Environmental Exposure to Persistent Organic Pollutants and Its Association with Endometriosis Risk: Implications in the Epithelial-Mesenchymal Transition Process.

We aimed to explore the relationship of adipose tissue concentrations of some persistent organic pollutants (POPs) with the risk of endometriosis and the endometriotic tissue expression profile of genes related to the endometriosis-related epithelial-mesenchymal transition (EMT) process. This case-control study enrolled 109 women (34 cases and 75 controls) between January 2018 and March 2020. Adipose tissue samples and endometriotic tissues were intraoperatively collected to determine concentrations of nine POPs and the gene expression profiles of 36 EMT-related genes, respectively. Associations of POPs with endometriosis risk were explored with multivariate logistic regression, while the relationship between exposure and gene expression profiles was assessed through Spearman correlation or Mann-Whitney U tests. After adjustment, increased endometriosis risk was associated with p,p'-DDT, PCB-180, and ΣPCBs. POP exposure was also associated with reduced gene expression levels of the CLDN7 epithelial marker and increased levels of the ITGB2 mesenchymal marker and a variety of EMT promoters (HMGA1, HOXA10, FOXM1, DKK1, CCR1, TNFRSF1B, RRM2, ANG, ANGPT1, and ESR1). Our findings indicate that exposure to POPs may increase the risk of endometriosis and might have a role in the endometriosis-related EMT development, contributing to the disease onset and progression. Further studies are warranted to corroborate these findings.

Total Effective Xenoestrogen Burden in Serum Samples and Risk of Endometrial Cancer in the Spanish Screenwide Case-Control Study.

BACKGROUND: Endometrial cancer is a hormone-dependent cancer, and estrogens play a relevant role in its etiology. However, little is known about the effects of environmental pollutants that act as xenoestrogens or that influence estrogenic activity through different pathways. OBJECTIVE: We aimed to assess the relationship between the combined estrogenic activity of mixtures of xenoestrogens present in serum samples and the risk of endometrial cancer in the Screenwide case-control study. METHODS: The total effective xenoestrogen burden (TEXB) attributable to organohalogenated compounds (TEXB-α) and to endogenous hormones and more polar xenoestrogens (TEXB-ß) was assessed in serum from 156 patients with endometrial cancer (cases) and 150 controls by combining chemical extraction and separation by high-performance liquid chromatography with the E-SCREEN bioassay for estrogenicity. RESULTS: Median TEXB-α and TEXB-ß levels for cases (0.30 and 1.25 Eeq pM/mL, respectively) and controls (0.42 and 1.28 Eeq pM/mL, respectively) did not significantly differ (p=0.653 and 0.933, respectively). An inverted-U risk trend across serum TEXB-α and TEXB-ß levels was observed in multivariate adjusted models: Positive associations were observed for the second category of exposure in comparison to the lowest category of exposure [odds ratio (OR)=2.11 (95% CI: 1.13, 3.94) for TEXB-α, and OR=3.32 (95% CI: 1.62, 6.81) for TEXB-ß], whereas no significant associations were observed between the third category of exposure and the first [OR=1.22 (95% CI: 0.64, 2.31) for TEXB-α, and OR=1.58 (95% CI: 0.75, 3.33) for TEXB-ß]. In mutually adjusted models for TEXB-α and TEXB-ß levels, the association of TEXB-α with endometrial cancer risk was attenuated [OR=1.45 (95% CI: 0.61, 3.47) for the second category of exposure], as well as estimates for TEXB-ß (OR=2.68; 95% CI: 1.03, 6.99). Most of the individual halogenated contaminants showed no associations with both TEXB and endometrial cancer. CONCLUSIONS: We evaluated serum total xenoestrogen burden in relation to endometrial cancer risk and found an inverted-U risk trend across increasing categories of exposure. The use of in vitro bioassays with human samples may lead to a paradigm shift in the way we understand the negative impact of chemical mixtures on human health effects. These results are relevant from a public health perspective and for decision-makers in charge of controlling the production and distribution of chemicals with xenoestrogenic activity. https://doi.org/10.1289/EHP13202.

Efficient removal of triclosan from water through activated carbon adsorption and photodegradation processes.

