Sweat-based analytics have recently caught the attention of researchers and medical professionals alike because they do not require professionally trained personnel or invasive collection techniques to obtain a sample. The following presents a small form-factor biosensor for reporting physiological ranges of cortisol present in ambient sweat (8-151 ng/ml). This device obtains cortisol measurements through low volumes of unstimulated sweat from the user's wrist. We designed a potentiostatic circuit on a printed circuit board to perform electrochemical testing techniques. The detection modality developed for quantifying sensor response to varying cortisol concentrations is a current based electrochemical technique, chronoamperometry (CA). From the results, the sensor can detect cortisol in the physiologically relevant ranges of cortisol; thus, the sensor is a noninvasive, label free, cost-effective solution for tracking cortisol levels for circadian diagnostics.

Parkinson's disease is one of the most insidious neurodegenerative diseases in developed countries. Today, human pluripotent stem cells are produced from embryonic or adult cells, multiplied, differentiated into neural cell lines and ultimately transplanted into disease animal models or patients. Nowadays, DOPAminergic neurons derived from human pluripotent stem cells and human parthenogenetic cells are being clinically tested in China and Australia, respectively. More importantly, good manufacturing practices have been developed and the neurons obtained have been successfully tested in nonhuman primates by teams in Europe, USA and Japan. However, there is a need for translational clinical studies with small molecules tested in vitro, as well as testing of the the efficacy of additional therapies.

Rorqual whales are among the most species rich group of baleen whales (or mysticetes) alive today, yet the monophyly of the traditional grouping (i.e., Balaenopteridae) remains unclear. Additionally, many fossil mysticetes putatively assigned to either Balaenopteridae or Balaenopteroidea may actually belong to stem lineages, although many of these fossil taxa suffer from inadequate descriptions of fragmentary skeletal material. Here we provide a redescription of the holotype of Megaptera miocaena, a fossil balaenopteroid from the Monterey Formation of California, which consists of a partial cranium, a fragment of the rostrum, a single vertebra, and both tympanoperiotics. Kellogg (1922) assigned the type specimen to the genus Megaptera Gray (1846), on the basis of its broad similarities to distinctive traits in the cranium of extant humpback whales (Megaptera novaeangliae (Borowski, 1781)). Subsequent phylogenetic analyses have found these two species as sister taxa in morphological datasets alone; the most recent systematic analyses using both molecular and morphological data sets place Megaptera miocaena as a stem balaenopteroid unrelated to humpback whales. Here, we redescribe the type specimen of Megaptera miocaena in the context of other fossil balaenopteroids discovered nearly a century since Kellogg's original description and provide a morphological basis for discriminating it from Megaptera novaeangliae. We also provide a new generic name and recombine the taxon as Norrisanima miocaena, gen. nov., to reflect its phylogenetic position outside of crown Balaenopteroidea, unrelated to extant Megaptera. Lastly, we refine the stratigraphic age of Norrisanima miocaena, based on associated microfossils to a Tortonian age (7.6-7.3 Ma), which carries implications for understanding the origin of key features associated with feeding and body size evolution in this group of whales.

Alfalfa (Medicago sativa) is an important forage material widely used for animal feed production. Ensiling is an effective method for preserving alfalfa, but it has shown some limitations in the production of high-quality alfalfa silage due to its low water soluble carbohydrates (WSC) content and high buffering capacity. Lactic acid bacteria (LAB) and cellulase are often used as silage additives to promote the ensiling process and enhance fermentation quality.

