218 research outputs found

    Predictors of positive health in disability pensioners: a population-based questionnaire study using Positive Odds Ratio

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    BACKGROUND: Determinants of ill-health have been studied far more than determinants of good and improving health. Health promotion measures are important even among individuals with chronic diseases. The aim of this study was to find predictors of positive subjective health among disability pensioners (DPs) with musculoskeletal disorders. METHODS: Two questionnaire surveys were performed among 352 DPs with musculoskeletal disorders. Two groups were defined: DPs with positive health and negative health, respectively. In consequence with the health perspective in this study the conception Positive Odds Ratio was defined and used in the logistic regression analyses instead of the commonly used odds ratio. RESULTS: Positive health was associated with age ≄ 55 years, not being an immigrant, not having fibromyalgia as the main diagnosis for granting an early retirement, no regular use of analgesics, a high ADL capacity, a positive subjective health preceding the study period, and good quality of life. CONCLUSION: Positive odds ratio is a concept well adapted to theories of health promotion. It can be used in relation to positive outcomes instead of risks. Suggested health promotion and secondary prevention efforts among individuals with musculoskeletal disorders are 1) to avoid a disability pension for individuals <55 years of age; if necessary, to make sure rehabilitation actions continue, 2) to increase efforts to support immigrants to adjust to circumstances connected to ill-health and retirement, 3) to pay special attention to individuals with fibromyalgia and other general pain disorders, and 4) to strengthen ADL activities to support an independent active life among disability pensioners

    Neurochemical biomarkers to study CNS effects of COVID-19: a narrative review and synthesis

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    Neurological symptoms are frequently reported in patients suffering from COVID-19. Common CNS-related symptoms include anosmia, caused by viral interaction with either neurons or supporting cells in nasal olfactory tissues. Diffuse encephalopathy is the most common sign of CNS dysfunction, which likely results from the CNS consequences of the systemic inflammatory syndrome associated with severe COVID-19. Additionally, microvascular injuries and thromboembolic events likely contribute to the neurologic impact of acute COVID-19. These observations are supported by evidence of CNS immune activation in cerebrospinal fluid (CSF) and in autopsy tissue, along with detection of microvascular injuries in both pathological and neuroimaging studies. The frequent occurrence of thromboembolic events in patients with COVID-19 has generated different hypotheses, among which viral interaction with perivascular cells is particularly attractive, yet unproven. A distinguishing feature of CSF findings in SARS-CoV-2 infection is that clinical signs characteristic of neurotropic viral infections (CSF pleocytosis and blood brain barrier injury) are mild or absent. Moreover, virus detection in CSF is rare, and often of uncertain significance. In this review, we provide an overview of the neurological impact that occur in the acute phase of COVID-19, and the role of CSF biomarkers in the clinical management and research to better treat and understand the disease. In addition to aiding as diagnostic and prognostic tools during acute infection, the use of comprehensive and well characterized CSF and blood biomarkers will be vital in understanding the potential impact on the CNS in the rapidly increasing number of individuals recovering from COVID-19

    CSF Biomarkers in Patients With COVID-19 and Neurologic Symptoms: A Case Series

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    OBJECTIVE: To explore whether hospitalized patients with SARS-CoV-2 and neurologic symptoms have evidence of CNS infection, inflammation and injury using CSF biomarker measurements. METHODS: We assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, ÎČ2-microglobulin (ÎČ2M) 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. RESULTS: 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 ÎČ2-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/”L) were normal in all, while CSF NfL was elevated in 2 patients. CONCLUSION: 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

