Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52

<div><p>Manganese is essential to life, and humans typically absorb sufficient quantities of this element from a normal healthy diet; however, chronic, elevated ingestion or inhalation of manganese can be neurotoxic, potentially leading to <i>manganism</i>. Although imaging of large amounts of accumulated Mn(II) is possible by MRI, quantitative measurement of the biodistribution of manganese, particularly at the trace level, can be challenging. In this study, we produced the positron-emitting radionuclide ⁵²Mn (<i>t</i>_<i>1/2</i> = 5.6 d) by proton bombardment (<i>E</i>_<i>p</i><15 MeV) of chromium metal, followed by solid-phase isolation by cation-exchange chromatography. An aqueous solution of [⁵²Mn]MnCl₂ was nebulized into a closed chamber with openings through which mice inhaled the aerosol, and a separate cohort of mice received intravenous (IV) injections of [⁵²Mn]MnCl₂. <i>Ex vivo</i> biodistribution was performed at 1 h and 1 d post-injection/inhalation (p.i.). In both trials, we observed uptake in lungs and thyroid at 1 d p.i. Manganese is known to cross the blood-brain barrier, as confirmed in our studies following IV injection (0.86%ID/g, 1 d p.i.) and following inhalation of aerosol, (0.31%ID/g, 1 d p.i.). Uptake in salivary gland and pancreas were observed at 1 d p.i. (0.5 and 0.8%ID/g), but to a much greater degree from IV injection (6.8 and 10%ID/g). In a separate study, mice received IV injection of an imaging dose of [⁵²Mn]MnCl₂, followed by <i>in vivo</i> imaging by positron emission tomography (PET) and <i>ex vivo</i> biodistribution. The results from this study supported many of the results from the biodistribution-only studies. In this work, we have confirmed results in the literature and contributed new results for the biodistribution of inhaled radiomanganese for several organs. Our results could serve as supporting information for environmental and occupational regulations, for designing PET studies utilizing ⁵²Mn, and/or for predicting the biodistribution of manganese-based MR contrast agents.</p></div

Phonological Translation in Bilingual and Monolingual Children

Bilingual children face a variety of challenges that their monolingual peers do not. For instance, switching between languages requires the phonological translation of proper names, a skill that requires mapping the phonemic units of one language onto the phonemic units of the other. Proficiency of phonological awareness has been linked to reading success, but little information is available about phonological awareness across multiple phonologies. Furthermore, the relationship between this kind of phonological awareness and reading has never been addressed. The current study investigated phonological translation using a task designed to measure children\u27s ability to map one phonological system onto another. A total of 425 kindergarten and second grade monolingual and bilingual students were evaluated. The results suggest that monolinguals generally performed poorly. Bilinguals translated real names more accurately than fictitious names, in both directions. Correlations between phonological translation and measures of reading ability were moderate, but reliable. Phonological translation is proposed as a tool with which to evaluate phonological awareness through the perspective of children who live with two languages and two attendant phonemic systems

Hallucinations Are Real to Patients With Dementia

In this case study, we present a patient with preexistent posttraumatic stress disorder and psychosis who has been recently diagnosed with Dementia with Lewy Bodies. He is experiencing vivid hallucinations. What went wrong between him and his wife as a result of these hallucinations is presented. Alternative actions that could have been used are suggested

Variation de la masse et des caractères morphologiques des lémuriens nocturnes dans les forêts primaires et dégradées de Menabe Sud, Belo sur Mer, Madagascar

