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Disjunct distributions and evolutionary diversification of Australasian geometrid moths : subfamilies Epidesmiinae, Desmobathrinae and Oenochrominae (Lepidoptera)
No full textDisjunct distribution patterns have long intrigued biogeographers, sparking ongoing debates about the mechanisms driving the current distribution of biodiversity. Among the most discussed patterns are long-distance dispersal and vicariance. While these patterns have been extensively studied in plants, marine taxa, mammals, and some invertebrates, they remain less explored in groups like moths. In this study, we use the Epidesmiinae + Oenochrominae + Desmobathrinae complex—three closely related subfamilies within the Geometridae family—as a model to examine disjunct distribution patterns in Australasian moths. Epidesmiinae + Oenochrominae moths are primarily distributed within the Australasian region, with some taxa being endemic to New Zealand. In contrast, their sister group, Desmobathrinae, exhibits a trans-continental and mainly pantropical distribution. The biogeography and evolution of these subfamilies, which currently have different distribution areas, have not been analysed in an evolutionary context before. To investigate this, we inferred phylogenetic trees using a Maximum-Likelihood approach and used the topology to estimate time-calibrated trees and reconstruct ancestral biogeographical areas using a Bayesian method. Additionally, we explored the diversification rates of these lineages. Our results suggest that the ancestor of the three subfamilies most likely originated in Australasia during the Eocene (~58 Ma). Bayesian biogeographical analyses suggested dispersal events of the Desmobathrinae into the Indo-Malayan region and other areas, with an important jump to the Neotropics, while Epidesmiinae and Oenochrominae dispersed mainly within Australasia. Diversification analysis revealed no significant shifts in diversification rates, with the phylogeny showing a pattern of declining speciation rates over time. Our study exemplifies how phylogenetics in combination with biogeographical reconstruction uncovers macroevolutionary patterns in moths.Peer reviewe
Myogelin Optimointi Kolmiulotteisena Kasvualustana Pään ja Kaulan Levyepiteelikarsinooman Tutkimuksessa
No full textHead and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy with limited treatment options and poor prognosis. Dysregulated apoptosis is a hallmark of HNSCC, with members of the Bcl-2 protein family acting as central regulators. Anti-apoptotic proteins such as Bcl-2, Bcl-xL and Mcl-1 are frequently overexpressed in HNSCC tumors, promoting cell survival and therapeutic resistance. Consequently, inhibitors targeting these proteins, known as BH3 mimetics, have been developed, and their efficacy is often enhanced in combination with conventional chemotherapeutics.
To improve the translational relevance of preclinical drug testing, human tumor–derived extracellular matrices such as Myogel have been developed as 3D culture platforms. In this thesis, we aimed to enhance the properties of Myogel to further support its use in HNSCC research. The improved Myogel formulation was evaluated using spheroid invasion assays and high-throughput combination screening (HTCS). The study investigated whether the optimized Myogel maintains its functionality and enables identification of effective synergistic drug combinations.
The performance of the improved Myogel was assessed in HTCS of five HNSCC cell lines and in a spheroid invasion assay using the UT-SCC-42A cell line. Cell viability, morphology, zero interaction potency (ZIP) scores and invasion parameters (length and area) were analyzed. The results demonstrated that the optimized Myogel supported cell growth, invasion, and synergy analysis across different conditions. Cells maintained normal morphology and culture surfaces remained comparable to controls. Three novel drug combinations, A1331852-MIK665, A1331852-Docetaxel and MIK665-Navitoclax, showed consistent synergistic effects across multiple HNSCC cell lines, while Cisplatin-based combinations exhibited limited synergy.
