Background: The immunological environment during pregnancy may differ between allergic and non-allergic women. This study investigates the effect of maternal allergy on the allergen-induced cytokine and chemokine levels and whether pregnancy modulates these immune responses differently in allergic and non-allergic women. Methods: The birch-, cat-, phytohemagglutinin- and tetanus toxoid-induced interferon-gamma(IFN-gamma), interleukin (IL)-4, IL-5, IL-10, IL-13, the T-helper 1 (Th1)-associated chemokine CXCL10 and the Th2-associated chemokine CCL17 levels were quantified in 20 women with allergic symptoms (sensitized, n=13) and 36 women without allergic symptoms (non-sensitized, n=30) at gestational weeks 10-12, 15-16, 25, 35 and 2 and 12months post-partum. Results: Birch-, but not cat-induced, IL-5, IL-13 and CCL17 levels were increased during pregnancy as compared to post-partum in the sensitized women with allergic symptoms. In contrast, cat-, but not birch-induced, IL-5 and IL-13 levels were increased during pregnancy as compared to post-partum in the non-sensitized women without allergic symptoms. Furthermore, IFN-gamma secretion was increased in the first and decreased in the second and third trimesters in response to birch and decreased in the third trimester in response to cat as compared to post-partum in the non-sensitized women without allergic symptoms. Increased allergen-induced IL-4, IL-5 and IL-13 levels were associated with allergic symptoms and sensitization. Conclusions: Pregnancy had a clear effect on the allergen-induced IL-5, IL-13, CCL17, IFN-gamma and CXCL10 production, with distinct enhanced Th2-responses to birch in the allergic group and to cat in the non-allergic group.

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The complex and diverse intestinal microbiome is recognized as important in promoting human health. An altered gut microflora, referred to as dysbiosis, is increasingly recognized as having an etiologic role in a variety of conditions, including functional gastrointestinal disorders: colic in infants and irritable bowel syndrome in older children. Probiotics are defined as live microorganisms that, if ingested in sufficient amounts, restore microbial homeostasis and have a benefit on health. Randomized controlled trials indicate that probiotics can be effective in a variety of intestinal conditions, including colic and irritable bowel syndrome. Probiotics may promote gut microbial diversity, but timing of the intervention appears crucial. Strain-specific effects on colonization resistance, epithelial barrier integrity, modulation of signal transduction, impacts on innate and adaptive immune responses, and effects on visceral hyperalgesia likely explain the observed variability in various probiotic strains. In the future, probiotics are likely to be chosen for use in a defined clinical setting based on underlying mechanism(s) of action. The precise component of the probiotic agent mediating observed effects is the subject of current research. Unresolved issues relate to optimal dosages, timing of ingestion, single versus combination formulations, maintenance of viability in storage, and the merits of employing probiotic- derived products. (C) 2017 Nestec Ltd., Vevey/S. Karger AG, Basel

Poor adherence with growth hormone (GH) therapy has been associated with worse clinical outcomes, which in children relates specifically to their linear growth and loss of quality of life. The "360 degrees GH in Europe" meeting, held in Lisbon, Portugal, in June 2016 and funded by Merck KGaA (Germany), examined many aspects of GH diseases. The three sessions, entitled "Short Stature Diagnosis and Referral," "Optimizing Patient Management," and "Managing Transition," each benefited from three guest speaker presentations, followed by an open discussion and are reported as a manuscript, authored by the speakers. Reported here is a summary of the proceedings of the second session, which reviewed the determinants of GH therapy response, factors affecting GH therapy adherence and the development of innovative technologies to improve GH treatment in children. Response to GH therapy varies widely, particularly in regard to the underlying diagnosis, although there is little consensus on the definition of a poor response. If the growth response is seen to be less than expected, the possible reasons should be discussed with patients and their parents, including compliance with the therapy regimen. Understanding and addressing the multiple factors that influence adherence, in order to optimize GH therapy, requires a multi-disciplinary approach. Because therapy continues over many years, various healthcare professionals will be involved at different periods of the patients journey. The role of the injection device for GH therapy, frequent monitoring of response, and patient support are all important for maintaining adherence. New injection devices are incorporating electronic technologies for automated monitoring and recording of clinically relevant information on injections. Study results are indicating that such devices can at least maintain GH adherence; however, acceptance of novel devices needs to be assessed and there remains an on-going need for innovations.

Background: Parenthood is a life transition that can be especially demanding for vulnerable individuals. Young maternal age and maternal single status have been reported to increase the risk for adverse outcomes for both mother and child. The aim of this study was to investigate the effect of young maternal age and maternal single status on maternal and child mental health and child development at age 3. Methods: A birth-cohort of 1723 mothers and their children were followed from birth to age 3. Sixty-one mothers (3.5%) were age 20 or younger, and 65 (4.0%) reported single status at childbirth. The mothers filled out standardized instruments and medical information was retrieved from the standardized clinical assessment of the children at Child Welfare Centers, (CWC). Results: Young maternal age was associated with symptoms of postpartum depression whereas single status was not. Young mothers were more prone to report internalizing and externalizing problems in their children, while there was no association between single status and child behavioral problems. No differences were seen on child development (CWC scores). School drop-out was, however, a more influential factor on depressive symptoms postpartum than maternal age. Conclusion: Young mothers are at increased risk for symptoms of postpartum depression which indicates the need for attention in pre- and postnatal health care programs. Single mothers and their children were not found to be at increased risk for adverse outcomes. The importance of schooling was demonstrated, indicating the need for societal support to encourage adolescents to remain in school.

In the adult population, psychiatric disorders are associated with somatic illness. Explanatory life style factors have been found, but also a failure to recognize somatic illness in this group. Another factor is side effects from long-term use of antipsychotic drugs. Given the psychiatric-somatic comorbidity in the adult population, it is of interest to investigate whether an association exists already during childhood. The aim of the present study was to investigate the frequency of somatic illness in children and adolescents with a psychiatric diagnose. Data were obtained from the regional health care database Vega, Sweden. Psychiatric and somatic diagnoses obtained during 2011-2013 for individuals aged 3-18 years were extracted. Descriptive statistics were used to examine difference in somatic morbidity between children with and without psychiatric diagnoses. Logistic regression was used in age-stratified models to test the association between psychiatric and somatic diagnoses. Anxiety and behavioral disorders were associated with all somatic conditions investigated at nearly all ages. The same applied to substance use, investigated at age 9-18 years. Affective disorders were associated with all somatic conditions at age 12-18 years. Psychotic conditions were associated with asthma, bowel disorders and myalgia in adolescents. Children with psychiatric disorders are at remarkably high risk for concurrent somatic illness. The associations span across many types of conditions and across all ages. The results support the need for awareness of somatic morbidity in child and adolescent psychiatric clinical settings, and the need for coordinated health care for children with comorbid states.

An increasing prevalence of mental health problems calls for more knowledge into factors associated with resilience. The present study used multiple statistical methodologies to examine a biopsychosocial model of risk and resilience on preadolescence behavior. Data from 889 children and mothers from a birth cohort were used. An adversity score was created by combining maternal symptoms of depression, psychosocial risk and childrens experiences of life events. The proposed resilience factors investigated were candidate genetic polymorphisms, child temperament, social functioning, and maternal sense of coherence. The l/ l genotype of the serotonin transporter linked polymorphic region was associated with lower internalizing scores, but not mainly related to the level of adversity. An easy temperament was associated with resilience for children exposed to high adversity. Social functioning was found to be promotive independent of the risk level. The results support a multiple-level model of resilience indicating effects, though small, of both biological and psychosocial factors.

