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  • The enhancement of 12αOH BA secretion may contribute to hepatic steatosis by the promotion of dietary fat absorption and hepatic Cidea mRNA expression. The increase in 12αOH BAs was associated with enhanced liver cholesterol 7α-hydroxylase (Cyp7a1) and sterol 12α-hydroxylase (Cyp8b1) mRNA expression. There was a significant increase in 7α-hydroxycholesterol, a precursor of BAs, in the liver of HF-fed rats. Altogether, these data suggest that the HF diet increases preferentially 12αOH BAs synthesis by utilizing the accumulated hepatic cholesterol and enhancing mRNA expression of Cyp7a1 and Cyp8b1 in the liver.Objectives Vagus nerve stimulation (VNS) is an established adjunctive therapy for medically refractory epilepsy, which is commonly associated with cognitive impairment, especially in children in whom seizures may disrupt development that is essential to their intellectual and social maturation. The Taiwan Child Neurology Society intends to expand the use of VNS by reporting the experience in a nationwide population, displaying the demographic features and neuropsychological outcomes of VNS. Methods The enrollment included 105 patients of all ages and seizure types who underwent VNS implantation for refractory epilepsy. Basic data included etiology, past history, seizure phenotypes, and epileptiform syndromes. For efficacy analysis, seizure frequencies were recorded at the baseline and at 3, 12, 24, and 36 months after VNS implantation. For psychological assessment, intelligence quotients (IQ) and Parental Stress Index (PSI) scores were evaluated before and after the VNS. Results During the study period, 95 patients with VNS had followed seizure frequency, IQ and PSI recording. After implantation, there was a decreased frequency at 3 (P less then .001), 12 (P less then .001), 24 (P = .010), and 36 (P less then .01) months. After implantation, the reduction rate (0-50%) of seizure frequency ranged around 26.1-36.1% from 3 to 36 months. For PSI scores, the VNS significantly improved the PSI- total score (P = .001) and PSI-parent domain (P = .001) but not the PSI-children domain (P = .052). No significant improvement in the IQ test performance was observed. Conclusions This prospective nationwide database of VNS in Taiwan indicates long-term efficacy of VNS therapy, which has achieved a trend of seizure frequency reduction over a period of up to 36 months. It also shows the trend of decreased parental stress after VNS implantation.Video-electroencephalogram (EEG) monitoring in the epilepsy monitoring unit (EMU) is essential for managing epilepsy and seizure mimics. Evaluation of care in the EMU would benefit from a validated code set capable of identifying EMU admissions from administrative databases comprised of large, diverse cohorts. We assessed the ability of code-based queries to parse EMU admissions from administrative billing records in a large academic medical center over a four-year period, 2016-2019. We applied prespecified queries for admissions coded as follows 1) elective, 2) receiving video-EEG monitoring, and 3) including diagnoses typically required by major US healthcare payers for EMU admission. Sensitivity (Sn), specificity (Sp), and predictive value positive/negative (PVP, PVN) were determined. Two approaches were highly effective. Incorporating epilepsy, seizure, or seizure mimic codes as the admitting diagnosis (assigned at admission; Sn 96.3%, Sp 100.0%, PVP 98.3%, and PVN 100.0%) or the principal diagnosis (assigned after discharge; Sn 94.9%, Sp 100.0%, PVP 98.8%, and PVN 100.0%) identified elective adult EMU admissions with comparable reliability (p = 0.096). The addition of surgical procedure codes further separated EMU admissions for intracranial EEG monitoring. When applied to larger, more comprehensive datasets, these code-based queries should enhance our understanding of EMU utilization and access to care on a scalable basis.Objective Obstructive sleep apnea (OSA) is common in patients with epilepsy (PWE), and treatment may improve seizure control. However, OSA is often undiagnosed in PWE, and understanding of the risk profile for OSA is important. In this study, we sought to determine if OSA risk is similar in patients with generalized versus focal epilepsy. Methods We recruited 115 patients presenting to the Rutgers-Robert Wood Johnson Epilepsy Clinic with focal or generalized epilepsy. Obstructive sleep apnea risk was assessed using the Sleep Apnea Scale of the Sleep Disorders Questionnaire (SA-SDQ). Sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Demographic and clinical information was gathered from the electronic medical record. Unadjusted and adjusted analyses were carried out to assess differences in the SA-SDQ between patients with generalized versus focal epilepsy. Further analyses were done to assess the relationship between seizure frequency, epilepsy type, and the SA-SDQ. Results Unadjusted mean SA-SDQ scores, as well as scores high enough to represent likely OSA, were similar in patients with generalized versus focal epilepsy. However, in adjusted analyses, patients with generalized epilepsy had a significantly higher mean SA-SDQ score. https://www.selleckchem.com/products/gambogic-acid.html Older age, higher body mass index (BMI), and a history of hypertension (HTN) were also associated with higher SA-SDQ scores. Sleep Apnea Scale of the Sleep Disorders Questionnaire scores were not significantly affected by the presence of a seizure within the prior one month or six months. Average ESS scores and the percentage of scores consistent with an abnormal degree of sleepiness were statistically similar in patients with generalized versus focal epilepsy. Significance Our study suggests that patients with generalized epilepsy have a higher risk of OSA. Further studies measuring OSA directly as well as assessing potential benefits of treatment are needed.Objective The aim of the present study was to explore the factors related to the severity of the adverse effects of antiepileptic drugs (AEDs), experienced by patients with epilepsy. Materials and methods A case study was conducted in adult patients with epilepsy and followed up at the Epilepsy Outpatients of the University Hospital of Ioannina in Northwest Greece. The Adverse Event Profile (AEP) questionnaire for AEDs adverse effects assessment, the Defense style questionnaire (DSQ-88) and the Patient Health Questionnaire (PHQ-9) for depression' severity evaluation were used to estimate the severity of adverse effects, the defense style, and the depressive symptoms, respectively. Results Sixty-three patients with epilepsy (M/F28/35), with a mean age of 37.6 ± 13.41, were recruited in the study. The univariate analysis showed that both the Maladaptive style of defense and the PHQ-9 score were significantly associated with the AEP score. After multivariate regression analysis female gender, the load of AEDs, the PHQ-9 score, and the Adaptive defense style remained significant coefficients.
    The enhancement of 12αOH BA secretion may contribute to hepatic steatosis by the promotion of dietary fat absorption and hepatic Cidea mRNA expression. The increase in 12αOH BAs was associated with enhanced liver cholesterol 7α-hydroxylase (Cyp7a1) and sterol 12α-hydroxylase (Cyp8b1) mRNA expression. There was a significant increase in 7α-hydroxycholesterol, a precursor of BAs, in the liver of HF-fed rats. Altogether, these data suggest that the HF diet increases preferentially 12αOH BAs synthesis by utilizing the accumulated hepatic cholesterol and enhancing mRNA expression of Cyp7a1 and Cyp8b1 in the liver.Objectives Vagus nerve stimulation (VNS) is an established adjunctive therapy for medically refractory epilepsy, which is commonly associated with cognitive impairment, especially in children in whom seizures may disrupt development that is essential to their intellectual and social maturation. The Taiwan Child Neurology Society intends to expand the use of VNS by reporting the experience in a nationwide population, displaying the demographic features and neuropsychological outcomes of VNS. Methods The enrollment included 105 patients of all ages and seizure types who underwent VNS implantation for refractory epilepsy. Basic data included etiology, past history, seizure phenotypes, and epileptiform syndromes. For efficacy analysis, seizure frequencies were recorded at the baseline and at 3, 12, 24, and 36 months after VNS implantation. For psychological assessment, intelligence quotients (IQ) and Parental Stress Index (PSI) scores were evaluated before and after the VNS. Results During the study period, 95 patients with VNS had followed seizure frequency, IQ and PSI recording. After implantation, there was a decreased frequency at 3 (P less then .001), 12 (P less then .001), 24 (P = .010), and 36 (P less then .01) months. After implantation, the reduction rate (0-50%) of seizure frequency ranged around 26.1-36.1% from 3 to 36 months. For PSI scores, the VNS significantly improved the PSI- total score (P = .001) and PSI-parent domain (P = .001) but not the PSI-children domain (P = .052). No significant improvement in the IQ test performance was observed. Conclusions This prospective nationwide database of VNS in Taiwan indicates long-term efficacy of VNS therapy, which has achieved a trend of seizure frequency reduction over a period of up to 36 months. It also shows the trend of decreased parental stress after VNS implantation.Video-electroencephalogram (EEG) monitoring in the epilepsy monitoring unit (EMU) is essential for managing epilepsy and seizure mimics. Evaluation of care in the EMU would benefit from a validated code set capable of identifying EMU admissions from administrative databases comprised of large, diverse cohorts. We assessed the ability of code-based queries to parse EMU admissions from administrative billing records in a large academic medical center over a four-year period, 2016-2019. We applied prespecified queries for admissions coded as follows 1) elective, 2) receiving video-EEG monitoring, and 3) including diagnoses typically required by major US healthcare payers for EMU admission. Sensitivity (Sn), specificity (Sp), and predictive value positive/negative (PVP, PVN) were determined. Two approaches were highly effective. Incorporating epilepsy, seizure, or seizure mimic codes as the admitting diagnosis (assigned at admission; Sn 96.3%, Sp 100.0%, PVP 98.3%, and PVN 100.0%) or the principal diagnosis (assigned after discharge; Sn 94.9%, Sp 100.0%, PVP 98.8%, and PVN 100.0%) identified elective adult EMU admissions with comparable reliability (p = 0.096). The addition of surgical procedure codes further separated EMU admissions for intracranial EEG monitoring. When applied to larger, more comprehensive datasets, these code-based queries should enhance our understanding of EMU utilization and access to care on a scalable basis.Objective Obstructive sleep apnea (OSA) is common in patients with epilepsy (PWE), and treatment may improve seizure control. However, OSA is often undiagnosed in PWE, and understanding of the risk profile for OSA is important. In this study, we sought to determine if OSA risk is similar in patients with generalized versus focal epilepsy. Methods We recruited 115 patients presenting to the Rutgers-Robert Wood Johnson Epilepsy Clinic with focal or generalized epilepsy. Obstructive sleep apnea risk was assessed using the Sleep Apnea Scale of the Sleep Disorders Questionnaire (SA-SDQ). Sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Demographic and clinical information was gathered from the electronic medical record. Unadjusted and adjusted analyses were carried out to assess differences in the SA-SDQ between patients with generalized versus focal epilepsy. Further analyses were done to assess the relationship between seizure frequency, epilepsy type, and the SA-SDQ. Results Unadjusted mean SA-SDQ scores, as well as scores high enough to represent likely OSA, were similar in patients with generalized versus focal epilepsy. However, in adjusted analyses, patients with generalized epilepsy had a significantly higher mean SA-SDQ score. https://www.selleckchem.com/products/gambogic-acid.html Older age, higher body mass index (BMI), and a history of hypertension (HTN) were also associated with higher SA-SDQ scores. Sleep Apnea Scale of the Sleep Disorders Questionnaire scores were not significantly affected by the presence of a seizure within the prior one month or six months. Average ESS scores and the percentage of scores consistent with an abnormal degree of sleepiness were statistically similar in patients with generalized versus focal epilepsy. Significance Our study suggests that patients with generalized epilepsy have a higher risk of OSA. Further studies measuring OSA directly as well as assessing potential benefits of treatment are needed.Objective The aim of the present study was to explore the factors related to the severity of the adverse effects of antiepileptic drugs (AEDs), experienced by patients with epilepsy. Materials and methods A case study was conducted in adult patients with epilepsy and followed up at the Epilepsy Outpatients of the University Hospital of Ioannina in Northwest Greece. The Adverse Event Profile (AEP) questionnaire for AEDs adverse effects assessment, the Defense style questionnaire (DSQ-88) and the Patient Health Questionnaire (PHQ-9) for depression' severity evaluation were used to estimate the severity of adverse effects, the defense style, and the depressive symptoms, respectively. Results Sixty-three patients with epilepsy (M/F28/35), with a mean age of 37.6 ± 13.41, were recruited in the study. The univariate analysis showed that both the Maladaptive style of defense and the PHQ-9 score were significantly associated with the AEP score. After multivariate regression analysis female gender, the load of AEDs, the PHQ-9 score, and the Adaptive defense style remained significant coefficients.
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  • Therefore, we also discuss mechanisms that regulate CK1α steady-state homeostasis, which may contribute to the deregulation of Wnt pathway activity in cancer and underlie the enhanced therapeutic index of CK1α activators.Wolbachia symbionts are maternally inherited bacteria that are widely distributed among Arthropoda hosts. Wolbachia influence their host biology in diverse ways. They may induce reproductive abnormalities, protect hosts against pathogens and parasites, or benefit hosts through metabolic provisioning. The progeny of an infected female are ordinarily infected with Wolbachia; however, Wolbachia have no future in male host progeny because they cannot transmit the symbiont to the next generation. Here, we analyze native and invasive populations of the four-eyed fir bark beetle (Polygraphus proximus) for Wolbachia prevalence and symbiont genetic diversity. This species is a dangerous pest of Siberian fir (Abies sibirica) forests. The native range of P. proximus includes the territories of the Russian Far East, Japan, Korea, and Northeast China, whereas its invasive range includes West Siberia, with further expansion westward. Surprisingly, we revealed a difference in the patterns of Wolbachia prevalence for males and females. Infection rate and Wolbachia titers were higher in females than in males. ST-533, the only haplotype of Wolbachia supergroup B, was associated with a minimum of three out of the five described mitochondrial haplotypes.Heavy ions refer to charged particles with a mass greater than four (i.e., alpha particles). The heavy ion irradiation used in radiotherapy or that astronauts suffer in space flight missions induces toxicity in normal tissue and leads to short-term and long-term damage in both the structure and function of the brain. However, the underlying molecular alterations caused by heavy ion radiation have yet to be completely elucidated. https://www.selleckchem.com/products/cordycepin.html Herein, untargeted and targeted lipidomic profiling of the whole brain tissue and blood plasma 7 days after the administration of the 15 Gy (260 MeV, low linear energy (LET) = 13.9 KeV/μm) plateau irradiation of disposable 12C6+ heavy ions on the whole heads of rats was explored to study the lipid damage induced by heavy ion radiation in the rat brain using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) technology. Combined with multivariate variables and univariate data analysis methods, our results indicated that an orthogonal partial least squares discriminant analysis (OPLS-DA) could clearly distinguish lipid metabolites between the irradiated and control groups. Through the combination of variable weight value (VIP), variation multiple (FC), and differential (p) analyses, the significant differential lipids diacylglycerols (DAGs) were screened out. Further quantitative targeted lipidomic analyses of these DAGs in the rat brain tissue and plasma supported the notion that DAG 471 could be used as a potential biomarker to study brain injury induced by heavy ion irradiation.Carbonic anhydrase IX (CA9), a pH-regulating transmembrane protein, is highly expressed in solid tumors, and particularly in clear cell renal cell carcinoma (ccRCC). The catalytic mechanisms of CA9 are well defined, but its roles in mediating cell migration/invasion and survival in ccRCC remain to be determined. Here, we confirmed that the mRNA expression of CA9 in ccRCC was significantly higher than that in para-carcinoma tissues from analysis of the datasets in The Cancer Genome Atlas. CA9 knockdown upregulated oxidative phosphorylation-associated proteins and increased mitochondrial biogenesis, resulting in the reversal of the Warburg phenotype and the inhibition of cell growth. Our study revealed that CA9 knockdown upregulated mitochondrial arginase 2 (ARG2), leading to the accumulation of putrescine, which suppressed ccRCC proliferation. Surfaceomics analysis revealed that CA9 knockdown downregulated proteins associated with extracellular matrix (ECM)-receptor interaction and cell adhesion, resulting in decreased cell migration. CA9 silencing also downregulated amino acid transporters, leading to reduced cellular amino acids. Collectively, our data show that CA9 knockdown suppresses proliferation via metabolic reprogramming and reduced cell migration, reaffirming that CA9 is a potential therapeutic target for ccRCC treatment.This study investigated people's attitudes towards noise inside their homes. Online questionnaire surveys were conducted in Seoul, London, and São Paulo. The questionnaire was designed to assess annoyance caused by noise from neighbours and environmental noise (transportation). Information was also collected on situational, personal, and socio-demographic variables. Respondents that were more annoyed by outdoor noise inside their dwelling reported higher neighbour noise annoyance. In Seoul, neighbour noise was found to be more annoying than outdoor noise, and those with higher noise sensitivity reported higher annoyance towards neighbour noise. However, neighbour noise and outdoor noise was found to be equally annoying in London and São Paulo. For neighbour noise, the average percentage of respondents hearing structure-borne sources compared to airborne sources differed in each city. Most neighbour noise sources in São Paulo gave rise to higher annoyance ratings than Seoul and London. Education and income levels had a limited effect on annoyance and coping strategy. Annoyance with indoor noise from neighbours was found to have stronger relationships with cognitive and behavioural coping strategies than outdoor noise annoyance.Acute kidney injury (AKI) is a frequent occurrence following major abdominal surgery and is independently associated with both in-hospital and long-term mortality, as well as with a higher risk of progressing to chronic kidney disease (CKD) and cardiovascular events. Postoperative AKI can account for up to 40% of in-hospital AKI cases. Given the differences in patient characteristics and the pathophysiology of postoperative AKI, it is inappropriate to assume that the management after noncardiac and nonvascular surgery are the same as those after cardiac and vascular surgery. This article provides a comprehensive review on the available evidence on the management of postoperative AKI in the setting of major abdominal surgery.
