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  • ts with psychometric tests conducted by parents and teachers as well as differences in the levels of inflammatory cytokines were ambiguous. Based on these results, we propose some study modifications a longer observation period (6-12 months); inclusion of more children's self-report assessments; recruitment of non-drug naive patients and the possible omission of serum cytokines measurements. Clinical Trial Registration Medical Ethics Committee (UKC-MB-KME-19-06/16). Copyright © 2020 Kumperscak, Gricar, Ülen and Micetic-Turk.Background A deficit in empathy has repeatedly been described in individuals with conduct disorder (CD), and in particular in those with callous unemotional traits. Until now, little is known about the neural basis of empathy in children and adolescents with early onset conduct disorder. The aim of this study was to examine neural responses during empathizing in children and adolescents with CD with a task that allowed to differentiate between the judgment of the emotional states of other people and the own emotional response to other people's emotional state. Moreover, we investigated associations of callous-unemotional traits and neural activations during empathizing. Methods Using functional magnetic resonance imaging (fMRI) we investigated 14 boys with early onset CD and 15 typically developing (TDC) age matched controls between 8 and 16 years of age. Happy and sad faces were presented, and participants were asked to either infer the emotional state from the face (other-task) or to judge their own emotionst a pivotal influence of impaired amygdala processing in early-onset CD, in particular for deficits in empathic behavior and related callous-unemotional-traits. Elevated response in the medial prefrontal cortex in boys with CD point toward increased involvement of brain areas related to self-referential processing and cognitive empathy during empathizing. Copyright © 2020 von Polier, Greimel, Konrad, Großheinrich, Kohls, Vloet, Herpertz-Dahlmann and Schulte-Rüther.Introduction Post-Traumatic Stress Disorder (PTSD) is often associated with impairments in emotional and cognitive domains. Contrarily to the emotional sphere, neural basis underpinnings to cognitive impairments are still not well known. Methods We performed a bibliographic search on PUBMED of all the studies investigating the cognitive impairments in PTSD individuals. We considered only studies that applied cognitive tasks using a functional Magnetic Resonance Imaging technique. The inclusion criteria were met by nine studies. Results Overall, PTSD individuals reported significant impairments in the dorsolateral prefrontal cortex, anterior cingulate cortex, inferior frontal gyrus, insula, inferior temporal cortex, supplement motor area, and Default Mode Network (DMN). Moreover, abnormal activity was reported in subcortical structures (e.g. hippocampus, amygdala, thalamus) and in the cerebellum. Limitations Cognitive functioning was assessed using different cognitive tasks. Potential confounding factors such as age, sex, symptoms intensity, and comorbidities might have influenced the results. Conclusion So far, the evidence reported that PTSD is characterized by cognitive impairments in several domains, such as attention, memory and autonomic arousal, which may be due to selective dysfunctions in brain regions that are part of cortical networks, the limbic system and DMN. However, further studies are needed in order to better assess the role of cognitive impairments in PTSD and to develop more targeted therapeutic approaches. Copyright © 2020 Dossi, Delvecchio, Prunas, Soares and Brambilla.Cerebellum plays a role in the regulation of cognitive processes. Cerebellar alterations could explain cognitive impairments in schizophrenia. We describe the case of a 50 years old patient with schizophrenia whom underwent cerebellar transcranial direct current stimulation (tDCS). In order to study the effect of cerebellar stimulation on cognitive functions, the patient underwent a neuropsychological assessment and an eyeblink conditioning (EBC) protocol. Although the effect of brain stimulation cannot be only assessed in a single-case study, our results suggest that cerebellar stimulation may have an effect on a broad range of cognitive functions typically impaired in patients with schizophrenia, including verbal episodic, short term, and working memory. In addition to neuropsychological tests, we evaluated the cerebellar function by performing EBC before and after tDCS. Our data suggest that tDCS can improve EBC. Further clinical trials are required for better understanding of how cerebellar stimulation can modulate cognitive processes in patients with schizophrenia and healthy controls. Copyright © 2020 Laidi, Levenes, Suarez-Perez, Février, Durand, Bouaziz and Januel.Functional dyspepsia (FD) and gastroparesis (GP) are common disorders of the upper gastrointestinal tract. The pathophysiology of these conditions is likely to be heterogenous, and factors such as altered motility, sensitivity and response to nutrition have been identified as putative underlying mechanisms. Motility, sensitivity as well as responses to nutrition can be influenced or mediated by peptide hormones and serotonin released from the gastrointestinal mucosa. This review summarizes the role of GI peptides in functional dyspepsia and gastroparesis. In most studies, the levels of somatostatin, ghrelin, and motilin did not differ between healthy volunteers and FD or GP patients, but higher symptom burden was often correlated with higher peptide levels. https://www.selleckchem.com/products/ml351.html Ghrelin and motilin receptor agonists showed promising results in improvement of the gastric emptying, but the link with improvement of symptoms is less predictable. Serotonin agonists have a potential to improve symptoms in both FD and idiopathic gastroparesis. Drugs acting on the GLP-1 and on the PYY receptors deserve further investigation. There is a need for systematic large scale studies. Copyright © 2020 Van den Houte, Scarpellini, Verbeure, Mori, Schol, Masuy, Carbone and Tack.Objectives Individuals suffering from major depressive disorder (MDD) often report workplace-related stress as the major cause of their disorder. Accordingly, workplace-related stress was established as a fifth psychosocial problem area of Interpersonal Psychotherapy (workplace-related Interpersonal Psychotherapy, W-IPT). The aim of the study was to investigate the influence of W-IPT on depressive symptoms and on workplace-related issues in individuals with MDD compared to a treatment-as-usual (TAU) condition. Methods A total of 27 individuals with MDD (mean age = 43 years, 48% males) were randomly assigned either to eight weekly group sessions of W-IPT or to the TAU condition. At baseline, 8 weeks later at the end of the intervention, and 20 weeks later at follow-up, the Hamilton Rating Scale for Depression was conducted. In addition, the participants completed the **** Depression Inventory, the Work Ability Index (WAI), the Return to Work Attitude (RTW-SE), and the Insomnia Severity Index (ISI). Results Symptoms of depression in experts' ratings as well as in self-rated ratings decreased over time, but more so in the W-IPT condition compared to the TAU condition [experts rating large effect size (d = 1.
    ts with psychometric tests conducted by parents and teachers as well as differences in the levels of inflammatory cytokines were ambiguous. Based on these results, we propose some study modifications a longer observation period (6-12 months); inclusion of more children's self-report assessments; recruitment of non-drug naive patients and the possible omission of serum cytokines measurements. Clinical Trial Registration Medical Ethics Committee (UKC-MB-KME-19-06/16). Copyright © 2020 Kumperscak, Gricar, Ülen and Micetic-Turk.Background A deficit in empathy has repeatedly been described in individuals with conduct disorder (CD), and in particular in those with callous unemotional traits. Until now, little is known about the neural basis of empathy in children and adolescents with early onset conduct disorder. The aim of this study was to examine neural responses during empathizing in children and adolescents with CD with a task that allowed to differentiate between the judgment of the emotional states of other people and the own emotional response to other people's emotional state. Moreover, we investigated associations of callous-unemotional traits and neural activations during empathizing. Methods Using functional magnetic resonance imaging (fMRI) we investigated 14 boys with early onset CD and 15 typically developing (TDC) age matched controls between 8 and 16 years of age. Happy and sad faces were presented, and participants were asked to either infer the emotional state from the face (other-task) or to judge their own emotionst a pivotal influence of impaired amygdala processing in early-onset CD, in particular for deficits in empathic behavior and related callous-unemotional-traits. Elevated response in the medial prefrontal cortex in boys with CD point toward increased involvement of brain areas related to self-referential processing and cognitive empathy during empathizing. Copyright © 2020 von Polier, Greimel, Konrad, Großheinrich, Kohls, Vloet, Herpertz-Dahlmann and Schulte-Rüther.Introduction Post-Traumatic Stress Disorder (PTSD) is often associated with impairments in emotional and cognitive domains. Contrarily to the emotional sphere, neural basis underpinnings to cognitive impairments are still not well known. Methods We performed a bibliographic search on PUBMED of all the studies investigating the cognitive impairments in PTSD individuals. We considered only studies that applied cognitive tasks using a functional Magnetic Resonance Imaging technique. The inclusion criteria were met by nine studies. Results Overall, PTSD individuals reported significant impairments in the dorsolateral prefrontal cortex, anterior cingulate cortex, inferior frontal gyrus, insula, inferior temporal cortex, supplement motor area, and Default Mode Network (DMN). Moreover, abnormal activity was reported in subcortical structures (e.g. hippocampus, amygdala, thalamus) and in the cerebellum. Limitations Cognitive functioning was assessed using different cognitive tasks. Potential confounding factors such as age, sex, symptoms intensity, and comorbidities might have influenced the results. Conclusion So far, the evidence reported that PTSD is characterized by cognitive impairments in several domains, such as attention, memory and autonomic arousal, which may be due to selective dysfunctions in brain regions that are part of cortical networks, the limbic system and DMN. However, further studies are needed in order to better assess the role of cognitive impairments in PTSD and to develop more targeted therapeutic approaches. Copyright © 2020 Dossi, Delvecchio, Prunas, Soares and Brambilla.Cerebellum plays a role in the regulation of cognitive processes. Cerebellar alterations could explain cognitive impairments in schizophrenia. We describe the case of a 50 years old patient with schizophrenia whom underwent cerebellar transcranial direct current stimulation (tDCS). In order to study the effect of cerebellar stimulation on cognitive functions, the patient underwent a neuropsychological assessment and an eyeblink conditioning (EBC) protocol. Although the effect of brain stimulation cannot be only assessed in a single-case study, our results suggest that cerebellar stimulation may have an effect on a broad range of cognitive functions typically impaired in patients with schizophrenia, including verbal episodic, short term, and working memory. In addition to neuropsychological tests, we evaluated the cerebellar function by performing EBC before and after tDCS. Our data suggest that tDCS can improve EBC. Further clinical trials are required for better understanding of how cerebellar stimulation can modulate cognitive processes in patients with schizophrenia and healthy controls. Copyright © 2020 Laidi, Levenes, Suarez-Perez, Février, Durand, Bouaziz and Januel.Functional dyspepsia (FD) and gastroparesis (GP) are common disorders of the upper gastrointestinal tract. The pathophysiology of these conditions is likely to be heterogenous, and factors such as altered motility, sensitivity and response to nutrition have been identified as putative underlying mechanisms. Motility, sensitivity as well as responses to nutrition can be influenced or mediated by peptide hormones and serotonin released from the gastrointestinal mucosa. This review summarizes the role of GI peptides in functional dyspepsia and gastroparesis. In most studies, the levels of somatostatin, ghrelin, and motilin did not differ between healthy volunteers and FD or GP patients, but higher symptom burden was often correlated with higher peptide levels. https://www.selleckchem.com/products/ml351.html Ghrelin and motilin receptor agonists showed promising results in improvement of the gastric emptying, but the link with improvement of symptoms is less predictable. Serotonin agonists have a potential to improve symptoms in both FD and idiopathic gastroparesis. Drugs acting on the GLP-1 and on the PYY receptors deserve further investigation. There is a need for systematic large scale studies. Copyright © 2020 Van den Houte, Scarpellini, Verbeure, Mori, Schol, Masuy, Carbone and Tack.Objectives Individuals suffering from major depressive disorder (MDD) often report workplace-related stress as the major cause of their disorder. Accordingly, workplace-related stress was established as a fifth psychosocial problem area of Interpersonal Psychotherapy (workplace-related Interpersonal Psychotherapy, W-IPT). The aim of the study was to investigate the influence of W-IPT on depressive symptoms and on workplace-related issues in individuals with MDD compared to a treatment-as-usual (TAU) condition. Methods A total of 27 individuals with MDD (mean age = 43 years, 48% males) were randomly assigned either to eight weekly group sessions of W-IPT or to the TAU condition. At baseline, 8 weeks later at the end of the intervention, and 20 weeks later at follow-up, the Hamilton Rating Scale for Depression was conducted. In addition, the participants completed the Beck Depression Inventory, the Work Ability Index (WAI), the Return to Work Attitude (RTW-SE), and the Insomnia Severity Index (ISI). Results Symptoms of depression in experts' ratings as well as in self-rated ratings decreased over time, but more so in the W-IPT condition compared to the TAU condition [experts rating large effect size (d = 1.
