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Infancy is a period of continuous growth and development, where inadequate intake of essential elements and exposure to non-essential elements may have lifelong health consequences. Thus, the aim of this study is to evaluate the urine concentration of essential and non-essential elements as a proxy for internal exposure during the weaning period, from 3 to 18 months of age. The Nutrition in Early Life and Asthma (NELA) birth cohort generated the data for this study. Sociodemographic, dietary, and urine concentration of essential (Co, Cu, Mo, I, Fe, Mn, Se, Zn, and Ni) and non-essential elements (Al, V, As, Cd, Sb, Tl, and Pb) data were available for 490 participants at 3 months of age and 216 participants at 18 months of age. Paired urine samples at both time periods were available for 175 infants. At 3 months of age, exclusively breastfed infants had lower urine concentrations of Al, V, Fe, Co, Se, Sb, and Tl. Notably, the concentration of Mo had a median (IQR) of 0.60 (0.40-2.10) µg/L compared to a median (IQR) of 39.80 (25.00-56.40) µg/L observed in infants exclusively fed with formula. When we analyzed the change in urine elements concentrations between 3 and 18 months of age, we observed increased As (0.75 vs. 18.60 µg/L), Co (0.05 vs. 0.24 µg/L), Mo (1.98 vs. 50.0 µg/L), Pb (0.15 vs. 0.69 µg/L), Se (11.3 vs. 23.1 µg/L), Tl (0.02 vs. 0.11 µg/L), and V (0.05 vs. 0.11 µg/L). For Cu, lower urine concentrations were observed at 18 months of age in comparison with concentrations at 3 months (5.77 vs. 4.41 µg/L). Among the main food items identified as driving the changes in urine concentration between 3 and 18 months of age were white fish, rice and pasta, potato chips, custard, small blue fish, and legumes. Exclusively breastfed infants showed lower exposure to non-essential elements compared to those who were fed with a mixture or formula. With the introduction of solid foods, the exposure to some non-essential elements increased drastically, as in the case of As and Pb. In addition, exposure to the essential metal Mo also increased substantially with the introduction of solid food.

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The E3 ubiquitin ligase TRAIP associates with the replisome and helps this molecular machine deal with replication stress. Thus, TRAIP promotes DNA inter-strand crosslink repair by triggering the disassembly of CDC45-MCM2-7-GINS (CMG) helicases that have converged on these lesions. However, disassembly of single CMGs that have stalled temporarily would be deleterious, suggesting that TRAIP must be carefully regulated. Here, we demonstrate that human cells lacking the de-ubiquitylating enzyme USP37 are hypersensitive to topoisomerase poisons and other replication stress-inducing agents. We further show that TRAIP loss rescues the hypersensitivity of USP37 knockout cells to topoisomerase inhibitors. In Xenopus egg extracts depleted of USP37, TRAIP promotes premature CMG ubiquitylation and disassembly when converging replisomes stall. Finally, guided by AlphaFold-Multimer, we discovered that binding to CDC45 mediates USP37's response to topological stress. In conclusion, we propose that USP37 protects genome stability by preventing TRAIP-dependent CMG unloading when replication stress impedes timely termination.

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AIM: To determine the proportion of people who undergo discharge follow-up when indicated. DESIGN: Retrospective longitudinal observational study, with an analytical approach. POPULATION: persons discharged from the Hospital Universitario de la Princesa of any age and sex, with any reason for admission and with an indication for discharge follow-up in Primary Care. Users who did not have an assigned Autonomous Personal Identification Code (CIPA) were excluded. Random sample (n=289). VARIABLES: Discharge follow-up and readmissions (<30 days). Sociodemographic, clinical and discharge follow-up variables were included from the electronic medical records of Primary and Hospital Care. A descriptive analysis of the sociodemographic and clinical characteristics of the study population was conducted. To analyze the association between discharge follow-up and readmissions, a logistic regression model was used. RESULTS: Age 72.4 years (RIQ 60-87). 55.2% of the population were women. Follow-up was conducted in 61.2% of those indicated. According to the logistic regression model performed between early readmission and discharge follow-up, adjusted for all other factors, the group with discharge follow-up had a 66% lower likelihood of hospital readmission (OR 0.34, 95% CI (0.18-0.67)). CONCLUSIONS: These findings suggest that nursing discharge follow-up conducted in primary care reduces the risk of early readmission.

