| 1. |
- Wiessner, M., et al.
(författare)
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Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia
- 2021
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144:5, s. 1422-1434
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Tidskriftsartikel (refereegranskat)abstract
- Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays. © 2021 The Author(s).
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| 2. |
- Gielen, Marij, et al.
(författare)
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Body mass index is negatively associated with telomere length : A collaborative cross-sectional meta-analysis of 87 observational studies
- 2018
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 108:3, s. 453-475
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Tidskriftsartikel (refereegranskat)abstract
- Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectionalmeta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Studyspecific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a-3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI:-10.03,-5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10-3 unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10-3, -1.01 × 10-3) difference in ageand sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10-3 unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10-3, -1.25 × 10-3). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL arewarranted.
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| 3. |
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| 4. |
- Melton, LJ, et al.
(författare)
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Osteoporosis and the global competition for health care resources
- 2004
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Ingår i: Journal of Bone and Mineral Research. - 1523-4681. ; 19:7, s. 1055-1058
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Tidskriftsartikel (refereegranskat)abstract
- Global aging superimposed on existing infectious diseases and trauma will aggravate competition for health care resources to diagnose and treat osteoporosis. Efforts to implement public health measures are needed, but the targeted approach to assessment and treatment of high-risk individuals must also be refined.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Kanis, J, et al.
(författare)
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Letter
- 2006
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 17:3, s. 493-494
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 11. |
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| 12. |
- Kanis, JA, et al.
(författare)
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The perspective of the International Osteoporosis Foundation on the official positions of the International Society for Clinical Densitometry
- 2005
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Ingår i: Journal of Clinical Densitometry. - 1094-6950. ; 8:2, s. 145-147
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Tidskriftsartikel (refereegranskat)abstract
- The International Society for Clinical Densitometry (ISCD) has published position statements on topics relating to the use and interpretation of measurements of bone mineral density (BMD). The most recent appeared in the Journal of Clinical Densitometry (1) and was republished in the Journal of Endocrinology and Metabolism and in Osteoporosis International (2,3). The topics included the indications for testing with BMD, the use of central dual energy X-ray absorptiometry (DXA) for the diagnosis of osteoporosis, the use of the Z-score and some recommendations for the spelling of the T-score and Z-score. Although these topics were chosen in an attempt to produce international consistency and consensus, most of the position statements lack a scientific basis.
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| 13. |
- Karlsson, M K, et al.
(författare)
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Age, gender, and fragility fractures are associated with differences in quantitative ultrasound independent of bone mineral density
- 2001
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Ingår i: Bone. - 1873-2763. ; 28:1, s. 118-122
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Tidskriftsartikel (refereegranskat)abstract
- Bone strength is determined by bone mineral density (BMD) and bone structure. Dual-energy X-ray absorptiometry (DXA) measures BMD. Whether quantitative ultrasound (qUS) measures a property of bone distinct from BMD is uncertain. To evaluate this, DXA and qUS were measured in 58 fracture patients and 428 controls. To study the independent effects of age and gender on qUS measurements and control for BMD by study design rather than statistical methods, subgroups from the normative database were created and intentionally matched by the same femoral neck (FN) BMD. Speed of sound (SOS; m/sec), broadband ultrasound attenuation (BUA; dB/MHz), and stiffness index (SI) were then compared in individuals matched by FN BMD but differing in age, gender, and presence or absence of fractures. The results are presented as percentage difference (mean +/- SD). Elderly women with the same FN BMD as young women had 1 +/- 2% lower SOS (p < 0.05), 8 +/- 15% lower SI (p < 0.05), and 4 +/- 9% lower BUA (p = 0.07). Elderly women with the same FN BMD as elderly men had 5 +/- 9% lower BUA (p < 0.05). Elderly men with the same FN BMD as young men had 1 +/- 2% lower SOS (p = 0.1), 5 +/- 14% lower SI (p = 0.2), and 1 +/- 9% lower BUA (n.s.). Young women with the same FN BMD as young men had 2 +/- 7% lower BUA (n.s.). Women with fragility fractures had 8 +/- 11% lower BUA (p < 0.001) and 13 +/- 22% lower SI (p < 0.01) than controls with no fractures matched by FN BMD, age, and gender. Men with fragility fractures had 13 +/- 12% lower BUA (p < 0.01) and 16 +/- 19% lower SI (p < 0.05) than controls with no fractures matched by FN BMD, age, and gender. Despite comparable femoral neck BMD, qUS measurements differed according to age, gender, and fracture status, suggesting that qUS may provide additional information independent of femoral neck BMD, such as differences in connectivity or other properties yet to be identified.
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| 14. |
- Karlsson, M K, et al.
(författare)
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Bone loss following tibial osteotomy: a model for evaluating post-traumatic osteopenia
- 2000
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 11:3, s. 261-264
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Tidskriftsartikel (refereegranskat)abstract
- The reduced bone mineral density (BMD) found in patients with fractures may, in part, follow rather than precede the fracture. We studied the magnitude and reversibility of bone loss in the 15 months following osteotomy in 21 men and 5 women with localized medial arthritis of the knee. BMD (mean +/- SD), measured using dual-energy X-ray absorptiometry, decreased by a maximum of 35 +/- 21% in the mid-diaphysis of the affected tibia at 9 months after surgery (p < 0.001). At 15 months, reversal of bone loss in non-fractured bones was incomplete; the remaining deficit was 20 +/- 27% relative to baseline (p < 0.001). Maximum bone loss occurred at 9 months at the total body (5 +/- 2%), spine (15 +/- 17%) and at Ward's triangle of the proximal femur of the unoperated limb (10 +/- 17%) (all p < 0.01). In summary, post-traumatic bone loss is region-specific with incomplete reversibility, at least after about 15 months. Deficits in BMD in cross-sectional studies of patients with fractures, held to be responsible for the bone fragility, may, in part, follow rather than precede the fracture.
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| 15. |
- Karlsson, M K, et al.
(författare)
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Exercise during growth and bone mineral density and fractures in old age
- 2000
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Ingår i: The Lancet. - 1474-547X. ; 355:9202, s. 469-470
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Tidskriftsartikel (refereegranskat)abstract
- If exercise is to be recommended during growth, benefits in bone mineral density (BMD) must be maintained in old age and shown to prevent fractures. Our cross-sectional study of soccer players suggests that a high BMD is no longer recorded after retirement and fracture frequency is no less than predicted in old age.
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| 16. |
- Kroigaard, M., et al.
(författare)
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Scandinavian Clinical Practice Guidelines on the diagnosis, management and follow-up of anaphylaxis during anaesthesia
- 2007
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Ingår i: Acta Anaesthesiologica Scandinavica. - Copenhagen : Blackwell Munksgaard. - 0001-5172 .- 1399-6576. ; 51:6, s. 655-670
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Forskningsöversikt (refereegranskat)abstract
- The present approach to the diagnosis, management and follow-up of anaphylaxis during anaesthesia varies in the Scandinavian countries. The main purpose of these Scandinavian Clinical Practice Guidelines is to increase the awareness about anaphylaxis during anaesthesia amongst anaesthesiologists. It is hoped that increased focus on the subject will lead to prompt diagnosis, rapid and correct treatment, and standardised management of patients with anaphylactic reactions during anaesthesia across Scandinavia. The recommendations are based on the best available evidence in the literature, which, owing to the rare and unforeseeable nature of anaphylaxis, mainly includes case series and expert opinion (grade of evidence IV and V). These guidelines include an overview of the epidemiology of anaphylactic reactions during anaesthesia. A treatment algorithm is suggested, with emphasis on the incremental titration of adrenaline (epinephrine) and fluid therapy as first-line treatment. Recommendations for primary and secondary follow-up are given, bearing in mind that there are variations in geography and resources in the different countries. A list of National Centres from which anaesthesiologists can seek advice concerning follow-up procedures is provided. In addition, an algorithm is included with advice on how to manage patients with previous suspected anaphylaxis during anaesthesia. Lastly, Appendix 2 provides an overview of the incidence, mechanisms and possibilities for follow-up for some common drug groups.
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| 19. |
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| 20. |
- Solmi, M, et al.
(författare)
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Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies
- 2022
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 27:1, s. 281-295
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Tidskriftsartikel (refereegranskat)abstract
- Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11–34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7–16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9–25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14–29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15–23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17–48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20–41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20–34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20–33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21–46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.
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| 21. |
- Solmi, Marco, et al.
(författare)
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Disparities in Screening and Treatment of Cardiovascular Diseases in Patients With Mental Disorders Across the World : Systematic Review and Meta-Analysis of 47 Observational Studies
- 2021
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Ingår i: American Journal of Psychiatry. - : HighWire Press. - 0002-953X .- 1535-7228. ; 178:9, s. 793-803
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: This study used meta-analysis to assess disparities in cardiovascular disease (CVD) screening and treatment in people with mental disorders, a group that has elevated CVD incidence and mortality.METHODS: The authors searched PubMed and PsycInfo through July 31, 2020, and conducted a random-effect meta-analysis of observational studies comparing CVD screening and treatment in people with and without mental disorders. The primary outcome was odds ratios for CVD screening and treatment. Sensitivity analyses on screening and treatment separately and on specific procedures, subgroup analyses by country, and by controlling for confounding by indication, as well as meta-regressions, were also run, and publication bias and quality were assessed.RESULTS: Forty-seven studies (N=24,400,452 patients, of whom 1,283,602 had mental disorders) from North America (k=26), Europe (k=16), Asia (k=4), and Australia (k=1) were meta-analyzed. Lower rates of screening or treatment in patients with mental disorders emerged for any CVD (k=47, odds ratio=0.773, 95% CI=0.742, 0.804), coronary artery disease (k=34, odds ratio=0.734, 95% CI=0.690, 0.781), cerebrovascular disease (k=8, odds ratio=0.810, 95% CI=0.779, 0.842), and other mixed CVDs (k=11, odds ratio=0.839, 95% CI=0.761, 0.924). Significant disparities emerged for any screening, any intervention, catheterization or revascularization in coronary artery disease, intravenous thrombolysis for stroke, and treatment with any and with specific medications for CVD across all mental disorders (except for CVD medications in mood disorders). Disparities were largest for schizophrenia, and they differed across countries. Median study quality was high (Newcastle-Ottawa Scale score, 8); higher-quality studies found larger disparities, and publication bias did not affect results.CONCLUSIONS: People with mental disorders, and those with schizophrenia in particular, receive less screening and lower-quality treatment for CVD. It is of paramount importance to address underprescribing of CVD medications and underutilization of diagnostic and therapeutic procedures across all mental disorders.
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