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  • The decrease of viroid levels during pollen development correlated with mRNA accumulation of several RNA-degrading factors, such as AGO5 nuclease, DICER-like and TUDOR S-like nuclease. In addition, the functional status of pollen, as a tissue with high ribosome content, could play a role during suppression of AFCVd replication involving transcription factors IIIA and ribosomal protein L5.Fusarium head blight (FHB) is one of the most important diseases of wheat, causing yield losses and mycotoxin contamination of harvested grain. A complex of different toxigenic Fusarium species is responsible for FHB and the composition and predominance of species within the FHB complex are determined by meteorological and agronomic factors. In this study, grain of three different susceptible winter wheat cultivars from seven locations in northern Germany were analysed within a five-year survey from 2013 to 2017 by quantifying DNA amounts of different species within the Fusarium community as well as deoxynivalenol (DON) and zearalenone (ZEA) concentrations. Several Fusarium species co-occur in wheat grain samples in all years and cultivars. F. graminearum was the most prevalent species, followed by F. culmorum, F. avenaceum and F. poae, while F. tricinctum and F. langsethiae played only a subordinate role in the FHB complex in terms of DNA amounts. In all cultivars, a comparable year-specific quantitative occng (early and late milk stage).Today, consumers are increasingly demanding safety alternatives concerning the use of synthetic additives in the food industry, as well as healthy food. As a result, a major number of plant-derived preservatives have been tested in the food industry. These natural ingredients have antioxidant properties and have shown to increase the bioactive molecules levels and the microbiological stability of the food items. The effect of the plant-based preservatives on the sensorial properties of the new products has also to be considered, because natural preservatives could result in sensorial characteristics that may not be accepted by the consumers. Cheese is a dairy product widely appreciated all over the world, but it is also susceptible to contamination by pathogenic and spoilage microorganisms; therefore, the use of preservatives in cheese making represents an important step. This review deals with one of the innovation in the cheese sector, which is the addition of natural preservatives. Several aspects are discussed, such as the effect of natural ingredients on the microbial stability of cheese, and their influence on the chemical, nutritional and sensorial characteristics of the cheeses. Although the promising results, further studies are needed to confirm the use of natural preservatives from plants in cheese making.Growing urbanization leads to an increased risk of parasite spread in densely inhabited areas. Free-ranging cats can be locally numerous and come into frequent contact with both wildlife and humans. Cats are thus expected to contribute to parasitic disease transmission. In our study, we investigated the prevalence of endoparasites in free ranging cats in urban areas of Kraków city, based on necropsy of road-killed cats in relation to sex and diet of cat, season and habitat type. We found that 62% of 81 cats were infected with endoparasites with Toxocara cati being the most prevalent. In total, we identified seven parasite species. The number of parasite species was higher in suburban habitats and aside from Eucoleus aerophilus the prevalence of all parasites was higher in cats from suburban areas than in the individuals living in the city urban core. The prey of examined cats included mostly rodents, followed by soricomorphs and birds, which can all serve as paratenic hosts. Based on our results, we suggest that cats in urban areas should be considered as a serious potential zoonotic threat. Implementation of proper veterinary control and wider education on the topic is recommended.The aim of this study is to observe the influence of Medication-Related Osteonecrosis of the Jaw (MRONJ) on the physical and mental conditions of cancer patients using a Quality of Life (QoL) questionnaire during regular dental practice measures. Twenty cancer patients (8 males and 12 females) with established MRONJ were enrolled in the "MoMax" (Oral Medicine and Maxillofacial) project of the Department of Oral Sciences and Maxillofacial Surgery at "Sapienza" University of Rome, and were included in the study. The 12-item Short Form Survey was used to evaluate the QoL. Statistical analysis revealed a significant difference for Mental Component Summary (MCS) scores based on age (p = 0.018). The regression analysis revealed that the Physical Component Summary (PCS) scores were negatively influenced by the anti-resorptive medication duration (p = 0.031 and β = -1.137). No significant differences were observed with the other variables considered. The QoL of cancer patients is generally deteriorated and MRONJ may cause a further negative impact. This study highlights the possible need to include psychosocial and physical evaluations in the management process of MRONJ in cancer patients.In asthmatic adults, monoclonals directed against Type 2 airway inflammation have led to major improvements in quality of life, reductions in asthma attacks and less need for oral corticosteroids. The paediatric evidence base has lagged behind. All monoclonals currently available for children are anti-eosinophilic, directed against the T helper (TH2) pathway. However, in children and in low and middle income settings, eosinophils may have important beneficial immunological actions. Furthermore, there is evidence that paediatric severe asthma may not be TH2 driven, phenotypes may be less stable than in adults, and adult biomarkers may be less useful. Children being evaluated for biologicals should undergo a protocolised assessment, because most paediatric asthma can be controlled with low dose inhaled corticosteroid if taken properly and regularly. https://www.selleckchem.com/products/mk-8719.html For those with severe therapy resistant asthma, and refractory asthma which cannot be addressed, the two options if they have TH2 inflammation are omalizumab and mepolizumab.
    The decrease of viroid levels during pollen development correlated with mRNA accumulation of several RNA-degrading factors, such as AGO5 nuclease, DICER-like and TUDOR S-like nuclease. In addition, the functional status of pollen, as a tissue with high ribosome content, could play a role during suppression of AFCVd replication involving transcription factors IIIA and ribosomal protein L5.Fusarium head blight (FHB) is one of the most important diseases of wheat, causing yield losses and mycotoxin contamination of harvested grain. A complex of different toxigenic Fusarium species is responsible for FHB and the composition and predominance of species within the FHB complex are determined by meteorological and agronomic factors. In this study, grain of three different susceptible winter wheat cultivars from seven locations in northern Germany were analysed within a five-year survey from 2013 to 2017 by quantifying DNA amounts of different species within the Fusarium community as well as deoxynivalenol (DON) and zearalenone (ZEA) concentrations. Several Fusarium species co-occur in wheat grain samples in all years and cultivars. F. graminearum was the most prevalent species, followed by F. culmorum, F. avenaceum and F. poae, while F. tricinctum and F. langsethiae played only a subordinate role in the FHB complex in terms of DNA amounts. In all cultivars, a comparable year-specific quantitative occng (early and late milk stage).Today, consumers are increasingly demanding safety alternatives concerning the use of synthetic additives in the food industry, as well as healthy food. As a result, a major number of plant-derived preservatives have been tested in the food industry. These natural ingredients have antioxidant properties and have shown to increase the bioactive molecules levels and the microbiological stability of the food items. The effect of the plant-based preservatives on the sensorial properties of the new products has also to be considered, because natural preservatives could result in sensorial characteristics that may not be accepted by the consumers. Cheese is a dairy product widely appreciated all over the world, but it is also susceptible to contamination by pathogenic and spoilage microorganisms; therefore, the use of preservatives in cheese making represents an important step. This review deals with one of the innovation in the cheese sector, which is the addition of natural preservatives. Several aspects are discussed, such as the effect of natural ingredients on the microbial stability of cheese, and their influence on the chemical, nutritional and sensorial characteristics of the cheeses. Although the promising results, further studies are needed to confirm the use of natural preservatives from plants in cheese making.Growing urbanization leads to an increased risk of parasite spread in densely inhabited areas. Free-ranging cats can be locally numerous and come into frequent contact with both wildlife and humans. Cats are thus expected to contribute to parasitic disease transmission. In our study, we investigated the prevalence of endoparasites in free ranging cats in urban areas of Kraków city, based on necropsy of road-killed cats in relation to sex and diet of cat, season and habitat type. We found that 62% of 81 cats were infected with endoparasites with Toxocara cati being the most prevalent. In total, we identified seven parasite species. The number of parasite species was higher in suburban habitats and aside from Eucoleus aerophilus the prevalence of all parasites was higher in cats from suburban areas than in the individuals living in the city urban core. The prey of examined cats included mostly rodents, followed by soricomorphs and birds, which can all serve as paratenic hosts. Based on our results, we suggest that cats in urban areas should be considered as a serious potential zoonotic threat. Implementation of proper veterinary control and wider education on the topic is recommended.The aim of this study is to observe the influence of Medication-Related Osteonecrosis of the Jaw (MRONJ) on the physical and mental conditions of cancer patients using a Quality of Life (QoL) questionnaire during regular dental practice measures. Twenty cancer patients (8 males and 12 females) with established MRONJ were enrolled in the "MoMax" (Oral Medicine and Maxillofacial) project of the Department of Oral Sciences and Maxillofacial Surgery at "Sapienza" University of Rome, and were included in the study. The 12-item Short Form Survey was used to evaluate the QoL. Statistical analysis revealed a significant difference for Mental Component Summary (MCS) scores based on age (p = 0.018). The regression analysis revealed that the Physical Component Summary (PCS) scores were negatively influenced by the anti-resorptive medication duration (p = 0.031 and β = -1.137). No significant differences were observed with the other variables considered. The QoL of cancer patients is generally deteriorated and MRONJ may cause a further negative impact. This study highlights the possible need to include psychosocial and physical evaluations in the management process of MRONJ in cancer patients.In asthmatic adults, monoclonals directed against Type 2 airway inflammation have led to major improvements in quality of life, reductions in asthma attacks and less need for oral corticosteroids. The paediatric evidence base has lagged behind. All monoclonals currently available for children are anti-eosinophilic, directed against the T helper (TH2) pathway. However, in children and in low and middle income settings, eosinophils may have important beneficial immunological actions. Furthermore, there is evidence that paediatric severe asthma may not be TH2 driven, phenotypes may be less stable than in adults, and adult biomarkers may be less useful. Children being evaluated for biologicals should undergo a protocolised assessment, because most paediatric asthma can be controlled with low dose inhaled corticosteroid if taken properly and regularly. https://www.selleckchem.com/products/mk-8719.html For those with severe therapy resistant asthma, and refractory asthma which cannot be addressed, the two options if they have TH2 inflammation are omalizumab and mepolizumab.
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  • data reveal a clear and consistent pattern Attributing a social identity to God predicts perceiving individuals who share that identity as more fit for leadership. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Objectives Despite the fact that Christopher Columbus did not discover America and was arguably one of the most brutal colonizers in recorded history, the United States continues to celebrate a holiday in his honor. A growing movement by Native American activists and allies aims to adopt Indigenous Peoples Day in lieu of Columbus Day to shed light on historical inaccuracies, acknowledge the legacy of colonialism, and celebrate Indigenous Peoples. Research suggests that national narratives, such as those undergirding Columbus Day, build on negative stereotypes about minoritized groups to help bolster national identities. We examined whether national identification and negative stereotyping of Native Americans shapes support for each holiday. Method We conducted 2 large-scale national studies (Study 1 college students, N = 4,625; Study 2 adults, N = 2,805). Results Across both samples, people who endorsed the continued celebration of Columbus Day and people who were least supportive of adopting Indigenous Peoples Day were those high in national identification. In contrast, people who endorsed eliminating Columbus Day and people who supported adopting Indigenous Peoples Day were relatively low in national identification who also believed that negative stereotypes about Native Americans were highly unacceptable (Studies 1 and 2) and/or inaccurate (Study 2). Conclusions The results suggest that garnering support for eliminating Columbus Day and adopting Indigenous Peoples Day requires interrogating the roots of national identification and rejecting negative stereotypes about Native Americans. Implications for why people continue to hold onto national narratives that reify the continued subordination of minority groups are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The present study examined associations between parents' and their children's ages of onset of cannabis use using a data synthesis methodology to pool data from 3 similarly designed intergenerational studies. Regarding age of first use of cannabis, prospective data were collected at one or more assessments from early to late adolescence in each generation. The extent to which parent and offspring gender separately or jointly moderated intergenerational effects was examined. Data were harmonized from studies originating in the states of Washington (Bailey, Hill, Epstein, Steeger, & Hawkins, 2018), New York (Thornberry, Henry, Krohn, Lizotte, & Nadel, 2018), and Oregon (Capaldi, Kerr, & Tiberio, 2018) when the parents were in late childhood to early adolescence; analyses concerned 1,081 parents and their children from 971 unique families. Parents' and their children's age of cannabis use onset during adolescence were modeled using discrete-time survival analysis techniques. Although data were successfully synthesized across the studies, the primary hypothesis was not supported parents' earlier age of first cannabis use during adolescence was not significantly associated with earlier onset of cannabis use in the offspring generation. Rather, parents' histories of any cannabis use in adolescence-regardless of timing-were linked with increased risk for early onset cannabis use by their children compared to parents with no history of use during adolescence. There were no significant parent, child, or parent-by-child gender moderation effects. Thus, prevention of adolescent onset of cannabis in one generation may have prevention benefits for the next. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Why do some workers experience less insecurity than others even when facing the same objectively insecure work situation? Combining appraisal theory with the construct of proactive coping, we propose that proactive career behavior represents a form of resource accumulation that mitigates the extent to which insecure work situations result in perceived insecurity. We hypothesize that proactive career behavior moderates the effect of an acute insecure work situation (time remaining before contract expiration) and a chronic insecure work situation (probability of digitalization) on control appraisals of these situations and, in turn, perceptions of job and employment insecurity. We tested this moderated mediation model in a 3-wave field study with 2 samples. First, workers in unstable temporary jobs (with no renewed contract, N = 227) perceived higher lack of control and hence higher job insecurity as their contract got closer to expiring. As hypothesized, this process was mitigated by proactive career behavior. Second, workers in stable jobs (with a renewed contract or a permanent contract, N = 205) perceived higher lack of control and hence higher employment insecurity, as their occupation had a higher probability of digitalization. https://www.selleckchem.com/ In contrast to our hypothesis, proactive career behavior did not mitigate this effect. Results further replicated established relationships between perceived insecurity and later stress and career dissatisfaction. By moving up the causal chain and focusing on the emergence of insecurity rather than the more common emphasis on consequences of insecurity, our study uncovers the role of proactive coping in the job insecurity process. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The past decades of research on predictors of depression have frequently emphasized interactive diathesis-stress questions What kinds of vulnerabilities under stressful circumstances increase risk of developing depression? This study addresses 3 theoretically important gaps in our knowledge regarding diathesis-stress models of depression the role of temperament (neuroticism), interactive versus additive effects of neuroticism-stress relationships, and effects of stressor characteristics (acute vs. chronic, major vs. minor events, interpersonal vs. noninterpersonal content). We addressed these gaps in the prediction of major depressive episodes (MDEs) in a sample of high schoolers (n = 559) oversampled for high neuroticism and assessed for presence of MDEs annually for 5 years. Survival analyses provided relatively consistent support for the main effects of the broad vulnerability factor of the general neuroticism factor, acute stressors, and chronic stressors in the prediction of MDEs. In contrast, the majority of our analyses failed to support interactive neuroticism-stress accounts of MDE risk.
