The Influence of HeartMath® on Resilience and Empowerment in Female College Athletes.

PURPOSE: The purpose of this pilot study was to examine the influence of HeartMath® on female college athletes' abilities to holistically care for self as assessed through resiliency and power. DESIGN: The descriptive design used mixed methods and was approved by the university's institutional review board. The purposive sample was female college student athletes who were currently enrolled in a university program of study and played in a National Collegiate Athletic Association sanctioned sport. METHOD: There were eight weekly sessions where the holistic intervention HeartMath® was taught and reinforced. Participants completed two tools to measure resilience and power Weeks 1, 4, and 8: the Connor-Davidson Resilience Scale and the Power as Knowing Participation in Change Tool. At Session 8, a focus group interview was conducted to explore perception of how HeartMath® influenced caring for self as a student athlete. FINDINGS: Although no statistical significance, emergent themes support that with HeartMath®, participants experienced an increase in resilience and power influencing their holistic caring for self. CONCLUSIONS: Findings support the need for additional research on the influence of HeartMath® on student athlete resilience and power in any team on and off the playing field.

Three members of a peptide family are differentially distributed and elicit differential state-dependent responses in a pattern generator-effector system.

C-type allatostatins (AST-Cs) are pleiotropic neuropeptides that are broadly conserved within arthropods; the presence of three AST-C isoforms, encoded by paralog genes, is common. However, these peptides are hypothesized to act through a single receptor, thereby exerting similar bioactivities within each species. We investigated this hypothesis in the American lobster, Homarus americanus, mapping the distributions of AST-C isoforms within relevant regions of the nervous system and digestive tract, and comparing their modulatory influences on the cardiac neuromuscular system. Immunohistochemistry showed that in the pericardial organ, a neuroendocrine release site, AST-C I and/or III and AST-C II are contained within distinct populations of release terminals. Moreover, AST-C I/III-like immunoreactivity was seen in midgut epithelial endocrine cells and the cardiac ganglion (CG), whereas AST-C II-like immunoreactivity was not seen in these tissues. These data suggest that AST-C I and/or III can modulate the CG both locally and hormonally; AST-C II likely acts on the CG solely as a hormonal modulator. Physiological studies demonstrated that all three AST-C isoforms can exert differential effects, including both increases and decreases, on contraction amplitude and frequency when perfused through the heart. However, in contrast to many state-dependent modulatory changes, the changes in contraction amplitude and frequency elicited by the AST-Cs were not functions of the baseline parameters. The responses to AST-C I and III, neither of which is COOH-terminally amidated, are more similar to one another than they are to the responses elicited by AST-C II, which is COOH-terminally amidated. These results suggest that the three AST-C isoforms are differentially distributed in the lobster nervous system/midgut and can elicit distinct behaviors from the cardiac neuromuscular system, with particular structural features, e.g., COOH-terminal amidation, likely important in determining the effects of the peptides. NEW & NOTEWORTHY Multiple isoforms of many peptides exert similar effects on neural circuits. In this study we show that each of the three isoforms of C-type allatostatin (AST-C) can exert differential effects, including both increases and decreases in contraction amplitude and frequency, on the lobster cardiac neuromuscular system. The distribution of effects elicited by the nonamidated isoforms AST-C I and III are more similar to one another than to the effects of the amidated AST-C II.

Non-amidated and amidated members of the C-type allatostatin (AST-C) family are differentially distributed in the stomatogastric nervous system of the American lobster, Homarus americanus.

