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Supramolecular chemistry is, broadly, the study of noncovalent interactions. Electrochemistry inherently involves supramolecular organisation of ions and solvent, so the use of supramolecular chemistry in electrochemistry has the potential for great utility in various applications. Studies of supramolecular host–guest electrochemistry have been reported for decades. In recent years, these studies have moved past investigations of basic principles and towards functional systems. This perspective will describe the main directions in which applications of functional supramolecular host–guest electrochemical systems are being developed: sensing, ion transport, and catalysis. While these research directions have shown promising results, study of supramolecular host–guest electrochemistry remains relatively rare. Challenges in the development of these systems and an outlook for future research will be outlined. [ABSTRACT FROM AUTHOR]

Introduction: Adamantinoma‐like Ewing sarcoma (ALES) is a rare aggressive malignancy occasionally diagnosed in the thyroid gland. ALES shows basaloid cytomorphology, expresses keratins, p63, p40, frequently CD99, and harbours the t(11;22) EWSR1::FLI1 translocation. There is debate on whether ALES resembles more sarcoma or carcinoma. Methods: We performed RNA sequencing from two ALES cases and compared findings with skeletal Ewing's sarcomas and nonneoplastic thyroid tissue. ALES was investigated by in situ hybridization (ISH) for high‐risk human papillomavirus (HPV) DNA and immunohistochemistry for the following antigens: keratin 7, keratin 20, keratin 5, keratins (AE1/AE3 and CAM5.2), CD45, CD20, CD5, CD99, chromogranin, synaptophysin, calcitonin, thyroglobulin, PAX8, TTF1, S100, p40, p63, p16, NUT, desmin, ER, FLI1, INI1, and myogenin. Results: An uncommon EWSR1::FLI transcript with retained EWSR1 exon 8 was detected in both ALES cases. Regulators of EWSR1::FLI1 splicing (HNRNPH1, SUPT6H, SF3B1) necessary for production of a functional fusion oncoprotein, as well as 53 genes (including TNNT1, NKX2.2) activated downstream to the EWSR1::FLI1 cascade, were overexpressed. Eighty‐six genes were uniquely overexpressed in ALES, most of which were related to squamous differentiation. Immunohistochemically, ALES strongly expressed keratins 5, AE1/AE3 and CAM5.2, p63, p40, p16, and focally CD99. INI1 was retained. The remaining immunostains and HPV DNA ISH were negative. Conclusion: Comparative transcriptomic profiling reveals overlapping features of ALES with skeletal Ewing's sarcoma and an epithelial carcinoma, as evidenced by immunohistochemical expression of keratin 5, p63, p40, CD99, the transcriptome profile, and detection of EWSR1::FLI1 fusion transcript by RNA sequencing. [ABSTRACT FROM AUTHOR]

Objectives Polymorphism in a coding region of deoxyribonuclease I-like III (DNASE1L3), causing amino acid substitution of Arg-206 to Cys (R206C), is a robustly replicated heritable risk factor for SSc and other autoimmune diseases. DNASE1L3 is secreted into the circulation, where it can digest genomic DNA (gDNA) in apoptosis-derived membrane vesicles (AdMVs). We sought to determine the impact of DNASE1L3 R206C on digestion of circulating gDNA in SSc patients and healthy controls (HCs). Methods The ability of DNASE1L3 to digest AdMV-associated gDNA was tested in vitro. The effect of R206C substitution on extracellular secretion of DNASE1L3 was determined using a transfected cell line and primary monocyte-derived dendritic cells from SSc patients. Plasma samples from SSc patients and HCs with DNASE1L3 R206C or R206 wild type were compared for their ability to digest AdMV-associated gDNA. The digestion status of endogenous gDNA in plasma samples from 123 SSc patients and 74 HCs was determined by measuring the proportion of relatively long to short gDNA fragments. Results The unique ability of DNASE1L3 to digest AdMV-associated gDNA was confirmed. Extracellular secretion of DNASE1L3 R206C was impaired. Plasma from individuals with DNASE1L3 R206C had reduced ability to digest AdMV-associated gDNA. The ratio of long: short gDNA fragments was increased in plasma from SSc patients with DNASE1L3 R206C, and this ratio correlated inversely with DNase activity. Conclusion Our results confirm that circulating gDNA is a physiological DNASE1L3 substrate and show that its digestion is reduced in SSc patients with the DNASE1L3 R206C variant. [ABSTRACT FROM AUTHOR]

