Sex differences and similarities in the neuroimmune response to central administration of poly I:C.

BACKGROUND: The neuroimmune system is required for normal neural processes, including modulation of cognition, emotion, and adaptive behaviors. Aberrant neuroimmune activation is associated with dysregulation of memory and emotion, though the precise mechanisms at play are complex and highly context dependent. Sex differences in neuroimmune activation and function further complicate our understanding of its roles in cognitive and affective regulation. METHODS: Here, we characterized the physiological sickness and inflammatory response of the hippocampus following intracerebroventricular (ICV) administration of a synthetic viral mimic, polyinosinic:polycytidylic acid (poly I:C), in both male and female C57Bl/6N mice. RESULTS: We observed that poly I:C induced weight loss, fever, and elevations of cytokine and chemokines in the hippocampus of both sexes. Specifically, we found transient increases in gene expression and protein levels of IL-1α, IL-1ß, IL-4, IL-6, TNFα, CCL2, and CXCL10, where males showed a greater magnitude of response compared with females. Only males showed increased IFNα and IFNγ in response to poly I:C, whereas both males and females exhibited elevations of IFNß, demonstrating a specific sex difference in the anti-viral response in the hippocampus. CONCLUSION: Our data suggest that type I interferons are one potential node mediating sex-specific cytokine responses and neuroimmune effects on cognition. Together, these findings highlight the importance of using both males and females and analyzing a broad set of inflammatory markers in order to identify the precise, sex-specific roles for neuroimmune dysregulation in neurological diseases and disorders.

Polyunsaturated fatty acids and child neurodevelopment among a population exposed to DDT: a cohort study.

BACKGROUND: Child neurodevelopment has been positively linked to maternal intake of polyunsaturated fatty acids (PUFAs) during pregnancy; however, it is unknown if that relationship persists among populations exposed to environmental neurotoxicants. OBJECTIVE: The aim of this work was to assess whether maternal dietary intake of PUFAs during pregnancy is positively associated with child neurodevelopment, whose mothers were environmentally exposed to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). METHODS: A prospective cohort study with 276 mother-child pairs was performed in Mexico. Neurodevelopment was assessed by Bayley Scales II from children age 1 to 30 months. Dietary PUFAs intake was estimated by Food Frequency Questionnaire at 1st and 3rd trimester of pregnancy. DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene, the main metabolite of DDT) maternal serum levels were determined by electron capture gas chromatography. Longitudinal multivariate linear mixed-effects analysis, which combines mental (MDI) and motor (PDI) Bayley scales in a single model, were performed. RESULTS: Our results show that in a sample environmentally exposed to DDT, maternal ingestion of DPA during the first trimester of pregnancy was positively associated with MDI (ß = 0.10, 95% CI 0.02, 0.18) in children from 1 to 30 months. Likewise, our results suggest that dietary ALA may be also related to MDI. CONCLUSION: DPA may benefit neurodevelopment even in populations exposed to DDT. Our results strengthen the importance of PUFAs intake during the prenatal period.

Maternal exposure to PM2.5 in south Texas, a pilot study.

In this study, we characterized personal exposure to fine particulate matter (PM2.5), black carbon (BC), and nicotine in pregnant women in Hidalgo County, where the hospitalization rates of childhood asthma are the highest in the state of Texas. The measurements were conducted over three non-consecutive sampling days for 17 participants in their third trimester. Measurements were partitioned into four microenvironments, i.e., Residential, Vehicular, Commercial, and Other, on the basis of GPS coordinates and temperature and humidity measurements. The daily average PM2.5 mass concentration was 24.2 (standard deviation=22.0) µg/m3, with the highest daily mass concentration reaching 126.0µg/m3. The daily average BC concentration was 1.44 (SD=0.82) µg/m3, ranging from 0.5 to 5.4µg/m3. Hair nicotine concentrations were all near the detection level (i.e., 49.2pg/mg), indicating that the participants were not routinely exposed to tobacco smoke. The Residential microenvironment contributed dominantly to the mass concentration since the participants chiefly remained at home and cooking activities contributed significantly to the total PM2.5. When compared to an ambient monitoring station, the person-specific PM2.5 was frequently more than double the ambient measurement (10.4µg/m3 overall), revealing that even in regions where ambient concentrations are below national standards, individuals may be still be exposed to elevated PM2.5 mass concentrations.

Maternal dietary intake of polyunsaturated fatty acids modifies association between prenatal DDT exposure and child neurodevelopment: A cohort study.

