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Kratom is an herbal supplement which is used for its stimulating properties and pain reduction due to interaction with opioid receptors. Kratom overdose may cause fatality. A 56-year-old man was admitted to the emergency department with severe jaundice and liver failure. His total bilirubin reached at 70.6 mg/dL, but extensive workup did not show any liver mass. Family informed that the patient was taking Kratom. Plasma exchange was suggested as an unconventional therapy and consent from the patient was obtained because this procedure has never been performed to treat Kratom toxicity before. After four procedures, his total bilirubin was reduced to 23.9 mg/dL and his clinical condition improved significantly. Finally on day 5 he was discharged at stable condition with a total bilirubin value of 21.3 mg/dL. There is no antidote for Kratom, and treatment is supportive. To our knowledge this is the first report of reversing Kratom poisoning using plasma exchange. [ABSTRACT FROM AUTHOR]

The processing of dietary lipids in the intestinal lumen involves metabolic processes of the host and also of the microbial organisms that reside in the gut. Whereas, in the edible oil, there are also other minor content of components, such as fat-soluble micronutrients. The dietary oils and fats, as well as these accompanied components have different effects on the gut microbiota structure, which is also closely associated with gut inflammation, and the host health. This review of the literature highlights the effects of dietary oils and fats, as well as the minor content of accompanied components on the gut microbiota, and the gut inflammation, with special respect to illustrating the roles of high fat diet (HFD), fatty acid composition, the n6/n3 poly-unsaturated fatty acid (PUFA) ratio, the conjugated linoleic acids (CLAs), the fatty acid chain length and triacylglycerol (TAG) structure, the fat-soluble micronutrients, and some other minor content of components, such as trans -fatty acids (TFAs). The interactions between the dietary oils and fats and gut microbiota are also briefly discussed. The diversity in dietary oils and fats composition affects the gut microbiota structure, and the unhealthy dietary lipid pattern, such as HFD or diet rich in saturated fats may lead to the gut microbiota dysbiosis not only by decreasing their richness and diversity, but also by changing the Firmicutes to Bacteroidetes ratio, further raising the intestinal pro-inflammatory cytokines levels and permeability of the intestine mucosa. The balanced dietary oils and fats intake is recommended to achieve the appropriate fatty acid consumption ratio, especially for the n6/n3 PUFA ratio, thereafter, maintaining both of the gut microbiota homeostasis and host health. The accompanied minor content of fat-soluble bioactive components also showed positive roles for the overall gut health. However, more clinic evidence should be provided in future studies. [Display omitted] • Influences of dietary oils and fats composition on the gut microbiota and gut inflammation were elaborated. • The roles of the accompanied minor components in dietary oils and fats on gut homeostasis were reported. • Interactions between dietary oils and fats, and gut microbiota in the intestinal inflammation regulation were discussed. [ABSTRACT FROM AUTHOR]

The cooking fumes generated from thermal cooking oils contains various of hazardous components and shows deleterious health effects. The edible oil refining is designed to improve the oil quality and safety. While, there remains unknown about the connections between the characteristics and health risks of the cooking fumes and oils with different refining levels. In this study, the hazardous compounds, including aldehydes, ketones, polycyclic aromatic hydrocarbons (PAHs), and particulate matter (PM) in the fumes emitted from heated soybean oils with different refining levels were characterized, and their health risks were assessed. Results demonstrated that the concentration range of aldehydes and ketones (from 328.06 ± 24.64 to 796.52 ± 29.67 μg/m3), PAHs (from 4.39 ± 0.19 to 7.86 ± 0.51 μg/m3), and PM (from 0.36 ± 0.14 to 5.08 ± 0.15 mg/m3) varied among soybean oil with different refining levels, respectively. The neutralized oil showed the highest concentration of aldehydes and ketones, whereas the refined oil showed the lowest. The highest concentration levels of PAHs and PM were observed in fumes emitted from crude oil. A highly significant (p < 0.001) positive correlation between the acid value of cooking oil and the concentrations of PM was found, suggesting that removing free fatty acids is critical for mitigating PM concentration in cooking fumes. Additionally, the incremental lifetime cancer risk (ILCR) values of PAHs and aldehydes were 5.60 × 10−4 to 8.66 × 10−5 and 5.60 × 10−4 to 8.66 × 10−5, respectively, which were substantially higher than the acceptable levels (1.0 × 10−6) established by US EPA. The present study quantifies the impact of edible oil refining on hazardous compound emissions and provides a theoretical basis for controlling the health risks of cooking fumes via precise edible oil processing. [Display omitted] • Hazardous compound profiles changed with increasing cooking oil refining levels. • Neutralized oil showed highest aldehydes and ketones concentrations and associated health risks. • Degumming and neutralization significantly affected the PAHs concentrations. • Removal of FFAs in cooking oil is critical for mitigating PM concentrations. • ILCR values of all groups were found substantially higher than the acceptable levels. [ABSTRACT FROM AUTHOR]

