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Aberrant DNA methylation patterns have been used for cancer detection. However, DNA hemi-methylation, present at about 10% CpG dinucleotides, has been less well studied. Here we show that a majority of differentially hemi-methylated regions (DHMRs) in liver tumor DNA or plasma cells free (cf) DNA do not overlap with differentially methylated regions (DMRs) of the same samples, indicating that DHMRs could serve as independent biomarkers. Furthermore, we analyzed the cfDNA methylomes of 215 samples from individuals with liver or brain cancer and individuals without cancer (controls), and trained machine learning models using DMRs, DHMRs or both. The models incorporated with both DMRs and DHMRs show a superior performance compared to models trained with DMRs or DHMRs, with AUROC being 0.978, 0.990, and 0.983 in distinguishing control, liver and brain cancer, respectively, in a validation cohort. This study supports the potential of utilizing both DMRs and DHMRs for multi-cancer detection. Alterations in DNA methylation patterns are known as predictors of cancer diagnosis. Here, the authors develop a method to analyze both symmetric- and hemi-methylated regions in plasma cell free DNA and show its utility in detecting both liver and brain cancer. [ABSTRACT FROM AUTHOR]

Introduction: The World Health Organization has reported submersion injuries as the third most common cause of death due to unintentional injury in the world. Greater detail in the rates, risk factors, and healthcare associated costs of submersion injuries could be instrumental in demonstrating the need for further funding and intervention. Methods: The study was a cross-sectional analysis of a nationally representative dataset of inpatient and emergency department (ED) encounters between 2006 and 2015 in the United States (US). Healthcare utilization costs were provided within the datasets and adjusted to reflect actual charges and provider fees. Lastly, the final cost values were adjusted to the 2020 US dollar (USD) and summarized using a log adjusted mean. Results: On average, there were 11,873 submersion injuries per year that presented to the ED in the US. Resulting in a rate where approximately 9 out of every 100,000 ED visits were associated with a submersion injury. Slightly more than 6% died in the ED, 24.2% were admitted, and 69.3% were discharged from the ED. In total, annual cost of submersion injuries in the US for ED care is approximately $12.5 million, inpatient care is approximately $27.5 million, and total annual healthcare cost exceeds $40 million. Discussion: While these results only represent a fraction of the total cost associated with submersion injuries, it remains substantial and unchanged over the 10-year study period. Certain demographic groups showed higher rates of injury and disease burden, thus bearing a greater amount of the cost. [ABSTRACT FROM AUTHOR]

Early studies conceptualized the "anxious bully" as different from typical bullies due to their anxiety and home problems. Yet, empirical findings are mixed, and no study has reported associations between youth bullying perpetration, youth anxiety, and parent distress in a clinically anxious sample. We assessed 220 youths' anxiety symptom severity, frequency of the bullying perpetration in the past month, and parent levels of distress. Fifty percent of youths endorsed at least one perpetration act and 17% endorsed six or more. Youth anxiety, but not parent distress, was significantly associated with perpetration. We also found a significant interaction such that youth anxiety was positively associated with bullying perpetration when parent distress was high, but not low. Findings fill a glaring knowledge gap regarding this overlooked group of youth, anxious bullies, and provide novel insights into the interplay between youth distress and parent distress in predicting bullying perpetration. [ABSTRACT FROM AUTHOR]

As a strategy to improve the therapeutic success of chimeric antigen receptor T cells (CART) directed against solid tumors, we here test the combinatorial use of CART and IMSA101, a newly developed stimulator of interferon genes (STING) agonist. In two syngeneic tumor models, improved overall survival is observed when mice are treated with intratumorally administered IMSA101 in addition to intravenous CART infusion. Transcriptomic analyses of CART isolated from tumors show elevated T cell activation, as well as upregulated cytokine pathway signatures, in particular IL-18, in the combination treatment group. Also, higher levels of IL-18 in serum and tumor are detected with IMSA101 treatment. Consistent with this, the use of IL-18 receptor negative CART impair anti-tumor responses in mice receiving combination treatment. In summary, we find that IMSA101 enhances CART function which is facilitated through STING agonist-induced IL-18 secretion. It has been previously suggested that STING agonists can improve response to CAR-T therapy. Here the authors report the characterization of the STING agonist IMSA101, showing that STING-induced IL18 secretion enhances CAR-T activity in preclinical cancer models. [ABSTRACT FROM AUTHOR]

Purpose: Liver cancer incidence among American Indians/Alaska Natives has risen over the past 20 years. Peripheral blood DNA methylation may be associated with liver cancer and could be used as a biomarker for cancer risk. We evaluated the association of blood DNA methylation with risk of liver cancer. Methods: We conducted a prospective cohort study in 2324 American Indians, between age 45 and 75 years, from Arizona, Oklahoma, North Dakota and South Dakota who participated in the Strong Heart Study between 1989 and 1991. Liver cancer deaths (n = 21) were ascertained using death certificates obtained through 2017. The mean follow-up duration (SD) for non-cases was 25.1 (5.6) years and for cases, 11.0 (8.8) years. DNA methylation was assessed from blood samples collected at baseline using MethylationEPIC BeadChip 850 K arrays. We used Cox regression models adjusted for age, sex, center, body mass index, low-density lipoprotein cholesterol, smoking, alcohol consumption, and immune cell proportions to examine the associations. Results: We identified 9 CpG sites associated with liver cancer. cg16057201 annotated to MRFAP1) was hypermethylated among cases vs. non-cases (hazard ratio (HR) for one standard deviation increase in methylation was 1.25 (95% CI 1.14, 1.37). The other eight CpGs were hypomethylated and the corresponding HRs (95% CI) ranged from 0.58 (0.44, 0.75) for cg04967787 (annotated to PPRC1) to 0.77 (0.67, 0.88) for cg08550308. We also assessed 7 differentially methylated CpG sites associated with liver cancer in previous studies. The adjusted HR for cg15079934 (annotated to LPS1) was 1.93 (95% CI 1.10, 3.39). Conclusions: Blood DNA methylation may be associated with liver cancer mortality and may be altered during the development of liver cancer. [ABSTRACT FROM AUTHOR]

Inflammaging refers to the low-grade systemic inflammation that occurs with aging present in chronic non-communicable diseases. MicroRNAs (miRNAs) are potential biomarkers for these diseases in older adults. This study aimed to assess the expression of 21 circulating miRNAs and their associations with inflammatory biomarkers in older adults. This cross-sectional study was performed with 200 individuals participating in ISA-Nutrition. The systemic low-grade inflammation score (SIS) was calculated from the plasma concentration of 10 inflammatory biomarkers. Circulating miRNA expression was assessed using the Fluidigm method. Wilcoxon-Mann–Whitney test was employed to determine differences in SIS among groups distributed according to sex and presence of MetS. Spearman's correlation was used to estimate correlations among SIS, leptin levels, miRNA expression, and variables of interest. Analyses were performed using software R version 4.2.3, with a significance level of 0.05. The final sample consisted of 193 individuals with a mean age of 69.1 (SE = 0.5) years, being 64.7% individuals with metabolic syndrome (MetS). Positive correlations were observed between leptin concentration and metabolic risk factors, and leptin concentration was higher in individuals with MetS compared to those without MetS. The expression of 15 circulating miRNAs was negatively correlated with leptin concentration. GLMs showed negative associations between miRNAs (miR-15a, miR-16, miR-223, miR-363, miR-532), leptin, and/or SIS values; and only miR-21 showed positive association with SIS values. The results suggest the presence of peripheral leptin resistance associated with low-grade inflammation and plasma expression of miRNAs in older adults. These findings suggest the potential role of miRNAs as biomarkers for cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Brain radiation has been medically used to alter the metabolism of cancerous cells and induce their elimination. Rarely, though, brain radiation has been used to interfere with the pathomechanisms of non-cancerous brain disorders, especially neurodegenerative disorders. Data from low-dose radiation (LDR) on swine brains demonstrated reduced levels of phosphorylated-tau (CP13) and amyloid precursor protein (APP) in radiated (RAD) versus sham (SH) animals. Phosphorylated-tau and APP are involved in Alzheimer's disease (AD) pathogenesis. We determined if the expression levels of hyperphosphorylated-tau, 3R-tau, 4R-tau, synaptic, intraneuronal damage, and DNA damage/oncogenic activation markers were altered in RAD versus SH swine brains. Quantitative analyses demonstrated reduced levels of AT8 and 3R-tau in hippocampus (H) and striatum (Str), increased levels of synaptophysin and PSD-95 in frontal cortex (FCtx), and reduced levels of NF-L in cerebellum (CRB) of RAD versus SH swine. DNA damage and oncogene activation markers levels did not differ between RAD and SH animals, except for histone-H3 (increased in FCtx and CRB, decreased in Str), and p53 (reduced in FCtx, Str, H and CRB). These findings confirm the region-based effects of sLDR on proteins normally expressed in larger mammalian brains and support the potential applicability of LDR to beneficially interfere against neurodegenerative mechanisms. [ABSTRACT FROM AUTHOR]

A tsunami is one of nature's most hazardous and unpredictable natural disasters. Modeling is a useful technique for anticipating how complicated systems will behave. It is used to predict the characteristics of devastating waves when a tsunami strikes. The need for modeling study is to determine the tsunami's travel time to the coast, as well as its amplitude and inundation distance, to safeguard society from catastrophic destruction with minimal computing time and this paper provides the mathematical formulation involved in the modeling of tsunami wave propagation to attain the above-mentioned parameters. The modeling of a dynamic system of tsunami wave propagation is investigated and presented in detail for various generation phenomena which are explained with case studies, parameters, and distinct modeling methodologies. A brief review of the literature about tsunami wave propagation is given to explain the properties of tsunami changes with changes in the depth of the ocean (frequency dispersion) and the environmental impacts due to tsunamis are addressed here. [ABSTRACT FROM AUTHOR]

New eco-friendly approaches were proposed for the synthesis of cis-cyclopentene-annulated heterocyclic compounds containing a tetrahydroquinoline moiety. For the first time we implemented a one-pot three-component cyclocondensation of aromatic amines (aniline, 5-aminoquinoline, o-phenylenediamine), aldehydes, and cyclopentadiene (CPD) in water and in the ionic liquid. The effect of synthesized substituted 3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolines on the reproduction of house fly imago and on the initial stage of offspring ontogeny was evaluated in comparison with the effect of natural insect hormone using biological screening (Musca domestica). The most probable factors of stabilization of prepared compounds 7–10 in the active site of the Heliothis virescens receptor were identified using AutoDock 4.2, AutoDock Vina, and GOLD Suite molecular docking software. According to the results of three scoring functions, 4-(3-chlorophenyl)-8-fluoro-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline forms the most stable complex with the chosen receptor. The results of bioassays and molecular docking indicate that these compounds may be considered as potential ecdysone agonists. [ABSTRACT FROM AUTHOR]

To advance meaningful guidelines in the design of electrocatalytically active catalysts, a knowledge of the nature of active sites is the starting point. However, multiple factors such as material composition, site coordination, electrolyte effects, the support material, surface strain, and others influence catalytic behavior. Therefore, the identification of active sites can be complex. A substantial contributor can be in-situ experiments, which are able to identify active centers in a specific system while the reaction takes place. An example of such a technique is electrochemical scanning tunneling microscopy (EC-STM), which relates locally confined noise features to local electrocatalytic activity. In this work, we spotlight recent achievements of this technique with respect to palladium (Pd) surfaces for the hydrogen reduction reaction, where strain due to hydride formation comes into play in addition to surface coordination. Secondly, we demonstrate the high resolution of the technique on graphite-based surfaces. Here, edge sites are particularly active. Thus, with the EC-STM technique, we take strain effects (like on Pd) or effects of coordination (like on carbon) into account. Therefore, we can determine active sites with great accuracy under reaction conditions. [ABSTRACT FROM AUTHOR]

The value of a company's ethical reputation has become a focal point for management researchers. We seek to join this conversation and extend the research centered on a firm's ethical reputation. We accomplish this by shifting our focus away from its impact on external stakeholders to its impact on internal stakeholders. To this end, we rely on signaling theory to explain why a firm's ethical reputation matters to its employees in an effort to bridge the macro–micro research gap. Across two studies, we propose and demonstrate that a firm's ethical reputation impacts employee subjective career success in form of career opportunities and work–life balance. Given our signaling theory framework, we also identify and explain when two industry-level characteristics operate as boundary conditions that distort a firm's ethical reputation signaling properties. Specifically, the results demonstrate that a firm's ethical reputation is positively related to employees' perceptions of career opportunities and work–life balance. The results of our studies also demonstrate that the relatively high levels of industry competition and industry regulation weaken the positive impact of a firm's ethical reputation on career opportunities and work–life balance. Theoretical and practical implications are discussed. [ABSTRACT FROM AUTHOR]

This study evaluated two types of barriers that the authors deemed important to resolve during the early stage of cancer clinical trial exploration by Latinx community members. One was the accessibility of information provided on cancer centers' websites. The other was the telephone responders' clinical trial knowledge and their conveyance of a warm welcome to Latinx callers inquiring about the centers' clinical trials. Simulated clinical trial inquiry calls were made to 17 National Cancer Institute-designated centers in this study. The centers were located in cities where the Latinx community accounted for at least 25% of the population, thereby justifying center-wide efforts to encourage the Latinx community to explore clinical trial participation. A rubric was developed to determine and quantify a Total Score that was partially composed of the accessibility of clinical trial information displayed on each cancer center's website. A research assistant gathered information by posing as a person calling the cancer center to inquire about clinical trials on behalf of a family member with limited English proficiency and evaluated their response using a "mystery shopper" method of data collection. The warmth and sense of welcome conveyed by the telephone responder was also quantified and included in the rubric's Total Score. A perfect Total Score reflected the likely existence of an environment that would encourage Latinx community members to continue exploring clinical trials, i.e., removed or diminished possible barriers. Welcoming characteristics, such as those elements included in the scoring rubric, can be monitored regularly to assure that centers are consistently conveying an optimal sense of welcome to the Latinx community, while also providing accessible clinical trial information. Among the 17 cancer centers, no correlation was found between the size of the Latinx population served and each center's Total Score. [ABSTRACT FROM AUTHOR]

In many species, including mice, female animals show markedly different pup-directed behaviours based on their reproductive state1,2. Naive wild female mice often kill pups, while lactating female mice are dedicated to pup caring3,4. The neural mechanisms that mediate infanticide and its switch to maternal behaviours during motherhood remain unclear. Here, on the basis of the hypothesis that maternal and infanticidal behaviours are supported by distinct and competing neural circuits5,6, we use the medial preoptic area (MPOA), a key site for maternal behaviours7–11, as a starting point and identify three MPOA-connected brain regions that drive differential negative pup-directed behaviours. Functional manipulation and in vivo recording reveal that oestrogen receptor α (ESR1)-expressing cells in the principal nucleus of the bed nucleus of stria terminalis (BNSTprESR1) are necessary, sufficient and naturally activated during infanticide in female mice. MPOAESR1 and BNSTprESR1 neurons form reciprocal inhibition to control the balance between positive and negative infant-directed behaviours. During motherhood, MPOAESR1 and BNSTprESR1 cells change their excitability in opposite directions, supporting a marked switch of female behaviours towards the young.ESR1-expressing cells in the principal nucleus of the bed nucleus of stria terminalis are necessary, sufficient and naturally activated during infanticide, and they form reciprocal inhibition with the maternal cells to control young-directed behaviours in female mice. [ABSTRACT FROM AUTHOR]

Homophily, the tendency for individuals to preferentially interact with others similar to themselves is typically documented via self-report and, for children, adult report. Few studies have investigated homophily directly using objective measures of social movement. We quantified homophily in children with developmental disabilities (DD) and typical development (TD) using objective measures of position/orientation in preschool inclusion classrooms, designed to promote interaction between these groups of children. Objective measurements were collected using ultra-wideband radio-frequency tracking to determine social approach and social contact, measures of social movement and interaction. Observations of 77 preschoolers (47 with DD, and 30 TD) were conducted in eight inclusion classrooms on a total of 26 days. We compared DD and TD groups with respect to how children approached and shared time in social contact with peers using mixed-effects models. Children in concordant dyads (DD-DD and TD-TD) both moved toward each other at higher velocities and spent greater time in social contact than discordant dyads (DD-TD), evidencing homophily. DD-DD dyads spent less time in social contact than TD-TD dyads but were comparable to TD-TD dyads in their social approach velocities. Children's preference for similar peers appears to be a pervasive feature of their naturalistic interactions. [ABSTRACT FROM AUTHOR]

Purpose: To investigate how a healthy lifestyle index (HLI) is associated with breast cancer risk and survival in a population-based breast cancer study. Methods: The study included 1319 breast cancer cases and 1310 controls from the population-based Long Island Breast Cancer Study Project and its follow-up study where vital status was ascertained using the National Death Index (521 deaths, 210 from breast cancer; median follow-up 214.5 months). HLI scores were generated from body mass index, physical activity, intake of plant and animal foods, alcohol consumption, breastfeeding, and smoking, with higher values corresponding to healthier behaviors obtained from baseline questionnaire. Multivariable logistic and Cox regression models were used to estimate breast cancer odds ratios (ORs) and mortality hazards ratios (HRs), respectively. Results: Compared to women in the low HLI tertile, a significant reduction in risk of breast cancer was observed for women in the intermediate (OR = 0.78, 95% CI 0.64–0.93) and high (OR = 0.73, 95% CI 0.60–0.88) tertiles; a one-point increase in HLI score was associated with a 14% reduction in breast cancer risk (OR = 0.86, 95% CI 0.80–0.93). For survival, a significant reduction in all-cause mortality was also observed in women in the intermediate (HR = 0.68, 95% CI 0.56–0.84) and high (HR = 0.72, 95% CI 0.58–0.88) HLI tertiles with a 17% reduction in all-cause mortality (HR = 0.83, 95% CI 0.76–0.91) for one-point increase in HLI score. These inverse associations were more prominent among postmenopausal women. Conclusion: A healthy lifestyle is beneficial not only in reducing breast cancer risk but also in improving overall survival after breast cancer diagnosis, especially among postmenopausal women. [ABSTRACT FROM AUTHOR]

Very effective genetic control of some root-knot nematode (RKN) species (Meloidogyne spp.) is obtained by the employment of the tomato (Solanum lycopersicum L.) dominant Mi-1.2 gene. However, the phenotypic expression conferred by the Mi-1.2 gene may be impaired by high soil temperatures (above 28 °C) and by previously reported virulent RKN species and/or populations. Here, a putative Mi-1.2 gene-virulent RKN population was found inducing severe gall symptoms in roots of the tomato rootstock 'Guardião' (a homozygous Mi-1.2 hybrid of S. lycopersicum × S. peruvianum) under protected crop conditions in Southern Brazil. Females were extracted from severely infected roots displaying large galls and used for biochemical characterization of α-esterase (EST) and confirmed by SCAR markers. Additional pathogenicity assays were carried out in order to confirm the virulence (= resistance-breaking) feature of this RKN population by employing other or the same Mi-1.2 gene-carrying rootstocks. This virulent RKN population was identified as M. javanica (EST J3 and J2). The pathogenicity tests confirmed that this M. javanica population can overcome the Mi-1.2 resistance gene, and it is able to induce severe root-gall symptoms and to reproduce in two dominant resistant rootstocks ('Muralha' and 'Guardião') under greenhouse conditions. In addition, an initial inoculum of 2000–7000 eggs was considered ideal for future studies with the virulent M. javanica population. It is the first report of a Mi-1.2 gene-virulent M. javanica population in Brazil, which may represent a potential threat to the tomato agribusiness sector. [ABSTRACT FROM AUTHOR]

Monterey formation crude oil spilled from an onshore pipeline and entered the surf zone near Refugio State Beach, Santa Barbara County, CA, USA on 19 May 2015. Exposure to nearshore fish was evaluated by measuring biliary polycyclic aromatic hydrocarbon (PAH) metabolite concentrations in surfperch (Embiotocidae), collected near the release point, at a lesser oiled area, Gaviota State Beach, and near the Coal Oil Point oil seep, Campus Point, at both four days and approximately one year after the oil spill. Three to four weeks after the spill, fish, invertebrates, and kelp were collected near the same three sites for PAH analysis of edible tissues to support the fishery closure assessment. Additionally, thirteen days after the spill, vegetation, and invertebrate tissue samples from the seafloor near Refugio State Beach were analyzed for PAHs. In surfperch bile, mean naphthalene, phenanthrene and benzo(a)pyrene metabolite equivalents were significantly higher at Refugio State Beach, compared to Gaviota State Beach or Campus Point in 2015. One year later, there was no significant difference between the three sites. Spatial and depth zone patterns of PAH tissue concentrations from composited invertebrate, vegetation and fish showed highest concentrations were measured in invertebrates collected near Refugio State Beach. Overall, results show elevated PAH levels in nearshore organisms and provide a useful reference for potential PAH exposures in fish and subtidal invertebrates following a large nearshore oil spill. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) associated with atmospheric particles represent a significant risk to human health. This issue is even more relevant in environments where biomass combustion processes are considered as the major potential emission sources, such as the rural ecosystem. This study aimed to assess the levels of PM10-bound PAHs in several rural locations, their distribution along a year and how weather variables could influence them. Also, we focused on the emission sources and the comparison of the PAH mixtures to assess similitude among the sampling points. PM10-bound PAHs levels were monitored at three rural locations (north, center, and south) of Spain between April 2017 and February 2018. The study revealed that there were substantial differences regarding the levels of ΣPAHs, being higher in the central zone (IS; 65.4 mg/m3), then in the south (VA; 35.8 ng/m3) and finally in the north (NA; 20.9 ng/m3). IS and VA showed a similar distribution of emission sources, and temperature and wind speed seemed to influence negatively over the levels of PAHs likely. At both locations, PAH levels ran parallel throughout the year, with maximum levels during cold seasons and a greater presence of high molecular weight PAHs; however, the levels of PAHs and the most representative PAHs differed. On the other hand, NA was characterized for having another distribution of emission sources, which determined other representative PAHs, higher levels during spring, and a similar presence of high/medium/low molecular weight. Finally, the levels of ambient air PAHs represented an acceptable risk to people. [ABSTRACT FROM AUTHOR]

Synthetic receptor signalling has the potential to endow adoptively transferred T cells with new functions that overcome major barriers in the treatment of solid tumours, including the need for conditioning chemotherapy1,2. Here we designed chimeric receptors that have an orthogonal IL-2 receptor extracellular domain (ECD) fused with the intracellular domain (ICD) of receptors for common γ-chain (γc) cytokines IL-4, IL-7, IL-9 and IL-21 such that the orthogonal IL-2 cytokine elicits the corresponding γc cytokine signal. Of these, T cells that signal through the chimeric orthogonal IL-2Rβ-ECD–IL-9R-ICD (o9R) are distinguished by the concomitant activation of STAT1, STAT3 and STAT5 and assume characteristics of stem cell memory and effector T cells. Compared to o2R T cells, o9R T cells have superior anti-tumour efficacy in two recalcitrant syngeneic mouse solid tumour models of melanoma and pancreatic cancer and are effective even in the absence of conditioning lymphodepletion. Therefore, by repurposing IL-9R signalling using a chimeric orthogonal cytokine receptor, T cells gain new functions, and this results in improved anti-tumour activity for hard-to-treat solid tumours.Synthetic chimeric orthogonal IL-2 receptors that incorporate the intracellular domain of receptors for other γ-chain cytokines such as IL-9 can reroute orthogonal signalling and alter the phenotype of T cells to improve anti-tumour responses. [ABSTRACT FROM AUTHOR]

DNA repair phenotype can be measured in blood and may be a potential biomarker of cancer risk. We conducted a systematic review and meta-analysis of epidemiological studies of DNA repair phenotype and cancer through March 2021. We used random-effects models to calculate pooled odds ratios (ORs) of cancer risk for those with the lowest DNA repair capacity compared with those with the highest capacity. We included 55 case–control studies that evaluated 12 different cancers using 10 different DNA repair assays. The pooled OR of cancer risk (all cancer types combined) was 2.92 (95% Confidence Interval (CI) 2.49, 3.43) for the lowest DNA repair. Lower DNA repair was associated with all studied cancer types, and pooled ORs (95% CI) ranged from 2.02 (1.43, 2.85) for skin cancer to 7.60 (3.26, 17.72) for liver cancer. All assays, except the homologous recombination repair assay, showed statistically significant associations with cancer. The effect size ranged from 1.90 (1.00, 3.60) for the etoposide-induced double-strand break assay to 5.06 (3.67, 6.99) for the γ-H2AX assay. The consistency and strength of the associations support the use of these phenotypic biomarkers; however large-scale prospective studies will be important for understanding their use related to age and screening initiation. [ABSTRACT FROM AUTHOR]

In the U.S., Hepatocellular carcinoma (HCC) incidence rates have increased. We aimed to determine whether environmental exposure plays a role in the high incidence of HCC observed in New York City. We conducted a hospital-based case only study to examine the prevalence of aflatoxin B1 (AFB1)- and polycyclic aromatic hydrocarbon (PAH)-albumin adducts and the distribution of adducts by different characteristics of HCC patients. Blood samples were collected from 155 HCC patients for biomarker analyses. We observed that about 46% and 49% of cases had detectable AFB1- and PAH-albumin adducts, respectively. There were significant differences between AFB1-albumin adducts and selected factors such as HCV infection status (p = 0.04), diabetes (p = 0.03) and Barcelona Clinic Liver Cancer stage (p = 0.02). Cases with detectable PAH-albumin adducts had a smoking history compared with those with nondetectable levels (p = 0.04). The level of AFB1-albumin adducts was positively correlated with plasma bilirubin (rs = 0.32, p < 0.0001) and adiponectin concentrations (rs = 0.28, p = 0.0005). The level of aflatoxin B1-albumin adducts was negatively associated with blood albumin concentration (rs = − 0.28, p = 0.0009) and plasma DNA LINE-1 methylation (rs = − 0.16, p = 0.04). Our study provides additional evidence that environmental exposures including to aflatoxin might drive the high incidence of HCC observed in the New York City. [ABSTRACT FROM AUTHOR]

The vascular system is sensitive to radiation injury, and vascular damage is believed to play a key role in delayed tissue injury such as pulmonary fibrosis. However, the response of endothelial cells to radiation is not completely understood. We examined the response of primary human lung microvascular endothelial cells (HLMVEC) to 10 Gy (1.15 Gy/min) X-irradiation. HLMVEC underwent senescence (80–85%) with no significant necrosis or apoptosis. Targeted RT-qPCR showed increased expression of genes CDKN1A and MDM2 (10–120 min). Western blotting showed upregulation of p2/waf1, MDM2, ATM, and Akt phosphorylation (15 min–72 h). Low levels of apoptosis at 24–72 h were identified using nuclear morphology. To identify novel pathway regulation, RNA-seq was performed on mRNA using time points from 2 to 24 h post-irradiation. Gene ontology and pathway analysis revealed increased cell cycle inhibition, DNA damage response, pro- and anti- apoptosis, and pro-senescence gene expression. Based on published literature on inflammation and endothelial-to-mesenchymal transition (EndMT) pathway genes, we identified increased expression of pro-inflammatory genes and EndMT-associated genes by 24 h. Together our data reveal a time course of integrated gene expression and protein activation leading from early DNA damage response and cell cycle arrest to senescence, pro-inflammatory gene expression, and endothelial-to-mesenchymal transition. [ABSTRACT FROM AUTHOR]

Main conclusion: Host-derived suppression of nematode essential genes decreases reproduction of Meloidogyne incognita in cotton. Root-knot nematodes (RKN) represent one of the most damaging plant-parasitic nematode genera worldwide. RNAi-mediated suppression of essential nematode genes provides a novel biotechnological strategy for the development of sustainable pest-control methods. Here, we used a Host Induced Gene Silencing (HIGS) approach by stacking dsRNA sequences into a T-DNA construct to target three essential RKN genes: cysteine protease (Mi-cpl), isocitrate lyase (Mi-icl), and splicing factor (Mi-sf), called dsMinc1, driven by the pUceS8.3 constitutive soybean promoter. Transgenic dsMinc1-T4 plants infected with Meloidogyne incognita showed a significant reduction in gall formation (57–64%) and egg masses production (58–67%), as well as in the estimated reproduction factor (60–78%), compared with the susceptible non-transgenic cultivar. Galls of the RNAi lines are smaller than the wild-type (WT) plants, whose root systems exhibited multiple well-developed root swellings. Transcript levels of the three RKN-targeted genes decreased 13- to 40-fold in nematodes from transgenic cotton galls, compared with those from control WT galls. Finally, the development of non-feeding males in transgenic plants was 2–6 times higher than in WT plants, indicating a stressful environment for nematode development after RKN gene silencing. Data strongly support that HIGS of essential RKN genes is an effective strategy to improve cotton plant tolerance. This study presents the first application of dsRNA sequences to target multiple genes to promote M. incognita tolerance in cotton without phenotypic penalty in transgenic plants. [ABSTRACT FROM AUTHOR]

Odor perception can both evoke emotional states and be shaped by emotional or hedonic states. The amygdala complex plays an important role in recognition of, and response to, hedonically valenced stimuli, and has strong, reciprocal connectivity with the primary olfactory (piriform) cortex. Here, we used differential odor-threat conditioning in rats to test the role of basolateral amygdala (BLA) input to the piriform cortex in acquisition and expression of learned olfactory threat responses. Using local field potential recordings, we demonstrated that functional connectivity (high gamma band coherence) between the BLA and posterior piriform cortex (pPCX) is enhanced after differential threat conditioning. Optogenetic suppression of activity within the BLA prevents learned threat acquisition, as do lesions of the pPCX prior to threat conditioning (without inducing anosmia), suggesting that both regions are critical for acquisition of learned odor threat responses. However, optogenetic BLA suppression during testing did not impair threat response to the CS+ , but did induce generalization to the CS−. A similar loss of stimulus control and threat generalization was induced by selective optogenetic suppression of BLA input to pPCX. These results suggest an important role for amygdala-sensory cortical connectivity in shaping responses to threatening stimuli. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the prognostic ability of immunohistochemistry (IHC)-based vs. PAM50-based subtypes for breast cancer mortality in a population-based study of breast cancer. Methods: We included a total of 463 breast cancer cases from the population-based Long Island Breast Cancer Study Project (LIBCSP). IHC-based markers were abstracted from the medical records, while the PAM50-based intrinsic subtypes were assessed from tumor tissues using NanoString nCounter® Analysis System. Cox proportional hazards models were used to estimate hazards ratios (HRs) for breast cancer-specific mortality associated with subtypes. Results: For IHC-based hormone receptor-positive (HR+) tumors (n = 361), 68.7% were classified as luminal subtypes by PAM50; for HR− tumors (n = 102), 95.1% were classified as non-luminal subtypes. Compared to HR+/HER2− subtype, HR− patients had significantly higher breast cancer mortality (HR−/HER2+: HR = 2.84, 95% CI = 1.58–5.11; triple-negative breast cancer: HR = 2.42, 95% CI = 1.44–4.06). Compared to luminal A, a higher mortality rate was observed for all other PAM50-based subtypes: luminal B (HR = 4.03, 95% CI = 1.97–8.22), HER2-enriched (HR = 6.82, 95% CI = 3.29–14.14) and basal-like (HR = 4.71, 95% CI = 2.24–9.93). Additional subtyping of HR+ patients by PAM50 provided future risk stratification where luminal B patients in this group had significant higher mortality than luminal A patients (HR = 3.93, 95% CI = 1.92–8.03). Similar results were also observed among 291 HR+/HER2− patients, but not among the HR− patients. Conclusions: Our study suggests that for HR+ patients, especially HR+/HER2− patients, additional PAM50-based subtyping would provide better prognostic stratification and improve disease management. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) incidence is increasing around the globe, including in Taiwan, though the cause of the increasing incidence is less clear. We followed up 11,296 Taiwanese females who did not have BC at baseline, and ascertained new invasive BC (N = 351) through data linkage to the National Cancer Registry from 1991 to 2018 to examine whether reproductive, lifestyle and environmental risk factors including polycyclic aromatic hydrocarbons (PAH) were associated with BC risk. We conducted a nested case–control study using baseline blood available from a total of 305 women with BC and 598 women without BC matched on time in cohort. We examined the association of PAH-albumin adducts and BC risk using conditional logistic regression models. Age at menarche (HR 0.6 (95% CI 0.5–0.9) for ≥ 15 vs. < 13 years) and multiparity were associated with BC risk (HR 2.0 (95% CI 1.4–2.8), 2.8 (1.9–4.2), and 2.4 (1.0–5.0) for 3–4, 1–2 and 0 live birth, compared with women ≥ 5 births). PAH-albumin adducts were not associated with BC risk. Given the increasing BC incidence in Taiwan, there is a need to identify environmental factors that are important to this population. [ABSTRACT FROM AUTHOR]

Astronium graveolens is a native tree species from Atlantic Forest considered sensitive to O3. This study aimed to determine which environmental factors, including air quality and meteorological conditions, have the most significant influence on gas exchange and the appearance of visible foliar symptoms in this species. Saplings were potted and exposed in a standardized manner in an open area in the southeastern city of São Paulo, Brazil. Gas exchange was measured weekly in the morning (9 am to 10 am), midday (11 am to 12 pm), and afternoon (2 pm to 3 pm) during the spring and summer seasons (n = 10). Data on O3 concentration and meteorological conditions were obtained on-site. Principal component analysis identified that the morning hours provide the most favorable meteorological conditions for gas exchange. High temperature and VPD reduced gas exchange in the midday and afternoon. Although the AOT40 was high, there were no visible foliar symptoms, which was an unexpected result. We propose that the meteorological conditions, mainly the VPD and temperature, caused stomatal closure, and consequently prevented the absorption of O3; therefore, there was no association between O3 and reduction of gas exchange, nor manifestation of foliar visible symptoms. We consider that more studies are necessary for the proper use of A. graveolens as an O3 bioindicator species. [ABSTRACT FROM AUTHOR]

The development of anuran larvae from hatchling through metamorphosis is a particularly sensitive life stage that often is studied to assess adverse effects of water pollution, such as metal contamination. As an integral part of the food chain, high metal exposure and accumulation in developing anuran larvae may not only affect their survival but also pose a threat to secondary consumers. The presented work examines metal accumulation in wood frog tadpoles (Lithobates sylvaticus) before and after reaching metamorphic climax at emergence of the forelimbs. Metal levels were determined in whole tadpoles pre- and post-metamorphic climax in tadpole tissue excluding the stomach and intestines, as well as in water, via inductively coupled plasma-mass spectrometry. Wood frog tadpoles concentrated metals in their gut coil, with a rapid decline coincident with metamorphic climax. Tadpoles raised in a diluted bitumen-contaminated environment had higher levels of vanadium, molybdenum and cadmium, but not at levels expected to negatively impact development. In conclusion, metal accumulation in wood frog tadpoles varies greatly depending on developmental stage surrounding metamorphic climax. Metabolic changes and intestinal remodelling must be considered when studying pollutants in developing anuran larvae. [ABSTRACT FROM AUTHOR]

Granulovacuolar degeneration (GVD) is a common feature in Alzheimer's disease (AD). The occurrence of GVD is closely associated with that of neurofibrillary tangles (NFTs) and GVD is even considered to be a pre-NFT stage in the disease process of AD. Currently, the composition of GVD bodies, the mechanisms associated with GVD and how GVD exactly relates to NFTs is not well understood. By combining immunohistochemistry (IHC) and laser microdissection (LMD) we isolated neurons with GVD and those bearing tangles separately from human post-mortem AD hippocampus (n = 12) using their typical markers casein kinase (CK)1δ and phosphorylated tau (AT8). Control neurons were isolated from cognitively healthy cases (n = 12). 3000 neurons per sample were used for proteome analysis by label free LC–MS/MS. In total 2596 proteins were quantified across samples and a significant change in abundance of 115 proteins in GVD and 197 in tangle bearing neurons was observed compared to control neurons. With IHC the presence of PPIA, TOMM34, HSP70, CHMP1A, TPPP and VXN was confirmed in GVD containing neurons. We found multiple proteins localizing specifically to the GVD bodies, with VXN and TOMM34 being the most prominent new protein markers for GVD bodies. In general, protein groups related to protein folding, proteasomal function, the endolysosomal pathway, microtubule and cytoskeletal related function, RNA processing and glycolysis were found to be changed in GVD neurons. In addition to these protein groups, tangle bearing neurons show a decrease in ribosomal proteins, as well as in various proteins related to protein folding. This study, for the first time, provides a comprehensive human based quantitative assessment of protein abundances in GVD and tangle bearing neurons. In line with previous functional data showing that tau pathology induces GVD, our data support the model that GVD is part of a pre-NFT stage representing a phase in which proteostasis and cellular homeostasis is disrupted. Elucidating the molecular mechanisms and cellular processes affected in GVD and its relation to the presence of tau pathology is highly relevant for the identification of new drug targets for therapy. [ABSTRACT FROM AUTHOR]

Chronic arsenic exposure is associated with a number of systemic diseases, including cardiovascular disease. Selenium has been shown to promote arsenic excretion from the body. We investigated if a high-selenium lentil diet has an effect on blood pressure and plasma lipid levels in an arsenic-exposed population by conducting a 6-month randomized controlled dietary intervention trial with 405 participants. [ABSTRACT FROM AUTHOR]

The laser induced curing of acryloxy terminated ethyleneoxide dimethylsiloxane-ethyleneoxide ABA block copolymer (PDMS-AO) and (3-glycidoxypropyl)trimethoxysilane (GPTMS) was carried out with 2-hydroxy-2-methylpropiophenone as radical photoinitiator and p-(octyloxyphenyl)phenyliodonium hexafluoroantimonate as cationic photoinitiator, respectively. The cross-linking mechanisms for both mixtures were determined through monitoring of photocuring by SSNMR, FTIR and Raman spectroscopies. The obtained silicone rubbers were tested by swelling measurements and thermogravimetric analysis. In comparison with PDMS-AO, cross-linked GPTMS had slightly more cross-linking density (by approximately 20% more). The cross-linked GPTMS was more thermally stable in air than cured PDMS-AO (by c.a. 190° C) due to both mechanisms: epoxy polymerization and Si–O–Si formation. The possibility of laser printing with defined framework for PDMS-AO was successfully demonstrated that allows obtaining laser printed polymer objects. [ABSTRACT FROM AUTHOR]

Brain radiation can occur from treatment of brain tumors or accidental exposures. Brain radiation has been rarely considered, though, as a possible tool to alter protein levels involved in neurodegenerative disorders. We analyzed possible molecular and neuropathology changes of phosphorylated-Tau (pTau), all-Tau forms, β-tubulin, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ionized calcium binding adaptor molecule 1 (IBA-1), myelin basic protein (MBP), and GAP43 in Frontal Cortex (FC), Hippocampus (H) and Cerebellum (CRB) of swine brains following total-body low-dose radiation (1.79 Gy). Our data show that radiated-animals had lower levels of pTau in FC and H, APP in H and CRB, GAP43 in CRB, and higher level of GFAP in H versus sham-animals. These molecular changes were not accompanied by obvious neurohistological changes, except for astrogliosis in the H. These findings are novel, and might open new perspectives on brain radiation as a potential tool to interfere with the accumulation of specific proteins linked to the pathogenesis of various neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

A root-knot nematode (RKN) parasitizing rice (Oryza sativa L.) and causing damage in Santa Catarina (SC), Rio Grande do Sul (RS) and Paraná (PR) states (Brazil) was identified as Meloidogyne ottersoni (Thorne 1969) Franklin 1971. The species is redescribed from the Brazilian population from Meleiro (SC) and compared with the description of M. ottersoni from Wind Lake (Wisconsin, USA) with additional morphological, biochemical and molecular characterization. The female and male bear smaller stylets: 10-12 μm, 14-16 μm, respectively, when compared with M. graminicola: 12-14 μm, 16-18 μm, and M. oryzae: 14-16 μm, 18-20 μm. Meloidogyne ottersoni presents perineal patterns located on the contour of a slight protuberance. Striae are mostly continuous, never raised by transverse irregular striae, as frequently observed in M. graminicola and M. oryzae. Meloidogyne ottersoni belongs to the RKN group 11 described by Jepson (1987); the reproduction is by meiotic parthenogenesis and the somatic chromosome number is 18. The tail of second-stage juveniles is very long and thin, and tapers to a long, narrow, irregular hyaline terminus (M. ottersoni, 20.5 μm vs M. graminicola, 17.9 μm and M. oryzae, 22.0 μm, respectively). The ability of the Brazilian M. ottersoni population to parasitize canary grass, Phalaris arundinacea L. (type host), and barnyard grass, Echinocloa crus-galli, was confirmed. Biochemically, the esterase profile of M. ottersoni lacks any band (Est Ot0, Rm=0), which differentiates it from M. graminicola and M. oryzae (Est VS1, Rm=0.70 and Est O1, Rm=1.02, respectively). In Maximum Likelihood analysis of ITS, D2D3 and COXII-16S rRNA sequences, populations of M. ottersoni from different states of Brazil clustered together and were separated from other Meloidogyne spp., thus confirming that all four populations are very similar and conspecific. [ABSTRACT FROM AUTHOR]

Many bacteria and archaea produce the polydisperse fructose polymer levan from sucrose upon biofilm formation via extracellular levansucrases (EC 2.4.1.10). We have investigated levansucrase-release and -activities as well as molecular size of the levan formed by the acetic acid bacterium Gluconobacter albidus TMW 2.1191 at varying environmental pH conditions to obtain insight in the ecological role of its constitutively expressed levansucrase and the produced levan. A buffer system was established enabling the recovery of levansucrase-containing supernatants from preincubated cell suspensions at pH 4.3–pH 5.7. The enzyme solutions were used to produce levans at different pH values and sucrose concentrations. Finally, the amounts and size distributions of the produced levans as well as the corresponding levansucrase activities were determined and correlated with each other. The data revealed that the levansucrase was released into the environment independently of its substrate sucrose, and that more levansucrase was released at pH ≥ 5.0. The glucose release and formation of high molecular weight levans (> 3.5 kDa) from 0.1 M initial sucrose was comparable between pH ~ 4.3–5.7 using equal amounts of released levansucrase. Hence, this type of levansucrase appears to be structurally adapted to changes in the extracellular pH and to exhibit a similar total activity over a wide acidic pH range, while it produced higher amounts of larger levan molecules at higher production pH and sucrose concentrations. These findings indicate the physiological adaptation of G. albidus TMW 2.1191 to efficient colonisation of sucrose-rich habitats via released levansucrases despite changing extracellular pH conditions in course of acid formation. [ABSTRACT FROM AUTHOR]

CaCu3Ti4O12 (CCTO) is a complex oxide with a perovskite structure that is widely studied due to its dielectric and non-ohmic properties. The formation and composition of grains and grain boundaries are very important factors to improve these electrical properties. In this work, CCTO-based ceramics were processed by solid-state reaction at different calcination temperatures (700 °C to 1000 °C, for 4 h) and sintering at 1100 °C for 6 h aiming optimization in capacitor–varistor properties. The changes in crystal phase composition observed via XRD and chemical contrasts visualized by SEM/EDS point out that the disappearance of the secondary CuO phase of calcined powders is linked to complete Cu ion incorporation to the crystal structure of CCTO. This phenomenon culminated in sinterization via liquid phase formation, with abnormal grain growth for samples calcined at temperatures higher than 900 °C. The calcination occurring at 800 °C for 4 h, to produce CCTO with a more homogeneous microstructure, with apparent porosity of 2.67%, α of 5.49, EB of 1505 V cm−1, ε′ (1 kHz) of 7506 and ΦB of 0.754 eV, was considered the best processing condition. [ABSTRACT FROM AUTHOR]

Phthalates are commonly included as ingredients in personal care products such as cosmetics, shampoos and perfumes. Diethyl phthalate (DEP) has been found to be anti-androgenic and linked with adverse reproductive effects on males, but effects on females are poorly understood. We designed an integrative and translational study to experimentally examine the effects of DEP exposure at a human-equivalent dose on the mammary transcriptome in rats and to subsequently examine the DEP gene signature in breast tissues (both pre-malignant and tumor) from a population study. In Sprague-Dawley rats treated orally with DEP from birth to adulthood, we identified a signature panel of 107 genes predominantly down-regulated by DEP exposure. Univariate analysis of this 107 DEP gene signature in pre-malignant breast tissues revealed that six genes (P4HA1, MPZL3, TMC4, PLEKHA6, CA8, AREG) were inversely associated with monoethyl phthalate (MEP; the urinary metabolite of DEP) concentration (p < 0.05) among postmenopausal women; all six genes loaded on to one of seven factors identified by factor analysis. Transcription factor enrichment analysis revealed that genes in this factor were enriched for androgen receptor binding sites. These six genes were also significantly down-regulated in pre-malignant adjacent tissues compared to the corresponding tumor tissues in pair-wise analyses (p < 0.05). Results from our translational study indicate that low level exposure to diethyl phthalate results in measurable genomic changes in breast tissue with implications in breast carcinogenesis. [ABSTRACT FROM AUTHOR]

Purpose: Glioblastoma (GBM) remains one of the most lethal primary brain tumors in children and adults. Targeting tumor metabolism has emerged as a promising-targeted therapeutic strategy for GBM and characteristically resistant GBM stem-like cells (GSCs). Methods: Gene expression data was obtained from the online patient-histology database, GlioVis. GSC mitochondria morphology was examined by TEM. Cell viability and effect on GSC self-renewal was determined via MTS assay and neurosphere assay, respectively. Proteins were evaluated by Western Blot. Results: Enzymes necessary for ketone catabolism (BDH1, OXCT1 and ACAT1) are significantly downregulated in adult and pediatric GBM. GSC mitochondrial ultrastructure suggested defects in oxidative phosphorylation. Treatment of both GBM and GSC cell lines resulted in dose-dependent decreases in viability in response to glycolytic inhibitor 2-deoxy-D-glucose (2-DG), and ketone body Acetoacetate (AA), but not β-hydroxybutyrate (βHB). AA induced apoptosis was confirmed by western blot analysis, indicating robust caspase activation and PARP cleavage. AA reduced neurosphere formation at concentrations as low as 1 mM. Combined treatment of low dose 2-DG (50 μM) with AA resulted in more cell death than either treatment alone. The effect was greater than additive at low concentrations of AA, reducing viability approximately 50% at 1 mM AA. AA was found to directly upregulate mitochondrial uncoupling protein 2 (UCP2), which may explain this potential drug synergism via multi-faceted inhibition of the glycolytic pathway. Conclusion: Targeting the metabolic pathway of GBM via glycolytic inhibition in conjunction with ketogenic diet or exogenous ketone body supplementation warrants further investigation as a promising adjunctive treatment to conventional therapy. [ABSTRACT FROM AUTHOR]

The roots of psychopathology frequently take shape during infancy in the context of parentinfant interactions and adversity. Yet, neurobiological mechanisms linking these processes during infancy remain elusive. Here, using responses to attachment figures among infants who experienced adversity as a benchmark, we assessed rat pup cortical local field potentials (LFPs) and behaviors exposed to adversity in response to maternal rough and nurturing handling by examining its impact on pup separation-reunion with the mother. We show that during adversity, pup cortical LFP dynamic range decreased during nurturing maternal behaviors, but was minimally impacted by rough handling. During reunion, adversityexperiencing pups showed aberrant interactions with mother and blunted cortical LFP. Blocking pup stress hormone during either adversity or reunion restored typical behavior, LFP power, and cross-frequency coupling. This translational approach suggests adversity-rearing produces a stress-induced aberrant neurobehavioral processing of the mother, which can be used as an early biomarker of later-life pathology. [ABSTRACT FROM AUTHOR]

Purpose of Review: Pediatric central nervous system demyelinating diseases include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and acute disseminated encephalomyelitis (ADEM). As diagnostic criteria become more inclusive, the risk of misdiagnosis of atypical demyelinating diseases of rheumatologic, infectious, and autoimmune etiology increases. Recent Findings: We review mimics of multiple sclerosis, neuromyelitis optica spectrum disorder, and acute disseminated encephalomyelitis, including rheumatologic diseases: systemic lupus erythematosus and neuro-Behçet disease; infectious diseases: human immunodeficiency virus, progressive multifocal leukoencephalopathy, and subacute sclerosis panencephalitis; and autoimmune diseases including X-linked Charcot-Marie-Tooth disease, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) and autoimmune glial fibrillary acidic protein (GFAP) encephalopathy. Summary: Atypical demyelinating disease may mimic classic neuroinflammatory diseases of the central nervous system. Imaging may meet criteria for a diagnosis of multiple sclerosis, or patients may present with optic neuritis and transverse myelitis consistent with neuromyelitis optica spectrum or myelin oligodendrocyte glycoprotein (MOG) antibody disorders. Through careful history-taking and review of atypical MRI findings, we may avoid misdiagnosis and mistreatment. [ABSTRACT FROM AUTHOR]

The Deaf community members of this community-campus partnership identified the lack of health information in American Sign Language (ASL) as a significant barrier to increasing the Deaf community's health knowledge. Studies have shown that the delivery of health messages in ASL increased Deaf study participants' cancer knowledge. Once health messages are available on the Internet, strategies are needed to attract viewers to the website and to make repeat visits in order to promote widespread knowledge gains. This feasibility study used the entertainment-education strategy of coupling cancer information with jokes in ASL to increase the appeal and impact of the health messages. ASL-delivered cancer control messages coupled with Deaf-friendly jokes were shown to 62 Deaf participants. Participants completed knowledge questionnaires before, immediately after, and 1 week after viewing the paired videos. Participants' health knowledge statistically significantly increased after viewing the paired videos and the gain was retained 1 week later. Participants also reported sharing the newly acquired information with others. Statistically significant results were demonstrated across nearly all measures, including a sustained increase in cancer-information-seeking behavior and intent to improve health habits. Most participants reported that they would be motivated to return to such a website and refer others to it, provided that it was regularly updated with new jokes. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the antibacterial activity, bacterial viability, cytotoxicity, and mechanical/physical properties of a novel methacrylate triclosan-derivative monomer (TM) incorporated in dental resin composite.Methods: TM was synthesized by esterification and, after characterization by FT-IR, was added to an experimental composite. Samples were divided into two groups according to TM presence, i.e., C1 (control) and C2 (C1 + 14.4% TM). Microbiological properties: Specimens (C1 and C2) were prepared and placed on bacterial suspensions of Streptococcus mutans. Antibacterial activity, MTT, and live/dead bacterial viability were used to test the resin composites. All assays were performed in triplicates. Mechanical properties: Specimens underwent compression (CS) and flexural strength (FS) tests conducted in an Instron universal testing machine at a crosshead speed of 0.5 mm/min. Physical properties: Specimens were assessed for Knoop hardness (KHN) and crosslink density (CD). Fourier transform infrared spectroscopy allowed the degree of conversion (DC) to be evaluated. Data were subjected to appropriate statistical tests according to data distribution and assay (p < 0.05).Results: Microbiological properties: C2 showed the lowest biofilm accumulation and the highest membrane-compromised bacteria in the biofilm. Mechanical/physical properties: For CS, FS, KHN, and DC, there was no significant difference between groups C1 and C2; however, significant difference was observed for the CD assay.Conclusions: The triclosan methacrylate reduces bacterial adhesion of S. mutans and decreased the formation of bacterial biofilm without affecting important polymer properties. The triclosan methacrylate incorporated in resin composite could greatly reduce the live bacterial adhesion of S. mutans and decrease the formation of bacterial biofilm without affecting important polymer properties.Clinical significance: The resin composites containing triclosan methacrylate could greatly reduce the bacterial adhesion and biofilm formation. That might prevent the secondary caries round the margins of the restorations. [ABSTRACT FROM AUTHOR]

Introduction: People with chronic obstructive pulmonary disease (COPD) present high prevalence of physical inactivity that leads to a negative effect on health-related quality of life (HRQoL). The present study investigated COPD phenotypes according to their levels of physical activity and sedentary behaviour, as well as body composition and skeletal muscle strength.Methods: This is an observational and cross-sectional study. Anthropometric data and COPD clinical control were collected and all participants underwent assessments of lung function, HRQoL, dyspnoea, levels of physical activity and sedentary behaviour, body composition and skeletal muscle strength. Participants were classified using hierarchical cluster analysis. Age, dyspnoea and obstruction (ADO) index was used to determine prognosis and calculated for each cluster.Results: One hundred and fifty-two participants were included. Three distinct phenotypes were identified. Participants in phenotype 1 were more physically active, less sedentary and had better body composition and lower ADO index (p < 0.0001 for all variables). Overall, participants in phenotypes 2 and 3 were less physically active, more sedentary having a higher ADO index. However, participants in phenotype 2 were older, whereas participants in phenotype 3 had worse HRQoL, clinical control and body composition. Lung function did not differ across the three phenotypes.Conclusions: Our results show that physical activity, sedentary behaviour and body composition should be considered to determine phenotypes in people with COPD and are involved in the prognosis of the disease. Less sedentary patients have better prognosis while age, body composition and clinical control seems to differentiate physically inactive patients. [ABSTRACT FROM AUTHOR]

Transcriptomics is developing into an invaluable tool in toxicology. The aim of this study was, using a transcriptomics approach, to identify genes that respond similar to many different chemicals (including drugs and industrial compounds) in both rat liver in vivo and in cultivated hepatocytes. For this purpose, we analyzed Affymetrix microarray expression data from 162 compounds that were previously tested in a concentration-dependent manner in rat livers in vivo and in rat hepatocytes cultivated in sandwich culture. These data were obtained from the Japanese Toxicogenomics Project (TGP) and North Rhine-Westphalian (NRW) data sets, which represent 138 and 29 compounds, respectively, and have only 5 compounds in common between them. The in vitro gene expression data from the NRW data set were generated in the present study, while TGP is publicly available. For each of the data sets, the overlap between up- or down-regulated genes in vitro and in vivo was identified, and named in vitro-in vivo consensus genes. Interestingly, the in vivo-in vitro consensus genes overlapped to a remarkable extent between both data sets, and were 21-times (upregulated genes) or 12-times (down-regulated genes) enriched compared to random expectation. Finally, the genes in the TGP and NRW overlap were used to identify the upregulated genes with the highest compound coverage, resulting in a seven-gene set of Cyp1a1, Ugt2b1, Cdkn1a, Mdm2, Aldh1a1, Cyp4a3, and Ehhadh. This seven-gene set was then successfully tested with structural analogues of valproic acid that are not present in the TGP and NRW data sets. In conclusion, the seven-gene set identified in the present study responds similarly in vitro and in vivo to a wide range of different chemicals. Despite these promising results with the seven-gene set, transcriptomics with cultivated rat hepatocytes remains a challenge, because in general many genes are up- or downregulated by in vitro culture per se, respond differently to test compounds in vitro and in vivo, and/or show higher variability in the in vitro system compared to the corresponding in vivo data. [ABSTRACT FROM AUTHOR]

Implicit change leadership theory (ICLT) highlights the importance of determining congruence between the ideal and actual change leadership schemas of employees in successful change management. This paper utilized ICLT in exploring effective change leadership and management in secondary schools and examined how these influence teachers’ commitment to change. Data were gathered from 707 secondary school teachers from both private and public high schools in the Philippines. Findings indicated that (1) teachers seem to have a more holistic and integrative view of change leadership schemas than employees of business organizations, (2) teachers’ change leadership schemas significantly predicts perceived effectiveness of change management, and teachers’ affective commitment to change, and (3) perceived effectiveness of change management significantly mediates the effect of change leadership schemas on teachers’ affective commitment to change. This study expanded the applicability of ICLT in basic education settings and contributes to the understanding of effective change leadership and change management in schools. Implications on practice and further recommendations for school leaders are also discussed. [ABSTRACT FROM AUTHOR]