In conclusion, the improved Myogel formulation retains key functional properties and provides a reliable and practical platform for preclinical assays. Furthermore, the identification of potent drug synergies highlights the potential of this system to advance the discovery of effective therapeutic strategies for HNSCC.Pään ja kaulan levyepiteelikarsinooma (HNSCC) on edelleen vaikeasti hoidettava syöpä, jonka ennuste on usein huono ja hoitovaihtoehdot rajalliset. Apoptoosin eli ohjelmoidun solukuoleman häiriintyminen on HNSCC:lle tyypillistä. Bcl-2-proteiiniperheen jäsenet säätelevät tätä prosessia, ja monet niistä, kuten Bcl-2, Bcl-xL ja Mcl-1 – ovat usein liiallisesti aktiivisia HNSCC-kasvaimissa. Tämä lisää syöpäsolujen elinkelpoisuutta ja hoitoresistenssiä. Näiden proteiinien estämiseksi on kehitetty niin kutsuttuja BH3-mimeettejä, joiden teho kasvaa usein, kun niitä käytetään yhdessä perinteisten solunsalpaajien kanssa.
Ennusteiden parantamiseksi tarvitaan kuitenkin realistisempia koealustoja, jotka jäljittelevät ihmisen kudoksia. Tätä varten on kehitetty ihmisperäiseen kasvainmatriisiin perustuva Myogeeli, jota käytetään kolmiulotteisena (3D) soluviljelyalustana. Tämän tutkielman tavoitteena oli parantaa Myogelin ominaisuuksia, jotta se soveltuisi entistä paremmin HNSCC-tutkimukseen. Parannettua Myogelia arvioitiin invaasiokokeissa ja laajamittaisessa lääkeyhdistelmäseulonnassa (HTCS, high-throughput combination screening). Tutkimuksessa tarkasteltiin, säilyttääkö optimoitu Myogeeli toimintakykynsä sekä soveltuvuutensa lääkeyhdistelmä tutkimuksessa.
Optimoitua Myogeeliä testattiin viidellä HNSCC-solulinjalla HTCS-kokeissa sekä UT-SCC-42A-solulinjalla invaasiokokeessa. Analysoitavia muuttujia olivat solujen elinkyky, morfologia, ZIP (zero interaction potency) -arvot ja invaasioparametrit (pituus ja pinta-ala). Tulokset osoittivat, että optimoitu Myogeeli tuki solujen kasvua, invaasiota ja lääkeyhdistelmien synergia-analyysiä eri olosuhteissa. Solut säilyttivät normaalin muotonsa, ja viljelypinnat vastasivat laadultaan kontrolleja. Erityisesti kolme lääkeyhdistelmää, A1331852–MIK665, A1331852–Docetaxel ja MIK665–Navitoclax, osoittivat johdonmukaista synergiaa useissa HNSCC-solulinjoissa, kun taas sisplatiinipohjaiset yhdistelmät olivat vähemmän tehokkaita.
Yhteenvetona optimoitu Myogel säilytti keskeiset toiminnalliset ominaisuutensa ja tarjosi luotettavan, käytännöllisen alustan prekliinisiin kokeisiin. Lisäksi tutkimuksessa tunnistetut lääkesynergiat osoittavat, että lääkeyhdistelmiä voidaan hyödyntää uusien hoitostrategioiden kehittämisessä HNSCC:n hoitoon
Mechanism of biomimetic virus-like nanoparticles in triggering immune response elucidated by proteomics
No full textThe use of biomimetic nanoparticles (NPs) with virus-like morphology have recently attracted research interest as novel delivery platforms and immune adjuvants. However, the exact interactions between the nanoparticles and immune cells as well as the mechanism involved are not known in detail. This motivated us to develop virus-like mesoporous silica nanoparticles (VLP) to characterize their physicochemical properties, and to determine the immune pathways induced by the particles in mouse macrophages. The results showed inclusion of spikes mimicking viral structures on the surface increased cellular uptake and enhanced immune response as compared to spherical NPs. Proteomic analysis revealed that the pathways of RIG-I-like receptor signaling, MAPK, NF-κB, and Toll-like receptor signaling were involved in regulating the immune response when macrophages interacted with VLP. When the spikes increased from 5 to 30 nm, the expression of immune-related proteins including TRAF6 and PIAS4 proteins was upregulated. This study revealed the interaction pathways and key proteins in the activation of immune response with VLP, which may provide insights to develop novel immunotherapy for enhanced efficacy.Peer reviewe
High-resolution model for assessing the impact of climate change on the outage risk caused by crown snow load in distribution networks
