| 1. |
- Bernabe, Beatriz Penalver, et al.
(författare)
-
Interactions between perceived stress and microbial-host immune components : two demographically and geographically distinct pregnancy cohorts
- 2023
-
Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Higher stress during pregnancy associates with negative outcomes and elevated inflammation. The gut microbiota, reflecting environment and social interactions, alongside host immune responses have the potential to better understand perceived stress and identify when stress is excessive in pregnancy. Two U.S. cohorts of 84 pregnant individuals, composed of urban women of color and suburban white women, completed the Perceived Stress Scale-10 (PSS-10) and provided fecal and blood samples at two time points. Confirmatory Factor Analysis assessed the robustness of a two-factor PSS-10 model (Emotional Distress/ED and Self-Efficacy/SE). Gut microbiota composition was measured by 16 S rRNA amplicon sequencing and the immune system activity was assessed with a panel of 21 T-cell related cytokines and chemokines. ED levels were higher in the suburban compared to the urban cohort, but levels of SE were similar. ED and SE levels were associated with distinct taxonomical signatures and the gut microbiota data improved the prediction of SE levels compared with models based on socio-demographic characteristics alone. Integration of self-reported symptoms, microbial and immune information revealed a possible mediation effect of Bacteroides uniformis between the immune system (through CXCL11) and SE. The study identified links between distinct taxonomical and immunological signatures with perceived stress. The data are congruent with a model where gut microbiome and immune factors, both impacting and reflecting factors such as close social relationships and dietary fiber, may modulate neural plasticity resulting in increased SE during pregnancy. The predictive value of these peripheral markers merit further study.
|
|
| 2. |
- Bhandage, Amol K., 1988-, et al.
(författare)
-
Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers
- 2019
-
Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 20:24
-
Tidskriftsartikel (refereegranskat)abstract
- Immunomodulation is increasingly being recognised as a part of mental diseases. Here, we examined whether levels of immunological protein markers changed with depression, age, or the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). An analysis of plasma samples from patients with a major depressive episode and control blood donors (CBD) revealed the expression of 67 inflammatory markers. Thirteen of these markers displayed augmented levels in patients compared to CBD. Twenty-one markers correlated with the age of the patients, whereas 10 markers correlated with the age of CBD. Interestingly, CST5 and CDCP1 showed the strongest correlation with age in the patients and CBD, respectively. IL-18 was the only marker that correlated with the MADRS-S scores of the patients. Neuronal growth factors (NGFs) were significantly enhanced in plasma from the patients, as was the average plasma GABA concentration. GABA modulated the release of seven cytokines in anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) from the patients. The study reveals significant changes in the plasma composition of small molecules during depression and identifies potential peripheral biomarkers of the disease.
|
|
| 3. |
- Bixo, Liv, et al.
(författare)
-
'Sick and tired' : Patients reported reasons for not participating in clinical psychiatric research
- 2021
-
Ingår i: Health Expectations. - : John Wiley & Sons. - 1369-6513 .- 1369-7625. ; 24:S1, s. 20-29
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Meaningful and generalizable research depends on patients' willingness to participate. Studies often fail to reach satisfactory representativeness.Objective: This paper aims to investigate reasons for not participating in research among young adult patients with psychiatric illness.Method: A quantitative cross-sectional study was performed based on questionnaires reported on by 51 psychiatric patients (14 males, 35 females and two unspecified) who had previously declined participation in an ongoing research project. Thereafter, a qualitative interview with subsequent content analysis was conducted with ten additional patients (five males, five females).Results: The questionnaires indicate being 'too tired/too sick to participate' as the most common barrier. Lack of time and fear of needles were other common barriers. Lack of trust or belief in the value of research was less inhibitive. In the interviews, disabling psychiatric symptoms were confirmed as the main reason for not participating. Several potential ways to increase participation were identified, such as simplification of procedures and information as well as providing rewards and feedback, and building relationships before asking.Conclusion: This study is unusual as it focuses on the group of young people attending psychiatry outpatient clinics we know very little about - those who do not partake in research. Our results indicate that fatigue and sickness reduce research participation and identify factors that may facilitate enrolment of this important group.
|
|
| 4. |
- Brunet-Ratnasingham, Elsa, et al.
(författare)
-
Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.
- 2024
-
Ingår i: Nature Communications. - 2041-1723. ; 15:1, s. 4177-
-
Tidskriftsartikel (refereegranskat)abstract
- Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
|
|
| 5. |
|
|
| 6. |
- Bränn, Emma, et al.
(författare)
-
Inflammatory markers in women with postpartum depressive symptoms
- 2020
-
Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 98:7, s. 1309-1321
-
Tidskriftsartikel (refereegranskat)abstract
- Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.
|
|
| 7. |
- Couch, Fergus J., et al.
(författare)
-
Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
-
Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Cui, Tao, et al.
(författare)
-
Olfactory receptor 51E1 protein as a potential novel tissue biomarker for small intestine neuroendocrine carcinomas
- 2013
-
Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 168:2, s. 253-261
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Late diagnosis hinders proper management of small intestine neuroendocrine carcinoma (SI-NEC) patients. The olfactory receptor, family 51, subfamily E, member 1 (OR51E1) has been reported as a potential novel SI-NEC marker, without protein expression recognition. Thus, we further studied whether the encoded protein may be a novel SI-NEC clinical biomarker.DESIGN: OR51E1 coding sequence was cloned using total RNA from SI-NEC patient specimens. Quantitative real-time PCR analysis explored OR51E1 expression in laser capture microdissected SI-NEC cells and adjacent microenvironment cells. Moreover, immunohistochemistry investigated OR51E1 protein expression on operation and biopsy material from primary SI-NECs, mesentery, and liver metastases from 70 patients. Furthermore, double immunofluorescence studies explored the potential co-localization of the vesicular monoamine transporter 1 (SLC18A1, generally referred to as VMAT1) and OR51E1 in the neoplastic cells and in the intestinal mucosa adjacent to the tumor.RESULTS: OR51E1 coding sequence analysis showed absence of mutation in SI-NEC patients at different stages of disease. OR51E1 expression was higher in microdissected SI-NEC cells than in the adjacent microenvironment cells. Furthermore, both membranous and cytoplasmic OR51E1 immunostaining patterns were detected in both primary SI-NECs and metastases. Briefly, 18/43 primary tumors, 7/28 mesentery metastases, and 6/18 liver metastases were 'positive' for OR51E1 in more than 50% of the tumor cells. In addition, co-localization studies showed that OR51E1 was expressed in >50% of the VMAT1 immunoreactive tumor cells and of the enterochromaffin cells in the intestinal mucosa adjacent to the tumor.CONCLUSION: OR51E1 protein is a potential novel clinical tissue biomarker for SI-NECs. Moreover, we suggest its potential therapeutic molecular target development using solid tumor radioimmunotherapy.
|
|
| 11. |
- Cunningham, Anthony L., et al.
(författare)
-
Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older
- 2018
-
Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 217:11, s. 1750-1760
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01(B) Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods. Participants (ZOE-50: >= 50; ZOE-70: >= 70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing >= 2 of 4 activation markers assessed (CD4(2+)) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results. After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD4(2+) T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained >= 5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions. Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination.
|
|
| 12. |
- Cunningham, Janet, et al.
(författare)
-
Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms
- 2022
-
Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 225:6, s. 965-970
-
Tidskriftsartikel (refereegranskat)abstract
- Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.
|
|
| 13. |
- Cunningham, Janet, et al.
(författare)
-
Impact of time and temperature on gut microbiota and SCFA composition in stool samples
- 2020
-
Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 15:8
-
Tidskriftsartikel (refereegranskat)abstract
- Gut dysbiosis has been implicated in the pathophysiology of a growing number of non-communicable diseases. High through-put sequencing technologies and short chain fatty acid (SCFA) profiling enables surveying of the composition and function of the gut microbiota and provide key insights into host-microbiome interactions. However, a methodological problem with analyzing stool samples is that samples are treated and stored differently prior to submission for analysis potentially influencing the composition of the microbiota and its metabolites. In the present study, we simulated the sample acquisition of a large-scale study, in which stool samples were stored for up to two days in the fridge or at room temperature before being handed over to the hospital. To assess the influence of time and temperature on the microbial community and on SCFA composition in a controlled experimental setting, the stool samples of 10 individuals were exposed to room and fridge temperatures for 24 and 48 hours, respectively, and analyzed using 16S rRNA gene amplicon sequencing, qPCR and nuclear magnetic resonance spectroscopy. To best of our knowledge, this is the first study to investigate the influence of storage time and temperature on the absolute abundance of methanogens, and ofLactobacillus reuteri. The results indicate that values obtained for methanogens,L.reuteriand total bacteria are still representative even after storage for up to 48 hours at RT (20 degrees C) or 4 degrees C. The overall microbial composition and structure appeared to be influenced more by laboratory errors introduced during sample processing than by the actual effects of temperature and time. Although microbial activity was demonstrated by elevated SCFA at both 4 degrees C and RT, SCFAs ratios were more stable over the different conditions and may be considered as long as samples are come from similar storage conditions.
|
|
| 14. |
- Cunningham, Janet L., et al.
(författare)
-
Agreement between physicians' and patients' ratings on the Montgomery-Asberg Depression Rating Scale
- 2011
-
Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 135:1-3, s. 148-153
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Self-rating scales developed for monitoring depression severity are potentially informative and cost effective tools. There is an increasing tendency to use the Montgomery-Asberg Depression Rating Scale (MADRS) and the self-rating version (MADRS-S) interchangeably. Methods: 400 patients with major depressive disorder were included. Concordance between patient and physician ratings was measured by means of repeated MADRS and MADRS-S ratings during a six-month drug trial and one-year follow-up. Results: Overall scores from patients and physicians show the same trends and both are sensitive to improvements. Our results, however, show only moderate to good agreement between patient and physician ratings. Intraclass coefficients ranged from 0.47 to 0.75 with highest agreement at week 8. Limitations: Generalizability is restricted to outpatients in general practice with moderate to severe depression. MADRS-S and MADRS scale definitions are similar but not identical concerning language and are scaled differently, 0-6 vs. 0-3, respectively, which may have influenced the results. The exclusion criteria restricted the range of values for the item Suicidal thoughts/Zest for life, which may have reduced the correlations. Conclusions: MADRS-S is a suitable tool for following patients' symptoms on a regular basis over time and may also be used to compensate for bias in physicians' ratings in drug trials.
|
|
| 15. |
- Cunningham, Janet L, et al.
(författare)
-
Anti-SARS-CoV2 antibody responses in serum and cerebrospinal fluid of COVID-19 patients with neurological symptoms.
- 2022
-
Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 225:6, s. 965-970
-
Tidskriftsartikel (refereegranskat)abstract
- Antibody responses to SARS-CoV-2 in serum and CSF from 16 COVID-19 patients with neurological symptoms were assessed using two independent methods. IgG specific for the virus spike protein was found in 81% of cases in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in two cases with negative serology. Levels of IgG in both serum and CSF were associated with disease severity (p<0.05). All patients with elevated markers of CNS damage in CSF also had CSF antibodies (p=0.002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.
|
|
| 16. |
- Cunningham, Janet L., et al.
(författare)
-
Common pathogenetic mechanism involving human chromosome 18 in familial and sporadic ileal carcinoid tumors
- 2011
-
Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 50:2, s. 82-94
-
Tidskriftsartikel (refereegranskat)abstract
- Serotonin producing endocrine carcinoma of small intestine (ileal carcinoid) is a clinically distinct endocrine tumor. It is generally considered as a sporadic disease and its molecular etiology is poorly understood. We report comprehensive clinical and molecular studies of 55 sporadic and familial patients diagnosed with this condition. Nine pedigrees encompassing 23 affected subjects were established, consistent with autosomal dominant mode of inheritance. Familial and sporadic patients demonstrated indistinguishable clinical pictures. Molecular analyses of 61 tumors from 45 individuals, including eight familial and 37 sporadic patients, aimed at determination of global copy number aberrations using BAC and Illumina SNP arrays and gene expression profiling by Affymetrix chips. Chromosome 18 aberrations were identified in both sporadic and in familial tumors; 100% vs. 38%, respectively. Other, less frequent aberrations were also common for both groups. Global expression profiles revealed no differentially expressed genes. Frequent gain of chromosome 7 was exclusively observed in metastases, when patient matched primary tumors and metastases were compared. Notably, the latter aberration correlated with solid growth pattern morphology (P < 0.01), a histopathological feature that has previously been related to worse prognosis. The clinical and molecular similarities identified between sporadic and familial cases suggest a common pathogenetic mechanism involved in tumor initiation. The familial variant of ileal carcinoid represents a previously unrecognized autosomal dominant inherited tumor disease, which we propose to call Familial Ileal Endocrine Carcinoma (FIEC). Our findings indicate the location of a FIEC tumor suppressor gene near the telomere of 18q, involved in development of inherited and sporadic tumors.
|
|
| 17. |
|
|
| 18. |
- Cunningham, Janet L., et al.
(författare)
-
Connective tissue growth factor expression in endocrine tumors is associated with high stromal expression of alpha-smooth muscle actin
- 2010
-
Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 163:4, s. 691-697
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Complications due to fibrosis development are common in patients with well-differentiated endocrine carcinomas in the small intestine (ileal carcinoids). Connective tissue growth factor (CTGF) expression in ileal carcinoids may be related to this fibrosis development. This study aimed to examine CTGF expression in relation to local myofibroblast differentiation in a large series of ileal carcinoids and in different types of endocrine tumors. METHODS Immunoreactivity (IR) for CTGF and α-smooth muscle actin (α-SMA), a marker for myofibroblasts, was compared in serial tumor tissue sections from 42 patients with ileal carcinoids and from 80 patients with other endocrine tumors. Western blot was performed on an additional 21 patients with ileal carcinoids. RESULTS CTGF IR was present in >50% of tumor cells in all 42 ileal carcinoids and in 2 out of 14 endocrine pancreatic tumors, 4 out of 6 rectal carcinoids, and 1 out of 5 lung carcinoids. Tumors with abundant CTGF expression also displayed α-SMA IR in stromal fibroblast-like cells, whereas other endocrine tumors displayed less or no CTGF and α-SMA IR. Protein bands corresponding to full-length CTGF (36-42 kDa) were detected in protein lysates from ileal carcinoids. CONCLUSION CTGF is uniquely prevalent in ileal carcinoids when compared with most other endocrine tumor types. Immunoreactive cells are adjacent areas with increased fibrovascular stroma that express α-SMA. This supports a potential role for CTGF in myofibroblast-mediated fibrosis associated with ileal carcinoids, and indicates that CTGF should be investigated as a target for future therapy.
|
|
| 19. |
- Cunningham, Janet L., et al.
(författare)
-
Experiences in implementing immunopsychiatry in real life
- 2023
-
Ingår i: Journal of Affective Disorders Reports. - : Elsevier. - 2666-9153. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Immunological mechanisms, both alone and in combination, are associated with a broad range of psychiatric disorders encompassing autoimmune, autoinflammatory disorders but also genetic, metabolic, or other immunological disorders. Early treatment improves the outcome for autoimmune disorders, but early diagnosis is more difficult when isolated psychiatric symptoms are manifestations of autoimmunity. Treatment of these cases must encompass integrated models of disease, as both systemic autoimmunity and psychological processes influence mental health. Several challenges need to be overcome to efficiently merge psychiatric and somatic disease paradigms and medical care ranging from language and conceptual barriers to organizational barriers. Since 2015, the Immunopsychiatry team at Uppsala University has developed a collaborative multidisciplinary approach to improve and integrate care for patients with moderate to severe psychiatric disorders. Based on this experience, we have outlined the obstacles to be overcome in taking steps forward to achieve the long-term goal of understanding and early detection and identification of treatable immunological conditions within the psychiatric patient population; the described framework of evaluations and work-flow may serve as a model for other centers.
|
|
| 20. |
- Cunningham, Janet Lynn, et al.
(författare)
-
Malignant ileocaecal serotonin-producing carcinoid tumours : the presence of a solid growth pattern and/or Ki67 index above 1% identifies patients with a poorer prognosis
- 2007
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 46:6, s. 747-756
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with malignant serotonin-producing carcinoid tumours in the jejunum, ileum and caecum generally have long survival expectancy. In some patients, however, tumour progression is more rapid and there is a need to identify them at an early stage. The purpose of this study was to determine if histopathological characteristics and/or Ki67 and apoptotic indices are of prognostic value in cases of metastatic disease. Eighty-one patients with this tumour were included in the study; all had metastases and their survival range was 1-223 months. Five growth patterns were identified and described. For 57 patients whose tumour material was available, the Ki67 and apoptotic indices were calculated for ten randomly selected tumour areas and 'hot spots'. A Cox regression analysis was used to test if histopathology and/or Ki67 index ≥1% could identify patients whose survival might be shorter than anticipated. One of the histopathological growth patterns-the solid (non-organoid) cell pattern-was correlated to shorter survival in both primary tumours and metastases, when compared with the organoid growth patterns (hazard ratio 2.9 and 2.3, p≤0.01). In 75% of primary tumours and 67% of metastases, the average Ki67 index was<0.5%. Ki67 index in 'hot spots' ranged from 0.1 to 14%. Ki67 index ≥1%, in both primary tumour and metastases, identified patients at increased risk of shorter survival (hazard ratio 5.4 and 2.5, p≤0.01). The apoptotic index was very low in all cases. We conclude that in patients with metastazising serotonin-producing carcinoids, two independent criteria, a solid growth pattern and Ki67 index ≥1%, can be used to identify patients with a poorer prognosis. This study also showed that Ki67 index <2% cannot, as previously suggested, be used to indicate a benign progression for this tumour category.
|
|
| 21. |
- Cunningham, Janet L., et al.
(författare)
-
No regrets : Young adult patients in psychiatry report positive reactions to biobank participation
- 2017
-
Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 17
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Research in vulnerable individuals must insure voluntariness and minimize negative reactions caused by participation. This study aimed to describe consent and completion rate in young psychiatric patients in relation to study components, degree of disability and to compare response to research participation in patients and controls.METHODS: Between 2012 and 2015, 463 patients with psychiatric disorders between the ages of 18-25 from the Dept. of General Psychiatry at Uppsala University Hospital and 105 controls were recruited to donate data and samples to a biobank. Consent and completion in relation to questionnaires, biological sampling of blood, saliva or feces, were monitored. Both groups were also asked about their perceived disability and how research participation affected them.RESULTS: Most patients who participated consented to and completed questionnaires and blood sampling. The majority also consented to saliva sampling, while less than half consented to collect feces. Of those who gave consent to saliva and feces only half completed the sampling. Both patients and controls reported high voluntariness and were positive to research participation. Within the patient group, those with greater perceived disability reported greater distress while participating in research, but there was no difference in consent or completion rates or level of regret.CONCLUSIONS: With the described information procedures, psychiatric patients, regardless of perceived disability, reported high voluntariness and did not regret participation in biobanking. Compared to questionnaires and blood sampling, given consent was reduced for feces and completion was lower for both saliva and feces sampling.
|
|
| 22. |
- Cunningham, Janet L., et al.