BACKGROUND: Maternal 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) serum levels during pregnancy have been negatively linked to child neurodevelopment in contrast to intake of omega-3 and -6 (ω-3 and ω-6) fatty acids. OBJECTIVES: To assess whether maternal dietary intake of ω-3 and ω-6 during pregnancy modifies the association between exposure to DDE and child neurodevelopment from age 42-60 months. METHODS: Prospective cohort study with 142 mother-child pairs performed in Mexico. DDE serum levels were determined by electron capture gas chromatography. Dietary ω-3 and ω-6 intake was estimated by questionnaire. Child neurodevelopment was assessed by McCarthy Scales. RESULTS: Docosahexaenoic (DHA) fatty acid intake significantly modified the association between DDE and motor component: increased maternal DDE was associated with lower motor development in children whose mothers had lower DHA intake (ßlog2DDE = -1.25; 95% CI: -2.62, 0.12), in contrast to the non-significant increase among children whose mothers had higher DHA intake (ßlog2DDE-motor = 0.50; 95% CI: 0.55, 1.56). Likewise, arachidonic fatty acid (ARA) intake modified the association between DDE and memory component: increased maternal DDE was associated with a significantly larger reduction in the memory component in children whose mothers had lower ARA intake (ßlog2DDE = -1.31; 95% CI: -2.29, -0.32) than children whose mothers had higher ARA intake (ßlog2DDE-memory = 0.17; 95% CI: -0.78, 1.11). CONCLUSIONS: Dietary intake of DHA and ARA during pregnancy may protect against child neurodevelopment damage associated with prenatal maternal DDE levels.

Prenatal p,p´-DDE exposure and neurodevelopment among children 3.5-5 years of age.

BACKGROUND: The results of previous studies suggest that prenatal exposure to bis[p-chlorophenyl]-1,1,1-trichloroethane (DDT) and to its main metabolite, 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), impairs psychomotor development during the first year of life. However, information about the persistence of this association at later ages is limited. OBJECTIVES: We assessed the association of prenatal DDE exposure with child neurodevelopment at 42-60 months of age. METHODS: Since 2001 we have been monitoring the neurodevelopment in children who were recruited at birth into a perinatal cohort exposed to DDT, in the state of Morelos, Mexico. We report McCarthy Scales of Children's Abilities for 203 children at 42, 48, 54, and 60 months of age. Maternal DDE serum levels were available for at least one trimester of pregnancy. The Home Observation for Measurement of the Environment scale and other covariables of interest were also available. RESULTS: After adjustment, a doubling of DDE during the third trimester of pregnancy was associated with statistically significant reductions of -1.37, -0.88, -0.84, and -0.80 points in the general cognitive index, quantitative, verbal, and memory components respectively. The association between prenatal DDE and the quantitative component was weaker at 42 months than at older ages. No significant statistical interactions with sex or breastfeeding were observed. CONCLUSIONS: These findings support the hypothesis that prenatal DDE impairs early child neurodevelopment; the potential for adverse effects on development should be considered when using DDT for malaria control.

Prenatal dichlorodiphenyldichloroethylene (DDE) exposure and neurodevelopment: a follow-up from 12 to 30 months of age.

In order to evaluate the persistency of the association between DDE and infant neurodevelopment we assessed mental and psychomotor development between 12 and 30 months of age in an ongoing cohort in Mexico. A total of 270 singleton children without perinatal asphyxia diagnosis, with a birth weight > or =2 kg, mothers>15 years of age with organochlorine maternal serum levels measured at least in one trimester of pregnancy, and who were evaluated at least in two of the four visits at 12, 18, 24 and 30 months of age, were included in this report. The Spanish version of Bayley Scales of Infant Development II (BSID_II; Bayley, 1993) was administered to the children and Psychomotor Development Index (PDI) and Mental Development Index (MDI) were calculated. Information about stimulation at home was measured using the Home Observation of Measurement of the Environment (HOME) at 6 months, and breastfeeding history was obtained through direct interviews with the mothers. Maternal serum DDE levels were determined during pregnancy by means of electron capture gas-liquid chromatography. The association between DDE prenatal exposure and neurodevelopment was estimated using separate generalized mixed effects models. Our results suggest that the association between prenatal DDE and infant neurodevelopment does not persist beyond 12 months of age even after adjusting for known risk factors for neurodevelopment. In addition, we observed an interaction between early home stimulation and mental improvement at 24 and 30 months of age (p<0.001). The association of DDE with infant neurodevelopment seems to be reversible. However, we cannot rule out that other DDT metabolites may play a role in neurodevelopment.

Dichlorodiphenyldichloroethylene exposure during the first trimester of pregnancy alters the anal position in male infants.

Anogenital distance (AGD) at birth is regarded as a useful measurement that reflects the prenatal androgenic status in rodents. However, the impact of xenoantiandrogens on human development is largely unknown. The aim of this study was to evaluate the potential antiandrogenic impact of prenatal DDT metabolites (p,p'-DDE and p,p'-DDT) exposure on infant AGD, using a non-age-dependent anal position index (API). As part of an ongoing perinatal cohort study on the effects of organochlorine pesticides in children's neurodevelopment, we conducted a cross-sectional study in 71 infants (37 males and 34 females). Maternal serum levels of DDT metabolites (p,p'-DDE and p,p'-DDT) before and during each trimester of pregnancy were determined by electron capture gas-liquid chromatography. During postnatal home visits at 3, 6, and 12 or 18 months of age, the children's weight and API were evaluated. Multiple lineal regression models were used to estimate the potential endocrine disruptor activity of prenatal p,p'-DDE exposure. Boys had significantly higher API values than girls (0.6 versus 0.5; P < 0.001). Only among boys, a doubling increase of maternal p,p'-DDE serum levels during the first trimester of pregnancy, were associated with a significant reduction of API (beta=-0.02; P= 0.02). No effect of p,p'-DDT on AGD was observed. Evidence of the effect of prenatal p,p'-DDE on external genital differentiation is scarce and not consistent in the literature. Further studies are needed to confirm a hormonal disruptive effect on the development of external genitalia, due not only to p,p'-DDE but also due to other antiandrogenic persistent compounds.

