Herpes Simplex Virus Type 1 Us3 Gene Deletion Influences Toll-like Receptor Responses in Cultured Monocytic Cells

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors have a key role in innate immune response to microbial infection. The toll-like receptor (TLR) family consists of ten identified human TLRs, of which TLR2 and TLR9 have been shown to initiate innate responses to herpes simplex virus type 1 (HSV-1) and TLR3 has been shown to be involved in defence against severe HSV-1 infections of the central nervous system. However, no significant activation of the TLR3 pathways has been observed in wild type HSV-1 infections. In this work, we have studied the TLR responses and effects on TLR gene expression by HSV-1 with Us3 and ICP4 gene deletions, which also subject infected cells to apoptosis in human monocytic (U937) cell cultures.</p> <p>Results</p> <p>U937 human monocytic cells were infected with the Us3 and ICP4 deletion herpes simplex virus (d120), its parental virus HSV-1 (KOS), the Us3 deletion virus (R7041), its rescue virus (R7306) or wild type HSV-1 (F). The mRNA expression of TLR2, TLR3, TLR4, TLR9 and type I interferons (IFN) were analyzed by quantitative real-time PCR. The intracellular expression of TLR3 and type I IFN inducible myxovirus resistance protein A (MxA) protein as well as the level of apoptosis were analyzed by flow cytometry. We observed that the mRNA expression of TLR3 and type I IFNs were significantly increased in d120, R7041 and HSV-1 (F)-infected U937 cells. Moreover, the intracellular expression of TLR3 and MxA were significantly increased in d120 and R7041-infected cells. We observed activation of IRF-3 in infections with d120 and R7041. The TLR4 mRNA expression level was significantly decreased in d120 and R7041-infected cells but increased in HSV-1 (KOS)-infected cells in comparison with uninfected cells. No significant difference in TLR2 or TLR9 mRNA expression levels was seen. Both the R7041 and d120 viruses were able to induce apoptosis in U937 cell cultures.</p> <p>Conclusion</p> <p>The levels of TLR3 and type I IFN mRNA were increased in d120, R7041 and HSV-1 (F)-infected cells when compared with uninfected cells. Also IRF-3 was activated in cells infected with the Us3 gene deletion viruses d120 and R7041. This is consistent with activation of TLR3 signaling in the cells. The intracellular TLR3 and type I IFN inducible MxA protein levels were increased in d120 and R7041-infected cells but not in cells infected with the corresponding parental or rescue viruses, suggesting that the HSV-1 Us3 gene is involved in control of TLR3 responses in U937 cells.</p

Music for Social Impact: An overview of context, policy and activity in four countries, Belgium, Colombia, Finland, and the UK

peer reviewe

Baseline findings and safety of infrequent vs. frequent screening of human papillomavirus vaccinated women

Less frequent cervical cancer screening in human papillomavirus (HPV) vaccinated birth cohorts could produce considerable savings without increasing cervical cancer incidence and loss of life-years. We report here the baseline findings and interim results of safety and accuracy of infrequent screening among HPV16/18 vaccinated females. The entire 1992-1994 birth-cohorts (30,139 females) were invited to a community-randomized HPV16/18-vaccination trial. A total of 9,482 female trial participants received HPV16/18-vaccination in 2007-2009 at age of 13-15. At age 22, 4,273 (45%) of these females consented to attend a randomized trial on frequent (ages 22/25/28; Arm 1: 2,073 females) vs. infrequent screening (age 28; Arm 2: 2,200 females) in 2014-2017. Females (1,329), who had got HPV16/18 vaccination at age 18 comprised the safety Arm 3. Baseline prevalence and incidence of HPV16/18 and other high-risk HPV types were: 0.5% (53/1,000 follow-up years, 10(4)) and 25% (2,530/10(4)) in the frequently screened Arm 1; 0.2% (23/10(4)) and 24% (2,413/10(4)) in the infrequently screened Arm 2; and 3.1% (304/10(4)) and 23% (2,284/10(4)) in the safety Arm 3. Corresponding prevalence of HSIL/ASC-H and of any abnormal cytological findings were: 0.3 and 4.2% (Arm 1), 0.4 and 5.3% (Arm 2) and 0.3 and 4.7% (Arm 3). Equally rare HSIL/CIN3 findings in the infrequently screened safety Arm A3 (0.4%) and in the frequently screened Arm 1 (0.4%) indicate no safety concerns on infrequent screening despite the up to 10 times higher HPV16/18 baseline prevalence and incidence in the former.Peer reviewe

Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers : population-based follow-up of a cluster-randomised trial

Background Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer. Methods Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002-2005. HPV vaccine cohorts comprised originally 16-17 year-old HPV 16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2465) and HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866). Altogether, 3341 vaccines were followed by the Finnish Cancer Registry in the same way as 16 526 non-HPV-vaccinated controls. The control cohort stemmed from 15 665 originally 18-19 years-old women enrolled in 2003 (6499) or 2005 (9166) and 861 placebo recipients of the FUTURE II trial. The follow-up started 6 months after the clinical trials in 2007 and 2009 and ended in 2019. It was age aligned for the cohorts. Findings During a follow-up time of up to 11 years, we identified 17 HPV-positive invasive cancer cases (14 cervical cancers, 1 vaginal cancer, 1 vulvar cancer and 1 tongue cancer) in the non-HPV-vaccinated cohorts and no cases in the HPV-vaccinated cohorts. HPV typing of diagnostic tumour blocks found HPV16 in nine cervical cancer cases, HPV18, HPV33 and HPV52 each in two cases and HPV45 in one cervical cancer case. The vaginal, vulvar and tongue cancer cases were, respectively, positive for HPV16, HPV52/66 and HPV213. Intention-to-treat vaccine efficacy against all HPV-positive cancers was 100% (95% CI 2 to 100, p Interpretation Vaccination is effective against invasive HPV-positive cancer.Peer reviewe

”EN TIIÄ KUKA TÄN ON KEKSINY, MUTTA TÄÄ ON AIKA NAPPIIN SANOSIN” – SELVITYS JOENSUUN SETLEMENTIN IKÄÄNTYNEIDEN KOHTAAMISPAIKKATOIMINNAN MERKITYKSISTÄ KÄVIJÖILLEEN

Opinnäytetyömme tutkimustehtävä oli selvittää Joensuun Setlementin senioreiden kohtaamispaikkatoimintojen merkityksiä kävijöilleen. Opinnäytetyömme tarkoitus on tarkastella järjestötyön merkitystä toimintaan osallistuneiden omien kokemusten pohjalta Joensuun Setlementin senioriryhmissä. Tutkimuksen tarkoitus on myös toimia toimeksiantajan työn kehittämisen ja raportoinnin tukena. Opinnäytetyömme toteutettiin laadullisena tutkimuksena. Aineisto kerättiin tekemällä kuusi teemahaastattelua yksilöhaastatteluina. Aineiston analyysi toteutettiin aineistolähtöisen sisällönanalyysin menetelmin. Tutkimustulosten mukaan kohtaamispaikkatoiminta toimii ikääntyneiden hyvinvointia vahvistavana tekijänä. Ryhmätoiminta tuo mukanaan sosiaalisia suhteita ja vuorovaikutusmahdollisuuksia toisten saman ikäisten kanssa, uusia kokemuksia ja elämyksiä sekä mielekästä sisältöä arkeen. Tutkimusta voivat hyödyntää sosiaali- ja terveysalan alan ammattilaiset ja opiskelijat. Erityisesti ikääntyneiden kanssa työskentelevät voivat saada työstä uusia näkökulmia ja ideoita työnsä kehittämiseksi. Tutkimuksen tulokset avaavat näkökulmia ennaltaehkäisevästä työstä ja sen mahdollisuuksista ikääntyneiden kanssa. Toiminnan lähtökohta voi hoitaja-hoidettava -asetelman sijaan olla myös lähtöisin ikääntyneen omasta aktiivisuudesta, toiveista, tarpeista ja voimavaroista.The aim of the thesis was to research the meanings of senior group activities to the participants in Settlement of Joensuu. The purpose of the thesis was to explore experiences of participators in a civic organization. The results will be used in developing the work of Settlement of Joensuu and on their reporting. This thesis is a qualitative research. The material of this thesis was collected by making six interviews. The analysis of the material was made by using the methods of the material focused content analysis. The result of the research was that group activities improves the welfare of ageing people. Group activities give possibilities to interact with other elderly people and they provide them new social relationships. They also give them new experiences and meaningful contents to their lives. Social- and healthcare professionals and students can use this research and its results. Especially professionals working with elderly people can get new perspectives on preventive work and its possibilities to their jobs. Working with elderly people can be based on their own activity and reserves of strength instead of nursing