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  • Udden, Fabian; Filipe, Matuba; Reimer, Ake; Paul, Maria; Matuschek, Erika; Thegerstrom, John; Hammerschmidt, Sven; Pelkonen, Tuula; Riesbeck, Kristian (2018)
    Background: Chronic suppurative otitis media (CSOM) is an important cause of hearing loss in children and constitutes a serious health problem globally with a strong association to resource-limited living conditions. Topical antibiotics combined with aural toilet is the first-hand treatment for CSOM but antimicrobial resistance and limited availability to antibiotics are obstacles in some areas. The goal of this study was to define aerobic pathogens associated with CSOM in Angola with the overall aim to provide a background for local treatment recommendations. Methods: Samples from ear discharge and the nasopharynx were collected and cultured from 152 patients with ear discharge and perforation of the tympanic membrane. Identification of bacterial species was performed with matrix-assisted laser desorption/ionization-time of flight mass spectrometry and pneumococci were serotyped using multiplex polymerase chain reactions. Antimicrobial susceptibility testing was done according to EUCAST. Results: One hundred eighty-four samples from ear discharge and 151 nasopharyngeal swabs were collected and yielded 534 and 289 individual isolates, respectively. In all patients, correspondence rate of isolates from 2 ears in patients with bilateral disease was 27.3% and 9.3% comparing isolates from the nasopharynx and ear discharge, respectively. Proteus spp. (14.7%), Pseudomonas aeruginosa (13.2%) and Enterococcus spp. (8.8%) were dominating pathogens isolated from ear discharge. A large part of the remaining species belonged to Enterobacteriaceoe (23.5%). Pneumococci and Staphylococcus aureus were detected in approximately 10% of nasopharyngeal samples. Resistance rates to quinolones exceeded 10% among Enterobacterioceae and was 30.8% in S. aureus, whereas 6.3% of P. aeruginosa were resistant. Conclusions: The infection of the middle ear in CSOM is highly polymicrobial, and isolates found in nasopharynx do not correspond well with those found in ear discharge. Pathogens associated with CSOM in Angola are dominated by gram-negatives including Enterobacteriaceoe and P. aeruginosa, while gram-positive enterococci also are common. Based on the results of antimicrobial susceptibility testing topical quinolones would be the preferred antibiotic therapy of CSOM in Angola. Topical antiseptics such as aluminium acetate, acetic acid or boric acid, however, may be more feasible options due to a possibly emerging antimicrobial resistance.
  • Arju, Georg; Taivosalo, Anastassia; Pismennoi, Dmitri; Lints, Taivo; Vilu, Raivo; Daneberga, Zanda; Vorslova, Svetlana; Renkonen, Risto; Joenvaara, Sakari (2020)
    Until now, cheese peptidomics approaches have been criticised for their lower throughput. Namely, analytical gradients that are most commonly used for mass spectrometric detection are usually over 60 or even 120 min. We developed a cheese peptide mapping method using nano ultra-high-performance chromatography data-independent acquisition high-resolution mass spectrometry (nanoUHPLC-DIA-HRMS) with a chromatographic gradient of 40 min. The 40 min gradient did not show any sign of compromise in milk protein coverage compared to 60 and 120 min methods, providing the next step towards achieving higher-throughput analysis. Top 150 most abundant peptides passing selection criteria across all samples were cross-referenced with work from other publications and a good correlation between the results was found. To achieve even faster sample turnaround enhanced DIA methods should be considered for future peptidomics applications.
