| 1. |
- Baryawno, Ninib, et al.
(författare)
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Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target
- 2011
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 121:10, s. 4043-4055
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Tidskriftsartikel (refereegranskat)abstract
- Medulloblastomas are the most common malignant brain tumors in children. They express high levels of COX-2 and produce PGE(2), which stimulates tumor cell proliferation. Human cytomegalovirus (HCMV) is prevalent in the human population and encodes proteins that provide immune evasion strategies and promote oncogenic transformation and oncomodulation. In particular, HCMV induces COX-2 expression; STAT3 phosphorylation; production of PGE2, vascular endothelial growth factor, and IL-6; and tumor formation in vivo. Here, we show that a large proportion of primary medulloblastomas and medulloblastoma cell lines are infected with HCMV and that COX-2 expression, along with PGE2 levels, in tumors is directly modulated by the virus. Our analysis indicated that both HCMV immediate-early proteins and late proteins are expressed in the majority of primary medulloblastomas. Remarkably, all of the human medulloblastoma cell lines that we analyzed contained HCMV DNA and RNA and expressed HCMV proteins at various levels in vitro. When engrafted into immunocompromised mice, human medulloblastoma cells induced expression of HCMV proteins. HCMV and COX-2 expression correlated in primary tumors, cell lines, and medulloblastoma xenografts. The antiviral drug valganciclovir and the specific COX-2 inhibitor celecoxib prevented HCMV replication in vitro and inhibited PGE2 production and reduced medulloblastoma tumor cell growth both in vitro and in vivo. Ganciclovir did riot affect the growth of HCMV-negative tumor cell lines. These findings imply an important role for HCMV in medulloblastoma and suggest HCMV as a novel therapeutic target for this tumor.
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| 2. |
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| 3. |
- Forsström, David, 1981-, et al.
(författare)
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A systematic review of educational programs and consumer protection measures for gambling : an extension of previous reviews
- 2021
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Ingår i: Addiction Research and Theory. - : Informa UK Limited. - 1606-6359 .- 1476-7392. ; 29:5, s. 398-412
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Besides supply reduction, preventive interventions to reduce harm from gambling include interventions for the reduction of demand and to limit negative consequences. Several interventions are available for gamblers, e.g. limit-setting. Reviews have been published examining the evidence for specific measures as well as evaluating the effect of different measures at an overall level. Only a few of these have used a systematic approach for their literature review. The aim of this systematic review and meta-analysis is twofold. First, to assess the certainty of evidence of different preventive measures in the field of educational programs and consumer protection measures, including both land-based and online gambling. The second is to present shortcomings in eligible studies to highlight what type of information is needed in future studies.Method: This systematic review included measures administered in both real-life settings and online. Twenty-eight studies fulfilled our inclusion criteria and had low or moderate risk of bias.Results: The results showed that only two measures (long term educational programs and personalized feed-back) had an impact on gambling behavior. Follow-up period was short, and measures did not include gambling as a problem. The certainty in most outcomes, according to GRADE, was very low. Several shortcomings were found in the studies.Discussion: We concluded that the support for preventive measures is low and that a consensus statement regarding execution and methods to collect and analyze data for preventive gambling research is needed. Our review can serve as a starting point for future responsible gambling reviews since it evaluated certainty of evidence.
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| 4. |
- Franzén, Karin M, 1958-, et al.
