Die S19 mRNS-Expression in Plattenepithelkarzinomen des oberen Aerodigestivtraktes

Ziel dieser Arbeit war die Analyse von Ausmaß, Häufigkeit und Charakter der mRNS-Expression des ribosomalen Proteins S19 (S19) in Head and Neck Squamous Cell Carcinoma (HNSCC). Als Methode wurde die Reverse Transkription-Polymerase Chain Reaction mit spezifischen S19 Primern gewählt. Untersucht wurden 18 HNSCC Zelllinien im Vergleich mit 17 benignen Keratinozytenzelllinien sowie 30 HNSCC Gewebeproben im Vergleich mit 8 Referenz-Gewebeproben. Für den Vergleich der HNSCC Zelllinien mit den benignen Keratinozytenzelllinien konnten die DDRT-PCR Voruntersuchungen bestätigt werden: In den HNSCC Zelllinien fand sich eine signifikante S19 mRNS-Repression. Niedrige S19 mRNS-Level korrelierten mit einem stärker entdifferenzierten Zellbild. Für die Gewebe zeichnete sich eine ähnliche Tendenz ab - signifikante Ergebnisse konnten jedoch nicht ermittelt werden. Lediglich eine große Karzinomausbreitung korrelierte signifikant mit niedrigen S19 mRNS-Leveln, wodurch die für die Zelllinien gewonnenen Ergebnisse gestützt werden. Um zu prüfen, ob die S19 mRNS-Repression lediglich auf veränderte Ribosomenzahlen zurückzuführen war, wurden zwei weiterer ribosomale Proteine, S6 und S14, mit derselben Methodik untersucht. Die mRNS-Expressionslevel aller drei ribosomalen Proteine zeigten hohe Korrelationen. Dies spricht für einen Zusammenhang der ribosomalen Rolle des S19 mit seiner mRNS-Repression in HNSCC. Die Ursachen der S19 mRNS-Repression in HNSCC wurden im Rahmen dieser Arbeit nicht näher untersucht. Ungeklärt bleibt die Frage, ob die S19 mRNS-Repression Ursache oder Folge der malignen Degeneration ist und ob ribosomale oder extraribosomale Funktionen des S19 betroffen sind. Weitere Untersuchungen sind nötig, um einen möglichen Einsatz des S19 als Tumormarker und Verlaufsparameter oder aber Zielprotein für therapeutische Interventionen abzuklären

Die S19 mRNS-Expression in Plattenepithelkarzinomen des oberen Aerodigestivtraktes

Ziel dieser Arbeit war die Analyse von Ausmaß, Häufigkeit und Charakter der mRNS-Expression des ribosomalen Proteins S19 (S19) in Head and Neck Squamous Cell Carcinoma (HNSCC). Als Methode wurde die Reverse Transkription-Polymerase Chain Reaction mit spezifischen S19 Primern gewählt. Untersucht wurden 18 HNSCC Zelllinien im Vergleich mit 17 benignen Keratinozytenzelllinien sowie 30 HNSCC Gewebeproben im Vergleich mit 8 Referenz-Gewebeproben. Für den Vergleich der HNSCC Zelllinien mit den benignen Keratinozytenzelllinien konnten die DDRT-PCR Voruntersuchungen bestätigt werden: In den HNSCC Zelllinien fand sich eine signifikante S19 mRNS-Repression. Niedrige S19 mRNS-Level korrelierten mit einem stärker entdifferenzierten Zellbild. Für die Gewebe zeichnete sich eine ähnliche Tendenz ab - signifikante Ergebnisse konnten jedoch nicht ermittelt werden. Lediglich eine große Karzinomausbreitung korrelierte signifikant mit niedrigen S19 mRNS-Leveln, wodurch die für die Zelllinien gewonnenen Ergebnisse gestützt werden. Um zu prüfen, ob die S19 mRNS-Repression lediglich auf veränderte Ribosomenzahlen zurückzuführen war, wurden zwei weiterer ribosomale Proteine, S6 und S14, mit derselben Methodik untersucht. Die mRNS-Expressionslevel aller drei ribosomalen Proteine zeigten hohe Korrelationen. Dies spricht für einen Zusammenhang der ribosomalen Rolle des S19 mit seiner mRNS-Repression in HNSCC. Die Ursachen der S19 mRNS-Repression in HNSCC wurden im Rahmen dieser Arbeit nicht näher untersucht. Ungeklärt bleibt die Frage, ob die S19 mRNS-Repression Ursache oder Folge der malignen Degeneration ist und ob ribosomale oder extraribosomale Funktionen des S19 betroffen sind. Weitere Untersuchungen sind nötig, um einen möglichen Einsatz des S19 als Tumormarker und Verlaufsparameter oder aber Zielprotein für therapeutische Interventionen abzuklären

