Association between exposure to perfluoroalkyl substances (PFAS) and endometriosis in the ENDEA case-control study.

BACKGROUND: Perfluoroalkyl substances (PFAS) are environmental contaminants present in a wide range of consumer products and frequently detected in drinking water. They have been linked to adverse reproductive health outcomes in women, but there is limited human evidence on the association of PFAS exposure with endometriosis. OBJECTIVE/AIM: To explore the association between plasma concentrations of several PFAS, considered individually and as a mixture, and the risk of endometriosis in women of childbearing age. METHODS: Between 2018 and 2020, 42 patients with endometriosis and 90 controls undergoing abdominal surgery were recruited at two public hospitals in Granada, Spain. The presence or absence of endometriosis was ascertained by laparoscopic inspection of the pelvis and biopsy of suspected lesions (histological diagnosis). Concentrations of 10 PFAS were quantified in plasma samples from participants. Unconditional logistic regression was employed to examine associations of individual PFAS and summed concentrations of short (∑SC) and long-chain (∑LC) PFAS with odds of endometriosis, and quantile g-computation was used to assess their mixture effect. RESULTS: In models adjusted for age, schooling, and parity, perfluorotridecanoic acid (PFTrDA) was associated with higher odds of endometriosis (odds ratio [OR] = 1.74; 95 % CI = 1.11-2.73 per 2-fold increase in plasma concentrations), while marginally significant associations were found for perfluorohexane sulfonate (PFHxS) (OR = 1.45, 95 % CI = 0.94-2.21) and ∑SC PFAS (OR = 1.48; 95 % CI = 0.96-2.30). No associations were found for the remaining PFAS. The PFAS mixture was non-significantly associated with 1.7-fold higher odds of endometriosis (95 % CI = 0.73-3.80), with perfluorononanoic acid (PFNA), PFHxS, and PFTrDA being the major contributors to this effect. CONCLUSIONS: These findings suggest that exposure to certain PFAS may increase the odds of endometriosis. However, given the modest sample size, further studies are warranted to verify these results.

Prenatal mucopolysaccharidosis VII: A novel pathogenic variant identified in GUSB gene.

Clinical exome sequencing is a powerful approach to overcome the wide clinical and genetic heterogeneity of mucopolysaccharidosis. These data could be useful for prenatal diagnosis of MPS VII, genetic counseling, and preimplantation genetic testing.

Influence of a Concurrent Exercise Training Program During Pregnancy on Colostrum and Mature Human Milk Inflammatory Markers: Findings From the GESTAFIT Project.

BACKGROUND: Although exercise reduces systemic inflammation, information regarding its influence on human milk is scarce or inexistent. Research Aim: The aim of this study was to investigate the influence of an exercise intervention during pregnancy on colostrum and mature human milk inflammatory markers. METHODS: The authors conducted a pseudorandomized controlled trial. The exercise group followed a concurrent aerobic and strength training, three 60-minutes sessions per week, from the 17th gestational week until delivery. For the specific aims of this study, only women able to produce enough milk were included for data analyses, resulting in 24 exercise and 23 control women. Colostrum and mature human milk proinflammatory and anti-inflammatory cytokines (fractalkine, interleukin [IL]-1ß, IL-6, IL-8, IL-10, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α) were measured using Luminex xMAP technology. RESULTS: The mothers who followed the exercise program had 36% lower IL-8 and 27% lower TNF-α concentrations in their colostrum than those in the control group ( p < .05 and p < .01, respectively). The colostrum from mothers who followed the exercise program also presented borderline significant 22% lower IL-6 ( p < .100). The mature milk from mothers who followed the exercise program had 30% greater fractalkine ( p = .05) and borderline significant 20% higher IL-10 ( p = .100). The exercise intervention did not affect IFN-γ concentrations. CONCLUSIONS: This concurrent exercise program promoted a less proinflammatory profile in human milk, especially in colostrum. Moreover, it might increase mature human milk fractalkine, which could induce a greater neurodevelopment and neuroprotection in the newborn. This trial was registered at ClinicalTrials.gov (NCT02582567) on October 20, 2015.