(författare)
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Surgery for urinary incontinence in women 65 years and older : a systematic review
- 2015
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Ingår i: International Urogynecology Journal. - : Springer. - 0937-3462 .- 1433-3023. ; 26:8, s. 1095-1102
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Forskningsöversikt (refereegranskat)abstract
- Introduction and hypothesis: Urinary incontinence (UI) is common among the elderly, but the literature is sparse on the surgical treatment of UI among the elderly. This systematic review aims to assess the effectiveness of surgical interventions as treatment for urinary incontinence in the elderly population ≥65 years of age.Methods: Randomized controlled trials (RCT) and prospective nonrandomized studies (NRS) were included. The databases PubMed (NLM), EMBASE (Elsevier), Cochrane Library (Wiley), and Cinahl (EBSCO) were searched for the period 1966 up to October 2013. The population had to be ≥65 years of age and had to have undergone urethral sling procedures, periurethral injection of bulking agents, artificial urinary sphincter surgery, bladder injection treatment with onabotulinumtoxin A or sacral neuromodulation treatment. Eligible outcomes were episodes of incontinence/urine leakage, adverse events, and quality of life.The studies included had to be at a moderate or low risk of bias. Mean difference (MD) or standard mean difference (SMD)as well as risk difference (RD) and the 95 % CI were calculated.Results: Five studies-all on the suburethral sling procedure in women- that fulfilled the inclusion criteria were identified. The proportion of patients reporting persistent SUI after surgery ranged from 5.2 to 17.6 %. One study evaluating quality of life (QoL) showed a significant improvement after surgery. The complication rates varied between 1 and 26 %, mainly bladder perforation, bladder emptying disturbances, and de novo urge.Conclusion: The suburethral sling procedure improves continence as well as QoL among elderly women with SUI; however, evidence is limited.
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| 5. |
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| 6. |
- Klingberg, Gunilla, et al.
(författare)
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How old are you? : a systematic review investigating the relationship between age and mandibular third molar maturity
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:5, s. 1-14
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Forskningsöversikt (refereegranskat)abstract
- Introduction and objective: Radiographic evaluation of the maturity of mandibular third molars is a common method used for age estimation of adolescents and young adults. The aim of this systematic review was to examine the scientific base for the relationship between a fully matured mandibular third molar based on Demirjian's method and chronological age, in order to assess whether an individual is above or below the age of 18 years.Methods: The literature search was conducted in six databases until February 2022 for studies reporting data evaluating the tooth maturity using Demirjian´s method (specifically stage H) within populations ranging from 8 to 30 years (chronological age). Two reviewers screened the titles and abstracts identified through the search strategy independently. All studies of potential relevance according to the inclusion criteria were obtained in full text, after which they were assessed for inclusion by two independent reviewers. Any disagreement was resolved by a discussion. Two reviewers independently evaluated the risk of bias using the assessment tool QUADAS-2 and extracted the data from the studies with low or moderate risk of bias. Logistic regression was used to estimate the relationship between chronological age and proportion of subjects with a fully matured mandibular third molar (Demirjian´s tooth stage H).Results: A total of 15 studies with low or moderate risk of bias were included in the review. The studies were conducted in 13 countries and the chronological age of the investigated participants ranged from 3 to 27 years and the number of participants ranged between 208 and 5,769. Ten of the studies presented the results as mean age per Demirjian´s tooth stage H, but only five studies showed the distribution of developmental stages according to validated age. The proportion of subjects with a mandibular tooth in Demirjian´s tooth stage H at 18 years ranged from 0% to 22% among males and 0 to 16% in females. Since the studies were too heterogenous to perform a meta-analysis or a meaningful narrative review, we decided to refrain from a GRADE assessment.Conclusion: The identified literature does not provide scientific evidence for the relationship between Demirjian´s stage H of a mandibular third molar and chronologic age in order to assess if an individual is under or above the age of 18 years.
