Browsing by Title

Yläruoansulatuskanavan syöpien tärkeimpiä riskitekijöitä ovat tupakointi, alkoholin suurkulutus ja huono suuhygienia. Näiden tekijöiden vaikutuksesta sylkeen erittyy korkeita pitoisuuksia asetaldehydiä, jonka Kansainvälinen syöväntutkimuslaitos (IARC) on luokitellut 1-ryhmän karsinogeeniksi. Suuri osa syljen asetaldehydistä on suun mikrobien tuottamaa. Tiedetään, että suun mikrobiomiin kuuluvat bakteerit ja Candida albicans -hiivat kykenevät tuottamaan mutageenisiä määriä asetaldehydiä. C. albicansin aiheuttaman kroonisen mukosiitin onkin todettu olevan karsinogeeninen. Muiden kandidalajien (non- albicans Candida, NAC) määrän on todettu kasvavan etenkin suusyöpähoitoja saavilla potilailla ja toisinaan osalle näistä potilaista kehittyy uusi primäärikarsinooma kandidamukosiitin läheisyyteen. NAC-lajien kykyä tuottaa asetaldehydiä ei kuitenkaan ole aiemmin tutkittu. Tutkimuksen tavoitteena oli selvittää pystyvätkö NAC-lajit tuottamaan karsinogeenisiä määriä asetaldehydiä etanoli- ja glukoosi-inkubaatiossa in vitro. Kaikkiaan kolmenkymmenen (n=30) kliinisen ja kantapankkiNAC-kannan kyky tuottaa asetaldehydiä etanoli- ja glukoosi-inkubaatiossa mitattiin kaasukromatografilla. Yksi C. albicans kantapankkikanta oli mukana kontrollina. Kaikki kandidahiivat tuottivat merkittäviä määriä asetaldehydiä etanoli-inkubaatiossa in vitro. C. tropicalis –kannat tuottivat eniten (252,3 µM) ja C. krusei –kannat vähiten (54,6 µM) asetaldehydiä etanolista. NAC-lajeista ainoastaan C. glabrata tuotti merkittäviä määriä asetaldehydiä glukoosia fermentoimalla. Suuontelon kolonisoituminen merkittävään asetaldehydituotantoon pystyvällä NAC-lajilla kuten C. glabratalla voi altistaa suun limakalvon paikallisesti korkeille määrille asetaldehydiä, mikä voi johtaa suusyövän kehittymiseen.

Background: 5-year survival rate of oral tongue squamous cell carcinoma (OTSCC) has been low (less than 60%) despite developing treatment modalities. A previous research revealed that different populations of inflammatory cells infiltration in OTSCC were associated with different clinical outcomes. On the other hand, extracellular vesicles (EVs) secreted by OTSCC cells suggested crosstalk between OTSCC cells and tumor infiltrating inflammatory cells. Study aims: This study aims to investigate the interaction between OTSCC cells and inflammatory cells and answer 3 questions: (1) Can human peripheral blood mononuclear cells (MNCs) affect activities of OTSCC cells such as proliferation, migration and invasion? (2) Can EVs of OTSCC cells affect polarization of macrophages? (3) Can EVs of OTSCC cells affect cytotoxic activity of CD8+ T cells and NK cells? Materials and methods: Two OTSCC cell lines (HSC-3 and SCC-25) were used. OTSCC cells and human peripheral blood MNCs were co-cultured using a 3D organotypic myoma model. Proliferation and invasion into myoma tissue of OTSCC cells were detected by Immunohistochemical staining of pan-cytokeratin and Ki67. Invasion area and depth of OTSCC cells were measured using ImageJ software. Migration of OTSCC cells in the presence of MNCs was monitored using a scratch wound healing assay with IncuCyte™ system. OTSCC EVs were isolated with ultracentrifugation and characterized with NTA and Immuno-EM. Human primary monocytes, CD8+ T cells and NK cells were isolated using MACS, and their purity was checked using FACS. Expression of macrophage phenotypic markers was checked with qPCR. Cytotoxic activity was evaluated using an IncyCyte™ cell killing assay. Results: Activated human peripheral blood MNCs significantly reduced proliferation of both OTSCC cell lines, and invasion area of only HSC-3. None of the inflammatory cells in the experiment had any effect on invasion depth and migration of OTSCC cells. On the other hand, OTSCC cell-derived EVs didn't influence macrophage polarization, but had heterogeneous modulating effects on cytotoxic activity of CD8+ T cells and NK cells. Conclusion: We detected effects of OTSCC cells and inflammatory cells on each other by secreted molecule mediators or EVs, but the results were not uniform and varied in different OTSCC cell lines or inflammatory cell populations and sources. The outcome of the study emphasizes the importance of a personalized design of cancer treatment, which takes other components in tumor microenvironment such as inflammatory cells and EVs into consideration.

