| 1. |
- Bauer, M., et al.
(författare)
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Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder
- 2023
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Ingår i: International Journal of Bipolar Disorders. - 2194-7511. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample.MethodsData for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P <= 0.001.ResultsThe 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger.ConclusionUVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.
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| 2. |
- Escartin, C., et al.
(författare)
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Reactive astrocyte nomenclature, definitions, and future directions
- 2021
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 24, s. 312-325
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Tidskriftsartikel (refereegranskat)abstract
- Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions. Good-bad binary classifications fail to describe reactive astrocytes in CNS disorders. Here, 81 researchers reach consensus on widespread misconceptions and provide definitions and recommendations for future research on reactive astrocytes.
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| 3. |
- Berg, Johanna, et al.
(författare)
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Perceived usefulness of trauma audit filters in urban India: a mixed-methods multicentre Delphi study comparing filters from the WHO and low and middle-income countries
- 2022
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective To compare experts' perceived usefulness of audit filters from Ghana, Cameroon, WHO and those locally developed; generate context-appropriate audit filters for trauma care in selected hospitals in urban India; and explore characteristics of audit filters that correlate to perceived usefulness. Design A mixed-methods approach using a multicentre online Delphi technique. Setting Two large tertiary hospitals in urban India. Methods Filters were rated on a scale from 1 to 10 in terms of perceived usefulness, with the option to add new filters and comments. The filters were categorised into three groups depending on their origin: low and middle-income countries (LMIC), WHO and New (locally developed), and their scores compared. Significance was determined using Kruskal-Wallis test followed by Wilcoxon rank-sum test. We performed a content analysis of the comments. Results 26 predefined and 15 new filter suggestions were evaluated. The filters had high usefulness scores (mean overall score 9.01 of 10), with the LMIC filters having significantly higher scores compared with those from WHO and those newly added. Three themes were identified in the content analysis relating to medical relevance, feasibility and specificity. Conclusions Audit filters from other LMICs were deemed highly useful in the urban India context. This may indicate that the transferability of defined trauma audit filters between similar contexts is high and that these can provide a starting point when implemented as part of trauma quality improvement programmes in low-resource settings.
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| 4. |
- Keddie, Stephen, et al.
(författare)
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Peripherin is a biomarker of axonal damage in peripheral nervous system disease
- 2023
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Ingår i: Brain. - 0006-8950 .- 1460-2156. ; 146:11, s. 4562-4573
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Tidskriftsartikel (refereegranskat)abstract
- Valid, responsive blood biomarkers specific to peripheral nerve damage would improve management of peripheral nervous system (PNS) diseases. Neurofilament light chain (NfL) is sensitive for detecting axonal pathology but is not specific to PNS damage, as it is expressed throughout the PNS and CNS. Peripherin, another intermediate filament protein, is almost exclusively expressed in peripheral nerve axons. We postulated that peripherin would be a promising blood biomarker of PNS axonal damage. We demonstrated that peripherin is distributed in sciatic nerve, and to a lesser extent spinal cord tissue lysates, but not in brain or extra-neural tissues. In the spinal cord, anti-peripherin antibody bound only to the primary cells of the periphery (anterior horn cells, motor axons and primary afferent sensory axons). In vitro models of antibody-mediated axonal and demyelinating nerve injury showed marked elevation of peripherin levels only in axonal damage and only a minimal rise in demyelination. We developed an immunoassay using single molecule array technology for the detection of serum peripherin as a biomarker for PNS axonal damage. We examined longitudinal serum peripherin and NfL concentrations in individuals with Guillain-Barr © syndrome (GBS, n = 45, 179 time points), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 35, 70 time points), multiple sclerosis (n = 30), dementia (as non-inflammatory CNS controls, n = 30) and healthy individuals (n = 24). Peak peripherin levels were higher in GBS than all other groups (median 18.75 pg/ml versus < 6.98 pg/ml, P < 0.0001). Peak NfL was highest in GBS (median 220.8 pg/ml) and lowest in healthy controls (median 5.6 pg/ml), but NfL did not distinguish between CIDP (17.3 pg/ml), multiple sclerosis (21.5 pg/ml) and dementia (29.9 pg/ml). While peak NfL levels were higher with older age (rho = +0.39, P < 0.0001), peak peripherin levels did not vary with age. In GBS, local regression analysis of serial peripherin in the majority of individuals with three or more time points of data (16/25) displayed a rise-and-fall pattern with the highest value within the first week of initial assessment. Similar analysis of serial NfL concentrations showed a later peak at 16 days. Group analysis of serum peripherin and NfL levels in GBS and CIDP patients were not significantly associated with clinical data, but in some individuals with GBS, peripherin levels appeared to better reflect clinical outcome measure improvement. Serum peripherin is a promising new, dynamic and specific biomarker of acute PNS axonal damage.