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Introduction: Respiratory syncytial virus (RSV) infection is one of the main causes of morbidity and mortality from lower respiratory tract infections in children under 5 years of age worldwide. Given that, the objective of this study was estimate the effectiveness of nirsevimab (a single-dose, long-acting, human recombinant monoclonal antibody against RSV) over time for the prevention of respiratory episodes treated at different levels of care. Methods: A prospective and dynamic population-based cohort study was performed including infants born between April 1 and December 31, 2023, in the Madrid region who resided there during the follow-up period from October 1, 2023, to February 29, 2024. Infants were considered immunized from the day after receiving one dose (50 or 100 mg) of nirsevimab or nonimmunized individuals if they did not receive any dose. Results: There were 4,100 episodes of primary care, 1,954 hospital emergencies, and 509 admissions, 82 of which required intensive care in the 33,859 participants analyzed. The adjusted effectiveness of nirsevimab in preventing hospitalization due to RSV infection was 93.6% (95% CI: 89.7 to 96.1) at 30 days and 87.6% (95% CI: 67.7 to 95.3) at 150 days. The number needed to treat to prevent one hospitalization were 314.19 (95% CI: 306.22 to 327.99) at 30 days and 24.30 (95% CI: 22.31 to 31.61) at 150 days. The adjusted effectiveness of nirsevimab in avoiding admission to an intensive care unit was 94.4% (95% CI: 87.3 to 97.5) at 30 days and 92.1% (95% CI: 64.0 to 98.3) at 90 days. The adjusted effectiveness of nirsevimab for avoiding primary care consultations and hospital emergency visits was lower. Discussion: Immunization with nirsevimab is an effective measure for reducing the burden of care related to RSV at all levels of care albeit it decreases throughout follow-up. At 150 days it remained high for preventing hospital admissions. Other articles already published have also demonstrated high effectiveness although with preliminary results, short follow-up periods and wide confidence intervals. None have detected a decrease in effectiveness over time. These results can be quite useful in individual infant prevention and in the design of immunization campaigns.

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Activation of heterotrimeric G-proteins (Gαßγ) by G-protein-coupled receptors (GPCRs) is not only a mechanism broadly used by eukaryotes to transduce signals across the plasma membrane, but also the target for a large fraction of clinical drugs. However, approaches typically used to assess this signaling mechanism by directly measuring G-protein activity, like optical biosensors, suffer from limitations. On one hand, many of these biosensors require expression of exogenous GPCRs and/or G-proteins, compromising readout fidelity. On the other hand, biosensors that measure endogenous signaling may still interfere with the signaling process under investigation or suffer from having a small dynamic range of detection, hindering broad applicability. Here, we developed an optical biosensor that detects the endogenous G-protein active species Gαi-GTP upon stimulation of endogenous GPCRs more robustly than current state-of-the-art sensors for the same purpose. Its design is based on the principle of bystander Bioluminescence Resonance Energy Transfer (BRET) and leverages the Gαi-binding protein named GINIP as a high affinity and specific detector module of the GTP-bound conformation of Gαi. We optimized this design to prevent interference with Gi-dependent signaling (cAMP inhibition) and to enable implementation in different experimental systems with endogenous GPCRs, including neurotransmitter receptors in primary astroglial cells or opioid receptors in cell lines, which revealed opioid neuropeptide-mediated activation profiles different from those observed with other biosensors involving exogenous GPCRs and G-proteins. Overall, we introduce a biosensor that directly and sensitively detects endogenous activation of G-proteins by GPCRs across different experimental settings without interfering with the subsequent propagation of signaling.