Forest structure effects primate morphology because it determines the availability and characteristics of resources, such as substrates for locomotion, sleeping trees, and trees food. However, forest degradation may alter environmental condition of habitats and influence lemur behavior and morphology. We evaluated the links between forest degradation, lemur body mass, and lemur morphometric. We surveyed red-tailed sportive lemurs (Lepilemur ruficaudatus) and gray mouse lemurs (Microcebus murinus) in the dry, deciduous forest of southern Menabe, Morondava, Madagascar. The study was conducted in the dry season in 2014 (November–December) and 2015 (July–September). Lemur captures were conducted in five forest sites: two primary forest and three disturbed forest. Sherman and Tomahawk style traps were used to capture mouse lemurs. We conducted three capture sessions in site B in 2014 and three capture sessions for each site in 2015, for a total of 5616 night traps. During each capture session, 80 Sherman traps and 24 Tomahawk traps were installed for three consecutive nights. To capture the red-tailed sportive lemur, we used a gun (Dan Inject Model JM air rifle) with a tranquillizer dart to immobilize the animal. We collected morphometric measurements from 232 mouse lemurs and 31 red-tailed sportive lemurs. Botanic plots (5m x 5m) allowed us to characterize the forest characteristics: tree diameter at breast height (DBH), tree height, tree abundance, tree crown height and diameter. Tree abundance with DBH ≥ 5 cm and trees diversity varied significantly between sites (P &lt; 0.001). Mouse lemur body mass did not vary with seasonality of the capture (P &gt; 0.05). For mouse lemurs, all morphometric from two populations in the pristine forest were similar (P &gt; 0.05). Mouse lemurs in one disturbed habitat had greater body length and body mass than mouse lemurs in the pristine forest (P &lt; 0.05). The difference may be linked with fruit abundance of two trees species (Tamarindus indica and Ziziphus mauritiana) and more insect availability in the disturbed site. In the altered habitat, mouse lemur females had longest body size and heavier than males (P &lt; 0.05). Red-tailed sportive lemur body mass and length did not change between sites (P &gt; 0.05). Our study is consistent with the hypothesis that lemur morphometric and body mass may change with forest degradation in southern forest of Menabe. Additionally, the range of the response varies between species and sex: mouse lemurs had a wider reaction norm to the habitat disturbance than did red-tailed sportive lemurs. Mouse lemurs may have higher ecological flexibility and tolerance for forest changes, specifically the alteration of forest habitats. Understanding how lemur morphology responds to habitat disturbance may be used as a tool to prioritize lemur conservation.   Résumé La perte d’habitat due à l’activité humaine est une menace qui affecte tous les primates à Madagascar. Les lémuriens, primates arboricoles, ont des réponses variées face au changement de leur habitat. La présente recherche vise à déterminer le lien entre la dégradation forestière, la masse et les caractères morphologiques des lémuriens nocturnes de Menabe Sud : Lepilemur ruficaudatus et Microcebus murinus. L’étude a été effectuée dans cinq sites dont deux sites sont des forêts primaires et trois autres sont des forêts perturbées. La capture et la mesure des caractères morphologiques des lémuriens ont été réalisées entre novembre et décembre 2014, puis entre juillet et septembre 2015. Des parcelles botaniques (5m x 5m) ont été utilisées pour décrire les caractéristiques des sites dont l’abondance des arbres, le diamètre à hauteur de poitrine ou la hauteur et le diamètre de la couronne. La masse de M. murinus n’était pas influencée par la saison de capture (P &gt; 0,05), mais elle variait avec le sexe (P &lt; 0,005) et le site (P &lt; 0,001). Tous les caractères morphologiques de M. murinus dans les deux forêts primaires étaient similaires (P &gt; 0,05). Par contre, dans les forêts perturbées, les femelles de M. murinus étaient plus lourdes et avaient des corps plus longs que les mâles (P &lt; 0,05). La masse et la longueur du corps de L. ruficaudatus entre les différents sites étaient similaires (P &gt; 0,05). Comparé à L. ruficaudatus, M. murinus répondrait davantage à la dégradation forestière. Comprendre l’étendue de la réponse morphologique des lémuriens face à la dégradation de leur habitat pourrait être utilisé comme outil pour prioriser leur conservation

Enrollment of adolescents and young adults onto SWOG cancer research network clinical trials: A comparative analysis by treatment site and era.

BackgroundFew adolescents and young adults (AYAs, 15-39 years old) enroll onto cancer clinical trials, which hinders research otherwise having the potential to improve outcomes in this unique population. Prior studies have reported that AYAs are more likely to receive cancer care in community settings. The National Cancer Institute (NCI) has led efforts to increase trial enrollment through its network of NCI-designated cancer centers (NCICC) combined with community outreach through its Community Clinical Oncology Program (CCOP; replaced by the NCI Community Oncology Research Program in 2014).MethodsUsing AYA proportional enrollment (the proportion of total enrollments who were AYAs) as the primary outcome, we examined enrollment of AYAs onto SWOG therapeutic trials at NCICC, CCOP, and non-NCICC/non-CCOP sites from 2004 to 2013 by type of site, study period (2004-08 vs 2009-13), and patient demographics.ResultsOverall, AYA proportional enrollment was 10.1%. AYA proportional enrollment decreased between 2004-2008 and 2009-2013 (13.1% vs 8.5%, P &lt; .001), and was higher at NCICCs than at CCOPs and non-NCICC/non-CCOPs (14.1% vs 8.3% and 9.2%, respectively; P &lt; .001). AYA proportional enrollment declined significantly at all three site types. Proportional enrollment of AYAs who were Black or Hispanic was significantly higher at NCICCs compared with CCOPs or non-NCICC/non-CCOPs (11.5% vs 8.8, P = .048 and 11.5% vs 8.6%, P = .03, respectively).ConclusionNot only did community sites enroll a lower proportion of AYAs onto cancer clinical trials, but AYA enrollment decreased in all study settings. Initiatives aimed at increasing AYA enrollment, particularly in the community setting with attention to minority status, are needed