Pregnancy outcomes in women with a prior cervical intraepithelial neoplasia grade 3 diagnosis : a nationwide population-based cohort study with sibling comparison design

Background: Treatment of cervical intraepithelial neoplasia grade 3 (CIN3) removes or destroys part of the cervix and might subsequently influence pregnancy outcomes. Objective: To investigate pregnancy outcomes in women diagnosed with CIN3. Design: Population- and sibling-matched cohort study. Setting: Sweden, 1973-2018. Participants: General population comparison included 78 450 singletons born to women diagnosed with CIN3 and 784 500 matched singletons born to women in the general population who had no CIN3 diagnosis; sibling comparison included 23 199 singletons born to women diagnosed with CIN3 and 28 135 singletons born to their sisters without a CIN3 diagnosis. Measurements: Preterm birth, including spontaneous or iatrogenic preterm birth; Infection-related outcomes, including chorioamnionitis and infant sepsis; and early neonatal death, defined as death during the first week after birth. Results: Compared with the matched general population, women previously diagnosed with CIN3 were more likely to have a preterm birth especially extremely preterm (22-28 weeks; OR, 3.00; 95% CI, 2.69-3.34) and spontaneous preterm (OR, 2.12; 95% CI, 2.05-2.20) birth, infection-related outcomes including chorioamnionitis (OR, 3.23; 95% CI, 2.89-3.62) and infant sepsis (OR, 1.72; 95% CI, 1.60-1.86), and early neonatal death (OR, 1.83; 95% CI, 1.61-2.09). Sibling comparison analyses rendered largely similar results. Over time the risk difference attenuated for all outcomes and disappeared for early neonatal death. Limitations: Lack of data on CIN3 treatment and spontaneous abortion. Conclusion: Prior history of CIN 3 is associated with adverse pregnancy outcomes even after accounting for familial factors. Decreasing risk estimates over time suggest that adverse pregnancy outcomes among women diagnosed with CIN3 may be minimized by improving treatment modalities.Swedish Research Council, 2018-02547Swedish Cancer Society, 19 0266Swedish Research Council for Health, Working Life and Welfare, 2016-00081 and 2018-00877Zhejiang University through the Hundred Talents ProgramManuscrip

Maternal selenium intake and selenium status during pregnancy in relation to preeclampsia and pregnancy-induced hypertension in a large Norwegian Pregnancy Cohort Study

Background: Pregnancy-induced hypertensive disorders (PIHD), including preeclampsia, cause maternal and perinatal morbidity and mortality worldwide. Several studies have linked selenium supplementation and selenium status to the risk of preeclampsia, but there are no published prospective population-based studies examining associations between dietary selenium intake and preeclampsia. Aim: To examine associations between selenium intake from diet and supplements and selenium blood status and PIHD incidence, with sub-analyses for pregnancy-induced hypertension (PIH) and preeclampsia, in a large pregnancy cohort. Method: The study is based on 69,972 singleton pregnancies from the Norwegian Mother, Father and Child Cohort Study. Maternal dietary selenium intake was assessed with a validated, semi-quantitative food frequency questionnaire at about gestational week 22. Maternal selenium concentrations were measured in whole blood collected around gestational week 18 in a subset of 2572 women. Preeclampsia and PIH diagnosges were obtained from the Medical Birth Registry of Norway. Results: Participants had a median dietary selenium intake of 53 μg/day (IQR 44–62). Dietary selenium intake was not significantly associated with PIHD (adjusted (a) OR 1.03, 95% CI 0.98, 1.08 per SD of selenium intake), preeclampsia or PIH. Threshold analyses for deciles of dietary selenium intake did not show any significant associations. Neither inorganic (aOR 1.01, 95% CI 0.98, 1.05) or organic selenium supplement intake (aOR 0.98, 95% CI 0.95, 1.02) or selenium blood status was significantly associated with PIHD (aOR 1.03, 95% CI 0.86, 1.22) or PIHD subgroups. Conclusion: No significant associations were found between reported selenium intake from diet, or dietary supplements or whole-blood selenium status and PIHD in general or preeclampsia specifically. Hence, the results of this large population-based study, with selenium intake close to the recommended daily intake, do not support previous findings indicating a possible protective effect of selenium supplementation or selenium status with regard to preeclampsia incidence

Maternal probiotic milk intake during pregnancy and breastfeeding complications in the Norwegian Mother and Child Cohort Study

