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1.
BJOG ; 131(9): 1229-1237, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38351638

ABSTRACT

OBJECTIVE: To investigate fetal growth trajectories and risks of small and large for gestational age (SGA and LGA), and macrosomia in pregnancies after fresh and frozen embryo transfer (ET), and natural conception (NC). DESIGN: Longitudinal population-based cohort study. SETTING: Swedish national registers. POPULATION: A total of 196 008 singleton pregnancies between 2013 and 2017. METHODS: Of all singleton pregnancies resulting in live births in the Swedish Pregnancy Register, 10 970 fresh ET, 6520 frozen ET, and 178 518 NC pregnancies with ultrasound data were included. A general least squares model was used to examine the effect of fresh or frozen ET on fetal growth while adjusting for confounders. MAIN OUTCOME MEASURES: Fetal growth velocity. SGA, LGA and macrosomia. RESULTS: At 120 days, fetal weights were lower in fresh ET pregnancies compared with NC pregnancies. Thereafter fresh ET as well as FET fetuses had higher fetal weights than NC fetuses, with no differences between themselves until the second trimester. From 210 days, FET fetuses were heavier than fresh ET fetuses, whereas fresh ET fetuses had lower fetal weights than NC fetuses from 245 days. After fresh ET, SGA was more frequent, whereas LGA and macrosomia were less frequent, than after FET. CONCLUSIONS: This study gives new insights into the differences in fetal growth dynamics between fresh and frozen ET and NC pregnancies. Clinically relevant differences in proportions of SGA, LGA and macrosomia were observed.


Subject(s)
Embryo Transfer , Fetal Development , Fetal Macrosomia , Infant, Small for Gestational Age , Registries , Humans , Female , Pregnancy , Embryo Transfer/statistics & numerical data , Embryo Transfer/methods , Fetal Macrosomia/epidemiology , Adult , Fetal Development/physiology , Sweden/epidemiology , Longitudinal Studies , Cryopreservation , Infant, Newborn , Fertilization , Fetal Weight
2.
Eur J Contracept Reprod Health Care ; 26(4): 312-322, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33855916

ABSTRACT

PURPOSE: The aim of this study was to investigate medical undergraduate students' fertility awareness and parenthood intentions in three European countries, as well as possible differences across genders and countries. MATERIALS AND METHODS: A cross sectional survey among 656 medical students in Sweden, Belgium and Greece. The utilised questionnaire comprised 23 questions. RESULTS: Three fourth of participants (n = 472/629) correctly stated that women are most fertile at 20-25 years of age. Approximately 91% correctly answered that women's fertility starts to significantly decline before the age of 35, which differed among countries of participation. Social oocyte or sperm freezing was considered by 67% of Belgians, 49% Greeks, and 16.5% Swedes (p < 0.001). Approximately 95% expressed a wish of having a child in the future and the median age was 29 years for the first and 35 years for the last child. CONCLUSIONS: Knowledge about fertility among medical students was in general satisfactory, albeit varying by country and gender. Medical curricula and social policies for childbearing should be respectively updated in EU countries suffering population growth.


Subject(s)
Fertility , Health Knowledge, Attitudes, Practice , Intention , Reproductive Behavior , Students, Medical/psychology , Adult , Cross-Sectional Studies , Female , Humans , Male , Sweden
3.
J Neurosci Res ; 98(7): 1268-1282, 2020 07.
Article in English | MEDLINE | ID: mdl-30723972

ABSTRACT

Maternal perinatal depression (PND), a common mental disorder with a prevalence of over 10%, is associated with long-term health risks for both mothers and offspring. This study aimed at describing characteristics related to background and lifestyle, pregnancy, delivery, and postpartum of different PND trajectories defined according to the onset of depressive symptoms. Participants were drawn from a large population-based cohort study in Uppsala, Sweden (n = 2,466). Five trajectory groups of depressive symptom onset were created using the Edinburgh Postnatal Depression Scale ≥13 (pregnancy) or ≥12 points (postpartum): (a) healthy (60.6%), (b) pregnancy depression (8.5%), (c) early postpartum onset (10.9%), (d) late postpartum onset (5.4%), and (e) chronic depression (14.6%). In multinomial logistic regressions, the associations between trajectories and the included characteristics were tested using the healthy trajectory as reference. Background characteristics (younger age, lower education, unemployment) were primarily associated with pregnancy depression and chronic depression. Characteristics associated with all PND trajectories were smoking prior to pregnancy, migraine, premenstrual mood symptoms, intimate partner violence, interpersonal trauma, negative delivery expectations, pregnancy nausea, and symphysiolysis. Nulliparity, instrumental delivery, or a negative delivery experience was associated with early postpartum onset. Postpartum factors (e.g., infantile colic, lack of sleep, low partner support, and bonding difficulties) were associated with early and late postpartum onset together with chronic depression. The findings suggest that different PND trajectories have divergent characteristics, which could be used to create individualized treatment options. To find the most predictive characteristics for different PND trajectories, studies with even larger and more diverse samples are warranted.