Vitiligo is an autoimmune depigmenting disorder with no effective and safe treatments. Its pathogenesis is not fully elucidated. This substudy of a randomized, double-blind, placebo-controlled phase 2b trial (NCT03715829) evaluated effects of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on skin and blood biomarkers in participants with nonsegmental vitiligo (NSV). Sixty-five adults with NSV participated in the substudy and received daily treatment for 24 weeks with placebo (n = 14) or ritlecitinib with or without a 4-week loading dose: 200 (loading dose)/50 mg (n = 13), 100/50 mg (n = 12), 50 mg (n = 11), 30 mg (n = 8), or 10 mg (n = 6). Skin (lesional and nonlesional) biopsy samples were obtained at baseline and at 4 and 24 weeks. Changes from baseline to weeks 4 and 24 in skin and blood molecular and cellular biomarkers were evaluated by RNA sequencing, quantitative real-time PCR, proteomic analysis, and flow cytometry. Ritlecitinib-treated groups showed downregulation of immune biomarkers and upregulation of melanocyte-related markers at weeks 4 and 24 compared to baseline and/or placebo. Significant reductions were seen in CD3+/CD8+ T-cell infiltrates, with significant increases in melanocyte markers (tyrosinase; Melan-A) in NSV lesions in the 50 mg ritlecitinib groups (both P <.05). There was significant, dose-dependent downregulation in T-cell activation, NK, cytotoxic, and regulatory markers in lesional skin (IL-2, IL2-RA, IL-15, CCR7, CD5, CRTAM, NCR1, XCL1, KIR3DL1, FASLG, KLRD; P <.05). T H 1 and T H 2 markers were also downregulated in lesional skin and blood in a dose-dependent manner (P <.05). Changes in immune biomarkers correlated with clinical response. Ritlecitinib significantly downregulated proinflammatory biomarkers and increased melanocyte products in skin and blood of participants with NSV, suggesting its potential in treatment. Ritlecitinib-mediated changes positively correlated with clinical response. [ABSTRACT FROM AUTHOR]

The retinal pigment epithelium (RPE) serves dual roles: it acts as a selective barrier and also as a regulator for the photoreceptor layer situated above it. The RPE is considered a crucial target for halting the development and progression of diabetic retinopathy (DR). This study focuses on understanding the protective role of blueberry anthocyanin extracts (BAEs), particularly its anti-oxidant constituent, cyanidin-3-O-glucoside (C3G), against damage to RPE cells induced by high glucose (HG) levels. The findings revealed that the BAEs mitigated damage to HG-induced ARPE-19 cells by decreasing the intracellular reactive oxygen species (ROS) levels, which improved cell morphology and cell viability (p < 0.01). Importantly, these cytoprotective effects were linked to the C3G rich in BAEs. The underlying mechanism may involve C3G interrupting the ROS generation feedback loop by downregulating REDD1 expression, which in turn enhanced the retinal Nrf2 antioxidant response to HG through the promotion of the GSK3β phosphorylation at Ser-9. Moreover, C3G suppressed VEGFA expression by inhibiting REDD1 levels in HG-induced ARPE-19 cells, subsequently preventing an increase in vascular permeability. In conclusion, this study suggested that the C3G relieved HG-induced oxidative stress damage in ARPE-19 cells via REDD1/GSK3β pathway and inhibited an increase in vascular permeability by downregulating VEGFA expression. These insights could shed light on how this natural bioactive compound can help manage HG-associated eye disorders like DR. [Display omitted] • BAEs effectively alleviated the oxidative damage of ARPE-19 cells caused by high glucose. • The protective effect of BAEs on ARPE-19 cells was positively correlated with the C3G content. • C3G regulated the functional impairment of ARPE-19 cells caused by high glucose through the REDD1/GSK3β pathway. • C3G inhibited the generation of VEGF in ARPE-19 cells induced by high glucose to maintain retinal homeostasis. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Fatty acid species and locations within TAGs affect lipid digestion rate and extent. • Maximum FFA release extent upon pancreatic lipase reaction: PO > RO > LINO > SO > LO. • Apparent FFA release constants were PO > SO ≈ RO > LO ≈ LINO during in-vitro digestion. • Short-chain saturated fatty acids released faster than long-chain poly-unsaturated fatty acids. • Correlations were found between lipid compositions, lipid digestion and serum fatty acids profiles. Abstract The objective of the present study was to investigate the influences of dietary lipid composition on the gastrointestinal digestion and postprandial serum lipid profiles, and the connections between them. The in-vitro digestion results showed that maximum free fatty acid (FFA) release level of different lipid samples was PO (Palm oil) > RO (Rapeseed oil) > LINO (Linseed oil) > SO (Sunflower oil) > LO (Lard oil), and the first-order kinetics apparent rate constant was PO > SO ≈ RO > LO ≈ LINO, this may probably be ascribed to their specific lipid fatty acid composition and TAG structure. The individual FFA released during 240 min in-vitro digestion time was measured, and it showed that the release rate of short-chain saturated fatty acids (e.g. C16:0 in PO) were higher than the long-chain poly-unsaturated fatty acids (e.g. C18:3n-3 in LINO). Besides, the position of fatty acids within TAG molecules could also impose influences on the lipid hydrolysis process upon pancreas lipase in gastrointestinal tract using in-vitro digestion model. The postprandial serum fatty acid composition of the adult SD male rats were examined within 240 min after oral gavage administration, and the Pearson correlations between lipid fatty acid composition and the serum fatty acid profiles were analyzed. Certain correlations were summarized between lipid compositions (i.e. fatty acid composition and TAG structure), lipid digestion fates and serum fatty acid content in postprandial. The present work may provide some basic understandings of the connections among lipid compositions, lipid gastrointestinal digestion differences and the postprandial serum lipid profiles, and provide useful information about their nutritional and functional evaluation. [ABSTRACT FROM AUTHOR]

The digestion fates of different edible oils are different. The objective of this study was to understand the influences of lipid composition on their digestion fates, and investigate the roles of bile salts (BS) played in emulsified lipid system (whey protein isolate as emulsifier) in the in-vitro small intestine digestion stage. Three typical oils (palm oil (PO), rapeseed oil (RO) and linseed oil (LINO)) were chosen. Results showed that with the BS addition increased from 0.0 to 2.0 mg/mL, the increasing magnitude of the different fatty acid (FA) apparent release rate constants were: PO > RO ≈ LINO. Although the maximum FA release extent changed with BS addition, the order were: PO > RO > LINO. These may probably be attributed to palmitic acids, the most abundant FA in PO, was mostly located on the Sn-1, 3 positions of triacylglycerol (TAG) molecules, which contributed to the pancreatic lipase hydrolysis action. The relatively short chain length and the lower hydrophobicity also favored this process. However, Sn-1, 3 positions of TAGs in RO and LINO were mainly long chain mono- or poly-unsaturated FAs, which restricted the continuous lipid hydrolysis. Furthermore, the lipid composition may also affect the BS behavior on the O/W emulsion droplet surface, thus modulating lipase hydrolysis reaction. These findings can provide some basic understandings of the digestion differences of different oils. [ABSTRACT FROM AUTHOR]