Purpose of Review: Triple-negative breast cancer (TNBC) is a heterogeneous disease group with a known aggressive phenotype and poor prognosis. To date, it remains a challenging disease given its lack of oncogenic targets as seen in hormone receptor + or HER2 + breast cancers, and limited efficacy with traditional chemotherapy. This article is a review of the latest key literature in the management of metastatic TNBC and offers a glimpse of ongoing drug development. Recent Findings: Recent paradigm-shifting trials led to the incorporation of immune checkpoint inhibitors with chemotherapy in the frontline setting for TNBC with positive PDL1-expression. Novel antibody–drug conjugates with new targets (Trop2, HER2) now offer additional treatment options for metastatic TNBC. Summary: There have been significant strides in understanding the tumor-immune microenvironment and molecular vulnerabilities in TNBC. As the treatment of metastatic TNBC evolves rapidly, novel combination therapies and therapeutic strategies will continue to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Establishing preventive measures to improve cognitive health of the growing older adult population is a public health priority. Though, the links between low-cost non-pharmacologist interventions that target activities like hobbies and cognitive health remain unclear. Objective: We conducted a topical review of extant literature to characterize prior findings in context and identify potential research opportunities. Methods: Search criteria was conducted with search terms "Hobbies and Dementia", "Hobbies and Cognitive Health," "Leisure Activities and Dementia," and "Leisure Activities and Cognitive Health". From the initial 383 articles, 25 articles were selected for review by using broad inclusion and exclusion criteria. Results: Of the 25 articles included in this review, 19 were longitudinal cohort, 1 was a retrospective cohort, 2 were case–control, and 3 were cross-sectional. These studies classified hobbies as leisure activities that were cognitive/intellectual, cultural, religious, social, gardening, traveling, or physical. These studies were conducted in the United States (9), United Kingdom (3), Sweden (3), France (5), Finland (1), Korea (1), Japan (2), and China (1). The associations of different types of hobbies with dementia from these studies were not consistent. Inconsistencies could be due to limitations of study design, lack of standardized methods, sample diversity, and differences in factors like social/cultural environment across the study populations. Conclusion: This review examined existing evidence for the association between engagement in different types of hobbies and dementia and identified key knowledge gaps and promising approaches for future research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The benefit of exercise to colorectal cancer patients has been advocated. However, comparative data to quantify the survival benefit is lacking. The aim of this review was to assess the effect of exercise on colorectal cancer survival. Methods: An up-to-date systematic review was performed on the available literature between 2000 and 2021 on PubMed, EMBASE, Medline, and Cochrane Library databases. All studies reporting on the impact of exercise and colorectal cancer outcomes in patients treated for non-metastatic colorectal cancer were analysed. The main outcome measures were the overall survival (OS), cancer specific survival (CSS) and disease free survival (DFS). Results: A total of 13 prospective observational studies were included, accounting for 19,135 patients. Compared to negligible physical activity, overall survival (OS) was significantly increased for both moderate and highest activity group (HR 0.82, 95% CI: 0.74–0.90, p < 0.001 and HR 0.64, 0.56–0.72, p < 0.001 respectively). This was also reflected in cancer specific survival (CSS) analysis, but not disease-free survival (DFS) analysis. Conclusion: Exercise was associated with an increased in overall survival after a colorectal cancer resection. This would support the promotion of exercise interventions amongst colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Background: Public health guidance and associated interventions seek to bring about change in diet and physical activity behaviours to improve life expectancy and healthy life expectancy in the population. Low socioeconomic status (SES) groups suffer from reduced life/healthy life expectancy compared with the population as a whole. This in-depth qualitative study, investigates the lives and experiences of mothers with young children living in a low SES area in a London (UK) borough, to understand the context in which current public health guidance on diet and physical activity is received and viewed, and how this understanding could be used to inform the development of public health guidance and interventions for this group.Methods: The mothers (n = 20), were recruited from a Surestart Centre, Children's Centres and through the local branch of a national charity. The mothers took part in a series of three in depth interviews over two years (2016-2017). Thematic analysis was used to generate an iterative set of codes informing an understanding of motherhood, diet and physical activity.Results: Motherhood was found to be a major factor for understanding and interpreting how women in low SES areas respond to public health guidance on diet and physical activity. The mothers were well informed about dietary guidance, considered that provision of healthy food was critical to the mothering role, but found it difficult to implement the guidance in their own lives. In contrast, physical activity was not seen as integral to the mothering role, although it was acknowledged that it played a part in ensuring that the mothers remained healthy enough to fulfil all their duties. Constrained by the ethic of care, and a lack of material and time resources, the mothers prioritised their family's health above their own. This study, enabled the mothers to articulate ideas for interventions that would be supportive of a healthy lifestyle and of practical application in their busy lives.Conclusions: Mothers from this low SES area responded differently to the public health guidance on diet and on physical activity. Whilst providing and modelling a healthy diet was seen as an essential part of the mother's role, participating in leisure based physical activity was problematic, and unless carefully framed, could be perceived as selfish behaviour, inappropriate for the "good" mother. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes (T1D) places an extraordinary burden on individuals and their families, as well as on the healthcare system. Despite recent advances in glucose sensors and insulin pump technology, only a minority of patients meet their glucose targets and face the risk of both acute and long-term complications, some of which are life-threatening. The JAK-STAT pathway is critical for the immune-mediated pancreatic beta cell destruction in T1D. Our pre-clinical data show that inhibitors of JAK1/JAK2 prevent diabetes and reverse newly diagnosed diabetes in the T1D non-obese diabetic mouse model. The goal of this study is to determine if the JAK1/JAK2 inhibitor baricitinib impairs type 1 diabetes autoimmunity and preserves beta cell function.Methods: This will be as a multicentre, two-arm, double-blind, placebo-controlled randomized trial in individuals aged 10-30 years with recent-onset T1D. Eighty-three participants will be randomized in a 2:1 ratio within 100 days of diagnosis to receive either baricitinib 4mg/day or placebo for 48 weeks and then monitored for a further 48 weeks after stopping study drug. The primary outcome is the plasma C-peptide 2h area under the curve following ingestion of a mixed meal. Secondary outcomes include HbA1c, insulin dose, continuous glucose profile and adverse events. Mechanistic assessments will characterize general and diabetes-specific immune responses.Discussion: This study will determine if baricitinib slows the progressive, immune-mediated loss of beta cell function that occurs after clinical presentation of T1D. Preservation of beta cell function would be expected to improve glucose control and prevent diabetes complications, and justify additional trials of baricitinib combined with other therapies and of its use in at-risk populations to prevent T1D.Trial Registration: ANZCTR ACTRN12620000239965 . Registered on 26 February 2020.Clinicaltrials: gov NCT04774224. Registered on 01 March 2021. [ABSTRACT FROM AUTHOR]