  • Pussinen, Pirkko J.; Paju, Susanna; Koponen, Jaana; Viikari, Jorma; Taittonen, Leena; Laitinen, Tomi; Burgner, David; Kähönen, Mika; Hutri-Kähönen, Niina; Raitakari, Olli; Juonala, Markus (2019)
    IMPORTANCE Severe forms of common chronic oral infections or inflammations are associated with increased cardiovascular risk in adults. To date, the role of childhood oral infections in cardiovascular risk is not known because no long-term studies have been conducted. OBJECTIVE To investigate whether signs of oral infections in childhood are associated with cardiovascular risk factors and subclinical atherosclerosis in adulthood. DESIGN, SETTING, AND PARTICIPANTS The cohort study (n = 755) was derived from the Cardiovascular Risk in Young Finns Study, an ongoing prospective cohort study in Finland initiated in 1980. Participants underwent clinical oral examinations during childhood, when they were aged 6, 9, or 12 years and a clinical cardiovascular follow-up in adulthood in 2001 at age 27, 30, or 33 years and/or in 2007 at age 33, 36, or 39 years. Cardiovascular risk factors were measured at baseline and during the follow-up until the end of 2007. Final statistical analyses were completed on February 19, 2019. MAIN OUTCOMES AND MEASURES Four signs of oral infections (bleeding on probing, periodontal probing pocket depth, caries, and dental fillings) were documented. Cumulative lifetime exposure to 6 cardiovascular risk factors was calculated from dichotomized variables obtained by using the area-under-the-curve method. Subclinical atherosclerosis (ie, carotid artery intima-media thickness [IMT]) was quantified in 2001 (n = 468) and 2007 (n = 489). RESULTS This study included 755 participants, of whom 371 (49.1%) were male; the mean (SD) age at baseline examination was 8.07 (2.00) years. In this cohort, 33 children (4.5%) had no sign of oral infections, whereas 41 (5.6%) had 1 sign, 127 (17.4%) had 2 signs, 278 (38.3%) had 3 signs, and 248 (34.1%) had 4 signs. The cumulative exposure to risk factors increased with the increasing number of oral infections both in childhood and adulthood. In multiple linear regression models, childhood oral infections, including signs of either periodontal disease (R-2 = 0.018; P = .01), caries (R-2 = 0.022; P = .008), or both (R-2 = 0.024; P = .004), were associated with adulthood IMT. The presence of any sign of oral infection in childhood was associated with increased IMT (third tertile vs tertiles 1 and 2) with a relative risk of 1.87 (95% CI, 1.25-2.79), whereas the presence of all 4 signs produced a relative risk of 1.95 (95% CI, 1.28-3.00). The associations were more obvious in boys: if periodontal disease were present, the corresponding estimate was 1.69 (95% CI, 1.21-2.36); if caries, 1.46 (95% CI, 1.04-20.05); and if all 4 signs of oral infections, 2.25 (95% CI, 1.30-3.89). The associations were independent of cardiovascular risk factors. CONCLUSIONS AND RELEVANCE Oral infections in childhood appear to be associated with the subclinical carotid atherosclerosis seen in adulthood.
  • Joensuu, Eveliina; Munck, Petriina; Setänen, Sirkku; Lipsanen, Jari; Huhtala, Mira; Lapinleimu, Helena; Stolt, Suvi K. J. (2021)
    Preterm children (born
  • Halonen, Jaana I.; Dehbi, Hakim-Moulay; Hansell, Anna L.; Gulliver, John; Fecht, Daniela; Blangiardo, Marta; Kelly, Frank J.; Chaturvedi, Nish; Kivimaki, Mika; Tonne, Cathryn (2017)
    Background: Road traffic noise has been linked to increased risk of stroke, for which hypertension and carotid intima-media thickness (cIMT) are risk factors. A link between traffic noise and hypertension has been established, but there are few studies on blood pressure and no studies on cIMT. Objectives: To examine cross-sectional associations for long-term exposure to night-time noise with cIMT, systolic blood pressure (SBP), diastolic blood pressure (DBP) and hypertension. Methods: The study population consisted of 2592 adults from the Whitehall II and SABRE cohort studies living within Greater London who had cIMT, SBP and DBP measured. Exposure to night-time road traffic noise (A-weighted dB, referred to as dBA) was estimated at each participant's residential postcode centroid. Results: Mean night-time road noise levels were 52 dBA (SD=4). In the pooled analysis adjusted for cohort, sex, age, ethnicity, marital status, smoking, area-level deprivation and NOx there was a 9.1 mu m (95% CI: -7.1, 25.2) increase in cIMT in association with 10 dBA increase in night-time noise. Analyses by noise categories of 5560 dBA (16.2 mu m, 95% CI:-8.7, 41.2), and N60 dBA (21.2 mu m, 95% CI:-2.5, 44.9) vs. 60 dBA vs. Conclusions: After adjustments, including for air pollution, the association between night-time road traffic noise and cIMT was only observed among non-medication users but associations with blood pressure and hypertension were largely null. (C) 2016 Elsevier Ltd. All rights reserved.
