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We investigated the basic characteristics of a new murine cytomegalovirus (MCMV) vector platform. Using BAC technology, we engineered replication-competent recombinant MCMVs with deletions of up to 26% of the wild-type genome. To this end, we targeted five gene blocks (m01-m17, m106-m109, m129-m141, m144-m158, and m159-m170). BACs featuring deletions from 18% to 26% of the wild-type genome exhibited delayed virus reconstitution, while smaller deletions (up to 16%) demonstrated reconstitution kinetics similar to those of the wild type. Utilizing an innovative methodology, we introduced large genomic DNA segments, up to 35 kbp, along with reporter genes into a newly designed vector with a potential cloning capacity of 46 kbp (Q4). Surprisingly, the insertion of diverse foreign DNAs alleviated the delayed plaque formation phenotype of Q4, and these large inserts remained stable through serial in vitro passages. With reporter-gene-expressing recombinant MCMVs, we successfully transduced not only mouse cell lines but also non-rodent mammalian cells, including those of human, monkey, bovine, and bat origin. Remarkably, even non-mammalian cell lines derived from chickens exhibited successful transduction.
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Introduction: Mental health services have transitioned from treating symptoms to emphasizing personal recovery. Despite its importance, integrating personal recovery into clinical practice remains work in progress. This study evaluates the psychometric qualities of the Brief INSPIRE-O, a five-item patient-reported outcome measure assessing personal recovery. Method: The study collected data from 2018 to 2020 at the Mental Health Services, Capital Region of Denmark, using an internet-based system examining 8,192 non-psychotic patients - receiving outpatient treatment. Materials: This study evaluated the Brief INSPIRE-O and used measures of symptomatology (SCL-10), well-being (WHO-5), and social functioning (modified SDS). Results: The study population comprised 76.8% females with a mean age of 32.9 years, and diagnoses included anxiety (28%), depression (34%), and personality disorder (19%). The mean Brief INSPIRE-O score (39.9) was lower than the general population norm (71.1). The Brief INSPIRE-O showed acceptable test-retest reliability (0.75), scalability (0.39), and internal consistency (0.73). Correlations with other mental health criteria were in the expected direction for symptomatology (-0.46), well-being (0.60), and social functioning (-0.43) and remained consistent across diagnoses. Discussion: The Brief INSPIRE-O demonstrated strong psychometric qualities and could be recommended as a measure of personal recovery for use in both research and clinical practice. Its strong theoretical basis and short completion time make it suitable for use for research. Incorporating Brief INSPIRE-O into clinical assessment will further support the process of mental health systems re-orientating towards personal recovery.
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BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood psychiatric disorder with severe and lifelong impact on mental health and socioeconomic achievements. Environmental factors may play a role in the increasing incidens rates. Previous studies on associations between prenatal and childhood exposure to organophosphate and pyrethroid insecticides and ADHD symptoms have yielded mixed findings. OBJECTIVES: To investigate associations between prenatal and childhood exposure to chlorpyrifos and pyrethroids and ADHD symptoms in 5-year-old children from the Odense Child Cohort. METHODS: Spot urine samples from pregnant women in gestational week 28 (n = 614) and offspring at 5 years of age (n = 814) were collected and analyzed for the specific metabolite of chlorpyrifos, TCPY (3,5,6-trichloro-2-pyridinol), as well as the generic pyrethroid metabolite, 3-PBA (3-phenoxybenzoic acid). Offspring ADHD symptoms were assessed at age 5 years using the parent reported "ADHD scale" from the "Child Behavior Checklist 1½-5" (n = 1114). Associations between insecticide exposure variables and an ADHD score ≥90th percentile were analyzed using logistic regression for all children and stratified by sex. RESULTS: Most pregnant women had detectable concentrations of 3-PBA (93%) and TCPY (91%) with median concentrations of 0.20 µg/L and 1.62 µg/L, respectively. In children, 3-PBA and TCPY concentrations were detectable in 88% and 82% of the samples, and the median concentrations were 0.17 and 1.16 µg/L. No statistically significant associations were observed between insecticide metabolites and an ADHD score ≥90th percentile at age 5. CONCLUSION: In this relatively large Danish birth cohort study with mainly low dietary insecticide exposure, we found no statistically significant associations between prenatal or childhood exposure to chlorpyrifos or pyrethroids, and excess ADHD-symptom load, in 5-year-old children. Prospective studies with multiple urine samples across vulnerable windows of neurodevelopment is warranted to improve assessment of safe exposure levels, which is particularly relevant for pyrethroids, since their use is increasing.
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Transtorno do Deficit de Atenção com Hiperatividade , Clorpirifos , Inseticidas , Efeitos Tardios da Exposição Pré-Natal , Piretrinas , Humanos , Feminino , Pré-Escolar , Gravidez , Criança , Clorpirifos/toxicidade , Clorpirifos/urina , Inseticidas/toxicidade , Inseticidas/urina , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Piretrinas/toxicidade , Piretrinas/urina , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologiaRESUMO
Introduction: Impaired quality of life (QoL) and premature death in patients with primary non-affective psychotic disorders is related to lifestyle-induced comorbidities. Current municipal health-promoting treatment and care do not embrace the challenges of living with psychotic disorders. Aim: This cross-sectional study aimed to identify the proportion of outpatients diagnosed with primary psychotic disorders who need health-promoting treatment and care, and who receive municipal health-promoting interventions. Methods: Of 206 eligible invited outpatients from three psychiatric services clinics in Southern Denmark, 165 participated. Demographic and health characteristics, and use of alcohol, cannabis, drugs, and cigarettes were identified via a screening tool. Blood test information, body measurements, and medication status were extracted from the outpatients' medical records. The need for health promotion was assessed based on body mass index (BMI), and use of alcohol, cannabis, drugs, and cigarettes. Results: Seventy-three percent of outpatients needed health promotion, of whom 61 % were not offered municipal health-promoting treatment and care. Thirty-six percent had one or more somatic comorbidities, including diabetes mellitus (15 %) and cardiovascular disease (10 %); 41 % smoked a mean (SD) of 19 (10) cigarettes daily. Mean (SD) BMI was 34 (8) kg/m2 for women and 29 (7) kg/m2 for men. Conclusion: The majority of outpatients with non-affective psychotic disorders need health-promoting interventions, but only about 40 % of these patients receive such municipal health-promoting treatment and care. Future studies should clarify the impact of these interventions on the health status, QoL, and life expectancy of these patients.
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PURPOSE: Severe malnourishment may reduce cognitive performance in anorexia nervosa (AN). We studied cognitive functioning during intensive nutritional and medical stabilization in patients with severe or extreme AN and investigated associations between weight gain and cognitive improvement. METHODS: A few days after admission to a specialized hospital unit, 33 patients with severe or extreme AN, aged 16-42 years, completed assessments of memory, cognitive flexibility, processing speed, and attention. Mean hospitalization was 6 weeks. Patients completed the same assessments at discharge (n = 22) following somatic stabilization and follow-up up to 6 months after discharge (n = 18). RESULTS: The patients displayed normal cognitive performance at admission compared to normative data. During nutritional stabilization, body weight increased (mean: 11.3%; range 2.6-22.2%) and memory, attention, and processing speed improved (p values: ≤ 0.0002). No relationship between weight gain and cognitive improvement was observed at discharge or follow-up. CONCLUSIONS: Cognitive performance at hospital admission was normal in patients with severe or extreme AN and improved during treatment although without association to weight gain. Based on these results, which are in line with previous studies, patients with severe or extreme AN need not be excluded from cognitively demanding tasks, possibly including psychotherapy. As patients may have other symptoms that interfere with psychotherapy, future research could investigate cognitive functioning in everyday life in patients with severe AN. TRIAL REGISTRATION NUMBER: The study is registered at clinicaltrials.gov (NCT02502617). LEVEL OF EVIDENCE: Level III, cohort study.
