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Breaking symmetry in colloidal crystals is challenging due to the inherent chemical and structural isotropy of many nanoscale building blocks. If a non-particle component could be used to anisotropically encode such building blocks with orthogonal recognition properties, one could expand the scope of structural and compositional possibilities of colloidal crystals beyond what is thus far possible with purely particle-based systems. Herein, we report the synthesis and characterization of novel DNA dendrimers that function as symmetry-breaking synthons, capable of programming anisotropic and orthogonal interactions within colloidal crystals. When the DNA dendrimers have identical sticky ends, they hybridize with DNA-functionalized nanoparticles to yield three distinct colloidal crystals, dictated by dendrimer size, including a structure not previously reported in the field of colloidal crystal engineering, Si

Crystal methamphetamine (“meth”) use is on the rise in the USA, having devastating effects on individuals and communities. Innovative prevention strategies are therefore critical. Through an exploratory qualitative study, we examined the perspectives and experiences of teenagers and parents around meth prevention messaging formats and strategies. Teens and adults were recruited through middle and high schools, libraries, local sporting events, and word of mouth in three communities in North Idaho, May–September 2016. Guided by the theoretical framework of the Extended Parallel Process Model, we conducted focus groups and small group interviews (three teen; two adults). Using a deductive content analytic approach, we developed teen- and adult-specific codebooks, analyzed the transcripts with NVivo 12-Plus, and identified themes. Teens and adults were all acutely aware of meth use in their communities, personally knowing people who were addicted to meth, and all understood the oral (“meth mouth”) and physical (“crank bugs”) consequences of meth use. Three primary themes were identified, which focused on the effects of, addiction to, and messaging around crystal meth use. For teens and adults, images illustrating the effects of meth were least effective if they appeared unrealistic or comical. Teens resonated most with messages focusing on pain and vanity (bad teeth and breath), and there was consensus that showing teens images simulating changes in their appearance over time as a result of meth use in a clinical setting would be an effective prevention strategy. Teens and adults who had exposure to meth addiction in North Idaho felt that prevention messages focused on meth are imperative, given its high prevalence and deleterious effects. Future work will entail developing and testing a communication-based meth prevention strategy along with tailored messaging that can be used with teens in dental settings.

Although examples of colloidal crystal analogues to metal alloys have been reported, general routes for preparing 3D analogues to random substitutional alloys do not exist. Here, we use the programmability of DNA (length and sequence) to match nanoparticle component sizes, define parent lattice symmetry and substitutional order, and achieve faceted crystal habits. We synthesized substitutional alloy colloidal crystals with either ordered or random arrangements of two components (Au and Fe

Objectives. Crystal methamphetamine (“meth”) use among youth living in rural areas is higher than the national average. Given how drastically meth affects teeth (i.e., “meth mouth”), engaging dental professionals as one of multiple channels in rural areas to deliver meth prevention messaging is a novel approach. The objective of this research was to assess the feasibility and acceptability of incorporating meth use prevention messaging into dental visits with teenagers. Methods. We conducted phenomenological, qualitative research with dental practitioners, teens, and parents/guardians in three communities in North Idaho, from 2015 to 2016. We recruited practitioners using a snowball sampling strategy and placed phone calls to dental practices and contacted teens and parents through schools, libraries, local sporting events, and word-of-mouth. Using NVivo 12-Plus, parent- and teen-specific codebooks and themes were developed from guides and transcripts. Transcripts of the dentists and hygienists were reviewed to ascertain the main ideas and themes. Results. Overall, practitioner, teen, and parent participants viewed meth prevention messages delivered by dental professionals as acceptable and feasible. Compared to those in private practice, public health dental providers were invested in meth prevention and were eager to help. Barriers to overall acceptability and feasibility included hygienists’ low self-efficacy to deliver a communication-based intervention, infrequency of dental visits impacting the ability to reach enough teens through this venue, and the fact that teens could feel “targeted” by providers. Teens also raised concerns about scary messages exacerbating preexisting dental visit anxiety. Facilitators included the following: dental practitioners already engaging in health education with their patients, parents, and teens seeing dental professionals as appropriate purveyors of antimeth messaging and support for increased meth prevention efforts given the impact of meth use in their communities. Conclusions. Well-crafted, developmentally appropriate meth prevention messages would likely be well received by teens and supported by parents in dental offices. These data are being used to develop a novel, theory-based communication and behavioral strategy to integrate dental professionals into the delivery of messages aimed at preventing the initiation of meth use among rural Idaho teens.

