Safety Profile of Stromal Hydration of Clear Corneal Incisions with Cefuroxime in the Mouse Model

PURPOSE: The use of sutureless clear corneal incisions (CCIs) for phacoemulsification is an established surgical technique, but the dynamic morphology of the wound and poor construction can lead to an increased risk of postoperative endophthalmitis. Stromal hydration with balanced salt solution (BSS) can improve the self-sealing status. Intracameral cefuroxime has reduced endophthalmitis rates. This study investigates the safety profile of stromal hydration with cefuroxime, as sequestering antibiotic at the wound may potentially provide added protection against infection. METHODS: MF-1 mice underwent bilateral CCI, followed by stromal hydration with 5 μL of 10 mg/mL cefuroxime, cefuroxime-texas red conjugate (for detection using confocal microscopy), or BSS. Corneas were harvested from 1 h to 12 weeks postoperatively; gross morphology, histology, and apoptotic cell death levels were investigated to determine the safety profile. Bactericidal activity of cefuroxime was assayed using homogenized whole cornea following stromal hydration at 1 h, 24 h, and day 7 against gram-negative Escherichia coli. RESULTS: Cefuroxime stromal hydration did not alter corneal morphology, with no evidence of corneal scarring or vascularization. Corneal histology and levels of apoptosis were minimal and comparable to the BSS groups up to 12 weeks. Confocal microscopy detected cefuroxime-texas red up to 1 week surrounding the corneal wound. Whole corneal tissue homogenates displayed bactericidal activity up to 24 h postoperatively. CONCLUSIONS: Stromal hydration of CCI with cefuroxime is safe in mouse corneas. A reservoir of antibiotic at the wound can potentially act as a barrier of defense against infection following cataract and associated ocular surgery

High-mobility Group Box 1 Protein Initiates Postoperative Cognitive Decline by Engaging Bone Marrow-derived Macrophages

Background: Aseptic trauma engages the innate immune response to trigger a neuroinflammatory reaction that results in postoperative cognitive decline. The authors sought to determine whether high-mobility group box 1 protein (HMGB1), an ubiquitous nucleosomal protein, initiates this process through activation and trafficking of circulating bone marrow-derived macrophages to the brain. Methods: The effects of HMGB1 on memory (using trace fear conditioning) were tested in adult C57BL/6J male mice; separate cohorts were tested after bone marrow-derived macrophages were depleted by clodrolip. The effect of anti-HMGB1 neutralizing antibody on the inflammatory and behavioral responses to tibial surgery were investigated. Results: A single injection of HMGB1 caused memory decline, as evidenced by a decrease in freezing time (52 11% vs. 39 +/- 5%; n = 16-17); memory decline was prevented when bone marrow-derived macrophages were depleted (39 +/- 5% vs. 50 +/- 9%; n = 17). Disabling HMGB1 with a blocking monoclonal antibody, before surgery, reduced postoperative memory decline (52 +/- 11% vs. 29 +/- 5%; n = 15-16); also, hippocampal expression of monocyte chemotactic protein-1 was prevented by the neutralizing antibody (n = 6). Neither the systemic nor the hippocampal inflammatory responses to surgery occurred in mice pretreated with anti-HMGB1 neutralizing antibody (n = 6). Conclusion: Postoperative neuroinflammation and cognitive decline can be prevented by abrogating the effects of HMGB1. Following the earlier characterization of the resolution of surgery-induced memory decline, the mechanisms of its initiation are now described. Together, these data may be used to preoperatively test the risk to surgical patients for the development of exaggerated and prolonged postoperative memory decline that is reflected in delirium and postoperative cognitive dysfunction, respectively

The effect of infection with tobacco-mosaic virus on the levels of nitrogen, phosphorus, protease, and pectase in tobacco leaves and on their response to fertilizers

RESP-273

The effect of fertilizers on the levels of nitrogen, phosphorus, protease, and pectase in healthy tobacco leaves

RESP-273

Desistance and Legitimacy: The Impact of Offender Notification Meetings on Recidivism Among High Risk Offenders

