Ecosystem-based management for military training, biodiversity, carbon storage and climate resiliency on a complex coastal land/water-scape.

The Defense Coastal/Estuarine Research Program (DCERP) was a 10-year multi-investigator project funded by the Department of Defense to improve understanding of ecosystem processes and their interactions with natural and anthropogenic stressors at the Marine Corps Base Camp Lejeune (MCBCL) located in coastal North Carolina. The project was aimed at facilitating ecosystem-based management (EBM) at the MCBCL and other coastal military installations. Because of its scope, interdisciplinary character, and duration, DCERP embodied many of the opportunities and challenges associated with EBM, including the need for explicit goals, system models, long-term perspectives, systems complexity, change inevitability, consideration of humans as ecosystem components, and program adaptability and accountability. We describe key elements of this program, its contributions to coastal EBM, and its relevance as an exemplar of EBM.

An Exercise Program for Peritoneal Dialysis Patients in the United States: A Feasibility Study.

BACKGROUND: People with end-stage kidney disease receiving peritoneal dialysis (PD) are generally physically inactive and frail. Exercise studies in PD are scarce and currently there are no PD exercise programs in the United States. The primary objective of this study was to test the feasibility of a combined resistance and cardiovascular exercise program for PD patients under the care of a dedicated home dialysis center in the United States. STUDY DESIGN: Parallel randomized controlled feasibility study. SETTING & PARTICIPANTS: PD patients were recruited from a single center and randomly assigned to the intervention (exercise; n = 18) or control (nonexercise; n = 18) group. INTERVENTION: The intervention group received monthly exercise physiologist consultation, exercise prescription (resistance and aerobic exercise program using exercise bands), and 4 exercise support telephone calls over 12 weeks. The control group received standard care. OUTCOMES: The primary outcome was study feasibility as measured by eligibility rates, recruitment rates, retention rates, adherence rates, adverse events, and sustained exercise rates. Secondary outcome measures were changes in physical function (sit-to-stand test, timed-up-and-go test, and pinch-strength tests) and patient-reported outcome measures. RESULTS: From a single center with 75 PD patients, 57 (76%) were deemed eligible, resulting in a recruitment rate of 36 (63%) patients. Participants were randomly assigned into 2 groups of 18 (1:1). 10 patients discontinued the study (5 in each arm), resulting in 26 (72%) patients, 13 in each arm, completing the study. 10 of 13 (77%) intervention patients were adherent to the exercise program. A t test analysis of covariance found a difference between the treatment groups for the timed-up-and-go test (P = 0.04) and appetite (P = 0.04). No serious adverse events caused by the exercise program were reported. LIMITATIONS: Single center, no blinded assessors. CONCLUSIONS: A resistance and cardiovascular exercise program appears feasible and safe for PD patients. We recommend that providers of PD therapy consider including exercise programs coordinated by exercise professionals to reduce the physical deterioration of PD patients. FUNDING: None. TRIAL REGISTRATION: NCT03980795.

Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as potential therapeutic agents for the treatment of Huntington's disease.

We report on the development of a series of pyrimidine carboxylic acids that are potent and selective inhibitors of kynurenine monooxygenase and competitive for kynurenine. We describe the SAR for this novel series and report on their inhibition of KMO activity in biochemical and cellular assays and their selectivity against other kynurenine pathway enzymes. We describe the optimization process that led to the identification of a program lead compound with a suitable ADME/PK profile for therapeutic development. We demonstrate that systemic inhibition of KMO in vivo with this lead compound provides pharmacodynamic evidence for modulation of kynurenine pathway metabolites both in the periphery and in the central nervous system.

Noninsulinoma pancreatogenous hypoglycemia syndrome: quantitative and immunohistochemical analyses of islet cells for insulin, glucagon, somatostatin, and pancreatic and duodenal homeobox protein.

OBJECTIVE: To present a case of an elderly man with noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) and to determine the pathogenesis of this syndrome. METHODS: The pancreas of our patient with NIPHS was immunocytochemically stained for insulin-, glucagon-, and somatostatin-secreting cells and pancreatic and duodenal homeobox protein (PDX-1). The clinical findings and morphologic and immunocytochemical analyses of the islets of our patient are described, along with a review of related published reports. RESULTS: A 78-year-old man presented with hyperinsulinemic hypoglycemia, with episodes unrelated to meals or fasting. An insulinoma could not be localized by preoperative imaging or by intraoperative ultrasonography or palpation. He underwent a 70% distal pancreatectomy. For assessment of the possibility that a nuclear transcription factor regulating islet beta-cell growth and development is overexpressed in this disease and is responsible for diffuse islet hyperfunction and proliferation of beta-cells, pancreatic sections from our patient were stained immunocytochemically for PDX-1, insulin, glucagon, and somatostatin. Morphologic findings were compared with pancreatic sections from normal control patients and normative data reported in the literature. Clinical findings and morphologic analyses were consistent with NIPHS. Islets were arranged in long clusters, both in the pancreatic tissue and in peripancreatic adipose tissue. Islets were small but increased in number, and insulin, glucagon, and somatostatin were present in the islets. The relative intensity of insulin staining was increased in our patient in comparison with that in the control patients, and PDX-1 was not overexpressed. CONCLUSION: The etiopathogenesis of NIPHS in this patient involved (1) an increased number of islets with development of ectopic islets in the peripancreatic adipose tissue; (2) alpha- and delta- as well as beta-cell proliferation; and (3) an early step in the development of the islet not involving overexpression of PDX-1.

Vitamin A deficiency impairs fetal islet development and causes subsequent glucose intolerance in adult rats.

To determine the role of vitamin A in fetal islet development, beta- and alpha-cell mass, apoptosis, and alpha- and beta-cell replication were measured in rats using a model of marginal vitamin A deficiency. Female rats before and during pregnancy and their offspring postweaning were fed a diet containing retinol as retinyl palmitate at a low marginal (LM, 0.25 mg/kg diet) or a sufficient (SUFF, 4.0 mg/kg diet) level. Fetal islet size, replication, apoptosis, and offspring glucose tolerance were examined. Both beta-cell area and number per islet were reduced approximately 50% in fetuses from dams fed an LM vitamin A diet compared with those from dams fed the SUFF vitamin A diet. The alpha-cell area and number per fetal islet were not affected by vitamin A deficiency. Apoptosis was not increased. The percentage of newly replicated beta-cells in the LM fetal pancreas was 42% less than that of SUFF offspring, but alpha-cell replication was not affected. To determine whether this decrease in beta-cell area affected adult glucose tolerance and insulin secretion, 65-d-old offspring were subject to glucose tolerance tests. LM rats had a 55% lower plasma insulin level and a 76% higher serum glucose than SUFF rats. The same pattern could be seen in 35-d-old rats. These findings show that vitamin A deficiency decreases beta-cell mass and this reduction can be attributed to a reduced rate of fetal beta-cell replication in LM offspring. This may contribute to impaired glucose tolerance later in adult life.