Obstructive sleep apnea (OSA) is a common condition in patients with chronic kidney disease (CKD). It may worsen renal function in CKD patients and is associated with uncontrolled blood pressure. Although OSA is found in up to 80% of CKD patients, there are limited data available on its clinical features in patients with and without CKD.

Wild animals are faced with a broad range of environmental stressors and research is needed to better understand their effect on populations. Hormone analysis based on enzyme immunoassays (EIAs) can provide valuable information on adrenocortical activity (stress), and assessment of cortisol in hair may allow the quantification of cortisol production. To validate hair hormone analysis, we compared two EIAs based on antibodies against cortisol-3-CMO-BSA and cortisol-21-HS-BSA for hair glucocorticoid (hGC) measurements in Egyptian mongoose, Iberian lynx, Alpine marmot, Asiatic black bear, spotted hyena and cheetah, with results obtained by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) measurements. Both EIAs were also characterized by HPLC immunograms. Our results revealed that the cortisol-21-HS EIA measured 2.3- to 12-fold higher hGC concentrations than the cortisol-3-CMO assay. In dependence of the species, high-performance liquid chromatography (HPLC) immunograms showed that up to 70% of immunoreactivities determined by the cortisol-21-HS constituted of unknown unpolar compounds leading to an overestimation of hGC. The cortisol-3-CMO EIA expressed a better specificity, with 32.1-67.4% of immunoreactivity represented by cortisol and cortisone. The LC-MS/MS analyses (gold standard) revealed that the cortisol-3-CMO EIA also resulted in an (up to 3-fold) overestimation of hGC, but EIA results were correlated with LC-MS/MS in the mongoose, the lynx, the spotted hyena and the marmot. No correlation was obtained for Asiatic black bears. As a result of our study, we strongly recommend to test any cortisol EIA for its specificity towards extracted hair components. In all analyzed species, except the Asiatic black bear, cortisone and cortisol were simultaneously present in hair extracts; consequently, an appropriate EIA should cross-react to these two glucocorticoid hormones and express negligible affinity towards substances with less polarity than corticosterone. Choosing the wrong EIA for hGC analyses may lead to overestimations of hGC or-in the worst case-to results that do not mirror real adrenocortical activity.

The physical status of patients who received enteral nutrition is still unclear. We aimed to compare the physical functional status among older adult patients who underwent percutaneous endoscopic gastrostomy (PEG) and those with nasogastric feeding.

Ball velocity, accuracy and game statistics represent three methods used to measure pitching performance. However, individual determinants of pitching performance are more elusive.

The selection of pluripotent stem cell (PSC)-derived cells for tissue modeling and cell therapy will be influenced by their response to the tissue environment, including the extracellular matrix (ECM). Whether and how instructive memory is imprinted in adult ECM and able to impact on the tissue specific determination of human PSC-derived developmentally fetal mesodermal precursor (P-meso) cells is investigated. Decellularized ECM (dECM) is generated from human heart, kidney, and lung tissues and recellularized with P-meso cells in a medium not containing any differentiation inducing components. While P-meso cells on kidney dECM differentiate exclusively into nephronal cells, only beating clusters containing mature and immature cardiac cells form on heart dECM. No tissue-specific differentiation of P-meso cells is observed on endoderm-derived lung dECM. P-meso-derived endothelial cells, however, are found on all dECM preparations independent of tissue origin. Clearance of heparan-sulfate proteoglycans (HSPG) from dECM abolishes induction of tissue-specific differentiation. It is concluded that HSPG-bound factors on adult tissue-derived ECM are essential and sufficient to induce tissue-specific specification of uncommitted fetal stage precursor cells.

