Early relationship between very preterm infant and mother: The role of infant, maternal and dyadic factors

Pienipainoisen keskosen ja äidin varhainen suhde: Lapsen, äidin ja dyadisten muuttujien vaikutus Tämän tutkimuksen tavoitteena oli tutkia keskosvauvan ja äidin varhaista suhdetta. Tutkimuksessa selvitettiin myös vauvan itkukäyttäytymisen, vauvan sylissä olon ja äidin masentuneisuuden yhteyttä äidin ja keskosvauvan varhaiseen suhteeseen. Tutkimusryhmät koostuivat 32:sta (tutkimus I-II) ja 38:sta (tutkimus III-IV) keskosena syntyneestä vauvasta (syntymäpaino < 1501 g tai GI < 32 viikkoa) sekä 46:sta täysiaikaisena syntyneestä terveestä verrokkivauvasta. Lapsen ja äidin vuorovaikutusta arvioitiin 6 ja 12 kuukauden iässä (korjattu ikä) PCERAmenetelmällä. Äidin mielikuvia lapsestaan tutkittiin WMCI-haastattelulla, kun lapsi oli 12 kuukautta. Baby Day Diary -menetelmää käytettiin vauvan itkukäyttäytymisen ja sylissä olon keston mittaamisessa vauvan ollessa 5 kuukautta. Äidin masentuneisuutta arvioitiin EDPS-lomakkeella, kun lapsi oli 6 kuukautta. Tulokset osoittivat, että turvallisten kiintymyssuhdemielikuvien määrä tai vuorovaikutuksen laatu eivät keskosvauvan äideillä eronneet täysiaikaisina syntyneiden vauvojen äitien vastaavista. Ryhmien välillä ei löytynyt eroja myöskään dyadisen vuorovaikutuksen laadussa. Keskosena syntyneet lapset olivat kuitenkin vetäytyvämpiä ja heillä oli laadullisesti heikommat keskittymisen ja leikin taidot vuorovaikutustilanteessa 12 kuukauden iässä täysiaikaisina syntyneisiin lapsiin nähden. Lisäksi äidin masentuneisuus ja lapsen pitkittynyt itkuisuus olivat negatiivisessa yhteydessä vuorovaikutuksen laatuun keskosvauvojen ryhmässä. Vauvan itkukertojen määrän, sylissä olon keston sekä äidin ja vauvan vuorovaikutuksen laadun välillä löytyi positiivinen yhteys ainoastaan keskosena syntyneiden lasten ryhmässä. Tulostemme perusteelle toteamme, että lapsen ennenaikainen syntymä itsessään ei näytä muodostavan riskiä äidin vuorovaikutuksen laadulle tai turvalliselle kiintymyssuhteelle. Yhdessä muiden riskitekijöiden kanssa keskosuus kuitenkin altistaa vauvat ja heidän äitinsä varhaisen vuorovaikutuksen ongelmille. Lisäksi tuloksemme viittaavat siihen, että vauvan itku ja siitä seuraava sylissä olo toimivat suojaavana mekanismina pienipainoisen keskosen ja äidin varhaisessa suhteessa.

Dental Health in Primary Teeth after Prevention of Mother-Child Transmission of Mutans Streptococci. A Historical Cohort Study on Restorative Visits and Maternal Prevention Costs

