RESUMO
BACKGROUND: ERAP2 is an aminopeptidase involved in antigen processing and presentation, and harbor genetic variants linked to several inflammatory diseases such as Inflammatory Bowel Disease (IBD). The lack of an ERAP2 gene homologue in mice has hampered functional studies, and most human studies have focused on cells of hematopoietic origin. Using an IBD biobank as vantage point, this study explores how genetic variation in ERAP2 affects gene expression in human-derived epithelial organoids upon proinflammatory stimulation. METHODS: An IBD patient cohort was genotyped with regards to two single nucleotide polymorphisms (SNP) (rs2910686/rs2248374) associated with ERAP2 expression levels, and we examined the correlation between colon gene expression and genotype, specifically aiming to establish a relationship with ERAP2 expression proficiency. Human-derived colon organoids (colonoids) with known ERAP2 genotype were established and used to explore differences in whole genome gene expression between ERAP2-deficient (n = 4) and -proficient (n = 4) donors upon pro-inflammatory encounter. RESULTS: When taking rs2910686 genotype into account, ERAP2 gene expression is upregulated in the inflamed colon of IBD patients. Colonoids upregulate ERAP2 upon IFNÉ£ stimulation, and ERAP2 expression proficiency is dependent on rs2910686 genotype. Colonoid genotyping confirms that mechanisms independent of the frequently studied SNP rs2248374 can cause ERAP2-deficiency. A total of 586 genes involved in various molecular mechanisms are differentially expressed between ERAP2 proficient- and deficient colonoids upon proinflammatory stimulation, including genes encoding proteins with the following molecular function: catalytic activity (AOC1, CPE, ANPEP and MEP1A), regulator activity (TNFSF9, MDK, GDF15, ILR6A, LGALS3 and FLNA), transmembrane transporter activity (SLC40A1 and SLC5A1), and extracellular matrix structural constituents (FGL2, HMCN2, and MUC17). CONCLUSIONS: ERAP2 is upregulated in the inflamed IBD colon mucosa, and expression proficiency is highly correlated with genotype of rs2910686. While the SNP rs2248374 is commonly used to determine ERAP2 expressional proficiency, our data confirms that mechanisms independent of this SNP can lead to ERAP2 deficiency. Our data demonstrates that epithelial ERAP2 presence affects the inflammatory response in colonoids, suggesting a pleiotropic role of ERAP2 beyond MHC class I antigen processing.
Assuntos
Aminopeptidases , Colo , Inflamação , Doenças Inflamatórias Intestinais , Polimorfismo de Nucleotídeo Único , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Aminopeptidases/genética , Aminopeptidases/metabolismo , Inflamação/genética , Inflamação/patologia , Colo/patologia , Colo/metabolismo , Organoides/metabolismo , Genótipo , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/metabolismo , Feminino , Masculino , Estudos de Coortes , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Células Epiteliais/metabolismoRESUMO
Information technologies are increasingly used when informing patients about their disease, treatment and prognosis. These digital platforms have many advantages compared to traditional education interventions. However, there are concerns that some patients may have difficulty with this mode of information delivery. Newly diagnosed breast cancer patients are dependent on understanding their treatment options to make informed treatment decisions. Yet, there is a lack of published material on breast cancer patients and their relationship with technology. We aimed to assess health technology readiness profiles amongst women with a suspected breast cancer diagnosis. Secondly, we wanted to investigate the potential differences between these profiles according to sociodemographic factors and the patients´ current use of technology. This cross-sectional study used the Readiness and Enablement Index for Health Technology (READHY) questionnaire. We included all patients (n = 92) referred to our department with suspected breast cancer. Cluster analysis revealed three distinct profiles: medium (n = 54), high (n = 18), and low (n = 20) health technology readiness. The third profile showed difficulties in health literacy, eHealth literacy, and health insights, along with higher emotional stress. Our study found that most patients had medium to high health technology readiness, but we also identified a group with lower health technology readiness. Based on our results, healthcare personnel dealing with women with suspected breast cancer should be aware of patients struggling with health technology. Age and technology familiarity may indicate vulnerable patients. Future studies should explore optimal methods for information delivery to these distinct profiles and evaluate the long-term impacts.
