Repression of Irs2 by let-7 miRNAs is essential for homeostasis of the telencephalic neuroepithelium.

Structural integrity and cellular homeostasis of the embryonic stem cell niche are critical for normal tissue development. In the telencephalic neuroepithelium, this is controlled in part by cell adhesion molecules and regulators of progenitor cell lineage, but the specific orchestration of these processes remains unknown. Here, we studied the role of microRNAs in the embryonic telencephalon as key regulators of gene expression. By using the early recombiner Rx-Cre mouse, we identify novel and critical roles of miRNAs in early brain development, demonstrating they are essential to preserve the cellular homeostasis and structural integrity of the telencephalic neuroepithelium. We show that Rx-Cre;DicerF/F mouse embryos have a severe disruption of the telencephalic apical junction belt, followed by invagination of the ventricular surface and formation of hyperproliferative rosettes. Transcriptome analyses and functional experiments in vivo show that these defects result from upregulation of Irs2 upon loss of let-7 miRNAs in an apoptosis-independent manner. Our results reveal an unprecedented relevance of miRNAs in early forebrain development, with potential mechanistic implications in pediatric brain cancer.

Exploring the association between urinary bisphenol A, S, and F levels and semen quality parameters: Findings from Led-Fertyl cross-sectional study.

Infertility is recognized as a multifaceted condition affecting approximately 15% of couples globally, influenced by various factors including genetic predisposition and environmental exposures. Among these environmental factors, bisphenol A (BPA) emerges as a prominent Endocrine-disrupting chemical (EDCs) widely distributed, leading to chronic human exposure in daily life. As regulations on BPA became more stringent, alternative substances such as bisphenol S (BPS) and bisphenol F (BPF) have emerged. Animal studies have demonstrated a dose-dependent decline in fertility and embryotoxicity following chronic exposure to BPA. However, literature data on human studies are limited and heterogeneous. Additionally, even less is known about the relationship between exposure to the BPA analogues (BPS and BPF) and sperm quality. Therefore, the present study aimed to examine the association between urinary concentrations of BPA, BPF, and BPS and semen quality parameters among 195 adult Spanish men from the Led-Fertyl study cohort using multiple linear regression models adjusted by potential confounding variables. Our results revealed an inverse association between log-transformed creatinine-adjusted concentration (ng/mg) of BPA and BPF levels and the percentage of sperm vitality (ß: 3.56 %; 95%CI: 6.48 to -0.63 and ß: 4.14 %; 95%CI: 6.97 to -1.31; respectively). Furthermore, participants in the highest quartile of BPA and BPF urinary concentration exhibited lower sperm vitality compared to those in the lowest quartile (ß: 6.90 %; 95%CI: 11.60 to -2.15 and ß: 9.68 %; 95%CI: 14.43 to -4.94; respectively). These results supply epidemiological evidence establishing a relationship between bisphenols urine exposure and sperm quality, suggesting that a re-evaluation of the overall safety of BPA alternatives is warranted.

[Initial assessment of immigrant patients in primary care]. / Atención inicial al paciente inmigrante en atención primaria.

The clinical interview of immigrant patients requires cultural competence to ensure good understanding and correct communication, in addition to collecting specific information that differs from that of native patients, such as origin and migratory route or cultural identity. Screening for latent tuberculosis infection is recommended in certain cases and screening for other infections, both cosmopolitan with a higher prevalence in migrants (HIV, syphilis, hepatitis B and C) and imported (Chagas, intestinal parasites, strongyloidiasis, schistosomiasis), depending on origin. It is essential to check the vaccination status and complete the vaccination schedule, adapting it to the current calendar, prioritizing vaccines such as measles, rubella and poliomyelitis. We propose preventive activities to be carried out when traveling to countries of origin, due to their special characteristics and risks: general advice, exploring the risk of malaria, assessing specific vaccinations, advice regarding sexually transmitted infections and special considerations if they have chronic diseases; and addressing, if appropriate, the risks of female genital mutilation.