Liver vessels provide lots of important information for liver-disease diagnosis and liver surgery. This paper presents an effective liver vessel segmentation method from abdominal computer tomography angiography (CTA) images. The proposed method applies two techniques including centerline constraint and intensity model for effective detection of liver vessels, in which the former aims at generating the position and distance restraints for the detection of thin vessels by the offset medialness filter and height ridge traversal algorithm, while the latter is mainly used to extract intensity feature for the detection of thick vessels based on Kernel Fuzzy C-Means (KFCM). And then, the centerline constraint and intensity model are integrated into graph cuts for ultimate liver vessel segmentation. The proposed method does not require any manual selection of the initial vessel regions, and is capable of dealing with complex liver vessel systems. The experimental results on clinical CTA data sets give an average accuracy, sensitivity, and specificity of 97.4%, 83.0%, and 98.1%, respectively, which show the efficiency of the proposed method on liver vessel segmentation. [ABSTRACT FROM AUTHOR]

Odorant binding proteins (OBPs) play important roles in the insect olfaction and other diverse physiological processes. Forty OBP genes have been molecularly identified from Chilo suppressalis (Walker), a notorious rice pest in Asian countries, but little is known about the olfactory function for most of these genes. In the present study, we first determined the tissue expression profiles of 34 OBP s (excluding two general odorant bonding proteins ( GOBPs ) and four pheromone binding protein ( PBPs )) by quantitative real-time PCR (qPCR), and found that 9 genes ( OBP 1, 3, 4, 11, 15, 17, 19, 20 and 24) were specifically or predominantly expressed in antennae of both sexes, suggesting their roles in olfaction, while three genes ( OBP 29, 30 and 32) were almost not expressed in antennae. Focusing on olfactory roles, the ligand specificities of six antenna specifically or predominantly expressed genes were further investigated for 35 plant volatiles, using the fluorescence competitive binding assays. The results revealed that six OBPs displayed different ligand preference, suggesting a differentiation of OBPs in ligand binding spectrum. Of six tested OBPs, OBP 3, 11, 17, 19 and 31 showed moderate (Ki = 10.21–19.85 μM) or high (Ki < 10.00 μM) binding affinity for 11 and one plant volatiles, respectively. In particular, a plant volatile β-ionone had high or moderate binding to all five OBPs. Our study suggests that these five OBP genes play important roles in the perception of different host plant volatiles, providing insight into the olfactory mechanism in C. suppressalis . [ABSTRACT FROM AUTHOR]

[Display omitted] • The major species of the polyphenols derived from rapeseeds were summarized. • The typical biofunctional roles of these polyphenols were elucidated. • The influences of rapeseed oil processing technologies on these polyphenols were elaborated. • Future directions of the studies for illustrating the roles of these polyphenols, and technologies for green manufacturing of rapeseed oil were prospected. The rapeseed (Brassica napus L.) are the important oil bearing material worldwide, which contain wide variety of bioactive components with polyphenolic compounds considered the most typical. The rapeseed polyphenols encompass different structural variants, and have been considered to have many bioactive functions, which are beneficial for the human health. Whereas, the rapeseed oil processing technologies affect their content and the biofunctional activities. The present review of the literature highlighted the major types of the rapeseed polyphenols, and summarized their biofunctional roles. The influences of rapeseed oil processing technologies on these polyphenols were also elucidated. Furthermore, the directions of the future studies for producing nutritional rapeseed oils preserved higher level of polyphenols were prospected. The rapeseed polyphenols are divided into the phenolic acids and polyphenolic tannins, both of which contained different subtypes. They are reported to have multiple biofunctional roles, thus showing outstanding health improvement effects. The rapeseed oil processing technologies have significant effects on both of the polyphenol content and activity. Some novel processing technologies, such as aqueous enzymatic extraction (AEE), subcritical or supercritical extraction showed advantages for producing rapeseed oil with higher level of polyphenols. The oil refining process involved heat or strong acid and alkali conditions affected their stability and activity, leading to the loss of polyphenols of the final products. Future efforts are encouraged to provide more clinic evidence for the practical applications of the rapeseed polyphenols, as well as optimizing the processing technologies for the green manufacturing of rapeseed oils. [ABSTRACT FROM AUTHOR]

Carboxylesterases (CXEs) belong to a family of metabolic enzymes that are widely distributed in insects and other organisms and can rapidly degrade the components of sex pheromones and plant volatiles with an acetate functional group. The common cutworm, Spodoptera litura , is an important agricultural pest around the world, causing vast economic losses every year. The female sex pheromones of S. litura comprise four acetates, Z9, E11-14:OAc; Z9, E12-14:OAc; Z9-14:OAc; and E11-14:OAc, but the degradation mechanisms of these components are not well understood. By analysing previously obtained transcriptomic data of the sex pheromone glands, we identified a total of 24 putative CXE genes in S. litura . Gene expression patterns and phylogenetic analysis revealed 5 genes with antennae-specific or biased expression, and clustered with genes showed involvement in the degradation of sex pheromones or other detoxification in other insects. SlitCXE10 was expressed specifically in the antennae of both sexes, and SlitCXE14 , 17 , 19 , and 21 had high antenna biased expression. Interestingly, RT-PCR and qPCR tests indicated that SlitCXE24 had significantly higher expression in PG than in other tissue, and that it could be a potential candidate gene for sex pheromone degradation in PG. This study is the first to provide solid background information for the further elucidation of sex pheromone degradation, and ultimately provides potential targets for the disruption of sexual communication in S. litura for new pest management. [ABSTRACT FROM AUTHOR]

