Mayaro virus (MAYV) is a mosquito-transmitted alphavirus that is being recognized with increasing frequency in South America. As part of on-going surveillance of a school cohort in Haiti, we identified MAYV infections in 5 children across a 7-month time span, at two different school campuses. All had a history of fever, and three had headaches; none complained of arthralgias. On analysis of whole genome sequence data, three strains were genotype D, and two were genotype L; phylogenetic and molecular clock analysis was consistent with at least 3 independent introductions of the virus into Haiti, with ongoing transmission of a common genotype D strain in a single school. Our data highlight the clear potential for spread of the virus in the northern Caribbean and North America.

Median overall survival (OS) has improved for patients with newly diagnosed multiple myeloma (NDMM), but prognosis varies depending on baseline patient characteristics. Current models use data from selected clinical trial populations, which prevent application to patients in an unselected community setting that reflects routine clinical practice. Using data from the Connect® MM Registry, a large, US, multicentre, prospective observational cohort study (Cohort 1: 2009-2011; Cohort 2: 2012-2016) of 3011 patients with NDMM, we identified prognostic variables for OS via the multivariable analysis of baseline patient characteristics in Cohort 1 (n = 1493) and developed a tool to examine individual outcomes. Factors associated with OS (n = 1450 treated patients; P < 0·05) were age, del(17p), triplet therapy use, EQ-5D mobility, International Staging System stage, solitary plasmacytoma, history of diabetes, platelet count, Eastern Cooperative Oncology Group performance status and serum creatinine, which were used to create survival matrices for 3- and 5-year OS. The model was internally and externally validated using Connect MM Cohort 2 (Harrell's concordance index, 0·698), MM-015 (0·649), and the phase 3 FIRST (0·647) clinical trials. This novel prognostic tool may help inform outcomes for NDMM in the era of triplet therapy use with novel agents.

Radiosensitizing properties of substituted uridines are of great importance for radiotherapy. Very recently, we confirmed 5-iodo-4-thio-2'-deoxyuridine (ISdU) as an efficient agent, increasing the extent of tumor cell killing with ionizing radiation. To our surprise, a similar derivative of 4-thio-2'-deoxyuridine, 5-bromo-4-thio-2'-deoxyuridine (BrSdU), does not show radiosensitizing properties at all. In order to explain this remarkable difference, we carried out a radiolytic (stationary and pulse) and quantum chemical studies, which allowed the pathways to all radioproducts to be rationalized. In contrast to ISdU solutions, where radiolysis leads to 4-thio-2'-deoxyuridine and its dimer, no dissociative electron attachment (DEA) products were observed for BrSdU. This observation seems to explain the lack of radiosensitizing properties of BrSdU since the efficient formation of the uridine-5-yl radical, induced by electron attachment to the modified nucleoside, is suggested to be an indispensable attribute of radiosensitizing uridines. A larger activation barrier for DEA in BrSdU, as compared to ISdU, is probably responsible for the closure of DEA channel in the former system. Indeed, besides DEA, the XSdU anions may undergo competitive protonation, which makes the release of X- kinetically forbidden.

Even though the reversal of multi-drug resistance (MDR) by numerous nanoparticles has been extensively studied, limited success has been achieved. To overcome this barrier, we report a rationally-designed pH-sensitive micelle, in which doxorubicin (Dox) and resveratrol (Res) were co-loaded. The micelle was based on methoxy poly (ethylene glycol)-poly(d,l-lactide)-poly(l-histidine) (mPEG-PLA-PHis), which integrated passive targeting, endo-lysosomal escape and pH-responsive payloads release. At a physiological pH of 7.4 (slightly alkali), Dox and Res were incorporated into the micelles core using the thin-film hydration method (pH-endoSM/Dox/Res). After cellular uptake, the micelles exhibited an enhanced dissociation in response to the acidic endosomes, triggering the release of Res and Dox. Furthermore, Res was observed to synergistically improve the cytotoxicity of Dox by down-regulating the P-glycoprotein (P-gp) expression, decreasing the membrane potential of the mitochondrial and ATP level, as well as inducing cell apoptosis mediated by mitochondria. The pH-endoSM/Dox/Res showed a prominent ability to decrease the IC50 of Dox by a factor of 17.38 in cell cytotoxicity against the MCF-7/ADR cell line. In vivo distribution demonstrated the excellent tumor-targeting ability of the pH-endoSM/Dox/Res. All results indicated that pH-endoSM/Dox/Res held great potential for the treatment of Dox-resistance breast cancer cells.