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The main agents for tick control are chemical acaricides. However, when used without technical guidance, they can lead to environmental damage and the development of resistant tick strains. In this context, vaccines are alternative o be used in integrated tick management format by combining with other effective tools. We isolated RNA from ticks Rhipicephalus microplus, prepared the library, and performed next-generation sequencing; a pipeline analysis was applied to identify the hypothetical proteins having immunogenic potential and their predicted immunogenic peptides. Twelve peptides, ranging from 12 to 38 amino acid residues, containing the selected epitopes from different targets were selected and synthesized in two forms: the pure peptide; and the peptide conjugated to keyhole limpet hemocyanin (KLH) carrier. These peptides were divided into two groups of six peptides each. The antigen formulations (groups 1 and 2) were prepared with conjugated peptides containing 200 µg of each peptide per dose emulsified with Montanide ISA 61VG (SEPPIC); the control treatment had the adjuvant formulation without peptides (group 3). To evaluate the protective efficacy, 15 weaned male calves (Angus breed) aged around 6 months to one year and weighing approximately 200-250 kg were divided into three groups of five animals each; they were immunized thrice, at an interval of 28 days. After immunization, all the calves infested with 15,000 larvae of Rhipicephalus microplus. Peptide epitopes were recognized by antibodies against host-specific IgGs using indirect ELISA. The mean of the antibody level was determined for each group and compared using analysis of variance with two factors (ANOVA). F-test was used to determine the significance of differences observed between the groups. The percentage efficacy was calculated based on the number of ticks, the weight of teleoginas, and the weight and hatchability of the eggs, compared to that in the control group. The evaluation of immunoprotection indicated efficacies of 69 and 51 %, respectively in Group 1 and 2.

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BACKGROUND: Acute poisoning often results in decreased consciousness, necessitating airway assessment and management. Existing literature in the trauma setting suggests the importance of airway protection in unconscious patients to prevent complications, including aspiration. Practices for endotracheal intubation in non-traumatic acute poisoning are poorly described and variable, particularly regarding the use of a Glasgow Coma Scale (GCS) ≤ 8 threshold for intubation. METHODS: A systematic review and meta-analysis of proportions was conducted to evaluate intubation rates and outcomes in patients presenting for acute non-traumatic poisoning. Studies were excluded if the primary indication for intubation was not airway protection. We analyzed rates of intubation, mortality, and aspiration by subgrouping patients into GCS ≤ 8, GCS 9-15, or mixed GCS. Common and random-effects analysis were used, supplemented by subgroup analyses. RESULTS: 39 studies were included in the analysis, involving 15,959 patients. Random-effects pooled intubation rates varied significantly across GCS categories: GCS ≤ 8 (30.0%, I2 = 92%, p < 0.01), GCS 9-15 (1.0%, I2 = 0%, p = 0.91), and mixed GCS (11.0%, I2 = 94%, p < 0.01), p-value <0.01 for subgroup difference. Aspiration rates also varied: GCS ≤ 8 (19.0%, I2 = 84%, p < 0.01), GCS 9-15 (4.0%, I2 = 78%, p < 0.01), and mixed group (5.0%, I2 = 72%, p < 0.01), p-value <0.01 for subgroup difference. Mortality rates remained low across all groups: GCS ≤ 8 (1.0%, I2 = 0%, p = 0.62), GCS 9-15 (1.0%, I2 = 0%, p = 0.99), and mixed group (2.0%, I2 = 68%, p < 0.01). CONCLUSION: The conventional "less than 8, intubate" approach may not be directly applicable to acute poisoning patients due to heterogeneity in patient presentation, intubation practices, and low mortality. Therefore, a nuanced approach is warranted to optimize airway management strategies tailored to individual patient needs.

