Hypoxia within subcutaneously implanted macroencapsulation devices limits the viability and functionality of densely loaded islets.

Introduction: Subcutaneous macroencapsulation devices circumvent disadvantages of intraportal islet therapy. However, a curative dose of islets within reasonably sized devices requires dense cell packing. We measured internal PO2 of implanted devices, mathematically modeled oxygen availability within devices and tested the predictions with implanted devices containing densely packed human islets.

Validating self-reported Toxic Release Inventory data using Benford's Law: investigating toxic chemical release hazards in floodplains.

Introduction: Acute and long-term health impacts from flooding related toxic chemical releases are a significant local health concern and can disproportionately impact communities with vulnerable populations; reliable release data are needed to quantify this hazard.

Methods: In this paper, we analyze US Federal Emergency Management Agency designated floodplain data and US Environmental Protection Agency Toxic Release Inventory (TRI) data to determine if geographically manipulated databases adhere to Benford's Law.

Results: We investigated multiple variants and discovered pollution releases adhere to Benford's Law and tests which thereby validates the self-reported toxic release dataset.

Using Artificial Intelligence to Identify Sources and Pathways of Lead Exposure in Children.

Context: Sources and pathways of lead exposure in young children have not been analyzed using new artificial intelligence methods.

Objective: To collect environmental, behavioral, and other data on sources and pathways in 17 rural homes to predict at-risk households and to compare urban and rural indicators of exposure.

Design: Cross-sectional pilot study.

Encapsulated Cells for the Treatment of Diabetes: Danger of Acute Hypoglycemia Following Injury?

Transplants comprised of encapsulated islets have shown promise in treating insulin-dependent diabetes. A question raised in the scientific and clinical communities is whether the insulin released from an implanted encapsulation device damaged in an accident could cause a serious hypoglycemic event. In this commentary, we consider the different types of damage that a device can sustain, including the encapsulation membrane and the islets within, and the amount of insulin released in each case.

Chemical facility risks to natural flooding hazards in the United States.

Toxic release inventory (TRI) facilities contain chemicals, most must be kept in process equipment, otherwise leaks are possible. An analysis of the National Flood Hazard Layer and TRI facilities within ArcGIS. The national analysis included TRI facilities intersecting the 100-year floodplain based on the National Flood Hazard Layer.

A Data Driven Approach for Prioritizing COVID-19 Vaccinations in the Midwestern United States.

Considering the potential for widespread adoption of social vulnerability indices (SVI) to prioritize COVID-19 vaccinations, there is a need to carefully assess them, particularly for correspondence with outcomes (such as loss of life) in the context of the COVID-19 pandemic. The University of Illinois at Chicago School of Public Health Public Health GIS team developed a methodology for assessing and deriving vulnerability indices based on the premise that these indices are, in the final analysis, classifiers. Application of this methodology to several Midwestern states with a commonly used SVI indicates that by using only the SVI rankings there is a risk of assigning a high priority to locations with the lowest mortality rates and low priority to locations with the highest mortality rates.

A Web-Based Interactive Map to Promote Health-Care Facility Flood Preparedness.

Objectives: Little is known about how flood risk of health-care facilities (HCFs) is evaluated by emergency preparedness professionals and HCFs administrators. This study assessed knowledge of emergency preparedness and HCF management professionals regarding locations of floodplains in relation to HCFs. A Web-based interactive map of floodplains and HCF was developed and users of the map were asked to evaluate it.

Peritoneal dissolved oxygen and function of encapsulated adult porcine islets transplanted in streptozotocin diabetic mice.

Background: Alginate-encapsulated islet xenografts have restored normoglycemia in diabetic animals for various periods of time. Plausible mechanisms of graft failure in vivo include immune rejection and hypoxia. We sought to understand the effects of encapsulated adult porcine islet (API) dosage on the peritoneal dissolved oxygen (DO) level in correlation to the achieved glycemic regulation in diabetic mice.

A second wave of COVID-19 in Cook County: What lessons can be applied?

