Browsing by Subject "YOUNG"

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  • Adam, Magdy; Salla, Kati; Aho, Riikka; Hänninen, Laura; Taponen, Suvi; Norring, Marianna; Raekallio, Marja; Hokkanen, Ann-Helena (2021)
    Objective To compare the sedative effects of intramuscular xylazine alone or combined with levomethadone or ketamine in calves before cautery disbudding. Study design Randomized, blinded, clinical trial. Animals A total of 28 dairy calves, aged 21 +/- 5 days and weighing 61.0 +/- 9.3 kg (mean +/- standard deviation). Methods Calves were randomly allocated to three groups: xylazine (0.1 mg kg(-1)) and levomethadone (0.05 mg kg(-1); group XL), xylazine (0.1 mg kg(-1)) and ketamine (1 mg kg(-1); group XK) and xylazine alone (0.2 mg kg(-1); group X). Local anaesthesia (procaine hydrochloride) and meloxicam were administered subcutaneously 15 minutes after sedation and 15 minutes before disbudding. The calves' responses to the administration of local anaesthesia and disbudding were recorded. Sedation was assessed at baseline and at intervals up to 240 minutes postsedation. Times of recumbency, first head lift and first standing were recorded. Drug plasma concentrations were measured. Results Data were obtained from 27 animals. All protocols resulted in sedation sufficient to administer local anaesthesia and to perform disbudding. Sedation scores significantly correlated with drug plasma concentrations (p Conclusions and clinical relevance Levomethadone or ketamine with a low dose of xylazine produced short but sufficient sedation for local anaesthesia and disbudding with minimum resistance.
  • Marshall, H. H.; Johnstone, R. A.; Thompson, F. J.; Nichols, H. J.; Wells, D.; Hoffman, J. I.; Kalema-Zikusoka, G.; Sanderson, J. L.; Vitikainen, E. I. K.; Blount, J. D.; Cant, M. A. (2021)
    Rawls argued that fairness in human societies can be achieved if decisions about the distribution of societal rewards are made from behind a veil of ignorance, which obscures the personal gains that result. Whether ignorance promotes fairness in animal societies, that is, the distribution of resources to reduce inequality, is unknown. Here we show experimentally that cooperatively breeding banded mongooses, acting from behind a veil of ignorance over kinship, allocate postnatal care in a way that reduces inequality among offspring, in the manner predicted by a Rawlsian model of cooperation. In this society synchronized reproduction leaves adults in a group ignorant of the individual parentage of their communal young. We provisioned half of the mothers in each mongoose group during pregnancy, leaving the other half as matched controls, thus increasing inequality among mothers and increasing the amount of variation in offspring birth weight in communal litters. After birth, fed mothers provided extra care to the offspring of unfed mothers, not their own young, which levelled up initial size inequalities among the offspring and equalized their survival to adulthood. Our findings suggest that a classic idea of moral philosophy also applies to the evolution of cooperation in biological systems. Obscuring knowledge of personal gains from individuals can theoretically maintain fairness in a cooperative group. Experiments show that wild, cooperatively breeding banded mongooses uncertain of kinship allocate postnatal care in a way that reduces inequality among offspring, suggesting a classic idea of moral philosophy can apply in biological systems.