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BACKGROUND: Invasive cardiopulmonary exercise testing (iCPET) combines traditional cardiopulmonary exercise testing with invasive hemodynamic measurements to assess exercise intolerance, which can be caused by preload insufficiency (PI), characterized by low ventricular filling pressures and reduced cardiac output during exertion. We hypothesize that plasma catecholamine levels at rest and during exercise correlate with hemodynamic parameters in PI. METHODS: We included adult patients who underwent iCPET for exercise intolerance and had plasma catecholamines measured at rest and peak exercise. RESULTS: Among 84 patients, PI was identified in 57 (67.8 %). Compared to patients without PI, those with PI were younger [median (IQR) 37 (28, 46) vs 47 (39,55) years, p = 0.005] and had lower workload at peak exercise [81 (66, 96) vs 95 (83.5, 110.50) Watts, p = 0.006]. Patients with PI had higher heart rates at rest and peak exercise [87 (78, 97) vs 79 (74, 87) bpm, p = 0.04; and 167 (154, 183) vs 156 (136, 168) bpm, p = 0.01, respectively]. In all patients, epinephrine and norepinephrine at peak exercise directly correlated with peak workload (r:0.41, p < 0.001 and r:0.47, p < 0.001, respectively). Resting epinephrine was higher in patients with PI [136 (60, 210) vs 77 (41, 110) pg/mL, p = 0.02]. There was no significant difference in the change in catecholamines from rest to peak exercise between patients with or without PI. CONCLUSION: PI patients exhibited elevated heart rate and epinephrine at rest, indicating increased sympathetic activity. We did not find strong associations between catecholamines and cardiac filling pressures, suggesting that catecholamine levels are predominantly influenced by peak workload.

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The Two-Photon Absorption-Transient Current Technique (TPA-TCT) is a device characterisation technique that enables three-dimensional spatial resolution. Laser light in the quadratic absorption regime is employed to generate excess charge carriers only in a small volume around the focal spot. The drift of the excess charge carriers is studied to obtain information about the device under test. Neutron-, proton-, and gamma-irradiated p-type pad silicon detectors up to equivalent fluences of about 7 × 1015 neq/cm2 and a dose of 186 Mrad are investigated to study irradiation-induced effects on the TPA-TCT. Neutron and proton irradiation lead to additional linear absorption, which does not occur in gamma-irradiated detectors. The additional absorption is related to cluster damage, and the absorption scales according to the non-ionising energy loss. The influence of irradiation on the two-photon absorption coefficient is investigated, as well as potential laser beam depletion by the irradiation-induced linear absorption. Further, the electric field in neutron- and proton-irradiated pad detectors at an equivalent fluence of about 7 × 1015 neq/cm2 is investigated, where the space charge of the proton-irradiated devices appears inverted compared to the neutron-irradiated device.

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RATIONALE: Imbalance between forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) (dysanapsis) has been reported in children who are obese. This dysanaptic growth might begin at an early age, although there are no data on children younger than 6 years. OBJETIVES: To assess whether body mass index (BMI) and early weight gain, in healthy infants born at term, plays a significant role in the imbalance between FEV1 and FVC, even in the absence of obesity. METHODS: Lung function was measured by means of raised volume rapid thoracic compression in 69 healthy infants born at term from the Nutrition in Early Life and Asthma cohort. Dysanapsis was defined as zFVC >0.674, zFEV0 .5 ≥-1.645, and FEV0 .5/FVC ≤-1.645. Weight gain (g/day) and growth rate (cm/year) were calculated as the difference between weight and length on the test date and those at birth. To assess the relationship between zBMI and dysanapsis, a receiver operating characteristic curve was performed. Multivariable analysis was carried out by means of linear regressions (one for each lung function index) and by logistic regression for dysanapsis (yes/no). RESULTS: Higher zBMI was associated with risk of dysanapsis (odds ratio: 3.53, [95% confidence interval: 1.30; 9.66]; p = .014): Each additional zBMI unit was associated with ~10 mL higher FVC and with ~3.5% lower FEV0.5/FVC. Weight gain was associated with lower FEV0.5/FVC ratio. CONCLUSION: Dysanaptic development of lung function begins very early in infancy and is related with weight gain and body mass index, even in the absence of obesity.

