Comparison and evaluation of dietary quality between older and younger Mexican-American women.

OBJECTIVE: To compare and evaluate the dietary quality of young and older sedentary Mexican-American women. Understanding key dietary concerns, while considering developmental transition periods and cultural relevance, can provide insight for developing appropriate nutrition interventions. DESIGN: Cross-sectional dietary data were collected using unannounced 24 h diet recalls to assess nutrient intake adequacy (Estimated Average Requirement cut-point method) and dietary quality (Healthy Eating Index (HEI) 2010). SETTING: Mujeres en Acción and Madres para la Salud, two community-based physical activity interventions. SUBJECTS: Participants were 139 young (28 (sd 6) years) and 124 older (55 (sd 7) years) overweight/obese sedentary Mexican-American women (BMI=25·0-35·0 kg/m2) of low socio-economic status. RESULTS: Older women consumed less Ca, Fe, folate, empty calories and energy from carbohydrate, but more fruit, vegetables, greens and beans, and fibre than younger women (all P<0·05). Over 60 % of all participants had an intake below recommendations for fibre, Ca, vitamin E, vitamin C and folate. Both groups had low total HEI-2010 scores (62 for older and 63 for younger women; NS), with 57 % of older and 48 % of younger women classified as having a poor diet. CONCLUSIONS: Despite differences in nutrient requirements according to developmental transition periods (childbearing v. perimenopausal), overall, older and younger Mexican-American women generally had low-quality diets and may benefit from dietary quality improvement.

Correlates of depressive symptoms after birth for Latinas who are overweight or obese.

Depression symptoms and overweight/obesity are common concerns during childbearing. Both conditions are associated with poor outcomes at birth and can have long-lasting consequences. Predictors of depressive symptoms among overweight and obese low-income and ethnically diverse women are not known. Data are from the Madres para la Salud trial with 139 postpartum Latinas. Depressive symptoms during a prior pregnancy were positively related, while social support and moderate intensity physical activity (PA) were negatively related to depressive symptoms after birth. Social support and PA may be effective interventions, particularly for women who have experienced depressive symptoms in a prior pregnancy.

A comparison of a social support physical activity intervention in weight management among post-partum Latinas.

BACKGROUND: Weight gain during the childbearing years and failure to lose pregnancy weight after birth contribute to the development of obesity in postpartum Latinas. METHODS: Madres para la Salud [Mothers for Health] was a 12-month, randomized controlled trial exploring a social support intervention with moderate-intensity physical activity (PA) seeking to effect changes in body fat, fat tissue inflammation, and depression symptoms in sedentary postpartum Latinas. This report describes the efficacy of the Madres intervention. RESULTS: The results show that while social support increased during the active intervention delivery, it declined to pre-intervention levels by the end of the intervention. There were significant achievements in aerobic and total steps across the 12 months of the intervention, and declines in body adiposity assessed with bioelectric impedance. CONCLUSIONS: Social support from family and friends mediated increases in aerobic PA resulting in decrease in percent body fat. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01908959.

Social marketing: approach to cultural and contextual relevance in a community-based physical activity intervention.

We report the social marketing strategies used for the design, recruitment and retention of participants in a community-based physical activity (PA) intervention, Madres para la Salud (Mothers for Health). The study example used to illustrate the use of social marketing is a 48-week prescribed walking program, Madres para la Salud (Mothers for Health), which tests a social support intervention to explore the effectiveness of a culturally specific program using 'bouts' of PA to effect the changes in body fat, fat tissue inflammation and postpartum depression symptoms in sedentary Hispanic women. Using the guidelines from the National Benchmark Criteria, we developed intervention, recruitment and retention strategies that reflect efforts to draw on community values, traditions and customs in intervention design, through partnership with community members. Most of the women enrolled in Madres para la Salud were born in Mexico, largely never or unemployed and resided among the highest crime neighborhoods with poor access to resources. We developed recruitment and retention strategies that characterized social marketing strategies that employed a culturally relevant, consumer driven and problem-specific design. Cost and benefit of program participation, consumer-derived motivation and segmentation strategies considered the development transition of the young Latinas as well as cultural and neighborhood barriers that impacted retention are described.

