Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis.

CONTEXT: Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. OBJECTIVE: To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes. METHODS: We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders. RESULTS: The final study population comprised 33 118 mother-child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA. CONCLUSION: This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.

Associations of Maternal Educational Level, Proximity to Greenspace During Pregnancy, and Gestational Diabetes With Body Mass Index From Infancy to Early Adulthood: A Proof-of-Concept Federated Analysis in 18 Birth Cohorts.

International sharing of cohort data for research is important and challenging. We explored the feasibility of multi-cohort federated analyses by examining associations between three pregnancy exposures (maternal education, exposure to green vegetation and gestational diabetes) with offspring BMI from infancy to 17 years. We used data from 18 cohorts (n=206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0-1, 2-3, 4-7, 8-13 and 14-17 years. Associations were estimated using linear regression via one-stage IPD meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z-score comparing low with high education age 2-3 years = 0.03 [95% CI 0.00, 0.05], 4-7 years = 0.16 [95% CI 0.14, 0.17], 8-13 years = 0.24 [95% CI 0.22, 0.26]). Gestational diabetes was positively associated with BMI from 8 years (BMI z-score difference = 0.18 [CI 0.12, 0.25]) but not at younger ages; however associations attenuated towards the null when restricted to cohorts which measured GDM via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age one but not at older ages. Opportunities of cross-cohort federated analyses are discussed.

Sleep problems at ages 8-9 and ADHD symptoms at ages 10-11: evidence in three cohorts from INMA study.

Sleep problems and attention deficit hyperactivity disorder (ADHD) are interrelated during childhood and preadolescence. The objective of this work is assessing if sleep problems at ages 8-9 represent an alarm sign for presenting ADHD problems at ages 10-11 in three cohorts from INMA Study. Participants were 1244 children from Gipuzkoa, Sabadell, and Valencia cohorts. Sleep problems were assessed (ages 8-9) with the sleep items of the Child's Behaviour Checklist (CBCL), and ADHD problems were collected through the Conner's Parent Rating Scales-Revised: Short Form (CPRS-R:S) (age 10-11). Minimally and fully adjusted negative binomial models were fitted for each CPRS-R:S scale. Linearity of the relationship was assessed with generalized additive models (cubic smoothing splines with 2, 3, and 4 knots). For sensitivity analyses, children with previous symptoms, those born preterm and small for gestational age, and cases with extreme values, were excluded. Sleep problems presented IRR (95% CI) of 1.14 (1.10-1.19), 1.20 (1.14-1.26), 1.18 (1.11-1.25), and 1.18 (1.13-1.23) for opposition, inattention, hyperactivity, and ADHD scales, respectively. Fully adjusted models slightly decreased the IRR, but the association remained similar and significant. Sensitivity analyses showed similar results to fully adjusted models with only hyperactivity shown a slight decrease on significance (p = 0.051) when ADHD cases at age 9 were excluded.   Conclusion: Sleep problems are an alarm sign for later neurodevelopment problems such as ADHD. Healthcare systems could take advantage implementing policies to pay special attention on the sleep habits and sleep hygiene. This could contribute to add evidence to public health programmes such as the Healthy Child Programme.

Mediators of the association between maternal body mass index and breastfeeding duration in 3 international cohorts.

BACKGROUND: Maternal obesity has been associated with shorter breastfeeding duration, but little is known about mediating factors explaining this association. It is important to assess these relationships across diverse populations because breastfeeding is culturally patterned. OBJECTIVES: We investigated the association of prepregnancy maternal body mass index (BMI) with breastfeeding outcomes and potential mediators of this relationship in 3 culturally diverse international cohorts. METHODS: We analyzed 5120 singleton pregnancies from mother-child cohorts in Spain (INfancia y Medio Ambiente), Greece (Rhea), and the United States (Project Viva). Outcome variables were duration of any and exclusive breastfeeding. A priori hypothesized mediators in the association of maternal prepregnancy BMI with breastfeeding were birthweight (BW), maternal prenatal C-reactive protein (CRP), cesarean delivery, maternal dietary inflammatory index (DII) during pregnancy, gestational age at delivery, and gestational diabetes mellitus (GDM). We estimated the association between BMI and breastfeeding duration using linear regression adjusting for confounders. Mediation analysis estimated direct and indirect effects of maternal overweight/obesity on breastfeeding for each mediator. RESULTS: Women with overweight and obesity had shorter duration of any and exclusive breastfeeding compared with normal-weight women (any: overweight ß = -0.79 mo, 95% CI: -1.17, -0.40; obese ß = -1.75 mo 95% CI: -2.25, -1.25; exclusive: overweight ß = -0.30 mo, 95% CI: -0.42, -0.16; obese ß = -0.73 mo, 95% CI: -0.90, -0.55). Significant mediators (% change in effect estimate) of this association were higher CRP (exclusive: 5.12%), cesarean delivery (any: 6.54%; exclusive: 7.69%), and higher DII (any: 6.48%; exclusive: 7.69%). GDM, gestational age, and BW did not mediate the association of maternal weight status with breastfeeding. CONCLUSIONS: Higher prepregnancy BMI is associated with shorter duration of any and exclusive breastfeeding. Maternal dietary inflammation, systemic inflammation, and mode of delivery may be key modifiable mediators of this association. Identification of mediators provides potential targets for interventions to improve breastfeeding outcomes.