This study investigated the application of adsorption with activated carbons (ACs) and photodegradation to reduce the concentration of triclosan (TCS) in aqueous solutions. Concerning adsorption, ACs (Darco, Norit, and F400) were characterised and batch experiments were performed to elucidate the effect of pH on equilibrium. The results showed that at pH = 7, the maximum adsorption capacity of TCS onto the ACs was 18.5 mg g-1 for Darco, 16.0 mg g-1 for Norit, and 15.5 mg g-1 for F400. The diffusional kinetic model allowed an adequate interpretation of the experimental data. The effective diffusivity varied and increased with the amount of TCS adsorbed, from 1.06 to 1.68 × 10-8 cm2 s-1. In the case of photodegradation, it was possible to ensure that the triclosan molecule was sensitive to UV light of 254 nm because the removal was over 80 % using UV light. The removal of TCS increased in the presence of sulfate radicals. It was possible to identify 2,4-dichlorophenol as one of the photolytic degradation products of triclosan, which does not represent an environmental hazard at low concentrations of triclosan in water. These results confirm that the use of AC Darco, Norit, and F400 and that photodegradation processes with UV light and persulfate radicals are effective in removing TCS from water, reaching concentration levels that do not constitute a risk to human health or environmental hazard. Both methods effectively eliminate pollutants with relatively easy techniques to implement.

Expression Profiles of Genes Related to Development and Progression of Endometriosis and Their Association with Paraben and Benzophenone Exposure.

Increasing evidence has been published over recent years on the implication of endocrine-disrupting chemicals (EDCs), including parabens and benzophenones in the pathogenesis and pathophysiology of endometriosis. However, to the best of our knowledge, no study has been published on the ways in which exposure to EDCs might affect cell-signaling pathways related to endometriosis. We aimed to describe the endometriotic tissue expression profile of a panel of 23 genes related to crucial cell-signaling pathways for the development and progression of endometriosis (cell adhesion, invasion/migration, inflammation, angiogenesis, and cell proliferation/hormone stimulation) and explore its relationship with the exposure of patients to parabens (PBs) and benzophenones (BPs). This cross-sectional study included a subsample of 33 women with endometriosis from the EndEA study, measuring their endometriotic tissue expressions of 23 genes, while urinary concentrations of methyl-, ethyl-, propyl-, butyl-paraben, benzophenone-1, benzophenone-3, and 4-hydroxybenzophenone were determined in 22 women. Spearman's correlations test and linear and logistic regression analyses were performed. The expression of 52.2% of studied genes was observed in >75% of endometriotic tissue samples and the expression of 17.4% (n = 4) of them in 50-75%. Exposure to certain PB and BP congeners was positively associated with the expression of key genes for the development and proliferation of endometriosis. Genes related to the development and progression of endometriosis were expressed in most endometriotic tissue samples studied, suggesting that exposure of women to PBs and BPs may be associated with the altered expression profile of genes related to cellular pathways involved in the development of endometriosis.

Effect of a Multimodal Supervised Therapeutic Exercise Program on Quality of Life, Pain, and Lumbopelvic Impairments in Women With Endometriosis Unresponsive to Conventional Therapy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness of "Physio-EndEA", a multimodal nine-week supervised exercise intervention, on quality of life, pain, and lumbopelvic impairments in women with endometriosis unresponsive to conventional therapy. DESIGN: Parallel-group randomized controlled trial. Outcomes were measured at baseline, post-intervention, and at 1 year. SETTING: Two Public University Hospitals. PARTICIPANTS: This trial included 31 women with endometriosis (N=31) randomly allocated to "Physio-EndEA" group (n=16) or control group (n=15). Four participants dropped out of the study for causes unrelated to the intervention. INTERVENTIONS: The "Physio-EndEA" program consisted of a 1-week lumbopelvic stabilization learning phase followed by an 8-week phase of stretching, aerobic, and resistance exercises focused on the lumbopelvic area. It was sequentially instructed and supervised by a trained physiotherapist (with volume and intensity progression) and adapted daily to the potential of each participant. Control group received the usual treatment stipulated by their gynecologist. MAIN OUTCOME MEASURES: The primary outcome was quality of life. Secondary outcomes were pain intensity, pressure pain thresholds, pain-related catastrophic thoughts, abdominal and back strength, lumbopelvic stability, and muscle architecture. RESULTS: Adherence rate was 90.6% and mean (±standard deviation) satisfaction was 9.44±0.73 out of 10. No remarkable health problems were reported during the trial. In comparison with controls, the quality of life was improved post-intervention and at 1 year in the Physio-EndEA group with large effect sizes (d>0.80). This group also evidenced: a reduced intensity of dyspareunia, catastrophic thoughts; an increase in pelvic, lumbar, and distal pressure pain thresholds; increases in abdominal and back strength and lumbopelvic stability; and increased thickness of transversus abdominis (right side) and width of lumbar multifidus (left side). CONCLUSION: A 9-week program of multimodal supervised therapeutic exercise is a feasible and effective intervention to improve QoL in women with endometriosis. This program also offers benefits in terms of pain/sensitization and lumbopelvic impairments.