The utilization of artificial intelligence (AI) in psychiatry has risen over the past several years to meet the growing need for improved access to mental health solutions. Additionally, shortages of mental health providers during the COVID-19 pandemic have continued to exacerbate the burden of mental illness worldwide. AI applications already in existence include those enabled to assist with psychiatric diagnoses, symptom tracking, disease course prediction, and psychoeducation. Modalities of AI mental health care delivery include availability through the internet, smartphone applications, and digital gaming. Here we review emerging AI-based interventions in the form of chat and therapy bots, specifically conversational applications that teach the user emotional coping mechanisms and provide support for people with communication difficulties, computer generated images of faces that form the basis of avatar therapy, and intelligent animal-like robots with new advances in digital psychiatry. We discuss the implications of incorporating AI chatbots into clinical practice and offer perspectives on how these AI-based interventions will further impact the field of psychiatry. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that either a transanal stent (TAS) or rectal tube (RT) can decrease the risk of anastomotic leakage (AL) after anterior resection for rectal cancer, in which a diverting stoma may not be required. Objectives: The aim of this review was to investigate the efficacy and safety of RT/TAS in preventing AL after anterior resections. Data sources: An up-to-date systematic review was performed on the available literature between 2000 and 2020 on PubMed, EMBASE, Medline and Cochrane Library databases. Study selection: All studies reporting on anterior resections in adults, comparing transanal tube/stent versus non-tube/stent, were analysed. Main outcome measure: The primary outcome was rates of AL, whereas secondary outcomes compared associated unplanned re-operation for AL and hospital length of stay (LOS). Results: Two randomized controlled trials and 13 observational studies were included, with 1714 patients receiving RT/TAS and 1741 patients without. There were 119 (7%) patients with AL in the RT/TAS group compared to 216 (12.3%) patients in the non-RT/TAS group (OR: 0.48, 95% CI: 0.38–0.62, p < 0.001). There were 47 (2.9%) patients with AL complications requiring surgery in the RT/TAS group compared to 132 (8%) patients in the non-RT/TAS group (OR: 0.29, 95% CI: 0.20–0.42, p < 0.001) and no significant difference identified with the standardized mean difference (SMD) favouring the RT/TAS group for hospital LOS (SMD: −0.23, 95% CI: −0.51 to 0.06, p = 0.115). Conclusion: The use of RT/TAS post restorative anterior resection for rectal cancer should be considered, given the benefits shown from this meta-analysis. [ABSTRACT FROM AUTHOR]

Background: There is concern that transanal total mesorectal excision (TaTME) may result in poorer functional outcomes as compared to laparoscopic TME (LaTME). These concerns arise from the fact that TaTME entails both a low anastomosis and prolonged dilatation of the anal sphincter from the transanal platform. Objectives: This paper aimed to assess the comparative functional outcomes following TaTME and LaTME, with a focus on anorectal and genitourinary outcomes. Data sources: A meta-analysis and systematic review was performed on available literature between 2000 and 2020 from the PubMed, EMBASE, Medline, and Cochrane Library databases. Study selection: All comparative studies assessing the functional outcomes following taTME versus LaTME in adults were included. Main outcome measure: Functional anorectal and genitourinary outcomes were evaluated using validated scoring systems. Results: A total of seven studies were included, consisting of one randomised controlled trial and six non-randomised studies. There were 242 (52.0%) and 233 (48.0%) patients in the TaTME and LaTME groups respectively. Anorectal functional outcomes were similar in both groups with regard to LARS scores (30.6 in the TaTME group and 28.3 in the LaTME group), Jorge-Wexner incontinence scores, and EORTC QLQ C30/29 scores. Genitourinary function was similar in both groups with IPSS scores of 5.5 to 8.0 in the TaTME group, and 3.5 to 10.1 in the LaTME group. (p = 0.835). Conclusion: This review corroborates findings from previous studies in showing that the transanal approach is not associated with increased anal sphincter damage. Further prospective clinical trials are needed in this field of research. [ABSTRACT FROM AUTHOR]

Background: While complete mesocolic excision (CME) has been shown to have an oncological benefit as compared to conventional colonic surgery for colon surgery, this benefit must be weighed up against the risk of major intra‐abdominal complications. This paper aimed to assess the comparative oncological benefits of CME. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines, a systematic review of the literature until May 2020 was performed. Comparative studies assessing CME versus conventional colonic surgery for colon cancer were compared, and outcomes were pooled. Results: A total of 700 publications were identified, of which 19 were found to meet the inclusion criteria. A total of 25 886 patients were compared, with 14 431 patients in the CME arm. CME was associated with a significantly higher rate of vascular injury (odds ratio 3, P < 0.001). Rates of local and distant recurrence were lower in the CME group (odds ratio 0.66 and 0.73, respectively, both P < 0.001). CME patients had a significantly higher lymph node yield (P < 0.001). While no significant differences were noted between the two groups in terms of pooled 3‐ or 5‐year disease‐free survival, pooled 5‐year overall survival was significantly higher in the CME group (relative risk 0.82, P < 0.001). Conclusion: Based on the available evidence, CME is associated with improved oncologic outcomes at the expense of higher complication rates, including vascular injury. The oncological benefits need to weighed up against a multitude of factors including the level of hospital support, surgeon experience, patient age, and associated comorbidities. [ABSTRACT FROM AUTHOR]