We previously reported that microRNA-205-5p (miR-205-5p) is significantly decreased in the ErbB2-overexpressing breast epithelial cell line MCF10A-ErbB2 compared with control cells. In this study, we identified a direct target of miR-205-5p, chloride voltage-gated channel 3 (CLCN3). CLCN3 expression was induced by ErbB2 overexpression; this induced expression was then reduced to control levels by the transfection of the miR-205-5p precursor. In RNA-binding protein immunoprecipitation with Ago1/2/3 antibody, CLCN3 was significantly enriched in 293T embryonic kidney cells with miR-205-5p mimic transfection compared with negative control mimic transfection. In luciferase reporter assays using CLCN3 3'-UTR constructs, the miR-205-5p mimic significantly decreased reporter activity of both wild-type and partial mutant constructs in MCF10A-ErbB2 cells. In contrast, no inhibitory effects of the miR-205-5p mimic were detected using the complete mutant constructs. Since miR-205-5p expression in exosomes derived from MCF10A-neo cells was substantially higher than in exosomes derived from MCF10A-ErbB2 cells, we next investigated whether an exosome-mediated miR-205-5p transfer could control CLCN3 expression. To this end, exosomal miR-205-5p derived from MCF10A-neo cells was functionally transferred to MCF10A-ErbB2 cells, which served to decrease the expression of CLCN3. To assess the roles of CLCN3 in breast cancer, we next performed three-dimensional (3D) spheroid proliferation analyses using MCF10A-ErbB2 cells treated with MCF10A-neo-derived exosomes or CLCN3 shRNA stably expressing SKBR3 and MDA-MB-453 breast cancer cells. Our results showed that both treatment with MCF10A-neo-derived exosome and CLCN3 shRNA expression suppressed 3D spheroid proliferation. Collectively, these novel findings suggest that CLCN3 may be a novel direct target of miR-205-5p and this CLCN3/miR-205-5p interaction may serve a pivotal role in regulating breast cancer cellular proliferation under physiological conditions.

Cumulative evidence suggests that long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. This study aims to identify lncRNAs that can serve as new biomarkers for breast cancer diagnosis or screening.

Simulation has emerged as a useful educational tool for the continued training of paramedics. Practicing paramedics are thought to learn through reflecting on their own actions in practice, and it is hoped that simulation could spur similar reflection, which could then lead to practice change. Despite this, there is limited data on how these practitioners use simulated experiences to set learning objectives. This study aimed to explore how simulation training affects self-identification of learning objectives in emergency medical services (EMS) providers (a.k.a. paramedics).

Laboratories unexpectedly carried out pre-heating of polypropylene beverage cups prior to performing a migration test in a proficiency test. Principal component analysis of the data collected showed that the preheating temperature of the cups contributed to an increased variance of the data and distinguishing pre-heating and non-pre-heating groups. This triggered to study the effect of applying such pre-heating on the physical structure of the material and on the migration of additives to food simulant D1 (ethanol 50% v/v). Several cups were pre-heated at selected temperatures and either analyzed with differential scanning calorimetry to establish the degree of crystallinity or used for the migration test. Six target additives from Regulation (EU) No 10/2011 were quantified in the food simulant using HPLC-FLD and LC-MS. Results show that pre-heating of the beverage cups led to a significant change in the degree of crystallinity, resulting in a change of analyte migration in comparison to the migration results from non-pre-heated cups.

Background and Aims: Although autologous bone marrow stem cell (BMSC) transplantation is an effective treatment for liver cirrhosis, there are few reports describing the optimal delivery route and number of injected BMSCs. Methods: A literature search was conducted using PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, and EBSCO. A meta-analysis was performed to assess the effect of BMSCs on liver and coagulation function indices. Subgroup analysis was performed based on number of injected BMSCs, delivery route, and length of follow-up. Results: A total of 15 studies were selected from among 1903 potential studies for analysis. Autologous BMSC transplantation significantly improved aspartate aminotransferase, total bilirubin, albumin, prothrombin time, prothrombin activity, prothrombin concentration, Child-Pugh score, and model for end-stage liver disease. In the subgroup analysis of cell numbers, all four of the indices were significantly improved when the number of BMSCs was >4 × 108. The subgroup analysis referring to the delivery route showed that arterial infusion increased the therapeutic effect over venous infusion. Finally, in the subgroup analysis of follow-up length, the results showed that BMSC therapy significantly improved liver function at 2 weeks after transplantation. In addition, this therapy improved coagulation 4 weeks after the transplant, with a maintenance of efficacy for up to 24 weeks. Conclusions: Autologous BMSC therapy is beneficial for liver improvement and coagulation in patients with liver cirrhosis. The therapeutic effect was generated at 2-4 weeks after transplantation. The effect lasted for 24 weeks but no more than 48 weeks. The greatest benefit to patients was observed with a 4 × 108 autologous BMSC transplant via the hepatic artery.

