Prenatal and childhood lead exposure is prospectively associated with biological markers of aging in adolescence.

Few studies have related early life lead exposure to adolescent biological aging, a period characterized by marked increases in maturational tempo. We examined associations between prenatal and childhood lead exposure and adolescent biological age (mean 14.5 years) utilizing multiple epigenetic clocks including: intrinsic (IEAA), extrinsic (EEAA), Horvath, Hannum, PhenoAge, GrimAge, Skin-Blood, Wu, PedBE, as well as DNA methylation derived telomere length (DNAmTL). Epigenetic clocks and DNAmTL were calculated via adolescent blood DNA methylation measured by Infinium MethylationEPIC BeadChips. We constructed general linear models (GLMs) with individual lead measures predicting biological age. We additionally examined sex-stratified models and lead by sex interactions, adjusting for adolescent age and lead levels, maternal smoking and education, and proportion of cell types. We also estimated effects of lead exposure on biological age using generalized estimating equations (GEE). First trimester blood lead was positively associated with a 0.14 increase in EEAA age in the GLMs though not the GEE models (95%CI 0.03, 0.25). First and 2nd trimester blood lead levels were associated with a 0.02 year increase in PedBE age in GLM and GEE models (1st trimester, 95%CI 0.004, 0.03; 2nd trimester, 95%CI 0.01, 0.03). Third trimester and 24 month blood lead levels were associated with a -0.06 and -0.05 decrease in Skin-Blood age, respectively, in GLM models. Additionally, 3rd trimester blood lead levels were associated with a 0.08 year decrease in Hannum age in GLM and GEE models (95%CI -0.15, -0.01). There were multiple significant results in sex-stratified models and significant lead by sex interactions, where males experienced accelerated biological age, compared to females who saw a decelerated biological age, with respect to IEAA, EEAA, Horvath, Hannum, and PedBE clocks. Further research is needed to understand sex-specific relationships between lead exposure and measures of biological aging in adolescence and the trajectory of biological aging into young adulthood.

Associations of prenatal and childhood Pb exposure with allostatic load in adolescence: Findings from the ELEMENT cohort study.

The biological pathways which link lead (Pb) and long-term outcomes are unclear, though rodent models and a few human studies suggest Pb may alter the body's stress response systems, which over time, can elicit dysregulated stress responses with cumulative impacts. This study examined associations between prenatal and early childhood Pb exposure and adolescent allostatic load, an index of an individual's body burden of stress in multiple biological systems, and further examined sex-based associations. Among 391 (51% male) participants in the ELEMENT birth cohort, we related trimester-specific maternal blood Pb, 1-month postpartum maternal tibia and patella Pb, and child blood Pb at 12-24 months to an allostatic load index in adolescence comprised of biomarkers of cardiovascular, metabolic, neuroendocrine, and immune function. The results were overall mixed, with prenatal exposure, particularly maternal bone Pb, being positively associated with allostatic load, and early childhood Pb showing mixed results for males and females. In adjusted Poisson regression models, 1 mcg/g increase in tibia Pb was associated with a 1% change in expected allostatic load (IRR = 1.01; 95%CI 0.99, 1.02). We found a significant Pb × sex interaction (IRR = 1.05; 95%CI 1.01, 1.10); where males saw an increasing percent change in allostatic load as 12 month Pb levels increased compared to females who saw a decreasing allostatic load. Further examination of allostatic load will facilitate the determination of potential mechanistic pathways between developmental toxicant exposures and later-in-life cardiometabolic outcomes.

Prenatal Pb exposure is associated with reduced abundance of beneficial gut microbial cliques in late childhood: an investigation using Microbial Co-occurrence Analysis (MiCA).