Liver segmentation from abdominal computed tomography (CT) volumes is extremely important for computer-aided liver disease diagnosis and surgical planning of liver transplantation. Due to ambiguous edges, tissue adhesion, and variation in liver intensity and shape across patients, accurate liver segmentation is a challenging task. In this paper, we present an efficient semi-automatic method using intensity, local context, and spatial correlation of adjacent slices for the segmentation of healthy liver regions in CT volumes. An intensity model is combined with a principal component analysis (PCA) based appearance model to exclude complex background and highlight liver region. They are then integrated with location information from neighboring slices into graph cuts to segment the liver in each slice automatically. Finally, a boundary refinement method based on bottleneck detection is used to increase the segmentation accuracy. Our method does not require heavy training process or statistical model construction, and is capable of dealing with complicated shape and intensity variations. We apply the proposed method on XHCSU14 and SLIVER07 databases, and evaluate it by MICCAI criteria and Dice similarity coefficient. Experimental results show our method outperforms several existing methods on liver segmentation. [ABSTRACT FROM AUTHOR]

Liver-vessel segmentation plays an important role in vessel structure analysis for liver surgical planning. This paper presents a liver-vessel segmentation method based on extreme learning machine (ELM). Firstly, an anisotropic filter is used to remove noise while preserving vessel boundaries from the original computer tomography (CT) images. Then, based on the knowledge of prior shapes and geometrical structures, three classical vessel filters including Sato, Frangi and offset medialness filters together with the strain energy filter are used to extract vessel structure features. Finally, the ELM is applied to segment liver vessels from background voxels. Experimental results show that the proposed method can effectively segment liver vessels from abdominal CT images, and achieves good accuracy, sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Background: Identification and evaluation of incidental findings in patients following whole exome (WGS) or whole genome sequencing (WGS) is challenging for both practicing physicians and researchers. The American College of Medical Genetics and Genomics (ACMG) recently recommended a list of reportable incidental genetic findings. However, no informatics tools are currently available to support evaluation of incidental findings in next-generation sequencing data.Methods: The Wisconsin Hierarchical Analysis Tool for Incidental Findings (WHATIF), was developed as a stand-alone Windows-based desktop executable, to support the interactive analysis of incidental findings in the context of the ACMG recommendations. WHATIF integrates the European Bioinformatics Institute Variant Effect Predictor (VEP) tool for biological interpretation and the National Center for Biotechnology Information ClinVar tool for clinical interpretation.Results: An open-source desktop program was created to annotate incidental findings and present the results with a user-friendly interface. Further, a meaningful index (WHATIF Index) was devised for each gene to facilitate ranking of the relative importance of the variants and estimate the potential workload associated with further evaluation of the variants. Our WHATIF application is available at: http://tinyurl.com/WHATIF-SOFTWARE CONCLUSIONS: The WHATIF application offers a user-friendly interface and allows users to investigate the extracted variant information efficiently and intuitively while always accessing the up to date information on variants via application programming interfaces (API) connections. WHATIF׳s highly flexible design and straightforward implementation aids users in customizing the source code to meet their own special needs. [ABSTRACT FROM AUTHOR]

As the major oxidized triglycerides (ox-TGs), epoxy triglyceride is one of the toxic polar components from deep frying oil. However, the conventional methods are difficult to separate epoxy triglyceride from other ox-TGs due to their similar molecular and structures. To address the problem, a novel magnetic solid-phase extraction approach based on a surface molecularly imprinted polymers was developed. The polymers coated on Fe 3 O 4 nanoparticles (Fe 3 O 4 @MIPs) were synthesized and used as highly selective sorbents for capture epoxy triglyceride from deep frying oil. They have high adsorption capacity (58.3 mg/g), stable equilibrium adsorption time (60 min) and excellent specificity. This method had a satisfactory linear relationship in the range of 0.2–10 mg/L (R 2 = 0.997), and the detection limit of epoxy triglyceride was 0.0599 mg/L. Results indicated that Fe 3 O 4 @MIPs could not only specifically separate epoxy triglycerides, but also provided a potent idea for the separation of other ox-TGs from deep frying oil. [ABSTRACT FROM AUTHOR]

Abstract: Insect chemosensory proteins (CSPs) are proposed to capture and transport hydrophobic chemicals across the sensillum lymph to olfactory receptors (ORs), but this has not been clarified in moths. In this study, we built on our previously reported segment sequence work and cloned the full length CSP19 gene (SinfCSP19) from the antennae of Sesamia inferens by using rapid amplification of cDNA ends. Quantitative real time-PCR (qPCR) assays indicated that the gene was expressed in a unique profile, i.e. predominant in antennae and significantly higher in male than in female. To explore the function, recombinant SinfCSP19 was expressed in Escherichia coli cells and purified by Ni–ion affinity chromatography. Binding affinities of the recombinant SinfCSP19 with 39 plant volatiles, 3 sex pheromone components and 10 pheromone analogs were measured using fluorescent competitive binding assays. The results showed that 6 plant volatiles displayed high binding affinities to SinfCSP19 (Ki=2.12–8.75μM), and more interesting, the 3 sex pheromone components and analogs showed even higher binding to SinfCSP19 (Ki=0.49–1.78μM). Those results suggest that SinfCSP19 plays a role in reception of female sex pheromones of S. inferens and host plant volatiles. [Copyright &y& Elsevier]