Effects of supervised aerobic and strength training in overweight and grade I obese pregnant women on maternal and foetal health markers: the GESTAFIT randomized controlled trial.

BACKGROUND: During pregnancy, a sedentary lifestyle may have negative consequences on maternal and foetal health status. The main objective of this project is to assess the effects of an exercise intervention in overweight and grade I obese pregnant on maternal and foetal health markers. METHODS/DESIGN: The present study aims to recruit 60 overweight and grade I obese women interested in participating in an exercise intervention program from the 17th gestational week until delivery. Women will be randomized to either an exercise (three 60-min sessions/week of combined aerobic and strength training and pelvic floor exercises), or usual care (control) group (30 women per group). The primary outcome measures are maternal weight gain, and maternal and neonatal glycaemic profile. Secondary outcome measures are: i) perinatal obstetric records; i) body composition; iii) dietary patterns; iv) physical fitness; v) low-back pain; vi) objectively measured physical activity and sedentary behaviour; vii) haematology and biochemical analyses; viii) oxidative stress; ix) pro- and anti-inflammatory markers; x) bone health biomarkers; xi) sleep quality; xii) mental health, quality of life and positive health. DISCUSSION: The findings of this project will help to identify strategies for primary prevention and health promotion based on this exercise-based intervention program among overweight and grade I obese pregnant women. TRIAL REGISTRATION: NCT02582567 ; Date of registration: 20/10/2015.

Benefits of physical exercise in postmenopausal women.

Physical inactivity not only places women's health at risk during menopause, but also increases menopausal problems. Abundant evidence links habitual physical exercise (PE) to a better status on numerous health indicators and better quality of life and to the prevention and treatment of the ailments that typically occur from mid-life onwards. We can infer that PE is something more than a lifestyle: it constitutes a form of therapy in itself. A panel of experts from various Spanish scientific societies related to PE and menopause (Spanish Menopause Society, Spanish Cardiology Society, Spanish Federation of Sports Medicine) met to reach a consensus on these issues and to decide the optimal timing of and methods of exercise, based on the best evidence available.

Trends in children's exposure to second-hand smoke in the INMA-Granada cohort: an evaluation of the Spanish anti-smoking law.

The smoke-free legislation implemented in Spain in 2006 imposed a partial ban on smoking in public and work places, but the result did not meet expectations. Therefore, a more restrictive anti-smoking law was passed five years later in 2011 prohibiting smoking in all public places, on public transport, and the workplace. With the objective of assessing the impact of the latter anti-smoking legislation on children's exposure to second-hand smoke (SHS), we assessed parent's smoking habits and children's urine cotinine (UC) concentrations in 118 boys before (2005-2006) and after (2011-2012) the introduction of this law. Repeated cross-sectional follow-ups of the "Environment and Childhood Research Network" (INMA-Granada), a Spanish population-based birth cohort study, at 4-5 years old (2005-2006) and 10-11 years old (2011-2012), were designed. Data were gathered by ad-hoc questionnaire, and median UC levels recorded as an objective indicator of overall SHS exposure. Multivariable logistic regression was used to examine the association between parent's smoking habits at home and SHS exposure, among other potential predictors. An increase was observed in the prevalence of families with at least one smoker (39.0% vs. 50.8%) and in the prevalence of smoking mothers (20.3% vs. 29.7%) and fathers (33.9% vs. 39.0%). Median UC concentration was 8.0ng/mL (interquartile range [IQR]: 2.0-21.8) before legislation onset and 8.7ng/mL (IQR: 2.0-24.3) afterwards. In the multivariable analysis, the smoking status of parents and smoking habits at home were statistically associated with the risk of SHS exposure and with UC concentrations in children. These findings indicate that the recent prohibition of smoking in enclosed public and workplaces in Spain has not been accompanied by a decline in the exposure to SHS among children, who continue to be adversely affected. There is a need to target smoking at home in order to avoid future adverse health effects in a population that has no choice in the acceptance or not of SHS exposure-derived risk.