Crystal methamphetamine ("meth") use is on the rise in the USA, having devastating effects on individuals and communities. Innovative prevention strategies are therefore critical. Through an exploratory qualitative study, we examined the perspectives and experiences of teenagers and parents around meth prevention messaging formats and strategies. Teens and adults were recruited through middle and high schools, libraries, local sporting events, and word of mouth in three communities in North Idaho, May-September 2016. Guided by the theoretical framework of the Extended Parallel Process Model, we conducted focus groups and small group interviews (three teen; two adults). Using a deductive content analytic approach, we developed teen- and adult-specific codebooks, analyzed the transcripts with NVivo 12-Plus, and identified themes. Teens and adults were all acutely aware of meth use in their communities, personally knowing people who were addicted to meth, and all understood the oral ("meth mouth") and physical ("crank bugs") consequences of meth use. Three primary themes were identified, which focused on the effects of, addiction to, and messaging around crystal meth use. For teens and adults, images illustrating the effects of meth were least effective if they appeared unrealistic or comical. Teens resonated most with messages focusing on pain and vanity (bad teeth and breath), and there was consensus that showing teens images simulating changes in their appearance over time as a result of meth use in a clinical setting would be an effective prevention strategy. Teens and adults who had exposure to meth addiction in North Idaho felt that prevention messages focused on meth are imperative, given its high prevalence and deleterious effects. Future work will entail developing and testing a communication-based meth prevention strategy along with tailored messaging that can be used with teens in dental settings.

Next generation displays and lighting applications are increasingly using inorganic quantum dots (QDs) embedded in polymer matrices to impart bright and tunable emission properties. The toxicity of some heavy metals present in commercial QDs (e.g. cadmium) has, however, raised concerns about the potential for QDs embedded in polymer matrices to be released during the manufacture, use, and end-of-life phases of the material. One important potential release scenario that polymer composites can experience in the environment is photochemically induced matrix degradation. This process is not well understood at the molecular level. To study this process, the effect of an artificially accelerated weathering process on QD–polymer nanocomposites has been explored by subjecting CdSe and CdSe/ZnS QDs embedded in poly(methyl methacrylate) (PMMA) to UVC irradiation in aqueous media. Significant matrix degradation of QD–PMMA was observed along with measurable mass loss, yellowing of the nanocomposites, and a loss of QD fluorescence. While ICP-MS identified the release of ions, confocal laser scanning microscopy and dark-field hyperspectral imaging were shown to be effective analytical techniques for revealing that QD-containing polymer fragments were also released into aqueous media due to matrix degradation. Viability experiments, which were conducted with Shewanella oneidensis MR-1, showed a statistically significant decrease in bacterial viability when the bacteria were exposed to highly degraded QD-containing polymer fragments. Results from this study highlight the need to quantify not only the extent of nanoparticle release from a polymer nanocomposite but also to determine the form of the released nanoparticles (e.g. ions or polymer fragments).