During the ongoing public health crisis, many agencies are reporting COVID-19 health outcome information based on the overall population. This practice can lead to misleading results and underestimation of high risk areas. To gain a better understanding of spatial and temporal distribution of COVID-19 deaths; the long term care facility (LTCF) and household population (HP) deaths must be used.

Microencapsulated islet allografts in diabetic NOD mice and nonhuman primates.

Objective: Our goal was to assess the efficacy of encapsulated allogeneic islets transplanted in diabetic NOD mice and streptozotocin (STZ)-diabetic nonhuman primates (NHPs).

Materials And Methods: Murine or NHP islets were microencapsulated and transplanted in non-immunosuppressed mice or NHPs given clinically-acceptable immunosuppressive regimens, respectively. Two NHPs were treated with autologous mesenchymal stem cells (MSCs) and peri-transplant oxygen therapy.

Multiple clinically relevant immunotherapies prolong the function of microencapsulated porcine islet xenografts in diabetic NOD mice without the use of anti-CD154 mAb.

Background: Our goal was to identify clinically relevant immunotherapies that synergize with microencapsulation to protect adult porcine islet (API) xenografts in diabetic NOD mice. We have shown previously that dual costimulatory blockade (CTLA4-Ig plus anti-CD154 mAb) combined with encapsulation protects APIs long-term in NOD mice. Since no anti-CD154 mAbs currently are approved for use in humans, we tested the efficacy of other targeted immunosuppression regimens that might be used for diabetic patients receiving encapsulated islets.

Noninvasive Fluorine-19 Magnetic Resonance Relaxometry Measurement of the Partial Pressure of Oxygen in Acellular Perfluorochemical-loaded Alginate Microcapsules Implanted in the Peritoneal Cavity of Nonhuman Primates.

Background: We have utilized a noninvasive technique for measuring the partial pressure of oxygen (pO2) in alginate microcapsules implanted intraperitoneally in healthy nonhuman primates (NHPs). Average pO2 is important for determining if a transplant site and capsules with certain passive diffusion characteristics can support the islet viability, metabolic activity, and dose necessary to reverse diabetes.

Methods: Perfluoro-15-crown-5-ether alginate capsules were infused intraperitoneally into 3 healthy NHPs.

Microencapsulated adult porcine islets transplanted intraperitoneally in streptozotocin-diabetic non-human primates.

Background: Xenogeneic donors would provide an unlimited source of islets for the treatment of type 1 diabetes (T1D). The goal of this study was to assess the function of microencapsulated adult porcine islets (APIs) transplanted ip in streptozotocin (STZ)-diabetic non-human primates (NHPs) given targeted immunosuppression.

Methods: APIs were encapsulated in: (a) single barium-gelled alginate capsules or (b) double alginate capsules with an inner, islet-containing compartment and a durable, biocompatible outer alginate layer.

Advanced Cell and Tissue Biomanufacturing.

This position paper assesses state-of-the-art advanced biomanufacturing and identifies paths forward to advance this emerging field in biotechnology and biomedical engineering, including new research opportunities and translational and corporate activities. The vision for the field is to see advanced biomanufacturing emerge as a discipline in academic and industrial communities as well as a technological opportunity to spur research and industry growth. To navigate this vision, the paths to move forward and to identify major barriers were a focal point of discussions at a National Science Foundation-sponsored workshop focused on the topic.

Hospitalizations for heat-stress illness varies between rural and urban areas: an analysis of Illinois data, 1987-2014.

Background: The disease burden due to heat-stress illness (HSI), which can result in significant morbidity and mortality, is expected to increase as the climate continues to warm. In the United States (U.S.

The effect of hypoxia on free and encapsulated adult porcine islets-an in vitro study.

Background: Adult porcine islets (APIs) constitute a promising alternative to human islets in treating type 1 diabetes. The intrahepatic site has been used in preclinical primate studies of API xenografts; however, an estimated two-thirds of donor islets are destroyed after intraportal infusion due to a number of factors, including the instant blood-mediated inflammatory reaction (IBMIR), immunosuppressant toxicity, and poor reestablishment of extracellular matrix connections. Intraperitoneal (ip) transplantation of non-vascularized encapsulated islets offers several advantages over intrahepatic transplantation of free islets, including avoidance of IBMIR, immunoprotection, accommodation of a larger graft volume, and reduced risk of hemorrhage.

mRNA destabilization improves glycemic responsiveness of transcriptionally regulated hepatic insulin gene therapy in vitro and in vivo.

