Research with neurologically impaired patients suggests that temporal order memory (TOM) and item memory (IM) are associated with the frontal lobes and medial-temporal lobes, respectively. Issues concerning the aging of TOM and IM still remain. First, the frontal lobes may show greater age-related decline than posterior portions of the brain and/or the right hemisphere may show greater decline than the left. Second, TOM and IM may or may not be independent, because findings of double dissociations have not been replicated. Third, the relationship between TOM for items in primary vs. secondary memory is unknown. Finally, the mechanisms controlling TOM are poorly understood, partly because many TOM tests maximize working memory demands, thus masking the roles of strategy, sequencing and inhibition. Thirty-two college-age and 32 older participants completed four sets of TOM and IM tests, each of which measured left- or right-hemisphere function (words vs. faces) and maximized or minimized working memory demands. Participants also completed neuropsychological tests of frontal-lobe function. Composite measures of frontal-lobe and medial-temporal-lobe status based on the age-independent performance on additional neuropsychological tests were used to categorize participants as above or below the mean. These composites were used to predict TOM and IM performance, thus measuring their independence. Results showed greater age-related declines in TOM than IM, regardless of whether faces or words were studied, supporting the frontal-lobe hypothesis of aging. The right-hemisphere hypothesis of aging was not supported. IM and TOM were not found to be independent on any of the four sets of tests. However, frontal-lobe status but not medial-temporal-lobe status predicted TOM performance when one or more test item was in primary memory. Frontal-lobe status did not predict IM performance, regardless of whether items were in primary or secondary memory, suggesting that the frontal-lobes may be specifically involved in TOM when information must be held in mind. Correlations between TOM and neuropsychological tests yielded limited support for the theory that cognitive sequencing is involved in TOM.

DHEA (dehydroepiandrosterone) is a major adrenal hormone, with known accepted function. In both animals and humans low DHEA and DHEA-sulfate levels are associated with a number of problems in the aging: immunosenescence, increased mortality, increased incidence of several cancers, loss of sleep, decreased feelings of well-being, osteoporosis, atherosclerosis and premature death. DHEA hormone replacement in aged mice significantly normalized immunosenescence suggesting that this hormone plays a key role in aging and stimulating immune regulation in mice. Similarly osteoclasts and lymphoid cells, were stimulated by DHEA replacement which should delay osteoporosis. Recent studies do not support the original suggestion that low serum DHEA levels were associated with Alzheimer's and other losses of mental function in aged people. As DHEA modulates energy metabolism low levels should affect lipogenesis and gluconeogenesis, increasing the risk of diabetes and heart disease. Most of the actions of DHEA restoration are hypothesized from epidemiological or animal model studies and need to be tested in human trials. Those conducted in humans show essentially no toxicity of DHEA treatment at levels restoring serum DHEAS levels without evidence of altering some aging physiological systems. Thus DHEA is a steroid whose deficiency could facilitate development of some diseases common to the aged. Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) are steroids, synthesized from cholesterol (Fig. 1.1). While DHEA is secreted primarily by the adrenal gland in larger quantities than any other adrenal steroid including cortisol, the precise functions of DHEA and DHEAS in humans are not known (1-5). The decline of DHEAS levels during aging is parallel to development of immunosensecence, an inability to conserve protein, a physical frailty, decreased muscle mass, an increased fat mass, decreased ability to cope, disrupted sleep patterns and increased incidence of disease. Thus DHEAS serves as a marker of aging in humans. While the precise biological functions of DHEA and DHEAS are not known, both animal and human studies suggest some hypotheses while dispelling others. Therefore key physiological dysfunctions are investigated here to determine biological relationships which participate in the declining blood levels of DHEA with age.

Osteoporosis is a condition of reduced bone mineral density (BMD) resulting in an increased susceptibility to bone fractures. The purpose of this study was to determine the effects of 12 months of weight bearing and resistance exercise on BMD, bone formation, measured by serum osteocalcin (OC) and bone resorption, measured by urinary excretion of deoxypyridinoline crosslinks (Dpd), in 2 groups of postmenopausal women who were either taking or not taking hormone replacement therapy (HRT). Secondary aims were to characterize the changes in insulin-like growth factors-l and -2 (IGF-l and -2) and IGF binding protein 3 (IGFBP3) in response to exercise training, and to determine the contribution of these growth factors in predicting changes in bone mineral density in the 2 populations of postmenopausal women. Women who were three to ten years postmenopausal and aged 40-65 years were included in the study. Women in HRT and no HRT groups were randomized into the exercise intervention resulting in four groups: (1) women not taking HRT, not exercising; (2) women taking HRT, not exercising; (3) women exercising, not taking HRT; and (4) women exercising, taking HRT. The number of subjects per group after one year was 27, 21, 25, and 16, respectively. Exercise training and HRT increase BMD similarly at most BMD sites whereas the combination of exercise and HRT produced increases in BMD greater than either treatment alone. Bone remodeling was surpressed in the groups taking HRT regardless of exercise status. The bone remodeling response to exercise training in women not taking HRT was not significantly different from those not exercising but the direction of change suggests an elevation in bone remodeling in response to exercise training. Exercise training does not stimulate a change in IGF-1, IGF-2, IGF-1:IGF-2, and IGFBP3. Markers of bone remodeling and IGF-1 are significant predictors of BMD changes but the overall amount of variation in BMD changes accounted for is low. Exercise and HRT status were significant predictors of changes in BMD even after accounting for variation due to bone remodeling indicating that bone changes are regulated by factors not addressed in this study.

