and is mostly seen in those with osteoarthritis. The identified causes of spontaneous hemarthrosis in this demographic include subchondral bone bleeding, meniscal tear, genicular artery bleeding, and the use of anticoagulants. Hemarthrosis caused by isolated patellofemoral bleeding, as in this case series, has been rarely documented and poorly described. Case: Three patients presented with recurrent hemarthrosis secondary to erosive patellofemoral arthritis. Recurrent hemarthrosis from the eroded patellofemoral subchondral bone has not been well described. Each patient presented with symptoms secondary to painful effusions that were identified by aspiration. Each patient was successfully treated with patellofemoral or total knee arthroplasty Conclusion: Spontaneous or recurrent effusions in the setting of erosivepatellofemoral arthritis should prompt orthopaedic surgeons to consider hemarthrosis as the cause of such effusions. Patellofemoral or total knee arthroplasty is effective in resolving the hemarthroses, resolving pain, and restoring function in these patients

\u27\u27When we speak faculty listen:\u27\u27 Exploring potential spaces for students to support lecturer academic development

Lecturers’ engagement in professional development activities to enhance their academic practice is firmly embedded within the landscape of higher education. Although enhancing the student learning experience underpins teaching-related continuing professional development (CPD), interestingly the role of students in supporting such activities has been underexplored. Drawing on data captured from eight student representatives interviewed in the context of an international impact evaluation, we examine student awareness of, and attitudes towards, lecturers’ CPD. Participants recognised the value of lecturers engaging in CPD but believed it to be an activity they were removed from, and had little opportunity to engage with. We consider how this perspective could be changed in two ways. Firstly, we reflect on the experiences of students at one university where their contributions to lecturers’ development were legitimised and valued. Secondly, we discuss the potential of integrative approaches, such as students as consultants or reverse mentoring. We argue that these approaches may challenge existing hierarchies that limit students engaging in lectures and create spaces through which students can positively contribute to lecturers’ CPD

Hepatic transcriptomic profiles from barramundi, Lates calcarifer, as a means of assessing organism health and identifying stressors in rivers in northern Queensland

Resource managers need to differentiate between sites with and without contaminants and those where contaminants cause impacts. Potentially, transcriptomes could be used to evaluate sites where contaminant-induced effects may occur, to identify causative stressors of effects and potential adverse outcomes. To test this hypothesis, the hepatic transcriptomes in Barramundi, a perciforme teleost fish, (Lates calcarifer) from two reference sites, two agriculturally impacted sites sampled during the dry season, and an impacted site sampled during the wet season were compared. The hepatic transcriptome was profiled using RNA-Seq. Multivariate analysis showed that transcriptomes were clustered based on site and by inference water quality, but not sampling time. The largest differences in transcriptomic profile were between reference sites and a site sampled during high run-off, showing that impacted sites can be identified via RNA-Seq. Transcripts with altered abundance were linked to xenobiotic metabolism, peroxisome proliferation and stress responses, indicating putative stressors with the potential for adverse outcomes in barramundi

Transcriptomic, lipid, and histological profiles suggest changes in health in fish from a pesticide hot spot.

Barramundi (Lates calcarifer) were collected at the beginning (1st sampling) and end (2nd sampling) of the wet season from Sandy Creek, an agriculturally impacted catchment in the Mackay Whitsundays region of the Great Barrier Reef catchment area, and from Repulse Creek, located approximately 100 km north in Conway National Park, to assess the impacts of pesticide exposure. Gill and liver histology, lipid class composition in muscle, and the hepatic transcriptome were examined. The first sample of Repulse Creek fish showed little tissue damage and low transcript levels of xenobiotic metabolism enzymes. Sandy Creek fish showed altered transcriptomic patterns, including those that regulate lipid metabolism, xenobiotic metabolism, and immune response; gross histological alterations including lipidosis; and differences in some lipid classes. The second sampling of Repulse Creek fish showed similar alterations in hepatic transcriptome and tissue structure as fish from Sandy Creek. These changes may indicate a decrease in health of pesticide exposed fish

Digital Technology Use and Mental Health Consultations:Survey of the Views and Experiences of Clinicians and Young People