Background: Hepatic insulin gene therapy (HIGT) employing a glucose and insulin sensitive promoter to direct insulin transcription can lower blood sugars within 2 h of an intraperitoneal glucose challenge. However, post-challenge blood sugars frequently decline to below baseline. We hypothesize that this 'over-shoot' hypoglycemia results from sustained translation of long-lived transgene message, and that reducing pro-insulin message half-life will ameliorate post-challenge hypoglycemia.

Alginate encapsulant incorporating CXCL12 supports long-term allo- and xenoislet transplantation without systemic immune suppression.

Islet transplantation represents a potentially curative approach for individuals with Type I Diabetes. The requirement for systemic immune suppression to control immune-mediated rejection of transplanted islets and the limited human islet supply represent significant roadblocks to progress for this approach. Islet microencapsulation in alginate offers limited protection in the absence of systemic immunosuppression, but does not support long-term islet survival.

Trichostatin A affects the secretion pathways of beta and intestinal endocrine cells.

Histone deacetylase inhibitors (HDACi) were recently identified as having significant clinical potential in reversing β-cell functional inhibition caused by inflammation, a shared precursor of Type 1 and Type 2 diabetes. However, HDACi are highly complex and little is known of their direct effect on important cell secretion pathways for blood glucose regulation. The aims of the present study were to investigate the effect of HDACi on insulin secretion from β-cells, GLP-1 secretion from L-cells, and recombinant insulin secretion from engineered L-cells.

Bioluminescence tracking of alginate micro-encapsulated cell transplants.

Cell-based therapies to treat loss-of-function hormonal disorders such as diabetes and Parkinson's disease are routinely coupled with encapsulation strategies, but an understanding of when and why grafts fail in vivo is lacking. Consequently, investigators cannot clearly define the key factors that influence graft success. Although bioluminescence is a popular method to track the survival of free cells transplanted in preclinical models, little is known of the ability to use bioluminescence for real-time tracking of microencapsulated cells.

Therapeutic effects of a non-β cell bioartificial pancreas in diabetic mice.

Background: Cell-based insulin therapies can potentially improve glycemic regulation in insulin-dependent diabetic patients. Enteroendocrine cells engineered to secrete recombinant insulin have exhibited glycemic efficacy, but have been primarily studied as uncontrollable growth systems in immune incompetent mice. Furthermore, reports suggest that suboptimal insulin secretion remains a barrier to expanded application.

Cryopreservation effects on recombinant myoblasts encapsulated in adhesive alginate hydrogels.

Cell encapsulation in hydrogels is widely used in tissue engineering applications, including encapsulation of islets or other insulin-secreting cells in pancreatic substitutes. Use of adhesive, biofunctionalized hydrogels is receiving increasing attention as cell-matrix interactions in three-dimensional (3-D) environments can be important for various cell processes. With pancreatic substitutes, studies have indicated benefits of 3-D adhesion on the viability and/or function of insulin-secreting cells.

Dual factor delivery of CXCL12 and Exendin-4 for improved survival and function of encapsulated beta cells under hypoxic conditions.

A bioartifical pancreas (BAP) remains a promising approach for treating insulin-dependent diabetes. Several obstacles to the clinical implementation of a BAP remain, including hypoxia following implantation. Within native pancreatic islets, CXCL12 and glucagon-like peptide-1 (GLP-1) act in a paracrine fashion to promote the survival, function, and proliferation of β-cells.

Alginate microencapsulation of human mesenchymal stem cells as a strategy to enhance paracrine-mediated vascular recovery after hindlimb ischaemia.

Stem cell-based therapies hold great promise as a clinically viable approach for vascular regeneration. Preclinical studies have been very encouraging and early clinical trials have suggested favourable outcomes. However, significant challenges remain in terms of optimizing cell retention and maintenance of the paracrine effects of implanted cells.