Steroid receptor coactivator-2 expression in brain and physical associations with steroid receptors.

Estradiol and progesterone bind to their respective receptors in the hypothalamus and hippocampus to influence a variety of behavioral and physiological functions, including reproduction and cognition. Work from our lab and others has shown that the nuclear receptor coactivators, steroid receptor coactivator-1 (SRC-1) and SRC-2, are essential for efficient estrogen receptor (ER) and progestin receptor (PR) transcriptional activity in brain and for hormone-dependent behaviors. While the expression of SRC-1 in brain has been studied extensively, little is known about the expression of SRC-2 in brain. In the present studies, we found that SRC-2 was highly expressed throughout the hippocampus, amygdala and hypothalamus, including the medial preoptic area (MPOA), ventral medial nucleus (VMN), arcuate nucleus (ARC), bed nucleus of the stria terminalis, supraoptic nucleus and suprachiasmatic nucleus. In order for coactivators to function with steroid receptors, they must be expressed in the same cells. Indeed, SRC-2 and ER(alpha) were coexpressed in many cells in the MPOA, VMN and ARC, all brain regions known to be involved in female reproductive behavior and physiology. While in vitro studies indicate that SRC-2 physically associates with ER and PR, very little is known about receptor-coactivator interactions in brain. Therefore, we used pull-down assays to test the hypotheses that SRC-2 from hypothalamic and hippocampal tissue physically associate with ER and PR subtypes in a ligand-dependent manner. SRC-2 from both brain regions interacted with ER(alpha) bound to agonist, but not in the absence of ligand or in the presence of the selective ER modulator, tamoxifen. Analysis by mass spectrometry confirmed these ligand-dependent interactions between ER(alpha) and SRC-2 from brain. In dramatic contrast, SRC-2 from brain showed little to no interaction with ERbeta. Interestingly, SRC-2 from both brain regions interacted with PR-B, but not PR-A, in a ligand-dependent manner. Taken together, these findings reveal that SRC-2 is expressed in brain regions known to mediate a variety of steroid-dependent functions. Furthermore, SRC-2 is expressed in many ER(alpha) containing cells in the hypothalamus. Finally, SRC-2 from brain interacts with ER and PR in a subtype-specific manner, which may contribute to the functional differences of these steroid receptor subtypes in brain.

Burn disasters in the middle belt of Ghana from 2007 to 2008 and their consequences.

AIM: To study the survival and mortality trends in four fire disasters in the middle belt of Ghana from 2007 to 2008 and to explore measures that could minimize the risk of future disasters. METHODS: Data were collected from clinical records from the Burns Intensive Care Unit and the Casualty Unit of the Komfo Anokye Teaching Hospital, Kumasi, Ghana and from the various disaster sites and the Ghana Police Service. RESULTS: A total of 212 were injured from four burn disasters; 37 (17%) died on the spot; 175 (83%) reported to the Casualty Unit out of which 46 (26%) were admitted. The victims admitted had mean age 24.6 years with male to female ratio 2.3:1; 25 (54%) of the admitted victims died. The average burned surface area of the admitted victims was 63%, with a mean survival rate of 46%. Statistical analysis for mortality when the surface area of the burn was >70% was 0.0005 (P-value). CONCLUSION: The four petrol-related fire disasters showed variable mortality rates. Death and severe disability of victims of future disasters can be avoided if intensive road accident preventive measures and massive public education are encouraged.

5196 mandible fractures among 4381 active duty army soldiers, 1980 to 1998.