Patients over 65 years are more prone to face difficulties in their care due to not only complex and chronic multimorbid conditions, but also fragmentation of health care services. Current healthcare systems are designed for single-disease conditions that do not align with the care needs of the multimorbid elderly. Multimorbid long-term home care clients use a wide range of home care services but also other health and social services outside of home care, which can lead to fragmentation. The study aimed to map out services used by multimorbid home care clients, present disruptions related to their care, and suggest feasible and scalable solutions for the identified disruptions. Home care professionals (N=10) and clients (N=5) were interviewed focusing on the services and disruptions, and a focus group workshop was conducted for health and elderly care specialists (N=9) for creating the solutions. A total of 38 individual disruptions were discovered, of which 58% (22 cases) mentioned more than one interviewee. The results indicate that multimorbid home care clients faced the most care disruptions when care was prescribed outside of home care and caused fragmentation in the care coordination and sharing of patient information between multiple care providers and actors. Other disruptions were caused by a lack of co-creation of health, inconsistencies within home care protocols, and other factors outside of home care such as rapid workforce turnover. The disruptions discovered were mainly related to healthcare service networks rather than social-related care, due to the healthcare services’ lack of care-related integration at multiple levels and dimensions which was not necessarily needed with social services. Possible solutions suggested by health and elderly care specialists included adapting current healthcare systems to the needs of the home care, improving care coordination through various means, utilizing digital solutions, creating tools to track the status of the client’s care, and increasing co-creation of health with the client. With the current challenges in recruiting and maintaining health care personnel in the home care and constant training of personnel; this study suggests that different types of technological solutions are needed to improve care coordination and integration.

Objectives. A new theory of personality is presented. The A-TRiC is unique in having a substantive theoretical basis in human evolutionary history and the phylogenetic constraints on development of dimensional psychological traits. Trust, Reactivity (to threat) and (need for) Control are personality traits found in all social mammals. Independence affects need for social reward, Analytical Thinking affects willingness to adhere to mechanistic/reductionistic vs intuitive/holistic explanations to phenomena. Since it would be futile academic egotism to propose a new theory unless one is needed, the psychometric and theoretical problems of the mainstream Five-Factor theory are also analysed. Methods. 1027 participants (61% female; Mage 41) completed the A-TRiC questionnaire online. Internal consistencies of the traits and model fit were investigated and predictions about traits and some outcomes were tested. Results & conclusions. Internal consistency was acceptable. Central model fit indices showed acceptable to poor fit. Levels of Reactivity and Control were associated with lifetime diagnoses of depression and anxiety. Reactivity was associated with addiction. High scores in Analytical thinking were associated with male gender and a degree in natural science. Women scored higher on Control. Some conceptual confusions hindering progress in the scientific study of personality are discussed in light of the theory and its background assumptions.

