Piloting Your Nanovehicle to Overcome Biological Barriers.

Designing an effective nanoparticle for selective drug transport requires careful consideration of the complex biological barriers encountered in transit to the desired target. Here, we review several of these barriers, and provide possible methods for formulating liposomal nanoparticles to overcome them. The methods include the biotinylation of an antibody, and subsequent conjugation to a PEGylated cationic lipid nanoparticle.

Water for Warfighters in Iraq and Afghanistan: A Summary of Lessons Learned.

The Army is the Department of Defense executive agent for land-based field water supplies. The Army Corps of Engineers, Army Quartermaster Corps, and Army Medical Department coordinate to provide the necessary support to obtain, treat, disinfect, certify, distribute, and monitor drinking water during deployments. This collaboration is necessary to ensure that an adequate quantity of acceptable quality drinking water is available for deployed personnel at all base camps and in all operations.

Depression and coping in subthreshold eating disorders.

Objective: The eating disorder literature has sought to understand the role of comorbid psychiatric diagnoses and coping in relation to eating disorders. The present research extends these findings by studying the relationships among depression, coping, and the entire continuum of disordered eating behaviors, with an emphasis on subthreshold eating disorders.

Method: 109 undergraduate females completed questionnaires to assess disordered eating symptoms, depressive symptoms, and the use of active and avoidant coping mechanisms.

US veterinary support to standardization of food and water safety and animal care and use within NATO.

NATO requires all standardization agreements and Al-lied Medical Publications to be reviewed at least once every 3 years to ensure they reflect current technologies and national military policies and procedures. This is particularly applicable with regard to veterinary medi-cine and food and water safety where advances in scientific knowledge and practices may result in documents quickly becoming obsolete. Such is the case with the 8 standardization agreements for which the FWSVS has responsibility; all are currently undergoing major revisions.

Discovery of XL413, a potent and selective CDC7 inhibitor.

CDC7 is a serine/threonine kinase that has been shown to be required for the initiation and maintenance of DNA replication. Up-regulation of CDC7 is detected in multiple tumor cell lines, with inhibition of CDC7 resulting in cell cycle arrest. In this paper, we disclose the discovery of a potent and selective CDC7 inhibitor, XL413 (14), which was advanced into Phase 1 clinical trials.

Discovery and characterization of an inhibitor of glucosylceramide synthase.

Targeting glycosphingolipid synthesis has emerged as a novel approach for treating metabolic diseases. 32 (EXEL-0346) represents a new class of glucosylceramide synthase (GCS) inhibitors. This report details the elaboration of hit 8 with the goal of achieving and maintaining maximum GCS inhibition in vivo.

Treating depressed and anxious smokers in smoking cessation programs.

Objective: Cigarette smoking is the leading cause of preventable death in the United States. In addition, smoking rates among depressed and anxious smokers are higher than in the population at large. Furthermore, treating depressed and anxious smokers effectively is particularly challenging because of their significant negative affect, dysfunctional emotional regulation, severe withdrawal symptoms, and numerous institutional barriers to successful treatment.

Discovery of a new class of glucosylceramide synthase inhibitors.

A novel series of potent inhibitors of glucosylceramide synthase are described. The optimization of biochemical and cellular potency as well as ADME properties led to compound 23c. Broad tissue distribution was obtained following oral administration to mice.

Comorbidity between depression and disordered eating in adolescents.

Depression is one of the most common mental health disorders seen in adolescence. Low self-esteem, lack of social support and poor body image have been found to be risk factors for depression. However, these risk factors have not adequately explained why adolescent female rates of depressive episodes rise to almost twice that of males.

Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes.

Dipeptidyl peptidase-IV (DPP-IV) inhibitors are poised to be the next major drug class for the treatment of type 2 diabetes. Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9. Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.

Discovery of potent and selective inhibitors of 11beta-HSD1 for the treatment of metabolic syndrome.

High throughput screening efforts have identified a novel class of dichloroaniline amide 11beta-HSD1 inhibitors. SAR studies initiated from dichloroaniline 4 focused on retaining the potency and selectivity profile of the lead.

Synthesis and activity of novel bile-acid conjugated glucocorticoid receptor antagonists.

A series of potent steroidal glucocorticoid receptor antagonists has been discovered. After conjugation to cholic acid, the compounds retained an affinity for GR in vitro and had modest in vivo efficacy.

What should non-US behavioral health systems learn from the USA?: US behavior health services trends in the 1980s and 1990s.

Several countries, such as the USA, inadvertently created a different behavioral health payment system from the rest of medicine through the introduction of diagnostic-related group exemptions for psychiatric care. This led to isolation in the administration and delivery of care for patients with mental health and substance abuse disorders from other medical services with significant, yet unintended, consequences. To insure an efficient and effective health-care system, it is necessary to recognize the problems introduced by segregating behavioral health from the rest of medical care.

The effectiveness of an interactive small group diabetes intervention in improving knowledge, feeling of control, and behavior.

The objective of this study is to evaluate the effectiveness of a small group intervention in improving knowledge, feeling of control, and behaviors related to self-management of diabetes. The intervention includes educational content on diabetes self-management as well as discussion of attitudes, feelings, and motivations about living with diabetes. The authors randomized volunteers into an intervention group that participated in the small-group learning activity and a control group that received a diabetes self-care book.