  • Carlsson, Annelie; Shepherd, Maggie; Ellard, Sian; Weedon, Michael; Lernmark, Ake; Forsander, Gun; Colclough, Kevin; Brahimi, Qefsere; Valtonen-Andre, Camilla; Ivarsson, Sten A.; Elding Larsson, Helena; Samuelsson, Ulf; Ortqvist, Eva; Groop, Leif; Ludvigsson, Johnny; Marcus, Claude; Hattersley, Andrew T. (2020)
    OBJECTIVE Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population. RESEARCH DESIGN AND METHODS Swedish patients (n = 3,933) aged 1-18 years, diagnosed with diabetes May 2005 to December 2010, were recruited from the national consecutive prospective cohort Better Diabetes Diagnosis. Clinical data, islet autoantibodies (GAD insulinoma antigen-2, zinc transporter 8, and insulin autoantibodies), HLA type, and C-peptide were collected at diagnosis. MODY was identified by sequencing GCK, HNF1A, and HNF4A, through either routine clinical or research testing. RESULTS The minimal prevalence of MODY was 1.2%. Discriminatory factors for MODY at diagnosis included four islet autoantibody negativity (100% vs. 11% not-known MODY; P = 2 x 10(-44)), HbA(1c) (7.0% vs. 10.7% [53 vs. 93 mmol/mol]; P = 1 x 10(-20)), plasma glucose (11.7 vs. 26.7 mmol/L; P = 3 x 10(-19)), parental diabetes (63% vs. 12%; P = 1 x 10(-15)), and diabetic ketoacidosis (0% vs. 15%; P = 0.001). Testing 303 autoantibody-negative patients identified 46 patients with MODY (detection rate 15%). Limiting testing to the 73 islet autoantibody-negative patients with HbA(1c)
  • Kämppi, Antti; Tanner, Tarja; Viitanen, Olavi; Pohjola, Vesa; Päkkilä, Jari; Tjäderhane, Leo; Anttonen, Vuokko; Patinen, Pertti (2022)
    The main aim of this cross-sectional study was to examine the prevalence of dental fear among Finnish conscripts. Other aims were to study the association between dental fear and cariological status as well as their self-reported, dentition-related well-being. The study material consisted of 13,564 men and 255 women conscripts who underwent oral examinations. Of those, 8713 responded to a computer-based questionnaire. The mean number of decayed teeth (DT) was used in analyses for cariological status. Self-reported dental fear, dentition-related well-being and regular check-ups were analysed. Data were analysed with cross tables, Pearson Chi-Square tests, Fisher's exact test and binary logistic regressive analysis. High dental fear or finding dental visits very scary was associated with DT > 2 both among women (14.6%, when DT = 0; 33.3%, when DT > 2) and men conscripts (2.3% and 10.8%, respectively). In addition, those reporting that dental health had a negative impact on their well-being and had no regular check-ups were more likely to need cariological treatment than the rest. A high education level, both one's own and parental, was a protective factor for restorative treatment need in male conscripts. The findings of this study support the concept of a vicious cycle of dental fear and dental caries. A preventive, interactive way of work by dental teams would most likely be beneficial for dental health, avoiding the development of dental fear, and dentition-related well-being.
  • Kettunen, Jarno L. T.; Parviainen, Helka; Miettinen, Päivi J.; Färkkilä, Martti; Tamminen, Marjo; Salonen, Pia; Lantto, Eila; Tuomi, Tiinamaija (2017)
    Context: The clinical spectrum of organogenetic anomalies associated with HNF1B mutations is heterogeneous. Besides cystic kidney disease, diabetes, and various other manifestations, odd cases of mainly neonatal and posttransplantation cholestasis have been described. The biliary phenotype is incompletely defined. Objective: To systematically characterize HNF1B-related anomalies in the bile ducts by imaging with magnetic resonance imaging (MRI) or magnetic resonance cholangiopancreatography (MRCP). Setting and Patients: Fourteen patients with HNF1B mutations in the catchment area of the Helsinki University Hospital were evaluated with upper abdominal MRI and MRCP. Blood samples and clinical history provided supplemental data on the individual phenotype. Main Outcome Measure(s): Structural anomalies in the biliary system, medical history of cholestasis, other findings in abdominal organs, diabetes and antihyperglycemic treatment, hypomagnesemia, and hyperuricemia. Results: Structural anomalies of the bile ducts were found in seven of 14 patients (50%). Six patients had choledochal cysts, which are generally considered premalignant. Conclusions: Structural anomalies of the biliary system were common in HNF1B mutation carriers. The malignant potential of HNF1B-associated choledochal cysts warrants further studies.
  • Merikanto, Ilona; Pesonen, Anu-Katriina; Paunio, Tiina; Partonen, Timo (2022)
    Background: Circadian phenotype has a crucial role in determining wellbeing and health prospective. Evening-types have higher risk for sleep and mental health problems, which is also reflected in work wellbeing. However, there are no population-based studies examining the association of working ability and circadian typology at different working-age-groups. Also, the role of predisposing factors, ie, sleep-related differences between circadian types, has not been studied in relation to working ability among circadian types in a population-based sample. Methods: In this population-based sample of 13,114 working-age Finnish adults from 18 to 64 years of age, we examined the associations between circadian type, exhaustion and working ability and the roles of sleep-wake rhythm misalignment and insufficient sleep on these associations in 10-years-wide age-groups. Circadian type was assessed with the widely-used single item for selfassessed morningness/eveningness from the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ). Results: Evening-types, especially definite evening-types, were more exhausted and had poorer working ability than morning-types. Higher exhaustion among evening-types was apparent in all working ages with a peak at ages 45 to 54 years. Poorer working ability in definite evening-types as compared to definite morning-types was found only at ages 35 to 54 years. Evening-types, especially definiteevening-types, had also more social jet lag and they reported more insufficient sleep than definite morning-types. More frequent insufficient sleep associated with poorer working ability and partly mediated the association between circadian type and working ability. Conclusion: Circadian phenotypes were found to differ in risk for exhaustion and in working ability, and this association was partly mediated by insufficient sleep. Our findings emphasize the importance to improve sleep especially among evening-types to ensure better work wellbeing.
