Involvement of B cells in non-infectious uveitis

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Non-infectious uveitis—or intraocular inflammatory disease—causes substantial visual morbidity and reduced quality of life amongst affected individuals. To date, research of pathogenic mechanisms has largely been focused on processes involving T lymphocyte and/or myeloid leukocyte populations. Involvement of B lymphocytes has received relatively little attention. In contrast, B-cell pathobiology is a major field within general immunological research, and large clinical trials have showed that treatments targeting B cells are highly effective for multiple systemic inflammatory diseases. B cells, including the terminally differentiated plasma cell that produces antibody, are found in the human eye in different forms of non-infectious uveitis; in some cases, these cells outnumber other leukocyte subsets. Recent case reports and small case series suggest that B-cell blockade may be therapeutic for patients with non-infectious uveitis. As well as secretion of antibody, B cells may promote intraocular inflammation by presentation of antigen to T cells, production of multiple inflammatory cytokines and support of T-cell survival. B cells may also perform various immunomodulatory activities within the eye. This translational review summarizes the evidence for B-cell involvement in non-infectious uveitis, and considers the potential contributions of B cells to the development and control of the disease. Manipulations of B cells and/or their products are promising new approaches to the treatment of non-infectious uveitis

Managing Roof Rats in Citrus Orchards: Initial Efforts toward Building an Integrated Pest Management Program

Roof rats cause extensive damage in orchards throughout the world. Integrated Pest Management (IPM) systems are the best option for managing rodents, yet few management systems have been developed and tested to control roof rats in agricultural settings. We initiated a study in 2020 to provide the foundation for an IPM program to manage roof rats in California citrus orchards. Our initial efforts centered on developing effective monitoring strategies for roof rats to determine when management actions are needed, assessing rat movement patterns to determine proper placement of management tools, and conducting initial tests of Goodnature A24 self-resetting traps and elevated bait stations containing 0.005% diphacinone-treated oats. We determined that the use of both tracking tunnels and remote-triggered cameras served as effective monitoring tools for roof rats in citrus orchards, and a smaller 3 × 3 grid placement of these monitoring tools was as effective as a 5 × 5 grid, indicating that substantial material and labor costs could be saved by using the smaller grid size. Placement of the monitoring tools on the ground or up in trees did not influence the effectiveness of this approach. We determined that roof rats exclusively used orchard habitats rather than surrounding fields, so control efforts should be focused in these areas. Roof rats moved substantial distances daily (~170-190 m), but results from bait station trials suggest that spacing of bait stations and traps should be closer together to increase roof rat encounter rates of these devices. Our trial with A24 traps elevated in orchard canopies suggest that there is an advantage to including a platform underneath the trap to increase trap activation. Collectively, this information provides a baseline for future research targeted at developing an effective IPM program for managing roof rats in citrus orchards

Humans, but not their dogs, displace pumas from their kills: An experimental approach

Domestic dogs are the most abundant large carnivore on the planet, and their ubiquity has led to concern regarding the impacts of dogs as predators of and competitors with native wildlife. If native large carnivores perceive dogs as threatening, impacts could extend to the community level by altering interactions between large carnivores and their prey. Dog impacts may be further exacerbated if these human-associated predators are also perceived as indicators of risk from humans. However, observational approaches used to date have led to ambiguity regarding the effects of dog presence on wildlife. We experimentally quantified dog impacts on the behavior of a native large carnivore, presenting playbacks of dog vocalizations to pumas in central California. We show that the perceived presence of dogs has minimal impacts on puma behavior at their kill sites, and is no more likely to affect total feeding time at kills than non-threatening controls. We previously demonstrated that pumas exhibit strong responses to human cues, and here show that perceived risk from human presence far exceeds that from dogs. Our results suggest that protected areas management policies that restrict dogs but permit human access may in some cases be of limited value for large carnivores

A proper understanding of Millikan

Ruth Millikan’s teleological theory of mental content is complex and often misunderstood. This paper motivates and clarifies some of the complexities of the theory, and shows that paying careful attention to its details yields answers to a number of common objections to teleological theories, in particular, the problem of novel mental states, the problem of functionally false beliefs, and problems about indeterminacy or multiplicity of function

Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer

Background Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. Methods All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. Results The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet Trialists’ Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P = 0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes. Conclusions Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months’ duration. (Current Controlled Trials number, ISRCTN98278138.

