A review of the long-term use of proton pump inhibitors and risk of celiac disease in the context of HLA-DQ2 and HLA-DQ8 genetic predisposition.

Proton pump inhibitors (PPIs) are among the most prescribed and widely used medications; however, the long-term effects of these medications are only beginning to be investigated. Since the introduction of omeprazole in 1989, PPIs have become the first-choice treatment for esophagitis, peptic ulcer disease, Zoster-Ellison syndrome, dyspepsia, and the prevention of ulcers with non-steroidal anti-inflammatory drugs. Recent studies have specifically examined the rise in celiac disease (CD) in this context. This review explores how PPIs may impact the development of CD and highlights the need for additional research into the environmental and genetic factors that influence the development and progression of the disease. A literature search was performed using the keywords celiac disease, proton pump inhibitors, human leukocyte antigen (HLA)-DQ2, HLA-DQ8. The pathogenesis of CD is multifactorial, and human leukocyte antigens are one factor that may contribute to its development. Additionally, pharmaceuticals, such as PPIs, that cause gut dysbiosis have been linked to the inflammatory response present in CD. Recent studies have suggested that the rise in CD could be attributed to changes in the gut microbiome, highlighting the significant role that gut microbiota is proposed to play in CD pathogenesis. Although PPI therapy is helpful in reducing acid production in gastroesophageal disorders, additional information is needed to determine whether PPIs are still an appropriate treatment option with the possibility of developing CD in the future, particularly in the context of HLA-DQ2 and HLA-DQ8 predispositions. This review emphasizes the importance of personalized medicine for individuals with gastroesophageal disorders that require long-term use of PPIs.

The effect of physical and psychological stress on the oral microbiome.

Background: The oral microbiome is incredibly complex, containing a diverse complement of microbiota that has previously been categorized into 6 broad phyla. While techniques such as next-generation sequencing have contributed to a better understanding of the composition of the oral microbiome, the role it plays in human health and disease is still under investigation. Previous studies have identified that a more diverse microbiome is advantageous for health. Therefore, alterations to the physical or mental health that are of interest in this study, such as stress, are the factors that decrease microbial diversity, leading to the potential for dysbiosis and disease disposition. Intensive Surgical Skills Week (ISSW) is a hyper-realistic simulation training week for military medical students that takes place at the Strategic Operations (STOPS) facility in San Diego, CA. This training week puts students through mass causality simulations and requires them to work through distinct roles within the healthcare team, providing an almost ideal environment to assess the impact of acute stress on oral microbiome diversity. Based on the literature on stress and microbiota, we hypothesized that the high stress simulation events at ISSW will impact the composition and diversity of the oral microbiome. Methods: To investigate this hypothesis, thirty-seven (n = 37) second-or third-year medical students who are enlisted in a branch of the military and who attended ISSW in July of 2021 were included in the study. Student participants were divided into 7 teams to complete the hyper-realistic simulations (SIMs) at ISSW. A pilot of sixty-four buccal samples (n = 64) from three of the seven teams were sent for analysis at the University of Missouri Metagenomic Center. Results: We saw an overall increase in species richness at the end of ISSW when looking at all samples (n = 64). Fourteen significantly different bacteria were identified from the beginning to the end of data collection. Additionally, third year medical students appear to have a greater species richness compared to second year medical students. Further, third year medical students had a statically significant difference in their oral microbiome richness from beginning to end of data collection (p = 0.008). Conclusion: Our preliminary data indicates that physical and psychological stress can impact the composition of the oral microbiome. The analyses in this study show that using the oral microbiome as an indicator of stress is promising and may provide evidence to support stress management practices.

3D Bioprinting in Otolaryngology: A Review.

The evolution of tissue engineering and 3D bioprinting has allowed for increased opportunities to generate musculoskeletal tissue grafts that can enhance functional and aesthetic outcomes in otolaryngology-head and neck surgery. Despite literature reporting successes in the fabrication of cartilage and bone scaffolds for applications in the head and neck, the full potential of this technology has yet to be realized. Otolaryngology as a field has always been at the forefront of new advancements and technology and is well poised to spearhead clinical application of these engineered tissues. In this review, current 3D bioprinting methods are described and an overview of potential cell types, bioinks, and bioactive factors available for musculoskeletal engineering using this technology is presented. The otologic, nasal, tracheal, and craniofacial bone applications of 3D bioprinting with a focus on engineered graft implantation in animal models to highlight the status of functional outcomes in vivo; a necessary step to future clinical translation are reviewed. Continued multidisciplinary efforts between material chemistry, biological sciences, and otolaryngologists will play a key role in the translation of engineered, 3D bioprinted constructs for head and neck surgery.

