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  • Nasopharyngeal carcinoma (NPC) is an epithelial cancer associated with Epstein-Barr virus. Despite NPC is a widespread malignancy, little is known about association of tumor growth with gene expression. This study is aimed to detect potential genes implicated in the molecular mechanism of NPC. To this end, we downloaded GSE12452, GSE53819 and GSE64634 libraries from GEO database. GEO2R interface was used to search for the differentially expressed genes (DEGs) with R and LIMMA software, which yielded the Venn diagrams of co-expressed genes. The GO and KEGG databases were used to find DEGs with up- and down-regulated expression. Then Cytoscape software constructed and analyzed the protein-protein interaction (PPI) networks corresponding to revealed DEGs, thereupon the hub genes were analyzed in tissues and cell cultures with qRT-PCR. This combined analysis yielded 483 co-expressed DEGs, including 258 DEGs with up-regulated expression and 225 DEGs with down-regulated expression, which are mainly implicated in the cell cycle, DNA replication, as well as in formation and maturation of extracellular vesicles and exosomes. In comparison with normal nasopharyngeal tissues of healthy persons, expression of CDK1 gene was down-regulated in NPC tissue; in contrast, expression of PCNA, MAD2L1, PRC1, CENPF, and ZWINT genes was up-regulated in the tumor. The genes PCNA, MAD2L1, and ZWINT were differently expressed in EBV+ and EBV- nasopharyngeal carcinoma cells. The use of bioinformatic methods to reveal and analyze the differences in gene expression between the normal and NPC tissues opens the vista to further progress in deciphering the molecular mechanisms of NPC formation and development.The study focuses on the effects of azithromycin on severity of ischemia/reperfusion myocardial injury during simulated systemic inflammatory response syndrome (SIRS) in primary visceral obesity (PVO). Total ischemia/reperfusion was modeled by Langendorff perfusion of isolated heart with following estimation of the size of myocardial infarction. SIRS was accompanied by an increase in blood levels of proinflammatory cytokines and LPS. Combination of PVO and SIRS produced no significant changes in the infarct size compared to the control. Administration of azithromycin to rats with PVO and SIRS resulted in pronounced alterations of biochemical and immunological parameters, although it did not affect the infarct size. In contrast, the use of tetracycline increased the size of myocardial infarction. This phenomenon should be taken into consideration in antimicrobial therapy.Glucagon-like peptide-1 (GLP-1), a product of partial proteolysis of proglucagon, is involved not only in regulation of carbohydrates, but also in water-salt metabolism. The study examined the role of proglucagon derivatives GLP-1, GLP-2, and oxyntomodulin in rat osmoregulation. https://www.selleckchem.com/products/yk-4-279.html Of them, only blood plasma GLP-1 increased in response to water load (20 ml/kg). Administration of glucose (1.5 g/kg) elevated GLP-1 and oxyntomodulin but did not change the level of GLP-2. GLP-1 accelerated excretion of excess water during hyperhydration, whereas GLP-2 decreased this parameter. No physiological effects of oxyntomodulin in the kidneys were revealed. Probably, the blood levels of proglucagon derivatives are independently regulated for each peptide. In contrast to GLP-2 and oxyntomodulin, GLP-1 is involved in osmoregulation.The liposomal form of isonicotinic acid hydrazide conjugate with oxidized dextran (liposomeencapsulated dextrazide, LEDZ) injected intraperitoneally for 3 months to BALB/c **** with chronic BCG-induced granulomatosis (6 month after infection) down-regulated activities of protease (MMP) and antiprotease (TIMP-1, TIMP-2, α2-macroglobulin) components of the regulation system, which indicates a drop of destructive and inflammatory potential of BCGinduced granulomatosis. The persistent enhanced hyaluronidase activity in the liver and its reduced (normalized to control level) activity in the lungs after administration of LEDZ indicates a greater hydrolysis of hyaluronan in the liver than in the lungs. LEDZ-induced changes in MMP/TIMP system in mouse liver and lungs are characterized with relative elevation of protease activity over that of antiprotease one.The study examined transcriptional regulation of adrenal zona reticularis development in male Wistar rats exposed to low doses of endocrine disruptor dichlorodiphenyltrichloroethane (DDT) prenatally and postnatally. At pubertal age, zona reticularis demonstrated a retarded growth with a low proliferative activity of its cells. At this age, zona reticularis was characterized with overexpression of β-catenin by steroid-producing cells; a high percentage of cells with membrane and cytoplasmic localization of β-catenin, and reduced number of cells with nuclear β-catenin attesting to insufficient activation of Wnt signaling. Expression of transcriptional factor Oct4 by reticularis cells was down-regulated indicating their diminished proliferative potency. No significant alterations in Sonic Hedgehog expression were observed. Thus, DDT-provoked disorders of transcriptional regulation result in abnormal development of zona reticularis thereby disturbing sexual maturation in males.The protective effect of antioxidant SkQR1 was examined on the model of left-sided compression ischemia in rat sensorimotor cortex. The special tests aimed to determine the neurologic deficit in the limbs and assess performance of the forelimbs showed that a 2.5-min ischemia produced no disturbance in the limb functions on postsurgery days 1, 3, and 7. Elevation of compression time resulted in neurologic deficit in animals, and its severity depended on this time. A single intravenous injection of SkQR1 (250 nmol/kg body weight) performed 30 min after ischemia significantly reduced the degree of neurologic deficit. In vitro model of ischemia in surviving rat hippocampal slices showed that a 15-min-long ischemia significantly inhibited the population excitatory postsynaptic potentials, which did not restore during reperfusion. Preincubation of the slices with SkQR1 did not significantly affect recovery of these potentials.
    Nasopharyngeal carcinoma (NPC) is an epithelial cancer associated with Epstein-Barr virus. Despite NPC is a widespread malignancy, little is known about association of tumor growth with gene expression. This study is aimed to detect potential genes implicated in the molecular mechanism of NPC. To this end, we downloaded GSE12452, GSE53819 and GSE64634 libraries from GEO database. GEO2R interface was used to search for the differentially expressed genes (DEGs) with R and LIMMA software, which yielded the Venn diagrams of co-expressed genes. The GO and KEGG databases were used to find DEGs with up- and down-regulated expression. Then Cytoscape software constructed and analyzed the protein-protein interaction (PPI) networks corresponding to revealed DEGs, thereupon the hub genes were analyzed in tissues and cell cultures with qRT-PCR. This combined analysis yielded 483 co-expressed DEGs, including 258 DEGs with up-regulated expression and 225 DEGs with down-regulated expression, which are mainly implicated in the cell cycle, DNA replication, as well as in formation and maturation of extracellular vesicles and exosomes. In comparison with normal nasopharyngeal tissues of healthy persons, expression of CDK1 gene was down-regulated in NPC tissue; in contrast, expression of PCNA, MAD2L1, PRC1, CENPF, and ZWINT genes was up-regulated in the tumor. The genes PCNA, MAD2L1, and ZWINT were differently expressed in EBV+ and EBV- nasopharyngeal carcinoma cells. The use of bioinformatic methods to reveal and analyze the differences in gene expression between the normal and NPC tissues opens the vista to further progress in deciphering the molecular mechanisms of NPC formation and development.The study focuses on the effects of azithromycin on severity of ischemia/reperfusion myocardial injury during simulated systemic inflammatory response syndrome (SIRS) in primary visceral obesity (PVO). Total ischemia/reperfusion was modeled by Langendorff perfusion of isolated heart with following estimation of the size of myocardial infarction. SIRS was accompanied by an increase in blood levels of proinflammatory cytokines and LPS. Combination of PVO and SIRS produced no significant changes in the infarct size compared to the control. Administration of azithromycin to rats with PVO and SIRS resulted in pronounced alterations of biochemical and immunological parameters, although it did not affect the infarct size. In contrast, the use of tetracycline increased the size of myocardial infarction. This phenomenon should be taken into consideration in antimicrobial therapy.Glucagon-like peptide-1 (GLP-1), a product of partial proteolysis of proglucagon, is involved not only in regulation of carbohydrates, but also in water-salt metabolism. The study examined the role of proglucagon derivatives GLP-1, GLP-2, and oxyntomodulin in rat osmoregulation. https://www.selleckchem.com/products/yk-4-279.html Of them, only blood plasma GLP-1 increased in response to water load (20 ml/kg). Administration of glucose (1.5 g/kg) elevated GLP-1 and oxyntomodulin but did not change the level of GLP-2. GLP-1 accelerated excretion of excess water during hyperhydration, whereas GLP-2 decreased this parameter. No physiological effects of oxyntomodulin in the kidneys were revealed. Probably, the blood levels of proglucagon derivatives are independently regulated for each peptide. In contrast to GLP-2 and oxyntomodulin, GLP-1 is involved in osmoregulation.The liposomal form of isonicotinic acid hydrazide conjugate with oxidized dextran (liposomeencapsulated dextrazide, LEDZ) injected intraperitoneally for 3 months to BALB/c mice with chronic BCG-induced granulomatosis (6 month after infection) down-regulated activities of protease (MMP) and antiprotease (TIMP-1, TIMP-2, α2-macroglobulin) components of the regulation system, which indicates a drop of destructive and inflammatory potential of BCGinduced granulomatosis. The persistent enhanced hyaluronidase activity in the liver and its reduced (normalized to control level) activity in the lungs after administration of LEDZ indicates a greater hydrolysis of hyaluronan in the liver than in the lungs. LEDZ-induced changes in MMP/TIMP system in mouse liver and lungs are characterized with relative elevation of protease activity over that of antiprotease one.The study examined transcriptional regulation of adrenal zona reticularis development in male Wistar rats exposed to low doses of endocrine disruptor dichlorodiphenyltrichloroethane (DDT) prenatally and postnatally. At pubertal age, zona reticularis demonstrated a retarded growth with a low proliferative activity of its cells. At this age, zona reticularis was characterized with overexpression of β-catenin by steroid-producing cells; a high percentage of cells with membrane and cytoplasmic localization of β-catenin, and reduced number of cells with nuclear β-catenin attesting to insufficient activation of Wnt signaling. Expression of transcriptional factor Oct4 by reticularis cells was down-regulated indicating their diminished proliferative potency. No significant alterations in Sonic Hedgehog expression were observed. Thus, DDT-provoked disorders of transcriptional regulation result in abnormal development of zona reticularis thereby disturbing sexual maturation in males.The protective effect of antioxidant SkQR1 was examined on the model of left-sided compression ischemia in rat sensorimotor cortex. The special tests aimed to determine the neurologic deficit in the limbs and assess performance of the forelimbs showed that a 2.5-min ischemia produced no disturbance in the limb functions on postsurgery days 1, 3, and 7. Elevation of compression time resulted in neurologic deficit in animals, and its severity depended on this time. A single intravenous injection of SkQR1 (250 nmol/kg body weight) performed 30 min after ischemia significantly reduced the degree of neurologic deficit. In vitro model of ischemia in surviving rat hippocampal slices showed that a 15-min-long ischemia significantly inhibited the population excitatory postsynaptic potentials, which did not restore during reperfusion. Preincubation of the slices with SkQR1 did not significantly affect recovery of these potentials.
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  • We introduce a novel dataset containing 3-dimensional biomechanical and wearable sensor data from 22 able-bodied adults for multiple locomotion modes (level-ground/treadmill walking, stair ascent/descent, and ramp ascent/descent) and multiple terrain conditions of each mode (walking speed, stair height, and ramp inclination). In this paper, we present the data collection methods, explain the structure of the open dataset, and report the sensor data along with the kinematic and kinetic profiles of joint biomechanics as a function of the gait phase. This dataset offers a comprehensive source of locomotion information for the same set of subjects to motivate applications in locomotion recognition, developments in robotic assistive devices, and improvement of biomimetic controllers that better adapt to terrain conditions. With such a dataset, models for these applications can be either subject-dependent or subject-independent, allowing greater flexibility for researchers to advance the field.Although the literature indicates children with autism spectrum disorder (ASD) walk at slower speeds and altered kinematics compared to neurotypical controls, no research has examined walking at matched speeds. This study examined biomechanical differences between adolescents with ASD and matched (age, sex, and body mass index) neurotypical controls. Lower extremity biomechanics of seventeen adolescents with ASD and seventeen controls were compared at matched speeds self-selected and a standardized 1.3 m/s. Controls exhibited greater eversion angles and hip abduction moments compared to those with ASD. This study found adolescents, which may have a more mature gait than young children, walk with a similar pattern in the propulsive plane (i.e. sagittal) as neurotypical controls, but with alterations in the supportive plane (i.e. frontal).
    Individuals with Sturge-Weber syndrome (SWS) often expereince intractable epilepsy and cognitive decline. We hypothesized that the extent of the leptomeningeal capillary malformation (LCM) may correlate with the severity of neurological impairment due to SWS. We tested the hypothesis in a cross-sectional study of seizure severity and electroencephalographic (EEG) findings and a retrospective cohort study for surgical indications related to the extent of the LCM.

