| 1. |
- Valassi, E., et al.
(författare)
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High mortality within 90 days of diagnosis in patients with Cushing's syndrome: results from the ERCUSYN registry
- 2019
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 181:5, s. 461-472
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality. Methods: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years. Results: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment. Conclusion: Mortality rate was highest in patients with ectopic CS. Infectious diseases the commonest cause of death soon after diagnosis, emphasizing the need for careful vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.
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| 2. |
- Rosa, Isabel M. D., et al.
(författare)
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Multiscale scenarios for nature futures
- 2017
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Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 1:10, s. 1416-1419
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Targets for human development are increasingly connected with targets for nature, however, existing scenarios do not explicitly address this relationship. Here, we outline a strategy to generate scenarios centred on our relationship with nature to inform decision-making at multiple scales.
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| 3. |
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| 4. |
- Goodwin, G. M., et al.
(författare)
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Evidence-based guidelines for treating bipolar disorder : Revised third edition recommendations from the British Association for Psychopharmacology
- 2016
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Ingår i: Journal of Psychopharmacology. - : SAGE PUBLICATIONS LTD. - 0269-8811 .- 1461-7285. ; 30:6, s. 495-553
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Forskningsöversikt (refereegranskat)abstract
- The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.
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| 5. |
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| 6. |
- Babchishin, K. M., et al.
(författare)
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Parental and perinatal risk factors for sexual offending in men : a nationwide case-control study
- 2017
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Ingår i: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 47:2, s. 305-315
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Tidskriftsartikel (refereegranskat)abstract
- Background. Prior studies suggest parental and perinatal risk factors are associated with later offending. It remains uncertain, however, if such risk factors are similarly related to sexual offending. Method. We linked socio-demographic, family relations, and perinatal (obtained at birth) data from the nationwide Swedish registers from 1973 to 2009 with information on criminal convictions of cases and control subjects. Male sex offenders (n = 13 773) were matched 1: 5 on birth year and county of birth in Sweden to male controls without sexual or non-sexual violent convictions. To examine risk-factor specificity for sexual offending, we also compared male violent, non-sexual offenders (n = 135 953) to controls without sexual or non-sexual violent convictions. Predictors included parental (young maternal or paternal age at son's birth, educational attainment, violent crime, psychiatric disorder, substance misuse, suicide attempt) and perinatal (number of older brothers, low Apgar score, low birth weight, being small for gestational age, congenital malformations, small head size) variables. Results. Conditional logistic regression models found consistent patterns of statistically significant, small to moderate independent associations of parental risk factors with sons' sexual offending and non-sexual violent offending. For perinatal risk factors, patterns varied more; small for gestational age and small head size exhibited similar risk effects for both offence types whereas a higher number of older biological brothers and any congenital malformation were small, independent risk factors only for non-sexual violence. Conclusions. This nationwide study suggests substantial commonalities in parental and perinatal risk factors for the onset of sexual and non-sexual violent offending.
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| 7. |
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| 8. |
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| 9. |
- Hossain, M. Akhter, et al.
(författare)
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Synthesis, conformation, and activity of human insulin-like peptide 5 (INSL5)
- 2008
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 9:11, s. 1816-1822
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like peptide 5 (INSL5) was first identified through searches of the expressed sequence tags (EST) databases. Primary sequence analysis showed it to be a prepropeptide that was predicted to be processed in vivo to yield a two-chain sequence (A and B) that contained the insulin-like disulfide cross-links. The high affinity interaction between INSL5 and the receptor RXFP4 (GPCR142) coupled with their apparent coevolution and partially overlapping tissue expression patterns strongly suggest that INSL5 is an endogenous ligand for RXFP4. Given that the primary function of the INSL5–RXFP4 pair remains unknown, an effective means of producing sufficient quantities of this peptide and its analogues is needed to systematically investigate its structural and biological properties. A combination of solid-phase peptide synthesis methods together with regioselective disulfide bond formation were used to obtain INSL5. Both chains were unusually resistant to standard synthesis protocols and required highly optimized conditions for their acquisition. In particular, the use of a strong tertiary amidine, DBU, as Nα-deprotection base was required for the successful assembly of the B chain; this highlights the need to consider incomplete deprotection rather than acylation as a cause of failed synthesis. Following sequential disulfide bond formation and chain combination, the resulting synthetic INSL5, which was obtained in good overall yield, was shown to possess a similar secondary structure to human relaxin-3 (H3 relaxin). The peptide was able to inhibit cAMP activity in SK-N-MC cells that expressed the human RXFP4 receptor with a similar activity to H3 relaxin. In contrast, it had no activity on the human RXFP3 receptor. Synthetic INSL5 demonstrates equivalent activity to the recombinant-derived peptide, and will be an important tool for the determination of its biological function.
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| 10. |
- Yeung, Andy Wai Kan, et al.