An immune component of inflammatory bowel disease is up-regulated tumor necrosis factor-like ligand 1A (TL1A). Anti-TL1A antibodies such as PF-06480605, a fully human immunoglobulin G1 monoclonal antibody, may have therapeutic potential. This Phase 2a, multicenter, single-arm, open-label study (TUSCANY) evaluated safety, tolerability, efficacy, pharmacokinetics, and immunogenicity in PF-06480605–treated participants with moderate to severe ulcerative colitis (UC). Participants received 500 mg intravenous PF-06480605 every 2 weeks, 7 doses total, with a 3-month follow-up period. Primary safety and efficacy endpoints were the incidence of adverse events (AEs) and week 14 endoscopic improvement (EI) (Mayo endoscopic subscore = 0 or 1), respectively. Secondary endpoints included total soluble TL1A (free/drug-bound) (sTL1A), incidence of anti-drug and neutralizing antibodies, PF-06480605 concentrations, and changes in fecal calprotectin and high-sensitivity C-reactive protein. Histology was assessed at week 14. The study enrolled 50 participants; 42 completed. Of 109 treatment-emergent AEs, 18 were treatment-related. The most common AEs were UC disease exacerbation and arthralgia (6 participants each). Four serious AEs, no deaths, and no malignancies were reported. Week 14 EI was observed in a statistically significant proportion of participants (38.2% [uniformly minimum-variance unbiased estimator, per protocol population]). Minimal histologic disease was observed after treatment (Robarts Histopathology Index ≤5: 33.3%; Geboes Index ≤3.2: 47.6%). sTL1A increase over time from baseline indicated sustained target engagement. Forty-one participants (82%) tested positive for anti-drug antibodies and 5 (10%) for neutralizing antibodies. PF-06480605 demonstrated an acceptable safety profile and statistically significant EI in participants with moderate to severe UC, warranting further study in a larger participant cohort. Tissue histopathology analyses support this conclusion. Trial registration number: https://clinicaltrials.gov/NCT02840721. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The influence of coronal streamer background with nested and closed magnetic fields on the of the triggering of coronal mass ejections (CMEs) is investigated in the meridian plane. In the coronal streamers’ background magnetic structure there are three small-scale closed magnetic fields, of which the middle one has a direction opposite to that of the global dipolar field of coronal streamers. The trigger model of CMEs emerges from beneath this small-scale closed magnetic field and possesses a concentric circular structure with radius of a =0.1R s (R s being the solar radius). The direction of the magnetic field in the front half of the CME trigger model is opposite to that of the small-scale closed field and is the same as that of the streamers’ global dipolar field. As revealed by numerical simulation, when the ratio of the plasma pressure at the center of the CME trigger model to the boundary pressure is m ≤2, then the emerging model can trigger CMEs. When m <2, then it cannot. The error in this critical value of 2 is less than 1%. [Copyright &y& Elsevier]

Abstract: The method of Orthogonal Function Series Expansion (OFSE) is generalized and applied to the study of the evolution of the coupling of nondissipative torsional Alfven wave and fast wave in coronal loops. Using this method, the intrinsic angular frequency of the overall wave mode can be described mathematically and that of the Alfven waves along the magnetic lines in the coronal loop during the coupling of the Alfven and fast waves can be analyzed both theoretically and numerically. Also with this method, the relation between the coupling driven term and the Alfven wave resonance may be analyzed. Results of computation reveal the place of appearance of coupling resonance as well as the characteristics of the amplitudes of the Alfven and fast waves. As found by the calculations, if the footpoint driven angular frequency is not equal to the intrinsic angular frequency of the overall wave mode of the coronal loop and when a δ section appears at the place of coupled resonance, the radial gradient of the fast wave''s amplitude is quite large. Sometimes it approximates to a discontinuity, and this is extremely favorable for the dissipation of the fast wave. If the footpoint driven angular frequency is equal to the intrinsic angular frequency of the overall wave mode and when a δ section occurs in the Alfven wave amplitude, abundant small-scale structures appear in the radial direction. Then the location of resonance approximately becomes a discontinuity, very favorable to the dissipation of the Alfven wave. [Copyright &y& Elsevier]

The three-dimensional (3-D) coronal structure in Carrington rotation 1935 in May 1998 is obtained with a 3-D numerical model of ideal MHD equations. In this model, the MacCormack-II scheme is employed for the discretization of the governing equations in the computational domain and the non-reflecting projected-characteristic condition is adopted at the inner boundary in order to keep the simulation stable and the solution self-consistent. The observed photospheric magnetic field in Carrington rotation 1935 is used as the initial guessed magnetic field. The 3-D structure of solar corona acquired by our computation rather well agrees with reality. The results of our computation are as follows: (1) The magnetic field on source surface is nearly a radial one, and the non-radial component is weaker than 2μT near the neutral line. (2) The strength of the radial component of the magnetic field on the source surface does not exhibit large variations except in the vicinity of the neutral line, and this agrees with the observation. (3) The strength of the radial magnetic field component at 1 AU, calculated with inverse square law, agrees with observation better than that given by the potential model. (4) The 3-D numerical coronal structure qualitatively coincides with observation. Besides, the magnetic field dominates global solar wind structure. The density is high and velocity is low in closed magnetic fields or near current sheets, while the density is low and velocity is high in open magnetic fields. [Copyright &y& Elsevier]