Respiratory Health Associated with Systemic Metal Exposure in Post 9/11 Veterans in the Department of Veterans Affairs Toxic Embedded Fragment Registry.

OBJECTIVE: Adverse respiratory outcomes in post-9/11 Veterans with elevated urinary metal measures and enrolled in the VA's Toxic Embedded Fragment registry were compared to those without elevated urinary metals. METHODS: Veterans completed questionnaires, pulmonary physiology tests (pulmonary function and oscillometry) and provided urine samples for analysis of 13 metals. Respiratory symptoms, diagnoses and physiology measures were compared in Veterans with ≥1 urine metal elevation to those without metal elevations, adjusted for covariates, including smoking. RESULTS: Among 402 study participants, 24% had elevated urine metals, often just exceeding upper limits of reference values. Compared to Veterans without elevated metals, those with elevated metals had had higher FEV1 values but similar frequencies of respiratory symptoms and diagnoses and abnormalities on pulmonary physiology tests. CONCLUSIONS: Mild systemic metal elevations in post 9/11 Veterans are not associated with adverse respiratory health outcomes.

Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity.

Elevated blood branched-chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes, which might result from a reduced cellular utilization and/or incomplete BCAA oxidation. White adipose tissue (WAT) has become appreciated as a potential player in whole body BCAA metabolism. We tested if expression of the mitochondrial BCAA oxidation checkpoint, branched-chain α-ketoacid dehydrogenase (BCKD) complex, is reduced in obese WAT and regulated by metabolic signals. WAT BCKD protein (E1α subunit) was significantly reduced by 35-50% in various obesity models (fa/fa rats, db/db mice, diet-induced obese mice), and BCKD component transcripts significantly lower in subcutaneous (SC) adipocytes from obese vs. lean Pima Indians. Treatment of 3T3-L1 adipocytes or mice with peroxisome proliferator-activated receptor-γ agonists increased WAT BCAA catabolism enzyme mRNAs, whereas the nonmetabolizable glucose analog 2-deoxy-d-glucose had the opposite effect. The results support the hypothesis that suboptimal insulin action and/or perturbed metabolic signals in WAT, as would be seen with insulin resistance/type 2 diabetes, could impair WAT BCAA utilization. However, cross-tissue flux studies comparing lean vs. insulin-sensitive or insulin-resistant obese subjects revealed an unexpected negligible uptake of BCAA from human abdominal SC WAT. This suggests that SC WAT may not be an important contributor to blood BCAA phenotypes associated with insulin resistance in the overnight-fasted state. mRNA abundances for BCAA catabolic enzymes were markedly reduced in omental (but not SC) WAT of obese persons with metabolic syndrome compared with weight-matched healthy obese subjects, raising the possibility that visceral WAT contributes to the BCAA metabolic phenotype of metabolically compromised individuals.

Promotoras' roles in integrative validity and treatment fidelity efforts in randomized controlled trials.

Promotoras from the communities in which interventions are implemented can be effective contributors to validity and fidelity efforts. This article describes a 48-week randomized controlled trial Madres para la Salud (Mothers for Health) and illustrates the use of promotoras as collaborative members of the research team to contribute to attaining integrative validity and treatment fidelity. Madres para la Salud implements a culturally tailored physical activity program to effect changes in body fat, systemic and fat tissue inflammation, and depression symptoms. The significance of Madres para la Salud treatment validity and fidelity processes includes cultural tailoring of a social support intervention, and a promotora model to incorporate initial and ongoing fidelity monitoring.

Implementation of low-dose CT screening in two different health care systems: Mount Sinai Healthcare System and Phoenix VA Health Care System.