Glioma initiating cells (GICs) function as the seed for the propagation and relapse of glioma. Designing a smart and efficient strategy to target the GICs and to suppress the multiple signaling pathways associated with stemness and chemoresistance is essential to achieving a cancer cure. Inspired by the metabolic difference in endocytosis between GICs, differentiated glioma cells, and normal cells, a tailored lipoprotein-like nanostructure is developed to amplify their internalization into GICs through receptor-stimulated macropinocytosis. As CXCR4 is highly expressed on GICs and glioma tumor sites, meanwhile, the activation of CXCR4 induces the receptor-stimulated macropinocytosis pathway in GICs, this CXCR4 receptor-stimulated lipoprotein-like nanoparticle (SLNP) achieves efficient accumulation in GICs in vitro and in vivo. By carrying microRNA-34a in the core, this tailored SLNP reduces sex-determining region Y-box 2 and Notch1 expression, powerfully inhibits GICs stemness and chemoresistance, and significantly prolongs the survival of GICs-bearing mice. Taken together, a tailored lipoprotein-based nanostructure realizes efficient GICs accumulation and therapeutic effect through receptor-stimulated macropinocytosis, providing a powerful nanoplatform for RNA interference drugs to combat glioma.

Aerial spraying of products to kill larvae or adult mosquitoes is a public health measure used to control vector-borne diseases. In some outbreaks, the intervention has evoked controversy and community resistance. This study evaluated how local opinion leaders in US localities affected by Zika think about community engagement in public health policies for outbreak response. In December 2017 through March 2018, 4 focus groups were convened in Houston, TX, New Orleans, LA, Miami, FL, and Brooklyn, NY. They discussed a hypothetical scenario that featured vector control by aerial spraying. Participants (N = 20) more readily accepted this vector control method under 4 conditions: They were informed of alternatives, benefits, and risks for human health and the environment. Public health claims were backed by objective evidence and an authority figure genuinely working in the community's interests. They received timely notice about how to mitigate toxin exposure. And, aerial spraying helped to protect vulnerable individuals. The community engagement requirements of the local opinion leaders resonate with core principles of recent public health ethics frameworks: namely, personal autonomy, transparency, reasonableness, and solidarity. Participants foresaw problems with community consent in an era of growing social media use and mistrust in governmental and scientific authority. They also debated whether health authorities should use moral-based arguments, in addition to science-based ones, to communicate aerial spraying's risks and benefits.

•An online MI intervention was recently developed to complement ICBT.•Intervention consists of videos, exercises, feedback to better simulate face-to-face MI.•Study evaluated intervention impact on motivation and perceptions of MI.•Ratings of motivation and MI perceptions significantly increased from pre- to post-MI.•Future research should explore longer term impact of online MI on ICBT.

Chemosensitization is an effective strategy to overcome the drawbacks of arsenic trioxide (As2O3) treatment, which may be possible through the use of dietary supplements in combination. The present investigation evaluates the synergistic mechanism of action of vitamins, such as L-ascorbic acid (L-AA) and α-tocopherol (α-TOC) in As2O3 chemotherapy using human leukemia (HL-60) cells. In vitro assays on the cytotoxicity of As2O3 and vitamins and cellular apoptotic evidences were done; a proteomic investigation with mass spectrometry was also performed. The combination of L-AA and α-TOC potentiates As2O3 cytotoxicity in HL-60 cells, substantiated by depletion in antioxidant status, mitochondrial transmembrane potential, and inhibition of nuclear factor erythroid 2-related factor 2 and B-cell lymphoma 2 transcription factors. Mass spectrometry results showed decreased expression of proteins regulating cell cycle and translation in cells treated with As2O3, L-AA, and α-TOC when compared with As2O3-treated sample. In addition, this combination treatment identified numerous proteins associated with apoptosis and cell stress. HL-60 cells became more prone to As2O3 on exposure to L-AA and α-TOC, indicating that this combination may be a promising approach to increase the outcome of As2O3 chemotherapy.