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G protein-coupled receptors (GPCRs) are the largest class of transmembrane receptors encoded in the human genome, and they initiate cellular responses triggered by a plethora of extracellular stimuli ranging from neurotransmitters and hormones to photons. Upon stimulation, GPCRs activate heterotrimeric G proteins (Gαßγ) in the cytoplasm, which then convey signals to their effectors to elicit cellular responses. Given the broad biological and biomedical relevance of GPCRs and G proteins in physiology and disease, there is great interest in developing and optimizing approaches to measure their signaling activity with high accuracy and across experimental systems pertinent to their functions in cellular communication. This review provides a historical perspective on approaches to measure GPCR-G protein signaling, from quantification of second messengers and other indirect readouts of activity to biosensors that directly detect the activity of G proteins. The latter is the focus of a more detailed overview of the evolution of design principles for various optical biosensors of G protein activity with different experimental capabilities. We will highlight advantages and limitations of biosensors that detect different G protein activation hallmarks, like dissociation of Gα and Gßγ or nucleotide exchange on Gα, as well as their suitability to detect signaling mediated by endogenous versus exogenous signaling components or in physiologically relevant systems like primary cells. Overall, this review intends to provide an assessment of the state-of-the-art for biosensors that directly measure G protein activity to allow readers to make informed decisions on the selection and implementation of currently available tools. SIGNIFICANCE STATEMENT: G protein activity biosensors have become essential and widespread tools to assess GPCR signaling and pharmacology. Yet, investigators face the challenge of choosing from a growing list of G protein activity biosensors. This review provides an overview of the features and capabilities of different optical biosensor designs for the direct detection of G protein activity in cells, with the aim of facilitating the rational selection of systems that align with the specific scientific questions and needs of investigators.

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PURPOSE: To identify risk factors predisposing patients to poor outcomes after fixation of periprosthetic hip fractures around femoral stems. METHODS: Prospective multicentre cohort study of fractures around a hip replacement stem managed by internal fixation. The primary outcome was one-year mortality, while secondary outcomes were local complications and healthcare burden-related outcomes (nursing facility utilization and hospital length of stay). RESULTS: One-year mortality was 16.2%. Age-adjusted Charlson Comorbidity Index score (OR=1.17; 95%CI=1.03-1.33)), Pfeiffer Short Portable Mental Status Questionnaire (SPMSQ) score (OR=1.16; 1.06-1.28), prosthetic dysfunction (OR=1.90; 1.00-3.61), and postoperative medical complications (OR=1.97; 1.06-3.68) were predictors of mortality. Patients with prior prosthetic dysfunction, lower Pfeiffer SPMSQ scores, Vancouver A fractures, and fractures fixed only using cerclages were at higher risk of local complications, which occurred in 9.3% of cases. Medical (OR=1.81; 1.05-3.13) and local complications (OR=5.56; 2.42-3.13) emerged as consistent risk factors for new institutionalization. Average hospitalization time was 13.9±9.2 days. Each day of fixation delay led to an average 1.4-day increase in total hospitalization. CONCLUSION: Frail periprosthetic hip-fracture patients with poorer functional status, dysfunctional replacements, and postoperative complications are at increased risk of mortality. Postoperative complications are more common in patients with dysfunctional arthroplasties, Vancouver A fractures, and fixation using cerclages alone. Postoperative complications were the most consistent predictor of higher healthcare resource utilization.

