Four and a half LIM protein 1C (FHL1C)

Four-and-a-half LIM domain protein 1 isoform A (FHL1A) is predominantly expressed in skeletal and cardiac muscle. Mutations in the FHL1 gene are causative for several types of hereditary myopathies including X-linked myopathy with postural muscle atrophy (XMPMA). We here studied myoblasts from XMPMA patients. We found that functional FHL1A protein is completely absent in patient myoblasts. In parallel, expression of FHL1C is either unaffected or increased. Furthermore, a decreased proliferation rate of XMPMA myoblasts compared to controls was observed but an increased number of XMPMA myoblasts was found in the G(0)/G(1) phase. Furthermore, low expression of K(v1.5), a voltage-gated potassium channel known to alter myoblast proliferation during the G(1) phase and to control repolarization of action potential, was detected. In order to substantiate a possible relation between K(v1.5) and FHL1C, a pull-down assay was performed. A physical and direct interaction of both proteins was observed in vitro. In addition, confocal microscopy revealed substantial colocalization of FHL1C and K(v1.5) within atrial cells, supporting a possible interaction between both proteins in vivo. Two-electrode voltage clamp experiments demonstrated that coexpression of K(v1.5) with FHL1C in Xenopus laevis oocytes markedly reduced K(+) currents when compared to oocytes expressing K(v1.5) only. We here present the first evidence on a biological relevance of FHL1C

Reconsidering the developmental origins of adult disease paradigm: the ‘metabolic coordination of childbirth’ hypothesis

In uncomplicated pregnancies, birthweight is inversely associated with adult non-communicable disease (NCD) risk. One proposed mechanism is maternal malnutrition during pregnancy. Another explanation is that shared genes link birthweight with NCDs. Both hypotheses are supported, but evolutionary perspectives address only the environmental pathway. We propose that genetic and environmental associations of birthweight with NCD risk reflect coordinated regulatory systems between mother and fetus, that evolved to reduce risks of obstructed labour. First, the fetus must tailor its growth to maternal metabolic signals, as it cannot predict the size of the birth canal from its own genome. Second, we predict that maternal alleles that promote placental nutrient supply have been selected to constrain fetal growth and gestation length when fetally expressed. Conversely, maternal alleles that increase birth canal size have been selected to promote fetal growth and gestation when fetally expressed. Evidence supports these hypotheses. These regulatory mechanisms may have undergone powerful selection as hominin neonates evolved larger size and encephalisation, since every mother is at risk of gestating a baby excessive for her pelvis. Our perspective can explain the inverse association of birthweight with NCD risk across most of the birthweight range: any constraint of birthweight, through plastic or genetic mechanisms, may reduce the capacity for homeostasis and increase NCD susceptibility. However, maternal obesity and diabetes can overwhelm this coordination system, challenging vaginal delivery while increasing offspring NCD risk. We argue that selection on viable vaginal delivery played an over-arching role in shaping the association of birthweight with NCD risk

HLA-G - evolvement from a trophoblast specific marker to a checkpoint molecule in cancer, a narrative review about the specific role in breast- and gynecological cancer

Human leukocyte antigen G (HLA-G) is known as a non-classical molecule of the major histocompatibility complex class Ib and downregulates the mother's immune response against the fetus during pregnancy, thereby generating immune tolerance. Due to the latter effect, HLA-G is also referred to as an immune checkpoint molecule. Originally identified on extravillous trophoblasts, HLA-G is already known to induce immune tolerance at various stages of the immune response, for example through cell differentiation and proliferation, cytolysis and cytokine secretion. Because of these functions, HLA-G is involved in various processes of cancer progression, but a comprehensive review of the role of HLA-G in gynecologic cancers is lacking. Therefore, this review focuses on the existing knowledge of HLA-G in ovarian cancer, endometrial cancer, cervical cancer and breast cancer. HLA-G is predominantly expressed in cancer tissues adjacent to the extravillous trophoblast. Therefore, modulating its expression in the cancer target tissues of cancer patients could be a potential therapeutic approach to treat these diseases

Physical activity and sedentary time across pregnancy and associations with neonatal weight, adiposity and cord blood parameters:a secondary analysis of the DALI study

