Investigating the effect of lifestyle risk factors upon number of aspirated and mature oocytes in in vitro fertilization cycles: Interaction with antral follicle count.

INTRODUCTION: There is evidence demonstrating that certain lifestyle factors have a detrimental effect on fertility. Since such factors often coexist, possible synergistic effects merit further investigation. Thus we aimed to examine the cumulative impact of lifestyle factors on in vitro fertilization (IVF) early reproductive treatment outcomes and their interaction with measures of ovarian reserve. MATERIALS AND METHODS: By following women who were starting their first fresh IVF cycle in 2 cohorts, the "Lifestyle study cohort" (hypothesis generating cohort, n = 242) and the "UppSTART study" (validation cohort, n = 432) in Sweden, we identified two significant risk factors acting independently, smoking and BMI, and then further assessed their cumulative effects. RESULTS: Women with both these risk factors had an Incidence Rate Ratio (IRR) of 0.75 [(95% CI 0.61-0.94)] regarding the number of aspirated oocytes compared to women without these risk factors. Concerning the proportion of mature oocytes in relation to the total number of aspirated oocytes, the interaction between BMI and Antral Follicle Count (AFC) was significant (p-value 0.045): the lower the value of AFC, the more harmful the effect of BMI with the outcome. CONCLUSIONS: Data shows that there is an individual as well as a cumulative effect of smoking and BMI on the number of aspirated and mature oocytes in fresh IVF treatment cycles. AFC might modify associations between BMI and the proportion of mature oocytes in relation to the total number of aspirated oocytes. These results highlight the importance of lifestyle factors on IVF early reproductive outcomes and provide additional evidence for the importance of preconception guidance for the optimization of IVF cycle outcome.

TANGO2 deficiency as a cause of neurodevelopmental delay with indirect effects on mitochondrial energy metabolism.

Exome sequencing has recently identified mutations in the gene TANGO2 (transport and Golgi organization 2) as a cause of developmental delay associated with recurrent crises involving rhabdomyolysis, cardiac arrhythmias, and metabolic derangements. The disease is not well understood, in part as the cellular function and subcellular localization of the TANGO2 protein remain unknown. Furthermore, the clinical syndrome with its heterogeneity of symptoms, signs, and laboratory findings is still being defined. Here, we describe 11 new cases of TANGO2-related disease, confirming and further expanding the previously described clinical phenotype. Patients were homozygous or compound heterozygous for previously described exonic deletions or new frameshift, splice site, and missense mutations. All patients showed developmental delay with ataxia, dysarthria, intellectual disability, or signs of spastic diplegia. Of importance, we identify two subjects (aged 12 and 17 years) who have never experienced any overt episode of the catabolism-induced metabolic crises typical for the disease. Mitochondrial complex II activity was mildly reduced in patients investigated in association with crises but normal in other patients. In one deceased patient, post-mortem autopsy revealed heterotopic neurons in the cerebral white matter, indicating a possible role for TANGO2 in neuronal migration. Furthermore, we have addressed the subcellular localization of several alternative isoforms of TANGO2, none of which were mitochondrial but instead appeared to have a primarily cytoplasmic localization. Previously described aberrations in Golgi morphology were not observed in cultured skin fibroblasts.

Copy-choice recombination during mitochondrial L-strand synthesis causes DNA deletions.

Mitochondrial DNA (mtDNA) deletions are associated with mitochondrial disease, and also accumulate during normal human ageing. The mechanisms underlying mtDNA deletions remain unknown although several models have been proposed. Here we use deep sequencing to characterize abundant mtDNA deletions in patients with mutations in mitochondrial DNA replication factors, and show that these have distinct directionality and repeat characteristics. Furthermore, we recreate the deletion formation process in vitro using only purified mitochondrial proteins and defined DNA templates. Based on our in vivo and in vitro findings, we conclude that mtDNA deletion formation involves copy-choice recombination during replication of the mtDNA light strand.

The Impact of Constructive and Destructive Leadership on Soldier's Job Satisfaction.

