Small Molecule Optoacoustic Contrast Agents: An Unexplored Avenue for Enhancing In Vivo Imaging.

Almost every variety of medical imaging technique relies heavily on exogenous contrast agents to generate high-resolution images of biological structures. Organic small molecule contrast agents, in particular, are well suited for biomedical imaging applications due to their favorable biocompatibility and amenability to structural modification. PET/SPECT, MRI, and fluorescence imaging all have a large host of small molecule contrast agents developed for them, and there exists an academic understanding of how these compounds can be developed. Optoacoustic imaging is a relatively newer imaging technique and, as such, lacks well-established small molecule contrast agents; many of the contrast agents used are the same ones which have found use in fluorescence imaging applications. Many commonly-used fluorescent dyes have found successful application in optoacoustic imaging, but others generate no detectable signal. Moreover, the structural features that either enable a molecule to generate a detectable optoacoustic signal or prevent it from doing so are poorly understood, so design of new contrast agents lacks direction. This review aims to compile the small molecule optoacoustic contrast agents that have been successfully employed in the literature to bridge the information gap between molecular design and optoacoustic signal generation. The information contained within will help to provide direction for the future synthesis of optoacoustic contrast agents.

Developing culturally diverse direct caregivers for care work with older adults: challenges and potential strategies.

This discussion presents real-world examples of challenges that occur in geriatric training as a contribution to the ongoing conversation about tailored training for direct caregivers. Numerous discussions are available on the need for more geriatric training in nursing, including aspects of care for patients with dementia, but few if any studies have identified a similar need on behalf of direct care workers, including home health care aides,personal care aides, and nursing assistants who are not part of a licensure track or a baccalaureate-based nursing curriculum. This discussion examines three cultural factors that underlie challenges for nursing educators and supervisors in dementia care who oversee direct care workers: (1) the effect of immigrant cultures and languages; (2) the effect of different intergenerational cultural constructs; and (3) the effect of culturally derived attitudes about aging and dementia. Strategies to address these challenges are offered.

Automated enumeration of Eimeria oocysts in feces for rapid coccidiosis monitoring.

Coccidiosis represents a major driver in the economic performance of poultry operations, as coccidia control is expensive, and infections can result in increased feed conversion ratios, uneven growth rates, increased co-morbidities with pathogens such as Salmonella, and mortality within flocks. Shifts in broiler production to antibiotic-free strategies, increased attention on pre-harvest food safety, and growing incidence of anti-coccidial drug resistance has created a need for increased understanding of interventional efficacy and methods of coccidia control. Conventional methods to quantify coccidia oocysts in fecal samples involve manual microscopy processes that are time and labor intensive and subject to operator error, limiting their use as a diagnostic and monitoring tool in animal parasite control. To address the need for a high-throughput, robust, and reliable method to enumerate coccidia oocysts from poultry fecal samples, a novel diagnostic tool was developed. Utilizing the PIPER instrument and MagDrive technology, the diagnostic eliminates the requirement for extensive training and manual counting which currently limits the application of conventional microscopic methods of oocysts per gram (OPG) measurement. Automated microscopy to identify and count oocysts and report OPG simplifies analysis and removes potential sources of operator error. Morphometric analysis on identified oocysts allows for the oocyst counts to be separated into 3 size categories, which were shown to discriminate the 3 most common Eimeria species in commercial broilers, E. acervulina, E. tenella, and E. maxima. For 75% of the samples tested, the counts obtained by the PIPER and hemocytometer methods were within 2-fold of each other. Additionally, the PIPER method showed less variability than the hemocytometer counting method when OPG levels were below 100,000. By automated identification and counting of oocysts from 12 individual fecal samples in less than one hour, this tool could enable routine, noninvasive diagnostic monitoring of coccidia in poultry operations. This approach can generate large, uniform, and accurate data sets that create new opportunities for understanding the epidemiology and economics of coccidia infections and interventional efficacy.

Twelve important minutes: introducing enhanced online materials about elder abuse to nursing assistants.

A pilot project introduced 12 minutes of text and video materials and a reflective online interaction about elder abuse into the online component of a hybrid course in nursing assistant training leading to certification. Didactic presentations on issues of ethics and standards had been given in two different units of the face-to-face component of the course using both the course textbook and an online module keyed to state certification standards. However, student responses suggested that their online writing to each other about the new materials brought issues of elder abuse to the forefront in ways that they could finally internalize.

Technical note: improving the efficiency of generating bovine extraembryonic endoderm cells.