Background/Objectives: Obesity during pregnancy is associated with neonatal adiposity, which is a risk factor for childhood obesity. Maternal physical activity (PA) and sedentary behaviours during pregnancy might modify this risk. We therefore studied associations between maternal PA and sedentary time (ST) during pregnancy and neonatal anthropometry and cord blood parameters and investigated whether associations differed by offspring sex. Subjects/Methods: Participants of the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention (DALI) study with a BMI ≥ 29 kg/m2 were analysed as a cohort. Maternal moderate-to-vigorous PA (MVPA) and ST were measured repeatedly with accelerometers across pregnancy. Associations between mean levels and changes in MVPA and ST and birthweight, neonatal adiposity (fat mass (FM)%) and cord blood parameters, including C-peptide, leptin and lipids, were analysed in 213 mother-child pairs with Bayesian multilevel models. Interactions with offspring sex were considered. Results: Almost all women decreased MVPA levels and increased ST throughout gestation. Both higher maternal mean MVPA and increasing MVPA were associated with lower offspring FM% in males (−0.520%; 95% CI: −1.011%, −0.031% and −4.649%; −7.876%, −1.432% respectively). In female offspring, mean ST was associated with lower cord blood C-peptide (−0.145 µg/l; −0.279 µg/l, −0.005 µg/l). No associations were found with birthweight or other cord blood parameters. Conclusions: Maternal MVPA is associated with neonatal fat mass, but not birthweight, in male offspring. Our findings underline the importance of physical activity throughout pregnancy.</p

Beliefs, barriers and preferences of European overweight women to adopt a healthier lifestyle in pregnancy to minimize risk of developing gestational diabetes mellitus: an explorative study

Introduction: Overweight and obese women are at high risk of developing gestational diabetes mellitus (GDM). Lifestyle programs might help curb the GDM risk. We explored beliefs, perceived barriers and preferences regarding lifestyle changes among overweight European pregnant women to help inform the development of future high quality lifestyle interventions. Methods: An explorative mixed methods, two-staged study was conducted to gather information from pregnant European women (BMI≥25kg/m2). In three European countries (Belgium, Netherlands, United Kingdom) interviews were conducted, followed by questionnaires in six other European countries (Austria, Denmark, Ireland, Italy, Poland, Spain). Content analysis, descriptive and chi square statistics were applied (p&#60;0.05). Results: Women preferred to obtain detailed information about their personal risk. The health of their baby was major motivating factor. Perceived barriers for physical activity included pregnancy-specific issues such as tiredness and experiencing physical complaints. Insufficient time was a barrier more frequently reported by women with children. Abstaining from snacking was identified as a challenge for the majority of women, especially for those without children. Women preferred to obtain support from their partner, as well as health professionals and valued flexible lifestyle programs. Conclusions: Healthcare professionals need to inform overweight pregnant women about their personal risk, discuss lifestyle modification and assist in weight management. Lifestyle programs should be tailored to the individual, taking into account barriers experienced by overweight first-time mothers and multipara women

Placental structural adaptation to maternal physical activity and sedentary behavior:Findings of the DALI lifestyle study

STUDY QUESTION: Are maternal levels of moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) in obese pregnant women associated with placental structural adaptations for facilitating oxygen delivery to the fetus?SUMMARY ANSWER: Higher maternal MVPA and ST are associated with a higher density of villi, a proxy measure of placental surface area for oxygen delivery to the fetus, without further added placental vessels. WHAT IS KNOWN ALREADY: Physical activity during pregnancy intermittently reduces uterine blood flow, potentially limiting placental and fetal oxygen supply. The placenta can mount several adaptive responses, including enlargement of the surface area of villi and/or feto-placental vessels to accommodate fetal needs. Early research on the morphology and growth of the placenta with exercise interventions has shown inconsistencies and is lacking, particularly in non-lean pregnant women. STUDY DESIGN, SIZE, DURATION: This study is a secondary longitudinal analysis of the vitamin D and lifestyle intervention for gestational diabetes prevention (DALI) randomized controlled trial. The prospective study was conducted between 2012 and 2015 in nine European countries at 11 different sites. In this analysis, 92 pregnant women with a BMI ≥ 29 kg/m2 were combined into one cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: MVPA and percentage of time spent sedentary (% ST) were measured with accelerometers during gestation. Placental sections were immunostained for endothelial cell-specific CD34. Artificial intelligence (AI)-based stereology assessed villous density, number, and cross-sectional area of vessels on whole-slide images and in selected regions comprising peripheral villi only, where the majority of vascular adaptations occur. Expression of pro- and anti-angiogenic factors was quantified using molecular counting analysis. MAIN RESULTS AND THE ROLE OF CHANCE: In multivariable regression, higher levels of maternal MVPA (min/day) were associated with a higher density of villi in both whole-slide images (beta 0.12; 95% CI 0.05, 0.2) and selected regions (0.17; CI 0.07, 0.26). Unexpectedly, ST was also positively associated with density of villi (0.23; CI 0.04, 0.43). MVPA and ST were not associated with vessel count/mm2 villous area, vessel area, or pro- and anti-angiogenic factor mRNA expression. All estimates and statistical significance of the sensitivity analyses excluding smokers, women who developed gestational diabetes or pre-eclampsia and/or pregnancy-induced hypertension were similar in the main analysis. LIMITATIONS, REASONS FOR CAUTION: The placenta is a complex organ undergoing dynamic changes. While various adjustments were made to account for different maternal contributing factors, in addition to the outcome measures, various other factors could impact oxygen delivery to the fetus. WIDER IMPLICATIONS OF THE FINDINGS:For the first time, we evaluated the association between placental structures quantified using an AI-based approach with objectively measured physical activity and ST at multiple time points in pregnant women with obesity. The observed adaptations contribute to the advancement of our understanding of the hemodynamics and adaptations of the placental unit in response to MVPA and ST. However, our results might not be generalizable to lean pregnant women. STUDY FUNDING/COMPETING INTEREST(S):The DALI project has received funding from the European Community's 7th Framework Program (FP7/2007-2013) under grant agreement no. 242187. The funders had no role in study design, collection of data, analyses, writing of the article, or the decision to submit it for publication. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER:ISRCTN70595832.</p