    data reveal a clear and consistent pattern Attributing a social identity to God predicts perceiving individuals who share that identity as more fit for leadership. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Objectives Despite the fact that Christopher Columbus did not discover America and was arguably one of the most brutal colonizers in recorded history, the United States continues to celebrate a holiday in his honor. A growing movement by Native American activists and allies aims to adopt Indigenous Peoples Day in lieu of Columbus Day to shed light on historical inaccuracies, acknowledge the legacy of colonialism, and celebrate Indigenous Peoples. Research suggests that national narratives, such as those undergirding Columbus Day, build on negative stereotypes about minoritized groups to help bolster national identities. We examined whether national identification and negative stereotyping of Native Americans shapes support for each holiday. Method We conducted 2 large-scale national studies (Study 1 college students, N = 4,625; Study 2 adults, N = 2,805). Results Across both samples, people who endorsed the continued celebration of Columbus Day and people who were least supportive of adopting Indigenous Peoples Day were those high in national identification. In contrast, people who endorsed eliminating Columbus Day and people who supported adopting Indigenous Peoples Day were relatively low in national identification who also believed that negative stereotypes about Native Americans were highly unacceptable (Studies 1 and 2) and/or inaccurate (Study 2). Conclusions The results suggest that garnering support for eliminating Columbus Day and adopting Indigenous Peoples Day requires interrogating the roots of national identification and rejecting negative stereotypes about Native Americans. Implications for why people continue to hold onto national narratives that reify the continued subordination of minority groups are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The present study examined associations between parents' and their children's ages of onset of cannabis use using a data synthesis methodology to pool data from 3 similarly designed intergenerational studies. Regarding age of first use of cannabis, prospective data were collected at one or more assessments from early to late adolescence in each generation. The extent to which parent and offspring gender separately or jointly moderated intergenerational effects was examined. Data were harmonized from studies originating in the states of Washington (Bailey, Hill, Epstein, Steeger, & Hawkins, 2018), New York (Thornberry, Henry, Krohn, Lizotte, & Nadel, 2018), and Oregon (Capaldi, Kerr, & Tiberio, 2018) when the parents were in late childhood to early adolescence; analyses concerned 1,081 parents and their children from 971 unique families. Parents' and their children's age of cannabis use onset during adolescence were modeled using discrete-time survival analysis techniques. Although data were successfully synthesized across the studies, the primary hypothesis was not supported parents' earlier age of first cannabis use during adolescence was not significantly associated with earlier onset of cannabis use in the offspring generation. Rather, parents' histories of any cannabis use in adolescence-regardless of timing-were linked with increased risk for early onset cannabis use by their children compared to parents with no history of use during adolescence. There were no significant parent, child, or parent-by-child gender moderation effects. Thus, prevention of adolescent onset of cannabis in one generation may have prevention benefits for the next. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Why do some workers experience less insecurity than others even when facing the same objectively insecure work situation? Combining appraisal theory with the construct of proactive coping, we propose that proactive career behavior represents a form of resource accumulation that mitigates the extent to which insecure work situations result in perceived insecurity. We hypothesize that proactive career behavior moderates the effect of an acute insecure work situation (time remaining before contract expiration) and a chronic insecure work situation (probability of digitalization) on control appraisals of these situations and, in turn, perceptions of job and employment insecurity. We tested this moderated mediation model in a 3-wave field study with 2 samples. First, workers in unstable temporary jobs (with no renewed contract, N = 227) perceived higher lack of control and hence higher job insecurity as their contract got closer to expiring. As hypothesized, this process was mitigated by proactive career behavior. Second, workers in stable jobs (with a renewed contract or a permanent contract, N = 205) perceived higher lack of control and hence higher employment insecurity, as their occupation had a higher probability of digitalization. https://www.selleckchem.com/ In contrast to our hypothesis, proactive career behavior did not mitigate this effect. Results further replicated established relationships between perceived insecurity and later stress and career dissatisfaction. By moving up the causal chain and focusing on the emergence of insecurity rather than the more common emphasis on consequences of insecurity, our study uncovers the role of proactive coping in the job insecurity process. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The past decades of research on predictors of depression have frequently emphasized interactive diathesis-stress questions What kinds of vulnerabilities under stressful circumstances increase risk of developing depression? This study addresses 3 theoretically important gaps in our knowledge regarding diathesis-stress models of depression the role of temperament (neuroticism), interactive versus additive effects of neuroticism-stress relationships, and effects of stressor characteristics (acute vs. chronic, major vs. minor events, interpersonal vs. noninterpersonal content). We addressed these gaps in the prediction of major depressive episodes (MDEs) in a sample of high schoolers (n = 559) oversampled for high neuroticism and assessed for presence of MDEs annually for 5 years. Survival analyses provided relatively consistent support for the main effects of the broad vulnerability factor of the general neuroticism factor, acute stressors, and chronic stressors in the prediction of MDEs. In contrast, the majority of our analyses failed to support interactive neuroticism-stress accounts of MDE risk.
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  • There is currently no established injury criterion for the spine in compression with lateral load components despite this load combination commonly contributing to spinal injuries in rollover vehicle crashes, falls and sports. This study aimed to determine an injury criterion and accompanying tolerance values for cervical spine segments in axial compression applied with varying coronal plane eccentricity. Thirty-three human cadaveric functional spinal units were subjected to axial compression at three magnitudes of lateral eccentricity of the applied force. Injury was identified by high-speed video and graded by spine surgeons. Linear regression was used to define neck injury tolerance values based on a criterion incorporating coronal plane loads accounting for specimen sex, age, size and bone density. Larger coronal plane eccentricity at injury was associated with smaller resultant coronal plane force. The level of coronal plane eccentricity at failure appears to distinguish between the types of injuries sustained, with hard tissue structure injuries more common at low levels of eccentricity and soft tissue structure injuries more common at high levels of eccentricity. There was no relationship between axial force and lateral bending moment at injury which has been previously proposed as an injury criterion. These results provide the foundation for designing and evaluating strategies and devices for preventing severe spinal injuries.Adipose-derived mesenchymal stem cells (hADMSC) retaining proliferation and multi-differentiation potential may support the central nervous system (CNS) regeneration. Multipotency of ****may result in both desirable and undesirable cells, post-transplantation. A better strategy to attain desired cells may be in vitro commitment of hADMSCs to uni-/bi- potent neural progenitor cells (NPCs), prior to transplantation. Derivation of stable NPCs may require a suitable niche eliciting proliferation and differentiation signals. The present study designed a biomimetic niche comprising insoluble fibrin supported adhesion matrix and exogenously added growth factors (GFs) for deriving different neural cells and established the role of Notch and Wnt signals for proliferation and differentiation of hADMSCs, respectively. The stable transformation of hADMSCs into neurospheres (NS) comprising Nestin+ve NPCs was achieved consistently. Slight modifications of niche enable differentiation of NS to NPCs; NPCs to neurons; NPCs to oligodendrocyte progenitor cells (OPCs); and OPCs to oligodendrocytes (OLG). Fibrin plays a crucial role in the conversion of hADMSC to NS and NPCs to OPCs; but, not essential for OPC to OLG maturation. Co-survival and cell-cell interaction of NPC derived neurons and OPCs promoting OLG maturation is illustrated. The designed biomimetic niche shows the potential for directing autologous ADMSCs to neural cells for applications in regenerative medicine.The role of rotational molecular motors of the ATP synthase class is integral to the metabolism of cells. Yet the function of FliI6-FliJ complex, a homolog of the F1 ATPase motor, within the flagellar export apparatus remains unclear. We use a simple two-state model adapted from studies of linear molecular motors to identify key features of this motor. https://www.selleckchem.com/products/gliocidin.html The two states are the 'locked' ground state where the FliJ coiled coil filament experiences angular fluctuations in an asymmetric torsional potential, and a 'free' excited state in which FliJ undergoes rotational diffusion. Michaelis-Menten kinetics was used to treat transitions between these two states, and obtain the average angular velocity of the unloaded FliJ filament within the FliI6 stator ωmax ≈ 9.0 rps. The motor was then studied under external counter torque conditions in order to ascertain its maximal power output Pmax ≈ 42 kBT/s (or 102 kW/mol), and the stall torque Gstall ≈ 3 kBT/rad (or 0.01 nN·nm/rad). Two modes of action within the flagellar export apparatus are proposed, in which the motor performs useful work either by continuously 'grinding' through the resistive environment of the export gate, or by exerting equal and opposite stall force on it. In both cases, the resistance is provided by flagellin subunits entering the flagellar export channel prior to their unfolding. We therefore propose that the function of the FliI6-FliJ complex is to lower the energy barrier, and therefore assist in unfolding of the flagellar proteins before feeding them into the transport channel.Most of the existing recognition algorithms are proposed for closed set scenarios, where all categories are known beforehand. However, in practice, recognition is essentially an open set problem. There are categories we know called "knowns", and there are more we do not know called "unknowns". Enumerating all categories beforehand is never possible, consequently, it is infeasible to prepare sufficient training samples for those unknowns. Applying closed set recognition methods will naturally lead to unseen-category errors. To address this problem, we propose the prototype-based Open Deep Network (P-ODN) for open set recognition tasks. Specifically, we introduce prototype learning into open set recognition. Prototypes and prototype radiuses are trained jointly to guide a CNN network to derive more discriminative features. Then P-ODN detects the unknowns by applying a multi-class triplet thresholding method based on the distance metric between features and prototypes. Manual labeling the unknowns which are detected in the previous process as new categories. Predictors for new categories are added to the classification layer to "open" the deep neural networks to incorporate new categories dynamically. The weights of new predictors are initialized exquisitely by applying a distances based algorithm to transfer the learned knowledge. Consequently, this initialization method speeds up the fine-tuning process and reduce the samples needed to train new predictors. Extensive experiments show that P-ODN can effectively detect unknowns and needs only few samples with human intervention to recognize a new category. In the real world scenarios, our method achieves state-of-the-art performance on the UCF11, UCF50, UCF101 and HMDB51 datasets.