Subject(s)
Depression, Postpartum/psychology , Depression/psychology , Depressive Disorder/psychology , Pregnancy Complications/psychology , Adult , Age Factors , Educational Status , Employment , Female , Humans , Mothers , Pregnancy , Risk Factors , Stress, Psychological/psychology , Young Adult
4.
Liver Transpl ; 22(2): 237-46, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26479304

ABSTRACT

Inflammation-associated oxidative stress contributes to hepatic ischemia/reperfusion injury (IRI). Detrimental inflammatory event cascades largely depend on activated Kupffer cells (KCs) and neutrophils, as well as proinflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL) 18. The aim of our study was to evaluate the effects of IL 18 binding protein (IL 18Bp) in hepatic IRI of mice. Thirty C57BL/6 mice were allocated into 3 groups: sham operation, ischemia/reperfusion (I/R), and I/R with intravenous administration of IL 18Bp. Hepatic ischemia was induced for 30 minutes by Pringle's maneuver. After 120 minutes of reperfusion, mice were euthanized, and the liver and blood samples were collected for histological, immunohistochemical, molecular, and biochemical analyses. I/R injury induced the typical liver pathology and upregulated IL-18 expression in the liver of mice. Binding of IL 18 with IL 18Bp significantly reduced the histopathological indices of I/R liver injury and KC apoptosis. The I/R-induced increase of TNF-α, malondialdehyde, aspartate aminotransferase, and alanine aminotransferase levels was prevented in statistically significant levels because of the pretreatment with IL 18Bp. Likewise, blocking of IL 18 ablated the I/R-associated elevation of nuclear factor kappa B, c-Jun, myeloperoxidase, and IL 32 and the up-regulation of neutrophils and T-helper lymphocytes. Administration of IL 18Bp protects the mice liver from I/R injury by intervening in critical inflammation-associated pathways and KC apoptosis.


Subject(s)
Intercellular Signaling Peptides and Proteins/pharmacology , Liver Diseases/therapy , Liver/injuries , Reperfusion Injury/metabolism , Alanine Transaminase/blood , Animals , Apoptosis , Aspartate Aminotransferases/blood , Cytokines/metabolism , DNA Primers , Gene Expression Regulation , Immunohistochemistry , Inflammation , Interleukin-18/metabolism , Liver/metabolism , Liver Transplantation/adverse effects , Male , Malondialdehyde/metabolism , Mice , Mice, Inbred C57BL , Models, Animal , Neutrophils/metabolism , Oxidative Stress , Peroxidase/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation
5.
Depress Anxiety ; 33(11): 1023-1030, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27232288

ABSTRACT

BACKGROUND: Peripartum depression is a common cause of pregnancy- and postpartum-related morbidity. The production of corticotropin-releasing hormone (CRH) from the placenta alters the profile of hypothalamus-pituitary-adrenal axis hormones and may be associated with postpartum depression. The purpose of this study was to assess, in nondepressed pregnant women, the possible association between CRH levels in pregnancy and depressive symptoms postpartum. METHODS: A questionnaire containing demographic data and the Edinburgh Postnatal Depression Scale (EPDS) was filled in gestational weeks 17 and 32, and 6 week postpartum. Blood samples were collected in week 17 for assessment of CRH. A logistic regression model was constructed, using postpartum EPDS score as the dependent variable and log-transformed CRH levels as the independent variable. Confounding factors were included in the model. Subanalyses after exclusion of study subjects with preterm birth, newborns small for gestational age (SGA), and women on corticosteroids were performed. RESULTS: Five hundred thirty-five women without depressive symptoms during pregnancy were included. Logistic regression showed an association between high CRH levels in gestational week 17 and postpartum depressive symptoms, before and after controlling for several confounders (unadjusted OR = 1.11, 95% CI 1.01-1.22; adjusted OR = 1.13, 95% CI 1.02-1.26; per 0.1 unit increase in log CRH). Exclusion of women with preterm birth and newborns SGA as well as women who used inhalation corticosteroids during pregnancy did not alter the results. CONCLUSIONS: This study suggests an association between high CRH levels in gestational week 17 and the development of postpartum depressive symptoms, among women without depressive symptoms during pregnancy.