Emerging evidence suggests that alternative splicing (AS) is modified in cancer and is associated with cancer progression. Systematic analysis of AS signature in glioblastoma (GBM) is lacking and is greatly needed. We profiled genome-wide AS events in 498 GBM patients in TCGA using RNA-seq data, and splicing network and prognostic predictor were built by integrated bioinformatics analysis. Among 45,610 AS events in 10,434 genes, we detected 1,829 AS events in 1,311 genes, and 1,667 AS events in 1,146 genes that were significantly associated with overall survival and disease-free survival of GBM patients, respectively. Five potential feature genes, S100A4, ECE2, CAST, ASPH, and LY6K, were discovered after network mining as well as correlation analysis between AS and gene expression, most of which were related to carcinogenesis and development. Multivariate survival model analysis indicated that these five feature genes could classify the prognosis at AS event and gene expression level. This report opens up a new avenue for exploration of the pathogenesis of GBM through AS, thus more precisely guiding clinical treatment and prognosis judgment.

Background: Exosomes are cell-derived vesicles and bear a specific set of nucleic acids including DNA (exoDNA). Thus, this study is to explore whether exoDNA in malignant pleural effusions (MPEs) could be a novel DNA source for mutation detection of epidermal growth factor receptor (EGFR). Methods: In this study, 52 lung adenocarcinoma patients were enrolled, and EGFR mutation status was detected with tumor tissues as well as cell blocks and exosomes in MPEs. The sensitivity, specificity and consistency of EGFR detection using exosomes were evaluated, compared with gene detection using tumor tissues and cell blocks. And the clinical response of patients who were detected as EGFR mutation in exosomes and treated with EGFR tyrosine kinase inhibitor (EGFR-TKI) was explored. Results: Gene detection using exosomes showed sensitivity of 100%, specificity of 96.55% and coincidence rate of 98.08% (Kappa = 0.961, P < 0.001), compared with detection using tumor tissues and cell blocks. After EGFR-TKI treatment, patients detected as EGFR mutation by exosomes showed efficacy rate of 83% and disease control rate of 100%. And patients who were detected as wild type in tumor tissues or cell blocks but EGFR mutation in exosomes turned up as PR or SD. Conclusions: These results demonstrated that exoDNA in MPEs could be used as a DNA source for EGFR detection in lung adenocarcinoma.

Atypical enteropathogenic E. coli (aEPEC) is a group of diarrhoeagenic Escherichia coli with high diversity of serogroups, which lack the bundle-forming pili (BFP) and genes encoding for shiga toxins. The aim of this study was to isolate, identify and determine virulence and antibiotic resistance profiles of aEPEC O177 strains from cattle feces. A total of 780 samples were collected from beef and dairy cattle and analyzed for the presence of E. coli O177. One thousand two hundred and seventy-two (1272) presumptive isolates were obtained and 915 were confirmed as E. coli species. Three hundred and seventy-six isolates were positively confirmed as E. coli O177 through amplification of rmlB and wzy gene sequences using multiplex PCR. None of these isolates harbored bfpA gene. A larger proportion (12.74%) of the isolates harbored hlyA gene while 11.20, 9.07, 7.25, 2.60, and 0.63% possessed stx2, stx1, eaeA, stx2a , and stx2d , respectively. Most of E. coli O177 isolates carried stx2/hlyA (9.74%). Furthermore, 7.40% of the isolates harbored stx1/stx2 while 7.09% possessed stx1/stx2/hlyA genes. Only one isolate harbored stx1/stx2/hly/eaeA/stx2a/stx2d while 5.11% of the isolates harbored all the four major virulence genes stx1/stx2/hlyA/eaeA, simultaneously. Further analysis revealed that the isolates displayed varied antimicrobial resistance to erythromycin (63.84%), ampicillin (21.54%), tetracycline (13.37%), streptomycin (17.01%), kanamycin (2.42%), chloramphenicol (1.97%), and norfloxacin (1.40%). Moreover, 20.7% of the isolates exhibited different phenotypic multi-drug resistance patterns. All 73 isolates harbored at least one antimicrobial resistance gene. The aadA, streA, streB, erm, and tetA resistance genes were detected separately and/or concurrently. In conclusion, our findings indicate that environmental isolates of aEPEC O177 strains obtained from cattle in South Africa harbored virulence and antimicrobial resistance gene determinants similar to those reported in other shiga-toxin producing E. coli strains and suggest that these determinants may contribute to the virulence of the isolates.