  • Mills, E. A. C.; Gorski, M.; Emig, K. L.; Bolatto, A. D.; Levy, R. C.; Leroy, A. K.; Ginsburg, A.; Henshaw, J. D.; Zschaechner, L. K.; Veilleux, S.; Tanaka, K.; Meier, D. S.; Walter, F.; Krieger, N.; Ott, J. (2021)
    We present new 3 mm observations of the ionized gas toward the nuclear starburst in the nearby (D similar to 3.5 Mpc) galaxy NGC 253. With ALMA, we detect emission from the H40 alpha and He40 alpha lines in the central 200 pc of this galaxy on spatial scales of similar to 4 pc. The recombination line emission primarily originates from a population of approximately a dozen embedded super star clusters in the early stages of formation. We find that emission from these clusters is characterized by electron temperatures ranging from 7000 to 10,000 K and measures an average singly ionized helium abundance Y (+) = 0.25 +/- 0.06, both of which are consistent with values measured for H ii regions in the center of the Milky Way. We also report the discovery of unusually broad line width recombination line emission originating from seven of the embedded clusters. We suggest that these clusters contribute to the launching of the large-scale hot wind observed to emanate from the central starburst. Finally, we use the measured recombination line fluxes to improve the characterization of overall embedded cluster properties, including the distribution of cluster masses and the fractional contribution of the clustered star formation to the total starburst, which we estimate is at least 50%.
  • Allegaert, Karel; Olkkola, Klaus T.; Owens, Katie H.; Van de Velde, Marc; de Maat, Monique M.; Anderson, Brian J.; PACIA Study Grp (2014)
  • European Soc Human Genetics; European Council Legal Med; European Soc Cardiology Working; European Reference Network Rare; Assoc European Cardiovasc; Fellmann, Florence; van El, Carla G.; Sajantila, Antti (2019)
    Sudden cardiac death (SCD) accounts for 10-20% of total mortality, i.e., one in five individuals will eventually die suddenly. Given the substantial genetic component of SCD in younger cases, postmortem genetic testing may be particularly useful in elucidating etiological factors in the cause of death in this subset. The identification of genes responsible for inherited cardiac diseases have led to the organization of cardiogenetic consultations in many countries worldwide. Expert recommendations are available, emphasizing the importance of genetic testing and appropriate information provision of affected individuals, as well as their relatives. However, the context of postmortem genetic testing raises some particular ethical, legal, and practical (including economic or financial) challenges. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with international experts, developed recommendations on management of SCD after a workshop sponsored by the Brocher Foundation and ESHG in November 2016. These recommendations have been endorsed by the ESHG Board, the European Council of Legal Medicine, the European Society of Cardiology working group on myocardial and pericardial diseases, the ERN GUARD-HEART, and the Association for European Cardiovascular Pathology. They emphasize the importance of increasing the proportion of both medical and medicolegal autopsies and educating the professionals. Multidisciplinary collaboration is of utmost importance. Public funding should be allocated to reach these goals and allow public health evaluation.