    Infection of brain pericytes underlying neuropathology of covid‐19 patients

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    A wide range of neurological manifestations have been associated with the development of COVID‐19 following SARS‐CoV‐2 infection. However, the etiology of the neurological sympto-matology is still largely unexplored. Here, we used state‐of‐the‐art multiplexed immunostaining of human brains (n = 6 COVID‐19, median age = 69.5 years; n = 7 control, median age = 68 years) and demonstrated that expression of the SARS‐CoV‐2 receptor ACE2 is restricted to a subset of neuro-vascular pericytes. Strikingly, neurological symptoms were exclusive to, and ubiquitous in, patients that exhibited moderate to high ACE2 expression in perivascular cells. Viral dsRNA was identified in the vascular wall and paralleled by perivascular inflammation, as signified by T cell and macro-phage infiltration. Furthermore, fibrinogen leakage indicated compromised integrity of the blood– brain barrier. Notably, cerebrospinal fluid from additional 16 individuals (n = 8 COVID‐19, median age = 67 years; n = 8 control, median age = 69.5 years) exhibited significantly lower levels of the pericyte marker PDGFRÎČ in SARS‐CoV‐2‐infected cases, indicative of disrupted pericyte homeostasis. We conclude that pericyte infection by SARS‐CoV‐2 underlies virus entry into the privileged central nervous system space, as well as neurological symptomatology due to perivascular inflammation and a locally compromised blood–brain barrier

    Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up

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    Background: Neurologic manifestations are well-recognized features of coronavirus disease 2019 (COVID-19). However, the longitudinal association of biomarkers reflecting CNS impact and neurological symptoms is not known. We sought to determine whether plasma biomarkers of CNS injury were associated with neurologic sequelae after COVID-19. / Methods: Patients with confirmed acute COVID-19 were studied prospectively. Neurological symptoms were recorded during the acute phase of the disease and at six months follow-up, and blood samples were collected longitudinally. Healthy age-matched individuals were included as controls. We analysed plasma concentrations of neurofilament light-chain (NfL), glial fibrillary acidic protein (GFAp), and growth differentiation factor 15 (GDF-15). / Findings: One hundred patients with mild (n = 24), moderate (n = 28), and severe (n = 48) COVID-19 were followed for a median (IQR) of 225 (187–262) days. In the acute phase, patients with severe COVID-19 had higher concentrations of NfL than all other groups (all p < 0·001), and higher GFAp than controls (p < 0·001). GFAp was also significantly increased in moderate disease (p < 0·05) compared with controls. NfL (r = 0·53, p < 0·001) and GFAp (r = 0·39, p < 0·001) correlated with GDF-15 during the acute phase. After six months, NfL and GFAp concentrations had normalized, with no persisting group differences. Despite this, 50 patients reported persistent neurological symptoms, most commonly fatigue (n = 40), “brain-fog” (n = 29), and changes in cognition (n = 25). We found no correlation between persistent neurological symptoms and CNS injury biomarkers in the acute phase. / Interpretation: The normalization of CNS injury biomarkers in all individuals, regardless of previous disease severity or persisting neurological symptoms, indicates that post COVID-19 neurological sequelae are not accompanied by ongoing CNS injury. / Funding: The Swedish State Support for Clinical Research, SciLifeLab Sweden, and the Knut and Alice Wallenberg Foundation have provided funding for this project

    Explicit Model Realizing Parton-Hadron Duality

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    We present a model that realizes both resonance-Regge (Veneziano) and parton-hadron (Bloom-Gilman) duality. We first review the features of the Veneziano model and we discuss how parton-hadron duality appears in the Bloom-Gilman model. Then we review limitations of the Veneziano model, namely that the zero-width resonances in the Veneziano model violate unitarity and Mandelstam analyticity. We discuss how such problems are alleviated in models that construct dual amplitudes with Mandelstam analyticity (so-called DAMA models). We then introduce a modified DAMA model, and we discuss its properties. We present a pedagogical model for dual amplitudes and we construct the nucleon structure function F2(x,Q2). We explicitly show that the resulting structure function realizes both Veneziano and Bloom-Gilman duality.Comment: 11 pages, 8 figure

    Reduction of the HIV-1 reservoir in resting CD4+ T-lymphocytes by high dosage intravenous immunoglobulin treatment: a proof-of-concept study