6.
Sex Reprod Healthc ; 41: 100984, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38815451

ABSTRACT

OBJECTIVE: To explore men's and women's experiences regarding their history of sexual health when attending a fertility clinic. METHODS: A qualitative study with semi-structured individual interviews was conducted among heterosexual males and females seeking infertility care at a public fertility clinic in Sweden in 2022-2023. The interviews were audio-recorded, transcribed verbatim and analyzed using qualitative content analysis. RESULTS: Eight males and ten females were included. The analysis resulted in an overarching theme: A change from spontaneous to scheduled intercourse affects various aspects of sexual health. In the beginning of the relationship sex had been spontaneous, joyful and satisfying. However, sex was not always unproblematic, and there had been sexual changes. Sex with a reproductive purpose was scheduled according to ovulation, leading to changes in sexual behavior. Increased erectile problems in men and decreased frequency of orgasms in women, and a lack of sexual desire in both, were experienced. Men and women felt pressured to have sex when it became a requirement. Men's sexual and women's reproductive failures led to negative emotional reactions, including stress, frustration, disappointment, anxiety and guilt. Sexual and reproductive problems affected the relational well-being, leading to feelings of sharing the burden but also conflicts and sexual avoidance. CONCLUSIONS: Experiencing reproductive failures, sexual problems and negative emotional reactions can affect men's and women's sexual health. Therefore, an implication for clinical practice among healthcare professionals during evaluation of infertility, is a need to be aware of and ask questions about sexual health after reproductive failures.

7.
Eur Psychiatry ; 67(1): e14, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38254262

ABSTRACT

BACKGROUND: Postpartum depression affects around 12% of mothers in developed countries, with consequences for the whole family. Many women with depressive symptoms remain undetected and untreated. The aim of this study was to investigate to what extent women with depressive symptoms at 6 weeks postpartum are identified by the healthcare system, the interventions they received, and remission rates at 6 months postpartum. METHODS: Postpartum women scoring 12-30 on the Edinburgh Postnatal Depression Scale (EPDS) at 6 weeks after delivery (n = 697) were identified from the longitudinal cohort study "Biology, Affect, Stress, Imaging and Cognition" (BASIC) in Uppsala, Sweden. A total of 593 women were included. Background and remission information at 6 months was collected from the BASIC dataset. Medical records were examined to identify interventions received. RESULTS: Most women (n = 349, 58.7%) were not identified by the healthcare system as having depressive symptoms and 89% lacked any record of interventions. Remission rates at 6 months postpartum were 69% in this group. Among women identified by the healthcare system, 90% received interventions and about 50% were in remission at 6 months postpartum. The EPDS reduction during the study period was largest in the group identified by the child health services (CHS, -5.15) compared to the non-identified (-4.24, p < 0.001). CONCLUSIONS: Despite screening guidelines, many women with depressive symptoms had no documentation of screening or interventions by the healthcare system. Furthermore, a significant proportion did not achieve remission despite interventions. Being identified by CHS was associated with the largest reduction of symptoms. Research is needed to understand gaps in the healthcare processes, to better identify peripartum depression.


Subject(s)
Depression, Postpartum , Depression , Child , Female , Humans , Cohort Studies , Longitudinal Studies , Sweden , Postpartum Period , Depression, Postpartum/diagnosis , Depression, Postpartum/therapy
8.
Sci Rep ; 13(1): 5861, 2023 04 11.
Article in English | MEDLINE | ID: mdl-37041242