In the transition from high school to university, vegetable consumption tends to deteriorate, potentially influencing immediate and longer-term health outcomes. Nudges, manipulation of the environment to influence choice, have emerged as important to behavior change goals. This quasi-experimental pilot study examined the impact of a contextually feasible evidence-informed nudge intervention on food purchasing behavior of older adolescents (1st year students) in a university residence cafeteria in British Columbia, Canada. A co-design process with students and staff identified a student relevant and operationally feasible nudge intervention; a placement nudge, fresh vegetables at the hot food table, combined with a sensory and cognitive nudge, signage encouraging vegetable purchase). Using a 12-week single-case A-B-A-B design, observations of the proportion of vegetables purchased were used to assess intervention efficacy. Data analysis included visual trend inspection, central tendency measures, data overlap, variability and latency. Visual trend inspection showed a positive trend when nudges were in place, which was more apparent with female purchases and during the first intervention (B) phase. However, further analysis showed lack of baseline stability, high variability across phases and overlapping data, limiting efficacy conclusions. Menu choices, staff encouragement, term timing and student finances are other potential influences. Further 'real world' nudge research is needed.

Control of the release properties of drugs has been considered a key factor in the development of drug delivery systems (DDSs). However, drug delivery has limitations including cytotoxicity, low loading efficiency, and burst release. To overcome these challenges, nano or micro-particles have been suggested as carrier systems to deliver chemical drugs. Herein, nano-sized DNA particles (DNAp) were manufactured to deliver netropsin, which is known to bind to DNA minor grooves. The rationally designed particles with exposed rich minor grooves were prepared by DNAp synthesis via rolling circle amplification (RCA). DNAp could load large quantities of netropsin in its minor grooves. An analytical method was also developed for the quantification of netropsin binding to DNAp by UV-visible spectrometry. Moreover, controlled release of netropsin was achieved by forming a layer of Ca2+ on the DNAp (CaDNAp). As a proof of concept, the sustained release of netropsin by CaDNAp highlights the potential of the DNAp-based delivery approach.

Nickel-based superalloys have become key materials for turbine disks and other aerospace components due to their excellent mechanical properties at high temperatures. Mechanical properties of nickel-based superalloys are closely related to their microstructures. Various heat treatment processes were conducted to obtain the desired microstructures of a nickel-based superalloy in this study. The effect of the initial microstructures on the tensile deformation and fracture behaviors was investigated via in situ digital image correlation (DIC) and synchrotron radiation X-ray tomography (SRXT). The results showed that the size and volume fraction of γ″ and γ' phases increased with the aging time. The yield strength and the ultimate tensile strength increased due to the precipitation strengthening at the expense of ductility. The surface strain analysis showed severely inhomogeneous deformation. The local strains at the edge of specimens were corresponded to higher void densities. The fracture of carbides occurred owing to the stress concentration, which was caused by the dislocation accumulation. The fracture mode was dimple coalescence ductile fracture.

The phenolic composition of hydroethanolic extracts of Mentha aquatica L., Lavandula dentata L. and Leonurus cardiaca L., obtained from plants grown under organic cultivation, was determined and their hepatoprotective effects were investigated in vitro. L. cardiaca extract was rich in phenylethenoid glycosides, especially lavandolifolioside (254 ± 36 μg/mg), whereas rosmarinic acid and eriodictyol-O-rutinoside were the major phenolic compounds of L. dentata and M. aquatica extracts, accounting for 68 ± 7 μg/mg and 145 ± 22 μg/mg, respectively. These differential phenolic components presumably account for their dissimilar antioxidant properties. While L. cardiaca extract showed moderate biological effects, M. aquatica extract displayed high antioxidant activity in chemical models, and that of L. dentata was effective in counteracting potassium dichromate-induced ROS generation in human hepatocarcinoma cells. Moreover, M. aquatica extract (50 μg/mL) and its mixture (50%/50%) with L. dentata extract displayed an effective cytoprotective effect.