Influence of different surgical techniques on primary implant stability in the posterior maxilla: a randomized controlled clinical trial.

BACKGROUND AND OBJECTIVE: Primary stability (PS) is remarkable for secondary stability and implant success. Surgical technique modifications seem to improve primary stability, especially in poor quality bone. The aim of this study was to compare the insertion torque (IT) and implant stability quotients (ISQ) of implants placed with underpreparation, expanders, and standard surgical instrumentation in different bone types. MATERIAL AND METHODS: This randomized controlled clinical trial enrolled 108 patients (n=108 implants) distributed in three study groups: group 1 (n=36) underpreparation technique, group 2 (n=36) expander technique, and group 3 (n=36) conventional drilling. IT was recorded with a torque indicator. ISQ was recorded with resonance frequency analysis immediately after surgery. RESULTS: ISQ values were associated with the patient's bone quality and were higher in bone quality type II (76.65) and type III (73.60) and lower in bone quality type IV (67.34), with statistically significant differences (p<0.0001). Lower stability results were obtained when conventional drilling (69.31) was used compared to the use of underpreparation (74.29) or expanders (73.99) with a level of significance of p=0.008 and p=0.005, respectively. CONCLUSIONS: The surgical technique influences the PS when there is low-quality bone. In low-quality bones, conventional drilling obtains lower ISQ values. CLINICAL RELEVANCE: Replace the conventional drilling technique for an alternative, underpreparation or expanders, in low-quality bone in order to achieve greater primary stability.

Benzophenone-3: Comprehensive review of the toxicological and human evidence with meta-analysis of human biomonitoring studies.

BACKGROUND: Benzophenone-3 (BP-3) and its major metabolite benzophenone-1 (BP-1) are widely used as UV filters in sunscreens and cosmetics to prevent sunburn and skin damage, or as stabilizers to prevent photodegradation in many commercial products. As a result, their presence is ubiquitous in the environment, wildlife and humans. Based on endocrine disruption concerns, international regulatory agencies are performing a closer evaluation. OBJECTIVE AND METHODS: This work aimed to comprehensively review the available human relevant evidence for safety issues in MEDLINE/PubMed in order to create a structured database of studies, as well as to conduct an integrative analysis as part of the Human Biomonitoring for Europe (HBM4EU) Initiative. RESULTS: A total of 1,635 titles and abstracts were screened and 254 references were evaluated and tabulated in detail, and classified in different categories: i) exposure sources and predictors; ii) human biomonitoring (HBM) exposure levels to perform a meta-analysis; iii) toxicokinetic data in both experimental animals and humans; iv) in vitro and in vivo rodent toxicity studies; and v) human data on effect biomarkers and health outcomes. Our integrative analysis showed that internal peak BP-3 concentrations achieved after a single whole-body application of a commercially available sunscreen (4% w/w) may overlap with concentrations eliciting endocrine disrupting effects in vitro, and with internal concentrations causing in vivo adverse female reproductive effects in rodents that were supported by still limited human data. The adverse effects in rodents included prolonged estrous cycle, altered uterine estrogen receptor gene expression, endometrium hyperplasia and altered proliferation and histology of the mammary gland, while human data indicated menstrual cycle hormonal alterations and increased risk of uterine fibroids and endometriosis. Among the modes of action reported (estrogenic, anti-androgenic, thyroid, etc.), BP-3 and especially BP-1 showed estrogenic activity at human-relevant concentrations, in agreement with the observed alterations in female reproductive endpoints. The meta-analysis of HBM studies identified a higher concern for North Americans, showing urinary BP-3 concentrations on average 10 and 20 times higher than European and Asian populations, respectively. DISCUSSION AND CONCLUSIONS: Our work supports that these benzophenones present endocrine disrupting properties, endorsing recent European regulatory efforts to limit human exposure. The reproducible and comprehensive database generated may constitute a point of departure in future risk assessments to support regulatory initiatives. Meanwhile, individuals should not refrain from sunscreen use. Commercially available formulations using inorganic UV filters that are practically not absorbed into systemic circulation may be recommended to susceptible populations.

