Manganese (Mn) is an essential metal that can exert toxic effects at high concentrations, eventually leading to Parkinsonism. A major transporter of Mn in mammals is the divalent-metal transporter (DMT1). We characterize here DMT1-like proteins in the nematode C. elegans, which regulate and are regulated by Mn and iron (Fe) content. We identified three new DMT1-like genes in C. elegans: smf-1, smf-2 and smf-3. All three can functionally substitute for loss of their yeast orthologues in S. cerevisiae. In the worm, deletion of smf-1 or smf-3 led to an increased Mn tolerance, while loss of smf-2 led to increased Mn sensitivity. smf mRNA levels measured by QRT-PCR were up-regulated upon low Mn and down-regulated upon high Mn exposures. Translational GFP-fusions revealed that SMF-1 and SMF-3 strongly localize to partially overlapping apical regions of the gut epithelium, suggesting a differential role for SMF-1 and SMF-3 in Mn nutritional intake. Conversely, SMF-2 was detected in the marginal pharyngeal epithelium, possibly involved in metal-sensing. Analysis of metal content upon Mn exposure in smf mutants revealed that SMF-3 is required for normal Mn uptake, while smf-1 was dispensable. Higher smf-2 mRNA levels correlated with higher Fe content, supporting a role for SMF-2 in Fe uptake. In smf-1 and smf-3 but not in smf-2 mutants, increased Mn exposure led to decreased Fe levels, suggesting that both metals compete for transport by SMF-2. Finally, SMF-3 was post-translationally and reversibly down-regulated following Mn-exposure. In sum, we unraveled a complex interplay of transcriptional and post-translational regulations of 3 DMT1-like transporters in two adjacent tissues, which regulate metal-content in C. elegans.

Objectives: Complementary therapies are often used as adjuncts to conventional treatment by individuals with cancer. Patterns of use of these practices and products represent important data for health care providers in delivering adequate patient care. Design: This study compared use of complementary therapies between the cancer and noncancer populations in the United States through secondary analyses of the 2007 National Health Interview Survey data. The analysis compared use by cancer survivors (those individuals self-reporting a diagnosis of cancer; n=1785) and individuals without cancer (n=21,585), as well as self-report of symptoms affecting health-related quality of life (HQoL). Results: Data suggest similar patterns of use between cancer survivors and the general population; however, a greater percentage of cancer survivors use complementary modalities. Individuals with cancer reported a greater percentage of use of complementary therapies overall, with cancer status significantly associated with ever having used complementary and alternative medicine (p<0.001). The five most common complementary practices and products used by individuals with cancer and controls were vitamin/mineral supplements, prayer for self, intercessory prayer, chiropractic/osteopathic manipulation, and herbal therapies. Additionally, as might be expected, individuals with cancer experience greater frequency of deleterious symptoms associated with decreased HQoL. Individuals with cancer were more likely to sleep fewer than 7 hours (p=0.0108) or greater than 9 hours (p=0.0108), and have increased insomnia (p<0.001), excessive sleepiness (p<0.001), depression (p<0.001), and anxiety (p<0.001) versus those without cancer. Conclusions: The current findings may inform health care providers about the use of complementary and integrative practices and products by patients with cancer in an effort to manage symptoms of the disease. Additionally, these results may also be used to promote research to define the merits of the use of such complementary and integrative practices and products.

Crohn disease is a chronic disorder characterized by episodes of epithelial inflammation in the gastrointestinal tract for which there is no cure. The prevalence of Crohn disease increased in civilized nations during the time period in which food sources were industrialized in those nations. A characteristic of industrialized diets is the conspicuous absence of cereal fiber. The purpose of this 2-group, randomized, controlled study was to investigate the effects of fiber-related dietary instructions specifying wheat bran consumption on health-related quality of life and gastrointestinal function in individuals diagnosed with Crohn disease, as measured by the Inflammatory Bowel Disease Questionnaire and the partial Harvey Bradshaw Index, respectively. Results demonstrated that consuming a wheat bran–inclusive diet was feasible and caused no adverse effects, and participants consuming whole wheat bran in the diet reported improved health-related quality of life (p = .028) and gastrointestinal function (p = .008) compared to the attention control group. The results of a secondary aim, to investigate differences in measures of systemic inflammation, found no group differences in C-reactive protein or erythrocyte sedimentation rates. This study suggests that diet modification may be a welcomed complementary therapy for individuals suffering gastrointestinal disruption associated with Crohn disease.

Chronic exposure to manganese (Mn) may lead to a movement disorder due to preferential Mn accumulation in the globus pallidus and other basal ganglia nuclei. Iron (Fe) deficiency also results in increased brain Mn levels, as well as dysregulation of other trace metals. The relationship between Mn and Fe transport has been attributed to the fact that both metals can be transported via the same molecular mechanisms. It is not known, however, whether brain Mn distribution patterns due to increased Mn exposure vs. Fe deficiency are the same, or whether Fe supplementation would reverse or inhibit Mn deposition. To address these questions, we utilized four distinct experimental populations. Three separate groups of male Sprague–Dawley rats on different diets (control diet [MnT], Fe deficient [FeD], or Fe supplemented [FeS]) were given weekly intravenous Mn injections (3 mg Mn/kg body mass) for 14 weeks, whereas control (CN) rats were fed the control diet and received sterile saline injections. At the conclusion of the study, both blood and brain Mn and Fe levels were determined by atomic absorption spectroscopy and magnetic resonance imaging. The data indicate that changes in dietary Fe levels (either increased or decreased) result in regionally specific increases in brain Mn levels compared with CN or MnT animals. Furthermore, there was no difference in either Fe or Mn accumulation between FeS or FeD animals. These data suggest that dietary Fe manipulation, whether increased or decreased, may contribute to brain Mn deposition in populations vulnerable to increased Mn exposure.

Many individuals, including dementia caregivers, use blogs to share their experiences. These blogs contain rich narratives representing an untapped resource for understanding the psychosocial impact of caring for a person with dementia at the family level. The present study used blogs written by caregivers of persons with dementia to explore how these individuals leveraged this medium as part of the caregiving experience. Blogs written by self-identified informal caregivers of persons with dementia were identified using a systematic search method, and data were analyzed using a qualitative thematic analysis. Four themes emerged from the narratives: social support through communication and engagement, information gathering and seeking, reminiscing and legacy building, and altruism. By understanding the ways in which individuals providing care for persons with dementia use social media as part of the caregiving experience, family nurses can develop interventions and services aimed at improving caregiver burden and quality of life.