The crustacean stomatogastric nervous system (STNS) is a well-known model for investigating neuropeptidergic control of rhythmic behavior. Among the peptides known to modulate the STNS are the C-type allatostatins (AST-Cs). In the lobster, Homarus americanus, three AST-Cs are known. Two of these, pQIRYHQCYFNPISCF (AST-C I) and GNGDGRLYWRCYFNAVSCF (AST-C III), have non-amidated C-termini, while the third, SYWKQCAFNAVSCFamide (AST-C II), is C-terminally amidated. Here, antibodies were generated against one of the non-amidated peptides (AST-C I) and against the amidated isoform (AST-C II). Specificity tests show that the AST-C I antibody cross-reacts with both AST-C I and AST-C III, but not AST-C II; the AST-C II antibody does not cross-react with either non-amidated peptide. Wholemount immunohistochemistry shows that both subclasses (non-amidated and amidated) of AST-C are distributed throughout the lobster STNS. Specifically, the antibody that cross-reacts with the two non-amidated peptides labels neuropil in the CoGs and the stomatogastric ganglion (STG), axons in the superior esophageal (son) and stomatogastric (stn) nerves, and ~ 14 somata in each commissural ganglion (CoG). The AST-C II-specific antibody labels neuropil in the CoGs, STG and at the junction of the sons and stn, axons in the sons and stn, ~ 42 somata in each CoG, and two somata in the STG. Double immunolabeling shows that, except for one soma in each CoG, the non-amidated and amidated peptides are present in distinct sets of neuronal profiles. The differential distributions of the two AST-C subclasses suggest that the two peptide groups are likely to serve different modulatory roles in the lobster STNS.

Radiation exposure from depleted uranium: The radiation bystander effect.

Depleted uranium (DU) is a radioactive heavy metal used primarily in military applications. Published data from our laboratory have demonstrated that DU exposure in vitro to immortalized human osteoblast cells (HOS) is both neoplastically transforming and genotoxic. In vivo studies have also demonstrated that DU is leukemogenic and genotoxic. DU possesses both a radiological (alpha particle) and chemical (metal) component but is generally considered a chemical biohazard. Studies have shown that alpha particle radiation does play a role in DU's toxic effects. Evidence has accumulated that non-irradiated cells in the vicinity of irradiated cells can have a response to ionization events. The purpose of this study was to determine if these "bystander effects" play a role in DU's toxic and neoplastic effects using HOS cells. We investigated the bystander responses between DU-exposed cells and non-exposed cells by co-culturing the two equal populations. Decreased cell survival and increased neoplastic transformation were observed in the non-DU exposed cells following 4 or 24h co-culture. In contrast Ni (II)- or Cr(VI)- exposed cells were unable to alter those biological effects in non-Ni(II) or non-Cr(VI) exposed co-cultured cells. Transfer experiments using medium from the DU-exposed and non-exposed co-cultured cells was able to cause adverse biological responses in cells; these results demonstrated that a factor (s) is secreted into the co-culture medium which is involved in this DU-associated bystander effect. This novel effect of DU exposure could have implications for radiation risk and for health risk assessment associated with DU exposure.

Role of lateral hypothalamus in two aspects of attention in associative learning.

Orexin (hypocretin) and melanin-concentrating hormone (MCH) neurons are unique to the lateral hypothalamic (LH) region, but project throughout the brain. These cell groups have been implicated in a variety of functions, including reward learning, responses to stimulants, and the modulation of attention, arousal and the sleep/wakefulness cycle. Here, we examined roles for LH in two aspects of attention in associative learning shown previously to depend on intact function in major targets of orexin and MCH neurons. In experiments 1 and 2, unilateral orexin-saporin lesions of LH impaired the acquisition of conditioned orienting responses (ORs) and bilaterally suppressed FOS expression in the amygdala central nucleus (CeA) normally observed in response to food cues that provoke conditioned ORs. Those cues also induced greater FOS expression than control cues in LH orexin neurons, but not in MCH neurons. In experiment 3, unilateral orexin-saporin lesions of LH eliminated the cue associability enhancements normally produced by the surprising omission of an expected event. The magnitude of that impairment was positively correlated with the amount of LH damage and with the loss of orexin neurons in particular, but not with the loss of MCH neurons. We suggest that the effects of the LH orexin-saporin lesions were mediated by their effect on information processing in the CeA, known to be critical to both behavioral phenomena examined here. The results imply close relations between LH motivational amplification functions and attention, and may inform our understanding of disorders in which motivational and attentional impairments co-occur.

Preconceptional paternal exposure to depleted uranium: transmission of genetic damage to offspring.

