| 1. |
- Ahlgren, Erika, et al.
(författare)
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Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the role of homocysteine in neuronal injury in HIV infection. Methods Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. Results A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). Conclusion A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.
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| 2. |
- Blom, Elin S., et al.
(författare)
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Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype.
- 2009
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 27:5, s. 458-64
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-beta42 (Abeta42) and the apolipoprotein E gene (APOE) epsilon4 allele predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Here, we investigated these markers to assess their predictive value and influence on the rate of disease progression. METHODS: Using ELISA, we measured the CSF biomarkers in 47 AD patients, 58 patients with MCI and 35 healthy control subjects. Twenty-eight MCI patients revisited the clinic and half of them progressed to AD during a period of 3-12 years. RESULTS: The expected changes in CSF total (T)-tau, phosphorylated (P)-tau and Abeta42 levels were found in AD, confirming the diagnostic value of these biomarkers. We were also able to corroborate an increased risk for progression from MCI to AD with elevated CSF T-tau and P-tau and with the presence of the APOE epsilon4/epsilon4 genotype, but not with decreased Abeta42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE epsilon4 homozygosity progressed faster from MCI to AD. CONCLUSIONS: CSF T-tau and P-tau as well as the APOE epsilon4/epsilon4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD.
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| 3. |
- Danielsson, Mattias, et al.
(författare)
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Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery.
- 2021
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Ingår i: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 126:2, s. 467-76
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Tidskriftsartikel (refereegranskat)abstract
- Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function.In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid β (Aβ1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery.CSF and blood concentrations of T-tau, neurone-specific enolase, and Aβ1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aβ1-42.The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.
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| 4. |
- Edén, Arvid, 1975, et al.
(författare)
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CSF biomarkers in patients with COVID-19 and neurological symptoms: A case series.
- 2021
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Ingår i: Neurology. - 1526-632X. ; 96:2
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Tidskriftsartikel (refereegranskat)abstract
- To explore whether hospitalized patients with SARS-CoV-2 and neurologic symptoms have evidence of CNS infection, inflammation and injury using CSF biomarker measurements.We assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, β2-microglobulin (β2M) and immunoglobulin G-index), blood-brain-barrier (BBB) integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in 6 patients with moderate to severe COVID-19 and neurologic symptoms who had undergone a diagnostic lumbar puncture. Neurologic symptoms and signs included features of encephalopathies (4/6), suspected meningitis (1/6) and dysgeusia (1/6). SARS-CoV-2 infection was confirmed by rtPCR analysis of nasopharyngeal swabs.SARS-CoV-2 RNA was detected in the plasma of 2 patients (Cycle threshold [Ct] value 35.0-37.0) and in CSF at low levels (Ct 37.2, 38.0, 39.0) in 3 patients in one but not in a second rtPCR assay. CSF neopterin (median, 43.0 nmol/L) and β2-microglobulin (median, 3.1 mg/L) were increased in all. Median IgG-index (0.39), albumin ratio (5.35) and CSF white blood cell count (<3 cells/µL) were normal in all, while CSF NfL was elevated in 2 patients.Our results on patients with COVID-19 and neurologic symptoms suggest an unusual pattern of marked CSF inflammation in which soluble markers were increased but white cell response and other immunologic features typical of CNS viral infections were absent. While our initial hypothesis centered on CNS SARS-CoV-2 invasion, we could not convincingly detect SARS-CoV-2 as the underlying driver of CNS inflammation. These features distinguish COVID-19 CSF from other viral CNS infections, and raise fundamental questions about the CNS pathobiology of SARS-CoV-2 infection.
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| 5. |
- Erlandsson, Martin, et al.
(författare)
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PCR guide for construction products and works - Specifications to and evaluation of EN 15804
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The main question handled in the project ‘Robust LCA’ is how to use LCA for a robust comparison of construction products or any construction works. The project is divided into two parts where the first part deals with a general introduction to methodology problems related to LCA and what we here call ‘choice of system perspective’. The latter aspect deals with the question when to use to use attributional or consequential LCA. An LCA typology is developed in this part of the project, where different ISO 14044 methodologies are classified. The typology also deals with what question these different methodologies address. The second part of the project, given in this report, deals with commonly methodology aspects that are important to find consensus about. These methodical aspects selected and handled here are based on a workshop result. Already existing standards is used as a baseline to describe the current best common practice. The main LCA methodology used as basis for this work is EN 15804, a so call ‘core PCR’, (product category rules) for all constructions products. However, since the common goal within an LCA case study is to use a harmonized method in the entirely study, such PCR are valid for all products and services used in the life cycle of any construction works. For instance, this implies that the impact from different energy wares is to be handled with the same methodology as used for the construction products. This PCR guide includes specifications to EN 15804, as well as the potential development for aspects that are not handled in this standard today. The outlined suggestions and recommendations are the result of a series of workshops, with delegates from different parties within the Swedish building material, construction and real estate sector, including civil engineering work. The PCR guides have been subject to an open consultation that was closed on the 20th of October 2013, where all parties have had the possibility to put forward their opinions. The final recommendation in this report is based on a common understanding within the project group and takes into account the submitted written contributions to the open consultation (version dated 2013-09-18). The recommendation therefore describes the current consensus in the Swedish group participating in this project. Moreover, the PCR Guide was also sent to some EPD program operators (EPD Norway, International EPD system, Institut Bauen und Umwelt (Germany)) and the working group behind EN 16485. This was done to create an opportunity to bring forward dissenting opinion to the specifications given here. Please note that this report shall not be regarded as a PCR, but as an inspiration for future development of such work.
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| 6. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Amyloid and tau cerebrospinal fluid biomarkers in HIV infection.
- 2009
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Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients. METHODS: In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPalpha and sAPPbeta), amyloid beta fragment 1-42 (Abeta1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease. RESULTS: CSF sAPPalpha and sAPPbeta concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Abeta1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections. CONCLUSIONS: Parallel reductions of CSF sAPPalpha and sAPPbeta in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.
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| 7. |
- Gisslén, Magnus, 1962, et al.
(författare)
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CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection
- 2019
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Ingår i: Neurology-Neuroimmunology & Neuroinflammation. - : Ovid Technologies (Wolters Kluwer Health). - 2332-7812. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective To explore changes in CSF sTREM2 concentrations in the evolving course of HIV-1 infection. In this retrospective cross-sectional study, we measured concentrations of the macrophage/ microglial activation marker sTREM2 in CSF samples from 121 HIV-1-infected adults and 11 HIV-negative controls and examined their correlations with other CSF and blood biomarkers of infection, inflammation, and neuronal injury. CSF sTREM2 increased with systemic and CNS HIV-1 disease severity, with the highest levels found in patients with HIV-associated dementia (HAD). In untreated HIV-1-infected patients without an HAD diagnosis, levels of CSF sTREM2 increased with decreasing CD4(+) T-cell counts. CSF concentrations of both sTREM2 and the neuronal injury marker neurofilament light protein (NFL) were significantly associated with age. CSF sTREM2 levels were also independently correlated with CSF NFL. Notably, this association was also observed in HIV-negative controls with normal CSF NFL. HIV-infected patients on suppressive antiretroviral treatment had CSF sTREM2 levels comparable to healthy controls. Elevations in CSF sTREM2 levels, an indicator of macrophage/microglial activation, are a common feature of untreated HIV-1 infection that increases with CD4(+) T-cell loss and reaches highest levels in HAD. The strong and independent association between CSF sTREM2 and CSF NFL suggests a linkage between microglial activation and neuronal injury in HIV-1 infection. CSF sTREM2 has the potential of being a useful biomarker of innate CNS immune activation in different stages of untreated and treated HIV-1 infection.
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| 8. |
- Gode, Jenny, et al.
(författare)
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Swedish long-term low carbon scenario - Exploratory study on opportunities and barriers
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In 2009, the Swedish government proposed a vision of reaching zero net emissions of greenhouse gases in the year 2050. However, there are few details on concrete actions after 2020. In the light of the long investment cycles associated with energy, housing, transport infrastructure and heavy industry, we believe that the society now needs to start identifying possible pathways for reaching this vision. The pathways also need to be investigated in terms of their feasibility and consequences. The aim of our study has been to develop and elaborate on one potential future energy scenario where Sweden minimises the use of fossil fuels in 2050 and to identify opportunities and barriers. The scenario we present is one of several possible scenarios and is obviously not a forecast. Our purpose is not to show a likely development, but rather to illustrate, by example, a society that is largely independent of fossil fuels and what would be required to get there. In a next step, more detailed scenarios as well as accurate impact assessments are needed. For example, the impact of high bioenergy utilisation needs to be carefully examined. The results also show several cross-sectoral measures and/or effects that need further study. There is also a need for thorough cost analyses as well as analyses of what is required to implement these measures in practice. We have analysed potential fossil fuel reductions in the sectors industry, residential/service, transports and energy conversion. For these sectors, systematic investigations have been made on measures for replacing fossil fuels, improving energy efficiency and applying new technologies and industrial processes. Our scenario is to a great extent based on existing technologies. In addition to sector specific measures, we have applied cross-sectoral measures such as using industrial surplus heat in the residential sector or forest residues for producing heat and power. Furthermore, we have assumed a system change in transportation and limited use of carbon capture and storage (CCS). The applied measures influence the demand for electricity, heat/steam and fuels. The results indicate a very high demand for biofuels in the future.
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| 9. |
- Hagberg, Linus, et al.
(författare)
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Svenska skogsindustrins emissioner och upptag av växthusgaser
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I denna studie har upptag och emissioner av växthusgaser för aktiviteter förknippade med den svenska skogsindustrins beräknats för åren 2001-2003. Emissioner och upptag i svensk skog och emissioner vid skogsbruk, vid produktion av skogsprodukter och vid transporter inom Sverige har ingått i inventeringen. Studien kommer fram till att nettoresultatet för svenska skogsindustrin är ett årligt upptag på ca 1,6 milj ton CO2-ekvivalenter. Upptaget i skogsekosystemet beräknades till ca 5,2 milj ton CO2-ekvivalenter och emissionerna i det skogsindustriella produktionssystemet beräknades till 3,5 milj ton CO2-ekvivalenter.
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| 10. |
- Krut, Jan Jessen, et al.
(författare)
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Biomarker Evidence of Axonal Injury in Neuroasymptomatic HIV-1 Patients
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method.With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use.
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