    Therefore, we also discuss mechanisms that regulate CK1α steady-state homeostasis, which may contribute to the deregulation of Wnt pathway activity in cancer and underlie the enhanced therapeutic index of CK1α activators.Wolbachia symbionts are maternally inherited bacteria that are widely distributed among Arthropoda hosts. Wolbachia influence their host biology in diverse ways. They may induce reproductive abnormalities, protect hosts against pathogens and parasites, or benefit hosts through metabolic provisioning. The progeny of an infected female are ordinarily infected with Wolbachia; however, Wolbachia have no future in male host progeny because they cannot transmit the symbiont to the next generation. Here, we analyze native and invasive populations of the four-eyed fir bark beetle (Polygraphus proximus) for Wolbachia prevalence and symbiont genetic diversity. This species is a dangerous pest of Siberian fir (Abies sibirica) forests. The native range of P. proximus includes the territories of the Russian Far East, Japan, Korea, and Northeast China, whereas its invasive range includes West Siberia, with further expansion westward. Surprisingly, we revealed a difference in the patterns of Wolbachia prevalence for males and females. Infection rate and Wolbachia titers were higher in females than in males. ST-533, the only haplotype of Wolbachia supergroup B, was associated with a minimum of three out of the five described mitochondrial haplotypes.Heavy ions refer to charged particles with a mass greater than four (i.e., alpha particles). The heavy ion irradiation used in radiotherapy or that astronauts suffer in space flight missions induces toxicity in normal tissue and leads to short-term and long-term damage in both the structure and function of the brain. However, the underlying molecular alterations caused by heavy ion radiation have yet to be completely elucidated. https://www.selleckchem.com/products/cordycepin.html Herein, untargeted and targeted lipidomic profiling of the whole brain tissue and blood plasma 7 days after the administration of the 15 Gy (260 MeV, low linear energy (LET) = 13.9 KeV/μm) plateau irradiation of disposable 12C6+ heavy ions on the whole heads of rats was explored to study the lipid damage induced by heavy ion radiation in the rat brain using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) technology. Combined with multivariate variables and univariate data analysis methods, our results indicated that an orthogonal partial least squares discriminant analysis (OPLS-DA) could clearly distinguish lipid metabolites between the irradiated and control groups. Through the combination of variable weight value (VIP), variation multiple (FC), and differential (p) analyses, the significant differential lipids diacylglycerols (DAGs) were screened out. Further quantitative targeted lipidomic analyses of these DAGs in the rat brain tissue and plasma supported the notion that DAG 471 could be used as a potential biomarker to study brain injury induced by heavy ion irradiation.Carbonic anhydrase IX (CA9), a pH-regulating transmembrane protein, is highly expressed in solid tumors, and particularly in clear cell renal cell carcinoma (ccRCC). The catalytic mechanisms of CA9 are well defined, but its roles in mediating cell migration/invasion and survival in ccRCC remain to be determined. Here, we confirmed that the mRNA expression of CA9 in ccRCC was significantly higher than that in para-carcinoma tissues from analysis of the datasets in The Cancer Genome Atlas. CA9 knockdown upregulated oxidative phosphorylation-associated proteins and increased mitochondrial biogenesis, resulting in the reversal of the Warburg phenotype and the inhibition of cell growth. Our study revealed that CA9 knockdown upregulated mitochondrial arginase 2 (ARG2), leading to the accumulation of putrescine, which suppressed ccRCC proliferation. Surfaceomics analysis revealed that CA9 knockdown downregulated proteins associated with extracellular matrix (ECM)-receptor interaction and cell adhesion, resulting in decreased cell migration. CA9 silencing also downregulated amino acid transporters, leading to reduced cellular amino acids. Collectively, our data show that CA9 knockdown suppresses proliferation via metabolic reprogramming and reduced cell migration, reaffirming that CA9 is a potential therapeutic target for ccRCC treatment.This study investigated people's attitudes towards noise inside their homes. Online questionnaire surveys were conducted in Seoul, London, and São Paulo. The questionnaire was designed to assess annoyance caused by noise from neighbours and environmental noise (transportation). Information was also collected on situational, personal, and socio-demographic variables. Respondents that were more annoyed by outdoor noise inside their dwelling reported higher neighbour noise annoyance. In Seoul, neighbour noise was found to be more annoying than outdoor noise, and those with higher noise sensitivity reported higher annoyance towards neighbour noise. However, neighbour noise and outdoor noise was found to be equally annoying in London and São Paulo. For neighbour noise, the average percentage of respondents hearing structure-borne sources compared to airborne sources differed in each city. Most neighbour noise sources in São Paulo gave rise to higher annoyance ratings than Seoul and London. Education and income levels had a limited effect on annoyance and coping strategy. Annoyance with indoor noise from neighbours was found to have stronger relationships with cognitive and behavioural coping strategies than outdoor noise annoyance.Acute kidney injury (AKI) is a frequent occurrence following major abdominal surgery and is independently associated with both in-hospital and long-term mortality, as well as with a higher risk of progressing to chronic kidney disease (CKD) and cardiovascular events. Postoperative AKI can account for up to 40% of in-hospital AKI cases. Given the differences in patient characteristics and the pathophysiology of postoperative AKI, it is inappropriate to assume that the management after noncardiac and nonvascular surgery are the same as those after cardiac and vascular surgery. This article provides a comprehensive review on the available evidence on the management of postoperative AKI in the setting of major abdominal surgery.
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  • Copyright © 2020 Han, Yang, Sun, Liu, Zhou and Li.Among all cancers, lung, breast, and prostate carcinoma are the three most fatal cancers. Although general therapeutic strategies and existent nanomedicine have been applied in relating cancer treatments, the side effects and potential damage induced by the off-target effect greatly lower the therapeutic efficiency. Recently, an increasing number of bioresponsive nanomaterials is recruited in fighting these deadliest cancers. Therefore, these latest bioresponsive nanomedicine are summarized in the current review. More specifically, the various novel nano-agents that could selectively respond to specific bio-conditions in malignant areas (e.g., pH, temperature, enzyme, Redox, elevated copper ion, etc.) are discussed in detail for their applications in cancer imaging (e.g., fluorescence, NIR, and MRI, etc.) and therapy (e.g., antiangiogenesis, chemotherapy, photothermal, and chemodynamic therapy, etc.). The development of next-generation of bioresponsive nanomedicine and challenges involved are further discussed for future design. Copyright © 2020 Mao and Liu.Chiral diketopyrrolopyrrole (DPP)-helicene polymers were synthesized to develop efficient red circularly polarized (CP) light emitters. These original chiral dyes display intense electronic circular dichroism (ECD) and CP luminescence (CPL) in the far-red spectral region owing to the presence of excitonic coupling between achiral DPPs within the chiral environment of the polymeric structure. This work affords an interesting example illustrating the potential of π-conjugated helical polymers for chiral optoelectronic applications. Copyright © 2020 Dhbaibi, Shen, Jean, Vanthuyne, Roisnel, Górecki, Jamoussi, Favereau and Crassous.Though molecules exhibiting thermally activated delayed fluorescence (TADF) have seen extensive development in organic light-emitting diodes, their incorporation into polymer nanomaterials and thin films has led to a range of applications in sensing and imaging probes. Triplet quenching can be used to probe oxygen concentration, and the reverse intersystem crossing mechanism which gives rise to TADF can also be used to measure temperature. https://www.selleckchem.com/products/azd6738.html Moreover, the long emission lifetimes of TADF materials allows for noise reduction in time-gated microscopy, making these compounds ideal for time-resolved fluorescence imaging (TRFI). A polymer matrix enables control over energy transfer between molecules, and can be used to modulate TADF behavior, solubility, biocompatibility, or desirable mechanical properties. Additionally, a polymer's oxygen permeability can be tuned to suit imaging applications in a range of media. Here we review the applications of polymer nanoparticles and films exhibiting TADF in sensing and imaging, demonstrating that this class of materials has great potential beyond electroluminescent devices still waiting to be explored. Copyright © 2020 Paisley, Tonge and Hudson.Magnetic and temperature-sensitive solid lipid particles (mag. SLPs) were prepared in the presence of oleic acid-coated iron oxide (IO-OA) nanoparticles with 1-tetradecanol and poly(ethylene oxide)-block-poly(ε-caprolactone) as lipid and stabilizing surfactant-like agents, respectively. The particles, typically ~850 nm in hydrodynamic size, showed heat dissipation under the applied alternating magnetic field. Cytotoxic activity of the mag.SLPs, non-magnetic SLPs, and iron oxide nanoparticles was compared concerning the mammalian cancer cell lines and their drug-resistant counterparts using trypan blue exclusion test and MTT assay. The mag.SLPs exhibited dose-dependent cytotoxicity against human leukemia cell lines growing in suspension (Jurkat and HL-60/wt), as well as the doxorubicin (Dox)- and vincristine-resistant HL-60 sublines. The mag.SLPs showed higher cytotoxicity toward drug-resistant sublines as compared to Dox. The human glioblastoma cell line U251 growing in a monolayer culture was also sensitive ag.SLPs-induced cytotoxicity. Accordingly, hydrogen peroxide and superoxide radical levels in mag.SLPs-treated Jurkat leukemic cells were increased by ~20-40 and ~70%, respectively. In contrast, the non-magnetic SLPs and neat iron oxides did not influence ROS levels significantly. Thus, the developed mag.SLPs can be used for effective killing of human tumor cells, including drug-resistant ones. Copyright © 2020 Świętek, Panchuk, Skorokhyd, Černoch, Finiuk, Klyuchivska, Hrubý, Molčan, Berger, Trousil, Stoika and Horák.Antiapoptotic members of B-cell leukemia/lymphoma-2 (BCL-2) family proteins are one of the overexpressed proteins in cancer cells that are oncogenic targets. As such, targeting of BCL-2 family proteins raises hopes for new therapeutic discoveries. Thus, we used multistep screening and filtering approaches that combine structure and ligand-based drug design to identify new, effective BCL-2 inhibitors from a small molecule database (Specs SC), which includes more than 210,000 compounds. This database is first filtered based on binary "cancer-QSAR" model constructed with 886 training and 167 test set compounds and common 26 toxicity quantitative structure-activity relationships (QSAR) models. Predicted non-toxic compounds are considered for target-driven studies. Here, we applied two different approaches to filter and select hit compounds for further in vitro biological assays and human cell line experiments. In the first approach, a molecular docking and filtering approach is used to rank compounds based on theCL-2. Short MD simulations are performed for the top-docking poses for each compound in complex with BCL-2. The complexes are again ranked based on their MM/GBSA values to select hit molecules for further long MD simulations and in vitro studies. In total, seven molecules are subjected to biological activity tests in various human cancer cell lines as well as Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) assay. Inhibitory concentrations are evaluated, and biological activities and apoptotic potentials are assessed by cell culture studies. Four molecules are found to be limiting the proliferation capacity of cancer cells while increasing the apoptotic cell fractions. Copyright © 2020 Tutumlu, Dogan, Avsar, Orhan, Calis and Durdagi.