OBJECTIVE: We present the frequencies of various types of mandibular fractures along with associated mechanisms and injuries. METHODS: Retrospective analysis of 5196 mandible fractures in 4381 patients extracted from the Total Army Injury and Health Outcomes Database (TAIHOD), a comprehensive database developed by the U.S. Army Research Institute of Environmental Medicine (USARIEM) that links population data to all hospitalizations among active duty army soldiers. The database is based on the ICD-9 CM coding system. RESULTS: We found the following frequencies for specific mandible fracture locations: angle 35.6%, symphysis 20.1%, subcondylar 14.2%, body 12.7%, condylar process 9.1%, ramus 4.5%, alveolar border 2.7%, and coronoid process 1%. The mechanisms of injury were separated into seven categories. Fighting accounts for 36.2%, automobile accidents for 18.6%, athletics for 13.6%, falls for 9.7%, motorcycle accidents for 3.1%, other land transport accidents for 3%, and miscellaneous causes for 15.8%. A few fracture locations appear to be associated with specific mechanisms. Of 82 alveolar border fractures with known mechanisms, 37% resulted from automobile accidents. Of 1094 angle fractures with known mechanisms, 48.6% resulted from fighting. Our data show that the majority of fractures were isolated to one location. Only one fracture was recorded for 70.6%, 29.2% have two fractures recorded, 0.2% have three or more fractures recorded. Associated injuries were common and include facial lacerations 1236 (28.2%), non-mandible facial bone fractures 733 (16.7%), intracranial injury 403(9.2%), internal injuries 229 (5.2%), fractures of the upper limb 295 (6.7%), fractures of the lower extremity 302 (6.9%), and cervical fractures 34 (0.8%). CONCLUSIONS: The mechanism of injury is important in determining the most likely resultant mandible fracture in the case of angle of mandible and alveolar ridge fractures. The clinician should maintain a high level of suspicion for associated injuries that occur more than one fourth of the time and even more frequently in motor vehicle accident victims. Associated intracranial injury is particularly important to rule out. Associated facial fractures, intracranial injury, internal injuries, and extremity injuries are all more common than cervical fractures.

Alcohol and other risk factors for drowning among male active duty U.S. army soldiers.

BACKGROUND: Risk factors for drowning are largely undocumented among military populations. HYPOTHESIS: Accident report narratives will provide important information about the role of alcohol use and other behaviors in drownings among active duty male U.S. Army soldiers. METHODS: Using a case series design, we describe drowning deaths reported to the U.S. Army Safety Center (1980-1997), documenting associated demographic factors, alcohol use, and other risk-taking behaviors. RESULTS: Drowning victims (n = 352) were disproportionately young, black, and single, with less time-in-service, and no college experience. Most drownings occurred off-duty (89%). Alcohol use was involved in at least 31% of the cases overall. Alcohol use was also associated with a 10-fold increase in reckless behavior (OR 9.6, 95% Cl 4.5-20.7) and was most common among drownings in Europe (OR = 4.3, 95% Cl 1.5-13.4). Most drownings occurred where no lifeguard was present (68%), but almost two-thirds occurred in the presence of others, with CPR initiated in less than one-third of these cases. Drownings involving minority victims were less likely to involve alcohol, but more likely to occur in unauthorized swimming areas. While most drownings did not involve violations of safety rules, over one-third of the cases involved some form of reckless behavior, particularly for those under age 21. CONCLUSIONS: Intervention programs should be tailored to meet the needs of the demographic subgroups at highest risk since behavioral risk factors vary by race and age. CPR training and skills maintenance can improve survival rates. Narrative data are important for developing hypotheses and understanding risk factors for injuries.

Demographic, physical, and mental health factors associated with deployment of U.S. Army soldiers to the Persian Gulf.

A total of 675,626 active duty Army soldiers who were known to be at risk for deployment to the Persian Gulf were followed from 1980 through the Persian Gulf War. Hospitalization histories for the entire cohort and Health Risk Appraisal surveys for a subset of 374 soldiers were used to evaluate prewar distress, health, and behaviors. Deployers were less likely to have had any prewar hospitalizations or hospitalization for a condition commonly reported among Gulf War veterans or to report experiences of depression/suicidal ideation. Deployers reported greater satisfaction with life and relationships but displayed greater tendencies toward risk-taking, such as drunk driving, speeding, and failure to wear safety belts. Deployed veterans were more likely to receive hazardous duty pay and to be hospitalized for an injury than nondeployed Gulf War-era veterans. If distress is a predictor of postwar morbidity, it is likely attributable to experiences occurring during or after the war and not related to prewar exposures or health status. Postwar excess injury risk may be explained in part by a propensity for greater risk-taking, which was evident before and persisted throughout the war.

Progress toward attainment of the Healthy People 2000 objectives in the U.S. Army: measured by health risk appraisal results.

BACKGROUND: Healthy People 2000 (HP2000) is a national agenda of health promotion and disease prevention objectives, with specific health behavior goals in 22 priority areas. The U.S. Army Health Risk Appraisal (HRA) is a self-administered health-habits survey, inquiring about tobacco and alcohol use, physical activity, nutrition, and safety-related practices, given to more than 400,000 active-duty U.S. Army soldiers in the 1990s. This article compares the health behaviors of U.S. Army soldiers, as measured by the HRA, with the HP2000 objectives. METHODS: We compared cross-sectional analyses of self-reported health behaviors of active-duty Army personnel responding to HRA questionnaires in 1991 (n=78,256) and in 1997-1998 (n=59,771) with corresponding HP2000 objectives. We also calculated longitudinal changes for personnel who took more than one HRA (n=86,393). RESULTS: By 1997-1998, the Army exceeded HP2000 physical fitness goals by at least 50% and also exceeded goals for eating high-fiber foods and using bicycle helmets. The Army did not meet goals for nutrition, tobacco use, and seat-belt use. CONCLUSIONS: The Army has made good progress toward the HP2000 goals. However, improvement is needed to meet the tobacco, nutrition, and safety goals.