Depleted uranium (DU) is an alpha particle emitter and radioactive heavy metal used in military applications. Due to internalization of DU during military operations and the ensuing chronic internal exposure to DU, there are concerns regarding its potential health effects. Preconceptional paternal irradiation has been implicated as a causal factor in childhood cancer and it has been suggested that this paternal exposure to radiation may play a role in the occurrence of leukemia and other cancers to offspring. Similarly, in vivo heavy metal studies have demonstrated that carcinogenic effects can occur in unexposed offspring. Using a transgenic mouse system employing a lambda shuttle vector allowing mutations (in the lacI gene) to be analyzed in vitro, we have investigated the possibility that chronic preconceptional paternal DU exposure can lead to transgenerational transmission of genomic instability. The mutation frequencies in vector recovered from the bone marrow cells of the F1 offspring of male parents exposed to low, medium, and high doses of internalized DU for 7 mo were evaluated and compared to control, tantalum, nickel, and gamma radiation F1 samples. Results demonstrate that as paternal DU-dose increased there was a trend towards higher mutation frequency in vector recovered from the DNA obtained from bone marrow of F1 progeny; medium and high dose DU exposure to P1 fathers resulted in a significant increase in mutation frequency in F1 offspring (3.57 +or - 0.37 and 4.81 + or - 0.43 x 10; p < 0.001) in comparison to control (2.28 + or - 0.31 x 10). The mutation frequencies from F1 offspring of low dose DU, Ta- or Ni-implanted fathers (2. 71 + or - 0.35, 2.38 + or - 0.35, and 2.93 + or - 0.39 x 10, respectively) were not significantly different than control levels (2.28 + or - 0.31 x 10). Offspring from Co (4 Gy) irradiated fathers did demonstrate an increased lacI mutation frequency (4.69 + or - 0.48 x 10) as had been shown previously. To evaluate the role of radiation involved in the observed DU effects, males were exposed to equal concentrations (50 mg U L) of either enriched uranium or DU in their drinking water for 2 mo prior to breeding. A comparison of these offspring indicated that there was a specific-activity dependent increase in offspring bone marrow mutation frequency. Taken together these uranyl nitrate data support earlier results in other model systems showing that radiation can play a role in DU-induced biological effects in vitro. However, since the lacI mutation model measures point mutations and cannot measure large deletions that are characteristic of radiation damage, the role of DU chemical effects in the observed offspring mutation frequency increase may also be significant. Regardless of the question of DU-radiation vs. DU-chemical effects, the data indicate that there exists a route for transgenerational transmission of factor(s) leading to genomic instability in F1 progeny from DU-exposed fathers.

DNA methylation during depleted uranium-induced leukemia.

OBJECTIVES: The radioactive heavy metal depleted uranium (DU) is used in kinetic-energy penetrators in military applications. The objective of this study was to determine involvement of DNA methylation in DU-induced leukemia. METHODS: Methylation was measured by direct analysis of 5-methylcytosine content of spleen DNA in DU leukemic mice. RESULTS: Spleen hypomethylation occurred during DU-induced leukemogenesis (chronic internal DU exposure). Aberrant gene transcription was also detected. CONCLUSIONS: Epigenetic mechanisms are implicated in DU-induced leukemia. These data are evidence of aberrant DNA hypomethylation being associated with DU leukemogenesis.

A review of depleted uranium biological effects: in vitro and in vivo studies.

The use of depleted uranium in armor-penetrating munitions remains a source of controversy because of the numerous unanswered questions about its long-term health effects. Although no conclusive epidemiologic data have correlated DU exposure to specific health effects, studies using cultured cells and laboratory rodents continue to suggest the possibility of leukemogenic, genetic, reproductive, and neurological effects from chronic exposure. Until issues of concern are resolved with further research, the use of depleted uranium by the military will continue to be controversial.

Leukemic transformation of hematopoietic cells in mice internally exposed to depleted uranium.