    We enrolled 112 patients and classified them according to LCM distribution (1) bilateral, (2) hemispheric, (3) multilobar, and (4) single lobe. Age at seizure onset, seizure semiology and frequency, and EEG findings were compared. Surgical indications were evaluated for each group by Fisher exact test, and predictors for surgery were evaluated by univariate and multivariate analyses. Therapeutic efficacy was evaluated by the SWS-Neurological Score (SWS-NS).

    The bilateral and hemispheric groups had early seizure onset (4.0 months old and 3.0 months old), frequent seizures (88.9% and 80.6% had more than one per month), focal-to-bilateral tonic-clonic seizures (88.9% and 74.2%), and status epilepticus (100% and 87.1%). The groups' EEG findings did not differ substantially. Surgical indications were present in 77.8% of the bilateral, 88.1% of the hemispheric, and 46.8% of the multilobar groups. Seizure more than once per month was a predictor of surgical treatment. Seizure subscore improved postoperatively in the hemispheric and multilobar groups. Even after surgical treatment, the bilateral and hemispheric groups exhibited higher SWS-NSs than members of the other groups.

    Our study demonstrated a strong association between extensive LCM and epilepsy severity. Surgical intervention improved seizure outcome in patients with SWS with large LCMs.
    Our study demonstrated a strong association between extensive LCM and epilepsy severity. Surgical intervention improved seizure outcome in patients with SWS with large LCMs.Granulocyte colony-stimulating factor (G-CSF) is a cytokine most well-known for maturation and mobilization of bone marrow neutrophils. https://www.selleckchem.com/products/mito-tempo.html Although it is used therapeutically to treat chemotherapy induced neutropenia, it is also highly expressed in some tumors. Case reports suggest that tumors expressing high levels of G-CSF are aggressive, more difficult to treat, and present with poor prognosis and high mortality rates. Research on this topic suggests that G-CSF has tumor-promoting effects on both tumor cells and the tumor microenvironment. G-CSF has a direct effect on tumor cells to promote tumor stem cell longevity and overall tumor cell proliferation and migration. Additionally, it may promote pro-tumorigenic immune cell phenotypes such as M2 macrophages, myeloid-derived suppressor cells, and regulatory T cells. Overall, the literature suggests a plethora of pro-tumorigenic activity that should be balanced with the therapeutic use. In this review, we present an overview of the multiple complex roles of G-CSF and G-CSFR in tumors and their microenvironment and discuss how clinical advances and strategies may open new therapeutic avenues.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 which has infected millions of people worldwide. The main protease of SARS-CoV-2 (MPro) has been recognized as a key target for the development of antiviral compounds. Taking advantage of the X-ray crystal complex with reversible covalent inhibitors interacting with the catalytic cysteine 145 (Cys145), we explored flexible docking studies to select alternative compounds able to target this residue as covalent inhibitors. First, docking studies of three known electrophilic compounds led to results consistent with co-crystallized data validating the method for SARS-CoV-2 MPro covalent inhibition. Then, libraries of soft electrophiles (overall 41 757 compounds) were submitted to docking-based virtual screening resulting in the identification of 17 molecules having their electrophilic group close to the Cys145 residue. We also investigated flexible docking studies of a focused approved covalent drugs library including 32 compounds with various electrophilic functional groups. Among them, the calculations resulted in the identification of four compounds, namely dimethylfumarate, fosfomycin, ibrutinib and saxagliptin, able first, to bind to the active site of the protein and second, to form a covalent bond with the catalytic cysteine.
    We introduce a novel dataset containing 3-dimensional biomechanical and wearable sensor data from 22 able-bodied adults for multiple locomotion modes (level-ground/treadmill walking, stair ascent/descent, and ramp ascent/descent) and multiple terrain conditions of each mode (walking speed, stair height, and ramp inclination). In this paper, we present the data collection methods, explain the structure of the open dataset, and report the sensor data along with the kinematic and kinetic profiles of joint biomechanics as a function of the gait phase. This dataset offers a comprehensive source of locomotion information for the same set of subjects to motivate applications in locomotion recognition, developments in robotic assistive devices, and improvement of biomimetic controllers that better adapt to terrain conditions. With such a dataset, models for these applications can be either subject-dependent or subject-independent, allowing greater flexibility for researchers to advance the field.Although the literature indicates children with autism spectrum disorder (ASD) walk at slower speeds and altered kinematics compared to neurotypical controls, no research has examined walking at matched speeds. This study examined biomechanical differences between adolescents with ASD and matched (age, sex, and body mass index) neurotypical controls. Lower extremity biomechanics of seventeen adolescents with ASD and seventeen controls were compared at matched speeds self-selected and a standardized 1.3 m/s. Controls exhibited greater eversion angles and hip abduction moments compared to those with ASD. This study found adolescents, which may have a more mature gait than young children, walk with a similar pattern in the propulsive plane (i.e. sagittal) as neurotypical controls, but with alterations in the supportive plane (i.e. frontal). Individuals with Sturge-Weber syndrome (SWS) often expereince intractable epilepsy and cognitive decline. We hypothesized that the extent of the leptomeningeal capillary malformation (LCM) may correlate with the severity of neurological impairment due to SWS. We tested the hypothesis in a cross-sectional study of seizure severity and electroencephalographic (EEG) findings and a retrospective cohort study for surgical indications related to the extent of the LCM. We enrolled 112 patients and classified them according to LCM distribution (1) bilateral, (2) hemispheric, (3) multilobar, and (4) single lobe. Age at seizure onset, seizure semiology and frequency, and EEG findings were compared. Surgical indications were evaluated for each group by Fisher exact test, and predictors for surgery were evaluated by univariate and multivariate analyses. Therapeutic efficacy was evaluated by the SWS-Neurological Score (SWS-NS). The bilateral and hemispheric groups had early seizure onset (4.0 months old and 3.0 months old), frequent seizures (88.9% and 80.6% had more than one per month), focal-to-bilateral tonic-clonic seizures (88.9% and 74.2%), and status epilepticus (100% and 87.1%). The groups' EEG findings did not differ substantially. Surgical indications were present in 77.8% of the bilateral, 88.1% of the hemispheric, and 46.8% of the multilobar groups. Seizure more than once per month was a predictor of surgical treatment. Seizure subscore improved postoperatively in the hemispheric and multilobar groups. Even after surgical treatment, the bilateral and hemispheric groups exhibited higher SWS-NSs than members of the other groups. Our study demonstrated a strong association between extensive LCM and epilepsy severity. Surgical intervention improved seizure outcome in patients with SWS with large LCMs. Our study demonstrated a strong association between extensive LCM and epilepsy severity. Surgical intervention improved seizure outcome in patients with SWS with large LCMs.Granulocyte colony-stimulating factor (G-CSF) is a cytokine most well-known for maturation and mobilization of bone marrow neutrophils. https://www.selleckchem.com/products/mito-tempo.html Although it is used therapeutically to treat chemotherapy induced neutropenia, it is also highly expressed in some tumors. Case reports suggest that tumors expressing high levels of G-CSF are aggressive, more difficult to treat, and present with poor prognosis and high mortality rates. Research on this topic suggests that G-CSF has tumor-promoting effects on both tumor cells and the tumor microenvironment. G-CSF has a direct effect on tumor cells to promote tumor stem cell longevity and overall tumor cell proliferation and migration. Additionally, it may promote pro-tumorigenic immune cell phenotypes such as M2 macrophages, myeloid-derived suppressor cells, and regulatory T cells. Overall, the literature suggests a plethora of pro-tumorigenic activity that should be balanced with the therapeutic use. In this review, we present an overview of the multiple complex roles of G-CSF and G-CSFR in tumors and their microenvironment and discuss how clinical advances and strategies may open new therapeutic avenues.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 which has infected millions of people worldwide. The main protease of SARS-CoV-2 (MPro) has been recognized as a key target for the development of antiviral compounds. Taking advantage of the X-ray crystal complex with reversible covalent inhibitors interacting with the catalytic cysteine 145 (Cys145), we explored flexible docking studies to select alternative compounds able to target this residue as covalent inhibitors. First, docking studies of three known electrophilic compounds led to results consistent with co-crystallized data validating the method for SARS-CoV-2 MPro covalent inhibition. Then, libraries of soft electrophiles (overall 41 757 compounds) were submitted to docking-based virtual screening resulting in the identification of 17 molecules having their electrophilic group close to the Cys145 residue. We also investigated flexible docking studies of a focused approved covalent drugs library including 32 compounds with various electrophilic functional groups. Among them, the calculations resulted in the identification of four compounds, namely dimethylfumarate, fosfomycin, ibrutinib and saxagliptin, able first, to bind to the active site of the protein and second, to form a covalent bond with the catalytic cysteine.
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  • In this review, we will summarize and discuss the literature currently available on various mechanisms within the relationship between thrombocytopenia and virus infections.The prognostic value of multiple glycemic parameters in poisoned patients was never assessed. We aim to explore the effects of glucose variability on short-term outcomes in nondiabetic and diabetic patients acutely poisoned with undifferentiated xenobiotics. We performed a prospective observational study in a tertiary center for toxicology in northeastern Romania. Over the course of 3 years, we included 1076 adults, older than 18 years, admitted for acute poisoning with a xenobiotic. The mortality rate was 4.1%. The admission blood glucose level (BGL) predicted mortality (OR 1.015, 95% CI 1.011-1.019, p less then 0.001) and complications (OR 1.005, 95% CI 1.001-1.009, p 0.02). The mean glucose level (MGL) after admission (OR 1.007, 95% CI 1.000-1.013, p 0.034) and coefficient of glucose variability (CV) were predictive for complications (OR 40.58, 95% CI 1.35-1220.52, p 0.033), using the same multivariable model. The receiver operating characteristic curve (ROC) analysis revealed that BGL had good predictive value for in-hospital mortality (area under the curve (AUC) = 0.744, 95% CI = 0.648-0.841, p less then 0.001), and complications (AUC = 0.618, 95% CI = 0.584-0.653, p less then 0.001). In patients acutely poisoned with xenobiotics, the BGL, MGL and CV can be useful as mortality and short-outcome predictors.In skeletal muscle, long noncoding RNAs (lncRNAs) are involved in dystrophin protein stabilization but also in the regulation of myocytes proliferation and differentiation. Hence, they could represent promising therapeutic targets and/or biomarkers for Duchenne and Becker muscular dystrophy (DMD/BMD). DMD and BMD are X-linked myopathies characterized by a progressive muscular dystrophy with or without dilatative cardiomyopathy. Two-thirds of DMD gene mutations are represented by deletions, and 63% of patients carrying DMD deletions are eligible for 45 to 55 multi-exons skipping (MES), becoming BMD patients (BMDΔ45-55). We analyzed the genomic lncRNA presence in 38 BMDΔ45-55 patients and characterized the lncRNA localized in introns 44 and 55 of the DMD gene. We highlighted that all four lncRNA are differentially expressed during myogenesis in immortalized and primary human myoblasts. In addition, the lncRNA44s2 was pointed out as a possible accelerator of differentiation. Interestingly, lncRNA44s expression was associated with a favorable clinical phenotype. These findings suggest that lncRNA44s2 could be involved in muscle differentiation process and become a potential disease progression biomarker. Based on these results, we support MES45-55 therapy and propose that the design of the CRISPR/Cas9 MES45-55 assay consider the lncRNA sequences bordering the exonic 45 to 55 deletion.Aging causes a decline in skeletal muscle function, resulting in a progressive loss of muscle mass, quality, and strength. A weak regenerative capacity is one of the critical causes of dysfunctional skeletal muscle in elderly individuals. The extracellular matrix (ECM) maintains the tissue framework structure in skeletal muscle. As shown by previous reports and our data, the gene expression of ECM components decreases with age, but the accumulation of collagen substantially increases in skeletal muscle. We examined the structural changes in ECM in aged skeletal muscle and found restricted ECM degradation. In aged skeletal muscles, several genes that maintain ECM structure, such as transforming growth factor β (TGF-β), tissue inhibitors of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs), and cathepsins, were downregulated. Muscle injury can induce muscle repair and regeneration in young and adult skeletal muscles. Surprisingly, muscle injury could not only efficiently induce regeneration in aged skeletal muscle, but it could also activate ECM remodeling and the clearance of ECM deposition. These results will help elucidate the mechanisms of muscle fibrosis with age and develop innovative antifibrotic therapies to decrease excessive collagen deposition in aged muscle.The current standard for diagnosing cervical intraepithelial neoplasia (CIN) is colposcopy followed by punch biopsy. We have developed flexible magnifying endoscopy with narrow band imaging (ME-NBI) for the diagnosis of CIN. Here, we investigated the feasibility of targeted endoscopic forceps biopsy (E-Bx) under guidance of ME-NBI for the diagnosis of CIN. We prospectively enrolled 32 consecutive patients with confirmed or suspected high-grade CIN undergoing cervical conization. Next to colposcopy, the same patients underwent ME-NBI just before conization. ME-NBI was performed, and 30 E-Bx samples were taken from lesions suspicious for high-grade CIN and 15 from non-suspicious mucosa. We recalled 82 punch biopsy (P-Bx) specimens taken from lesions suspicious for high-grade CIN under colposcopic examination before enrollment. The proportion of sufficient biopsy samples, which had an entire mucosal layer with subepithelial tissue, for the diagnosis of CIN was evaluated by both methods. Performance of targeted E-Bx for the final diagnosis of at least high-grade CIN was calculated. Seventeen P-Bx specimens were unavailable. The proportion of sufficient samples with E-Bx was 84%, which was similar to that with P-Bx (87%) (p = 0.672). The sensitivity, specificity, and accuracy of ME-NBI using E-Bx was 92%, 81%, and 88%, respectively. In conclusion, ME-NBI-guided E-Bx samples were feasible for histological diagnoses of CIN, and further investigation of its diagnostic accuracy is warranted.KL-6 is a sialoglycoprotein antigen which proved elevated in the serum of patients with different interstitial lung diseases, especially in those with a poorer outcome. Given that interstitial pneumonia is the most common presentation of SARS-CoV2 infection, we evaluated the prognostic role of KL-6 in patients with COVID-19 pneumonia. Patients with COVID-19 pneumonia were prospectively enrolled. Blood samples were collected at the time of enrolment (TOE) and on day 7 (T1). Serum KL-6 concentrations were measured by chemiluminescence enzyme immunoassay using a KL-6 antibody kit (LUMIPULSE G1200, Fujirebio) and the cut-off value was set at >1000 U/mL. Fifteen out of 34 enrolled patients (44.1%) died. Patients with unfavourable outcome showed significantly lower P/F ratio and higher IL-6 values and plasmatic concentrations of KL-6 at TOE compared with those who survived (median KL-6 1188 U/mL vs. https://www.selleckchem.com/products/bozitinib.html 260 U/mL, p 1000 U/mL resulted independently associated with death and showed good accuracy in predicting a poorer outcome.