Traumapotilaan golden hour Kainuun ensihoidossa : Tutkimus traumapotilaan golden hour:n toteutumisesta sekä siihen vaikuttavista tekijöistä Kainuun ensihoidossa

Tutkimuksen tarkoituksena oli kuvailla Kainuun ensihoidon laatua traumapotilaiden hoidossa. Opinnäytetyömme on tehty yhteistyössä Kainuun sosiaali- ja terveydenhuollon kuntayhtymän ensihoidon kanssa. Tutkimuksen tavoitteena oli hyödyntää tutkimusta Kainuun ensihoidossa traumapotilaiden hoidon kehittämisessä. Tutkimuksemme on toteutettu kvantitatiivisena ja retrospektiivisena tutkimuksena. Aineiston keräämiseen käytimme valmista tiedonkeruupohjaa, johon keräsimme 391 ensihoitotehtävän tiedot. Analysoimme tutkimuksen tulokset Excel- ja SPSS-ohjelmilla. Tutkimuksen perusteella 50 % (N= 196) traumapotilaista pääsi kultaisen tunnin aikana lopulliseen hoitopaikkaan. Keskimäärin ensihoitajilla kului kohteessa 21 minuuttia, joka on yli suositellun 10 minuutin. Tutkimuksen mukaan 15 %:lla (N= 58) ensihoitotehtävistä kuljetus päästiin aloittamaan 10 minuutin sisällä. Tutkimuksessa kävi ilmi, että mitä enemmän kohteessa tehtiin hoitotoimenpiteitä, sitä pidempi kohteessa oloaika oli. Tutkimuksessa kävi ilmi, että ensihoitotehtävien kokonaisajasta suurin osa kului matkalla potilaan luokse ja potilaan kuljettamiseen hoitolaitokseen. Tämä selittyy Kainuun alueen pitkillä välimatkoilla. Ensihoitotehtävien kokonaisaika kasvoi huomattavasti, mikäli potilas jatkokuljetettiin Kainuun keskussairaalasta yliopistolliseen sairaalaan Ouluun. Ensihoitotehtävillä, joissa potilas jatkokuljetettiin, aikaa kului merkittävästi keskussairaalassa potilaan tilan stabilointiin ennen jat-kokuljetuksen aloittamista. Tutkimme myös vaikuttaako ensihoitotehtävien kokonaisaikaan eri viranomaisjohtajuudet. Tutkimuksen perusteella voidaan todeta, että poliisijohtoisilla ensihoitotehtävillä kohteessa oloaika oli keskimäärin kaikista lyhyin. Opinnäytetyötämme voidaan hyödyntää ensihoidon laadun kehittämiseksi Kainuun ensihoidossa sekä henkilöstön ammattitaidon ylläpitämiseksi. Tutkimustuloksia voidaan käyttää simulaatiokoulutuksen suunnittelun tukena, jolloin tunnistetaan mahdolliset kehittämishaasteet ensihoitajien toiminnassa. Traumapotilaiden lopullinen hoito tapahtuu aina sairaalassa, jossa on mahdollista saada mm. leikkaushoitoa. Jotta traumapotilas saa parasta mahdollista hoitoa, tulee ensihoidossa pyrkiä mahdollisimman nopeaan kuljetukseen, jolla pyritään turvaamaan traumapotilaan nopea sairaalahoitoon pääsy.Purpose of this study was to describe the quality of emergency care in Kainuu in trauma patients care. Our thesis is made in co-operation with emergency care centre of Kainuu. Objective of the study was to exploit research in developing of care for trauma patients in emergency care of Kainuu. Our study is implemented as a quantitative and retrospective research. For collecting the material, we used ready data collection sheet which we gathered the information of 391 alarms. We analyzed the result of the research by using Excel- and SPSS-programs. Based on the study 50% (N= 196) of trauma patients were transported in the final sequel care facility during the golden hour. Paramedics spent approximately 21 minutes on scene which is over than the recommended 10 minutes. According to the study in 15% (N= 58) of the alarms transportation was achieved to start within 10 minutes. The study showed that the on-scene time was the longer the more procedures were accomplished in the destination. The study also showed that most of the time on the alarms were spent by travelling to the patient and transporting the patient to care facility. This is explained by the long distances of the area of Kainuu. The total time of alarms was highly increased if the patient was sequel transported from central Hospital of Kainuu to University Hospital in Oulu. In alarms which the patient was sequel transported, significant amount of time was spent in central Hospital stabilizing the patient before continuing the transport. We also investigated if authority leaderships affect to the total time spent on alarms. The study lightened out that in those alarms which was lead by police, the on-scene time was averagely shortest. Our thesis can be utilized in developing the quality of emergency care in Kainuu and maintaining the professionality of personnel. Results of the study can be used as a support of simulation education which allows to identify the possible developing challenges in the action of paramedics. The final care of trauma patients always occurs at hospital where multiple procedures are availa-ble. To guarantee that the patient receives best care, must emergency care always strive to quick transportation which secures that patients gets quickly the care they need