In this study we investigated the antidiabetic and antiobesity effects of aqueous ethanol extracts of traditional kochujang and doenjang. The average α-glucosidase inhibitory activity and adipogenesis inhibitory activity for the kochujang samples were 29.6% and 20.8%, respectively, while those of the doenjang samples were 46.3% and 11.6%, respectively. Therefore, antidiabetic activity is high in doenjang and antiobesity activity is high in kochujang. Kochujang and doenjang components responsible for suppressing the functional effects were investigated by metabolomic analysis. For kochujang, p-coumaric acid, N6,N6,N6-trimethyllysine, threonine, and methionine positively correlated with inhibition of adipogenesis activity, whereas for doenjang, betaine and betaine aldehyde were thought to be responsible for the antidiabetic effects. As p-coumaric acid and betaine were the most probable candidates with functional effects, these two compounds were selected for further analysis. Inhibition of adipogenesis was shown to be 14.0±1.85% for betaine chloride and 38.3±3.27% for p-coumaric acid, suggesting that p-coumaric acid is more effective than betaine against obesity. However, betaine exhibited higher α-glucosidase inhibitory activity than p-coumaric acid. Our results suggest that both kochujang and doenjang can be used against diabetes and obesity. However, clinical trials are necessary to support these results.

Vitamin E, phytosterol, and phospholipids are classes of lipids that are also referred to as nutraceuticals. These lipids are components of foods, which have nutritional as well as numerous other health benefits, and consumption has been shown to prevent certain deadly diseases. These compounds can only be obtained from plant products; there is therefore a need for more research on the availability of these compounds from common food sources. Oils extracted from Citrullus colocynthis and Parkia biglobosa seeds were analysed for vitamin E, phospholipid, and phytosterol contents using a chromatographic technique. The seeds had total vitamin E contents of 53.47 and 42.57 mg/100 g, phytosterol contents of 260 and 451 mg/100 g, and phospholipid contents of 409 and 1,603 mg/100 g for C. colocynthis and P. biglobosa, respectively. Thus, consumption of these two plants as condiments will help people consume these essential lipids and could serve as dietary supplements to prevent and combat occurrence of certain deadly diseases; this is important as the world is revolving towards disease prevention rather than curing, which is often more expensive and difficult.

Grass carp (Ctenopharyngodon idellus; n = 320) were received four different diets for 56 days. The experimental diets were: fishmeal (FM) containing 10% fishmeal (without rapeseed meal), and rapeseed meal (RM) containing 50% rapeseed meal (without fishmeal), and two semi-purified diets either without (T0) or with 1.25% (T1) supplemental hydrolysable tannin. The approximate content of tannin in the RM diet was 1.31%, which was close to that of T1, while the tannin content of FM was close to that of T0. The weight gain rate of grass carp of the RM group was significantly lower than that of the FM group, while the feeding conversion ratio and the feeding rate were significantly higher in the T1 group than in T0. The muscle lipid content was significantly lower in RM than in FM, while T1 was lower than T0. Intestinal activities of trypsin and α-amylase were significantly higher in T1 and RM groups compared with the other treatments. The hepatic activities of aspartate aminotransferase and alanine aminotransferase were lower in T1 and RM groups compared with the other treatments, while hepatic glycogen, and malonaldehyde were significantly higher in T1 and RM groups. In serum, the total protein and globulin contents were significantly higher in T1 and RM groups, while albumin was significantly lower in the RM group compared to the FM group. High-throughput sequencing showed that Proteobacteria, Firmicutes, and Actinobacteria were the dominant bacterial phyla among groups. The intestinal microbial diversity was higher in T1 and RM. Redundancy analysis showed that tannin, rapeseed meal, and intestinal trypsin activity were positively or negatively correlated with the relative abundance of several different intestinal microbiota at phylum and/or genus levels. The results indicated that 1.25% tannin could not be the main reason for the poor growth of grass carp of the RM group; however, the protein metabolism was disturbed, the absorption of carbohydrate was improved, and the accumulation of lipid had decreased. Furthermore, tannin and rapeseed meal supplementations modulated the intestinal microbiota, and may sequentially regulate the intestinal function by fermenting dietary nutrition, producing digestive enzymes, and modulating probiotics.