Assuntos
Neoplasias da Mama , Telemedicina , Humanos , Feminino , Estudos Transversais , Neoplasias da Mama/diagnóstico , Inquéritos e Questionários , Telemedicina/métodos , Pessoal de SaúdeRESUMO
Hepatitis C virus (HCV) infection triggers Golgi fragmentation through the Golgi-resident protein immunity-related GTPase M (IRGM). Here, we report the roles of NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) and ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain [CARD]), two inflammasome components, in the initial events leading to this fragmentation. We show that ASC resides at the Golgi with IRGM at homeostasis. Upon infection, ASC dissociates from both IRGM and the Golgi and associates with HCV-induced NLRP3. NLRP3 silencing inhibits Golgi fragmentation. ASC silencing disrupts the Golgi structure in both control and infected cells and reduces the localization of IRGM at the Golgi. IRGM depletion in the ASC-silenced cells cannot totally restore the Golgi structure. These data highlight a role for ASC, upstream of the formation of the inflammasome, in regulating IRGM through its control on the Golgi. A similar mechanism occurs in response to nigericin treatment, but not in cells infected with another member of the Flaviviridae family, Zika virus (ZIKV). We propose a model for a newly ascribed function of the inflammasome components in Golgi structural remodeling during certain stimuli.IMPORTANCE Numerous pathogens can affect cellular homeostasis and organelle dynamics. Hepatitis C virus (HCV) triggers Golgi fragmentation through the immunity-related GTPase M (IRGM), a resident Golgi protein, to enhance its lipid supply for replication. Here, we reveal the role of the inflammasome components NLRP3 and ASC in this process, thus uncovering a new interplay between effectors of inflammation and viral infection or stress. We show that the inflammasome component ASC resides at the Golgi under homeostasis and associates with IRGM. Upon HCV infection, ASC is recruited to NLRP3 and dissociates from IRGM, causing Golgi fragmentation. Our results uncover that aside from their known function in the inflammation response, these host defense regulators also ensure the maintenance of intact intracellular structure in homeostasis, while their activation relieves factors leading to Golgi remodeling.
Assuntos
Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Complexo de Golgi/fisiologia , Hepacivirus/isolamento & purificação , Hepatite C/virologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Apoptose , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas de Ligação ao GTP/genética , Complexo de Golgi/virologia , Hepatite C/metabolismo , Hepatite C/patologia , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genéticaRESUMO
This paper explores the trajectories of Norwegians who, in their late-thirties, possessed financial assets, such as securities, company shares and stocks, qualifying them as the wealthiest one percent nationally. We describe the accumulation of financial wealth over a 25-year period in adulthood and study how different wealth sequences are linked to family origins and kinship ties. Although some Norwegians manage to build up large fortunes from relatively modest starting points over their life courses, we find that the value of the assets possessed by self-made individuals, and their ability to retain wealth over time, differ significantly to those based on dynastic lineage. Among the latter group, profound wealth early in adulthood and strategic positions in the economy add to propel exponential ownership of financial wealth from a young age and throughout adulthood. This chimes with C. Wright Mills' suggestion that the amassing of great fortunes is driven by two mechanisms of the big jump that enables initial asset build-up, and the accumulation of advantages that flows from advantageous economic and social ties. Kinship seems of key importance to ensure the efficacy of both mechanisms. Differences in the relationship of wealth accumulation and class origin seem to have little to do with educational strategies. We draw attention to direct wealth transfers and the institution of marriage as two little explored dimensions involved in dynastic closure.
Assuntos
Propriedade , Adulto , Humanos , NoruegaRESUMO
Ulcerative colitis is characterized by relapsing and remitting colonic mucosal inflammation. During the early stages of viral infection, innate immune defenses are activated, leading to the rapid release of cytokines and the subsequent initiation of downstream responses including inflammation. Previously, intestinal viruses were thought to be either detrimental or neutral to the host. However, persisting viruses may have a role as resident commensals and confer protective immunity during inflammation. On the other hand, the dysregulation of gut mucosal immune responses to viruses can trigger excessive, pathogenic inflammation. The purpose of this review is to discuss virus-induced innate immune responses that are at play in ulcerative colitis.