  • Juntunen, Miia; Heinonen, Sini; Huhtala, Heini; Rissanen, Aila; Kaprio, Jaakko; Kuismanen, Kirsi; Pietiläinen, Kirsi H.; Miettinen, Susanna; Patrikoski, Mimmi (2021)
    Background Adipose stromal/stem cells (ASCs) are promising candidates for future clinical applications. ASCs have regenerative capacity, low immunogenicity, and immunomodulatory ability. The success of future cell-based therapies depends on the appropriate selection of donors. Several factors, including age, sex, and body mass index (BMI), may influence ASC characteristics. Our aim was to investigate the effect of acquired weight on ASC characteristics under the same genetic background using ASCs derived from monozygotic (MZ) twin pairs. Methods ASCs were isolated from subcutaneous adipose tissue from five weight-discordant (WD, within-pair difference in BMI > 3 kg/m(2)) MZ twin pairs, with measured BMI and metabolic status. The ASC immunophenotype, proliferation and osteogenic and adipogenic differentiation capacity were studied. ASC immunogenicity, immunosuppression capacity and the expression of inflammation markers were investigated. ASC angiogenic potential was assessed in cocultures with endothelial cells. Results ASCs showed low immunogenicity, proliferation, and osteogenic differentiation capacity independent of weight among all donors. ASCs showed a mesenchymal stem cell-like immunophenotype; however, the expression of CD146 was significantly higher in leaner WD twins than in heavier cotwins. ASCs from heavier twins from WD pairs showed significantly greater adipogenic differentiation capacity and higher expression of TNF and lower angiogenic potential compared with their leaner cotwins. ASCs showed immunosuppressive capacity in direct cocultures; however, heavier WD twins showed stronger immunosuppressive capacity than leaner cotwins. Conclusions Our genetically matched data suggest that a higher weight of the donor may have some effect on ASC characteristics, especially on angiogenic and adipogenic potential, which should be considered when ASCs are used clinically.
  • Karppinen, Jari E.; Rottensteiner, Mirva; Wiklund, Petri; Hamalainen, Kaisa; Laakkonen, Eija K.; Kaprio, Jaakko; Kainulainen, Heikki; Kujala, Urho M. (2019)
    Purpose We aimed to investigate if hereditary factors, leisure-time physical activity (LTPA) and metabolic health interact with resting fat oxidation (RFO) and peak fat oxidation (PFO) during ergometer cycling. Methods We recruited 23 male monozygotic twin pairs (aged 32-37 years) and determined their RFO and PFO with indirect calorimetry for 21 and 19 twin pairs and for 43 and 41 twin individuals, respectively. Using physical activity interviews and the Baecke questionnaire, we identified 10 twin pairs as LTPA discordant for the past 3 years. Of the twin pairs, 8 pairs participated in both RFO and PFO measurements, and 2 pairs participated in either of the measurements. We quantified the participants' metabolic health with a 2-h oral glucose tolerance test. Results Fat oxidation within co-twins was correlated at rest [intraclass correlation coefficient (ICC) = 0.54, 95% confidence interval (CI) 0.15-0.78] and during exercise (ICC = 0.67, 95% CI 0.33-0.86). The LTPA-discordant pairs had no pairwise differences in RFO or PFO. In the twin individual-based analysis, PFO was positively correlated with the past 12-month LTPA (r = 0.26, p = 0.034) and the Baecke score (r = 0.40, p = 0.022) and negatively correlated with the area under the curve of insulin (r = - 0.42, p = 0.015) and glucose (r = - 0.31, p = 0.050) during the oral glucose tolerance test. Conclusions Hereditary factors were more important than LTPA for determining fat oxidation at rest and during exercise. Additionally, PFO, but not RFO, was associated with better metabolic health.
  • Leroy, Adam K.; Bolatto, Alberto D.; Ostriker, Eve C.; Walter, Fabian; Gorski, Mark; Ginsburg, Adam; Krieger, Nico; Levy, Rebecca C.; Meier, David S.; Mills, Elisabeth; Ott, Juergen; Rosolowsky, Erik; Thompson, Todd A.; Veilleux, Sylvain; Zschaechner, Laura K. (2018)
    NGC 253 hosts the nearest nuclear starburst. Previous observations show a region rich in molecular gas, with dense clouds associated with recent star formation. We used the Atacama Large Submillimeter/Millimeter Array (ALMA) to image the 350 GHz dust continuum and molecular line emission from this region at 2 pc resolution. Our observations reveal similar to 14 bright, compact (similar to 2-3 pc FWHM) knots of dust emission. Most of these sources are likely to be forming super star clusters (SSCs) based on their inferred dynamical and gas masses, association with 36 GHz radio continuum emission, and coincidence with line emission tracing dense, excited gas. One source coincides with a known SSC, but the rest remain invisible in Hubble near-infrared (IR) imaging. Our observations imply that gas still constitutes a large fraction of the overall mass in these sources. Their high brightness temperature at 350 GHz also implies a large optical depth near the peak of the IR spectral energy distribution. As a result, these sources may have large IR photospheres, and the IR radiation force likely exceeds L/c. Still, their moderate observed velocity dispersions suggest that feedback from radiation, winds, and supernovae are not yet disrupting most sources. This mode of star formation appears to produce a large fraction of stars in the burst. We argue for a scenario in which this phase lasts similar to 1 Myr, after which the clusters shed their natal cocoons but continue to produce ionizing photons. The strong feedback that drives the observed cold gas and X-ray outflows likely occurs after the clusters emerge from this early phase.