We aim to establish the effect of environmental diversity in evaluating nanotoxicity to bacteria. We assessed the toxicity of 4 nm polyallylamine hydrochloride-wrapped gold nanoparticles to a panel of bacteria from diverse environmental niches. The bacteria experienced a range of toxicities as evidenced by the different minimum bactericidal concentrations determined; the sensitivities of the bacteria was A. vinelandii = P. aeruginosa > S. oneidensis MR-4 > A. baylyi > S. oneidensis MR-1. Interactions between gold nanoparticles and molecular components of the cell wall were investigated by TEM, flow cytometry, and computational modeling. Binding results showed a general trend that bacteria with smooth LPS bind more PAH AuNPs than bacteria with rough LPS. Computational models reveal that PAH migrates to phosphate groups in the core of the LPS structure. Overall, our results demonstrate that simple interactions between nanoparticles and the bacterial cell wall cannot fully account for observed trends in toxicity, which points to the importance of establishing more comprehensive approaches for modeling environmental nanotoxicity.

There has been a surge of consumer products that incorporate nanoparticles, which are used to improve or impart new functionalities to the products based on their unique physicochemical properties. With such an increase in products containing nanomaterials, there is a need to understand their potential impacts on the environment. This is often done using various biological models that are abundant in the different environmental compartments where the nanomaterials may end up after use. Beyond studying whether nanomaterials simply kill an organism, the molecular mechanisms by which nanoparticles exhibit toxicity have been extensively studied. Some of the main mechanisms include (1) direct nanoparticle association with an organism's cell surface, where the membrane can be damaged or initiate internal signaling pathways that damage the cell, (2) dissolution of the material, releasing toxic ions that impact the organism, generally through impairing important enzyme functions or through direct interaction with a cell's DNA, and (3) the generation of reactive oxygen species and subsequent oxidative stress on an organism, which can also damage important enzymes or an organism's genetic material. This Account reviews these toxicity mechanisms, presenting examples for each with different types of nanomaterials. Understanding the mechanism of nanoparticle toxicity will inform efforts to redesign nanoparticles with reduced environmental impact. The redesign strategies will need to be chosen based on the major mode of toxicity, but also considering what changes can be made to the nanomaterial without impacting its ability to perform in its intended application. To reduce interactions with the cell surface, nanomaterials can be designed to have a negative surface charge, use ligands such as polyethylene glycol that reduce protein binding, or have a morphology that discourages binding with a cell surface. To reduce the nanoparticle dissolution to toxic ions, the toxic species can be replaced with less toxic elements that have similar properties, the nanoparticle can be capped with a shell material, the morphology of the nanoparticle can be chosen to minimize surface area and thus minimize dissolution, or a chelating agent can be co-introduced or functionalized onto the nanomaterial's surface. To reduce the production of reactive oxygen species, the band gap of the material can be tuned either by using different elements or by doping, a shell layer can be added to inhibit direct contact with the core, or antioxidant molecules can be tethered to the nanoparticle surface. When redesigning nanoparticles, it will be important to test that the redesign strategy actually reduces toxicity to organisms from relevant environmental compartments. It is also necessary to confirm that the nanomaterial still demonstrates the critical physicochemical properties that inspired its inclusion in a product or device.

Objectives:Prominent impairment of visuospatial processing is a feature of dementia with Lewy bodies (DLB), and diagnosis of this impairment may help clinically distinguish DLB from Alzheimer’s disease (AD). The current study compared autopsy-confirmed DLB and AD patients on the Hooper Visual Organization Test (VOT), a test that requires perceptual and mental reorganization of parts of an object into an identifiable whole. The VOT may be particularly sensitive to DLB since it involves integration of visual information processed in separate dorsal and ventral visual “streams”.Methods:Demographically similar DLB (n=28), AD (n=115), and normal control (NC;n=85) participants were compared on the VOT and additional neuropsychological tests. Patient groups did not differ in dementia severity at time of VOT testing. High and Low AD-Braak stage DLB subgroups were compared to examine the influence of concomitant AD pathology on VOT performance.Results:Both patient groups were impaired compared to NC participants. VOT scores of DLB patients were significantly lower than those of AD patients. The diagnostic sensitivity and specificity of the VOT for patientsversuscontrols was good, but marginal for DLBversusAD. High-Braak and low-Braak DLB patients did not differ on the VOT, but High-Braak DLB performed worse than Low-Braak DLB on tests of episodic memory and language.Conclusions:Visual perceptual organization ability is more impaired in DLB than AD but not strongly diagnostic. The disproportionate severity of this visual perceptual deficit in DLB is not related to degree of concomitant AD pathology, which suggests that it might primarily reflect Lewy body pathology. (JINS, 2016,22, 609–619)