Fungal rhinosinusitis occurs in different forms depending on race and region. While allergic fungal rhinosinusitis is common in Caucasians, fungal ball (FB) is more common in Asians. However, most cases are reported as unilateral, and clinical data on bilateral FB (BFB) are rare. Therefore, the purpose of this study was to analyze and to compare the clinical characteristics of BFB and unilateral FB (UFB) in Koreans.

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Genome Resource Banks are keystones in the ex-situ conservation of wild species. Post-mortem (PM) collection of epididymal spermatozoa is an opportunistic and valuable source of germplasm, the time from the death of the animal limits its use. Seeking to improve germplasm preservation strategies for the chamois (Rupicapra sp.), the effect of PM time on epididymal sperm quality and freezability was studied using the Cantabrian chamois. Samples were classified according to PM collection time, up to 216 h (refrigerated), and cryopreserved (Tris-citric acid-fructose, 430 mOsm/kg, 15% egg yolk, 8% glycerol; freezing at - 20 degrees C/min). Sperm quality was assessed after recovery and post-thawing (motility by CASA, HOS test, abnormal forms, cytoplasmic droplets, and viability and acrosomal damage by flow cytometry). The sperm mass pH and osmolality showed a positive correlation with time. Total sperm motility dropped after 2 days PM, with progressivity and sperm velocities remained similar up to 3 days PM. Sperm freezability was acceptable, with the post-thawing HOST, motility, progressivity, VAP, VCL, VSL and BCF negatively correlating with PM time. Overall, chamois epidydimal samples were not adequate for preservation after 6 days PM. Freezability capacity could make these spermatozoa suitable for specific ART even if kept refrigerated for several days PM.

Mating or cervical deposition of spermatozoa or seminal plasma (SP) modifies the expression of genes affecting local immune defense processes at the oviductal sperm reservoir in animals with internal fertilization, frequently by down-regulation. Such responses may occur alongside sperm transport to or even beyond the reservoir. Here, immune-related gene expression was explored with cDNA microarrays on porcine cervix-to-infundibulum tissues, pre-/peri-ovulation. Samples were collected 24 h post-mating or cervical deposition of sperm-peak spermatozoa or SP (from the sperm-peak fraction or the whole ejaculate). All treatments of this interventional study affected gene expression. The concerted action of spermatozoa and SP down-regulated chemokine and cytokine (P00031), interferon-gamma signaling (P00035), and JAK/STAT (P00038) pathways in segments up to the sperm reservoir (utero-tubal junction (UTJ)/isthmus). Spermatozoa in the vanguard sperm-peak fraction (P1-AI), uniquely displayed an up-regulatory effect on these pathways in the ampulla and infundibulum. Sperm-free SP, on the other hand, did not lead to major effects on gene expression, despite the clinical notion that SP mitigates reactivity by the female immune system after mating or artificial insemination.

Seminal plasma (SP) is a complex fluid containing proteins, peptides, enzymes, hormones as well as extracellular vesicles (EVs). The SP interacts with spermatozoa and the inner cell lining of the female genital tract, adsorbing proteins and exosomes that modulate sperm functions and female immune responsiveness. In the present study, boar sperm-free SP was studied using flow cytometry (FC) after membrane tetraspanins (CD9, CD63 and CD81) and membrane receptor CD44 marking of non-enriched (whole SP) or gradient fractions enriched through two-step discontinuous KBr-density-gradient ultracentrifugation, in whole ejaculate or in selected ejaculate fractions. The results, evaluated by transmission electron microscopy, confirmed the presence of exosomes in all fractions of the pig SP. Noteworthy, these pig SP-exosomes were CD44-bearing when analysed by FC, with bands detected by western blotting (WB) at the expected 85 kD size. The two-step discontinuous KBr-density-gradient ultracentrifugation enriched the population of exosomes in two specific gradient fractions, indicating exosomes (either prostasomes or epididymosomes) could be separated from low-density lipoprotein (LDL) but they co-sediment with the high-density lipoprotein (HDL)-bearing fraction. The findings pave for the selective isolation of exosomes in functional studies of their function when interacting with spermatozoa, the oocyte and/or the female genitalia, including hyaluronan-CD44 interplay. (C) 2019 Elsevier Inc. All rights reserved.

Presence of the hyaluronan (hyaluronic acid, HA) receptor CD44 on spermatozoa has been difficult to pursue, mostly obeying to the use of different commercial mono- and/or polyclonal antibodies, often lacking proper controls. Here, we describe how the presence (Western blotting) and specific location (immunocytochemistry) of the CD44 receptor differs in ejaculated pig spermatozoa depending on the type of antibody and protocol used. While we were able to detect binding to spermatozoa and mark its presence in the sperm membrane, the use of blocking peptides clearly indicated that only the monoclonal antibody could confirm the specific presence and location of the CD44 receptor, whereas the polyclonal antibody was detecting multiple presumed CD44 isoforms or degraded proteins thus proving unspecific. These results call for strict protocols when attempting immunological determination of sperm membrane receptors.

Hyaluronan (hyaluronic acid, HA) apparently improves sperm survival in vitro and in vivo (oviduct), maintaining sperm motility and inducing capacitation, but not acrosome exocytosis, either by direct action as a macromolecule or via CD44 membrane receptors. This study explored ejaculated, liquid-extended pig spermatozoa to ascertain (i) the presence (Western blotting) and specific location (immunocytochemistry) of the CD44 receptor, using a specific monoclonal commercial antibody; (ii) whether the CD44 receptor changed location when exposed to bicarbonate, a capacitating trigger, in vitro; and (iii) whether the addition of HA, of molecular size comparable to that produced in the oviduct sperm reservoir (0.0625 to 2.0 mg/ml; 0 HA: control), to semen extenders would improve sperm liquid storage in vitro or cryosurvival post freezing. Variables tested were sperm velocity and progressive motility (Qualisperm (TM)), sperm viability and acrosome status, membrane integrity and early destabilization, mitochondrial activation, and superoxide production (flow cytometry). The CD44 receptor presence in ejaculated, liquid-stored AI boar spermatozoa, as confirmed by a porcine-specific monoclonal antibody, maintained its membrane location under in vitro capacitation-inducing conditions. HA exposure to 24-, 48-, or 72-h liquid-stored (17-20 degrees C) spermatozoa lowered sperm velocity in membrane-intact spermatozoa, but increased mitochondrial superoxide production. Finally, HA addition during cooling did not improve cryosurvival but did increase mitochondrial activation and membrane destabilization in surviving cells. These results confirm the existence of a CD44 receptor in pig spermatozoa, but the usefulness of adding HA for long-term storage or cryopreservation of liquid-stored, extended boar semen remains in question, thereby warranting further non-empirical analyses of HA-sperm membrane interactions.

Objective: Despite the use of high proportions of the chemically undefined lipoprotein/phospholipid-rich egg-yolk in extenders, boar sperm are highly sensitive to cooling, which induces ROS generation and disrupts the plasma membrane.

Here, we studied whether replacement of hen egg-yolk by commercially defined lecithin phospholipids, derived from egg (LPGE: phosphatidyl glycerol, LPCE: phosphatidyl choline) or soybean (LPCS: phosphatidyl choline), could individually ameliorate such oxidative effects during cryopreservation of ejaculated (sperm rich fraction, SRF) or of cauda-epididymal sperm, retrieved post-mortem from the same males.

Methods: A conventional extender (lactose buffer, with 20% egg-yolk, 0.5% OEP and 3% glycerol) was used as control. Cryodamage was assessed as loss of sperm motility, membrane and acrosome intactness, early membrane destabilization changes, mitochondrial potential, superoxide and ROS production, to finally determine lipid peroxidation (LPO) using specific probes.