Depleted uranium (DU) is a dense heavy metal used in military applications. During military conflicts, US military personnel have been wounded by DU shrapnel. The health effects of embedded DU are unknown. Published data from our laboratory demonstrated that DU exposure in vitro can transform immortalized human osteoblast cells (HOS) to the tumorigenic phenotype. Results from our laboratory have also shown that DU is genotoxic and mutagenic in cultured human cells. Internalized DU could be a carcinogenic risk and concurrent alpha particle and heavy metal toxic effects complicate this potential risk. Anecdotal reports have suggested that DU can cause leukemia. To better assess this risk, we have developed an in vivo leukemogenesis model. This model involves using murine hematopoietic cells (FDC-P1) that are dependent on stimulation by granulocyte-macrophage colony stimulating factor (GM-CSF) or interleukin 3 (IL-3) and injected into mice to produce myeloid leukemia. Although immortalized, these cells are not tumorigenic on subcutaneous inoculation in mice. Intravenous injection of FDC-P1 cells into DU-implanted DBA/2 mice was followed by the development of leukemias in 76% of all mice implanted with DU pellets. In contrast, only 12% of control mice developed leukemia. Karyotypic analysis confirmed that the leukemias originated from FDC-P1 cells. The growth properties of leukemic cells from bone marrow, spleen, and lymph node were assessed and indicate that the FDC-P1 cells had become transformed in vivo. The kidney, spleen, bone marrow, muscle, and urine showed significant elevations in tissue uranium levels prior to induction of leukemia. These results demonstrated that a DU altered in vivo environment may be involved in the pathogenesis of DU induced leukemia in an animal model.

Effect of the militarily-relevant heavy metals, depleted uranium and heavy metal tungsten-alloy on gene expression in human liver carcinoma cells (HepG2).

Depleted uranium (DU) and heavy-metal tungsten alloys (HMTAs) are dense heavy-metals used primarily in military applications. Chemically similar to natural uranium, but depleted of the higher activity 235U and 234U isotopes, DU is a low specific activity, high-density heavy metal. In contrast, the non-radioactive HMTAs are composed of a mixture of tungsten (91-93%), nickel (3-5%), and cobalt (2-4%) particles. The use of DU and HMTAs in military munitions could result in their internalization in humans. Limited data exist however, regarding the long-term health effects of internalized DU and HMTAs in humans. Both DU and HMTAs possess a tumorigenic transforming potential and are genotoxic and mutagenic in vitro. Using insoluble DU-UO2 and a reconstituted mixture of tungsten, nickel, cobalt (rWNiCo), we tested their ability to induce stress genes in thirteen different recombinant cell lines generated from human liver carcinoma cells (HepG2). The commercially available CAT-Tox (L) cellular assay consists of a panel of cell lines stably transfected with reporter genes consisting of a coding sequence for chloramphenicol acetyl transferase (CAT) under transcriptional control by mammalian stress gene regulatory sequences. DU, (5-50 microg/ml) produced a complex profile of activity demonstrating significant dose-dependent induction of the hMTIIA FOS, p53RE, Gadd153, Gadd45, NFkappaBRE, CRE, HSP70, RARE, and GRP78 promoters. The rWNiCo mixture (5-50 microg/ml) showed dose-related induction of the GSTYA, hMTIIA, p53RE, FOS, NFkappaBRE, HSP70, and CRE promoters. An examination of the pure metals, tungsten (W), nickel (Ni), and cobalt (Co), comprising the rWNiCo mixture, demonstrated that each metal exhibited a similar pattern of gene induction, but at a significantly decreased magnitude than that of the rWNiCo mixture. These data showed a synergistic activation of gene expression by the metals in the rWNiCo mixture. Our data show for the first time that DU and rWNiCo can activate gene expression through several signal transduction pathways that may be involved in the toxicity and tumorigenicity of both DU and HMTAs.

Genomic instability in human osteoblast cells after exposure to depleted uranium: delayed lethality and micronuclei formation.

It is known that radiation can induce a transmissible persistent destabilization of the genome. We have established an in vitro cellular model using HOS cells to investigate whether genomic instability plays a role in depleted uranium (DU)-induced effects. Transmissible genomic instability, manifested in the progeny of cells exposed to ionizing radiation, has been characterized by de novo chromosomal aberrations, gene mutations, and an enhanced death rate. Cell lethality and micronuclei formation were measured at various times after exposure to DU, Ni, or gamma radiation. Following a prompt, concentration-dependent acute response for both endpoints, there was de novo genomic instability in progeny cells. Delayed reproductive death was observed for many generations (36 days, 30 population doublings) following exposure to DU, Ni, or gamma radiation. While DU stimulated delayed production of micronuclei up to 36 days after exposure, levels in cells exposed to gamma-radiation or Ni returned to normal after 12 days. There was also a persistent increase in micronuclei in all clones isolated from cells that had been exposed to nontoxic concentrations of DU. While clones isolated from gamma-irradiated cells (at doses equitoxic to metal exposure) generally demonstrated an increase in micronuclei, most clonal progeny of Ni-exposed cells did not. These studies demonstrate that DU exposure in vitro results in genomic instability manifested as delayed reproductive death and micronuclei formation.