    In this review, we will summarize and discuss the literature currently available on various mechanisms within the relationship between thrombocytopenia and virus infections.The prognostic value of multiple glycemic parameters in poisoned patients was never assessed. We aim to explore the effects of glucose variability on short-term outcomes in nondiabetic and diabetic patients acutely poisoned with undifferentiated xenobiotics. We performed a prospective observational study in a tertiary center for toxicology in northeastern Romania. Over the course of 3 years, we included 1076 adults, older than 18 years, admitted for acute poisoning with a xenobiotic. The mortality rate was 4.1%. The admission blood glucose level (BGL) predicted mortality (OR 1.015, 95% CI 1.011-1.019, p less then 0.001) and complications (OR 1.005, 95% CI 1.001-1.009, p 0.02). The mean glucose level (MGL) after admission (OR 1.007, 95% CI 1.000-1.013, p 0.034) and coefficient of glucose variability (CV) were predictive for complications (OR 40.58, 95% CI 1.35-1220.52, p 0.033), using the same multivariable model. The receiver operating characteristic curve (ROC) analysis revealed that BGL had good predictive value for in-hospital mortality (area under the curve (AUC) = 0.744, 95% CI = 0.648-0.841, p less then 0.001), and complications (AUC = 0.618, 95% CI = 0.584-0.653, p less then 0.001). In patients acutely poisoned with xenobiotics, the BGL, MGL and CV can be useful as mortality and short-outcome predictors.In skeletal muscle, long noncoding RNAs (lncRNAs) are involved in dystrophin protein stabilization but also in the regulation of myocytes proliferation and differentiation. Hence, they could represent promising therapeutic targets and/or biomarkers for Duchenne and Becker muscular dystrophy (DMD/BMD). DMD and BMD are X-linked myopathies characterized by a progressive muscular dystrophy with or without dilatative cardiomyopathy. Two-thirds of DMD gene mutations are represented by deletions, and 63% of patients carrying DMD deletions are eligible for 45 to 55 multi-exons skipping (MES), becoming BMD patients (BMDΔ45-55). We analyzed the genomic lncRNA presence in 38 BMDΔ45-55 patients and characterized the lncRNA localized in introns 44 and 55 of the DMD gene. We highlighted that all four lncRNA are differentially expressed during myogenesis in immortalized and primary human myoblasts. In addition, the lncRNA44s2 was pointed out as a possible accelerator of differentiation. Interestingly, lncRNA44s expression was associated with a favorable clinical phenotype. These findings suggest that lncRNA44s2 could be involved in muscle differentiation process and become a potential disease progression biomarker. Based on these results, we support MES45-55 therapy and propose that the design of the CRISPR/Cas9 MES45-55 assay consider the lncRNA sequences bordering the exonic 45 to 55 deletion.Aging causes a decline in skeletal muscle function, resulting in a progressive loss of muscle mass, quality, and strength. A weak regenerative capacity is one of the critical causes of dysfunctional skeletal muscle in elderly individuals. The extracellular matrix (ECM) maintains the tissue framework structure in skeletal muscle. As shown by previous reports and our data, the gene expression of ECM components decreases with age, but the accumulation of collagen substantially increases in skeletal muscle. We examined the structural changes in ECM in aged skeletal muscle and found restricted ECM degradation. In aged skeletal muscles, several genes that maintain ECM structure, such as transforming growth factor β (TGF-β), tissue inhibitors of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs), and cathepsins, were downregulated. Muscle injury can induce muscle repair and regeneration in young and adult skeletal muscles. Surprisingly, muscle injury could not only efficiently induce regeneration in aged skeletal muscle, but it could also activate ECM remodeling and the clearance of ECM deposition. These results will help elucidate the mechanisms of muscle fibrosis with age and develop innovative antifibrotic therapies to decrease excessive collagen deposition in aged muscle.The current standard for diagnosing cervical intraepithelial neoplasia (CIN) is colposcopy followed by punch biopsy. We have developed flexible magnifying endoscopy with narrow band imaging (ME-NBI) for the diagnosis of CIN. Here, we investigated the feasibility of targeted endoscopic forceps biopsy (E-Bx) under guidance of ME-NBI for the diagnosis of CIN. We prospectively enrolled 32 consecutive patients with confirmed or suspected high-grade CIN undergoing cervical conization. Next to colposcopy, the same patients underwent ME-NBI just before conization. ME-NBI was performed, and 30 E-Bx samples were taken from lesions suspicious for high-grade CIN and 15 from non-suspicious mucosa. We recalled 82 punch biopsy (P-Bx) specimens taken from lesions suspicious for high-grade CIN under colposcopic examination before enrollment. The proportion of sufficient biopsy samples, which had an entire mucosal layer with subepithelial tissue, for the diagnosis of CIN was evaluated by both methods. Performance of targeted E-Bx for the final diagnosis of at least high-grade CIN was calculated. Seventeen P-Bx specimens were unavailable. The proportion of sufficient samples with E-Bx was 84%, which was similar to that with P-Bx (87%) (p = 0.672). The sensitivity, specificity, and accuracy of ME-NBI using E-Bx was 92%, 81%, and 88%, respectively. In conclusion, ME-NBI-guided E-Bx samples were feasible for histological diagnoses of CIN, and further investigation of its diagnostic accuracy is warranted.KL-6 is a sialoglycoprotein antigen which proved elevated in the serum of patients with different interstitial lung diseases, especially in those with a poorer outcome. Given that interstitial pneumonia is the most common presentation of SARS-CoV2 infection, we evaluated the prognostic role of KL-6 in patients with COVID-19 pneumonia. Patients with COVID-19 pneumonia were prospectively enrolled. Blood samples were collected at the time of enrolment (TOE) and on day 7 (T1). Serum KL-6 concentrations were measured by chemiluminescence enzyme immunoassay using a KL-6 antibody kit (LUMIPULSE G1200, Fujirebio) and the cut-off value was set at >1000 U/mL. Fifteen out of 34 enrolled patients (44.1%) died. Patients with unfavourable outcome showed significantly lower P/F ratio and higher IL-6 values and plasmatic concentrations of KL-6 at TOE compared with those who survived (median KL-6 1188 U/mL vs. https://www.selleckchem.com/products/bozitinib.html 260 U/mL, p 1000 U/mL resulted independently associated with death and showed good accuracy in predicting a poorer outcome.
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  • terogeneous electron transfer. When the Sr2+ concentration is high, the charge on the DNA backbone is compensated by the electrolyte and the charge on the electrode dominates the electron transfer dynamics and the opposite potential dependence is observed. These results open up the possibility of electromechanical switching using DNA superstructures.JQ1, a specific inhibitor of bromodomain-containing protein 4 (BRD4), could have great potential in the treatment of cervical cancer. However, its clinical application is limited by its short plasma half-life and limited antitumor efficacy. In this work, cisplatin (CDDP) was first utilized as the stabilizer and cooperator in the nanosystem (mPEG113-b-P(Glu10-co-Phe10)-CDDP/JQ1, called PGP-CDDP/JQ1) to break through the efficiency limitation of JQ1. The PGP-CDDP/JQ1 had a combination index (CI) of 0.21, exerting a strong cytotoxic synergistic effect. In vivo experiments revealed that PGP-CDDP/JQ1 had a significantly higher tumor inhibition effect (tumor inhibition rate 85% vs 14%) and plasma stability of JQ1 (area under the curve (AUC0-∞) 335.97 vs 16.88 μg × h/mL) than free JQ1. The mechanism underling the synergism of JQ1 with CDDP in PGP-CDDP/JQ1 was uncovered to be inhibiting Plk1-mutant Trp53 axis. Thus, this study provides an optional method for improving the clinical application of JQ1 in cervical cancer.Plasmonic self-assembled nanocavities are ideal platforms for extreme light localization as they deliver mode volumes of 105. Plasmon interference in these hybrid microresonator nanocavities produces surface-enhanced Raman scattering (SERS) signals many-fold larger than in the bare plasmonic constructs. These now allow remote access to molecules inside the ultrathin gaps, avoiding direct irradiation and thus preventing molecular damage. Combining subnanometer gaps with micrometer-scale resonators places a high computational demand on simulations, so a generalized boundary element method (BEM) solver is developed which requires 100-fold less computational resources to characterize these systems. Our results on extreme near-field enhancement open new potential for single-molecule photonic circuits, mid-infrared detectors, and remote spectroscopy.Semiconductor plasmonics is a recently emerging field that expands the chemical and physical bandwidth of the hitherto well-established noble metallic nanoparticles. Achieving tunable plasmonics from colloidal semiconductor nanocrystals has drawn enormous interest and is promising for plasmon-related applications. However, realizing this goal of tunable semiconductor nanocrystals is currently still a synthetic challenge. Here, we report a colloidal synthesis strategy for highly dispersed, platelet-shaped, antimony-doped copper sulfide semiconductor nanocrystals (Sb y -Cu x S NCs) with a dominant localized surface plasmon resonance (LSPR) band tunable from the near-infrared into the midvisible spectral range. This work presents the synthesis and quantifies the resulting plasmonic features. It furthermore elucidates the underlying carrier concentration requirements to realize a continuum of LSPR spectra. Building on our previous work on binary plasmonics Cu x S, Cu x Se, and Cu x Te NCs, the present method introduces a **** wider and finer tunability with ternary semiconductor plasmonics.Graphene-based one-dimensional macroscopic assemblies (GBOMAs) have attracted great attention and extensive efforts have been devoted to enabling great progress. However, their applications are still restricted to less functionalized electronics, and the superior potentials remain scarce. Herein, inspired by natural scallion structure, a novel strategy was introduced to effectively improve battery performances through the mesoscale scallion-like wrapping of graphene. The obtained RGO/Ag-Li anodes demonstrated an ultralow overpotential of ∼11.3 mV for 1800 h at 1 mA cm-2 in carbonate electrolytes, which is superior to those of the most previous reports. Besides, this strategy can also be further expanded to the high mass loading of various cathode nanomaterials, and the resulting RGO/LiFePO4 cathodes exhibited remarkable rate performance and cycle stability. This work opens a new avenue to explore and broaden the applications of GBOMAs as scaffolds in fabricating full lithium batteries via maximizing their advantages derived from the unique structure and properties.The synthesis of γ-lactams is reported by a formal (3+2) cycloaddition between readily available ketenes and aziridines or a one-pot formal (2+1+2) cycloaddition using imines as aziridine precursors. The method is practical, is scalable, and affords high yields. It also offers a high level of regio- and diastereoselectivity on a wide range of substrates as well as a high stereoselectivity in the case of enantiopure aziridines.This work presents the facile synthesis of heteroatom-doped fluorescent carbon quantum dots (C-dots), which could serve as an antioxidant. Herein, nitrogen, phosphorous, and sulfur codoped carbon dots (NPSC-dots) have been synthesized by a single-step hydrothermal strategy. https://www.selleckchem.com/products/ml264.html Owing to the radical scavenging activity of the NPSC-dots, they were tested against several methods as well as in practical applications. The antioxidant ability of the NPSC-dots was efficiently utilized on plastic films by coating with these NPSC-dots. For the very first time, NPSC-dots were immobilized onto nonpolar plastic films (polypropylene) via photochemical covalent grafting to extend the shelf life of food items or storage without affecting the quality of plastic films. The NPSC-dot-coated PP film with negligible deterioration of transparency was extensively studied using scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared (FTIR) analysis, X-ray photoelectron spectroscopy (XPS), contact angle measurement, and thermogravimetric analysis (TGA). The fluorescent character, antioxidant ability, and durability under different solvent systems of the coated film were examined. Also, the coated films were extensively and rigorously evaluated against simulated drastic environmental conditions to ensure the durability and antifogging application.