In utero p,p'-DDE exposure and infant neurodevelopment: a perinatal cohort in Mexico.

BACKGROUND: Evidence suggests that p,p'-dichlorodiphenyldichloroethene (DDE) affects neurodevelopment in infants, although a critical exposure window has not yet been identified. OBJECTIVES: Our goal was to assess the prenatal DDE exposure window and its effect on the psychomotor development index (PDI) and mental development index (MDI) during the first year of life. METHODS: We recruited 244 children whose pregnancies and deliveries were uncomplicated, and whose mothers were monitored throughout the pregnancy. Participating mothers were not occupationally exposed to DDT (dichlorodiphenyltrichloroethane) but were residents of a zone in Mexico with endemic malaria. We measured serum levels of DDE before pregnancy and during each trimester of the pregnancy. We evaluated PDI and MDI of the Bayley Scales for Infant Development (BSID-II), at 1, 3, 6, and 12 months of age. We adjusted for quality of the home environment and maternal intellectual coefficient (IQ). We used generalized mixed-effects models for statistical analysis. RESULTS: Third-trimester DDE level (7.8 +/- 2.8 ppb) was significantly higher than the level at baseline, first, and second trimesters, but the differences never exceeded 20%. Only DDE levels during the first trimester of pregnancy were associated with a significant reduction in PDI (every doubled increase of DDE level reduced the PDI 0.5 points). DDE was not associated with MDI. CONCLUSIONS: A critical window of exposure to DDE in utero may be the first trimester of the pregnancy, and psychomotor development is a target of this compound. Residues of DDT metabolites may present a risk of developmental delay for years after termination of DDT use.

[Critical care nursing and continuous renal replacement techniques in the Madrid Community]. / Enfermería de cuidados críticos y técnicas continuas de reemplazo renal en la Comunidad de Madrid.

The continuous renal replacement techniques (CRRT) aim to substitute the altered renal function during a period of time, presenting advantages compared to conventional hemodialysis (CH). This study aims to determine the situation of the CRRT in the Intensive care units (ICU) of the Madrid Community (MC) using a survey distributed to nurses (n = 131) of 14 ICU. It evaluates four aspects of the CRRT: management model, knowledge, problems and degree of satisfaction. It identified four models, the most frequent is that in which ICU nurse and intensivist participate (60%). Self-evaluation of knowledge was fair in 55.7% of the cases and the mean of correct responses in an evaluation of 10 questions was 4.19 and 5.45 in those with previous courses. A total of 84.7% think that CRRT significantly increases the workloads and 62.6% believe that they should be done by the ICU nurses. The main problem is the lack of knowledge to resolve complications during the technique. We conclude that the ICU nursing can handle the CRRT, adapting the nurse/patient ratio; training programs should be established and the role of the teaching nurse defined in critical renal cares.

Enfermería de cuidados críticos y técnicas continuas de reemplazo renal en la Comunidad de Madrid / Critical care nursing and continuous renal replacement techniques in the Madrid Community

Las técnicas continuas de reemplazo renal (TCRR) intentan sustituir la función renal alterada durante un perÍodo, y presentan ventajas frente a la hemodiálisis convencional (HC). Este estudio pretende determinar la situación de las TCRR en las unidades de cuidados críticos (UCC) de la Comunidad de Madrid (CAM) mediante una encuesta repartida a enfermeras/os (n = 131) de 14 UCC. Evalúa 4 aspectos de las TCRR: modelo de manejo, conocimientos, problemas y grado de satisfacción. Identificó 4 modelos, el más frecuente es el que comparten la enfermera de UCC y el intensivista (60 por ciento). La autovaloración de conocimientos fue regular en un 55,7 por ciento de los casos, y en una evaluación de10 preguntas la media de respuestas correctas fue de 4,19, y de 5,45 en los que tenían cursos previos. El 84,7 por ciento piensa que las TCRR aumentan significativamente las cargas de trabajo. El 62,6 por ciento cree que deben ser asumidas por la enfermería de UCC. El principal problema es el déficit de conocimientos para resolver complicaciones durante la técnica. Concluimos que la enfermería de UCC puede y debe manejar las TCRR adecuándose la ratio enfermera/paciente; deberían establecerse programas de formación y perfilar el rol de enfermera docente en cuidados críticos renales (AU)