IL-21/type I interferon interplay regulates neutrophil-dependent innate immune responses to Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major hospital- and community-acquired pathogen, but the mechanisms underlying host-defense to MRSA remain poorly understood. Here, we investigated the role of IL-21 in this process. When administered intra-tracheally into wild-type mice, IL-21 induced granzymes and augmented clearance of pulmonary MRSA but not when neutrophils were depleted or a granzyme B inhibitor was added. Correspondingly, IL-21 induced MRSA killing by human peripheral blood neutrophils. Unexpectedly, however, basal MRSA clearance was also enhanced when IL-21 signaling was blocked, both in Il21r KO mice and in wild-type mice injected with IL-21R-Fc fusion-protein. This correlated with increased type I interferon and an IFN-related gene signature, and indeed anti-IFNAR1 treatment diminished MRSA clearance in these animals. Moreover, we found that IFNß induced granzyme B and promoted MRSA clearance in a granzyme B-dependent fashion. These results reveal an interplay between IL-21 and type I IFN in the innate immune response to MRSA.

IGG4-RELATED OPHTHALMIC DISEASE PRESENTING AS CHOROIDAL AND ORBITAL LESIONS.

PURPOSE: To report a case of IgG4-related ophthalmic disease (IgG4-ROD) which presented as choroidal and orbital lesions. METHODS: Case report. RESULTS: A 64-year-old man presented with left eye photopsias and a history of IgG4-related perirenal fibrosis. Fundoscopic examination showed multiple bilateral yellow choroidal lesions, and optical coherence tomography showed multiple choroidal lesions. Magnetic resonance imaging of the orbits showed an enhancing lesion present circumferential to the optic nerve, but greater medially, abutting the posterior surface of the left globe. Workup for infectious, autoimmune, and malignant etiologies was negative, and the patient has responded well to treatment with rituximab. CONCLUSION: IgG4-related disease is a systemic fibroinflammatory disease, which often presents in another location, as in our patient. In cases of uncertain choroidal and orbital lesions, a thorough workup for other etiologies is indicated, and lymphoma must be ruled out. Steroids are the mainstay of treatment for IgG4-ROD, however, small case series and our patient responded well to rituximab. To our knowledge, this is the first reported case of choroidal and orbital lesions secondary to IgG4-ROD.

Retrospective analyses of optical coherence tomography in recurrent macular edema following intravitreal therapy in patients with retinal vein occlusion.

BACKGROUND: Optical coherence tomography has focused mainly on central subfield thickness to quantify macular edema in central and branch retinal vein occlusion. We examined macular fields other than the central subfield to determine if they are possibly independent indicators of recurrent macular edema. METHODS: Single center, retrospective, consecutive case study of patients with recurrent macular edema secondary to either central or branch retinal vein occlusion. Thickness estimates of serial domain optical coherence tomography macular fields were obtained at the time of recurrent macular edema and analyzed retrospectively. Changes were expressed as a percentage of previous baseline levels. Change in thickness at each retreatment episode as well as average changes in thickness were calculated for each macular field for each eye. Data were analyzed via analysis of variance and Fisher's post hoc analyses. The macular field which most frequently had the largest percent increase at the time of recurrence was also assessed using averages for each subject as well as for each retreatment episode. Individual episodes of recurrent macular edema were also examined to ascertain the frequency in which there was minimal foveal edema (<15 µm increase), but non-foveal edema was considered severe enough to warrant retreatment. RESULTS: 429 episodes of recurrent macular edema in 80 eyes were examined. In addition to the central subfield, the average mean change in thickness of the most affected quadrant (central vein occlusion) or hemisphere (branch vein occlusion) of the extrafoveal 3 mm band had the largest mean changes and also most frequently had the largest increases at the time of recurrent macular edema. In approximately 20 % of both central and branch occlusions, recurrent macular edema was detected in non-central macular fields in the absence of significant edema in the central subfield. CONCLUSIONS: Analyses of non-central macular fields as well as the central subfield may be useful in the early detection and treatment of recurrent macular edema in retinal vein occlusion.