ABSTRACT

Conservative management of endometrial cancer (CMEC) is viable for women with early-stage disease wishing to preserve fertility, but there is poor knowledge regarding clinicians' attitudes towards treatment or guidelines adherence. This 55-item survey study investigated CMEC-related experience, practice and attitudes among clinically active Swedish gynecologists and gynecological oncologists, focusing on reproductive eligibility criteria. The survey consisted of a general and two specific subsets, selectively delivered to clinicians active in infertility (subset A) and endometrial cancer (subset B) care. Answers from 218 clinicians were included. More than half agreed on CMEC whereas only 5% explicitly disagreed. The majority supported a fertility work-up to substantiate reasonable chances to pregnancy and live birth. Most disagreed about CMEC in case of previous unsuccessful fertility treatments, while more than 1/3 disagreed about CMEC in known fertility problems, recurrent miscarriages or previous children. Over 50% of respondents in subset A (n = 107) found it applicable with fertility investigations such as ovarian reserve testing or, in case of male partner, semen analysis. Respondents in subset B (n = 165) agreed on items based on existing recommendations regarding the oncological management of CMEC, including the use of continuous progestins, hysteroscopic resection of macroscopic lesions, control biopsy with curettage or hysteroscopy after 6 months of treatment, pursuing pregnancy as soon as possible after complete response, and performing a hysterectomy once live birth is achieved. While many clinicians were familiar with CMEC, the overall experience is limited. Fertility specialists seem less involved than oncologists in patient care but there is broad support for fertility-related eligibility criteria.


Subject(s)
Endometrial Neoplasms , Fertility Preservation , Pregnancy , Child , Male , Female , Humans , Conservative Treatment , Sweden , Gynecologists , Antineoplastic Agents, Hormonal/therapeutic use , Endometrial Neoplasms/pathology
9.
Front Behav Neurosci ; 17: 1096122, 2023.
Article in English | MEDLINE | ID: mdl-36778131

ABSTRACT

Introduction: Investigations of biofeedback (BF) and neurofeedback (NF) training for nicotine addiction have been long documented to lead to positive gains in smoking status, behavior and to changes in brain activity. We aimed to: (a) evaluate a multi-visit combined BF/NF intervention as an alternative smoking cessation approach, (b) validate training-induced feedback learning, and (c) document effects on resting-state functional connectivity networks (rsFCN); considering gender and degree of nicotine dependence in a longitudinal design. Methods: We analyzed clinical, behavioral, and electrophysiological data from 17 smokers who completed five BF and 20 NF sessions and three evaluation stages. Possible neuroplastic effects were explored comparing whole-brain rsFCN by phase-lag index (PLI) for different brain rhythms. PLI connections with significant change across time were investigated according to different resting-state networks (RSNs). Results: Improvements in smoking status were observed as exhaled carbon monoxide levels, Total Oxidative Stress, and Fageström scores decreased while Vitamin E levels increased across time. BF/NF promoted gains in anxiety, self-esteem, and several aspects of cognitive performance. BF learning in temperature enhancement was observed within sessions. NF learning in theta/alpha ratio increase was achieved across baselines and within sessions. PLI network connections significantly changed across time mainly between or within visual, default mode and frontoparietal networks in theta and alpha rhythms, while beta band RSNs mostly changed significantly after BF sessions. Discussion: Combined BF/NF training positively affects the clinical and behavioral status of smokers, displays benefit in smoking harm reduction, plays a neuroprotective role, leads to learning effects and to positive reorganization of RSNs across time. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02991781.

10.
J Clin Med ; 12(5)2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36902538

ABSTRACT

Neutrophil and T-cell recruitment contribute to hepatic ischemia/reperfusion injury. The initial inflammatory response is orchestrated by Kupffer cells and liver sinusoid endothelial cells. However, other cell types, including γδ-Τ cells, seem to be key mediators in further inflammatory cell recruitment and proinflammatory cytokine release, including IL17a. In this study, we used an in vivo model of partial hepatic ischemia/reperfusion injury (IRI) to investigate the role of the γδ-Τ-cell receptor (γδTcR) and the role of IL17a in the pathogenesis of liver injury. Forty C57BL6 mice were subjected to 60 min of ischemia followed by 6 h of reperfusion (RN 6339/2/2016). Pretreatment with either anti-γδΤcR antibodies or anti-IL17a antibodies resulted in a reduction in histological and biochemical markers of liver injury as well as neutrophil and T-cell infiltration, inflammatory cytokine production and the downregulation of c-Jun and NF-κΒ. Overall, neutralizing either γδTcR or IL17a seems to have a protective role in liver IRI.