Background New highly effective medications are available to treat the hepatitis C virus (HCV). However, little is known about HCV treatment knowledge and readiness among young people who inject drugs (PWID), or factors that may contribute to treatment uptake and adherence in this treatment era. Purpose Using a framework for understanding healthcare utilization, we examined perspectives and experiences of young PWID tied to the HCV care continuum in Boston, Massachusetts, to inform future strategies. Methods We conducted 24 in-depth interviews with active and recent PWID aged 22–30 years living with HCV in Boston, February-August 2016. At the time of the interviews, no participants had been prescribed or had taken the new direct acting antivirals. We developed a codebook deductively from the interview guide and coded and analyzed the data into themes using a consensus-based process. Results The following five themes emerged, which captured PWID’s knowledge of and experiences with HCV along the care continuum through social determinants of engagement in care, as well as illness level: (1) deservingness of HCV treatment and stigma, (2) dissatisfaction with provider interactions, (3) perceived lack of referral to treatment and care continuity, (4) disincentives around HCV treatment for PWID; and (5) perceived need for treatment. Young PWID living with HCV face unique barriers to HCV testing, counseling, and treatment. Conclusion Breakdowns in the HCV care continuum may have adverse effects on HCV-treatment readiness and willingness. Improved public health and practice approaches are needed to address these barriers to effectively engage young PWID in care.

Visual search is an aspect of visual cognition that may be more impaired in Dementia with Lewy Bodies (DLB) than Alzheimer's disease (AD). To assess this possibility, the present study compared patients with DLB (n = 17), AD (n = 30), or Parkinson's disease with dementia (PDD; n = 10) to non-demented patients with PD (n = 18) and normal control (NC) participants (n = 13) on single-feature and feature-conjunction visual search tasks. In the single-feature task participants had to determine if a target stimulus (i.e., a black dot) was present among 3, 6, or 12 distractor stimuli (i.e., white dots) that differed in one salient feature. In the feature-conjunction task participants had to determine if a target stimulus (i.e., a black circle) was present among 3, 6, or 12 distractor stimuli (i.e., white dots and black squares) that shared either of the target's salient features. Results showed that target detection time in the single-feature task was not influenced by the number of distractors (i.e., "pop-out" effect) for any of the groups. In contrast, target detection time increased as the number of distractors increased in the feature-conjunction task for all groups, but more so for patients with AD or DLB than for any of the other groups. These results suggest that the single-feature search "pop-out" effect is preserved in DLB and AD patients, whereas ability to perform the feature-conjunction search is impaired. This pattern of preserved single-feature search with impaired feature-conjunction search is consistent with a deficit in feature binding that may be mediated by abnormalities in networks involving the dorsal occipito-parietal cortex.

Painful conditions are a huge medical burden with an estimated prevalence of 32% of the population, and an economic cost of $635 billion, or 4% of the GDP. Currently, the best available medical analgesics are opioids, but due to their vast side effect profile and risk of overdose, these are far from ideal drugs. Recently, the study of genetic mutations leading to congenital insensitivity to pain (CIP) has resulted in submission of novel drugs to the FDA for clinical trial. Here, we show our work on one such mutation of the gene Prdm12. We first characterized the expression pattern of Prdm12 within different sensory neurons present in the dorsal root ganglia (DRG) by performing in-situ hybridization paired with immunohistochemistry, and found it to be expressed in both myelinated and unmyelinated small-diameter axons of the thoracic and lumbar DRGs. We then generated a new strain of mice in which Prdm12 has been conditionally knocked out of neurons in DRG and cranial ganglia, and subjected these mice to a variety of behavioral assays alongside littermate controls. We have shown that the Prdm12cKO mice have reduced sensitivity to nociceptive thermal and mechanical stimuli, and correlated this with a decrease in the number of pain-sensitive IB4+ and CGRP+ Aδ and C fibers in the DRG. We believe that further study of this mouse model, along with investigation of the downstream effectors and genomic targets of PRDM12, will provide a new avenue for the pursuit of analgesic drug discovery.