Concentrations and predictors of aluminum, antimony, and lithium in breast milk: A repeated-measures study of donors.

Aluminum (Al), antimony (Sb), and lithium (Li) are relatively common toxic metal(oid)s that can be transferred into breast milk and potentially to the nursing infant. This study assessed concentrations of Al, Sb, and Li in breast milk samples collected from donor mothers and explored the predictors of these concentrations. Two hundred forty-two pooled breast milk samples were collected at different times post-partum from 83 donors in Spain (2015-2018) and analyzed for Al, Sb, and Li concentrations. Mixed-effect linear regression was used to investigate the association of breast milk concentrations of these elements with the sociodemographic profile of the women, their dietary habits and utilization of personal care products (PCPs), the post-partum interval, and the nutritional characteristics of milk samples, among other factors. Al was detected in 94% of samples, with a median concentration of 57.63 µg/L. Sb and Li were detected in 72% and 79% of samples at median concentrations of 0.08 µg/L and 0.58 µg/L, respectively. Concentrations of Al, Sb, and Li were not associated with post-partum time. Al was positively associated with total lipid content of samples, weight change since before pregnancy, and coffee and butter intakes and inversely with meat intake. Li was positively associated with intake of chocolate and use of face cream and eyeliner and inversely with year of sample collection, egg, bread, and pasta intakes, and use of hand cream. Sb was positively associated with fatty fish, yoghurt, rice, and deep-fried food intakes and use of eyeliner and inversely with egg and cereal intakes and use of eyeshadow. This study shows that Al, Sb, and Li, especially Al, are widely present in donor breast milk samples. Their concentrations in the milk samples were most frequently associated with dietary habits but also with the lipid content of samples and the use of certain PCPs.

Associations of circulating levels of phthalate metabolites with cytokines and acute phase reactants in a Spanish human cohort.

The associations between human phthalate exposure and the onset of chronic diseases with an immunological component (e.g., metabolic syndrome, cancer) remain unclear, partly due to the uncertainties in the underlying mechanisms. This study investigates cross-sectional associations of the concentrations of 10 phthalate metabolites with 19 cytokines and acute phase proteins in 213 serum samples of Spanish adults. The associations were explored by Spearman's correlation, multivariable linear regression, and weighted quantile sum regression analyses. In the multivariable analyses, levels of plasminogen activator inhibitor (PAI)-1 were positively associated with mono-n-butyl phthalate (fold-change per one IQR increase in phthalate levels, 95% Confidence Interval: 1.65, 1.45-1.88) and mono-iso-butyl phthalate (3.07, 2.39-3.95), mono-ethyl phthalate (2.05, 1.62-2.61), as well as categorized mono-iso-decyl and mono-benzyl phthalates. The same phthalates also were significantly associated with leptin, interleukin (IL)-18 and monocyte chemoattractant protein-1. Moreover, the proinflammatory markers IL-1ß, IL-17, IL-8, IL-6, IL-12, tumor necrosis factor, and lipopolysaccharide-binding protein showed positive and negative associations with, respectively, mono-(2-ethyl-hexyl) and mono-methyl phthalates. Finally, phthalate mixtures were positively associated with PAI-1, leptin, IL-18, IL-12, IL-8 and IL-1ß. Despite the cross-sectional design limitation, these associations point to relevant subclinical immuno-inflammatory actions of these pollutants, warranting confirmation in future studies.

'Physio-EndEA' Study: A Randomized, Parallel-Group Controlled Trial to Evaluate the Effect of a Supervised and Adapted Therapeutic Exercise Program to Improve Quality of Life in Symptomatic Women Diagnosed with Endometriosis.