(författare)
-
Predicting disagreement between physicians and patients on depression response and remission
- 2013
-
Ingår i: International Clinical Psychopharmacology. - 0268-1315 .- 1473-5857. ; 28:3, s. 134-140
-
Tidskriftsartikel (refereegranskat)abstract
- Demographic, personality, and disease-related factors all contribute when patients disagree with physicians on the severity of subjective symptoms. This study aims to create a model, on the basis of patient factors at treatment initiation, for longitudinal prediction of disagreement on treatment response and remission in depressed patients. Four hundred patients with major depressive disorder were studied during a clinical drug trial. Repeated assessments with the Montgomery-Asberg Depression Rating Scale (MADRS) and the self-rating version (MADRS-S) were used to indicate response or remission. Factors at baseline and week 2 were tested for inclusion in a model for the prediction of discordance on remission and response between patients and physicians at week 8. The models were then tested, in the same population, at weeks 12, 16, and 24. Model AUCs ranged from 0.71 to 0.74 for week 8. The models that were validated at weeks 12, 16, and 24 indicated stability in the predictive value of the models. The risk for longitudinal disagreement in the evaluation of depression treatment response and remission in clinical practice and drug trials can be predicted using factors at study initiation and at week 2.
|
|
| 23. |
- Cunningham, Janet L., et al.
(författare)
-
Tachykinins in endocrine tumors and the carcinoid syndrome
- 2008
-
Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 159:3, s. 275-282
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveA new antibody, active against the common tachykinin (TK) C-terminal. was used to study TK expression in patients with endocrine tumors and a possible association between plasma-TK levels and symptoms of diarrhea and flush in patients with metastasizing ileocecal serotonin-producing carcinoid tumors (MSPCs).MethodTK, serotonin and chromogranin A (CgA) immunoreactivity (IR) was studied by immunohistochemistry in tissue samples from 33 midgut carcinoids and 72 other endocrine tumors. Circulating TK (P-TK) and urinary-5 hydroxyindoleacetic acid (U-5HIAA) concentrations were measured in 42 patients with MSPCs before treatment and related to symptoms in patients with the carcinoid syndrome. Circulating CgA concentrations were also measured in 39 out of the 42 patients.ResultsAll MSPCs displayed serotonin and strong TK expression. TK-IR was also seen in all serotonin-producing lung and appendix carcinoids. None of the other tumors examined contained TK-IR cells. Concentrations of P-TK, P-CgA, and U-5HIAA were elevated in patients experiencing daily episodes of either flush or diarrhea, when compared with patients experiencing occasional or none of these symptoms. In a Spearman partial rank test, the correlation of P-TK with daily diarrhea was independent of both U-5HIAA and CgA levels.ConclusionWe found that TK synthesis occurs in serotonin-IR tumors and that P-TK levels are significantly correlated with symptoms of flush and diarrhea in patients with MSPCs. This is. to our knowledge, the first report demonstrating an independent correlation of P-TKs with carcinoid diarrhea, a symptom that is customarily regarded as serotonin mediated. Further investigations may present opportunities for new therapeutic possibilities.
|
|
| 24. |
|
|
| 25. |
- Cunningham, Janet L., et al.
(författare)
-
The biological hallmarks of ileal carcinoids
- 2011
-
Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 41:12, s. 1353-1360
-
Forskningsöversikt (refereegranskat)abstract
- Endocrine tumours derived from the small intestine, ileal carcinoids, produce and secrete the hormones tachykinins and serotonin, which induces the specific symptoms related to the tumour. Because of their low proliferation rate, they are often discovered at late stages when metastases have occurred. The biology that characterizes these tumours differs in many ways from what is generally recognized for other malignancies. In this overview, the current knowledge on the development and progression of ileal carcinoids is described.
|
|
| 26. |
|
|
| 27. |
- Cunningham, Janet Lynn, 1974-
(författare)
-
Tumour Biological Factors Characterizing Metastasizing Serotonin-producing Ileocaecal Carcinoids
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this study, metastasizing serotonin-producing ileocaecal carcinoid tumours (MSPCs) were examined for biological characteristics that could be used to define clinically relevant subgroups within this patient population. Possible targets for new treatment options were also explored.It was found that MSPCs share several biological characteristics such as expression of serotonin, tachykinins (TKs), chromogranin A, islet autoantigen-2 and connective tissue growth factor (CTGF). TKs and serotonin were demonstrated in the same endocrine tumours in the gut and lung. IA-2 expression was shown to be up-regulated in MSPCs, possibly in connection with active hormone secretion. CTGF expression was high in tumour areas adjacent to extensive stroma expressing alpha-smooth muscle actin. This indicated myofibroblast differentiation, which may be associated with fibrosis-related complications prevalent in patients with MSPCs. When compared with other endocrine tumours, MSPCs behaved as a relatively homogeneous group, though within the MSPC population several subgroups could be defined. Patients with tumours displaying either a solid growth pattern and/or a Ki67 index ≥1% had a less favourable prognosis than those who did not. Another group of patients, who had increased plasma TK concentrations, were more likely to suffer from severe diarrhea. This information should be considered when discussing clinical treatment and when undertaking tumour biological studies. New treatment possibilities, such as drugs that specifically target TK receptors and antibodies to CTGF, are also discussed.In conclusion, MSPCs comprise a clinically relevant tumour group with similar biological features that are distinct from other endocrine tumours. Subgroups of patients within this patient category can be defined which may be relevant when establishing prognosis and when selecting future treatment modalities.
|
|
| 28. |
- Dumanski, Jan P., et al.
(författare)
-
A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors
- 2017
-
Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 24:8, s. 427-443
-
Tidskriftsartikel (refereegranskat)abstract
- The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/or whole-genome of blood DNA, and in selected cases, tumor DNA, from 24 patients from 15 families with the history of SI-NETs. We identified seven candidate mutations in six genes that were further studied using 215 sporadic SI-NET patients. The result was compared with the frequency of the candidate mutations in three control cohorts with a total of 35,688 subjects. A heterozygous variant causing an amino acid substitution p.(Gly396Asp) in the MutY DNA glycosylase gene (MUTYH) was significantly enriched in SI-NET patients (minor allele frequencies 0.013 and 0.003 for patients and controls respectively) and resulted in odds ratio of 5.09 (95% confidence interval 1.56-14.74; P value = 0.0038). We also found a statistically significant difference in age at diagnosis between familial and sporadic SI-NETs. MUTYH is involved in the protection of DNA from mutations caused by oxidative stress. The inactivation of this gene leads to specific increase of G:C- > T:A transversions in DNA sequence and has been shown to cause various cancers in humans and experimental animals. Our results suggest that p.(Gly396Asp) in MUTYH, and potentially other mutations in additional members of the same DNA excision-repair pathway (such as the OGG1 gene) might be involved in driving the tumorigenesis leading to familial and sporadic SI-NETs.
|
|
| 29. |
- Edvinsson, Åsa, 1982-, et al.
(författare)
-
Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction
- 2017
-
Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 80, s. 15-25
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Antenatal depression and use of serotonin reuptake inhibitors (SSRI) in pregnancy have both been associated with an increased risk of poor pregnancy outcomes, such as preterm birth and impaired fetal growth. While the underlying biological pathways for these complications are poorly understood, it has been hypothesized that inflammation may be a common physiological pathway. The aim of the present study was to assess peripheral inflammatory markers in healthy women, women with antenatal depression, and in women using SSRI during pregnancy.Methods: 160 healthy pregnant controls, 59 women with antenatal depression and 39 women on treatment with SSRIs were included. The relative levels of 92 inflammatory proteins were analyzed by proximity extension assay technology.Results: Overall, 23 of the inflammatory markers were significantly lower in women with antenatal depression and in women on treatment with SSRIs in comparison with the healthy controls. No difference in any of the inflammatory markers was observed between women with antenatal depression and those who were using SSRI. Top three inflammatory markers that were down-regulated in women with antenatal depression were TNF-related apoptosis-inducing ligand (TRAIL), p = 0.000001, macrophage colony-stimulating factor 1 (CSF-1), p = 0.000004, and fractalkine (CX3CL1), p =0.000005. Corresponding inflammatory markers in SSRI users were CSF-1, p = 0.000011, vascular endothelial growth factor A (VEGF-A), p =0.000016, and IL-15 receptor subunit alpha (IL-15RA), p = 0.000027. The inflammatory markers were negatively correlated with cortisone serum concentrations in controls, but not in the cases. Differential DNA methylation of was found for seven of these inflammatory markers in an independent epigenetics cohort.Conclusion: Women with antenatal depression or on SSRI treatment have lower levels of a number of peripheral inflammatory markers than healthy pregnant controls. Hypothetically, this could be due to dysregulated switch to the pro-M2 milieu that characterizes normal third trimester pregnancy. However, longitudinal blood sampling is needed to elucidate whether the presumably dysregulated M2 shift is driving the development of antenatal depression or is a result of the depression.
|
|
| 30. |
- Endres, Dominique, et al.
(författare)
-
Immunological causes of obsessive-compulsive disorder : is it time for the concept of an "autoimmune OCD" subtype?
- 2022
-
Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1
-
Forskningsöversikt (refereegranskat)abstract
- Obsessive-compulsive disorder (OCD) is a highly disabling mental illness that can be divided into frequent primary and rarer organic secondary forms. Its association with secondary autoimmune triggers was introduced through the discovery of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS) and Pediatric Acute onset Neuropsychiatric Syndrome (PANS). Autoimmune encephalitis and systemic autoimmune diseases or other autoimmune brain diseases, such as multiple sclerosis, have also been reported to sometimes present with obsessive-compulsive symptoms (OCS). Subgroups of patients with OCD show elevated proinflammatory cytokines and autoantibodies against targets that include the basal ganglia. In this conceptual review paper, the clinical manifestations, pathophysiological considerations, diagnostic investigations, and treatment approaches of immune-related secondary OCD are summarized. The novel concept of "autoimmune OCD" is proposed for a small subgroup of OCD patients, and clinical signs based on the PANDAS/PANS criteria and from recent experience with autoimmune encephalitis and autoimmune psychosis are suggested. Red flag signs for "autoimmune OCD" could include (sub)acute onset, unusual age of onset, atypical presentation of OCS with neuropsychiatric features (e.g., disproportionate cognitive deficits) or accompanying neurological symptoms (e.g., movement disorders), autonomic dysfunction, treatment resistance, associations of symptom onset with infections such as group A streptococcus, comorbid autoimmune diseases or malignancies. Clinical investigations may also reveal alterations such as increased levels of anti-basal ganglia or dopamine receptor antibodies or inflammatory changes in the basal ganglia in neuroimaging. Based on these red flag signs, the criteria for a possible, probable, and definite autoimmune OCD subtype are proposed.
|
|
| 31. |
- Endres, Dominique, et al.
(författare)
-
Spectrum of Novel Anti-Central Nervous System Autoantibodies in the Cerebrospinal Fluid of 119 Patients With Schizophreniform and Affective Disorders
- 2022
-
Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 92:4, s. 261-274
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune psychosis may be caused by well-characterized anti-neuronal autoantibodies, such as those against the NMDA receptor. However, the presence of additional anti-central nervous system (CNS) autoantibodies in these patients has not been systematically assessed.METHODS: Serum and cerebrospinal fluid (CSF) from patients with schizophreniform and affective syndromes were analyzed for immunoglobulin G anti-CNS autoantibodies using tissue-based assays with indirect immunofluorescence on unfixed murine brain tissue as part of an extended routine clinical practice. After an initial assessment of patients with red flags for autoimmune psychosis (n = 30), tissue-based testing was extended to a routine procedure (n = 89).RESULTS: Based on the findings from all 119 patients, anti-CNS immunoglobulin G autoantibodies against brain tissue were detected in 18% (n = 22) of patients (serum 9%, CSF 18%) following five principal patterns: 1) against vascular structures, most likely endothelial cells (serum 3%, CSF 8%); 2) against granule cells in the cerebellum and/or hippocampus (serum 4%, CSF 6%); 3) against myelinated fibers (serum 2%, CSF 2%); 4) against cerebellar Purkinje cells (serum 0%, CSF 2%); and 5) against astrocytes (serum 1%, CSF 1%). The patients with novel anti-CNS autoantibodies showed increased albumin quotients (p =.026) and white matter changes (p =.020) more frequently than those who tested negative for autoantibodies.CONCLUSIONS: The study demonstrates five novel autoantibody-binding patterns on brain tissue of patients with schizophreniform and affective syndromes. CSF yielded positive findings more frequently than serum analysis. The frequency and spectrum of autoantibodies in these patient groups may be broader than previously thought.
|
|
| 32. |
- Feresiadou, Amalia, et al.
(författare)
-
Measurement of sCD27 in the cerebrospinal fluid identifies patients with neuroinflammatory disease
- 2019
-
Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 332, s. 31-36
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Laboratory tests to assist in the diagnosis and monitoring of neuroinflammatory diseases are scarce. The soluble form of the CD27 molecule (sCD27) is shed in high concentrations by activated T cells and can be detected in the cerebrospinal fluid. The aim of this study was to investigate whether CSF quantitation of sCD27 could discriminate between inflammatory and non-inflammatory neurological diseases.METHODS: The concentration of sCD27 was measured using a commercially available ELISA in 803 well-defined subjects from a study cohort comprised of 338 patients with neuroinflammatory disease, 338 with non-inflammatory neurological disease and 127 controls without neurological disease.RESULTS: The median value of cerebrospinal fluid sCD27 was 64 pg/mL (IQR 0-200) in controls, 58 pg/mL (IQR 0-130) in patients with non-inflammatory disease and 740 pg/mL (IQR 230-1800) in patients with inflammatory disease. The likelihood ratio of having an inflammatory disease was 10 (sensitivity 74% and specificity 93%) if the sCD27 concentration was >250 pg/mL. In patients with a known inflammatory condition, the likelihood ratio of having an infection was 10 (sensitivity 40% and specificity 96%) if the sCD27 concentration was >2500 pg/mL.CONCLUSIONS: The likelihood of having an inflammatory neurological condition is increased with elevated concentrations of sCD27 in cerebrospinal fluid. Rapid tests of sCD27 should be developed to assist clinicians in diagnosis of neuroinflammatory disease.
|
|
| 33. |
- Forouzanfar, Mohammad H, et al.
(författare)
-
Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
|
|
| 34. |
|
|
| 35. |
- Hollestelle, Antoinette, et al.
(författare)
-
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
|
|
| 36. |
- Hörberg, Niklas, et al.
(författare)
-
Early Trauma Inventory Self-Report Short Form (ETISR-SF) : validation of the Swedish translation in clinical and non-clinical samples.
- 2019
-
Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 73:2, s. 81-89
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Childhood trauma in an important public health concern, and there is a need for brief and easily administered assessment tools. The Early Trauma Inventory (ETI) is one such instrument. The aim of this paper is to test the psychometric properties of the Swedish translation of the short, self-rated version (ETISR-SF), and to further validate the instrument.MATERIALS AND METHODS: In this cross-sectional study, 243 psychiatric patients from an open care unit in Sweden and 56 controls were recruited. Participants were interviewed and thereafter completed the ETISR-SF. Internal consistency was calculated using Cronbach's alpha, a confirmatory factor analysis (CFA) was performed and goodness-of-fit was determined. Intra Class Correlation (ICC) was used to calculate test-retest reliability. Discriminant validity between groups was gauged using the Mann-Whitney U-test.RESULTS: Cronbach's alpha varied between 0.55 and 0.76, with higher values in clinical samples than in controls. Of the four domains, general trauma showed a lower alpha than the other domains. The CFA confirmed the four-factor model previously seen and showed good to acceptable fit. The ICC value was 0.93, indicating good test-retest reliability. According to the Mann-Whitney U-test, the non-clinical sample differed significantly from the clinical sample, as did those with PTSD or borderline diagnosis from those without these diagnoses.CONCLUSIONS: The Swedish translation of the ETISR-SF was found to have similar psychometric properties as both the original version and translations. ETISR-SF scores could also distinguish between different diagnostic groups associated with various degrees of trauma, which supports its discriminant validity.
|
|
| 37. |
- Jacobson, Annica, et al.
(författare)
-
Connective tissue growth factor in tumor pathogenesis
- 2012
-
Ingår i: Fibrogenesis & Tissue Repair. - 1755-1536. ; 5:Suppl.1, s. S8-S8
-
Tidskriftsartikel (refereegranskat)abstract
- Key roles for connective tissue growth factor (CTGF/CCN2) are demonstrated in the wound repair process where it promotes myofibroblast differentiation and angiogenesis. Similar mechanisms are active in tumor-reactive stroma where CTGF is expressed. Other potential roles include prevention of hypoxia-induced apoptosis and promoting epithelial-mesenchymal transistion (EMT). CTGF expression in tumors has been associated to both tumor suppression and progression. For example, CTGF expression in acute lymphoblastic leukemia, breast, pancreas and gastric cancer correlates to worse prognosis whereas the opposite is true for colorectal, lung and ovarian cancer. This discrepancy is not yet understood.High expression of CTGF is a hallmark of ileal carcinoids, which are well-differentiated endocrine carcinomas with serotonin production originating from the small intestine and proximal colon. These tumors maintain a high grade of differentiation and low proliferation. Despite this, they are malignant and most patients have metastatic disease at diagnosis. These tumors demonstrate several phenotypes potentially related to CTGF function namely: cell migration, absent tumor cell apoptosis, as well as, reactive and well vascularised myofibroblast rich stroma and fibrosis development locally and in distal organs. The presence of CTGF in other endocrine tumors indicates a role in the progression of well-differentiated tumors.
|
|
| 38. |
|
|
| 39. |
- Just, David, et al.
(författare)
-
Autoantibodies against the C-terminus of Lipopolysaccharide binding protein are elevated in young adults with psychiatric disease
- 2021
-
Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 126
-
Tidskriftsartikel (refereegranskat)abstract
- Growing evidence implies interactions between infections, the immune system and vulnerability for psychiatric disease. This study applies an affinity proteomic-based method to investigate potential disease associated autoantibody signatures in serum from patients from the "Young Adults" section of the Department of General Psychiatry at Uppsala University Hospital (n = 395) and population-based controls (n = 102). We found serum levels of antibodies against Lipopolysaccharide Binding Protein (LBP), a protein that is important for mediating innate immune responses involving the toll-like receptor-4 (TLR-4), to be higher in patients compared to controls (Mann Whitney U-test p = 5.248 x 10(-10)). The patients were divided into three groups based on their relative levels of autoantibodies against LBP. The distribution of autism spectra disorders (p = 2.0 x 10(-4)) and hospital care for an infection as adults (p = 0.036) differed between the anti-LBP groups, with low incidence in the group of patients with the highest levels of anti-LBP who were diagnosed with primarily affective and anxiety disorders. In a sub-group analysis, the controls who screened positive for current or previous psychiatric diagnosis (n = 20) had higher anti-LBP compared to non-psychiatric controls with negative screening for psychiatric disorders (Mann Whitney U-test p = 0.006). Inflammatory markers were found to differ across anti-LBP groups and several pro-inflammatory markers, including IL-1 beta, were low in patients with high anti-LBP and serum LBP levels were lowest in patients with the highest levels of antibodies against LBP (p = 3.5 x 10(-5)). A cell-based model showed that polyclonal rabbit anti-LBP, obtained through purification via the same protein fragment used in the initial autoantibody analysis, could interfere with LBP signaling since addition of anti-LBP to the assay reduced both IL-1 beta and IL-6 release from activated monocytes in response to LBP and LPS (p = 0.0001 and p = 0.02). This novel finding of antibodies against LBP, where high levels were only found in young adults with psychiatric disease, merits further study. Our results suggest that these antibodies may have relevance for TLR4 based immune responses and vulnerability for both infection and psychiatric disorders.
|
|
| 40. |
- Just, David, et al.
(författare)
-
Exploring autoantibody signatures in brain tissue from patients with severe mental illness
- 2020
-
Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- In recent years, studies have shown higher prevalence of autoantibodies in patients with schizophrenia compared to healthy individuals. This study applies an untargeted and a targeted affinity proteomics approach to explore and characterize the autoantibody repertoire in brain tissues from 73 subjects diagnosed with schizophrenia and 52 control subjects with no psychiatric or neurological disorders. Selected brain tissue lysates were first explored for IgG reactivity on planar microarrays composed of 11,520 protein fragments representing 10,820 unique proteins. Based on these results of ours and other previous studies of autoantibodies related to psychosis, we selected 226 fragments with an average length of 80 amino acids, representing 127 unique proteins. Tissue-based analysis of IgG reactivities using antigen suspension bead arrays was performed in a multiplex and parallel fashion for all 125 subjects. Among the detected autoantigens, higher IgG reactivity in subjects with schizophrenia, as compared to psychiatrically healthy subjects, was found against the glutamate ionotropic receptor NMDA type subunit 2D (anti-GluN2D). In a separate cohort with serum samples from 395 young adults with a wider spectrum of psychiatric disorders, higher levels of serum autoantibodies targeting GluN2D were found when compared to 102 control individuals. By further validating GluN2D and additional potential autoantigens, we will seek insights into how these are associated with severe mental illnesses.
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Kaltsas, Gregory, et al.
(författare)
-
Expression of connective tissue growth factor and IGF1 in normal and neoplastic gastrointestinal neuroendocrine cells and their clinico-pathological significance
- 2011
-
Ingår i: Endocrine-Related Cancer. - Uppsala : Uppsala University. - 1351-0088 .- 1479-6821. ; 18:1, s. 61-71
-
Tidskriftsartikel (refereegranskat)abstract
- Connective tissue growth factor (CTGF) and IGF1 are both expressed in a variety of tumours and are involved in tumourigenesis. However, information about their expression in the gastrointestinal (GI) neuroendocrine (NE) cells and tumours is mainly limited, with the exception of midgut carcinoids where abundant CTGF expression has been demonstrated. Normal mucosa specimens from stomach and ileum, as well as tumour tissue specimens from gastric NE tumours (GNETs; n=58) and midgut NETs (n=38) were included. Immunohistochemical techniques were used to investigate the possible expression of CTGF and IGF1 in GI NE cells and tumours. The latter results were correlated with various clinico-biochemical and histopathological variables. CTGF was expressed in a proportion of NE cells of the normal GI mucosa but not in enterochromaffin-like (ECL) cells, whereas IGF1 was undetectable. CTGF was absent in the foci of ECL cell hyperplasia, and in most of the poorly differentiated carcinomas, but present in some GNETs (mainly in type III ECL cell carcinoids (ECL-CCs)) and in all but one midgut NETs. CTGF correlated with tumour stage in well-differentiated GNETs and with size larger than 1 cm but only in the subgroup of type I ECL-CCs. IGF1 was detected in the foci of ECL cell hyperplasia and in all GI NETs. These findings suggest that both CTGF and IGF1 may be involved in the neoplastic transformation of GI NE cells, whereas IGF1 may play an important role even at early stage.
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
- Kimmel, Mary C., et al.
(författare)
-
Heart rate variability in late pregnancy : exploration of distinctive patterns in relation to maternal mental health
- 2021
-
Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Exploration of photoplethysmography (PPG), a technique that can be translated to the clinic, has the potential to assess the autonomic nervous system (ANS) through heart rate variable (HRV) in pregnant individuals. This novel study explores the complexity of mental health of individuals in a clinical sample responding to a task in late pregnancy; finding those with several types of past or current anxiety disorders, greater trait anxiety, or greater exposure to childhood traumatic events had significantly different HRV findings from the others in the cohort. Lower high frequency (HF), a measure of parasympathetic activity, was found for women who met the criteria for the history of obsessive-compulsive disorder (OCD) (p = 0.004) compared with women who did not meet the criteria for OCD, and for women exposed to greater than five childhood traumatic events (p = 0.006) compared with those exposed to four or less childhood traumatic events. Conversely higher low frequency (LF), a measure thought to be impacted by sympathetic system effects, and the LF/HF ratio was found for those meeting criteria for a panic disorder (p = 0.006), meeting criteria for social phobia (p = 0.002), had elevated trait anxiety (p = 0.006), or exposure to greater than five childhood traumatic events (p = 0.004). This study indicates further research is needed to understand the role of PPG and in assessing ANS functioning in late pregnancy. Study of the impact of lower parasympathetic functioning and higher sympathetic functioning separately and in conjunction at baseline and in relation to tasks during late pregnancy has the potential to identify individuals that require more support and direct intervention.
|
|
| 48. |
- Kimmel, Mary C.