  • Saure, Emma; Lepistö-Paisley, Tuulia; Raevuori, Anu; Laasonen, Marja (2022)
    Background:Elevated autism spectrum disorder (ASD) traits are associated with anorexia nervosa (AN). Conversely, eating disturbances, which are core characteristics of AN, are common in ASD. Among individuals with ASD, atypical sensory processing is associated with eating disturbance. Because AN and ASD appear to overlap, it would be crucial to understand whether sensory processing atypicality exist also in AN. Further, it would be essential to find if atypical sensory processing is associated with eating disturbances in individuals with AN, since treatment modifications may be needed. We therefore aimed to examine whether atypical sensory processing is associated with AN and its core characteristics. MethodsParticipants of the current study included 42 individuals with AN and 40 healthy controls (HCs). All participants were adult women. Sensory processing, other ASD traits, and eating disorder symptoms were assessed with self-report questionnaires. ResultsIndividuals with AN reported lower registration, decreased sensation seeking, increased sensory sensitivity, and increased sensation avoiding compared to HCs. When analyzing groups with restrictive AN (AN-R) and binge-purge type AN (AN-BP) separately, only individuals with AN-R exhibited decreased sensation seeking, and only those with AN-BP exhibited lower registration. After controlling for body mass index as a covariate, group differences remained significant only in sensory sensitivity between individuals with AN and HCs. Increased atypical sensory processing predicted lower body mass index and increased disordered eating. ConclusionResults suggest that sensory processing appears to differ between AN and HC women, and AN subtypes may exhibit distinct sensory processing atypicality. Sensory sensitivity may be stable traits whereas other aspects of atypical sensory processing may be related to acute AN. Atypical sensory processing may contribute to the severity of AN, and thus it is crucial to recognize sensory processing differences when treating individuals with AN.
  • Hakala, JO; Pahkala, K; Juonala, M; Salo, P; Kahonen, M; Hutri-Kahonen, N; Lehtimaki, T; Laitinen, TP; Jokinen, E; Taittonen, L; Tossavainen, P; Viikari, JSA; Raitakari, OT; Rovio, SP (2021)
    Background: Cardiovascular risk factors, such as high blood pressure, adverse serum lipids, and elevated body mass index in midlife, may harm cognitive performance. It is important to note that longitudinal accumulation of cardiovascular risk factors since childhood may be associated with cognitive performance already since childhood, but the previous evidence is scarce. We studied the associations of cardiovascular risk factors from childhood to midlife, their accumulation, and midlife cognitive performance. Methods: From 1980, a population-based cohort of 3596 children (3-18 years of age) have been repeatedly followed up for 31 years. Blood pressure, serum lipids, and body mass index were assessed in all follow-ups. Cardiovascular risk factor trajectories from childhood to midlife were identified using latent class growth mixture modeling. Cognitive testing was performed in 2026 participants 34 to 49 years of age using a computerized test. The associations of the cardiovascular risk factor trajectories and cognitive performance were studied for individual cardiovascular risk factors and cardiovascular risk factor accumulation. Results: Consistently high systolic blood pressure (beta=-0.262 SD [95% CI, -0.520 to -0.005]) and serum total cholesterol (beta=-0.214 SD [95% CI, -0.365 to -0.064]) were associated with worse midlife episodic memory and associative learning compared with consistently low values. Obesity since childhood was associated with worse visual processing and sustained attention (beta=-0.407 SD [95% CI, -0.708 to -0.105]) compared with normal weight. An inverse association was observed for the cardiovascular risk factor accumulation with episodic memory and associative learning (P for trend=0.008; 3 cardiovascular risk factors: beta=-0.390 SD [95% CI, -0.691 to -0.088]), with visual processing and sustained attention (P for trend Conclusions: Longitudinal elevated systolic blood pressure, high serum total cholesterol, and obesity from childhood to midlife were inversely associated with midlife cognitive performance. It is important to note that the higher the number of cardiovascular risk factors, the worse was the observed cognitive performance. Therefore, launching preventive strategies against cardiovascular risk factors beginning from childhood might benefit primordial promotion of cognitive health in adulthood.