Selective androgen receptor modulator microparticle formulation reverses muscle hyperalgesia in a mouse model of widespread muscle pain.

ABSTRACT: Chronic pain is a significant health problem associated with disability and reduced quality of life. Current management of chronic pain is inadequate with only modest effects of pharmacological interventions. Thus, there is a need for the generation of analgesics for treating chronic pain. Although preclinical and clinical studies demonstrate the analgesic effects of testosterone, clinical use of testosterone is limited by adverse androgenic effects. Selective androgen receptor modulators (SARMs) activate androgen receptors and overcome treatment limitations by minimizing androgenic side effects. Thus, we tested whether daily soluble SARMs or a SARM-loaded microparticle formulation alleviated muscle hyperalgesia in a mouse-model of widespread pain (male and female C57BL/6J mice). We tested whether the analgesic effects of the SARM-loaded microparticle formulation was mediated through androgen receptors by blocking androgen receptors with flutamide pellets. In vitro and in vivo release kinetics were determined for SARM-loaded microparticles. Safety and toxicity of SARM treatment was determined using serum cardiac and liver toxicity panels, heart histology, and conditioned place preference testing. Subcutaneous daily SARM administration, and 2 injections, 1 week apart, of SARM-loaded microparticles alleviated muscle hyperalgesia in both sexes and was prevented with flutamide treatment. Sustained release of SARM, from the microparticle formulation, was observed both in vitro and in vivo for 4 weeks. Selective androgen receptor modulator treatment produced no cardiac or liver toxicity and did not produce rewarding behaviors. These studies demonstrate that SARM-loaded microparticles, which release drug for a sustained period, alleviate muscle pain, are safe, and may serve as a potential therapeutic for chronic muscle pain.

Hydrogel microspheres for spatiotemporally controlled delivery of RNA and silencing gene expression within scaffold-free tissue engineered constructs.

Delivery systems for controlled release of RNA interference (RNAi) molecules, including small interfering (siRNA) and microRNA (miRNA), have the potential to direct stem cell differentiation for regenerative musculoskeletal applications. To date, localized RNA delivery platforms in this area have focused predominantly on bulk scaffold-based approaches, which can interfere with cell-cell interactions important for recapitulating some native musculoskeletal developmental and healing processes in tissue regeneration strategies. In contrast, scaffold-free, high density human mesenchymal stem cell (hMSC) aggregates may provide an avenue for creating a more biomimetic microenvironment. Here, photocrosslinkable dextran microspheres (MS) encapsulating siRNA-micelles were prepared via an aqueous emulsion method and incorporated within hMSC aggregates for localized and sustained delivery of bioactive siRNA. siRNA-micelles released from MS in a sustained fashion over the course of 28 days, and the released siRNA retained its ability to transfect cells for gene silencing. Incorporation of fluorescently labeled siRNA (siGLO)-laden MS within hMSC aggregates exhibited tunable siGLO delivery and uptake by stem cells. Incorporation of MS loaded with siRNA targeting green fluorescent protein (siGFP) within GFP-hMSC aggregates provided sustained presentation of siGFP within the constructs and prolonged GFP silencing for up to 15 days. This platform system enables sustained gene silencing within stem cell aggregates and thus shows great potential in tissue regeneration applications. STATEMENT OF SIGNIFICANCE: This work presents a new strategy to deliver RNA-nanocomplexes from photocrosslinked dextran microspheres for tunable presentation of bioactive RNA. These microspheres were embedded within scaffold-free, human mesenchymal stem cell (hMSC) aggregates for sustained gene silencing within three-dimensional cell constructs while maintaining cell viability. Unlike exogenous delivery of RNA within culture medium that suffers from diffusion limitations and potential need for repeated transfections, this strategy provides local and sustained RNA presentation from the microspheres to cells in the constructs. This system has the potential to inhibit translation of hMSC differentiation antagonists and drive hMSC differentiation toward desired specific lineages, and is an important step in the engineering of high-density stem cell systems with incorporated instructive genetic cues for application in tissue regeneration.

Craniofacial fasciitis of the face: Case report and review of the recent literature.