    There is currently no established injury criterion for the spine in compression with lateral load components despite this load combination commonly contributing to spinal injuries in rollover vehicle crashes, falls and sports. This study aimed to determine an injury criterion and accompanying tolerance values for cervical spine segments in axial compression applied with varying coronal plane eccentricity. Thirty-three human cadaveric functional spinal units were subjected to axial compression at three magnitudes of lateral eccentricity of the applied force. Injury was identified by high-speed video and graded by spine surgeons. Linear regression was used to define neck injury tolerance values based on a criterion incorporating coronal plane loads accounting for specimen sex, age, size and bone density. Larger coronal plane eccentricity at injury was associated with smaller resultant coronal plane force. The level of coronal plane eccentricity at failure appears to distinguish between the types of injuries sustained, with hard tissue structure injuries more common at low levels of eccentricity and soft tissue structure injuries more common at high levels of eccentricity. There was no relationship between axial force and lateral bending moment at injury which has been previously proposed as an injury criterion. These results provide the foundation for designing and evaluating strategies and devices for preventing severe spinal injuries.Adipose-derived mesenchymal stem cells (hADMSC) retaining proliferation and multi-differentiation potential may support the central nervous system (CNS) regeneration. Multipotency of MSC may result in both desirable and undesirable cells, post-transplantation. A better strategy to attain desired cells may be in vitro commitment of hADMSCs to uni-/bi- potent neural progenitor cells (NPCs), prior to transplantation. Derivation of stable NPCs may require a suitable niche eliciting proliferation and differentiation signals. The present study designed a biomimetic niche comprising insoluble fibrin supported adhesion matrix and exogenously added growth factors (GFs) for deriving different neural cells and established the role of Notch and Wnt signals for proliferation and differentiation of hADMSCs, respectively. The stable transformation of hADMSCs into neurospheres (NS) comprising Nestin+ve NPCs was achieved consistently. Slight modifications of niche enable differentiation of NS to NPCs; NPCs to neurons; NPCs to oligodendrocyte progenitor cells (OPCs); and OPCs to oligodendrocytes (OLG). Fibrin plays a crucial role in the conversion of hADMSC to NS and NPCs to OPCs; but, not essential for OPC to OLG maturation. Co-survival and cell-cell interaction of NPC derived neurons and OPCs promoting OLG maturation is illustrated. The designed biomimetic niche shows the potential for directing autologous ADMSCs to neural cells for applications in regenerative medicine.The role of rotational molecular motors of the ATP synthase class is integral to the metabolism of cells. Yet the function of FliI6-FliJ complex, a homolog of the F1 ATPase motor, within the flagellar export apparatus remains unclear. We use a simple two-state model adapted from studies of linear molecular motors to identify key features of this motor. https://www.selleckchem.com/products/gliocidin.html The two states are the 'locked' ground state where the FliJ coiled coil filament experiences angular fluctuations in an asymmetric torsional potential, and a 'free' excited state in which FliJ undergoes rotational diffusion. Michaelis-Menten kinetics was used to treat transitions between these two states, and obtain the average angular velocity of the unloaded FliJ filament within the FliI6 stator ωmax ≈ 9.0 rps. The motor was then studied under external counter torque conditions in order to ascertain its maximal power output Pmax ≈ 42 kBT/s (or 102 kW/mol), and the stall torque Gstall ≈ 3 kBT/rad (or 0.01 nN·nm/rad). Two modes of action within the flagellar export apparatus are proposed, in which the motor performs useful work either by continuously 'grinding' through the resistive environment of the export gate, or by exerting equal and opposite stall force on it. In both cases, the resistance is provided by flagellin subunits entering the flagellar export channel prior to their unfolding. We therefore propose that the function of the FliI6-FliJ complex is to lower the energy barrier, and therefore assist in unfolding of the flagellar proteins before feeding them into the transport channel.Most of the existing recognition algorithms are proposed for closed set scenarios, where all categories are known beforehand. However, in practice, recognition is essentially an open set problem. There are categories we know called "knowns", and there are more we do not know called "unknowns". Enumerating all categories beforehand is never possible, consequently, it is infeasible to prepare sufficient training samples for those unknowns. Applying closed set recognition methods will naturally lead to unseen-category errors. To address this problem, we propose the prototype-based Open Deep Network (P-ODN) for open set recognition tasks. Specifically, we introduce prototype learning into open set recognition. Prototypes and prototype radiuses are trained jointly to guide a CNN network to derive more discriminative features. Then P-ODN detects the unknowns by applying a multi-class triplet thresholding method based on the distance metric between features and prototypes. Manual labeling the unknowns which are detected in the previous process as new categories. Predictors for new categories are added to the classification layer to "open" the deep neural networks to incorporate new categories dynamically. The weights of new predictors are initialized exquisitely by applying a distances based algorithm to transfer the learned knowledge. Consequently, this initialization method speeds up the fine-tuning process and reduce the samples needed to train new predictors. Extensive experiments show that P-ODN can effectively detect unknowns and needs only few samples with human intervention to recognize a new category. In the real world scenarios, our method achieves state-of-the-art performance on the UCF11, UCF50, UCF101 and HMDB51 datasets.
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  • These findings demonstrate that macrophage IRF-7 is critical for LPS-induced type I IFN responses, which in turn facilitate IL-1β production in ****. Copyright © 2020 Sin, Yeong, Lim, Su, Connolly and Chin.Following allogeneic blood and marrow transplantation (BMT), graft-versus-host disease (GvHD) continues to represent a significant cause of treatment failure, despite the routine use of conventional, mainly calcineurin inhibitor-based prophylaxis. Recently, post-transplant cyclophosphamide (PTCy) has emerged as a safe and efficacious alternative. First, omitting the need for ex vivo T-cell depletion in the setting of haploidentical transplantation, growing evidence supports PTCy role in GvHD prevention in matched-related and matched-unrelated transplants. Through improved understanding of GvHD pathophysiology and advancements in drug development, PTCy emerges as a unique opportunity to design calcineurin inhibitor-free strategies by integrating agents that target different stages of GvHD development. Copyright © 2020 Williams, Cirrone, Cole, Abdul-Hay, Luznik and Al-Homsi.Mycobacterium tuberculosis (Mtb) infects alveolar macrophages (AMs), causing pulmonary tuberculosis (PTB), the most common form of the disease. Less frequently, Mtb is disseminated to many other organs and tissues, resulting in different extrapulmonary forms of TB. Nevertheless, very few studies have addressed the global mRNA response of human AMs, particularly from humans with the active form of the disease. Strikingly, almost no studies have addressed the response of human extrapulmonary macrophages to Mtb infection. In this pilot study, using microarray technology, we examined the transcriptomic ex vivo response of AMs from PTB patients (AMTBs) and AMs from control subjects (AMCTs) infected with two clinical isolates of Mtb. Furthermore, we also studied the infection response of human splenic macrophages (SMs) to Mtb isolates, as a model for extrapulmonary infection, and compared the transcriptomic response between AMs and SMs. Our results showed a striking difference in global mRNA profiles in response to infection between AMs and SMs, implicating a tissue-specific macrophage response to Mtb. Copyright © 2020 Lavalett, Ortega and Barrera.Pathogen-initiated chronic inflammation or autoimmune diseases accelerate proliferation and promote differentiation of hematopoietic stem cells (HSCs) but simultaneously reduce reconstitution capacity. Nevertheless, the effect of acute infection and inflammation on functional HSCs is still largely unknown. Here we found that acute infection elicited by heat-inactivated Escherichia coli (HIEC) expanded bone marrow lineage-negative (Lin)- stem-cell antigen 1 (Sca-1)+cKit+ (LSK) cell population, leading to reduced frequency of functional HSCs in LSK population. However, the total number of BM phenotypic HSCs (Flk2-CD48-CD150+ LSK cells) was not altered in HIEC-challenged ****. Additionally, the reconstitution capacity of the total BM between infected and uninfected **** was similar by both the competitive repopulation assay and measurement of functional HSCs by limiting dilution. Thus, occasionally occurring acute inflammation, which is critical for host defenses, is unlikely to affect HSC self-renewal and maintenance of long-term reconstitution capacity. During acute bacterial infection and inflammation, the hematopoietic system can replenish hematopoietic cells consumed in the innate inflammatory response by accelerating hematopoietic stem and progenitor cell proliferation, but preserving functional HSCs in the BM. Copyright © 2020 Zhang, Karatepe, Chiewchengchol, Zhu, Guo, Liu, Yu, Ren, Luo, Cheng, Ma, Xu, Han and Luo.Background Genetic tests for primary immunodeficiency disorders (PIDs) are expensive, time-consuming, and not easily accessible in developing countries. Therefore, we studied the feasibility of a customized single nucleotide variant (SNV) microarray that we developed to detect disease-causing variants and copy number variation (CNV) in patients with PIDs for only 40 Euros. Methods Probes were custom-designed to genotype 9,415 variants of 277 PID-related genes, and were added to the genome-wide Illumina Global Screening Array (GSA). Data analysis of GSA was performed using Illumina GenomeStudio 2.0, Biodiscovery Nexus 10.0, and R-3.4.4 software. Validation of genotype calling was performed by comparing the GSA with whole-genome sequencing (WGS) data of 56 non-PID controls. DNA samples of 95 clinically diagnosed PID patients, of which 60 patients (63%) had a genetically established diagnosis (by Next-Generation Sequencing (NGS) PID panels or Sanger sequencing), were analyzed to test the performance of the GSA. https://www.selleckchem.com/products/CP-690550.html ing in developing countries. The technique is scalable, allows numerous new genetic variants to be added, and offers the potential for genetic testing not only in PIDs, but also in many other genetic diseases. Copyright © 2020 Suratannon, van Wijck, Broer, Xue, van Meurs, Barendregt, van der Burg, Dik, Chatchatee, Langerak, Swagemakers, Goos, Mathijssen, Dalm, Suphapeetiporn, Heezen, Drabwell, Uitterlinden, van der Spek, van Hagen and the South East Asia Primary Immunodeficiencies (SEAPID) Consortium.Transplant vasculopathy (TV), a hallmark of chronic allograft rejection, is the primary cause of allograft loss after organ transplantation. Because multiple mechanisms are involved in TV pathogenesis, effective therapy for it remains elusive. Here, we identify the role of triptolide, which has a wide spectrum of immuno-suppressive activities, in inhibiting TV development. Murine aortic transplants models were constructed and divided into triptolide-treated and untreated groups. We found that triptolide significantly alleviated intima thickening of allografts by inhibiting multiple pathways. Triptolide significantly reduced infiltration of T lymphocytes and macrophages and inhibited the levels of pro-inflammatory (TNF-α, IL-2, and IL-6) and pro-fibrotic factors (TGF-β, α-SMA, and MMP-9) in the graft. Additionally, triptolide significantly decreased the numbers of IFN-γ-producing T lymphocytes, as well as the expression of IFN-γ and IFN-γ-inducing factor (CXCL9 and CXCL10) in recipient. Moreover, triptolide decreased the numbers of B lymphocytes and plasma cells, as well as the levels of donor specific antibodies (DSAs) in recipient.