  • Oksuz, Tugba; Tacer-Caba, Zeynep; Nilufer-Erdil, Dilara; Boyacioglu, Dilek (2019)
    In this study, it is aimed to understand the changes in sour cherry phytochemicals when their co-digestions are simulated in dairy model systems comprising skim milk, non-fat-yoghurt, probiotic yoghurt or cream. These co-digestions were analyzed for their total phenolic and anthocyanin contents, total antioxidant activity (TAA) in addition to phenolic and anthocyanin profiles, individually. Sour cherry phenolics were stable during gastric conditions (120%); 54% lost in pancreatic digestion and being available (59%) in serum available fraction (IN). Anthocyanins were lost both in gastric (30%) and pancreatic digestions (16%), being only little available (0.6%) in IN. Soymilk had inhibitory effects on TAA. Dairy food matrix components evaluated were found to have distinct effects on the measured bioavailability of individual sour cherry phenolics. This study might aid both consumers and industry on selecting the food matrices to aiding increase in bioavailability.
  • Kiiveri, K.; Gruen, D.; Finoguenov, A.; Erben, T.; van Waerbeke, L.; Rykoff, E.; Miller, L.; Hagstotz, S.; Dupke, R.; Henry, J. Patrick; Kneib, J-P; Gozaliasl, G.; Kirkpatrick , C. C.; Cibirka, N.; Clerc, N.; Costanzi, M.; Cypriano, E. S.; Rozo, E.; Shan, H.; Spinelli, P.; Valiviita, J.; Weller, J. (2021)
    The COnstrain Dark Energy with X-ray clusters (CODEX) sample contains the largest flux limited sample of X-ray clusters at 0.35 <z <0.65. It was selected from ROSAT data in the 10 000 square degrees of overlap with BOSS, mapping a total number of 2770 high-z galaxy clusters. We present here the full results of the CFHT CODEX programme on cluster mass measurement, including a reanalysis of CFHTLS Wide data, with 25 individual lensing-constrained cluster masses. We employ LENSFIT shape measurement and perform a conservative colour-space selection and weighting of background galaxies. Using the combination of shape noise and an analytic covariance for intrinsic variations of cluster profiles at fixed mass due to large-scale structure, miscentring, and variations in concentration and ellipticity, we determine the likelihood of the observed shear signal as a function of true mass for each cluster. We combine 25 individual cluster mass likelihoods in a Bayesian hierarchical scheme with the inclusion of optical and X-ray selection functions to derive constraints on the slope alpha, normalization beta, and scatter sigma(ln lambda vertical bar mu) of our richness-mass scaling relation model in log-space: <In lambda vertical bar mu > = alpha mu + beta, with mu = ln (M-200c/M-piv), and M-piv = 10(14.81)M(circle dot). We find a slope alpha = 0.49(-0.15)(+0.20) , normalization exp(beta) = 84.0(-14.8)(+9.2) , and sigma(ln lambda vertical bar mu) = 0.17(-0.09)(+0.13) using CFHT richness estimates. In comparison to other weak lensing richness-mass relations, we find the normalization of the richness statistically agreeing with the normalization of other scaling relations from a broad redshift range (0.0 <z <0.65) and with different cluster selection (X-ray, Sunyaev-Zeldovich, and optical).