• An adaptive region growing method based on Kullback-Leibler divergence is proposed. • Graph cuts combined with nonlinear mapping are developed to segment liver tumors. • The method can segment the tumors with low contrast and weak boundary precisely. • It does not require a heavy training process or a pre-segmentation of liver region. • It can also be extended to some other organ or tissue segmentation tasks. Segmenting liver tumors from computed tomography (CT) images plays a very important role in computer-aided diagnosis, surgical planning, and treatment monitoring. However, accurate and robust segmentation of the tumors remains a challenging issue, due to low contrast and vague boundaries between the tumors and surrounding tissues as well as the wide variations of the tumors in intensity, shape, and location across patients. In this paper, we developed an effective method for liver tumor segmentation with adaptive region growing and graph cuts. First, initial segmentation results for liver tumors and the regions of interest (ROIs) that contain the tumors are extracted by adaptive region growing with a manual selected seed specified for each tumor region. Then, the ROIs are enhanced by Gaussian fitting based nonlinear mapping according to the intensity distributions of the initially segmented tumor regions. Finally, the enhanced information combined with gradient information is integrated into graph cuts to extract the tumors from the ROIs effectively and accurately. The method is non-sensitive to noise and does not involve a pre-segmentation of liver or a complicated and tedious procedure of training. Results on 3Dircadb dataset demonstrate that the method achieves much better comprehensive performance on liver tumor segmentation compared with many art-of-state methods and has a huge advantage in segmenting the tumors with low contrast, small size, and weak boundaries. [ABSTRACT FROM AUTHOR]

Emergent Red Blood Cell (RBC) exchange is indicated in sickle cell disease (SCD) patients with severe acute chest syndrome. However, fully matched RBC units may not be available for patients with multiple RBC antibodies. Intravenous immunoglobulin (IVIG) and steroids were reported for preventing potential delayed hemolytic transfusion reaction (HTR) in simple transfusion of antigen-positive RBCs. We investigated the efficacy and safety of IVIG and steroids in two SCD patients presented with acute chest syndrome receiving RBC exchange with multiple incompatible units. The first patient had multiple historical alloantibodies, including anti-Jsb, although none of them were reactive. IVIG (1 g/kg) was given before and after RBC exchange with methylprednisolone (500 mg IV) one hour before exchange. Her sickle hemoglobin (HbS) was reduced from 89.4% to 17.4% after the exchange with five Jsb-positive units. The patient improved clinically without acute or delayed hemolysis. The second patient had reactive anti-Jsb on two different admissions 18 months apart. Only one of the sixteen units used in the exchanges was Jsb negative. He received the same IVIG regimen during both admissions but 100 mg IV hydrocortisone instead of methylprednisolone. His HbS was reduced from 63.4% to 22.4% after the first exchange. Significant clinical improvements were achieved after both exchanges. No delayed HTR was observed. Our experience of these two patients suggested that IVIG and steroids may be used in preventing potential delayed HTR in some SCD patients with rare antibodies receiving large amounts of antigen-positive RBC products. [ABSTRACT FROM AUTHOR]

An ongoing need exists for safe and effective lipid-lowering therapies (LLTs) for patients unable to achieve desired lipid levels with current treatment options. The objective of this study was to describe the safety profile of bempedoic acid, an oral, first-in-class, adenosine triphosphate (ATP)–citrate lyase inhibitor that significantly reduces low-density lipoprotein cholesterol (LDL-C) levels by 17.4%–28.5% vs placebo. This was a pooled analysis of four phase 3, randomized (2:1), double-blind, placebo-controlled studies in patients with hypercholesterolemia who required additional LDL-C lowering, despite stable maximally-tolerated LLT. Patients received 180 mg of bempedoic acid (n = 2424) or placebo (n = 1197) once daily for 12 to 52 weeks. Assessments included treatment-emergent adverse events (TEAEs) and clinical laboratory tests. Of 3621 patients (the median drug exposure: 363 days), exposure-adjusted TEAE rates were 87.1/100 and 82.9/100 person-years (PY) for bempedoic acid and placebo, respectively. No single TEAE influenced the difference in rates. TEAEs leading to discontinuation occurred at rates of 13.4/100 and 8.9/100 PY for bempedoic acid vs placebo, with the most common cause being myalgia, which occurred less frequently with bempedoic acid vs placebo (1.5/100 vs 2.0/100 PY). Rates of myalgia and muscle weakness were comparable vs placebo. Bempedoic acid was associated with mild increases in blood urea nitrogen, creatinine, and uric acid and decreases in hemoglobin. These laboratory abnormalities were apparent by week 4, stable over time, and reversible after treatment cessation. Gout incidence was 1.6/100 vs 0.5/100 PY in the bempedoic acid vs placebo groups. New-onset diabetes/hyperglycemia occurred less frequently with bempedoic acid vs placebo (4.7/100 vs 6.4/100 PY). The safety profile was consistent across subgroups. Bempedoic acid is generally safe and well tolerated among patients with hypercholesterolemia who require additional LLT. • Bempedoic acid significantly lowered low-density lipoprotein cholesterol in 4 phase 3 placebo-controlled trials. • Bempedoic acid was associated with increases in uric acid and incidence of gout. • New-onset diabetes/hyperglycemia incidence was lower with bempedoic acid than placebo. • Bempedoic acid was generally well-tolerated with consistent safety in subgroups. [ABSTRACT FROM AUTHOR]

• Effects of lipids on serum lipid, colonic SCFAs and colon morphology were studied. • PO and LO had negative effects on serum lipid and colon histology. • An efficient and accurate method was promoted to qualify the colonic SCFAs. • SFA was negatively correlated with colonic isobutyric acid concentration. • Lipids contain high SFA up-regulate the genes related with colon inflammatory. Palm oil (PO), leaf lard oil (LO), rapeseed oil (RO), sunflower oil (SO), and linseed oil (LINO) are the five of the most typical dietary lipids, while few studies have explored and compared their influences on the serum lipid profiles, colonic short chain fatty acids (SCFAs) composition and colon health of Sprague Dawley (SD) rats. Results from the present work showed that PO and LO groups showed significantly higher serum TG and TC level compared with Ctrl group, whereas, the LDL-C/HDL-C and TC/HDL-C ratio were significantly lower in the RO, SO and LINO groups. Different dietary lipid consumption (15% of the normal diet) decreased the colonic SCFAs concentration. The saturated fatty acid (SFA) was negatively correlated, while unsaturated fatty acid (UFA)/SFA ratio was positively correlated, with colonic isobutyric acid concentration. The C18:2ω6 and ω3 fatty acids were positively correlated with colonic butyric acid and isovaleric acid concentration, respectively. Results also demonstrated that PO and LO could decrease the colon villus length and crypt depth, and led to colon injury, which might be due to their high SFAs content. Moreover, results suggested that PO and LO could specifically up-regulate the colon inflammation related gene expression levels and down-regulate the Muc2 expression levels, thus, imposing negative impact on the mucus layers. The present study could provide some information for nutritional evaluation about these dietary lipids. [ABSTRACT FROM AUTHOR]