Results and conclusion: In general, the exogenous phospholipids assayed were unable of maintaining neither sperm motility nor viability post-thaw compared to controls, owing to increased ROS production and lipid peroxidation. In our study, mitochondrial superoxide production resulted in very high levels for all groups, whereas both ROS production and lipid peroxidation were reduced in the control group, containing emulsified hen egg yolk. Further studies using various dosage and combination of LPCS should be followed for their eventual protective effect.

Keywords: Cryodamage; Sperm; Boar; Mitochondrial activation; Mitochondrial superoxide; ROS production; Lipid peroxidation

Introduction. Our aim was to investigate the rate of vascular dementia and dementia in women with previous hypertensive disorders in pregnancy, since white matter lesions of the brain and cardiovascular disease are linked both to dementia and hypertensive disorders in pregnancy. Material and methods. Prospective population-based registry study on all women giving birth in Sweden between 1973 and 1975 (284 598). Women with and without hypertensive disorders in pregnancy were identified by means of the Swedish Medical Birth Register and linked to the National Patient Register, where data on somatic disease later in life were obtained. International classification of disease was used. The Cox proportional hazard model was used to calculate hazard ratios for both groups and adjusted for possible confounders. Main outcome measures were in-hospital diagnosis of cardiovascular disease, vascular dementia and dementia. Results. No increased risks were seen for vascular dementia or dementia after any hypertensive disorders in pregnancy. If broken down in specific diagnoses for hypertensive disease in pregnancy, adjusted risks for vascular dementia after hypertension and proteinuria during pregnancy the hazard ratio was 6.27 (95% CI 1.65-27.44). Higher risks for cardiovascular disease were confirmed. Conclusions. Because of the very low absolute risk, the wide confidence interval and risk of misclassification, our results on vascular dementia could be questioned. Considering the pathophysiology of preeclampsia, the findings of brain lesions and the increased risk for cardiovascular disease, the possibly increased risk for all kinds of dementia must be investigated in larger and more well-defined cohorts.

PURPOSE: The whole family is affected when a child has atopic dermatitis (AD), and parents experience sleep disruption related to the child's condition leading to physical and mental exhaustion, mood swings, loss of concentration and lower job performance. This study aimed to explore and describe perceptions of sleep in parents of children <2 years old with AD, consequences of parental sleep loss, and what strategies the parents used to manage sleep loss and to improve sleep.

DESIGN AND METHODS: This qualitative interview study had an inductive and descriptive design. Twelve parents (eleven mothers and one father) participated in the study. Data analysis was performed using a phenomenographic approach.

RESULTS: Three categories of description were found: Acceptance and normalization of parental sleep loss; Changed routines and behavior to compensate for sleep loss; and Support is needed to gain sleep and manage daily life.

CONCLUSIONS: Sleep loss due to the child's AD affected the parents' emotional state, mood, well-being, cognitive function, ability to concentrate and take initiative, and sensitivity to stress and sound negatively. The parents managed their sleep loss mainly by changing their behavior and creating new routines, by taking me-time and through support from partners.

PRACTICE IMPLICATIONS: Pediatric nurses should acknowledge sleep loss in parents of small children with AD in time to prevent negative consequences, which affect the well-being of the entire family. Advice on how to improve sleep should be given early to increase the parents' understanding, make them feel safer and strengthen them in their parenthood.

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AimIn February 2016, Sweden upheld its ban on surrogacy following a Government enquiry. This survey investigated attitudes towards surrogacy among primary health professionals working with children and their experiences of working with families following surrogacy abroad. MethodsFrom April to November 2016, nurses, physicians and psychologist working in primary child health care in four counties in Sweden were invited to participate in a cross-sectional online survey about surrogacy. ResultsThe mean age of the 208 participants was 49.2years (range 27-68) and nearly 91% were women. Approximately 60% supported legalised surrogacy. Wanting a conscience clause to be introduced in Sweden was associated with not supporting surrogacy for any groups, while personal experiences of infertility and clinical experiences with families following surrogacy were associated with positive attitudes towards surrogacy for heterosexual couples. The majority (64%) disagreed that surrogate children were as healthy as other children, and many believed that they risked worse mental health (21%) and social stigmatisation (21%). ConclusionWe found that 60% supported legalised surrogacy, but many expressed concerns about the childrens health and greater knowledge about the medical and psychosocial consequences of surrogacy is needed.

Introduction Cancer treatment during childhood may lead to late adverse effects, such as reduced musculoskeletal development or vascular, endocrine and pulmonary dysfunction, which in turn may have an adverse effect on later pregnancy and childbirth. The aim of the present study was to investigate pregnancy and obstetric outcomes as well as the offsprings health among childhood and adolescent female cancer survivors. Material and methods This register-based study included all women born between 1973 and 1977 diagnosed with cancer in childhood or adolescence (age amp;lt;21), as well as an age-matched comparison group. A total of 278 female cancer survivors with their first childbirth were included in the study, together with 829 age-matched individuals from the general population. Logistic regression and analysis of variance were used to investigate associations between having been treated for cancer and the outcome variables, adjusting for maternal age, nicotine use and comorbidity. Results Survivors were more likely to have preeclampsia (adjusted odds ratio [aOR] 3.46, 95% confidence interval [CI] 1.58 to 7.56), undergo induction of labor (aOR 1.66, 95% CI 1.05 to 2.62), suffer labor dystocia (primary labor dystocia aOR 3.54, 95% CI 1.51 to 8.34 and secondary labor dystocia aOR 2.43, 95% CI 1.37 to 4.31), malpresentation of fetus (aOR 2.02, 95% CI 1.12 to 3.65) and imminent fetal asphyxia (aOR 2.55, 95% CI 1.49 to 4.39). In addition, deliveries among survivors were more likely to end with vacuum extraction (aOR 2.53, 95% CI 1.44 to 4.47), with higher risk of clitoral lacerations (aOR 2.18, 95% CI 1.47 to 3.23) and anal sphincter injury (aOR 2.76, 95% CI 1.14 to 6.70) and emergency cesarean section (aOR 2.34 95% CI 1.39 to 3.95). Survivors used pain-reliving methods to a higher extent compared with the comparison group. There was no increased risk of neonate diagnoses and malformations. The results showed that survivors who had been diagnosed with cancer when they were younger than 14 had an increased risk of adverse obstetric outcomes. Conclusions The study demonstrates increased risk of pregnancy and childbirth complications among childhood and adolescent cancer survivors. There is a need to optimize perinatal care, especially among survivors who were younger than 14 at time of diagnosis.

The number of families conceived through sperm donation to single women is increasing. However, there is limited knowledge about health care professionals attitudes towards solo-mothers by choice, and there is some indication that professionals personal opinions influence their care of individuals who use alternate ways to build a family. The primary aim of the study was to investigate attitudes towards, and experiences of, families following sperm donation to single women among healthcare professionals working in primary child healthcare.

Purpose To compare the probability of a first live birth, age at time of birth, and time between diagnosis/referent date and birth between childhood and adolescent cancer survivors and an age-matched comparison group. Materials and Methods A total of 1,206 survivors was included in the study, together with 2,412 age-matched individuals from the general population. A Cox proportional hazards model was used to investigate first live birth after diagnosis/referent date. Data were stratified by sex, age at diagnosis, and diagnostic era (ie, diagnosis before 1988 v in 1988 or later). Results Overall, the probability of having a first live birth (hazard ratio [HR]) was significantly lower; men had lower HRs than women (HR, 0.65 v 0.79). There were no significant differences in the probability of having a first live birth among women diagnosed during adolescence (HR, 0.89), but the HR was lower among women with childhood cancers (HR, 0.47). Among male survivors, the situation was the opposite; men diagnosed during adolescence had lower HRs than survivors of childhood cancer (HR, 0.56 v 0.70). Examination of the data from the two diagnostic eras (before 1988 and 1988 or later) shows that the HR increased among female survivors after 1988 (HR, 0.71 v 0.90) and decreased among male survivors (HR, 0.72 v 0.59). A shorter time had elapsed between diagnosis/referent date and the birth of a first child among both male and female survivors compared with controls. In addition, female survivors were younger at time of birth. Conclusion The study demonstrates reduced probability of having a first live birth among cancer survivors diagnosed during childhood or adolescence; men were particularly vulnerable.