AIM: The 'Physio-EndEA' study aims to explore the potential benefits of a therapeutic exercise program (focused on lumbopelvic stabilization and tolerance to exertion) on the health-related quality of life (HRQoL) of symptomatic endometriosis women. DESIGN: The present study will use a parallel-group randomized controlled trial design. METHODS: A total of 22 symptomatic endometriosis women will be randomized 1:1 to the Physio-EndEA or usual care groups. The 'Physio-EndEA' program will consist of a one-week lumbopelvic stabilization learning phase followed by an eight-week phase of stretching, aerobic and resistance exercises focused on the lumbopelvic area that will be sequentially instructed and supervised by a trained physiotherapist (with volume and intensity progression) and adapted daily to the potential of each participant. The primary outcome measure is HRQoL. The secondary outcome measures included clinician-reported outcomes (pressure pain thresholds, muscle thickness and strength, flexibility, body balance and cardiorespiratory fitness) and patient-reported outcomes (pain intensity, physical fitness, chronic fatigue, sexual function, gastrointestinal function and sleep quality). DISCUSSION: Findings of this study will help to identify cost-effective non-pharmacological options (such as this exercise-based intervention) that may contribute to the improvement of HRQoL in symptomatic endometriosis women.

Concentrations and determinants of lead, mercury, cadmium, and arsenic in pooled donor breast milk in Spain.

AIM: To measure concentrations of lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As) in longitudinally collected donor breast milk samples and to determine associated factors. METHODS: Pb, Hg, Cd, and As concentrations were measured in 242 pooled breast milk samples from 83 donors to a Human Milk Bank in Spain, in 2015-2018, determining their association with the donors' sociodemographic profile, dietary and lifestyle habits, and post-partum time, among other factors, and with the nutritional characteristics of samples. Mixed-effect linear regression was used to identify predictors of Hg and As concentrations in breast milk and mixed-effect logistic regression to identify predictors of the presence of Pb and Cd. RESULTS: As was the element most frequently detected in milk samples (97.1%), followed by Hg (81.2%), Pb (50.6%), and Cd (38.0%). Their median breast milk concentrations were 1.49 µg/L, 0.26 µg/L, 0.14 µg/L, and <0.04 µg/L, respectively. Concentrations of As were higher in breast milk from primiparous donors, while Hg was higher in donors with a greater intake of fatty fish and meat and lower in samples collected after a longer post-partum time and with higher lactose content. Detection of Pb was higher among multiparous donors, those gaining weight since before pregnancy, and ex-smokers and was lower in samples collected more recently and from donors with greater intake of red meat and eggs. Cd detection was higher for donors with university education and those with greater intake of fried and canned food and more frequent use of hand cream and was lower for donors with greater bread intake. CONCLUSIONS: These findings reveal relatively high As concentrations, moderate Hg concentrations, and low Pb and Cd concentrations in pooled donor breast milk. Several factors including post-partum time, parity, smoking habit, and the intake of certain food items were associated with the metal content of milk samples.

Case Report: Dynamic Interdependencies Between Complementary and Alternative Medicine (CAM) Practice, Urinary Interleukin-6 Levels, and Fatigue in a Breast Cancer Survivor.