Genetic Load of SARS-CoV-2 in Aerosols Collected in Operating Theaters.

After the outbreak of COVID-19, additional protocols have been established to prevent the transmission of the SARS-CoV-2 from the patient to the health personnel and vice versa in health care settings. However, in the case of emergency surgeries, it is not always possible to ensure that the patient is not infected with SARS-CoV-2, assuming a potential source of transmission of the virus to health personnel. This work aimed to evaluate the presence of the SARS-CoV-2 and quantify the viral load in indoor air samples collected inside operating rooms, where emergency and scheduled operations take place. Samples were collected for 3 weeks inside two operating rooms for 24 h at 38 L/min in quartz filters. RNA was extracted from the filters and analyzed using RT-qPCR targeting SARS-CoV-2 genes E, N1 and N2 regions. SARS-CoV-2 RNA was detected in 11.3% of aerosol samples collected in operating rooms, despite with low concentrations (not detected at 13.5 cg/m3 and 10.5 cg/m3 in the scheduled and emergency operating rooms, respectively). Potential sources of airborne SARS-CoV-2 could be aerosolization of the virus during aerosol-generating procedures and in open surgery from patients that might have been recently infected with the virus, despite presenting a negative COVID-19 test. Another source could be related to health care workers unknowingly infected with the virus and exhaling SARS-CoV-2 virions into the air. These results highlight the importance of reinforcing preventive measures against COVID-19 in operating rooms, such as the correct use of protective equipment, screening programs for health care workers, and information campaigns. IMPORTANCE Operating rooms are critical environments in which asepsis must be ensured. The COVID-19 pandemic entailed the implementation of additional preventative measures in health care settings, including operating theaters. Although one of the measures is to operate only COVID-19 free patients, this measure cannot be always implemented, especially in emergency interventions. Therefore, a surveillance campaign was conducted during 3 weeks in two operating rooms to assess the level of SARS-CoV-2 genetic material detected in operating theaters with the aim to assess the risk of COVID-19 transmission during operating procedures. SARS-CoV-2 genetic material was detected in 11% of aerosol samples collected in operating rooms, despite with low concentrations. Plausible SARS-CoV-2 sources have been discussed, including patients and health care personnel infected with the virus. These results highlight the importance of reinforcing preventive measures against COVID-19 in operating rooms, such as the correct use of protective equipment, screening programs for health care workers and information campaigns.

Arsenic exposure and respiratory outcomes during childhood in the INMA study.

Ingested inorganic arsenic (iAs) is a human carcinogen that is also linked to other adverse health effects, such as respiratory outcomes. Yet, among populations consuming low-arsenic drinking water, the impact of iAs exposure on childhood respiratory health is still uncertain. For a Spanish child study cohort (INfancia y Medio Ambiente-INMA), low-arsenic drinking water is usually available and ingestion of iAs from food is considered the major source of exposure. Here, we explored the association between iAs exposure and children's respiratory outcomes assessed at 4 and 7 years of age (n = 400). The summation of 4-year-old children's urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) was used as a biomarker of iAs exposure (∑As) (median of 4.92 µg/L). Children's occurrence of asthma, eczema, sneeze, wheeze, and medication for asthma and wheeze at each assessment time point (i.e., 4- and 7-year) was assessed with maternal interviewer-led questionnaires. Crude and adjusted Poisson regression models using Generalized Estimating Equation (GEE) were performed to account for the association between natural logarithm transformed (ln) urinary ∑As in µg/L at 4 years and repeated assessments of respiratory symptoms at 4 and 7 years of age. The covariates included in the models were child sex, maternal smoking status, maternal level of education, sub-cohort, and children's consumption of vegetables, fruits, and fish/seafood. The GEE-splines function using Poisson regression showed an increased trend of the overall expected counts of respiratory symptoms with high urinary ∑As. The adjusted expected counts (95% confidence intervals) at ln-transformed urinary ∑As 1.57 (average concentration) and 4.00 (99th percentile concentration) were 0.63 (0.36, 1.10) and 1.33 (0.61, 2.89), respectively. These exploratory findings suggest that even relatively low-iAs exposure levels, relevant to the Spanish and other populations, may relate to an increased number of respiratory symptoms during childhood.