Exploring the Occurrence of Organic Contaminants in Human Semen through an Innovative LC-HRMS-Based Methodology Suitable for Target and Nontarget Analysis.

Understanding the potential impact of organic contaminants on male fertility is crucial, yet limited studies have examined these chemicals in semen, with most focusing on urine and blood. To address this gap, we developed and validated a robust LC-HRMS methodology for semen analysis, with a focus on polar and semipolar chemicals. Our methodology enables the quantitative (or semiquantitative) analysis of >2000 chemicals being compatible with suspect and nontarget strategies and providing unprecedented insights into the occurrence and potential bioaccumulation of diverse contaminants in this matrix. We comprehensively analyzed exogenous organic chemicals and associated metabolites in ten semen samples from Spanish participants collected in an area with a large presence of the chemical industry included in the LED-FERTYL Spanish study cohort. This investigation revealed the presence of various contaminants in semen, including plastic additives, PFAS, flame retardants, surfactants, and insecticides. Notably, prevalent plastic additives such as phthalic acid esters and bisphenols were identified, indicating potential health risks. Additionally, we uncovered previously understudied chemicals like the tire additive 2-mercaptobenzothiazole and specific organophosphate flame retardants. This study showcases the potential of our methodology as a valuable tool for large-scale cohort studies, providing insights into the association between contaminant exposure and the risk of male fertility impairments.

Lack of association between endocrine disrupting chemicals and male fertility: A systematic review and meta-analysis.

The incidence of infertility currently affects about 15% of the world's population. Male factors are estimated to be responsible for up to 40-50% of these cases. While the cause of these reproductive disorders is still unclear, the exposure to a family of ubiquitous compounds in our daily life, named endocrine disrupting chemicals (EDCs) could be involved. This paper was aimed at performing a systematic review and meta-analysis of population studies exploring whether human male exposure to EDCs affects male fertility. Clinical and observational studies assessing the exposure to EDCs along with sperm quality, the most common reproductive disorders, sperm DNA damage, sperm oxidative stress, fertilization rate, implantation rate, clinical pregnancy rate, live birth rate, and miscarriage rate were included. The quality assessment tool from the NHLBI-NIH was used to assure that studies met standardized quality criteria. Sensitivity analysis and heterogeneity among studies was assessed. Overall, the 32 selected articles, including 7825 individuals in the systematic review, explored 12 families of EDCs. The results revealed a high heterogeneity among studies in relation to the association between exposure to EDCs and the endpoints analyzed. Meta-analyses were performed with data from 7 articles including 479 individuals, 4 articles assessing the association between BPA in urine and sperm quality, and 3 articles evaluating PCB153 in serum and sperm quality. In the meta-analysis, we identified an unpredicted significant positive association between PCB153 exposure and sperm concentration. However, it would not be clinically relevant. No positive or inverse associations were found neither for BPA, nor for PCB153 and the rest of sperm parameters analyzed. The high disparity between studies made difficult to draw conclusions on the potential harmful effects of EDCs on male fertility. Consequently, to delineate the potential relationship that EDCs can have on male fertility, an important condition stressing the health system, further investigations are required.

Dietary intake of polychlorinated dibenzo-p-dioxins and furans, adiposity and obesity status.