The aim of this study was to investigate whether constructive or destructive leadership behaviors are the best predictors of soldiers' experienced meaningfulness of work and general job satisfaction. Data were collected among 300 employed soldiers using a questionnaire. The questionnaire contained questions about the immediate leader's constructive and destructive leadership, meaningfulness of work and general job satisfaction. The results show that the constructive leadership factor inspiration and motivation was the best predictor of both experienced meaningfulness of work and general job satisfaction. None of the destructive leadership factors gave a significant contribution to the models although both the passive and active forms of destructive leadership showed a weak to moderate significant, negative correlation with experienced meaningfulness of work and general job satisfaction.

A two-nuclease pathway involving RNase H1 is required for primer removal at human mitochondrial OriL.

The role of Ribonuclease H1 (RNase H1) during primer removal and ligation at the mitochondrial origin of light-strand DNA synthesis (OriL) is a key, yet poorly understood, step in mitochondrial DNA maintenance. Here, we reconstitute the replication cycle of L-strand synthesis in vitro using recombinant mitochondrial proteins and model OriL substrates. The process begins with initiation of DNA replication at OriL and ends with primer removal and ligation. We find that RNase H1 partially removes the primer, leaving behind the last one to three ribonucleotides. These 5'-end ribonucleotides disturb ligation, a conclusion which is supported by analysis of RNase H1-deficient patient cells. A second nuclease is therefore required to remove the last ribonucleotides and we demonstrate that Flap endonuclease 1 (FEN1) can execute this function in vitro. Removal of RNA primers at OriL thus depends on a two-nuclease model, which in addition to RNase H1 requires FEN1 or a FEN1-like activity. These findings define the role of RNase H1 at OriL and help to explain the pathogenic consequences of disease causing mutations in RNase H1.

Nucleotide pools dictate the identity and frequency of ribonucleotide incorporation in mitochondrial DNA.

Previous work has demonstrated the presence of ribonucleotides in human mitochondrial DNA (mtDNA) and in the present study we use a genome-wide approach to precisely map the location of these. We find that ribonucleotides are distributed evenly between the heavy- and light-strand of mtDNA. The relative levels of incorporated ribonucleotides reflect that DNA polymerase γ discriminates the four ribonucleotides differentially during DNA synthesis. The observed pattern is also dependent on the mitochondrial deoxyribonucleotide (dNTP) pools and disease-causing mutations that change these pools alter both the absolute and relative levels of incorporated ribonucleotides. Our analyses strongly suggest that DNA polymerase γ-dependent incorporation is the main source of ribonucleotides in mtDNA and argues against the existence of a mitochondrial ribonucleotide excision repair pathway in human cells. Furthermore, we clearly demonstrate that when dNTP pools are limiting, ribonucleotides serve as a source of building blocks to maintain DNA replication. Increased levels of embedded ribonucleotides in patient cells with disturbed nucleotide pools may contribute to a pathogenic mechanism that affects mtDNA stability and impair new rounds of mtDNA replication.

[Having been exposed to violence increases the risk of health problems later in life]. / Att ha varit utsatt för våld ökar risken för ohälsa senare i livet - Kunskap om våldets förekomst och konsekvenser behövs i hela vården - anamnesen bör innefatta fråga om våld.