Mutansstreptokokkitartunnan ehkäisemisen pitkäaikaisvaikutukset maitohampaiden terveyteen. Kohorttitutkimus korjaavan hoidon määrästä ja kariesehkäisyn kustannuksista. Tutkimuksen tarkoituksena oli selvittää varhaisen mutansstreptokokki (MS)-kolonisaation ehkäisyn pitkäaikaisvaikutuksia korkean kariesriskin omaavien lasten maitohampaistossa sekä tarkastella MS-tartunnan estämisen kustannuksia. Tiedot lasten hampaiden terveydestä ja hammashoitotoimenpiteistä syntymästä 10-vuotiaaksi sekä äiteihin kohdistuneen kariesehkäisyn kustannuksista kerättiin Ylivieskan terveyskeskuksen asiakirjoista. Tutkimuksessa oli mukana yhteensä 507 lasta, heistä 148 oli osallistunut aikaisempaan Ylivieskan äiti-lapsitutkimukseen, jossa verrattiin äitien käyttämän ksylitolipurukumin ja äidille tehtyjen fluori- tai klooriheksidiinilakkausten vaikutusta pikkulasten hampaiden terveyteen. Maitohammaskariesta esiintyi 10-vuotiaaksi asti merkitsevästi vähemmän lapsilla, jotka eivät olleet saaneet MS-tartuntaa alle 2-vuotiaana, heidän maitohampaansa säilyivät 3,4 vuotta kauemmin täysin ehjinä (p<0.001) ja he tarvitsivat vähemmän maitohampaiden korjaavaa hoitoa (p=0.005) kuin lapset, joiden hampaisto oli kolonisoitunut MS-bakteerilla jo 2-vuotiaana. Koska ksylitoliryhmän lasten MS-kolonisaatio oli vähäisintä, heidän maitohampaissaan oli vähemmän kariesta ja korjaavan hoidon tarvetta kuin kahden muun korkeariskisen ryhmän lapsilla. Äitien käyttämän ksylitolipurukumin kustannukset olivat yhteensä 116 euroa ja lapsen maitohampaiden säilyminen täysin ehjinä vuoden pidempään maksoi 37 euroa. Kun MS-tartunta oli saatu estettyä, korkean kariesriskin omaavien lasten hampaiden terveys oli samalla tasolla kuin keskimäärin koko ikäkohortilla. Lapsen maitohampaat säilyvät terveinä pidempään ja korjaavan hoidon tarve vähenee, kun MS-kolonisaatio alle 2-vuotiaana saadaan estettyä. Lapsen MS-kolonisaatio vähenee merkitsevästi, kun äiti käyttää ksylitolipurukumia lapsen ollessa 0-2 vuoden ikäinen, siten pikkulapsen äidin säännöllinen ksylitolipurukumin käyttö saattaa olla julkisen tereydenhuollon kannalta tarkoituksenmukainenterveyttä edistävä menetelmä.

The effects of maternal hyperglycemia on human umbilical vascular gene expression and neonatal rat lung development

Background: Maternal diabetes affects many fetal organ systems, including the vasculature and the lungs. The offspring of diabetic mothers have respiratory adaptation problems after birth. The mechanisms are multifactorial and the effects are prolonged during the postnatal period. An increasing incidence of diabetic pregnancies accentuates the importance of identifying the pathological mechanisms, which cause the metabolic and genetic changes that occur in offspring, born to diabetic mothers. Aims and methods: The aim of this thesis was to determine changes both in human umbilical cord exposed to maternal type 1 diabetes and in neonatal rat lungs after streptozotocin-induced maternal hyperglycemia, during pregnancy. Rat lungs were used as a model for the potential disease mechanisms. Gene expression alterations were determined in human umbilical cords at birth and in rat pup lungs at two week of age. During the first two postnatal weeks, rat lung development was studied morphologically and histologically. Further, the effect of postnatal hyperoxia on hyperglycemia-primed rat lungs was investigated at one week of age to mimic the clinical situation of supplemental oxygen treatment. Results: In the umbilical cord, maternal diabetes had a major negative effect on the expression of genes involved in blood vessel development. The genes regulating vascular tone were also affected. In neonatal rat lungs, intrauterine hyperglycemia had a prolonged effect on gene expression during late alveolarization. The most affected pathway was the upregulation of extracellular matrix proteins. Newborn rat lungs exposed to intrauterine hyperglycemia had thinner saccular walls without changes in airspace size, a smaller relative lung weight and lung total tissue area, and increased cellular apoptosis and proliferation compared to control lungs, possibly reflecting an aberrant maturational adaptation. At one and two weeks of age, cell proliferation and secondary crest formation were accelerated in hyperglycemia-exposed lungs. Postnatal hyperoxic exposure, alone caused arrested alveolarization with thin-walled and enlarged alveoli. In contrast, the dual exposure of intrauterine hyperglycemia and postnatal hyperoxia resulted in the phenotype of thick septa together with arrested alveolarization and decreased number of small pulmonary arteries. Conclusions: Maternal diabetic environment seems to alter the umbilical cord gene expression profile of the regulation of vascular development and function. Fetal hyperglycemia may additionally affect the genetic regulation of the postnatal lung development and may actually induce prolonged structural alterations in neonatal lungs together with a modifying effect on the deleterious pulmonary exposure of postnatal hyperoxia. This, combined with the novel human umbilical cord gene data could serve as stepping stones for future therapies to curb developmental aberrations.