Fear of the human ‘super predator’ reduces feeding time in large carnivores

Large carnivores’ fear of the human ‘super predator’ has the potential to alter their feeding behaviour and result in human-induced trophic cascades. However, it has yet to be experimentally tested if large carnivores perceive humans as predators and react strongly enough to have cascading effects on their prey. We conducted a predator playback experiment exposing pumas to predator (human) and non-predator control (frog) sounds at puma feeding sites to measure immediate fear responses to humans and the subsequent impacts on feeding. We found that pumas fled more frequently, took longer to return, and reduced their overall feeding time by more than half in response to hearing the human ‘super predator’. Combined with our previous work showing higher kill rates of deer in more urbanized landscapes, this study reveals that fear is the mechanism driving an ecological cascade from humans to increased puma predation on deer. By demonstrating that the fear of humans can cause a strong reduction in feeding by pumas, our results support that non-consumptive forms of human disturbance may alter the ecological role of large carnivores

Gene expression profiling of whole blood: Comparison of target preparation methods for accurate and reproducible microarray analysis

<p>Abstract</p> <p>Background</p> <p>Peripheral blood is an accessible and informative source of transcriptomal information for many human disease and pharmacogenomic studies. While there can be significant advantages to analyzing RNA isolated from whole blood, particularly in clinical studies, the preparation of samples for microarray analysis is complicated by the need to minimize artifacts associated with highly abundant globin RNA transcripts. The impact of globin RNA transcripts on expression profiling data can potentially be reduced by using RNA preparation and labeling methods that remove or block globin RNA during the microarray assay. We compared four different methods for preparing microarray hybridization targets from human whole blood collected in PAXGene tubes. Three of the methods utilized the Affymetrix one-cycle cDNA synthesis/in vitro transcription protocol but varied treatment of input RNA as follows: i. no treatment; ii. treatment with GLOBINclear; or iii. treatment with globin PNA oligos. In the fourth method cDNA targets were prepared with the Ovation amplification and labeling system.</p> <p>Results</p> <p>We find that microarray targets generated with labeling methods that reduce globin mRNA levels or minimize the impact of globin transcripts during hybridization detect more transcripts in the microarray assay compared with the standard Affymetrix method. Comparison of microarray results with quantitative PCR analysis of a panel of genes from the NF-kappa B pathway shows good correlation of transcript measurements produced with all four target preparation methods, although method-specific differences in overall correlation were observed. The impact of freezing blood collected in PAXGene tubes on data reproducibility was also examined. Expression profiles show little or no difference when RNA is extracted from either fresh or frozen blood samples.</p> <p>Conclusion</p> <p>RNA preparation and labeling methods designed to reduce the impact of globin mRNA transcripts can significantly improve the sensitivity of the DNA microarray expression profiling assay for whole blood samples. While blockage of globin transcripts during first strand cDNA synthesis with globin PNAs resulted in the best overall performance in this study, we conclude that selection of a protocol for expression profiling studies in blood should depend on several factors, including implementation requirements of the method and study design. RNA isolated from either freshly collected or frozen blood samples stored in PAXGene tubes can be used without altering gene expression profiles.</p

Prevalence of toxoplasmic retinochoroiditis in an Australian adult population: A community-based study

Purpose: Toxoplasmic retinochoroiditis is the most common clinical manifestation of an infection with the protozoan parasite, Toxoplasma gondii. Up to 50 % of the human population is estimated to be infected with T. gondii; however, the epidemiology of toxoplasmic retinochoroiditis has not been widely reported. We sought to estimate the prevalence of toxoplasmic retinochoroiditis in Australia using data that were collected as part of the Busselton Healthy Ageing Study. Design: oss-sectional, community-based, prospective cohort study. Participants: 5020 Australian adults (2264 men and 2756 women; age range, 45–69 years, and median age, 58 years). Methods : Retinal color photographs, centered on the optic disc and macula, were captured using a digital retinal camera after the dilation of the pupils. Three uveitis-subspecialized ophthalmologists assessed each pigmented retinal lesion, and complete concordance of opinion was required to assign a toxoplasmic etiology. Serum T. gondii immunoglobulin (Ig)G levels were measured for those participants with retinal lesions judged to be toxoplasmic retinochoroiditis. Main Outcome Measures : Prevalence of toxoplasmic retinochoroiditis. Results: Eight participants (0.16 %) had retinal lesions that were considered to have the characteristic appearance of toxoplasmic retinochoroiditis, plus detectable serum T. gondii IgG, consistent with the diagnosis of toxoplasmic retinochoroiditis. On the assumption that 23.81 % of retinal lesions occur at the posterior pole, as reported in a community-based survey conducted in Brazil (Sci Rep. 2021;11:3420), the prevalence of toxoplasmic retinochoroiditis was estimated to be 0.67 % or 1 per 149 persons. Conclusions: Toxoplasmic retinochoroiditis is common in Australian adults. Efforts to quantify and address risk factors for human infection with T. gondii are justified