BackgroundThe aim of this study was to investigate attitudes towards embryo donation and embryo donation families among professionals working in primary child healthcare, and their experiences of these families.MethodsA cross-sectional online survey was conducted in Sweden between April and November 2016. A total of 712 primary healthcare physicians, registered nurses and psychologists were approached to participate in this study. The study-specific questionnaire measured attitudes and experiences in the following four domains: legalisation and financing, the family and the childs health, clinical experience of meeting families following embryo donation, and knowledge of embryo donation.ResultsOf the 189 women and 18 men who completed the questionnaire (response rate 29%), relatively few (13%) had clinical experience of caring for families following embryo donation. Overall, 69% supported legalisation of embryo donation for infertile couples, and 54% agreed it should be publicly funded. The majority (88%) agreed the child should have the right to know the donors identity. Respondents did not believe that children conceived through embryo donation are as healthy as other children (50%), citing the risks of poor mental health (17%) and social stigmatization (18%). Approximately half reported low confidence in their own knowledge of embryo donation (47%) and wanted to know more (58%).ConclusionsThese results indicate relatively large support among healthcare professionals in Sweden for the legalisation of embryo donation. In order to provide adequate healthcare to families following embryo donation, there is a need to develop educational resources to increase knowledge about the medical and psychosocial consequences of embryo donation among healthcare professionals working in primary healthcare.

Infertility is a recognised potential sequel of cancer treatment which impacts negatively on the quality of survival. The aim of this study was to explore how men and women experience the threat of infertility by cancer treatment and individuals thoughts about having children after cancer during the first 2years following diagnosis. Nine women and seven men (aged 24-41) participated in two interviews in this longitudinal interview study, after the initiation of cancer treatment and 2years thereafter. The interviews focused on participants thoughts and feelings about threatened fertility and having children. The interviews were analysed with qualitative content analysis with a particular focus on identifying experiences over time. The Traits-Desires-Intentions model was used to reflect upon the study findings. The analysis resulted in the identification of four themes: Continue calmly on chosen path, Abandoning plans for children, Avoiding the subject of fertility and Struggling towards life goals. The results emphasise the need to offer individualised fertility-related treatment communication and counselling, both at the time of cancer diagnosis and also in connection with follow-up care. Appropriate fertility-related communication should be included in young cancer patients survivor care plans.

The aim of this descriptive review is to summarise the current knowledge of non-invasive bioelectrical impedance analysis (BIA) used with gynaecological surgical patients in regard to postoperative development of lymphoedema and determination of perioperative fluid balance, and as a prognostic factor in cancer mortality and a predictor of postoperative complications. The databases PubMed, MEDLINE, Scopus Web of Science, the Cochrane Library, and reference lists of selected articles were searched for relevant articles published during the period January 2008-April 2018. Only papers published in English were retrieved. Thirty-seven articles were evaluated. Where gynaecological studies were lacking, studies with a study population from neighbouring clinical fields were used instead. Studies on the clinical use of BIA with gynaecological surgical patients were divided into three categories: the postoperative development of lower limb lymphoedema (n = 7), perioperative hydration measuring (n = 3), and the BIA parameter phase angle as a prognostic factor in cancer survival and as predictive for postoperative complications (n = 6). Of these 16 studies only three used a pure gynaecological study population. Three different methods of BIA were used in these articles: single frequency-BIA, multifrequency-BIA and bioimpedance spectroscopy. BIA was found to detect lymphoedema with a sensitivity of 73% and a specificity of 84%. Studies indicated that BIA was able to detect lower limb lymphoedema at an early stage even before it became clinically detectable. During postoperative hydration measurements, an increase in extracellular fluid volume and extracellular fluid volume in relation to total body fluid volume, as well as a decrease in phase angle, were associated with higher frequencies of postoperative complications. Moreover, low values for the phase angle have been associated with increased mortality in cancer patients. However, the number of studies in this field was limited. From our review, BIA seems to be a useful tool for use in the clinical setting of the gynaecological surgical patient. The theoretical approach of using bioelectrical impedance values to measure the fluid distribution in the body compartments offers wide opportunities in the clinical setting. However, so far, all studies have set up cut-off limits within the study population, and reference values for a general population need to be defined. There are also rather few studies on a gynaecological study population. Hence, there is a need for further studies within gynaecological surgery focusing on early detection of lower limb lymphoedema, perioperative fluid balance, and postoperative complications in order to establish the value of BIA in clinical praxis. (C) 2018 Elsevier B.V. All rights reserved.

BACKGROUND: Spermatozoa are stored in the oviductal functional sperm reservoir in animals with internal fertilization, including zoologically distant classes such as pigs or poultry. They are held fertile in the reservoir for times ranging from a couple of days (in pigs), to several weeks (in chickens), before they are gradually released to fertilize the newly ovulated eggs. It is currently unknown whether females from these species share conserved mechanisms to tolerate such a lengthy presence of immunologically-foreign spermatozoa. Therefore, global gene expression was assessed using cDNA microarrays on tissue collected from the avian utero-vaginal junction (UVJ), and the porcine utero-tubal junction (UTJ) to determine expression changes after mating (entire semen deposition) or in vivo cloacal/cervical infusion of sperm-free seminal fluid (SF)/seminal plasma (SP).

RESULTS: In chickens, mating changed the expression of 303 genes and SF-infusion changed the expression of 931 genes, as compared to controls, with 68 genes being common to both treatments. In pigs, mating or SP-infusion changed the expressions of 1,722 and 1,148 genes, respectively, as compared to controls, while 592 genes were common to both treatments. The differentially expressed genes were significantly enriched for GO categories related to immune system functions (35.72-fold enrichment). The top 200 differentially expressed genes of each treatment in each animal class were analysed for gene ontology. In both pig and chicken, an excess of genes affecting local immune defence were activated, though frequently these were down-regulated. Similar genes were found in both the chicken and pig, either involved in pH-regulation (SLC16A2, SLC4A9, SLC13A1, SLC35F1, ATP8B3, ATP13A3) or immune-modulation (IFIT5, IFI16, MMP27, ADAMTS3, MMP3, MMP12).

CONCLUSION: Despite being phylogenetically distant, chicken and pig appear to share some gene functions for the preservation of viable spermatozoa in the female reservoirs.