11.
Sci Rep ; 11(1): 7877, 2021 04 12.
Article in English | MEDLINE | ID: mdl-33846362

ABSTRACT

Postpartum depression (PPD) is a detrimental health condition that affects 12% of new mothers. Despite negative effects on mothers' and children's health, many women do not receive adequate care. Preventive interventions are cost-efficient among high-risk women, but our ability to identify these is poor. We leveraged the power of clinical, demographic, and psychometric data to assess if machine learning methods can make accurate predictions of postpartum depression. Data were obtained from a population-based prospective cohort study in Uppsala, Sweden, collected between 2009 and 2018 (BASIC study, n = 4313). Sub-analyses among women without previous depression were performed. The extremely randomized trees method provided robust performance with highest accuracy and well-balanced sensitivity and specificity (accuracy 73%, sensitivity 72%, specificity 75%, positive predictive value 33%, negative predictive value 94%, area under the curve 81%). Among women without earlier mental health issues, the accuracy was 64%. The variables setting women at most risk for PPD were depression and anxiety during pregnancy, as well as variables related to resilience and personality. Future clinical models that could be implemented directly after delivery might consider including these variables in order to identify women at high risk for postpartum depression to facilitate individualized follow-up and cost-effectiveness.


Subject(s)
Depression, Postpartum/diagnosis , Machine Learning , Mothers/psychology , Adult , Female , Humans , Prospective Studies , Risk Factors , Surveys and Questionnaires , Sweden
12.
Sci Rep ; 11(1): 13963, 2021 07 07.
Article in English | MEDLINE | ID: mdl-34234211

ABSTRACT

The aim of this study was to investigate sexual behavior, contraceptive use, risk factors as well as sources of sex information among first-year high-school students in Sweden. Secondly, to assess differences between genders and study programs as well as changes over a 40-year period. A repeated cross-sectional survey was conducted in two cities. A questionnaire comprising 77 items was used. The study population consisted of 415 students (63.4% females). The median age of sexual intercourse was 15 years. In total, 37% had had sexual intercourse, compared to 56.3% in 2009 and 45% in 1999 (p < 0.001), and the proportion of students who had their first sexual intercourse was not influenced by gender. More students in vocational programs (46.3%), compared to theoretical (33.3%), had experience of at least one sexual intercourse (p = 0.019). The same extend of contraception use at first and latest intercourse was reported, compared to previous studies. Forty-nine percent were mostly informed about sex from the internet, while in previous years, magazines, family and youth clinics were the main information sources. Comparing over time, students were in general less sexually experienced and less engaged in non-penetrative sex and physical intimacy. These findings call for a new approach, when designing sex and relationship education and health-care counseling in adolescents.


Subject(s)
Sexual Behavior/statistics & numerical data , Students , Adolescent , Adolescent Behavior , Contraception Behavior , Cross-Sectional Studies , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Schools , Sexual Partners , Surveys and Questionnaires , Sweden/epidemiology
13.
J Surg Res ; 159(2): 720-8, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19394642

ABSTRACT

INTRODUCTION: Hepatic ischemia/reperfusion (I/R) activates Kupffer cells and initiates severe oxidative stress with enhanced production of reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-alpha). ROS and TNF-alpha mediate the expression of nuclear factors and kinases, activating the signal transduction pathway, and triggering apoptosis. The aim of our study was to evaluate the potential protective effect of (-)-epigallocatechin-3-gallate (EGCG) administration in inhibition of apoptosis by attenuating the expression of NF-kappaB, c-Jun, and caspase-3 in a model of severe hepatic I/R. MATERIALS AND METHODS: Thirty Wistar rats were allocated into three groups. Sham operation, I/R, and I/R-EGCG 50mg/kg. Hepatic ischemia was induced for 60min by Pringle's maneuver. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, scanning electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry for NF-kappaB, c-Jun, caspase-3, analysis on liver specimens and aspartate (AST), and alanine (ALT) transferases analysis in serum, were performed 120min after reperfusion. RESULTS: Apoptosis as indicated by TUNEL and caspase-3 was widely expressed in the I/R group but very limited in the EGCG treated group. Liver was stained positive for NF-kappaB and c-Jun in the I/R group but failed to be stained positive in the EGCG treated group. MDA, MPO, AST, and ALT showed marked increase in the I/R group and significant decrease in EGCG treated group. Significant alterations of liver specimens were observed by light histology and transmission electron microscopy whilst pretreatment with EGCG resulted in parenchymal preservation. CONCLUSIONS: Administration of EGCG is likely to inhibit I/R-induced apoptosis and protect liver by down-regulating NF-kappaB and c-Jun signal transduction pathways.