Implementation of lung screening (LS) programs is challenging even among health care organizations that have the motivation, the resources, and more importantly, the goal of providing for life-saving early detection, diagnosis, and treatment of lung cancer. We provide a case study of LS implementation in different healthcare systems, at the Mount Sinai Healthcare System (MSHS) in New York City, and at the Phoenix Veterans Affairs Health Care System (PVAHCS) in Phoenix, Arizona. This will illustrate the commonalities and differences of the LS implementation process in two very different health care systems in very different parts of the United States. Underlying the successful implementation of these LS programs was the use of a comprehensive management system, the Early Lung Cancer Action Program (ELCAP) Management SystemTM. The collaboration between MSHS and PVAHCS over the past decade led to the ELCAP Management SystemTM being gifted by the Early Diagnosis and Treatment Research Foundation to the PVAHCS, to develop a "VA-ELCAP" version. While there remain challenges and opportunities to continue improving LS and its implementation, there is an increasing realization that most patients who are diagnosed with lung cancer as a result of annual LS can be cured, and that of all the possible risks associated with LS, the greater risk of all is for heavy cigarette smokers not to be screened. We identified 10 critical components in implementing a LS program. We provided the details of each of these components for the two healthcare systems. Most importantly, is that continual re-evaluation of the screening program is needed based on the ongoing quality assurance program and database of the actual screenings. At minimum, there should be an annual review and updating. As early diagnosis of lung cancer must be followed by optimal treatment to be effective, treatment advances for small, early lung cancers diagnosed as a result of screening also need to be assessed and incorporated into the entire screening and treatment program.

Insulin metabolism in human adipocytes from subcutaneous and visceral depots.

Subjects with the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, hypertension, etc.) have a relative increase in abdominal fat tissue compared to normal individuals and obesity has also been shown to be associated with a decrease in insulin clearance. The majority of the clearance of insulin is due to the action of insulin-degrading enzyme (IDE) and IDE is present throughout all tissues. Since abdominal fat is increased in obesity we hypothesized that IDE may be altered in the different fat depots. Adipocytes were isolated from fat samples obtained from subjects during elective abdominal surgery. Fat samples were taken from subcutaneous (SQ) and visceral (VIS) sites. Insulin metabolism was compared in adipocytes isolated from SQ and VIS fat tissue. Adipocytes from the VIS site degraded more insulin that those from SQ fat tissue. Inhibitors of cathepsins B and D has no effect on the degradation of insulin, while bacitracin, an inhibitor of IDE, inhibited degradation by approx. 33% in both SQ and VIS adipocytes. These data show that insulin metabolism is relatively greater in VIS than in SQ fat tissue and potentially due to IDE.

Adipogenic human adenovirus Ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells.

Human adenovirus Ad-36 is causatively and correlatively linked with animal and human obesity, respectively. Ad-36 enhances differentiation of rodent preadipocytes, but its effect on adipogenesis in humans is unknown. To indirectly assess the role of Ad-36-induced adipogenesis in human obesity, the effect of the virus on commitment, differentiation, and lipid accumulation was investigated in vitro in primary human adipose-derived stem/stromal cells (hASC). Ad-36 infected hASC in a time- and dose-dependent manner. Even in the presence of osteogenic media, Ad-36-infected hASC showed significantly greater lipid accumulation, suggestive of their commitment to the adipocyte lineage. Even in the absence of adipogenic inducers, Ad-36 significantly increased hASC differentiation, as indicated by a time-dependent expression of genes within the adipogenic cascade-CCAAT/Enhancer binding protein-beta, peroxisome proliferator-activated receptor-gamma, and fatty acid-binding protein-and consequentially increased lipid accumulation in a time- and viral dose-dependent manner. Induction of hASC to the adipocyte state by Ad-36 was further supported by increased expression of lipoprotein lipase and the accumulation of its extracellular fraction. hASC from subjects harboring Ad-36 DNA in their adipose tissue due to natural infection had significantly greater ability to differentiate compared with Ad-36 DNA-negative counterparts, which offers a proof of concept. Thus, Ad-36 has the potential to induce adipogenesis in hASC, which may contribute to adiposity induced by the virus.