Objectives. The most prevailing theory on developmental dyslexia (DD) is the phonological deficit theory, according to which individuals with DD have impairments in neural processing of speech sounds. However, there is evidence that the cause of DD could be related to a fundamental impairment called categorical speech perception (CSP) deficit that is related to the perception of auditory phonemes categories. CSP deficits have been reported in children with or at risk for DD but the results are inconsistent and under debate. Therefore, the present study aimed to determine whether the CSP deficit can be detected in preschoolers at family risk for DD when compared to chronological-age controls and whether the performance on the CSP task predicts age-appropriate pre-reading skills. Methods. The study sample consisted of 49 5-year-old Finnish preschoolers of which 36 had a familial risk for DD and 13 were controls with no such risk. The CSP performance was evaluated with a behavioral speech sound categorization task and pre-reading skills with the LUKIVA scale. The data structure represented a hierarchical nested design, and therefore, the CSP performance was analyzed by using the Linear Mixed-Effects Model, and pre-reading skills by the Generalized Linear Mixed Model. Results and Conclusions. The at-risk children had a poorer performance on the CSP task than the control group; however, the difference was only marginally significant. The performance on the CSP task had no significant relationship with pre-reading skills. Since the difference in CSP performance between the groups was marginal, more research is needed to further validate the relationship between DD and CSP.

Tausta: Pään ja kaulan alueen syövät diagnosoidaan yleensä myöhäisessä vaiheessa, mikä johtaa huonompaan ennusteeseen. Viive voi johtua potilaasta itsestään tai perusterveydenhuollosta. Menetelmät: Keräsimme tietoja potilaiden hoitoon hakeutumisesta kyselylomakkeella, joka kartoitti potilaiden oirekuvaa, oireiden alkamisajankohtaa ja muita tekijöitä, joilla saattoi olla vaikutusta hoitoon hakeutumiseen. Vertasimme kyselylomakkeesta saatuja tietoja potilaan sairauskertomuksissa oleviin tietoihin. Tulokset: Potilaskohorttimme koostui 142 uudesta pään ja kaulan alueen syöpäpotilaasta. Mediaani potilasviive, eli aika ensioireesta hoitoon hakeutumiseen, oli 35 päivää. Mediaani perusterveydenhuollosta johtuva viive, eli aika hoitoon hakeutumisesta lähetteen kirjoittamiseen erikoissairaanhoitoon, oli 20 päivää. Potilailla, joilla oli äänen käheyttä tai hengitysvaikeuksia, oli pidemmät potilasviiveet. Kaulakyhmy sai puolestaan potilaat hakeutumaan nopeasti hoitoon. Potilaan iällä, sukupuolella, asuinpaikalla, koulutuksella, tupakan ja alkoholin kulutuksella ei ollut vaikutusta viiveisiin. Tärkeimmät perusterveydenhuollon viiveeseen vaikuttavat tekijät olivat hoitoon hakeutumisen kohde ja se, sovittiinko ensikäynnillä kontrollia. Mikäli potilas hakeutui yksityiselle korva-, nenä-, ja kurkkutautien erikoislääkärille, viive oli selvästi lyhyempi. Vastaavasti potilailla, jotka ohjattiin suoraan erikoissairaanhoitoon, tai joille sovittiin kontrollikäynti, oli lyhyemmät viiveet. Johtopäätökset: Vaikka viiveet olivat lyhyitä enemmistöllä potilaista, pitkiäkin, jopa yli vuoden viiveitä, esiintyi. Tehokkain tapa lyhentää potilaasta ja perusterveydenhuollosta johtuvia viiveitä on tiedon levittäminen pään ja kaulan alueen syöpien oireista etenkin syöpäriskissä oleville potilaille ja heitä perusterveydenhuollossa hoitaville lääkäreille.