BackgroundDigital technologies play an increasingly important role in the lives of young people and have important effects on their mental health. ObjectiveWe aimed to explore 3 key areas of the intersection between digital technology and mental health: the views and experiences of young people and clinicians about digital technology and mental health; implementation and barriers to the UK national guidance recommendation—that the discussion of digital technology use should form a core part of mental health assessment; and how digital technology might be used to support existing consultations. MethodsTwo cross-sectional web-based surveys were conducted in 2020 between June and December, with mental health clinicians (n=99) and young people (n=320). Descriptive statistics were used to summarize the proportions. Multilinear regression was used to explore how the answers varied by gender, sexuality, and age. Thematic analysis was used to explore the contents of the extended free-text answers. Anxiety was measured using the Generalized Anxiety Disorder Questionnaire-7 (GAD-7). ResultsDigital technology use was ubiquitous among young people, with positive and negative aspects acknowledged by both clinicians and young people. Negative experiences were common (131/284, 46.1%) and were associated with increased anxiety levels among young people (GAD-7 3.29; 95% CI 1.97-4.61; P<.001). Although the discussion of digital technology use was regarded as important by clinicians and acceptable by young people, less than half of clinicians (42/85, 49.4%) routinely asked about the use of digital technology and over a third of young people (48/121, 39.6%) who had received mental health care had never been asked about their digital technology use. The conversations were often experienced as unhelpful. Helpful conversations were characterized by greater depth and exploration of how an individual’s digital technology use related to mental health. Despite most clinicians (59/83, 71.1%) wanting training, very few (21/86, 24.4%) reported receiving training. Clinicians were open to viewing mental health data from apps or social media to help with consultations. Although young people were generally, in theory, comfortable sharing such data with health professionals, when presented with a binary choice, most reported not wanting to share social media (84/117, 71.8%) or app data (67/118, 56.8%) during consultations. ConclusionsDigital technology use was common, and negative experiences were frequent and associated with anxiety. Over a third of young people were not asked about their digital technology use during mental health consultations, and potentially valuable information about relevant negative experiences on the web was not being captured during consultations. Clinicians would benefit from having access to training to support these discussions with young people. Although young people recognized that app data could be helpful to clinicians, they appeared hesitant to share their own data. This finding suggests that data sharing has barriers that need to be further explored

Detecting the Companions and Ellipsoidal Variations of RS CVn Primaries: I. sigma Geminorum

To measure the properties of both components of the RS CVn binary sigma Geminorum (sigma Gem), we directly detect the faint companion, measure the orbit, obtain model-independent masses and evolutionary histories, detect ellipsoidal variations of the primary caused by the gravity of the companion, and measure gravity darkening. We detect the companion with interferometric observations obtained with the Michigan InfraRed Combiner (MIRC) at Georgia State University's Center for High Angular Resolution Astronomy (CHARA) Array with a primary-to-secondary H-band flux ratio of 270+/-70. A radial velocity curve of the companion was obtained with spectra from the Tillinghast Reflector Echelle Spectrograph (TRES) on the 1.5-m Tillinghast Reflector at Fred Lawrence Whipple Observatory (FLWO). We additionally use new observations from the Tennessee State University Automated Spectroscopic and Photometric Telescopes (AST and APT, respectively). From our orbit, we determine model-independent masses of the components (M_1 = 1.28 +/- 0.07 M_Sun, M_2 = 0.73 +/- 0.03 M_Sun), and estimate a system age of 5 -/+ 1 Gyr. An average of the 27-year APT light curve of sigma Gem folded over the orbital period (P = 19.6027 +/- 0.0005 days) reveals a quasi-sinusoidal signature, which has previously been attributed to active longitudes 180 deg apart on the surface of sigma Gem. With the component masses, diameters, and orbit, we find that the predicted light curve for ellipsoidal variations due to the primary star partially filling its Roche lobe potential matches well with the observed average light curve, offering a compelling alternative explanation to the active longitudes hypothesis. Measuring gravity darkening from the light curve gives beta < 0.1, a value slightly lower than that expected from recent theory.Comment: Accepted to ApJ, 11 pages, 6 figures, 8 table