Pioglitazone inhibits the expression of inflammatory cytokines from both monocytes and lymphocytes in patients with impaired glucose tolerance.

OBJECTIVE: The current study determines whether pioglitazone (PIO) therapy reduces both monocyte and lymphocyte inflammatory activity and their ability to induce inflammation in other tissues. METHODS AND RESULTS: Monocyte and lymphocyte cytokine gene and protein expression of interleukin (IL)-6 were first shown to be greater in subjects with impaired glucose tolerance (IGT) than in subjects with normal glucose tolerance. Sixty-six IGT subjects were then randomized to 4,5 months of placebo or PIO therapy. After receiving PIO, subjects had lower triglycerides and higher HDL cholesterol (P<0.05) than did subjects receiving placebo. Monocyte gene and protein expression of IL-1 beta, IL-6, and IL-8 (and IL-2, IL-6 and IL-8 from lymphocytes) was significantly lower after PIO therapy in the resting state, as well as after lipopolysaccharide (LPS) stimulation (P<0.05 for all). Moreover, IL-6, IL-8, and MCP-1 gene expression were decreased by nearly 50% in human adipocytes exposed to conditioned media from monocytes or lymphocytes from PIO treated subjects. CONCLUSIONS: These results demonstrate that PIO therapy in IGT can reduce proinflammatory gene and protein expression from both monocytes and lymphocytes. This intervention also reduces the inflammatory cross-talk between these immune cells and adipose tissue, which could in turn contribute to the metabolic improvements resulting from PIO therapy.

Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals.

BACKGROUND: Enlargement of adipocytes from subcutaneous abdominal adipose tissue (SAT), increased intrahepatic lipid content (IHL), intramyocellular lipid content (IMCL), and low circulating adiponectin concentrations are associated with insulin resistance. OBJECTIVE: Because adiponectin increases fat oxidation in skeletal muscle and liver, and the expression of the adiponectin gene in SAT is inversely associated with adipocyte size, we hypothesized that hypoadiponectinemia links hypertrophic obesity with insulin resistance via increased IMCL and IHL. DESIGN: Fifty-three obese Pima Indians with a mean (+/-SD) age of 27 +/- 8 y, body fat of 35 +/- 5%, and normal glucose regulation (normal fasting and 2-h glucose concentration per WHO 1999 criteria) underwent euglycemic-hyperinsulinemic clamp, biopsies of SAT and vastus lateralis muscle, and magnetic resonance imaging of the abdomen. RESULTS: Adipocyte diameter (AD) correlated positively with body fat (P < 0.0001) and IHL (estimated from magnetic resonance imaging intensity of liver; P = 0.047). No association was found between AD and plasma adiponectin or IMCL. Plasma adiponectin negatively correlated with type II IMCL (IIA, P = 0.004; IIX, P = 0.009) or IHL (P = 0.02). In a multivariate analysis, plasma adiponectin, AD, and visceral adipose tissue (VAT) independently predicted IHL. Low insulin-mediated glucose disposal was associated with low plasma adiponectin (P = 0.02) and high IHL (P = 0.0003), SAT (P = 0.02), and VAT (P = 0.04). High IHL was the only predictor of reduced insulin-mediated suppression of hepatic glucose production (P = 0.02) and the only independent predictor of insulin-mediated glucose disposal in a multivariate analysis. CONCLUSIONS: Increased lipid content in the liver may independently link hypoadiponectinemia, hypertrophic obesity, and increased visceral adiposity with peripheral and hepatic insulin resistance.

Gamma-synuclein is an adipocyte-neuron gene coordinately expressed with leptin and increased in human obesity.

