Annals of the New York Academy of Sciences
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The discovery of novel antibiotic classes has not kept pace with the growing threat of bacterial resistance. Antibiotic candidates that act at new targets or via distinct mechanisms have the greatest potential to overcome resistance; however, novel approaches are also associated with higher attrition and longer timelines. This uncertainty has contributed to the withdrawal from antibiotic programs by many pharmaceutical companies. ⋯ Antibacterial compound lead optimization faces hurdles associated with the high plasma exposures required for efficacy. Lead optimization would be enhanced by the identification of new antibiotic classes with improved tractability and by expanding the predictability of in vitro safety assays. Implementing multiple screening and target identification strategies is recommended for improving the likelihood of discovering new antibacterial compounds that address unmet needs.
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Ann. N. Y. Acad. Sci. · Nov 2010
ReviewCNS leptin and insulin action in the control of energy homeostasis.
The obesity and diabetes pandemics have made it an urgent necessity to define the central nervous system (CNS) pathways controlling body weight, energy expenditure, and fuel metabolism. The pancreatic hormone insulin and the adipose tissue-derived leptin are known to act on diverse neuronal circuits in the CNS to maintain body weight and metabolism in a variety of species, including humans. Because these homeostatic circuits are disrupted during the development of obesity, the pathomechanisms leading to CNS leptin and insulin resistance are a focal point of research. In this review, we summarize the recent findings concerning the mechanisms and novel neuronal mediators of both insulin and leptin action in the CNS.
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Rates of suicide among veterans of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) rose significantly from 2005 to 2007, adding to existing concerns about veteran suicide risk by the Department of Veterans Affairs. This paper summarizes the available data about risk and rates of suicide in veterans, including the choice of appropriate comparison groups and the identification of risk factors. ⋯ Thus, the experiences of war and the downstream sequelae, in particular the individuals' psychological reactions and societal responses, lead to suicide risk. This paper describes the VA's response to these data in developing and implementing suicide prevention interventions.
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Ann. N. Y. Acad. Sci. · Oct 2010
Clinical TrialDevelopment and early evaluation of the Virtual Iraq/Afghanistan exposure therapy system for combat-related PTSD.
Numerous reports indicate that the growing incidence of posttraumatic stress disorder (PTSD) in returning Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) military personnel is creating a significant health care and economic challenge. These findings have served to motivate research on how to better develop and disseminate evidence-based treatments for PTSD. ⋯ The system consists of a series of customizable virtual scenarios designed to represent relevant Middle Eastern contexts for exposure therapy, including a city and desert road convoy environment. The process for gathering user-centered design feedback from returning OEF/OIF military personnel and from a system deployed in Iraq (as was needed to iteratively evolve the system) will be discussed, along with a brief summary of results from an open clinical trial using Virtual Iraq with 20 treatment completers, which indicated that 16 no longer met PTSD checklist-military criteria for PTSD after treatment.
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Ann. N. Y. Acad. Sci. · Oct 2010
Clinical TrialVirtual reality exposure therapy for combat-related posttraumatic stress disorder.
Posttraumatic stress disorder (PTSD) is a chronic, debilitating, psychological condition that occurs in a subset of individuals who experience or witness life-threatening traumatic events. PTSD is highly prevalent in those who served in the military. ⋯ Three virtual reality scenarios used to treat PTSD in active duty military and combat veterans and survivors of terrorism are presented: Virtual Vietnam, Virtual Iraq, and Virtual World Trade Center. Preliminary results of ongoing trials are presented.