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The high egg-laying capacity of the modern domestic chicken (i.e. White Leghorn, WL) has arisen from the low egg-laying ancestor Red Junglefowl (RJF) via continuous trait selection and breeding. To investigate whether this long-term selection impacted the seminal fluid (SF)-proteome, 2DE electrophoresis-based proteomic analyses and immunoassays were conducted to map SF-proteins/cytokines in RJF, WL and a 9th generation Advanced Intercross Line (AIL) of RJF/WL-L13, including individual SF (n = 4, from each RJF, WL and AIL groups) and pools of the SF from 15 males of each group, analyzed by 2DE to determine their degree of intra-group (AIL, WL, and RJF) variability using Principal Component Analysis (PCA); respectively an inter-breed comparative analysis of intergroup fold change of specific SF protein spots intensity between breeds. The PCA clearly highlighted a clear intra-group similarity among individual roosters as well as a clear inter-group variability (e.g. between RJF, WL and AIL) validating the use of pools to minimize confounding individual variation. Protein expression varied considerably for processes related to sperm motility, nutrition, transport and survival in the female, including signaling towards immunomodulation. The major conserved SF-proteins were serum albumin and ovotransferrin. Aspartate aminotransferase, annexin A5, arginosuccinate synthase, glutathione S-transferase 2 and l-lactate dehydrogenase-A were RJF-specific. Glyceraldehyde-3-phosphate dehydrogenase appeared specific to the WL-SF while angiotensin-converting enzyme, γ-enolase, coagulation factor IX, fibrinogen α-chain, hemoglobin subunit α-D, lysozyme C, phosphoglycerate kinase, Src-substrate protein p85, tubulins and thioredoxin were AIL-specific. The RJF-SF contained fewer immune system process proteins and lower amounts of the anti-inflammatory/immunomodulatory TGF-β2 compared to WL and AIL, which had low levels- or lacked pro-inflammatory CXCL10 compared to RJF. The seminal fluid proteome differs between ancestor and modern chicken, with a clear enrichment of proteins and peptides related to immune-modulation for sperm survival in the female and fertility.

Background: Postpartum infections are a major cause of maternal mortality and morbidity worldwide. Breast infection, endometritis, urinary tract infection and wound infections are the most common postpartum infections and together they affect almost 20% of women after childbirth. Some risk factors for postpartum infections, for example cesarean section, have been relatively well studied, but other presumable risk factors are yet to be confirmed.

The proportion of pregnant women who are overweight or obese is increasing in most parts of the world. Increased maternal body mass index (BMI) is associated with maternal and infant morbidity. The association between overweight / obesity and postpartum infections is incompletely understood. Vitamin D deficiency has in epidemiological studies been shown to increase the risk of various infections. Furthermore, vitamin D is an important factor in the human immune system. Concomitantly, vitamin D supplementation seems protective against some types of infections. Whether vitamin D deficiency is a risk factor for postpartum infections has not been studied.

Material and Methods: In a population-based observational study using questionnaires, the prevalences of postpartum wound infections, endometritis, urinary tract infections and mastitis in the southeast region of Sweden were estimated (Paper I). All women giving birth in the region during one year (n=11 124) were asked to participate. Papers II and III were cohort studies based on all deliveries in Sweden during eight years (2005-2012). Data sources were the Swedish Medical Birth Register, the Swedish National Patient Register and the Swedish Prescribed Drugs Register. In paper II all term deliveries were included (n=795 072). Risk factors for postpartum wound infections, endometritis and urinary tract infection were evaluated. Paper III included all deliveries (n=841 780) and examined the impact of BMI on the risk of postpartum wound infections, endometritis and breast abscess after different modes of delivery. Infections were defined as the presence of applicable ICD-10 codes. The Mantel-Haenszel technique was used to calculate adjusted odds ratios. In paper IV the association between vitamin D deficiency and overall postpartum infectious morbidity was analyzed. Serum samples from the Pregnancy Biobank in Linköping, drawn at the time of delivery, were used to determine concentrations of 25-hydroxyvitamin D in 1397 women. ICD-10 codes were extracted from the women’s medical records. The prevalence of vitamin D deficiency was calculated and adjusted odds ratios for postpartum infections were estimated with multivariable logistic regression analysis.

Results: More than one out of ten women in southeast Sweden reported wound infections; endometritis, urinary tract infection or mastitis postpartum and 7.5% reported antibiotic treatment for infection. Cesarean section was the strongest risk factor for wound infection, followed by obstetric anal sphincter injuries and episiotomy. For endometritis, the strongest risk factors were anemia, manual placental removal and emergency cesarean section. Urinary tract infection was associated with anemia, instrumental vaginal delivery and emergency cesarean section. There was a dose-dependent increased risk of postpartum infection with higher BMI. For morbidly obese women the risk of infection was over 50% higher than for normal weight women. The risk of endometritis after normal vaginal delivery increased the higher the BMI, as did the risk of wound infection after cesarean section, regardless of the type of cesarean section. For breast abscess, there was an inverse association with BMI.

Vitamin D deficiency was present among almost 60% of pregnant women at the time of delivery. No association between vitamin D deficiency and postpartum infections was found.

Conclusions: Every tenth Swedish woman acquired an infection postpartum and three quarters of them received antibiotics for infection. Anemia was an important risk factor for postpartum infection, and the strongest risk factor for endometritis and urinary tract infection. Strong efforts should be made to reduce blood loss during and after childbirth. This thesis confirmed cesarean section as a major risk factor for postpartum infection, especially wound infection. The risk increased if the woman was overweight or obese, regardless of whether it was a planned or an emergency cesarean section.

Vitamin D deficiency was common among Swedish pregnant women, but it was not found to be associated with postpartum infections.

Background: The objective was to estimate whether maternal obesity and/or obstetric interventions are associated with diagnosed maternal post-partum sepsis. Methods: A retrospective observational cohort study including all deliveries in Sweden between 1997 and 2012 (N=1,558,752). Cases of sepsis (n=376) were identified by International Classification of Diseases, (ICD-10) codes A40, A41 and O 85 in the Medical Birth Register and the National Patient Register. The reference population was non-infected, and therefore, women with any other infection diagnosis and/or with dispensed antibiotics within eight weeks post-partum were excluded. Information on dispensed drugs was available in the prescribed drug Register. Women with sepsis were compared with non-infected women concerning maternal characteristics and obstetric interventions. Adjusted odds ratios (aOR) were determined using the Mantel-Haenszel technique. Adjustments were made for maternal age, parity and smoking. Results: Obese women (body mass index 30) had a doubled risk of sepsis (3.6/10,000) compared with normal weight women (2.0/10,000) (aOR 1.85 (95%CI: 1.37-2.48)). Induction of labour (aOR 1.44 (95%CI: 1.09-1.91)), caesarean section overall (aOR 3.06 (95%CI: 2.49-3.77)) and elective caesarean section (aOR 2.41 (95%CI: 1.68-3.45)) increased the risk of sepsis compared with normal vaginal delivery. Post-partum anaemia due to acute blood loss was associated with maternal sepsis (aOR 3.40 (95%CI: 2.59-4.47)). Conclusions: Maternal obesity, obstetric interventions and post-partum anaemia due to acute blood loss increased the risk of diagnosed post-partum sepsis indicating that interventions in obstetric care should be considered carefully and anaemia should be treated if resources are available.

The purpose was to evaluate the association between maternal characteristics, obstetrical interventions/complications and postpartum wound infections (WI), urinary tract infection (UTI) and endometritis. Furthermore, this study aimed to determine the time from delivery to onset of infections after discharge from the hospital. Three large Swedish Medical Health Registers were scrutinized for the period 2005-2012. A total of 582,576 women had 795,072 deliveries. Women with diagnosis codes for WIs, UTIs or endometritis, from delivery to 8 weeks postpartum, were compared to non-infected women. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated. Increasing age and body mass index (BMI) were both associated with increasing prevalence of postpartum infections. WIs were most strongly associated with cesarean section (CS) (OR 17.2; 95% CI 16.1-18.3), 3rd and 4th degree tears (OR 10.7%; 95% CI 9.80-11.9) and episiotomy (OR 10.2; 95% CI 8.94-11.5). Endometritis was associated with anemia (OR 3.16; 95% CI 3.01-3.31) and manual placental removal (OR 2.72; 95% CI 2.51-2.95). UTI was associated with emergency CS (OR 3.46; 95% CI 3.07-3.89) and instrumental delivery (OR 3.70; 95% CI 3.29-4.16). For women discharged from the delivery hospital the peak occurrence of UTI was 6 days postpartum, while for WIs and endometritis it was 7 days postpartum.