Background: This study investigated the influence of complementary and alternative medicine (CAM) techniques (i.e., Jin Shin Jyutsu, music, physiotherapy, Tai Chi, and energy healing) on urinary interleukin-6 (IL-6) levels and fatigue in a 49-year-old breast cancer survivor suffering from cancer-related fatigue and depression. Data were sampled under conditions of "life as it is lived." Methods: For 28 days, a female breast cancer survivor collected her full urine output in 12-h intervals from about 8 a.m. to 8 p.m. and from about 8 p.m. to 8 a.m. These urine samples were used to determine urinary IL-6 levels through ELISA and creatinine concentrations via HPLC. In 12-h intervals (every morning and evening), the patient completed the DIARI, which included fatigue measurement and notes on incidents and activities such as CAM practice. In addition, the patient was interviewed weekly to identify meaningful everyday incidents. In this context, CAM practice was also discussed. Time series analysis consisted of ARIMA modeling and cross-correlational analyses (p < 0.05). Results: When each CAM technique was considered separately in time series analysis, CAM was consistently associated with increases in urinary IL-6 release and decreases in fatigue. Furthermore, when all CAM techniques experienced as positive were included in one time series, a biphasic urinary IL-6 response pattern was found in which CAM practice was first preceded by decreases in IL-6 by 12-0 h and then followed by increases in IL-6 after 108-120 h. Finally, cross-correlations between IL-6 and fatigue showed that increases in IL-6 were followed by decreases in fatigue intensity after 48-60 h and, conversely, that decreases in fatigue intensity were followed by decreases in IL-6 after 24-36 h and 48-60 h. Conclusion: IL-6 increases and fatigue decreases highlight potential health-promoting effects of CAM practice. Moreover, a cyclic IL-6 pattern in response to all CAM activities experienced as positive underscores that CAM was meaningful to the patient. Additionally, a negative feedback circuit between IL-6 and fatigue intensity was detected. Taken together, this study confirms the necessity of integrating subjective meaning and dynamic complexity into biopsychosocial research in order to understand human functioning under real-life conditions.

Real-Life Cause-Effect Relations Between Urinary IL-6 Levels and Specific and Nonspecific Symptoms in a Patient With Mild SLE Disease Activity.

Background: Little is known about the real-time cause-effect relations between IL-6 concentrations and SLE symptoms. Methods: A 52-year-old woman with mild SLE activity collected her entire urine for the determination of IL-6/creatinine and protein/creatinine levels (ELISA, HPLC) for a period of 56 days in 12 h intervals (total: 112 measurements). Additionally, she answered questionnaires (VAS) on oral ulceration, facial rash, joint pain, fatigue and tiredness and measured her temperature orally twice a day. Time-series analyses consisted of ARIMA modeling and cross-correlational analyses (one lag = 12 h, significance level = p < 0.05). Results: Statistical analyses showed that increased urinary IL-6 concentrations preceded increased urinary protein levels by 36-48 h (lag3: r=+.225; p=.017) and that, in the opposite direction of effect, increased urinary protein preceded urinary IL-6 decreases by 12-24 h (lag1: r=-.322; p<.001). Moreover, urinary IL-6 increases co-occurred with increased oral ulceration (lag0: r=+.186; p=.049); after 48-60 h, however, IL-6 increases showed a strong tendency to precede oral ulceration decreases (lag4: r=-.170; p=.072). Increases in facial rash preceded decreases in urinary IL-6 after 84-96 h (lag7: r=-.215; p=.023). As to fatigue, increases in urinary IL-6 co-occurred with decreased fatigue (lag0: r=-.193; p=.042); after 84-96 h, however, IL-6 increases preceded fatigue increases (+lag7: r=+.189; p=.046). Finally, joint pain, tiredness and body temperature did not significantly correlate with urinary IL-6 concentrations in either direction of effect. Conclusions: The results of this evaluation point to real-life feedback mechanisms between immune activity and SLE symptoms. Comparison with a previous evaluation of this patient suggests a counterregulatory mechanism between Th1 activity and IL-6. These findings are preliminary and require replication to draw firm conclusions about the real-time relation between IL-6 and SLE disease activity.

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness.

Here, the role of non-invasive biomarkers in liquid biopsy was evaluated, mainly in exosomes and mitochondrial DNA (mtDNA) as promising, novel, and stable biomarkers for renal cell carcinoma (RCC). A total of 140 fractions (named from B to F) obtained by ultracentrifugations of whole blood samples from 28 individuals (13 patients and 15 controls) were included. Nanoparticle Tracking Analysis (NTA) was conducted to characterized exosomal fraction. Subsequently, an analysis of digital PCR (dPCR) using the QuantStudio™ 3D Digital PCR platform was performed and the quantification of mtDNA copy number by QuantStudioTM 12K Flex Real-Time PCR System (qPCR) was developed. Moreover, Next Generation Sequencing (NGS) analyses were included using MiSeq system (Illumina, San Diego, CA, USA). An F fraction, which contains all exosome data and all mitochondrial markers, was identified in dPCR and qPCR with statistically significant power (adjusted p values ≤ 0.03) when comparing cases and controls. Moreover, present analysis in mtDNA showed a relevant significance in RCC aggressiveness. To sum up, this is the first time a relation between exosomal mtDNA markers and clinical management of RCC is analyzed. We suggest a promising strategy for future liquid biopsy RCC analysis, although more analysis should be performed prior to application in routine clinical practice.