  • Rasa, Tapio; Palmgren, Elina; Laherto, Antti (2022)
    To promote students' value-based agency, responsible science and sustainability, science education must address how students think about their personal and collective futures. However, research has shown that young people find it difficult to fully relate to the future and its possibilities, and few studies have focused on the potential of science education to foster futures thinking and agency. We report on a project that further explored this potential by developing future-oriented science courses drawing on the field of futures studies. Phenomenographic analysis was used on interview data to see what changes upper-secondary school students saw in their futures perceptions and agentic orientations after attending a course which adapted futures thinking skills in the context of quantum computing and technological approaches to global problems. The results show students perceiving the future and technological development as more positive but also more unpredictable, seeing their possibilities for agency as clearer and more promising (especially by identifying with their peers or aspired career paths), and feeling a deeper connection to the otherwise vague idea of futures. Students also felt they had learned to question deterministic thinking and to think more creatively about their own lives as well as technological and non-technological solutions to global problems. Both quantum physics and futures thinking opened new perspectives on uncertainty and probabilistic thinking. Our results provide further validation for a future-oriented approach to science education, and highlight essential synergies between futures thinking skills, agency, and authentic socio-scientific issues in developing science education for the current age.
  • Patel, Kashyap A.; Kettunen, Jarno; Laakso, Markku; Stancakova, Alena; Laver, Thomas W.; Colclough, Kevin; Johnson, Matthew B.; Abramowicz, Marc; Groop, Leif; Miettinen, Paivi J.; Shepherd, Maggie H.; Flanagan, Sarah E.; Ellard, Sian; Inagaki, Nobuya; Hattersley, Andrew T.; Tuomi, Tiinamaija; Cnop, Miriam; Weedon, Michael N. (2017)
    Finding new causes of monogenic diabetes helps understand glycaemic regulation in humans. To find novel genetic causes of maturity-onset diabetes of the young (MODY), we sequenced MODY cases with unknown aetiology and compared variant frequencies to large public databases. From 36 European patients, we identify two probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating variants are enriched in the MODY discovery cohort compared to the European control population within ExAC (odds ratio = 131, P = 1 x 10(-4)). We find similar results in non-Finnish European (n = 348, odds ratio = 43, P = 5 x 10(-5)) and Finnish (n = 80, odds ratio = 22, P = 1 x 10(-6)) replication cohorts. RFX6 heterozygotes have reduced penetrance of diabetes compared to common HNF1A and HNF4A-MODY mutations (27, 70 and 55% at 25 years of age, respectively). The hyperglycaemia results from beta-cell dysfunction and is associated with lower fasting and stimulated gastric inhibitory polypeptide (GIP) levels. Our study demonstrates that heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance.
  • Hekkala, Anne M.; Ilonen, Jorma; Toppari, Jorma; Knip, Mikael; Veijola, Riitta (2018)
    We studied the frequency of diabetic ketoacidosis (DKA) in children at diagnosis of type 1 diabetes (T1D) in a region where newborn infants have since 1995 been recruited for genetic screening for human leukocyte antigen (HLA)-conferred disease susceptibility and prospective follow up. The aim was to study whether participation in newborn screening and follow up affected the frequency of DKA, and to follow the time trends in DKA frequency. We first included children born in Oulu University Hospital since 1995 when the prospective studies have been ongoing and diagnosed with T1D
  • Nyholm, Iiris; Hukkinen, Maria; Koivusalo, Antti; Merras-Salmio, Laura; Kolho, Kaija-Leena; Rintala, Risto J.; Pakarinen, Mikko P. (2019)
    Background and Aims Childhood-onset ulcerative colitis [UC] requires total colectomy in one-quarter of patients at some point of their disease. The study objective was to evaluate long-term outcomes after proctocolectomy with ileoanal anastomosis [IAA] for paediatric UC. Methods Medical records of all children undergoing proctocolectomy with IAA for UC during 1985-2016 in Helsinki University Hospital were retrospectively assessed. Data on disease history, diagnostic and operative details, occurrence of surgical complications, functional outcome, postoperative diagnosis of Crohn's disease [CD] and pouch failure were collected. Risk factors for IAA failure were analysed with Cox regression. Results Of 87 patients, 85 [98%] had UC and 2 [2%] inflammatory bowel disease unclassified [IBD-U] preoperatively. Altogether 66% underwent two-stage and 34% underwent three-stage procedures. During 7.8 [4.1-14.5] years' follow-up, nine [10%] patients were diagnosed with postoperative CD. Postoperative leakages [n = 8, 9%] and strictures [n = 10, 11%] were equally common, whereas fistulas [78% vs 9%, p Conclusions For paediatric UC, long-term surgical and functional outcomes after proctocolectomy with IAA are reassuring. Need for three-stage surgery and occurrence of postoperative fistulas and abscesses, but not leakages or strictures, associate with postoperative CD diagnosis and the risk for ileostomy.