INTRODUCTION: The principal source of exposure to Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) in humans comes from food intake. PCDD/Fs, are a family of potential endocrine disruptors and have been associated with different chronic diseases such as diabetes and hypertension. However, studies assessing the relationship between dietary exposure to PCDD/Fs and adiposity or obesity status in a middle-aged population are limited. OBJECTIVE: To assess cross-sectionally and longitudinally the associations between estimated dietary intake (DI) of PCDD/Fs and body mass index (BMI), waist circumference, and the prevalence/incidence of obesity and abdominal obesity in a middle-aged population. METHODS: In 5899 participants aged 55-75 years (48% women) living with overweight/obesity from the PREDIMED-plus cohort, PCDD/Fs DI was estimated using a 143-item validated food-frequency questionnaire, and the levels of food PCDD/F expressed as Toxic Equivalents (TEQ). Consequently, cross-sectional and prospective associations between baseline PCDD/Fs DI (in pgTEQ/week) and adiposity or obesity status were assessed at baseline and after 1-year follow-up using multivariable cox, logistic or linear regression models. RESULTS: Compared to participants in the first PCDD/F DI tertile, those in the highest tertile presented a higher BMI (ß-coefficient [confidence interval]) (0.43kg/m2 [0.22; 0.64]; P-trend <0.001), a higher waist circumference (1.11 cm [0.55; 1.66]; P-trend <0.001), and a higher prevalence of obesity and abdominal obesity (1.05 [1.01; 1.09] and 1.02 [1.00; 1.03]; P-trend = 0.09 and 0.027, respectively). In the prospective analysis, participants in the top PCDD/F DI baseline tertile showed an increase in waist circumference compared with those in the first tertile after 1-year of follow-up (ß-coefficient 0.37 cm [0.06; 0.70]; P-trend = 0.015). CONCLUSION: Higher DI of PCDD/Fs was positively associated with adiposity parameters and obesity status at baseline and with changes in waist circumference after 1-year of follow-up in subjects living with overweight/obesity. Further large prospective studies using a different population with longer follow-up periods are warranted in the future to strengthen our results.

Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study.

BACKGROUND AND AIM: Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions. METHODS AND RESULTS: Case-cohort study from the PREDIMED trial involving participants aged 55-80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20-1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12-1.58) for fumarate and 1.47 (95%CI:1.21-1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32-1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention. CONCLUSION: Plasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk. CLINICAL TRIAL NUMBER: ISRCTN35739639.

Association between serum copper levels and risk of cardiovascular disease: A nested case-control study in the PREDIMED trial.

BACKGROUND AND AIM: Certain trace elements have been associated with increased cardiovascular risk. The aim of this study was to evaluate the association between serum copper (S-Cu) levels and the risk of a first event of cardiovascular disease (CVD) in a population of older adults with high cardiovascular risk. METHODS AND RESULTS: We conducted a case-control study nested within the PREDIMED trial. During a median follow-up of 4.8 years, a total of 207 incident cases diagnosed with CVD were matched for sex, age, and intervention group with 436 controls. Personal interviews, reviews of medical records, and validated questionnaires were used to assess known CVD risk factors. Biological serum samples were collected annually. Inductively coupled plasma mass spectrometry analysis was used to determine S-Cu levels. Adjusted odds ratios were calculated using multivariate conditional logistic regression models. All participants had S-Cu levels within the reference values, 750 µg/L to 1450 µg/L. Among men, but not among women, the mean S-Cu concentration was higher in cases 1014.1 µg/L than in controls 959.3 µg/L; (p = 0.004). In men, the multivariable-adjusted odds ratio for CVD was 2.36 (95% CI 1.07-5.20 for the comparison of the highest vs. the lowest quartile; p for trend = 0.02), in women, it was 0.43 (95% CI 0.11-1.70; p for trend = 0.165). CONCLUSION: In older Spanish men with high cardiovascular risk, a significant association was observed between high S-Cu levels, but still within the reference values, and an increased risk of a first event of CVD. Our findings suggest a sex difference in CVD risk and S-Cu levels. To confirm this relationship and to analyze the differences observed between men and women, further studies are needed.

Efficacy of Specific Trunk Exercises in the Balance Dysfunction of Patients with Parkinson's Disease: A Systematic Review and Meta-Analysis.