Cigarette smoking and suicide: a prospective study of 300,000 male active-duty Army soldiers.

The authors examined the relation between cigarette smoking and suicide by conducting a cohort study of 300,000 male US Army personnel followed prospectively from January 1987 through December 1996 for 961,657 person-years. They found that the risk of suicide increased significantly with the number of cigarettes smoked daily (p for trend < 0.001). In multivariable-adjusted analyses, smokers of more than 20 cigarettes a day, compared with never smokers, were more than twice as likely to commit suicide. For male active-duty army personnel, the dose-related association between smoking and suicide was not entirely explained by the greater tendency of smokers to be White, drink heavily, have less education, and exercise less often.

Self-reported risk-taking behaviors and hospitalization for motor vehicle injury among active duty army personnel.

BACKGROUND: Motor vehicle crashes are a leading cause of injury in the Army. Behaviors increasing risk for motor vehicle crashes are also prevalent, but research has not linked these behaviors directly to injury outcomes (e.g., hospitalizations). METHODS: To evaluate the relationship between behavior and motor vehicle crash injuries, 99, 981 Army personnel who completed Health Risk Appraisal surveys in 1992 were followed for up to 6 years. Cox proportional hazards modeling was used to evaluate speeding, seat belt use, drinking patterns, and demographics. RESULTS: A total of 429 soldiers were hospitalized for motor vehicle injury. Unadjusted analyses revealed that heavy drinking, drinking and driving, speeding, low seat belt use, younger age, minority race/ethnicity, and enlisted rank were significantly associated with motor vehicle injury, but neither smoking nor gender was. Multivariate models showed a significant trend of increasing injury risk with younger ages. Soldiers under age 21 were injured almost five times more often than those over age 40 (HR 4.89, 2.56-9.33). Also associated with risk for hospitalizations were minority race (HR 1.78, 1.46-2.18), heaviest drinkers versus abstainers (HR 1.81, 1.11-2.94), and seat belt use of 50% or less versus 100% (HR 1.40, 1.07-1.85). Although nonsignificant, there was evidence of an age-drinking interaction where the difference in injury risk between those older and those younger than 21 was greatest at low alcohol consumption levels. CONCLUSIONS: Modifiable risk factors associated with motor vehicle injuries include heavy drinking and low seat belt use. Programs targeting these behaviors that meet the needs of young and minority soldiers are needed. The high density of young, at-risk soldiers residing in base housing may provide a unique opportunity for a residential intervention program.

What is the risk associated with being a qualified military parachutist?

Military parachuting has been recognized as a hazardous activity since it was first introduced in World War II. Other risks associated with military service include actual war-fighting, training with weapons and explosives, operating with armoured vehicles or deployment to climatic extremes. These other hazards should be considered in any assessment of the additional risk associated with military parachuting. The aim of this study was to identify the risk attributable to parachuting amongst US Army enlisted soldiers. This study identified a cohort of infantry soldiers who served between 1990-94. They were separated by receipt of parachute hazardous duty pay. There was a total of 329,794 person-years (PY) available for study of which 18% were in the exposed group. The rate of hospitalization was very similar in both groups [123.9 per 1,000 PYs for the exposed group, 127 in the non-exposed group: relative risk (RR) = 0.98, 95% confidence interval (CI) = 0.96-1.00). The exposed group was 1.49 times (CI = 1.42-1.57) more likely to be admitted as a result of an injury as compared with the non-exposed group. Military parachuting was 20 times (CI = 16.6-24.3) more likely to be the cause of an injury. This study has shown that receipt of hazardous duty pay for military parachuting can be used as a marker in identifying significant additional risks to the health of infantry soldiers associated with military parachuting. This was reflected in an increased incidence of admission for acute injury and musculoskeletal trauma (particularly a trauma pattern associated with parachuting) as a result of military parachuting. Other risks, which are associated with parachute pay, are admission for the effects of heat, battle injury and helicopter accidents.