Many MALDI-MS imaging experiments make a case versus control studies of different tissue regions in order to highlight significant compounds affected by the variables of study. This is a challenge because the tissue samples to be compared come from different biological entities, and therefore they exhibit high variability. Moreover, the statistical tests available cannot properly compare ion concentrations in two regions of interest (ROIs) within or between images. The high correlation between the ion concentrations due to the existence of different morphological regions in the tissue means that the common statistical tests used in metabolomics experiments cannot be applied. Another difficulty with the reliability of statistical tests is the elevated number of undetected MS ions in a high percentage of pixels. In this study, we report a procedure for discovering the most important ions in the comparison of a pair of ROIs within or between tissue sections. These ROIs were identified by an unsupervised segmentation process, using the popular k-means algorithm. Our ion filtering algorithm aims to find the up or down-regulated ions between two ROIs by using a combination of three parameters: (a) the percentage of pixels in which a particular ion is not detected, (b) the Mann-Whitney U ion concentration test, and (c) the ion concentration fold-change. The undetected MS signals (null peaks) are discarded from the histogram before the calculation of (b) and (c) parameters. With this methodology, we found the important ions between the different segments of a mouse brain tissue sagittal section and determined some lipid compounds (mainly triacylglycerols and phosphatidylcholines) in the liver of mice exposed to thirdhand smoke.

Skim milk has a poor flavor due to the lack of fat. Finding ways to improve the flavor quality of skim milk has attracted the attention of more and more researchers. The purpose of this study was to create a skim milk product with good flavor by processing. Briefly, raw milk was treated by preheating at pasteurization (85 °C, 15 s) and ultra-high temperature (UHT) instantaneous sterilization (137-141 °C, 4 s). Subsequently, the sample was centrifuged to remove fat and obtain two kinds of skim milk, namely, PSM (skim milk obtained by preheating at 85 °C, 15 s) and USM (skim milk obtained by preheating at 137-141 °C, 4 s). The results showed that the intensity of the main sensory attributes (overall liking, milk aroma, etc.) and the concentrations of the key flavor compounds (2-heptanone, 2-nonanone, decanal, hexanoic acid, etc.) were significantly higher in the USM (p < 0.05) than that of the PSM and RSM (skim milk without preheating). Principal component analysis (PCA) with E-Nose (electronic nose) showed that the RSM had significant differences in the milk aroma compared with the PSM and USM. Furthermore, it was found that there were good relationships between volatile compounds and sensory attributes by partial least squares regression (PLSR) analysis. These findings provided insights into improving the flavor quality of skim milk by preheating treatment instead of any flavor additives.

Recently, nanofibers (NFs) formed from antigenic peptides conjugated to β-sheet-forming peptides have attracted much attention as a new generation of vaccines. However, studies describing how the hydrophilic-hydrophobic balance of NF components affects cellular interactions of NFs are limited. In this report, three different NFs were prepared by self-assembly of β-sheet-forming peptides conjugated with model antigenic peptides (SIINFEKL) from ovalbumin and hydrophilic oligo-ethylene glycol (EG) of differing chain lengths (6-, 12- and 24-mer) to investigate the effect of EG length of antigen-loaded NFs on their cellular uptake, cytotoxicity, and dendritic cell (DC)-stimulation ability. We used an immortal DC line, termed JAWS II, derived from bone marrow-derived DCs of a C57BL/6 p53-knockout mouse. The uptake of NFs, consisting of the EG 12-mer by DCs, was the most effective and activated DC without exhibiting significant cytotoxicity. Increasing the EG chain length significantly reduced cellular entry and DC activation by NFs. Conversely, shortening the EG chain enhanced DC activation but increased toxicity and impaired water-dispersibility, resulting in low cellular uptake. These results show that the interaction of antigen-loaded NFs with cells can be tuned by the EG length, which provides useful design guidelines for the development of effective NF-based vaccines.