Assuntos
Colite Ulcerativa/patologia , Interações entre Hospedeiro e Microrganismos , Imunidade Inata/imunologia , Animais , Colite Ulcerativa/etiologia , HumanosRESUMO
This article explores the relationship between social class and educational achievement measured by grades among Norwegian law graduates over a span of 200 years. We argue that class inequalities may arise due to mechanisms favouring 'insiders', meaning students whose families have legal backgrounds. Alternatively, a broader category of students with origins in educated or elite families could also enjoy special advantages. Our results indicate that there were insignificant class inequalities in grades before the beginning of the 20th century, when they first appeared, and that class inequalities increased to some extent subsequently. Graduates with origins from families with legal backgrounds or origins in the cultural upper class tend to be awarded the highest grades and those with farming or working-class origins tend to be awarded the lowest grades. Inequalities according to class origin can be explained only to a limited extent by performance at secondary school. Unlike class origin, however, the impact of grades at secondary school appears to be highly stable over time. We ask whether mechanisms favouring legal 'insiders' may have become less important over time, whereas the impact of cultural capital may have increased.
Assuntos
Ocupações , Classe Social , Escolaridade , Humanos , Instituições Acadêmicas , EstudantesRESUMO
BACKGROUND: Studies have shown that terrorist attacks affect the mental and physical health of persons exposed to terrorism. When terror strikes at the workplace where people spend much time, and should feel safe, the health consequences for those affected might be severe. The aim of the study was to determine whether psychological and social work factors moderates effects of exposure to a workplace terrorist attack on subsequent doctor-certified sickness absence. METHODS: The study design combined survey data with register data on sickness absence. Data on exposure to the attack, and psychosocial working conditions were collected by a web-based questionnaire 10 months after the attack. Survey data was linked to registry data on doctor-certified sickness absence over the one-year time period following baseline. The survey response rate was 56% (n = 1974), where 80.6% (1591) gave consent to link survey data to data on sickness absence. Exposure to the attack was assessed as "Directly-", or "Indirectly exposed". Psychological and social work factors were measured by the General Questionnaire for Psychological and Social factors at Work (QPSNordic). Data were analyzed with negative binominal hurdle regressions. RESULTS: Direct exposure to the attack increased the odds of becoming sick-listed if role clarity was average (OR = 1.50) or high (OR = 2.13), but not if low (OR = 1.17). Direct exposure was associated with higher sickness absence rates if control over work pace was low (RR = 1.61). Role conflict, support from co-workers, and -superior showed weaker evidence of moderating effects of exposure on sickness absence. CONCLUSIONS: Exposure to the bomb explosion, as well as psychosocial working conditions affect the risk of employee sickness absence. Psychosocial working conditions seems to moderate effects of exposure to workplace terrorism on subsequent sickness absence. Organizations would benefit from striving for good psychological and social working conditions both as preventions against illness and sickness absence, and as measures in the aftermath of a workplace terrorist attack.
Assuntos
Exposição Ocupacional/estatística & dados numéricos , Licença Médica/estatística & dados numéricos , Terrorismo/psicologia , Local de Trabalho/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Inquéritos e QuestionáriosRESUMO
Positive-stranded RNA viruses, such as hepatitis C virus (HCV), assemble their viral replication complexes by remodeling host intracellular membranes to a membranous web. The precise composition of these replication complexes and the detailed mechanisms by which they are formed are incompletely understood. Here we show that the human immunity-related GTPase M (IRGM), known to contribute to autophagy, plays a previously unrecognized role in this process. We show that IRGM is localized at the Golgi apparatus and regulates the fragmentation of Golgi membranes in response to HCV infection, leading to colocalization of Golgi vesicles with replicating HCV. Our results show that IRGM controls phosphorylation of GBF1, a guanine nucleotide exchange factor for Arf-GTPases, which normally operates in Golgi membrane dynamics and vesicle coating in resting cells. We also find that HCV triggers IRGM-mediated phosphorylation of the early autophagy initiator ULK1, thereby providing mechanistic insight into the role of IRGM in HCV-mediated autophagy. Collectively, our results identify IRGM as a key Golgi-situated regulator that links intracellular membrane remodeling by autophagy and Golgi fragmentation with viral replication.
Assuntos
Autofagia , Proteínas de Ligação ao GTP/metabolismo , Complexo de Golgi/metabolismo , Hepacivirus/fisiologia , Membranas Intracelulares/metabolismo , Replicação Viral/fisiologia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Linhagem Celular Tumoral , Proteínas de Ligação ao GTP/genética , Complexo de Golgi/genética , Complexo de Golgi/virologia , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Membranas Intracelulares/virologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fosforilação/genéticaRESUMO
BACKGROUND: Little is known about whether and to what extent loneliness impacts the lives of people with visual impairment (VI). Thus, the aim of this study was to examine the prevalence of and factors associated with loneliness in adults with VI, and to examine its association with life satisfaction. METHODS: This cross-sectional interview study included a probability sample of 736 adults (≥18 years old) with VI who were members of the Norwegian Association of the Blind and Partially Sighted. The interviews took place from January to May 2017, collecting information about sociodemographics, VI characteristics, adverse life events, loneliness (Three Item Loneliness Scale), and life satisfaction (Cantril's Ladder of Life Satisfaction). The prevalence of loneliness was compared to data obtained from the general Norwegian population (N = 14,884; mean age 46.4 years; 50.7% females). RESULTS: The prevalence of moderate and severe loneliness in the VI population was 28.7% (95% CI: 25.4, 32.1) and 19.7% (95% CI: 16.9, 22.8), respectively. The rates were consistently higher across age groups compared to the general population. Loneliness was associated with younger age, blindness, having other impairments, unemployment, and a history of bullying or abuse. In addition, higher scores on loneliness were associated with lower levels of life satisfaction (fully adjusted ß = - 0.48, 95% CI: - 0.55, - 0.41). CONCLUSIONS: Loneliness is common in adults with VI. Strategies capable of reducing loneliness could improve life satisfaction among people who are blind or visually impaired.
Assuntos
Cegueira/psicologia , Solidão/psicologia , Qualidade de Vida/psicologia , Baixa Visão/psicologia , Pessoas com Deficiência Visual/psicologia , Adulto , Fatores Etários , Idoso , Cegueira/epidemiologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Satisfação Pessoal , Baixa Visão/epidemiologia , Adulto JovemRESUMO
OBJECTIVES: To estimate the rate of sick leave and sick leave diagnosis among employees before and after a work-place targeted terror attack, and to compare sick leave in subgroups of employees based on gender and trauma exposure. METHODS: Data on sick leave and diagnosis in ministerial employees from the period 3 years before to 3 years after the 2011 bombing in the governmental district of Oslo was retrieved from the Norwegian Social Insurance Administration Registries. RESULTS: Prior to the attack, sick leave was twice as high in women as in men. Compared to the period prior to the attack, sick leave increased the first year after the attack, for both women and men that were directly exposed to the event. Sick leave stabilized to the initial level 3 years after the incident. For indirectly exposed employees, i.e., those who were not present at the site of the attack, there was no significant increase in sick leave from before to after the attack. There were no statistical significant changes in diagnoses applied before and after the terrorist attack. However, there was a tendency towards an increase in sick leave due to psychological diagnoses among the directly exposed women. CONCLUSIONS: After a work-place terrorist attack a transient increase in sick leave may occur among employees who were present at the site of the attack. The increase may seem relatively modest and last for 1-3 years.
Assuntos
Exposição Ocupacional/efeitos adversos , Licença Médica/estatística & dados numéricos , Terrorismo/psicologia , Adulto , Idoso , Estudos de Coortes , Feminino , Empregados do Governo/estatística & dados numéricos , Humanos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Noruega/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Inquéritos e Questionários , Local de TrabalhoRESUMO
BACKGROUND: Umbilical hernia is one of the most prevalent congenital defect in pigs, causing economic losses and substantial animal welfare problems. Identification and implementation of genomic regions controlling umbilical hernia in breeding is of great interest to reduce incidences of hernia in commercial pig production. The aim of this study was to identify such regions and possibly identify causative variation affecting umbilical hernia in pigs. A case/control material consisting of 739 Norwegian Landrace pigs was collected and applied in a GWAS study with a genome-wide distributed panel of 60 K SNPs. Additionally candidate genes were sequenced to detect additional polymorphisms that were used for single SNP and haplotype association analyses in 453 of the pigs. RESULTS: The GWAS in this report detected a highly significant region affecting umbilical hernia around 50 Mb on SSC14 (P < 0.0001) explaining up to 8.6% of the phenotypic variance of the trait. The region is rather broad and includes 62 significant SNPs in high linkage disequilibrium with each other. Targeted sequencing of candidate genes within the region revealed polymorphisms within the Leukemia inhibitory factor (LIF) and Oncostatin M (OSM) that were significantly associated with umbilical hernia (P < 0.001). CONCLUSIONS: A highly significant QTL for umbilical hernia in Norwegian Landrace pigs was detected around 50 Mb on SSC14. Resequencing of candidate genes within the region revealed SNPs within LIF and OSM highly associated with the trait. However, because of extended LD within the region, studies in other populations and functional studies are needed to determine whether these variants are causal or not. Still without this knowledge, SNPs within the region can be used as genetic markers to reduce incidences of umbilical hernia in Norwegian Landrace pigs.
Assuntos
Estudo de Associação Genômica Ampla , Hérnia Umbilical/genética , Locos de Características Quantitativas/genética , Animais , Haplótipos , Polimorfismo de Nucleotídeo Único , SuínosRESUMO
OBJECTIVE: This study examined relationships between victimization from bullying and symptoms of posttraumatic stress (PTSS) after exposure to a terror attack at the workplace. It was hypothesized that (1) victims of bullying report higher and more stable levels of PTSS over time compared to their non-bullied colleagues and (2) that PTSS provides an increased risk of subsequent victimization from bullying. METHODS: The hypotheses were tested in a two-wave prospective sample comprising 2337 employees from Norwegian governmental ministries who were exposed to the 2011 Oslo terror attack. The two waves of data collection were conducted 10 and 22 months after the terror attack. RESULTS: Hypothesis 1 was partially supported: victims of bullying reported significantly higher levels of PTSS than non-bullied employees at both measurement points, but bullying was not related to the stability in PTSS over time. In support of hypothesis 2, PTSS at 10 months was significantly associated with an increased risk of feeling victimized by bullying 1 year later. CONCLUSIONS: The results indicate that victimization from bullying is associated with elevated levels of PTSS in the aftermath of a workplace terror attack, but that bullying does not have any impact on the long-term development of PTSS. PTSS may be a potential antecedent of bullying. These findings suggest that organizations must give high priority to the psychosocial work environment of traumatized employees to prevent further detrimental health consequences.
Assuntos
Bullying , Vítimas de Crime/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Terrorismo/psicologia , Local de Trabalho/psicologia , Adulto , Idoso , Bullying/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Questionário de Saúde do Paciente , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Adulto JovemRESUMO
Prospective studies describing and predicting individual differences in the course of posttraumatic stress symptoms (PTSS) after disasters are scarce. The present study aimed to describe and predict individual differences in both the level and the rate of change in PTSS after the 2011 Oslo bombing, a terrorist attack directed at the Norwegian government. Survey data from ministerial employees (N = 256) were collected 10, 22, and 34 months after the bombing. We used latent growth modeling to examine the development of PTSS, and to identify the strength of predictor variables. High exposure, female sex, and high levels of neuroticism were associated with higher levels of PTSS 10 months after the traumatic event (ß ranged from .25 to .30, p < .001), whereas social support was associated with lower levels of PTSS (ß = -.30, p < .001). The combination of being female and high in neuroticism was associated with a faster decline in PTSS (ß range: -.20 to -.39, p = .010 < .05). High exposure seemed to have a lasting influence by maintaining high levels of PTSS. Our findings suggested that being female, being highly exposed, and having low levels of social support were risk markers for enduring PTSS.
