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Objectives: Bisphenol A (BPA) is commonly used plasticizer that has endocrine disrupting properties. Fetal exposure to BPA has been associated with offspring behavioural problems. These associations may be mediated through BPA-induced alterations in the offspring DNA methylation (DNAm). This study examined whether fetal BPA exposure associates with behavioural problems and whether DNAm biomarker score for early pregnancy BPA exposure is linked with behavioural problems in the offspring. Methods: Participants were 442 mother-child pairs of the Finnish PREDO-cohort. I measured BPA from the early pregnancy urine samples and assayed DNAm in the cord blood with Illumina 450k or EPIC array. Mothers reported behavioural problems of their offspring with the Child Behaviour Checklist/1.5-5 (CBCL/1.5-5) at the mean child age of 3.8 years (SD = 1.0 years). I used LASSO regression to create a DNAm score for early pregnancy BPA exposure and tested the associations between BPA exposure, the DNAm score, and CBCL/1.5-5 scores with linear and logistic regressions. Results: After adjustments, early pregnancy BPA exposure was associated with higher risk for clinically meaningful internalizing (p = .02) and externalizing (p = .04) behavioural problems in the offspring. The DNAm score included eight CpG sites, explained 4.8% of the BPA variation, and was borderline significantly associated with a risk for clinically meaningful internalizing (p = .05) and externalizing behavioural problems (p = .06). Conclusions: Early pregnancy BPA exposure associated and DNAm biomarker for BPA exposure borderline associated with offspring behavioural problems. DNAm biomarker score for fetal BPA exposure showed promise and should be studied further in subsequent studies.

Aortic stenosis is the most important type of valvular heart disease among elderly patients, that often lead to valve replacement interventions. As the age structure shifts towards older age and life expectancy continues to rise, the prevalence of aortic stenosis is presumed to rise, resulting in more patients and additional expenses. Echocardiography is the most important tool for assessing aortic stenosis among patients. An experienced clinician can determine the severity of the disease with echocardiography alone, although the complete picture of a patient’s health must be evaluated during examination. The choice of intervention and timing thereof should be done by a heart team consisting consists of cardiologists, cardiac surgeons, radiologists, interventional radiologists and anaesthesiologists. Intervention is done by replacing the stenotic aortic valve with a functional synthetic valve either by surgical aortic valve replacement (SAVR) or by transcatheter aortic valve implant (TAVI). Echocardiography is used for evaluating prognosis and selecting type of care for each patient, based on the ECHO findings. This overview presents the use of transthoracic echocardiography as a tool for assessment of disease severity among patients with aortic stenosis, as well as advantages and limitations. The overview incudes a study of the clinical outcome of 30 patients with aortic stenosis treated with surgical aortic valve replacement and transcatheter aortic valve implant within the AS-AMYL study at the Helsinki University Hospital.