The formation of extraembryonic endoderm (XEN) occurs early in embryonic development. The cell types that develop from the XEN remain poorly studied in ruminant species because of the lack of suitable cell culture model systems. The goal of this work was to establish a protocol for producing XEN cell cultures from bovine blastocysts. Previous work identified fibroblast growth factor 2 (FGF2) as a facilitator of bovine XEN development. Further refinements in culture conditions studied here included exposure to 20% fetal bovine serum and FGF2 replenishment. These modifications yielded an endoderm outgrowth formation incidence of 81.6% ± 5.5% compared with 33.3% ± 5.5% in bovine serum albumin (BSA)-supplemented controls. These cells resembled XEN when examined morphologically and contained XEN transcripts (GATA binding protein 4 [GATA4] and GATA binding protein 6 [GATA6]) as well as transcripts present in visceral (BCL2 interacting protein 1 [BNIP1] and vascular endothelial growth factor A [VEGFA]) and parietal (C-X-C motif chemokine receptor 4 [CXCR4], thrombomodulin [THBD], and hematopoietically expressed homeobox [HHEX]) XEN. Two XEN cell lines were maintained for prolonged culture. Both lines continued to proliferate for approximately 6 wk before becoming senescent. These cultures maintained an XEN-like state and continued to express GATA4 and GATA6 until senescence. An increase in the abundance of visceral and parietal XEN transcripts was observed with continued culture, suggesting that these cells either undergo spontaneous differentiation or retain the ability to form various XEN cell types. Stocks of cultured cells exposed to a freeze-thaw procedure possessed similar phenotypic and genotypic behaviors as nonfrozen cells. To conclude, a procedure for efficient production of primary bovine XEN cell cultures was developed. This new protocol may assist researchers in exploring this overlooked cell type for its roles in nutrient supply during embryogenesis.

Palladium-Catalyzed Synthesis of Conjugated Allenynes via Decarboxylative Coupling.

A new strategy to access conjugated allenynes via a decarboxylative coupling of propargyl esters of propiolates has been developed. In this process, allenyl-palladium intermediates are coupled with acetylides that are generated in situ to form the conjugated allenynes. Finally, the coupling is demonstrated to be highly stereospecific, providing a route to enantioenriched allenes.

Chloroplastic responses of ponderosa pine (Pinus ponderosa) seedlings to ozone exposure.

Integrity of chloroplast membranes is essential to photosynthesis. Loss of thylakoid membrane integrity has been proposed as a consequence of ozone (O(3)) exposure and therefore may be a mechanistic basis for decreased photosynthetic rates commonly associated with ozone exposure. To investigate this hypothesis, Pinus ponderosa seedlings were exposed to ambient air or ozone concentrations maintained at 0.15 or 0.30 microliter l(-1) for 10 h day(-1) for 51 days during their second growing season. Over the course of the study, foliage samples were periodically collected for thylakoid membrane, chlorophyll and protein analyses. Additionally, gas-exchange measurements were made in conjunction with foliage sampling to verify that observed chloroplastic responses were associated with ozone-induced changes in photosynthesis. Needles exposed to elevated ozone exhibited decreases in chlorophyll a and b content. The decreases were dependent on the duration and intensity of ozone exposure. When based on equal amounts of chlorophyll, ozone-exposed sample tissue exhibited an increase in total protein. When based on equal amounts of protein, ozone-exposed samples exhibited an increase in 37 kDa proteins, possibly consisting of breakdown products, and a possible decrease in 68 kDa proteins, Rubisco small subunit. There was also a change in the ratio of Photosystem I protein complexes CPI and CPII that may have contributed to decreased photosynthesis. Net photosynthetic rates were decreased in the high ozone treatment suggesting that observed structural and biochemical changes in the chloroplast were associated with alterations of the photosynthetic process.

Infusing cultural competence training into the curriculum: describing the development of culturally sensitive training on dementia communication.

The need for training in cultural sensitivity and cultural competence exists at every level of medical care. This discussion reports on an interdisciplinary project to infuse cultural competence training in dementia communication care into nursing and nurse assistant training. We describe the core curriculum and its subsequent cross-cultural and linguistic adaptations to meet multiple educational and training needs of language-challenged learners, and discuss implications for others developing cross-disciplinary curricula.

Differential expression of TRAIL and TRAIL receptors in allergic asthmatics following segmental antigen challenge: evidence for a role of TRAIL in eosinophil survival.

Asthma is a chronic lung disease exhibiting airway obstruction, hyperresponsiveness, and inflammation, characterized by the infiltration of eosinophils into the airways and the underlying tissue. Prolonged eosinophilic inflammation depends on the balance between the cell's inherent tendency to undergo apoptosis and the local eosinophil-viability enhancing activity. TRAIL, a member of the TNF family, induces apoptosis in most transformed cells; however, its role in health and disease remains unknown. To test the hypothesis that Ag-induced inflammation is associated with TRAIL/TRAIL-R interactions, we used a segmental Ag challenge (SAC) model in ragweed-allergic asthmatics and nonasthmatic patients and analyzed bronchoalveolar lavage (BAL) material for 2 wk. In asthmatic patients, the level of TRAIL in BAL fluid dramatically increased 24 h after SAC, which significantly correlated with BAL eosinophil counts. Immunohistochemical analysis of bronchial biopsies from asthmatic patients demonstrated that TRAIL staining was increased in epithelial, airway smooth muscle, and vascular smooth muscle cells and throughout the interstitial tissue after SAC. This was confirmed by quantitative immunocytochemical image analysis of BAL eosinophils and alveolar macrophages, which demonstrated that expression levels of TRAIL and DcR2 increased, whereas expression levels of the TRAIL-Rs DR4 and DR5 decreased in asthmatic subjects after SAC. We also determined that TRAIL prolongs eosinophil survival ex vivo. These data provide the first in vivo evidence that TRAIL expression is increased in asthmatics following Ag provocation and suggest that modulation of TRAIL and TRAIL-R interactions may play a crucial role in promoting eosinophil survival in asthma.