Assuntos
Exposição à Violência/psicologia , Neuroticismo , Apoio Social , Transtornos de Estresse Pós-Traumáticos/etiologia , Terrorismo/psicologia , Bombas (Dispositivos Explosivos) , Explosões , Feminino , Inquéritos Epidemiológicos , Humanos , Individualidade , Masculino , Saúde Mental , Noruega , Fatores de Risco , Fatores Sexuais , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Avaliação de Sintomas , Fatores de TempoRESUMO
Thyroid hormones (triiodothyronine, T3; and thyroxine, T4) play significant roles in development, metamorphosis, metabolism, homeostasis, cellular proliferation, and differentiation, for which the effects are mediated through thyroid hormone receptors (TRα and TRß). Similarly, the insulin-like growth factor (IGF) is involved in growth and development through regulation of somatic growth. This study was designed to examine the effects of the dioxin-like 3,3',4,4'-tetrachlorobiphenyl (PCB-77) on responses related to growth and thyroid hormone system in eyed eggs and yolk-sac larvae of Atlantic salmon. Salmon eggs were continuously exposed to two waterborne concentrations of PCB-77 (1 or 10 ng/L) over a period of 50 d covering hatching and through yolk-sac absorption stages. Sampling was performed regularly throughout the exposure period and at different time intervals. Gene expression patterns were performed on whole-body homogenate at age 500, 548, 632, 674, and 716 dd (dd: day degrees) using quantitative polymerase chain reaction (PCR). Total T3 (TT3) and total T4 (TT4) were measured using radioimmunoassay (RIA). Data showed that 10 ng PCB-77 increased dioiodinase 2 (Dio2) at 500 dd and both PCB-77 concentrations decreased dio2 expression at 548 dd. PCB-77 elevated cellular TT3 at 500 dd and was lowered at 548 dd only at 10 ng. Otherwise, time-related reduction was not affected by PCB-77 exposure as observed for the rest of the exposure period. For TT4, 1 ng PCB-77 produced a rise at 500 dd, and an apparent concentration decrease at 548 dd, before a total inhibition at 632 dd. The IGF-1 and IGF-1R were variably affected by PCB-77. For IGF-2, PCB-77 produced a concentration-dependent increase at 548 dd, and thereafter an elevation (1 ng) and fall (10 ng) at 632 dd. TRß mRNA demonstrated PCB-77 related increases during the exposure period, and this effect returned to control levels at 716 dd. For TRα, a rise was noted only after exposure to 10 ng PCB-77 at 500 dd. Overall, the present study demonstrates some possible growth and developmental consequences following exposure to PCB-77 during early life stages of Atlantic salmon.
Assuntos
Exposição Ambiental/análise , Bifenilos Policlorados/toxicidade , Salmo salar/crescimento & desenvolvimento , Glândula Tireoide/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Proliferação de Células/efeitos dos fármacos , Expressão Gênica , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Óvulo/efeitos dos fármacos , Óvulo/crescimento & desenvolvimento , Radioimunoensaio , Reação em Cadeia da Polimerase em Tempo Real , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismoRESUMO
BACKGROUND: Experiencing potentially traumatic events is associated with psychological distress. However, some survivors also experience positive personal and psychological changes in the aftermath of trauma. METHODS: The present study investigated perceived posttraumatic growth in 197 ministerial employees who were present at work during the 2011 Oslo bombing attack. The relationships between trauma-exposure, peritraumatic reactions and posttraumatic growth were studied. Moreover, the adaptive significance of posttraumatic growth was addressed. RESULTS: The results showed that higher levels of trauma-exposure and immediate reactions were significantly related to perceived posttraumatic growth. No support for an adaptive significance of posttraumatic growth was found. On the contrary, posttraumatic growth was associated with higher symptom levels of posttraumatic stress. After adjusting for posttraumatic stress symptoms no association was found between perceived growth and work and social adjustment. However, perceived growth was associated with higher levels of life satisfaction. CONCLUSION: The present results are in line with previous findings indicating that perceived growth may be unrelated to psychological adjustment, and suggest that the concept and significance of posttraumatic growth should be interpreted with caution.