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G-protein-coupled receptors (GPCRs) are essential mediators of neuromodulation and prominent pharmacological targets. While activation of heterotrimeric G-proteins (GαßÉ£) by GPCRs is essential in this process, much less is known about the postreceptor mechanisms that influence G-protein activity. Neurons express G-protein regulators that shape the amplitude and kinetics of GPCR-mediated synaptic responses. Although many of these operate by directly altering how G-proteins handle guanine-nucleotides enzymatically, recent discoveries have revealed alternative mechanisms by which GPCR-stimulated G-protein responses are modulated at the synapse. In this review, we cover the molecular basis for, and consequences of, the action of two G-protein regulators that do not affect the enzymatic activity of G-proteins directly: Gα inhibitory interacting protein (GINIP), which binds active Gα subunits, and potassium channel tetramerization domain-containing 12 (KCTD12), which binds active Gßγ subunits.

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Background: Hospitals are required to have rapid response (RR) systems in place to respond to acute changes in a patient's condition. In high-stress situations like RR, medical residents face decision-making challenges due to time constraints and perceived pressure. Instituting order panels (OPs) can facilitate clinical decision making and improve residents' and nurses' satisfaction and patient safety. Objective: This quality improvement (QI) project aimed to create and institute standardized OPs for common RR clinical scenarios to improve satisfaction of internal medicine residents and nurses with the RR process. Methods: This was a single tertiary care center QI project that developed OPs for 10 common RR scenarios. Resident and nursing satisfaction with RR was assessed before and after OP implementation via survey and qualitative data collection. Results: Residents and nurses expressed high levels of satisfaction across various aspects of the RR process before and after OP implementation in both quantitative and qualitative analysis. Increased satisfaction was observed among residents regarding time spent placing orders (94%; P = 0.02) and time spent correcting wrong orders (87%; P = 0.03) after OP implementation. The nurses' survey revealed no statistically significant differences in satisfaction before and after the implementation of OPs regarding communication, collaboration, efficiency, and organization of the team. Conclusion: The introduction of standardized OPs for RRs resulted in increased satisfaction among internal medicine residents in terms of order placement and correcting wrong orders. Nurse satisfaction based on survey responses remained neutral. Qualitative data from both groups demonstrated a positive impact on communication, efficiency, and teamwork.

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Asthma is, worldwide, the most frequent non-communicable disease affecting both children and adults, with high morbidity and relatively low mortality, compared to other chronic diseases. In recent decades, the prevalence of asthma has increased in the pediatric population, and, in general, the risk of developing asthma and asthma-like symptoms is higher in children during the first years of life. The "gut-lung axis" concept explains how the gut microbiota influences lung immune function, acting both directly, by stimulating the innate immune system, and indirectly, through the metabolites it generates. Thus, the process of intestinal microbial colonization of the newborn is crucial for his/her future health, and the alterations that might generate dysbiosis during the first 100 days of life are most influential in promoting hypersensitivity diseases. That is why this period is termed the "critical window". This paper reviews the published evidence on the numerous factors that can act by modifying the profile of the intestinal microbiota of the infant, thereby promoting or inhibiting the risk of asthma later in life. The following factors are specifically addressed in depth here: diet during pregnancy, maternal adherence to a Mediterranean diet, mode of delivery, exposure to antibiotics, and type of infant feeding during the first three months of life.

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Among cattle, Bos taurus breeds and their crosses are more sensitive to tick infestations than Bos indicus breeds that are more resistant to infestation and more adaptable to tropical climates. The presence of susceptible individuals in herds and inadequate tick control lead to direct and indirect losses in the meat production chain, in addition to increased mortality due to cattle tick fever. The objective of this study was to describe, compare and rank the sensitivity of different breeds of stabled cattle to the tick Rhipicephalus microplus and to present, as an innovative result, a scale called the Tick Ruler. Secondary data on the number of retrieved engorged females, engorged female ticks' weight, egg mass weight and number of larvae were extracted from research reports of experiments conducted over 18 years with eight breeds to describe and report the sensitivity of the breeds to artificial infestation by R. microplus larvae. For analyses, the recovery rate of engorged female ticks and the percentile of dispersion of individuals in their respective races were calculated, and comparison of these percentiles between races was performed. The ranking of the percentiles resulted in the organization of the breeds by their susceptibility to R. microplus; we call this scale the "Tick Ruler." The ruler is a simple, easy-to-understand tool that can be used by technicians and producers to evaluate the tick sensitivity of a breed of interest and can assist producers in decision-making to find a balance between increased production gains and the risk of economic losses depending on the breed composition in a cattle herd.

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Ticks parasitize various hosts, including humans, and are known to transmit pathogens that can be harmful not only to animals but also to humans. To evaluate the possible presence of pathogens in ticks, we aimed to collect and identify tick fauna specimens in Lagoa Comprida Municipal Natural Park, an anthropogenic urban area located in Aquidauana, Mato Grosso do Sul, Brazil. A total of 1216 ticks, of which 51.2% were Amblyomma sculptum, 1.2% were Amblyomma dubitatum, and 41% were Amblyomma spp. were collected. These results show that the prevalence of A. sculptum is significantly higher than that of A. dubitatum across all four seasons. Molecular analyses revealed positive samples for the genus Babesia, including the confirmation of Babesia bigemina in an A. sculptum specimen, marking the first record of this relationship. This unexpected finding demands greater attention and deeper analysis in the context of the epidemiology of tick-borne diseases.

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The synthesis, physicochemical, and functional properties of composite solids resulting from the surface spread of oxidized indium species onto nanoplatelets of anatase were investigated. Both the size and the interaction between the indium- and titanium-containing components control the functional properties. In the reduction of CO2 to CO, the best samples have an indium content between ca. 2 and 5 mol % and showed an excess rate over the photo and thermo-alone processes above 33% and an energy efficiency of 1.3%. Subnanometric (monomeric and dimeric) indium species present relatively weak thermal catalytic response but strong thermo-photo promotion of the activity. A gradual change in functional properties was observed with the growth of the indium content of the solids, leading to a progressive increase of thermal activity but lower thermo-photo promotion. The study provides a well-defined structure-activity relationship rationalizing the dual thermo-photo properties of the catalysts and establishes a guide for the development of highly active and stable composite solids for the elimination and valorization of CO2.

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BACKGROUND: Some studies have reported that polyamine levels may influence immune system programming. The aim of this study was to evaluate the polyamine profile during gestation and its associations with maternal allergy and cytokine production in cord blood cells in response to different allergenic stimuli. METHODS: Polyamines were determined in plasma of pregnant women (24 weeks, N = 674) and in umbilical cord samples (N = 353 vein and N = 160 artery) from the Mediterranean NELA birth cohort. Immune cell populations were quantified, and the production of cytokines in response to different allergic and mitogenic stimuli was assessed in cord blood. RESULTS: Spermidine and spermine were the most prevalent polyamines in maternal, cord venous, and cord arterial plasma. Maternal allergies, especially allergic conjunctivitis, were associated with lower spermine in umbilical cord vein. Higher levels of polyamines were associated with higher lymphocyte number but lower Th2-related cells in cord venous blood. Those subjects with higher levels of circulating polyamines in cord showed lower production of inflammatory cytokines, especially IFN-α, and lower production of Th2-related cytokines, mainly IL-4 and IL-5. The effects of polyamines on Th1-related cytokines production were uncertain. CONCLUSIONS: Spermidine and spermine are the predominant polyamines in plasma of pregnant women at mid-pregnancy and also in umbilical cord. Maternal allergic diseases like allergic conjunctivitis are related to lower levels of polyamines in cord vein, which could influence the immune response of the newborn. Cord polyamine content is related to a decreased Th2 response and inflammatory cytokines production, which might be important to reduce an allergenic phenotype in the neonate.

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