Tausta: Subaraknoidaalivuoto (SAV) on akuutisti henkeäuhkaava tila, ja sen insidenssi on noin 9/100 000 henkilövuotta. SAV:n tärkeimmät riskitekijät ovat tupakointi, korkea verenpaine, alkoholin liikakäyttö ja naissukupuoli. SAV:n sairastaneilla ja siitä selvinneillä potilailla on aikaisemman tutkimustiedon valossa pitkässä seurannassa ylikuolleisuutta. Tutkimuksen tarkoituksena oli selvittää laajemmin ylikuolleisuuden syitä. Menetelmät: Vertailimme keskenään vuosien 1996-2016 aneurysmaattisen SAV:n saaneiden potilaiden ja muun suomalaisen väestön kuolinsyitä ikä, sukupuoli, sairaanhoitopiiri ja ajanjakso vakioituna. Käytimme Tilastokeskuksen 54-luokkaista kuolemansyyluokitusta tarkentaen kuitenkin aivoverisuonitautien diagnooseja, jotta näiden syiden tarkempi analysointi olisi mahdollista. Tulokset: Kaikki aivoperäiset kuolemansyyt olivat yliedustettuina vertailuryhmään nähden: SAV:hen liittyvien ongelmien lisäksi nousivat siis esiin myös aivoinfarktit SMR (standardized mortality ratio, vakioitu kuolleisuussuhde) 2,19 (95%LV=1,57-2,97), spontaanit aivoverenvuodot SMR 4,42 (3,23-5,92) sekä näiden myöhäisvaikutukset. Aivoperäisten syiden osalta SMR pysyi merkitsevästi taustaväestöä suurempana koko seuranta-ajan. Ei-aivoperäisistä syistä ylikuolleisuutta aneurysmaattisen SAV:n sairastaneilla potilailla aiheuttivat kurkunpään, henkitorven ja keuhkon syöpä SMR 1,89 (1,43-2,44), dementia ja Alzheimerin tauti SMR 1,52 (1,16-1,96), iskeemiset sydäntaudit SMR 1,67 (1,43-1,94), muut paitsi reumaattiset ja alkoholiset sydäntaudit SMR 1,57 (1,03-2,28) sekä tapaturmat ja väkivalta SMR 1,39 (1,02-1,84). Pohdinta: Tutkimuksemme perusteella SAV on yhteydessä korkeampaan vaskulaarikuolleisuuteen. Erityisesti aivoverisuonien sairaudet ovat yliedustettuina, mutta myös muiden kardiovaskulaarisyiden rooli on selkeä. SAV:ta voitaneen siis pitää, ainakin osittain, merkkinä huonontuneesta verenkiertoelimistön tilasta, ja näiden potilaiden kohdalla tulisikin kiinnittää erityistä huomiota kardiovaskulaarisairauksien riskitekijöiden tehokkaaseen hallintaan.

Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) form a novel neurotrophic factor family due to their unique structure and different mode of action when compared to classical neurotrophic factors. CDNF and MANF have shown to protect dopaminergic neurons in Parkinson's disease animal models and therefore they are considered potential therapy agents. However, their target molecules, i.e., putative receptor(s) and signalling pathways are still unknown. 78 kDa glucose-regulated protein (GRP78) member of the heat shock protein (HSP) family is a major chaperone that under Endoplasmic Reticulum (ER) stress conditions is up-regulated and prevents protein aggregation as well as facilitates degradation of misfolded proteins. It locates mainly in the ER but location can change in different conditions. In cancer research, GRP78 has been found highly expressed on the surface of cancer cells where it regulates critical oncogenic signalling pathways. For example, it was recently shown that Par-4 (Prostate apoptosis response-4) induces apoptosis via activation of caspase-3 by binding to GRP78, expressed at the surface of cancer cells. GRP78 has been shown capable of relocating extracellularly also in neurons. Especially, it was recently shown that accumulating extracellular α-synuclein induces an increase in surface-exposed GRP78 in cultured neurons. α-synuclein interacts with cell surface GRP78 and activates a signalling cascade affecting the morphology and dynamics of actin cytoskeleton. Our group has recent, yet unpublished data suggesting that CDNF and MANF interact with GRP78 protein. The emerging role for GRP78 also in the neurodegeneration requests further investigation on its possible interaction with CDNF and MANF and on the biological meaning of that interaction. In order to test whether CDNF and MANF would interact with cell surface GRP78 and possibly compete with par-4 for the binding and in this way prevent apoptosis, we built a plasmid that would guide the expression and extracellular localization of GRP78 in the transfected cells. We transfected HEK293 cells with this plasmid and incubated them for 24h with two concentrations of par-4. We could see a trend of increasing apoptosis in PAR-4 –treated cells, but this was not enhanced in the cells expressing GRP78 extracellularly, as we had hypothesised. Thus we did not continue further with testing CDNF and MANF on this setting. Transfected HEK293 cells were incubated with alkaline phosphatase tagged MANF or CDNF (AP-MANF or AP-CDNF) and using the alkaline phosphatase substrate pNitrophenylphosphate (pNPP), we were able to study the binding between GRP78 and CDNF and MANF. Even though we could not prove the cell surface GRP78 interaction with MANF with this method, we show a high affinity binding between cell surface GRP78 and CDNF when transfected cells are incubated with different concentrations of AP-CDNF.