Madres adolescentes de Valparaíso: Riesgo relacional, apego y síntomas depresivos en comparación a madres adultas / Teenage mothers of Valparaiso: relational risk, attachment and depressive symptoms compared to adult others

El embarazo adolescente es considerado un factor de riesgo tanto para la salud de la madre como para la de su futuro hijo por significar una doble crisis del ciclo vital, poniendo en riesgo el proceso de vinculación. Objetivos. El presente estudio busca analizar el riesgo relacional, tipo de apego y comparar la aparición de síntomas depresivos en madres adolescentes y adultas durante la gestación y en el período postparto. Métodos. Estudio prospectivo de dos cohortes de primigestas adolescentes y adultas, pertenecientes a centros de atención primaria de Valparaíso durante el año 2013. Resultados. Las madres adolescentes presentaron una mayor prevalencia de apego no seguro, mayores tasas de alto riesgo relacional materno-fetal y madre-bebé y mayor prevalencia de síntomas depresivos en comparación a madres adultas. Sin embargo, sólo la diferencia en la prevalencia de apego no seguro entre ambas cohortes fue estadísticamente significativa.

Teenage pregnancy is considered a risk factor for both the mother and her child's health and wellbeing. It can be hypothesized that going through a double psychological crisis might be harmful to the development of a secure relationship of attachment in the dyad. Objectives. This investigation seeks to analyze relational risks, attachment styles, and to compare the prevalence of depressive symptoms between teenage mothers and adult mothers during pregnancy and postpartum. Methods. An observational prospective cohort study was carried out, considering primiparous mothers, both teenage and adults, who attended primary public healthcare centers in Valparaíso during 2013. Results: In comparison to adult mothers, teenage mothers were more likely to exhibit insecure attachment styles, depressive symptoms in pregnancy and postpartum, and scored higher in the relational risk assessment scale. However, only the difference on the rate of insecure attachment styles between teenage and adult mothers was statistically significant.

Salud mental primaria para niños, niñas y adolescentes institucionalizados: perspectiva de equipos de salud / Primary mental health care for institutionalized children and adolescents: a health team perspective / Saúde mental primária para crianças e adolescentes institucionalizados: uma visão das equipes de saúde

Resumen (Analítico) La salud mental de los niños, niñas y adolescentes institucionalizados en hogares es un desafío clínico y ético para Chile y América Latina. Con el objetivo de explorar experiencias y desafíos percibidos por profesionales de la atención primaria de salud que atienden esta población, se realizó una investigación cualitativa, utilizando un cuestionario con preguntas abiertas. Los datos se analizaron mediante teoría fundamentada. Los resultados mostraron que la atención era parcializada y discontinua. La información sobre el desarrollo vital, la familia, los contextos de vulneración e institucionalización era insuficiente y fragmentada. Además, existía escasa coordinación entre las instituciones que intervienen simultáneamente con los niños, niñas y adolescentes. Se discuten las implicancias para la formación de equipos de salud mental de la atención primaria de salud y la implementación efectiva del trabajo intersectorial y multinivel.

Abstract (analytical) Mental health care for vulnerable and institutionalized children and adolescents is a clinical and ethical challenge in Chile and Latin America. This study explores experiences and challenges encountered when providing mental health care among primary health care professionals. Qualitative research was conducted using an open-ended questionnaire for interviewing professionals in a rural area of Chile. The data was analyzed using Grounded Theory. The results show a fragmented and discontinuous delivery of care as a large portion of the children's clinical and social history is unknown. There is lack of coordination with other institutions that intervene in this area. The authors discuss implications for primary health care training for children's mental health teams and the need for the implementation of effective integrated and multilevel care systems.

Resumo (Analítico) A saúde mental de crianças e adolescentes vulneráveis e institucionalizados é um desafio clínico e ético no Chile e na América Latina. O presente estudo explorou experiências e desafios do cuidado por profissionais da atenção primária à saúde que atendem esta população. A pesquisa qualitativa foi realizada utilizando um questionário de perguntas abertas para entrevistar profissionais da área rural do Chile. Os dados foram analisados usando a Grounded Theory. Os resultados mostraram um atendimento fragmentado e descontínuo. As informações sobre parte da história clínica e social das crianças, e os contextos de vulnerabilidade e institucionalização são insuficientes. Além disso, existia pouca coordenação entre as instituições que intervêm simultaneamente com os crianças e adolescentes. São discutidas implicações para o treinamento de equipes de saúde mental na atenção primária à saúde e para a implementação de sistemas efetivos de atendimento integrado e multinível.