Assuntos
Adaptação Psicológica , Explosões , Transtornos de Estresse Pós-Traumáticos/psicologia , Terrorismo/psicologia , Adulto , Feminino , Humanos , Modelos Lineares , Masculino , Noruega , Inquéritos e QuestionáriosRESUMO
There are many unanswered questions regarding responses to proinflammatory signals in intestinal epithelial cells (IECs). For example, chemokines secreted by IECs upon external stimuli play multifunctional roles in both homeostasis and during inflammation. Several chemokines are upregulated during active inflammatory bowel disease (IBD), which is associated with an increased influx of immune cells into the gut mucosa. Therefore, studies on how chemokines are regulated in the intestinal epithelium may identify putative treatment targets in IBD. More recently, patient-derived ex vivo models such as intestinal organoids have facilitated molecular analysis of epithelial alterations in IBD patients own cells. Here, we describe refined experimental protocols and methods for the generation and maintenance of IBD patient-derived colonic organoids (colonoids) culture. We also give detailed description of medium, and supplements needed for colonoid establishment, growth, and differentiation, including production of Wnt-3A and Rspondin1 enriched media. Further, we present protocols for RNA and protein isolation from human colonoids, and subsequent gene expression analysis and Western blotting for e.g., signal transduction studies. We also describe how to process colonoids for chemokine protein expression analysis such as immunostaining, confocal imaging, and detection of secreted chemokines by e.g., enzyme-linked immunosorbent assay (ELISA). As proof of principle, we give examples of how the chemoattractant CCL20 can be regulated and expressed in colonoids derived from IBD-patients and healthy controls upon ligands-driven inflammation.
Assuntos
Colo , Doenças Inflamatórias Intestinais , Humanos , Colo/metabolismo , Células Epiteliais/metabolismo , Organoides , Inflamação/metabolismoRESUMO
Major Histocompatibility Complex (MHC)-I and -II genes are upregulated in intestinal epithelial cells (IECs) during active inflammatory bowel diseases (IBD), but little is known about how IBD-relevant pro-inflammatory signals and IBD drugs can regulate their expression. We have previously shown that the synthetic analog of double-stranded RNA (dsRNA) Polyinosinic:polycytidylic acid (Poly(I:C)), induces interferon stimulated genes (ISGs) in colon organoids (colonoids). These ISGs may be involved in the induction of antigen presentation. In the present study, we applied colonoids derived from non-IBD controls and ulcerative colitis patients to identify induction and effects of IBD-drugs on antigen presentation in IECs in the context of Tumor Necrosis Factor (TNF)-driven inflammation. By RNA sequencing, we show that a combination of TNF and Poly(I:C) strongly induced antigen-presentation gene signatures in colonoids, including expression of MHC-II genes. MHC-I and -II protein expression was confirmed by immunoblotting and immunofluorescence. TNF+Poly(I:C)-dependent upregulation of MHC-II expression was associated with increased expression of Janus Kinases JAK1/2 as well as increased activation of transcription factor Signal transducer and activator of transcription 1 (STAT1). Accordingly, pre-treatment of colonoids with IBD-approved pan-Janus Kinase (JAK) inhibitor Tofacitinib led to the downregulation of TNF+Poly(I:C)-dependent MHC-II expression associated with the abrogation of STAT1 activation. Pre-treatment with corticosteroid Budesonide, commonly used in IBD, did not alter MHC-II expression. Collectively, our results identify a regulatory role for IBD-relevant pro-inflammatory signals on MHC-II expression that is influenced by Tofacitinib.
Assuntos
Doenças Inflamatórias Intestinais , Inibidores de Janus Quinases , Colo/patologia , Epitélio/metabolismo , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Inibidores de Janus Quinases/uso terapêutico , Complexo Principal de Histocompatibilidade , Piperidinas , Poli I-C/farmacologia , Poli I-C/uso terapêutico , Pirimidinas , Fator de Necrose Tumoral alfa/uso terapêuticoRESUMO
BACKGROUND: Boar taint is observed in a high proportion of uncastrated male pigs and is characterized by an unpleasant odor/flavor in cooked meat, primarily caused by elevated levels of androstenone and skatole. Androstenone is a steroid produced in the testis in parallel with biosynthesis of other sex steroids like testosterone and estrogens. This represents a challenge when performing selection against androstenone in breeding programs, without simultaneously decreasing levels of other steroids. The aim of this study was to use high-density genome wide association (GWA) in combination with linkage disequilibrium-linkage analysis (LDLA) to identify quantitative trait loci (QTL) associated with boar taint compounds and related sex steroids in commercial Landrace (n = 1,251) and Duroc (n = 918) breeds. RESULTS: Altogether, 14 genome wide significant (GWS) QTL regions for androstenone in subcutaneous fat were obtained from the LDLA study in Landrace and 14 GWS QTL regions in Duroc. LDLA analysis revealed that 7 of these QTL regions, located on SSC 1, 2, 3, 7 and 15, were obtained in both breeds. All 14 GWS androstenone QTLs in Landrace are also affecting the estrogens at chromosome wise significance (CWS) or GWS levels, while in Duroc, 3 of the 14 QTLs affect androstenone without affecting any of the estrogens. For skatole, 10 and 4 QTLs were GWS in the LDLA analysis for Landrace and Duroc respectively, with 4 of these detected in both breeds. The GWS QTLs for skatole obtained by LDLA are located at SSC 1, 5, 6, 7, 10, 11, 13 and 14. CONCLUSION: This is the first report applying the Porcine 60 K SNP array for simultaneous analysis of boar taint compounds and related sex hormones, using both GWA and LDLA approaches. Several QTLs are involved in regulation of androstenone and skatole, and most of the QTLs for androstenone are also affecting the levels of estrogens. Seven QTLs for androstenone were detected in one breed and confirmed in the other, i.e. in an independent sample, although the majority of QTLs are breed specific. Most QTLs for skatole do not negatively affect other sex hormones and should be easier to implement into the breeding scheme.
