Comparative efficacy of a secretory phospholipase A2 inhibitor with conventional anti-inflammatory agents in a rat model of antigen-induced arthritis

INTRODUCTION: Previously, secretory phospholipase A(2 )(sPLA(2)) inhibition has been used as an adjunct to conventional rheumatoid arthritis therapy in human clinical trials without significant improvement of arthritic pathology. In this study, we compared the efficacy of a potent and orally active group IIa secretory phospholipase A(2 )inhibitor (sPLA(2)I) to conventional anti-arthritic agents; infliximab, leflunomide and prednisolone, in a rat model of antigen-induced arthritis. METHODS: Initially, to establish efficacy and dose-response, rats were orally dosed with the sPLA(2)I (1 and 5 mg/kg) two days prior to arthritis induction, and then daily throughout the 14-day study period. In the second trial, rats were orally dosed with the sPLA(2)I (5 and 10 mg/kg/day) beginning two days after the induction of arthritis, at the peak of joint swelling. Separate groups of rats were also dosed with the tumour necrosis factor-alpha (TNF-α) inhibitor infliximab (single 3 mg/kg i.v. injection), leflunomide (10 mg/kg/day, oral) or prednisolone (1 mg/kg/day, oral) at this same time point and used as comparative treatments. RESULTS: In the pathology prevention trial, both 1 and 5 mg/kg dose groups of sPLA(2)I demonstrated a significant reduction in joint swelling and gait disturbances; however, only the higher 5 mg/kg dose resulted in significantly reduced histopathology scores. In the post-induction trial, rats dosed with sPLA(2)I showed a significant improvement in joint swelling and gait scoring, whereas none of the conventional therapeutics achieved a significant decrease in both of these two disease markers. Histopathological scoring at the end-point of the study demonstrated significantly reduced median scores in rats treated with 10 mg/kg sPLA(2)I and leflunomide. CONCLUSIONS: The results from this study suggest a pathogenic role for sPLA(2 )enzymes in this model of arthritis in rats, and the potential clinical utility of sPLA(2 )inhibition as a safer, and more effective, alternative to conventional anti-arthritic therapeutics

Developing a COVID-19 Medical Respite Unit for Adults Experiencing Homelessness: Lessons Learned from an Interdisciplinary Community-Academic Partnership

Individuals experiencing homelessness are at particularly high risk for infection, severe illness, and death from COVID19. Local public health initiatives to address the pandemic should include medical respite services for individuals experiencing homelessness with documented or suspected COVID-19 infection, who are well enough to not be admitted to the hospital. We are a group of public health officials, clinicians, academics, and non-profit leaders who partnered with the City of New Haven, Connecticut to develop a COVID-19 medical respite program for people experiencing homelessness in our community. We seek to describe the key processes and challenges inherent to designing the COVID-19 respite including: the balance between patient autonomy and a public health agenda, how to deliver trauma informed, equitable, patient-centered, high quality care with low resources, and approaches to program evaluation.There is no funding specific to this article. This publication was made possible by the Yale National Clinician Scholars Program and by CTSA Grant Number TL1 TR001864 from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH.https://deepblue.lib.umich.edu/bitstream/2027.42/155396/1/Nash main article.pdfDescription of Nash main article.pdf : Main articl

Adaptation to climate change in the Ontario public health sector

Background: Climate change is among the major challenges for health this century, and adaptation to manage adverse health outcomes will be unavoidable. The risks in Ontario – Canada’s most populous province – include increasing temperatures, more frequent and intense extreme weather events, and alterations to precipitation regimes. Socio-economic-demographic patterns could magnify the implications climate change has for Ontario, including the presence of rapidly growing vulnerable populations, exacerbation of warming trends by heat-islands in large urban areas, and connectedness to global transportation networks. This study examines climate change adaptation in the public health sector in Ontario using information from interviews with government officials. Methods: Fifty-three semi-structured interviews were conducted, four with provincial and federal health officials and 49 with actors in public health and health relevant sectors at the municipal level. We identify adaptation efforts, barriers and opportunities for current and future intervention. Results: Results indicate recognition that climate change will affect the health of Ontarians. Health officials are concerned about how a changing climate could exacerbate existing health issues or create new health burdens, specifically extreme heat (71%), severe weather (68%) and poor air-quality (57%). Adaptation is currently taking the form of mainstreaming climate change into existing public health programs. While adaptive progress has relied on local leadership, federal support, political will, and inter-agency efforts, a lack of resources constrains the sustainability of long-term adaptation programs and the acquisition of data necessary to support effective policies. Conclusions: This study provides a snapshot of climate change adaptation and needs in the public health sector in Ontario. Public health departments will need to capitalize on opportunities to integrate climate change into policies and programs, while higher levels of government must improve efforts to support local adaptation and provide the capacity through which local adaptation can succeed

Prelude to Artifact

The book is a place, a moral and intellectual site. With any luck, a well-written book calls the real condition of a reader\u27s perception into question. Amid books written for leisure, instruction, or the sake of sheer indulgence, there are those books which can be classified as fated providers of Truth. The function of such books is not mere representation, but rather transformation and transfiguration of the reader\u27s soul--and consequently, the world. As writer/scholar Henry Corbin illustrates: All the elements [in a work of Symbolic Art] are represented in their real dimension in the present , in each case perpendicularly to the axis of the viewer\u27s vision. The viewer is not meant to immobilize himself at a particular point, enjoying the privilege of presentness and to raise his eyes from this fixed point; he must raise himself toward each of the elements represented. Contemplation of the image becomes a mental itinerary, an inner accomplishment; the image fulfills the function of a mandala. Because each of the elements is presented not in its proper dimension, but being that same dimension, to contemplate them is to enter into a multidimensional world... 1 Let this passage act as retrospective inspiration for my MFA thesis project. Though in my wildest dreams am I not delusional enough to consider what I have created Symbolic Art, I do wish to teeter alongside such a capacity in hopes that (in my wildest dreams) I may someday create a work that falls close to such achievement. In the pages of my thesis, I attempted to strike a balance between form and formlessness, although I often placed more importance on the energy from which each piece was created, rather than the form each part eventually acquired. This follows my beliefs that 1) form is the debris of energy, 2) the poem is the debris of poetry; and 3) only through the loss of form are we led to the true spirit of things. Or perhaps there are just excused for my inability to commit to one particular shape for this thesis project. My view of the novel as a social contract, as story-telling around the tribal fire, kept me wanting to contribute to the cultural story-telling canon--yet I was born with a poet\u27s soul--and poetry is far from a contract; a poem is created away from the social order, in solitary happiness. Thank you Don for writing, Humanness is, after all, a little portion shared. But the gospel of happiness...delights in itself all alone. 2/ In these pages, you may also find the curiosity of a child integrated with the intellectual and emotional life of an adult. While I crave the clarity rendered from an examined life, I refuse to be corralled by the rational mind. I\u27m sure this is reflected in my work. As is my love affair with `the new\u27. To avoid being named and consequently killed, I continue to (very sanely) change my affiliations with the world--always seeking the original and unusual discovery. I experiment. That is who I am. I hope the mirror I\u27ve created in which to contemplate my own world is, at the very least, clear enough so that you might catch glimpse of your own reflection. Thanks for reading. 1: The World Turned Inside Out, Henry Corbin and Islamic Mysticism, by Tom Cheetham 2: From the Translator\u27s afterward found in Arthur Rimbaud\u27s The Illumination, translated by Donald Revel