  • Ellul, Susan; Wake, Melissa; Clifford, Susan A.; Lange, Katherine; Würtz, Peter; Juonala, Markus; Dwyer, Terence; Carlin, John B.; Burgner, David P.; Saffery, Richard (2019)
    Objectives Nuclear magnetic resonance (NMR) metabolomics is high throughput and cost-effective, with the potential to improve the understanding of disease and risk. We examine the circulating metabolic profile by quantitative NMR metabolomics of a sample of Australian 11-12 year olds children and their parents, describe differences by age and sex, and explore the correlation of metabolites in parent-child dyads. Design The population-based cross-sectional Child Health CheckPoint study nested within the Longitudinal Study of Australian Children. Setting Blood samples collected from CheckPoint participants at assessment centres in seven Australian cities and eight regional towns; February 2015-March 2016. Participants 1180 children and 1325 parents provided a blood sample and had metabolomics data available. This included 1133 parent-child dyads (518 mother-daughter, 469 mother-son, 68 father-daughter and 78 father-son). Outcome measures 228 metabolic measures were obtained for each participant. We focused on 74 biomarkers including amino acid species, lipoprotein subclass measures, lipids, fatty acids, measures related to fatty acid saturation, and composite markers of inflammation and energy homeostasis. Results We identified differences in the concentration of specific metabolites between childhood and adulthood and in metabolic profiles in children and adults by sex. In general, metabolite concentrations were higher in adults than children and sex differences were larger in adults than in children. Positive correlations were observed for the majority of metabolites including isoleucine (CC 0.33, 95% CI 0.27 to 0.38), total cholesterol (CC 0.30, 95% CI 0.24 to 0.35) and omega 6 fatty acids (CC 0.28, 95% CI 0.23 to 0.34) in parent-child comparisons. Conclusions We describe the serum metabolite profiles from mid-childhood and adulthood in a population-based sample, together with a parent-child concordance. Differences in profiles by age and sex were observed. These data will be informative for investigation of the childhood origins of adult non-communicable diseases and for comparative studies in other populations.
  • Talman, Virpi; Teppo, Jaakko Sakari; Pöhö, Päivi Anneli; Movahedi, Parisa; Vaikkinen, Anu; Karhu, Suvi Tuuli; Trošt, Kajetan; Suvitaival, Tommi; Heikkonen, Jukka; Pahikkala, Tapio; Kotiaho, Ahti Antti Tapio; Kostiainen, Risto Kalervo; Varjosalo, Markku Tapio; Ruskoaho, Heikki Juhani (2018)
    Background The molecular mechanisms mediating postnatal loss of cardiac regeneration in mammals are not fully understood. We aimed to provide an integrated resource of mRNA, protein, and metabolite changes in the neonatal heart for identification of metabolism‐related mechanisms associated with cardiac regeneration. Methods and Results Methods and results Mouse ventricular tissue samples taken on postnatal day 1 (P01), P04, P09, and P23 were analyzed with RNA sequencing and global proteomics and metabolomics. Gene ontology analysis, KEGG pathway analysis, and fuzzy c‐means clustering were used to identify up‐ or downregulated biological processes and metabolic pathways on all 3 levels, and Ingenuity pathway analysis (Qiagen) was used to identify upstream regulators. Differential expression was observed for 8547 mRNAs and for 1199 of 2285 quantified proteins. Furthermore, 151 metabolites with significant changes were identified. Differentially regulated metabolic pathways include branched chain amino acid degradation (upregulated at P23), fatty acid metabolism (upregulated at P04 and P09; downregulated at P23) as well as the HMGCS (HMG‐CoA [hydroxymethylglutaryl‐coenzyme A] synthase)–mediated mevalonate pathway and ketogenesis (transiently activated). Pharmacological inhibition of HMGCS in primary neonatal cardiomyocytes reduced the percentage of BrdU‐positive cardiomyocytes, providing evidence that the mevalonate and ketogenesis routes may participate in regulating the cardiomyocyte cell cycle. Conclusions This study is the first systems‐level resource combining data from genomewide transcriptomics with global quantitative proteomics and untargeted metabolomics analyses in the mouse heart throughout the early postnatal period. These integrated data of molecular changes associated with the loss of cardiac regeneration may open up new possibilities for the development of regenerative therapies