The present study introduces a recently developed compact hybrid device for real-time monitoring of skin oxygen saturation and temperature distribution. The prototype involves a snapshot hyperspectral camera, multi-wavelength illuminator, thermal camera, and built-in computer with custom-developed software. To validate this device in-vivo we performed upper arm vascular occlusion on eight healthy volunteers. Palm skin oxygen saturation maps were analyzed in real-time using k-means segmentation algorithm and two-layer optical diffuse model. The prototype system demonstrated a satisfying performance of skin hyperspectral measurements in the spectral range of 507-625 nm. The results confirmed the reliability of the proposed system for in-vivo assessment of skin hemoglobin saturation with oxygen and microcirculation.

Framed within Self-Determination Theory, the objective of this study was to analyze the relationship between satisfaction and frustration of basic psychological needs, levels of motivation, physical activity, and satisfaction with life.

Xeroderma is a frequent complication in diabetic patients. In this study, we investigated the mechanism underlying the onset of diabetic xeroderma, focusing on aquaporin-3 (AQP3), which plays an important role in water transport in the skin. Dermal water content in diabetic mice was significantly lower than that in control mice. The expression level of AQP3 in the skin was significantly lower in diabetic mice than in control mice. One week after streptozotocin (STZ) treatment, despite their increased blood glucose levels, mice showed no changes in the expression levels of AQP3, Bmal1, Clock, and D site-binding protein (Dbp) in the skin and 8-hydroxydeoxyguanosine (8-OHdG) in the urine. In contrast, two weeks after STZ treatment, mice showed increases in the blood glucose level, decreases in AQP3, Bmal1, Clock, and Dbp levels, and increases in the urinary levels of 8-OHdG. The results of this study suggest that skin AQP3 expression decreases in diabetes, which may limit water transport from the vessel side to the corneum side, causing dry skin. In addition, in diabetic mice, increased oxidative stress triggered decreases in the expression levels of Bmal1 and Clock in the skin, thereby inhibiting the transcription of Aqp3 by Dbp, which resulted in decreased AQP3 expression.

Porcine epidemic diarrhea virus (PEDV) is currently detected as the main pathogen causing severe diarrhea in pig farms. The phenotypic alterations induced by pathogenic infections are usually tightly linked with marked changes in epigenetic modification and gene expression. We performed global mapping of H3K4 trimethylation (H3K4me3) and transcriptomic analyses in the jejunum of PEDV-infected and healthy piglets using chromatin immunoprecipitation sequencing and RNA-seq techniques. A total of 1885 H3K4me3 peaks that are associated with 1723 genes were characterized. Moreover, 290 differentially expressed genes were identified, including 104 up-regulated and 186 down-regulated genes. Several antiviral genes including 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase 2 (OAS2), ephrin B2 (EFNB2), and CDC28 protein kinase regulatory subunit 1B (CKS1B) with higher H3K4me3 enrichment and expression levels in PEDV-infected samples suggested the potential roles of H3K4me3 deposition in promoting their expressions. Transcription factor annotation analysis highlighted the potential roles of two transcription factors interferon regulatory factor 8 (IRF8) and Kruppel like factor 4 (KLF4) in modulating the differential expression of genes involved in PEDV infection. The results provided novel insights into PEDV infection from the transcriptomic and epigenetic layers and revealed previously unknown and intriguing elements potentially involved in the host responses.

The results of epidemiological studies on the relationship between fruit and vegetable intake and lung cancer risk were inconsistent among participants with different smoking status. The purpose of this study was to investigate these relationships in participants with different smoking status with prospective cohort studies. A systematic literature retrieval was conducted using PubMed and Scopus databases up to June 2019. The summary relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were calculated by random-effects model. The nonlinear dose-response analysis was carried out with restricted cubic spline regression model. Publication bias was estimated using Begg's test. Nine independent prospective studies were included for data synthesis. Dietary consumption of fruit was negatively correlated with lung cancer risk among current smokers and former smokers, and the summery RRs were 0.86 (95% CI: 0.78, 0.94) and 0.91 (95% CI: 0.84, 0.99), respectively. Consumption of vegetable was significantly associated with reduced risk of lung cancer for current smokers (summary RR = 87%; 95% CI: 0.78, 0.94), but not for former smokers and never for smokers. Dose-response analysis suggested that risk of lung cancer was reduced by 5% (95% CI: 0.93, 0.97) in current smokers, and reduced by 4% (95% CI: 0.93, 0.98) in former smokers with an increase of 100 grams of fruit intake per day, respectively. Besides, dose-response analysis indicated a 3% reduction in lung cancer risk in current smokers for 100 gram per day increase of vegetable intake (95% CI: 0.96, 1.00). The findings of this study provide strong evidence that higher fruit consumption is negatively associated with the risk of lung cancer among current smokers and former smokers, while vegetable intake is significantly correlated with reducing the risk of lung cancer in current smokers. These findings might have considerable public health significance for the prevention of lung cancer through dietary interventions.