    terogeneous electron transfer. When the Sr2+ concentration is high, the charge on the DNA backbone is compensated by the electrolyte and the charge on the electrode dominates the electron transfer dynamics and the opposite potential dependence is observed. These results open up the possibility of electromechanical switching using DNA superstructures.JQ1, a specific inhibitor of bromodomain-containing protein 4 (BRD4), could have great potential in the treatment of cervical cancer. However, its clinical application is limited by its short plasma half-life and limited antitumor efficacy. In this work, cisplatin (CDDP) was first utilized as the stabilizer and cooperator in the nanosystem (mPEG113-b-P(Glu10-co-Phe10)-CDDP/JQ1, called PGP-CDDP/JQ1) to break through the efficiency limitation of JQ1. The PGP-CDDP/JQ1 had a combination index (CI) of 0.21, exerting a strong cytotoxic synergistic effect. In vivo experiments revealed that PGP-CDDP/JQ1 had a significantly higher tumor inhibition effect (tumor inhibition rate 85% vs 14%) and plasma stability of JQ1 (area under the curve (AUC0-∞) 335.97 vs 16.88 μg × h/mL) than free JQ1. The mechanism underling the synergism of JQ1 with CDDP in PGP-CDDP/JQ1 was uncovered to be inhibiting Plk1-mutant Trp53 axis. Thus, this study provides an optional method for improving the clinical application of JQ1 in cervical cancer.Plasmonic self-assembled nanocavities are ideal platforms for extreme light localization as they deliver mode volumes of 105. Plasmon interference in these hybrid microresonator nanocavities produces surface-enhanced Raman scattering (SERS) signals many-fold larger than in the bare plasmonic constructs. These now allow remote access to molecules inside the ultrathin gaps, avoiding direct irradiation and thus preventing molecular damage. Combining subnanometer gaps with micrometer-scale resonators places a high computational demand on simulations, so a generalized boundary element method (BEM) solver is developed which requires 100-fold less computational resources to characterize these systems. Our results on extreme near-field enhancement open new potential for single-molecule photonic circuits, mid-infrared detectors, and remote spectroscopy.Semiconductor plasmonics is a recently emerging field that expands the chemical and physical bandwidth of the hitherto well-established noble metallic nanoparticles. Achieving tunable plasmonics from colloidal semiconductor nanocrystals has drawn enormous interest and is promising for plasmon-related applications. However, realizing this goal of tunable semiconductor nanocrystals is currently still a synthetic challenge. Here, we report a colloidal synthesis strategy for highly dispersed, platelet-shaped, antimony-doped copper sulfide semiconductor nanocrystals (Sb y -Cu x S NCs) with a dominant localized surface plasmon resonance (LSPR) band tunable from the near-infrared into the midvisible spectral range. This work presents the synthesis and quantifies the resulting plasmonic features. It furthermore elucidates the underlying carrier concentration requirements to realize a continuum of LSPR spectra. Building on our previous work on binary plasmonics Cu x S, Cu x Se, and Cu x Te NCs, the present method introduces a much wider and finer tunability with ternary semiconductor plasmonics.Graphene-based one-dimensional macroscopic assemblies (GBOMAs) have attracted great attention and extensive efforts have been devoted to enabling great progress. However, their applications are still restricted to less functionalized electronics, and the superior potentials remain scarce. Herein, inspired by natural scallion structure, a novel strategy was introduced to effectively improve battery performances through the mesoscale scallion-like wrapping of graphene. The obtained RGO/Ag-Li anodes demonstrated an ultralow overpotential of ∼11.3 mV for 1800 h at 1 mA cm-2 in carbonate electrolytes, which is superior to those of the most previous reports. Besides, this strategy can also be further expanded to the high mass loading of various cathode nanomaterials, and the resulting RGO/LiFePO4 cathodes exhibited remarkable rate performance and cycle stability. This work opens a new avenue to explore and broaden the applications of GBOMAs as scaffolds in fabricating full lithium batteries via maximizing their advantages derived from the unique structure and properties.The synthesis of γ-lactams is reported by a formal (3+2) cycloaddition between readily available ketenes and aziridines or a one-pot formal (2+1+2) cycloaddition using imines as aziridine precursors. The method is practical, is scalable, and affords high yields. It also offers a high level of regio- and diastereoselectivity on a wide range of substrates as well as a high stereoselectivity in the case of enantiopure aziridines.This work presents the facile synthesis of heteroatom-doped fluorescent carbon quantum dots (C-dots), which could serve as an antioxidant. Herein, nitrogen, phosphorous, and sulfur codoped carbon dots (NPSC-dots) have been synthesized by a single-step hydrothermal strategy. https://www.selleckchem.com/products/ml264.html Owing to the radical scavenging activity of the NPSC-dots, they were tested against several methods as well as in practical applications. The antioxidant ability of the NPSC-dots was efficiently utilized on plastic films by coating with these NPSC-dots. For the very first time, NPSC-dots were immobilized onto nonpolar plastic films (polypropylene) via photochemical covalent grafting to extend the shelf life of food items or storage without affecting the quality of plastic films. The NPSC-dot-coated PP film with negligible deterioration of transparency was extensively studied using scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared (FTIR) analysis, X-ray photoelectron spectroscopy (XPS), contact angle measurement, and thermogravimetric analysis (TGA). The fluorescent character, antioxidant ability, and durability under different solvent systems of the coated film were examined. Also, the coated films were extensively and rigorously evaluated against simulated drastic environmental conditions to ensure the durability and antifogging application.
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  • This paper investigates how humans adapt next learning activity selection (in particular the knowledge it assumes and the knowledge it teaches) to learner personality and competence to inspire an adaptive learning activity selection algorithm. First, the paper describes the investigation to produce validated materials for the main study, namely the creation and validation of learner competence statements. Next, through an empirical study, we investigate the impact on learning activity selection of learners' emotional stability and competence. Participants considered a fictional learner with a certain competence, emotional stability, recent and prior learning activities engaged in, and selected the next learning activity in terms of the knowledge it used and the knowledge it taught. Three algorithms were created to adapt the selection of learning activities' knowledge complexity to learners' personality and competence. Finally, we evaluated the algorithms through a study with teachers, resulting in an algorithm that selects learning activities with varying assumed and taught knowledge adapted to learner characteristics.This paper discusses how the transcription hurdle in dialect corpus building can be cleared. While corpus analysis has strongly gained in popularity in linguistic research, dialect corpora are still relatively scarce. This scarcity can be attributed to several factors, one of which is the challenging nature of transcribing dialects, given a lack of both orthographic norms for many dialects and speech technological tools trained on dialect data. This paper addresses the questions (i) how dialects can be transcribed efficiently and (ii) whether speech technological tools can lighten the transcription work. These questions are tackled using the Southern Dutch dialects (SDDs) as case study, for which the usefulness of automatic speech recognition (ASR), respeaking, and forced alignment is considered. Tests with these tools indicate that dialects still constitute a major speech technological challenge. In the case of the SDDs, the decision was made to use speech technology only for the word-level segmentation of the audio files, as the transcription itself could not be sped up by ASR tools. The discussion does however indicate that the usefulness of ASR and other related tools for a dialect corpus project is strongly determined by the sound quality of the dialect recordings, the availability of statistical dialect-specific models, the degree of linguistic differentiation between the dialects and the standard language, and the goals the transcripts have to serve.Data analytics as a field is currently at a crucial point in its development, as a commoditization takes place in the context of increasing amounts of data, more user diversity, and automated analysis solutions, the latter potentially eliminating the need for expert analysts. A central hypothesis of the present paper is that data visualizations should be adapted to both the user and the context. This idea was initially addressed in Study 1, which demonstrated substantial interindividual variability among a group of experts when freely choosing an option to visualize data sets. To lay the theoretical groundwork for a systematic, taxonomic approach, a user model combining user traits, states, strategies, and actions was proposed and further evaluated empirically in Studies 2 and 3. The results implied that for adapting to user traits, statistical expertise is a relevant dimension that should be considered. Additionally, for adapting to user states different user intentions such as monitoring and analysis should be accounted for. These results were used to develop a taxonomy which adapts visualization recommendations to these (and other) factors. A preliminary attempt to validate the taxonomy in Study 4 tested its visualization recommendations with a group of experts. While the corresponding results were somewhat ambiguous overall, some aspects nevertheless supported the claim that a user-adaptive data visualization approach based on the principles outlined in the taxonomy can indeed be useful. While the present approach to user adaptivity is still in its infancy and should be extended (e.g., by testing more participants), the general approach appears to be very promising.The digitalization of financial services opened a window for new players in the financial industry. These start-ups take on tasks and functions previously reserved for banks, such as financing, asset management, and payments. In this article, we trace the transformation of the industry after digitalization. By using data on FinTech formations in Germany, we provide first evidence that entrepreneurial dynamics in the FinTech sector are not so **** driven by technology as by the educational and business background of the founders. Furthermore, we investigate the reactions of traditional banks to the emergence of these start-ups. In contrast with other emerging industries such as biotechnology, a network analysis shows that FinTechs have mostly engaged in strategic partnerships and only a few banks have acquired or obtained a financial interest in a FinTech. We explain the restraint of traditional banks to fully endorse the new possibilities of digitalized financial services with the characteristics of the technology itself and with the postponed fundamental decisions of banks to modernize their IT infrastructure.Persuasive technology (PT) is increasingly being used in the health and wellness domain to motivate and assist users with different lifestyles and behavioral health issues to change their attitudes and/or behaviors. There is growing evidence that PT can be effective at promoting behaviors in many health and wellness domains, including promoting physical activity (PA), healthy eating, and reducing sedentary behavior (SB). SB has been shown to pose a risk to overall health. https://www.selleckchem.com/products/nsc-23766.html Thus, reducing SB and increasing PA have been the focus of **** PT work. This paper aims to provide a systematic review of PTs for promoting PA and reducing SB. Specifically, we answer some fundamental questions regarding its design and effectiveness based on an empirical review of the literature on PTs for promoting PA and discouraging SB, from 2003 to 2019 (170 papers). There are three main objectives (1) to evaluate the effectiveness of PT in promoting PA and reducing SB; (2) to summarize and highlight trends in the outcomes such as system design, research methods, persuasive strategies employed and their implementaions, behavioral theories, and employed technological platforms; (3) to reveal the pitfalls and gaps in the present literature that can be leveraged and used to inform future research on designing PT for PA and SB.