Violence is a common problem in society worldwide, and recent research has shown links to various signs of ill-health among victims. In a Swedish population based study, 46 per cent of women and 38 per cent of men had, at some point, been subjected to severe sexual, physical or emotional violence. The respondents were also asked about their present health. The study showed a significant over-representation of respondents subjected to serious violence in all ill-health indicators (PTSD, depression, psychosomatic symptoms, self-harm behaviour, risky alcohol intake, low self-rated physical health and heart attacks in the older age group). Several other Swedish studies have addressed abuse and future health. In a study among young people attending youth clinics the last year prevalence of sexual, physical and emotional violence was high, as expected. Young women were to a higher extent than young men exposed to sexual (14 and 4 per cent, respectively) and emotional violence (33 and 18 per cent respectively) and young men more to physical violence than young women (27 and 18 per cent respectively). Those who had been exposed to more than two types of violence were significantly more likely to resort to self-harm behaviour and suicide ideation and rated their psychological wellbeing lower than others. In one study the violence victimization and self-reported physical and mental ill-health among young women belonging to a sexual minority and heterosexual young women was assessed. Being subjected to two or more types of violence was significantly more frequent among the minority women compared to heterosexual women. However all victimized women had significantly higher risk for ill-health in all outcomes (PTSD, sleeping difficulties, and recurrent bowel problems). The impact of being subjected to more than one type of violence has been shown to be even more strongly linked to mental ill-health also in adult patients. Hence, research supports that violence victimisation is associated with various symptoms and conditions for which people seek medical care. Therefore questions about violence victimization should routinely be included in the medical history.

Preconception health and care (PHC)-a strategy for improved maternal and child health.

Maternal health status before pregnancy is a decisive factor for pregnancy outcomes and for risk for maternal and infant complications. Still, maternity care does not start until the pregnancy is established and in most low-income settings not until more than half of the pregnancy has passed, which often is too late to impact outcomes. In Western societies preconception care (PCC) is widely recognized as a way to optimize women's health through biomedical and behavioural changes prior to conception with the aim of improving pregnancy outcomes. But the content of PCC is inconsistent and limited to single interventions or preconception counselling to women with chronic illnesses. It has been suggested that PCC should be extended to preconception health and care (PHC), including interventions prior to pregnancy in order to optimize women's health in general, and thereby subsequent pregnancy outcomes, the well-being of the family, and the health of the future child. With this definition, almost every activity that can improve the health of girls and women can be included in the concept. In the World Health Report of 2005 a longitudinal approach to women's wellness and reproductive health was highlighted, and the World Health Organization has proposed a more comprehensive maternal and child health care, also including psychosocial issues and intimate partner violence. The present article gives an overview of the recent literature and discusses contents and delivery of PCC/PHC in Western as well as low-income countries. The article puts special emphasis on why violence against women is an issue for PHC.

Daily hassles, their antecedents and outcomes among professional first responders: A systematic literature review.

Occupational groups such as firefighters, military officers, paramedics and police officers are exposed to a combination of acute, severe and accumulated everyday stress. Drawing on the daily hassles perspective on stress, the aim was to synthesize existing research on daily hassles in professional first responder settings into a theoretical model. A systematic mixed studies review with an integrated design was undertaken. The selection process resulted in 40 articles meeting the inclusion criteria. The selected papers represented two literature reviews, one qualitative study, eight longitudinal studies and 29 cross-sectional studies. Five superior categories emerged in the analysis: Individual antecedent and continuously framing factors, Environmental antecedent and continuously framing factors, Appraisal and coping processes, Daily hassles and Outcome. Suggestions for future research are presented.

Do subfertile women adjust their habits when trying to conceive?

AIM: The aim of this study was to investigate lifestyle habits and lifestyle adjustments among subfertile women trying to conceive. MATERIALS AND METHODS: Women (n = 747) were recruited consecutively at their first visit to fertility clinics in mid-Sweden. Participants completed a questionnaire. Data were analyzed using logistic regression, t tests, and chi-square tests. RESULTS: The response rate was 62% (n = 466). Mean duration of infertility was 1.9 years. During this time 13.2% used tobacco daily, 13.6% drank more than three cups of coffee per day, and 11.6% consumed more than two glasses of alcohol weekly. In this sample, 23.9% of the women were overweight (body mass index, BMI 25-29.9 kg/m(2)), and 12.5% were obese (BMI ≥30 kg/m(2)). Obese women exercised more and changed to healthy diets more frequently than normal-weight women (odds ratio 7.43; 95% confidence interval 3.7-14.9). Six out of ten women (n = 266) took folic acid when they started trying to conceive, but 11% stopped taking folic acid after some time. Taking folic acid was associated with a higher level of education (p < 0.001). CONCLUSIONS: Among subfertile women, one-third were overweight or obese, and some had other lifestyle factors with known adverse effects on fertility such as use of tobacco. Overweight and obese women adjusted their habits but did not reduce their body mass index. Women of fertile age would benefit from preconception counseling, and the treatment of infertility should routinely offer interventions for lifestyle changes.