Subject(s)
Apoptosis/drug effects , Catechin/analogs & derivatives , Ischemia/surgery , Liver Diseases/genetics , NF-kappa B/genetics , Proto-Oncogene Proteins c-jun/genetics , Reperfusion Injury/prevention & control , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Catechin/pharmacology , Down-Regulation , Immunohistochemistry , In Situ Nick-End Labeling , Ischemia/pathology , Liver Diseases/drug therapy , Liver Diseases/metabolism , Liver Diseases/pathology , Malondialdehyde/metabolism , NF-kappa B/drug effects , Peroxidase/metabolism , Proto-Oncogene Proteins c-jun/drug effects , Rats , Rats, Wistar , Reperfusion Injury/pathology
14.
Sci Rep ; 10(1): 18701, 2020 10 29.
Article in English | MEDLINE | ID: mdl-33122633

ABSTRACT

The Transgender Congruence Scale (TCS) is a non-binary tool used in Sweden for gender dysphoria (GD) assessment; however, its Swedish version has not been validated. To investigate the psychometric properties of the TCS, its capacity to distinguish individuals with GD and its concurrent validity compared to other scales. Patients with GD (n = 135) and controls (n = 443) filled in a questionnaire containing sociodemographic questions, the TCS, the Utrecht Gender Dysphoria Scale (UGDS), and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA). TCS had good discriminatory validity and internal consistency. Patients with GD, stratified by birth-assigned sex, had lower TCS scores compared to controls. Confirmatory factor analysis (CFA) supported the two-factor model of the TCS. Multiple-group CFA suggested measurement invariance between birth-assigned sexes and configural invariance between patients with GD and controls. Area under the ROC curve for birth-assigned males was 0.991 and for females 0.994. A TCS mean value of three provided sensitivity 94.3% and 95.1% as well as specificity 98.6% and 98% for aM and aF, respectively. The TCS was significantly correlated to UGDS and GIDYQ-AA. The TCS may be a valuable tool in the clinical assessment of individuals with GD.


Subject(s)
Psychometrics , Transgender Persons , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Reproducibility of Results , Surveys and Questionnaires , Sweden , Young Adult
15.
Onco Targets Ther ; 13: 5575-5588, 2020.
Article in English | MEDLINE | ID: mdl-32606772

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and a leading cause of cancer-related death worldwide. Its rapid progression, combined with the limited treatment options at late stages, imposes the need for early detection and aggressive intervention. Based on the knowledge that hepatocarcinogenesis is significantly influenced by histone acetylation, we directed our search for novel HCC therapeutics among histone deacetylation inhibitors (HDACi). The aim of the present study was to investigate the effect of HDAC1/2 inhibitor Romidepsin in the well-established mouse model of diethylnitrosamine (DEN)-induced HCC. MATERIALS AND METHODS: C56BL/6 mice were treated with Romidepsin at the critical point of 10 months after DEN challenge and their livers were examined 2 months later using histopathology and morphometry. Protein levels were assessed in serum using ELISA and in liver tissues using Western blot and immunohistochemistry (in-situ detection). Gene expression was quantified using real-time PCR. RESULTS: Romidepsin suppressed cancer progression. This effect was associated with decreased proliferation and increased apoptosis of cancer cells. The cell cycle regulator CK2a, the anti-inflammatory molecule PPAR-γ, and the tumor suppressors PTEN and CYLD were upregulated in treated HCC. By contrast, the expression of PI3K, NF-κB p65 and c-Jun was reduced. In line with this result, the levels of two major apoptosis regulators, ie, BAD and the multifunctional protein c-Met, were lower in the blood serum of treated mice compared to the untreated mice with HCC. CONCLUSION: These findings suggest that Romidepsin, a drug currently used in the treatment of lymphoma, could also be considered in the management of early-stage HCC.