Validation of three predictive models for suboptimal cytoreductive surgery in advanced ovarian cancer.

The standard treatment for advanced ovarian cancer (AOC) is cytoreduction surgery and adjuvant chemotherapy. Tumor volume after surgery is a major prognostic factor for these patients. The ability to perform complete cytoreduction depends on the extent of disease and the skills of the surgical team. Several predictive models have been proposed to evaluate the possibility of performing complete cytoreductive surgery (CCS). External validation of the prognostic value of three predictive models (Fagotti index and the R3 and R4 models) for predicting suboptimal cytoreductive surgery (SCS) in AOC was performed in this study. The scores of the 3 models were evaluated in one hundred and three consecutive patients diagnosed with AOC treated in a tertiary hospital were evaluated. Clinicopathological features were collected prospectively and analyzed retrospectively. The performance of the three models was evaluated, and calibration and discrimination were analyzed. The calibration of the Fagotti, R3 and R4 models showed odds ratios of obtaining SCSs of 1.5, 2.4 and 2.4, respectively, indicating good calibration. The discrimination of the Fagotti, R3 and R4 models showed an area under the ROC curve of 83%, 70% and 81%, respectively. The negative predictive values of the three models were higher than the positive predictive values for SCS. The three models were able to predict suboptimal cytoreductive surgery for advanced ovarian cancer, but they were more reliable for predicting CCS. The R4 model discriminated better because it includes the laparotomic evaluation of the peritoneal carcinomatosis index.

Pre and postnatal exposure to mercury and respiratory health in preschool children from the Spanish INMA Birth Cohort Study.

Effects of mercury on maturing immune system have been reported, however the association with respiratory and allergy problems during infancy remains unclear. The aim of this study is to evaluate the association between pre and postnatal mercury exposure and respiratory and allergy problems among preschool children and to examine the role of potential modifying factors. Study subjects were children participant in Spanish Childhood and Environment Project (INMA, 2003-2008). We measured total mercury levels in cord blood (n = 1868) and hair at 4 years of age (n = 1347). Respiratory outcomes (wheezing, severe wheezing, chestiness, persistent cough, eczema and otitis) were obtained by questionnaires administered to parents. Associations were investigated by logistic regression adjusted for socio-demographic and lifestyle-related variables in each cohort and subsequent meta-analysis. We tested effect modification by factors related to individual susceptibility, diet and co-exposure with other pollutants. The geometric mean of cord blood and hair total mercury was 8.20 µg/L and 0.97 µg/g, respectively. No statistically significant association between pre or postnatal mercury exposure and respiratory and allergy outcomes was found. Notwithstanding, lower maternal intake of fruits and vegetables increased the risk of some respiratory outcomes due to the prenatal exposure to mercury (pint < 0.05). Moreover, an inverse association between prenatal mercury exposure and some respiratory outcomes was observed among children with higher maternal exposure to organocholorine compounds or smoking (pint < 0.05). Also, sex and postnatal smoking exposure modulated mercury postnatal effects on persistent cough (pint < 0.05). In conclusion, no association between pre and postnatal mercury exposure and respiratory and allergy problems among the whole population at study was found. However, diet and other toxicants could modulate this relation, especially during prenatal period. More research on this topic is warranted due to the limited evidence.

Postoperative Intestinal Fistula in Primary Advanced Ovarian Cancer Surgery.

BACKGROUND: Advanced ovarian cancer (AOC) requires an aggressive surgery with large visceral resections in order to achieve an optimal or complete cytoreduction and increase the patient's survival. However, the surgical aggressiveness in the treatment of AOC is not exempt from major complications, such as the gastrointestinal fistula (GIF), which stands out among others due to its high morbidity and mortality. METHODS: We evaluated the clinicopathological features in patients with AOC and their association with GI. Data for 107 patients with AOC who underwent primary debulking surgery were analyzed retrospectively. Clinicopathological features, including demographic, surgical procedures and follow-up data, were analyzed in relation to GIF. RESULTS: GIF was present in 11% of patients in the study, 5 (4.5%) and 7 (6.4%) of colorectal and small bowel origin, respectively. GIF was significantly associated with peritoneal cancer index (PCI) >20, more than 2 visceral resections, and multiple digestive resections. Overall and disease-free survival were also associated with GIF. Multivariate analysis identified partial bowel obstruction and operative bleeding as independent prognostic factors for survival. The presence of GIF is positively associated with poor prognosis in patients with AOC. CONCLUSION: Given the importance of successful cytoreductive surgery in AOC, the assessment of the amount of tumor and the aggressiveness of the surgery to avoid the occurrence of GIF become a priority in patients with AOC.