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Anorexia Nervosa , Humanos , Anorexia Nervosa/complicações , Anorexia Nervosa/terapia , Anorexia Nervosa/diagnóstico , Estudos de Coortes , Peso Corporal , Aumento de Peso , CogniçãoRESUMO
BACKGROUND: Hospital visits constitute a 'window of opportunity' for initiating smoking cessation attempts, and healthcare providers (HCPs) play an important role in supporting patients to stop smoking. Yet, the current practices of supporting smoking cessation in the hospital setting are largely unexplored. The aim of this study was to explore practices of smoking cessation support among hospital-based HCPs. METHODS: HCPs working in a large hospital in the secondary care sector completed an online, cross-sectional survey, including sociodemographic and work-related factors as well as 21 questions assessing practices of smoking cessation support based on the "five As" framework. Descriptive statistics were computed, and predictors of HCPs giving patients advice to stop smoking were explored using logistic regression analysis. RESULTS: All employees (N = 3998) in the hospital received a survey link; 1645 (41.1%) HCPs with daily patient contact completed the survey. Smoking cessation support in the hospital setting was limited with regard to assessment of smoking; providing information and advice; planning and referral for further support; and follow-up on smoking cessation attempts. Almost half (44.8%) of participating HCPs with daily patient contact never or rarely advise their patients to stop smoking. Physicians were more likely than nurses to advice patients to stop smoking, and HCPs in outpatient clinics were more likely to give advice than inpatient clinic HCPs. CONCLUSION: Smoking cessation support is very limited in the hospital-based healthcare setting. This is problematic, as hospital visits can be windows of opportunity to help patients change their health behaviour. An intensified focus on the implementation of hospital-based smoking cessation support is needed.
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Abandono do Hábito de Fumar , Humanos , Estudos Transversais , Pessoal de Saúde , Hospitais , Atenção à SaúdeRESUMO
Advances in diagnostics and treatment of childhood cancer during the past few decades have substantially increased survival, resulting in a growing population of survivors of childhood cancer. Somatic and mental late effects of the cancer and the treatment may impact the quality of life (QoL). Previous reviews of QoL in survivors of childhood cancer have shown contradictory findings across studies and the majority of studies included have been based on data from North America and may not be directly comparable to a European setting. The aim of our study was to critically evaluate and summarise the latest evidence on the QoL of childhood cancer survivors in Europe and to identify survivors at particular risk. The eligible studies were published between 2008 and 2022, conducted in Europe and included participants who had survived at least 5 years after diagnosis of a childhood cancer. The main outcome of interest was QoL of survivors which was measured with validated qualitative and quantitative QoL questionnaires. A systematic literature search conducted in PubMed, EMBASE, PsycINFO and CINALH resulted in inclusion of 36 articles with a total of 14 342 survivors of childhood cancer. The majority of included studies found that childhood cancer survivors reported poorer QoL than comparisons. Female gender, treatment with haematopoietic stem cell transplantation and a brain tumour diagnosis were associated with lower QoL. With a growing population of childhood cancer survivors with many years ahead of them, targeted interventions and optimal follow-up care are important to improve the QoL of survivors.
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Neoplasias Encefálicas , Sobreviventes de Câncer , Adulto , Criança , Humanos , Feminino , Adolescente , Qualidade de Vida , Sobreviventes , Europa (Continente)/epidemiologiaRESUMO
Fetal androgen exposure may be associated with autism spectrum disorder (ASD). We studied 1777 mother-child pairs in the prospective Odense Child Cohort. Prenatal androgen exposure was assessed by maternal 3rd trimester testosterone concentrations, maternal polycystic ovary syndrome (PCOS), and 3 months offspring anogenital distance. ASD traits were assessed at age 3 years with the ASD-symptom scale of the Child Behavior Checklist for ages 1½-5 years. Maternal testosterone was positively associated with traits of ASD in boys (p < 0.05). Maternal PCOS was associated with increased offspring ASD traits (p = 0.046), but became non-significant after excluding parental psychiatric diagnosis. Offspring anogenital distance was not linked to ASD traits. Higher prevalence of ASD in boys could be linked to higher susceptibility to fetal androgen exposure.
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Transtorno do Espectro Autista , Síndrome do Ovário Policístico , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Masculino , Feminino , Humanos , Pré-Escolar , Androgênios , Transtorno do Espectro Autista/epidemiologia , Estudos Prospectivos , Testosterona , Síndrome do Ovário Policístico/complicaçõesRESUMO
OBJECTIVES: Patients with personality disorders (PDs) are often treated with non-manualized psychodynamic group therapy (PDT) lasting for several years. Non-manualized PDT often combines a variety of therapeutic approaches from different PDT traditions, including mentalization-based therapy. Currently, little is known about the effect of this long-term, costly treatment. This study investigated the extent to which patients with different PDs benefit from mentalization-oriented PDT as it is implemented in clinical practice in terms of symptom severity, interpersonal problems, and general functioning. METHODS: The design was a naturalistic, prospective cohort study. Seventy-five consecutive PD patients were assessed before treatment with the Symptom Checklist-90 Revised (SCL-90-R) as the primary outcome measure and the Inventory of Interpersonal Problems (IIP) and Global Assessment of Functioning (GAF) as secondary outcome measures. The sample was repeatedly assessed every 12 months for up to 36 months. Paired t-tests were applied to examine the effectiveness of the intervention. RESULTS: Among completers (n = 42; 56%), improvement was observed on the SCL-90-R: Global Severity Index (mean change = -0.45 [95% CI = -0.72, -0.19]; Cohen's d = -0.55), Positive Symptom Distress Index (-0.40 [-0.63, -0.17]; -0.56); Positive Symptoms Total (-10.70 [-17.31, -4.09]; -0.52). Secondary outcomes also improved: IIP-total (mean change = -0.50 [95%CI = -0.74, -0.25]; Cohen's d = -0.66); GAF-Functioning (8.79 [6.32, 11.27]; 1.15); and GAF-Symptoms (10.67 [8.09, 13.25]; 1.34). CONCLUSIONS: Completers improved on symptom severity, interpersonal problems, and general functioning, with within-group effect sizes ranging from medium to large. Approximately half the sample dropped out, suggesting that mentalization-oriented PDT spanning several years may be unrealistic for many patients with PD. Significant outcomesThere are no clear guidelines for psychological interventions targeting personality disorders (PDs), and currently eclectic and non-manualized psychodynamic approaches lasting for up to 3 years are prevailing in some clinical practices.Although this treatment approach may have an effect on compliant patients, the high drop-out rate indicates that it may not be suitable for a large proportion of PD patients since it requires long-term commitment. Furthermore, it is difficult to identify the content of the non-manualized psychodynamic therapy and what helps the patients.More specific clinical guidelines emphasizing the application of evidence-based treatments or at least manualized treatments are warranted for the treatment of emotionally unstable PDs and other PDs. LimitationsThe naturalistic study design, without any control group, limits conclusions about mechanisms of action of the intervention.Since the intervention was not manualized, it is unknown exactly which treatment was actually administered, which reduces external validity.The outcomes are based on completer data of a relatively small sample size with high drop-out rate.
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Mentalização , Psicoterapia de Grupo , Psicoterapia Psicodinâmica , Humanos , Estudos Prospectivos , Transtornos da Personalidade/psicologia , Resultado do TratamentoRESUMO
Objective: Lack of motivation is widely acknowledged as a significant factor in treatment discontinuity and poor treatment outcomes in eating disorders. Treatment adherence is lower in internet-based treatment. The current study aimed to assess the relationship between treatment motivation and treatment outcomes in an internet-based therapist-guided intervention for Binge Eating Disorder (BED). Method: Adults (N = 153) with mild to moderate symptoms of BED participated in a 10-session internet-based treatment program. Baseline and between-session scores of "Readiness to change" and "Belief in change" were used to predict treatment completion and eating disorder symptom reduction (EDE-Q Global, BED-Q, and weekly number of binge eating episodes) at post-treatment. Results: Baseline treatment motivation could not predict treatment completion or symptom reduction. Early measures of treatment motivation (regression slope from sessions 1-5) significantly predicted both treatment completion and post-treatment symptom reduction. "Belief in change" was the strongest predictor for completing treatment (OR = 2.18, 95%-CI: 1.06, 4.46) and reducing symptoms (EDE-Q Global: B = -0.53, p = 0.001; number of weekly binge eating episodes: B = 0.81, p < 0.01). Discussion: The results indicated that patients entering online treatment for BED feel highly motivated. However, baseline treatment motivation could not significantly predict treatment completion, which contradicts previous research. The significant predictive ability of early measures of treatment motivation supports the clinical relevance of monitoring the development of early changes to tailor and optimize individual patient care. Further research is needed to examine treatment motivation in regard to internet-based treatment for BED with more validated measures.
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Rift Valley fever (RVF) is a zoonotic and emerging disease, caused by the RVF virus (RVFV). In ruminants, it leads to "abortion storms" and enhanced mortality rates in young animals, whereas in humans it can cause symptoms like severe hemorrhagic fever or encephalitis. The role of the innate and adaptive immune response in disease initiation and progression is still poorly defined. The present study used the attenuated RVFV strain clone 13 to investigate viral spread, tissue tropism, and histopathological lesions after intranasal infection in C57BL/6 wild type (WT) and type I interferon (IFN-I) receptor I knockout (IFNAR-/-) mice. In WT mice, 104 PFU RVFV (high dose) resulted in a fatal encephalitis, but no hepatitis 7-11 days post infection (dpi), whereas 103 PFU RVFV (low dose) did not cause clinical disease or significant histopathological lesions in liver and the central nervous system (CNS). In contrast, IFNAR-/- mice infected with 103 PFU RVFV developed hepatocellular necrosis resulting in death at 2-5 dpi and lacked encephalitis. These results show that IFNAR signaling prevents systemic spread of the attenuated RVFV strain clone 13, but not the dissemination to the CNS and subsequent fatal disease. Consequently, neurotropic viruses may be able to evade antiviral IFN-I signaling pathways by using the transneuronal instead of the hematogenous route.
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Carcinoma Hepatocelular , Encefalite , Interferon Tipo I , Neoplasias Hepáticas , Vírus da Febre do Vale do Rift , Humanos , Animais , Camundongos , Vírus da Febre do Vale do Rift/genética , Receptor de Interferon alfa e beta/genética , Camundongos Endogâmicos C57BL , Antivirais , NecroseRESUMO
Introduction: While online consultations have shown promise to be a means for the effective delivery of high-quality mental healthcare and the first implementations of these digital therapeutic contacts go back nearly two decades, uptake has remained limited over the years. The onset of the COVID-19 pandemic dramatically altered this relative standstill and created a unique turning point, with a massive amount of both professionals and clients having first hands-on experiences with technology in mental healthcare. Objective: The current study aimed to document the uptake of online consultations and explore if specific characteristics of mental health professionals across and beyond Europe could predict this. Methods: An international survey was designed to assess mental health professionals' (initial) experiences with online consultations at the onset of the pandemic: their willingness to make use of them and their prior and current experiences, alongside several personal characteristics. Logistic mixed-effects models were used to identify predictors of the use of online consultations, personal experience with this modality, and the sense of telepresence. Results: A total of 9115 healthcare professionals from 73 countries participated of which about two-thirds used online consultations during the initial COVID-19 outbreak. The current study identifies multiple determinants relating to the use and experience of online consultations, including the professionals' age, experience with the technology before the outbreak, the professional context, and training. Conclusions: Despite strong evidence supporting the relevance of training in digital mental health, this is clearly still lacking. Nevertheless, the COVID-19 pandemic presented a first, and potentially transformative, experience with online consultations for many healthcare professionals. The insights from this study can help support professionals and, importantly, (mental) healthcare organisations to create optimal circumstances for selective and high-quality continued use of online consultations.
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Introduction: Depression and anxiety are well-known comorbid conditions in patients with anorexia nervosa (AN). Hypercortisolemia in patients with AN may be pathogenic and contribute to depression and anxiety symptomatology. Objective: The aim of this study was to investigate short-term changes in cortisol levels and depression and anxiety symptomatology following intensive re-nutrition in patients with severe AN and hospitalized in a specialized unit. Furthermore, we investigated the potential association between cortisol levels and psychometric parameters. Methods: A total of 36 patients with AN were enrolled in the study. Nine dropped out before follow-up. Patients underwent paraclinical and psychometric examinations at admission and discharge. Measurements included plasma cortisol, cortisol binding globulin (CBG), 24-h urine cortisol, and self-report questionnaires regarding eating disorder, depression, anxiety, and stress symptoms. Patients were hospitalized in the unit for somatic stabilization and intensive re-nutrition. Mean admission length was 41 days. The study was registered at ClinicalTrials.gov (NCT02502617). Results: Cortisol levels in blood and urine did not change from admission to discharge in patients with severe AN. Symptoms of depression, anxiety, stress, and eating disorder remained elevated at discharge. There were no associations between changes in cortisol levels and changes in psychometrics. Discussion: Our results suggest that short-term intensive re-nutrition did not alter hypothalamic-pituitary-adrenal axis activity or mental health in patients with severe AN. Long-term stabilization and longer follow-up after hospital discharge may be needed to detect changes in cortisol levels and whether these changes are associated with depression and anxiety symptomatology. Greater knowledge about cortisol levels and mental health in patients with severe AN may help in the development of new treatment choices for the chronically ill patients. Future studies could investigate whether cortisol-lowering drugs have a therapeutic effect on mental health in AN.
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Beauvericin (BEA), a mycotoxin of the enniatin family produced by various toxigenic fungi, has been attributed multiple biological activities such as anti-cancer, anti-inflammatory, and anti-microbial functions. However, effects of BEA on dendritic cells remain unknown so far. Here, we identified effects of BEA on murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-cultured bone marrow derived dendritic cells (BMDCs) and the underlying molecular mechanisms. BEA potently activates BMDCs as signified by elevated IL-12 and CD86 expression. Multiplex immunoassays performed on myeloid differentiation primary response 88 (MyD88) and toll/interleukin-1 receptor (TIR) domain containing adaptor inducing interferon beta (TRIF) single or double deficient BMDCs indicate that BEA induces inflammatory cytokine and chemokine production in a MyD88/TRIF dependent manner. Furthermore, we found that BEA was not able to induce IL-12 or IFNß production in Toll-like receptor 4 (Tlr4)-deficient BMDCs, whereas induction of these cytokines was not compromised in Tlr3/7/9 deficient BMDCs. This suggests that TLR4 might be the functional target of BEA on BMDCs. Consistently, in luciferase reporter assays BEA stimulation significantly promotes NF-κB activation in mTLR4/CD14/MD2 overexpressing but not control HEK-293 cells. RNA-sequencing analyses further confirmed that BEA induces transcriptional changes associated with the TLR4 signaling pathway. Together, these results identify TLR4 as a cellular BEA sensor and define BEA as a potent activator of BMDCs, implying that this compound can be exploited as a promising candidate structure for vaccine adjuvants or cancer immunotherapies.
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Micotoxinas , Receptor 4 Toll-Like , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Citocinas/metabolismo , Células Dendríticas , Depsipeptídeos , Células HEK293 , Humanos , Interleucina-12/metabolismo , Camundongos , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismoRESUMO
Objective: Breast cancer may profoundly affect a couple's sex life. The present study examines whether patient-, partner- and relationship-related characteristics are associated with sexual activity of couples following breast cancer diagnosis in the treatment phase and over time. Methods: Women with breast cancer and their male cohabiting partners participated in a longitudinal study in Denmark. Logistic regression was used to examine associations of patient-, partner- and relationship-related characteristics at baseline (≤4 months following surgery) with couples' sexual activity at baseline, 5 and 12 months later. The longitudinal analyses were stratified for couples' sexual activity status at baseline. Results: A total of 722, 533 and 471 couples were included in the analyses at baseline, 5- and 12-months follow-up, respectively. Older age, depressive symptoms and lower vitality of patients were associated with lower odds of couples' sexual activity at baseline; chemotherapy treatment and older age of patients were associated with lower odds at 5-months follow-up in couples who were not sexually active at baseline. Higher ratings of emotional closeness, affectionate behavior and satisfaction with dyadic coping were associated with higher odds for sexual activity at baseline and over time in couples who were sexually active at baseline. Conclusion: Sexual counseling during cancer treatment and rehabilitation should include a couple perspective. Relationship-related variables may be a protective factor for remaining sexually active after breast cancer diagnosis. Interventions could focus on strengthening these factors. Health professionals also need to consider the patients' breast cancer treatment, vitality, and emotional distress in counselling on sexuality.
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CD8+ memory T cells (TM ) are crucial for long-term protection from infections and cancer. Multiple cell types and cytokines are involved in the regulation of CD8+ T cell responses and subsequent TM formation. Besides their direct antiviral effects, type I interferons (IFN-I) modulate CD8+ T cell immunity via their action on several immune cell subsets. However, it is largely unclear how nonimmune cells are involved in this multicellular network modulating CD8+ TM formation. Fibroblastic reticular cells (FRCs) form the 3D scaffold of secondary lymphoid organs, express the IFN-I receptor (IFNAR), and modulate adaptive immune responses. However, it is unclear whether and how early IFNAR signals in lymph node (LN) FRCs affect CD8+ TM differentiation. Using peptide vaccination and viral infection, we studied CD8+ TM differentiation in mice with an FRC-specific IFNAR deletion (FRCΔIFNAR ). We show here that the differentiation of CD8+ TCR-transgenic T cells into central memory cells (TCM ) is enhanced in peptide-vaccinated FRCΔIFNAR mice. Conversely, vesicular stomatitis virus infection of FRCΔIFNAR mice is associated with impaired TCM formation and the accumulation of vesicular stomatitis virus specific double-positive CD127hi KLRG-1hi effector memory T cells. In summary, we provide evidence for a context-dependent contribution of FRC-specific IFNAR signaling to CD8+ TM differentiation.
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Vacinas Anticâncer , Estomatite Vesicular , Animais , Linfócitos T CD8-Positivos , Fibroblastos , Camundongos , Camundongos Endogâmicos C57BL , Vacinas de Subunidades Antigênicas , Estomatite Vesicular/metabolismo , Estomatite Vesicular/patologiaRESUMO
PURPOSE: The aim of this study was to explore the factor structure of the Danish translation of the eating disorder quality of life scale and evaluate the internal reliability and convergent validity of the scale in a Danish cohort of women with AN. METHODS: The total sample comprised 211 patients diagnosed with anorexia nervosa age 13-40 years. Patients completed questionnaires assessing eating disorder psychopathology, physical and social functioning, and well-being. RESULTS: Factor analyses were not able to support the current division of the scale into 12 factors. We found excellent internal consistency of the eating disorder quality-of-life scale total score. We found relevant associations between quality of life and pre-determined variables. CONCLUSION: This study supports the use of the total score of the eating disorder quality of life scale in assessing quality of life in patients with anorexia nervosa. However, future studies should explore the factor structure of the scale further. LEVEL OF EVIDENCE: III: Evidence obtained from cohort or case-control analytic studies.
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Anorexia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Adolescente , Adulto , Anorexia Nervosa/diagnóstico , Dinamarca , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Feminino , Humanos , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto JovemRESUMO
PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has a severe impact on the general population. During the pandemic, children may develop emotional and psychological symptoms, including increased worries about health and illness, known as health anxiety symptoms (HASs). We aimed to explore HAS in 7-9-year-old children from the Danish Odense Child Cohort (OCC) during the first COVID-19 lockdown period in Denmark, and to examine associations with potential risk factors. MATERIAL AND METHODS: OCC is a cohort of children born between 2010 and 2012, which originally recruited 2874 of 6707 pregnancies (43%). Among the current OCC population of 2430 singleton children, 994 participated in this study (response rate 40%). Children and their parents filled out questionnaires about child HAS, family exposure to COVID-19 infection and parental HAS. Adjusted odds ratios (aORs) were calculated between high score child HAS (≥90th percentile) and covariates by use of logistic regression. RESULTS: Most children (n = 686, 69%) reported few worries about their health. Children reporting high score HAS also had higher levels of internalizing symptoms at age 5; aOR 2.15 (1.20;3.85), p = .010, and higher levels of maternal and paternal HAS; aOR 2.40 (1.44;3.97), p = .001, and 2.00 (1.10;3.65), p = .023, whereas no association with child sex or familial exposure to COVID-19 was detected (n = 65, 6.5%). CONCLUSIONS: High score child HAS during the first lockdown period of the COVID-19 pandemic was not associated with family exposure to COVID-19 infection, but to being a more anxious child a priori and to HAS in parents.
