Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response.

Biomedical devices comprise a major component of modern medicine, however immune-mediated fibrosis and rejection can limit their function over time. Here, we describe a humanized mouse model that recapitulates fibrosis following biomaterial implantation. Cellular and cytokine responses to multiple biomaterials were evaluated across different implant sites.

Long-term implant fibrosis prevention in rodents and non-human primates using crystallized drug formulations.

Implantable medical devices have revolutionized modern medicine. However, immune-mediated foreign body response (FBR) to the materials of these devices can limit their function or even induce failure. Here we describe long-term controlled-release formulations for local anti-inflammatory release through the development of compact, solvent-free crystals.

Reduction of measurement noise in a continuous glucose monitor by coating the sensor with a zwitterionic polymer.

Continuous glucose monitors (CGMs), used by patients with diabetes mellitus, can autonomously track fluctuations in blood glucose over time. However, the signal produced by CGMs during the initial recording period following sensor implantation contains substantial noise, requiring frequent recalibration via fingerprick tests. Here, we show that coating the sensor with a zwitterionic polymer, found via a combinatorial-chemistry approach, significantly reduces signal noise and improves CGM performance.

Guidelines and mHealth to Improve Quality of Hypertension and Type 2 Diabetes Care for Vulnerable Populations in Lebanon: Longitudinal Cohort Study.

Background: Given the protracted nature of the crisis in Syria, the large noncommunicable disease (NCD) caseload of Syrian refugees and host Lebanese, and the high costs of providing NCD care, the implications for Lebanon's health system are vast.

Objective: The aim of this study was to evaluate the effectiveness of treatment guidelines and a mobile health (mHealth) app on quality of care and health outcomes in primary care settings in Lebanon.

Methods: A longitudinal cohort study was implemented from January 2015 to August 2016 to evaluate the effectiveness of treatment guidelines and an mHealth app on quality of care and health outcomes for Syrian and Lebanese patients in Lebanese primary health care (PHC) facilities.

Pilot Testing and Implementation of a mHealth tool for Non-communicable Diseases in a Humanitarian Setting.

Introduction: Given the protracted nature of the crisis in Syria, national and international assistance agencies face immense challenges in providing for the needs of refugees and the host Lebanese due to the high burden of noncommunicable diseases (NCDs) among both populations. These are complex conditions to manage, and the resources for refugee care limited, having dramatic implications for Lebanon's health system.

Methods: A longitudinal cohort study was implemented from January 2015 through August 2016 to evaluate the effectiveness of treatment guidelines and an mHealth application on quality of care and health outcomes for patients in primary health care facilities in Lebanon serving Syrian refugees and host communities.

Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates.

Host recognition and immune-mediated foreign body response to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not.

Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination.

Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime.

Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice.

The transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in individuals with diabetes. Pancreas transplantation and the infusion of cadaveric islets are currently implemented clinically, but these approaches are limited by the adverse effects of immunosuppressive therapy over the lifetime of the recipient and the limited supply of donor tissue. The latter concern may be addressed by recently described glucose-responsive mature beta cells that are derived from human embryonic stem cells (referred to as SC-β cells), which may represent an unlimited source of human cells for pancreas replacement therapy.

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates.

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate.

Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates.

The efficacy of implanted biomedical devices is often compromised by host recognition and subsequent foreign body responses. Here, we demonstrate the role of the geometry of implanted materials on their biocompatibility in vivo. In rodent and non-human primate animal models, implanted spheres 1.

Correlation of Klebsiella pneumoniae comparative genetic analyses with virulence profiles in a murine respiratory disease model.

Klebsiella pneumoniae is a bacterial pathogen of worldwide importance and a significant contributor to multiple disease presentations associated with both nosocomial and community acquired disease. ATCC 43816 is a well-studied K. pneumoniae strain which is capable of causing an acute respiratory disease in surrogate animal models.

Methods for high-throughput MethylCap-Seq data analysis.

Background: Advances in whole genome profiling have revolutionized the cancer research field, but at the same time have raised new bioinformatics challenges. For next generation sequencing (NGS), these include data storage, computational costs, sequence processing and alignment, delineating appropriate statistical measures, and data visualization. Currently there is a lack of workflows for efficient analysis of large, MethylCap-seq datasets containing multiple sample groups.

Coordination state probabilities and the solvation free energy of Zn2+ in aqueous methanol solutions.

Coordination state probabilities for the [Zn(H(2)O)(n)(CH(3)OH)(m)](2+) complex in aqueous methanol solutions are calculated as a function of the bulk solution concentration, and the number of methanol ligands, m = 0, 1, ...

Genome-wide methylation profiling in decitabine-treated patients with acute myeloid leukemia.

The outcome of older (≥ 60 years) acute myeloid leukemia (AML) patients is poor, and novel treatments are needed. In a phase 2 trial for older AML patients, low-dose (20 mg/m(2) per day for 10 days) decitabine, a DNA hypomethylating azanucleoside, produced 47% complete response rate with an excellent toxicity profile. To assess the genome-wide activity of decitabine, we profiled pretreatment and post treatment (day 25/course 1) methylomes of marrow samples from patients (n = 16) participating in the trial using deep-sequencing analysis of methylated DNA captured by methyl-binding protein (MBD2).

A Scalable, Flexible Workflow for MethylCap-Seq Data Analysis.

Advances in whole genome profiling have revolutionized the cancer research field, but at the same time have raised new bioinformatics challenges. For next generation sequencing (NGS), these include data storage, computational costs, sequence processing and alignment, delineating appropriate statistical measures, and data visualization. The NGS application MethylCap-seq involves the in vitro capture of methylated DNA and subsequent analysis of enriched fragments by massively parallel sequencing.