Synnytyksen käynnistyksen yleisimmät syyt Suomessa ovat yliaikaisuus ja lapsivedenmeno, jotka ovat miltei tasavertaiset yleisyydessään. Vuonna 2017 Suomessa synnytyksistä käynnistettiin 28,9 % ja tällöin lapsivedenmeno oli toiseksi yleisin syy käynnistykseen HYKS:ssä. HYKS:ssä synnytys käynnistetään 12 tunnin kuluessa lapsivedenmenosta GBS-positiivisilla synnyttäjillä ja 24 tunnin kuluttua GBS-negatiivisilla. Tutkimuksen tavoitteena oli selvittää lapsivedenmenon vaikutusta synnytyksen kulkuun ja lopputuloksiin niillä synnyttäjillä, joiden synnytys on käynnistetty lapsivedenmenon takia. Tutkimus on retrospektiivinen ja aineisto koostuu HYKS synnytyssairaaloiden synnyttäjistä vuodelta 2017. Synnyttäjien esitiedot, tiedot synnytysten käynnistyksestä ja etenemisestä sekä synnytysten päätetapahtumat ja syntyneiden lasten tiedot on kerätty sairaskertomuksista Obstetrix- ja Miranda-potilastietojärjestelmistä. Tiedot on analysoitu SPSS-taulukkolaskentaohjelman avulla. Tutkimuksessa todettiin ensisynnyttäjyyden, synnyttäjän lyhyen pituuden, ylipainon, aiemman keisarileikkauksen ja epäkypsän kohdunkaulan käynnistyksen alussa liittyvän lisääntyneeseen keisarileikkauksen riskiin, kuten aiemmissakin tutkimuksissa. Infektioita todettiin enemmän ensisynnyttäjillä ja keisarileikkaukseen päätyneillä. Synnytyksissä, jotka olivat keskimääräiseltä kestoltaan pidempiä lapsivedenmenosta ja/tai synnytyksen käynnistyksen alusta syntymään, ilmeni enemmän synnytyksen aikaisia tai jälkeisiä infektioita. GBS-positiivisille synnyttäjille annetaan HYKS:n hoitokäytännön mukaisesti ennaltaehkäisevä antibioottihoito lapsiveden mentyä ja heidän lapsillaan oli vähemmän infektioita kuin GBS-negatiivisten synnyttäjien lapsilla. Lapsivedenmenon ajankohdalla ei ollut vaikutusta lasten infektioiden esiintymiseen. Lapsivedenmenon vuoksi käynnistetyissä synnytyksissä äitien ja lasten infektioiden esiintyvyys ei poikennut muista HYKS:ssä vuonna 2017 käynnistetyistä synnytyksistä.

The role of decompressive craniectomy as a cure in traumatic brain injuries has been widely been discussed. Therefore our aim was to assess the independent effect of decompressive craniectomy the outcome and mortality of the patient. We conducted an open-cohort retrospective study on adult blunt TBI patients. Patients were divided into three groups; conservative treatment, acute craniotomy and mass lesion evacuation (craniotomy) and decompressive craniectomy. Outcome was assessed using Glasgow Outcome Scale and overall mortality six months after the operation. The adjusted multivariate analysis did not show an independent association between decompressive craniectomy and mortality. Decompressive craniectomy prooved to be an independent risk factor for poor neurological outcome with an OR of 3.06. In conclusion, operating TBI patients with decompressive craniectomy was found to be a life-saving intervention for patients who in other cases were destined to die. For stronger evidence this subject needs more research of a prospective type.

Tutkimuksen tavoite: Hydroklooritiatsidi on usein käytetty verenpainelääke, jonka yleinen haittavaikutus on veren uraattipitoisuuden nousu. Veren korkea uraattipitoisuus lisää riskiä sairastua sydän- ja veri- suonitauteihin. Halusimme tutkia hydroklooritiatsidin aiheuttaman plasman uraattipitoisuu- den nousun geneettistä taustaa, jota on vielä vasta vähän tutkittu. Potilaat ja menetelmät: GENRES on satunnaistettu, kaksoissokkoutettu ja lumekontrolloitu tutkimus, jossa 35-60- vuotiaille verenpainetautia sairastaville suomalaisille miehille annettiin neljää eri verenpai- nelääkettä neljän viikon jaksoissa. Jokaista verenpainelääkejaksoa edelsi 4 viikon lumelääke- hoitojakso. LIFE on satunnaistettu ja kaksoissokkoutettu tutkimus, jossa verrattiin losartaanin ja atenololin tehoa verenpainetaudin hoidossa. Ellei losartaanilla tai atenololilla saavutettu riittävän hyvää verenpainevastetta, rinnalle liitettiin hydroklooritiatsidi. Tutkimme 214 suo- malaisella miehellä GENRES-aineistossa genetiikan vaikutusta hydroklooritiatsidin aiheut- tamaan plasman uraattipitoisuuden nousuun koko perimän kattavalla assosiaatioanalyysillä. Teimme toistoanalyysin GENRES-tutkimuksen parhaille tuloksille käyttäen 465 suomalaisen LIFE-tutkimuspotilaan näytteitä. Valitsimme toistoanalyysiin SNP:t, joiden P-arvo oli alle 5 x 10-5 GENRES:ssä. Tulokset: GENRES-tutkimuksessa keskimääräinen plasman uraattipitoisuuden nousu hydroklooritiatsi- dihoidon aikana oli 50 ± 39 μmol/l. GENRES-tutkimuksessa löysimme 31 lokusta, jotka liit- tyivät hydroklooritiatsidin aiheuttamaan plasman uraattipitoisuuden nousuun P-arvolla < 5 x 10-5. rs1002976 lähellä VEGFC-geeniä assosioitui hydroklooritiatsidin aiheuttamaan muutok- seen molemmissa aineistoissa merkitsevästi. rs950569 lähellä BRINP3-geeniä replikoitui LI- FE:ssa osittain merkitsevästi. Aikaisemmin hydroklooritiatsidin aiheuttamaan uraattipitoi- suuden nousuun liitettyjen SNP:iden ja geenien analyysi tuotti lisää tietoa PADI4- ja ABCC4- geenien vaikutuksista. Yhteenveto: Olemme löytäneet muutaman uuden SNP:n ja löytäneet lisää tietoa jo tunnettujen geenivaih- teluiden vaikutuksesta hydroklooritiatsidin aiheuttamaan seerumin uraattipitoisuuden nou- suun.

As life expectancy increases, the effectiveness of cervical cancer screening programs needs to be reassessed for the older population. We addressed the effect of test history in and outside organized screening at age 50–64 years on later cervical cancer risk. A case-control study was conducted by deriving 229 cases of 65–79-year-old women with invasive cervical cancer in 2010–2019 from the Finnish Cancer Registry. Ten controls were matched for each case by birth year and hospital district. The effect of test uptake and abnormal results in 50–64-year-olds on cancer risk was investigated using conditional logistic regression and adjusted for self-selection. Test uptake within the 50–64-year age-group showed 75% lower odds of cervical cancer (adjusted odds ratio [aOR] = 0.25; 95% confidence interval [95% CI], 0.18–0.35). Untested women had 4.9 times higher odds than those tested with normal results (aOR = 4.86; 95% CI, 3.42–6.92). Having at least one abnormal test result increased the odds by 2.5 when compared to only normal results but showed lower odds when compared to untested women. The importance of testing is exhibited by the result showing a reduction of odds of cancer to one-fourth for those tested compared to untested. Similarly, receiving abnormal results was protective of cancer compared to having no tests highlighting the importance of proper follow-up. Therefore, screening history should be considered when further developing cervical cancer screening programs with special interest in non-attenders and those receiving abnormal results at older ages.

In our research we studied if the overexpression of VEGF-A would save the impaired tumor growth in PROX1 silenced colorectal cancer xenografts. We conducted both small hairpin PROX1 and VEGF-A gene transfers to SW1222 colorectal cancer cells using lentiviral vectors. SW1222 cell lines were then injected to Nod scid gamma mice and grown for 14 days for analysis. We also established 3D cocultures of genetically modified SW1222 cell line together with lymphatic endothelial cells or blood endothelial cells to analyze lymphangiogenesis and angiogenesis in vitro. We found out that overexpression of VEGF-A rescues the growth of PROX1 silenced tumors. Large necrotic areas in the central of the PROX1 silenced tumors remain even though VEGF-A overexpression induces greater vascularity in these xenografts. In 3D cocultures silencing of PROX1 did not affect in vitro lymphangiogenesis or angiogenesis.

This 12-week study explored the efficacy of gene therapy using AAV-Pro-MSTN and AAV-VEGF-B vectors on 40 male mice to enhance muscle growth, vasculature, and metabolic functions in a diabetic mouse model. The mice were randomly split into five groups: one healthy group on a chow diet, one diabetic control group on a high-fat diet (HFD), and three diabetic groups on HFD, each receiving different gene therapies. Alterations in body composition were quantified, and metabolic rates and physical activity levels were assessed. The results indicated that combined gene therapy with VEGF-B and Pro-MSTN promoted muscle growth and mitigated muscle atrophy. However, changes in capillary density and muscle fiber size were not statistically significant. Healthy mice exhibited higher activity levels than diabetic controls. Diabetic control mice showed a reduction in lean mass, whereas treatment groups experienced significant reductions in fat mass and increases in lean and total mass. Diabetic controls had increased oxygen consumption (OC) and energy expenditure rates than the healthy mice, indicating a higher metabolic rate due to their diabetic state and diet. Treatment with VEGF-B and Pro-MSTN led to even higher OC compared to the diabetic control group. Statistical analysis confirmed significant group and mass effects on metabolic parameters, underscoring the potential of gene therapy in treating diabetes in mouse models, though further studies are needed for validation.

Objectives Fatigue is a major factor affecting driving performance and traffic accident risk. Driving conditions influence how people experience fatigue while driving. Driving in demanding conditions may increase vigilance in tired drivers; however, it may also increase cognitive load and become an additional source of fatigue. The current study investigated how driving on a slippery road interacts with fatigue caused by sleep deprivation and how it influences driving performance. Methods Twelve male participants (aged 19–21) drove 52.5 km in a driving simulator in four different conditions (day vs night and dry vs slippery road). Subjective sleep-related fatigue was measured with the Karolinska Sleepiness Scale and physiological fatigue in blink durations with electro-oculography. Three measures were used for driver performance: standard deviation of lateral position, mean steering wheel movement amplitude and mean steering wheel movement peak velocity. After each driving session, participants negotiated a cone track. The success rate for this task was analysed separately. Results Driving on slippery roads improved performance in all three performance metrics in sleep-deprived drivers. The three-way interaction between driver condition, road condition and time-on-task was significant for subjective sleep-related fatigue but not for performance. Sleep-deprived drivers became increasingly sleepy over time when driving in slippery conditions; however, this did not negatively affect their performance. Conclusions Driving in demanding weather conditions can increase the fatigue experienced by drivers; however, this change may not be initially detectable in performance. Large individual variability in response to both fatigue and driving conditions requires further research.

Objectives – Neonatal hyperbilirubinemia (HB), also referred to as neonatal jaundice, can alter child’s neurodevelopment, and thus significantly increase infant’s risk for severe neurological disability. Although the majority of neonatal HB cases benign, there are several cases where bilirubin levels grow alarmingly and remain elevated, eventually causing permanent physical harm and frequently altering the development of central nervous system. Research on the long-term effects of HB has been lacking: the follow-ups have been relative short, and there are not many studies focusing on how neonatal HB might influence neurocognition in later adulthood (> 30 year of age). The aim of this study is to further investigate the association between neonatal HB and later cognitive performance in adulthood by using data from over 40-year-long Finnish follow-up study. Methods – In a longitudinal prospective study, data were collected from 125 subject who had experienced neonatal HB and from 77 controls. Cognitive performance was assessed at age of 40 by using various previously validated methods designed to assess executive function and attention, memory, verbal functions, and visuo-perceptual functions. Four factors were formed for neuropsychological variables: Cognitive flexibility, Visual memory and perception, Verbal memory, and Reading. In addition, all subjects had performed WAIS-IV assessments. Data from these assessments were used to create four new factors – Verbal comprehension, Working Memory, Perceptual Reasoning, and Processing Speed – reflecting different cognitive areas. Also, Full-Scale Intelligence Quotient (FSIQ) was included. Linear regression analyses were used to assess the relation between HB-classification and neuropsychological variables. Differences between the groups were further studied by pair-wise comparisons using t-test, after which Mann–Whitney-U test was used to take into account moderate to highly skewed distributions of the variables. Effects of different HB levels on later neurocognition was studied by using linear regression, where sex, mother’s age at birth, and mother’s education level were controlled. Results – Neonatal HB was associated with slower performance in Cognitive Flexibility, and with lower performance in Perceptual Reasoning and in FSIQ. Highest measured neonatal bilirubin levels within HB group had a linear effect on Verbal Comprehension at age of 40; however, the effect was not found in other cognitive domains. Conclusions – Neonatal HB has effect on performance in FSIQ at age of 40 years. In addition, it was associated with both poorer Perceptual Reasoning and slower Cognitive Flexibility. Results might be due to perceptual reasoning’s high vulnerability to neuronal damage and to difficulty of compensating perceptual biological limitations with learning. Since the measured neonatal bilirubin levels within HB group was associated only with lower performance in Verbal Reasoning in this study, it could be concluded that after reaching the inclusion criteria the excess level of bilirubin was no longer significant influence on severity of the outcome.