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Abstract Microscopic organisms are often overlooked in traditional diversity assessments due to the difficulty of identifying them based on morphology. Metabarcoding is a method for rapidly identifying organisms where Environmental DNA (eDNA) is used as a template. However, legacy DNA is problematically detected from organisms no longer in the environment during sampling. Environmental RNA (eRNA), which is only produced by living organisms, can also be collected from environmental samples and used for metabarcoding. The aim of this study was to determine differences in community composition and diversity between eRNA and eDNA templates for metabarcoding. Using mesocosms containing field-collected communities from an estuary, RNA and DNA were co-extracted from sediment, libraries were prepared for two loci (18S and COI), and sequenced using an Illumina MiSeq. Results show a higher number of unique sequences detected from eRNA in both markers and higher α-diversity compared to eDNA. Significant differences between eRNA and eDNA for all β-diversity metrics were also detected. This study is the first to demonstrate community differences detected with eRNA compared to eDNA from an estuarine system and illustrates the broad applications of eRNA as a tool for assessing benthic community diversity, particularly for environmental conservation and management applications.

Purpose: To report the case of an immunocompetent 62-year old woman with acute syphilitic posterior placoid chorioretinitis. Observations: The patient presented with sudden, painless vision loss in the left eye (OS) four months after self-resolving decreased vision in the right eye (OD) which was incorrectly attributed to ischemic optic neuropathy. At the time of presentation, visual acuity (VA) was hand motion OS and 20/30 OD. The dilated fundus exam demonstrated a flat, yellow-white macular lesion, deep to the retinal vasculature with a temporal, curvilinear demarcation line OS and was unremarkable OD. Trace vitreous cells and veils OS were observed. Optical coherence tomography demonstrated loss of photoreceptor layers. Rapid plasma reagin and fluorescent treponemal antibody absorption were positive. The patient was treated with intravenous penicillin and prednisolone acetate drops with resolution of vitreous cells and return of VA. Conclusions and Importance: Acute syphilitic posterior placoid chorioretinitis can be the single presenting symptom in syphilis. It is imperative for ophthalmologists to consider this relatively uncommon manifestation of syphilis in the differential in immunocompetent patients presenting with unsuspecting histories and perplexing vision loss.

Abstract Background Chylothorax is a rare complication of pediatric cardiac operations that occurs more frequently in children with Noonan syndrome, a genetic disorder associated with cardiac defects and lymphatic anomalies. Case presentation We report a case of postoperative chylothorax in a 6-month-old infant with Noonan syndrome where multimodality lymphatic imaging guided management was followed. Drainage patterns of the lymphatic capillaries in the lower and upper extremities were visualized during near-infrared fluorescence lymphatic imaging (NIRFLI). Dynamic magnetic resonance lymphangiography (MRL) further identified the site of leakage in the thoracic duct and subsequently guided surgical intervention. Conclusions Application of multimodality imaging allows for greater individualization of treatment and should be considered in patients with complex cases such as those with syndromes associated with a higher incidence of chylothorax. IRB Number: HSC-MS-13–0754, December 10, 2013

One of the most important components of language is Vocabulary, a set of words or the combinations of symbols, signs, or letters that have evolved to identify things and ideas. It is an important component of language and language learning as the lack of it hampers a person’s ability to comprehend and communicate effectively. This research analyzes the derivational affixes found in the selected poems of Fernando A. Bernardo in his book entitled The Silent Voice of Your Soul. This research is important as it can help enrich and widen the vocabulary of readers by helping them identify derivational affixes and the functions of these affixes. This study will also help the readers understand how certain words change their word class and meaning as different affixes are added to them Descriptive Qualitative Content Analysis was used to analyze thoroughly the derivational affixes found in the poems. Based on the analysis, there are a total of fifty-five (55) words with derivational affixes found in the poem. Twenty-five (25) words have noun-forming affixes which consist of -ance, -ence, -ity, -ness, -ion, and -or. Sixteen (16) words have adjective-forming affixes which consist of -ty, -ful, -less, -ous, -al, -ry, -tial, and -ed. Eight (8) words in the poems consist of verb-forming affixes such as un-, dis-, ate, and -ing. Lastly, six (6) words from the poems are formed with the adverb-forming affix -ly. Through understanding the different words used, the readers can improve their vocabulary and understanding of the language and literary texts.