    This paper investigates how humans adapt next learning activity selection (in particular the knowledge it assumes and the knowledge it teaches) to learner personality and competence to inspire an adaptive learning activity selection algorithm. First, the paper describes the investigation to produce validated materials for the main study, namely the creation and validation of learner competence statements. Next, through an empirical study, we investigate the impact on learning activity selection of learners' emotional stability and competence. Participants considered a fictional learner with a certain competence, emotional stability, recent and prior learning activities engaged in, and selected the next learning activity in terms of the knowledge it used and the knowledge it taught. Three algorithms were created to adapt the selection of learning activities' knowledge complexity to learners' personality and competence. Finally, we evaluated the algorithms through a study with teachers, resulting in an algorithm that selects learning activities with varying assumed and taught knowledge adapted to learner characteristics.This paper discusses how the transcription hurdle in dialect corpus building can be cleared. While corpus analysis has strongly gained in popularity in linguistic research, dialect corpora are still relatively scarce. This scarcity can be attributed to several factors, one of which is the challenging nature of transcribing dialects, given a lack of both orthographic norms for many dialects and speech technological tools trained on dialect data. This paper addresses the questions (i) how dialects can be transcribed efficiently and (ii) whether speech technological tools can lighten the transcription work. These questions are tackled using the Southern Dutch dialects (SDDs) as case study, for which the usefulness of automatic speech recognition (ASR), respeaking, and forced alignment is considered. Tests with these tools indicate that dialects still constitute a major speech technological challenge. In the case of the SDDs, the decision was made to use speech technology only for the word-level segmentation of the audio files, as the transcription itself could not be sped up by ASR tools. The discussion does however indicate that the usefulness of ASR and other related tools for a dialect corpus project is strongly determined by the sound quality of the dialect recordings, the availability of statistical dialect-specific models, the degree of linguistic differentiation between the dialects and the standard language, and the goals the transcripts have to serve.Data analytics as a field is currently at a crucial point in its development, as a commoditization takes place in the context of increasing amounts of data, more user diversity, and automated analysis solutions, the latter potentially eliminating the need for expert analysts. A central hypothesis of the present paper is that data visualizations should be adapted to both the user and the context. This idea was initially addressed in Study 1, which demonstrated substantial interindividual variability among a group of experts when freely choosing an option to visualize data sets. To lay the theoretical groundwork for a systematic, taxonomic approach, a user model combining user traits, states, strategies, and actions was proposed and further evaluated empirically in Studies 2 and 3. The results implied that for adapting to user traits, statistical expertise is a relevant dimension that should be considered. Additionally, for adapting to user states different user intentions such as monitoring and analysis should be accounted for. These results were used to develop a taxonomy which adapts visualization recommendations to these (and other) factors. A preliminary attempt to validate the taxonomy in Study 4 tested its visualization recommendations with a group of experts. While the corresponding results were somewhat ambiguous overall, some aspects nevertheless supported the claim that a user-adaptive data visualization approach based on the principles outlined in the taxonomy can indeed be useful. While the present approach to user adaptivity is still in its infancy and should be extended (e.g., by testing more participants), the general approach appears to be very promising.The digitalization of financial services opened a window for new players in the financial industry. These start-ups take on tasks and functions previously reserved for banks, such as financing, asset management, and payments. In this article, we trace the transformation of the industry after digitalization. By using data on FinTech formations in Germany, we provide first evidence that entrepreneurial dynamics in the FinTech sector are not so much driven by technology as by the educational and business background of the founders. Furthermore, we investigate the reactions of traditional banks to the emergence of these start-ups. In contrast with other emerging industries such as biotechnology, a network analysis shows that FinTechs have mostly engaged in strategic partnerships and only a few banks have acquired or obtained a financial interest in a FinTech. We explain the restraint of traditional banks to fully endorse the new possibilities of digitalized financial services with the characteristics of the technology itself and with the postponed fundamental decisions of banks to modernize their IT infrastructure.Persuasive technology (PT) is increasingly being used in the health and wellness domain to motivate and assist users with different lifestyles and behavioral health issues to change their attitudes and/or behaviors. There is growing evidence that PT can be effective at promoting behaviors in many health and wellness domains, including promoting physical activity (PA), healthy eating, and reducing sedentary behavior (SB). SB has been shown to pose a risk to overall health. https://www.selleckchem.com/products/nsc-23766.html Thus, reducing SB and increasing PA have been the focus of much PT work. This paper aims to provide a systematic review of PTs for promoting PA and reducing SB. Specifically, we answer some fundamental questions regarding its design and effectiveness based on an empirical review of the literature on PTs for promoting PA and discouraging SB, from 2003 to 2019 (170 papers). There are three main objectives (1) to evaluate the effectiveness of PT in promoting PA and reducing SB; (2) to summarize and highlight trends in the outcomes such as system design, research methods, persuasive strategies employed and their implementaions, behavioral theories, and employed technological platforms; (3) to reveal the pitfalls and gaps in the present literature that can be leveraged and used to inform future research on designing PT for PA and SB.
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  • MicroRNA-21 (miR-21) is one of the most frequently upregulated miRNAs in liver diseases such as nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). However, mechanistic pathways that connect NAFLD and HCC remain elusive. We developed a doxycycline (Dox)-inducible transgenic zebrafish model (LmiR21) which exhibited an upregulation of miR-21 in the liver, which in turn induced the full spectrum of NAFLD, including steatosis, inflammation, fibrosis, and HCC, in the LmiR21 fish. Diethylnitrosamine (DEN) treatment led to accelerated liver tumor formation and exacerbated their aggressiveness. Moreover, prolonged miR-21 expression for up to ten months induced nonalcoholic steatohepatitis (NASH)-related HCC (NAHCC). Immunoblotting and immunostaining confirmed the presence of miR-21 regulatory proteins (i.e., PTEN, SMAD7, p-AKT, p-SMAD3, and p-STAT3) in human nonviral HCC tissues and LmiR21 models. Thus, we demonstrated that miR-21 can induce NAHCC via at least three mechanisms First, the occurrence of hepatic steatosis increases with the decrease of ptenb, pparaa, and activation of the PI3K/AKT pathway; second, miR-21 induces hepatic inflammation (or NASH) through an increase in inflammatory gene expression via STAT3 signaling pathways, and induces liver fibrosis through hepatic stellate cell (HSC) activation and collagen deposition via TGF-β/Smad3/Smad7 signaling pathways; finally, oncogenic activation of Smad3/Stat3 signaling pathways induces HCC. Our LmiR21 models showed similar molecular pathology to the human cancer samples in terms of initiation of lipid metabolism disorder, inflammation, fibrosis and activation of the PI3K/AKT, TGF-β/SMADs and STAT3 (PTS) oncogenic signaling pathways. Our findings indicate that miR-21 plays critical roles in the mechanistic perspectives of NAHCC development via the PTS signaling networks.Soft matter that undergoes programmed macroscopic responses to molecular analytes has potential utility in a range of health and safety-related contexts. In this study, we report the design of a nematic liquid crystal (LC) composition that forms through dimerization of carboxylic acids and responds to the presence of vapors of organoamines by undergoing a visually distinct phase transition to an isotropic phase. Specifically, we screened mixtures of two carboxylic acids, 4-butylbenzoic acid and trans-4-pentylcyclohexanecarboxylic acid, and found select compositions that exhibited a nematic phase from 30.6 to 111.7 °C during heating and 110.6 to 3.1 °C during cooling. The metastable nematic phase formed at ambient temperatures was found to be long-lived (>5 days), thus enabling the use of the LC as a chemoresponsive optical material. By comparing experimental infrared (IR) spectra of the LC phase with vibrational frequencies calculated using density functional theory (DFT), we show that it is possible to distimers formed in the LC, hinting that the phase transition (including spatial-temporal characteristics of the pathway) induced in this class of hydrogen bonded LC may offer the basis of a facile and chemically selective way of reporting the presence of volatile amines. This proposal is supported by exploratory experiments in which we show that it is possible to trigger a phase transition in the LC by exposure to volatile amines emitted from rotting fish. Overall, these results provide new principles for the design of chemoresponsive soft matter based on hydrogen bonded LCs that may find use as the basis of low-cost visual indicators of chemical environments.Increased glycolytic activity is a hallmark of cancer initiation and progression and is often observed in non-small cell lung cancer (NSCLC). Pyruvate dehydrogenase (PDH) complex acts as a gatekeeper between glycolysis and oxidative phosphorylation, and activation of PDH is known to inhibit glycolytic activity. As part of a standard therapeutic regimen, patients with NSCLC harboring oncogenic mutations in the epidermal growth factor receptor (EGFR) are treated with EGFR tyrosine kinase inhibitors (EGFR TKIs). Independent of good initial response, development of resistance to this therapy is inevitable. In the presented work, we propose that inhibition of glycolysis will add to the therapeutic effects and possibly prevent development of resistance against both EGFR TKIs and ionizing radiation in NSCLC. Analysis of transcriptome data from two independent NSCLC patient cohorts identified increased expression of pyruvate dehydrogenase kinase 1 (PDHK1) as well as upregulated expression of genes involved in glucoseNSCLC.Local quantum uncertainty and interferometric power were introduced by Girolami et al. as geometric quantifiers of quantum correlations. The aim of the present paper is to discuss their properties in a unified manner by means of the metric adjusted skew information defined by Hansen.During pregnancy, physical activity relates to better maternal and child mental and physical health. https://www.selleckchem.com/products/mhy1485.html Accelerometry is thought to be effective for assessing free-living physical activity, but the feasibility/acceptability of accelerometer use in pregnant adolescents has not been reported. In this short communication, we conducted secondary analysis of a small pilot study to describe the feasibility/acceptability of accelerometry in pregnant adolescents and the preliminary results of physical activity characteristics. Participants were recruited from a multidisciplinary adolescent perinatal clinic. Physical activity was assessed with wrist-worn accelerometers. Feasibility was described as median days of valid wear (≥10 h of wear/day) for the total sample and the number/percentage of participants with ≥4 days of valid wear. Sensitivity analyses of wear time were performed. Acceptability ratings were collected by structured interview. Thirty-six pregnant (14.6 ± 2.1 gestational weeks) adolescents (17.9 ± 1.0 years) participated. Median days of valid wear were 4 days. Seventeen participants (51.5%) had ≥4 days of valid wear. There were no differences in characteristics of adolescents with vs. without ≥4 days of valid wear. Twenty participants (60.6%) had ≥3 days of valid wear, 24 (72.7%) ≥2 valid days, and 27 (81.8%) ≥1 valid wear day. Acceptability ratings were neutral. Assessing physical activity with accelerometry in pregnant adolescents was neither feasible nor acceptable with the current conditions. Future research should investigate additional incentives and the potential utility of a lower wear-time criterion in pregnant adolescents.
    MicroRNA-21 (miR-21) is one of the most frequently upregulated miRNAs in liver diseases such as nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). However, mechanistic pathways that connect NAFLD and HCC remain elusive. We developed a doxycycline (Dox)-inducible transgenic zebrafish model (LmiR21) which exhibited an upregulation of miR-21 in the liver, which in turn induced the full spectrum of NAFLD, including steatosis, inflammation, fibrosis, and HCC, in the LmiR21 fish. Diethylnitrosamine (DEN) treatment led to accelerated liver tumor formation and exacerbated their aggressiveness. Moreover, prolonged miR-21 expression for up to ten months induced nonalcoholic steatohepatitis (NASH)-related HCC (NAHCC). Immunoblotting and immunostaining confirmed the presence of miR-21 regulatory proteins (i.e., PTEN, SMAD7, p-AKT, p-SMAD3, and p-STAT3) in human nonviral HCC tissues and LmiR21 models. Thus, we demonstrated that miR-21 can induce NAHCC via at least three mechanisms First, the occurrence of hepatic steatosis increases with the decrease of ptenb, pparaa, and activation of the PI3K/AKT pathway; second, miR-21 induces hepatic inflammation (or NASH) through an increase in inflammatory gene expression via STAT3 signaling pathways, and induces liver fibrosis through hepatic stellate cell (HSC) activation and collagen deposition via TGF-β/Smad3/Smad7 signaling pathways; finally, oncogenic activation of Smad3/Stat3 signaling pathways induces HCC. Our LmiR21 models showed similar molecular pathology to the human cancer samples in terms of initiation of lipid metabolism disorder, inflammation, fibrosis and activation of the PI3K/AKT, TGF-β/SMADs and STAT3 (PTS) oncogenic signaling pathways. Our findings indicate that miR-21 plays critical roles in the mechanistic perspectives of NAHCC development via the PTS signaling networks.Soft matter that undergoes programmed macroscopic responses to molecular analytes has potential utility in a range of health and safety-related contexts. In this study, we report the design of a nematic liquid crystal (LC) composition that forms through dimerization of carboxylic acids and responds to the presence of vapors of organoamines by undergoing a visually distinct phase transition to an isotropic phase. Specifically, we screened mixtures of two carboxylic acids, 4-butylbenzoic acid and trans-4-pentylcyclohexanecarboxylic acid, and found select compositions that exhibited a nematic phase from 30.6 to 111.7 °C during heating and 110.6 to 3.1 °C during cooling. The metastable nematic phase formed at ambient temperatures was found to be long-lived (>5 days), thus enabling the use of the LC as a chemoresponsive optical material. By comparing experimental infrared (IR) spectra of the LC phase with vibrational frequencies calculated using density functional theory (DFT), we show that it is possible to distimers formed in the LC, hinting that the phase transition (including spatial-temporal characteristics of the pathway) induced in this class of hydrogen bonded LC may offer the basis of a facile and chemically selective way of reporting the presence of volatile amines. This proposal is supported by exploratory experiments in which we show that it is possible to trigger a phase transition in the LC by exposure to volatile amines emitted from rotting fish. Overall, these results provide new principles for the design of chemoresponsive soft matter based on hydrogen bonded LCs that may find use as the basis of low-cost visual indicators of chemical environments.Increased glycolytic activity is a hallmark of cancer initiation and progression and is often observed in non-small cell lung cancer (NSCLC). Pyruvate dehydrogenase (PDH) complex acts as a gatekeeper between glycolysis and oxidative phosphorylation, and activation of PDH is known to inhibit glycolytic activity. As part of a standard therapeutic regimen, patients with NSCLC harboring oncogenic mutations in the epidermal growth factor receptor (EGFR) are treated with EGFR tyrosine kinase inhibitors (EGFR TKIs). Independent of good initial response, development of resistance to this therapy is inevitable. In the presented work, we propose that inhibition of glycolysis will add to the therapeutic effects and possibly prevent development of resistance against both EGFR TKIs and ionizing radiation in NSCLC. Analysis of transcriptome data from two independent NSCLC patient cohorts identified increased expression of pyruvate dehydrogenase kinase 1 (PDHK1) as well as upregulated expression of genes involved in glucoseNSCLC.Local quantum uncertainty and interferometric power were introduced by Girolami et al. as geometric quantifiers of quantum correlations. The aim of the present paper is to discuss their properties in a unified manner by means of the metric adjusted skew information defined by Hansen.During pregnancy, physical activity relates to better maternal and child mental and physical health. https://www.selleckchem.com/products/mhy1485.html Accelerometry is thought to be effective for assessing free-living physical activity, but the feasibility/acceptability of accelerometer use in pregnant adolescents has not been reported. In this short communication, we conducted secondary analysis of a small pilot study to describe the feasibility/acceptability of accelerometry in pregnant adolescents and the preliminary results of physical activity characteristics. Participants were recruited from a multidisciplinary adolescent perinatal clinic. Physical activity was assessed with wrist-worn accelerometers. Feasibility was described as median days of valid wear (≥10 h of wear/day) for the total sample and the number/percentage of participants with ≥4 days of valid wear. Sensitivity analyses of wear time were performed. Acceptability ratings were collected by structured interview. Thirty-six pregnant (14.6 ± 2.1 gestational weeks) adolescents (17.9 ± 1.0 years) participated. Median days of valid wear were 4 days. Seventeen participants (51.5%) had ≥4 days of valid wear. There were no differences in characteristics of adolescents with vs. without ≥4 days of valid wear. Twenty participants (60.6%) had ≥3 days of valid wear, 24 (72.7%) ≥2 valid days, and 27 (81.8%) ≥1 valid wear day. Acceptability ratings were neutral. Assessing physical activity with accelerometry in pregnant adolescents was neither feasible nor acceptable with the current conditions. Future research should investigate additional incentives and the potential utility of a lower wear-time criterion in pregnant adolescents.