Association of Urinary Levels of Bisphenols A, F, and S with Endometriosis Risk: Preliminary Results of the EndEA Study.

Aim: The aim of this study was to explore associations of urinary concentrations of bisphenols A (BPA), S (BPS), and F (BPF) and of thiobarbituric acid reactive substances (TBARS) with the risk of endometriosis in women of childbearing age. Methods: This case-control study enrolled 124 women between January 2018 and July 2019: 35 women with endometriosis (cases) and 89 women without endometriosis undergoing abdominal surgery for other reasons (controls). Endometriosis was diagnosed (cases) or ruled out (controls) by laparoscopic inspection of the pelvis and the biopsy of suspected lesions (histological diagnosis). Fasting urine samples were collected before surgery to determine concentrations of BPA, BPS, BPF, and TBARS. Associations of bisphenol and TBARS concentrations with endometriosis risk were explored with multivariate logistic and linear regression analyses. Results: After adjustment for urinary creatinine, age, BMI, parity, and residence, endometriosis risk was increased with each 1 log unit of BPA [OR 1.5; 95%CI 1.0-2.3] and Σbisphenols [OR 1.5; 95%CI 0.9-2.3] but was not associated with the presence of BPS and BPF. Classification of the women by tertiles of exposure revealed statistically significant associations between endometriosis risk and the second tertile of exposure to BPA [OR 3.7; 95%CI 1.3-10.3] and Σbisphenols [OR 5.4; 95%CI 1.9-15.6]. In addition, TBARS concentrations showed a close-to-significant relationship with increased endometriosis risk [OR 1.6; 95%CI 1.0-2.8], and classification by TBARS concentration tertile revealed that the association between endometriosis risk and concentrations of BPA [OR 2.0; 95%CI 1.0-4.1] and Σbisphenols [OR 2.2; 95%CI 1.0-4.6] was only statistically significant for women in the highest TBARS tertile (>4.23 µM). Conclusion: Exposure to bisphenols may increase the risk of endometriosis, and oxidative stress may play a crucial role in this association. Further studies are warranted to verify these findings.

Risk Assessments of Epidural Analgesia During Labor and Delivery.

Epidural analgesia (EA) is one of the methods of choice for labor pain relief, but its adverse effects on the mother and child remain controversial. The objective of this study was to determine whether there is an association between the use of EA and different aspects of labor. The author(s) analyzed the effect of EA on different aspects of labor in a retrospective cohort observational study of deliveries in a public Spanish hospital during a 3-year period. Women with EA administration were found to increase the risk of stimulated labor, reduce the percentage of spontaneous deliveries, increase the risk of instrumental labor due to stalled labor or loss of fetal well-being, and increase the percentage of episiotomies. However, women with EA were not and increased risk for perineal laceration or the condition of the membranes at the delivery or with the type of placental expulsion. Thus, the administration of EA should be assessed in each case by the health care professional.

Subjective Positive and Negative Sleep Variables Differentially Affect Cellular Immune Activity in a Breast Cancer Survivor: A Time-series Analysis Approach.

This study on a breast cancer survivor suffering from cancer-related fatigue (CaRF) and depression investigated the bidirectional relationship between cellular immune activity and subjective sleep. The 49-year-old patient (breast cancer diagnosis 5 years before the study, currently in remission) collected her full urine output for 28 days in 12-h intervals (8:00 p.m. to 8:00 a.m. and 8:00 a.m. to 8:00 p.m.). These urine samples were used to determine urinary neopterin (cellular immune activation marker) and creatinine concentrations via high-pressure liquid chromatography (HPLC). Each morning, the patient answered questions on five sleep variables: sleep quality (SQ), sleep recreational value (SRV), total sleep time (TST), total wake time (TWT), and awakenings during sleep period (ADS). For the purpose of this study, the time series of the nighttime urinary neopterin levels and the five sleep variables were determined. Using centered moving average (CMA) smoothing and cross-correlational analysis, this study showed that increases in the positive sleep variables SQ and SRV were followed by urinary neopterin concentration decreases after 96-120 h (SQ, lag 4: r = -0.411; p = 0.044; SRV: lag 4: r = -0.472; p = 0.021) and 120-144 h (SRV, lag 5: r = -0.464; p = 0.026). Increases in the negative sleep variable TWT, by contrast, were followed by increases in urinary neopterin concentrations 72-96 h later (lag 3: r = 0.522; p = 0.009). No systematic effects in the other direction, i.e., from urinary neopterin levels to sleep, were observed in this study. Although preliminary, the findings of this study highlight the benefit of carefully investigating temporal delays and directions of effects when studying the dynamic relationship between sleep and immune variables in the natural context of everyday life.