  • Peltomaa, Elina; Hällfors, Heidi; Taipale, Sami J. (2019)
    Recent studies have clearly shown the importance of omega-3 (-3) and omega-6 (-6) polyunsaturated fatty acids (PUFAs) for human and animal health. The long-chain eicosapentaenoic acid (EPA; 20:5-3) and docosahexaenoic acid (DHA; 22:6-3) are especially recognized for their nutritional value, and ability to alleviate many diseases in humans. So far, fish oil has been the main human source of EPA and DHA, but alternative sources are needed to satisfy the growing need for them. Therefore, we compared a fatty acid profile and content of 10 diatoms and seven dinoflagellates originating from marine, brackish and freshwater habitats. These two phytoplankton groups were chosen since they are excellent producers of EPA and DHA in aquatic food webs. Multivariate analysis revealed that, whereas the phytoplankton group (46%) explained most of the differences in the fatty acid profiles, habitat (31%) together with phytoplankton group (24%) explained differences in the fatty acid contents. In both diatoms and dinoflagellates, the total fatty acid concentrations and the -3 and -6 PUFAs were markedly higher in freshwater than in brackish or marine strains. Our results show that, even though the fatty acid profiles are genetically ordered, the fatty acid contents may vary greatly by habitat and affect the -3 and -6 availability in food webs.
  • Mantyselka, Pekka; Niskanen, Leo; Kautiainen, Hannu; Saltevo, Juha; Wurtz, Peter; Soininen, Pasi; Kangas, Antti J.; Ala-Korpela, Mika; Vanhala, Mauno (2014)
  • Jansen, Y. J. L.; Rozeman, E. A.; Mason, R.; Goldinger, S. M.; Foppen, M. H. Geukes; Hoejberg, L.; Schmidt, H.; van Thienen, J.; Haanen, J. B. A. G.; Tiainen, L.; Svane, I. M.; Mäkelä, S.; Seremet, T.; Arance, A.; Dummer, R.; Bastholt, L.; Nyakas, M.; Straume, O.; Menzies, A. M.; Long, G.; Atkinson, Jeffrey; Blank, C. U.; Neyns, B. (2019)
    Background Programmed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established. Patients and Methods This academic real-world cohort study investigated the outcome of 185 advanced melanoma patients who electively discontinued anti-PD-1 therapy with pembrolizumab (N=167) or nivolumab (N=18) in the absence of disease progression (PD) or treatment limiting toxicity (TLT) at 14 medical centres across Europe and Australia. Results Median time on treatment was 12months (range 0.7-43). The best objective tumour response at the time of treatment discontinuation was complete response (CR) in 117 (63%) patients, partial response (PR) in 44 (24%) patients and stable disease (SD) in 16 (9%) patients; 8 (4%) patients had no evaluable disease (NE). After a median follow-up of 18months (range 0.7-48) after treatment discontinuation, 78% of patients remained free of progression. Median time to progression was 12months (range 2-23). PD was less frequent in patients with CR (14%) compared with patients with PR (32%) and SD (50%). Six out of 19 (32%) patients who were retreated with an anti-PD-1 at the time of PD obtained a new antitumour response. Conclusions In this real-world cohort of advanced melanoma patients discontinuing anti-PD-1 therapy in the absence of TLT or PD, the duration of anti-PD-1 therapy was shorter when compared with clinical trials. In patients obtaining a CR, and being treated for >6months, the risk of relapse after treatment discontinuation was low. Patients achieving a PR or SD as best tumour response were at higher risk for progression after discontinuing therapy, and defining optimal treatment duration in such patients deserves further study. Retreatment with an anti-PD-1 at the time of progression may lead to renewed antitumour activity in some patients. Clinical trial registration NCT02673970 (https://clinicaltrials.gov/ct2/show/NCT02673970?cond=melanoma&cntry=BE&city=Jette&rank=3)
  • Borssen, Magnus; Haider, Zahra; Landfors, Mattias; Noren-Nystrom, Ulrika; Schmiegelow, Kjeld; Asberg, Ann E.; Kanerva, Jukka; Madsen, Hans O.; Marquart, Hanne; Heyman, Mats; Hultdin, Magnus; Roos, Goran; Forestier, Erik; Degerman, Sofie (2016)
    Background. Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Procedure. Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Results. Two distinct CpG island methylator phenotype (CIMP) groups were identified. Patients with a CIMP-negative profile had an inferior response to treatment compared to CIMP-positive patients (3-year cumulative incidence of relapse (CIR3y) rate: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high-risk T-ALL patients (MRD >= 0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ regarding ETP phenotype, but the CIMP-negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP-positive group. Conclusions. CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making. (C) 2016 Wiley Periodicals, Inc.