Objective: Legitimacy-based approaches to crime prevention operate under the assumption that individuals — including violent offenders — are more likely to comply with the law when they believe that the law and its agents are legitimate and act in ways that seem inherently “fair” and “just.” While mounting evidence finds an association between such legitimacy-based programs and reductions in aggregate levels of crime and violence, no study has investigated whether such programs influence individual offending. This study evaluates the effectiveness of one such program — Project Safe Neighborhoods’ (PSN) Offender Notification Meetings — at reducing individual recidivism among a population of returning prisoners in Chicago. Methods: This study uses a quasi-experimental design and two types of survival analyses (Cox hazard models and competing risk models) to evaluate the effects of PSN on the subsequent recidivism of program participants relative to the control group. Results: Cox hazard models and competing risk models suggest that involvement in PSN significantly reduces the risk of subsequent incarceration. In fact, participation in PSN Offender Notification Forums is associated with a significant lengthening of the time that offenders remain on the street and out of prison. Conclusion: This study provides some of the first individual-level evidence of the efficacy of such programs on patterns of individual offending. Results suggest that interventions such as these do indeed reduce rates of recidivism in the treatment group

Improving the measurement of QALYs in dementia: developing patient- and carer-reported health state classification systems using Rasch analysis

Objectives: Cost-utility analysis is increasingly used to inform resource allocation. This requires a means of valuing health states before and after intervention. Although generic measures are typically used to generate values, these do not perform well with people with dementia. We report the development of a health state classification system amenable to valuation for use in studies of dementia, derived from the DEMQOL system, a measure of health-related quality of life in dementia by patient self-report (DEMQOL) and carer proxy-report (DEMQOL-Proxy). Methods: Factor analysis was used to determine the dimensional structure of DEMQOL and DEMQOL-Proxy. Rasch analysis was subsequently used to investigate item performance across factors in terms of item-level ordering, functioning across subgroups, model fit and severity-range coverage. This enabled the selection of one item from each factor for the classification system. A sample of people with a diagnosis of mild/moderate dementia (n=644) and a sample of carers of those with mild/moderate dementia (n=683) were used. Results: Factor analysis found different 5-factor solutions for DEMQOL and DEMQOL-Proxy. Following item reduction and selection using Rasch analysis, a 5-dimension classification for DEMQOL and a 4-dimension classification for DEMQOL-Proxy were developed. Each item contained 4 health state levels. Conclusion: Combining Rasch and classical psychometric analysis is a valid method of selecting items for dementia health state classifications from both the patient and carer perspectives. The next stage is to obtain preference weights so that the measure can be used in the economic evaluation of treatment, care and support arrangements for dementia.quality adjusted life years; health related quality of life; Rasch analysis; preference-based measures of health; health states; dementia

The occurrence of chitinase in some bacteria

RESP-355

Editorial: Deep Pelagic Ecosystem Dynamics in a Highly Impacted Water Column: The Gulf of Mexico After Deepwater Horizon

The intermediate-sized midwater fauna (fishes, shrimps, and cephalopods; “micronekton” collectively) are dominant components of the pelagic ocean, which is by far the largest ecosystem type on Earth by several metrics (volume, organismal numbers, biomass, and productivity). Deep-pelagic micronekton, those animals residing in the water column below 200 m depth during the day, are the direct link between plankton and oceanic top predators, and through the linked processes of feeding and daily vertical migration facilitate one of Earth\u27s most important ecosystem services to humans, carbon sequestration. Despite increasing recognition of this importance, a disconnect exists between stewardship and human impact; only a miniscule fraction of the deep-pelagic ocean has been studied in detail, while anthropogenic threats to that system are increasing rapidly. Perhaps nowhere on Earth is that dichotomy more demonstrable than the Gulf of Mexico (Gulf hereafter), a complex, high-diversity ecosystem under intense human usage and subjected to arguably the worst marine pollution event in human history. Assessment of the impacts of the Deepwater Horizon disaster to the deep-pelagic biota was impeded from the start by the lack of pre-event information, both in terms of baselines (faunal composition, abundance, and distribution) and in terms of understanding natural variability, against which impacts of anthropogenic disturbance could be detected and quantified. In this Research Topic, we present a description of three interlinked research programs (ONSAP, DEEPEND, and DEEPEND|RESTORE, described below) that began in 2010 and continue as of this writing. These programs were designed to investigate key aspects of the Gulf pelagic ecosystem, including its faunal structure, biophysical drivers of that structure, organismal and community ecology, natural variability, and potential resilience to disturbance. The contributed papers are grouped below by major themes, indicated in the conceptual model (Figure 1) of DEEPEND (Deep Pelagic Nekton Dynamics; www.deependconsortium.org), the largest of the three aforementioned research programs