Treatment outcomes on neovascularization after CRAO treated with hyperbaric oxygen.

Central retinal artery occlusion (CRAO) is a condition that causes sudden vision loss due to obstruction of the retinal artery, typically from a thrombotic or embolic source. It is often associated with atherosclerotic risk factors, including cardiovascular disease, diabetes, hyperlipidemia, and a history of cerebrovascular disease. CRAO often leads to a poor visual outcome as well as neovascularization of the iris, retina, and optic disc, which can exacerbate vision loss and cause pain. While there are several treatment modalities for CRAO, few have been proven to be effective in decreasing the effects of neovascularization. The use of hyperbaric oxygen (HBO2) therapy is often used in the treatment of CRAO due to its ease of use and relatively benign side effect profile. This study aims to assess the degree of improvement in visual acuity (VA) and neovascularization following HBO2. Our data ultimately shows that 20% of patients developed neovascularization after HBO2 compared to 29.8% of those who did not undergo HBO2 (p<.05). Our findings suggest that HBO2 has a statistically significant protective effect against neovascularization and may improve long-term visual acuity.

Sterile iris abscess associated with herpes zoster ophthalmicus.

PURPOSE: To report a case of a sterile iris abscess associated with herpes zoster ophthalmicus (HZO). OBSERVATIONS: A 69-year-old African American female presented to SUNY Downstate Medical Center complaining of left-sided eye pain for two weeks. The patient had a best-corrected visual acuity of 20/30 OD and 20/200 OS. On external exam, vesicles were noted on the left upper lid and tip of the nose. Anterior segment exam was notable for decreased sensation without epithelial defects. The patient had 2+ stromal edema with 3+ cell and flare. The iris was flat with 1+ nuclear sclerosis OU. The intraocular pressure (IOP) was 14 mmHg OD and 40 mmHg OS. The patient was diagnosed with HZO with secondary uveitic glaucoma.At ten weeks, anterior segment inflammation resolved and IOP stabilized. However, an iris nodule was noted superior nasal which continued to enlarge by 16 weeks follow up. Iris ultrasound revealed a 3 × 3 mm elevated lesion with internal homogeneity suggestive of an abscess.At five months, a dense, mature cataract developed. The patient underwent cataract extraction with sector iridectomy. Gram staining and cultures were negative for organisms but positive for polymorphic neutrophils. Histopathology revealed fibrosis, surface necrosis, and stromal infiltration with chronic inflammatory cells consistent with chronic iritis and a sterile abscess secondary to HZO. CONCLUSIONS AND IMPORTANCE: HZO is associated with a range of ocular sequelae with acquired iris nodule only mentioned once in the literature. As the second documented case, our findings will add to the general fund of knowledge regarding iris lesions and HZO.

Recurrent Herpes Zoster Ophthalmicus Preceded by Anabolic Steroids and High-Dose L-Arginine.

PURPOSE: To report a case of a 34-year-old male with recurrent herpes zoster ophthalmicus (HZO) preceded by a 6-week cycle of anabolic steroids and high-dose amino acid supplementation. Case Presentation. A 34-year-old man presented to our institution for left eye pain for one week associated with a vesicular rash in the V1 dermatome, respecting the midline. The patient had no significant past medical or past ocular history, including systemic immunosuppressive agents or HIV. However, prior to the onset of his symptoms the patient had completed a 6-week course of anabolic steroids including trenbolone, deca-durabolin, and testosterone as well as high-dose arginine supplementation averaging more than 40 grams a day. The best-corrected vision was 20/25 OS with slit-lamp examination remarkable for punctate staining and pseudodendrites at 6 o'clock, outside the visual axis. The patient was treated with oral acyclovir 800 mg five times a day for seven days along with prednisolone QID and moxifloxacin QID which was tapered over a month. Four months after resolution, the patient developed a recurrent HZO keratitis preceded by another cycle of anabolic steroids and amino acid supplementation. CONCLUSION: In vitro L-arginine supplementation has been associated with the proliferation and virulence of a variety of herpes viruses. Anabolic steroids have also been demonstrated by various studies to negatively affect cell-mediated immunity necessary to prevent viral infection. Thus, it is possible that anabolic steroids in conjunction with increased L-arginine intake may have precipitated a recurrent HZO in a previously healthy, immunocompetent individual.

Ets transcription factor GABP controls T cell homeostasis and immunity.

Peripheral T cells are maintained in the absence of vigorous stimuli, and respond to antigenic stimulation by initiating cell cycle progression and functional differentiation. Here we show that depletion of the Ets family transcription factor GA-binding protein (GABP) in T cells impairs T-cell homeostasis. In addition, GABP is critically required for antigen-stimulated T-cell responses in vitro and in vivo. Transcriptome and genome-wide GABP-binding site analyses identify GABP direct targets encoding proteins involved in cellular redox balance and DNA replication, including the Mcm replicative helicases. These findings show that GABP has a nonredundant role in the control of T-cell homeostasis and immunity.

Foxp3-independent mechanism by which TGF-ß controls peripheral T cell tolerance.

Peripheral T cell tolerance is promoted by the regulatory cytokine TGF-ß and Foxp3-expressing Treg cells. However, whether TGF-ß and Treg cells are part of the same regulatory module, or exist largely as distinct pathways to repress self-reactive T cells remains incompletely understood. Using a transgenic model of autoimmune diabetes, here we show that ablation of TGF-ß receptor II (TßRII) in T cells, but not Foxp3 deficiency, resulted in early-onset diabetes with complete penetrance. The rampant autoimmune disease was associated with enhanced T cell priming and elevated T cell expression of the inflammatory cytokine GM-CSF, concomitant with pancreatic infiltration of inflammatory monocytes that triggered immunopathology. Ablation of the GM-CSF receptor alleviated the monocyte response and inhibited disease development. These findings reveal that TGF-ß promotes T cell tolerance primarily via Foxp3-independent mechanisms and prevents autoimmunity in this model by repressing the cross talk between adaptive and innate immune systems.

"Just be a light": Experiences of peers working on acute inpatient psychiatric units.

OBJECTIVE: The study aimed to clarify the potential role and impact of behavioral health peer support providers on community hospital acute inpatient psychiatric units. METHOD: Qualitative interviews were conducted to examine perspectives of peer support providers (peers) and individuals who initially received peer services (recipients) during an inpatient stay on a community hospital psychiatric unit. Interviews elicited perspectives on interactions between peers and recipients, the role of peers vis-à-vis the clinical treatment team, and involvement of peers in discharge planning and transitions to community-based care. Fourteen interviews were completed (6 peers and 8 recipients of peer services); all were recorded, transcribed, and coded using a thematic analysis approach. RESULTS: Emergent themes were grouped into 3 domains: (a) initial impressions and client engagement, (b) peer interventions to support discharge planning, and (c) shared or sharing experiences in an inpatient setting. Recipients described inpatient experiences as disempowering and humiliating and reported powerful positive initial reactions to peers who had had similar experiences but who also displayed competence and professionalism. Peers and recipients described strong emotional connections that differed from traditional attitudes and relationships with clinical staff. Peers described challenges and obstacles related to interactions with the clinical treatment team, and both peers and recipients strongly endorsed the role of peers in facilitating successful care transitions. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Behavioral health peers can play important roles in acute inpatient psychiatric care, supplementing clinical treatment team activities and filling important gaps related to engagement, discharge planning, and care transitions. (PsycINFO Database Record

The cellular and molecular origin of tumor-associated macrophages.

Long recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being rediscovered as regulators of several diseases, including cancer. Here we show that in mice, mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). TAMs express the adhesion molecule Vcam1 and proliferate upon their differentiation from inflammatory monocytes, but do not exhibit an "alternatively activated" phenotype. TAM terminal differentiation depends on the transcriptional regulator of Notch signaling, RBPJ; and TAM, but not MTM, depletion restores tumor-infiltrating cytotoxic T cell responses and suppresses tumor growth. These findings reveal the ontogeny of TAMs and a discrete tumor-elicited inflammatory response, which may provide new opportunities for cancer immunotherapy.

TGF-ß cytokine signaling promotes CD8+ T cell development and low-affinity CD4+ T cell homeostasis by regulation of interleukin-7 receptor α expression.

Interleukin-7 receptor α chain (IL-7Rα) is induced upon T cell positive selection and controls thymic CD8-lineage specification and peripheral naive T cell homeostasis. How IL-7Rα expression is regulated in developing thymocytes is unclear. Here, we show that transforming growth factor ß (TGF-ß) signaling promoted IL-7Rα expression and CD8+ T cell differentiation. In addition, TGF-ß signaling was required for high IL-7Rα expression in CD4+ T cells bearing low-affinity T cell receptors, and the abrogation of TGF-ß receptor expression led to failed maintenance of peripheral CD4+ T cells. Compromised IL-7Rα expression in TGF-ß-receptor-deficient T cells was associated with increased expression of the Il7ra transcriptional repressor, Gfi-1. IL-7Rα transgenesis or T-cell-specific ablation of Gfi-1 restored IL-7Rα expression and largely ameliorated the development and homeostasis defects of TGF-ß-receptor-deficient T cells. These findings reveal functions for TGF-ß signaling in controlling IL-7Rα expression and in promoting T cell repertoire diversification.