A new approach to oxidative stress and inflammatory signaling during labour in healthy mothers and neonates.

The objective of the current study was to investigate for the first time and simultaneously the oxidative stress and inflammatory signaling induced during the delivery in healthy mothers and their neonates. 56 mothers with normal gestational course and spontaneous delivery were selected. Blood samples were taken from mother (before and after delivery) both from vein and artery of umbilical cord. Lower antioxidant enzymes activities were observed in neonates compared with their mothers and lower oxidative stress in umbilical cord artery with respect to vein. There was an overexpression of inflammatory cytokines in the mother, such as IL-6 and TNF-α, and, in addition, PGE2 was also increased. Neonates showed lower levels of IL-6 and TNF-α and higher values of sTNF-RII and PGE2 in comparison with their mothers. Parturition increases oxidative damage in the mother, although the indicators of oxidative damage were lower in umbilical cord artery with respect to umbilical vein. The overexpression of inflammatory cytokines reveals that fetus suffers its own inflammatory process during parturition.

Umbilical cord serum lipids between early and late clamping in full-term newborns. A systematic assignment treatment group.

OBJECTIVE: The aim of the current study was to determine any relationship between the timing of clamping of the umbilical cord and the lipid levels circulating in umbilical artery and vein. METHODS: We studied a clinical trial with systematic assignment in 229 single-fetus full-term deliveries with normal gestational course and spontaneous delivery; out of these, 111 were subjected to early clamping (EC, within 10 s of delivery) and 118 to late clamping (LC, at 2 min). In all cases, total cholesterol (TC), triglycerides (TG), and phospholipids were measured in sera from umbilical artery and vein. RESULTS: TC and TG values were significantly higher in the EC group than in the LC group in both umbilical artery and vein. Comparing values between umbilical artery and vein in the two clamping groups, in the EC group, all studied lipids TC, TG and phospholipids were significantly higher in vein than in artery. In the LC group, only TC was higher in vein. CONCLUSION: Umbilical cord lipid levels are related to the timing of umbilical cord clamping, finding which is noteworthy, because they are essential component of postnatal development. Our study confirms that delivery acts as an important modifier of fetal lipid levels.

Factores relacionados con la supervivencia libre de enfermedad en el cáncer de mama / Disease-free survival related factors in breast cancer

Objetivo: Evaluar la relación entre los parámetros clínicos y anatomopatológicos del tumor primario y la supervivencia libre de enfermedad (SLE) en una serie hospitalaria de casos de cáncer de mama invasivo. Material y método: Estudio de cohortes retrospectivo con 635 pacientes diagnosticadas en el Hospital Universitario San Cecilio de Granada entre 1994 y 2006. La información relativa al tumor primario y a la evolución de la enfermedad se recogió mediante revisión de historias clínicas. La identificación de factores relacionados con el riesgo de recidiva y/o metástasis, y la SLE se realizó, a corto (3 y 5 años) y medio plazo (10 años), mediante análisis de regresión de Cox. Resultados: Tras ajustar por edad, tamaño tumoral, afectación ganglionar, grado histológico y expresión de receptores de estrógenos y de progesterona, se relacionan con mayor riesgo de recaída y menor SLE: el tamaño tumoral (3 años: riesgo relativo ajustado 3,00, intervalo de confianza del 95% 1,79-5,03; 5 años: 2,56, 1,65-3,98; 10 años: 2,16, 1,44-3,24), la infiltración ganglionar (3 años: 4,58, 2,42-8,65; 5 años: 3,84, 2,35-6,30; 10 años: 3,08, 2,05-4,61), la invasión linfovascular (5 años: 1,88, 1,16-3,04; 10 años: 2,19, 1,43-3,35), la multifocalidad/multicentricidad (3 años: 2,69, 1,46-4,96; 5 años: 1,90, 1,08-3,35) y p53 (3 años: 2,03, 1,00-4,09). Se relacionan con mayor SLE, la expresión de receptores de progesterona (3 años: 0,48, 0,26-0,89; 5 años: 0,58, 0,35-0,97; 10 años: 0,59, 0,38-0,90). Conclusiones: Las características biológicas del tumor primario permiten identificar pacientes con diferente pronóstico y SLE, pudiendo contribuir a la planificación de estrategias de seguimiento más personalizadas (AU)