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| 5. |
- Morcos, M. N. F., et al.
(författare)
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Continuous mitotic activity of primitive hematopoietic stem cells in adult mice
- 2020
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 217:6
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Tidskriftsartikel (refereegranskat)abstract
- The proliferative activity of aging hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP) transgenic mice are important tools for tracking the mitotic history of murine HSCs in label dilution experiments. A recent study proposed that primitive HSCs symmetrically divide only four times to then enter permanent quiescence. We observed that background fluorescence due to leaky H2B-FP expression, occurring in all H2B-FP transgenes independent of label induction, accumulated with age in HSCs with high repopulation potential. We argue that this background had been misinterpreted as stable retention of induced label. We found cell division-independent half-lives of H2B-FPs to be short, which had led to overestimation of HSC divisional activity. Our data do not support abrupt entry of HSCs into permanent quiescence or sudden loss of regeneration potential after four divisions, but show that primitive HSCs of adult mice continue to cycle rarely.
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| 6. |
- Ward, C., et al.
(författare)
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Determining the Agreement Between an Automated Respiratory Rate Counter and a Reference Standard for Detecting Symptoms of Pneumonia in Children: Protocol for a Cross-Sectional Study in Ethiopia
- 2020
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Ingår i: Jmir Research Protocols. - : JMIR Publications Inc.. - 1929-0748. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acute respiratory infections (ARIs), primarily pneumonia, are the leading infectious cause of under-5 mortality worldwide. Manually counting respiratory rate (RR) for 60 seconds using an ARI timer is commonly practiced by community health workers to detect fast breathing, an important sign of pneumonia. However, correctly counting breaths manually and classifying the RR is challenging, often leading to inappropriate treatment. A potential solution is to introduce RR counters, which count and classify RR automatically. Objective: This study aims to determine how the RR count of an Automated Respiratory Infection Diagnostic Aid (ARIDA) agrees with the count of an expert panel of pediatricians counting RR by reviewing a video of the child's chest for 60 seconds (reference standard), for children aged younger than 5 years with cough and/or difficult breathing. Methods: A cross-sectional study aiming to enroll 290 children aged 0 to 59 months presenting to pediatric in- and outpatient departments at a teaching hospital in Addis Ababa, Ethiopia, was conducted. Enrollment occurred between April and May 2017. Once enrolled, children participated in at least one of three types of RR evaluations: (1) agreement-measure the RR count of an ARIDA in comparison with the reference standard, (2) consistency-measure the agreement between two ARIDA devices strapped to one child, and (3) RR fluctuation-measure RR count variability over time after ARIDA attachment as measured by a manual count. The agreement and consistency of expert clinicians (ECs) counting RR for the same child with the Mark 2 ARI timer for 60 seconds was also measured in comparison with the reference standard. Results: Primary outcomes were (1) mean difference between the ARIDA and reference standard RR count (agreement) and (2) mean difference between RR counts obtained by two ARIDA devices started simultaneously (consistency). Conclusions: Study strengths included the design allowing for comparison between both ARIDA and the EC with the reference standard RR count. A limitation is that exactly the same set of breaths were not compared between ARIDA and the reference standard since ARIDA can take longer than 60 seconds to count RR. Also, manual RR counting, even when aided by a video of the child's chest movements, is subject to human error and can result in low interrater reliability. Further work is needed to reach global consensus on the most appropriate reference standard and an acceptable level of agreement to provide ministries of health with evidence to make an informed decision on whether to scale up new automated RR counters.
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| 7. |
- Altmann, P., et al.
(författare)
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Seven day pre-analytical stability of serum and plasma neurofilament light chain
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light chain (NfL) has emerged as a biomarker of neuroaxonal damage in several neurologic conditions. With increasing availability of fourth-generation immunoassays detecting NfL in blood, aspects of pre-analytical stability of this biomarker remain unanswered. This study investigated NfL concentrations in serum and plasma samples of 32 patients with neurological diagnoses using state of the art Simoa technology. We tested the effect of delayed freezing of up to 7 days and statistically determined stability and validity of measured concentrations. We found concentrations of NfL in serum and plasma to remain stable at room temperature when processing of samples is delayed up to 7 days (serum: mean absolute difference 0.9 pg/mL, intraindividual variation 1.2%; plasma: mean absolute difference 0.5 pg/mL, intraindividual variation 1.3%). Consistency of these results was nearly perfect for serum and excellent for plasma (intraclass correlation coefficients 0.99 and 0.94, respectively). In conclusion, the soluble serum and plasma NfL concentration remains stable when unprocessed blood samples are stored up to 7 days at room temperature. This information is essential for ensuring reliable study protocols, for example, when shipment of fresh samples is needed.