    These findings demonstrate that macrophage IRF-7 is critical for LPS-induced type I IFN responses, which in turn facilitate IL-1β production in mice. Copyright © 2020 Sin, Yeong, Lim, Su, Connolly and Chin.Following allogeneic blood and marrow transplantation (BMT), graft-versus-host disease (GvHD) continues to represent a significant cause of treatment failure, despite the routine use of conventional, mainly calcineurin inhibitor-based prophylaxis. Recently, post-transplant cyclophosphamide (PTCy) has emerged as a safe and efficacious alternative. First, omitting the need for ex vivo T-cell depletion in the setting of haploidentical transplantation, growing evidence supports PTCy role in GvHD prevention in matched-related and matched-unrelated transplants. Through improved understanding of GvHD pathophysiology and advancements in drug development, PTCy emerges as a unique opportunity to design calcineurin inhibitor-free strategies by integrating agents that target different stages of GvHD development. Copyright © 2020 Williams, Cirrone, Cole, Abdul-Hay, Luznik and Al-Homsi.Mycobacterium tuberculosis (Mtb) infects alveolar macrophages (AMs), causing pulmonary tuberculosis (PTB), the most common form of the disease. Less frequently, Mtb is disseminated to many other organs and tissues, resulting in different extrapulmonary forms of TB. Nevertheless, very few studies have addressed the global mRNA response of human AMs, particularly from humans with the active form of the disease. Strikingly, almost no studies have addressed the response of human extrapulmonary macrophages to Mtb infection. In this pilot study, using microarray technology, we examined the transcriptomic ex vivo response of AMs from PTB patients (AMTBs) and AMs from control subjects (AMCTs) infected with two clinical isolates of Mtb. Furthermore, we also studied the infection response of human splenic macrophages (SMs) to Mtb isolates, as a model for extrapulmonary infection, and compared the transcriptomic response between AMs and SMs. Our results showed a striking difference in global mRNA profiles in response to infection between AMs and SMs, implicating a tissue-specific macrophage response to Mtb. Copyright © 2020 Lavalett, Ortega and Barrera.Pathogen-initiated chronic inflammation or autoimmune diseases accelerate proliferation and promote differentiation of hematopoietic stem cells (HSCs) but simultaneously reduce reconstitution capacity. Nevertheless, the effect of acute infection and inflammation on functional HSCs is still largely unknown. Here we found that acute infection elicited by heat-inactivated Escherichia coli (HIEC) expanded bone marrow lineage-negative (Lin)- stem-cell antigen 1 (Sca-1)+cKit+ (LSK) cell population, leading to reduced frequency of functional HSCs in LSK population. However, the total number of BM phenotypic HSCs (Flk2-CD48-CD150+ LSK cells) was not altered in HIEC-challenged mice. Additionally, the reconstitution capacity of the total BM between infected and uninfected mice was similar by both the competitive repopulation assay and measurement of functional HSCs by limiting dilution. Thus, occasionally occurring acute inflammation, which is critical for host defenses, is unlikely to affect HSC self-renewal and maintenance of long-term reconstitution capacity. During acute bacterial infection and inflammation, the hematopoietic system can replenish hematopoietic cells consumed in the innate inflammatory response by accelerating hematopoietic stem and progenitor cell proliferation, but preserving functional HSCs in the BM. Copyright © 2020 Zhang, Karatepe, Chiewchengchol, Zhu, Guo, Liu, Yu, Ren, Luo, Cheng, Ma, Xu, Han and Luo.Background Genetic tests for primary immunodeficiency disorders (PIDs) are expensive, time-consuming, and not easily accessible in developing countries. Therefore, we studied the feasibility of a customized single nucleotide variant (SNV) microarray that we developed to detect disease-causing variants and copy number variation (CNV) in patients with PIDs for only 40 Euros. Methods Probes were custom-designed to genotype 9,415 variants of 277 PID-related genes, and were added to the genome-wide Illumina Global Screening Array (GSA). Data analysis of GSA was performed using Illumina GenomeStudio 2.0, Biodiscovery Nexus 10.0, and R-3.4.4 software. Validation of genotype calling was performed by comparing the GSA with whole-genome sequencing (WGS) data of 56 non-PID controls. DNA samples of 95 clinically diagnosed PID patients, of which 60 patients (63%) had a genetically established diagnosis (by Next-Generation Sequencing (NGS) PID panels or Sanger sequencing), were analyzed to test the performance of the GSA. https://www.selleckchem.com/products/CP-690550.html ing in developing countries. The technique is scalable, allows numerous new genetic variants to be added, and offers the potential for genetic testing not only in PIDs, but also in many other genetic diseases. Copyright © 2020 Suratannon, van Wijck, Broer, Xue, van Meurs, Barendregt, van der Burg, Dik, Chatchatee, Langerak, Swagemakers, Goos, Mathijssen, Dalm, Suphapeetiporn, Heezen, Drabwell, Uitterlinden, van der Spek, van Hagen and the South East Asia Primary Immunodeficiencies (SEAPID) Consortium.Transplant vasculopathy (TV), a hallmark of chronic allograft rejection, is the primary cause of allograft loss after organ transplantation. Because multiple mechanisms are involved in TV pathogenesis, effective therapy for it remains elusive. Here, we identify the role of triptolide, which has a wide spectrum of immuno-suppressive activities, in inhibiting TV development. Murine aortic transplants models were constructed and divided into triptolide-treated and untreated groups. We found that triptolide significantly alleviated intima thickening of allografts by inhibiting multiple pathways. Triptolide significantly reduced infiltration of T lymphocytes and macrophages and inhibited the levels of pro-inflammatory (TNF-α, IL-2, and IL-6) and pro-fibrotic factors (TGF-β, α-SMA, and MMP-9) in the graft. Additionally, triptolide significantly decreased the numbers of IFN-γ-producing T lymphocytes, as well as the expression of IFN-γ and IFN-γ-inducing factor (CXCL9 and CXCL10) in recipient. Moreover, triptolide decreased the numbers of B lymphocytes and plasma cells, as well as the levels of donor specific antibodies (DSAs) in recipient.
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  • BACKGROUND The rumen contains a myriad of microbes whose primary role is to degrade and ferment dietary nutrients, which then provide the host with energy and nutrients. Rumen microbes commonly attach to ingested plant materials and form biofilms for effective plant degradation. Quorum sensing (QS) is a well-recognised form of bacterial communication in most biofilm communities, with homoserine lactone (AHL)-based QS commonly being used by Gram-negative bacteria alone and AI-2 Lux-based QS communication being used to communicate across Gram-negative and Gram-positive bacteria. However, bacterial cell to cell communication in the rumen is poorly understood. In this study, rumen bacterial genomes from the Hungate collection and Genbank were prospected for QS-related genes. To check that the discovered QS genes are actually expressed in the rumen, we investigated expression levels in rumen metatranscriptome datasets. RESULTS A total of 448 rumen bacterial genomes from the Hungate collection and Genbank, comprise microbiome to date. This study shows that AI-2-based QS is rife in the rumen. These results allow a greater understanding on plant-microbe interactions in the rumen.Following publication of the original article [1], the authors reported an error on the legend of of P.damicornis in Fig. 1.BACKGROUND This study examined physicians' perspectives on sexuality in later life. METHODS In-depth interviews were conducted among 38 physicians with various specialties and they were asked to discuss sexuality in later life within the medical context. RESULTS Perceptions on older adult's sexuality emerged from the interviews were organized into three themes What, why and how. What, referred to physician's definition to what role sexuality plays in later life and what is considered sex. Why, referred to the reasons why physicians assumed older adults experience sexual difficulties, and how these assumptions effect the diagnostic process. How, referred to how sexual difficulties were treated by physicians. Physicians employed a bio-medical approach when treating older, as compared to young adults with sexual dysfunction. CONCLUSIONS The findings highlight a potential for differential treatment of older adults, based on age, rather than on other objective reasons.BACKGROUND The best evidence-enhanced recovery care pathway is yet to be defined for patients undergoing spinal surgery. Minimally invasive surgery, multimodal analgesia, early mobilization, and early postoperative nutrition have been considered as critical components of enhanced recovery in spinal surgery (ERSS). The objective of this study will be to synthesize the evidence underpinning individual components of a proposed multidisciplinary enhanced recovery pathway for patients undergoing spinal surgery. METHODS This is the study protocol for a systematic review of complex interventions. Our team identified 22 individual care components of a proposed pathway based on clinical practice guidelines and published reviews. We will include systematic reviews and meta-analysis, randomized controlled trials, non-randomized controlled trials, and observational studies in adults or pediatric patients evaluating any one of the pre-determined care components. Our primary outcomes will be all-cause mortality, morbidity ify, evaluate, and integrate the evidence underpinning individual components of a pathway for patients undergoing spinal surgery. The formation of an evidence-based pathway will allow for the standardization of clinical care delivery within the context of enhanced recovery in spinal surgery. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019135289.OBJECTIVE Bipartite graphs are widely used to model relationships between pairs of heterogeneous data types. Maximal bicliques are foundational structures in such graphs, and their enumeration is an important task in systems biology, epidemiology and many other problem domains. Thus, there is a need for an efficient, general purpose, publicly available tool to enumerate maximal bicliques in bipartite graphs. The statistical programming language R is a logical choice for such a tool, but until now no R package has existed for this purpose. Our objective is to provide such a package, so that the research community can more easily perform this computationally demanding task. RESULTS Biclique is an R package that takes as input a bipartite graph and produces a listing of all maximal bicliques in this graph. Input and output formats are straightforward, with examples provided both in this paper and in the package documentation. Biclique employs a state-of-the-art algorithm previously developed for basic research in functional genomics. This package, along with its source code and reference manual, are freely available from the CRAN public repository at https//cran.r-project.org/web/packages/biclique/index.html.BACKGROUND Recently, attempts have been made to use the pulse rate variability (PRV) as a surrogate for heart rate variability (HRV). PRV, however, may be caused by the fluctuations of left ventricular pre-ejection period and pulse transit time besides HRV. We examined whether PRV differs not only from HRV but also depending on the measurement site. RESULTS In five healthy subjects, pulse waves were measured simultaneously on both wrists and both forearms together with single-lead electrocardiogram (ECG) in the supine and sitting positions. Although average pulse interval showed no significant difference from average R-R interval in either positions, PRV showed greater power for the low-frequency (LF) and high-frequency (HF) components and lower LF/HF than HRV. The deviations of PRV from HRV in the supine and sitting positions were 13.2% and 7.9% for LF power, 24.5% and 18.3% for HF power, and - 15.0% and - 30.2% for LF/HF, respectively. While the average pulse interval showed 0.8% and 0.5% inter-site variations among the four sites in the supine and sitting positions, respectively, the inter-site variations in PRV were 4.0% and 3.6% for LF power, 3.8% and 4.7% for HF power, and 18.0% and 17.5% for LF/HF, respectively. https://www.selleckchem.com/products/cc-99677.html CONCLUSIONS These suggest that PRV shows not only systemic differences from HRV but also considerable inter-site variations.
    BACKGROUND The rumen contains a myriad of microbes whose primary role is to degrade and ferment dietary nutrients, which then provide the host with energy and nutrients. Rumen microbes commonly attach to ingested plant materials and form biofilms for effective plant degradation. Quorum sensing (QS) is a well-recognised form of bacterial communication in most biofilm communities, with homoserine lactone (AHL)-based QS commonly being used by Gram-negative bacteria alone and AI-2 Lux-based QS communication being used to communicate across Gram-negative and Gram-positive bacteria. However, bacterial cell to cell communication in the rumen is poorly understood. In this study, rumen bacterial genomes from the Hungate collection and Genbank were prospected for QS-related genes. To check that the discovered QS genes are actually expressed in the rumen, we investigated expression levels in rumen metatranscriptome datasets. RESULTS A total of 448 rumen bacterial genomes from the Hungate collection and Genbank, comprise microbiome to date. This study shows that AI-2-based QS is rife in the rumen. These results allow a greater understanding on plant-microbe interactions in the rumen.Following publication of the original article [1], the authors reported an error on the legend of of P.damicornis in Fig. 1.BACKGROUND This study examined physicians' perspectives on sexuality in later life. METHODS In-depth interviews were conducted among 38 physicians with various specialties and they were asked to discuss sexuality in later life within the medical context. RESULTS Perceptions on older adult's sexuality emerged from the interviews were organized into three themes What, why and how. What, referred to physician's definition to what role sexuality plays in later life and what is considered sex. Why, referred to the reasons why physicians assumed older adults experience sexual difficulties, and how these assumptions effect the diagnostic process. How, referred to how sexual difficulties were treated by physicians. Physicians employed a bio-medical approach when treating older, as compared to young adults with sexual dysfunction. CONCLUSIONS The findings highlight a potential for differential treatment of older adults, based on age, rather than on other objective reasons.BACKGROUND The best evidence-enhanced recovery care pathway is yet to be defined for patients undergoing spinal surgery. Minimally invasive surgery, multimodal analgesia, early mobilization, and early postoperative nutrition have been considered as critical components of enhanced recovery in spinal surgery (ERSS). The objective of this study will be to synthesize the evidence underpinning individual components of a proposed multidisciplinary enhanced recovery pathway for patients undergoing spinal surgery. METHODS This is the study protocol for a systematic review of complex interventions. Our team identified 22 individual care components of a proposed pathway based on clinical practice guidelines and published reviews. We will include systematic reviews and meta-analysis, randomized controlled trials, non-randomized controlled trials, and observational studies in adults or pediatric patients evaluating any one of the pre-determined care components. Our primary outcomes will be all-cause mortality, morbidity ify, evaluate, and integrate the evidence underpinning individual components of a pathway for patients undergoing spinal surgery. The formation of an evidence-based pathway will allow for the standardization of clinical care delivery within the context of enhanced recovery in spinal surgery. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019135289.OBJECTIVE Bipartite graphs are widely used to model relationships between pairs of heterogeneous data types. Maximal bicliques are foundational structures in such graphs, and their enumeration is an important task in systems biology, epidemiology and many other problem domains. Thus, there is a need for an efficient, general purpose, publicly available tool to enumerate maximal bicliques in bipartite graphs. The statistical programming language R is a logical choice for such a tool, but until now no R package has existed for this purpose. Our objective is to provide such a package, so that the research community can more easily perform this computationally demanding task. RESULTS Biclique is an R package that takes as input a bipartite graph and produces a listing of all maximal bicliques in this graph. Input and output formats are straightforward, with examples provided both in this paper and in the package documentation. Biclique employs a state-of-the-art algorithm previously developed for basic research in functional genomics. This package, along with its source code and reference manual, are freely available from the CRAN public repository at https//cran.r-project.org/web/packages/biclique/index.html.BACKGROUND Recently, attempts have been made to use the pulse rate variability (PRV) as a surrogate for heart rate variability (HRV). PRV, however, may be caused by the fluctuations of left ventricular pre-ejection period and pulse transit time besides HRV. We examined whether PRV differs not only from HRV but also depending on the measurement site. RESULTS In five healthy subjects, pulse waves were measured simultaneously on both wrists and both forearms together with single-lead electrocardiogram (ECG) in the supine and sitting positions. Although average pulse interval showed no significant difference from average R-R interval in either positions, PRV showed greater power for the low-frequency (LF) and high-frequency (HF) components and lower LF/HF than HRV. The deviations of PRV from HRV in the supine and sitting positions were 13.2% and 7.9% for LF power, 24.5% and 18.3% for HF power, and - 15.0% and - 30.2% for LF/HF, respectively. While the average pulse interval showed 0.8% and 0.5% inter-site variations among the four sites in the supine and sitting positions, respectively, the inter-site variations in PRV were 4.0% and 3.6% for LF power, 3.8% and 4.7% for HF power, and 18.0% and 17.5% for LF/HF, respectively. https://www.selleckchem.com/products/cc-99677.html CONCLUSIONS These suggest that PRV shows not only systemic differences from HRV but also considerable inter-site variations.