INTRODUCTION: Craniofacial fasciitis (CFFF) an uncommon, benign pseudosarcomatous proliferation of unknown etiology that occurs almost exclusively in children less than 6 years old. CFF lesions occur most frequently in the deep fascial layers and the periosteal layer of the calvarium, resulting in a rapidly enlarging scalp mass with potential underlying bony erosion. Presentation of CFF on the midface is rare. OBJECTIVE: The objective of this report is to describe a case of paranasal CFF involving the nasolacrimal duct in an infant and perform a literature review of cases of CFF of the midface in children. METHODS: A literature review of children ≤18 years old who were diagnosed with CFF of the midface was performed. A single case report is presented. RESULTS: A 7-month-old girl presented with a rapidly enlarging facial mass with edema, epiphora, difficulty breathing, and issues with feeding. She underwent urgent biopsy which revealed spindle cells with fibrous background. Patient was diagnosed with paranasal CFF based on clinical presentation and pathology report. She subsequently underwent near complete surgical excision. Patient is doing well with no progression of disease with follow up MRI revealing minimal residual disease in the nasal cavity. Review of the literature identified 4 additional cases of CFF of the midface which presented on sites including the mandible, frontonasal region, nasal process of the maxilla, and orbit/maxilla. The patient in this case is the first presentation of CFF involving the nasolacrimal duct. Lesions presented anywhere from 2 days to 3 months prior to treatment, and immunohistochemistry was positive for either vimentin or beta-catenin. Interestingly, all cases in this series occurred within the first year of life and were treated with complete or near complete resection with no evidence of recurrence. CONCLUSION: Although CFF is a rare diagnosis, it should be considered in the evaluation and treatment of soft-tissue masses of the midface in children. Surgical excision is curative and there appears to be a low rate of recurrence based on the small series presented in literature.

Comparison of Materials Used for 3D-Printing Temporal Bone Models to Simulate Surgical Dissection.

OBJECTIVE: To identify 3D-printed temporal bone (TB) models that most accurately recreate cortical mastoidectomy for use as a training tool by comparison of different materials and fabrication methods. BACKGROUND: There are several different printers and materials available to create 3D-printed TB models for surgical planning and trainee education. Current reports using Acrylonitrile Butadiene Styrene (ABS) plastic generated via fused deposition modeling (FDM) have validated the capacity for 3D-printed models to serve as accurate surgical simulators. Here, a head-to-head comparison of models produced using different materials and fabrication processes was performed to identify superior models for application in skull base surgical training. METHODS: High-resolution CT scans of normal TBs were used to create stereolithography files with image conversion for application in 3D-printing. The 3D-printed models were constructed using five different materials and four printers, including ABS printed on a MakerBot 2x printer, photopolymerizable polymer (Photo) using the Objet 350 Connex3 Printer, polycarbonate (PC) using the FDM-Fortus 400 mc printer, and two types of photocrosslinkable acrylic resin, white and blue (FLW and FLB, respectively), using the Formlabs Form 2 stereolithography printer. Printed TBs were drilled to assess the haptic experience and recreation of TB anatomy with comparison to the current paradigm of ABS. RESULTS: Surgical drilling demonstrated that FLW models created by FDM as well as PC and Photo models generated using photopolymerization more closely recreated cortical mastoidectomy compared to ABS models. ABS generated odor and did not represent the anatomy accurately. Blue resin performed poorly in simulation, likely due to its dark color and translucent appearance. CONCLUSIONS: PC, Photo, and FLW models best replicated surgical drilling and anatomy as compared to ABS and FLB models. These prototypes are reliable simulators for surgical training.

A Modular Strategy to Engineer Complex Tissues and Organs.

Currently, there are no synthetic or biologic materials suitable for long-term treatment of large tracheal defects. A successful tracheal replacement must (1) have radial rigidity to prevent airway collapse during respiration, (2) contain an immunoprotective respiratory epithelium, and (3) integrate with the host vasculature to support epithelium viability. Herein, biopolymer microspheres are used to deliver chondrogenic growth factors to human mesenchymal stem cells (hMSCs) seeded in a custom mold that self-assemble into cartilage rings, which can be fused into tubes. These rings and tubes can be fabricated with tunable wall thicknesses and lumen diameters with promising mechanical properties for airway collapse prevention. Epithelialized cartilage is developed by establishing a spatially defined composite tissue composed of human epithelial cells on the surface of an hMSC-derived cartilage sheet. Prevascular rings comprised of human umbilical vein endothelial cells and hMSCs are fused with cartilage rings to form prevascular-cartilage composite tubes, which are then coated with human epithelial cells, forming a tri-tissue construct. When prevascular- cartilage tubes are implanted subcutaneously in mice, the prevascular structures anastomose with host vasculature, demonstrated by their ability to be perfused. This microparticle-cell self-assembly strategy is promising for engineering complex tissues such as a multi-tissue composite trachea.