A 42-year-old Hispanic female underwent intravitreal autologous adipose-tissue derived stem cell injection to her left eye in the Dominican Republic for treatment of retinitis pigmentosa associated with Usher Syndrome. Prior to intravitreal injection, the patient's best-corrected-visual-acuity (BCVA) was 1/200. The patient experienced decreased vision gradually over a 3-month period. The patient presented with no light perception (NLP) vision with a total funnel retinal detachment, as well as hyphema, iris neovascularization, and nearly 360 posterior synechiae of the iris to the lens capsule. The patient suffered from ocular pain with an intraocular pressure (IOP) of 37 mm Hg. Transcleral cyclophotocoagulation was performed. The IOP was 6 mm Hg six weeks after treatment and the patient was pain free.

Self-sufficiency (autonomy) in growth signaling, the earliest recognized hallmark of cancer, is fueled by the tumor cell's ability to "secrete-and-sense" growth factors (GFs); this translates into cell survival and proliferation that is self-sustained by autocrine/paracrine secretion. A Golgi-localized circuitry comprised of two GTPase switches has recently been implicated in the orchestration of growth signaling autonomy. Using breast cancer cells that are either endowed or impaired (by gene editing) in their ability to assemble the circuitry for growth signaling autonomy, here we define the transcriptome, proteome, and phenome of such an autonomous state, and unravel its role during cancer progression. We show that autonomy is associated with enhanced molecular programs for stemness, proliferation, and epithelial-mesenchymal plasticity. Autonomy is both necessary and sufficient for anchorage-independent GF-restricted proliferation and resistance to anticancer drugs and is required for metastatic progression. Transcriptomic and proteomic studies show that autonomy is associated, with a surprising degree of specificity, with self-sustained epidermal growth factor receptor (EGFR)/ErbB signaling. Derivation of a gene expression signature for autonomy revealed that growth signaling autonomy is uniquely induced in circulating tumor cells (CTCs), the harshest phase in the life of tumor cells when it is deprived of biologically available epidermal growth factor (EGF). We also show that autonomy in CTCs tracks therapeutic response and prognosticates outcome. These data support a role for growth signaling autonomy in multiple processes essential for the blood-borne dissemination of human breast cancer.

Conventional risk factors for coronary heart disease (CHD) do not completely account for the observed increase in premature CHD in people from the Indian subcontinent or for Asian Indians who have immigrated to the USA. The objective of this study was to determine the effect of immigration to the USA on plasma levels of lipoprotein [a] (Lp[a]) and other independent risk factors for CHD in Asian Indians. Three subject groups were studied: group 1, 57 subjects living in India and diagnosed with CHD (CHD patients); group 2, 46 subjects living in India and showing no symptoms of CHD (control subjects); group 3, 206 Asian Indians living in the USA. Fasting blood samples were drawn to determine plasma levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein [LDL cholesterol (LDL-Chol)], high density lipoprotein [HDL cholesterol (HDL-Chol)], apolipoprotein B-100 (apoB-100), and Lp[a]. Apolipoprotein [a] (apo[a]) size polymorphism was determined by immunoblotting. Plasma TG, apoB-100, and Lp[a] concentrations were higher in CHD patients than in control and USA groups. CHD patients had higher levels of TC and LDL-Chol and lower HDL-Chol than control subjects. However, the USA population had higher levels of TC, LDL-Chol, and apoB-100 and lower HDL-Chol than control subjects. Plasma Lp[a] levels were inversely correlated with the relative molecular weight of the more abundant of each subject's two apo[a] isoforms (MAI), and CHD patients showed higher frequencies of lower relative molecular weights among MAI. Our observed changes in lipid profiles suggest that immigrating to the USA may place Asian Indians at increased risk for CHD. This study suggests that elevated plasma Lp[a] confers genetic predisposition to CHD in Asian Indians, and nutritional and environmental factors further increase the risk of CHD. This is the first report implicating MAI size as a predictor for development of premature CHD in Asian Indians. Including plasma Lp[a] concentration and apo[a] phenotype in screening procedures may permit early detection and preventive treatment of CHD in this population. —Hoogeveen, R. C., J. K. Gambhir, D. S. Gambhir, K. T. Kimball, K. Ghazzaly, J. W. Gaubatz, M. Vaduganathan, R. S. Rao, M. Koschinsky, and J. D. Morrisett. Evaluation of Lp[a] and other independent risk factors for CHD in Asian Indians and their USA counterparts. J. Lipid Res. 2001. 42: 631–638.