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| 7. |
- Odeberg, Jenny
(författare)
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Human cytomegalovirus immune evasion strategies
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human cytomegalovirus (HCMV) is a member of the herpes virus family. HCMV is a ubiquitous pathogen, causing severe morbidity and mortality in immunocompromised patients, and is a major factor in congenital birth defects. Most adult individuals become carriers of latent HCMV after an asymptomatic infection, and have antibodies against HCMV proteins (are seropositive). Experimental studies of HCMV infection has revealed many interesting features and effects of virally encoded genes to enable infected cells to escape immune recognition as well as to be protected from immune effector mechanisms. T cells recognize virus-encoded peptides presented in the context of HLA class I and class II surface molecules. CD4+ T lymphocytes primarily react against HLA class II-viral peptide complexes, whereas CD8+ T lymphocytes react against HLA class I-peptide complexes. NK cells, on the other hand, are usually thought to be more cytotoxic against cells that express lower concentrations of HLA class I molecules. HCMV has developed multiple immune evasion mechanisms to be able to co-exist with its host. Here, we have investigated the mechanisms of HCMV immune evasion strategies. Several new strategies to avoid specific T cell activation and to resist NK cytotoxicity have been described. Resistance to NK killing is independent on the expression of the virally encoded class I homologue UL18, which has been suggested to be a major candidate for delivering inhibitory signals to NK cells. We have defined a new inhibitory pathway that leads to increased resistance of HCMV infected cells to cytolytic proteins released by activated NK cells. This insensitivity to cytolytic proteins is mediated by the viral protein UL16 and is presumably caused by a redistribution of calreticulin, a protein that has been shown to protect cells from perforin destruction through a membrane stabilization effect. In addition, we have found that HCMV infected macrophages have a reduced capacity to activate a specific T cell proliferative response, compared to uninfected cells. This, in part, is caused by an abundant viral protein pp65, which mediates an accumulation of HLA-DR to lysosomes and degradation of the HLA-DR a-chain. Interestingly, UL18 interacts directly with immunoreactive T lymphocytes, to limit T cell activation. T cells exposed to HCMV express activation markers, produce lower levels of cytokines, but lack proliferative capacity. These cells do not enter apoptosis and can therefore be described as "anergic". These findings increase the current knowledge of how HCMV can avoid detection and elimination by the host immune system.
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| 8. |
- Pettersson, Agneta, et al.
(författare)
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Förebygga självskadebeteende och suicidförsök hos barn och ungdomar – effekter av riktade interventioner. : En systematisk översikt och utvärdering av medicinska, hälsoekonomiska och etiska aspekter
- 2024. - 378
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Ingår i: SBU Utvärderar. ; :378
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- HuvudbudskapDialektisk beteendeterapi för ungdomar (DBT-A) förebygger återfall i självskadebeteende. Internetförmedlad känsloregleringsterapi (IERITA) kan förebygga nya episoder av icke-suicidalt självskadebeteende.SlutsatserEfter att ha granskat den vetenskapliga litteraturen har SBU dragit följande slutsatser:DBT-A minskar antalet ungdomar med självskadebeteende som får ett återfall. Behandlingen uppskattas av ungdomarna och deras föräldrar. DBT-A under fyra månader kan vara kostnadseffektivt jämfört med sedvanlig vård, men svenska hälsoekonomiska studier behövs.IERITA som bygger på DBT-A kan möjligen minska antalet ungdomar med icke-suicidalt självskadebeteende som får ett återfall men här behövs fler randomiserade studier som bekräftar resultaten. I svenska studier är IERITA uppskattat av ungdomar, föräldrar och vården.Ungdomar som identifierar sig som att tillhöra en sexuell minoritet eller har ett riskfyllt substansbruk, eller är omhändertagna i rättssystemet, har en förhöjd risk för självskadebeteende. Studier på förebyggande interventioner saknas eller är få och små.Det behövs forskning om specifika behandlingar som ökar säkerheten kring en ungdom akut efter ett suicidförsök. En säkerhetsplan, färdighetsträning och komponenter riktade till familjen verkar vara centralt, exempelvis familjeinterventionen SAFETY.Det behövs effektiv heldygnsvård med mindre risk för långa vårdförlopp och försämring