(författare)
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Dietary natural products and their potential to influence health and disease including animal model studies
- 2018
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Ingår i: Animal Science Papers and Reports. - : POLSKA AKAD NAUK, INST GENETYKI I HODOWLI ZWIERZAT. - 0860-4037. ; 36:4, s. 345-358
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Forskningsöversikt (refereegranskat)abstract
- Although biological and pharmacological effects of dietary natural products have been intensively studied, there has been no bibliometric analysis performed on this research field up to now. The current study has aimed to identify and analyze the manuscripts on dietary natural products and their potential to influence health and disease including studies using animal models. Data, including words from titles and abstracts, publication and citation data, have been extracted from Web of Science database and analyzed by the VOSviewer software. Our search has yielded 1,014 manuscripts. The ratio of original articles to reviews was identified to be 1.5:1. Over half of the manuscripts have been published since 2010. The manuscripts have been contributed by 4,301 authors from 1,445 organizations in 76 countries/territories and published in 499 journals. The results from the current study point out that scientific research focusing on the potential of dietary natural products to affect health and disease status (including animal model studies) is expanding, and suggests an increasing significance of this scientific area. With the progressive development and improvement of animal studies, it should be expected that animal models of different human diseases (especially civilization ones) would be an integral part of the research for the evaluation of pharmaceuticals originated from dietary natural products like plants or plant materials. Moreover, natural products can also be fed to animals to improve the quality of animal products, with numerous resulting functional effects.
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| 11. |
- Yu, Rongqin, et al.
(författare)
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Mental disorders and intimate partner violence perpetrated by men towards women : A Swedish population-based longitudinal study
- 2019
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intimate partner violence (IPV) against women is associated with a wide range of adverse outcomes. Although mental disorders have been linked to an increased risk of perpetrating IPV against women, the direction and magnitude of the association remain uncertain. In a longitudinal design, we examined the association between mental disorders and IPV perpetrated by men towards women in a population-based sample and used sibling comparisons to control for factors shared by siblings, such as genetic and early family environmental factors.METHODS AND FINDINGS: Using Swedish nationwide registries, we identified men from 9 diagnostic groups over 1998-2013, with sample sizes ranging from 9,529 with autism to 88,182 with depressive disorder. We matched individuals by age and sex to general population controls (ranging from 186,017 to 1,719,318 controls), and calculated the hazard ratios of IPV against women. We also estimated the hazard ratios of IPV against women in unaffected full siblings (ranging from 4,818 to 37,885 individuals) compared with the population controls. Afterwards, we compared the hazard ratios for individuals with psychiatric diagnoses with those for siblings using the ratio of hazard ratios (RHR). In sensitivity analyses, we examined the contribution of previous IPV against women and common psychiatric comorbidities, substance use disorders and personality disorders. The average follow-up time across diagnoses ranged from 3.4 to 4.8 years. In comparison to general population controls, all psychiatric diagnoses studied except autism were associated with an increased risk of IPV against women in men, with hazard ratios ranging from 1.5 (95% CI 1.3-1.7) to 7.7 (7.2-8.3) (p-values < 0.001). In sibling analyses, we found that men with depressive disorder, anxiety disorder, alcohol use disorder, drug use disorder, attention deficit hyperactivity disorder, and personality disorders had a higher risk of IPV against women than their unaffected siblings, with RHR values ranging from 1.7 (1.3-2.1) to 4.4 (3.7-5.2) (p-values < 0.001). Sensitivity analyses showed higher risk of IPV against women in men when comorbid substance use disorders and personality disorders were present, compared to risk when these comorbidities were absent. In addition, increased IPV risk was also found in those without previous IPV against women. The absolute rates of IPV against women ranged from 0.1% to 2.1% across diagnoses over 3.4 to 4.8 years. Individuals with alcohol use disorders (1.7%, 1,406/82,731) and drug use disorders (2.1%, 1,216/57,901) had the highest rates. Our analyses were restricted to IPV leading to arrest, suggesting that the applicability of our results may be limited to more severe forms of IPV perpetration.CONCLUSIONS: Our results indicate that most of the studied mental disorders are associated with an increased risk of perpetrating IPV towards women, and that substance use disorders, as principal or comorbid diagnoses, have the highest absolute and relative risks. The findings support the development of IPV risk identification and prevention services among men with substance use disorders as an approach to reduce the prevalence of IPV.
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| 12. |
- Abdi, Saida, et al.
(författare)
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Promoting positive development among refugee adolescents
- 2023
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Ingår i: Journal of research on adolescence. - : John Wiley & Sons. - 1050-8392 .- 1532-7795. ; 33:4, s. 1064-1084
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Forskningsöversikt (refereegranskat)abstract
- Of the estimated 35.3 million refugees around the world (UNHCR, Figures at a Glance, 2022), approximately 50% are children under the age of 18. Refugee adolescents represent a unique group as they navigate developmental tasks in an unstable and often threatening environment or in resettlement contexts in which they often face marginalization. In addition to physiological, social, and psychological changes that mark adolescence, refugee youth often face traumatic experiences, acculturative stress, discrimination, and a lack of basic resources. In this consensus statement, we examine research on refugee adolescents' developmental tasks, acculturative tasks, and psychological adjustment using Suarez-Orozco and colleague's integrative risk and resilience model for immigrant-origin children and youth proposed by Suarez-Orozco et al. Finally, we discuss recommendations-moving from proximal to more distal contexts.
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| 13. |
- Abdolahpur Monikh, Fazel, et al.
(författare)
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Parental and trophic transfer of nanoscale plastic debris in an assembled aquatic food chain as a function of particle size
- 2021
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Ingår i: Environmental Pollution. - : Springer. - 0269-7491 .- 1873-6424. ; 269
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Tidskriftsartikel (refereegranskat)abstract
- The existing limitations in analytical techniques for characterization and quantification of nanoscale plastic debris (NPD) in organisms hinder understanding of the parental and trophic transfer of NPD in organisms. Herein, we used iron oxide-doped polystyrene (PS) NPD (Fe-PS-NPD) of 270 nm and Europium (Eu)-doped PS-NPD (Eu-PS-NPD) of 640 nm to circumvent these limitations and to evaluate the influence of particle size on the trophic transfer of NPD along an algae-daphnids food chain and on the reproduction of daphnids fed with NPD-exposed algae. We used Fe and Eu as proxies for the Fe-PS-NPD and Eu-Ps-NPD, respectively. The algae cells (Pseudokirchinella subcapitata) were exposed to 4.8 × 1010 particles/L of Fe-PS-NPD or Eu-PS-NPD for 72 h. A high percentage (>60%) of the NPD was associated with algal cells. Only a small fraction (<11%) of the NPD, however, was transferred to daphnids fed for 21 days on the NPD-exposed algae. The uptake and trophic transfer of the 270 nm Fe-PS-NPD were higher than those for the 640 nm Eu-PS-NPD, indicating that smaller NPD are more likely to transfer along food chains. After exposure to Fe-PS-NPD, the time to first brood was prolonged and the number of neonates per adult significantly decreased compared to the control without any exposure and compared to daphnids exposed to the Eu-Ps-NPD. The offspring of daphnids exposed to Eu-PS-NPD through algae, showed a traceable concentration of Eu, suggesting that NPD are transferred from parents to offspring. We conclude that NPD can be transferred in food chains and caused reproductive toxicity as a function of NPD size. Studies with prolonged exposure and weathered NPD are endeavored to increase environmental realism of the impacts determined.
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| 14. |
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| 15. |
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| 16. |
- Au, C. E., et al.
(författare)
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Compartmentalization of membrane trafficking, glucose transport, glycolysis, actin, tubulin and the proteasome in the cytoplasmic droplet/Hermes body of epididymal sperm
- 2015
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Ingår i: Open Biology. - : The Royal Society. - 2046-2441. ; 5:8
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Tidskriftsartikel (refereegranskat)abstract
- Discovered in 1909 by Retzius and described mainly by morphology, the cytoplasmic droplet of sperm (renamed here the Hermes body) is conserved among all mammalian species but largely undefined at the molecular level. Tandem mass spectrometry of the isolated Hermes body from rat epididymal sperm characterized 1511 proteins, 43 of which were localized to the structure in situ by light microscopy and two by quantitative electron microscopy localization. Glucose transporter 3 (GLUT-3) glycolytic enzymes, selected membrane traffic and cytoskeletal proteins were highly abundant and concentrated in the Hermes body. By electron microscope gold antibody labelling, the Golgi trafficking protein TMED7/p27 localized to unstacked flattened cisternae of the Hermes body, as did GLUT-3, the most abundant protein. Its biogenesis was deduced through the mapping of protein expression for all 43 proteins during male germ cell differentiation in the testis. It is at the terminal step 19 of spermiogenesis that the 43 characteristic proteins accumulated in the nascent Hermes body.
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| 17. |
- Au, C. E., et al.
(författare)
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Expression, sorting, and segregation of Golgi proteins during germ cell differentiation in the testis
- 2015
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Ingår i: Molecular Biology of the Cell. - 1059-1524. ; 26:22, s. 4015-4032
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Tidskriftsartikel (refereegranskat)abstract
- The molecular basis of changes in structure, cellular location, and function of the Golgi apparatus during male germ cell differentiation is unknown. To deduce cognate Golgi proteins, we isolated germ cell Golgi fractions, and 1318 proteins were characterized, with 20 localized in situ. The most abundant protein, GL54D of unknown function, is characterized as a germ cell-specific Golgi-localized type II integral membrane glycoprotein. TM9SF3, also of unknown function, was revealed to be a universal Golgi marker for both somatic and germ cells. During acrosome formation, several Golgi proteins (GBF1, GPP34, GRASP55) localize to both the acrosome and Golgi, while GL54D, TM9SF3, and the Golgi trafficking protein TMED7/p27 are segregated from the acrosome. After acrosome formation, GL54D, TM9SF3, TMED4/p25, and TMED7/p27 continue to mark Golgi identity as it migrates away from the acrosome, while the others (GBF1, GPP34, GRASP55) remain in the acrosome and are progressively lost in later steps of differentiation. Cytoplasmic HSP70.2 and the endoplasmic reticulum luminal protein-folding enzyme PDILT are also Golgi recruited but only during acrosome formation. This resource identifies abundant Golgi proteins that are expressed differentially during mitosis, meiosis, and postacrosome Golgi migration, including the last step of differentiation.
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| 18. |
- Babchishin, Kelly M., et al.
(författare)
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Are There Early Risk Markers for Pedophilia? : A Nationwide Case-Control Study of Child Sexual Exploitation Material Offenders
- 2019
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Ingår i: Journal of Sex Research. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 0022-4499 .- 1559-8519. ; 56:2, s. 203-212
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Tidskriftsartikel (refereegranskat)abstract
- Although prior research suggests associations between parental characteristics and later sexual offending in offspring, possible links between early pregnancy-related factors and sexual offending remain unclear. Early risk markers unique to sexual offending, however, may be more prominent among sexual offenders with atypical sexual interests, such as individuals involved with child sexual exploitation material (CSEM; also referred to as child pornography). We examined the prospective association between parental and pregnancy-related risk markers and a behavioral indicator of pedophilic interest, CSEM offending. All 655 men born in Sweden and convicted of CSEM offending between 1988 to 2009 were matched 1:5 on sex, birth year, and county of birth in Sweden to 3,928 controls without sexual or nonsexual violent convictions. Paternal age (adjusted odds ratio [AOR] = 1.3, 95% confidence interval [CI] [1.1, 1.7]), parental education (AOR = 0.8, 95% CI [0.6, 0.9]), parental violent criminality (AOR = 2.9, 95% CI [2.2, 3.8]), number of older brothers (AOR = 0.8, 95% CI [0.6, 0.9] per brother), and congenital malformations (AOR = 1.7, 95% CI [1.2, 2.4]) all independently predicted CSEM convictions. This large-scale, nationwide study suggests parental risk markers for CSEM offending. We did not, however, find convincing evidence for pregnancy-related risk markers, with the exception of congenital malformations and having fewer older brothers.
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| 19. |
- Chen, Qi, et al.
(författare)
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Predicting suicide attempt or suicide death following a visit to psychiatric specialty care : A machine learning study using Swedish national registry data
- 2020
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Ingår i: PLoS Medicine. - San Francisco : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a major public health concern globally. Accurately predicting suicidal behavior remains challenging. This study aimed to use machine learning approaches to examine the potential of the Swedish national registry data for prediction of suicidal behavior.METHODS AND FINDINGS: The study sample consisted of 541,300 inpatient and outpatient visits by 126,205 Sweden-born patients (54% female and 46% male) aged 18 to 39 (mean age at the visit: 27.3) years to psychiatric specialty care in Sweden between January 1, 2011 and December 31, 2012. The most common psychiatric diagnoses at the visit were anxiety disorders (20.0%), major depressive disorder (16.9%), and substance use disorders (13.6%). A total of 425 candidate predictors covering demographic characteristics, socioeconomic status (SES), electronic medical records, criminality, as well as family history of disease and crime were extracted from the Swedish registry data. The sample was randomly split into an 80% training set containing 433,024 visits and a 20% test set containing 108,276 visits. Models were trained separately for suicide attempt/death within 90 and 30 days following a visit using multiple machine learning algorithms. Model discrimination and calibration were both evaluated. Among all eligible visits, 3.5% (18,682) were followed by a suicide attempt/death within 90 days and 1.7% (9,099) within 30 days. The final models were based on ensemble learning that combined predictions from elastic net penalized logistic regression, random forest, gradient boosting, and a neural network. The area under the receiver operating characteristic (ROC) curves (AUCs) on the test set were 0.88 (95% confidence interval [CI] = 0.87-0.89) and 0.89 (95% CI = 0.88-0.90) for the outcome within 90 days and 30 days, respectively, both being significantly better than chance (i.e., AUC = 0.50) (p < 0.01). Sensitivity, specificity, and predictive values were reported at different risk thresholds. A limitation of our study is that our models have not yet been externally validated, and thus, the generalizability of the models to other populations remains unknown.CONCLUSIONS: By combining the ensemble method of multiple machine learning algorithms and high-quality data solely from the Swedish registers, we developed prognostic models to predict short-term suicide attempt/death with good discrimination and calibration. Whether novel predictors can improve predictive performance requires further investigation.
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| 29. |
- Fazel, S, et al.
(författare)
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Risk factors for criminal recidivism in older sexual offenders
- 2006
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Ingår i: Sexual abuse : a journal of research and treatment. - : SAGE Publications. - 1079-0632. ; 18:2, s. 159-167
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Tidskriftsartikel (refereegranskat)abstract
- Sexual offenders constitute a substantial proportion of the older male prison population. Recent research findings, with potential consequences for risk management, indicate that recidivism risk might be lower in older sexual offenders. We followed up all adult male sexual offenders released from prison in Sweden during 1993-1997 (N =1,303) for criminal reconviction for an average of 8.9 years. We studied rates of repeat offending (sexual and any violent) by four age bands (<25, 25-39, 40-54, and 55 +years), and examined whether risk factors for recidivism remained stable across age groups. Results showed that recidivism rates decreased significantly in older age bands. In addition, the effect of certain risk factors varied by age band. These findings on recidivism rates in older sexual offenders concur with studies from the United Kingdom, United States, and Canada and may suggest some generalizability in Western settings. Further research is needed to address underlying mechanisms.
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| 30. |
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| 31. |
- Fazel, Seena, et al.
(författare)
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Risk of death by suicide following self-harm presentations to healthcare : development and validation of a multivariable clinical prediction rule (OxSATS)
- 2023
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Ingår i: BMJ Mental Health. - : BMJ Publishing Group Ltd. - 2755-9734. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Assessment of suicide risk in individuals who have self-harmed is common in emergency departments, but is often based on tools developed for other purposes. OBJECTIVE: We developed and validated a predictive model for suicide following self-harm.METHODS: We used data from Swedish population-based registers. A cohort of 53 172 individuals aged 10+ years, with healthcare episodes of self-harm, was split into development (37 523 individuals, of whom 391 died from suicide within 12 months) and validation (15 649 individuals, 178 suicides within 12 months) samples. We fitted a multivariable accelerated failure time model for the association between risk factors and time to suicide. The final model contains 11 factors: age, sex, and variables related to substance misuse, mental health and treatment, and history of self-harm. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis guidelines were followed for the design and reporting of this work.FINDINGS: An 11-item risk model to predict suicide was developed using sociodemographic and clinical risk factors, and showed good discrimination (c-index 0.77, 95% CI 0.75 to 0.78) and calibration in external validation. For risk of suicide within 12 months, using a 1% cut-off, sensitivity was 82% (75% to 87%) and specificity was 54% (53% to 55%). A web-based risk calculator is available (Oxford Suicide Assessment Tool for Self-harm or OxSATS).CONCLUSIONS: OxSATS accurately predicts 12-month risk of suicide. Further validations and linkage to effective interventions are required to examine clinical utility.CLINICAL IMPLICATIONS: Using a clinical prediction score may assist clinical decision-making and resource allocation.
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| 36. |
- Fazel, S., et al.
(författare)
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Suicides by violent means in individuals taking SSRIs and other antidepressants : A postmortem study in Sweden, 1992-2004
- 2007
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Ingår i: Journal of Clinical Psychopharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0271-0749 .- 1533-712X. ; 27:5, s. 503-506
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Tidskriftsartikel (refereegranskat)abstract
- A number of reports have linked consumption of selective serotonin reuptake inhibitors (SSRIs) with suicide by violent methods. We aimed to determine whether suicides with postmortem evidence of SSRI consumption are more likely to have used violent methods compared with suicides with no detectable antidepressants. Blood samples from all suicides in Sweden during 1992-2004 were examined. Suicides were classified into those who died by violence and nonviolent (self-poisoning) methods using information from police records and autopsy. In addition, we investigated proportions of violent suicide in individuals who died with detectable levels of tricyclic and other antidepressants.The sample consisted of 14,691 suicides. Of the 1958 suicides with detectable levels of SSRIs, 1247 were by violent means (63.7%) compared with 7835 of 11,045 suicides (70.9%) in antidepressant-free group (?1 = 7.6, P < 0.01). We found no significant differences in the proportion of violent suicides in the SSRI group compared with the antidepressant-free group by sex or age band (15-24, 25-39, and over 40 years). When subdivided by gender and age-bands, we found specific groups with significantly lower proportions of violent suicides compared with the antidepressants-free group, including men aged 15-24 years. © 2007 Lippincott Williams & Wilkins, Inc.
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| 40. |
- Gannon, J., et al.
(författare)
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ARFGAP1 Is Dynamically Associated with Lipid Droplets in Hepatocytes
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- The ARF GTPase Activating Protein 1 (ARFGAP1) associates mainly with the cytosolic side of Golgi cisternal membranes where it participates in the formation of both COPI and clathrin-coated vesicles. In this study, we show that ARFGAP1 associates transiently with lipid droplets upon addition of oleate in cultured cells. Also, that addition of cyclic AMP shifts ARFGAP1 from lipid droplets to the Golgi apparatus and that overexpression and knockdown of ARFGAP1 affect lipid droplet formation. Examination of human liver tissue reveals that ARFGAP1 is found associated with lipid droplets at steady state in some but not all hepatocytes.
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| 41. |
- Ghirardi, Laura, et al.
(författare)
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Neurodevelopmental disorders and subsequent risk of violent victimization : exploring sex differences and mechanisms
- 2022
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 53:4, s. 1510-1517
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neurodevelopmental disorders (NDs) are associated with experiences of victimization, but mechanisms remain unclear. We explored sex differences and the role of familial factors and externalizing problems in the association between several NDs and violent victimization in adolescence and young adulthood.Methods: Individuals born in Sweden 1985-1997, residing in Sweden at their 15th birthday, were followed until date of violent victimization causing a hospital visit or death, death due to other causes, emigration, or December 31, 2013, whichever came first. The exposures were diagnoses of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID) and other NDs. We used three different Cox regression models: a crude model, a model adjusted for familial confounding using sibling-comparisons, and a model additionally adjusted for externalizing problems.Results: Among 1 344 944 individuals followed, on average, for 5 years, 74 487 were diagnosed with NDs and 37 765 had a hospital visit or died due to violence. ADHD was associated with an increased risk of violent victimization in males [hazard ratio (HR) 2.56; 95% confidence interval (CI) 2.43-2.70) and females (HR 5.39; 95% CI 4.97-5.85). ASD and ID were associated with an increased risk of violent victimization in females only. After adjusting for familial factors and externalizing problems, only ADHD was associated with violent victimization among males (HR 1.27; 95% CI 1.06-1.51) and females (HR 1.69; 95% CI 1.21-2.36).Conclusions: Females with NDs and males with ADHD are at greater risk of being victim of severe violence during adolescence and young adulthood. Relevant mechanisms include shared familial liability and externalizing problems. ADHD may be independently associated with violent victimization.
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| 44. |
- Haugaard-Kedström, Linda M., et al.
(författare)
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Design, synthesis, and characterization of a single-chain peptide antagonist for the relaxin-3 receptor RXFP3
- 2011
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 133:13, s. 4965-4974
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Tidskriftsartikel (refereegranskat)abstract
- Relaxin-3 is a two-chain disulfide-rich peptide that is the ancestral member of the relaxin peptide family and, together with its G protein-coupled receptor RXFP3, is highly expressed in the brain. Strong evolutionary conservation of relaxin-3 suggests a critical biological function and recent studies have demonstrated modulation of sensory, neuroendocrine, metabolic, and cognitive systems. However, detailed studies of central relaxin-3-RXFP3 signaling have until now been severely hampered by the lack of a readily available high-affinity antagonist for RXFP3. Previous studies have utilized a complex two-chain chimeric relaxin peptide, R3(B Delta 23-27)R/I5, in which a truncated relaxin-3 B-chain carrying an additional C-terminal Arg residue was combined with the insulin-like peptide S (INSL5) A-chain. In this study we demonstrate that, by replacing the native Cys in this truncated relaxin-3 B-chain with Ser, a single-chain linear peptide of 23 amino acids that retains high-affinity antagonism for RXFP3 can be achieved. In vivo studies demonstrate that this peptide, R3 B1-22R, antagonized relaxin-3/RXFP3 induced increases in feeding in rats after intracerebroventricular injection. Thus, R3 B1-22R represents an excellent tool for biological studies probing relaxin pharmacology and a lead molecule for the development of synthetically tractable, single-chain RXFP3 modulators for clinical use.
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| 45. |
- Hegvik, Tor-Arne, et al.