In previous meta-analyses, tea consumption has been associated with lower incidence of type 2 diabetes. It is unclear, however, if tea is associated inversely over the entire range of intake. Therefore, we investigated the association between tea consumption and incidence of type 2 diabetes in a European population.The EPIC-InterAct case-cohort study was conducted in 26 centers in 8 European countries and consists of a total of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,835 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Country-specific Hazard Ratios (HR) for incidence of type 2 diabetes were obtained after adjustment for lifestyle and dietary factors using a Cox regression adapted for a case-cohort design. Subsequently, country-specific HR were combined using a random effects meta-analysis. Tea consumption was studied as categorical variable (0, >0-

The results of quantum chemical and molecular dynamics calculations reveal that polyanionic gallium-based cages accelerate cyclization reactions of pentadienyl alcohols as a result of substrate cage interactions, preferential binding of reactive conformations of substrate/H3O+ pairs, and increased substrate basicity. However, the increase in basicity dominates. Experimental structure-activity relationship studies in which the metal vertices and overall charge of the cage are varied confirm the model derived via calculations.

Quantum dots (QDs) are engineered semiconductor nanocrystals with unique fluorescent, quantum confinement, and quantum yield properties, making them valuable in a range of commercial and consumer imaging, display, and lighting technologies. Production and usage of QDs are increasing, which increases the probability of these nanoparticles entering the environment at various phases of their life cycle. This review discusses the major types and applications of QDs, their potential environmental exposures, fates, and adverse effects on organisms. For most applications, release to the environment is mainly expected to occur during QD synthesis and end-product manufacturing since encapsulation of QDs in these devices prevents release during normal use or landfilling. In natural waters, the fate of QDs is controlled by water chemistry, light intensity, and the physicochemical properties of QDs. Research on the adverse effects of QDs primarily focuses on sublethal endpoints rather than acute toxicity, and the differences in toxicity between pristine and weathered nanoparticles are highlighted. A proposed oxidative stress adverse outcome pathway framework demonstrates the similarities among metallic and carbon-based QDs that induce reactive oxygen species formation leading to DNA damage, reduced growth, and impaired reproduction in several organisms. To accurately evaluate environmental risk, this review identifies critical data gaps in QD exposure and ecological effects, and provides recommendations for future research. Future QD regulation should emphasize exposure and sublethal effects of metal ions released as the nanoparticles weather under environmental conditions. To date, human exposure to QDs from the environment and resulting adverse effects has not been reported.

BackgroundExtracellular vehicles (EVs) released by malignant tumor cells can mediate the immune response and promote metastasis through intercellular communication. EV analysis is an emerging cancer surveillance tool with advantages over traditional liquid biopsy methods. The aim of this pilot study is to identify actionable EV signatures in metastatic breast cancer.Materials and methodsUnder an IRB-approved protocol for the analysis of patient plasma, samples were collected from women with newly diagnosed or progressive metastatic breast cancer and from women without cancer. Enriched EVs were analyzed via a bead-based multiplex assay designed to detect 37 distinct tumor-relevant epitopes. The mean fluorescent intensity of EV epitopes meeting a minimum threshold of detectability was compared between groups via independent samples t-test. Subgroup analysis was conducted for metastatic breast cancer patients who were positive for estrogen and/or progesterone receptors and negative for HER2. Other variables potentially affecting CD105 levels were also analyzed.ResultsCD105 was found to have a significantly higher mean fluorescent intensity in participants with metastatic breast cancer compared to control participants (P = 0.04). ER/PR+ subgroup analysis revealed a similar pattern compared to control participants (P = 0.01). Other analyzed variables were not found to have a significant correlation with CD105 levels.ConclusionsCD105 EV levels were significantly higher in samples from participants with breast cancer compared to controls. Given that CD105 is known to mediate angiogenesis and promote metastasis, EV-associated CD105 in plasma represents a potential biomarker for diagnosis, surveillance and therapeutic targeting in patients with metastatic breast cancer.

Since the trailblazing discoveries of Lehn, Cram and Pedersen, supramolecular chemistry has established itself as a cornerstone of organic chemistry. Supramolecular hosts offer defined microenvironments that mimic the active sites of enzymes, utilizing specific host–guest interactions to enable remarkable rate enhancements and product selectivity. The development of a diverse array of self-assembled hosts, coupled with the increased demand for shorter and greener synthetic routes, have spurred significant progress in the field of supramolecular catalysis. This Review Article covers recent advances in the field, ranging from novel organic reactivity aided by supramolecular hosts to catalytic cooperation between hosts and organometallic compounds or metal nanoparticles. Strides have also been made in the synthetic application of these hosts in site-selective substrate modifications and challenging photochemical reactions. These efforts have enabled the incorporation of non-covalent macromolecular catalysis in natural product syntheses, evidencing their unique advantages as a synthetic tool, and their powerful potential for practical applications. [Figure not available: see fulltext.].

