Because several well-studied strains of rats manifest spontaneous hypertension, we set out to design a renin inhibitor suitable for use in this species. On the basis of the sequence of the renin substrate, a series of substrate analogue inhibitory peptides were synthesized by systematically modifying the P5, P3, P2, P1P1', P2', P3', and P4' positions. In assays against rat plasma renin, we found that modifications at the C-terminal segment have a marked influence on potency, and that a secondary butyl side chain at the P2' position is important for obtaining optimal activity. The structure at the P3' position, however, could vary considerably without significant effect. The steric effect of the P2 position was important; there an isopropyl side chain provided optimal binding between the inhibitor and the enzyme. At the P3 and P5 positions, potency appeared to depend on aromatic side chains. The effects at the P1P1' position of the transition-state residue (3S,4S)-4-amino-3-hydroxy -6-methylheptanoic acid (statine) and its congeners (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA) and (3S,4S)-4-amino-3-hydroxy-5-cyclohexylpentanoic acid (ACHPA) were found to depend on the sequence of the C-terminal segment. For peptides with an unfavorable C-terminal segment (-Ile-Phe-NH2), AHPPA and ACHPA resulted in a surprising retention of potency. For peptides with a favorable C-terminal segment (-Leu-Phe-NH2), the effect of AHPPA was mild, even though ACHPA still significantly enhanced potency. The hypotensive and plasma renin inhibitory effects of three of the analogues were then studied in anesthetized sodium-depleted rats. One of the compounds, acetyl-His-Pro-Phe-Val-Statine-Leu-Phe-NH2 (IC50 against rat plasma renin of 30 nM at pH 7.4), proved to be a potent hypotensive agent and a potentially useful probe for the study of the renin-angiotensin system in rats.

The recent publication of the American Psychological Association's "Clinical Practice Guideline for the Treatment of PTSD in Adults" resulted in debates concerning multiple issues, among them, an overreliance on randomized controlled trials (RCT) to the exclusion of other research methods, the application of the guideline recommendations to clinical practice, generalizability, and whether cognitive-behavioral approaches are superior to other modalities for the treatment of posttraumatic stress disorder (PTSD) symptoms. The guideline not only has far-reaching implications for practice and research, but for training and education as well. Training is often quite limited regarding when and how to apply trauma-responsive intervention, whether evidence-based or evidence-informed, particularly when the presenting problems are more complex than are typically addressed by an RCT design. The Trauma Resolution and Integration Program, a training program specifically for the treatment of trauma based on the contextual trauma therapy (CTT) model, was developed at a university-based training clinic staffed entirely by doctoral psychology students. Central to this treatment approach is the observation that clients with PTSD and those with complex trauma histories suffer not only from trauma symptoms, but also from gaps and warps in their personal development that interfere with their ability to function effectively. We begin by delineating the principles undergirding the CTT model and their application to supervision. We also discuss how foundational training in trauma psychology and treatment modalities for PTSD, along with supervision, are essential, but often unavailable, components of the implementation of evidence-based and evidence-informed recommendations made in the available PTSD treatment guidelines. Clinical Impact StatementThis article focuses on the principles guiding a supervisory approach to providing supervision and mentoring to students working with survivors of complex trauma. We delineate the principles guiding our supervisory approach that can be beneficial to clinicians in private practice, group practice, or in academic/medical institutions.

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Urban development is a form of anthropogenic environmental disturbance that globally threatens waterways by altering the hydrology and water quality. We are assessing how increased urbanization near rivers of Puerto Rico impacts the aquatic biota. Here we compare the abundance of Macrobrachium carcinus prawns in representative rivers and asses the effects of water chemicals found in those near urban areas on prawn locomotor activity and aggression.A monthly census of prawns along different gradients of urban intensity was conducted in four rivers of the island. The relative number of prawns collected by traps was significantly higher (144) in the non‐urban river, compared with 0, 0, and 2 prawns in comparable areas of three urban rivers.Prawns from non‐urban rivers were exposed in the lab to concentrations the EPA defines as limits for drinking water of specific phthalates (0.006 mg/L) and metal contaminants (Cr3+;0.1 mg/L, Cd2+;0.005 mg/L, Mn2+;0.05mg/L). All contaminants increased locomotion and DBP, Cr3+ and Cd2+ increased total area covered by prawns in the tank, and altered their locomotor patterns. Prawns injected with DBP ventured more towards the center than remaining near edges. Submissive prawns injected with DBP, Cr3+, Cd2+ and Mn2+ also escalated aggression levels.Results suggest that contaminants in urbanized watersheds are associated with prawn assemblage degradation and also have an impact on locomotion and aggressive behavior. These findings serve as important indicators of how low levels of anthropogenic contaminants, such as phthalates and metals, can impact behaviors essential for survival.