  • Grotenfelt, N. E.; Wasenius, N.; Eriksson, J. G.; Huvinen, E.; Stach-Lempinen, B.; Koivusalo, S. B.; Rönö, K. (2020)
    Aim. - To assess in women at high risk of gestational diabetes mellitus (GDM) the effect of a lifestyle intervention on the metabolic health of their offspring around 5 years after delivery. Methods. - For the original Finnish gestational diabetes prevention study (RADIEL), 720 women with a prepregnancy body mass index (BMI) >= 30 kg/m(2) and/or previous GDM were enrolled before or during early pregnancy and allocated to either an interventional (n = 126) or conventional (n = 133) care group. The present 5-year follow-up substudy assessed the metabolic health outcomes of their offspring. Ageand gender-standardized residuals of metabolic health components (waist circumference, mean arterial pressure, high-density lipoprotein and triglyceride levels, and fasting insulin/glucose ratio) were also combined to determine the accumulation of metabolic effects. Body composition was assessed by electrical bioimpedance. Results. - Offspring of women in the intervention group had a less optimal metabolic profile after the 5-year follow-up compared with offspring in the usual care group (P = 0.014). This difference in metabolic health was primarily related to lipid metabolism, and was more prominent among boys (P = 0.001) than girls (P = 0.74). Neither GDM, gestational weight gain, prepregnancy BMI, offspring age nor timing of randomization (before or during pregnancy) could explain the detected difference, which was also more pronounced among the offspring of GDM pregnancies (P= 0.010). Offspring body composition was similar in both groups (P> 0.05). Conclusion. - The lifestyle intervention aimed at GDM prevention was associated with unfavourable metabolic outcomes among offspring at around 5 years of age. (C) 2019 Elsevier Masson SAS. All rights reserved.
  • Char, Arundhati; Gaudel, Pramila; Kulathinal, Sangita; Kinnunen, Tarja I. (2022)
    Introduction: Mobile technology has been increasingly used as part of dietary interventions, but the effects of such interventions have not been systematically evaluated in the South Asian context. The systematic review aimed to determine the effects of technology-based interventions on dietary intake or anthropometrics among adolescents and adults in South Asia. Methods: Five electronic databases were searched (PubMed, Scopus, Web of Science, Global Health Library and Health Technology Assessment). Studies published in English between 1st January 2011 and 31st December 2021were included. Interventions that evaluated the effects of dietary interventions using technology on dietary outcomes and anthropometrics in adolescents or adults in the age group of 13-44 years (or a broader age group) from South Asia were eligible for inclusion. The risk of bias was assessed using the Cochrane Risk-of-bias 2 tool and ROBINS-I tool. A narrative synthesis was conducted. Results: Twenty-one studies met the inclusion criteria (20,667 participants). Eleven of the 17 randomised controlled trials (RCTs) had a high overall risk of bias. The four non-randomised intervention studies had a serious or critical overall risk of bias. When including studies with low risk or some concern for bias, the interventions had a beneficial effect on at least one dietary outcome in four of the six RCTs that measured changes in diet, and no effect on the anthropometric outcomes in the six RCTs that measured changes in anthropometric outcomes.Discussion: Technology-based dietary interventions have had some positive effects on dietary intake, but no effects on anthropometry in South Asia. More evidence is needed as the overall risk of bias was high in a majority of the studies.