Distinct maternal metabolites are associated with obesity and glucose-insulin axis in the first trimester of pregnancy

BACKGROUND/OBJECTIVES: Obesity in pregnancy associates with changes in the glucose-insulin axis. We hypothesized that these changes affect the maternal metabolome already in the first trimester of human pregnancy and, thus, aimed to identify these metabolites.PATIENTS/METHODS: We performed untargeted metabolomics (HPLC-MS/MS) on maternal serum (n = 181, gestational weeks 4+0-11+6). For further analysis, we included only non-smoking women as assessed by serum cotinine levels (ELISA) (n = 111). In addition to body mass index (BMI) and leptin as measures of obesity and adiposity, we metabolically phenotyped women by their fasting glucose, C-peptide and insulin sensitivity (ISHOMA index). To identify metabolites (outcome) associated with BMI, leptin, glucose, C-peptide and/or ISHOMA (exposures), we used a combination of univariable and multivariable regression analyses with multiple confounders and machine learning methods (Partial Least Squares Discriminant Analysis, Random Forest and Support Vector Machine). Additional statistical tests confirmed robustness of results. Furthermore, we performed network analyses (MoDentify package) to identify sets of correlating metabolites that are coordinately regulated by the exposures.RESULTS: We detected 2449 serum features of which 277 were annotated. After stringent analysis, 15 metabolites associated with at least one exposure (BMI, leptin, glucose, C-peptide, ISHOMA). Among these, palmitoleoyl ethanolamine (POEA), an endocannabinoid-like lipid endogenously synthesized from palmitoleic acid, and N-acetyl-L-alanine were consistently associated with C-peptide in all the analyses (95% CI: 0.10-0.34; effect size: 21%; p &lt; 0.001; 95% CI: 0.04-0.10; effect size: 7%; p &lt; 0.001). In network analysis, most features correlating with palmitoleoyl ethanolamide and N-acetyl-L-alanine and associated with C-peptide, were amino acids or dipeptides (n = 9, 35%), followed by lipids (n = 7, 27%).CONCLUSIONS: We conclude that the metabolome of pregnant women with overweight/obesity is already altered early in pregnancy because of associated changes of C-peptide. Changes of palmitoleoyl ethanolamide concentration in pregnant women with obesity-associated hyperinsulinemia may reflect dysfunctional endocannabinoid-like signalling.</p