    Copyright © 2020 Han, Yang, Sun, Liu, Zhou and Li.Among all cancers, lung, breast, and prostate carcinoma are the three most fatal cancers. Although general therapeutic strategies and existent nanomedicine have been applied in relating cancer treatments, the side effects and potential damage induced by the off-target effect greatly lower the therapeutic efficiency. Recently, an increasing number of bioresponsive nanomaterials is recruited in fighting these deadliest cancers. Therefore, these latest bioresponsive nanomedicine are summarized in the current review. More specifically, the various novel nano-agents that could selectively respond to specific bio-conditions in malignant areas (e.g., pH, temperature, enzyme, Redox, elevated copper ion, etc.) are discussed in detail for their applications in cancer imaging (e.g., fluorescence, NIR, and MRI, etc.) and therapy (e.g., antiangiogenesis, chemotherapy, photothermal, and chemodynamic therapy, etc.). The development of next-generation of bioresponsive nanomedicine and challenges involved are further discussed for future design. Copyright © 2020 Mao and Liu.Chiral diketopyrrolopyrrole (DPP)-helicene polymers were synthesized to develop efficient red circularly polarized (CP) light emitters. These original chiral dyes display intense electronic circular dichroism (ECD) and CP luminescence (CPL) in the far-red spectral region owing to the presence of excitonic coupling between achiral DPPs within the chiral environment of the polymeric structure. This work affords an interesting example illustrating the potential of π-conjugated helical polymers for chiral optoelectronic applications. Copyright © 2020 Dhbaibi, Shen, Jean, Vanthuyne, Roisnel, Górecki, Jamoussi, Favereau and Crassous.Though molecules exhibiting thermally activated delayed fluorescence (TADF) have seen extensive development in organic light-emitting diodes, their incorporation into polymer nanomaterials and thin films has led to a range of applications in sensing and imaging probes. Triplet quenching can be used to probe oxygen concentration, and the reverse intersystem crossing mechanism which gives rise to TADF can also be used to measure temperature. https://www.selleckchem.com/products/azd6738.html Moreover, the long emission lifetimes of TADF materials allows for noise reduction in time-gated microscopy, making these compounds ideal for time-resolved fluorescence imaging (TRFI). A polymer matrix enables control over energy transfer between molecules, and can be used to modulate TADF behavior, solubility, biocompatibility, or desirable mechanical properties. Additionally, a polymer's oxygen permeability can be tuned to suit imaging applications in a range of media. Here we review the applications of polymer nanoparticles and films exhibiting TADF in sensing and imaging, demonstrating that this class of materials has great potential beyond electroluminescent devices still waiting to be explored. Copyright © 2020 Paisley, Tonge and Hudson.Magnetic and temperature-sensitive solid lipid particles (mag. SLPs) were prepared in the presence of oleic acid-coated iron oxide (IO-OA) nanoparticles with 1-tetradecanol and poly(ethylene oxide)-block-poly(ε-caprolactone) as lipid and stabilizing surfactant-like agents, respectively. The particles, typically ~850 nm in hydrodynamic size, showed heat dissipation under the applied alternating magnetic field. Cytotoxic activity of the mag.SLPs, non-magnetic SLPs, and iron oxide nanoparticles was compared concerning the mammalian cancer cell lines and their drug-resistant counterparts using trypan blue exclusion test and MTT assay. The mag.SLPs exhibited dose-dependent cytotoxicity against human leukemia cell lines growing in suspension (Jurkat and HL-60/wt), as well as the doxorubicin (Dox)- and vincristine-resistant HL-60 sublines. The mag.SLPs showed higher cytotoxicity toward drug-resistant sublines as compared to Dox. The human glioblastoma cell line U251 growing in a monolayer culture was also sensitive ag.SLPs-induced cytotoxicity. Accordingly, hydrogen peroxide and superoxide radical levels in mag.SLPs-treated Jurkat leukemic cells were increased by ~20-40 and ~70%, respectively. In contrast, the non-magnetic SLPs and neat iron oxides did not influence ROS levels significantly. Thus, the developed mag.SLPs can be used for effective killing of human tumor cells, including drug-resistant ones. Copyright © 2020 Świętek, Panchuk, Skorokhyd, Černoch, Finiuk, Klyuchivska, Hrubý, Molčan, Berger, Trousil, Stoika and Horák.Antiapoptotic members of B-cell leukemia/lymphoma-2 (BCL-2) family proteins are one of the overexpressed proteins in cancer cells that are oncogenic targets. As such, targeting of BCL-2 family proteins raises hopes for new therapeutic discoveries. Thus, we used multistep screening and filtering approaches that combine structure and ligand-based drug design to identify new, effective BCL-2 inhibitors from a small molecule database (Specs SC), which includes more than 210,000 compounds. This database is first filtered based on binary "cancer-QSAR" model constructed with 886 training and 167 test set compounds and common 26 toxicity quantitative structure-activity relationships (QSAR) models. Predicted non-toxic compounds are considered for target-driven studies. Here, we applied two different approaches to filter and select hit compounds for further in vitro biological assays and human cell line experiments. In the first approach, a molecular docking and filtering approach is used to rank compounds based on theCL-2. Short MD simulations are performed for the top-docking poses for each compound in complex with BCL-2. The complexes are again ranked based on their MM/GBSA values to select hit molecules for further long MD simulations and in vitro studies. In total, seven molecules are subjected to biological activity tests in various human cancer cell lines as well as Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) assay. Inhibitory concentrations are evaluated, and biological activities and apoptotic potentials are assessed by cell culture studies. Four molecules are found to be limiting the proliferation capacity of cancer cells while increasing the apoptotic cell fractions. Copyright © 2020 Tutumlu, Dogan, Avsar, Orhan, Calis and Durdagi.
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  • LUSIONS In terms of clinically relevant outcomes (incidence of major complications and mortality), PSM in real life setting seems to be a very good alternative in properly trained patients.BACKGROUND Tuberculosis (TB) disease is a common opportunistic infection among people living with HIV (PLHIV). WHO recommends at least 6 months of isoniazid Preventive Therapy (IPT) to reduce the risk of active TB. It is important to monitor the six-month IPT completion since a suboptimal dose may not protect PLHIV from TB infection. This study determined the six-month IPT completion and factors associated with six-month IPT completion among PLHIV aged 15 years or more in Dar es Salaam region, Tanzania. METHODS Secondary analysis of routine data from PLHIV attending 58 care and treatment clinics in Dar es Salaam region was used. PLHIV, aged 15 years and above, who screened negative for TB symptoms and initiated IPT from January, 2013 to June, 2017 were recruited. Modified Poisson regression with robust standard errors was used to estimate prevalence ratios (PR) and 95% confidence interval (CI) for factors associated with IPT completion. Multilevel analysis was used to account for health facility random effectntly needed.BACKGROUND Great changes have taken place in terms of people's lifestyles and behavioral habits. Diabetes has become a threat to human health and is the most important noncommunicable disease. More than 60% of rural diabetic patients experience delayed diagnosis and treatment. https://www.selleckchem.com/products/z-lehd-fmk-s7313.html In this study, we explore the inner experience of the delayed diagnosis and treatment of patients with diabetes in rural areas and provide a reference for targeted intervention. METHODS A qualitative research design was used to examine the cognitive behavioral intention of patients in rural areas with delayed diagnosis and treatment of diabetes. Thirteen diabetes patients with delayed diagnosis and treatment were sampled with maximum variation in rural Daqing City and Tangshan City in China. The data analysis involved several levels of analysis consistent with qualitative research. RESULTS The following themes were relevant to diabetes patients in rural areas with delayed diagnosis and treatment delay "Lacked knowledge of diabetes", "Negative coping style", "Dissatisfaction with the existing medical service" and "Influence of social support". CONCLUSIONS The respondents' delayed diagnosis and treatment represent a common phenomenon. Medical personnel should provide interventions for patients and encourage them to go to the hospital on time.BACKGROUND In this study, we aimed to investigate the preoperative serum carcinoembryonic antigen (CEA) in the diagnosis of positive lymph node metastasis (LNM), and to evaluated the relationship between CEA and survival in patients with locally advanced gastric cancer (LAGC). METHODS The significance of the preoperative serum CEA level for the diagnose of LAGC and prediction of LNM was determined using the receiver operating characteristic (ROC) curve. The areas under the ROC of CEA were compared with those of other tumor markers or imaging examination including CT and MRI. Logistic regression was utilized to identify the risk factors predicting positive LNM. Independent prognosis factors were evaluated using univariate and multivariate COX regression analyses. RESULTS The ROC curves showed that the AUCs of CEA, CA199, and CA125 for diagnosing LAGC were 0.727, 0.594, and 0.566. When used to predict LNM, the AUC of CEA, CA199 and CA125 were 0.696, 0.531, and 0.588. Logistic regression analysis demonstrated that preoperative serum CEA were significantly associated with positive LNM. On combining imaging examination with CEA, the sensitivity and specificity were 85.3 and 79.4%, respectively, with the AUC equal to 0.853. The combination of CEA and imaging examination preformed the highest levels of AUC and sensitivity for diagnosing LNM, which is significantly higher than using either of them alone. Although patients with abnormal CEA have a poor prognosis, two models of multivariate analysis showed that CEA was not the independent prognosis factor for survival. CONCLUSIONS CEA can be used to diagnose gastric cancer and determine whether it has LNM. Moreover, combined with CEA could improve the diagnostic sensitivity of imaging examination for lymph node involvement.BACKGROUND The associations between the number of natural teeth/denture use and all-cause mortality remain unclear due to lake of investigation for the potential interaction between tooth loss and denture use and for the potential changes in these exposures over time in older adults. We undertake this study to evaluate the associations of the number of natural teeth and/or denture use with mortality in Chinese elderly. METHODS This is a prospective cohort study of 36,283 older adults (median age 90). The number of natural teeth and denture use were collected with structured questionnaire. We evaluated hazard ratios (HRs) and confidence intervals (CIs) using a Cox proportional hazards model adjusting for demographic factors, education, income, lifestyle factors, and comorbidities. RESULTS We documented 25,857 deaths during 145,947 person-years of observation. Compared to those with 20+ teeth, tooth loss was associated with a gradual increase in mortality, with an adjusted HR of 1.14 (95% CI, 1.06 to 1.23) for those with 10-19 teeth, 1.23 (95% CI, 1.15 to 1.31) for those with 1-9 teeth, and 1.35 (95% CI, 1.26 to 1.44) for those without natural teeth. Denture use was associated with lower risk of mortality (adjusted HR 0.81; 95% CI, 0.77 to 0.84). Subgroup analyses indicated that the benefit of denture use was greater in men than in women (P = 0.02) and tended to decrease with age (P  less then  0.001). The effects of denture use did not differ among various degrees of tooth loss (P = 0.17). CONCLUSIONS Tooth loss was associated with an increased risk of mortality in older adults. Denture use provided a protective effect against death for all degrees of tooth loss however, this effect appeared to be modified by sex and age.BACKGROUND The aim of the study was to describe prevalence, severity and distribution of periodontal disease as well as associated risk factors in an indigenous Sámi population in Northern Norway, and to investigate differences between the indigenous Sámi and the non-Sámi population. METHODS This cross-sectional study included data from the Dental Health in the North study (N = 2078; 18-75 years). Data on Ethnicity, household income, education, smoking habits, dental attendance, and tooth brushing habits were collected by a questionnaire. Periodontal conditions were assessed by clinical examination. A modified version of the new AAP/EFP classification system of periodontal disease was used to estimate the severity of periodontitis. Three stages were used 'Non-severe periodontitis', 'Stage II', and stage 'III/IV'. RESULTS Of the total study population 66.5% reported Sámi affiliation. The total prevalence of periodontitis was 49.7%, with 20.1% in Stage III/IV, but no differences between Sámi and non-Sámi. When controlled for sex, age, education, smoking and dental attendance the Sámi had higher probability of having more severe stages of periodontitis; Odds RatioStage II (OR) = 1.
    LUSIONS In terms of clinically relevant outcomes (incidence of major complications and mortality), PSM in real life setting seems to be a very good alternative in properly trained patients.BACKGROUND Tuberculosis (TB) disease is a common opportunistic infection among people living with HIV (PLHIV). WHO recommends at least 6 months of isoniazid Preventive Therapy (IPT) to reduce the risk of active TB. It is important to monitor the six-month IPT completion since a suboptimal dose may not protect PLHIV from TB infection. This study determined the six-month IPT completion and factors associated with six-month IPT completion among PLHIV aged 15 years or more in Dar es Salaam region, Tanzania. METHODS Secondary analysis of routine data from PLHIV attending 58 care and treatment clinics in Dar es Salaam region was used. PLHIV, aged 15 years and above, who screened negative for TB symptoms and initiated IPT from January, 2013 to June, 2017 were recruited. Modified Poisson regression with robust standard errors was used to estimate prevalence ratios (PR) and 95% confidence interval (CI) for factors associated with IPT completion. Multilevel analysis was used to account for health facility random effectntly needed.BACKGROUND Great changes have taken place in terms of people's lifestyles and behavioral habits. Diabetes has become a threat to human health and is the most important noncommunicable disease. More than 60% of rural diabetic patients experience delayed diagnosis and treatment. https://www.selleckchem.com/products/z-lehd-fmk-s7313.html In this study, we explore the inner experience of the delayed diagnosis and treatment of patients with diabetes in rural areas and provide a reference for targeted intervention. METHODS A qualitative research design was used to examine the cognitive behavioral intention of patients in rural areas with delayed diagnosis and treatment of diabetes. Thirteen diabetes patients with delayed diagnosis and treatment were sampled with maximum variation in rural Daqing City and Tangshan City in China. The data analysis involved several levels of analysis consistent with qualitative research. RESULTS The following themes were relevant to diabetes patients in rural areas with delayed diagnosis and treatment delay "Lacked knowledge of diabetes", "Negative coping style", "Dissatisfaction with the existing medical service" and "Influence of social support". CONCLUSIONS The respondents' delayed diagnosis and treatment represent a common phenomenon. Medical personnel should provide interventions for patients and encourage them to go to the hospital on time.BACKGROUND In this study, we aimed to investigate the preoperative serum carcinoembryonic antigen (CEA) in the diagnosis of positive lymph node metastasis (LNM), and to evaluated the relationship between CEA and survival in patients with locally advanced gastric cancer (LAGC). METHODS The significance of the preoperative serum CEA level for the diagnose of LAGC and prediction of LNM was determined using the receiver operating characteristic (ROC) curve. The areas under the ROC of CEA were compared with those of other tumor markers or imaging examination including CT and MRI. Logistic regression was utilized to identify the risk factors predicting positive LNM. Independent prognosis factors were evaluated using univariate and multivariate COX regression analyses. RESULTS The ROC curves showed that the AUCs of CEA, CA199, and CA125 for diagnosing LAGC were 0.727, 0.594, and 0.566. When used to predict LNM, the AUC of CEA, CA199 and CA125 were 0.696, 0.531, and 0.588. Logistic regression analysis demonstrated that preoperative serum CEA were significantly associated with positive LNM. On combining imaging examination with CEA, the sensitivity and specificity were 85.3 and 79.4%, respectively, with the AUC equal to 0.853. The combination of CEA and imaging examination preformed the highest levels of AUC and sensitivity for diagnosing LNM, which is significantly higher than using either of them alone. Although patients with abnormal CEA have a poor prognosis, two models of multivariate analysis showed that CEA was not the independent prognosis factor for survival. CONCLUSIONS CEA can be used to diagnose gastric cancer and determine whether it has LNM. Moreover, combined with CEA could improve the diagnostic sensitivity of imaging examination for lymph node involvement.BACKGROUND The associations between the number of natural teeth/denture use and all-cause mortality remain unclear due to lake of investigation for the potential interaction between tooth loss and denture use and for the potential changes in these exposures over time in older adults. We undertake this study to evaluate the associations of the number of natural teeth and/or denture use with mortality in Chinese elderly. METHODS This is a prospective cohort study of 36,283 older adults (median age 90). The number of natural teeth and denture use were collected with structured questionnaire. We evaluated hazard ratios (HRs) and confidence intervals (CIs) using a Cox proportional hazards model adjusting for demographic factors, education, income, lifestyle factors, and comorbidities. RESULTS We documented 25,857 deaths during 145,947 person-years of observation. Compared to those with 20+ teeth, tooth loss was associated with a gradual increase in mortality, with an adjusted HR of 1.14 (95% CI, 1.06 to 1.23) for those with 10-19 teeth, 1.23 (95% CI, 1.15 to 1.31) for those with 1-9 teeth, and 1.35 (95% CI, 1.26 to 1.44) for those without natural teeth. Denture use was associated with lower risk of mortality (adjusted HR 0.81; 95% CI, 0.77 to 0.84). Subgroup analyses indicated that the benefit of denture use was greater in men than in women (P = 0.02) and tended to decrease with age (P  less then  0.001). The effects of denture use did not differ among various degrees of tooth loss (P = 0.17). CONCLUSIONS Tooth loss was associated with an increased risk of mortality in older adults. Denture use provided a protective effect against death for all degrees of tooth loss however, this effect appeared to be modified by sex and age.BACKGROUND The aim of the study was to describe prevalence, severity and distribution of periodontal disease as well as associated risk factors in an indigenous Sámi population in Northern Norway, and to investigate differences between the indigenous Sámi and the non-Sámi population. METHODS This cross-sectional study included data from the Dental Health in the North study (N = 2078; 18-75 years). Data on Ethnicity, household income, education, smoking habits, dental attendance, and tooth brushing habits were collected by a questionnaire. Periodontal conditions were assessed by clinical examination. A modified version of the new AAP/EFP classification system of periodontal disease was used to estimate the severity of periodontitis. Three stages were used 'Non-severe periodontitis', 'Stage II', and stage 'III/IV'. RESULTS Of the total study population 66.5% reported Sámi affiliation. The total prevalence of periodontitis was 49.7%, with 20.1% in Stage III/IV, but no differences between Sámi and non-Sámi. When controlled for sex, age, education, smoking and dental attendance the Sámi had higher probability of having more severe stages of periodontitis; Odds RatioStage II (OR) = 1.