Background: Many analytical methods used in gut microbiome research focus on either single bacterial taxa or the whole microbiome, ignoring multi-bacteria relationships (microbial cliques). We present a novel analytical approach to identify multiple bacterial taxa within the gut microbiome of children at 9-11 years associated with prenatal Pb exposure. Methods: Data came from a subset of participants (n=123) in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort. Pb concentrations were measured in maternal whole blood from the second and third trimesters of pregnancy. Stool samples collected at 9-11 years old underwent metagenomic sequencing to assess the gut microbiome. Using a novel analytical approach, Microbial Co-occurrence Analysis (MiCA), we paired a machine-learning algorithm with randomization-based inference to first identify microbial cliques that were predictive of prenatal Pb exposure and then estimate the association between prenatal Pb exposure and microbial clique abundance. Results: With second-trimester Pb exposure, we identified a 2-taxa microbial clique that included Bifidobacterium adolescentis and Ruminococcus callidus, and a 3-taxa clique that added Prevotella clara. Increasing second-trimester Pb exposure was associated with significantly increased odds of having the 2-taxa microbial clique below the 50th percentile relative abundance (OR=1.03,95%CI[1.01-1.05]). In an analysis of Pb concentration at or above vs. below the United States and Mexico guidelines for child Pb exposure, odds of the 2-taxa clique in low abundance were 3.36(95%CI[1.32-8.51]) and 6.11(95%CI[1.87-19.93]), respectively. Trends were similar with the 3-taxa clique but not statistically significant. Discussion: Using a novel combination of machine-learning and causal-inference, MiCA identified a significant association between second-trimester Pb exposure and reduced abundance of a probiotic microbial clique within the gut microbiome in late childhood. Pb exposure levels at the guidelines for child Pb poisoning in the United States, and Mexico are not sufficient to protect against the potential loss of probiotic benefits.

BepiColombo mission confirms stagnation region of Venus and reveals its large extent.

The second Venus flyby of the BepiColombo mission offer a unique opportunity to make a complete tour of one of the few gas-dynamics dominated interaction regions between the supersonic solar wind and a Solar System object. The spacecraft pass through the full Venusian magnetosheath following the plasma streamlines, and cross the subsolar stagnation region during very stable solar wind conditions as observed upstream by the neighboring Solar Orbiter mission. These rare multipoint synergistic observations and stable conditions experimentally confirm what was previously predicted for the barely-explored stagnation region close to solar minimum. Here, we show that this region has a large extend, up to an altitude of 1900 km, and the estimated low energy transfer near the subsolar point confirm that the atmosphere of Venus, despite being non-magnetized and less conductive due to lower ultraviolet flux at solar minimum, is capable of withstanding the solar wind under low dynamic pressure.

Stmol: A component for building interactive molecular visualizations within streamlit web-applications.

Streamlit is an open-source Python coding framework for building web-applications or "web-apps" and is now being used by researchers to share large data sets from published studies and other resources. Here we present Stmol, an easy-to-use component for rendering interactive 3D molecular visualizations of protein and ligand structures within Streamlit web-apps. Stmol can render protein and ligand structures with just a few lines of Python code by utilizing popular visualization libraries, currently Py3DMol and Speck. On the user-end, Stmol does not require expertise to interactively navigate. On the developer-end, Stmol can be easily integrated within structural bioinformatic and cheminformatic pipelines to provide a simple means for user-end researchers to advance biological studies and drug discovery efforts. In this paper, we highlight a few examples of how Stmol has already been utilized by scientific communities to share interactive molecular visualizations of protein and ligand structures from known open databases. We hope Stmol will be used by researchers to build additional open-sourced web-apps to benefit current and future generations of scientists.

Postreperfusion Syndrome in Liver Transplant: A Risk Factor for Acute Kidney Failure: A Retrospective Analysis.