av hälsotillståndet. Forskning med före-eftermätningar och kvalitativa studier pekar på värdet av brukarstyrda inläggningar men det behövs svenska randomiserade studier.Vad skulle resultaten kunna innebära?Resultaten tyder på att det finns en potential för att fler ungdomar med självskadebeteende kan få tillgång till effektiva behandlingar. DBT-A är idag den enda metod som har vetenskapligt stöd för att minska risken för upprepade självskadeförsök men erbjuds i huvudsak i storstadsregionerna. Behandlingen kan pågå i upp till ett år. Studierna visar dock att redan fyra månaders DBT-A är effektivt, något som skulle kunna frigöra resurser för att behandla fler. För att införa DBT-A på fler kliniker kommer det att krävas omfattande utbildnings- och rekryteringsinsatser, sannolikt med förhöjda kostnader på kort sikt.Vidare skulle IERITA kunna komplettera vårdutbudet för ungdomar med icke-suicidalt självskadebeteende utan omedelbar suicidrisk. IERITA är inte lika etablerad som DBT-A och det kommer krävas utbildningsinsatser.Vad handlar rapporten om?Självskadebeteende, oavsett om avsikten är att avsluta sitt liv eller inte, hos barn och ungdomar är ett globalt hälsoproblem och suicid är den vanligaste dödsorsaken för ungdomar. Självskadebeteende ökar också risken för framtida suicidhandlingar, annan psykisk ohälsa, riskfyllt substansbruk och kriminalitet.Syftet med rapporten var att utvärdera om det finns några interventioner som kan förebygga självskadebeteende. Interventionerna skulle ges till barn och ungdomar som redan har ett självskadebeteende eller till sådana som tillhör några specifika riskgrupper.Utvärderingen gjordes som en systematisk översikt med metaanalyser, kompletterad med systematiska översikter till grund för hälsoekonomiska och etiska aspekter. Vilka studier ligger till grund för resultaten?Resultaten baseras på 28 randomiserade studier och en systematisk översikt. Två hälsoekonomiska studier och elva studier med kvalitativ metodik ingår också i rapporten. Studierna har publicerats från år 1990 och framåt och de flesta har genomförts i USA och Storbritannien.Samtliga studier utvärderade någon form av psykologisk behandling förutom en studie om brukarstyrda inläggningar. Studier på läkemedel och andra tänkbara behandlingar saknades för ungdomar med självskador eller suicidalt beteende.
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| 9. |
- Stenzelius, Karin, et al.
(författare)
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The effect of conservative treatment of urinary incontinence among older and frail older people : a systematic review
- 2015
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Ingår i: Age and Ageing. - Oxford, United Kingdom : Oxford University Press. - 0002-0729 .- 1468-2834. ; 44:5, s. 736-744
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Forskningsöversikt (refereegranskat)abstract
- Background: urinary incontinence (UI) is a common symptom among older people, with a higher prevalence among frail older persons living in nursing homes. Despite consequences such as reduced health and quality of life, many older people do not seek help for their symptoms, resulting in missed opportunity for treatment. Objective: the aim of this study was to investigate the evidence and the effect of conservative treatment of UI and the quality of life among older and frail older persons. Methods: a systematic review of randomised controlled studies and prospective, non-randomised studies was conducted, evaluating interventions of conservative treatment of UI in an older population (65 years or older). A total of 23 studies fulfilled the inclusion criteria and 9 were of high or moderate quality. Fourteen studies were of low quality and were therefore excluded from the analysis. Results: documented and effective conservative treatments are available even for older persons with UI. Pelvic muscle exercise, physical training in combination with ADL, prompted voiding and attention training, and help to toilet are important treatments. In some studies, however, the evidence of effectiveness is limited. Conclusions: this systematic review concludes that there are conservative treatments for UI for older and frail older persons that reduce leakage and increase quality of life. There is however a need for further high-quality studies.
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| 10. |
- Uhlén, Mathias, et al.
(författare)
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Tissue-based map of the human proteome
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6220, s. 1260419-
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Tidskriftsartikel (refereegranskat)abstract
- Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.
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