Objective: To evaluate the relationship between the clinical and pathological parameters of the primary tumor and disease-free survival (DFS) in a sample of hospital cases of invasive breast cancer. Material and method: We performed a retrospective cohort study in 635 patients recruited at San Cecilio University Hospital in Granada (Spain) between 1994 and 2006. Information on the primary tumor and the outcomes of patients was collected by reviewing the medical records. Predictors of recurrence and/or metastasis and DFS (follow up of 3, 5 and 10 years) were analyzed by using Cox regression analysis. Results: Multivariate models adjusted for age, tumor size, lymph nodal status, histological grade and estrogen and progesterone receptor expression showed a higher risk of recurrence and/or metastasis and lower DFS (adjusted relative risk, 95% confidence intervals) with tumor size (3 yrs: 3.00, 1.79-5.03; 5 yrs: 2.56, 1.65-3.98; 10 yrs: 2.16, 1.44-3.24), lymph nodal status (3 yrs: 4.58, 2.42-8.65; 5 yrs: 3.84, 2.35-6.30; 10 yrs: 3.08, 2.05-4.61), lymphovascular invasion (5 yrs: 1.88, 1.16-3.04; 10 yrs: 2.19, 1.43-3.35), multifocal and/or multicenter tumors (3 yrs: 2.69, 1.46-4.96; 5 yrs: 1.90, 1.08-3.35) and p53 protein expression (3 yrs: 2.03, 1.00-4.09). DFS was positively associated with an increased expression of progesterone receptor (3 yr: 0.48, 0.26-0.89; 5 yrs: 0.58, 0.35-0.97; 10 yrs: 0.59, 0.38-0.90). Conclusions: The biological characteristics of the primary tumor can be used to identify patients with distinctive prognoses and DFS, and could be helpful in making individual follow up strategies (AU)

Analysis of measurement process of placental volume in early pregnancy: an interobserver reliability study.

OBJECTIVE: To examine concordance among results obtained in measurement process of first-trimester placental volume using 3D ultrasound and eXtended Imaging Virtual Organ Computed-aided AnaLysis (XI-VOCAL®, 3DXITM, Medison, Seoul, Korea) image analysis by three different operators. METHODS: Twenty first-trimester normal pregnancy cases were selected for placental volume measuring using a Medison SA 8000 Live Prime® (Medison, Seoul, Korea) with a convex volumetric multifrequency abdominal probe. Images were processed and studied independently by three operators with different grade of training. Each operator obtained 50 slices per case. Thus, this study is based on 1000 measurements that have generated four different sets of placental volume determinations based on 5, 10, 15, and 20 slices, respectively. Results of measurement process were analyzed using reliability coefficients. RESULTS: There was a good degree of concordance in the placental length values obtained by all operators and not depend from the number of cuts measured [intraclass correlation coefficient (ICC)=0.734]. However, the number of cuts is important to obtain a placental volume with more accuracy. Reliability coefficients were low when determining placental volume adjusted to placental length (ICC=0.293), but combined results of the two operators that were trained in the same way showed higher coefficients of reliability (ICC=0.682), and therefore, greater concordance when comparing with the operator that was not trained in the same way. CONCLUSION: Higher coefficients of reliability guarantee high grades of concordance in the results among operators when measuring placental volumes independently, however, contouring process introduces high variability. Training in how to best use the image analysis software effectively assists in getting higher coefficients of reliability.

[Disease-free survival related factors in breast cancer]. / Factores relacionados con la supervivencia libre de enfermedad en el cáncer de mama.