Human cytosolic sulfotransferase 1A1 ( SULT1A1 ) is considered to be one of the most important SULT isoforms for metabolism, detoxification, and carcinogenesis. This theory is driven by observations that SULT1A1 is widely expressed in multiple tissues and acts on a wide range of phenolic substrates. SULT1A1 is subject to functional common copy number variation (CNV) including deletions or duplications. However, it is less clear how SULT1A1 CNV impacts health and disease. To better understand the biological role of SULT1A1 in human health, we genotyped CNV in 14,275 Marshfield Clinic patients linked to an extensive electronic health record. Since SULT1A1 is linked to steroid metabolism, select serum steroid hormones were measured in 100 individuals with a wide spectrum of SULT1A1 CNV genotypes. Furthermore, comprehensive phenome-wide association studies (PheWAS) were conducted using diagnostic codes and clinical text data. For the first time, individuals homozygous null for SULT1A1 were identified in a human population. Thirty-six percent of the population carried >2 copies of SULT1A1 whereas 4% had ≤ 1 copy. Results indicate SULT1A1 CNV was negatively correlated with estrone-sulfate to estrone ratio predominantly in males (E1S/E1; p = 0.03, r = −0.21) and may be associated with increased risk for common allergies. The effect of SULT1A1 CNV on circulating estrogen metabolites was opposite to the predicted CNV-metabolite trend based on enzymatic function. This finding, and the potential association with common allergies reported herein, warrants future studies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate two trials of combination therapy, pioglitazone together with metformin or sulfonylurea, for Type 2 diabetes mellitus and to examine how pretrial antidiabetic therapies may have influenced the results. Subjects and Methods: The results of two published trials that examine combination therapy, pioglitazone plus metformin or pioglitazone plus sulfonylurea were analyzed. A post hoc analysis was performed in which patients from both of these trials were subdivided on the basis of their oral antidiabetic therapy before enrollment into the trials. Those subsets receiving pretrial therapy with a sulfonylurea plus metformin — and discontinuing one of the agents before randomization — were compared to those receiving only one of the agents before enrollment. Results: Patients in the combination pioglitazone (30 mg/day) plus metformin therapy arm of one trial, who entered with stable metformin monotherapy, experienced a significant decrease in glycosylated hemoglobin (HbA1C) levels during the 16-week course of the trial (−1.0±0.1 [mean±S.E.] percentage points; P<.05). In contrast, those in the same arm of the trial whose pretrial therapy included metformin plus a sulfonylurea — and who discontinued the sulfonylurea before enrollment — experienced no significant change in HbA1C levels (0.2±0.2 percentage points; P>.05). The difference between groups was significant (P<.001). Patients in the combination pioglitazone (15 or 30 mg/day) plus sulfonylurea therapy arm of the other trial, who entered the trial on stable sulfonylurea monotherapy, experienced significant decreases in HbA1C levels (−1.0±0.1 and −1.4±0.1 percentage points, respectively, for the 15- and 30-mg pioglitazone arms; P<.05). Those in the same arm whose pretrial therapy included sulfonylurea plus metformin — and who discontinued the metformin before enrollment — experienced no significant change in HbA1C levels. Differences between the groups separated on the basis of pretrial antidiabetic regimen were significant (P<.001). Conclusions: The efficacy of pioglitazone as an add-on in combination therapy (with metformin or a sulfonylurea) is likely to be greater than in previous reports, because those trial results were influenced by treatment regimens used by a portion of the patients before enrollment. Trials of oral hypoglycemic agents must be carefully constructed to consider the effects of agents given prior to the trial. [Copyright &y& Elsevier]

External beam radiotherapy (EBRT) with neoadjuvant/adjuvant androgen deprivation therapy (ADT) is an established treatment option to prolong survival for patients with intermediate- and high-risk prostate cancer (PCa). Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, was evaluated in this clinical setting in comparison with degarelix, an injectable GnRH antagonist. To evaluate the safety and efficacy of relugolix to achieve and maintain castration. A phase 2 open-label study was conducted in 103 intermediate-risk PCa patients undergoing primary EBRT and neoadjuvant/adjuvant ADT between June 2014 and December 2015. Patients randomly assigned (3:2) to 24-wk treatment with either daily oral relugolix or 4-wk subcutaneous depot degarelix (reference control). The primary endpoint was the rate of effective castration (testosterone <1.73 nmol/l) in relugolix patients between 4 and 24 wk of treatment. Secondary endpoints included rate of profound castration (testosterone <0.7 nmol/l), prostate-specific antigen (PSA) levels, prostate volume, quality of life (QoL) assessed using the Aging Males' Symptoms scale, and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (30-item EORTC core questionnaire [EORTC QLQ-C30] and 25-item EORTC prostate cancer module [EORTC QLQ-PR25]) questionnaires, and safety. No formal statistical comparisons with degarelix were planned. Castration rates during treatment were 95% and 82% with relugolix and 89% and 68% with degarelix for 1.73 and 0.7 nmol/l thresholds, respectively. Median time to castration in the relugolix arm was 4 d. During treatment, PSA levels and prostate volumes were reduced in both groups. Three months after discontinuing treatment, 52% of men on relugolix and 16% on degarelix experienced testosterone recovery (statistical significance of differences not tested). Mean and median QoL scores improved following treatment discontinuation. The most common adverse event was hot flush (relugolix 57%; degarelix 61%). Lack of blinding was a potential limitation. Relugolix achieved testosterone suppression to castrate levels within days and maintained it over 24 wk with a safety profile consistent with its mechanism of action. Oral once-daily relugolix may be a novel oral alternative to injectable androgen deprivation therapies. The phase 2 study C27003 demonstrated relugolix, an oral gonadotropin-releasing hormone antagonist, achieves and maintains testosterone castration for 24 wk in >90% of men with localised intermediate- and high-risk prostate cancer requiring neoadjuvant and/or adjuvant androgen deprivation therapy to external beam radiation therapy. [ABSTRACT FROM AUTHOR]