Parkinson's disease (PD) is a neurodegenerative pathology classified as a movement disorder. Physical exercise within a physiotherapy program is an important element to improve postural stability, balance and mobility in order to reduce falls in people with PD. The aim of this work was to determine the efficacy of specific balance and trunk mobility exercises, as well as their benefits for and effects on patients with idiopathic PD. A systematic review and meta-analysis was conducted according to PRISMA standards. The search was performed in five databases: Cochrane Library, SciELO, PEDro, Scopus and PubMed, in February 2022 with the following descriptors: Parkinson's disease, trunk, exercise, therapy and physical therapy. The inclusion criteria were randomized controlled trials (RCTs) over the last ten years. A meta-analysis on static and dynamic balance was conducted with the software Review Manager. Nine articles met the objectives and inclusion criteria, with a total of 240 participants. The trials had moderate methodological quality according to the PEDro scale. The studies included differed with regard to intervention protocol and outcome measures. Finally, eight studies were included in a quantitative analysis in which it was shown that trunk-specific exercises interventions did not significantly improve static balance (SMD = -0.10, 95% CI = -0.29, 0.08; p = 0.28) or dynamic balance (SMD = 0.64 95% CI = -0.24, 1.52; p = 0.15). However, significant differences were found in static balance measured subjectively using the Berg Balance Scale (SMD = -0.52, 95% CI = -1.01, -0.02; p = 0.04). Although some differences were not significant, the studies included in this systematic review consider that specific trunk exercises or balance training combined with muscle strengthening in patients with idiopathic PD should be a complement to pharmacological treatment for improving balance dysfunction and postural instability, preventing falls and promoting wellness.

Effectiveness of Water-Based Exercise in Patients with Chronic Obstructive Pulmonary Disease: Systematic Review and Meta-Analysis.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease that, due to dyspnea, decreases patients' physical function and quality of life. The aim of the research was to evaluate the effectiveness of water-based exercise (WE) in improving functional capacity and respiratory muscle strength in patients with COPD. It consisted of a systematic review and meta-analysis of eight randomized clinical trials (RCTs) from the last 10 years, found in PubMed, PEDro, Scopus and Web of Science databases. Methodological quality was analyzed using the PEDro scale and the Cochrane Collaboration Risk of Bias Tool. Regarding the evaluation of functional capacity, mainly assessed were lung function, respiratory muscle strength, and maximal or aerobic exercise. The results showed that WE improves functional capacity compared to a non-exercising control group (SMD: 73.42; IC 95%: 40.40 to 106.45; I2: 0%). There are no statistically significant differences between a WE treatment and a land exercise (LE) treatment (p = 0.24) in functional capacity, nor with respect to respiratory muscle strength (p = 0.97). These data should be interpreted with caution, as more RCTs with aquatic intervention in COPD patients are needed to elucidate whether there are differences between WE or LE according to patient characteristics and comorbidities.

Integrative development of a short screening questionnaire of highly processed food consumption (sQ-HPF).

BACKGROUND: Recent lifestyle changes include increased consumption of highly processed foods (HPF), which has been associated with an increased risk of non-communicable diseases (NCDs). However, nutritional information relies on the estimation of HPF consumption from food-frequency questionnaires (FFQ) that are not explicitly developed for this purpose. We aimed to develop a short screening questionnaire of HPF consumption (sQ-HPF) that integrates criteria from the existing food classification systems. METHODS: Data from 4400 participants (48.1% female and 51.9% male, 64.9 ± 4.9 years) of the Spanish PREDIMED-Plus ("PREvention with MEDiterranean DIet") trial were used for this analysis. Items from the FFQ were classified according to four main food processing-based classification systems (NOVA, IARC, IFIC and UNC). Participants were classified into tertiles of HPF consumption according to each system. Using binomial logistic regression, food groups associated with agreement in the highest tertile for at least two classification systems were chosen as items for the questionnaire. ROC analysis was used to determine cut-off points for the frequency of consumption of each item, from which a score was calculated. Internal consistency of the questionnaire was assessed through exploratory factor analysis (EFA) and Cronbach's analysis, and agreement with the four classifications was assessed with weighted kappa coefficients. RESULTS: Regression analysis identified 14 food groups (items) associated with high HPF consumption for at least two classification systems. EFA showed that items were representative contributors of a single underlying factor, the "HPF dietary pattern" (factor loadings around 0.2). We constructed a questionnaire asking about the frequency of consumption of those items. The threshold frequency of consumption was selected using ROC analysis. Comparison of the four classification systems and the sQ-HPF showed a fair to high agreement. Significant changes in lifestyle characteristics were detected across tertiles of the sQ-HPF score. Longitudinal changes in HPF consumption were also detected by the sQ-HPF, concordantly with existing classification systems. CONCLUSIONS: We developed a practical tool to measure HPF consumption, the sQ-HPF. This may be a valuable instrument to study its relationship with NCDs. TRIAL REGISTRATION: Retrospectively registered at the International Standard Randomized Controlled Trial Registry ( ISRCTN89898870 ) on July 24, 2014.