The maximum expression of hemodynamic instability during liver transplant is the so-called postreperfusion syndrome (PRS) that increases both overall mortality and postoperative complications. It was first defined by Aggarwal et al in 1987, but the results are still conflicting when establishing the relationship between PRS and acute kidney failure (AKF). We conducted a retrospective observational study of transplant recipients with deceased-donor liver grafts between January 2002 and December 2018. We analyzed the incidence of PRS and its potential negative impact over kidney function. A total of 551 transplants were analyzed. PRS was recorded in 130 patients (23.6%). The incidence of AKF was 61.5%. A total of 111 patients required kidney replacement therapy (32.7%). Regarding the severity of AKF, 128 patients were classified as acute kidney injury (AKI) 1 (23.2%), 76 as AKI 2 (13.8%), and 135 as AKI 3 (24.5%). In the group with PRS, 75.4% (n = 98) developed AKF vs 57.2% (n = 241) in the group without PRS. In the multivariate analysis we found a relationship between PRS and AKF with an odds ratio of 2.18 (95% CI, 1.30-3.64; P = .003), once adjusted by the length of the anhepatic phase, donor age, Model for End-Stage Liver Disease score, history of ascites, and need for early surgical reintervention. The incidence of AKF decreased (44.5%) ever since the implementation of delayed calcineurin inhibitors therapy and piggyback surgical technique, but a clear influence of the occurrence of PRS on the development of AKF is still observed, with an OR of 3.78 (95% CI, 1.92-7.43; P < .001), once adjusted by albumin and hemoglobin levels, Model for End-Stage Liver Disease score, and Child classification.

Hemodynamic resuscitation with fluids bolus and norepinephrine increases severity of lung damage in an experimental model of septic shock.

OBJECTIVE: Hemodynamic resuscitation is considered a cornerstone of the initial treatment of septic shock. However, there is growing concern about its side effects. Our objective was to assess the relationship between fluid administration and norepinephrine infusion and the development of lung injury. DESIGN: Randomized in vivo study in rabbits. SETTING: University animal research laboratory. PATIENTS: Eighteen New Zealand rabbits. Control group (SHAM, n=6), Sepsis group with or without hemodynamic resuscitation (ETX-R, n=6; ETX-NR, n=6). INTERVENTIONS: Sepsis was induced by intravenous lipopolysaccharide administration and animals were followed-up for 4h. Hemodynamic resuscitation with Ringer lactate (20mL·kg-1) was administered and later norepinephrine was initiated 3h after sepsis induction. At the end, the left lung was excised. MAIN VARIABLES OF INTEREST: An indwelling arterial catheter and an esophageal Doppler were placed. Lung mechanics were monitored with side stream spirometry. Lung damage was analyzed by histopathological examination. RESULTS: The SHAM group did not show hemodynamic or respiratory changes. Lipopolysaccharide administration aimed an increase in cardiac output and arterial hypotension. In the ETX-NR group, animals remained hypotensive until the end of the experiment. Resuscitation with fluids and norepinephrine reversed arterial hypotension. Compared to the ETX-NR group, the remaining lung of the ETX-R group showed greater accumulation of neutrophils and reactive type-II pneumocytes, thicker alveolar wall, alveolar hemorrhage and non-aerated pulmonary areas. Lung injury score was larger in the ETX-R group. CONCLUSIONS: In our experimental study, following a strategy with bolus fluids and late norepinephrine used in the early phase of endotoxic septic shock has a negative influence on the development of lung injury.

Pathological and Therapeutic Approach to Endotoxin-Secreting Bacteria Involved in Periodontal Disease.

It is widely recognized that periodontal disease is an inflammatory entity of infectious origin, in which the immune activation of the host leads to the destruction of the supporting tissues of the tooth. Periodontal pathogenic bacteria like Porphyromonas gingivalis, that belongs to the complex net of oral microflora, exhibits a toxicogenic potential by releasing endotoxins, which are the lipopolysaccharide component (LPS) available in the outer cell wall of Gram-negative bacteria. Endotoxins are released into the tissues causing damage after the cell is lysed. There are three well-defined regions in the LPS: one of them, the lipid A, has a lipidic nature, and the other two, the Core and the O-antigen, have a glycosidic nature, all of them with independent and synergistic functions. Lipid A is the "bioactive center" of LPS, responsible for its toxicity, and shows great variability along bacteria. In general, endotoxins have specific receptors at the cells, causing a wide immunoinflammatory response by inducing the release of pro-inflammatory cytokines and the production of matrix metalloproteinases. This response is not coordinated, favoring the dissemination of LPS through blood vessels, as well as binding mainly to Toll-like receptor 4 (TLR4) expressed in the host cells, leading to the destruction of the tissues and the detrimental effect in some systemic pathologies. Lipid A can also act as a TLRs antagonist eliciting immune deregulation. Although bacterial endotoxins have been extensively studied clinically and in a laboratory, their effects on the oral cavity and particularly on periodontium deserve special attention since they affect the connective tissue that supports the tooth, and can be linked to advanced medical conditions. This review addresses the distribution of endotoxins associated with periodontal pathogenic bacteria and its relationship with systemic diseases, as well as the effect of some therapeutic alternatives.