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| 8. |
- Berntsen, S., et al.
(författare)
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A systematic review and meta-analysis on the association between ICSI and chromosome abnormalities
- 2021
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Ingår i: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 27:5, s. 801-847
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the decade following the introduction of ICSI, a higher prevalence of de novo chromosome abnormalities, in particular sex chromosome and autosomal structural abnormalities, as well as inherited abnormalities was described in children conceived by ICSI compared to both naturally conceived (NC) children and children conceived by standard IVF. The explanation for the observed increase in prevalence is not clear and has been suggested to reflect parental factors (e.g. age or sperm quality) or to be a result of the ICSI procedure itself. Over the years, the procedure, as well as the patient group, and indications for ICSI treatment have changed. OBJECTIVE AND RATIONALE: The objective of this systematic review and meta-analysis was to assess the prevalence of chromosome abnormalities in ICSI pregnancies and children and to examine any potentially increased risk compared to standard IVF and NC. SEARCH METHODS: Pubmed, Embase, Cochrane Libraries and Web of Science up to October 2020 were searched. Primary outcome measures were overall chromosome abnormalities and de novo abnormalities (including sex chromosome abnormalities and autosomal abnormalities). The secondary outcome was inherited abnormalities. We followed the PRISMA guidelines and relevant meta-analyses were performed. OUTCOMES: The search included 4648 articles, out of which 27 met the inclusion criteria, and 19 were included in quantitative synthesis (meta-analyses). The prevalence of chromosome abnormalities varied considerably between studies, possibly explained by large differences in sample size and patient demographics. Only five studies were eligible for pooled analyses on adjusted data. All studies had a critical risk of bias. Results from pooled adjusted data showed no evidence of an increased risk of overall chromosome abnormalities when comparing ICSI to either standard IVF (aOR 0.75 (95% CI 0.41-1.38)) or NC (aOR 1.29 (95% CI 0.69-2.43)). In contrast, meta-analyses on unadjusted data showed an increased risk of overall chromosome abnormalities in ICSI compared to both standard IVF (OR 1.42 (95% CI 1.09-1.85)) and NC (OR 2.46 (95% CI 1.52-3.99)) and an increased risk of de novo abnormalities in ICSI compared to NC (OR 2.62 (95% CI 2.07-3.31)). Yet, based on a very low certainty of evidence, the conclusion remains, that no indication of an increased risk of chromosome abnormalities in ICSI offspring could be found. If an increased risk of chromosome abnormalities in selected ICSI offspring should exist, the absolute risk continues to be small. WIDER IMPLICATIONS: This review provides an extensive overview of the existing evidence on the relationship between ICSI and chromosome abnormalities in the offspring. We highlight the need for well-designed large, prospective, controlled studies with systematic cytogenetic testing. Existing data are limited and, in many cases, marred by critical levels of bias.
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| 9. |
- Cresswell, J. A., et al.
(författare)
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Measurement of maternal functioning during pregnancy and postpartum: findings from the cross-sectional WHO pilot study in Jamaica, Kenya, and Malawi
- 2020
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Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe World Health Organization's definition of maternal morbidity refers to "a negative impact on the woman's wellbeing and/or functioning". Many studies have documented the, mostly negative, effects of maternal ill-health on functioning. Although conceptually important, measurement of functioning remains underdeveloped, and the best way to measure functioning in pregnant and postpartum populations is unknown.MethodsA cross-sectional study among women presenting for antenatal (N=750) and postpartum (N=740) care in Jamaica, Kenya and Malawi took place in 2015-2016. Functioning was measured through the World Health Organization Disability Assessment Schedule (WHODAS-12). Data on health conditions and socio-demographic characteristics were collected through structured interview, medical record review, and clinical examination. This paper presents descriptive data on the distribution of functioning status among pregnant and postpartum women and examines the relationship between functioning and health conditions.ResultsWomen attending antenatal care had a lower level of functioning than those attending postpartum care. Women with a health condition or associated demographic risk factor were more likely to have a lower level of functioning than those with no health condition. However, the absolute difference in functioning scores typically remained modest.ConclusionsFunctioning is an important concept which integrates a woman-centered approach to examining how a health condition affects her life, and ultimately her return to functioning after delivery. However, the WHODAS-12 may not be the optimal tool for use in this population and additional components to capture pregnancy-specific issues may be needed. Challenges remain in how to integrate functioning outcomes into routine maternal healthcare at-scale and across diverse settings.
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| 10. |
- Ginström Ernstad, Erica, et al.
(författare)
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Preimplantation genetic testing and child health: a national register-based study
- 2023
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 38:4, s. 739-750
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION Is preimplantation genetic testing (PGT) associated with adverse perinatal outcome and early childhood health? SUMMARY ANSWER Children born after PGT had comparable perinatal outcomes to children born after IVF/ICSI and comparable findings regarding early childhood health. WHAT IS KNOWN ALREADY PGT is offered to couples affected by monogenic disorders (PGT-M) or inherited chromosomal aberrations (PGT-SR), limiting the risk of transferring the disorder to the offspring. PGT, an invasive technique, requires genetic analysis of one or up to ten cells from the embryo and is combined with IVF or ICSI. Several studies, most of them small, have shown comparable results after PGT and IVF/ICSI concerning perinatal outcome. Only a few studies with limited samples have been published on PGT and childhood health. STUDY DESIGN, SIZE, DURATION We performed a register-based study including all singletons born after PGT (n = 390) in Sweden during 1 January 1996-30 September 2019. Singletons born after PGT were compared with all singletons born after IVF/ICSI (n = 61 060) born during the same period of time and with a matched sample of singletons (n = 42 034) born after spontaneous conception selected from the Medical Birth Register. Perinatal outcomes, early childhood health, and maternal outcomes were compared between pregnancies after PGT and IVF/ICSI as well as between pregnancies after PGT and spontaneous conception. Primary outcomes were preterm birth (PTB) and low birthweight (LBW) whereas childhood morbidity was the secondary outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS Data on women who went through PGT and gave birth were obtained from the local databases at the two PGT centres in Sweden, whereas data on IVF treatment for the IVF/ICSI group were obtained from the national IVF registers. These data were then cross-linked to national health registers; the Medical Birth Register, the Patient Register, and the Cause of Death Register. Logistic multivariable regression analysis and Cox proportional hazards models were performed with adjustment for relevant confounders. MAIN RESULTS AND THE ROLE OF CHANCE The mean follow-up time was 4.6 years for children born after PGT and 5.1 years for children born after spontaneous conception, whereas the mean follow-up time was 9.0 years for children born after IVF/ICSI. For perinatal outcomes, PTB occurred in 7.7% of children after PGT and in 7.3% of children after IVF/ICSI, whereas the rates were 4.9% and 5.2% for LBW (adjusted odds ratio (AOR) 1.22, 95% CI 0.82-1.81 and AOR 1.17, 95% CI 0.71-1.91, respectively). No differences were observed for birth defects. In comparison to spontaneous conception, children born after PGT had a higher risk for PTB (AOR 1.73, 95% CI 1.17-2.58). Regarding early childhood health, the absolute risk of asthma was 38/390 (9.7%) in children born after PGT and 6980/61 060 (11.4%) in children born after in IVF/ICSI, whereas the corresponding numbers were 34/390 (8.7%) and 7505/61 060 (12.3%) for allergic disorders. Following Cox proportional hazards models, no significant differences were found for these outcomes. Sepsis, hypothyroidism, attention deficit hyperactivity disorder, autism spectrum disorders, mental retardation, cerebral palsy, and epilepsy were diagnosed in a maximum of three PGT children. No PGT children died during the follow-up period. Regarding maternal outcomes, the rates of placenta praevia and caesarean delivery were significantly higher after PGT in comparison to spontaneous conception (AOR 6. 46, 95% CI 3.38-12.37 and AOR 1.52, 95% CI 1.20-1.92, respectively), whereas no differences were seen comparing pregnancies after PGT and IVF/ICSI. LIMITATIONS, REASONS FOR CAUTION The rather small sample size of children born after PGT made it impossible to adjust for all relevant confounders including fertilization method and culture duration. Moreover, the follow-up time was short for most of the children especially in the PGT group, probably lowering the absolute number of diagnoses in early childhood. WIDER IMPLICATIONS OF THE FINDINGS The results are reassuring and indicate that the embryo biopsy itself has no adverse effect on the perinatal, early childhood, or maternal outcomes. Although the results are comparable to IVF/ICSI also regarding early childhood outcome, they should be taken with caution due to the low number of children with diagnoses and short follow-up time. Long-term follow-up studies on children born after PGT are scarce and should be conducted considering the invasiveness of the technique. STUDY FUNDING/COMPETING INTEREST(S) The study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (LUA/ALF 70940), the Board of National Specialised Medical Care at Sahlgrenska University Hospital and Hjalmar Svensson Research Foundation. There are no conflicts of interest to declare.
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