Search

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is a serious public health problem. Current treatment is restricted to two drugs, benznidazole and nifurtimox, displaying serious efficacy and safety drawbacks. Nucleoside analogues represent a promising alternative as protozoans do not biosynthesize purines and rely on purine salvage from the hosts. Protozoan transporters often present different substrate specificities from mammalian transporters, justifying the exploration of nucleoside analogues as therapeutic agents. Previous reports identified nucleosides with potent trypanocidal activity; therefore, two 7-derivatized tubercidins (FH11706, FH10714) and a 3′-deoxytubercidin (FH8513) were assayed against T. cruzi. They were highly potent and selective, and the uptake of the tubercidin analogues appeared to be mediated by the nucleoside transporter TcrNT2. At 10 μM, the analogues reduced parasitemia >90% in 2D and 3D cardiac cultures. The washout assays showed that FH10714 sterilized the infected cultures. Given orally, the compounds did not induce noticeable mouse toxicity (50 mg/kg), suppressed the parasitemia of T. cruzi-infected Swiss mice (25 mg/kg, 5 days) and presented DNA amplification below the limit of detection. These findings justify further studies with longer treatment regimens, as well as evaluations in combination with nitro drugs, aiming to identify more effective and safer therapies for Chagas disease.

Family dementia caregiving can be frustrating due to communication challenges. Approximately 50% of family dementia caregivers admit to some form of mistreatment of their dependent elder living with dementia. The purpose of this interpretative phenomenological study was to discover family dementia caregivers’ perceptions of the Virtual Dementia Tour (VDT)®. The VDT® provided a simulation of dementia including a first person perspective of the cognitive deficits commonly seen in dementia. Participants spent eight -minutes attempting to perform common activities while experiencing sensory deprivation (poorly fitting gloves, noise producing headphones, and limited vision glasses). In-depth open semi-structured interviews were held with ten participants who were recruited from a community event offering the Virtual Dementia Tour®. The research questions were, “What are family dementia caregivers’ perception of the Virtual Dementia Tour®?” and “How might the Virtual Dementia Tour® impact the family dementia caregivers’ reality of the person living with dementia?” A modification of Colaizzi’s (1978) method was used for interpretative phenomenological analysis. Five overarching themes emerged from the participants’ language: Befuddled and Bewildered; I Just Didn’t Know, Eye Opener, Doing Differently; and It Changed Me. The study findings suggest that family dementia caregivers interpreted their VDT(r) experience with empathic understanding and responsiveness. In some, this had a powerful impact with a subsequent reality change toward their family member living with dementia, which might lessen frustration and improve dyadic relational harmony and care. This study begins to fill a knowledge gap about the Virtual Dementia Tour’s® value with family dementia caregivers in community settings.

The reaction $^{17}$O($n,\alpha$)$^{14}$C was studied at energies from $E_{cm}=0$ to $E_{cm}=350$ keV using the quasi-free deuteron break-up in the three body reaction $^{17}$O$+d \rightarrow \alpha+ ^{14}$C$+p$, extending the Trojan Horse indirect method (THM) to neutron-induced reactions. It is found that the $^{18}$O excited state at $E^*=8.125 \pm 0.002$ MeV observed in THM experiments is absent in the direct measurement because of its high centrifugal barrier. The angular distributions of the populated resonances have been measured for the first time. The results unambiguously indicate the ability of the THM to overcome the centrifugal barrier suppression effect and to pick out the contribution of the bare nuclear interaction., Comment: Accepted by PRC as Rapid Communication

A multiplexed approach to sample processing is essential to maximize data return of a single run on a next generation sequencing platform. The ability to process hundreds of samples per day will undoubtedly lead to faster discovery of underlying genetic markers for many of today's current diseases. Ion Torrent has invented the first device capable of directly translating chemical signals into digital information. The first application of this paradigm-changing technology is sequencing DNA on Ion's semiconductor sequencing device. The device leverages decades of semiconductor technology advances, and in just a few years has brought the entire design, fabrication and supply chain infrastructure of that industry-a trillion dollar investment-to bear on the challenge of sequencing. The result is the first commercial sequencing technology that does not use light-The Personal Genome Machine, Ion's novel sequencer delivers unprecedented speed, scalability and low cost. With the increased speed (2 hour runtime) and accuracy provided by the PGM, we have leveraged our existing multiplexed sample approach using the Access Array from Fluidigm to amplify 48 samples across 1 to 48 amplicons, depending on the experiment in question. The ability to generate genomic information for 48 samples under 2 hours using the PGM is critical to quickly confirm whether or not a particular novel discovery observed through whole genome or exome evaluation is the “hit” you are looking for. For our initial experiments, we used amplicons from exons of p53 to demonstrate we could evaluate and differentiate known genetic markers between individual samples within a pool of barcoded samples. Using the Ion Torrent 314 chips, we ran a series of chips that included chips with a single sample up to chips with 48 samples.