BACKGROUND: Postpartum infections are a common cause of morbidity after childbirth. Vitamin D deficiency has been shown to increase the risk for several infections in a non-pregnant population. Vitamin D deficiency has been described as common in pregnant women.

OBJECTIVE: To investigate whether vitamin D deficiency in pregnant women in labor was associated with an increased risk of overall postpartum infectious morbidity within eight weeks of delivery. A secondary aim was to estimate the prevalence of vitamin D deficiency among pregnant women in Linköping, Sweden at the time of delivery.

MATERIAL AND METHODS: Serum vitamin D levels in labor were analyzed for 1397 women. Vitamin D deficiency was defined as serum levels <50 nmol/L. All ICD-10 codes given to the women eight weeks postpartum were reviewed and postpartum infections were defined as the presence of an ICD-10 code suggestive of infection. The prevalence of postpartum infections among women with sufficient vitamin D levels was compared with women with vitamin D deficiency. Adjusted Odds Ratios and 95% confidence intervals for postpartum infections were calculated using multivariate logistic regression analysis.

RESULTS: Fifty eight per cent of the women had serum vitamin D levels <50 nmol/L. The proportion of women with vitamin D deficiency varied, as expected, with season. No association between vitamin D deficiency and postpartum infections was found. For vitamin D 25-50 nmol/L the adjusted Odds Ratio was 0.85 (95% confidence interval 0.56-1.29) and for vitamin D <25 nmol/L the adjusted Odds Ratio was 1.15 (95% confidence interval 0.66-2.03). Women who smoked or who had a cesarean section had an increased risk of postpartum infections.

CONCLUSIONS: Vitamin D deficiency was more common than previously reported in Swedish pregnant women. No association between vitamin D deficiency and postpartum infections was found. Other well-known risk factors for postpartum infection were identified.

Type 1 diabetes (T1D) involves the interaction of multiple gene variants, environmental factors, and immunoregulatory dysfunction. Major T1D genetic risk loci encode HLA-DR and -DQ. Genetic heterogeneity and linkage disequilibrium in the highly polymorphic HLA region confound attempts to identify additional T1D susceptibility loci. To minimize HLA heterogeneity, T1D patients (N = 365) and control subjects (N = 668) homozygous for the HLA-DR3 high-risk haplotype were selected from multiple large T1D studies and examined to identify new T1D susceptibility loci using molecular inversion probe sequencing technology. We report that risk for T1D in HLA-DR3 homozygotes is increased significantly by a previously unreported haplotype of three single nucleotide polymorphisms (SNPs) within the first intron of HLA-DRA1. The homozygous risk haplotype has an odds ratio of 4.65 relative to the protective homozygous haplotype in our sample. Individually, these SNPs reportedly function as "expression quantitative trait loci," modulating HLA-DR and -DQ expression. From our analysis of available data, we conclude that the tri-SNP haplotype within HLA-DRA1 may modulate class II expression, suggesting that increased T1D risk could be attributable to regulated expression of class II genes. These findings could help clarify the role of HLA in T1D susceptibility and improve diabetes risk assessment, particularly in high-risk HLA-DR3 homozygous individuals.

Objective Postpartum haemorrhage (PPH) is the most common obstetric emergency. A well-established postpartum haemorrhage protocol in the labour ward is crucial for effective treatment. The aim of the study was to investigate if practical obstetric team training improves the patient outcome and clinical management of PPH. Setting The practical obstetric team training (PROBE) at Linkoping University Hospital, Sweden, with approximate 3000 deliveries annually, was studied between the years of 2004-2011. Each team consisted of one or two midwives, one obstetrician or one junior doctor and one nurse assistant. Emergency obstetrics cases were trained in a simulation setting. PROBE was scheduled during work hours at an interval of 1.5 years. Population Pre-PROBE women (N = 419 were defined as all women with vaginal birth between the years of 2004-2007 with an estimated blood loss of amp;gt;= 1000 ml within the first 24 hours of delivery. Post-PROBE women (N = 483) were defined as all women with vaginal birth between the years of 2008-2011 with an estimated blood loss of amp;gt;= 1000 ml within the first 24 hours of delivery. The two groups were compared regarding blood loss parameters and management variables using retrospective data from medical records. Results No difference was observed in estimated blood loss, haemoglobin level, blood transfusions or the incidence of postpartum haemorrhage between the two groups. Post-PROBE women had more often secured venous access (pamp;lt;0.001), monitoring of vital signs (pamp;lt;0.001) and received fluid resuscitation (pamp;lt;0.001) compared to pre-PROBE women. The use of uterine massage was also more common among the post-PROBE women compared with the pre-PROBE women (pamp;lt;0.001). Conclusion PROBE improved clinical management but not patient outcome in women with postpartum haemorrhage in the labour ward. These new findings may have clinical implications since they confirm that training was effective concerning the management of postpartum haemorrhage. However, there is still no clear evidence that simulation training improve patient outcome in women with PPH.

Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin producing beta-cells. The time from onset of islet autoimmunity to manifest clinical disease can vary widely in length, and it is fairly uncharacterized both clinically and immunologically. In the current study, peripheral blood mononuclear cells from autoantibody-positive children with high risk for T1D, and from age-matched healthy individuals, were analyzed by mass cytometry using a panel of 32 antibodies. Surface markers were chosen to identify multiple cell types including T, B, NK, monocytes, and DC, and antibodies specific for identification of differentiation, activation and functional markers were also included in the panel. By applying dimensional reduction and computational unsupervised clustering approaches, we delineated in an unbiased fashion 132 phenotypically distinct subsets within the major immune cell populations. We were able to identify an effector memory Treg subset expressing HLA-DR, CCR4, CCR6, CXCR3, and GATA3 that was increased in the high-risk group. In addition, two subsets of NK cells defined by CD16(+) CD8(+) CXCR3(+) and CD16(+) CD8(+) CXCR3(+) CD11c(+) were also higher in the same subjects. High-risk individuals did not show impaired glucose tolerance at the time of sampling, suggesting that the changes observed were not the result of metabolic imbalance, and might be potential biomarkers predictive of T1D.

Seminal extracellular vesicles (EVs) include exosomes (phi 40-120 nm) and microvesicles (MVs, phi 120-1000 nm), which would be involved in multiple functional reproductive roles. The study aimed to establish which EV subtypes are present in pig semen, using a high-resolution flow cytometer to explore differences in their tetraspanin expression profile. The EVs were isolated from 12 pig ejaculates using serial ultracentrifugation and characterized by dynamic light scattering and electron microscopy for size and morphology as well as for tetraspanin expression using flow cytometry with Carboxyfluorescein succinimidyl ester (CFSE) and antibodies against CD9, CD63 and CD81. Pig semen contained a heterogeneous EV-population regarding size and morphology. Flow cytometric analysis demonstrated that the proportion of EVs expressing CD63 and CD9 was higher in MVs (P amp;lt; 0.001 and P amp;lt; 0.05, respectively) than in exosomes, while the opposite was true for CD81; higher (P amp;lt; 0.001) in exosomes than in MVs. In conclusion, (1) the new generation of flow cytometers are able to accurately identify EVs and to gate them in two size-different populations named exosomes and MVs. (2) Tetraspanins CD9, CD63 and CD81 are present in both seminal EVs, albeit with exosomes and MVs differing in expression profiles, suggesting dissimilar cargo and binding affinity.