Cause-effect relations between 55 kD soluble TNF receptor concentrations and specific and unspecific symptoms in a patient with mild SLE disease activity: an exploratory time series analysis study.

BACKGROUND: This integrative single-case study investigated the 12 h-to-12 h cause-effect relations between 55 kD soluble tumor necrosis factor receptor type 1 (sTNF-R55) and specific and unspecific symptoms in a 52-year-old Caucasian woman with mild systemic lupus erythematosus (SLE) disease activity. METHODS: The patient collected her entire urine for 56 days in 12 h-intervals to determine sTNF-R55/creatinine and protein/creatinine levels (ELISA, HPLC). Additionally, twice a day, she took notes on oral ulceration and facial rash; answered questionnaires (VAS) on fatigue, weakness, and joint pain; and measured body temperature orally. Time series analysis consisted of ARIMA modeling and cross-correlational analyses (significance level = p < 0.05). RESULTS: Time series analysis revealed both a circadian and a circasemiseptan rhythm in the urinary sTNF-R55 data. Moreover, several significant lagged correlations between urinary sTNF-R55 concentrations and SLE symptoms in both directions of effect were identified. Specifically, increased urinary sTNF-R55 concentrations preceded decreased urinary protein levels by 36-48 h (r = -0.213) and, in the opposite direction of effect, increased protein levels preceded increased sTNF-R55 concentrations by 24-36 h (r = +0.202). In addition, increased urinary sTNF-R55 levels preceded increased oral ulcers by 36-48 h (r = +0.277) and, conversely, increased oral ulceration preceded decreased sTNF-R55 levels by 36-48 h (r = -0.313). Moreover, increased urinary sTNF-R55 levels preceded decreased facial rash by 36-48 h (r = -0.223) and followed increased body temperature after 36-48 h (r = +0.209). Weakness, fatigue and joint pain were not significantly correlated with urinary sTNF-R55 levels. CONCLUSIONS: This study gathered first evidence of real-life, long-term feedback loops between cytokines and SLE symptoms in mild SLE disease activity. Such insights into the potential role of sTNF-R55 in SLE would not have been possible had we applied a pre-post design group study. These findings require replication before firm conclusions can be drawn.

Bacterial contamination levels of autogenous bone particles collected by 3 different techniques for harvesting intraoral bone grafts.

PURPOSE: The aim of this study was to compare levels of bacterial contamination of autogenous bone collected when using low-speed drilling, a back-action chisel, and a bone filter. MATERIALS AND METHODS: Bone tissue samples were taken from 31 patients who underwent surgical extraction of their third lower molars. Before surgical removal of the molar, bone particles were collected by a low-speed drill or a back-action chisel. Then, a stringent aspiration protocol was applied during the ostectomy to collect particulate bone by a bone filter. Processing of samples commenced immediately by incubation in an anaerobic or a CO2-rich atmosphere. The number of colony-forming units (CFUs) was determined at 48 hours of culture. RESULTS: No significant difference in the number of CFUs per milliliter was observed between the low-speed drilling group and the back-action chisel group in the anaerobic or CO2-rich condition (P = .34). However, significantly more micro-organisms were found in the bone filter group than in the low-speed drilling group or the back-action chisel group in the anaerobic and CO2-rich conditions (P < .001). CONCLUSIONS: Particulate bone harvested with low-speed drilling or a back-action chisel is safer for use as an autograft than are bone particles collected with a bone filter. These results suggest that bone obtained from low-speed drilling is safe and straightforward to harvest and could be the method of choice for collecting particulate bone. Further research is needed to lower the bacterial contamination levels of autogenous bone particles used as graft material.