16.
J Int Med Res ; 48(6): 300060520933452, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32602766

ABSTRACT

OBJECTIVES: In transplantation surgery, the ischaemic organ and reperfusion impairment after cold storage remains a considerable risk factor for impaired function and potential failure of the grafted organ. Substantial logistical efforts have been undertaken to reduce the cold ischaemic time because the demand for available transplant organs and the periods of cold ischaemia are increasing. METHODS: Four molecules were investigated (erythropoietin, sildenafil, lazaroid [U74389G], octreotide) in individual intravenous infusions 1 hour before the organ was harvested. This study was performed in 30 healthy landrace/large-white pigs (male; >10 weeks old; average weight, 22 ± 2 kg) in groups of six. The organs were studied at harvest, and at 8 and 24 hours post-harvest. RESULTS: The lazaroid molecule increased malondialdehyde (MDA) levels in the liver and pancreas at 8 hours. Hepatic lazaroid molecules improved liver histology at 8 and 24 hours. For kidneys, erythropoietin had a positive effect at 24 hours post-harvest. For the pancreas, octreotide showed better performance. In the lungs, there was less interstitial oedema with erythropoietin and lazaroid compared with the control group at 8 hours post-harvest. CONCLUSION: All molecules had a positive effect and decreased ischaemia/reperfusion graft injury. Thus, pretreatment before organ harvest has a beneficial role.


Subject(s)
Pregnatrienes , Reperfusion Injury , Animals , Antioxidants , Lung , Male , Malondialdehyde , Reperfusion Injury/prevention & control , Swine
17.
Sci Rep ; 9(1): 15328, 2019 10 25.
Article in English | MEDLINE | ID: mdl-31653981

ABSTRACT

Seasonal variations have recently been described in biomarkers, cell types, and gene expression associated with the immune system, but so far no studies have been conducted among women in the peripartum period. It is of note that pregnancy complications and outcomes, as well as autoimmune diseases, have also been reported to exhibit seasonal fluctuations. We report here a clear-cut seasonal pattern of 23 inflammatory markers, analysed using proximity-extension assay technology, in pregnant women. The inflammatory markers generally peaked in the spring and had a trough in the autumn. During the postpartum period we found seasonality in one inflammatory marker, namely monocyte chemotactic protein 4 (MCP-4). Our findings suggest that seasonal variations in peripheral inflammatory markers are only observed during pregnancy. The results of this study could be valuable to professionals working within the field of immunology-related areas, and provide insight for the understanding of obstetric complications.


Subject(s)
Biomarkers/blood , Inflammation Mediators/blood , Peripartum Period/blood , Seasons , Adult , Female , Humans , Macrophage Colony-Stimulating Factor/blood , Pregnancy , Vascular Endothelial Growth Factor A/blood
18.
Psychoneuroendocrinology ; 103: 296-305, 2019 05.
Article in English | MEDLINE | ID: mdl-30776573

ABSTRACT

Individual differences in the response of the stress system to hormonal changes during pregnancy and the postpartum period render some women susceptible to developing depression. The present study sought to investigate peripartum depression and stress hormones in relation to stress-related genotypes. The Edinburgh Postnatal Depression Scale was used to assess peripartum depressive symptoms in a sample of 1629 women, followed from pregnancy week seventeen to six months postpartum. Genotypes of ninety-four haplotype-tag single nucleotide polymorphisms (SNPs) in sixteen genes of the hypothalamus-pituitary-adrenal axis pathway were analyzed and data on psychosocial and demographic factors was collected. In sub-studies, salivary cortisol awakening response in gestational week 35-39, salivary evening cortisol levels in gestational week 36 and postpartum week 6, and blood cortisol and cortisone levels in gestational week 35-39 were analyzed. SNP-set kernel association tests were performed at the gene-level, considering psychosocial and demographic factors, followed by post-hoc analyses of SNPs of significant genes. Statistically significant findings at the 0.05 p-level included SNPs in the hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) gene in relation to self-rated depression scores in postpartum week six among all participants, and serpin family A member 6 (SERPINA6) gene at the same time-point among women with de novo onset of postpartum depression. SNPs in these genes also associated with stress hormone levels during pregnancy. The present study adds knowledge to the neurobiological basis of peripartum depression by systematically assessing SNPs in stress-regulatory genes and stress-hormone levels in a population-based sample of women.