Background: Boar seminal plasma is rich in cytokines, which could influence the capability of spermatozoa to tolerate preservation.

Objectives: To evaluate the involvement of boar seminal plasma cytokines in the changes experienced by boar spermatozoa during their storage, either in liquid or frozen state.

Materials and Methods: In two separated experiments, semen samples from healthy and fertile boars were split in two aliquots, one centrifuged twice (1,500 ×g for 10 min) to harvest seminal plasma, whereas the other was either commercially extended (3 × 107 sperm/mL) and liquid-stored at 17°C during 144 h (n = 28, Experiment 1) or frozen-thawed using a standard 0.5 mL protocol (n = 27, Experiment 2). Sixteen cytokines were quantified using Luminex xMAP®. Sperm attributes (CASA-evaluated total and progressive motility; flow cytometry-evaluated sperm viability, production of intracellular H2O2 and O2&#x2022;-" role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">O∙−2O2•- and levels of lipid peroxidation in viable spermatozoa) were evaluated either at 0, 72, or 144 h of liquid storage (Experiment 1) or before freezing and at 30- and 150-min post-thawing (Experiment 2).

Results: Multiple linear regression models, with Bayesian approach for variable selection, revealed that the anti-inflammatory TGF-β2, TGF-β3, IL-1Ra, and IL-4 and the pro-inflammatory IL-8 and IL-18, predicted changes in sperm motility for liquid-stored semen while the anti-inflammatory IFN-γ was included in the models predicting changes in all sperm attributes for cryopreserved semen.

Conclusion: Specific boar seminal plasma cytokines would contribute to modulate the structural and metabolic changes shown by spermatozoa during preservation, either in liquid or frozen state.

Superoxide dismutase (SOD) is a major antioxidant enzyme in boar seminal plasma (SP). This study evaluated how SP-SOD affected sperm attributes when semen of boars of various breeds, included in commercial artificial insemination (Al)-programs, was extended and liquid-stored at 17 degrees C for AI; as well as their in vivo fertility (farrowing rate and litter size of 10,952 AI-sows). SP-SOD-activity was assessed in 311 ejaculates (100 boars) while sperm motility (by CASA), viability and intracellular H2O2 generation in viable spermatozoa (by flow cytometry) were measured at 0 and 72 h of liquid storage. SP-SOD activity was not affected by breed but differed (P amp;lt; 0.001) between boars (n = 50), ranging from 1.16 +/- 0.11 to 7.02 +/- 0.75 IU/mL. Semen Al-doses (n =44) hierarchically grouped (P amp;lt; 0.001) with low SP-SOD activity showed lower (P amp;lt; 0.05) sperm motility and intracellular H2O2 at 72 h of liquid storage. Fertility did not differ between AI-boars (n = 39) hierarchically grouped (P amp;lt; 0.001) with high or low SP-SOD activity. In conclusion, SP-SOD activity is boar dependent and positively related with sperm functionality of liquid stored semen AI-doses. However, this positive effect is not reflected on in vivo fertility post-AI. (C) 2019 Elsevier Inc. All rights reserved.

The paraoxonase type 1 (PON1) is an enzyme with antioxidant properties recently identified in the seminal plasma (SP) of several species, including the porcine. The aims of the present study were to (1) describe the immunohistochemical localisation of PON1 in the genital organs of fertile boars and (2) evaluate the relationship among PON1 activity and high-density lipoprotein cholesterol (HDL-C) concentration in fluids of the boar genital organs. Immunohistochemical analysis demonstrated that PON1 was present in testis (specifically in Leydig cells, blood vessels, spermatogonia and elongated spermatids), epididymis (specifically in the cytoplasm of the principal epithelial cells, luminal secretion and in the surrounding smooth muscle) and the lining epithelia of the accessory sexual glands (cytoplasmic location in the prostate and membranous in the seminal vesicle and bulbourethral glands). The Western blotting analysis confirmed the presence of PON1 in all boar genital organs, showing in all of them a band of 51 kDa and an extra band of 45 kDa only in seminal vesicles. PON1 showed higher activity levels in epididymal fluid than those in SP of the entire ejaculate or of specific ejaculate portions. A highly positive relationship between PON1 activity and HDL-C concentration was found in all genital fluids. In sum, all boar genital organs contributing to sperm-accompanying fluid/s were able to express PON1, whose activity in these genital fluids is highly dependent on the variable HDL-C concentration present.

GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine). We estimate that there is a 98% probability that 20 mu g GAD with alum administered twice yields a positive biological effect. The effect is probably a 15-20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between -0.250 and -0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of -0.294 pmol/ml at 1 year for untreated newly diagnosed patients. The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.

Purpose: Previous studies have emphasised that women with pre-existing mood disorders are more inclined to discontinue hormonal contraceptive use. However, few studies have examined the effects of combined oral contraceptives (COC) on mood in women with previous or ongoing mental disorders. Materials and methods: This is a supplementary analysis of an investigator-initiated, double-blinded, randomised clinical trial during which 202 women were treated with either a COC (1.5mg estradiol and 2.5mg nomegestrolacetate) or placebo during three treatment cycles. The Mini International Neuropsychiatric Interview was used to collect information on previous or ongoing mental disorders. The primary outcome measure was the total change score in five mood symptoms on the Daily Record of Severity of Problems (DRSP) scale in the intermenstrual phase of the treatment cycle. Results: Women with ongoing or previous mood, anxiety or eating disorders allocated to COC had higher total DRSP -scores during the intermenstrual phase of the treatment cycle in comparison with corresponding women randomised to placebo, mean difference 1.3 (95% CI 0.3-2.3). In contrast, among women without mental health problems, no difference in total DRSP -scores between COC- and placebo users was noted. Women with a risk use of alcohol who were randomised to the COC had higher total DRSP -scores than women randomised to placebo, mean difference 2.1 (CI 95% 1.0-3.2). Conclusions: Women with ongoing or previous mental disorders or risk use of alcohol have greater risk of COC-induced mood symptoms. This may be worth noting during family planning and contraceptive counselling.

Objectives: To investigate the effect of 15 weeks of resistance training on the frequency of moderate to severe hot flushes in postmenopausal women. Study design: Postmenopausal women with at least 4 moderate or severe hot flushes or night sweats per day day were randomized to a 15-week resistance training intervention or unchanged physical activity. Participants did not exercise regularly at baseline and had not used any therapy for hot flushes two months prior to study entry. The resistance training was performed three times per week and the program contained 8 exercises performed with 8-12 repetitions in 2 sets. Loads were set individually from eight-repetition maximum-strength tests and increased progressively. Main outcome measures: The primary outcome was change in mean moderate or severe hot flushes per day from baseline to week 15, assessed with symptom diaries. Secondary outcomes included change in hot flush score and time spent on physical activity. Results: Between November 19, 2013, and October 26, 2016, 65 women were enrolled; 58 completed the trial and were included in the analyses. The mean age was 55 and the mean number of moderate or severe hot flushes per day at baseline was 7.1; there were no baseline differences between groups. The frequency of hot flushes decreased more in the intervention group than in the control group (mean difference -2.7, 95% CI -4.2 to -1.3). The mean percentage change was -43.6% (-56.0 to -31.3) in the intervention group and -2.0% (16.4-12.4) in the control group. Conclusion: A 15-week resistance-training program decreased the frequency of moderate and severe hot flushes among postmenopausal women and could be an effective and safe treatment option to alleviate vasomotor symptoms.