Background: Glioma is the most common malignant tumor of the central nervous system, and often displays invasive growth. Recently, circular RNA (circRNA), which is a novel non-coding type of RNA, has been shown to play a vital role in glioma tumorigenesis. However, the functions and mechanism of lipocalin-2 (Lcn2)-derived circular RNA (hsa_circ_0088732) in glioma progression remain unclear. Methods: We evaluated hsa_circ_0088732 expression by fluorescence in situ hybridization (FISH), Sanger sequencing, and PCR assays. Cell apoptosis was evaluated by flow cytometry and Hoechst 33258 staining. Transwell migration and invasion assays were performed to measure cell metastasis and viability. In addition, the target miRNA of hsa_circ_0088732 and the target gene of miR-661 were predicted by a bioinformatics analysis, and the interactions were verified by dual-luciferase reporter assays. RAB3D expression was analyzed by an immunochemistry assay, and E-cadherin, N-cadherin, and vimentin protein expression were examined by western blot assays. A mouse xenograft model was developed and used to analyze the effects of hsa_circ_0088732 on glioma growth in vivo. Results: We verified that hsa_circ_0088732 is circular and highly expressed in glioma tissues. Knockdown of hsa_circ_0088732 induced glioma cell apoptosis and inhibited glioma cell migration, invasion, and epithelial-mesenchymal transition (EMT). We found that hsa_circ_0088732 negatively regulated miR-661 by targeting miR-661, and RAB3D was a target gene of miR-661. In addition, inhibition of miR-661 promoted glioma cell metastasis and suppressed cell apoptosis. Knockdown of RAB3D induced cell apoptosis and suppressed cell metastasis. Moreover, hsa_circ_0088732 accelerated glioma progression through its effects on the miR-661/RAB3D axis. Finally, results from a mouse xenograft model confirmed that knockdown of hsa_circ_0088732 induced miR-661 expression, resulting in suppression of RAB3D expression and inhibition of tumor growth in vivo. Conclusion: We demonstrated that hsa_circ_0088732 facilitated glioma progression by sponging miR-661 to increase RAB3D expression. This study provides a theoretical basis for understanding the development and occurrence of glioma, as well as for the development of targeted drugs.

Chronic urticaria (CU) is defined as the continuous or intermittent presence of urticaria for a period exceeding 6 weeks and sometimes occurring with angioedema. Between 66 and 93% of patients with CU have chronic spontaneous urticaria (CSU), the precise pathogenesis of which is largely unknown. The aim of this study was to determine the relationship between gut microbiota and serum metabolites and the possible pathogenesis underlying CSU. We collected feces and blood samples from CSU patients and healthy controls and the relationship between gut microbiota and serum metabolites was assessed using 16S rRNA gene sequencing and untargeted metabolomic analyses. The CSU group exhibited decreased alpha diversity of the microbial population compared to the control group. The abundance of unidentified Enterobacteriaceae was increased, while the abundance of Bacteroides, Faecalibacterium, Bifidobacterium, and unidentified Ruminococcaceae was significantly reduced in CSU patients. The serum metabolome analysis revealed altered levels of docosahexaenoic acid, arachidonic acid, glutamate, and succinic acid, suggesting changes in unsaturated fatty acids and the butanoate metabolism pathway. The combined serum metabolomics and gut microbiome datasets were correlated; specifically, docosahexaenoic acid, and arachidonic acid were positively correlated with Bacteroides. We speculate that alterations in gut microbes and metabolites may contribute to exacerbated inflammatory responses and dysregulated immune function with or without regulatory T cell dependence in the pathogenesis of CSU.

For decades, mass drug treatment with praziquantel (PZQ) has been utilized to treat schistosomiasis, yet reinfection and the risk of drug resistance are among the various factors precluding successful elimination of schistosomiasis. Tractable models that replicate "real world" field conditions are crucial to effectively evaluate putative schistosomiasis vaccines. Herein, we describe the cellular immune responses and cytokine expression profiles under field conditions that include prior infection with schistosomes followed by treatment with PZQ. Baboons were exposed to Schistosoma mansoni cercariae through trickle infection over 5 weeks, allowed for chronic disease to develop, and then treated with PZQ. Peripheral blood mononuclear cells (PBMCs) were monitored for cellular immune response(s) at each disease stage and PZQ therapy. After initial infection and during chronic disease, there was an increase in non-classical monocytes, NK and NKT cells while the CD4:CD8 T cell ratio inverted from a 2:1 to 1:2.5. The cytokine expressions of PBMCs after trickle infections were polarized more toward a Th2 response with a gradual increase in Th1 cytokine expression at chronic disease stage. Following PZQ treatment, with the exception of an increase in B cells, immune cell populations reverted back toward naïve levels; however, expression of almost all Th1, Th2, and Th17 cytokines was significantly increased. This preliminary study is the first to follow the cellular immune response and cytokine expression profiles in a non-human primate model simulating field conditions of schistosomiasis and PZQ therapy, providing a promising reference in predicting the immune response to future vaccines for schistosomiasis.