The Role of the Membrane Potential in Chondrocyte Volume Regulation

Many cell types have significant negative resting membrane potentials (RMPs) resulting from the activity of potassium-selective and chloride-selective ion channels. In excitable cells, such as neurones, rapid changes in membrane permeability underlie the generation of action potentials. Chondrocytes have less negative RMPs and the role of the RMP is not clear. Here we examine the basis of the chondrocyte RMP and possible physiological benefits. We demonstrate that maintenance of the chondrocyte RMP involves gadolinium-sensitive cation channels. Pharmacological inhibition of these channels causes the RMP to become more negative (100 µM gadolinium: ΔVm = −30 ± 4 mV). Analysis of the gadolinium-sensitive conductance reveals a high permeability to calcium ions (PCa/PNa ≈80) with little selectivity between monovalent ions; similar to that reported elsewhere for TRPV5. Detection of TRPV5 by PCR and immunohistochemistry and the sensitivity of the RMP to the TRPV5 inhibitor econazole (ΔVm = −18 ± 3 mV) suggests that the RMP may be, in part, controlled by TRPV5. We investigated the physiological advantage of the relatively positive RMP using a mathematical model in which membrane stretch activates potassium channels allowing potassium efflux to oppose osmotic water uptake. At very negative RMP potassium efflux is negligible, but at more positive RMP it is sufficient to limit volume increase. In support of our model, cells clamped at −80 mV and challenged with a reduced osmotic potential swelled approximately twice as much as cells at +10 mV. The positive RMP may be a protective adaptation that allows chondrocytes to respond to the dramatic osmotic changes, with minimal changes in cell volume. J. Cell. Physiol. 226: 2979–2986, 2011. © 2011 Wiley-Liss, Inc

Computerized Adaptive Assessment of Infant-Toddler Language Development: Demonstration and Validation of an App for Screening

We have developed a computerized adaptive test (an app), based on the MacArthur-Bates Communicative Development Inventories (CDI), that can rapidly gauge infant and toddler language development based on parent report. The app can be very useful in screening for developmental disabilities in IDEA Part C or Section 619. We will demonstrate the app and present validation data for toddlers.https://digitalcommons.library.umaine.edu/ccids_posters/1005/thumbnail.jp

Patients With Dementia Are Easy Victims to Predators

Patients with dementia, especially Alzheimer’s disease and particularly those in early stages, are susceptible to become victims of predators: Their agnosia (see Case 1) prevents them from detecting and accurately interpreting subtle signals that otherwise would have alerted them that they are about to fall for a scam. Furthermore, their judgment is impaired very early in the disease process, often before other symptoms manifest themselves and usually before a diagnosis is made. Patients with early stages of dementia are therefore prime targets for unscrupulous predators, and it behooves caregivers and health care professionals to ensure the integrity of these patients. In this case study, we discuss how a man with mild Alzheimer’s disease was about to fall for a scam were it not for his vigilant wife. We discuss what went wrong in the patient/caregiver interaction and how the catastrophic ending could have been avoided or averted

Interactive Voice Response-An Innovative Approach to Post-Stroke Depression Self-Management Support

Automated interactive voice response (IVR) call systems can provide systematic monitoring and self-management support to depressed patients, but it is unknown if stroke patients are able and willing to engage in IVR interactions. We sought to assess the feasibility and acceptability of IVR as an adjunct to post-stroke depression follow-up care. The CarePartner program is a mobile health program designed to optimize depression self-management, facilitate social support from a caregiver, and strengthen connections between stroke survivors and primary care providers (PCPs). Ischemic stroke patients and an informal caregiver, if available, were recruited during the patient's acute stroke hospitalization or follow-up appointment. The CarePartner program was activated in patients with depressive symptoms during their stroke hospitalization or follow-up. The 3-month intervention consisted of weekly IVR calls monitoring both depressive symptoms and medication adherence along with tailored suggestions for depressive symptom self-management. After each completed IVR call, informal caregivers were automatically updated, and, if needed, the subject's PCP was notified. Of the 56 stroke patients who enrolled, depressive symptoms were identified in 13 (23 %) subjects. Subjects completed 74 % of the weekly IVR assessments. A total of six subjects did not complete the outcome assessment, including two non-study-related deaths. PCPs were notified five times, including two times for suicidal ideation and three times for medication non-adherence. Stroke patients with depressive symptoms were able to engage in an IVR call system. Future studies are needed to explore the efficacy of an IVR approach for post-stroke self-management and monitoring of stroke-related outcomes