Is pregnancy planning associated with background characteristics and pregnancy-planning behavior?

INTRODUCTION: Prevalence of planned pregnancies varies between countries but is often measured in a dichotomous manner. The aim of this study was to investigate to what level pregnant women had planned their pregnancies and whether pregnancy planning was associated with background characteristics and pregnancy-planning behavior. MATERIAL AND METHODS: A cross-sectional study that utilized the baseline measurements from the Swedish Pregnancy Planning study. Pregnant women (n = 3390) recruited at antenatal clinics answered a questionnaire. Data were analyzed with multinomial logistic regression, Kruskal-Wallis H and chi-squared tests. RESULTS: Three of four pregnancies were very or fairly planned and 12% fairly or very unplanned. Of women with very unplanned pregnancies, 32% had considered an induced abortion. Women with planned pregnancies were more likely to have a higher level of education, higher household income, to be currently working (≥50%) and to have longer relationships than women with unplanned pregnancies. The level of pregnancy planning was associated with planning behavior, such as information-seeking and intake of folic acid, but without a reduction in alcohol consumption. One-third of all women took folic acid 1 month prior to conception, 17% used tobacco daily and 11% used alcohol weekly 3 months before conception. CONCLUSIONS: A majority rated their pregnancy as very or fairly planned, with socio-economic factors as explanatory variables. The level of pregnancy planning should be queried routinely to enable individualized counseling, especially for women with unplanned pregnancies. Preconception recommendations need to be established and communicated to the public to increase health promoting planning behavior.

Adverse childhood experiences influence development of pain during pregnancy.

OBJECTIVE: To investigate the association between adverse childhood experiences (ACE) and pain with onset during pregnancy. DESIGN: Cross-sectional study. SETTING: Eighteen antenatal clinics in southern Mid-Sweden. SAMPLE: Of 293 women invited to participate, 232 (79%) women agreed to participate in early pregnancy and were assessed in late pregnancy. METHODS: Questionnaires were distributed in early and late pregnancy. The questionnaires sought information on socio-demography, ACE, pain location by pain drawing and pain intensity by visual analogue scales. Distribution of pain was coded in 41 predetermined areas. MAIN OUTCOME MEASURES: Pain in third trimester with onset during present pregnancy: intensity, location and number of pain locations. RESULTS: In late pregnancy, 62% of the women reported any ACE and 72% reported any pain location with onset during the present pregnancy. Among women reporting any ACE the median pain intensity was higher compared with women without such an experience (p = 0.01). The accumulated ACE displayed a positive association with the number of reported pain locations in late pregnancy (rs = 0.19, p = 0.02). This association remained significant after adjusting for background factors in multiple regression analysis (p = 0.01). When ACE was dichotomized the prevalence of pain did not differ between women with and without ACE. The subgroup of women reporting physical abuse as a child reported a higher prevalence of sacral and pelvic pain (p = 0.0003 and p = 0.02, respectively). CONCLUSIONS: Adverse childhood experiences were associated with higher pain intensities and larger pain distributions in late pregnancy, which are risk factors for transition to chronic pain postpartum.

Antifibrotic therapy in simian immunodeficiency virus infection preserves CD4+ T-cell populations and improves immune reconstitution with antiretroviral therapy.

Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4(+) T cells/µL, and CD4(+) T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4(+) T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4(+) T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4(+) T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution.

Mothers' experiences of feeding babies born with cleft lip and palate.