The purpose of this research was to investigate the relationship among selected environmental and perinatal variables and developmental outcomes in a group of low birth weight infants. A total of thirty infants and mothers were studied. Maternal education level (r =.36, p =.05), paternal education level (r =.44, p =.02), and five minute Apgar score (r =.42, p =.03) were significantly correlated to the quality of home environment; which predicted 28% of the variance in infant developmental status. The perinatal factors of birth weight (r = -.47, p =.01); mechanical ventilation (r =.40, p =.03); Respiratory Distress Syndrome (r =.53, p =.003); and estimated gestational age (r = -.53, p =.003) were correlated to level of maternal depressive symptoms. The relationship between level of maternal depressive symptoms and infant development approached significance (r = -.35, p =.058). These findings support the hypothesis that quality of home environment is a predictor of development for high risk infants.

The goal of the research described in this thesis is to further our understanding of the motor control strategies that are available to the child when learning to produce meaningful interactions with environmental surfaces. The principal aim is to explore the analytical techniques that could be used to evaluate the range of neuromechanical responses for the lower limb that would provide stability at the limb/environment interface during growth and development. Five studies are presented that provide both experimental data and theoretical perspectives that were coalesced in the formulation of a general model for the control of stability at the limb/environment interface. The first study presents an analytical technique that was devised to classify the spatial-temporal organization of the surface myoelectric activity into one of three distinct patterns: Burst, Tonic, and Tonic Burst. This classification permits the matching between the pattern of muscle activity and the kinematic and kinetic control of the ground contact phase of landing. In the second, and companion paper, different distributions of the Burst, Tonic, and Tonic Burst patterns across the muscles of the lower limb were associated with three mechanical responses of the limb to ground contact. Mechanically, the three limb responses show a progression toward an effective control of stability at the limb/environment interface and it was therefore proposed that the distribution of activity patterns could reflect the priorities of system at different stages of growth and development. The results support our hypothesis that more complex movements can be executed when the limits of stability are maximized. Study three presents a formal model for the control of stability at the limb/environment interface. The model was further applied to propose new theoretical approaches that could be used in the clinical milieu, shifting the focus of the evaluation to the range of feasible movements that would be available

<p>Hatchery reared Chinook salmon from California&rsquo;s Central Valley were fed for 67 days (Apr-Jun, 2008) on fish pellets mixed with either 0, 1, 3, or 5 &micro;g&middot;g^&minus;1 methylmercury hydroxide. Weight, fork length, condition factor, and Na⁺,K⁺-ATPase measurements were determined every two weeks and a 96-h seawater challenge was conducted at the conclusion of the experiment. </p><p> Results from two-way ANOVA, with treatment and date as independent variables, indicated no significant differences for weight (F_3,32 = 1.38; P = 0.280), length (F_3,32 = 0.986; P = 0.412) and condition factor (_F3,32 = 0.239; P = 0.869). Post-hoc analysis following two-way ANOVA indicated mean ATPase activity in the high (x&macr; = 3.08, S.E. = 0.19; P = 0.008) and medium treatments (x&macr; = 2.86, S.E. = 0.57; P = 0.017) was significantly increased in early May compared with the control group (x&macr; = 1.47, S.E. = 0.34). The results from the 96 h seawater challenge were consistent with those of other studies indicating weight has the greatest influence for survival in the transition from freshwater to seawater. Overall, results from this study indicated methylmercury, a known neurotoxin, altered ATPase activity in fall-run Chinook but did not significantly affect mortality in the transition from freshwater to seawater. </p>