Recently, we characterized tumor suppressor candidate 5 (Tusc5) as an adipocyte-neuron PPARgamma target gene. Our objective herein was to identify additional genes that display distinctly high expression in fat and neurons, because such a pattern could signal previously uncharacterized functional pathways shared in these disparate tissues. gamma-Synuclein, a marker of peripheral and select central nervous system neurons, was strongly expressed in white adipose tissue (WAT) and peripheral nervous system ganglia using bioinformatics and quantitative PCR approaches. Gamma-synuclein expression was determined during adipogenesis and in subcutaneous (SC) and visceral adipose tissue (VAT) from obese and nonobese humans. Gamma-synuclein mRNA increased from trace levels in preadipocytes to high levels in mature 3T3-L1 adipocytes and decreased approximately 50% following treatment with the PPARgamma agonist GW1929 (P < 0.01). Because gamma-synuclein limits growth arrest and is implicated in cancer progression in nonadipocytes, we suspected that expression would be increased in situations where WAT plasticity/adipocyte turnover are engaged. Consistent with this postulate, human WAT gamma-synuclein mRNA levels consistently increased in obesity and were higher in SC than in VAT; i.e. they increased approximately 1.7-fold in obese Pima Indian adipocytes (P = 0.003) and approximately 2-fold in SC and VAT of other obese cohorts relative to nonobese subjects. Expression correlated with leptin transcript levels in human SC and VAT (r = 0.887; P < 0.0001; n = 44). Gamma-synuclein protein was observed in rodent and human WAT but not in negative control liver. These results are consistent with the hypothesis that gamma-synuclein plays an important role in adipocyte physiology.

Application of DNA microarray to the study of human adipose tissue/cells.

Adipose tissue is increasingly recognized as a metabolically active endocrine organ with multiple functions beyond its lipid storage capability. Various constituents of the tissue, such as mature adipocytes and stromal vascular cells, have distinct functions. For example, they express and secrete different kinds of bioactive molecules collectively called adipokines. Altered adipokine secretion patterns characterize obesity and insulin resistance, which are major risk factors for type 2 diabetes mellitus. The contribution of dysregulated adipokine expression to these diseases may be assembled from transcriptomic profiles of the tissue and/or its cellular constituents. The gene expression profiles may also complement genetic approaches to identify disease susceptibility genes. Here, we describe an application of gene expression profiling using DNA microarrays to study human adipose tissue, adipocytes, and stromal vascular cells.

Interventions for weight management in postpartum women.

OBJECTIVE: To report the results of a comprehensive review of published intervention studies to identify the best evidence available for guiding weight management interventions in postpartum women. DATA SOURCES: Electronic searches were conducted of three electronic databases: Cumulative Index to Nursing and Allied Health Literature; Medline; and the Science Citation Index, Expanded, in the Web of Science from 1994 to May 2007. Keyword searches were conducted using the terms obesity, obese, overweight, postpartum, pregnancy weight, and weight management in postpartum women. STUDY SELECTION: Six studies were selected that met the inclusion criteria of testing interventions and one that reported preintervention planning and targeted a weight management intervention for postpartum women. DATA EXTRACTION: All six interventions showed significant impact with diet and exercise or some combination on body composition in the targeted sample of women. DATA SYNTHESIS: The strengths of previous studies include an emphasis on precision in outcome measures and experimental conditions; limitations were that the theoretical basis for the interventions was frequently omitted and limited attention given to the cultural, social, and contextual factors established in descriptive research. CONCLUSIONS: Interventions need to target women early in their childbearing years to have the most significant long-term impact.

Overweight and obesity in postpartum Hispanic women.

Overweight and obesity vary in prevalence among particular groups, and are especially problematic for childbearing Hispanic women. The complex interaction between physical changes associated with pregnancy, role changes accompanying birth, and family and cultural values related to childbearing are superimposed upon the underlying mechanisms that create or perpetuate obesity. In this article we review biological and behavioral research on obesity in postpartum Hispanic women to identify critical components for intervention studies focused on weight management. Recommendations are offered for health care providers and researchers.

Differential expression of matrix metalloproteinase 3 (MMP3) in preadipocytes/stromal vascular cells from nonobese nondiabetic versus obese nondiabetic Pima Indians.