Inflammatory potential of diet and bone mineral density in a senior Mediterranean population: a cross-sectional analysis of PREDIMED-Plus study.

PURPOSE: Inflammation could play a key role in tissue damage and bone metabolism. The modified dietary inflammatory score (M-DIS) is a validated tool to estimate the inflammatory potential of the diet. In the present study, we evaluate the associations between the M-DIS and bone mineral density (BMD) in a senior Mediterranean population with overweight/obesity and metabolic syndrome. METHODS: Baseline cross-sectional association between the M-DIS and bone mineral density was assessed in 1134 participants of the multicenter PREDIMED-Plus trial (aged 55-75 with overweight/obesity and metabolic syndrome). BMD was measured using Dual-energy X-ray Absorptiometry scans and participants answered a food frequency questionnaire to determine the M-DIS. BMD was categorized as low BMD when T score was equal or lower than -1 and normal BMD in another case. Associations between BMD and M-DIS were evaluated by using linear and logistic regressions adjusted by other co-variates. RESULTS: Participants in the top tertile of the M-DIS had a lower BMD at total femur [ß (95% CI) - 0.02 (- 0.04, - 0.01)], trochanter areas [ß (95% CI) - 0.03 (- 0.05, - 0.01)] and lumbar spine area [ß (95% CI) - 0.03 (- 0.07, 0.01)] (but in the last case, measures were less precise and hence not statistically significant) compared to those in the lower M-DIS tertile. Multiple logistic regression analyses showed that the odds of the total femur and femoral trochanter osteopenia/osteoporosis were higher in participants in the top tertile compared to those in the lowest tertile of M-DIS [OR (95% CI) 1.71 (1.12, 2.64), P for trend 0.015; 2.02 (1.29, 3.21), P for trend 0.002, respectively]. CONCLUSION: A high pro-inflammatory diet, measured by the M-DIS, is associated with lower BMD in a senior Mediterranean population with metabolic syndrome.

Effectiveness of Video Games as Physical Treatment in Patients with Cystic Fibrosis: Systematic Review.

Physical training at home by making individuals play active video games is a new therapeutic strategy to improve the condition of patients with cystic fibrosis (CF). We reviewed studies on the use of video games and their benefits in the treatment of CF. We conducted a systematic review with data from six databases (PubMed, Medline, Scopus, Web of Science, PEDro, and Cochrane library plus) since 2010, according to PRISMA standards. The descriptors were: "Cystic Fibrosis", "Video Game", "Gaming Console", "Pulmonary Rehabilitation", "Physiotherapy", and "Physical Therapy". Nine articles with 320 participants met the inclusion criteria and the study objective. Patients who played active video games showed a high intensity of exercise and higher ventilatory and aerobic capacity compared to the values of these parameters in tests such as the cardiopulmonary stress test or the six-minute walk test. Adequate values of metabolic demand in these patients were recorded after playing certain video games. A high level of treatment adherence and satisfaction was observed in both children and adults. Although the quality of the included studies was moderate, the evidence to confirm these results was insufficient. More robust studies are needed, including those on evaluation and health economics, to determine the effectiveness of the treatment.

