Cerebrospinal fluid signs of neuronal damage after antiretroviral treatment interruption in HIV-1 infection

BACKGROUND: The neurofilament is a major structural component of myelinated axons. Increased cerebrospinal fluid (CSF) concentrations of the light chain of the neurofilament protein (NFL) can serve as a sensitive indicator of central nervous system (CNS) injury. To assess whether interrupting antiretroviral treatment of HIV infection might have a deleterious effect on the CNS, we measured NFL levels in HIV-infected subjects interrupting therapy. We identified subjects who had CSF HIV RNA concentrations below 50 copies/mL at the time combination antiretroviral therapy was interrupted, and for whom CSF samples were available before and after the interruption. RESULTS: A total of 8 subjects were studied. The median (range) CSF NFL level at baseline was <125 (<125–220) ng/L (normal <250 ng/L). All 8 subjects exhibited an increase in CSF and plasma HIV RNA after stopping therapy, accompanied by intrathecal immunoactivation as evidenced by CSF lymphocytic pleocytosis (7/8 patients) and increased CSF neopterin concentration (5/6 patients). Three subjects showed a consistent increase in CSF NFL, rising from <125 ng/L to a maximum of 880 (at day 148), 1,010 (day 58) and 10,930 ng/L (day 101). None exhibited new neurological symptoms or signs, or experienced functional deterioration during the period off treatment; of 5 who underwent brief quantitative neurological testing, none showed worsening performance. CONCLUSION: These findings suggest that resurgence of active HIV replication may result in measurable, albeit subclinical, CNS injury. Further studies are needed to define the frequency and pathobiological importance of the increase in CSF NFL

Open access-böcker som vetenskapligt kommunikationsmedel i en svensk kontext : forskares attityder till den fritt tillgängliga digitala boken

Scholarly books still play an important role in some scientific disciplines, mainly the humanities and some social sciences. Publication in open access format is still not a requirement when it comes to scholarly books in Sweden, but will likely be in the near future. Academic libraries often play an important role when it comes to supporting researchers in scholarly communication and it is likely that this role will become even more prominent. Because of this, it is important from a library and information studies perspective that the libraries have a clear idea of the problems that face researchers in the context of open access book publishing. The aim of this master’s thesis is to study researcher’s perceptions of the ongoing technology shift within scholarly communication from printed books to openly accessible digital books, and also to investigate to what extent open access is established as the solution for the problems that researchers face in the context of scholarly communication through books. To study these questions, we have used the social construction of technology (SCOT) framework in combination with the unified theory of acceptance and use of technology (UTAUT). The SCOT-framework allows us to examine how open access is constructed as the solution to certain problems experienced by the relevant social group researchers. UTAUT has functioned as a tool to measure acceptance and identify central problems experienced by the researchers. We conducted a survey among researchers at a Swedish university about experience of and attitudes towards open access book publishing. In addition, we interviewed five researchers about attitudes and strategies towards publishing, the future of the academic book and open access. The study revealed four main problem areas associated with open access scholarly communication: 1) accessibility and dissemination, 2) quality control, 3) merit and prestige, 4) skepticism towards technology. In addition, we identified two more factors that are highly relevant in the context of open access book publishing: how digitization affects the book format, and other relevant social groups. Open access can only really be seen as a solution to the first problem, that of accessibility and dissemination, but is still generally accepted among researchers as the only way forward. Master’s thesis in library and information studies

Normalisation of cerebrospinal fluid biomarkers parallels improvement of neurological symptoms following HAART in HIV dementia – case report