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    <p>Abstract</p> <p>Background</p> <p>The latency of HIV-1 in resting CD4<sup>+ </sup>T-lymphocytes constitutes a major obstacle for the eradication of virus in patients on antiretroviral therapy (ART). As yet, no approach to reduce this viral reservoir has proven effective.</p> <p>Methods</p> <p>Nine subjects on effective ART were included in the study and treated with high dosage intravenous immunoglobulin (IVIG) for five consecutive days. Seven of those had detectable levels of replication-competent virus in the latent reservoir and were thus possible to evaluate. Highly purified resting memory CD4<sup>+ </sup>T-cells were activated and cells containing replication-competent HIV-1 were quantified. HIV-1 from plasma and activated memory CD4<sup>+ </sup>T-cells were compared with single genome sequencing (SGS) of the <it>gag </it>region. T-lymphocyte activation markers and serum interleukins were measured.</p> <p>Results</p> <p>The latent HIV-1 pool decreased with in median 68% after IVIG was added to effective ART. The reservoir decreased in five, whereas no decrease was found in two subjects with detectable virus. Plasma HIV-1 RNA ≄ 2 copies/mL was detected in five of seven subjects at baseline, but in only one at follow-up after 8–12 weeks. The decrease of the latent HIV-1 pool and the residual plasma viremia was preceded by a transitory low-level increase in plasma HIV-1 RNA and serum interleukin 7 (IL-7) levels, and followed by an expansion of T regulatory cells. The magnitude of the viral increase in plasma correlated to the size of the latent HIV-1 pool and SGS of the <it>gag </it>region showed that viral clones from plasma clustered together with virus from activated memory T-cells, pointing to the latent reservoir as the source of HIV-1 RNA in plasma.</p> <p>Conclusion</p> <p>The findings from this uncontrolled proof-of-concept study suggest that the reservoir became accessible by IVIG treatment through activation of HIV-1 gene expression in latently-infected resting CD4<sup>+ </sup>T-cells. We propose that IVIG should be further evaluated as an adjuvant to effective ART.</p

    Inequalities of quality of life in unemployed young adults: A population-based questionnaire study

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    BACKGROUND: It is well known that unemployment is a great problem both to the exposed individual and to the whole society. Unemployment is reported as more common among young people compared to the general level of unemployment. Inequity in health status and life-satisfaction is related to unemployment. The purpose of this population-based study was to describe QOL among unemployed young people compared to those who are not unemployed, and to analyse variables related to QOL for the respective groups. METHODS: The sample consisted of 264 young unemployed individuals and 528 working or studying individuals as a reference group. They all received a questionnaire about civil status, educational level, immigration, employment status, self-reported health, self-esteem, social support, social network, spare time, dwelling, economy and personal characteristics. The response rate was 72%. The significance of differences between proportions was tested by Fisher's exact test or by χ(2 )test. Multivariate analysis was carried out by means of a logistic regression model. RESULTS: Our results balance the predominant picture of youth unemployment as a principally negative experience. Although the unemployed reported lower levels of QOL than the reference group, a majority of unemployed young adults reported good QOL, and 24% even experienced higher QOL after being unemployed. Positive QOL related not only to good health, but also to high self-esteem, satisfaction with spare time and broad latitude for decision-making. CONCLUSION: Even if QOL is good among a majority of unemployed young adults, inequalities in QOL were demonstrated. To create more equity in health, individuals who report reduced subjective health, especially anxiety need extra attention and support. Efforts should aim at empowering unemployed young adults by identifying their concerns and resources, and by creating individual programmes in relation not only to education and work, but also to personal development

    Expression profiling to predict outcome in breast cancer: the influence of sample selection

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    Gene expression profiling of tumors using DNA microarrays is a promising method for predicting prognosis and treatment response in cancer patients. It was recently reported that expression profiles of sporadic breast cancers could be used to predict disease recurrence better than currently available clinical and histopathological prognostic factors. Having observed an overlap in those data between the genes that predict outcome and those that predict estrogen receptor-α status, we examined their predictive power in an independent data set. We conclude that it may be important to define prognostic expression profiles separately for estrogen receptor-α-positive and estrogen receptor-α-negative tumors
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