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  • Many bacterial small RNAs (sRNAs) efficiently inhibit translation of target mRNAs by forming a duplex that sequesters the Shine-Dalgarno (SD) sequence or start codon and prevents formation of the translation initiation complex. There are a growing number of examples of sRNA-mRNA binding interactions distant from the SD region, but how these mediate translational regulation remains unclear. Our previous work in Escherichia coli and Salmonella identified a mechanism of translational repression of manY mRNA by the sRNA SgrS through a binding interaction upstream of the manY SD. Here, we report that SgrS forms a duplex with a uridine-rich translation-enhancing element in the manY 5' untranslated region. Notably, we show that the enhancer is ribosome-dependent and that the small ribosomal subunit protein S1 interacts with the enhancer to promote translation of manY. In collaboration with the chaperone protein Hfq, SgrS interferes with the interaction between the translation enhancer and ribosomal protein S1 to repress translation of manY mRNA. Since bacterial translation is often modulated by enhancer-like elements upstream of the SD, sRNA-mediated enhancer silencing could be a common mode of gene regulation. This article is protected by copyright. All rights reserved.INTRODUCTION Lauraceae alkaloids are a structurally diverse class of plant specialised secondary metabolites that play an important role in modern pharmacotherapy, being useful as well as model compounds for the development of synthetic analogues. However, alkaloids characterisation is challenging due to low concentrations, the complexity of plant extracts, and long processes for accurate structural determinations. OBJECTIVE The use of high-performance thin layer chromatography coupled with desorption electrospray ionisation multistage mass spectrometry (HPTLC DESI-MSn ) as a fast tool to identify alkaloids present in Ocotea spixiana extract and evaluate the extract's acaricide activity. METHODS Ocotea spixiana twigs were extracted by conventional liquid-liquid partitioning. HPTLC analysis of the ethyl acetate extract was performed to separate isobaric alkaloids prior to DESI-MSn analysis, performed from MS3 up to MS7 . The extract's acaricide activity against Rhipicephalus microplus was evaluated by in vitro (larval immersion test) and in silico tests. RESULTS HPTLC-DESI-MSn analysis was performed to identify a total of 13 aporphine and four benzylisoquinoline-type alkaloids reported for the first time in O. spixiana. https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html In vitro evaluation of the extract and the alkaloid boldine showed significant activity against R. microplus larvae. It was established in silico that boldine had important intermolecular interactions with R. microplus acetylcholinesterase enzyme. CONCLUSION The present study demonstrated that HPTLC-DESI-MSn is a useful analytical tool to identify isoquinoline alkaloids in plant extracts. The acaricide activity of the O. spixiana ethyl acetate extract can be correlated to the presence of alkaloids. © 2020 John Wiley & Sons, Ltd.Few images are available in the literature of the Ross II procedure wherein the pulmonary valve is autotransplanted into the mitral position. These images are from a 33-year-old woman who underwent the procedure 18 years ago. © 2020 Wiley Periodicals, Inc.RNA interference (RNAi) is a promising technology for the development of next-generation insect pest control products. Though RNAi is efficient and systemic in coleopteran insects, it is inefficient and variable in lepidopteron insects. In this study, we explored the possibility of improving RNAi in the fall armyworm (FAW), Spodoptera frugiperda by conjugating double-stranded RNA (dsRNA) with biodegradable chitosan (Chi). dsRNA conjugated with chitosan was protected from degradation by endonucleases present in Sf9 cell-conditioned medium, hemolymph, and midgut lumen contents collected from the FAW larvae. Chi-dsRNA complexes showed reduced accumulation in the endosomes of Sf9 cells and FAW tissues. Exposing chitosan formulated dsRNA in Sf9 cells and the tissues induced a significant knockdown of endogenous genes. Chi-dsIAP fed to FAW larvae induced knockdown of iap gene, growth retardation, and mortality. Processing of dsRNA into small interfering RNA was detected with chitosan-conjugated 32 P-UTP-labeled ds green fluorescent protein in Sf9 cells and FAW larval tissues. Overall, these data suggest that dsRNA conjugated with chitosan helps dsRNA escape from the endosomes and improves RNAi efficiency in FAW cells and tissues. © 2020 Wiley Periodicals, Inc.BACKGROUND Risk for suicide attempt (SA) versus suicide ideation (SI) is clinically important and difficult to differentiate. We examined whether a history of self-injurious thoughts and behaviors (SITBs) differentiates soldiers with a recent SA from nonattempting soldiers with current/recent SI. METHODS Using a unique case-control design, we administered the same questionnaire (assessing the history of SITBs and psychosocial variables) to representative U.S. Army soldiers recently hospitalized for SA (n = 132) and soldiers from the same Army installations who reported 30-day SI but did not make an attempt (n = 125). Logistic regression analyses examined whether SITBs differentiated attempters and ideators after controlling for previously identified covariates. RESULTS In separate models that weighted for systematic nonresponse and controlled for gender, education, posttraumatic stress disorder, and intermittent explosive disorder, SA was positively and significantly associated with the history of suicide plan and/or intention to act (odds ratio [OR] = 12.1 [95% confidence interval CI = 3.6-40.4]), difficulty controlling suicidal thoughts during the worst week of ideation (OR = 3.5 [95% CI = 1.1-11.3]), and nonsuicidal self-injury (NSSI) (OR = 4.9 [95% CI = 1.3-18.0]). Area under the curve was 0.87 in a full model that combined these SITBs and covariates. The top ventile based on predicted risk had a sensitivity of 24.7%, specificity of 99.8%, and positive predictive value of 97.5%. CONCLUSIONS History of suicide plan/intention, difficult to control ideation, and NSSI differentiate soldiers with recent SA from those with current/recent SI independent of sociodemographic characteristics and mental disorders. Longitudinal research is needed to determine whether these factors are prospectively associated with the short-term transition from SI to SA. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.
    Many bacterial small RNAs (sRNAs) efficiently inhibit translation of target mRNAs by forming a duplex that sequesters the Shine-Dalgarno (SD) sequence or start codon and prevents formation of the translation initiation complex. There are a growing number of examples of sRNA-mRNA binding interactions distant from the SD region, but how these mediate translational regulation remains unclear. Our previous work in Escherichia coli and Salmonella identified a mechanism of translational repression of manY mRNA by the sRNA SgrS through a binding interaction upstream of the manY SD. Here, we report that SgrS forms a duplex with a uridine-rich translation-enhancing element in the manY 5' untranslated region. Notably, we show that the enhancer is ribosome-dependent and that the small ribosomal subunit protein S1 interacts with the enhancer to promote translation of manY. In collaboration with the chaperone protein Hfq, SgrS interferes with the interaction between the translation enhancer and ribosomal protein S1 to repress translation of manY mRNA. Since bacterial translation is often modulated by enhancer-like elements upstream of the SD, sRNA-mediated enhancer silencing could be a common mode of gene regulation. This article is protected by copyright. All rights reserved.INTRODUCTION Lauraceae alkaloids are a structurally diverse class of plant specialised secondary metabolites that play an important role in modern pharmacotherapy, being useful as well as model compounds for the development of synthetic analogues. However, alkaloids characterisation is challenging due to low concentrations, the complexity of plant extracts, and long processes for accurate structural determinations. OBJECTIVE The use of high-performance thin layer chromatography coupled with desorption electrospray ionisation multistage mass spectrometry (HPTLC DESI-MSn ) as a fast tool to identify alkaloids present in Ocotea spixiana extract and evaluate the extract's acaricide activity. METHODS Ocotea spixiana twigs were extracted by conventional liquid-liquid partitioning. HPTLC analysis of the ethyl acetate extract was performed to separate isobaric alkaloids prior to DESI-MSn analysis, performed from MS3 up to MS7 . The extract's acaricide activity against Rhipicephalus microplus was evaluated by in vitro (larval immersion test) and in silico tests. RESULTS HPTLC-DESI-MSn analysis was performed to identify a total of 13 aporphine and four benzylisoquinoline-type alkaloids reported for the first time in O. spixiana. https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html In vitro evaluation of the extract and the alkaloid boldine showed significant activity against R. microplus larvae. It was established in silico that boldine had important intermolecular interactions with R. microplus acetylcholinesterase enzyme. CONCLUSION The present study demonstrated that HPTLC-DESI-MSn is a useful analytical tool to identify isoquinoline alkaloids in plant extracts. The acaricide activity of the O. spixiana ethyl acetate extract can be correlated to the presence of alkaloids. © 2020 John Wiley & Sons, Ltd.Few images are available in the literature of the Ross II procedure wherein the pulmonary valve is autotransplanted into the mitral position. These images are from a 33-year-old woman who underwent the procedure 18 years ago. © 2020 Wiley Periodicals, Inc.RNA interference (RNAi) is a promising technology for the development of next-generation insect pest control products. Though RNAi is efficient and systemic in coleopteran insects, it is inefficient and variable in lepidopteron insects. In this study, we explored the possibility of improving RNAi in the fall armyworm (FAW), Spodoptera frugiperda by conjugating double-stranded RNA (dsRNA) with biodegradable chitosan (Chi). dsRNA conjugated with chitosan was protected from degradation by endonucleases present in Sf9 cell-conditioned medium, hemolymph, and midgut lumen contents collected from the FAW larvae. Chi-dsRNA complexes showed reduced accumulation in the endosomes of Sf9 cells and FAW tissues. Exposing chitosan formulated dsRNA in Sf9 cells and the tissues induced a significant knockdown of endogenous genes. Chi-dsIAP fed to FAW larvae induced knockdown of iap gene, growth retardation, and mortality. Processing of dsRNA into small interfering RNA was detected with chitosan-conjugated 32 P-UTP-labeled ds green fluorescent protein in Sf9 cells and FAW larval tissues. Overall, these data suggest that dsRNA conjugated with chitosan helps dsRNA escape from the endosomes and improves RNAi efficiency in FAW cells and tissues. © 2020 Wiley Periodicals, Inc.BACKGROUND Risk for suicide attempt (SA) versus suicide ideation (SI) is clinically important and difficult to differentiate. We examined whether a history of self-injurious thoughts and behaviors (SITBs) differentiates soldiers with a recent SA from nonattempting soldiers with current/recent SI. METHODS Using a unique case-control design, we administered the same questionnaire (assessing the history of SITBs and psychosocial variables) to representative U.S. Army soldiers recently hospitalized for SA (n = 132) and soldiers from the same Army installations who reported 30-day SI but did not make an attempt (n = 125). Logistic regression analyses examined whether SITBs differentiated attempters and ideators after controlling for previously identified covariates. RESULTS In separate models that weighted for systematic nonresponse and controlled for gender, education, posttraumatic stress disorder, and intermittent explosive disorder, SA was positively and significantly associated with the history of suicide plan and/or intention to act (odds ratio [OR] = 12.1 [95% confidence interval CI = 3.6-40.4]), difficulty controlling suicidal thoughts during the worst week of ideation (OR = 3.5 [95% CI = 1.1-11.3]), and nonsuicidal self-injury (NSSI) (OR = 4.9 [95% CI = 1.3-18.0]). Area under the curve was 0.87 in a full model that combined these SITBs and covariates. The top ventile based on predicted risk had a sensitivity of 24.7%, specificity of 99.8%, and positive predictive value of 97.5%. CONCLUSIONS History of suicide plan/intention, difficult to control ideation, and NSSI differentiate soldiers with recent SA from those with current/recent SI independent of sociodemographic characteristics and mental disorders. Longitudinal research is needed to determine whether these factors are prospectively associated with the short-term transition from SI to SA. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.