BACKGROUND: Since the introduction of HAART the incidence of HIV dementia has declined and HAART seems to improve neurocognitive function in patients with HIV dementia. Currently, HIV dementia develops mainly in patients without effective treatment, though it has also been described in patients on HAART and milder HIV-associated neuropsychological impairment is still frequent among HIV-1 infected patients regardless of HAART. Elevated cerebrospinal fluid (CSF) levels of markers of neural injury and immune activation have been found in HIV dementia, but neither of those, nor CSF HIV-1 RNA levels have been proven useful as diagnostic or prognostic pseudomarkers in HIV dementia. CASE PRESENTATION: We report a case of HIV dementia (MSK stage 3) in a 57 year old antiretroviral naïve man who was introduced on zidovudine, lamivudine and ritonavir boosted indinavir, and followed with consecutive lumbar punctures before and after two and 15 months after initiation of HAART. Improvement of neurocognitive function was paralleled by normalisation of CSF neural markers (NFL, Tau and GFAP) levels and a decline in CSF and serum neopterin and CSF and plasma HIV-1 RNA levels. CONCLUSION: The value of these CSF markers as prognostic pseudomarkers of the effect of HAART on neurocognitive impairment in HIV dementia ought to be evaluated in longitudinal studies

The effect of secondary inorganic aerosols, soot and the geographical origin of air mass on acute myocardial infarction hospitalisations in Gothenburg, Sweden during 1985 - 2010 : a case-crossover study

BACKGROUND: The relative importance of different sources of air pollution for cardiovascular disease is unclear. The aims were to compare the associations between acute myocardial infarction (AMI) hospitalisations in Gothenburg, Sweden and 1) the long-range transported (LRT) particle fraction, 2) the remaining particle fraction, 3) geographical air mass origin, and 4) influence of local dispersion during 1985–2010. METHODS : A case-crossover design was applied using lag0 (the exposure the same day as hospitalisation), lag1 (exposure one day prior hospitalisation) and 2-day cumulative average exposure (CA2) (mean of lag0 and lag1). The LRT fractions included PMion (sum of sulphate, nitrate and ammonium) and soot measured at a rural site. The difference between urban PM10 (particulate matter with an aerodynamic diameter smaller than 10 μm) and rural PMion was a proxy for locally generated PM10 (PMrest). The daily geographical origin of air mass was estimated as well as days with limited or effective local dispersion. The entire year was considered, as well as warm and cold periods, and different time periods. RESULTS : In total 28 215 AMI hospitalisations occurred during 26 years. PM10, PMion, PMrest and soot did not influence AMI for the entire year. In the cold period, the association was somewhat stronger for PMrest than for urban PM10; the strongest associations were observed during 1990–2000 between AMI and CA2 of PMrest (6.6% per inter-quartile range (IQR), 95% confidence interval 2.1 to 11.4%) and PM10 (4.1%, 95% CI 0.2% − 8.2%). Regarding the geographical air mass origins there were few associations. Days with limited local dispersion showed an association with AMI in the cold period of 2001–2010 (6.7%, 95% CI 0.0% − 13.0%). CONCLUSIONS : In the cold period, locally generated PM and days with limited local dispersion affected AMI hospitalisations, indicating importance of local emissions from e.g. traffic.The Swedish Research Council Formas funded the study.http://www.ehjournal.netam201

The effect of leisure-time physical activity on the risk of acute myocardial infarction depending on Body Mass Index: a population-based case-control study

BACKGROUND: High body mass index (BMI) and lack of physical activity have been recognized as important risk factors for coronary heart disease. The aim of the present study was to evaluate whether leisure-time physical activity compensates for the increased risk of acute myocardial infarction associated with overweight and obesity. METHODS: Data from the SHEEP (Stockholm Heart Epidemiology Program) study were used. The SHEEP study is a large Swedish population-based case-control study, comprising 1204 male and 550 female cases, and 1538 male and 777 female controls, conducted in Stockholm County, Sweden, during the period 1992–1994. Odds ratios (OR), together with 95 % confidence intervals (95% CI), were calculated using unconditional logistic regression, as estimates of the relative risks. RESULTS: Regular leisure-time physical activity was associated with a decreased risk of myocardial infarction among lean, normal-weight and overweight subjects, but not among obese subjects. Obese (BMI ≥ 30) and physically active persons had an almost twofold risk of myocardial infarction, compared with normal-weight and sedentary persons (OR 1.85, 95% CI 1.07–3.18). The results were similar for men and women. CONCLUSION: While regular leisure-time physical activity seems to provide protection against myocardial infarction among lean, normal-weight and overweight subjects, this does not appear to be the case in obese subjects

Rationale for a Swedish cohort consortium

We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.Peer reviewe

Angina, “Normal” Coronary Angiography, and Vascular Dysfunction: Risk Assessment Strategies

The authors discuss how to stratify risk in patients with chest pain and a normal coronary angiogram

Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism

<p>Abstract</p> <p>Background</p> <p>The metabolism of amyloid precursor protein (APP) and β-amyloid (Aβ) is widely studied in Alzheimer's disease, where Aβ deposition and plaque development are essential components of the pathogenesis. However, the physiological role of amyloid in the adult nervous system remains largely unknown. We have previously found altered cerebral amyloid metabolism in other neuroinflammatory conditions. To further elucidate this, we investigated amyloid metabolism in patients with Lyme neuroborreliosis (LNB).</p> <p>Methods</p> <p>The first part of the study was a cross-sectional cohort study in 61 patients with acute facial palsy (19 with LNB and 42 with idiopathic facial paresis, Bell's palsy) and 22 healthy controls. CSF was analysed for the β-amyloid peptides Aβ38, Aβ40 and Aβ42, and the amyloid precursor protein (APP) isoforms α-sAPP and β-sAPP. CSF total-tau (T-tau), phosphorylated tau (P-tau) and neurofilament protein (NFL) were measured to monitor neural cell damage. The second part of the study was a prospective cohort-study in 26 LNB patients undergoing consecutive lumbar punctures before and after antibiotic treatment to study time-dependent dynamics of the biomarkers.</p> <p>Results</p> <p>In the cross-sectional study, LNB patients had lower levels of CSF α-sAPP, β-sAPP and P-tau, and higher levels of CSF NFL than healthy controls and patients with Bell's palsy. In the prospective study, LNB patients had low levels of CSF α-sAPP, β-sAPP and P-tau at baseline, which all increased towards normal at follow-up.</p> <p>Conclusions</p> <p>Amyloid metabolism is altered in LNB. CSF levels of α-sAPP, β-sAPP and P-tau are decreased in acute infection and increase after treatment. In combination with earlier findings in multiple sclerosis, cerebral SLE and HIV with cerebral engagement, this points to an influence of neuroinflammation on amyloid metabolism.</p

Long-term exposure to transportation noise and risk of incident stroke:A pooled study of nine scandinavian cohorts

BACKGROUND: Transportation noise is increasingly acknowledged as a cardiovascular risk factor, but the evidence base for an association with stroke is sparse. OBJECTIVE: We aimed to investigate the association between transportation noise and stroke incidence in a large Scandinavian population. METHODS: We harmonized and pooled data from nine Scandinavian cohorts (seven Swedish, two Danish), totaling 135,951 participants. We identified residential address history and estimated road, railway, and aircraft noise for all addresses. Information on stroke incidence was acquired through link-age to national patient and mortality registries. We analyzed data using Cox proportional hazards models, including socioeconomic and lifestyle con-founders, and air pollution. RESULTS: During follow-up (median = 19:5 y), 11,056 stroke cases were identified. Road traffic noise (Lden ) was associated with risk of stroke, with a hazard ratio (HR) of 1.06 [95% confidence interval (CI): 1.03, 1.08] per 10-dB higher 5-y mean time-weighted exposure in analyses adjusted for indi-vidual-and area-level socioeconomic covariates. The association was approximately linear and persisted after adjustment for air pollution [particulate matter (PM) with an aerodynamic diameter of ≤2:5 lm (PM2:5 ) and NO2 ]. Stroke was associated with moderate levels of 5-y aircraft noise exposure (40–50 vs. ≤40 dB) (HR = 1:12; 95% CI: 0.99, 1.27), but not with higher exposure (≥50 dB, HR = 0:94; 95% CI: 0.79, 1.11). Railway noise was not associated with stroke. DISCUSSION: In this pooled study, road traffic noise was associated with a higher risk of stroke. This finding supports road traffic noise as an important cardiovascular risk factor that should be included when estimating the burden of disease due to traffic noise. https://doi.org/10.1289/EHP8949