Purpose: Speech-language pathologists (SLPs) are responsible for differentially diagnosing a speech or language difference versus disorder. However, in the absence of data on particular cultural or linguistic groups, misdiagnosis increases. This study seeks to bridge the gap in available resources for SLPs focusing on the phonological features of Guyanese Creole (GC), a Caribbean English-lexified Creole. This study addresses the following question: What are the differences between the phonological features of GC and Standard American English (SAE), which may potentially cause SLPs to misdiagnose Guyanese speakers? Method: A contrastive phonological analysis was conducted to identify the phonological differences of GC from SAE. Results: The study results indicate differences in vowels, dental fricatives, voiced alveolar liquids, voiceless glottal fricatives, voiced palatal glides, consonant clusters, final consonants, and unstressed syllables. Conclusions: The findings of this study support the literature that GC is distinct from SAE in its phonology. The results provide SLPs with data to make informed clinical and educational decisions when assessing the linguistic competencies of children from Caribbean backgrounds, specifically GC speakers. [ABSTRACT FROM AUTHOR]

As contaminant exposures in aquatic ecosystems continue to increase, the need for streamlining research efforts in environmental toxicology using predictive frameworks also grows. One such framework is the adverse outcome pathway (AOP). An AOP framework organizes and utilizes toxicological information to connect measurable molecular endpoints to an adverse outcome of regulatory relevance via a series of events at different levels of biological organization. Molecular endpoints or biomarkers are essential to develop AOPs and are valuable early warning signs of the toxicity of pollutants, including contaminants of emerging concern. Ecological risk‐assessment approaches using tools such as biomarkers and AOPs benefit from identification of molecular targets conserved across species. Bivalve models are useful in such approaches and integral to our understanding of ecological and human health risks associated with contaminant exposures. We discuss the value of using biomarker approaches in bivalve models to meet the demands of twenty‐first‐century toxicology. Environ Toxicol Chem 2020;39:1472–1484. © 2020 SETAC [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To estimate the causal association between intake of dairy products and incident type 2 diabetes.Research Design and Methods: The analysis included 21,820 European individuals (9,686 diabetes cases) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study. Participants were genotyped, and rs4988235 (LCT-12910C>T), a single nucleotide polymorphism (SNP) for lactase persistence (LP) that enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression.Results: Each additional LP allele was associated with a higher intake of milk (β 17.1 g/day, 95% CI 10.6-23.6) and milk beverages (β 2.8 g/day, 95% CI 1.0-4.5) but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits (β -7.0 g/day, 95% CI -12.4 to -1.7 per additional LP allele), nonalcoholic beverages (β -18.0 g/day, 95% CI -34.4 to -1.6), and wine (β -4.8 g/day, 95% CI -9.1 to -0.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratioper 15 g/day 0.99, 95% CI 0.93-1.05).Conclusions: rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations, we consider it unlikely that this caused the observed null result. [ABSTRACT FROM AUTHOR]

Patients with acute leukemia frequently develop catheter-related thrombosis (CRT) despite concurrent thrombocytopenia. The incidence, treatment and outcomes of this complication are poorly documented. We undertook this study to determine the incidence of CRT in patients with acute leukemia and assess the safety and effectiveness of a treatment strategy using a platelet-adjusted low molecular weight heparin (LMWH) dosing protocol. Patients (18 years and older) with newly diagnosed acute leukemia from January 2014 to December 2015 who received central venous catheters were included. The clinical data were reviewed up to 12 months from acute leukemia diagnosis to capture objectively documented CRT events. The outcome events including recurrent venous thromboembolism (VTE), bleeding events, infectious or mechanical complications, and death were reported up to 3 months from the time of CRT diagnosis. The incidence of CRT among 214 patients was 10.7% (23 patients) in the first 12 months after acute leukemia diagnosis. Among 18 patients who were treated with anticoagulation, 14 (78%) received reduced LMWH dosing due to concurrent thrombocytopenia. There were no recurrent VTE episodes, but 3 patients experienced bleeding events while on anticoagulation. Fifteen patients (83%) completed a minimum of 3 months anticoagulation. Twelve patients (52%) experienced an infectious complication, which was the main reason for catheter removal. Deaths occurred in 2 patients, related to underlying acute leukemia during 3 months period following CRT. Symptomatic CRT is frequent in patients with acute leukemia. Platelet-adjusted LMWH dosing may be effective and well tolerated despite thrombocytopenia. [ABSTRACT FROM AUTHOR]

Abstract: It is well known that copper (Cu) is toxic to marine organisms. We measured and compared the acute toxicity of several forms of Cu (including nanoCu) amended into a marine sediment with mysids and amphipods. For all the forms of Cu tested, toxicity, measured as the median lethal concentration, ranged from 708 to > 2400 mg Cu/kg (dry sediment) for mysids and 258 to 1070 mg Cu/kg (dry sediment) for amphipods. Environ Toxicol Chem 2018;37:2677–2681. © 2018 SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. [ABSTRACT FROM AUTHOR]

Abstract: One application of nanocopper is as a wood‐preserving pesticide in pressure‐treated lumber. Recent research has shown that pressure‐treated lumber amended with micronized copper azole (MCA), which contains nanosized copper, releases copper under estuarine and marine conditions. The form of copper released (i.e., ionic, nanocopper [1–100 nm in size]) is not fully understood but will affect the bioavailability and toxicity of the metal. In the present study, multiple lines of evidence, including size fractionation, ion‐selective electrode electrochemistry, comparative toxicity, and copper speciation were used to determine the form of copper released from lumber blocks and sawdust. The results of all lines of evidence supported the hypothesis that ionic copper was released from MCA lumber and sawdust, with little evidence that nanocopper was released. For example, copper concentrations in size fractionations of lumber block aqueous leachates including unfiltered, 0.1 μm, and 3 kDa were not significantly different, suggesting that the form of copper released was in the size range operationally defined as dissolved. These results correlated with the ion‐selective electrode data which detects only ionic copper. In addition, comparative toxicity testing resulted in a narrow range of median lethal concentrations (221–257 μg/L) for MCA lumber blocks and CuSO4. We conclude that ionic copper was released from the nanocopper pressure‐treated lumber under estuarine and marine conditions. Environ Toxicol Chem 2018;37:1969–1979. Published 2018 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. [ABSTRACT FROM AUTHOR]

Abstract: Little is known about the release of metal engineered nanomaterials (ENMs) from consumer goods, including lumber treated with micronized copper. Micronized copper is a recent form of antifouling wood preservative containing nanosized copper particles for use in pressure‐treated lumber. The present study investigated the concentrations released and the release rate of total copper over the course of 133 d under freshwater, estuarine, and marine salinity conditions (0, 1, 10, and 30‰) for several commercially available pressure‐treated lumbers: micronized copper azole (MCA) at 0.96 and 2.4 kg/m3, alkaline copper quaternary (ACQ) at 0.30 and 9.6 kg/m3, and chromated copper arsenate (CCA) at 40 kg/m3. Lumber was tested as blocks and as sawdust. Overall, copper was released from all treated lumber samples. Under leaching conditions, total release ranged from 2 to 55% of the measured copper originally in the lumber, with release rate constants from the blocks of 0.03 to 2.71 (units per day). Generally, measured release and modeled equilibrium concentrations were significantly higher in the estuarine conditions compared with freshwater or marine salinities, whereas rate constants showed very limited differences between salinities. Furthermore, organic carbon was released during the leaching and demonstrated a significant relationship with released copper concentrations as a function of salinity. The results indicate that copper is released into estuarine/marine waters from multiple wood treatments including lumber amended with nanoparticle‐sized copper. Environ Toxicol Chem 2018;37:1956–1968. Published 2018 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. [ABSTRACT FROM AUTHOR]

The article focuses on challenges associated with performing environmental research on titanium dioxide nanoparticles in aquatic environments. Topics discussed include information on self-aggregation which is a phenomenon not often found with many conventional contaminants except in cases of high concentrations; determination of engineered titanium dioxide nanoparticles (NPs) as widely used metal oxide nanomaterials; and challenges associated with performing research on titanium dioxide NPs.

Abstract: The widespread use of copper nanomaterials (CuNMs) as antibacterial and antifouling agents in consumer products increases the risk for metal contamination and adverse effects in aquatic environments. Information gaps exist on the potential toxicity of CuNMs in marine environments. We exposed field‐collected marine meio‐ and macrobenthic communities to sediments spiked with micronized copper azole (MCA) using a novel method that brings intact benthic cores into the laboratory and exposes the organisms via surface application of sediments. Treatments included field and laboratory controls, 3 spiked sediments: low‐MCA (51.9 mg/kg sediment), high‐MCA (519 mg/kg sediment), and CuSO4 (519 mg/kg sediment). In addition, single‐species acute testing was performed with both MCA and CuSO4. Our results indicate that meio‐ and macrofaunal assemblages exposed to High‐MCA and CuSO4 treatments differed significantly from both the laboratory control and the low‐MCA treatments. Differences in macrofauna were driven by decreases in 3 Podocopa ostracod species, the bivalve Gemma gemma, and the polychaetes Exogone verugera and Prionospio heterobranchia relative to the laboratory control. Differences in the meiofaunal community are largely driven by nematodes. The benthic community test results were more sensitive than the single‐species test results. Findings of this investigation indicate that CuNMs represent a source of risk to marine benthic communities comparable to that of dissolved Cu. Environ Toxicol Chem 2018;37:362–375. Published 2017 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. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is a common, complex, and costly complication in cancer patients undergoing surgery. VTE risk varies with types of cancer surgery as well as patient-, cancer-, and treatment-associated factors. Current VTE preventive measures with pharmacological, mechanical, and combination of both are shown to be effective. Clinical questions remain and more research is needed, focusing on the role of thromboprophylaxis for minimally invasive surgery and major cancer surgery other than abdominal/pelvic surgery, as well as optimal duration of thromboprophylaxis in high-risk patients. Routine individual VTE risk assessment and better adherence to thromboprophylaxis guidelines may offer improved outcomes in cancer patients undergoing surgery. A summary of currently available evidence and consensus guidelines on the primary prevention of VTE in cancer patients undergoing various types of surgery is presented here. [ABSTRACT FROM AUTHOR]

Engineered nanomaterials (ENM) are a growing aspect of the global economy, and their safe and sustainable development, use, and eventual disposal requires the capability to forecast and avoid potential problems. This review provides a framework to evaluate the health and safety implications of ENM releases into the environment, including purposeful releases such as for antimicrobial sprays or nano-enabled pesticides, and inadvertent releases as a consequence of other intended applications. Considerations encompass product life cycles, environmental media, exposed populations, and possible adverse outcomes. This framework is presented as a series of compartmental flow diagrams that serve as a basis to help derive future quantitative predictive models, guide research, and support development of tools for making risk-based decisions. After use, ENM are not expected to remain in their original form due to reactivity and/or propensity for hetero-agglomeration in environmental media. Therefore, emphasis is placed on characterizing ENM as they occur in environmental or biological matrices. In addition, predicting the activity of ENM in the environment is difficult due to the multiple dynamic interactions between the physical/chemical aspects of ENM and similarly complex environmental conditions. Others have proposed the use of simple predictive functional assays as an intermediate step to address the challenge of using physical/chemical properties to predict environmental fate and behavior of ENM. The nodes and interactions of the framework presented here reflect phase transitions that could be targets for development of such assays to estimate kinetic reaction rates and simplify model predictions. Application, refinement, and demonstration of this framework, along with an associated knowledgebase that includes targeted functional assay data, will allow betterde novopredictions of potential exposures and adverse outcomes. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses aquatic environment and the role of microplastics in it.

ABSTRACT The Pawtuxet River in Rhode Island, USA, has a long history of industrial activity and pollutant discharges. Metal contamination of the river sediments is well documented and historically exceeded toxicity thresholds for a variety of organisms. The Pawtuxet River dam, a low-head dam at the mouth of the river, was removed in August 2011. The removal of the dam was part of an effort to restore the riverine ecosystem after centuries of anthropogenic impact. Sediment traps were deployed below the dam to assess changes in metal concentrations and fluxes (Ag, Cd, Cr, Cu, Ni, Pb, and Zn) from the river system into Pawtuxet Cove. Sediment traps were deployed for an average duration of 24 days each, and deployments continued for 15 months after the dam was removed. Metal concentrations in the trapped suspended particulate matter dropped after dam removal (e.g., 460 to 276 mg/kg for Zn) and remained below preremoval levels for most of the study. However, particle-bound metal fluxes increased immediately after dam removal (e.g., 1206 to 4248 g/day for Zn). Changes in flux rates during the study period indicated that river volumetric flow rates acted as the primary mechanism controlling the flux of metals into Pawtuxet Cove and ultimately upper Narragansett Bay. Even though suspended particulate matter metal concentrations initially dropped after removal of the dam, no discernable effect on the concentration or flux of the study metals exiting the river could be associated with removal of the Pawtuxet River dam. Integr Environ Assess Manag 2017;13:675-685. Published 2016. This article is a US Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) develops when there are insufficient insulinproducing beta cells to maintain glucose homeostasis. The prevailing view has been that T1D is caused by immune-mediated destruction of the pancreatic beta cells. However, several recent papers have challenged the long-standing paradigm describing T1D as a tissue-specific autoimmune disease. These authors have highlighted the gaps in our knowledge and understanding of the aetiology of T1D in humans. Here we review the evidence and argue the case for the autoimmune basis of human T1D. In particular, recent analysis of human islet-infiltrating T cells brings important new evidence to this question. Further data in support of the autoimmune basis of T1D from many fields, including genetics, experimental therapies and immunology, is discussed. Finally, we highlight some of the persistent questions relating to the pathogenesis of human type 1 diabetes that remain to be answered. [ABSTRACT FROM AUTHOR]

Little is known about environmental biodegradability or biotransformations of single-walled carbon nanotubes (SWNT). Because of their strong association with aquatic organic matter, detailed knowledge of the ultimate fate and persistence of SWNT requires investigation of possible biotransformations (i.e., biodegradation) in environmental media. In the present study, [14C]SWNT were utilized to track biodegradation over 6 mo by pure liquid culture of the fungus Trametes versicolor and mixed bacterial isolates from field-collected sediment or aerated wastewater treatment plant sludge. The mixed cultures were chosen as more environmentally relevant media where SWNT will likely be deposited under both aerobic and anaerobic conditions. Activity of [14C] was assessed in solid, aqueous, and 14CO2 gaseous phases to determine amounts of intact SWNT, partially soluble SWNT degradation products, and mineralized SWNT, respectively, during the 6 mo of the experiment. Mass balances based on radiocarbon activity were approximately 100% over 6 mo, and no significant degradation of SWNT was observed. Approximately 99% of the [14C] activity remained in the solid phase, 0.8% in the aqueous phase, and less than 0.1% was mineralized to 14CO2, regardless of culture type. These results suggest that SWNT are not readily biodegraded by pure fungal cultures or environmental microbial communities, and are likely persistent in environmental media. Environ Toxicol Chem 2014;9999:1-5. © 2014 SETAC [ABSTRACT FROM AUTHOR]

Islet cell transplantation has emerged as a treatment modality for type 1 diabetes in the last 15 years due to the Edmonton protocol leading to consistent and sustained exogenous insulin independence post-transplantation. In recent years, consortia that involve both local and remote islet cell centers have been established, with local centers responsible for processing and shipping of islet cells, and remote centers only transplanting them. There are, however, few data on patient outcomes at remote centers. A tendency for high fasting glucose despite insulin independence was noted by us and others with an unknown mechanism. This review provides a brief history of islet cell transplantation, and focuses on the South Australian remote center experience: the challenges, screening criteria, and the impact on incretin hormone secretion of insulin independent transplant patients. [ABSTRACT FROM AUTHOR]

Background Expression of NRIF3 (Nuclear Receptor Interacting Factor-3) rapidly and selectively leads to apoptosis of breast cancer cells. This occurs through binding of NRIF3 or its 30 amino acid Death Domain-1 (DD1) region to the transcriptional repressor, DIF-1 (DD1 Interacting Factor-1). DIF-1 acts in a wide variety of breast cancer cells but not other cell types to repress the pro-apoptotic gene, FASTKD2. Expression of NRIF3 or DD1 inactivates the DIF-1 repressor leading to rapid derepression of FASTKD2, which initiates apoptosis within 5-8 h of expression. Although FASTKD2 is an inner mitochondrial membrane protein, it does not require mitochondrial localization to initiate apoptosis. Methods Androgen dependent LNCaP cells as well as two androgen independent LNCaP cell lines (LNCaP-AI and LNCaP-abl) were studied and LNCaP-AI cells were engineered to conditionally express DD1 or the inactive DD1-S28A with 4-hydroxytamoxifen. Apoptosis was assessed by TUNEL assay. FASTKD2 is related to 4 other proteins encoded in the human genome (FASTKD1, 3, 4, 5). All contain a poorly conserved putative bipartite kinase domain designated as FAST1_FAST2. We examined whether expression of any of the other FASTKD isoforms leads to apoptosis and sought to identify the region of FASTKD2 necessary to initiate the apoptotic pathway. Results Of the FASTKD1-5 isoforms only expression of FASTKD2 leads to apoptosis. Although, the NRIF3/DD1/DIF-1 pathway does not mediate apoptosis of a wide variety of non-breast cancer cell lines, because of certain similarities and gene signatures between breast and prostate cancer we explored whether the NRIF3/DD1/DIF-1/FASTKD2 pathway mediates apoptosis of prostate cancer cells. We found that the pathway leads to apoptosis in LNCaP cells, including the two androgen-independent LNCaP cell lines that are generally resistant to apoptosis. Lastly, we identified that FASTKD2-mediated apoptosis is initiated by the 81 amino acid FAST2 region. Conclusions The NRIF3/DIF-1/FASTKD2 pathway acts as a "death switch" in breast and prostate cancer cells. Deciphering how this pathway is regulated and how FASTKD2 initiates the apoptotic response will allow for the development of therapeutic agents for the treatment of androgen- independent prostate cancer or Tamoxifen-unresponsive Estrogen Receptor negative tumors as well as metastatic breast or prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Expression of NRIF3 (Nuclear Receptor Interacting Factor-3) rapidly and selectively leads to apoptosis of breast cancer cells. This occurs through binding of NRIF3 or its 30 amino acid Death Domain-1 (DD1) region to the transcriptional repressor, DIF-1 (DD1 Interacting Factor-1). DIF-1 acts in a wide variety of breast cancer cells but not other cell types to repress the pro-apoptotic gene, FASTKD2. Expression of NRIF3 or DD1 inactivates the DIF-1 repressor leading to rapid derepression of FASTKD2, which initiates apoptosis within 5-8 h of expression. Although FASTKD2 is an inner mitochondrial membrane protein, it does not require mitochondrial localization to initiate apoptosis. Methods: Androgen dependent LNCaP cells as well as two androgen independent LNCaP cell lines (LNCaP-AI and LNCaP-abl) were studied and LNCaP-AI cells were engineered to conditionally express DD1 or the inactive DD1-S28A with 4-hydroxytamoxifen. Apoptosis was assessed by TUNEL assay. FASTKD2 is related to 4 other proteins encoded in the human genome (FASTKD1, 3, 4, 5). All contain a poorly conserved putative bipartite kinase domain designated as FAST1_FAST2. We examined whether expression of any of the other FASTKD isoforms leads to apoptosis and sought to identify the region of FASTKD2 necessary to initiate the apoptotic pathway. Results: Of the FASTKD1-5 isoforms only expression of FASTKD2 leads to apoptosis. Although, the NRIF3/DD1/DIF-1 pathway does not mediate apoptosis of a wide variety of non-breast cancer cell lines, because of certain similarities and gene signatures between breast and prostate cancer we explored whether the NRIF3/DD1/DIF-1/FASTKD2 pathway mediates apoptosis of prostate cancer cells. We found that the pathway leads to apoptosis in LNCaP cells, including the two androgen-independent LNCaP cell lines that are generally resistant to apoptosis. Lastly, we identified that FASTKD2-mediated apoptosis is initiated by the 81 amino acid FAST2 region. Conclusions: The NRIF3/DIF-1/FASTKD2 pathway acts as a "death switch" in breast and prostate cancer cells. Deciphering how this pathway is regulated and how FASTKD2 initiates the apoptotic response will allow for the development of therapeutic agents for the treatment of androgen-independent prostate cancer or Tamoxifen-unresponsive Estrogen Receptor negative tumors as well as metastatic breast or prostate cancer. [ABSTRACT FROM AUTHOR]

Objective:To create a ‘one-stop’ clinic in which assessment, diagnosis, treatment and therapies for most patients presenting with balance and dizziness disorders are delivered simultaneously.Methods:Patients triaged via referral letters were selected to attend the balance clinic, which is led by specialist balance physiotherapists. Patients were seen by an audiologist, and a ‘balance’ ENT consultant was available for joint consultations when required. Further details of the clinic set up are discussed.Results:Over an 18-month period, 200 new ‘dizzy’ patients attended the clinic. Benign paroxysmal positional vertigo and labyrinthitis were the commonest diagnoses. Fifty per cent of all patients were discharged after a single clinic visit. Questionnaires showed that patient satisfaction was high.Conclusion:The physiotherapy-led balance clinic has reduced patient waiting times to be seen, has a high level of patient satisfaction and is economically beneficial. [ABSTRACT FROM PUBLISHER]

Adsorption of hydrophobic organic contaminants (HOCs) to black carbon is a well-studied phenomenon. One emerging class of engineered black carbon materials are single-walled carbon nanotubes (SWNTs). Little research has investigated the potential of SWNT to adsorb and sequester HOCs in complex environmental systems. This study addressed the capacity of SWNT, amended to polychlorinated biphenyl (PCB)-contaminated New Bedford Harbor (NBH) sediment, to reduce the toxicity and bioaccumulation of these HOCs to benthic organisms. Overall, SWNT amendments increased the survival of two benthic estuarine invertebrates, Americamysis bahia and Ampelisca abdita, and reduced the accumulation of PCBs to the benthic polychaete, Nereis virens. Reduction in PCB bioaccumulation by SWNT was independent of Kow. Further, passive sampling-based estimates of interstitial water concentrations indicated that SWNT reduced PCB bioavailability. Results from this study suggest that SWNT are a good adsorbent for PCBs and might be useful for remediation in the future once SWNT manufacturing technology improves and costs decrease. [ABSTRACT FROM AUTHOR]

The behavior and fate of nanoparticles (NPs) in the marine environment are largely unknown and potentially have important environmental and human health implications. The aggregation and fate of NPs in the marine environment are greatly influenced by their interactions with seawater and dissolved organic carbon (DOC). In the present study, the stability and aggregation of 30-nm-diameter silver nanoparticles (AgNPs) capped with citrate and polyvinylpyrrolidone (PVP; AgNP-citrate and AgNP-PVP) and 21-nm-diameter titanium dioxide (TiO2) NPs as affected by seawater salinity and DOC were investigated by measuring hydrodynamic diameters and zeta potentials. The added DOC (in humic acid form) stabilized the 3 types of NPs when the seawater salinities were ≤5 parts per thousand (ppt), but the stabilizing effect of DOC was reduced by a higher salinity (e.g., 30 ppt). In addition, AgNP-PVP was more stable than AgNP-citrate in seawater, indicating that surface capping agents and stabilization mechanisms govern the stability and aggregation of NPs. Statistical analysis showed that salinity is the most dominant influence on the stability and aggregation of AgNPs and TiO2NPs, followed by DOC. These findings expand our knowledge on the behavior of AgNPs and TiO2NPs in seawater and indicate that the fate of these NPs will be primarily to aggregate in the water column, precipitate, and accumulate in sediments following release into the marine environment. Environ Toxicol Chem 2014;33:1023-1029. © 2014 SETAC [ABSTRACT FROM AUTHOR]

Ecotoxicological information for most contaminants is limited to a small number of taxa, and these are generally restricted to comparatively hardy organisms that are readily extractable from test media and easily identifiable. Advances in DNA sequencing can now provide a comprehensive view of benthic invertebrate diversity. The authors applied 454 pyrosequencing to examine the responses of benthic communities in microcosms exposed to sediments with elevated concentrations of triclosan, the endpoint being eukaryl communities that have successfully vertically migrated through the manipulated sediments. The biological communities associated with the 3 treatments (control triclosan, low triclosan [14 mg/kg], and high triclosan [180 mg/kg]) clustered into 3 groups: control/low ( n = 6 controls and 4 low), moderate ( n = 2 low), and high ( n = 5 high). One sample was discarded as an outlier. The most pronounced change as a response to triclosan was the loss of number of metazoan operational taxonomic units (OTUs), indicative of the control/low and moderate groups, with this being most evident in the range of taxa associated with the classes Chromadorea and Bivalvia and the phylum Kinorhyncha. The authors also describe a range of other taxa that aided discrimination between the groups; compare findings with traditionally obtained meio- and macrofaunal communities obtained from the same experiment; and illustrate some of the advantages and limitations associated with both the molecular and traditional approaches. The described approach illustrates the capacity for amplicon sequencing to provide ecologically relevant information that can be used to strengthen an understanding of how sedimentary communities respond to a range of environmental stressors. Environ Toxicol Chem 2014;33:359-369. © 2014 SETAC [ABSTRACT FROM AUTHOR]