Identification of Structural and Molecular Signatures Mediating Adaptive Changes in the Mouse Kidney in Response to Pregnancy.

Pregnancy is characterized by adaptations in the function of several maternal body systems that ensure the development of the fetus whilst maintaining health of the mother. The renal system is responsible for water and electrolyte balance, as well as waste removal. Thus, it is imperative that structural and functional changes occur in the kidney during pregnancy. However, our knowledge of the precise morphological and molecular mechanisms occurring in the kidney during pregnancy is still very limited. Here, we investigated the changes occurring in the mouse kidney during pregnancy by performing an integrated analysis involving histology, gene and protein expression assays, mass spectrometry profiling and bioinformatics. Data from non-pregnant and pregnant mice were used to identify critical signalling pathways mediating changes in the maternal kidneys. We observed an expansion of renal medulla due to proliferation and infiltration of interstitial cellular constituents, as well as alterations in the activity of key cellular signalling pathways (e.g., AKT, AMPK and MAPKs) and genes involved in cell growth/metabolism (e.g., Cdc6, Foxm1 and Rb1) in the kidneys during pregnancy. We also generated plasma and urine proteomic profiles, identifying unique proteins in pregnancy. These proteins could be used to monitor and study potential mechanisms of renal adaptations during pregnancy and disease.

Human biomonitoring of bisphenol A along pregnancy: An exposure reconstruction of the EXHES-Spain cohort.

This study was aimed at reconstructing the exposure to bisphenol (BPA) of 60 pregnant women from the EXHES-Spain cohort. A biomonitoring study was conducted by determining BPA levels in urine samples over the three trimesters of pregnancy. Moreover, the correlations between BPA levels and the role of different potential exposure sources, with special emphasis on the dietary intake, were also studied. Urine samples were subjected to dispersive liquid-liquid microextraction and the subsequent analysis via gas chromatography-mass spectrometry. BPA was detected in 76% of the urine samples. A significant decrease of urinary BPA levels was observed along pregnancy, as mean concentrations of creatinine-adjusted BPA were 4.64, 4.84 and 2.51 µg/g in the first, second and third trimester, respectively. This decrease was essentially associated with changes in the dietary habits of the pregnant women, including a lower intake of canned food and drinks. However, the potential role of other pregnancy-related biochemical or physiological factors should not be disregarded. Very interestingly, significant differences in urine BPA levels were found according to the fruit consumption pattern, as women who ate more citrus fruits showed lower BPA concentrations in urine. The reconstructed exposure to BPA was estimated in 0.072, 0.069 and 0.038 µg BPA/kg of body weight/day in the first, second and third trimesters, respectively. These values are far below the temporary tolerable daily intake (t-TDI) established by the EFSA.

Anti-transcriptional intermediary factor 1 gamma antibodies in cancer-associated myositis: a longitudinal study.

OBJECTIVES: To investigate anti-TIF1-γ antibodies in longitudinally followed patients with myositis and cancer. METHODS: Serum levels of anti-TIF1-γ antibodies at different time-points in relation to myositis and cancer diagnosis were analysed by ELISA in 79 patients from a Swedish cohort with polymyositis (PM) and dermatomyositis (DM) and a Spanish cohort restricted to DM patients. Anti-TIF1-γ positive and negative patients were compared with Fisher's exact test, student t-tests and Wilcoxon test. RESULTS: Thirty-six patients (17 from cohort 1 and 19 from cohort 2) with myositis and cancer were anti-TIF1-γ antibody positive; all had DM. In 88% of anti-TIF1-γ positive patients, cancer was diagnosed within 3 years from DM diagnosis compared to 63% in anti-TIF1-γ negative. Four DM patients, anti-TIF1-γ positive at cancer diagnosis had positive serum samples even antedating cancer diagnosis up to five years. In cohort 1 the median (interquartile range) antibody level was higher, 2.13 au (1.82-2.15), in the seven patients who died <1 year after cancer diagnosis, compared to the seven that died >1 year after cancer diagnosis, 1.34 au (0.92-1.59), (p=0.004). Three patients were still alive and in remission from cancer and DM 14-16 years after cancer treatment of whom two became negative for anti-TIF1-γ antibodies. In the second cohort remission of cancer coincided with remission of DM and low or negative serum levels of autoantibodies. CONCLUSIONS: Anti-TIF1-γ antibodies may be detected before clinical symptoms of cancer and may disappear after successful treatment of cancer with remission of DM supporting DM being a paramalignant phenomenon.