Cesarean section - short term maternal complications related to the mode of delivery

Cesarean section (CS) is the most common major surgery performed on women worldwide. CS can save the life of the mother or the fetus, but is associated with the typical complications of any major surgery: hemorrhage, infection, venous thromboembolism and complications of anesthesia, sometimes leading to maternal death. Recently there have been several reports from well resourced countries on increased severe maternal morbidity and even mortality. Increased rates of CS, obesity and older mothers may explain this rise. The aim of this thesis is to study the rates and risk factors of short term maternal complications associated with CS. Also, we compared maternal morbidity by mode of delivery and over time. The complication rates were assessed in a prospective study involving 2496 CS performed in the 12 largest delivery units in Finland in 2005. The rates of severe complications were studied by mode of delivery in a register-based study comparing national cohorts in 1997 and 2002. The impact of several risk factors on severe maternal morbidity by mode of delivery was studied in a register-based study of all singleton deliveries in 2007-2011. In the prospective study, 27% of the women who underwent CS had one or more intraoperative or postoperative complications during their hospital stay, and 10% had a severe complication. In the register-based study the incidence of life-threatening maternal complications was 7.6 in 1000 deliveries. The incidence was lowest for vaginal delivery (VD), followed by instrumental VD and elective CS, and highest in emergency CS. An attempt of VD, including the risks associated with emergency CS, seems to be the safest mode of delivery, even for most high-risk women.

Comparing adult-youth and adult-adult online sexual solicitation: Manipulative behaviors, situational factors, and outcomes