There are no prior publications or submissions with any overlapping information, including studies and patients. The study data have not been presented as an abstract or poster before the submission. Objectives: The study was conducted to analyze the changes of baroreflex sensitivity and heart rate variability from supine to upright standing in children and adolescents with orthostatic hypertension to explore whether and how the autonomic nerve regulation was involved in the development of pediatric orthostatic hypertension. Methods: This case-control study included twenty-five children with orthostatic hypertension (the patient group) and twenty-six healthy controls (the control group). All subjects underwent a standing test, during which their hemodynamic parameters were continuously monitored by a Finapres Medical System, and baroreflex sensitivity and heart rate variability were calculated. Results: The demographic characteristics, supine baroreflex sensitivity, and supine heart rate variability including time domain and frequency domain indices did not differ between the patients with orthostatic hypertension and healthy subjects (P > 0.05). However, a more obvious drop of baroreflex sensitivity and a greater increase of low frequency/high frequency ratio from supine to upright were observed in subjects with orthostatic hypertension compared with those in the healthy children (P < 0.001 and P < 0.01, respectively). Changes of baroreflex sensitivity were negatively related to mean arterial pressure changes from supine to upright in all subjects (P < 0.01), and the increases in low frequency/high frequency ratio from supine to standing were positively correlated with those in mean arterial pressure in the study subjects (P < 0.001). Conclusion: Upright sympathetic overactivation is associated with pediatric orthostatic hypertension.

Background: Childhood obesity is an important public health issue. Approximately 20% of 2-4 year olds are overweight or obese, meaning 1 in 5 Australian children start school above a healthy weight. In the state of New South Wales (NSW) the combined prevalence of childhood overweight and obesity is significantly higher among children from low socioeconomic status backgrounds and children from regional, rural and remote areas. This paper describes implementation of a healthy eating and active play program (Munch & Move) for center-based early childhood education and care (ECEC) services aimed at influencing healthy behaviors in young children in NSW, Australia. It shows changes over time including a focus on disadvantaged, Aboriginal and remote communities. It also discusses the challenges and future opportunities for the program. Methods: Routine data in relation to service delivery (reach) and implementation indicators are collected by Local Health District staff. Fifteen implementation indicators (known as practices) were introduced to monitor the implementation of Munch & Move (six related to promoting and encouraging healthy eating, four related to improving physical activity, two related to small screen recreation; and three related to quality of service delivery). Results: As of 30 June 2017, 88.4% of ECEC services have staff trained in Munch & Move. Of the 15 practices related to promoting and encouraging healthy eating, increasing physical activity and improving the quality of service delivery 13 practices saw significant improvements between 2012 and 2017. This was consistent for services with a high proportion of Aboriginal children and for services in disadvantaged and remote communities. There has been a statistically significant increase in the proportion (37.6-81.0%, p < 0.0001) and type of ECEC services (preschools 36.1-81.3%, p < 0.0001, long day care 38.6-81.0%, p < 0.0001, and occasional care 34.0-74.6%, p < 0.0001) that have implemented the program since 2012 as well as in services with a high proportion of Aboriginal children (33.6-85.2% p < 0.0001), services in disadvantaged communities (37.4-83.3% p < 0.001), and services in remote communities (27.8-59.4% p < 0.0139). Discussion: This paper demonstrates that Munch & Move has seen large improvements in the delivery of training, practice achievements and program adoption in ECEC services across NSW including services in disadvantaged and remote communities and that have a higher proportion of Aboriginal children.