Cleft lip and palate (CLP) in newborns have implications for feeding. It might impede the child's attempts to seal around the nipple and to create intraoral pressure. Parents needed support and information about feeding after birth. Mothers' own experiences and how they coped with the challenges related to feeding have not been extensively studied. The aims of this study were twofold: to describe the experiences of feeding for mothers of children born with CLP and to elucidate how the mothers cope with the challenges related to feeding. A qualitative descriptive method and phenomenographic analysis were used to analyse the narratives. Twelve mothers of babies with CLP were strategically selected and interviewed. A semi-structured interview guide was used. Ethical approval for the study was granted by the local ethical committee. The findings resulted in two main categories and five subcategories. The first main category, Being a capable and good mother, included descriptions associated with the mothers' strong desire to do what was best for the child and about how they experienced feeding. The second main category, Coping with the challenges related to feeding, included descriptions of what the mothers perceived as important in order to cope with the challenges related to feeding; of how personal resources were used; of the significance of the father and close family; and of how healthcare professionals contributed. In conclusion, mothers of children born with CLP were in need of individual information by healthcare professionals with expertise, at the time of the diagnosis and until the feeding was manageable. Furthermore, the mothers' personal resources, the fathers and immediate family were of major importance for the mothers to cope with challenges related to feeding.

Thyroid testing and management of hypothyroidism during pregnancy: a population-based study.

CONTEXT: There are international guidelines on thyroid function testing and management of hypothyroidism during pregnancy. Few studies have evaluated how they are implemented into clinical practice. OBJECTIVE: In this descriptive study, we assessed the implementation of international guidelines in this field into local guidelines and also into clinical practice. DESIGN AND PARTICIPANTS: In a nationwide survey, all guidelines in Sweden were collected (n = 29), and the adherence of the local guidelines to The Endocrine Society Guidelines 2007 was evaluated. In a follow-up in 1 district, 5254 pregnant women with an estimated date of delivery between January 1, 2009, and December 31, 2011, were included for subsequent review of their medical reports. RESULTS: All but 1 district had guidelines on the subject. All local guidelines included fewer than the 10 listed reasons for thyroid testing recommended by The Endocrine Society Guidelines. Furthermore, most guidelines recommended additional types of thyroid function tests to TSH sampling and lower trimester-specific TSH upper reference limits for women on levothyroxine treatment (P < .001). In the follow-up, the thyroid testing rate was 20%, with an overall frequency of women with trimester-specific elevated TSH of 18.5%. More than half of the women (50.9%) who were on levothyroxine treatment at conception had an elevated TSH level at thyroid testing according to The Endocrine Society Guidelines. CONCLUSIONS: The local guidelines are variable and poorly compliant with international guidelines. Performance of thyroid testing is not optimal, and rates of elevated TSH at testing are extremely high in subgroups.

Patient's sexuality - a neglected area of cancer nursing?

PURPOSE: The purpose of this study was to describe nurses' conceptions of dialogues about sexuality with cancer patients. METHODS: The study was carried out using phenomenographic method. Ten nurses from different care contexts where nurses meet cancer patients in various phases of trajectory of care were interviewed. RESULTS: The analysis revealed one main category 'We should talk about sexuality - but we usually don't' and three descriptive categories consisting of nurses' qualitatively different conceptions of talks about sexuality: (1) nurses' attitudes, knowledge and skills are impacting, (2) patients' sexual problems are the basis for dialogues and (3) the ward environment is impacting. The main category was hierarchically ranged and could be further understood by the descriptive categories. CONCLUSION: The study showed that cancer patients' need of talks about and support regarding sexuality were conceived as being low during the whole trajectory of care. Despite this the nurses conceived that they should talk about sexuality with the patients, but due to own attitudes, knowledge and skills, as well as conditions in the ward environment they usually did not. Further studies are needed to clarify how cancer patients especially with non-sex specific diagnosis describe their sexual problems and needs of support in regard to sexuality. About what, when, how and by whom, cancer patients and their partners want information and supportive care related to sexuality need to be clarified.

The Swedish validation of Edinburgh Postnatal Depression Scale (EPDS) during pregnancy.