RNA interfering molecule delivery from in situ forming biodegradable hydrogels for enhancement of bone formation in rat calvarial bone defects.

RNA interference (RNAi) may be an effective and valuable tool for promoting the growth of functional tissue, as short interfering RNA (siRNA) and microRNA (miRNA) can block the expression of genes that have negative effects on tissue regeneration. Our group has recently reported that the localized and sustained presentation of siRNA against noggin (siNoggin) and miRNA-20a from in situ forming poly(ethylene glycol) (PEG) hydrogels enhanced osteogenic differentiation of encapsulated human bone marrow-derived mesenchymal stem cells (hMSCs). Here, the capacity of the hydrogel system to accelerate bone formation in a rat calvarial bone defect model is presented. After 12 weeks post-implantation, the hydrogels containing encapsulated hMSCs and miRNA-20a resulted in more bone formation in the defects than the hydrogels containing hMSCs without siRNA or with negative control siRNA. This localized and sustained RNA interfering molecule delivery system may provide an excellent platform for healing bony defects and other tissues. STATEMENT OF SIGNIFICANCE: Delivery of RNAi molecules may be a valuable strategy to guide cell behavior for tissue engineering applications, but to date there have been no reports of a biomaterial system capable of both encapsulation of cells and controlled delivery of incorporated RNA. Here, we present PEG hydrogels that form in situ via Michael type reaction, and that permit encapsulation of hMSCs and the concomitant controlled delivery of siNoggin and/or miRNA-20a. These RNAs were chosen to suppress noggin, a BMP-2 antagonist, and/or PPAR-γ, a negative regulator of BMP-2-mediated osteogenesis, and therefore promote osteogenic differentiation of hMSCs and subsequent bone repair in critical-sized rat calvarial defects. Simultaneous delivery of hMSCs and miRNA-20a enhanced repair of these defects compared to hydrogels containing hMSCs without siRNA or with negative control siRNA. This in situ forming PEG hydrogel system offers an exciting platform for healing critical-sized bone defects by localized, controlled delivery of RNAi molecules to encapsulated hMSCs and surrounding cells.

Dual non-viral gene delivery from microparticles within 3D high-density stem cell constructs for enhanced bone tissue engineering.

High-density mesenchymal stem cell (MSC) aggregates can be guided to form bone-like tissue via endochondral ossification in vitro when culture media is supplemented with proteins, such as growth factors (GFs), to first guide the formation of a cartilage template, followed by culture with hypertrophic factors. Recent reports have recapitulated these results through the controlled spatiotemporal delivery of chondrogenic transforming growth factor-ß1 (TGF-ß1) and chondrogenic and osteogenic bone morphogenetic protein-2 (BMP-2) from microparticles embedded within human MSC aggregates to avoid diffusion limitations and the lengthy, costly in vitro culture necessary with repeat exogenous supplementation. However, since GFs have limited stability, localized gene delivery is a promising alternative to the use of proteins. Here, mineral-coated hydroxyapatite microparticles (MCM) capable of localized delivery of Lipofectamine-plasmid DNA (pDNA) nanocomplexes encoding for TGF-ß1 (pTGF-ß1) and BMP-2 (pBMP-2) were incorporated, alone or in combination, within MSC aggregates from three healthy porcine donors to induce sustained production of these transgenes. Three donor populations were investigated in this work due to the noted MSC donor-to-donor variability in differentiation capacity documented in the literature. Delivery of pBMP-2 within Donor 1 aggregates promoted chondrogenesis at week 2, followed by an enhanced osteogenic phenotype at week 4. Donor 2 and 3 aggregates did not promote robust glycosaminoglycan (GAG) production at week 2, but by week 4, Donor 2 aggregates with pTGF-ß1/pBMP-2 and Donor 3 aggregates with both unloaded MCM and pBMP-2 enhanced osteogenesis compared to controls. These results demonstrate the ability to promote osteogenesis in stem cell aggregates through controlled, non-viral gene delivery within the cell masses. These findings also indicate the need to screen donor MSC regenerative potential in response to gene transfer prior to clinical application. Taken together, this work demonstrates a promising gene therapy approach to control stem cell fate in biomimetic 3D condensations for treatment of bone defects.

Endochondral Ossification in Critical-Sized Bone Defects via Readily Implantable Scaffold-Free Stem Cell Constructs.

The growing socioeconomic burden of musculoskeletal injuries and limitations of current therapies have motivated tissue engineering approaches to generate functional tissues to aid in defect healing. A readily implantable scaffold-free system comprised of human bone marrow-derived mesenchymal stem cells embedded with bioactive microparticles capable of controlled delivery of transforming growth factor-beta 1 (TGF-ß1) and bone morphogenetic protein-2 (BMP-2) was engineered to guide endochondral bone formation. The microparticles were formulated to release TGF-ß1 early to induce cartilage formation and BMP-2 in a more sustained manner to promote remodeling into bone. Cell constructs containing microparticles, empty or loaded with one or both growth factors, were implanted into rat critical-sized calvarial defects. Micro-computed tomography and histological analyses after 4 weeks showed that microparticle-incorporated constructs with or without growth factor promoted greater bone formation compared to sham controls, with the greatest degree of healing with bony bridging resulting from constructs loaded with BMP-2 and TGF-ß1. Importantly, bone volume fraction increased significantly from 4 to 8 weeks in defects treated with both growth factors. Immunohistochemistry revealed the presence of types I, II, and X collagen, suggesting defect healing via endochondral ossification in all experimental groups. The presence of vascularized red bone marrow provided strong evidence for the ability of these constructs to stimulate angiogenesis. This system has great translational potential as a readily implantable combination therapy that can initiate and accelerate endochondral ossification in vivo. Importantly, construct implantation does not require prior lengthy in vitro culture for chondrogenic cell priming with growth factors that is necessary for current scaffold-free combination therapies. Stem Cells Translational Medicine 2017;6:1644-1659.

Photocrosslinkable, biodegradable hydrogels with controlled cell adhesivity for prolonged siRNA delivery to hMSCs to enhance their osteogenic differentiation.

Photocrosslinked, biodegradable hydrogels have been extensively investigated for biomedical applications, including drug delivery and tissue engineering. Here, dextran (DEX) was chemically modified with mono(2-acryloyloxyethyl) succinate (MAES) via an esterification reaction, resulting in macromers that could be photocrosslinked to form hydrolytically degradable hydrogels. Hydrogel swelling ratio and degradation rate were controlled by varying the degree of MAES modification. Thiolated cell adhesion peptides (GRGDSPC) were conjugated to acrylated dextran via thiol-acrylate reaction to regulate the interactions of human mesenchymal stem cells (hMSCs) with the photocrosslinkable hydrogels. The hydrogels permitted sustained release of short interfering RNA (siRNA) over 7 weeks and were cytocompatible with hMSCs. Sustained presentation of siRNA from these photocrosslinked DEX hydrogels enhanced the osteogenic differentiation of encapsulated hMSCs. These DEX hydrogels with tunable siRNA delivery and cell adhesive properties may provide an excellent platform for bioactive molecule delivery and tissue regeneration applications.

Cytocompatible Catalyst-Free Photodegradable Hydrogels for Light-Mediated RNA Release To Induce hMSC Osteogenesis.

Macroscopic hydrogels provide valuable platforms for controlling the release of genetic materials such as small interfering RNA (siRNA) and microRNA (miRNA) for biomedical applications. However, after these hydrogels are formed, it is challenging to alter the release rate of genetic materials. In this report, a Michael addition catalyst-free photodegradable poly(ethylene glycol) (PEG)-based hydrogel system has been developed that provides an active means of controlling the release of genetic materials postgelation using external UV light application. Photodegradation of photolabile linkages in the hydrogel network changes the hydrogel physiochemical properties such as swelling and degradation rate, augmenting the release rate of loaded genetic materials. In the absence of UV light, RNAs were released in a sustained fashion from both photodegradable and nonphotodegradable hydrogels. In contrast, RNA release rate from the photodegradable hydrogels was accelerated via UV light application, whereas it was not elevated with nonphotodegradable hydrogels. Regardless of the UV light exposure to the hydrogels, released siRNA against green fluorescent protein (siGFP) retained its bioactivity via effectively silencing GFP expression in destabilized GFP (deGFP)-expressing HeLa cells cultured in monolayer. Moreover, cells encapsulated in these hydrogels exhibited high cell viability, and loaded siGFP inhibited GFP expression of encapsulated deGFP-expressing HeLa cells with or without UV light application to the hydrogels. Importantly, released siRNA targeting noggin (siNoggin) and miRNA-20a from the hydrogels, with and without UV light application, induced osteogenic differentiation of human mesenchymal stem cells (hMSCs). This photodegradable hydrogel system may be a promising strategy for real-time, user-controlled release of genetic materials for tissue engineering and treatment of diseases such as cancer.

Correction: Photocrosslinkable, biodegradable hydrogels with controlled cell adhesivity for prolonged siRNA delivery to hMSCs to enhance their osteogenic differentiation.

Correction for 'Photocrosslinkable, biodegradable hydrogels with controlled cell adhesivity for prolonged siRNA delivery to hMSCs to enhance their osteogenic differentiation' by Minh Khanh Nguyen et al., J. Mater. Chem. B, 2017, 5, 485-495.

Spatially organized differentiation of mesenchymal stem cells within biphasic microparticle-incorporated high cell density osteochondral tissues.

Giving rise to both bone and cartilage during development, bone marrow-derived mesenchymal stem cells (hMSC) have the unique capacity to generate the complex tissues of the osteochondral interface. Utilizing a scaffold-free hMSC system, biphasic osteochondral constructs are incorporated with two types of growth factor-releasing microparticles to enable spatially organized differentiation. Gelatin microspheres (GM) releasing transforming growth factor-ß1 (TGF-ß1) combined with hMSC form the chondrogenic phase. The osteogenic phase contains hMSC only, mineral-coated hydroxyapatite microparticles (MCM), or MCM loaded with bone morphogenetic protein-2 (BMP-2), cultured in medium with or without BMP-2. After 4 weeks, TGF-ß1 release from GM within the cartilage phase promotes formation of a glycosaminoglycan- and type II collagen-rich matrix, and has a local inhibitory effect on osteogenesis. In the osteogenic phase, type X collagen and osteopontin are produced in all conditions. However, calcification occurs on the outer edges of the chondrogenic phase in some constructs cultured in media containing BMP-2, and alkaline phosphatase levels are elevated, indicating that BMP-2 releasing MCM provides better control over region-specific differentiation. The production of complex, stem cell-derived osteochondral tissues via incorporated microparticles could enable earlier implantation, potentially improving outcomes in the treatment of osteochondral defects.

Synergistic effect of HIF-1alpha gene therapy and HIF-1-activated bone marrow-derived angiogenic cells in a mouse model of limb ischemia.

Ischemia induces the production of angiogenic cytokines and the homing of bone-marrow-derived angiogenic cells (BMDACs), but these adaptive responses become impaired with aging because of reduced expression of hypoxia-inducible factor (HIF)-1alpha. In this study, we analyzed the effect of augmenting HIF-1alpha levels in ischemic limb by intramuscular injection of AdCA5, an adenovirus encoding a constitutively active form of HIF-1alpha, and intravenous administration of BMDACs that were cultured in the presence of the prolyl-4-hydroxylase inhibitor dimethyloxalylglycine (DMOG) to induce HIF-1 expression. The combined therapy increased perfusion, motor function, and limb salvage in old mice subjected to femoral artery ligation. Homing of BMDACs to the ischemic limb was dramatically enhanced by intramuscular AdCA5 administration. DMOG treatment of BMDACs increased cell surface expression of beta(2) integrins, which mediated increased adherence of BMDACs to endothelial cells. The effect of DMOG was abolished by coadministration of the HIF-1 inhibitor digoxin or by preincubation with a beta(2) integrin-blocking antibody. Transduction of BMDACs with lentivirus LvCA5 induced effects similar to DMOG treatment. Thus, HIF-1alpha gene therapy increases homing of BMDACs to ischemic muscle, whereas HIF-1 induction in BMDACs enhances their adhesion to vascular endothelium, leading to synergistic effects of combined therapy on tissue perfusion.

A large pericardial cyst complicated by a pericarditis in a young man with a mediastinal mass.

This is a case report of a 30-year-old man who presented with acute right-sided pleuritic chest pain. A chest roentgenogram performed in the emergency room shows a large, well-circumscribed transparent lesion obscuring the right heart border. Further imaging revealed a large pericardial cyst. The patient was taken to surgery as a result of clinical deterioration, and the knowledge that large pericardial cysts, although usually benign, can cause serious complications, including death. Pathology revealed an inflamed pericardial cyst with fibrinous pericarditis.