Online sexual solicitation (solicitation) of youth has received widespread media and research attention during the last decade. The prevalence rates of youth who have experienced solicitation or solicitation attempts vary between studies depending on the methodology used (e.g., whether youth or adults are the target study group). In studies focusing on youth victims, the prevalence of solicitation attempts made by adults during the past year is typically reported to be between 5 and 9%. Adults who solicit youth online have been found to use deception and other manipulative behaviors to gain access to sexual activities with youth. However, previous studies have lacked a control group of adults who solicit other adults online. Without this comparison, one could argue that deceiving others online about one’s identity, and engaging in manipulative behaviors, is an inherent part of most online sexual interactions with strangers. Additionally, little is known about the associations between manipulative behaviors and the solicitation outcomes. In research concerning offline sexual behaviors, it has been noted that situational factors, such as sexual arousal, may alter both sexual interest and behavior. The effects of situational factors on online sexual behaviors have been less extensively studied (especially so with a quantitative approach); no studies have to date focused on adults’ solicitation of youth. Investigating the role of a lowered sexual age preference and the role of situational factors in the soliciting adults could be an important step in order to receive deeper knowledge of the role of traits and states in the context of solicitation. Additionally, there is a lack of knowledge of the effect of the age of the youth. Although previous studies on solicitation has found that older youth, compared with younger youth and children, are more often solicited, the possible reasons for this have not been investigated. Are adults who solicit youth affected by legal deterrence (through the legal age of consent), is it because older youth are more available online, or are the adults’ age preferences merely a product of a normally distributed age preference in the population? The purpose of the present thesis was fivefold: 1) to obtain an estimate of the frequency of adults’ solicitation of youth as self-reported and observed in actual behavior; 2) to explore whether the legal age of consent (LAC) affects solicitation frequency, or whether a normally distributed sexual age preference more accurately describe the proportion of solicited youth of different ages; 3) to investigate the associations of both traits (e.g., lower sexual age preference) and states (immediate situational factors, such as alcohol intoxication), and the solicitation target; 4) to explore whether adults who solicit youth and adults who solicit adults are equally deceitful and manipulative online, and whether the different solicitation outcomes are as common in both groups; and 5) to investigate whether the deceitful and manipulative behaviors engaged in had different associations with the solicitation outcomes depending on the age of the solicited. In the survey study, a convenience sample of 1393 adult participants (aged 18 years or older) self-reported any online communication with strangers during the past year. Of these, 56% (776 respondents) reported that they had solicited or attempted to solicit at least one stranger. Of the respondents, 453 (58.4%) were men, and 323 (41.6%) were women. Participants with only adult contacts (18 years or older) constituted the majority (640 respondents). In contrast, 136 individuals reported a youth contact (a 13 year old or younger, or a 14 to 17-year old). Approximately half of the participants were men in the adult contact group, while 75% of the participants were men in the youth contact group. Approximately 60% of the participants with youth contacts were recruited from two websites associated with a pedophilic sexual interest. In an online quasi-experimental study, with researchers impersonating youth of different ages (10–18 year olds) in chat rooms, 251 online conversations with chat room visitors made up the entire sample. All chat room visitors alleged to be men. The self-reported frequency of having solicited youth (0–17-year olds) during the past year was approximately 10% in our sample of adults who reported communicating with any strangers online. When we observed this behavior in chat rooms, we found that approximately 30% of the chat room visitors who believed they interacted with a 10 to 14 year old attempted to solicit the youth. We found that solicitation attempts increased equally much when increasing the age of the impersonated youth from 14 to 16, as from 16 to 18. Thus, we concluded that a normally distributed age preference in the population was a more plausible explanation to the effect of the age of the solicited, rather than the LAC (here; 15 and 16). If the chat room visitors would have been deterred only by the LAC, we would have expected that the change in amount of solicitation attempts from an illegal age group to a legal age group would have been significantly stronger than changes between age groups within illegal-illegal and legal-legal groups. Our subsample of survey participants from the pedophilia-related websites expectedly reported that they had solicited youth more often in comparison to the sample gathered through general (i.e., not associated with any particular sexual preference) websites. We also found that participants with a youth contact reported higher levels of sexual arousal and shame before the sexual interaction with their online contact, compared with participants with an adult contact. Additionally, the participants with youth contacts who reported consumption of child- and adolescent pornography also reported being more sexually aroused before the interaction, compared to the participants with youth contacts who did not report consumption of these kinds of pornography. We also found clear indications that the online sexual interaction had an alleviatory effect on reported levels of sadness, boredom and stress, independent of the age of the contact. Generally, the participants with youth and adult contacts reported deceiving their contacts as often and suggesting keeping the communication a secret from someone as often. Participants with a youth contact, however, reported using more persuasion techniques for online sexual purposes or for the purpose of an offline meeting, compared to those with an adult contact. In the chat rooms, we found that more indirect ways of future sexual communication (e.g., continuing chatting) was suggested by the chat room visitors that were under the assumption of interacting with youth aged 10 to 14, compared with more direct means (e.g., meeting offline). Survey participants with youth contacts who had used deception, suggested keeping the interactions a secret, and/or persuaded their contact by appealing to the contacts feelings of love and attachment for the participant had also more often engaged in cybersex with the contact. No other manipulative behaviors were associated with the other investigated solicitation outcomes (receiving a sexual picture, meeting offline, and engaging in sexual contact offline) within this group of participants. However, using deception, suggesting secrecy and using persuasion was also positively associated with certain solicitation outcomes within participants with an adult contact. In summary, adults’ solicitation of youth is much more frequent when observed in chat rooms than self-reported. Additionally, an underlying lowered sexual age preference seems to be a motivating factor on a group level in adults who solicit youth. We concluded that directed prevention efforts should be made on pedophiliarelated websites. Additionally, the role of situational factors, especially sexual arousal in persons with a pedo- or hebephilic sexual interest should be investigated further in the context of online sexual solicitation.