Platelets are needed to prevent or arrest bleeding and aggregate at the site of injury upon vascular damage. Platelets express receptors for estrogens which might affect the function of the platelets and their hemostatic ability. The aim was to identify possible differences in platelet function related to age, gender, and phases of the menstrual cycle by use of impedance aggregometry with Multiplate. In the first part of the study, platelet function was assessed in 60 healthy individuals (30 men and 30 women) in each of three age groups (20-25, 40-45, and 60-65 years). In the second part of the study, the platelet function was analyzed on four occasions during the menstrual cycle in women without oral contraceptives (OCs) (n = 17) and compared to 19 women on OCs and 18 men of similar age (20-40 years). For the women on OCs, aggregation was analyzed once during the tablet-free week and once late during the period with OCs. The men were sampled once. Women of younger age (amp;lt;45 years) had significantly higher agonist-induced aggregation response than both men and post-menopausal women (60-65 years). The agonist-induced aggregation response did not differ between phases of the menstrual cycle or OC use. The results suggest that estradiol and/or progesterone affect spontaneous aggregation since it was found to be lowest in the mid-luteal phase. Spontaneous aggregation was significantly lower in women on OCs than in both men and women without OCs. Our findings indicate that fertile age is associated with higher aggregation response capacity of the platelets, possibly to prevent excessive bleeding during menstruation, but this response capacity is not altered during the menstrual cycle or by use of OCs.

Objectives C-peptide (CP) loss in type 1 diabetes (T1D) is highly variable, and factors influencing it are poorly understood. We modelled CP values in T1D patients from diagnosis for up to 6 years, treating the serial data as growth curves plotted against time since diagnosis. The aims were to summarise the pattern of CP loss (i.e. growth curve shape) in individual patients in simple terms, and to identify baseline characteristics that predict this pattern in individuals. Materials and methods Between 1976 and 2011, 442 T1D patients initially aged amp;lt; 18y underwent 120-minute mixed meal tolerance tests (MMTT) to calculate area under the curve (AUC) CP, at 3, 9,18, 30, 48 and 72 months after diagnosis (n = 1537). The data were analysed using the novel SITAR mixed effects growth curve model (Superlmposition by Translation And Rotation). It fits a mean AUC growth curve, but also allows the curves mean level and rate of fall to vary between individuals so as to best fit the individual patient curves. These curve adjustments define individual curve shape. Results The square root (root) AUC scale provided the best fit. The mean levels and rates of fall for individuals were normally distributed and uncorrelated with each other. Age at diagnosis and root AUC at 3 months strongly predicted the patient-specific mean levels, while younger age at diagnosis (p amp;lt; 0.0001) and the 120-minute CP value of the 3-month MMTT (p = 0.002) predicted the patient-specific rates of fall. Conclusions SITAR growth curve analysis is a useful tool to assess CP loss in type 1 diabetes, explaining patient differences in terms of their mean level and rate of fall. A definition of rapid CP loss could be based on a quantile of the rate of fall distribution, allowing better understanding of factors determining CP loss and stratification of patients into targeted therapies.

Background: Health and well-being are better, on average, in countries that are more equal, but less is known about how this benefit is distributed across society. Height is a widely used, objective indicator of child health and predictor of lifelong well-being. We compared the level and slope of social gradients in children's height in high-income countries with different levels of income inequality, in order to investigate whether children growing up in all socioeconomic circumstances are healthier in more equal countries.

Methods: We conducted a coordinated analysis of data from five cohort studies from countries selected to represent different levels of income inequality (the USA, UK, Australia, the Netherlands and Sweden). We used standardised methods to compare social gradients in children's height at age 4-6 years, by parent education status and household income. We used linear regression models and predicted height for children with the same age, sex and socioeconomic circumstances in each cohort.

Results: The total analytic sample was 37 063 children aged 4-6 years. Gradients by parent education and household income varied between cohorts and outcomes. After adjusting for differences in age and sex, children in more equal countries (Sweden, the Netherlands) were taller at all levels of parent education and household income than children in less equal countries (USA, UK and Australia), with the greatest between-country differences among children with less educated parents and lowest household incomes.

Conclusions: The study provides preliminary evidence that children across society do better in more equal countries, with greatest benefit among children from the most disadvantaged socioeconomic groups.

Treatment of type 1 diabetes has been intensified aiming at normalizing blood glucose, which may increase the risk of severe hypoglycemia (SH). We aimed to compare the incidence of SH events in the four Nordic countries Denmark, Iceland, Norway and Sweden, and to assess the influence of hemoglobin A1c (HbA1c) and treatment modalities on the frequency of SH; particularly, to explore if a HbA1c target =6.7% (50 mmol/mol) is feasible.

Background: Intensified insulin therapy may increase body weight and cause obesity. This study compared body mass index standard deviation score (BMISDS) and obesity rate in children with type 1 diabetes (T1D) in Denmark, Iceland, Norway and Sweden, and uncovered predictors for increasing BMISDS. Methods: Data registered in the Nordic national childhood diabetes databases during the period 2008-2012 on children below 15 years with T1D for more than 3 months were compiled, including information on gender, age, diabetes duration, hemoglobin A(1c) (HbA(1c)), insulin dose, severe hypoglycemia (SH), treatment modality, height and weight. The Swedish reference chart for BMI was used for calculating BMISDS. Results: Totally, 11025 children (48% females) (30994 registrations) were included. Medians by the last recorded examination were: age, 13.5 years; diabetes duration, 4.3 years; HbA(1c), 7.9% (63 mmol/mol); insulin dose, 0.8 IU/kg/d and BMISDS, 0.70. Obesity rate was 18.5%. Adjusted mean BMISDS (BMISDS adj) was inversely related to HbA(1c) and directly to diabetes duration. Higher BMISDS adj was found in those with an insulin dose above 0.6 IU/kg/d, and in girls above 10 years. Pump users had higher BMISDS adj than pen users, and patients with registered SH had higher BMISDS adj than patients without SH (both P amp;lt; .001). Conclusion: Obesity rate in children with T1D in the Nordic countries is high, however, with country differences. Low HbA(1c), long diabetes duration, higher insulin dose, pump treatment and experiencing a SH predicted higher BMISDS. Diabetes caregivers should balance the risk of obesity and the benefit of a very low HbA(1c).

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Objective: Survival in cervical cancer has improved little over the last decades. We aimed to elucidate primary treatment patterns and survival. Methods: Population-based study of patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed 2011-2015. Main outcome was 5-year relative survival (RS). Age-standardised RS (AS-RS) was estimated for the total cohort and for the pooled study population of squamous, adenosquamous-, adenocarcinoma. Results: Median follow-up time was 4.6 years. The study population consisted of 2141 patients; 97% of the 2212 patients in the total cohort and the 5-year AS-RS was 71% and 70%, respectively. RS stage IB1: surgery alone 95% vs. 72% for definitive chemoradiotherapy (CT-RT) (p amp;lt; 0.001). In stage IIA1 74% had CTRL, and 47% of operated patients received adjuvant (CT)-RT. RS stage IB2: surgically treated 81% (69% received adjuvant (CT)-RT) vs. 76% for (CT)-RT (p = 0.73). RS stage IIB: 77% for CT-RT + brachytherapy BT), 37% for RT + BT (p = 0.045) and 27% for RT-BT (p amp;lt; 0.001). Stages III-IVA; amp;lt;40% received CT-RT + BT, RS 45% vs. 18% for RT-BT (RR 4.1, p amp;lt; 0.001). RS stage IVB 7%. Conclusion: Primary treatment of cervical cancer in Sweden adhered to evidence-based standard of care. Areas of improvement include optimising treatment for stages III-IVA, and avoiding combining surgery and radiotherapy. (C) 2019 Elsevier Inc. All rights reserved.

Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient.