| 1. |
|
|
| 2. |
- Schwarz, E, et al.
(författare)
-
Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder
- 2019
-
Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 12-
-
Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.
|
|
| 3. |
|
|
| 4. |
- Barker, ED, et al.
(författare)
-
Do ADHD-impulsivity and BMI have shared polygenic and neural correlates?
- 2021
-
Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:3, s. 1019-1028
-
Tidskriftsartikel (refereegranskat)abstract
- There is an extensive body of literature linking ADHD to overweight and obesity. Research indicates that impulsivity features of ADHD account for a degree of this overlap. The neural and polygenic correlates of this association have not been thoroughly examined. In participants of the IMAGEN study, we found that impulsivity symptoms and body mass index (BMI) were associated (r = 0.10, n = 874, p = 0.014 FWE corrected), as were their respective polygenic risk scores (PRS) (r = 0.17, n = 874, p = 6.5 × 10−6 FWE corrected). We then examined whether the phenotypes of impulsivity and BMI, and the PRS scores of ADHD and BMI, shared common associations with whole-brain grey matter and the Monetary Incentive Delay fMRI task, which associates with reward-related impulsivity. A sparse partial least squared analysis (sPLS) revealed a shared neural substrate that associated with both the phenotypes and PRS scores. In a last step, we conducted a bias corrected bootstrapped mediation analysis with the neural substrate score from the sPLS as the mediator. The ADHD PRS associated with impulsivity symptoms (b = 0.006, 90% CIs = 0.001, 0.019) and BMI (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. The BMI PRS associated with BMI (b = 0.014, 95% CIs = 0.003, 0.033) and impulsivity symptoms (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. A common neural substrate may (in part) underpin shared genetic liability for ADHD and BMI and the manifestation of their (observable) phenotypic association.
|
|
| 5. |
|
|
| 6. |
- Milton, A., et al.
(författare)
-
Development of an ICU discharge instrument predicting psychological morbidity : a multinational study
- 2018
-
Ingår i: Intensive Care Medicine. - : Springer. - 0342-4642 .- 1432-1238. ; 44:12, s. 2038-2047
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To develop an instrument for use at ICU discharge for prediction of psychological problems in ICU survivors.Methods: Multinational, prospective cohort study in ten general ICUs in secondary and tertiary care hospitals in Sweden, Denmark and the Netherlands. Adult patients with an ICU stay12h were eligible for inclusion. Patients in need of neurointensive care, with documented cognitive impairment, unable to communicate in the local language, without a home address or with more than one limitation of therapy were excluded. Primary outcome was psychological morbidity 3months after ICU discharge, defined as Hospital Anxiety and Depression Scale (HADS) subscale score11 or Post-traumatic Stress Symptoms Checklist-14 (PTSS-14) part B score>45.Results: A total of 572 patients were included and 78% of patients alive at follow-up responded to questionnaires. Twenty percent were classified as having psychological problems post-ICU. Of 18 potential risk factors, four were included in the final prediction model after multivariable logistic regression analysis: symptoms of depression [odds ratio (OR) 1.29, 95% confidence interval (CI) 1.10-1.50], traumatic memories (OR 1.44, 95% CI 1.13-1.82), lack of social support (OR 3.28, 95% CI 1.47-7.32) and age (age-dependent OR, peak risk at age 49-65years). The area under the receiver operating characteristics curve (AUC) for the instrument was 0.76 (95% CI 0.70-0.81).Conclusions: We developed an instrument to predict individual patients' risk for psychological problems 3months post-ICU, http://www.imm.ki.se/biostatistics/calculators/psychmorb/. The instrument can be used for triage of patients for psychological ICU follow-up.Trial registration: The study was registered at clinicaltrials.gov, NCT02679157.
|
|
| 7. |
- Calander, Ann-Marie, 1957, et al.
(författare)
-
Impact of staphylococcal protease expression on the outcome of infectious arthritis
- 2004
-
Ingår i: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 6:2, s. 202-6
-
Tidskriftsartikel (refereegranskat)abstract
- The exoproteases of Staphylococcus aureus have been proposed as virulence factors during S. aureus infections. To investigate this, we used the wild-type S. aureus strain 8325-4 and its mutants devoid of aureolysin, serine protease, and cysteine protease, respectively, in a well-established model of septic arthritis in mice. The inactivation of the exoprotease genes did not affect the frequency or the severity of joint disease. We conclude that in the model of haematogenously spread staphylococcal arthritis, the bacterial proteases studied do not act as virulence factors.
|
|
| 8. |
- Dohrn, Ing-Mari, et al.
(författare)
-
Device-measured sedentary behavior and physical activity in older adults differ by demographic and health-related factors
- 2020
-
Ingår i: European Review of Aging and Physical Activity. - : Springer Science and Business Media LLC. - 1813-7253 .- 1861-6909. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Our aim was to describe and explore older adults' device-measured sedentary behavior and physical activity (PA) pattern by sex, age, education, marital status, body mass index, and physical function; and to assess agreement regarding fulfillment of PA recommendations, i.e. 150 min/week of moderate-to-vigorous intensity PA (MVPA), between device-measured and self-reported PA. Method We included 656 older adults (64% women), aged 66, 81-87 or >= 90 years from a Swedish population-based cohort study. The activPAL3 accelerometer provided information on sedentary behavior (sedentary time, sedentary bouts, sit-to-stand transitions) and PA. Stepping >= 100 steps/min was considered MVPA; standing and stepping < 100 steps/min were considered light-intensity PA (LPA). Self-reported PA was compared with min/week in MVPA and steps/day. Results On average, 60% of wear time was spent sedentary, 36% in LPA, and 4% in MVPA. Relative to men, women, had significantly (p < 0.05) more sit-to-stand transitions, spent 33 min/day less sedentary and 27 min/day more in LPA, and were more likely to report meeting PA recommendations, but showed no difference in steps/day, MVPA, or sedentary bout duration. Older age was associated with more sedentary time, lower MVPA and fewer steps/day. The prevalence of meeting PA recommendations was 59% device-measured and 88% by self-report with limited agreement between methods (Cohen's Kappa = 0.21, Spearman's rho = 0.28). Age differences were much more pronounced with objective measures than by self-report. Conclusions We found significant sex differences in sedentary behavior and time in LPA in older adults, but not in MVPA, in contrast to previous findings. Sedentary time increased with age, with small differences in accumulation pattern. MVPA time was lower with older age, obesity, and poor physical function. A majority of the participants > 80 years did not meet the PA recommendations. Given the strong relationships between sedentary behavior, PA and health in older adults, programs are needed to address these behaviors. Agreement between device-measured and self-reported fulfillment of PA recommendations was limited. Device-based measurement adds value to PA studies, providing richer and different data than self-report.
|
|
| 9. |
- Ekelund, Ulf, et al.
(författare)
-
Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality : systematic review and harmonised meta-analysis
- 2019
-
Ingår i: The BMJ. - : BMJ. - 1756-1833 .- 0959-8138. ; 366
-
Forskningsöversikt (refereegranskat)abstract
- OBJECTIVETo examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality.DESIGNSystematic review and harmonised meta-analysis.DATA SOURCESPubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018.ELIGIBILITY CRITERIAProspective cohort studies assessing physical activity and sedentary time by accelerometry and associations with all cause mortality and reported effect estimates as hazard ratios, odds ratios, or relative risks with 95% confidence intervals.DATA EXTRACTION AND ANALYSISGuidelines for meta-analyses and systematic reviews for observational studies and PRISMA guidelines were followed. Two authors independently screened the titles and abstracts. One author performed a full text review and another extracted the data. Two authors independently assessed the risk of bias. Individual level participant data were harmonised and analysed at study level. Data on physical activity were categorised by quarters at study level, and study specific associations with all cause mortality were analysed using Cox proportional hazards regression analyses. Study specific results were summarised using random effects meta-analysis.MAIN OUTCOME MEASUREAll cause mortality.RESULTS39 studies were retrieved for full text review; 10 were eligible for inclusion, three were excluded owing to harmonisation challenges (eg, wrist placement of the accelerometer), and one study did not participate. Two additional studies with unpublished mortality data were also included. Thus, individual level data from eight studies (n=36 383; mean age 62.6 years; 72.8% women), with median follow-up of 5.8 years (range 3.0-14.5 years) and 2149 (5.9%) deaths were analysed. Any physical activity, regardless of intensity, was associated with lower risk of mortality, with a non-linear dose-response. Hazards ratios for mortality were 1.00 (referent) in the first quarter (least active), 0.48 (95% confidence interval 0.43 to 0.54) in the second quarter, 0.34 (0.26 to 0.45) in the third quarter, and 0.27 (0.23 to 0.32) in the fourth quarter (most active). Corresponding hazards ratios for light physical activity were 1.00, 0.60 (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51), and for moderate-to-vigorous physical activity were 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40 to 0.74), and 0.52 (0.43 to 0.61). For sedentary time, hazards ratios were 1.00 (referent; least sedentary), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15), and 2.63 (1.94 to 3.56).CONCLUSIONHigher levels of total physical activity, at any intensity, and less time spent sedentary, are associated with substantially reduced risk for premature mortality, with evidence of a non-linear dose-response pattern in middle aged and older adults.
|
|
| 10. |
- Pizzolla, A., et al.
(författare)
-
Reactive Oxygen Species Produced by the NADPH Oxidase 2 Complex in Monocytes Protect Mice from Bacterial Infections
- 2012
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 188:10, s. 5003-5011
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic granulomatous disease (CGD) is an inherited disorder characterized by recurrent life-threatening bacterial and fungal infections. CGD results from defective production of reactive oxygen species by phagocytes caused by mutations in genes encoding the NADPH oxidase 2 (NOX2) complex subunits. Mice with a spontaneous mutation in Ncf1, which encodes the NCF1 (p47(Phox)) subunit of NOX2, have defective phagocyte NOX2 activity. These mice occasionally develop local spontaneous infections by Staphylococcus xylosus or by the common CGD pathogen Staphylococcus aureus. Ncf1 mutant mice were more susceptible to systemic challenge with these bacteria than were wild-type mice. Transgenic Ncf1 mutant mice harboring the wild-type Ncf1 gene under the human CD68 promoter (MN+ mice) gained the expression of NCF1 and functional NOX2 activity specifically in monocytes/macrophages, although minimal NOX2 activity was also detected in some CD11b(+)Ly6G(+) cells defined as neutrophils. MN+ mice did not develop spontaneous infection and were more resistant to administered staphylococcal infections compared with MN- mice. Most strikingly, MN+ mice survived after being administered Burkholderia cepacia, an opportunistic pathogen in CGD patients, whereas MN- mice died. Thus, monocyte/macrophage expression of functional NCF1 protected against spontaneous and administered bacterial infections. The Journal of Immunology, 2012, 188: 5003-5011.
|
|