Purpose: During the time of breastfeeding, a third of all women contract (or: fall ill in) mastitis—the leading cause of precocious weaning. Recent studies indicate that probiotics intake may prevent mastitis by altering the breast’s bacterial flora. The aim of this study was to examine whether probiotic milk intake during pregnancy is associated with less breastfeeding complications and longer breastfeeding duration. Methods: This study included 57,134 women, with live singleton term births, participating in the Norwegian Mother and Child Cohort Study. Probiotic milk intake during the first half of pregnancy was self-reported in a validated food frequency questionnaire at gestational week 22. At 6 month postpartum, women reported complications, including mastitis, and duration and exclusivity of breastfeeding. The association between probiotic milk intake and breastfeeding complications and duration was studied by adjusted logistic regression models. Results: Probiotic milk intake was associated with increased risk for mastitis [adjusted odds ratio (aOR) 1.09, 95% confidence interval (CI) 1.02–1.16] and for any breastfeeding problems during the first month (aOR 1.19, 95% CI 1.10–1.21). However, cessation of predominant (aOR 0.95, 95% CI 0.91–0.96) or any (aOR 0.79, 95%\ua0CI 0.75–0.84) breastfeeding earlier than at 4 months was less frequent in probiotic milk consumers than in non-consumers. Conclusions: Even though probiotic milk intake during the first half of pregnancy was statistically associated with increased risk for breastfeeding complications, including mastitis, the association is probably not causal. Probiotics intake was namely associated with longer breastfeeding duration and there was indication of socioeconomic confounding. Further studies, i.e., large randomized-controlled trials, are needed to understand the association between probiotic intake and breastfeeding complications

Associations between cervical intraepithelial neoplasia during pregnancy, previous excisional treatment, cone-length and preterm delivery: a register-based study from western Sweden

BACKGROUND: Excisional treatment of cervical intraepithelial neoplasia (CIN) has been associated with increased risk of preterm delivery (PTD), although the underlying mechanism is as yet unclear. Studies on formalin-fixed excised tissue indicate that the risk increases with cone-length, but the magnitude of increase is uncertain, especially in case of minor excisions (≤10 mm), as well compared to women with untreated CIN during pregnancy. This study assesses the impact of cone-length at previous treatment for CIN as well as diagnosis of CIN during pregnancy on the risk of PTD. METHODS: A register-based cohort study in western Sweden linking cervical cytology, histology, and treatment data from the Swedish National Cervical Screening Registry to data on obstetric outcomes in singleton pregnancies 2008-2016 from the Swedish Medical Birth Registry. These groups were compared for PTD and other obstetric outcomes: (1) women with one excisional treatment (n=3250, including a subgroup (n=2408) with cone-length measured before fixation; (2) women with untreated CIN diagnosed during pregnancy (n=1380); and (3) women with normal cytology (n=42,398). Logistic regression analyses were adjusted for socioeconomic and health-related confounders. RESULTS: Treated women had increased risk of PTD (adjusted odds ratio (aOR) 1.60, 95% confidence interval (CI) 1.21-2.12), spontaneous PTD (aOR 1.95, 95% CI 1.40-2.72) and preterm prelabor rupture of membranes (pPROM) (aOR 2.74, 95% CI 1.66-4.51) compared to the CIN during pregnancy group. ORs were similar when compared to the normal cytology group. Risks of these outcomes increased with cone-length. Mean cone-length was 9.1 mm. Cone-length ≤10 mm was associated with increased risk of PTD (aOR 1.41, 95% CI 1.02-1.94), spontaneous PTD (aOR 1.73, 95% CI 1.18-2.54), and pPROM (aOR 2.44, 95% CI 1.40-4.28), compared to the CIN during pregnancy group. The PTD risk was similar for cone-lengths 3-10 mm, thereafter increasing by 15% with each additional millimeter. CONCLUSIONS: This study suggests that all excisional treatment, including small cones, are associated with increased risk of PTD and pPROM. Risks increase further with cone-length. In women of reproductive age, clinicians should aim to remove all CIN but minimal healthy cervical tissue. Cone-length should be recorded at treatment, for future prenatal risk estimation

Is maternal trait anxiety a risk factor for late preterm and early term deliveries?