Subject(s)
Depression/genetics , Peripartum Period/psychology , Stress, Psychological/genetics , 11-beta-Hydroxysteroid Dehydrogenase Type 1/genetics , Adult , Depression/metabolism , Depression/psychology , Depression, Postpartum/metabolism , Depressive Disorder/genetics , Depressive Disorder/metabolism , Female , Genotype , Humans , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Longitudinal Studies , Pituitary-Adrenal System/metabolism , Polymorphism, Single Nucleotide/genetics , Postpartum Period/psychology , Pregnancy , Psychiatric Status Rating Scales , Stress, Psychological/metabolism , Sweden/epidemiology , Transcortin/genetics
19.
Int J Hematol Oncol Stem Cell Res ; 13(2): 49-57, 2019 Apr 01.
Article in English | MEDLINE | ID: mdl-31372197

ABSTRACT

Background: Over the last few decades, there has been a dramatic increase in hematological malignancies (HMs) in the population of Sardinia. It is accepted that oxidative stress biomarkers have been demonstrated to be prognostically important in various neoplastic diseases. The aim of this study is to evaluate serum vitamin E, total antioxidant capacity (TAC), Malondialdehyde (MDA) and reactive oxygen species (ROS) levels in 80 Sardinian patients with different HMs [acute myeloid leukemia (AML)(n=20), myelodysplastic syndromes (MDS) (n=20), Hodgkin lymphoma (HL) (n=20) and non-Hodgkin lymphoma (NHL) (n=20)] on the day of their diagnosis. Materials and Methods: Samples from all participants were obtained after an overnight fast (at least 10 hours). This study was approved and conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. Patients and controls provided written, informed consent before entering the study. All study participants' medical history and their medication were documented upon enrolling. Results: Lower levels of TAC and Vitamin E were observed in most of the studied groups compared to healthy controls (0.41-0.49 mmol/L vs. 0.56 mmol/L) (19.55-28.55 µmol/L vs. 34.51 µmol/L). Moreover, higher average MDA levels were observed in HL and NHL patients compared to healthy controls (16.6 ng/ml-17.8 ng/ml vs. 7.4 ng/ml). Additionally, the ROS values of all studied groups were found elevated. Serum TAC showed significant negative correlations with MDA values (R= -0.51; P<0.001). Statistical significance was observed in all hematological parameters, producing either positive or negative correlation with at least one OS biomarker. Conclusion: The present data suggest that Sardinian patients with HL and NHL on the day of their diagnosis presented the highest OS in comparison to AML and healthy subjects. Moreover, MDS patients presented high OS status. Likewise, our results also indicated that changes in their hematological indices are eminent of their oxidative and antioxidative status.

20.
BMJ Open ; 9(10): e031514, 2019 10 22.
Article in English | MEDLINE | ID: mdl-31641004

ABSTRACT

PURPOSE: With the population-based, prospective Biology, Affect, Stress, Imaging and Cognition (BASIC) cohort, we aim to investigate the biopsychosocial aetiological processes involved in perinatal depression (PND) and to pinpoint its predictors in order to improve early detection. PARTICIPANTS: From September 2009 to November 2018, the BASIC study at Uppsala University Hospital, Sweden, has enrolled 5492 women, in 6478 pregnancies, of which 46.3% first-time pregnancies and with an average age of 31.5 years. After inclusion around gestational week 16-18, participants are followed-up with data collection points around gestational week 32, at childbirth, as well as three times postpartum: after 6 weeks, 6 months and 1 year. At the last follow-up, 70.8% still remain in the cohort. FINDINGS TO DATE: In addition to internet-based surveys with self-report instruments, participants contribute with biological samples, for example, blood samples (maternal and from umbilical cord), biopsies (umbilical cord and placenta) and microbiota samples. A nested case-control subsample also takes part in cognitive and emotional tests, heart rate variability tests and bioimpedance tests. Subprojects have identified various correlates of PND of psychological and obstetric origin in addition to factors of the hypothalamic-pituitary-adrenal axis and immune system. FUTURE PLANS: In parallel with the completion of data collection (final follow-up November 2019), BASIC study data are currently analysed in multiple subprojects. Since 2012, we are conducting an ongoing follow-up study on the participants and their children up to 6 years of age (U-BIRTH). Researchers interested in collaboration may contact Professor Alkistis Skalkidou (corresponding author) with their request to be considered by the BASIC study steering committee.


Subject(s)
Depression/etiology , Pregnancy Complications/etiology , Adult , Affect , Case-Control Studies , Cognition , Depression/diagnosis , Depression/physiopathology , Depression/psychology , Depression, Postpartum/diagnosis , Depression, Postpartum/etiology , Depression, Postpartum/physiopathology , Depression, Postpartum/psychology , Female , Follow-Up Studies , Heart Rate , Humans , Hypothalamo-Hypophyseal System , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/physiopathology , Pregnancy Complications/psychology , Prospective Studies , Risk Factors , Social Determinants of Health , Stress, Psychological/psychology , Sweden
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