Conjunctival epithelial response to experimental dryness is related to the degree of CD4+ T-cell infiltration and the level of IFN-gamma production. These findings suggest that IFN-gamma plays a pivotal role in promoting conjunctival squamous metaplasia in dry eye, and they provide insight into the immune pathogenesis of keratoconjunctivitis sicca.

Androgen and progesterone receptors (AR and PR) are two determining factors in gonadal differentiation that are highly expressed in developing and mature gonads. Loss of AR results in XY sex reversal and mutations causing reduced AR activity lead to varying degrees of defects in masculinization. Female PR knockout mice are infertile due to ovarian defects. While much has been discovered about positive regulation of these receptors by coactivators little is known about repression of the transcriptional activity of AR and PR in the presence of agonists. In this study we assessed the effect of SMRT and DAX-1 on AR and PR activity in the presence of both agonists and partial antagonists. We show that SMRT and DAX-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases. We demonstrate that endogenous agonist-bound PR and DAX-1 in T47D breast cancer cells and endogenous AR and DAX-1 in LNCaP prostate cancer cells can be coimmunoprecipitated suggesting that the interaction is physiological. Surprisingly, although DAX-1 represses partial antagonist activity of AR, it was ineffective in repressing partial antagonist induced activity of PR. In contrast to most reported repressors, the expression of DAX-1 is restricted. We found that although DAX-1 is expressed in normal human prostate, its expression is strongly reduced in benign prostatic hyperplasia suggesting that DAX-1 plays a role in limiting AR activity in prostate.Nuclear receptors are regulated both by coactivators and by corepressors. Although steroid receptor coactivators have been studied extensively, less is known about corepressors of agonist activated steroid receptors. Androgens, acting through AR, 1 play a role in both benign prostatic hyperplasia (BPH) and prostate cancer. In both cases, reduction in AR activity is an important component of treatment, although fully effective treatments are not yet available. Two well characterized corepressors of thyroid receptor (TR) activity, NCoR (nuclear receptor co-repressor) and SMRT (silencing mediator for retinoid acid receptor (RAR) and TR), have been identified previously (1, 2). They appear to work through binding to TR aporeceptor, recruiting complexes containing histone deacetylases (HDACs); they dissociate from the receptor upon agonist binding allowing coactivator complexes to form (3). In the case of estrogen receptor (ER), these repressors interact with the antagonist bound receptor through a region that largely overlaps with the coactivator binding interface, and recruit HDACs (4). An orphan nuclear receptor DAX-1 (dosage sex reversal, adrenal hypoplasia congenita critical region on the X chromosome, gene 1) has been reported to inhibit steroidogenic factor 1 (SF-1) and ER activity (5, 6). DAX-1 is an atypical nuclear receptor containing an ssDNA/RNA binding domain in its N terminus and a multihelical C-terminal domain, a putative ligand binding domain (LBD) (7). DAX-1 i...

Young adults are the highest consumers of food prepared outside home, which has been linked to weight gain. The aim of this qualitative research was to gather opinions from young adults about what influences their food choice when eating out and if they so desired, what might enable healthy choices. Thirty-one adults aged 18 to 30 years participated in four focus groups (females = 24). Predetermined questions were used to guide discussions which were audiotaped then transcribed. The content was organized into themes and sub-themes using NVivo software. Two broad groupings arose—personal behaviors and changes to physical and social food environments. For many, eating out was viewed as a special occasion so that healthy food was not a priority and despite understanding health consequences of poor diets this was not an immediate concern. Price discounts and menu-labelling were suggested and trust in credible organizations and peers’ endorsement of meals and venues expressed. The role of smartphones in the modern food environment emerged as a tool to enable immediate access to many restaurants to order food and access reviews and social media as a source of persuasive food imagery. Current menu-labelling initiatives should continue, food pricing be explored and influence of smartphones on diet further researched. However, these findings may be limited by the high proportion of women and higher socioeconomic status and urban residence of many participants.

These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.

The pathogenesis of CME without leakage is poorly understood; however, fluid accumulation in Muller cells due to toxicity has been proposed. The persistence of CME suggests that additional nonvascular endothelial growth factor-mediated mechanisms are involved. Improved understanding of the mechanisms underlying paclitaxel-associated CME is needed, especially in patients with limited systemic options for metastatic carcinoma.

BackgroundEndogenous endophthalmitis secondary to Nocardia species is extremely rare but often portends a poor visual prognosis often owing to the advanced nature of disease at presentation and delay in diagnosis. Patients who are systemically immunosuppressed are at greatest risk and early suspicion of the role of this organism in patients with acute panuveitis is paramount.FindingsA 66-year-old cardiac transplant patient on oral prednisone, Myfortic, and tacrolimus developed unilateral panuveitis with a focal white subretinal and retinal lesion. His past medical history was notable for Aspergillus pneumonia and cytomegalovirus retinitis in the contralateral eye 12 months prior. Aqueous humor sampling for eubacterial, eufungal, and viral PCR testing, as well as vitreous cultures for bacteria and fungi were unsuccessful in the identification of a causative organism. Progressive enlargement of the lesion was noted despite intravitreal foscarnet, vancomycin, ceftazidime, and voriconazole. A pars plana vitrectomy and retinal and subretinal biopsy led to the identification of Nocardia veterana, a recently identified Nocardia species. A combination of linezolid, meropenem, azithromycin, ceftriaxone, and intravitreal amikacin resulted in eradication of the infection.ConclusionThis is the first reported case of N. veterana endogenous endophthalmitis in an immunosuppressed patient. Pars plana vitrectomy with a subretinal biopsy was required to establish a diagnosis, as other testing including aqueous PCR and vitreous cultures were negative. The poor visual outcome in our patient highlights the importance of early consideration of Nocardia in the differential diagnosis of panuveitis with subretinal disease in the context of immunosuppression.

Both infectious and non-infectious forms of uveitis occur in individuals who are infected with human immunodeficiency virus and have preserved or restored peripheral CD4+ T cell levels. Individuals who are human immunodeficiency virus-positive and present with uveitis should be evaluated in the same way all patients with uveitis are assessed.

A 62-year-old man with lung cancer presented with a 2-week history of decreased vision and clinical features of cytomegalovirus retinitis. The patient was empirically treated for viral retinitis, but microbiological testing of the vitreous fluid was negative. Based on the suspicion for retinal metastasis, the patient underwent pars plana vitrectomy with retinal biopsy. Surgical techniques included the use of a chandelier illumination to enable bimanual manipulation of the retinal tissue, creation a focal retinal detachment with a 41-gauge subretinal cannula, diathermy demarcation of the biopsy site, localized retinectomy with vertical scissors, endolaser, and long-acting gas tamponade. Histopathologic examination revealed sheets of tumor cells with pleomorphic nuclei and positive staining for cytokeratins consistent with metastatic adenocarcinoma. The patient subsequently underwent external beam radiation and was alive 10 months after presentation. This surgical technique may be valuable in select patients with retinal metastasis for diagnostic, therapeutic, and counseling purposes.