The scanpaths of healthy subjects show biases towards the upper face, the eyes and the center of the face, which suggests that their fixations are guided by a feature hierarchy towards the regions most informative for face identification. However, subjects with developmental prosopagnosia have a lifelong impairment in face processing. Whether this is reflected in the loss of normal face-scanning strategies is not known. The goal of this study was to determine if subjects with developmental prosopagnosia showed anomalous scanning biases as they processed the identity of faces. We recorded the fixations of 10 subjects with developmental prosopagnosia as they performed a face memorization and recognition task, for comparison with 8 subjects with acquired prosopagnosia (four with anterior temporal lesions and four with occipitotemporal lesions) and 20 control subjects. The scanning of healthy subjects confirmed a bias to fixate the upper over the lower face, the eyes over the mouth, and the central over the peripheral face. Subjects with acquired prosopagnosia from occipitotemporal lesions had more dispersed fixations and a trend to fixate less informative facial regions. Subjects with developmental prosopagnosia did not differ from the controls. At a single-subject level, some developmental subjects performed abnormally, but none consistently across all metrics. Scanning distributions were not related to scores on perceptual or memory tests for faces. We conclude that despite lifelong difficulty with faces, subjects with developmental prosopagnosia still have an internal facial schema that guides their scanning behavior.

The glycoprotein osteopontin (OPN) possesses multiple functions in health and disease. To this end, osteopontin has beneficial roles in wound healing, bone homeostasis, and extracellular matrix (ECM) function. On the contrary, osteopontin can be deleterious for the human body during disease. Indeed, osteopontin is a cardinal mediator of tumor-associated inflammation and facilitates metastasis. The purpose of this review is to highlight the importance of osteopontin in malignant processes, focusing on lung and pleural tumors as examples.

A novel protocol has been established to prepare the kanamycin ring II/III fragment, which has been validated as a minimum structural motif for the development of new aminoglycosides on the basis of its bactericidal activity even against resistant strains. Furthermore, its ability to act as a AAC-(6') and APH-(3') binder, and as a poor substrate for the ravenous ANT-(4'), makes it an excellent candidate for the design of inhibitors of these aminoglycoside modifying enzymes.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease driven by genetic, environmental and epigenetic factors. Long non-coding RNAs (LncRNAs) are a key component of the epigenetic mechanisms and are known to be involved in the development of autoimmune diseases. In this work we aimed to identify significantly differentially expressed LncRNAs (DE-LncRNAs) that are functionally connected to modulated genes strictly associated with RA. In total, 542,500 transcripts have been profiled in peripheral blood mononuclear cells (PBMCs) from four patients with early onset RA prior any treatment and four healthy donors using Clariom D arrays. Results were confirmed by real-time PCR in 20 patients and 20 controls. Six DE-LncRNAs target experimentally validated miRNAs able to regulate differentially expressed genes (DEGs) in RA; among them, only FTX, HNRNPU-AS1 and RP11-498C9.15 targeted a large number of DEGs. Most importantly, RP11-498C9.15 targeted the largest number of signalling pathways that were found to be enriched by the global amount of RA-DEGs and that have already been associated with RA and RA-synoviocytes. Moreover, RP11-498C9.15 targeted the most highly connected genes in the RA interactome, thus suggesting its involvement in crucial gene regulation. These results indicate that, by modulating both microRNAs and gene expression, RP11-498C9.15 may play a pivotal role in RA pathogenesis.