Protective host immune responses to anthrax infection in humans and animal models are characterized by the development of neutralizing Abs against the receptor-binding anthrax protective Ag (PA), which, together with the lethal factor (LF) protease, composes anthrax lethal toxin (LT). We now report that B cells, in turn, are targets for LT. Anthrax PA directly binds primary B cells, resulting in the LF-dependent cleavage of the MAPK kinases (MAPKKs) and disrupted signaling to downstream MAPK targets. Although not directly lethal to B cells, anthrax LT treatment causes severe B cell dysfunction, greatly reducing proliferative responses to IL-4-, anti-IgM-, and/or anti-CD40 stimulation. Moreover, B cells treated with anthrax LT in vitro or isolated from mice treated with anthrax LT in vivo have a markedly diminished capacity to proliferate and produce IgM in response to TLR-2 and TLR-4 ligands. The suppressive effects of anthrax LT on B cell function occur at picomolar concentrations in vitro and at sublethal doses in vivo. These results indicate that anthrax LT directly inhibits the function of B cells in vitro and in vivo, revealing a potential mechanism through which the pathogen could bypass protective immune responses.
Little is known about what patients value in psychiatric crisis services or how they compare community-based services with those received in the emergency department. Three focus groups (n = 27) were held of participants who had received psychiatric crisis services in emergency departments or a community mental health center. Participants described care experiences and preferences. Focus groups were audio recorded, transcribed, and coded using a value-based lens. Themes included appreciation for feeling respected, basic comforts, and shared decision-making as foundations of quality care. Participants preferred the community mental health center. Research should address long-term outcomes to motivate change in psychiatric crisis care.
Public Health experts warn it is not a question of if but when the next flu pandemic will arrive. Historically, we experience three pandemics each century. Many experts suggest we are already overdue for another pandemic. "Today, many influenza experts, including those at the CDC, consider the threat of a serious influenza pandemic to the US to be high. Although the timing and impact of an influenza pandemic is unpredictable, the occurrence is inevitable and potentially devastating." Dr. Julie Gerberding, Director, CDC An influenza pandemic could consist of one or multiple waves with each wave lasting up to eight weeks. The Centers for Disease Control and Prevention predict between 90,000 to 1.8 million people nationally would die depending on the severity of the influenza virus.
A dedicated community mental health center is able to treat patients experiencing acute mental health crises. LOS times were significantly shorter compared to regional EDs. Successful broader programmatic implementation could improve care quality and significantly reduce the volume of patients treated in the ED for acute mental health disorders.
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