BACKGROUND Anxiety is associated with preterm deliveries in general (before week 37 of pregnancy), but is that also true for late preterm (weeks 34/0-36/6) and early term deliveries (weeks 37/0-38/6)? We aim to examine this association separately for spontaneous and provider-initiated deliveries. METHODS Participants were pregnant women from the Norwegian Mother and Child Cohort Study (MoBa), which has been following 95 200 pregnant women since 1999. After excluding pregnancies with serious health complications, 81 244 participants remained. National ultrasound records were used to delineate late preterm, early term, and full-term deliveries, which then were subdivided into spontaneous and provider-initiated deliveries. We measured trait anxiety based on two ratings of the anxiety items on the Symptom Checklist-8 (Acta Psychiatr Scand 87:364-7, 1993). Trait anxiety was transformed into categorizing the score at the mean and at ± 2 standard deviations. RESULTS Trait anxiety was substantially associated with late preterm and early term deliveries after adjusting for confounders. In the whole sample, women with the highest anxiety scores (+2 standard deviations) were more likely [(odds ratio (OR) = 1.7; 95 % confidence-interval (CI) 1.3-2.0)] to delivering late preterm than women with the lowest anxiety scores. Their odds of delivering early term were also high (OR = 1.4; CI 1.3-1.6). Women with spontaneous deliveries and the highest anxiety scores had higher odds (OR = 1.4; CI 1.1-1.8) of delivering late preterm and early term (OR = 1.3; CI = 1.3-1.5). The corresponding odds for women with provider-initiated deliveries were OR = 1.7 (CI = 1.2-2.4) for late preterm and OR = 1.3 for early term (CI = 1.01-1.6). Irrespective of delivery onset, women with provider-initiated deliveries had higher levels of anxiety than women delivering spontaneously. However, women with high anxiety were equally likely to have provider-initiated or spontaneous deliveries. CONCLUSIONS This study is the first to show substantial associations between high levels of trait anxiety and late preterm delivery. Increased attention should be given to the mechanism underlying this association, including factors preceding the pregnancy. In addition, acute treatment should be offered to women displaying high levels of anxiety throughout pregnancy to avoid suffering for the mother and the child

Maternal dietary patterns and preterm delivery: results from large prospective cohort study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.To examine whether an association exists between maternal dietary patterns and risk of preterm delivery.Prospective cohort study.Norway, between 2002 and 2008.66 000 pregnant women (singletons, answered food frequency questionnaire, no missing information about parity or previously preterm delivery, pregnancy duration between 22+0 and 41+6 gestational weeks, no diabetes, first enrolment pregnancy).Hazard ratio for preterm delivery according to level of adherence to three distinct dietary patterns interpreted as "prudent" (for example, vegetables, fruits, oils, water as beverage, whole grain cereals, fibre rich bread), "Western" (salty and sweet snacks, white bread, desserts, processed meat products), and "traditional" (potatoes, fish).After adjustment for covariates, high scores on the "prudent" pattern were associated with significantly reduced risk of preterm delivery hazard ratio for the highest versus the lowest third (0.88, 95% confidence interval 0.80 to 0.97). The prudent pattern was also associated with a significantly lower risk of late and spontaneous preterm delivery. No independent association with preterm delivery was found for the "Western" pattern. The "traditional" pattern was associated with reduced risk of preterm delivery for the highest versus the lowest third (hazard ratio 0.91, 0.83 to 0.99).This study showed that women adhering to a "prudent" or a "traditional" dietary pattern during pregnancy were at lower risk of preterm delivery compared with other women. Although these findings cannot establish causality, they support dietary advice to pregnant women to eat a balanced diet including vegetables, fruit, whole grains, and fish and to drink water. Our results indicate that increasing the intake of foods associated with a prudent dietary pattern is more important than totally excluding processed food, fast food, junk food, and snacks.Freemasons Directorate board for Children Adlerbertska Foundation Hjalmar Svensson Foundation Norwegian Research Council FUGE 183220/S10 FRIMEDKLI-05 ES236011 Jane and Dan Olsson Foundation Swedish Medical Society SLS 2008-21198 Swedish government ALFGBG-2863 ALFGBG-11522 Norwegian Ministry of Health Ministry of Education and Research NIH/NINDS 1 UO1 NS 047537-01 2 UO1 NS 047537-06A1 Norwegian Research Council/FUGE 151918/S10 NIH/NIEHS N01-ES-7555

Maternal dietary selenium intake during pregnancy and neonatal outcomes in the norwegian mother, father, and child cohort study

Properly working antioxidant defence systems are important for fetal development. One of the nutrients with antioxidant activity is selenium. Increased maternal selenium intake has been associated with reduced risk for being small for gestational age and preterm delivery. Based on the Norwegian Mother, Father, and Child Cohort Study and the Medical Birth Registry of Norway, we in-vestigated the association of maternal selenium intake from food and dietary supplements during the first half of pregnancy (n = 71,728 women) and selenium status in mid-pregnancy (n = 2628 women) with neonatal health, measured as two composite variables (neonatal morbidity/mortality and neonatal intervention). Low maternal dietary selenium intake (<30 \ub5g/day) was associated with increased risk for neonatal morbidity/mortality (adjusted odds ratio (adjOR) 1.36, 95% confidence interval (95% CI) 1.08–1.69) and neonatal intervention (adjOR 1.16, 95% CI 1.01–1.34). Using continuous variables, there were no associations between maternal selenium intake (from diet or supplements) or whole-blood selenium concentration and neonatal outcome in the adjusted models. Our findings suggest that sufficient maternal dietary selenium intake is associated with neonatal outcome. Adher-ing to the dietary recommendations may help ensure an adequate supply of selenium for a healthy pregnancy and optimal fetal development