Comparative cost analysis of cervical cancer screening programme based on molecular detection of HPV in Spain.

BACKGROUND: HPV cervical cancer screening (CCS) must use validated HPV tests based on the molecular detection of either viral mRNA (Aptima HPV Assay-AHPV) or DNA. AHPV has demonstrated the same cross-sectional and longitudinal sensitivity for the detection of HSIL/CIN2+ lesions but with greater specificity than HPV-DNA tests. The study aimed to estimate the total costs of a CCS with a primary HPV test based on the detection of mRNA compared to DNA in women aged 35-65 years for the National Health System. METHODS: A decision-tree-based model to estimate the cost of the CCS until the first colposcopy was designed based on Spanish CCS guidelines. The total cost (€, 2019) for CCS with AHPV or DNA tests (HC2 and Cobas) was calculated, including HPV test, liquid-based cytology (LBC) and colposcopy, for a population of 7,263,529 women aged 35-65 years (assuming 70% coverage). Clinical inputs derived from a literature review were validated by a multidisciplinary expert panel. Data from head-to-head studies between different HPV tests were selected. RESULTS: The use of AHPV showed reduction of 290,541 (- 35%) and 355,913 (- 40%) LBC compared to HC2 or Cobas, respectively. Furthermore, AHPV avoided 151,699 (- 47%) colposcopies versus HC2 and 151,165 (- 47%) versus Cobas. The total cost of CCS was € 282,747,877 with AHPV, € 322,587,588 with HC2 and € 324,614,490 with Cobas. Therefore, AHPV savings € - 39,839,711 versus HC2 and € - 41,866,613 versus Cobas. CONCLUSIONS: Assuming that 70% of women from 35 to 65 years attend the CCS programme, the cost of screening up to the first colposcopy using AHPV would provide cost savings of up to € 41.9 million versus DNA tests in Spain.

Essential oil of Cymbopogon martini, source of geraniol, as a potential antibacterial agent against Bacillus subtilis, a pathogen of the bakery industry.

Background: Bacteria can adhere and grow on any surface due to their chemical and physical interaction, leading to the development of biofilms. Essential oils have a great potential for use in the food industry, as they can effectively prevent the presence of some pathogenic microorganisms.  Species such as those in the Bacillus genus have the ability to produce toxins. Some strains of Bacillus subtilis have been related to cases of food-borne diseases. In the bakery industry, B. subtilis also has been related to "rope" disease, linked to bread preservation processes. Methods: The aim of the study was to analyse the antibacterial properties of 24 chemotyped essential oils against the growth of B. subtilis. The biological activity study was carried out using disk diffusion in agar and broth dilution methods. Results: The essential oil of Cymbopogon martinii var. motia had a high geraniol content (>80.53%) and showed a high antimicrobial effect against the Gram-positive bacterium B. subtilis. Binary combinations of Cymbopogon martinii var. motia oil with Eugenia caryophyllus showed antagonistic effects on B. subtilis. Conclusions:  The essential oil of Cymbopogon martinii var. motia has an interesting potential use in the bakery industry as a preservative, in applications such as nano encapsulation for bakery doughs, active packaging of baked products, or surface disinfectants.

The Spanish version of the Home Environment Survey (HES) among families of children with overweight/obesity: a validation study.