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COVID-19 , Ansiedade/epidemiologia , Ansiedade/psicologia , COVID-19/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Controle de Doenças Transmissíveis , Dinamarca/epidemiologia , Feminino , Humanos , GravidezRESUMO
OBJECTIVE: To examine the Multiple Sclerosis Impairment Scale (MSIS) in secondary progressive MS (SPMS) in relation to the Expanded Disability Status Scale (EDSS), magnetic resonance imaging (MRI) outcomes, and mobility. METHODS: In this observational single-center study, 68 secondary progressive multiple sclerosis (SPMS) patients were examined by MSIS, EDSS, functional mobility tests of upper/lower extremities, and multimodal MRI. Participants had EDSS ≥3.5, a decline in daily activities over the last year unrelated to relapses, and/or 6-month confirmed disability progression. RESULTS: Mean disease duration was 23.1 ± 8.3 years and mean age 54.4 ± 8.1 years. MSIS, EDSS, and their corresponding motor, cerebellar, and sensory subscores correlated (p < .0001). Motor subscores of MSIS correlated stronger with Timed-25-Foot-Walk (T25FW) than pyramidal functional system score (FSS) (p = .03), but EDSS had a stronger correlation to T25FW than the total MSIS score (p = .01). MSIS cerebellar subscore correlated stronger with 9-Hole Peg Test (9-HPT) than cerebellar FSS (p = .04). The sensory MSIS subscore also showed correlation with 9-HPT in contrast to sensory FSS (p = .006). MSIS subscores had stronger correlations with MRI volumetry measures than FSS scores (lesion volume and putamen, thalamus, corpus callosum volumetry, p = .0001-0.0017). CONCLUSION: In patients with SPMS, MSIS correlated with functional motor tests. MSIS showed stronger correlations with atrophy of central nervous system areas, and may be more sensitive to scale cerebellar and sensory function than EDSS.
Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Encéfalo/diagnóstico por imagem , Avaliação da Deficiência , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , CaminhadaRESUMO
AIMS: The aim of this study was to evaluate the association between coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) and recurrent chest pain (CP) at 1-year follow-up in patients with stable angina pectoris (SAP). METHODS AND RESULTS: Study of patients (n = 267) with SAP who underwent CCTA and FFRCT testing; 236 (88%) underwent invasive coronary angiography; and 87 (33%) were revascularized. Symptomatic status at 1-year follow-up was gathered by a structured interview. Three different FFRCT algorithms were applied using the following criteria for abnormality: (i) 2 cm-FFRCT ≤0.80; (ii) d-FFRCT ≤0.80; and (iii) a combination in which both a d-FFRCT ≤0.80 and a ΔFFRCT ≥0.06 must be present in the same vessel (c-FFRCT). Patients were classified into two groups based on the FFRCT test result and revascularization: completely revascularized/normal (CRN), patients in whom all coronary arteries with an abnormal FFRCT test result were revascularized or patients with completely normal FFRCT test results, and incompletely revascularized (IR), patients in whom ≥1 coronary artery with an abnormal FFRCT test result was not revascularized. Recurrent CP was present in 62 (23%) patients. Classification of patients (CRN or IR) was significantly associated with recurrent CP for all applied FFRCT interpretation algorithms. When applying the c-FFRCT algorithm, the association with recurrent CP was found, irrespective of the extent of coronary calcification and the degree of coronary stenosis. A negative association between per-patient minimal d-FFRCT and recurrent CP was demonstrated, P < 0.005. CONCLUSION: An abnormal FFRCT test result is associated with an increased risk of recurrent CP in patients with new-onset SAP.