Background: Normal motor development and adequate levels of physical activity engagement during the early years of life form the foundation of long-term psychological and physiological health. This is one of the very few studies that investigate the stability and relationships of motor competence and physical activity in preschool children. Methods: Baseline and 12 month follow-up data of physical activity and motor competence of 550 preschool children aged 2-6 years from the Swiss Preschoolers' Health Study were used for this work. Physical activity data, expressed in counts per minute for total physical activity and minutes per day for time spent moderately-to-vigorously physically active, were collected over 1 week using accelerometers. Motor competence was assessed with the Zurich Neuromotor Assessment. Both motor competence and physical activity were age- and sex-adjusted. To examine the individual stability of physical activity and motor competence and reciprocal cross-sectional and longitudinal effects between these two domains, a latent variable cross-lagged panel model where motor competence was represented through a latent construct was examined using structural equation modeling. Results: A weak cross-sectional correlation of motor competence with total physical activity (r = 0.24) and moderate-to-vigorous physical activity (r = 0.23) was found. Motor competence exhibited high stability (β = 0.82) in the preschool years and physical activity was moderately stable with estimates ranging from β = 0.37 for total physical activity to β = 0.48 for moderate-to-vigorous physical activity. In contrast to the autoregressive coefficients denoting individual stability, both cross-lagged effects were negligible indicating that physical activity was not a determinant of motor competence or vice versa. Conclusions: Motor competence and physical activity developed independently of each other in early childhood. Although measures of quantity and intensity of physical activity were not related to motor development, specific movement experiences and practice-which are not reflected by accelerometry-may be needed for skill development. Future research should focus on examining what type of physical activity is important for motor development and how to assess it, and also whether the relationship between physical activity and motor competence evolves over time. Clinical Trial Registration: Current Controlled Trials ISRCTN41045021 (date of registration: 21.03.14).

Protein ubiquitination is a key post-translational modification regulating a wide range of biological processes. Ubiquitination involves the covalent attachment of the small protein ubiquitin to a lysine of a protein substrate. In addition to its well-established role in protein degradation, protein ubiquitination plays a role in protein-protein interactions, DNA repair, transcriptional regulation, and other cellular functions. Understanding the mechanisms and functional relevance of ubiquitin as a signaling system requires the generation of antibodies or alternative reagents that specifically detect ubiquitin in a site-specific manner. However, in contrast to other post-translational modifications such as acetylation, phosphorylation, and methylation, the instability and size of ubiquitin-76 amino acids-complicate the preparation of suitable antigens and the generation antibodies detecting such site-specific modifications. As a result, the field of ubiquitin research has limited access to specific antibodies. This severely hampers progress in understanding the regulation and function of site-specific ubiquitination in many areas of biology, specifically in epigenetics and cancer. Therefore, there is a high demand for antibodies recognizing site-specific ubiquitin modifications. Here we describe a strategy for the development of site-specific ubiquitin antibodies. Based on a recently developed antibody against site-specific ubiquitination of histone H2B, we provide detailed protocols for chemical synthesis methods for antigen preparation and discuss considerations for screening and quality control experiments.

In this work, keratin sponges were prepared by freeze-drying method and tested for adsorption of Azure A and Methyl Orange dyes. The obtained materials showed a porosity of 99.92% and a mean pore size dimension of about 91 μm. The use of oxidized sucrose with a heating treatment at 150°C was demonstrated to be a useful crosslinking procedure alternative to the conventional glutaraldehyde. Keratin sponges showed a maximum adsorption capacity of 0.063 and of 0.037 mmol/g for Azure A and Methyl Orange, respectively. The absorption of the cationic dye Azure A onto keratin sponges was better described by Freundlich model while the isotherm adsorption of the anionic Methyl Orange was found to correlate with both Langmuir and Freundlich models. The mean free energies evaluated by using the D-R model indicated a physisorption of Methyl Orange and a chemisorptions of Azure A onto keratin sponges. Finally, the functionalization of keratin sponges with Zn Al hydrotalcites nanoparticles did not affect the adsorption performances of the adsorbent toward the cationic dye Azure A, while it improved those toward the anionic Methyl Orange, increasing the related removal efficiencies from 43 to 96%. Collectively, the reported data indicates that the combination of keratin with hydrotalcites nanoparticles is a good strategy to obtain more functional adsorbent materials of potential interest for water treatment and purification.