Organophosphate metabolite concentrations in maternal urine during pregnancy.

The burden of organophosphate (OP) pesticides in pregnant women from Tarragona (n = 157), a Mediterranean area of intense agricultural activity, has been assessed from the study of hydroxylated organic metabolites in urine samples in the three trimesters of pregnancy. 2-Diethylamino-6-methylpyrimidin-4-ol (DEAMPY), a metabolite of pirimiphos, was the compound found in higher concentration, medians 0.66-2.8 µg/g creatinine. 4-Nitrophenol (PNP), a metabolite of parathion, medians 0.24-0.41 µg/g creatinine, was the second most abundant compound. 2-Isopropyl-6-methyl-4-pyrimidol (IMPY), a metabolite of diazinon, was also present but in lower concentrations. Except for DEAMPY, the concentrations found in this cohort were lower than those reported in studies from other countries. Intraclass correlation coefficients (ICCs) were calculated for the compounds found in more than the 35% of the samples, the reliability between trimesters was poor (<0.40) to fair (0.40-0.60). Statistically significant differences were observed for the creatinine adjusted concentrations of the most abundant OP metabolites in these trimesters when examined with the Wilcoxon signed rank test for paired data. In general, no association was found between urinary OP metabolites and most demographic and lifestyle predictors. However, a positive significant association was observed for women with vegetarian diet and for women of higher economic status and eventual consumption of organic food which showed higher PNP concentrations. These results suggest that higher fruit and vegetable consumption may involve higher OP pesticide ingestion but the overall association was weak.

Changes of organochlorine compound concentrations in maternal serum during pregnancy and comparison to serum cord blood composition.

The concentrations of organochlorine compounds (OCs), including pentachlorobenzene, hexachlorobenzene (HCB), hexachlorocyclohexanes (α-, ß-, γ- and δ-HCH), polychlorobiphenyls (PCBs 28, 52, 101, 118, 138, 153 and 180), DDT and metabolites, were measured in maternal serum samples collected at the first trimester of pregnancy, at delivery and in umbilical cord from a cohort of mother-newborn pairs from Tarragona (Spain) (n = 50), representing general population of a Mediterranean area from Southern Europe. The observed concentrations were generally low in comparison with previous studies in other world areas. Higher OC concentrations were observed in the maternal serum collected at delivery than in the first trimester and the cord blood concentrations were lower than the maternal levels. These results show for the first time a small but statistically significant increase in maternal venous concentration of OCs between the first trimester and delivery when measured in ng/ml. HCB, ß-HCH and the PCB congeners in cord blood were significantly correlated with the concentrations of these compounds in maternal venous blood and the coefficients were stronger for the samples collected at delivery which was consistent with OC transfer from mother to foetus. In the case of DDT compounds, only 4,4'-DDT showed maternal-cord blood correlation which documented the low metabolic capacity of newborns for OC transformation, e.g. DDT into DDE. Maternal age was the most significant driver of the observed maternal venous OC concentrations in both periods, older ages involving higher concentrations. Higher body mass index was only significantly correlated with higher 4,4'-DDE concentrations in maternal venous blood and cord blood. In some cases, social class and education level were significantly correlated with OC concentrations, e.g. 4,4'-DDE in maternal venous blood from the first trimester and cord blood and PCB153 in maternal venous blood at delivery. In these cases, highest concentrations were found in the women with highest education level and most affluent social class. Comparison of the maternal OC concentrations of this cohort with those observed in 2002 in population of the same geographic area and age range shows decreases between two and ten times over this fourteen-year period.