Spot welded lap shear specimens were treated with the StressWave process to evaluate the effect of the process on the fatigue life of the joint. The StressWave process is a mechanical means of treating the spot weld to improve fatigue life. A potential drop method was used to track the stages of crack growth during fatigue testing. Results show that the fatigue strength of the specimens treated with the process increased by more than 150 %.

Memory for the temporal order of items or events in a sequence has been shown to be impaired in older adults and individuals with Parkinson’s disease (PD). The present study examined the effects of high and low interference on temporal order memory in individuals diagnosed with PD (n = 20) and demographically similar healthy older adults (n = 20) utilizing a computerized task used in previously published studies. During the sample phase of each trial, a series of eight circles were randomly presented one at a time in eight different spatial locations. Participants were instructed to remember the sequence in which the circles appeared in the locations. During the choice phase, participants were presented with two circles in two different locations and were asked to indicate which circle appeared earliest in the sample phase sequence. The two circles were separated by one of four possible temporal separation lags (0, 2, 4, and 6), defined as the number of circles occurring in the sample phase sequence between the two choice phase circles. Shorter temporal lags (e.g., 0 and 2 lags) were hypothesized to result in higher interference compared to longer temporal lags (e.g., 4 and 6 lags). The results demonstrated that on trials involving high interference, no differences were found between the two groups. However, healthy older adults significantly outperformed individuals with PD (p < .05) on trials involving low interference. Although differences were found between the PD and healthy older adult groups, both groups significantly improved on low interference trials compared to high interference trials (p < .001). The findings indicate that temporal order memory improves in healthy older adults and individuals with PD when interference is reduced. However, individuals with PD demonstrated poorer temporal order memory even with less interference. Therefore, temporal order memory is differentially affected by interference in healthy older adults and individuals with PD. Given that both groups did improve with lessened interference, behavioral interventions that minimize temporal interference potentially could improve memory function in older adults and to a lesser extent in individuals with PD.

Objective: Visual processing abilities of patients with dementia with Lewy bodies (DLB) or Alzheimer disease (AD) dementia were assessed psychophysically using a simple horizontal motion discrimination task that engages the dorsal visual processing stream. Methods: Participants included patients with mild dementia with DLB, AD dementia or Parkinson disease (PD) with dementia (PDD), without dementia with PD, and normal controls. Participants indicated the left or right direction of coherently moving dots that were embedded within dynamic visual noise provided by randomly moving dots. The proportion of coherently moving dots was increased or decreased across trials to determine a threshold at which participants could correctly indicate their direction with greater than 80% accuracy. Results: Motion discrimination thresholds of patients with DLB and PDD were comparable and significantly higher (i.e., worse) than those of patients with AD dementia. The thresholds of patients with AD dementia and patients with PD were normal. These results were confirmed in subgroups of patients with DLB/PDD and AD dementia with autopsy-confirmed disease. A motion discrimination threshold greater than 0.23 distinguished between DLB/PDD and AD dementia with 67% sensitivity and 85% specificity. Conclusions: Differential deficits in detecting direction of simple horizontal motion suggest that dorsal processing stream dysfunction is greater in DLB and PDD than in AD dementia. Therefore, impaired performance on simple visual motion discrimination tasks that specifically engage occipitoparietal brain regions suggests the presence of Lewy body pathology.