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  • BACKGROUND Generally, hemangiomas do not require surgical intervention; however, cases of large hemangiomas, potentially involving the throat and trachea, necessitate surgical therapy. Here, we present a case of hypopharyngeal hemangioma in an adult that was successfully treated with neodymium-doped yttrium aluminum garnet (Nd-YAG) laser. CASE SUMMARY Laryngoscopic examination of a 61-year-old man demonstrated the presence of a large, submucosal vascular lesion that extended into the epiglottis, left arytenoid cartilage, lateral to the aryepiglottic fold, and pyriform sinus. The lesion was resected and photocoagulated with limited hemorrhage using Nd YAG laser. The hypopharyngeal hemangioma was completely excised. The patient showed no recurrence of hypopharyngeal hemangioma during the 1.5-year follow-up period. CONCLUSION Laser therapy is one of the effective tools for treating hemangiomas with rapid, uncontrolled growth or in functional areas, with few side effects and complications. The present case of a male patient with a large hypopharyngeal hemangioma, treated with YAG laser, demonstrates the efficacy of laser photocoagulation in treating cases of hemangiomas, without the risk of bleeding or airway obstruction. The favorable postoperative outcomes demonstrated by our patient with Nd YAG laser therapy indicate its consideration in the therapy of similar cases. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.BACKGROUND Novel oral anticoagulants (NOACs) are commonly used for the anticoagulation of patients with atrial fibrillation. Reports of thrombocytopenic toxicity of NOACs are limited. In this report, we present a case of thrombocytopenia likely induced by rivaroxaban, which is an extremely rare adverse drug reaction. CASE SUMMARY A 70-year-old man presented to the cardiovascular department with a chief complaint of intermittent chest tightness and dyspnea over the last five years. Vital signs were within normal limits at presentation, with a heart rate of 65 beats/min, blood pressure of 138/78 mmHg, respiratory rate of 19 breaths/min, and temperature of 36.1°C. Laboratory tests indicated a platelet count of 163 × 109/L on admission. Anticoagulant therapy with rivaroxaban, a NOAC, was started on the second day of hospitalization. The platelet count decreased to 30 × 109/L on hospital day 11 and then 10 × 109/L on day 12. Rivaroxaban was stopped on day 13 when the platelet count decreased to 5 × 109/L. After the cessation of rivaroxaban, the platelet count returned to normal. The patient was diagnosed with thrombocytopenia, which was likely induced by rivaroxaban. The incidence of thrombocytopenic toxicity of NOACs is extremely low. CONCLUSION Thrombocytopenia during anticoagulation therapy may be associated with a high risk of life-threatening bleeding. For elderly patients, changes in platelet count should be carefully monitored at the beginning of NOAC treatment, and we should be on the alert for bleeding events as well. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.BACKGROUND Although few studies have reported hyponatremia due to carbamazepine or oxcarbazepine in patients with epilepsy, no study has investigated cases of carbamazepine- or oxcarbazepine-induced hyponatremia or unsteady gait in patients with neuropathic pain. Herein, we report a case of oxcarbazepine-induced lower leg weakness in a patient with trigeminal neuralgia and summarize the diagnosis, treatment, and changes of clinical symptoms. CASE SUMMARY A 78-year-old male with a history of lumbar spinal stenosis was admitted to the hospital after he experienced lancinating pain around his right cheek, eyes, and lip, and was diagnosed with trigeminal neuralgia at the right maxillary and mandibular branch. He was prescribed oxcarbazepine (600 mg/d), milnacipran (25 mg/d), and oxycodone/naloxone (20 mg/10 mg/d) for four years. Four years later, the patient experienced symptoms associated with spinal stenosis, including pain in the lower extremities and unsteady gait. His serum sodium level was 127 mmol/L. Assuming oxcarbazepine to be the cause of the hyponatremia, oxcarbazepine administration was put on hold and the patient was switched to topiramate. At subsequent visit, the patient's serum sodium level had normalized to 143 mmol/L and his unsteady gait had improved. CONCLUSION Oxcarbazepine-induced hyponatremia may cause lower extremity weakness and unsteady gait, which should be differentiated from those caused by spinal stenosis. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.BACKGROUND Allograft artery mycotic aneurysm (MA) represents a rare but life-threatening complication of kidney transplantation. Graftectomy is widely considered the safest option. Due to the rarity of the disease and the substantial risk of fatal consequences, experience with conservative strategies is limited. To date, only a few reports on surgical repair have been published. We describe a case of true MA successfully managed by aneurysm resection and arterial re-anastomosis. CASE SUMMARY An 18-year-old gentleman, on post-operative day 70 after deceased donor kidney transplantation, presented with malaise, low urinary output, and worsening renal function. Screening organ preservation fluid cultures, collected at the time of surgery, were positive for Candida albicans. Doppler ultrasound and contrast-enhanced computer tomography showed a 4-cm-sized, saccular aneurysm of the iuxta-anastomotic segment of the allograft artery, suspicious for MA. The lesion was wide-necked and extended to the distal bifurcation of the main arterial branch, thus preventing endovascular stenting and embolization. After multidisciplinary discussion, the patient underwent surgical exploration, aneurysm excision, and re-anastomosis between the stump of the allograft artery and the internal iliac artery. https://www.selleckchem.com/products/ml264.html The procedure was uneventful. Histology and microbiology evaluation of the surgical specimen confirmed the diagnosis of MA caused by Candida infection. Three years after the operation, the patient is doing very well with excellent allograft function and no signs of recurrent disease. CONCLUSION Surgical repair represents a feasible option in carefully selected patients with allograft artery MA. Anti-fungal prophylaxis is advised when preservation fluid cultures are positive. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
    BACKGROUND Generally, hemangiomas do not require surgical intervention; however, cases of large hemangiomas, potentially involving the throat and trachea, necessitate surgical therapy. Here, we present a case of hypopharyngeal hemangioma in an adult that was successfully treated with neodymium-doped yttrium aluminum garnet (Nd-YAG) laser. CASE SUMMARY Laryngoscopic examination of a 61-year-old man demonstrated the presence of a large, submucosal vascular lesion that extended into the epiglottis, left arytenoid cartilage, lateral to the aryepiglottic fold, and pyriform sinus. The lesion was resected and photocoagulated with limited hemorrhage using Nd YAG laser. The hypopharyngeal hemangioma was completely excised. The patient showed no recurrence of hypopharyngeal hemangioma during the 1.5-year follow-up period. CONCLUSION Laser therapy is one of the effective tools for treating hemangiomas with rapid, uncontrolled growth or in functional areas, with few side effects and complications. The present case of a male patient with a large hypopharyngeal hemangioma, treated with YAG laser, demonstrates the efficacy of laser photocoagulation in treating cases of hemangiomas, without the risk of bleeding or airway obstruction. The favorable postoperative outcomes demonstrated by our patient with Nd YAG laser therapy indicate its consideration in the therapy of similar cases. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.BACKGROUND Novel oral anticoagulants (NOACs) are commonly used for the anticoagulation of patients with atrial fibrillation. Reports of thrombocytopenic toxicity of NOACs are limited. In this report, we present a case of thrombocytopenia likely induced by rivaroxaban, which is an extremely rare adverse drug reaction. CASE SUMMARY A 70-year-old man presented to the cardiovascular department with a chief complaint of intermittent chest tightness and dyspnea over the last five years. Vital signs were within normal limits at presentation, with a heart rate of 65 beats/min, blood pressure of 138/78 mmHg, respiratory rate of 19 breaths/min, and temperature of 36.1°C. Laboratory tests indicated a platelet count of 163 × 109/L on admission. Anticoagulant therapy with rivaroxaban, a NOAC, was started on the second day of hospitalization. The platelet count decreased to 30 × 109/L on hospital day 11 and then 10 × 109/L on day 12. Rivaroxaban was stopped on day 13 when the platelet count decreased to 5 × 109/L. After the cessation of rivaroxaban, the platelet count returned to normal. The patient was diagnosed with thrombocytopenia, which was likely induced by rivaroxaban. The incidence of thrombocytopenic toxicity of NOACs is extremely low. CONCLUSION Thrombocytopenia during anticoagulation therapy may be associated with a high risk of life-threatening bleeding. For elderly patients, changes in platelet count should be carefully monitored at the beginning of NOAC treatment, and we should be on the alert for bleeding events as well. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.BACKGROUND Although few studies have reported hyponatremia due to carbamazepine or oxcarbazepine in patients with epilepsy, no study has investigated cases of carbamazepine- or oxcarbazepine-induced hyponatremia or unsteady gait in patients with neuropathic pain. Herein, we report a case of oxcarbazepine-induced lower leg weakness in a patient with trigeminal neuralgia and summarize the diagnosis, treatment, and changes of clinical symptoms. CASE SUMMARY A 78-year-old male with a history of lumbar spinal stenosis was admitted to the hospital after he experienced lancinating pain around his right cheek, eyes, and lip, and was diagnosed with trigeminal neuralgia at the right maxillary and mandibular branch. He was prescribed oxcarbazepine (600 mg/d), milnacipran (25 mg/d), and oxycodone/naloxone (20 mg/10 mg/d) for four years. Four years later, the patient experienced symptoms associated with spinal stenosis, including pain in the lower extremities and unsteady gait. His serum sodium level was 127 mmol/L. Assuming oxcarbazepine to be the cause of the hyponatremia, oxcarbazepine administration was put on hold and the patient was switched to topiramate. At subsequent visit, the patient's serum sodium level had normalized to 143 mmol/L and his unsteady gait had improved. CONCLUSION Oxcarbazepine-induced hyponatremia may cause lower extremity weakness and unsteady gait, which should be differentiated from those caused by spinal stenosis. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.BACKGROUND Allograft artery mycotic aneurysm (MA) represents a rare but life-threatening complication of kidney transplantation. Graftectomy is widely considered the safest option. Due to the rarity of the disease and the substantial risk of fatal consequences, experience with conservative strategies is limited. To date, only a few reports on surgical repair have been published. We describe a case of true MA successfully managed by aneurysm resection and arterial re-anastomosis. CASE SUMMARY An 18-year-old gentleman, on post-operative day 70 after deceased donor kidney transplantation, presented with malaise, low urinary output, and worsening renal function. Screening organ preservation fluid cultures, collected at the time of surgery, were positive for Candida albicans. Doppler ultrasound and contrast-enhanced computer tomography showed a 4-cm-sized, saccular aneurysm of the iuxta-anastomotic segment of the allograft artery, suspicious for MA. The lesion was wide-necked and extended to the distal bifurcation of the main arterial branch, thus preventing endovascular stenting and embolization. After multidisciplinary discussion, the patient underwent surgical exploration, aneurysm excision, and re-anastomosis between the stump of the allograft artery and the internal iliac artery. https://www.selleckchem.com/products/ml264.html The procedure was uneventful. Histology and microbiology evaluation of the surgical specimen confirmed the diagnosis of MA caused by Candida infection. Three years after the operation, the patient is doing very well with excellent allograft function and no signs of recurrent disease. CONCLUSION Surgical repair represents a feasible option in carefully selected patients with allograft artery MA. Anti-fungal prophylaxis is advised when preservation fluid cultures are positive. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