OBJECTIVE: To evaluate the relationship between the clinical and pathological parameters of the primary tumor and disease-free survival (DFS) in a sample of hospital cases of invasive breast cancer. MATERIAL AND METHOD: We performed a retrospective cohort study in 635 patients recruited at San Cecilio University Hospital in Granada (Spain) between 1994 and 2006. Information on the primary tumor and the outcomes of patients was collected by reviewing the medical records. Predictors of recurrence and/or metastasis and DFS (follow up of 3, 5 and 10 years) were analyzed by using Cox regression analysis. RESULTS: Multivariate models adjusted for age, tumor size, lymph nodal status, histological grade and estrogen and progesterone receptor expression showed a higher risk of recurrence and/or metastasis and lower DFS (adjusted relative risk, 95% confidence intervals) with tumor size (3 yrs: 3.00, 1.79-5.03; 5 yrs: 2.56, 1.65-3.98; 10 yrs: 2.16, 1.44-3.24), lymph nodal status (3 yrs: 4.58, 2.42-8.65; 5 yrs: 3.84, 2.35-6.30; 10 yrs: 3.08, 2.05-4.61), lymphovascular invasion (5 yrs: 1.88, 1.16-3.04; 10 yrs: 2.19, 1.43-3.35), multifocal and/or multicenter tumors (3 yrs: 2.69, 1.46-4.96; 5 yrs: 1.90, 1.08-3.35) and p53 protein expression (3 yrs: 2.03, 1.00-4.09). DFS was positively associated with an increased expression of progesterone receptor (3 yr: 0.48, 0.26-0.89; 5 yrs: 0.58, 0.35-0.97; 10 yrs: 0.59, 0.38-0.90). CONCLUSIONS: The biological characteristics of the primary tumor can be used to identify patients with distinctive prognoses and DFS, and could be helpful in making individual follow up strategies.

Comparison of the interferon-tau expression from primary trophectoderm outgrowths derived from IVP, NT, and parthenogenote bovine blastocysts.

The expression of interferon-tau (IFN-tau) is essential for bovine embryo survival in the uterus. An evaluation of IFN-tau production from somatic cell nuclear transfer (NT)-embryo-derived primary trophectoderm cultures in comparison to trophectoderm cultured from parthenogenote (P) and in vitro matured, fertilized, and cultured (IVP) bovine embryos was performed. In Experiment 1, the success/failure ratio for primary trophectoderm colony formation was similar for IVP and NT blastocysts [IVP = 155/29 (84%); NT 104/25 (81%)], but was decreased (P = .05) for P blastocysts [54/43 (56%)]. Most trophectoderm colonies reached diameters of at least 1 cm within 3-4 weeks, and at this time, 72 hr conditioned cell culture medium was measured for IFN-tau concentration by antiviral activity assay. The amount of IFN-tau produced by IVP-outgrowths [4311 IU/mL (n = 155)] was greater (P < .05) than that from NT- [626 IU/mL (n = 104)] and P - [1595 IU/mL (n = 54)] derived trophectoderm. Differential expression of IFN-tau was confirmed by immunoblotting. In Experiment 2, colony formation was again similar for IVP and NT blastocysts [IVP = 70/5 (93%); NT 67/1 (99%)] and less (P < .05) for P blastocysts [65/27 (70%)]. Analysis of trophectoderm colony size after 23 days in culture showed a similar relationship with P-derived colonies being significantly smaller in comparison to IVP and NT colonies. A differential expression of IFN-tau was also observed again, but this time as measured over time in culture. Maximal IFN-tau production was found at day-14 of primary culture and diminished to a minimum by the 23rd day.

Granulocyte-macrophage colony-stimulating-factor increases interferon-tau protein secretion in bovine trophectoderm cells.

PROBLEM: Uterine-derived factors are required for optimal conceptus development and secretion of the maternal recognition of pregnancy factor, interferon-tau (IFN-tau). Identifying these factors may lead to the development of schemes for increasing pregnancy success in cattle. METHOD OF STUDY: The objectives were to examine the effects of granulocyte-macrophage colony-stimulating-factor (GM-CSF) on trophectoderm proliferation rates and IFN-tau production, and verify the appropriateness of using an in vitro model of bovine trophectoderm (CT-1 cell). RESULTS: Rate of [(3)H]-thymidine incorporation into DNA was increased by supplementation of CT-1 medium with 10 or 100 ng/mL porcine (po) GM-CSF. GM-CSF supplementation to CT-1 medium also increased IFN-tau secretion. When results were normalized to account for number of CT-1 cells, 10 and 100 ng/mL poGM-CSF increased antiviral activity and IFN-tau concentrations (using an IFN-tau-specific enzyme-linked immunosorbent assay) in CT-1 conditioned medium compared with controls. CONCLUSIONS: These findings indicate that GM-CSF increases proliferation and IFN-tau production in bovine trophectoderm.

Fibroblast growth factor-2 is expressed by the bovine uterus and stimulates interferon-tau production in bovine trophectoderm.

Uterine-derived factors are essential for conceptus development and secretion of the maternal recognition-of-pregnancy factor, interferon-tau (IFNT), in ruminant species. The objectives of this study were to determine whether fibroblast growth factor-2 (FGF-2) is expressed in the bovine uterus during early pregnancy in cattle and to determine whether FGF-2 supplementation affects IFNT mRNA and protein abundance in bovine trophectoderm. FGF-2 mRNA was present in endometrium throughout the estrous cycle and was localized to the luminal and glandular endometrial epithelium at d 17-18 after estrus in pregnant and nonpregnant cows. Immunoreactive FGF-2 protein was detected within the endometrium and in the uterine lumen at d 17-18 after estrus, and concentrations did not differ based on pregnancy status. In a bovine trophectoderm cell line, CT-1, supplementation of medium with at least 1 ng/ml FGF-2 increased the incorporation of [(3)H]thymidine into DNA. Similarly, IFNT secretion from CT-1 cells increased after FGF-2 supplementation (1-100 ng/ml) for 72 h. Abundance of IFNT mRNA in CT-1 cells increased after 24 h exposure to 1, 10, or 100 ng/ml FGF-2. In bovine blastocysts, FGF-2 supplementation did not affect cell number after 72 h of culture but did stimulate IFNT protein concentrations in conditioned medium. In summary, FGF-2 is present in the uterine lumen during early pregnancy and increases IFNT mRNA and protein abundance in trophectoderm. The magnitude by which FGF-2 stimulates IFNT expression suggests that this uterine-derived factor plays an active role in regulating the establishment and maintenance of pregnancy in ruminants.

Adiponectin gene is expressed in multiple tissues in the chicken: food deprivation influences adiponectin messenger ribonucleic acid expression.

Adiponectin is a cytokine hormone originally found to be secreted exclusively by white adipose tissue. However, recent evidences suggest that adiponectin is also produced in brown adipose tissue and skeletal muscle. The present study investigated the expression of adiponectin mRNA in various tissues in the chicken. We also studied the effect of food deprivation on adiponectin gene expression in adipose tissue, liver, anterior pituitary gland, and diencephalon in the chicken. The open reading frame of chicken adiponectin cDNA consists of 735 nucleotides that were 65-68% homologous to various mammalian adiponectin cDNAs. The deduced amino acid sequence of chicken adiponectin contains 22 glycine-X-Y repeats (in which X and Y represent any amino acid) at the N-terminal end as found in the mammalian adiponectin. By RT-PCR and Northern analysis, we detected chicken adiponectin mRNA transcript in adipose tissue, liver, anterior pituitary gland, diencephalon, skeletal muscle, liver, kidney, ovary, and spleen but not in blood. Adiponectin mRNA expression in various tissues was quantitated using real-time quantitative PCR and found to be the highest in adipose tissue, followed by liver, anterior pituitary, diencephalon, kidney, and skeletal muscle. We also found that adiponectin mRNA quantity was significantly decreased after a 48-h food deprivation in adipose tissue, liver, and anterior pituitary gland but not in diencephalon. Our results provide novel evidence that, unlike mammals, adiponectin gene is expressed in several tissues in the chicken and that its expression is influenced by food deprivation.