No full textThis study presents a novel high-resolution model for estimating the effect of climate change in the outage risk caused by crown snow load in distribution networks. The model is based on an aerial inspection dataset collected during a large-scale outage event which occurred during December 2017–January 2018 in the network area of Kajave Oy, Finland. The proposed model is trained using crown snow load risk observation data as the response variable, and forest characteristics along with modeled long-term crown snow load levels as predictor variables. The trained model was used to estimate the scale and location of outages in the study area for different climate change scenarios for the period 2020–2050. The results showed that the model was capable of predicting outages accurately in a 100x40m overhead line section level. The development of the risk level for crown load damage was found to be highly dependent on the climate change pathway, with a 34% increased risk level in the moderate RCP4.5 scenario and up to 68% increase in the more extreme RCP8.5 pathway. The findings of this study provide new insights in the effects of climate change for distribution system operators, helping them adapt their network asset management processes, especially in terms of the overhead line network resiliency strategy and development of vegetation management practices in areas which are prone to crown snow loads accumulation
Association of Ocular Comorbidities on Long-term Patient-Reported Outcome Measures After Multifocal Intraocular Lens Implantation
No full textObjective: To evaluate the association of ocular comorbidities on long-term patient-reported outcome measures (PROMs) in patients bilaterally implanted with diffractive multifocal intraocular lenses (MFIOLs). Design: Retrospective clinical cohort study. Subjects: A total of 260 patients who underwent bilateral implantation of MFIOLs with postoperative emmetropia and follow-up exceeding 3 years. Methods: Uncorrected visual acuities at near, intermediate and distance, contrast sensitivities, optical quality, spectacle-independent Visual Function Index (VF-14) questionnaire scores and dysphotopsia (graded 0-100 for glare, halos, and starburst) were measured. Ocular comorbidities included dry eye disease, prior corneal refractive surgery, vitreous opacities, macular disease, nonproliferative diabetic retinopathy, and glaucoma. Main Outcome Measures: VF-14 scores at 3 years. Results: Eyes with comorbidities showed significantly worse uncorrected visual acuities at all distances (all P < .001), lower Strehl ratio (0.034±0.023 vs 0.042±0.027, P < .001), and reduced contrast sensitivity under both photopic (1.33±0.21 vs 1.40±0.18 area under the log contrast sensitivity function [AULCSF], P = .001) and mesopic conditions (1.01±0.20 vs 1.07±0.17 AULCSF, P < .001) compared with eyes without comorbidities. VF-14 scores were significantly lower in eyes with comorbidities (87.1±13.8 vs 95.6±5.1; P < .001), with more glare reported (13.6±25.0 vs 8.6±19.7; P = .015). On multivariable analysis with age, sex, concomitant ocular comorbidities, and MFIOL type adjustment, dry eye disease, prior refractive surgery, vitreous opacities, and macular disease were independently associated with lower VF-14 scores (all P < .001). Dry eye disease (B = 18.0, 95% CI 8.4-27.6, P < .001) and vitreous opacities (B = 21.1, 95% CI 0.0-42.2, P = .050) were associated with higher dysphotopsia overall scores. Increasing comorbidity burden, shorter tear film break-up time (r = 0.207, P = .005), and bilateral macular disease (P < .001) were further associated with worse VF-14 scores. Conclusions: Ocular comorbidities, particularly dry eye disease and vitreous opacities, which cause fluctuating visual disturbances, were associated with greater impairment in PROMs following diffractive MFIOL implantation.Peer reviewe
Vaginal use of estradiol is associated with a reduced risk of rectal cancer in postmenopausal women : A Finnish nationwide case-control study
No full textObjective: We assessed the impact of vaginal estradiol on the risk of rectal cancer. Study design: We identified in this nationwide case-control study primary rectal cancer cases with five age-matched control cases in 1994–2019 from our dataset of 1.1 million Finnish postmenopausal women. We excluded users of systemic hormone therapy. Then we traced users of vaginal estradiol (10–25 μg twice a week) from the reimbursement register in 1994–2013, a period in which users could be accurately traced in the database (which was not the case for 2014–2019). Main outcome measures: Odds ratios with 95 % confidence intervals were calculated for rectal cancer risk with adjusted logistic regression models separately for vaginal estradiol users in 1994–2013 (1640 cases, 7889 controls) and for the whole study period of 1994–2019 (2853 cases, 13865 controls). Results: During follow-up, 494 rectal cancer patients (17 %) and 2826 controls (20 %) used vaginal estradiol (p < 0.001). Users were diagnosed with rectal cancer on average nine years later than non-users (73.9 vs 65.1 years, p < 0.001). Use for ≥3 years was associated with a reduced risk of rectal cancer (OR 0.79, 95 % CI 0.63–0.97) in the 1994–2013 cohort. In the extended 1994–2019 follow-up, risk reductions were similar (0.79, 0.68–0.92), appeared already with <3 years' use (0.85, 0.74–0.97), and persisted for up to 5 years after cessation of vaginal estradiol (0.80, 0.71–0.91). Conclusions: Vaginal estradiol use may be associated with a reduced risk of rectal cancer - perhaps due to estradiol infiltration into the rectal mucosa. This possible protecting effect could be an important additional health benefit of vaginal estradiol.Peer reviewe
Tracking canopy conductance and transpiration of CAM-plants Agave sisalana with carbonyl sulfide fluxes
No full textCrassulacean acid metabolism (CAM) helps plants in arid regions to reduce water loss by opening their stomata and taking up carbon dioxide (CO2) during nighttime. While gas exchange in CAM plants has been mainly studied under controlled laboratory conditions, only a few ecosystem scale studies exist. Moreover, carbonyl sulfide (COS) has been used as a tracer for stomatal conductance, transpiration and photosynthesis in C3 and C4 plants, but no studies on CAM ecosystems have yet been published. Here we present the first ecosystem scale measurements of COS fluxes over Agave sisalana (CAM plant), commercially cultivated for its fiber. The measurements were made during the wet season in Kenya. The ecosystem was a consistent sink of COS, with higher uptake observed during nighttime (−11.5 pmol m−2 s−1) than during daytime (-5.6 pmol m−2 s−1). The magnitude of COS fluxes was comparable to non-growing season daytime fluxes reported for C3 and C4 plant dominated ecosystems. The soil was a small COS source (0.3 pmol m−2 s−1), with highest emissions under high radiation and temperature conditions. Using random forest modeling, we found that vapor pressure deficit, air temperature and soil water content were the most important drivers of nighttime ecosystem COS exchange (variable importance 0.25, 0.23 and 0.20, respectively), indicating the importance of stomatal limitation for COS fluxes. During daytime, air temperature, photosynthetically active radiation and soil temperature were the most important drivers (variable importances 0.19, 0.18 and 0.18, respectively). COS fluxes were further used to track canopy stomatal conductance and transpiration and compared to another transpiration estimate from the conditional eddy covariance method, which is based on raw water vapor and vertical wind data from eddy covariance. Conductance values ranged from 0.03 ± 0.06 mol m−2 s−1 during daytime to 0.06 ± 0.02 mol m−2 s−1 during nighttime. Transpiration was thus higher during nighttime than during daytime, reflecting the CAM gas exchange strategy.Peer reviewe
Auringonsäteilyn ennustaminen korkeilla leveysasteilla
No full textSolar energy production is increasing globally as the world transitions to renewable energy. This trend is also present in the Nordic countries, where production has risen significantly in recent years.
Solar energy is produced with PV panels, which convert incident sunlight, or solar irradiance, into electricity. The power output depends primarily on the amount of irradiance received. This causes fluctuations in the electricity production, as solar irradiance is highly affected by cloudiness; a passing cloud can cause the irradiance, and therefore the electricity production, to drop sharply.
To alleviate the problems caused by the fluctuating energy production, solar energy forecasts are used to plan and optimise production and use. Forecasting can target both the short term of minutes to hours ahead, as well as the longer term of days, predicting either PV power output directly, or irradiance. Irradiance may then be separately converted into power output using panel configurations. Various methods and data sources are used for forecasting, depending on the desired forecast horizon and output frequency. Ground-based imagers and sky cameras that track cloud movement are suitable for very short forecasts, whereas satellite-based methods perform well for forecasts of several hours and provide excellent spatial coverage. NWP methods, on the other hand, are recognised to be superior for the next day forecasts, when forecasting requires predicting the actual physical development of the atmosphere. Various ML methods are also used, with NWP forecasts often used as a data source. However, there are no methods developed directly or validated specifically for the high latitudes, where there are specific local challenges with forecasting irradiance.