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  • A disparity in the benefits that arise from a transaction between the parties does not indicate or entail that exploitation has taken place.Modern scholarship has drawn hasty and numerous parallels between the Yellow Peril discourses of the 19th- and 20th-century plagues and the recent racialization of infectious disease in the 21st-century. While highlighting these similarities is politically useful against Sinophobic epidemic narratives, Michel Foucault argues that truly understanding the past's continuity in the present requires a more rigorous genealogical approach. Employing this premise in a comparative analysis, this work demonstrates a critical discontinuity in the epidemic imaginary that framed the Chinese as pathogenic. Consequently, those seeking to prevent future disease racialization must understand modern Sinophobia as fundamentally distinct from that of the past.Disseminated talaromycosis caused by Talaromyces marneffei is a life-threatening opportunistic infection. Although amphotericin B deoxycholate (dAmB) remains the first-line induction treatment, voriconazole can also be used. However, no clinical trials have compared dAmB and voriconazole in the administration of talaromycosis. We retrospectively evaluated the efficacy and safety of voriconazole or dAmB as induction therapy for talaromycosis in HIV-infected patients. We enrolled HIV-infected patients with a confirmed Talaromyces marneffei infection who received intravenous dAmB (0.6 to 0.7 mg/kg daily for 2 weeks) or voriconazole (6 mg/kg every 12 h on day 1 and 4 mg/kg every 12 h afterward) as induction therapy, followed by oral itraconazole as consolidation and maintenance therapy. Drug efficacy was evaluated based on response rate. Drug safety was evaluated based on the occurrence of adverse events. In total, 58 patients who received voriconazole and 82 who received dAmB were enrolled from two hospitals. The voriconazole and dAmB treatment groups had similar response rates at the primary and follow-up efficacy evaluations. However, the durations of induction antifungal therapy and hospital stay were shorter for patients in the voriconazole group than in the dAmB group. Few adverse reactions occurred in either the voriconazole or dAmB group. Our retrospective study indicated that voriconazole is an effective and safe induction antifungal drug for HIV-associated disseminated talaromycosis. The duration of induction treatment with voriconazole was shorter, indicating its potential as a better choice in clinical practice. The duration of voriconazole induction therapy is 11 to 13 days.It is well established that inflammatory reactions and oxidative stress play an imperial role in cerebral ischemia-reperfusion pathogenesis. Fisetin is a flavonoid and has an antioxidant and anti-inflammatory effect on various diseases. In this study, we have been working to examine the neuroprotective effect of fisetin in brain injuries triggered by cerebral ischemic-reperfusion and explore the potential role of nuclear factor kappa B (NF-κB) signaling. In vitro, fisetin was examined against the cell viability, lactate dehydrogenase (LDH) leakage, cytokines, and apoptosis after ischemia/reperfusion (I/R) induced in the cells. In vivo, I/R injury was induced in the brain via transient middle cerebral artery occlusion (2 h) and reperfusion (20 h). The infarction area, brain water content, and neurofunctional parameters were also estimated. Inflammatory cytokines and brain injury markers were scrutinized at the end of the study. Fisetin treatment alleviated cell injury and suppressed the inflammatory cytokines (interleukin-1 (IL-1), tumor necrosis factor- α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), interleukin-16 (IL-6), and prostaglandin E2 (PGE2)) and antioxidant parameters in a dose-dependent manner. Fisetin significantly (P less then 0.001) reduced the infarct volume, brain water content. Fisetin significantly (P less then 0.001) suppressed the neurological parameters and inflammatory cytokines such as IL-1, TNF-α, iNOS, IL-1β, COX-2, IL-6, PGE2, and oxidative markers in a dose-dependent manner. Fisetin significantly (P less then 0.001) reduced the inflammatory mediators including NF-κB and intercellular adhesion molecule 1 (ICAM-1). Further studies also showed that fisetin significantly inhibited the NF-κB activity via inflammatory and antioxidant pathways. In conclusion, by suppressing inflammatory cytokines, fisetin protected the brain tissue against I/R injury, and this effect could be due to reduced NF-κB activity.This study was designed to study the effects of vitamin D3 supplementation on the cognitive dysfunction and neurological function of traumatic brain injury (TBI) and the possible underlying mechanisms. To this purpose, different doses of vitamin D3 were intraperitoneally injection to TBI rats for one week before TBI surgery and three consecutive weeks after TBI. Brain edema evaluation was conducted on the third day and Evans blue staining for blood-brain barrier (BBB) permeability on the seventh day after TBI. Rat behavior was assessed by evaluation of neurological scores and morris water maze. It was revealed that vitamin D levels increased in serum after the administration of vitamin D3 for one week. TBI led to neurological deficit, together with brain edema, BBB disruption and inflammation. Vitamin D3 supplement ameliorated neurological deficit and cognitive impairments induced by TBI. Vitamin D3 administration reduced brain edema and impairments of blood-brain barrier induced by TBI, as well as decreased inflammatory response in TBI rat brain. Our results showed that vitamin D3 administration alleviated neurobehavioral deficits and improved brain edema after TBI. Vitamin D3 inhibited inflammatory cytokines and decreased BBB disruption in TBI rats. Vitamin D3 may be used for the treatment of TBI as a protective intervention.Multi-location supervised field trials in India were conducted with a combination pesticide formulation (iprovalicarb 5.5% + propineb 61.25%, 66.75% WP) in tomato to study dissipation behavior at single (iprovalicarb 137.5 g a.i. ha-1 + propineb 1531.25 g a.i. ha-1) and double (iprovalicarb 275 g a.i. https://www.selleckchem.com/products/mito-tempo.html ha-1 + propineb 3062.5 g a.i. ha-1) dose. The samples were processed using a modified QuEChERS method for iprovalicarb and acid hydrolysis followed by carbon disulfide estimation for propineb and confirmation of their respective residues by LC-MS/MS and GC-MS. Both the fungicides in tomato fruits obey first-order kinetics irrespective of location and doses. Half-life (t1/2) values at all the four locations ranged from 1.08 to 4.67 days for iprovalicarb and 3.36 to 11.41 days for propineb in tomato. The Food Safety and Standards Authority of India (FSSAI) has set MRL of 1 mg kg-1 for propineb, but no MRL is yet fixed for iprovalicarb. Using OECD MRL calculator, the calculated MRL for iprovalicarb and propineb was found to be 2 and 4 mg kg-1, respectively.
    A disparity in the benefits that arise from a transaction between the parties does not indicate or entail that exploitation has taken place.Modern scholarship has drawn hasty and numerous parallels between the Yellow Peril discourses of the 19th- and 20th-century plagues and the recent racialization of infectious disease in the 21st-century. While highlighting these similarities is politically useful against Sinophobic epidemic narratives, Michel Foucault argues that truly understanding the past's continuity in the present requires a more rigorous genealogical approach. Employing this premise in a comparative analysis, this work demonstrates a critical discontinuity in the epidemic imaginary that framed the Chinese as pathogenic. Consequently, those seeking to prevent future disease racialization must understand modern Sinophobia as fundamentally distinct from that of the past.Disseminated talaromycosis caused by Talaromyces marneffei is a life-threatening opportunistic infection. Although amphotericin B deoxycholate (dAmB) remains the first-line induction treatment, voriconazole can also be used. However, no clinical trials have compared dAmB and voriconazole in the administration of talaromycosis. We retrospectively evaluated the efficacy and safety of voriconazole or dAmB as induction therapy for talaromycosis in HIV-infected patients. We enrolled HIV-infected patients with a confirmed Talaromyces marneffei infection who received intravenous dAmB (0.6 to 0.7 mg/kg daily for 2 weeks) or voriconazole (6 mg/kg every 12 h on day 1 and 4 mg/kg every 12 h afterward) as induction therapy, followed by oral itraconazole as consolidation and maintenance therapy. Drug efficacy was evaluated based on response rate. Drug safety was evaluated based on the occurrence of adverse events. In total, 58 patients who received voriconazole and 82 who received dAmB were enrolled from two hospitals. The voriconazole and dAmB treatment groups had similar response rates at the primary and follow-up efficacy evaluations. However, the durations of induction antifungal therapy and hospital stay were shorter for patients in the voriconazole group than in the dAmB group. Few adverse reactions occurred in either the voriconazole or dAmB group. Our retrospective study indicated that voriconazole is an effective and safe induction antifungal drug for HIV-associated disseminated talaromycosis. The duration of induction treatment with voriconazole was shorter, indicating its potential as a better choice in clinical practice. The duration of voriconazole induction therapy is 11 to 13 days.It is well established that inflammatory reactions and oxidative stress play an imperial role in cerebral ischemia-reperfusion pathogenesis. Fisetin is a flavonoid and has an antioxidant and anti-inflammatory effect on various diseases. In this study, we have been working to examine the neuroprotective effect of fisetin in brain injuries triggered by cerebral ischemic-reperfusion and explore the potential role of nuclear factor kappa B (NF-κB) signaling. In vitro, fisetin was examined against the cell viability, lactate dehydrogenase (LDH) leakage, cytokines, and apoptosis after ischemia/reperfusion (I/R) induced in the cells. In vivo, I/R injury was induced in the brain via transient middle cerebral artery occlusion (2 h) and reperfusion (20 h). The infarction area, brain water content, and neurofunctional parameters were also estimated. Inflammatory cytokines and brain injury markers were scrutinized at the end of the study. Fisetin treatment alleviated cell injury and suppressed the inflammatory cytokines (interleukin-1 (IL-1), tumor necrosis factor- α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), interleukin-16 (IL-6), and prostaglandin E2 (PGE2)) and antioxidant parameters in a dose-dependent manner. Fisetin significantly (P less then 0.001) reduced the infarct volume, brain water content. Fisetin significantly (P less then 0.001) suppressed the neurological parameters and inflammatory cytokines such as IL-1, TNF-α, iNOS, IL-1β, COX-2, IL-6, PGE2, and oxidative markers in a dose-dependent manner. Fisetin significantly (P less then 0.001) reduced the inflammatory mediators including NF-κB and intercellular adhesion molecule 1 (ICAM-1). Further studies also showed that fisetin significantly inhibited the NF-κB activity via inflammatory and antioxidant pathways. In conclusion, by suppressing inflammatory cytokines, fisetin protected the brain tissue against I/R injury, and this effect could be due to reduced NF-κB activity.This study was designed to study the effects of vitamin D3 supplementation on the cognitive dysfunction and neurological function of traumatic brain injury (TBI) and the possible underlying mechanisms. To this purpose, different doses of vitamin D3 were intraperitoneally injection to TBI rats for one week before TBI surgery and three consecutive weeks after TBI. Brain edema evaluation was conducted on the third day and Evans blue staining for blood-brain barrier (BBB) permeability on the seventh day after TBI. Rat behavior was assessed by evaluation of neurological scores and morris water maze. It was revealed that vitamin D levels increased in serum after the administration of vitamin D3 for one week. TBI led to neurological deficit, together with brain edema, BBB disruption and inflammation. Vitamin D3 supplement ameliorated neurological deficit and cognitive impairments induced by TBI. Vitamin D3 administration reduced brain edema and impairments of blood-brain barrier induced by TBI, as well as decreased inflammatory response in TBI rat brain. Our results showed that vitamin D3 administration alleviated neurobehavioral deficits and improved brain edema after TBI. Vitamin D3 inhibited inflammatory cytokines and decreased BBB disruption in TBI rats. Vitamin D3 may be used for the treatment of TBI as a protective intervention.Multi-location supervised field trials in India were conducted with a combination pesticide formulation (iprovalicarb 5.5% + propineb 61.25%, 66.75% WP) in tomato to study dissipation behavior at single (iprovalicarb 137.5 g a.i. ha-1 + propineb 1531.25 g a.i. ha-1) and double (iprovalicarb 275 g a.i. https://www.selleckchem.com/products/mito-tempo.html ha-1 + propineb 3062.5 g a.i. ha-1) dose. The samples were processed using a modified QuEChERS method for iprovalicarb and acid hydrolysis followed by carbon disulfide estimation for propineb and confirmation of their respective residues by LC-MS/MS and GC-MS. Both the fungicides in tomato fruits obey first-order kinetics irrespective of location and doses. Half-life (t1/2) values at all the four locations ranged from 1.08 to 4.67 days for iprovalicarb and 3.36 to 11.41 days for propineb in tomato. The Food Safety and Standards Authority of India (FSSAI) has set MRL of 1 mg kg-1 for propineb, but no MRL is yet fixed for iprovalicarb. Using OECD MRL calculator, the calculated MRL for iprovalicarb and propineb was found to be 2 and 4 mg kg-1, respectively.