<p> Puerto Rico has the highest prevalence of type 2 diabetes, low birth-weight, and the second highest prevalence of preterm-birth in all the U.S. and its non-incorporated territories. These conditions are related. Birth-weight at both ends of the spectrum and preterm-birth are associated with an increased risk for developing type 2 diabetes and immune-inflammatory dysregulations. Maternal psychosocial stressors during pregnancy have also been recognized as potential risk factors for type 2 diabetes, and have been consistently associated with preterm-birth and low birth-weight across populations. Current evidence points toward epigenetic fetal metabolic-programming as the mechanism that underlies the increased risk for the previously mentioned morbidities. However, the particular psychosocial stressors that may contribute to the high prevalence of low birth-weight and preterm-birth in the population of Puerto Rico have not been well studied.</p><p> The present study assesses the relationships between particular psychosocial stressors, socioeconomic status, food insecurity, and birth outcomes. The results of this study show that low-risk pregnancy women were more likely to have babies with a higher ponderal index if they were exposed to stressors during gestation months 5, 6, and 7, or if exposed to "relationship stress" at any time during pregnancy. Women exposed to "financial difficulties" at any time during pregnancy were more likely to deliver babies at an earlier gestational age. Differences in birth outcomes between the exposed and non-exposed women were independent of maternal anthropometric measurements, maternal age at birth, number of previous births, and sex of the baby. Significant differences in birth outcomes were found between categories of father's self-identified and identified by others ethnicity, but sample size within categories was small. Although mothers with children at home had higher levels of food insecurity, and the level of food insecurity was correlated with higher levels of stress, no birth outcome measure was associated with food insecurity.</p><p> Some results are atypical in comparison with other populations, and therefore these findings may contribute to the understanding of population differences in the relationship between maternal stress during pregnancy and birth outcomes. The relatively small sample size and strict exclusion criteria of this study may limit the generalizability of the findings. Epidemiological similarities between Puerto Rico and other populations, and the possibility of a higher ponderal index increasing the risk for type 2 diabetes in the population of Puerto Rico need to be examined in future research.</p>

In this thesis, the effects of an active analog of cyclophosphamide (4-hydroperoxycyclophosphamide, 4OOH-CPA), an alkylating agent and teratogen, on mouse limb development, cell death and the role of the p53 gene in this process were studied. A mouse limb bud culture system was used for this purpose. Limbs developed normally in this system and showed physiological apoptosis in a spatio-temporal-controlled manner. Drug treatment caused limb reduction malformations, increased the amount of apoptosis and triggered its occurrence prematurely, primarily in areas with physiological apoptosis. This indicated that drug-treatment might have engaged the already available program of apoptosis in the developing limb, and suggested this might be the cause of limb malformations. Next we examined the induction pattern of three proteins, cathepsin D, transglutaminase and clusterin, known to be involved in the molecular mechanism of apoptosis. The pattern of their induction suggested that cathepsin D was involved in the digestion of apoptotic debris, transglutaminase was active in preserving the cellular integrity during apoptosis, and clusterin played a role in later phases of apoptosis. Since 4OOH-CPA causes DNA damage, we studied the role of the p53 gene, a DNA-damage response gene involved in regulating cell cycle and apoptosis, in a p53-transgenic mouse model. Absence of p53 led to more severe limb malformations in the treated limbs. To investigate the reason(s) for this higher sensitivity to drug insult, cell death and cell cycle patterns were studied. While wild-type limbs showed an induction of apoptosis by drug treatment, which might be crucial in eliminating damaged cells, the null limbs were resistant to this effect. Furthermore, in response to 4OOH-CPA-treatment, the cell cycle was not arrested in p53 -/- limbs, in contrast to wild-type limbs; this arrest is necessary for DNA repair. Further investigation revealed the occurrence of necrosis in p53 -/- limbs. Thus, we

We studied the effect of Trichuris trichiura on growth in a randomized, double-blind trial in which 508 Mexican children (2 to 10 years) with asymptomatic infections were randomized to one of 3 medication regimes that were selected to differ in efficacy against Trichuris: a single II mg/kg dose of pyrantel pamoate (low efficacy), a single 400 mg dose of albendazole (moderate efficacy) and 3 daily 400 mg doses of albendazole (high efficacy). All three treatment regimes are effective against a range of parasites, and conventional wisdom at the start of the trial was that asymptomatic Trichuris infection is harmless and has no effect on growth. The hypothesis was that children treated with 3 doses of albendazole grow better than children treated with a single dose of albendazole who, in turn, grow better than children treated with pyrantel pamoate. The children were measured and treated at baseline and every 4 months over 12 months. In spite of the differential efficacy of the 3 treatments against Trichuris, there were no differences in overall increment in height, weight, and arm circumference between the three treatment groups. However, the children who received the 3 daily 400 mg regime of albendazole had a significantly lower increment in triceps skinfold thickness than those who received pyrantel pamoate. The children who had higher intensities of Trichuris at baseline and who received the single 400 mg albendazole regime grew more in height than children in the same treatment group with lower initial levels of infection. The increment in weight, arm circumference, and triceps skinfold thickness was also a positive function of the initial intensity of Trichuris infection in the children who received 3 daily 400 mg doses of albendazole. This study provides evidence that low, asymptomatic levels of Trichuris can impair growth, and suggests that either albendazole or pyrantel pamoate or both may have an effect on the growth of children, independent of a therapeuti

Master of Science / Department of Family Studies and Human Services / Anthony Jurich / Throughout this report, I focused on the effects that the loss of a parent has on an adolescent during the various stages of adolescent development. Drawing upon research already completed on divorce during adolescence, I speculated on the similarities and differences between losing a parent through divorce or death during the adolescent stages of development. Loss by any means is tragic and life altering. However, as I attempted to illustrate, it was even more defining when encountered during the period of adolescence.