  • Schalekamp-Timmermans, Sarah; Arends, Lidia R.; Alsaker, Elin; Chappell, Lucy; Hansson, Stefan; Harsem, Nina K.; Jalmby, Maya; Jeyabalan, Arundhathi; Laivuori, Hannele; Lawlor, Debbie A.; Macdonald-Wallis, Corrie; Magnus, Per; Myers, Jenny; Olsen, Jorn; Poston, Lucilla; Redman, Christopher W.; Staff, Anne C.; Villa, Pia; Roberts, James M.; Steegers, Eric A.; Global Pregnancy Collaboration (2017)
    Background: Pre-eclampsia (PE) is a major pregnancy disorder complicating up to 8% of pregnancies. Increasing evidence indicates a sex-specific interplay between the mother,placenta and fetus. This may lead to different adaptive mechanisms during pregnancy. Methods: We performed an individual participant data meta-analysis to determine associations of fetal sex and PE, with specific focus on gestational age at delivery in PE. This was done on 219 575 independent live-born singleton pregnancies, with a gestational age at birth between 22.0 and 43.0 weeks of gestation, from 11 studies participating in a worldwide consortium of international research groups focusing on pregnancy. Results: Of the women, 9033 (4.1%) experienced PE in their pregnancy and 48.8% of the fetuses were female versus 51.2% male. No differences in the female/male distribution were observed with respect to term PE (delivered >= 37 weeks). Preterm PE (delivered <37 weeks) was slightly more prevalent among pregnancies with a female fetus than in pregnancies with a male fetus [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.02-1.21]. Very preterm PE (delivered <34 weeks) was even more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus (OR 1.36, 95% CI 1.17-1.59). Conclusions: Sexual dimorphic differences in the occurrence of PE exist, with preterm PE being more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus and with no differences with respect to term PE.
  • Schalekamp-Timmermans, Sarah; Arends, Lidia R.; Alsaker, Elin; Chappell, Lucy; Hansson, Stefan; Harsem, Nina K.; Jalmby, Maya; Jeyabalan, Arundhathi; Laivuori, Hannele; Lawlor, Debbie A.; Macdonald-Wallis, Corrie; Magnus, Per; Myers, Jenny; Olsen, Jorn; Poston, Lucilla; Redman, Christopher W.; Staff, Anne C.; Villa, Pia; Roberts, James M.; Steegers, Eric A.; Global Pregnancy Collaboration (Oxford University Press, 2017)
    Background: Pre-eclampsia (PE) is a major pregnancy disorder complicating up to 8% of pregnancies. Increasing evidence indicates a sex-specific interplay between the mother,placenta and fetus. This may lead to different adaptive mechanisms during pregnancy. Methods: We performed an individual participant data meta-analysis to determine associations of fetal sex and PE, with specific focus on gestational age at delivery in PE. This was done on 219 575 independent live-born singleton pregnancies, with a gestational age at birth between 22.0 and 43.0 weeks of gestation, from 11 studies participating in a worldwide consortium of international research groups focusing on pregnancy. Results: Of the women, 9033 (4.1%) experienced PE in their pregnancy and 48.8% of the fetuses were female versus 51.2% male. No differences in the female/male distribution were observed with respect to term PE (delivered >= 37 weeks). Preterm PE (delivered <37 weeks) was slightly more prevalent among pregnancies with a female fetus than in pregnancies with a male fetus [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.02-1.21]. Very preterm PE (delivered <34 weeks) was even more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus (OR 1.36, 95% CI 1.17-1.59). Conclusions: Sexual dimorphic differences in the occurrence of PE exist, with preterm PE being more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus and with no differences with respect to term PE.