BACKGROUND: Around 10-15% of women suffer from depressive illness during pregnancy or the first year postpartum. Depression during pregnancy constitutes a risk for prenatal stress and preterm birth. No validated screening instrument for detecting depression during pregnancy was available in Swedish. AIMS: We aimed to validate the Edinburgh Postnatal Depression Scale (EPDS) against DSM-IV criteria for depression during pregnancy, establish a reliable cut-off and estimate the correlation between the EPDS and HAD-S (Hospital Anxiety and Depression Scale). METHODS: In a population-based community sample of 1175 pregnant women, 918 women (78%) answered questionnaires with the EPDS and HAD-S. In all, 121 were interviewed using the PRIME-MD (Primary Care Evaluation of Mental disorders) for diagnosing depression. Women were interviewed in mean gestational week 13 (range 8-21). For the EPDS, a receiver operating characteristic (ROC) curve was calculated for prediction of depression. Pearson's correlation coefficient was used to investigate the association between EPDS and HAD-S scores. RESULTS: The optimal cut-off score on the EPDS scale for detecting depression was ≥13 (standard error coefficient of 1.09 and c-statistics of 0.84) giving a sensitivity of 77% and specificity of 94%. The EPDS scores correlated strongly with the HAD-S, Pearson's correlation was 0.83 (P < 0.0001). CONCLUSIONS: This study confirms that the EPDS is a valid screening instrument for detection of depressive symptoms during pregnancy. The EPDS shows persuasive measuring outcomes with an optimal cut-off at ≥13. CLINICAL IMPLICATIONS: Healthcare for pregnant women should consider screening procedures and follow-up routines for depressive symptoms.

Targeting capacity and conservation of PreP homologues localization in mitochondria of different species.

Mitochondrial presequences and other unstructured peptides are degraded inside mitochondria by presequence proteases (PrePs) identified in Arabidopsis thaliana (AtPreP), humans (hPreP), and yeast (Cym1/Mop112). The presequences of A. thaliana and human PreP are predicted to consist of 85 and 29 amino acids, respectively, whereas the Saccharomyces cerevisiae Cym1/Mop112 presequence contains only 7 residues. These differences may explain the reported targeting of homologous proteins to different mitochondrial subcompartments. Here we have investigated the targeting capacity of the PreP homologues' presequences. We have produced fusion constructs containing N-terminal portions of AtPreP(1-125), hPreP(1-69), and Cym1(1-40) coupled to green fluorescent protein (GFP) and studied their import into isolated plant, mammalian, and yeast mitochondria, followed by mitochondrial subfractionation. Whereas the AtPreP presequence has the capacity to target GFP into the mitochondrial matrix of all three species, the hPreP presequence only targets GFP to the matrix of mammalian and yeast mitochondria. The Cym1/Mop112 presequence has an overall much weaker targeting capacity and only ensures mitochondrial sorting in its host species yeast. Revisiting the submitochondrial localization of Cym1 revealed that endogenous Cym1/Mop112 is localized to the matrix space, as has been previously reported for the plant and human homologues. Moreover, complementation studies in yeast show that native AtPreP restores the growth phenotype of yeast cells lacking Cym1, demonstrating functional conservation.

Pregnancy planning in Sweden--a pilot study among 270 women attending antenatal clinics.

OBJECTIVE: Health status and lifestyle before and at the time of conception could affect the health of both mother and child, but there is a lack of knowledge about the degree to which pregnancies are planned. The aim of this pilot study was to investigate whether and how women plan their pregnancies. MATERIAL AND METHODS: The main outcome measures were use of timetables, ovulation tests and lifestyle changes. Women (n= 322) visiting four antenatal clinics were asked to fill out a questionnaire (participation rate = 83.9%, n= 270). RESULTS: Three of four pregnancies (n= 202) were very or rather well planned, whereas 4.4% (n= 12) were totally unplanned. During the planning period, 37.1% (n= 100) made up a timetable for getting pregnant, 23% (n= 62) used ovulation tests, 20.7% (n= 56) took folic acid and 10.4% (n= 28) changed alcohol consumption. CONCLUSION: Although a majority of these women had planned pregnancies, only one in five had taken folic acid during the planning period.