JNK regulation of neurogenesis, neuroplasticity and anxiety-related behaviors in mice

I vår moderna värld har förekomsten av ångeststörningar drastiskt ökat, vilket påverkar välfärden i våra samhällen. Eftersom de molekylära mekanismerna bakom ångest är relativt okända, är möjligheterna till behandling av ångeststörningar begränsade. I och med utvecklingen av genetiska manipuleringmetoder och avbildningstekniker har strukturella förändringar associerade med ångeststörningar kunnat konstateras. Neuroanatomiska studier har påvisat störningar i dendritarkitektur, dendrittaggar och i neurogenesen hos vuxna individer. Särskilt neurogenesen i hippocampus anses viktig i detta sammanhang. Neurogenes i hippocampus har föreslagits spela en viktig roll i ångeststörningarnas patofysiologi och för hur vissa antidepressiva läkemedel förmedlar sin effekt. Under senare år har MAP-kinaser (MAPK) föreslagits vara involverade både i uppkomsten av affektiva störningar och i neurogenes i hippocampus. JNK är en grupp kinaser inom MAPK-familjen som aktiveras av olika externa stressfaktorer. I normala celler är aktiviteten hos JNK låg. Cell-stress ökar aktiviteten hos JNK vilket leder till bl.a. apoptos. JNK kinaser anses vara potentiella terapeutiska mål för behandling av neurodegenerativa sjukdomar men deras potential som mål för behandling av affektiva sjukdomar har tillsvidare inte utretts. Den här avhandlingen behandlar betydelsen av JNK för ångestrelaterat beteende hos möss. Med hjälp av Jnk1-knockout möss och farmakologisk inhibering av JNK-signalering, demonstreras att JNK reglerar neurogenes i hippocampus, vilket i sin tur ligger bakom mössens ångestrelaterade beteende. Jnk1-knockout möss var mindre ängsliga och uppvisade ökad neurogenes i hippcampus jämfört med kontrollmöss. Inhibering av JNK-signalering i hjärnan hos möss gjorde dem också mindre ängsliga och ökade neurogenesen i hippocampus på samma sätt som vissa antidepressiva läkemedel. Inhibering av JNK-aktivitet ledde inte bara till ökad neurogenes i hippocampus, utan främjade också mognandet av nybildade nervceller hos vuxna möss. Resultaten visar också att dendritarkitekturen och fördelningen av dendrittaggar hos CA3 neuroner i hippocampus är förändrad hos Jnk1-knockout möss. Genom screening av substratmolekyler för JNK hittades två JNKeffektormolekyler, MARCKSL1 (ett aktin-associerat protein) och MAP2 (ett mikrotubulus-associerat protein), som reglerade neuronernas sttruktur. Det här tyder på att JNK-signalering kan kontrollera ångeststörningsrelaterade förändringar hor dendriter och dendrittaggar. Sammanfattningsvis ger resultaten som presenteras i avhandlingen en ökad insikt i molekylära mekanismer som kan leda till ångeststörningsrelaterade förändringar i neurogenes och dendritstruktur. Därtill föreslås att JNKsignalbanan har potential som terapeutiskt mål för behandling av ångeststörningar.