In the present study, we tried to describe the role of miR-29c-3p in esophageal carcinoma (EC) and the relationship of miR-29c-3p with CCNA2 as well as cell cycle, accordingly revealing the potential molecular mechanism across cell proliferation, migration and invasion.

Bioprinting technology merges engineering and biological fields and together, they possess a great translational potential, which can tremendously impact the future of regenerative medicine and drug discovery. However, the molecular effects elicited by thermal inkjet bioprinting in breast cancer cells remains elusive. Previous studies have suggested that bioprinting can be used to model tissues for drug discovery and pharmacology. We report viability, apoptosis, phosphorylation, and RNA sequence analysis of bioprinted MCF7 breast cancer cells at separate timepoints post-bioprinting. An Annexin A5-FITC apoptosis stain was used in combination with flow cytometry at 2 and 24 h post-bioprinting. Antibody arrays using a Human phospho-MAPK array kit was performed 24 h post-bioprinting. RNA sequence analysis was conducted in samples collected at 2, 7, and 24 h post-bioprinting. The post-bioprinting cell viability averages were 77 and 76% at 24 h and 48 h, with 31 and 64% apoptotic cells at 2 and 24 h after bioprinting. A total of 21 kinases were phosphorylated in the bioprinted cells and 9 were phosphorylated in the manually seeded controls. The RNA seq analysis in the bioprinted cells identified a total of 12,235 genes, of which 9.7% were significantly differentially expressed. Using a ±2-fold change as the cutoff, 266 upregulated and 206 downregulated genes were observed in the bioprinted cells, with the following 5 genes uniquely expressed NRN1L, LUCAT1, IL6, CCL26, and LOC401585. This suggests that thermal inkjet bioprinting is stimulating large scale gene alterations that could potentially be utilized for drug discovery. Moreover, bioprinting activates key pathways implicated in drug resistance, cell motility, proliferation, survival, and differentiation.

In recent years, the biological synthesis of silver nanoparticles (AgNPs) from microorganisms has become an emerging trend for developing biocompatible nanomaterials that finds applications in nano and biomedical sectors. In the present study, we demonstrated a facile, green and eco-friendly method for AgNPs synthesis using the endophytic fungi (Colletotrichum incarnatum DM16.3) isolated from medicinal plant Datura metel and its in vitro antithrombin and cytotoxic activity. At first, biosynthesis of colloidal AgNPs was predicted by visual observation of color change and UV-visible spectra demonstrated specific surface plasmon resonance peak at 420 nm which confirmed the presence of nanoparticles. Microscopic analyses revealed the structure of highly aggregated, spherical and crystalline AgNPs in the diameter range of 5-25 nm. Transform infrared spectroscopy (FT-IR) spectral analysis confirmed the presence of probable biomolecules required for the reduction of silver ions. In vitro evaluation of thrombin activity demonstrates that AgNPs could exert strong inhibition against both thrombin activity (87%) and thrombin generation (84%), respectively. Further, in silico based mechanistic analysis yielded a better insight in understanding the probable amino acids responsible for AgNPs binding with thrombin protein. Similarly, in vitro cytotoxicity of synthesized AgNPs on human epithelial cells using MTT assay did not produce any substantial effects after 24 h exposure which indicates excellent biocompatibility nature, whereas notable toxicity was observed on human cancerous (HeLa) cells at 50 μg/mL (IC50 value). In addition, assessment of AgNPs at 10 μg/mL concentration via crystal violet method on biofilm forming Gram-positive (Vibrio cholerae) and Gram-negative bacteria (Bacillus cereus) revealed inhibition up to 85 and 46%, respectively. Overall, this study showed the possibility of microbially synthesized AgNPs as a potent inhibitor for managing acute thrombosis and highlighted their role for other biomedical applications.