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  • The abundance of biological particles showed no significant correlation with Na+ (r = -0.17), indicating the air masses from marine areas carried limited biological particles compared to those from continental areas. Constructed wetlands are an alternative biotechnology for wastewater treatment that have several advantages over conventional systems. In this work, a biokinetic model for surface flow constructed wetlands is presented (SURFWET). SURFWET belongs to a class of models that are not only interesting from a theoretical viewpoint, as they allow to improve the understanding of the underlying processes; but also from a practical viewpoint, because they can be useful for optimal designs of constructed wetlands, complementing current empirical methods. The proposed model is centered on the intervening physical and biochemical processes involved in pollutant removal in wastewater (organic matter, nitrogen, phosphorus, suspended solids), capturing the interplay of the main agents on contaminant removal (bacteria, macrophytes and phytoplankton). Furthermore, the hydraulic model considers water volume as a variable depending on the outlet hydraulic capacity, and dissolved oxygen has also been introduced as a key driver of reaction kinetics of wetlands. Beyond putting forward a theoretical framework, SURFWET has been applied to simulate a specific case to demonstrate its robustness, in a 12-year-interval simulation. The results show the typical seasonality of this biotechnology, highlighting the importance of dissolved oxygen, which is a key limiting factor on a large number of biochemical processes. Some studies have shown that maturation of dendritic cells (DCs) is modulated directly by pathogen components via pattern recognition receptors such as Toll-like receptors, but also by signal like CD40 ligand (CD40 L or CD154) mediated by activated T cells. Several reports indicate that invariant natural killer T (iNKT) cells up-regulate CD40 L upon stimulation and thereby induce activation and maturation of DCs through crosslink with CD40. Our previous findings indicated that iNKT cells promote Th2 cell responses through the induction of immunogenic maturation of lung DCs (LDCs) in the asthmatic murine, but its mechanism remains unclear. Therefore, we investigated the immunomodulatory effects of blockade of CD40 L using anti-CD40 L treatment on Th2 cell responses and immunogenic maturation of LDCs, and further analyzed whether these influences of blockade of CD40 L were related to lung iNKT cells using iNKT cell-deficient **** and the combination treatment of specific iNKT cell activation with anti-CD40 L trenic maturation of LDCs, which may be at least partially related to lung iNKT cells in murine models of asthma. In parts of developing countries, the over-exploitation of sands from inland waters has led to serious environmental concerns. However, understanding of the impacts of commercial sand dredging on inland water ecosystem functions remains limited. Herein, we assess the effects of this activity on the functional structure of the macroinvertebrate community and its recovery processes based on a 4-year survey, in the South Dongting Lake in China. Our result showed a simplified macroinvertebrate functional structures within the dredged area, as evidenced by a loss of certain trait categories (e.g., oval and conical body form) and a significant reduction in trait values due to the direct removal of macroinvertebrates and indirect alternations to physical environmental conditions (e.g., water depth and %Medium sand). Moreover, clear increases were observed in certain trait categories (e.g., small body size and swimmer) resulting from the dredging-related disturbance (e.g., increased turbidity) within the adjacent area. Furthermore, one year after the cessation of dredging, a marked recovery in the taxonomic and functional structure of macroinvertebrate assemblages was observed with most lost trait categories returning and an increase in the trait values of eight categories (e.g., body size 1.00-3.00 cm and oval body form) within the dredged and adjacent area. In addition, dispersal processes and sediment composition were the main driver for the structuring of the macroinvertebrate taxonomic and functional assemblages during the dredging stages, whilst water environmental conditions dominated the taxonomic structure and dispersal processes determined the functional structure during the recovery stage. Implications of our results for monitoring and management of this activity in inland waters are discussed. Zearalenone is a phenolic Fusarium mycotoxin, which is ubiquitous in human and animal feedstuff and often co-occurs with other mycotoxins. ZEA has been reported to disturb Leydig cell function and even cause the apoptosis to the Leydig cells. However, the effects of gestational exposure to zearalenone on fetal Leydig cells and the underlying mechanism remain unknown. Sprague Dawley dams were daily gavaged with 0, 2.5, 5, 10, and 20 mg/kg body weight ZEA from gestational day 14-21. On gestational day 21, rats were euthanized and serum testosterone levels were measured, and testes were collected for further evaluation of Leydig cell number, cell size, gene, and protein expression. Zearalenone significantly decreased anogenital distance and its index of male fetus, serum testosterone levels, Leydig cell proteins (SCARB1, STAR, CYP11A1, CYP17A1, and INSL3), and fetal Leydig cell number at 10 and/or 20 mg/kg by delaying the commitment of stem Leydig cells into the Leydig cell lineage and proliferation. Further study found that Notch signaling (RFNG, PSEN1, NOTCH1, and NOTCH3) was up-regulated by zearalenone. https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html In conclusion, gestational exposure to high doses of zearalenone (10 and 20 mg/kg) blocks fetal Leydig cell development, thus possibly causing the anomalies of the male reproductive tract. Despite growing concern about the occurrence of microplastics in aquatic ecosystems there is only rudimentary understanding of the pathways through which any adverse effects might occur. Here, we assess the effects of polystyrene microplastics (PS-MPs; less then 70 μm) on a common and widespread algal species, Chlorella sorokiniana. We used laboratory exposure to test the hypothesis that the lipids and fatty acids (FAs) are important molecules in the response reactions of algae to this pollutant. Cultivation with PS-MPs systematically reduced the concentration of essential linoleic acid (ALA, C183n-3) in C. sorokiniana, concomitantly increasing oleic acid (C181n-9). Among the storage triacylglycerols, palmitoleic and oleic acids increased at the expenses of two essential fatty acids, linoleic (LIN, C182n-6) and ALA, while PS-MPs had even more pronounced effects on the fatty acid and hydrocarbon composition of waxes and steryl esters. The FA composition of two major chloroplast galactolipids, monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), were affected implying changes in the conformational structure of photosynthetic complexes in ways that can impair the photosynthesis.
    The abundance of biological particles showed no significant correlation with Na+ (r = -0.17), indicating the air masses from marine areas carried limited biological particles compared to those from continental areas. Constructed wetlands are an alternative biotechnology for wastewater treatment that have several advantages over conventional systems. In this work, a biokinetic model for surface flow constructed wetlands is presented (SURFWET). SURFWET belongs to a class of models that are not only interesting from a theoretical viewpoint, as they allow to improve the understanding of the underlying processes; but also from a practical viewpoint, because they can be useful for optimal designs of constructed wetlands, complementing current empirical methods. The proposed model is centered on the intervening physical and biochemical processes involved in pollutant removal in wastewater (organic matter, nitrogen, phosphorus, suspended solids), capturing the interplay of the main agents on contaminant removal (bacteria, macrophytes and phytoplankton). Furthermore, the hydraulic model considers water volume as a variable depending on the outlet hydraulic capacity, and dissolved oxygen has also been introduced as a key driver of reaction kinetics of wetlands. Beyond putting forward a theoretical framework, SURFWET has been applied to simulate a specific case to demonstrate its robustness, in a 12-year-interval simulation. The results show the typical seasonality of this biotechnology, highlighting the importance of dissolved oxygen, which is a key limiting factor on a large number of biochemical processes. Some studies have shown that maturation of dendritic cells (DCs) is modulated directly by pathogen components via pattern recognition receptors such as Toll-like receptors, but also by signal like CD40 ligand (CD40 L or CD154) mediated by activated T cells. Several reports indicate that invariant natural killer T (iNKT) cells up-regulate CD40 L upon stimulation and thereby induce activation and maturation of DCs through crosslink with CD40. Our previous findings indicated that iNKT cells promote Th2 cell responses through the induction of immunogenic maturation of lung DCs (LDCs) in the asthmatic murine, but its mechanism remains unclear. Therefore, we investigated the immunomodulatory effects of blockade of CD40 L using anti-CD40 L treatment on Th2 cell responses and immunogenic maturation of LDCs, and further analyzed whether these influences of blockade of CD40 L were related to lung iNKT cells using iNKT cell-deficient mice and the combination treatment of specific iNKT cell activation with anti-CD40 L trenic maturation of LDCs, which may be at least partially related to lung iNKT cells in murine models of asthma. In parts of developing countries, the over-exploitation of sands from inland waters has led to serious environmental concerns. However, understanding of the impacts of commercial sand dredging on inland water ecosystem functions remains limited. Herein, we assess the effects of this activity on the functional structure of the macroinvertebrate community and its recovery processes based on a 4-year survey, in the South Dongting Lake in China. Our result showed a simplified macroinvertebrate functional structures within the dredged area, as evidenced by a loss of certain trait categories (e.g., oval and conical body form) and a significant reduction in trait values due to the direct removal of macroinvertebrates and indirect alternations to physical environmental conditions (e.g., water depth and %Medium sand). Moreover, clear increases were observed in certain trait categories (e.g., small body size and swimmer) resulting from the dredging-related disturbance (e.g., increased turbidity) within the adjacent area. Furthermore, one year after the cessation of dredging, a marked recovery in the taxonomic and functional structure of macroinvertebrate assemblages was observed with most lost trait categories returning and an increase in the trait values of eight categories (e.g., body size 1.00-3.00 cm and oval body form) within the dredged and adjacent area. In addition, dispersal processes and sediment composition were the main driver for the structuring of the macroinvertebrate taxonomic and functional assemblages during the dredging stages, whilst water environmental conditions dominated the taxonomic structure and dispersal processes determined the functional structure during the recovery stage. Implications of our results for monitoring and management of this activity in inland waters are discussed. Zearalenone is a phenolic Fusarium mycotoxin, which is ubiquitous in human and animal feedstuff and often co-occurs with other mycotoxins. ZEA has been reported to disturb Leydig cell function and even cause the apoptosis to the Leydig cells. However, the effects of gestational exposure to zearalenone on fetal Leydig cells and the underlying mechanism remain unknown. Sprague Dawley dams were daily gavaged with 0, 2.5, 5, 10, and 20 mg/kg body weight ZEA from gestational day 14-21. On gestational day 21, rats were euthanized and serum testosterone levels were measured, and testes were collected for further evaluation of Leydig cell number, cell size, gene, and protein expression. Zearalenone significantly decreased anogenital distance and its index of male fetus, serum testosterone levels, Leydig cell proteins (SCARB1, STAR, CYP11A1, CYP17A1, and INSL3), and fetal Leydig cell number at 10 and/or 20 mg/kg by delaying the commitment of stem Leydig cells into the Leydig cell lineage and proliferation. Further study found that Notch signaling (RFNG, PSEN1, NOTCH1, and NOTCH3) was up-regulated by zearalenone. https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html In conclusion, gestational exposure to high doses of zearalenone (10 and 20 mg/kg) blocks fetal Leydig cell development, thus possibly causing the anomalies of the male reproductive tract. Despite growing concern about the occurrence of microplastics in aquatic ecosystems there is only rudimentary understanding of the pathways through which any adverse effects might occur. Here, we assess the effects of polystyrene microplastics (PS-MPs; less then 70 μm) on a common and widespread algal species, Chlorella sorokiniana. We used laboratory exposure to test the hypothesis that the lipids and fatty acids (FAs) are important molecules in the response reactions of algae to this pollutant. Cultivation with PS-MPs systematically reduced the concentration of essential linoleic acid (ALA, C183n-3) in C. sorokiniana, concomitantly increasing oleic acid (C181n-9). Among the storage triacylglycerols, palmitoleic and oleic acids increased at the expenses of two essential fatty acids, linoleic (LIN, C182n-6) and ALA, while PS-MPs had even more pronounced effects on the fatty acid and hydrocarbon composition of waxes and steryl esters. The FA composition of two major chloroplast galactolipids, monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), were affected implying changes in the conformational structure of photosynthetic complexes in ways that can impair the photosynthesis.