(författare)
-
Pregnancy—A Critical Time for Mental Health : Interrogating Psychiatry with Microbiota-Gut-Brain Axis and Autonomic Nervous System Biomarkers
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Perinatal mood and anxiety disorders (PMADs) are common and impact the parent and child beyond the perinatal period of pregnancy and postpartum. The aim of this thesis was to study biomarkers that might reflect perinatal mental health. This work focused on multiple methods of mental health characterization and the autonomic nervous system as reflected by heart rate variability (HRV), the immune system, and the gut microbiome.Three observational longitudinal cohorts of pregnant individuals from three geographic regions were studied: 1) the Biology, Affect, Stress, Imaging and Cognition (BASIC) and the follow-up study U-BIRTH from Uppsala University Hospital; 2) the University of Illinois at Chicago (UIC) MoMent cohort; and 3) the University of North Carolina at Chapel Hill (UNC) cohort.The first paper assessed HRV before and after a mental task and in relation to psychiatric diagnoses, exposure to trauma, and self-report of mental distress. The second paper studied the Perceived Stress Scale (PSS-10) in relation to microbial composition and T-cell related cytokines and chemokines. The third paper studied the Edinburgh Postnatal Depression Scale (EPDS) in relation to whole genome sequencing and Gut Brain Modules for functioning. The fourth paper assessed trajectories of infant temperament in relation to depression and anxiety from the EPDS.The PSS-10 and the EPDS factored differently in the cohorts. HRV patterns differed based on anxiety disorder type, greater trait anxiety, and greater exposure to childhood traumatic eventsut microbiome data improved the prediction of PSS-10 self-efficacy; and self-efficacy was associated with a bacteria type more beneficial in the presence of dietary fiber that also associated with an immune factor important in immune tolerance. Greatest variation in microbial community functioning was due to cortisol degradation and synthesis of inositol, menaquinone, and the short chain fatty acid (SCFA) acetate. nxiety in pregnancy was associated with children who had higher levels of sensitivity and greater negative affectivity that increased over early life.These four papers highlight: 1) the course of mental health in pregnancy is critical to the development of parent and child; 2) the characterization of perinatal mental health requires a mix of methods that recognize there may be differences in the use of the methods based on the population; and 3) biomarkers of perinatal mental health need to reflect dynamic systems, and the components may not be as important as the patterns and interactions.
|
|
| 49. |
- Kimmel, Mary, et al.
(författare)
-
Maternal and Infant Autonomic Nervous System Dysfunction
- 2021
-
Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 89:9, s. S335-S335
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background:Studying heart rate variability (HRV) in thebehavioral laboratory provides the opportunity to understandAutonomic Nervous System function during stress. Specificaspects of maternal mental distress may help identify womenand infants with greater ANS dysfunction.Methods:A cohort of women was followed through theperinatal period with the Mood and Anxiety Symptoms Ques-tionnaire (MASQ) . The Trier Social Stress Test (TSST) and aninfant stressor (giving the infant a heel stick) were administeredwith HRV monitoring at the postpartum visit. HRV values wereaveraged for segments before, during, and after the stressor.There were 70 mothers and 32 infants with complete HRV datafrom the larger cohort. Maternal sleep was measured by thePittsburgh Sleep Quality Index. The relationship betweenMASQ symptoms, sleep, and maternal and infant HRV mea-sures was analyzed with linear regressions.Results:Maternal irritability, sleep difficulty, and restlessnessfrom the MASQ was associated with alterations in HRV mea-sures after the stressor (High Frequency (HF), p¼0.019; LowFrequency (LF), p¼0.007). The same maternal symptoms werealso associated with similar alterations for the infant after thestressor (p¼0.013; LF, p¼0.009). Poorer sleep quality in thethird trimester was similarly related to infant HRV measures(HF, p¼0.013; LF, p¼0.047).Conclusions:Mothers with higher amounts of irritability,restlessness, and sleep difficulty had associated ANS differ-ences in navigating a stressor that was also mirrored in theirinfants navigating a stressor. Maternal sleep in the thirdtrimester may be an area of intervention to improve stressreactivity for mother and infant.
|
|
| 50. |
- Latini, Francesco, Ph.D. 1982-, et al.
(författare)
-
Can diffusion tensor imaging (DTI) outperform standard magnetic resonance imaging (MRI) investigations in post-COVID-19 autoimmune encephalitis?
- 2022
-
Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 127:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Neurological and psychiatric manifestations related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are widely recognised. Standard magnetic resonance imaging (MRI) investigations are normal in 40-80% of symptomatic patients, eventually delaying appropriate treatment when MRI is unrevealing any structural changes. The aim of this study is to investigate white matter abnormalities during an early stage of post-COVID-19 (coronavirus disease 2019) encephalitis while conventional MRI was normal. Methods: A patient with post-COVID-19 autoimmune encephalitis was investigated by serial MRIs and diffusion tensor imaging (DTI). Ten healthy control individuals (HC) were utilised as a control group for the DTI analysis. Major projection, commissural and association white matter pathways were reconstructed, and multiple diffusion parameters were analysed and then compared to the HC average using a z-test for serial examinations. Results: Eleven days after the onset of neurological symptoms, DTI revealed early white matter changes, compared with HC, when standard MRI was normal. On day 68, DTI showed multiple white matter lesions compared with HC, visible at this time also by the MRI images, indicating inflammatory changes in different association and projection white matter pathways. Conclusion: We confirm a limitation in the sensitivity of conventional MRI at the acute setting of postCOVID-19 autoimmune encephalitis. A complementary DTI investigation could be a valuable diagnostic tool in early therapeutic decisions concerning COVID-19-related neurological symptoms.
|
|