PURPOSE: The aim of this article was to validate the Spanish version of the Home Environment Survey (HES-S) and was divided in two studies: (1) to assess the reliability, convergent validity of HES-S in a survey of 145 parents of children with overweight/obesity; (2) to study the magnitude of the association between children's BMI status with the latent scores theoretically defined by the HES model. METHODS: To test the scale and the model, a confirmatory factor analysis (CFA) and a path analysis were carried out among a sample of 156 parents of preadolescents (106 overweight/obesity and 50 normal-weight children). No CFA or EFA were carried out in the validation of the original instrument. RESULTS: Study 1, both the Physical Activity and the Eating Habits components of the scale showed adequate levels of internal consistency for the majority of the scales, except for two. One of them, Healthy Eating Parental Policies (HEP) subscale was reduced after excluded two items, although it did not improve substantially. This model indicated that there was a significant association between the two Eating Habits scales and the child's weight status, but child's weight was not associated with the Physical Activity components. Convergent validity was confirmed by correlations with related variables: family eating habits (F-EAT), parent's physical activity (IPAQ), and children's physical activity (assessed via accelerometers during one week). Study 2, our results replicated the original four factor structure proposed for physical activity (CFI = 0.99; RMSEA = 0.03), but the original factor structure of the eating habits component was not supported. In addition, the relationship of the child's weight status, the Physical Activity components, and the two scales of Eating Habits (Parental Modeling and Policies) was explored with a path analysis showing good fit indices (CFI = 0.95; RMSEA = 0.06). Child's BMI was negatively associated with Healthy Eating Parental Role Modeling (r = - 0.21) and with Healthy Eating Parental Policies (r = - 0.19), but not with the factors of Child's Physical Activity model. CONCLUSION: To our knowledge, this is the first instrument to assess obesogenic family environment in Spanish speaking countries, which is a relevant dimension within a health perspective so as to implement new policies and strategies in obesity tertiary prevention. Overall, the confirmatory factor analysis of the HES-S has only provided additional support for one part related to Physical Activity. In addition, Child's BMI was correlated with scales of Eating Habits but not with Child's Physical Activity factor. These results clearly suggest that further research is warranted. LEVEL III: Case-control analytic study.

Rapid response to COVID-19, escalation and de-escalation strategies to match surge capacity of Intensive Care beds to a large scale epidemic. / Respuesta rápida a COVID-19, estrategias de escalada y desescalada para ajustar la capacidad suplementaria de camas de UVI a una epidemia de gran magnitud.

BACKGROUND: A major challenge during the COVID-19 outbreak is the sudden increase in ICU bed occupancy rate. In this article we reviewed the strategies of escalation and de-escalation put in place at a large university hospital in Madrid during the COVID-19 outbreak, in order to meet the growing demand of ICU beds. MATERIALS AND METHODS: The data displayed originated from the hospital information system and the hospital contingency plan. RESULTS: The COVID-19 outbreak produced a surge of ICU patients which saturated the available ICU capacity within a few days. A total of four new ICUs had to be opened in order to accommodate all necessary new ICU admissions. Management challenges included infrastructure, material allocation and ICU staffing. Through the strategies put in place the hospital was able to generate a surge capacity of ICU beds of 340%, meet all requirements and also maintain minimal surgical activity. CONCLUSIONS: Hospital surge capacity is to date hardly quantifiable and often has to face physical limitations (material, personnel, spaces). However an extremely flexible and adaptable management strategy can help to overcome some of these limitations and stretch the system capacities during times of extreme need.

Accumulation of human pharmaceuticals and activity of biotransformation enzymes in fish from two areas of the lower Rio de la Plata Basin.