The aim of this thesis is to produce irradiance forecasts for the high latitudes by developing and validating a satellite-based forecasting system for the short term, and by adopting NWP ensemble irradiance forecasts from operational NWP models for lead times of up to two days. The forecasts are compared and validated against in situ measurements in Finland and Sweden to assess their relative accuracy and behaviour. Additionally, NWP forecasts are evaluated as an input to PV power forecasting, to assess their suitability and performance.
The developed satellite-based method performs well for up to 6 hours, with highest accuracy for the first 2-3 hours. The NWP model performs well overall from 5 hours onwards, with particular efficiency for next day forecasts. The results show that both satellite-based and operational NWP solar irradiance forecasts work well in the high latitudes, and highlight the importance of selecting a forecasting model based on the required temporal resolution and lead time.Aurinkoenergian tuotanto kasvaa maailmanlaajuisesti osana siirtymistä uusiutuvaan energiaan. Sama kehitys näkyy myös Pohjoismaissa, joissa tuotanto on kasvanut merkittävästi viime vuosina.
Aurinkoenergiaa tuotetaan aurinkopaneeleilla, jotka muuttavat auringonsäteilyn sähköksi. Tuotanto riippuu ensisijaisesti säteilyn määrästä, mikä aiheuttaa vaihtelua tuotannossa. Vaihtelusta aiheutuvien haasteiden hallitsemiseksi energian tuotannon ja kulutuksen suunnittelussa ja optimoinnissa käytetään aurinkoennusteita. Ennusteita laaditaan sekä lyhyille että pidemmille aikaväleille, ja ennustaa voidaan joko suoraan aurinkosähkötuotantoa, tai säteilyä, joka muunnetaan tuotannoksi paneelien ominaisuuksien perusteella.
Käytetyt ennustemenetelmät ja tietolähteet riippuvat ennusteen pituudesta ja tarkkuudesta. Lyhyen aikavälin ennusteisiin soveltuu hyvin pilvien liikettä seuraavat paikalliset kamerat, kun taas sääsatelliittihavaintohin perustuvat menetelmät toimivat useiden tuntien mittaisissa ennusteissa ja tarjoavat lisäksi laajan alueellisen kattavuuden. Numeeriset säämallit puolestaan osaavat ennustaa ilmakehän säätilan kehitystä, ja ovat tarkimpia seuraavan päivän ennusteissa. Koneoppimismenetelmiä hyödynnetään myös, ja säämalliennusteita käytetään niissä usein koulutus- ja testiaineistona. Korkeille leveysasteille ei kuitenkaan ole kehitetty omia menetelmiä, huolimatta alueen erityisistä paikallisista haasteista.
Tämän väitöstyön tavoitteena on tuottaa säteilyennusteita korkeille leveysasteille kehittämällä sääsatelliittikuviin pohjautuva lyhyen aikavälin ennustejärjestelmä sekä hyödyntämällä säämallien parviennusteita kahden vuorokauden päähän. Ennusteiden tarkkuutta arvioidaan vertaamalla niitä Suomessa ja Ruotsissa tehtyihin auringonsäteilymittauksiin. Lisäksi tarkastellaan säämalliennusteiden soveltuvuutta aurinkosähkötuotannon ennusteiden lähtötietoina.
Tulokset osoittavat, että kehitetty sääsatelliittipohjainen menetelmä tuottaa luotettavia ennusteita kuuden tunnin päähän, suurimmalla tarkkuudella ensimmäisten 2–3 tunnin aikana. Säämalliennusteet puolestaan toimivat hyvin viidestä tunnista eteenpäin, säilyttäen tarkkuuden varsin hyvänä myös seuraavan päivän ennusteissa. Molemmat menetelmät toimivat hyvin korkeilla leveysasteilla, ja tulokset korostavat ennustemallin valinnan merkitystä halutun ennustepituuden ja aika-askeleen perusteella
Potilaasta johdettujen indusoitujen pluripotenttien kantasolujen käyttö liikunnasta aiheutuvan hyperinsulinismin (EIHI) tautimallinnuksessa
No full textLiikunnasta aiheutuva hyperinsulinismi (EIHI) on sairaus, joka ilmenee epänormaalina insuliinin erityksenä rasituksen aikana. Monokarboksylaattien kuljettajaproteiini (MCT1), jota koodaa SLC16A1-geeni, on laajalti ilmentynyt lähes kaikissa kudoksissa paitsi haiman saarekesoluissa. Henkilöillä, jotka sairastavat EIHI:ä, SLC16A1 säätelyalueen deleetion uskotaan johtavan MCT1:n virheelliseen ilmenemiseen beta soluissa, mikä mahdollistaa kohonneiden laktaatti- ja pyruvaattipitoisuuksien virtauksen solukalvon läpi rasituksen aikana. Nämä substraatit käynnistävät Krebsin kierron, mikä lisää insuliinin eritystä. Ylimääräinen insuliinin eritys aiheuttaa alhaisen verensokeritason rasituksen aikana, mikä johtaa heikkouteen, pyörtymiseen ja sekavuuteen. Koska EIHI sairauden mekanismia ei ole aikaisemmin mallinnettu, tämän Pro-gradu tutkielman tavoitteena oli mallintaa taudin toimintamekanismeja sairaasta henkilöstä johdettujen indusoitujen pluripotenttien (iPS) kantasolujen avulla. Työssä uudelleenohjelmoitiin EIHI:ä sairastavan henkilön fibroblasteja iPS-soluiksi käynnistäen pluritpotenssia säätelevät geeniverkostot uudelleen. Tämän jälkeen sairaan henkilön sekä terveen henkilön (kontrolli) iPS solut erilaistettiin toiminnallisiksi haiman saarekesoluiksi in vitro ympäristössä rinnakkain. Seuraavassa vaiheessa soluja siirrettiin immuunipuutteisiin hiiriin, jolloin solut kypsyivät edelleen in vivo ympäristössä. Erilaisia laadunvalvontamittauksia (virtaussytometria) tehtiin erilaistamisprosessin aikana. Lisäksi tutkittiin SLC16A1-geenin ilmentymistä erilaistamisen eri vaiheissa. Lopuksi haiman betasoluiksi erilaistettujen solujen ominaisuuksia tutkittiin muun muassa mittaamalla insuliinin eritystä, sekä glukoosi-että pyruvaattistimulaation jälkeen, sekä MCT1-proteiinin immunohistokemiallisella analyysillä. Vastoin oletuksia, tutkielman tulokset osoittivat, että SCL16A1 promoottorialueen deleetiosta huolimatta sairaan henkilön beta solut erittivät insuliinia samalla tavalla kuin terveen henkilön kontrollisolut. SLC16A1-geenin ilmentyminen myös aleni vastoin odotuksia samalla tavalla kuin kontrollisoluilla. MCT1-proteiinin immunohistokemialliset värjäykset hiiren munuaiskapselin alle siirretyistä kantasolusaarekkeista kuitenkin osoitti selkeän eron; deleetion sisältävät solut ilmensivät MCT1:stä selkeästi enemmän kuin kontrollisolut. Yhteenvetona voidaan todeta, että sairauden oletetut patologiset piirteet eivät olleet selkeästi havaittavissa in vitro -mallissa. Kuitenkin munuaiskapselin alle tehtävän siirron jälkeen, in vivo -mallissa, mutanttisoluissa havaittiin MCT1:n ilmentymisen lisääntyneen huomattavasti. Tämä löydös viittaa siihen, että MCT1-ilmentymistä säätelee erillinen mekanismi, johon vaikuttaa ympäristöolosuhteet. Tulokset luovat hyvän pohjan tulevaisuudessa näitä mekanismeja tutkiville tutkimuksille.Exercise-induced hyperinsulinism (EIHI) is a pathological condition characterized by aberrant insulin secretion triggered by physical exercise or pyruvate exposure. The monocarboxylate transporter protein (MCT1), encoded by SLC16A1, is ubiquitously expressed in almost all cell types except pancreatic islet cells. In patients with EIHI, mutations in the regulatory regions of the SLC16A1 gene are thought to lead to the unwanted expression of MCT1 on the beta cell membrane, allowing the influx of elevated lactate and pyruvate blood levels during exercise. These substrates feed into the Krebs cycle, increasing insulin release. This excessive insulin secretion can lead to hypoglycemia during exercise, causing weakness, syncope, and confusion.
