Anti-tumor necrosis factor-alpha therapy during murine Klebsiella pneumoniae bacteremia: increased mortality in the absence of liver injury.

Klebsiella pneumoniae is a leading cause of gram-negative bacterial pneumonia, often resulting in bacteremia concurrent with the localized pulmonary infection. The beneficial role of tumor necrosis factor (TNF)-alpha during pulmonary infection has been well documented; however, consequences of TNF-alpha production during systemic bacterial infection are controversial. A murine model of K. pneumoniae was developed to address this important issue. Liver-associated TNF-alpha mRNA was induced within 30 min after intravenous bacterial inoculation and remained elevated through 6 h before returning to near-baseline at 24 h postinfection. Intravenous K. pneumoniae infection induced liver cellular injury that was completely ablated when mice were pretreated with a neutralizing anti-TNF-alpha antibody. Interestingly, this reduction in liver injury failed to translate into improved survival. Mice receiving anti-TNF-alpha continued to succumb to the infection even out to day 10 postinfection. Bacterial clearance after TNF-alpha neutralization was significantly impaired at later time points during infection. Correlating with impaired bacterial clearance was diminished production of liver-associated MIP-2, MIP-1alpha, MCP-1, and interferon-gamma. Further evidence of diminished antibacterial immune responses was noted when the activational status of splenic natural killer cells in anti-TNF-alpha-treated mice was examined 24 h postinfection. Natural killer cells displayed decreased CD69 expression. Combined, these data indicate that the beneficial effects of TNF-alpha during systemic K. pneumoniae infection outweigh the detrimental effects of TNF-alpha-mediated hepatocyte cellular injury. Anti-TNF-alpha therapy, although preventing liver injury during blood-borne bacterial infection, results in a dampened anti-bacterial host response, resulting in decreased bacterial clearance and overall survival

Ethanol Feeding Inhibits Proinflammatory Cytokine Expression from Murine Alveolar Macrophages Ex Vivo

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66427/1/j.1530-0277.1997.tb04440.x.pd

Blue oak stump sprouting evaluated after firewood harvest in northern Sacramento Valley

Colifornia's hardwood rangelands, an oak-dominated woodland system, cover 10 million acres. More than 80% of these lands are privately owned, with two-thirds grazed by domestic livestock. Public concerns about long-term damage to habitat in areas harvested for firewood — particularly in the northern Sacramento Valley — led to this study of resprouting, to assess long-term trends in oak cover following harvesting and the potential of sprout (coppice) management to sustain woodlands. In field surveys on 103 sample plots at 19 ranches where oak firewood was harvested, we found that 54% of all oak stumps resprouted. Stump diameter, herbicide application, overstory crown cover percentage, and slope and aspect were significant variables in models developed to assess the probability of stump sprouting. Ten-year sprout height and crown growth models were developed, and livestock grazing, residual overstory canopy, herbicide treatment and stump diameter were found to be significant variables. These models can be used to predict stand development following firewood harvest and can be integrated with forage growth, wildlife habitat and residual tree growth models

“Right to Refusal”: Practices of Consent in the Pittsburgh Swing Dance Community

In 2015, professional swing dancer Steven Mitchell was outed online by several women as a serial sexual abuser and was ostracized from the swing dance community both within the United States and globally. The first woman to share her story was Sarah Sullivan and her blog post detailing her sexual assault has been translated into at least seven languages. Within a week, swing dance organizers began having conversations online, leading to changes in practices of consent and the promotion of safer spaces during dance events. While etiquette of the swing dance revival starting in the mid-1980s dictated that dancers should say “yes” to any dance, current practices have shifted to encourage dancers to feel empowered to say “no” for any reason. This thesis joins a small but growing body of literature on social dance in the field of ethnomusicology and other fields including dance and performance studies. There are a number of scholarly works regarding swing dancing but their approach is typically historical while texts employing ethnography all focus on large cities. By investigating a small dance community in Pittsburgh, this thesis offers a perspective that may be applicable to other small swing dance communities in the United States. Based on interviews and participant observation in the Pittsburgh swing dance community, I will examine the ways that requesting consent for dances, accepting or declining dances, and expressing discomfort during movement has changed between the swing dance revival to the time of my research in 2019-2020. By recasting “no” as an anticipated and acceptable response, the Pittsburgh swing dance community creates more opportunities for participants to set healthy boundaries and normalizes rejection. Dancers learn both how to request consent and how to handle refusal, essential to discourses and practices surrounding bodily autonomy. Social dancing is unique as it demands physical contact, offering a place to rehearse respecting the bodily autonomy of others and asserting one’s own bodily autonomy. This thesis will conclude by looking at potential advantages of social dancing as a site of cultivating new rhetoric and practice around consent and safer spaces

PPARs in Alveolar Macrophage Biology

PPARs, most notably PPAR-γ, play a crucial role in regulating the activation of alveolar macrophages, which in turn occupy a pivotal place in the immune response to pathogens and particulates drawn in with inspired air. In this review, we describe the dual role of the alveolar macrophage as both a first-line defender through its phagocytotic activity and a regulator of the immune response. Depending on its state of activation, the alveolar macrophage may either enhance or suppress different aspects of immune function in the lung. We then review the role of PPAR-γ and its ligands in deactivating alveolar macrophages—thus limiting the inflammatory response that, if unchecked, could threaten the essential respiratory function of the alveolus—while upregulating the cell's phagocytotic activity. Finally, we examine the role that inadequate or inappropriate PPAR-γ responses play in specific lung diseases

The changing immune system in sepsis: Is individualized immuno-modulatory therapy the answer?

Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the immune response to sepsis provide the opportunity to develop more effective therapies. The immune response in sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immune-suppressive phase. Patients fail to eradicate invading pathogens and are susceptible to opportunistic organisms in the hypo-inflammatory phase. Many mechanisms are responsible for sepsis-induced immuno-suppression, including apoptotic depletion of immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion. Currently in clinical trial for sepsis are granulocyte macrophage colony stimulating factor and interferon gamma, immune-therapeutic agents that boost patient immunity. Immuno-adjuvants with promise in clinically relevant animal models of sepsis include anti-programmed cell death-1 and interleukin-7. The future of immune therapy in sepsis will necessitate identification of the immunologic phase using clinical and laboratory parameters as well as biomarkers of innate and adaptive immunity

A History of Borden Institute

This study has for its purpose the preserving for posterity of a brief account of one of the small private schools of Southern Indiana. Too frequently, perhaps, an institution like a flower, as expressed by Thomas Gray in his Elegy, is born to blush unseen and waste its sweetness on the desert air . This may have been true of Borden Institute which was founded out of an unselfish desire and in the spirit of service to mankind