  • Topa, Hande; Jonas, Agnes; Kofler, Robert; Kosiol, Carolin; Honkela, Antti (2015)
    Motivation: Recent advances in high-throughput sequencing (HTS) have made it possible to monitor genomes in great detail. New experiments not only use HTS to measure genomic features at one time point but also monitor them changing over time with the aim of identifying significant changes in their abundance. In population genetics, for example, allele frequencies are monitored over time to detect significant frequency changes that indicate selection pressures. Previous attempts at analyzing data from HTS experiments have been limited as they could not simultaneously include data at intermediate time points, replicate experiments and sources of uncertainty specific to HTS such as sequencing depth. Results: We present the beta-binomial Gaussian process model for ranking features with significant non-random variation in abundance over time. The features are assumed to represent proportions, such as proportion of an alternative allele in a population. We use the beta-binomial model to capture the uncertainty arising from finite sequencing depth and combine it with a Gaussian process model over the time series. In simulations that mimic the features of experimental evolution data, the proposed method clearly outperforms classical testing in average precision of finding selected alleles. We also present simulations exploring different experimental design choices and results on real data from Drosophila experimental evolution experiment in temperature adaptation.
  • Mariotti, Lorenzo; Huarancca Reyes, Thais; Ramos-Diaz, Jose Martin; Jouppila, Kirsi; Guglielminetti, Lorenzo (2021)
    Increased ultraviolet-B (UV-B) due to global change can affect plant development and metabolism. Quinoa tolerates extreme conditions including high UV levels. However, the physiological mechanisms behind its abiotic stress tolerance are unclear, especially those related to UV-B. We previously demonstrated that 9.12 kJ m−2 d−1 may induce UV-B-specific signaling while 18.24 kJ m−2 d−1 promotes a UV-B-independent response. Here, we explored the effects of these UV-B doses on hormonal regulation linked to plant morphology and defense among diverse varieties. Changes in fluorescence parameters of photosystem II, flavonoids and hormones (indoleacetic acid (IAA), jasmonic acid (JA), abscisic acid (ABA) and salicylic acid (SA)) were surveyed under controlled conditions. Here, we showed that the sensitivity to short acute UV-B doses in varieties from different habitats is influenced by their parental lines and breeding time. UV-B sensitivity does not necessarily correlate with quinoa’s geographical distribution. The role of flavonoids in the UV-B response seems to be different depending on varieties. Moreover, we found that the extent of changes in JA and SA correlate with UV-B tolerance, while the increase of ABA was mainly related to UV-B stress.
  • Mortensen, Jesper; Dich, Nadya; Clark, Alice Jessie; Ramlau-Hansen, Cecilia Host; Head, Jenny; Kivimäki, Mika; Kumari, Meena; Rod, Naja Hulvej (2019)
    The objective was to investigate the relationship between various aspects of informal caregiving and diurnal patterns of salivary cortisol, with special attention to the moderating effect of sex and work status. The study population was composed of 3727 men and women from the British Whitehall II study. Salivary cortisol was measured six times during a weekday. Aspects of caregiving included the relationship of caregiver to recipient, weekly hours of caregiving, and length of caregiving. Diurnal cortisol profiles were assessed using the cortisol awakening response (CAR) and diurnal cortisol slopes. Results showed that men, but not women, providing informal care had a blunted CAR compared with non-caregivers (P-Interaction = 0.03). Furthermore, we found a dose-response relationship showing that more weekly hours of informal care was associated with a more blunted CAR for men (P-trend = 0.03). Also, the blunted CAR for men was especially pronounced in short-term caregivers and those in paid work. In women, the steepest cortisol slope was seen among those in paid work who provided informal care (P-Interaction = 0.01). To conclude, we found different cortisol profiles in male and female informal caregivers. Male caregivers had a blunted CAR, which has previously been associated with chronic stress and burnout. Future research should investigate whether results are generalizable beyond UK citizens with a working history in the civil service.