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  • Perfluorooctanoic acid is a synthetic perfluoroalkyl-persistent in the environment and toxic to humans. N-acetylcysteine is a pro-drug of both amino acid l-cysteine and glutathione-a non-enzymatic antioxidant. N-acetylcysteine serves as an antidote for paracetamol poisoning and alleviates cellular oxidative and inflammatory stressors. We investigated N-acetylcysteine role against reproductive toxicity in male Wistar rats (weight 140-220 g; 10 weeks old) posed by perfluorooctanoic acid exposure. Randomised rat cohorts were dosed both with perfluorooctanoic acid (5 mg/kg; p.o) or co-dosed with N-acetylcysteine (25 and 50 mg/kg p.o) for 28 days. Sperm physiognomies, biomarkers of testicular function and reproductive hormones, oxidative stress and inflammation were evaluated. Co-treatment with N-acetylcysteine significantly (p less then .05) reversed perfluorooctanoic acid-mediated decreases in reproductive enzyme activities, and adverse effect on testosterone, luteinising and follicle-stimulating hormone concentrations. N-acetylcysteine treatment alone, improved sperm motility, count and viability, and reduced total sperm abnormalities. Co-treatment with N-acetylcysteine mitigated perfluorooctanoic acid-induced alterations in sperm function parameters. https://www.selleckchem.com/products/VX-680(MK-0457).html N-acetylcysteine abated (p less then .05) perfluorooctanoic acid-induced oxidative stress in experimental rats testes and epididymis, and generally improved antioxidant enzyme activities and cellular thiol levels. Furthermore, N-acetylcysteine suppressed inflammatory responses and remedied perfluorooctanoic acid-mediated histological injuries in rat. Cooperatively, N-acetylcysteine enhanced reproductive function in perfluorooctanoic acid dosed rats, by lessening oxidative and nitrative stressors and mitigated inflammatory responses in the examined organ.
    Health advocacy is a core component of physician competency frameworks. However, advocacy has lacked a clear definition and is understood and enacted variably across contexts. Due to their mobility across contexts, learners are uniquely positioned to provide insight into the tensions that have made this role so difficult to define, but that may be central to this role. The purpose of this study was to map the tensions and contours in conceptions of health advocacy among learners across a variety of learning contexts.

    We used constructivist grounded theory and interviewed nine medical students and twenty residents in family, paediatric and internal medicine from across our university's distributed programmes. Data were analysed concurrently using open, focussed and theoretical coding to establish themes and relationships between themes.

    Learners understood health advocacy in two overlapping but distinct ways as a set of behaviours and as a sense of 'going above and beyond', through additional effort, timcross contexts. 'Going above and beyond' describes a sense of grappling with sociocultural barriers to patient-centred care and striving towards better systems and better care for individuals. This more abstract and contextually bound notion of health advocacy may not lend itself easily to definition in competency frameworks and thus adds challenges to both teaching and assessment.
    To explore if R
    ' mapping can assess renal hypoxia in rabbits with ischemia reperfusion injury (IRI).

    Forty rabbits were randomly divided into 4 groups according to the clipping time the sham group and 45 min, 60 min, and 75 min for the mild, moderate, and severe groups (with n = 10 each group), respectively. Intravenous furosemide (FU) was administered 24 h after IRI. All rabbits were performed 5 times (IRI
    , IRI
    , FU
    , FU
    , and FU
    ) with a 3.0 Tesla MR. The R
    ' values and the hypoxic scores were then recorded. The repeated measurement analysis of variance and Spearman correlation analysis was used for statistical analysis.

    Compared to the baseline, the medullary R
    ' values increased significantly 24 h after the IRI (baseline 19.31 ± 1.21 s
    , mild group 20.05 ± 1.26 s
    , moderate group 25.38 ± 1.38 s
    , and severe group 25.79 ± 1.10 s
    ; each P < .001). FU led to a significant decrease in the medullary R
    ' value (sham group 11.17 ± 4.33 s
    , mild group 7.80 ± 0.74 s
    , moderate group 3.92 ± 0.28 s
    , and severe group 3.82 ± 0.23 s
    ; each P < .05). Quantitative hypoxic scores revealed significant differences among the 4 groups in the outer medulla (P < .001 each). The medullary R
    ' differences (before and after intravenous FU) were significantly correlated with the hypoxic scores, respectively (P < .001).

    R
    ' mapping can evaluate the renal hypoxia in the procession of IRI in rabbits and might serve as a quantitative biomarker for IRI.
    R2 ' mapping can evaluate the renal hypoxia in the procession of IRI in rabbits and might serve as a quantitative biomarker for IRI.
    Video capsule endoscopy (VCE) is a first-line procedure for the diagnosis of obscure gastrointestinal bleeding (OGIB). The opinions on the timing for such diagnostic evaluation remain unclear. We aimed to explore the role of early VCE in OGIB patients.

    A total of 997 patients that underwent VCE at Renji Hospital and Nagoya University from May 15, 2002, to December 28, 2016, were included in this study. We matched patients that underwent early VCE within 14days of bleeding (early group, n=678) to patients that did not (late group, n=319) via 11 propensity score matching (PSM). We then compared VCE diagnostic rates and the prevalence of post-VCE rebleeding in patients with initial negative VCE findings within 1year between these groups before and after PSM.

    Following PSM, early VCE was associated with a significantly higher rate of OGIB diagnosis (56.4% vs 45.5%, P=0.001) and with a significantly lower incidence of rebleeding within 1year following treatment (24.7% vs 36.7%, P=0.041). In univariate and multivariate analyses, VCE timing (odds ratio 0.648; 95% confidence interval 0.496-0.847, P=0.001 and odds ratio 0.666; 95% confidence interval 0.496-0.894, P=0.007, respectively) was found to be linked with a higher rate of positive findings.

    Early VCE can improve the reliability of OGIB diagnosis while also reducing rates of post-VCE rebleeding. This suggests that timely and accurate diagnosis can help to improve OGIB patient treatment and prognosis.
    Early VCE can improve the reliability of OGIB diagnosis while also reducing rates of post-VCE rebleeding. This suggests that timely and accurate diagnosis can help to improve OGIB patient treatment and prognosis.
    Perfluorooctanoic acid is a synthetic perfluoroalkyl-persistent in the environment and toxic to humans. N-acetylcysteine is a pro-drug of both amino acid l-cysteine and glutathione-a non-enzymatic antioxidant. N-acetylcysteine serves as an antidote for paracetamol poisoning and alleviates cellular oxidative and inflammatory stressors. We investigated N-acetylcysteine role against reproductive toxicity in male Wistar rats (weight 140-220 g; 10 weeks old) posed by perfluorooctanoic acid exposure. Randomised rat cohorts were dosed both with perfluorooctanoic acid (5 mg/kg; p.o) or co-dosed with N-acetylcysteine (25 and 50 mg/kg p.o) for 28 days. Sperm physiognomies, biomarkers of testicular function and reproductive hormones, oxidative stress and inflammation were evaluated. Co-treatment with N-acetylcysteine significantly (p less then .05) reversed perfluorooctanoic acid-mediated decreases in reproductive enzyme activities, and adverse effect on testosterone, luteinising and follicle-stimulating hormone concentrations. N-acetylcysteine treatment alone, improved sperm motility, count and viability, and reduced total sperm abnormalities. Co-treatment with N-acetylcysteine mitigated perfluorooctanoic acid-induced alterations in sperm function parameters. https://www.selleckchem.com/products/VX-680(MK-0457).html N-acetylcysteine abated (p less then .05) perfluorooctanoic acid-induced oxidative stress in experimental rats testes and epididymis, and generally improved antioxidant enzyme activities and cellular thiol levels. Furthermore, N-acetylcysteine suppressed inflammatory responses and remedied perfluorooctanoic acid-mediated histological injuries in rat. Cooperatively, N-acetylcysteine enhanced reproductive function in perfluorooctanoic acid dosed rats, by lessening oxidative and nitrative stressors and mitigated inflammatory responses in the examined organ. Health advocacy is a core component of physician competency frameworks. However, advocacy has lacked a clear definition and is understood and enacted variably across contexts. Due to their mobility across contexts, learners are uniquely positioned to provide insight into the tensions that have made this role so difficult to define, but that may be central to this role. The purpose of this study was to map the tensions and contours in conceptions of health advocacy among learners across a variety of learning contexts. We used constructivist grounded theory and interviewed nine medical students and twenty residents in family, paediatric and internal medicine from across our university's distributed programmes. Data were analysed concurrently using open, focussed and theoretical coding to establish themes and relationships between themes. Learners understood health advocacy in two overlapping but distinct ways as a set of behaviours and as a sense of 'going above and beyond', through additional effort, timcross contexts. 'Going above and beyond' describes a sense of grappling with sociocultural barriers to patient-centred care and striving towards better systems and better care for individuals. This more abstract and contextually bound notion of health advocacy may not lend itself easily to definition in competency frameworks and thus adds challenges to both teaching and assessment. To explore if R ' mapping can assess renal hypoxia in rabbits with ischemia reperfusion injury (IRI). Forty rabbits were randomly divided into 4 groups according to the clipping time the sham group and 45 min, 60 min, and 75 min for the mild, moderate, and severe groups (with n = 10 each group), respectively. Intravenous furosemide (FU) was administered 24 h after IRI. All rabbits were performed 5 times (IRI , IRI , FU , FU , and FU ) with a 3.0 Tesla MR. The R ' values and the hypoxic scores were then recorded. The repeated measurement analysis of variance and Spearman correlation analysis was used for statistical analysis. Compared to the baseline, the medullary R ' values increased significantly 24 h after the IRI (baseline 19.31 ± 1.21 s , mild group 20.05 ± 1.26 s , moderate group 25.38 ± 1.38 s , and severe group 25.79 ± 1.10 s ; each P < .001). FU led to a significant decrease in the medullary R ' value (sham group 11.17 ± 4.33 s , mild group 7.80 ± 0.74 s , moderate group 3.92 ± 0.28 s , and severe group 3.82 ± 0.23 s ; each P < .05). Quantitative hypoxic scores revealed significant differences among the 4 groups in the outer medulla (P < .001 each). The medullary R ' differences (before and after intravenous FU) were significantly correlated with the hypoxic scores, respectively (P < .001). R ' mapping can evaluate the renal hypoxia in the procession of IRI in rabbits and might serve as a quantitative biomarker for IRI. R2 ' mapping can evaluate the renal hypoxia in the procession of IRI in rabbits and might serve as a quantitative biomarker for IRI. Video capsule endoscopy (VCE) is a first-line procedure for the diagnosis of obscure gastrointestinal bleeding (OGIB). The opinions on the timing for such diagnostic evaluation remain unclear. We aimed to explore the role of early VCE in OGIB patients. A total of 997 patients that underwent VCE at Renji Hospital and Nagoya University from May 15, 2002, to December 28, 2016, were included in this study. We matched patients that underwent early VCE within 14days of bleeding (early group, n=678) to patients that did not (late group, n=319) via 11 propensity score matching (PSM). We then compared VCE diagnostic rates and the prevalence of post-VCE rebleeding in patients with initial negative VCE findings within 1year between these groups before and after PSM. Following PSM, early VCE was associated with a significantly higher rate of OGIB diagnosis (56.4% vs 45.5%, P=0.001) and with a significantly lower incidence of rebleeding within 1year following treatment (24.7% vs 36.7%, P=0.041). In univariate and multivariate analyses, VCE timing (odds ratio 0.648; 95% confidence interval 0.496-0.847, P=0.001 and odds ratio 0.666; 95% confidence interval 0.496-0.894, P=0.007, respectively) was found to be linked with a higher rate of positive findings. Early VCE can improve the reliability of OGIB diagnosis while also reducing rates of post-VCE rebleeding. This suggests that timely and accurate diagnosis can help to improve OGIB patient treatment and prognosis. Early VCE can improve the reliability of OGIB diagnosis while also reducing rates of post-VCE rebleeding. This suggests that timely and accurate diagnosis can help to improve OGIB patient treatment and prognosis.
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