Prior microarray studies comparing global gene expression patterns in preadipocytes/stromal vascular cells isolated from nonobese nondiabetic versus obese nondiabetic Pima Indians showed that matrix metalloproteinase 9 (MMP9) is upregulated in obese subjects. The current study targeted analysis of nine additional MMP genes that cluster to a region on chromosome 11q22 that is linked to BMI and percent body fat. Differential-display PCR showed that MMP3 is downregulated in preadipocytes/stromal vascular cells from obese subjects, and real-time PCR showed that MMP3 expression levels are negatively correlated with percent body fat. To determine whether variants within MMP3 are responsible for its altered expression, MMP3 was sequenced, and seven representative variants were genotyped in 1,037 Pima subjects for association analyses. Two variants were associated with both BMI and type 2 diabetes, and two additional variants were associated with type 2 diabetes alone; however, none of these variants were associated with MMP3 expression levels. We propose that the MMP3 pathway is altered in human obesity, but this alteration may be the result of a combination of genetic variation within the MMP3 locus itself, as well as variation in additional factors, either primary or secondary to obesity, that regulate expression of the MMP3 gene.

Regulation of protein degradation by insulin-degrading enzyme: analysis by small interfering RNA-mediated gene silencing.

Proteins are vital to the overall structure of cells and to the function of cells in the form of enzymes. Thus the control of protein metabolism is among the most important aspects of cellular metabolism. Insulin's major effect on protein metabolism in the adult animal is inhibition of protein degradation. This is via inhibition of proteasome activity via an interaction with insulin-degrading enzyme (IDE). IDE is responsible for the majority of cellular insulin degradation. We hypothesized that a reduction in IDE would reduce insulin degradation and insulin's ability to inhibit protein degradation. HepG2 cells were transfected with siRNA against human IDE and insulin degradation and protein degradation measured. Both IDE mRNA and protein were reduced by >50% in the IDE siRNA transfected cells. Insulin degradation was reduced by approximately 50%. Cells were labeled with [3H]-leucine to investigate protein degradation. Short-lived protein degradation was unchanged in the cells with reduced IDE expression. Long-lived and very-long-lived protein degradation was reduced in the cells with reduced IDE expression (14.0+/-0.16 vs. 12.5+/-0.07%/4h (long-lived), 9.6+/-2.2% vs. 7.3+/-0.2%/3h (very-long-lived), control vs. IDE transfected, respectively, P<0.005). The inhibition of protein degradation by insulin was reduced 37-76% by a decreased expression of IDE in HepG2 cells. This shows that IDE is involved in cellular insulin metabolism and provides further evidence that insulin inhibits protein degradation via an interaction with IDE.

Polymorphisms in the gene encoding 11B-hydroxysteroid dehydrogenase type 1 (HSD11B1) and lifetime cognitive change.

A rare polymorphism in the gene encoding 11B-hydroxysteroid dehydrogenase type 1 (HSD11B1: rs846911-C/A) has been associated with an increased risk of Alzheimer's disease. We tested the hypothesis that this and 2 other HSD11B1 polymorphisms (rs12086634-G/T and rs846910-A/G) were associated with lifetime cognitive change in humans. Subjects were 194 participants of the Scottish Mental Survey of 1932 who took the same well-validated mental test at age 11 and age 79. The subjects represented the highest and lowest quintiles with respect to cognitive decline between ages 11 and 79. Despite having non-significantly different IQs at age 11, by age 79 the groups had mean (S.D.) IQs of 80.3 (14.1) and 109.6 (9.1), respectively (p<.001). The polymorphism rs846911-C/A was absent from both groups. There were no significant differences in the frequency of polymorphisms of rs12086634-G/T (p=.91) and rs846910-A/G (p=.90) between the groups. We conclude that these variants in HSD11B1 are not significant contributors to the range of cognitive ageing examined here.

Diffuse traumatic brain injury affects chronic corticosterone function in the rat.

As many as 20-55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration-deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic-pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI.