This study evaluated the influence of formulation and thermal treatment on the degree of conversion, fracture toughness, flexural strength, and elastic modulus of experimental composites. Six composites were analyzed at BisGMA : TEGDMA molar ratios of 1 : 1 and 7 : 3 with filler at 30, 50, and 70 wt%. The degree of conversion was analyzed by Fourier transform infrared spectroscopy, fracture toughness was measured using the single-edge notched beam, and flexural strength and elastic modulus were measured with the 3-point bend test. For all tests, one-half of the specimens received thermal treatment at 170°C for 10 min. Data were analyzed by the Kruskal-Wallis or ANOVA/Tukey's test (α = 5%). The 1 : 1 BisGMA : TEGDMA ratio showed higher properties than the 7 : 3 ratio. Although the material with 70% filler had a conversion lower than the one with 50%, it showed higher mechanical properties. The thermal treatment improved all properties in all materials. Therefore, the use of an equimolar ratio of BisGMA : TEGDMA can be paired with 70 wt% filler to design dental composites that possess increased advantageous physical and chemical properties. Furthermore, the simple and low-cost method of thermal treatment proposed for use in clinical dentistry has been shown to effectively improve the properties of all evaluated materials.

Currently, treatment-emergent adverse events (TEAEs) during a clinical study are summarized over the entire study period.

Transient receptor potential (TRP) channels represent a superfamily of unselective cation channels that are subdivided into seven subfamilies based on their sequence homology and differences in gating and functional properties. Little is known about the molecular mechanisms of TRP channel regulation, particularly of the "canonical" TRP (TRPC) subfamily and their activation by polyunsaturated fatty acids (PUFAs). Here, we analyzed the structure-function relationship of Drosophila fruit fly TRPC channels. The primary aim was to uncover the molecular basis of PUFA sensitivity of Drosophila TRP-like (TRPL) and TRPgamma channels. Amino acid (aa) sequence alignment of the three Drosophila TRPC channels revealed 50 aa residues highly conserved in PUFA-sensitive TRPL and TRPgamma channels but not in the PUFA-insensitive TRP channel. Substitution of respective aa in TRPL by corresponding aa of TRP identified 18 residues that are necessary for PUFA-mediated activation of TRPL. Most aa positions are located within a stretch comprising transmembrane domains S2-S4, whereas six aa positions have been assigned to the proximal cytosolic C-terminus. Interestingly, residues I465 and S471 are required for activation by 5,8,11,14-eicosatetraynoic acid (ETYA) but not 5,8,11-eicosatriynoic acid (ETI). As proof of concept, we generated a PUFA-sensitive TRP channel by exchanging the corresponding aa from TRPL to TRP. Our study demonstrates a specific aa pattern in the transmembrane domains S2-S4 and the proximal C-terminus essential for TRP channel activation by PUFAs.

This systematic review identified patients have unmet information needs about the nature of osteoporosis, medication, self-management and follow-up. Clinician knowledge and attitudes appear to be of key importance in determining whether these needs are met. Unmet information needs appear to have psychosocial consequences and result in poor treatment adherence.

Basal forebrain cholinergic neurons (BFCN) are key modulators of learning and memory and are high energy-demanding neurons. Impaired neuronal metabolism and reduced insulin signaling, known as insulin resistance, has been reported in the early phase of Alzheimer's disease (AD), which has been suggested to be "Type 3 Diabetes." We hypothesized that BFCN may develop insulin resistance and their consequent failure represents one of the earliest event in AD. We found that a condition reminiscent of insulin resistance occurs in the medial septum of 3 months old 3×Tg-AD mice, reported to develop typical AD histopathology and cognitive deficits in adulthood. Further, we obtained insulin resistant BFCN by culturing them with high insulin concentrations. By means of these paradigms, we observed that nerve growth factor (NGF) reduces insulin resistance in vitro and in vivo. NGF activates the insulin receptor substrate 1 (IRS1) and rescues c-Fos expression and glucose metabolism. This effect involves binding of activated IRS1 to the NGF receptor TrkA, and is lost in presence of the specific IRS inhibitor NT157. Overall, our findings indicate that, in a well-established animal model of AD, the medial septum develops insulin resistance several months before it is detectable in the neocortex and hippocampus. Remarkably, NGF counteracts molecular alterations downstream of insulin-resistant receptor and its nasal administration restores insulin signaling in 3×Tg-AD mice by TrkA/IRS1 activation. The cross-talk between NGF and insulin pathways downstream the insulin receptor suggests novel potential therapeutic targets to slow cognitive decline in AD and diabetes-related brain insulin resistance.

Ischemic cardiomyopathy (ICM) represents a worldwide health issue owning to its high sudden death rate. Easy diagnosis and effective treatment of ICM are still lacking. Identification of novel molecular markers will help illustrate the pathophysiology of ICM and facilitate its diagnosis and targeted treatment. Transcription profiling could be an easy and efficient way for identifying new markers. However, the mega data in the available database may contain a large number of false-positive hits. To identify the true marker for ICM, we systematically compared available microarray datasets in the GEO database and identified 26 genes that are shared by all datasets. We further verified the expression pattern of these 26 genes in ICM rat model. Only 12 genes show significant differential expression in our animal model. Among them, we focused on PHLDA1, a well-documented pro-apoptotic factor. Expression of PHLDA1 was elevated in both ischemic cardiac cell lines and in rat model. Overexpression of PHLDA1 promotes apoptosis of cardiac muscle cell. Meanwhile, PHLDA1 not only inhibited AKT pathway, but also activated p53 pathway. We thus confirmed PHLDA1 as a true molecular marker for ICM.

Obesity is characterized by insulin resistance and low-grade systemic and adipose tissue (AT) inflammation. It remains unclear whether beneficial effects of weight loss are related to AT inflammation. We aimed to assess the effect of weight loss during low-calorie diet on insulin sensitivity, AT expression of genes associated with inflammation in young subjects with obesity. Furthermore, we estimated the effects of immunomodulatory (1, 3)(1, 6)-β-glucan (BG) on the above parameters.

Direct and indirect pathways in the basal ganglia work together for controlling behavior. However, it is still a controversial topic whether these pathways are segregated or merged with each other. To address this issue, we studied the connections of these two pathways in the caudal parts of the basal ganglia of rhesus monkeys using anatomical tracers. Our previous studies showed that the caudal basal ganglia control saccades by conveying long-term values (stable values) of many visual objects toward the superior colliculus. In experiment 1, we injected a tracer in the caudate tail (CDt), and found local dense plexuses of axon terminals in the caudal-dorsal-lateral part of substantia nigra pars reticulata (cdlSNr) and the caudal-ventral part of globus pallidus externus (cvGPe). These anterograde projections may correspond to the direct and indirect pathways, respectively. To verify this in experiment 2, we injected different tracers into cdlSNr and cvGPe, and found many retrogradely labeled neurons in CDt and, in addition, the caudal-ventral part of the putamen (cvPut). These cdlSNr-projecting and cvGPe-projecting neurons were found intermingled in both CDt and cvPut (which we call "striatum tail"). A small but significant proportion of neurons (<15%) were double-labeled, indicating that they projected to both cdlSNr and cvGPe. These anatomical results suggest that stable value signals (good vs. bad) are sent from the striatum tail to cdlSNr and cvGPe in a biased (but not exclusive) manner. These connections may play an important role in biasing saccades toward higher valued objects and away from lower valued objects.

Secondary hyperoxalemia is a multifactorial disease that affects several organs and tissues in patients with native or transplanted kidneys. Plasma oxalate may increase during renal failure because it is cleared from the body by the kidneys. However, there is scarce evidence about the association between glomerular filtration rate and plasma oxalate, especially in the early stages of chronic kidney disease (CKD).

A large number of antisense transcripts have been detected in diverse microbial genomes and considerable effort has been devoted to elucidating the functional role of antisense transcription. In this study, we reanalysed extensive RNA sequencing data from the opportunistic pathogen Pseudomonas aeruginosa and found that the majority of genes have a propensity for antisense transcription. Although antisense transcripts were found in more than 80 % of the genes of the P. aeruginosa genome, the majority of sequencing reads were mapping sense and only a minority (<2 %) were mapping antisense to genes. Similarly to the sense expression levels, the antisense expression levels varied under different environmental conditions, with the sense and antisense expression levels often being inversely regulated and modulated by the activity of alternative sigma factors. Environment-modulated antisense transcription showed a bias towards being antisense to genes within regions of genomic plasticity and to those encoding small regulatory RNAs. In the future, the validation and functional characterization of antisense transcripts, and novel transcripts that are antisense to small regulatory RNAs in particular, have the potential to contribute to our understanding of the various levels of transcriptional regulation and its dynamics in the bacterial pathogen P. aeruginosa.

Studies have recently reported an association between sleep duration and obesity in some individuals. Vitamin D deficiency is common in elderly populations and is also associated with obesity. In this study, the combined interaction effect of vitamin D levels and sleep duration on obesity-related variables was analyzed in 3757 individuals from an elderly Korean population using the Korean National Health and Nutrition Examination Survey. Significant differences were observed in the interaction effect of the vitamin D levels and sleep duration on obesity-related variables, including BMI (p = 0.004) and the risk of obesity (p < 0.001). Using vitamin D sufficient status and proper sleep duration as a reference, subjects with sufficient vitamin D did not differ in their risk of obesity regardless of their sleep duration. However, the risk of obesity tended to increase with short sleep duration rather than proper sleep duration among subjects who were vitamin D insufficient odds ratio (OR) (95% CI) = 1.293 (1.10⁻1.657) for proper sleep duration vs. 1.374 (1.066⁻1.770) for short sleep duration). Only the participants in the vitamin D deficient population who consumed less protein showed an increasing trend in the risk of obesity according to the sleep duration (OR (95% CI) = 1.645 (1.155⁻2.344) for proper sleep duration and 1.668 (1.156⁻2.406) for short sleep duration).

Personalized nutrition is of increasing interest to individuals actively monitoring their health. The relations between the duration of diet intervention and the effects on gut microbiota have yet to be elucidated. Here we examined the associations of short-term dietary changes, long-term dietary habits and lifestyle with gut microbiota. Stool samples from 248 citizen-science volunteers were collected before and after a self-reported 2-week personalized diet intervention, then analyzed using 16S rRNA sequencing. Considerable correlations between long-term dietary habits and gut community structure were detected. A higher intake of vegetables and fruits was associated with increased levels of butyrate-producing Clostridiales and higher community richness. A paired comparison of the metagenomes before and after the 2-week intervention showed that even a brief, uncontrolled intervention produced profound changes in community structure: resulting in decreased levels of Bacteroidaceae, Porphyromonadaceae and Rikenellaceae families and decreased alpha-diversity coupled with an increase of Methanobrevibacter, Bifidobacterium, Clostridium and butyrate-producing Lachnospiraceae- as well as the prevalence of a permatype (a bootstrapping-based variation of enterotype) associated with a higher diversity of diet. The response of microbiota to the intervention was dependent on the initial microbiota state. These findings pave the way for the development of an individualized diet.

Background: Quality improvement initiatives can help nursing homes strengthen psychosocial work environments. The aim of the present study was to examine the association between supportive psychosocial work environment, and professional and organizational characteristics regarding quality improvement initiatives in dementia care. Methods: A paper questionnaire survey was administered to a convenience sample of 365 professional caregivers in 12 special nursing homes in Japan. Psychosocial work environment was assessed using the Social Capital and Ethical Climate at the Workplace Scale to calculate a score of social capital in the workplace, ethical leadership, and exclusive workplace climate. Variables for quality improvement initiatives included type of home (unit-type or traditional), presence of additional benefit for dementia care, and professionalism in dementia care among caregivers evaluated using the Japanese version of the Sense of Competence in Dementia Care Staff Scale. Results: Elevated professionalism and unit-type home were significantly associated with high social capital, strong ethical leadership, and low exclusive workplace climate. The presence of dementia care benefit was not associated with any subscale of psychosocial work environment. Conclusions: Quality improvement initiatives to foster supportive psychosocial work environment should enhance professionalism in dementia care with unit-based team building of professional caregivers in special nursing homes.

Bortezomib (Btz) is an active agent used to treat multiple myeloma (MM). Not all patients who receive Btz-containing therapy show a favorable response. Interaction of cellular adhesion molecules with MM and bone marrow stromal cells is crucial for the survival of MM cells. However, little is known about the role of these molecules in the sensitivity of MM to Btz-containing therapy. Thus, we evaluated the correlation between the level of cellular adhesion molecules in MM cells and the efficacy of Btz plus dexamethasone (Bd) therapy. The expression of the neural cell adhesion molecule gene (NCAM, also known as CD56), ITGA4, CXCR4, and other genes were analyzed in 74 samples of primary MM cells collected from patients before they received Bd therapy. Of the eight genes tested, expression of NCAM was lower among patients who responded poorly to Bd therapy. In vitro expression of NCAM induced by transfection of MM cells enhanced their sensitivity to Btz treatment by causing accumulation of polyubiquitinated proteins. Our results indicate that expression of NCAM is associated with better response to Btz treatment and is a promising candidate biomarker for predicting response to therapies involving Btz.

Performed phytochemical study contributes to the knowledge of volatile organic compounds (VOCs) of Halopteris filicina (Grateloup) Kützing, Dictyota dichotoma (Hudson) J. V. Lamouroux, Posidonia oceanica (L.) Delile and Flabellia petiolata (Turra) Nizamuddin from the Adriatic Sea (single point collection). VOCs were investigated by headspace solid-phase microextraction (HS-SPME) and analysed by gas chromatography and mass spectrometry (GC-MS/FID). H. filicina headspace contained dimethyl sulfide (DMS; 12.8%), C8-compounds (e.g. fucoserratene (I; 9.5%)), benzaldehyde (II; 8.7%), alkane C17, dictyopterene D and C (III, IV), tribromomethane (V), 1-iodopentane, others. F. petiolata headspace was characterized by DMS (22.2%), 6-methylhept-5-en-2-one (9.5%), C17 (9.1%), II (6.5%), compounds I-V. DMS (59.3%), C15 (14.5%), C17 (7.2%) and C19 (6.3%) dominated in P. oceanica headspace. Sesquiterpenes were found in D. dichotoma, predominantly germacrene D (28.3%) followed by other cadinenyl (abundant), muurolenyl and amorphenyl structures. Determined VOCs may be significant for chemosystematics and chemical communications in marine ecosystem.

The red algal subclass Nemaliophycidae includes both marine and freshwater taxa that contribute to more than half of the freshwater species in Rhodophyta. Given that these taxa inhabit diverse habitats, the Nemaliophycidae is a suitable model for studying environmental adaptation. For this purpose, we characterized plastid genomes of two freshwater species, Kumanoa americana (Batrachospermales) and Thorea hispida (Thoreales), and one marine species Palmaria palmata (Palmariales). Comparative genome analysis identified seven genes (ycf34, ycf35, ycf37, ycf46, ycf91, grx, and pbsA) that were different among marine and freshwater species. Among currently available red algal plastid genomes (127), four genes (pbsA, ycf34, ycf35, ycf37) were retained in most of the marine species. Among these, the pbsA gene, known for encoding heme oxygenase, had two additional copies (HMOX1 and HMOX2) that were newly discovered and were reported from previously red algal nuclear genomes. Each type of heme oxygenase had a different evolutionary history and special modifications (e.g., plastid targeting signal peptide). Based on this observation, we suggest that the plastid-encoded pbsA contributes to the iron controlling system in iron-deprived conditions. Thus, we highlight that this functional requirement may have prevented gene loss during the long evolutionary history of red algal plastid genomes.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in the human population affecting an estimated 8% of the world population, especially those living in areas of past and present malaria endemicity. Decreased G6PD enzymatic activity is associated with drug-induced hemolysis and increased risk of severe neonatal hyperbilirubinemia leading to brain damage. The G6PD gene is on the X chromosome therefore mutations cause enzymatic deficiency in hemizygote males and homozygote females while the majority of heterozygous females have an intermediate activity (between 30-80% of normal) with a large distribution into the range of deficiency and normality. Current G6PD qualitative tests are unable to diagnose G6PD intermediate activities which could hinder wide use of 8-aminoquinolines for Plasmodium vivax elimination. The aim of the study was to assess the diagnostic performances of the new Carestart G6PD quantitative biosensor.

Identification of cancer driver mutations is critical for advancing cancer research and personalized medicine. Due to inter-tumor genetic heterogeneity, many driver mutations occur at low frequencies, which make it challenging to distinguish them from passenger mutations. Here, we show that a novel Bayesian hierarchical modeling approach, named rDriver can achieve enhanced prediction accuracy by identifying mutations that not only have high functional impact scores but also are associated with systemic variation in gene expression levels. In examining 3,080 tumor samples from 8 cancer types in The Cancer Genome Atlas, rDriver predicted 1,389 driver mutations. Compared with existing tools, rDriver identified more low frequency mutations associated with lineage specific functional properties, timing of occurrence and patient survival. Evaluation of rDriver predictions using engineered cell-line models resulted in a positive predictive value of 0.94 in PIK3CA genes. Our study highlights the importance of integrating multi-omic data in predicting cancer driver mutations and provides a statistically rigorous solution for cancer target discovery and development.

Immunoglobulin superfamily (IgSF), an extensive collection of proteins possessing at least one immunoglobulin-like (Ig-like) domain, performs a wide range of functions in recognition, binding or adhesion process of cells. In the present study, a cysteine-rich motif associated immunoglobulin domain containing protein (designated CgCAICP-1) was identified in Pacific oyster Crassostrea gigas. The deduced protein sequence of CgCAICP-1 contained 534 amino acidresidues, with three Ig domains which were designated as IG1, IG2 and IG3, and a cysteine-rich motif between the first and second Ig domain. The mRNA transcripts of CgCAICP-1 were highly expressed in hemocytes and up-regulated significantly (p < 0.05) after the stimulation of lipopolysaccharides (LPS), but not peptidoglycan (PGN). The recombinant CgCAICP-1 protein (rCgCAICP-1) exhibited binding activity to various pathogen-associated molecular patterns (PAMPs) including LPS, PGN, mannose (Man) and D-galactose (D-Gal), and microorganisms including Vibrio splendidus, Escherichia coli, Staphylococcus aureus, Micrococcus luteus and Pichia pastoris. The phagocytic rates of oyster hemocytes towards Gram-negative bacteria V. splendidus and Gram-positive bacteria M. luteus were significantly enhanced (p < 0.05) after pre-incubation of microbes with rCgCAICP-1. Furthermore, the transcripts of CgCAICP-1 exhibited high level of polymorphism among individuals. The ratio of nonsynonymous and synonymous distances (dN/dS) for AA'BCC'D strands of IG1 (the possible binding sites 1, pbs1) across all allelic variants was 2.09 (p < 0.05), while the ratio for the non-pbs regions was less than 1.0. The 1248 bp fragment amplified from the 5' end of CgCAICP-1 open reading frame (ORF) from 24 transcript variants could be divided artificially into seven regions of 50 elements, and all of the allelic variants might be derived from these elements by point mutation and recombination processes. These results collectively suggested that CgCAICP-1 might function as an important pattern recognition receptor (PRR) to recognize various PAMPs and facilitated the phagocytosis of oyster hemocytes towards both Gram-positive and Gram-negative bacteria. Diverse isoforms of CgCAICP-1 were generated through point mutation and recombination processes and maintained by balancing selection, which would provide a broader spectrum of interaction surface and be associated with immune resistance of oysters to infectious pathogens.

As a persistent and widespread toxic organic pollutant in the environment, perfluorooctane sulfonate (PFOS) has the potential to cause great harm to wildlife. In our study, the effects of PFOS on neurodevelopment gene expression, neurotransmitter content, neuronal morphology, acetylcholinesterase (AChE) activity were examined, and the potential neurotoxicity mechanisms of PFOS were also investigated in planarians, Dugesia japonica. Using quantitative real-time PCR analysis, five neurodevelopmental related genes were measured, among which, DjotxA, DjotxB, DjFoxD, and DjFoxG were found to be down-regulated, while Djnlg was found to be up-regulated, following exposure to PFOS for 10 days compared with control groups. In addition, the neurotransmitters including dopamine, serotonin, and γ-aminobutyricacid as well as the acitivity of AChE were altered by PFOS exposure. Furthermore, PFOS exposure altered brain morphology as well as smaller cephalic ganglia which displayed reduced nerve fiber density decreased brain branches compared to controls. Our results demonstrate that neurotransmission was disturbed after exposure to PFOS and that exposure to this pollutant can cause neurotoxic defects. Results from this study provide valuable information regarding the neuro- and ecological toxicity of PFOS in aquatic animals and aquatic environments.