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  • Concentrations of fatty acids, BHB, and PUN were consistently lower in primiparous goats compared with those in second or greater parity. Postpartum, HY goats had higher ratios of glucose, fatty acids, and BHB to insulin than did LY goats, which might explain the greater mobilization of body tissues and enhanced milk production observed in this group. Collectively, our results indicate that increased milk yield has the most significant influence on the magnitude of body tissue mobilization. Our results also show that goats of higher parity display higher levels of lipid mobilization, and that both pregnancy and lactation are less able to elicit lipomobilization in primiparous compared with multiparous goats. The objective of this study was to evaluate the effects of a commercially available fermentation by-product in a diet containing adequate rumen-degradable protein (RDP) on milk performance, intake, and total-tract nutrient digestion in lactating dairy cattle. Primiparous (n = 48) and multiparous (n = 144) lactating dairy cattle were stratified by milk production and randomly allocated into 12 pens containing 4 primiparous and 12 multiparous animals each. Cattle averaged 118 d in milk and 712 kg of body weight at trial start. Treatment diets, on a dry matter (DM) basis, consisted of 42% corn silage, 13% alfalfa hay and silage, 20% grain corn, and 25% protein premix containing either soybean meal, wheat middlings, and urea (SBM+U), soybean meal and fermentation by-product (SBM+F), or soybean meal and rumen-protected soybean meal (RP-SBM). https://www.selleckchem.com/products/n-nitroso-n-methylurea.html All 3 diets provided a similar level (DM basis) of neutral detergent fiber analyzed using α-amylase and sodium sulfite and corrected for ash content (31%), crude protein (CP, intake. Responses are consistent with previous research in our laboratory that demonstrated a decrease in ruminal CP degradation, leading to an increase in metabolizable protein supply in the small intestine. The fermentation by-product might be useful in diets containing adequate amounts of RDP from soybean meal or alfalfa. The results from this experiment demonstrate beneficial milk performance responses to fermentation by-product when fed with a source of RDP. The use of orchids in herbal medicine has a very long history. Dendrobium species are known to produce a variety of secondary metabolites such as phenanthrens, bibenzyls, fluorenones and sesquiterpenes, and alkaloids and are responsible for their wide variety of medicinal properties. For decades, bibenzyls, which are the main bioactive components derived from Dendrobium species, have been subjected to extensive investigation as likely candidates for cancer treatment. The present study was undertaken to investigate the effect of moscatilin, a bibenzyl derivative from the orchid Dendrobium loddigesii on human melanoma cells. In A375 cells compound moscatilin showed a clear dose-response relationship in the range of 6.25-50 μM concentrations. In addition, we demonstrated an apoptotic response after treatment of cancer cells with this bibenzyl compound at 6.25 and 12.5 μM concentrations that probably involves PTEN activity, inhibition of Hsp70 expression and reactive oxygen species production. Alternatively, the inhibition of the caspase cascade at higher concentrations, 25 and 50 μM, correlated with additional reactive oxygen species increase, probably switched the mode of moscatilin-induced cell death from apoptosis to necrosis. INTRODUCTION Sickle cell disease (SCD) is a monogenic disease and it is estimated that 300,000 infants are born annually with it. Most treatments available are only palliative, whereas the allogeneic hematopoietic stem cell transplantation offers the only potential cure for SCD. OBJECTIVE Generation of human autologous cells, when coupled with induced pluripotent stem cell (iPSC) technology, is a promising approach for developing study models. In this study, we provide a simple and efficient model for generating hematopoietic cells using iPSCs derived from a sickle cell anemia patient and an inexpensive in-house-prepared medium. METHOD This study used iPSCs previously generated from peripheral blood mononuclear cells (PBMCs) from a patient with sickle cell anemia (iPSC_scd). Hematopoietic and erythroid differentiation was performed in two steps. Firstly, with the induction of hematopoietic differentiation through embryoid body formation, we evaluated the efficiency of two serum-free media; and secondly, the induction of hematopoietic stem/progenitor cells to erythroid progenitor cells was performed. RESULTS The patient-specific cell line generated CD34+/CD45+ and CD45+/CD43+ hematopoietic stem/progenitor cells and erythroid progenitors, comprising CD36+, CD71+ and CD235a+ populations, as well as the formation of hematopoietic colonies, including erythroid colonies, in culture in a semi-solid medium. CONCLUSION In conjunction, our results described a simple serum-free platform to differentiate human the iPSCs into hematopoietic progenitor cells. This platform is an emerging application of iPSCs in vitro disease modeling, which can significantly improve the search for new pharmacological drugs for sickle cell disease. We report the dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a COVID-19 patient from successive negative results to successive single positive nucleocapsid gene, to two positive target genes (orf1ab and nucleocapsid) by RT-PCR testing of SARS-Cov-2, and describe the diagnosis, clinical course, and management of the case. In this case, negative results of RT-PCR testing was not excluded to diagnose a suspected COVID-19 patient, clinical signs and symptoms, other laboratory findings, and chest CT images should be taken into account for the absence of enough positive evidence. This case highlights the importance of successive sampling and testing SARS-Cov-2 by RT-PCR as well as the increased value of single positive target gene from pending to positive in two specimens to diagnose laboratory-confirmed COVID-19. V.BACKGROUND Androgen insensitivity syndrome (AIS) is the most common type of 46, XY disorders of sex development (DSD), with a wide range of clinical heterogeneity, from male infertility, hypospadias to completely normal female external genitalia. Mutation of the androgen receptor (AR) gene on the X chromosome (Xq11.2q12) is the main cause of AIS. METHODS By phenotype evaluation, hormone test, ultrasound scan and G-banding karyotype, 17 unrelated Chinese patients were clinical diagnosed with AIS. Sanger sequencing of the AR was performed in these 17 patients. Functional studies were carried out for the novel mutations. RESULTS We identified 16 mutations in all patients, including six novel mutations (Q59*, F171Sfs*4, E204*, G209E, I870T, *921R). It is the first time that a stop codon mutation (*921R) in AR has been identified. Expression and nuclear localization analysis showed the *921R mutation caused an elongated abnormal polypeptide chain of the AR protein, and the abnormal protein could not be transported to the nucleus to stimulate the expression of downstream genes after androgenic treatment.
    Concentrations of fatty acids, BHB, and PUN were consistently lower in primiparous goats compared with those in second or greater parity. Postpartum, HY goats had higher ratios of glucose, fatty acids, and BHB to insulin than did LY goats, which might explain the greater mobilization of body tissues and enhanced milk production observed in this group. Collectively, our results indicate that increased milk yield has the most significant influence on the magnitude of body tissue mobilization. Our results also show that goats of higher parity display higher levels of lipid mobilization, and that both pregnancy and lactation are less able to elicit lipomobilization in primiparous compared with multiparous goats. The objective of this study was to evaluate the effects of a commercially available fermentation by-product in a diet containing adequate rumen-degradable protein (RDP) on milk performance, intake, and total-tract nutrient digestion in lactating dairy cattle. Primiparous (n = 48) and multiparous (n = 144) lactating dairy cattle were stratified by milk production and randomly allocated into 12 pens containing 4 primiparous and 12 multiparous animals each. Cattle averaged 118 d in milk and 712 kg of body weight at trial start. Treatment diets, on a dry matter (DM) basis, consisted of 42% corn silage, 13% alfalfa hay and silage, 20% grain corn, and 25% protein premix containing either soybean meal, wheat middlings, and urea (SBM+U), soybean meal and fermentation by-product (SBM+F), or soybean meal and rumen-protected soybean meal (RP-SBM). https://www.selleckchem.com/products/n-nitroso-n-methylurea.html All 3 diets provided a similar level (DM basis) of neutral detergent fiber analyzed using α-amylase and sodium sulfite and corrected for ash content (31%), crude protein (CP, intake. Responses are consistent with previous research in our laboratory that demonstrated a decrease in ruminal CP degradation, leading to an increase in metabolizable protein supply in the small intestine. The fermentation by-product might be useful in diets containing adequate amounts of RDP from soybean meal or alfalfa. The results from this experiment demonstrate beneficial milk performance responses to fermentation by-product when fed with a source of RDP. The use of orchids in herbal medicine has a very long history. Dendrobium species are known to produce a variety of secondary metabolites such as phenanthrens, bibenzyls, fluorenones and sesquiterpenes, and alkaloids and are responsible for their wide variety of medicinal properties. For decades, bibenzyls, which are the main bioactive components derived from Dendrobium species, have been subjected to extensive investigation as likely candidates for cancer treatment. The present study was undertaken to investigate the effect of moscatilin, a bibenzyl derivative from the orchid Dendrobium loddigesii on human melanoma cells. In A375 cells compound moscatilin showed a clear dose-response relationship in the range of 6.25-50 μM concentrations. In addition, we demonstrated an apoptotic response after treatment of cancer cells with this bibenzyl compound at 6.25 and 12.5 μM concentrations that probably involves PTEN activity, inhibition of Hsp70 expression and reactive oxygen species production. Alternatively, the inhibition of the caspase cascade at higher concentrations, 25 and 50 μM, correlated with additional reactive oxygen species increase, probably switched the mode of moscatilin-induced cell death from apoptosis to necrosis. INTRODUCTION Sickle cell disease (SCD) is a monogenic disease and it is estimated that 300,000 infants are born annually with it. Most treatments available are only palliative, whereas the allogeneic hematopoietic stem cell transplantation offers the only potential cure for SCD. OBJECTIVE Generation of human autologous cells, when coupled with induced pluripotent stem cell (iPSC) technology, is a promising approach for developing study models. In this study, we provide a simple and efficient model for generating hematopoietic cells using iPSCs derived from a sickle cell anemia patient and an inexpensive in-house-prepared medium. METHOD This study used iPSCs previously generated from peripheral blood mononuclear cells (PBMCs) from a patient with sickle cell anemia (iPSC_scd). Hematopoietic and erythroid differentiation was performed in two steps. Firstly, with the induction of hematopoietic differentiation through embryoid body formation, we evaluated the efficiency of two serum-free media; and secondly, the induction of hematopoietic stem/progenitor cells to erythroid progenitor cells was performed. RESULTS The patient-specific cell line generated CD34+/CD45+ and CD45+/CD43+ hematopoietic stem/progenitor cells and erythroid progenitors, comprising CD36+, CD71+ and CD235a+ populations, as well as the formation of hematopoietic colonies, including erythroid colonies, in culture in a semi-solid medium. CONCLUSION In conjunction, our results described a simple serum-free platform to differentiate human the iPSCs into hematopoietic progenitor cells. This platform is an emerging application of iPSCs in vitro disease modeling, which can significantly improve the search for new pharmacological drugs for sickle cell disease. We report the dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a COVID-19 patient from successive negative results to successive single positive nucleocapsid gene, to two positive target genes (orf1ab and nucleocapsid) by RT-PCR testing of SARS-Cov-2, and describe the diagnosis, clinical course, and management of the case. In this case, negative results of RT-PCR testing was not excluded to diagnose a suspected COVID-19 patient, clinical signs and symptoms, other laboratory findings, and chest CT images should be taken into account for the absence of enough positive evidence. This case highlights the importance of successive sampling and testing SARS-Cov-2 by RT-PCR as well as the increased value of single positive target gene from pending to positive in two specimens to diagnose laboratory-confirmed COVID-19. V.BACKGROUND Androgen insensitivity syndrome (AIS) is the most common type of 46, XY disorders of sex development (DSD), with a wide range of clinical heterogeneity, from male infertility, hypospadias to completely normal female external genitalia. Mutation of the androgen receptor (AR) gene on the X chromosome (Xq11.2q12) is the main cause of AIS. METHODS By phenotype evaluation, hormone test, ultrasound scan and G-banding karyotype, 17 unrelated Chinese patients were clinical diagnosed with AIS. Sanger sequencing of the AR was performed in these 17 patients. Functional studies were carried out for the novel mutations. RESULTS We identified 16 mutations in all patients, including six novel mutations (Q59*, F171Sfs*4, E204*, G209E, I870T, *921R). It is the first time that a stop codon mutation (*921R) in AR has been identified. Expression and nuclear localization analysis showed the *921R mutation caused an elongated abnormal polypeptide chain of the AR protein, and the abnormal protein could not be transported to the nucleus to stimulate the expression of downstream genes after androgenic treatment.
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