Depleted uranium-catalyzed oxidative DNA damage: absence of significant alpha particle decay.

Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Published data from our laboratory have demonstrated that DU exposure in vitro to immortalized human osteoblast cells (HOS) is both neoplastically transforming and genotoxic. DU possesses both a radiological (alpha particle) and a chemical (metal) component. Since DU has a low-specific activity in comparison to natural uranium, it is not considered to be a significant radiological hazard. In the current study we demonstrate that DU can generate oxidative DNA damage and can also catalyze reactions that induce hydroxyl radicals in the absence of significant alpha particle decay. Experiments were conducted under conditions in which chemical generation of hydroxyl radicals was calculated to exceed the radiolytic generation by one million-fold. The data showed that markers of oxidative DNA base damage, thymine glycol and 8-deoxyguanosine could be induced from DU-catalyzed reactions of hydrogen peroxide and ascorbate similarly to those occurring in the presence of iron catalysts. DU was 6-fold more efficient than iron at catalyzing the oxidation of ascorbate at pH 7. These data not only demonstrate that DU at pH 7 can induced oxidative DNA damage in the absence of significant alpha particle decay, but also suggest that DU can induce carcinogenic lesions, e.g. oxidative DNA lesions, through interaction with a cellular oxygen species.

Health effects of embedded depleted uranium.

The health effects of embedded fragments of depleted uranium (DU) are being investigated to determine whether current surgical fragment-removal policies are appropriate for this metal. The authors studied rodents implanted with DU pellets as well as cultured human cells exposed to DU compounds. Results indicate that uranium from implanted DU fragments distributes to tissues distant from implantation sites, including bone, kidney, muscle, and liver. Despite levels of uranium in kidney that would be nephrotoxic after acute exposure, no histological or functional kidney toxicity was observed with embedded DU, indicating that the kidney adapts when exposed chronically. Nonetheless, further studies of the long-term health impact are needed. DU is mutagenic and transforms human osteoblastic cells into a tumorigenic phenotype. It alters neurophysiological parameters in rat hippocampus, crosses the placental barrier, and enters fetal tissue. Preliminary data also indicate decreased rodent litter size when animals are bred 6 months or longer after DU implantation.

Potential late health effects of depleted uranium and tungsten used in armor-piercing munitions: comparison of neoplastic transformation and genotoxicity with the known carcinogen nickel.

Limited data exist to permit an accurate assessment of risks for carcinogenesis and mutagenesis from embedded fragments or inhaled particulates of depleted uranium (DU). Ongoing studies have been designed to provide information about the carcinogenic potential of DU using in vitro and in vivo assessments of morphological transformation as well as cytogenetic, mutagenic, and oncogenic effects. For comparison, we also examined tungsten alloys used in military projectiles and the known carcinogen nickel. Quantitative and qualitative in vitro transformation studies were done to assess the carcinogenic potential of radiation and chemical hazards. Using a human osteosarcoma cell model, we demonstrated that soluble and insoluble DU compounds can transform cells to the tumorigenic phenotype, as characterized by morphological, biochemical, and oncogenic changes consistent with tumor cell behavior. Tungsten alloys and nickel were also shown to be neoplastic transforming agents, although at a frequency less than that of DU. Sister chromatid exchange, micronuclei, and alkaline filter elution assays showed DU and tungsten alloys were genotoxic. Exposure to a nontoxic, nontransforming dose of DU induced a small but statistically significant increase in the number of dicentrics formed in cells. These results suggest that long-term exposure to DU or tungsten alloys could be critical to the development of neoplastic disease in humans and that additional studies are needed.