Factor XIII deficiency is a rare bleeding disorder which could be severe if inherited or less severe if acquired. We report a case of acquired Factor XIII inhibitor in a 75-year-old male with a suspicious left renal mass treated perioperatively with therapeutic plasma exchange (TPE). To perform kidney biopsy and ablation of the renal mass, six daily TPE treatments were performed before and after biopsy to minimize bleeding risk because the patient did not respond to drug therapy. Both thromboelastography (TEG) and laboratory-based coagulation tests were performed to assess coagulation status prior to and after TPE. The biopsy indicated oncocytoma which was removed by surgical procedure. Factor XIII activity remained below 15 % throughout TPE treatments, but Factor XIII inhibitor titer reduced from initial positive value of 1:40 to negative following the third TPE and remained negative through the sixth TPE. Unfortunately, the inhibitor titer was positive at 1:20 in the fifth month and 1:5 in the sixth month during follow-up. TPE is useful in removing XIII inhibitory factor, but the effects are only short term. [ABSTRACT FROM AUTHOR]

[Display omitted] • The oxidation index raw pecan oil increased with storage time. • The oleosome structures were related to the degree of pecan kernel oxidation. • The hydrolysis of endogenous proteins, mainly oleosins, caused the rupture of the oleosomes. • Pecan kernel oil oxidation was accelerated by oleosome rupture. The oxidative stability of pecan kernels and its relationship with the in-vitro behavior of oleosomes during storage were analyzed. The oxidation index of oil extracted from pecans stored for 20 days increased significantly. At the same time oleosomes in pecans were damaged, indicating a relationship between oleosomes and the oxidative stability of pecans. The rupture of oleosomes increases contact between oil and oxygen leading to an acceleration of oil oxidation. Further analysis of oleosomes showed that their oil content decreased during storage while their particle size increased significantly. It is possible that hydrolysis of endogenous proteins, especially oleosins, was responsible for the rupture of oleosomes, as seen by Tricine-SDS-PAGE. As a result, the content of free fatty acids and oxidized triacylglycerols in oleosomes increased, whereas the polyunsaturated fatty acids content decreased significantly. An in-vitro model confirmed that rupture of oleosomes led to oil leakage and thus accelerated endogenous oil oxidation. [ABSTRACT FROM AUTHOR]

Functional gene analysis by using genome editing techniques is limited only in few model insects. Here, we reported an efficient and heritable gene mutagenesis analysis in an important lepidopteran pest, Spodoptera litura , using the CRISPR/Cas9 system. By using this system, we successfully obtained the homozygous S . litura strain by targeting the pheromone binding protein 3 gene ( SlitPBP3 ), which allowed us to elucidate the role of this gene in the olfaction of the female sex pheromones. By co-injection of Cas9 mRNA and sgRNA into S . litura eggs, highly efficient chimera mutation in SlitPBP3 loci was detected both in injected eggs (39.1%) and in the resulting individual moths (87.5%). We used the mutant moths as parents to obtain the G1 offspring and the homozygous mutant strain in G2. The function of SlitPBP3 was explored by Electroantennogram (EAG) recordings with a homozygous mutant strain. The result showed that the EAG responses were significantly decreased in mutant males than in control males when treated with the major sex pheromone component (Z9,E11-14:Ac) and a minor component (Z9-14:Ac) at higher dosages. The results demonstrate that s SlitPBP3 gene plays a minor role in the perception of the female sex pheromones. Furthermore, our study provides a useful methodology with the CRISPR/Cas9 system for gene in vivo functional study, particular for lepidopteran species in which the RNAi approach is not efficient. [ABSTRACT FROM AUTHOR]

Multifunctional theranostic nanoplatforms integrated of imaging function, multi-modality therapy, stimuli-responsiveness, and targeted delivery are of highly desirable attributes in achieving precise medicine. However, preparation of multifunctional nanoplatforms often involves laborious, multiple steps and inevitably utilizes low-biocompatible or non-functional components. Herein we report a facile, one-step self-assembly strategy to fabricate hyaluronic acid (HA)-based multifunctional tumor theranostic nanoplatform by employing magnetic resonance imaging (MRI) agent Mn2+ as a reversible crosslink agent for histidine-grafted HA, along with simultaneously loading chemotherapeutic agent doxorubicin hydrochloride (DOX) and photodynamic therapy agent chlorin e6, to realize MRI-guided targeted chemo-photodynamic cancer therapy. The targeted delivery and stimuli-responsive payload release were demonstrated in vitro and in vivo. Furthermore, the combined chemo-photodynamic therapy of the nanoassembly dramatically improved the cancer therapeutic outcome, in comparison with that of free DOX and nanoplatform solely loaded DOX in a melanoma bearing mice. Our one step assemble strategy is of great potential in clinic transformation. [Display omitted] • One-step strategy was employed to prepare multifunctional hyaluronic acid nanogels. • No extra low-biocompatible or non-functional components were used in this process. • Such platform achieved MRI-guided responsive chemo-photodynamic cancer therapy. [ABSTRACT FROM AUTHOR]