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  • Sodium trisulfide (Na2S3) releases hydrogen polysulfide (H2Sn) and is useful for the investigation of the effects of H2Sn on the cell functions. In the present study, we first examined the effects of Na2S3 on the gene expression of IEC-6 cells, a rat intestinal epithelial cell line. Microarray analysis and reverse transcription-polymerase chain reaction analysis revealed that Na2S3 increased the gene expression of early growth response 1 (EGR1) and Kruppel-like transcription factor 4 (KLF4). It was interesting that U0126, an inhibitor of the activation of extracellular signal-regulated kinase 1 (ERK1), ERK2, and ERK5, inhibited the Na2S3-induced gene expression of EGR1 and KLF4. Na2S3 activated ERK1 and ERK2 (ERK1/2) within 15 min. In addition to ERK1/2, Na2S3 activated ERK5. We noticed that the electrophoretic mobility of ERK5 was decreased after Na2S3 treatment. Phos-tag analysis and in vitro dephosphorylation of the cell extracts indicated that the gel-shift of ERK5 was due to its phosphorylation. The gel-shift of ERK5 was inhibited completely by both U0126 and ERK5-IN-1, a specific inhibitor of ERK5. From these results, we concluded that the gel-shift of ERK5 was induced through autophosphorylation by activated ERK5 after Na2S3 treatment. The present study suggested that H2Sn affected various functions of intestinal epithelial cells through the activation of the ERK1/2 and ERK5 pathways.The Gram-negative diplococcus Neisseria macacae is a commensal bacterium of the mucosal surfaces in humans. https://www.selleckchem.com/products/pyridostatin-trifluoroacetate-salt.html A 52-year-old woman receiving continuous ambulatory peritoneal dialysis was admitted because of abdominal pain and turbid peritoneal fluid. N. macacae was isolated from peritoneal fluid culture and showed susceptibility to ceftriaxone. Despite appropriate antibiotics, the peritonitis was refractory, leading to the removal of the peritoneal dialysis catheter. We herein report the first case of peritoneal dialysis peritonitis caused by Neisseria macacae and review previous case reports of N. macacae infection in humans.Methotrexate-related lymphoproliferative disorder (MTX-LPD) is known to be a side effect of MTX, but its involvement in the liver has been rarely reported. We herein report a 70-year-old woman with autoimmune hepatitis and rheumatoid arthritis who developed multiple liver tumors. We initially considered that she had developed rapid-growing HCC in the cirrhotic liver based on imaging tests. A tumor biopsy and transcatheter arterial chemoembolization were thus performed. The tumors were then diagnosed as diffuse large B-cell lymphoma pathologically and considered to be MTX-LPD. This case indicates that MTX-LPD should be considered even in cirrhotic patients with liver tumors resembling HCC.A 79-year-old man without a history of diabetes underwent orchiectomy for prostate cancer. Eight months after the operation, he suffered severe deterioration of visceral fat deposition, fatty liver and diabetes. Treatment for diabetes with canagliflozin and dulaglutide resulted in improvement in his glycemic control, visceral fat and fatty liver. Visceral fat-dominant deposition, which differs from the typical course after androgen deprivation therapy, may have been associated with severe exacerbation of diabetes and fatty liver. Glycemic management with a sodium glucose cotransporter 2 (SGLT2) inhibitor and glucagon-like peptide (GLP)-1 receptor agonist may help improve the glucose metabolism, visceral fat deposition and fatty liver after orchiectomy.We herein report a 50-year-old man with alcoholic cirrhosis who developed loss of consciousness and tremor of the upper limbs. Magnetic resonance imaging findings were suggestive of limbic encephalitis with bilateral hippocampal damage, and a cerebrospinal fluid (CSF) examination confirmed anti-N-methyl-D-aspartate (NMDA) and anti-glutamate receptor antibodies. Despite initial corticosteroid therapy, meningeal irritation symptoms appeared, owing to the development of cryptococcal meningitis (CM), diagnosed by the detection of cryptococcal capsular polysaccharide antigen in the follow-up CSF analysis. Cerebral infarction with reversible stenosis of major cerebral arteries during the clinical course was also observed. Following administration of antifungals and corticosteroids, the number of cells in the CSF gradually declined, and NMDA receptor antibodies disappeared. Our study demonstrates the unique coexistence of CM with anti-NMDA receptor encephalitis in adults.Spastic paraplegia type 4 (SPG4) is caused by mutations of the SPAST gene and is the most common form of autosomal-dominantly inherited pure hereditary spastic paraplegia (HSP). We herein report a Japanese patient with SPG4 with a confirmed de novo mutation of SPAST. On exome sequencing and Sanger sequencing, we identified the heterozygous missense mutation p.R460L in the SPAST gene. This mutation was absent in the parents, and the paternity and maternity of the parents were both confirmed. The patient showed a pure SPG4 phenotype with an infantile onset. This study may expand the clinical and genetic findings for SPG4.Objectives Hydroxychloroquine (HCQ) has been prescribed in Japan only relatively recently and is recommended for the treatment of skin lesions, arthritis and renal lesions according to the Japanese Guideline for the Management of systemic lupus erythematosus (SLE) (2019). However, the associations between the efficacy and safety and the HCQ dose in Japanese SLE patients remain unclear. We investigated the efficacy and safety of different HCQ doses in Japanese SLE patients with a low disease activity who were not receiving immunosuppressants. Methods The disease activity was evaluated using the SELENA-SLEDAI 2011 criteria, the Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum biomarkers. Safety was evaluated via the frequency of adverse events over a period of three months. Results We enrolled 61 SLE patients treated with HCQ and no additional immunosuppressive therapy for more than 3 months. HCQ was administered to 46 patients at the usual dose and to 15 cases at a lower than usual dose. Although the CLASI activity scores decreased significantly in both groups, the magnitude of this decrease was larger in the usual-dose HCQ group than in the low-dose HCQ group. SLEDAI scores and immunological activity were significantly improved only in the usual-dose HCQ group. In addition, changes in the serum complement levels in the usual-dose HCQ group were more dramatic than in the low-dose HCQ group six months after the initiation of HCQ administration. Adverse events were more frequent in the usual-dose HCQ group than in the low-dose HCQ group (30.4% and 13.3%, respectively). Conclusions HCQ therapy is effective for maintenance therapy of SLE patients. The usual dose of HCQ may have some advantage in ameliorating low complement levels.
    Sodium trisulfide (Na2S3) releases hydrogen polysulfide (H2Sn) and is useful for the investigation of the effects of H2Sn on the cell functions. In the present study, we first examined the effects of Na2S3 on the gene expression of IEC-6 cells, a rat intestinal epithelial cell line. Microarray analysis and reverse transcription-polymerase chain reaction analysis revealed that Na2S3 increased the gene expression of early growth response 1 (EGR1) and Kruppel-like transcription factor 4 (KLF4). It was interesting that U0126, an inhibitor of the activation of extracellular signal-regulated kinase 1 (ERK1), ERK2, and ERK5, inhibited the Na2S3-induced gene expression of EGR1 and KLF4. Na2S3 activated ERK1 and ERK2 (ERK1/2) within 15 min. In addition to ERK1/2, Na2S3 activated ERK5. We noticed that the electrophoretic mobility of ERK5 was decreased after Na2S3 treatment. Phos-tag analysis and in vitro dephosphorylation of the cell extracts indicated that the gel-shift of ERK5 was due to its phosphorylation. The gel-shift of ERK5 was inhibited completely by both U0126 and ERK5-IN-1, a specific inhibitor of ERK5. From these results, we concluded that the gel-shift of ERK5 was induced through autophosphorylation by activated ERK5 after Na2S3 treatment. The present study suggested that H2Sn affected various functions of intestinal epithelial cells through the activation of the ERK1/2 and ERK5 pathways.The Gram-negative diplococcus Neisseria macacae is a commensal bacterium of the mucosal surfaces in humans. https://www.selleckchem.com/products/pyridostatin-trifluoroacetate-salt.html A 52-year-old woman receiving continuous ambulatory peritoneal dialysis was admitted because of abdominal pain and turbid peritoneal fluid. N. macacae was isolated from peritoneal fluid culture and showed susceptibility to ceftriaxone. Despite appropriate antibiotics, the peritonitis was refractory, leading to the removal of the peritoneal dialysis catheter. We herein report the first case of peritoneal dialysis peritonitis caused by Neisseria macacae and review previous case reports of N. macacae infection in humans.Methotrexate-related lymphoproliferative disorder (MTX-LPD) is known to be a side effect of MTX, but its involvement in the liver has been rarely reported. We herein report a 70-year-old woman with autoimmune hepatitis and rheumatoid arthritis who developed multiple liver tumors. We initially considered that she had developed rapid-growing HCC in the cirrhotic liver based on imaging tests. A tumor biopsy and transcatheter arterial chemoembolization were thus performed. The tumors were then diagnosed as diffuse large B-cell lymphoma pathologically and considered to be MTX-LPD. This case indicates that MTX-LPD should be considered even in cirrhotic patients with liver tumors resembling HCC.A 79-year-old man without a history of diabetes underwent orchiectomy for prostate cancer. Eight months after the operation, he suffered severe deterioration of visceral fat deposition, fatty liver and diabetes. Treatment for diabetes with canagliflozin and dulaglutide resulted in improvement in his glycemic control, visceral fat and fatty liver. Visceral fat-dominant deposition, which differs from the typical course after androgen deprivation therapy, may have been associated with severe exacerbation of diabetes and fatty liver. Glycemic management with a sodium glucose cotransporter 2 (SGLT2) inhibitor and glucagon-like peptide (GLP)-1 receptor agonist may help improve the glucose metabolism, visceral fat deposition and fatty liver after orchiectomy.We herein report a 50-year-old man with alcoholic cirrhosis who developed loss of consciousness and tremor of the upper limbs. Magnetic resonance imaging findings were suggestive of limbic encephalitis with bilateral hippocampal damage, and a cerebrospinal fluid (CSF) examination confirmed anti-N-methyl-D-aspartate (NMDA) and anti-glutamate receptor antibodies. Despite initial corticosteroid therapy, meningeal irritation symptoms appeared, owing to the development of cryptococcal meningitis (CM), diagnosed by the detection of cryptococcal capsular polysaccharide antigen in the follow-up CSF analysis. Cerebral infarction with reversible stenosis of major cerebral arteries during the clinical course was also observed. Following administration of antifungals and corticosteroids, the number of cells in the CSF gradually declined, and NMDA receptor antibodies disappeared. Our study demonstrates the unique coexistence of CM with anti-NMDA receptor encephalitis in adults.Spastic paraplegia type 4 (SPG4) is caused by mutations of the SPAST gene and is the most common form of autosomal-dominantly inherited pure hereditary spastic paraplegia (HSP). We herein report a Japanese patient with SPG4 with a confirmed de novo mutation of SPAST. On exome sequencing and Sanger sequencing, we identified the heterozygous missense mutation p.R460L in the SPAST gene. This mutation was absent in the parents, and the paternity and maternity of the parents were both confirmed. The patient showed a pure SPG4 phenotype with an infantile onset. This study may expand the clinical and genetic findings for SPG4.Objectives Hydroxychloroquine (HCQ) has been prescribed in Japan only relatively recently and is recommended for the treatment of skin lesions, arthritis and renal lesions according to the Japanese Guideline for the Management of systemic lupus erythematosus (SLE) (2019). However, the associations between the efficacy and safety and the HCQ dose in Japanese SLE patients remain unclear. We investigated the efficacy and safety of different HCQ doses in Japanese SLE patients with a low disease activity who were not receiving immunosuppressants. Methods The disease activity was evaluated using the SELENA-SLEDAI 2011 criteria, the Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum biomarkers. Safety was evaluated via the frequency of adverse events over a period of three months. Results We enrolled 61 SLE patients treated with HCQ and no additional immunosuppressive therapy for more than 3 months. HCQ was administered to 46 patients at the usual dose and to 15 cases at a lower than usual dose. Although the CLASI activity scores decreased significantly in both groups, the magnitude of this decrease was larger in the usual-dose HCQ group than in the low-dose HCQ group. SLEDAI scores and immunological activity were significantly improved only in the usual-dose HCQ group. In addition, changes in the serum complement levels in the usual-dose HCQ group were more dramatic than in the low-dose HCQ group six months after the initiation of HCQ administration. Adverse events were more frequent in the usual-dose HCQ group than in the low-dose HCQ group (30.4% and 13.3%, respectively). Conclusions HCQ therapy is effective for maintenance therapy of SLE patients. The usual dose of HCQ may have some advantage in ameliorating low complement levels.
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  • OBJECTIVE In a previous study of patients newly enrolled in HIV care, we observed that clinicians were less likely to address emotional issues expressed by African-American patients compared to whites. We sought to verify and expand these findings in a larger group of patients established in HIV care. METHODS We used VR-CoDES to analyze transcripts from 342 audio-recorded medical visits in the United States. We used random intercept multilevel logistic regression to assess associations between patient and clinician characteristics and patterns of emotional talk. RESULTS African-American patients were less likely than others to spontaneously express emotions (OR 0.50; 95 % CI 0.29-0.85). https://www.selleckchem.com/products/jq1.html Clinicians, who were predominantly white, were more likely to respond to emotional expressions by African-American patients explicitly (OR 1.56; 95 % CI 1.11-2.20) but less likely to offer neutral/passive responses that provide space for emotional conversation (OR 0.56; 95 % CI 0.37-0.84) and more likely to block discussion of the emotional issue (OR 2.20; 95 % CI 1.05-4.63). Emotional talk did not vary by patient age or gender. CONCLUSION These results confirm our prior findings, demonstrating less open emotional communication between African-American patients and their providers. PRACTICE IMPLICATIONS Addressing racial differences in communicating about emotions may reduce disparities in patient-clinician relationships. Published by Elsevier B.V.The rate of drug-induced proliferation (DIP) has been proposed as an unbiased alternative drug effect metric. However, current assays are not easy and precise enough to track minor changes in cell growth. Here, we report the optimized EZMTT based detection method which can continuously measure time-dependent growth after drug treatment and reliably detect partial drug resistance for cancer cells. Importantly, tracking time-dependent growth after drug treatment demonstrated that a KGA allosteric inhibitor alone failed to completely inhibit cancer cell growth, but a drug combination was able to provide complete inhibition in cell-based assays that translated well in in vivo animal experiments. In conclusion, this simple EZMTT method provided precise measurement of loss of susceptibility after drug treatment and has great potential to be developed for drug efficacy and drug combination studies to solve the unmet medical need. Disulfiram in conjunction with copper has been shown to be a potent anticancer agent. However, disulfiram's therapeutic potential in prostate cancer is hindered by off-target effects due to its reactive and nucleophilic thiol-containing component, diethyldithiocarbamate (DTC). To minimize undesirable reactivity, we have strategically blocked the thiol moiety in DTC with a cleavable p-aminobenzyl (pAB) group linked to peptide substrates recognized by prostate specific antigen (PSA). Here we report the synthesis and evaluation in cancer cell models of two PSA-activatable prodrugs HPD (Ac-HSSKLQL-pAB-DTC and RPD (RSSYYSL-pAB-DTC). In vitro exposure to PSA was found to trigger activation of HPD and RPD to release diethyldithiocarbamate, and both prodrugs were found to induce toxicity in prostate cancer cells, with HPD showing the most promising selectivity. With copper supplementation, the IC50 of HPD was 1.4 µM in PSA-expressing LNCaP cells, and 11 µM in PC3 cells that do not express PSA. These studies demonstrate the utility of using peptide recognition handles to direct the activity of dithiocarbamate prodrugs for selective cytotoxicity of cancer cells. PURPOSE Forearm deformity is common in hereditary multiple osteochondromas (HMO). The results of ulnar lengthening and osteochondroma excision are generally favorable, both clinically and radiographically. This study aimed to assess the clinical, radiographic, and functional results of forearm reconstruction in patients with Masada type I deformity (osteochondroma in the distal ulna with radial bowing, without radial head dislocation). METHODS A retrospective review was performed on patients with HMO who underwent surgical reconstruction for a Masada type I forearm deformity over a 10-year period. Eleven forearms in 10 patients underwent gradual ulnar lengthening with an external fixator. Age at the time of surgery was 5 to 12 years. Radiographic evaluation included ulnar shortening, radial articular angle, and carpal slip. Clinical evaluation included range of motion of the elbow and wrist. Functional outcomes were evaluated with the Disabilities of the Arm, Shoulder, and Hand questionnaire and the Short Fortion, improved range of motion, and better cosmesis, which future research may help to clarify. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic V. PURPOSE Psittacosis is a bacterial zoonosis caused by Chlamydia (Chlamydophila) psittaci that infects birds. Although potentially fatal, infections can be reduced by controlling the source of infection. We therefore described the epidemiology of psittacosis, focusing on the infection source. METHODS We descriptively analyzed psittacosis cases reported through national surveillance in Japan from 2007 to 2016. We also analyzed Chlamydia psittaci prevalence among captive psittaciformes during the same period. RESULTS One hundred eleven cases were reported, and the annual number and notification rate of psittacosis declined. While 58% were male and the median age was 61 years, the median age differed by gender (males 63 years, females 53 years), with more female cases in those aged less then 50 years. In addition, the most common infection source differed by gender (men columbiformes; women psittaciformes). The decline in notifications was associated with a decline in psittaciformes-associated cases, with a concomitant decline in female cases. The prevalence of C. psittaci among captive psittaciformes also decreased over the period. CONCLUSIONS We found important differences in the epidemiology of psittacosis by gender, and the recent decrease in notifications correlated with decreasing C. psittaci prevalence in birds. Risk communications for psittacosis should consider the current epidemiology regarding gender, age, and infection source.
    OBJECTIVE In a previous study of patients newly enrolled in HIV care, we observed that clinicians were less likely to address emotional issues expressed by African-American patients compared to whites. We sought to verify and expand these findings in a larger group of patients established in HIV care. METHODS We used VR-CoDES to analyze transcripts from 342 audio-recorded medical visits in the United States. We used random intercept multilevel logistic regression to assess associations between patient and clinician characteristics and patterns of emotional talk. RESULTS African-American patients were less likely than others to spontaneously express emotions (OR 0.50; 95 % CI 0.29-0.85). https://www.selleckchem.com/products/jq1.html Clinicians, who were predominantly white, were more likely to respond to emotional expressions by African-American patients explicitly (OR 1.56; 95 % CI 1.11-2.20) but less likely to offer neutral/passive responses that provide space for emotional conversation (OR 0.56; 95 % CI 0.37-0.84) and more likely to block discussion of the emotional issue (OR 2.20; 95 % CI 1.05-4.63). Emotional talk did not vary by patient age or gender. CONCLUSION These results confirm our prior findings, demonstrating less open emotional communication between African-American patients and their providers. PRACTICE IMPLICATIONS Addressing racial differences in communicating about emotions may reduce disparities in patient-clinician relationships. Published by Elsevier B.V.The rate of drug-induced proliferation (DIP) has been proposed as an unbiased alternative drug effect metric. However, current assays are not easy and precise enough to track minor changes in cell growth. Here, we report the optimized EZMTT based detection method which can continuously measure time-dependent growth after drug treatment and reliably detect partial drug resistance for cancer cells. Importantly, tracking time-dependent growth after drug treatment demonstrated that a KGA allosteric inhibitor alone failed to completely inhibit cancer cell growth, but a drug combination was able to provide complete inhibition in cell-based assays that translated well in in vivo animal experiments. In conclusion, this simple EZMTT method provided precise measurement of loss of susceptibility after drug treatment and has great potential to be developed for drug efficacy and drug combination studies to solve the unmet medical need. Disulfiram in conjunction with copper has been shown to be a potent anticancer agent. However, disulfiram's therapeutic potential in prostate cancer is hindered by off-target effects due to its reactive and nucleophilic thiol-containing component, diethyldithiocarbamate (DTC). To minimize undesirable reactivity, we have strategically blocked the thiol moiety in DTC with a cleavable p-aminobenzyl (pAB) group linked to peptide substrates recognized by prostate specific antigen (PSA). Here we report the synthesis and evaluation in cancer cell models of two PSA-activatable prodrugs HPD (Ac-HSSKLQL-pAB-DTC and RPD (RSSYYSL-pAB-DTC). In vitro exposure to PSA was found to trigger activation of HPD and RPD to release diethyldithiocarbamate, and both prodrugs were found to induce toxicity in prostate cancer cells, with HPD showing the most promising selectivity. With copper supplementation, the IC50 of HPD was 1.4 µM in PSA-expressing LNCaP cells, and 11 µM in PC3 cells that do not express PSA. These studies demonstrate the utility of using peptide recognition handles to direct the activity of dithiocarbamate prodrugs for selective cytotoxicity of cancer cells. PURPOSE Forearm deformity is common in hereditary multiple osteochondromas (HMO). The results of ulnar lengthening and osteochondroma excision are generally favorable, both clinically and radiographically. This study aimed to assess the clinical, radiographic, and functional results of forearm reconstruction in patients with Masada type I deformity (osteochondroma in the distal ulna with radial bowing, without radial head dislocation). METHODS A retrospective review was performed on patients with HMO who underwent surgical reconstruction for a Masada type I forearm deformity over a 10-year period. Eleven forearms in 10 patients underwent gradual ulnar lengthening with an external fixator. Age at the time of surgery was 5 to 12 years. Radiographic evaluation included ulnar shortening, radial articular angle, and carpal slip. Clinical evaluation included range of motion of the elbow and wrist. Functional outcomes were evaluated with the Disabilities of the Arm, Shoulder, and Hand questionnaire and the Short Fortion, improved range of motion, and better cosmesis, which future research may help to clarify. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic V. PURPOSE Psittacosis is a bacterial zoonosis caused by Chlamydia (Chlamydophila) psittaci that infects birds. Although potentially fatal, infections can be reduced by controlling the source of infection. We therefore described the epidemiology of psittacosis, focusing on the infection source. METHODS We descriptively analyzed psittacosis cases reported through national surveillance in Japan from 2007 to 2016. We also analyzed Chlamydia psittaci prevalence among captive psittaciformes during the same period. RESULTS One hundred eleven cases were reported, and the annual number and notification rate of psittacosis declined. While 58% were male and the median age was 61 years, the median age differed by gender (males 63 years, females 53 years), with more female cases in those aged less then 50 years. In addition, the most common infection source differed by gender (men columbiformes; women psittaciformes). The decline in notifications was associated with a decline in psittaciformes-associated cases, with a concomitant decline in female cases. The prevalence of C. psittaci among captive psittaciformes also decreased over the period. CONCLUSIONS We found important differences in the epidemiology of psittacosis by gender, and the recent decrease in notifications correlated with decreasing C. psittaci prevalence in birds. Risk communications for psittacosis should consider the current epidemiology regarding gender, age, and infection source.
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  • This study evaluated common vetch stover as a feed in mixed rations for growing lambs. Four common vetch varieties were compared with alfalfa (control) for their effects on growth performance, ruminal fermentation, nutrient digestibility, and nitrogen retention. Male Hu lambs (n = 50) aged 3 months, with a mean body weight of 17.5 ± 0.34 kg were allocated randomly to one of the five dietary treatments, making 10 lambs per treatment. The experiment lasted 67 days with a 10-day adaptation period and a 50-day fattening period, and with the final 7 days used for a nutrient digestibility and nitrogen balance trial. All diets contained 30.0% maize straw and 50.0% concentrate, with different forage sources (on a fed basis) 20.0% alfalfa hay (control), 20.0% local common vetch variety 333A (C333A) stover, or 20.0% stover of one of three improved common vetch varieties Lanjian No. 1 (CLJ1), Lanjian No. 2 (CLJ2), or Lanjian No. 3 (CLJ3). For stover quality, CLJ1 stover had the greatest crude protein (CP), in vitro organic matter digestibility (IVOMD), and metabolizable energy (ME) content and the least cell wall contents, while C333A stover had the least CP, IVOMD, and ME contents and the greatest cell wall contents. Sheep fed the control diet had a greater average daily gain (ADG), apparent digestibility of organic matter (DOM), neutral detergent fiber, acid detergent fiber, and nitrogen retention, and greater ruminal total volatile fatty acids concentration than lambs fed the C333A or CLJ3 diet, but similar performance to lambs fed the CLJ1 and CLJ2 diets. The feed conversion ratio and predicted CH4 emission per unit of DOM intake and ADG of the control, CLJ1, and CLJ2 diets was significantly lower (p less then 0.05) than for the other diets. Based on these results, stovers of varieties CLJ1 and CLJ2 can be recommended as an alternative to alfalfa hay and for use in a legume crop rotation with cereals on the Tibetan plateau.Trophy hunting and mass tourism are the two major interventions designed to provide various socioeconomic and ecological benefits at the local and regional levels. However, these interventions have raised some serious concerns that need to be addressed. This study was conducted in Khunjerab National Park (KNP) with an aim to analyze comparatively the socioeconomic and ecological impacts of trophy hunting and mass tourism over the last three decades within the context of sustainability. Focus Group Discussions (FGDs) with key stakeholders and household interviews were conducted to collect data on trophy hunting and mass tourism, and on local attitudes towards these two interventions in and around KNP. The results revealed that 170 Ibex (Capra sibirica) and 12 Blue sheep (Pseudois nayaur) were hunted in the study area over the past three decades, and trophy hunting was not based on a sustainable harvest level. Trophy hunting on average generated USD 16,272 annual revenue, which was invested in community developy hunting and mass tourism, we suggest trophy hunting should be stopped and mass tourism should be shifted to ecotourism in and around KNP. Ecotourism could mitigate human-Snow leopard conflicts and help conserve the fragile ecosystem, while generating enough revenue incentives for the community to protect biodiversity and compensate for livestock depredation losses to Snow leopards. Our results may have implications for management of trophy hunting and mass tourism in other similar regions that deserve further investigation.Chitosan is an environmentally friendly agent that is used to achieve the antimicrobial properties of textiles. Nowadays, the binding of chitosan to the textiles has been thoroughly researched due to the increasing demands on the stability of achieved properties during the textile care processes. Most crosslinking agents for chitosan are not safe for humans or environment, such as glutaric aldehyde (GA) and formaldehyde derivatives. Eco-friendly polycarboxyilic acids (PCAs) are usually used in after-treatment. In this work, chitosan powder was dissolved in citric acid with sodium hydrophosphite (SHP) as a catalyst. Standard cotton (CO) and polyester/cotton (PES/CO) fabrics were pretreated in 20% NaOH, similar to mercerization, in order to open the structure of the cotton fibers and hydrolyze polyester fibers, continued by finishing in the gelatin chitosan bath. Afterwards, the hot rinsing process, followed by drying and curing, closed the achieved structure. The main objective was to achieve durable antimicrobial properties to multiple maintenance cycles CO and PES/CO fabric in order to apply it in a hospital environment. The characterization of fabrics was performed after treatment, first and fifth washing cycles according ISO 63302012 by field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FTIR-ATR), electrokinetic analysis (EKA), by the determination of tensile properties and mechanical damage (wear), and the antimicrobial activity. The application of 20% NaOH led to the swelling and mercerization of cotton cellulose, and hydrolysis of polyester, resulting in better mechanical properties. It has been confirmed that the chitosan particles were well implemented into the cotton fiber and onto to the polyester component of PES/CO blend. The presence of chitosan was confirmed after five washing cycles, but in lower quantity. However, achieved antimicrobial activity is persistent.The molecular structure of the 8-hydroxyquinoline-bis (2-phenylpyridyl) iridium (IrQ(ppy)2) dual emitter organometallic compound is determined based on detailed 1D and 2D nuclear magnetic resonance (NMR), to identify metal-ligands coordination, isomerization and chemical yield of the desired compound. Meanwhile, the extended X-ray absorption fine structure (EXAFS) was used to determine the interatomic distances around the iridium ion. https://www.selleckchem.com/products/ademetionine.html From the NMR results, this compound IrQ(ppy)2 exhibits a trans isomerization with a distribution of coordinated N-atoms in a similar way to facial Ir(ppy)3. The EXAFS measurements confirm the structural model of the IrQ(ppy)2 compound where the oxygen atoms from the quinoline ligands induce the splitting of the next-nearest neighboring C in the second shell of the Ir3+ ions. The high-performance liquid chromatography (HPLC), as a part of the detailed molecular analysis, confirms the purity of the desired IrQ(ppy)2 organometallic compound as being more than 95%, together with the progress of the chemical reactions towards the final compound.
    This study evaluated common vetch stover as a feed in mixed rations for growing lambs. Four common vetch varieties were compared with alfalfa (control) for their effects on growth performance, ruminal fermentation, nutrient digestibility, and nitrogen retention. Male Hu lambs (n = 50) aged 3 months, with a mean body weight of 17.5 ± 0.34 kg were allocated randomly to one of the five dietary treatments, making 10 lambs per treatment. The experiment lasted 67 days with a 10-day adaptation period and a 50-day fattening period, and with the final 7 days used for a nutrient digestibility and nitrogen balance trial. All diets contained 30.0% maize straw and 50.0% concentrate, with different forage sources (on a fed basis) 20.0% alfalfa hay (control), 20.0% local common vetch variety 333A (C333A) stover, or 20.0% stover of one of three improved common vetch varieties Lanjian No. 1 (CLJ1), Lanjian No. 2 (CLJ2), or Lanjian No. 3 (CLJ3). For stover quality, CLJ1 stover had the greatest crude protein (CP), in vitro organic matter digestibility (IVOMD), and metabolizable energy (ME) content and the least cell wall contents, while C333A stover had the least CP, IVOMD, and ME contents and the greatest cell wall contents. Sheep fed the control diet had a greater average daily gain (ADG), apparent digestibility of organic matter (DOM), neutral detergent fiber, acid detergent fiber, and nitrogen retention, and greater ruminal total volatile fatty acids concentration than lambs fed the C333A or CLJ3 diet, but similar performance to lambs fed the CLJ1 and CLJ2 diets. The feed conversion ratio and predicted CH4 emission per unit of DOM intake and ADG of the control, CLJ1, and CLJ2 diets was significantly lower (p less then 0.05) than for the other diets. Based on these results, stovers of varieties CLJ1 and CLJ2 can be recommended as an alternative to alfalfa hay and for use in a legume crop rotation with cereals on the Tibetan plateau.Trophy hunting and mass tourism are the two major interventions designed to provide various socioeconomic and ecological benefits at the local and regional levels. However, these interventions have raised some serious concerns that need to be addressed. This study was conducted in Khunjerab National Park (KNP) with an aim to analyze comparatively the socioeconomic and ecological impacts of trophy hunting and mass tourism over the last three decades within the context of sustainability. Focus Group Discussions (FGDs) with key stakeholders and household interviews were conducted to collect data on trophy hunting and mass tourism, and on local attitudes towards these two interventions in and around KNP. The results revealed that 170 Ibex (Capra sibirica) and 12 Blue sheep (Pseudois nayaur) were hunted in the study area over the past three decades, and trophy hunting was not based on a sustainable harvest level. Trophy hunting on average generated USD 16,272 annual revenue, which was invested in community developy hunting and mass tourism, we suggest trophy hunting should be stopped and mass tourism should be shifted to ecotourism in and around KNP. Ecotourism could mitigate human-Snow leopard conflicts and help conserve the fragile ecosystem, while generating enough revenue incentives for the community to protect biodiversity and compensate for livestock depredation losses to Snow leopards. Our results may have implications for management of trophy hunting and mass tourism in other similar regions that deserve further investigation.Chitosan is an environmentally friendly agent that is used to achieve the antimicrobial properties of textiles. Nowadays, the binding of chitosan to the textiles has been thoroughly researched due to the increasing demands on the stability of achieved properties during the textile care processes. Most crosslinking agents for chitosan are not safe for humans or environment, such as glutaric aldehyde (GA) and formaldehyde derivatives. Eco-friendly polycarboxyilic acids (PCAs) are usually used in after-treatment. In this work, chitosan powder was dissolved in citric acid with sodium hydrophosphite (SHP) as a catalyst. Standard cotton (CO) and polyester/cotton (PES/CO) fabrics were pretreated in 20% NaOH, similar to mercerization, in order to open the structure of the cotton fibers and hydrolyze polyester fibers, continued by finishing in the gelatin chitosan bath. Afterwards, the hot rinsing process, followed by drying and curing, closed the achieved structure. The main objective was to achieve durable antimicrobial properties to multiple maintenance cycles CO and PES/CO fabric in order to apply it in a hospital environment. The characterization of fabrics was performed after treatment, first and fifth washing cycles according ISO 63302012 by field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FTIR-ATR), electrokinetic analysis (EKA), by the determination of tensile properties and mechanical damage (wear), and the antimicrobial activity. The application of 20% NaOH led to the swelling and mercerization of cotton cellulose, and hydrolysis of polyester, resulting in better mechanical properties. It has been confirmed that the chitosan particles were well implemented into the cotton fiber and onto to the polyester component of PES/CO blend. The presence of chitosan was confirmed after five washing cycles, but in lower quantity. However, achieved antimicrobial activity is persistent.The molecular structure of the 8-hydroxyquinoline-bis (2-phenylpyridyl) iridium (IrQ(ppy)2) dual emitter organometallic compound is determined based on detailed 1D and 2D nuclear magnetic resonance (NMR), to identify metal-ligands coordination, isomerization and chemical yield of the desired compound. Meanwhile, the extended X-ray absorption fine structure (EXAFS) was used to determine the interatomic distances around the iridium ion. https://www.selleckchem.com/products/ademetionine.html From the NMR results, this compound IrQ(ppy)2 exhibits a trans isomerization with a distribution of coordinated N-atoms in a similar way to facial Ir(ppy)3. The EXAFS measurements confirm the structural model of the IrQ(ppy)2 compound where the oxygen atoms from the quinoline ligands induce the splitting of the next-nearest neighboring C in the second shell of the Ir3+ ions. The high-performance liquid chromatography (HPLC), as a part of the detailed molecular analysis, confirms the purity of the desired IrQ(ppy)2 organometallic compound as being more than 95%, together with the progress of the chemical reactions towards the final compound.
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  • SARS-CoV-2 (COVID-19) is a new Coronavirus, with first reported human infections in late 2019. COVID-19 has been officially declared as a universal pandemic by the World Health Organization (WHO). https://www.selleckchem.com/products/pf-543.html The epidemiological characteristics of COVID-2019 have not been completely understood yet. More than 200,000 persons were killed during this epidemic (till 1 May 2020). Therefore, developing forecasting models to predict the spread of that epidemic is a critical issue. In this study, statistical and artificial intelligence based approaches have been proposed to model and forecast the prevalence of this epidemic in Egypt. These approaches are autoregressive integrated moving average (ARIMA) and nonlinear autoregressive artificial neural networks (NARANN). The official data reported by The Egyptian Ministry of Health and Population of COVID-19 cases in the period between 1 March and 10 May 2020 was used to train the models. The forecasted cases showed a good agreement with officially reported cases. The obtained results of this study may help the Egyptian decision-makers to put short-term future plans to face this epidemic.Currently no specific medicinal treatment exists against the new SARS-CoV2 and chloroquine is widely used, since it can decrease the length of hospital stay and improve the evolution of the associated COVID-19 pneumonia. However, several safety concerns have been raised from chloroquine use due to the lack of essential information regarding its dosing. The aim of this study is to provide a critical appraisal of the safety information regarding chloroquine treatment and to apply simulation techniques to unveil relationships between the observed serious adverse events and overdosing, as well as to propose optimized dosage regimens. The dose related adverse events of chloroquine are unveiled and maximum tolerated doses and concentration levels are quoted. Among others, treatment with chloroquine can lead to severe adverse effects like prolongation of the QT interval and cardiomyopathy. In case of chloroquine overdosing, conditions similar to those produced by SARS-CoV2, such as pulmonary oedema with respiratory insufficiency and circulatory collapse, can be observed. Co-administration of chloroquine with other drugs for the treatment of COVID-19 patients, like azithromycin, can further increase the risk of QT prolongation and cardiomyopathy. For elder patients there is a high risk for toxicity and dose reduction should be made. This study unveils the risks of some widely used dosing regimens and binds the observed serious adverse events with dosing. Based on simulations, safer alternative dosage regimens are proposed and recommendations regarding chloroquine dosing are made.Recent advances in nucleic acid based testing using bio-optical sensor approaches have been introduced but most are based on hybridization between the optical sensor and the bio-molecule and not on an amplification mechanism. Direct nucleic acid amplification on an optical sensor has several technical limitations, such as the sensitivity of the temperature sensor, instrument complexity, and high background signal. We here describe a novel nucleic acid amplification method based on a whispering gallery mode active resonator and discuss its potential molecular diagnostic application. By implanting nanoclusters as active compounds, this active resonator operates without tapered fiber coupling and emits a strong photoluminescence signal with low background in the wavelength of low absorption in an aqueous environment that is typical of biosensors. Our method also offers an extremely low detection threshold down to a single copy within 10 min due to the strong light-matter interaction in a nano-gap structure. We envision that this active resonator provides a high refractive index contrast for tight mode confinement with simple alignment as well as the possibility of reducing the device size so that a point-of-care system with low-cost, high-sensitivity and simplicity.Prediction of individual mobility is crucial in human mobility related applications. Whereas, existing research on individual mobility prediction mainly focuses on next location prediction and short-term dependencies between traveling locations. Long-term location sequence prediction is of great importance for long-time traffic planning and location advertising, and long-term dependencies exist as individual mobility regularity typically occurs daily and weekly. This paper proposes a novel hierarchical temporal attention-based LSTM encoder-decoder model for individual location sequence prediction. The proposed hierarchical attention mechanism captures both long-term and short-term dependencies underlying in individual longitudinal trajectories, and uncovers frequential and periodical mobility patterns in an interpretable manner by incorporating the calendar cycle of individual travel regularities into location prediction. More specifically, the hierarchical attention consists of local temporal attention to identify highly related locations in each day, and global temporal attention to discern important travel regularities over a week. Experiments on individual trajectory datasets with varying degree of traveling uncertainty demonstrate that our method outperforms four baseline methods on three evaluation metrics. In addition, we explore the interpretability of the proposed model in understanding individual daily, and weekly mobility patterns by visualizing the temporal attention weights and frequent traveling patterns associated with locations.The airway/lung mechanics is usually represented with nonlinear 0-D models based on a pneumatic-electrical analogy. The aim of this work is to provide a detailed description of the human respiratory mechanics in healthy and diseased conditions. The model used for this purpose employs some known constitutive functions of the main components of the respiratory system. We give a detailed mathematical description of these functions and subsequently derive additional key ones. We are interested not only in the main output such as airflow at the mouth or alveolar pressure and volume, but also in other quantities such as resistance and pressure drop across each element of the system and even recoil and compliance of the chest wall. Pathological conditions are simulated by altering the parameters of the constitutive functions. Results show that increased upper airway resistance induces airflow reduction with concomitant narrowing of volume and pressure ranges without affecting lung compliance. Instead, increased elastic recoil leads to low volumes and decreased lung compliance.
    SARS-CoV-2 (COVID-19) is a new Coronavirus, with first reported human infections in late 2019. COVID-19 has been officially declared as a universal pandemic by the World Health Organization (WHO). https://www.selleckchem.com/products/pf-543.html The epidemiological characteristics of COVID-2019 have not been completely understood yet. More than 200,000 persons were killed during this epidemic (till 1 May 2020). Therefore, developing forecasting models to predict the spread of that epidemic is a critical issue. In this study, statistical and artificial intelligence based approaches have been proposed to model and forecast the prevalence of this epidemic in Egypt. These approaches are autoregressive integrated moving average (ARIMA) and nonlinear autoregressive artificial neural networks (NARANN). The official data reported by The Egyptian Ministry of Health and Population of COVID-19 cases in the period between 1 March and 10 May 2020 was used to train the models. The forecasted cases showed a good agreement with officially reported cases. The obtained results of this study may help the Egyptian decision-makers to put short-term future plans to face this epidemic.Currently no specific medicinal treatment exists against the new SARS-CoV2 and chloroquine is widely used, since it can decrease the length of hospital stay and improve the evolution of the associated COVID-19 pneumonia. However, several safety concerns have been raised from chloroquine use due to the lack of essential information regarding its dosing. The aim of this study is to provide a critical appraisal of the safety information regarding chloroquine treatment and to apply simulation techniques to unveil relationships between the observed serious adverse events and overdosing, as well as to propose optimized dosage regimens. The dose related adverse events of chloroquine are unveiled and maximum tolerated doses and concentration levels are quoted. Among others, treatment with chloroquine can lead to severe adverse effects like prolongation of the QT interval and cardiomyopathy. In case of chloroquine overdosing, conditions similar to those produced by SARS-CoV2, such as pulmonary oedema with respiratory insufficiency and circulatory collapse, can be observed. Co-administration of chloroquine with other drugs for the treatment of COVID-19 patients, like azithromycin, can further increase the risk of QT prolongation and cardiomyopathy. For elder patients there is a high risk for toxicity and dose reduction should be made. This study unveils the risks of some widely used dosing regimens and binds the observed serious adverse events with dosing. Based on simulations, safer alternative dosage regimens are proposed and recommendations regarding chloroquine dosing are made.Recent advances in nucleic acid based testing using bio-optical sensor approaches have been introduced but most are based on hybridization between the optical sensor and the bio-molecule and not on an amplification mechanism. Direct nucleic acid amplification on an optical sensor has several technical limitations, such as the sensitivity of the temperature sensor, instrument complexity, and high background signal. We here describe a novel nucleic acid amplification method based on a whispering gallery mode active resonator and discuss its potential molecular diagnostic application. By implanting nanoclusters as active compounds, this active resonator operates without tapered fiber coupling and emits a strong photoluminescence signal with low background in the wavelength of low absorption in an aqueous environment that is typical of biosensors. Our method also offers an extremely low detection threshold down to a single copy within 10 min due to the strong light-matter interaction in a nano-gap structure. We envision that this active resonator provides a high refractive index contrast for tight mode confinement with simple alignment as well as the possibility of reducing the device size so that a point-of-care system with low-cost, high-sensitivity and simplicity.Prediction of individual mobility is crucial in human mobility related applications. Whereas, existing research on individual mobility prediction mainly focuses on next location prediction and short-term dependencies between traveling locations. Long-term location sequence prediction is of great importance for long-time traffic planning and location advertising, and long-term dependencies exist as individual mobility regularity typically occurs daily and weekly. This paper proposes a novel hierarchical temporal attention-based LSTM encoder-decoder model for individual location sequence prediction. The proposed hierarchical attention mechanism captures both long-term and short-term dependencies underlying in individual longitudinal trajectories, and uncovers frequential and periodical mobility patterns in an interpretable manner by incorporating the calendar cycle of individual travel regularities into location prediction. More specifically, the hierarchical attention consists of local temporal attention to identify highly related locations in each day, and global temporal attention to discern important travel regularities over a week. Experiments on individual trajectory datasets with varying degree of traveling uncertainty demonstrate that our method outperforms four baseline methods on three evaluation metrics. In addition, we explore the interpretability of the proposed model in understanding individual daily, and weekly mobility patterns by visualizing the temporal attention weights and frequent traveling patterns associated with locations.The airway/lung mechanics is usually represented with nonlinear 0-D models based on a pneumatic-electrical analogy. The aim of this work is to provide a detailed description of the human respiratory mechanics in healthy and diseased conditions. The model used for this purpose employs some known constitutive functions of the main components of the respiratory system. We give a detailed mathematical description of these functions and subsequently derive additional key ones. We are interested not only in the main output such as airflow at the mouth or alveolar pressure and volume, but also in other quantities such as resistance and pressure drop across each element of the system and even recoil and compliance of the chest wall. Pathological conditions are simulated by altering the parameters of the constitutive functions. Results show that increased upper airway resistance induces airflow reduction with concomitant narrowing of volume and pressure ranges without affecting lung compliance. Instead, increased elastic recoil leads to low volumes and decreased lung compliance.
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  • The effectiveness of the proposed scheme is illustrated by an example.Classical drug design methodologies are hugely costly and time-consuming, with approximately 85% of the new proposed molecules failing in the first three phases of the FDA drug approval process. Thus, strategies to find alternative indications for already approved drugs that leverage computational methods are of crucial relevance. We previously demonstrated the efficacy of the Non-negative Matrix Tri-Factorization, a method that allows exploiting both data integration and machine learning, to infer novel indications for approved drugs. In this work, we present an innovative enhancement of the NMTF method that consists of a shortest-path evaluation of drug-protein pairs using the protein-to-protein interaction network. This approach allows inferring novel protein targets that were never considered as drug targets before, increasing the information fed to the NMTF method. Indeed, this novel advance enables the investigation of drug-centric predictions, simultaneously identifying therapeutic classes, protein targets and diseases associated with a particular drug. To test our methodology, we applied the NMTF and shortest-path enhancement methods to an outdated collection of data and compared the predictions against the most updated version, obtaining very good performance, with an Average Precision Score of 0.82. The data enhancement strategy allowed increasing the number of putative protein targets from 3,691 to 15,295, while the predictive performance of the method is slightly increased. Finally, we also validated our top-scored predictions according to the literature, finding relevant confirmation of predicted interactions between drugs and protein targets, as well as of predicted annotations between drugs and both therapeutic classes and diseases.A daily dietary assessment method named 24-hour dietary recall has commonly been used in nutritional epidemiology studies to capture detailed information of the food eaten by the participants to help understand their dietary behaviour. However, in this self-reporting technique, the food types and the portion size reported highly depends on users' subjective judgement which may lead to a biased and inaccurate dietary analysis result. As a result, a variety of visual-based dietary assessment approaches have been proposed recently. While these methods show promises in tackling issues in nutritional epidemiology studies, several challenges and forthcoming opportunities, as detailed in this study, still exist. This study provides an overview of computing algorithms, mathematical models and methodologies used in the field of image-based dietary assessment. It also provides a comprehensive comparison of the state of the art approaches in food recognition and volume/weight estimation in terms of their processing speed, model accuracy, efficiency and constraints. It will be followed by a discussion on deep learning method and its efficacy in dietary assessment. After a comprehensive exploration, we found that integrated dietary assessment systems combining with different approaches could be the potential solution to tackling the challenges in accurate dietary intake assessment.For a target task where the labeled data are unavailable, domain adaptation can transfer a learner from a different source domain. Previous deep domain adaptation methods mainly learn a global domain shift, i.e., align the global source and target distributions without considering the relationships between two subdomains within the same category of different domains, leading to unsatisfying transfer learning performance without capturing the fine-grained information. Recently, more and more researchers pay attention to subdomain adaptation that focuses on accurately aligning the distributions of the relevant subdomains. However, most of them are adversarial methods that contain several loss functions and converge slowly. Based on this, we present a deep subdomain adaptation network (DSAN) that learns a transfer network by aligning the relevant subdomain distributions of domain-specific layer activations across different domains based on a local maximum mean discrepancy (LMMD). Our DSAN is very simple but effective, which does not need adversarial training and converges fast. The adaptation can be achieved easily with most feedforward network models by extending them with LMMD loss, which can be trained efficiently via backpropagation. Experiments demonstrate that DSAN can achieve remarkable results on both object recognition tasks and digit classification tasks. Our code will be available at https//github.com/easezyc/deep-transfer-learning.Scene graph generation has received increasing attention in recent years. Enhancing the predicate representations is an important entry point to this task. There are various methods to fully investigate the context of representation enhancement. In this brief, we analyze the decisive factors that can significantly affect the relation detection results. Our analysis shows that spatial correlations between objects, focused regions of objects, and global hints related to the relations have strong influences in relation prediction and contradiction elimination. https://www.selleckchem.com/products/azd6738.html Based on our analysis, we propose a hierarchical context network (HCNet) to generate a scene graph. HCNet consists of three contexts, including interaction context, depression context, and global context, which integrates information from pair, object, and graph levels. The experiments show that our method outperforms the state-of-the-art methods on the Visual Genome (VG) data set.Parkinson's disease (PD) can gradually affect people's lives thus attracting tremendous attention. Early PD detection and treatment can help control the disease progress, relief from the symptoms and improve the patients' life quality. However, the current practice of PD diagnosis is conducted in a clinical setup and administrated by a PD specialist due to the early signs of PD are not noticeable in daily life. According to the report of CDC/NIH, the diagnosed time of PD ranges from 2-10 years after onset. Therefore, a more accessible PD diagnosis approach is urgently demanded. In recent years, mobile health (for short mHealth) technology has been intensively investigated for preventive medicine, particularly in chronic disease management. Notably, many types of research have explored the possibility of using mobile and wearable personal devices to detect the symptom of PD and shown promising results. It provides opportunities for transforming early PD detection from clinical to daily life. This survey paper attempts to conduct a comprehensive review of mHealth technologies for PD detection from 2000 to 2019, and compares their pros and cons in practical applications and provides insights to close the performance gap between state-of-the-art clinical approaches and mHealth technologies.
    The effectiveness of the proposed scheme is illustrated by an example.Classical drug design methodologies are hugely costly and time-consuming, with approximately 85% of the new proposed molecules failing in the first three phases of the FDA drug approval process. Thus, strategies to find alternative indications for already approved drugs that leverage computational methods are of crucial relevance. We previously demonstrated the efficacy of the Non-negative Matrix Tri-Factorization, a method that allows exploiting both data integration and machine learning, to infer novel indications for approved drugs. In this work, we present an innovative enhancement of the NMTF method that consists of a shortest-path evaluation of drug-protein pairs using the protein-to-protein interaction network. This approach allows inferring novel protein targets that were never considered as drug targets before, increasing the information fed to the NMTF method. Indeed, this novel advance enables the investigation of drug-centric predictions, simultaneously identifying therapeutic classes, protein targets and diseases associated with a particular drug. To test our methodology, we applied the NMTF and shortest-path enhancement methods to an outdated collection of data and compared the predictions against the most updated version, obtaining very good performance, with an Average Precision Score of 0.82. The data enhancement strategy allowed increasing the number of putative protein targets from 3,691 to 15,295, while the predictive performance of the method is slightly increased. Finally, we also validated our top-scored predictions according to the literature, finding relevant confirmation of predicted interactions between drugs and protein targets, as well as of predicted annotations between drugs and both therapeutic classes and diseases.A daily dietary assessment method named 24-hour dietary recall has commonly been used in nutritional epidemiology studies to capture detailed information of the food eaten by the participants to help understand their dietary behaviour. However, in this self-reporting technique, the food types and the portion size reported highly depends on users' subjective judgement which may lead to a biased and inaccurate dietary analysis result. As a result, a variety of visual-based dietary assessment approaches have been proposed recently. While these methods show promises in tackling issues in nutritional epidemiology studies, several challenges and forthcoming opportunities, as detailed in this study, still exist. This study provides an overview of computing algorithms, mathematical models and methodologies used in the field of image-based dietary assessment. It also provides a comprehensive comparison of the state of the art approaches in food recognition and volume/weight estimation in terms of their processing speed, model accuracy, efficiency and constraints. It will be followed by a discussion on deep learning method and its efficacy in dietary assessment. After a comprehensive exploration, we found that integrated dietary assessment systems combining with different approaches could be the potential solution to tackling the challenges in accurate dietary intake assessment.For a target task where the labeled data are unavailable, domain adaptation can transfer a learner from a different source domain. Previous deep domain adaptation methods mainly learn a global domain shift, i.e., align the global source and target distributions without considering the relationships between two subdomains within the same category of different domains, leading to unsatisfying transfer learning performance without capturing the fine-grained information. Recently, more and more researchers pay attention to subdomain adaptation that focuses on accurately aligning the distributions of the relevant subdomains. However, most of them are adversarial methods that contain several loss functions and converge slowly. Based on this, we present a deep subdomain adaptation network (DSAN) that learns a transfer network by aligning the relevant subdomain distributions of domain-specific layer activations across different domains based on a local maximum mean discrepancy (LMMD). Our DSAN is very simple but effective, which does not need adversarial training and converges fast. The adaptation can be achieved easily with most feedforward network models by extending them with LMMD loss, which can be trained efficiently via backpropagation. Experiments demonstrate that DSAN can achieve remarkable results on both object recognition tasks and digit classification tasks. Our code will be available at https//github.com/easezyc/deep-transfer-learning.Scene graph generation has received increasing attention in recent years. Enhancing the predicate representations is an important entry point to this task. There are various methods to fully investigate the context of representation enhancement. In this brief, we analyze the decisive factors that can significantly affect the relation detection results. Our analysis shows that spatial correlations between objects, focused regions of objects, and global hints related to the relations have strong influences in relation prediction and contradiction elimination. https://www.selleckchem.com/products/azd6738.html Based on our analysis, we propose a hierarchical context network (HCNet) to generate a scene graph. HCNet consists of three contexts, including interaction context, depression context, and global context, which integrates information from pair, object, and graph levels. The experiments show that our method outperforms the state-of-the-art methods on the Visual Genome (VG) data set.Parkinson's disease (PD) can gradually affect people's lives thus attracting tremendous attention. Early PD detection and treatment can help control the disease progress, relief from the symptoms and improve the patients' life quality. However, the current practice of PD diagnosis is conducted in a clinical setup and administrated by a PD specialist due to the early signs of PD are not noticeable in daily life. According to the report of CDC/NIH, the diagnosed time of PD ranges from 2-10 years after onset. Therefore, a more accessible PD diagnosis approach is urgently demanded. In recent years, mobile health (for short mHealth) technology has been intensively investigated for preventive medicine, particularly in chronic disease management. Notably, many types of research have explored the possibility of using mobile and wearable personal devices to detect the symptom of PD and shown promising results. It provides opportunities for transforming early PD detection from clinical to daily life. This survey paper attempts to conduct a comprehensive review of mHealth technologies for PD detection from 2000 to 2019, and compares their pros and cons in practical applications and provides insights to close the performance gap between state-of-the-art clinical approaches and mHealth technologies.
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  • Emphysematous osteomyelitis is a rare entity with potentially devastating consequences, even after prompt and aggressive intervention. It is characterized by intraosseous gas and may be complicated by adjacent abscess formation. There are a handful of previously reported cases of emphysematous osteomyelitis, but none to the degree as reported here. Specifically, we report an extremely rare case of extensive multifocal emphysematous osteomyelitis involving both the axial and appendicular skeleton in a 20-year-old woman.Adamantane polycyclic polyprenylated acylphloroglucinols (PPAPs) with caged architecture, a special class of hybrid natural products, is specifically rich in the plant family Guttiferae, especially Hypericum or Garcinia genus. Hypersampsone P is one of Adamantane PPAPs compounds extracted from Hypericum subsessile. Here we have chosen, screened ten PPAPs and identified one of them showed an activity in inhibiting of adipocytes differentiation. Particularly, the compound, hypersampsone P, blunted the adipocyte differentiation dose-dependently. Moreover, hypersampsone P down-regulated the expressions of several key regulators for adipogenesis, including PPARγ and FABP4. The treatment of cells at the early stage of adipogenesis by hypersampsone P induced the greatest blunting of adipocyte differentiation and the effect might be involved in the LKB1-AMPK signaling pathway.The diffusion of SARS-CoV-2 forced the Italian population to restrictive measures that modified the patients' response to non-SARS-CoV-2 medical conditions. https://www.selleckchem.com/products/jq1.html We evaluated all ACS-patients admitted in three high-volume hospitals during the first month of SARS-CoV-2 Italian-outbreak and compared them to ACS-patients admitted during the same period 1-year before. Hospitalization for ACS decreased from 162 patients in 2019 vs 202084 patients in 2020. In 2020 both door-to-balloon and symptoms-to-PCI were longer and admission levels of hs-cTnI were higher. They had a lower discharged residual LV-function and an increased predicted late cardiovascular mortality based on their GRACE score.Systematic reviews are secondary investigations that compile published results that have been obtained from studies involving human subjects. Meta-analysis is the term used to describe the carrying out of statistical analysis of the combination of the results of two or more original studies, which had to be selected from a systematic review. In this way, a meta-analysis cannot exist without a systematic review. Systematic reviews arise due to the exponential increase in the information; to provide all health personnel with a study that critically analyzes the results and discriminates those that may be useful in clinical practice. Systematic reviews are one of the fundamental tools in evidence-based medicine, in which two of the main steps refer to both the search and the critical analysis of the studies, which shall support medical decisions on aspects that are mainly related to diagnosis, treatment, or prognosis. On the other hand, systematic reviews have been essential for some time now when developing evidence-based clinical practice guidelines and they can be used to make decisions on health policies. The methodology for performing and interpreting systematic reviews and meta-analysis is described in this article.This study measured both nutrient and pesticide concentrations at up to 13 different freshwater stream sites in New Brunswick, Nova Scotia and Prince Edward Island between 2013 and 2018. Up to 62 different pesticides were analysed in 248 discreet samples. A large majority of pesticides were below the detection limit of the laboratory while seven pesticides had at least 20% or more detections throughout the years of this study. The four pesticides that had the highest frequency of detection were the insecticides chlorantraniliprole, clothianidin, imidacloprid, and thiamethoxam of which the last three are categorised as neonicotinoid insecticides.Considering the involvement of GABAergic system in the action of the fast-acting antidepressant ketamine, and that agmatine may exert an antidepressant-like effect through mechanisms similar to ketamine, the purpose of the present study was to evaluate the involvement of GABAA and GABAB receptors in the antidepressant-like effect of agmatine. The administration of muscimol (0.1 mg/kg, i.p., GABAA receptor agonist) or diazepam (0.05 mg/kg, p.o., GABAA receptor positive allosteric modulator) at doses that caused no effect in the tail suspension test (TST) combined with a subeffective dose of agmatine (0.0001 mg/kg, p.o.) produced a synergistic antidepressant-like effect in the TST. In another set of experiments, the administration of baclofen (1 mg/kg, i.p., GABAB receptor agonist) abolished the reduction of immobility time in the TST elicited by agmatine (0.1 mg/kg, p.o., active dose). In another cohort of animals, treatment with NMDA (0.1 pmol/site, i.c.v.) prevented the antidepressant-like effect of the combined administration of agmatine and muscimol as well as ketamine and muscimol in the TST. Results suggest that the effect of agmatine in the TST may involve an activation of GABAA receptors dependent on NMDA receptor inhibition, similar to ketamine, as well as modulation of GABAB receptors.Purpose This study sought to investigate the electromyographic activity of the vastus lateralis (VL) muscle during concentric-eccentric exercise using a new concept leg press machine enabling a preset overloading in the eccentric phase. Methods Ten young males familiar with resistive exercise were recruited for this study. Tests were performed on a Leg-press Biostrength® (Technogym S.p.A., Italy). The load was set to 70% and 80% of one-repetition maximum (1-RM). The participants performed 2 sets of 6 repetitions at each relative load with (ECC +) and without (ISOW) an eccentric overload equivalent to 150% of the concentric load. A metronome was employed to maintain the selected cadence. Sets were separated by a 5-min rest. Surface electromyography (EMG) of VL was recorded and integrated (iEMG). Results Results showed a higher iEMG in ECC + with respect to ISOW at both intensities (+ 29% for 70% 1-RM, p less then 0.01 and + 31% for 80% 1-RM, p less then 0.001). No statistically significant differences were detected between concentric and eccentric phase in both ECC + conditions.
    Emphysematous osteomyelitis is a rare entity with potentially devastating consequences, even after prompt and aggressive intervention. It is characterized by intraosseous gas and may be complicated by adjacent abscess formation. There are a handful of previously reported cases of emphysematous osteomyelitis, but none to the degree as reported here. Specifically, we report an extremely rare case of extensive multifocal emphysematous osteomyelitis involving both the axial and appendicular skeleton in a 20-year-old woman.Adamantane polycyclic polyprenylated acylphloroglucinols (PPAPs) with caged architecture, a special class of hybrid natural products, is specifically rich in the plant family Guttiferae, especially Hypericum or Garcinia genus. Hypersampsone P is one of Adamantane PPAPs compounds extracted from Hypericum subsessile. Here we have chosen, screened ten PPAPs and identified one of them showed an activity in inhibiting of adipocytes differentiation. Particularly, the compound, hypersampsone P, blunted the adipocyte differentiation dose-dependently. Moreover, hypersampsone P down-regulated the expressions of several key regulators for adipogenesis, including PPARγ and FABP4. The treatment of cells at the early stage of adipogenesis by hypersampsone P induced the greatest blunting of adipocyte differentiation and the effect might be involved in the LKB1-AMPK signaling pathway.The diffusion of SARS-CoV-2 forced the Italian population to restrictive measures that modified the patients' response to non-SARS-CoV-2 medical conditions. https://www.selleckchem.com/products/jq1.html We evaluated all ACS-patients admitted in three high-volume hospitals during the first month of SARS-CoV-2 Italian-outbreak and compared them to ACS-patients admitted during the same period 1-year before. Hospitalization for ACS decreased from 162 patients in 2019 vs 202084 patients in 2020. In 2020 both door-to-balloon and symptoms-to-PCI were longer and admission levels of hs-cTnI were higher. They had a lower discharged residual LV-function and an increased predicted late cardiovascular mortality based on their GRACE score.Systematic reviews are secondary investigations that compile published results that have been obtained from studies involving human subjects. Meta-analysis is the term used to describe the carrying out of statistical analysis of the combination of the results of two or more original studies, which had to be selected from a systematic review. In this way, a meta-analysis cannot exist without a systematic review. Systematic reviews arise due to the exponential increase in the information; to provide all health personnel with a study that critically analyzes the results and discriminates those that may be useful in clinical practice. Systematic reviews are one of the fundamental tools in evidence-based medicine, in which two of the main steps refer to both the search and the critical analysis of the studies, which shall support medical decisions on aspects that are mainly related to diagnosis, treatment, or prognosis. On the other hand, systematic reviews have been essential for some time now when developing evidence-based clinical practice guidelines and they can be used to make decisions on health policies. The methodology for performing and interpreting systematic reviews and meta-analysis is described in this article.This study measured both nutrient and pesticide concentrations at up to 13 different freshwater stream sites in New Brunswick, Nova Scotia and Prince Edward Island between 2013 and 2018. Up to 62 different pesticides were analysed in 248 discreet samples. A large majority of pesticides were below the detection limit of the laboratory while seven pesticides had at least 20% or more detections throughout the years of this study. The four pesticides that had the highest frequency of detection were the insecticides chlorantraniliprole, clothianidin, imidacloprid, and thiamethoxam of which the last three are categorised as neonicotinoid insecticides.Considering the involvement of GABAergic system in the action of the fast-acting antidepressant ketamine, and that agmatine may exert an antidepressant-like effect through mechanisms similar to ketamine, the purpose of the present study was to evaluate the involvement of GABAA and GABAB receptors in the antidepressant-like effect of agmatine. The administration of muscimol (0.1 mg/kg, i.p., GABAA receptor agonist) or diazepam (0.05 mg/kg, p.o., GABAA receptor positive allosteric modulator) at doses that caused no effect in the tail suspension test (TST) combined with a subeffective dose of agmatine (0.0001 mg/kg, p.o.) produced a synergistic antidepressant-like effect in the TST. In another set of experiments, the administration of baclofen (1 mg/kg, i.p., GABAB receptor agonist) abolished the reduction of immobility time in the TST elicited by agmatine (0.1 mg/kg, p.o., active dose). In another cohort of animals, treatment with NMDA (0.1 pmol/site, i.c.v.) prevented the antidepressant-like effect of the combined administration of agmatine and muscimol as well as ketamine and muscimol in the TST. Results suggest that the effect of agmatine in the TST may involve an activation of GABAA receptors dependent on NMDA receptor inhibition, similar to ketamine, as well as modulation of GABAB receptors.Purpose This study sought to investigate the electromyographic activity of the vastus lateralis (VL) muscle during concentric-eccentric exercise using a new concept leg press machine enabling a preset overloading in the eccentric phase. Methods Ten young males familiar with resistive exercise were recruited for this study. Tests were performed on a Leg-press Biostrength® (Technogym S.p.A., Italy). The load was set to 70% and 80% of one-repetition maximum (1-RM). The participants performed 2 sets of 6 repetitions at each relative load with (ECC +) and without (ISOW) an eccentric overload equivalent to 150% of the concentric load. A metronome was employed to maintain the selected cadence. Sets were separated by a 5-min rest. Surface electromyography (EMG) of VL was recorded and integrated (iEMG). Results Results showed a higher iEMG in ECC + with respect to ISOW at both intensities (+ 29% for 70% 1-RM, p less then 0.01 and + 31% for 80% 1-RM, p less then 0.001). No statistically significant differences were detected between concentric and eccentric phase in both ECC + conditions.
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  • BACKGROUND Tuberculin skin test (TST), which is used in the diagnosis of latent tuberculosis infection may cause Koebner's phenomenon and false positive results in psoriasis patients. OBJECTIVE The purpose of this study is to compare TST with QuantiFERON-TB Gold Plus (QFT-plus) test in psoriasis patients, and to determine the effects of psoriasis on TST results. METHODS Ninety-two psoriasis patients and 30 control subjects were included in the study. QFT-plus test, TST and ***** test to distinguish the increase of induration because of the skin trauma were performed on both groups. The demographics, risk factors for latent tuberculosis infection, BCG vaccination history, Koebner's history, psoriasis severity and treatment history of the patients were recorded. The effects of these variables on test results were investigated by comparing those with control group. The criteria of National Tuberculosis Diagnosis and Treatment Guideline were used in the evaluation of test results, and threshold value of positivitild and moderate-severe clinical manifestation, respectively (p=0.04). However, no effect of disease period and treatment was determined on both test results. CONCLUSION TST positivity was higher in psoriasis patients compared to control group. It was considered due to the increased reaction of the skin to mycobacterial antigens rather than the Koebner's response. While TST results were not affected by BCG, it was concluded that a 10 mm threshold value of positivity was a suitable approach in order to reduce the number of patients receiving unnecessary preventive treatment in patients who are considered to initiate biologic agents. Furthermore, it was also concluded that QFT-plus test may be preferred in psoriasis patients since it is applied in vitro, its specificity is higher and not affected by disease severity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.As of April 20, 2020, over time, the COVID-19 pandemic has resulted in 157 970 deaths out of 2 319 066 confirmed cases, at a Case Fatality Rate of ~6.8%. With the pandemic rapidly spreading, and health delivery systems being overwhelmed, it is imperative that safe and effective pharmacotherapeutic strategies are rapidly explored to improve survival. In this paper, we use established and emerging evidence to propose a testable hypothesis that, a vicious positive feedback loop of des-Arg(9)-bradykinin- and bradykinin-mediated inflammation → injury → inflammation, likely precipitates life threatening respiratory complications in COVID-19. Through our hypothesis, we make the prediction that the FDA-approved molecule, icatibant, might be able to interrupt this feedback loop and, thereby, improve the clinical outcomes. This hypothesis could lead to basic, translational, and clinical studies aimed at reducing COVID-19 morbidity and mortality. © 2020 Federation of American Societies for Experimental Biology.Obesity is a risk factor for breast cancer in postmenopausal and high-risk premenopausal women. Changes within the obese breast microenvironment may increase breast cancer risk. Transforming growth factor beta-1 (TGFβ1) is a major regulator of mammary epithelial stem/progenitor cells, and its activity is dysregulated under conditions of obesity. Using a high-fat diet model of obesity in **** and breast tissue from women, we observed that TGFβ1 activity is reduced in breast epithelial cells in obesity. Breast ducts and lobules demonstrated increased decorin in the extracellular matrix (ECM) surrounding epithelial cells, and we observed that decorin and latent TGFβ1 complexed together. Under conditions of obesity, macrophages expressed higher levels of decorin and were significantly increased in number surrounding breast epithelial cells. To investigate the relationship between macrophages and decorin expression, we treated obese **** with either IgG control or anti-F4/80 antibodies to deplete macrophages. **** treated with anti-F4/80 antibodies demonstrated reduced decorin surrounding mammary ducts and enhanced TGFβ1 activity within mammary epithelial cells. Given the role of TGFβ1 as a tumor suppressor, reduced epithelial TGFβ1 activity and enhanced TGFβ1 within the ECM of obese mammary tissue may enhance breast cancer risk. © 2020 Federation of American Societies for Experimental Biology.NEW FINDINGS What is the central question of this study? What does control the proliferation and apoptosis in the pathogenesis of psoriasis? What is the main finding and its importance? The pathogenesis of psoriasis is abnormal homeostasis of keratinocytes with hyperproliferation and decreasing apoptosis. We found that inhibitor of apoptosis protein (IAP) family molecule, Livin, is highly expressed in psoriasis vulgaris lesional skin tissue. Here we report that the expression of Livin was upregulated after being stimulated with Oncostatin M (OSM) at both the transcription and protein level. https://www.selleckchem.com/products/pf-543.html OSM promoted the survival of HaCaT cells in oxidative stress conditions. The expression of Livin and proliferation of HaCaT cells by OSM was regulated through ERK and STAT3 signaling pathways. This study may provide new insights into targeted therapy for psoriasis. ABSTRACT Background Psoriasis is an immune-mediated chronic inflammatory disease. Abnormal homeostasis of keratinocytes with hyperproliferation and decreasing aic inhibitors of ERK (U0126) and STAT3 (Cryptotaushinone) were applied to investigate the signaling pathways involving the regulation of Livin expression by OSM. RESULTS The expression of Livin was upregulated after being stimulated with OSM. OSM promoted the proliferation and survival of HaCaT cells. The expression of Livin and proliferation of HaCaT cells by OSM were regulated through ERK and STAT3 signaling pathways. CONCLUSION The expression of Livin in HaCaT cells is regulated by OSM, ERK, and STAT3 signaling pathways. OSM promotes HaCaT cell proliferation and survival in oxidative stress conditions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    BACKGROUND Tuberculin skin test (TST), which is used in the diagnosis of latent tuberculosis infection may cause Koebner's phenomenon and false positive results in psoriasis patients. OBJECTIVE The purpose of this study is to compare TST with QuantiFERON-TB Gold Plus (QFT-plus) test in psoriasis patients, and to determine the effects of psoriasis on TST results. METHODS Ninety-two psoriasis patients and 30 control subjects were included in the study. QFT-plus test, TST and prick test to distinguish the increase of induration because of the skin trauma were performed on both groups. The demographics, risk factors for latent tuberculosis infection, BCG vaccination history, Koebner's history, psoriasis severity and treatment history of the patients were recorded. The effects of these variables on test results were investigated by comparing those with control group. The criteria of National Tuberculosis Diagnosis and Treatment Guideline were used in the evaluation of test results, and threshold value of positivitild and moderate-severe clinical manifestation, respectively (p=0.04). However, no effect of disease period and treatment was determined on both test results. CONCLUSION TST positivity was higher in psoriasis patients compared to control group. It was considered due to the increased reaction of the skin to mycobacterial antigens rather than the Koebner's response. While TST results were not affected by BCG, it was concluded that a 10 mm threshold value of positivity was a suitable approach in order to reduce the number of patients receiving unnecessary preventive treatment in patients who are considered to initiate biologic agents. Furthermore, it was also concluded that QFT-plus test may be preferred in psoriasis patients since it is applied in vitro, its specificity is higher and not affected by disease severity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.As of April 20, 2020, over time, the COVID-19 pandemic has resulted in 157 970 deaths out of 2 319 066 confirmed cases, at a Case Fatality Rate of ~6.8%. With the pandemic rapidly spreading, and health delivery systems being overwhelmed, it is imperative that safe and effective pharmacotherapeutic strategies are rapidly explored to improve survival. In this paper, we use established and emerging evidence to propose a testable hypothesis that, a vicious positive feedback loop of des-Arg(9)-bradykinin- and bradykinin-mediated inflammation → injury → inflammation, likely precipitates life threatening respiratory complications in COVID-19. Through our hypothesis, we make the prediction that the FDA-approved molecule, icatibant, might be able to interrupt this feedback loop and, thereby, improve the clinical outcomes. This hypothesis could lead to basic, translational, and clinical studies aimed at reducing COVID-19 morbidity and mortality. © 2020 Federation of American Societies for Experimental Biology.Obesity is a risk factor for breast cancer in postmenopausal and high-risk premenopausal women. Changes within the obese breast microenvironment may increase breast cancer risk. Transforming growth factor beta-1 (TGFβ1) is a major regulator of mammary epithelial stem/progenitor cells, and its activity is dysregulated under conditions of obesity. Using a high-fat diet model of obesity in mice and breast tissue from women, we observed that TGFβ1 activity is reduced in breast epithelial cells in obesity. Breast ducts and lobules demonstrated increased decorin in the extracellular matrix (ECM) surrounding epithelial cells, and we observed that decorin and latent TGFβ1 complexed together. Under conditions of obesity, macrophages expressed higher levels of decorin and were significantly increased in number surrounding breast epithelial cells. To investigate the relationship between macrophages and decorin expression, we treated obese mice with either IgG control or anti-F4/80 antibodies to deplete macrophages. Mice treated with anti-F4/80 antibodies demonstrated reduced decorin surrounding mammary ducts and enhanced TGFβ1 activity within mammary epithelial cells. Given the role of TGFβ1 as a tumor suppressor, reduced epithelial TGFβ1 activity and enhanced TGFβ1 within the ECM of obese mammary tissue may enhance breast cancer risk. © 2020 Federation of American Societies for Experimental Biology.NEW FINDINGS What is the central question of this study? What does control the proliferation and apoptosis in the pathogenesis of psoriasis? What is the main finding and its importance? The pathogenesis of psoriasis is abnormal homeostasis of keratinocytes with hyperproliferation and decreasing apoptosis. We found that inhibitor of apoptosis protein (IAP) family molecule, Livin, is highly expressed in psoriasis vulgaris lesional skin tissue. Here we report that the expression of Livin was upregulated after being stimulated with Oncostatin M (OSM) at both the transcription and protein level. https://www.selleckchem.com/products/pf-543.html OSM promoted the survival of HaCaT cells in oxidative stress conditions. The expression of Livin and proliferation of HaCaT cells by OSM was regulated through ERK and STAT3 signaling pathways. This study may provide new insights into targeted therapy for psoriasis. ABSTRACT Background Psoriasis is an immune-mediated chronic inflammatory disease. Abnormal homeostasis of keratinocytes with hyperproliferation and decreasing aic inhibitors of ERK (U0126) and STAT3 (Cryptotaushinone) were applied to investigate the signaling pathways involving the regulation of Livin expression by OSM. RESULTS The expression of Livin was upregulated after being stimulated with OSM. OSM promoted the proliferation and survival of HaCaT cells. The expression of Livin and proliferation of HaCaT cells by OSM were regulated through ERK and STAT3 signaling pathways. CONCLUSION The expression of Livin in HaCaT cells is regulated by OSM, ERK, and STAT3 signaling pathways. OSM promotes HaCaT cell proliferation and survival in oxidative stress conditions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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