(författare)
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Labor epidural analgesia and subsequent risk of offspring autism spectrum disorder and attention-deficit/hyperactivity disorder : A cross-national cohort study of 4.5 million individuals and their siblings
- 2023
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 228:2, s. 233.e1-233.e12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A recent study has suggested that labor epidural analgesia may be associated with increased rates of offspring autism spectrum disorder (ASD). Subsequent replication attempts have lacked sufficient power to confidently exclude the possibility of a small effect and the causal nature of this association remains unknown.OBJECTIVE: To investigate the extent to which exposure to labor epidural analgesia is associated with offspring ASD and attention-deficit/hyperactivity disorder (ADHD) following adjustments for unmeasured familial confounding.STUDY DESIGN: We identified 4,498,462 singletons and their parents using the Medical Birth Registers in Finland (cohorts born 1987-2005), Norway (1999-2015), and Sweden (1987-2011), linked with population and patient registries. These cohorts were followed from birth until they either had the outcomes of interest, emigrated, died, or reached the end of the follow-up (at mean ages 13.6-16.8 years), whichever occurred first. Cox regression models were used to estimate country-specific associations between labor epidural analgesia recorded at birth and outcomes (e.g., at least one secondary care diagnosis of ASD and ADHD or at least one dispensed prescription of medication used for the treatment of ADHD). The models were adjusted for sex, birth year, birth order, and unmeasured familial confounders via sibling-comparisons. Pooled estimates across all three countries were estimated using inverse variance weighted fixed-effects meta-analysis models.RESULTS: A total of 4,498,462 individuals (48.7% female) were included, 1,091,846 (24.3%) of which were exposed to labor epidural analgesia. Of these, 1.2% were diagnosed with ASD and 4.0% with ADHD. On the population level, pooled estimates showed that labor epidural analgesia was associated with increased risk of offspring ASD (adjusted hazard ratio, aHR=1.12; 95% CI: 1.10-1.14, absolute risks: 1.20% vs. 1.07%) and ADHD (aHR=1.20; 1.19-1.21; 3.95% vs. 3.32%). However, when comparing full-siblings who were differentially exposed to labor epidural analgesia, the associations were fully attenuated for both conditions, with narrow confidence intervals (aHRASD=0.98; 0.93-1.03; aHRADHD=0.99; 0.96-1.02).CONCLUSION: In this large cross-national study, we found no support for the hypothesis that exposure to labor epidural analgesia causes either offspring autism spectrum disorder or attention-deficit/hyperactivity disorder.
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| 46. |
- Hossain, M. Akhter, et al.
(författare)
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The structural and functional role of the B-chain C-terminal arginine in the relaxin-3 peptide antagonist, R3(B Delta 23-27)R/I5.
- 2009
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Ingår i: Chemical Biology and Drug Design. - : Wiley. - 1747-0277 .- 1747-0285. ; 73:1, s. 46-52
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Tidskriftsartikel (refereegranskat)abstract
- Relaxin-3, a member of the insulin superfamily, is involved in regulating stress and feeding behavior. It is highly expressed in the brain and is the endogenous ligand for the receptor RXFP3. As relaxin-3 also interacts with the relaxin receptor RXFP1, selective agonists and antagonists are crucial for studying the physiological function(s) of the relaxin-3/RXFP3 pair. The analog R3(B Delta 23-27)R/I5, in which a C-terminally truncated human relaxin-3 (H3) B-chain is combined with the INSL5 A-chain, is a potent selective RXFP3 antagonist and has an Arg residue remaining on the B-chain C-terminus as a consequence of the recombinant protein production process. To investigate the role of this residue in the RXFP3 receptor binding and activation, the analogs R3(B Delta 23-27)R/I5 and R3(B Delta 23-27)R containing the B-chain C-terminal Arg as well as R3(B Delta 23-27)/I5 and R3(B Delta 23-27), both lacking the Arg, were chemically assembled and their secondary structure and receptor activity assessed. The peptides generally had a similar conformation but those with the extra Arg residue displayed a significantly increased affinity for the RXFP3. Interestingly, in contrast to R3(B Delta 23-27)R and R3(B Delta 23-27)R/I5, the peptide R3(B Delta 23-27) is a weak agonist. This suggests that the C-terminal Arg, although increasing the affinity, alters the manner in which the peptide binds to the receptor and thereby prevents activation, giving R3(B Delta 23-27)R/I5 its potent antagonistic activity.
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| 47. |
- Jones, Roland M., et al.
(författare)
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Alcohol Use Disorders in Schizophrenia : A National Cohort Study of 12,653 Patients
- 2011
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Ingår i: Journal of Clinical Psychiatry. - 0160-6689 .- 1555-2101. ; 72:6, s. 775-779
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Tidskriftsartikel (refereegranskat)abstract
- Background: Comorbid alcohol use disorders (AUDs) in schizophrenia are associated with increased morbidity, more inpatient treatment, and violent offending. It is of clinical importance to identify those with schizophrenia who may go on to develop an alcohol use disorder; however, the risk factors are not well understood. The aim of this study was to identify risk factors for the development of an AUD in patients after they had been diagnosed with schizophrenia. Method: We conducted a retrospective case-control study of 12,653 individuals diagnosed with ICD-defined schizophrenia in Sweden in 1973-2004, using data from national registers. We tested the associations between individual factors (marital status, immigrant status, and previous violent offending), sociodemographic factors (income and education), and parental risk factors (AUDs, psychosis, and violent offending) ICD-defined and AUD development using logistic regression modeling. Results: Over a median follow-up of 17.3 years, 7.6% of patients had at least 1 hospital diagnosis of AUD. After adjustment for gender and age at diagnosis in a multivariate regression model, previous violent offending (OR=2.1; 95% CI, 1.8-2.5), low education (OR=1.3; 95% CI, 1.1-1.5), maternal AUD (OR=1.9; 95% CI, 1.4-2.7), and paternal AUD (OR=1.9; 95% CI, 1.5-2.3) remained independently associated with increased risk of patient AUD. Conclusions: AUDs are a common sequela of schizophrenia. Risk factors that could be identified at the time of first presentation include low educational attainment, previous violent offending, and parental history of AUDs and may inform clinical treatment and follow-up of those most at risk.
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| 48. |
- Långström, Niklas, et al.
(författare)
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Sexual offending runs in families : a 37-year nationwide study
- 2015
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Ingår i: International Journal of Epidemiology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0300-5771 .- 1464-3685.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sexual crime is an important public health concern. The possible causes of sexual aggression, however, remain uncertain. METHODS: We examined familial aggregation and the contribution of genetic and environmental factors to sexual crime by linking longitudinal, nationwide Swedish crime and multigenerational family registers. We included all men convicted of any sexual offence (N = 21,566), specifically rape of an adult (N = 6131) and child molestation (N = 4465), from 1973 to 2009. Sexual crime rates among fathers and brothers of sexual offenders were compared with corresponding rates in fathers and brothers of age-matched population control men without sexual crime convictions. We also modelled the relative influence of genetic and environmental factors to the liability of sexual offending. RESULTS: We found strong familial aggregation of sexual crime [odds ratio (OR) = 5.1, 95% confidence interval (CI) = 4.5-5.9] among full brothers of convicted sexual offenders. Familial aggregation was lower in father-son dyads (OR = 3.7, 95% CI = 3.2-4.4) among paternal half-brothers (OR = 2.1, 95% CI = 1.5-2.9) and maternal half-brothers (OR = 1.7, 95% CI = 1.2-2.4). Statistical modelling of the strength and patterns of familial aggregation suggested that genetic factors (40%) and non-shared environmental factors (58%) explained the liability to offend sexually more than shared environmental influences (2%). Further, genetic effects tended to be weaker for rape of an adult (19%) than for child molestation (46%). CONCLUSIONS: We report strong evidence of familial clustering of sexual offending, primarily accounted for by genes rather than shared environmental influences. Future research should possibly test the effectiveness of selective prevention efforts for male first-degree relatives of sexually aggressive individuals, and consider familial risk in sexual violence risk assessment.
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| 49. |
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| 50. |
- Molero, Yasmina, et al.
(författare)
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Associations between gabapentinoids and suicidal behaviour, unintentional overdoses, injuries, road traffic incidents, and violent crime : population based cohort study in Sweden
- 2019
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833 .- 0959-8138. ; 365
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine associations between gabapentinoids and adverse outcomes related to coordination disturbances (head or body injuries, or both and road traffic incidents or offences), mental health (suicidal behaviour, unintentional overdoses), and criminality.DESIGN: Population based cohort study.SETTING: High quality prescription, patient, death, and crime registers, Sweden.PARTICIPANTS: 191 973 people from the Swedish Prescribed Drug Register who collected prescriptions for gabapentinoids (pregabalin or gabapentin) during 2006 to 2013.MAIN OUTCOME MEASURES: Primary outcomes were suicidal behaviour, unintentional overdoses, head/body injuries, road traffic incidents and offences, and arrests for violent crime. Stratified Cox proportional hazards regression was conducted comparing treatment periods with non-treatment periods within an individual. Participants served as their own control, thus accounting for time invariant factors (eg, genetic and historical factors), and reducing confounding by indication. Additional adjustments were made by age, sex, comorbidities, substance use, and use of other antiepileptics.RESULTS: During the study period, 10 026 (5.2%) participants were treated for suicidal behaviour or died from suicide, 17 144 (8.9%) experienced an unintentional overdose, 12 070 (6.3%) had a road traffic incident or offence, 70 522 (36.7%) presented with head/body injuries, and 7984 (4.1%) were arrested for a violent crime. In within-individual analyses, gabapentinoid treatment was associated with increased hazards of suicidal behaviour and deaths from suicide (age adjusted hazard ratio 1.26, 95% confidence interval 1.20 to 1.32), unintentional overdoses (1.24, 1.19 to 1.28), head/body injuries (1.22, 1.19 to 1.25), and road traffic incidents and offences (1.13, 1.06 to 1.20). Associations with arrests for violent crime were less clear (1.04, 0.98 to 1.11). When the drugs were examined separately, pregabalin was associated with increased hazards of all outcomes, whereas gabapentin was associated with decreased or no statistically significant hazards. When stratifying on age, increased hazards of all outcomes were associated with participants aged 15 to 24 years.CONCLUSIONS: This study suggests that gabapentinoids are associated with an increased risk of suicidal behaviour, unintentional overdoses, head/body injuries, and road traffic incidents and offences. Pregabalin was associated with higher hazards of these outcomes than gabapentin.
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