Assuntos
Ligação Genética , Estudo de Associação Genômica Ampla , Hormônios Esteroides Gonadais/genética , Desequilíbrio de Ligação , Locos de Características Quantitativas , Suínos/genética , Androstenos/metabolismo , Animais , Cruzamento , Genoma , Masculino , Carne/normas , Polimorfismo de Nucleotídeo Único , Escatol/metabolismoRESUMO
BACKGROUND: Knowledge about self-efficacy and its significance for the quality of life of people with visual impairment is lacking. The aims of the study were to compare general self-efficacy in individuals with visual impairment with the general population, and to investigate the association between self-efficacy and life satisfaction. METHODS: A telephone-based cross-sectional survey was conducted between January and May 2017 in a probability sample of adults who were members of the Norwegian Association of the Blind and Partially Sighted. Participants were asked questions about their sociodemographic characteristics, characteristics of vision loss, general self-efficacy (General Self-efficacy Scale), and life satisfaction (Cantril's Ladder of Life Satisfaction). We obtained norm data from a representative survey of the general Norwegian population (N = 1792; mean age 53.2 years; 52.5% females). RESULTS: People with visual impairment had higher levels of general self-efficacy than people in the general population (Mean: 31.5 versus 29.0, p < .001). Results from linear regression analyses of the visual impairment population showed that higher education and residential in an urban municipality were associated with higher self-efficacy. Having additional impairments and a previous history of physical or sexual assaults were associated with lower self-efficacy. A linear dose-response relationship was found between self-efficacy and life satisfaction, in the visual impairment population as well as in the general population. CONCLUSIONS: People with visual impairment have higher self-efficacy than people in the general population, possibly due to extensive mastery experience in how to handle life as visually impaired. Self-efficacy seems to be important in achieving the best possible life.
Assuntos
Autoeficácia , Pessoas com Deficiência Visual/psicologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Satisfação Pessoal , Análise de Regressão , Adulto JovemRESUMO
The psychosocial work environment is of great importance for regaining health and productivity after a workplace disaster. Still, there is a lack of knowledge about the impact of a disaster on the psychosocial work environment. The purpose of this study was to examine whether employees' perceptions of role clarity, role conflicts, and predictability in their work situation changed from before to after a workplace terrorist attack. We combined data from two prospective work environment surveys of employees in three governmental ministries that were the target of the 2011 Oslo terrorist attack. A first two-wave survey was conducted 4-5 years and 2-3 years before the attack, and a second three-wave survey took place 10 months, 2 years, and 3 years after the attack. Of 504 individuals who were employed at the time of the bombing, 220 were employed in both pre- and post-disaster periods, participated in both the first and the second survey, and consented to the linking of data from the two surveys. We found no significant changes in levels of role clarity, role conflict, and predictability from before to after the terrorist attack. Adjusting for sex, age and education had no effect on the results. The findings suggest that perceptions of the psychosocial working environment are likely to be maintained at previous levels in the aftermath of a workplace disaster. Considering the importance of the psychosocial work environment for regaining health and productivity, the findings are important for the preparation for, and management of, future crises.