Background and purpose: Cerebral venous thrombosis (CVT) is a rare, but serious disease, commonly occurring in young to middle-aged women. It is not yet known whether sinus size and shape confers a risk for thrombosis and whether clot size is correlated with recanalization rates, and because there is no established method for measuring sinus or clot size, we decided to develop one. Patients and methods: CVT patients with 3-D magnetic resonance imaging done early for diagnosis and follow-up imaging around 6 months or later were recruited. Age and sexmatched (1:2) control subjects were patients with various benign headache problems who underwent 3D MRI for excluding CVT or other acute structural disease. All major sinuses were measured in size (area and diameter). All detected clots underwent similar measurement (volume, area and length). Measurements were done with Osirix-software. Results: 25 CVT patients (17 females and 8 males) and 50 control subjects were measured. Volume of the thrombus was either dissolved or reduced in all except one case. Sinus area in CVT patients in follow-up imaging was slightly smaller compared to healthy subjects (P=0.052-0.170). Thrombus volumes were bigger (P=0.009) but also dissolved more effectively in women, with no difference in sex-groups in follow-up imaging. Residual clot volume was bigger in older patients (P=0.007). Other factors did not strongly correlate with thrombus volume. Measurement reproducibility with two individual investigators was good, with best interrater correlation of over 95% in volume measures. Conclusions: This is the first attempt in establishing a volumetric measurement of cerebral sinuses and clots. The methodology may help in estimating probability of recanalization and in trials with interventions such as local thrombolysis and thrombectomy.

Gastrointestinal symptoms such as diarrhea, cramping, nausea and gastric pain occur frequently in runners during training and competitions. The mechanisms leading to the distress are not fully understood, nor the reason why some remain asymptomatic. However, hyperthermia induced by exercise elevation of core temperature and oxidative damage due to reduced gastric blood flow have been postulated to affect the intestinal epithelial cells. Both sources of stress disrupt the binding of the epithelial tight junction proteins and increase permeability of the membrane to luminal endotoxins. Endotoxins reaching the blood stream through leaky tight junctions lead to an inflammatory response mediated by cytokines. These mechanisms may underlie the gastrointestinal symptoms often experienced by endurance athletes. The aim of this study was to measure running-induced changes in intestinal permeability and inflammatory markers and investigate their association with gastrointestinal symptoms. A secondary objective was to inspect possible correlations between gastrointestinal symptom occurrence and intake of certain nutrients. A total of 17 active runners were allocated into a control group (asymptomatic) or a symptomatic group based on a symptom history questionnaire and completed a 90-minute running test. Intestinal permeability at baseline and after the run were assessed via urine recovery of orally administered Iohexol . LPS (endotoxin) and zonulin concentrations were determined from serum samples. Participants kept a food diary for three days before each measurement and filled out a symptom questionnaire after the run. No significant difference was found in intestinal permeability between symptomatic and asymptomatic runners either at rest or following strenuous exercise. However, both groups experienced a significant increase in intestinal permeability from baseline to after running. LPS concentrations were significantly higher at baseline in the symptomatic group. This may explain the higher symptom occurrence in the symptomatic group. Zonulin levels were higher in control group than symptom group after the run. Zonulin concentration was also higher in the control group after the run compared to baseline. The symptom group reported more stomach pain and stool changes after running compared to controls. Comparison of average intake of various nutrients between the two groups showed no significant differences, indicating an individual predisposition as the cause of symptoms rather than diet alone. The lack of difference in intestinal permeability between the groups combined with the difference in symptom occurrence indicates that intestinal permeability changes alone do not account for symptom development. A possible factor may be individual differences in intestinal mucosa repair ability or some underlying pathology.