The accumulation of four human pharmaceuticals active compounds (HPhAC) in the muscle of four fish species of the Rio de la Plata Basin were assessed regarding the compound logP and pKa, and fish trophic levels. For Prochilodus lineatus, accumulation was compared to hepatic biotransformation enzymes and fish from two sampling areas with different urbanization degree. Species were the detritivore Prochilodus lineatus, the omnivores Megaleporinus obtusidens and Pimelodus maculatus, and the piscivorous Salminus brasiliensis. Sampling areas were the Inner Rio de la Plata Estuary (RLP), in front of the Buenos Aires Metropolitan Area, and at the Lower Uruguay River (URU), a relatively unpopulated area. Carbamazepine, atenolol, enalapril, and sildenafil concentrations in fish muscle were analyzed by HPLC-MS. EROD, BROD, and GST activities were measured in P. lineatus liver. Average (maximum) concentrations and detection frequency were: Atenolol 24.4 (69.4) µg kg-1, 60%; carbamazepine 5.5 (45.8) µg kg-1, 19%; enalapril 7.0 (56.9) µg kg-1, 28%; sildenafil 17.1 (71.6) µg kg-1, 56%. Enalapril and sildenafil detection in fish was first-time reported. Atenolol and carbamazepine concentrations were positively correlated. No correlation was observed between HPhAC accumulation and logP or pKa. A potential biomagnification trend was observed for atenolol, showing higher accumulation in S. brasiliensis. HPhACs accumulation was higher for P. lineatus collected at URU, but GST and BROD were significantly higher for individuals sampled at RLP and were positively correlated. A significant negative correlation was observed for enalapril and BROD. The study contributes to the knowledge of the accumulation of HPhACs in fish.

Unexpected Toxicity of Green Tea Polyphenols in Combination with the Sambucus RIL Ebulin.

The safety of concentrated food complements intake is a major health concern. It has been well established that green tea polyphenols (GTPs) consumption promotes healthy effects. However, the ingestion of large amounts of GTPs is a matter of controversy due to reported adverse effects. We underwent a preliminary exploration of the effects of the oral administration of a standardized concentrated GTPs preparation on mice which suffered from reversible intestinal derangement promoted by sublethal amounts of the antiribosomal lectin ebulin f from dwarf elder (Sambucus ebulus L.). Neither independent oral administration of 30 mg/kg body weight Polyphenon 60 nor intraperitoneal administration of 2.5 mg/kg body weight ebulin f triggered lethal toxicity. In contrast, the simultaneous administration of these same doses of both Polyphenon 60 and ebulin f triggered an important and unexpected synergistic toxic action featured by the biphasic reduction of weight, which continued after eight days, reaching a reduction of 40%. Lethality appeared 2 days after the onset of the combined treatment and reached more than 50% after 10 days.

Patient characteristics, clinical course and factors associated to ICU mortality in critically ill patients infected with SARS-CoV-2 in Spain: A prospective, cohort, multicentre study. / Características, evolución clínica y factores asociados a la mortalidad en UCI de los pacientes críticos infectados por SARS-CoV-2 en España: estudio prospectivo, de cohorte y multicéntrico.

BACKGROUND: The clinical course of COVID-19 critically ill patients, during their admission in the intensive care unit (UCI), including medical and infectious complications and support therapies, as well as their association with in-ICU mortality has not been fully reported. OBJECTIVE: This study aimed to describe clinical characteristics and clinical course of ICU COVID-19 patients, and to determine risk factors for ICU mortality of COVID-19 patients. METHODS: Prospective, multicentre, cohort study that enrolled critically ill COVID-19 patients admitted into 30 ICUs from Spain and Andorra. Consecutive patients from March 12th to May 26th, 2020 were enrolled if they had died or were discharged from ICU during the study period. Demographics, symptoms, vital signs, laboratory markers, supportive therapies, pharmacological treatments, medical and infectious complications were reported and compared between deceased and discharged patients. RESULTS: A total of 663 patients were included. Overall ICU mortality was 31% (203 patients). At ICU admission non-survivors were more hypoxemic [SpO2 with non-rebreather mask, 90 (IQR 83 to 93) vs. 91 (IQR 87 to 94); P<.001] and with higher sequential organ failure assessment score [SOFA, 7 (IQR 5 to 9) vs. 4 (IQR 3 to 7); P<.001]. Complications were more frequent in non-survivors: acute respiratory distress syndrome (ARDS) (95% vs. 89%; P=.009), acute kidney injury (AKI) (58% vs. 24%; P<10-16), shock (42% vs. 14%; P<10-13), and arrhythmias (24% vs. 11%; P<10-4). Respiratory super-infection, bloodstream infection and septic shock were higher in non-survivors (33% vs. 25%; P=.03, 33% vs. 23%; P=.01 and 15% vs. 3%, P=10-7), respectively. The multivariable regression model showed that age was associated with mortality, with every year increasing risk-of-death by 1% (95%CI: 1 to 10, P=.014). Each 5-point increase in APACHE II independently predicted mortality [OR: 1.508 (1.081, 2.104), P=.015]. Patients with AKI [OR: 2.468 (1.628, 3.741), P<10-4)], cardiac arrest [OR: 11.099 (3.389, 36.353), P=.0001], and septic shock [OR: 3.224 (1.486, 6.994), P=.002] had an increased risk-of-death. CONCLUSIONS: Older COVID-19 patients with higher APACHE II scores on admission, those who developed AKI grades ii or iii and/or septic shock during ICU stay had an increased risk-of-death. ICU mortality was 31%.