Since its discovery in 2004, graphene has been used in a wide variety of fields including biomedicine, electronics, filtration materials, and surface coatings. The rapidly expanding consumer market for graphene family nanomaterials (GFNs), such as graphene oxide (GO), raises concern regarding their environmental toxicity. The aim of this study was to evaluate the effects of GO exposures in a marine filter-feeding bivalve (Crassostrea virginica) using sublethal biomarker approaches that can contribute to the development of an adverse outcome pathway (AOP). A 14-day study was conducted to identify tissue-specific molecular markers of GO toxicity using a static renewal design. Elevated lipid peroxidation and changes in glutathione-s-transferase (GST) activities were observed in gills and digestive gland tissues of the GO-exposed oysters. These cellular changes were noted for 2.5 and 5 mg/L GO exposures in seawater. Based on our results, reactive oxygen species (ROS)-induced oxidative damage is identified as a key event in the proposed AOP. Additionally, detoxification enzymes, such as GST, are thought to be involved in stress signaling leading to adverse effects on cellular health. This study is a part of our two-tier approach towards the identification of short- and long-term effects of GO exposures. This work, together with our previous 72 h exposure, represents the application of biomarker-based investigations in the process of AOP development for graphene family nanomaterials.

The possibility of graphene oxide (GO) exposure to the environment has spurred several studies investigating the fate of this nanoparticle (NP). However, there is currently little or no data on the fate of GO in estuarine and marine waters. This study investigated the aggregation, sedimentation, and transformation of GO in saline waters, considering the roles of salinity (0-50 ‰), light (visible light and solar irradiation), and aging, among others. The attachment efficiency of GO reached unity at 1.33 ‰. The sedimentation rate of GO increased with salinity up to 10 ‰ after which it decreased due to formation of ramified GO agglomerates and media density. On the basis of the sedimentation rate determined at 30 ‰ (0.121 m/d), the residence time of GO agglomerates in the euphotic zone of typical open oceans will exceed 500 days. Aging in the presence of visible light increased the relative abundance of the GO's aromatic (C-C/C=C) fraction, reducing the NP. Reduction of GO in visible light was confirmed via UV-vis and Raman spectroscopic techniques. Reduction of GO was faster under solar irradiation. This study demonstrates that when introduced into saline waters, GO will undergo a range of transformations affecting its fate and potential effects to aquatic organisms.

Graphene is a 2-dimensional nanomaterial with unique mechanical, thermal, electrical, and optical properties. With increasing applications of graphene-family nanomaterials (GFNs) in electronics, biomedicine, and surface coatings, concern for their impacts on aquatic ecosystems is rising. Current information on the toxicity of GFNs, including graphene oxide, is scarce. Filter-feeding bivalves, such as eastern oysters, are good models for nanomaterial exposure studies. We present results from a 72-h static renewal oyster study using 1 and 10 mg/L graphene oxide, which, to our knowledge, is the first report on in vivo effects of graphene oxide exposures in marine bivalves. Water samples were analyzed for graphene oxide concentration and size assessments. Gill and digestive gland tissues were evaluated for lipid peroxidation and glutathione-S-transferase (GST) activity. In addition, gill sections were fixed for histopathological analyses. Elevated lipid peroxidation was noted in oysters exposed to 10 mg/L graphene oxide. No significant changes in GST activity were observed, but reduced total protein levels were found in digestive gland tissues of exposed oysters at both concentrations. Loss of mucous cells, hemocytic infiltration, and vacuolation were observed in gills of exposed oysters. The results indicate that short-term graphene oxide exposures can induce oxidative stress and epithelial inflammation and adversely affect overall oyster health. Further investigations regarding the fate and sublethal effects of graphene oxide are critical to understanding the risks associated with a rapidly growing graphene consumer market. Environ Toxicol Chem 2019;38:820-830. Published 2019 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