  • Mänty, M.; Kouvonen, A.; Nordquist, H.; Harkko, J.; Pietiläinen, O.; Halonen, J. I.; Rahkonen, O.; Lallukka, T. (2022)
    Purpose Physical work exposures are associated with sickness absence among older employees. We aimed to examine if they similarly contribute to all-cause sickness absence during early and mid-careers. Methods We used questionnaire data on physical work exposures linked to register data on sickness absence from 3542 municipal employees aged 19-39 years. Follow-up for the number of sickness absence days was 12 months. Exposures to physical workload, occupational environmental hazards, and sedentary work were divided into quartiles. In addition, duration of daily exposure to heavy work was included. Negative binomial regression models were used. Results Higher exposure to physical workload or hazardous exposures was associated with a higher number of sickness absence days. The age and gender adjusted rate ratios for sickness absence days among the participants whose exposure to physical workload was in the highest exposure quartile were 2.1 (95% CI 1.8-2.5) compared with those whose exposure was in the lowest quartile. In addition, rate ratios for sickness absence days among participants who reported that they do heavy physical work 1.1-2.0 h, 2.1-4.0 h or over 4 h daily were 1.6 (1.3-1.9), 1.5 (1.3-1.8) and 1.7 (1.5-2.1), respectively, compared with those who reported not doing physical work. Further adjustment for lifestyle factors or health characteristics attenuated the associations only slightly. Conclusion Exposure to physically demanding work is associated with a higher number of sickness absence days among municipal employees below 40 years of age. Physical working conditions should be considered when aiming to support later work ability.
  • Gyllenberg, Frida; Saloranta, Tuire; But, Anna; Gissler, Mika; Heikinheimo, Oskari (2020)
    Objective: To identify factors associated with choosing long-acting reversible contraception (LARC) (intrauterine device or contraceptive implant), when provided free-of-charge. Study design: This register-based cohort study comprises all women living in the city of Vantaa in the Helsinki metropolitan area during 2013-2014, with information on LARC initiations retrieved from electronic health records. Since January 2013, women in Vantaa can receive their first LARC method free-of-charge at public contraceptive clinics. We performed multivariable regression to assess seven predictors based on literature and four predictors based on gynecological history for association with choosing LARC in this population. Results: In 2013-2014, 9669 women entitled to a free-of-charge method visited a public clinic and 2035 (21.0%) women initiated LARC. Factors most associated with LARC initiation included history of delivery (odds ratio [OR] 5.4, 95% confidence intervals [CI] 4.7-6.2) and induced abortion (OR 1.4, 95%CI 1.2-1.6), and no previous visit at the clinic (OR 1.3, 95%CI 1.2-1.5). Previous delivery was associated with LARC initiation in all age-groups (OR, 95%CI by age-group; 15-19 years: 10.8, 5.1-23.4; 20-24 years: 6.4, 4.9-8.3; 25-29 years: 6.7, 5.2-8.6; 30-44 years: 3.6, 2.9-4.6). Conclusion: History of delivery and induced abortion were strongly associated with choosing a LARC method, even though all women in the population were entitled to their first free-of-charge LARC method. The association was particularly strong among women less than 25 years of age. Implications statement: Untargeted provision of free-of-charge LARC in public contraceptive services reached women with previous delivery or abortion well during the programs first years. However, as LARCs are recommended to all women, future research should focus on how uptake evolves and how to reach all women in need of long-term, effective contraception. (C) 2020 Elsevier Inc. All rights reserved.