Hemodynamic resuscitation with fluids bolus and norepinephrine increases severity of lung damage in an experimental model of septic shock.

OBJECTIVE: Hemodynamic resuscitation is considered a cornerstone of the initial treatment of septic shock. However, there is growing concern about its side effects. Our objective was to assess the relationship between fluid administration and norepinephrine infusion and the development of lung injury. DESIGN: Randomized in vivo study in rabbits. SETTING: University animal research laboratory. PATIENTS: Eighteen New Zealand rabbits. Control group (SHAM, n=6), Sepsis group with or without hemodynamic resuscitation (ETX-R, n=6; ETX-NR, n=6). INTERVENTIONS: Sepsis was induced by intravenous lipopolysaccharide administration and animals were followed-up for 4h. Hemodynamic resuscitation with Ringer lactate (20mL·kg-1) was administered and later norepinephrine was initiated 3h after sepsis induction. At the end, the left lung was excised. MAIN VARIABLES OF INTEREST: An indwelling arterial catheter and an esophageal Doppler were placed. Lung mechanics were monitored with side stream spirometry. Lung damage was analyzed by histopathological examination. RESULTS: The SHAM group did not show hemodynamic or respiratory changes. Lipopolysaccharide administration aimed an increase in cardiac output and arterial hypotension. In the ETX-NR group, animals remained hypotensive until the end of the experiment. Resuscitation with fluids and norepinephrine reversed arterial hypotension. Compared to the ETX-NR group, the remaining lung of the ETX-R group showed greater accumulation of neutrophils and reactive type-II pneumocytes, thicker alveolar wall, alveolar hemorrhage and non-aerated pulmonary areas. Lung injury score was larger in the ETX-R group. CONCLUSIONS: In our experimental study, following a strategy with bolus fluids and late norepinephrine used in the early phase of endotoxic septic shock has a negative influence on the development of lung injury.

Overweight and obesity status from the prenatal period to adolescence and its association with non-alcoholic fatty liver disease in young adults: cohort study.

OBJECTIVE: To examine the associations of maternal and child overweight status across multiple time-points with liver fat content in the offspring during young adulthood. DESIGN: Cohort study. SETTING: ELEMENT Cohort in Mexico City. POPULATION: Pregnant women with singleton births (n = 97). METHODS: We quantified hepatic triglyceride content (liver fat content) by proton magnetic resonance spectroscopy (1H MRS) and conventional T2-weighted MRIs (3T scanner) in 97 young adults from the ELEMENT birth cohort in Mexico City. Historical records of the cohort were used as a source of pregnancy, and childhood and adolescence anthropometric information, overweight and obesity (OWOB) were defined. Adjusted structural equation models were run to identify the association between OWOB in different life stages with liver fat content (log-transformed) in young adulthood. MAIN OUTCOME: Maternal OWOB at the time of delivery was directly and indirectly associated with the liver fat content in the offspring at young adulthood. RESULTS: Seventeen percent of the participants were classified as having NAFLD. We found a strong association of OWOB between all periods assessed. Maternal OWOB at time of delivery (ß = 1.97, 95% CI 1.28-3.05), and OWOB status in the offspring at young adulthood (ß = 3.17, 95% CI 2.10-4.77) were directly associated with the liver fat content in the offspring. Also, maternal OWOB was indirectly associated with liver fat content through offspring OWOB status. CONCLUSION: We found that maternal OWOB status is related to fatty liver content in the offspring as young adults, even after taking into account OWOB status and lifestyle factors in the offspring. TWEETABLE ABSTRACT: There was an association between pre-pregnancy overweight and the development of NAFLD in adult offspring.

Human pharmaceuticals in three major fish species from the Uruguay River (South America) with different feeding habits.

The accumulation of 17 human pharmaceuticals (HPs) was investigated in the muscle of three fish species characteristic of the "Rio de la Plata Basin" with different feeding habits and of relevance for human consumption: Megaleporinus obtusidens, Salminus brasiliensis, and Prochilodus lineatus. Fish were sampled in fall and spring from 8 localities distributed along 500 Km of the Uruguay River. Atenolol and carbamazepine were the most frequently detected HPs (>50%), but at concentrations always below 1 µg/kg wet weight (w/w). Hydrochlorothiazide, metoprolol, venlafaxine, propranolol, codeine, and the carbamazepine metabolite, 2-hydroxycarbamazepine, were accumulated at higher levels showing maximum concentrations between 1 and 10 µg/kg (w/w), but infrequently (<50%). The other HPs were always below 1 µg/kg (w/w) and at frequencies lower than 50%. Distinctive accumulation patterns were observed among species at different trophic levels. However, biomagnification trends were not identified for any compound. The highest number and concentration of HPs were found in M. obtusidens (omnivorous), followed by P. lineatus (detritivorous), and lastly S. brasiliensis (piscivorous). The most recurrent HPs (i.e. carbamazepine and atenolol) were present in all species, but others exclusively in one. Geographical variations were only found for carbamazepine and atenolol in M. obtusidens and P. lineatus, showing higher concentrations in localities closer to the Rio de la Plata estuary. Differences in the HPs concentrations among seasons were not identified. Acceptable daily intake and predicted no effect concentrations would indicate that measured muscle concentrations in fish from the Uruguay River do not pose a serious risk for human consumption nowadays. Further studies will be necessary for assessing the potential adverse effects on studied fish species.

Prenatal lead exposure in relation to age at menarche: results from a longitudinal study in Mexico City.

Animal and cross-sectional epidemiological studies suggest that prenatal lead exposure is related to delayed menarche, but this has not been confirmed in longitudinal studies. We analyzed this association among 200 girls from Mexico City who were followed since the first trimester of gestation. Maternal blood lead levels were analyzed once during each trimester of pregnancy, and daughters were asked about their first menstrual cycle at a visit between the ages of 9.8 and 18.1 years. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) for probability of menarche over the follow-up period using interval-censored Cox models, comparing those with prenatal blood lead level ⩾5 µg/dl to those with prenatal blood lead <5 µg/dl. We also estimated HRs and 95% CI with conventional Cox regression models, which utilized the self-reported age at menarche. In adjusted analyses, we accounted for maternal age, maternal parity, maternal education, and prenatal calcium treatment status. Across trimesters, 36-47% of mothers had blood lead levels ⩾5 µg/dl. Using interval-censored models, we found that during the second trimester only, girls with ⩾5 µg/dl prenatal blood lead had a later age at menarche compared with girls with prenatal blood lead levels <5 µg/dl (confounder-adjusted HR=0.59, 95% CI 0.28-0.90; P=0.05). Associations were in a similar direction, although not statistically significant, in the conventional Cox regression models, potentially indicating measurement error in the self-recalled age at menarche. In summary, higher prenatal lead exposure during the second trimester could be related to later onset of sexual maturation.