The enzyme ADP-glucose pyrophosphorylase (ADP-Glc PPase) controls the biosynthesis of glycogen in bacteria and starch in plants. It is regulated by various activators in different organisms according to their metabolic characteristics. In Escherichia coli, the major allosteric activator is fructose 1,6-bisphosphate (FBP). Other potent activator analogs include 1,6-hexanediol bisphosphate (HBP) and pyridoxal 5'-phosphate (PLP). Recently, a crystal structure with FBP bound was reported (PDB ID: 5L6S). However, it is possible that the FBP site found is not directly responsible for the activation of the enzyme. We hypothesized FBP activates by binding one of its phosphate groups to another site ("P1") in which a sulfate molecule was observed. In the E. coli enzyme, Arg40, Arg52, and Arg386 are part of this "P1" pocket and tightly complex this sulfate, which is also present in the crystal structures of ADP-Glc PPases from Agrobacterium tumefaciens and Solanum tuberosum. To test this hypothesis, we modeled alternative binding conformations of FBP, HBP, and PLP into "P1." In addition, we performed a scanning mutagenesis of Arg residues near potential phosphate binding sites ("P1," "P2," "P3"). We found that Arg40 and Arg52 are essential for FBP and PLP binding and activation. In addition, mutation of Arg386 to Ala decreased the apparent affinity for the activators more than 35-fold. We propose that the activator binds at this "P1" pocket, as well as "P2." Arg40 and Arg52 are highly conserved residues and they may be a common feature to complex the phosphate moiety of different sugar phosphate activators in the ADP-Glc PPase family.

Cranial radiotherapy (CRT) is an important part of brain tumor treatment, and although highly effective, survivors suffer from long-term cognitive side effects. In this study we aim to establish late-term imaging markers of CRT-induced brain injury and identify functional markers indicative of cognitive performance. Specifically, we aim to identify changes in executive function, brain metabolism, and neuronal organization.

Our aim was to compare the effects of Internet-delivered cognitive therapy (CT) and behavior therapy (BT) against a waitlist (WL) condition to better understand their unique contribution in the treatment of insomnia.

Cytomegalovirus (CMV) seropositivity and anti-CMV immunoglobulin G (IgG) levels are associated with adverse health outcomes in elderly populations. Among people living with human immunodeficiency virus (PLWH), CMV seropositivity has been associated with persistent CD8 T-cell elevation and increased risk of developing non-AIDS comorbidities despite long-term antiretroviral therapy (ART). Herein, we investigated whether CMV seropositivity and elevation of anti-CMV IgG levels were associated with increased epithelial gut damage, microbial translocation, and systemic inflammation.

Poor aqueous solubility and dissolution of drug candidates drive key decisions on lead series optimization during drug discovery, on formulation optimization, and clinical studies planning during drug development. The interpretation of the in vivo relevance of early pharmaceutical profiling is often confounded by the multiple factors affecting oral systemic exposure. There is growing evidence that in vitro drug solubility may underestimate the true in vivo solubility and lead to drug misclassification. Based on 10 poorly water-soluble tyrosine kinase inhibitors, this paper demonstrates the use of physiologically-based pharmacokinetic (PK) analysis in combination with early clinical PK data to identify drugs whose absorption is truly limited by solubility in vivo and, therefore, expected to exhibit food effect. Our study supports a totality of evidence approach using early clinical data to guide decisions on conducting drug interaction studies with food and acid-reducing agents.