One of the key components for environmental risk assessment of engineered nanomaterials (ENMs) is data on bioaccumulation potential. Accurately measuring bioaccumulation can be critical for regulatory decision making regarding material hazard and risk, and for understanding the mechanism of toxicity. This perspective provides expert guidance for performing ENM bioaccumulation measurements across a broad range of test organisms and species. To accomplish this aim, we critically evaluated ENM bioaccumulation within three categories of organisms: single-celled species, multicellular species excluding plants, and multicellular plants. For aqueous exposures of suspended single-celled and small multicellular species, it is critical to perform a robust procedure to separate suspended ENMs and small organisms to avoid overestimating bioaccumulation. For many multicellular organisms, it is essential to differentiate between the ENMs adsorbed to external surfaces or in the digestive tract and the amount absorbed across epithelial tissues. For multicellular plants, key considerations include how exposure route and the role of the rhizosphere may affect the quantitative measurement of uptake, and that the efficiency of washing procedures to remove loosely attached ENMs to the roots is not well understood. Within each organism category, case studies are provided to illustrate key methodological considerations for conducting robust bioaccumulation experiments for different species within each major group. The full scope of ENM bioaccumulation measurements and interpretations are discussed including conducting the organism exposure, separating organisms from the ENMs in the test media after exposure, analytical methods to quantify ENMs in the tissues or cells, and modeling the ENM bioaccumulation results. One key finding to improve bioaccumulation measurements was the critical need for further analytical method development to identify and quantify ENMs in complex matrices. Overall, the discussion, suggestions, and case studies described herein will help improve the robustness of ENM bioaccumulation studies.

ObjectiveA pilot study suggested that combination therapy with low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) preserves C-peptide in established type 1 diabetes (T1D) (duration 4 months to 2 years). We hypothesized that 1) low-dose ATG/GCSF or 2) low-dose ATG alone would slow the decline of β-cell function in patients with new-onset T1D (duration

An increase in production of commercial products containing graphene-family nanomaterials (GFNs) has led to concern over their release into the environment. The fate and potential ecotoxicological effects of GFNs in the environment are currently unclear, partially due to the limited analytical methods for GFN measurements. In this review, the unique properties of GFNs that are useful for their detection and quantification are discussed. The capacity of several classes of techniques to identify and/or quantify GFNs in different environmental matrices (water, soil, sediment, and organisms), after environmental transformations, and after release from a polymer matrix of a product is evaluated. Extraction and strategies to combine methods for more accurate discrimination of GFNs from environmental interferences as well as from other carbonaceous nanomaterials are recommended. Overall, a comprehensive review of the techniques available to detect and quantify GFNs are systematically presented to inform the state of the science, guide researchers in their selection of the best technique for the system under investigation, and enable further development of GFN metrology in environmental matrices. Two case studies are described to provide practical examples of choosing which techniques to utilize for detection or quantification of GFNs in specific scenarios. Because the available quantitative techniques are somewhat limited, more research is required to distinguish GFNs from other carbonaceous materials and improve the accuracy and detection limits of GFNs at more environmentally relevant concentrations.

Background: Machado-Joseph disease (or spinocerebellar ataxia type 3) is a late-onset polyglutamine neurodegenerative disorder caused by a mutation in the ATXN3 gene, which encodes for the ubiquitously expressed protein ataxin-3. Previous studies on cell and animal models have suggested that mutated ataxin-3 is involved in transcriptional dysregulation. Starting with a whole-transcriptome profiling of peripheral blood samples from patients and controls, we aimed to confirm abnormal expression profiles in Machado-Joseph disease and to identify promising up-regulated genes as potential candidate biomarkers of disease status. Methods: The Illumina Human V4-HT12 array was used to measure transcriptome-wide gene expression in peripheral blood samples from 12 patients and 12 controls. Technical validation and validation in an independent set of samples were performed by quantitative real-time polymerase chain reaction (PCR). Results: Based on the results from the microarray, twenty six genes, found to be up-regulated in patients, were selected for technical validation by quantitative real-time PCR (validation rate of 81% for the up-regulation trend). Fourteen of these were further tested in an independent set of 42 patients and 35 controls; 10 genes maintained the up-regulation trend (FCGR3B, CSR2RA, CLC, TNFSF14, SLA, P2RY13, FPR2, SELPLG, YIPF6, and GPR96); FCGR3B, P2RY13, and SELPLG were significantly up-regulated in patients when compared with controls. Conclusions: Our findings support the hypothesis that mutated ataxin-3 is associated with transcription dysregulation, detectable in peripheral blood cells. Furthermore, this is the first report suggesting a pool of up-regulated genes in Machado-Joseph disease that may have the potential to be used for fine phenotyping of this disease.