Human biomonitoring to evaluate exposure to toxic and essential trace elements during pregnancy. Part B: Predictors of exposure.

Maternal exposure to toxic and essential trace elements represents a surrogate of exposure to the unborn child. Variables of exposure as sociodemographic, lifestyles and diet may contribute to different exposure of pregnant women to specific trace elements. Blood, urine and cord blood samples of 53 pregnant women of the HEALS-EXHES cohort, recruited in Reus (Catalonia, Spain) between 2016 and 2017, were analysed for the concentrations of As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se and Zn. Univariate and multivariate models were built in order to assess associations between element concentrations in each matrix, and variables obtained by questionnaires on mothers' characteristics and dietary habits. Results showed several significant associations between various variables and essential trace and toxic elements. Age was associated with higher levels of Cd and Pb in cord blood samples. Multiparous women showed lower levels of Cd in maternal blood and Pb in both maternal and cord blood than nulliparous women. Hispanic mothers presented higher levels of blood As and lower levels of blood Se compared to mothers of different ethnicity. Higher education level was associated with higher As and Hg concentrations in both maternal and cord blood samples. Higher annual income diminished the level of Pb in maternal blood. Smoking in pregnancy incremented the levels of Cd in mothers' blood. Alcohol consumption may affect the absorption of Cu, Mn and Zn. Supplementations with multivitamins, folic acid and iron showed effects on elements as Cr, Mn, Se and Zn. Regarding food group intake, bluefish incremented Pb levels, while canned fish and seafood affected levels of some elements as As, Hg, Cu and Se. Other elements such as Mn and Pb were influenced by the intake of different kinds of foods. The present results showed that some modifiable lifestyles and food intakes could be the target of interventions to help pregnant women to maintain suitable concentrations of essential elements and lower levels of toxic ones, and to improve consequently neonatal health outcomes.

Alpha- and gammaherpesviruses in stranded striped dolphins (Stenella coeruleoalba) from Spain: first molecular detection of gammaherpesvirus infection in central nervous system of odontocetes.

BACKGROUND: Herpesvirus infections in cetaceans have always been attributed to the Alphaherpesvirinae and Gammaherpesvirinae subfamilies. To date, gammaherpesviruses have not been reported in the central nervous system of odontocetes. CASE PRESENTATION: A mass stranding of 14 striped dolphins (Stenella coeruleoalba) occurred in Cantabria (Spain) on 18th May 2019. Tissue samples were collected and tested for herpesvirus using nested polymerase chain reaction (PCR), and for cetacean morbillivirus using reverse transcription-PCR. Cetacean morbillivirus was not detected in any of the animals, while gammaherpesvirus was detected in nine male and one female dolphins. Three of these males were coinfected by alphaherpesviruses. Alphaherpesvirus sequences were detected in the cerebrum, spinal cord and tracheobronchial lymph node, while gammaherpesvirus sequences were detected in the cerebrum, cerebellum, spinal cord, pharyngeal tonsils, mesenteric lymph node, tracheobronchial lymph node, lung, skin and penile mucosa. Macroscopic and histopathological post-mortem examinations did not unveil the potential cause of the mass stranding event or any evidence of severe infectious disease in the dolphins. The only observed lesions that may be associated with herpesvirus were three cases of balanitis and one penile papilloma. CONCLUSIONS: To the authors' knowledge, this is the first report of gammaherpesvirus infection in the central nervous system of odontocete cetaceans. This raises new questions for future studies about how gammaherpesviruses reach the central nervous system and how infection manifests clinically.