Since EIHI has never been studied using a human stem cell-derived islets, this thesis aims to establish a robust model in which to investigate the disease mechanism in detail. To achieve this, we reprogrammed EIHI patients’ fibroblasts into a stable pluripotent state and further differentiated them into functional pancreatic stem cell-derived islets (SC-islets) in vitro. These SC-islets were then matured further in vivo (in immunocompromised mice) and compared to healthy SC-islet controls. Rigorous quality control measures were implemented throughout the differentiation process to ensure its efficacy and the expression regulation of SLC16A1 was studied during SC-islet development. Extensive phenotypic characterization was conducted using immunohistochemistry, quantitative gene expression level analysis, and insulin secretion assays with glucose and pyruvate.
Contrary to expectations, the results of this study demonstrated that despite the SLC16A1 promoter mutation, the expression of SLC16A1 was downregulated similarly to the control cell line during development in vitro, resulting in similar pyruvate-stimulated insulin secretion to the control cells. Interestingly, immunohistochemical analysis of in vivo implanted SC-islets showed a clear phenotype with an increased number of MCT1-positive cells only in the mutant grafts, some of which were endocrine cells. In conclusion, the phenotypic manifestations of EIHI were not visible in the setting of in vitro modeling, which was attributed to the similar expression levels of MCT1 in both the mutant and control cell lines. However, following in vivo implantation, there was a noticeable increase in MCT1 expression exclusively in the mutant cells. This finding suggests a distinct regulatory mechanism of MCT1 expression, which might be impacted by the in vivo surroundings and the maturation state of human islets
Factors Promoting and Hindering Medication Adherence in Cancer Treatment: A Patient Perspective
No full textSyövän hoitojen kehittyessä suun kautta annosteltavat syöpälääkkeet ovat yleistyneet ensisijaisena hoitomuotona, tarjoten etuja hoitotulosten parantamisessa sekä terveydenhuollon kuormituksen vähentämisessä. Lääkkeiden itsenäinen annostelu edellyttää potilaalta pitkäjänteistä lääkehoitoon sitoutumista. Vaikka syöpäpotilaiden lääkehoitoon sitoutuminen mielletään yleisesti vahvaksi, tutkimukset osoittavat sitoutumattomuuden olevan suhteellisen yleistä ja tasoltaan vaihtelevaa. Lääkehoitoon sitoutumattomuus on haaste, joka heikentää hoitovastetta, lisää haittavaikutusten riskejä ja kasvattaa terveydenhuollon kokonaiskustannuksia. Tämän tutkimuksen tavoitteena oli tutkia potilasnäkökulmasta syövän lääkehoitoon sitoutumista edistäviä ja heikentäviä tekijöitä.
Tutkimus toteutettiin yhteistyössä Helsingin yliopiston, HUS Apteekin ja Suomen Syöpäpotilaat ry:n kanssa. Aineistona käytettiin Suomen Syöpäpotilaat ry:n keräämää anonyymiä verkkokyselyaineistoa syöpäpotilaiden lääkehoitoon sitoutumisesta koskien syövän lääkkeellistä hoitoa. Tutkimusaineisto koostui 458 vastaajasta, jotka edustivat 10 eri syöpäluokkaa ja yhteensä 502 todettua syöpätapausta. Kyselyaineiston avoimista vastauksista pyrittiin tunnistamaan syöpäpotilaiden lääkehoitoon sitoutumiseen edistävästi ja heikentävästi vaikuttavia tekijöitä. Tutkimus toteutettiin laadullisena abduktiivisena sisällönanalyysina hyödyntäen Atlas.ti -ohjelmistoa sekä Microsoft Exceliä.
Aineiston koodausprosessissa muodostettiin 133 alatason koodia, joista 62 % liittyi lääkehoitoon sitoutumista edistäviin ja 38 % heikentäviin tekijöihin. Näistä muodostettiin 22 keskitason kategoriaa edistäville ja 15 heikentäville tekijöille, joista johdettiin 6 ylätason kategoriaa edistäville ja 5 heikentäville tekijöille. Analyysin pääluokat olivat lääkehoitoon sitoutumista edistävät ja heikentävät tekijät.
Tämän tutkimuksen mukaan lääkehoitoon sitoutumista edistivät erityisesti perheen ja läheisten tarjoama tuki, potilaan psykologiset voimavarat, riittävä ja laadukas tiedon saanti ja lääkehoidon merkityksen ymmärtäminen sekä luottamuksellinen yhteistyösuhde hoitotahoon. Haittavaikutukset olivat merkittävin lääkehoitoon sitoutumista heikentävä tekijä. Lisäksi informaation ja tiedonsaannin puutteet, epäselvyydet tiedonvälityksessä sekä lääkehoidon merkityksen puutteellinen ymmärtäminen heikensivät potilaiden motivaatiota sitoutua hoitoon.
Tutkimuksen tulokset osoittavat, että syöpäpotilaiden lääkehoitoon sitoutumiseen vaikuttavat tekijät ovat moniulotteisia. Potilaslähtöisyys, yksilöllisten tarpeiden huomioiminen, potilaan kiireetön kohtaaminen, tiedon saatavuuden ja laadun parantaminen sekä tehokas haittavaikutusten hallinta muodostavat kokonaisvaltaisen lähestymistavan, joka voisi huomattavasti parantaa syöpäpotilaiden sitoutumista lääkehoitoon.As cancer treatments have advanced, orally administered cancer medications have become increasingly prevalent as primary treatment options, offering advantages in improving treatment outcomes and reducing the burden on healthcare systems. Self-administration of these medications requires patients to commit to long-term adherence. While cancer patients are generally perceived as being strongly adherent to their treatment, studies show that nonadherence is relatively common and varies significantly. Nonadherence presents a challenge that undermines treatment effectiveness, increases the risk of adverse effects, and raises overall healthcare costs. This study aimed to examine, from the patient’s perspective, the factors that promote or hinder adherence to cancer therapy.
The research was conducted in collaboration with the University of Helsinki, HUS Pharmacy, and the Finnish Cancer Patients Association. The study utilized anonymous survey data collected by the Finnish Cancer Patients Association concerning adherence to cancer medications. The dataset comprises 458 respondents representing 10 different cancer categories and a total of 502 diagnosed cases. Open-ended responses in the survey were analyzed to identify factors influencing adherence both positively and negatively. The study employed qualitative abductive content analysis, utilizing Atlas.ti and Microsoft Excel software.
Through the coding process, 133 lower-level codes were created, of which 62 % pertained to adherence-promoting factors and 38 % to hindering factors. From these lower-level codes, 22 mid-level categories were created for promoting factors and 15 for hindering factors, which were further grouped into six higher-level categories for promoting factors and five for hindering factors. The main categories of analysis were factors promoting and hindering adherence to cancer therapy.
This study identified key factors that support medication adherence, including social support from family and close relations, the patient's psychological resilience, access to sufficient and high-quality information, and a clear understanding of the therapeutic importance of medication. A trusting and collaborative relationship with healthcare providers further enhanced adherence. Conversely, side effects emerged as the most significant barrier to medication adherence. Additionally, inadequate access to information, unclear communication, and a limited understanding of the medication's purpose diminished patients' motivation to adhere to their prescribed treatment plans.
The findings of this study indicate that the factors influencing adherence to cancer therapy are multifaceted. A comprehensive approach that integrates patient-centered care, recognition of individual needs, unhurried patient interactions, enhanced access to and quality of information, and effective management of side effects could significantly improve adherence to cancer therapy