Experiential benefits, place meanings, and environmental setting preferences between proximate and distant visitors to a national scenic trail.

Effective management of conserved natural areas often requires a good understanding of recreation visitors who possess various values for those areas. This study examined differences in experiential benefits sought, place meanings, and environmental setting preferences between proximate and distant visitors to a publicly managed national scenic trail, which transects a variety of conserved public lands. Data were collected using on-site post-hike interviews with visitors at low, moderate, and high use trailheads. Proximate visitors sought mental and physical health more strongly than distant visitors, while distant visitors sought environmental exploration more strongly than proximate visitors. No significant difference in family bonding and achievement benefits existed between the two groups. Meanings related to place dependence, family identity, community identity, and place identity were more strongly ascribed by proximate visitors, and both groups rated ecological integrity meanings highly. Distant visitors showed stronger tendencies toward preferring a lesser level of trail development, lower level of encounters with other groups, and higher level of natural landscapes, which indicated an inclination toward natural settings. These findings indicate a managerially relevant role of the degree of proximity to environmental resources on individuals' recreation behaviors, meanings ascribed to the resources and setting conditions. Understanding differences and similarities between groups dichotomized by proximity to natural resources should advance more effective management of recreation and benefit opportunities for diverse visitor groups.

Identifying differences between off-highway vehicle (OHV) and non-OHV user groups for recreation resource planning.

Off-highway vehicle (OHV) riding is among the fastest growing recreational activities in the United States. However, little research exists about the central components of outcomes-focused management (OFM) as it relates to motorized recreation. Utilizing a two-activity dichotomy, OHV and non-OHV centric user groups were compared on several key concepts associated with OFM, including desired experiences, perceived and desired recreation opportunity spectrum-type settings, and intentional behaviors (i.e., place-protective behavior, spending-time intentions) toward potential changes in settings. Results indicated that the two groups were different in terms of intensity and relative rankings of their perceived experiences and settings. Although both groups preferred social bonding, stress relief, nostalgia and learning experiences, the OHV user group ranked using equipment and achieving physical fitness experiences as more important than the non-OHV group. The non-OHV user group preferred enjoying nature and solitude/tranquility experiences more strongly than the OHV user group. Further analysis found that both groups perceived settings that they recreated in to be pristine and preferred such conditions, and both groups preferred moderate levels of rules and regulations. Finally, the OHV user group was more reactive to rules and regulations, while the non-OHV user group expressed stronger intentions to protect the environmental quality of recreation areas. The results suggest that planners and managers who understand OHV user's perceptions and behaviors could provide enhanced recreation opportunities potentially providing additional beneficial outcomes for motorized and non-motorized groups in spatially different zones. Additional implications for planners and managers and future studies are discussed.

Do humans use episodic memory to solve a What-Where-When memory task?

What-Where-When (WWW) memory tasks have been used to study episodic(-like) memory in non-human animals. In this study, we investigate whether humans use episodic memory to solve such a WWW memory task. Participants are assigned to one of two treatments, in which they hide different coin types (what) in different locations (where) on two separate occasions (when). In the Active treatment, which mimics the animal situation as closely as possible, participants are instructed to memorize the WWW information; in the Passive treatment, participants are unaware of the fact that memory will be tested. In both groups, the majority of participants report using a mental time travel strategy to solve the task, and performance on a different episodic memory test significantly predicts performance on the WWW memory task. This suggests that the WWW memory task is a good test of episodic memory in humans. Participants remember locations and coins from the first hiding session better than they do those of the second hiding session, suggesting their memories may be reinforced during the second hiding session. We also investigated how well episodic memory performance predicted performance on the three aspects of the WWW memory task separately. In the Passive treatment, episodic memory performance predicts performance on all three aspects of the WWW memory task equally. However, in the Active treatment it only predicts performance on the what component. This could imply that during active encoding a different memory system is used for where and when information than during passive encoding. Encoding of what information seems to rely on episodic memory processing in both conditions.