Percepción del equipo de salud sobre los beneficios del calostro como factor protector de enterocolitis necrotizante en recién nacidos prematuros / Health professionals perception about the use of human colostrum, as preventive measure for necrotizing enterocolitis in preterm newborns

INTRODUCCIÓN: La incidencia de enterocolitis necrotizante (ECN), en Chile es de 0,3 a 2,4 por mil recién nacidos vi vos, siendo principalmente afectados los neonatos prematuros, y de 8 a 12 por ciento en prematuros menores a 1.500 gramos. OBJETIVO: Describir la percepción de profesionales de salud sobre el uso de calostro en recién nacidos prematuros, como factor protector de enterocolitis necrotizante. SUJETOS Y MÉTODO: Estudio cualitativo, mediante entrevista semiestructurada a 18 profesionales de la salud en tres hospitales públicos de la región de Valparaíso. La pauta de entrevista incluyó 3 temas: Conocimientos, percepción del suministro temprano de calostro y opinión acerca de la extensión de la medida, y 6 subtemas, 2 para cada tema respectivamente: Autopercepción del nivel de conocimiento y fuentes de información; Experiencia: aspectos positivos/eventos adversos y opinión del calostro como factor protector de enterocolitis; aspectos facilitadores u obstaculizadores y opinión acerca de la medida como política nacional. Procesamiento de datos mediante análisis de contenido cualitativo, temático. RESULTADOS: El uso de calostro en prematuros se da de modo protocolizado en dos de las tres unidades de alta complejidad neonatal de la región de Valparaíso. Los participantes opinan positivamente acerca de los resultados preventivos de esta medida. Aun cuando en un tercer estable cimiento no se aplique, hay una percepción favorable acerca de su potencial beneficio y su bajo costo de implementación. Se señala, no obstante, que ésta requiere de mayor evidencia y de un protocolo de aplicación. Otras limitantes serían la insuficiente dotación y formación del personal, y la necesidad de adquirir equipamiento e insumos. CONCLUSIONES: Profesionales que han aplicado un protocolo de administración de calostro en neonatos prematuros en la Región de Valparaíso, reportan buenos resultados de salud, y promueven la motivación del equipo hacia esta praxis. Sin embargo, se considera relevante la difusión y discusión de protocolos nacionales e internacionales, así como el desarrollo de investigación local. Dadas las experiencias en curso en Chile, y el debate internacional, se considera oportuno que el tema sea abordado y discutido en la comunidad sanitaria nacional.

INTRODUCTION: In Chile, necrotizing enterocolitis (NEC) mainly affects preterm infants, with an incidence of 0.3 to 2.4 per 1,000 live births, and 8 to 12% in preterm infants weighing less than 1,500 grams. OBJECTIVE: To describe health professionals perceptions on the use of human colostrum as a preventive measu re against necrotizing enterocolitis in preterm newborns. SUBJECTS AND METHOD: Qualitative study, using 18 semi-structured individual interviews of health professionals in three public hospitals of the Valparaíso Region. The interview included 3 topics: Knowledge, Perception of early colostrum supply and Opinion about the extent of the measure, and 6 subtopics, 2 for each topic respectively: Self-perception of knowledge level and Sources of information; Experience: positive aspects/adverse events and Opinion of colostrum as a protective factor for enterocolitis; Facilitating or hindering aspects and Opinion about the measure as national policy. Data were processed through qualitative content analysis. RESULTS: Two of the three high-complexity neonatal units of the Valparaíso Re gion have a protocol for administrating colostrum in premature infants. Participants have a positive opinion about the preventive results of this measure. Even in the third hospital where there is no protocol, they have a favorable perception of its potential benefit and its low cost of implementa tion. However, we observed that this procedure requires more evidence and an application protocol. Other limitations would be the lack of staffing and training and the need for equipment and supplies. CONCLUSIONS: Professionals who have applied a colostrum administration protocol in preterm infants in the Valparaíso Region report good health outcomes and promote team motivation towards this practice. However, it is relevant to the dissemination and discussion of national and international protocols, as well as the development of local research. Given the ongoing experiences in Chile and the international debate, we considered appropriate to address and discuss the topic within the na tional health community.

[Health professional's perception about the use of human colostrum, as preventive measure for necrotizing enterocolitis in preterm newborns]. / Percepción del equipo de salud sobre los beneficios del calostro como factor protector de enterocolitis necrotizante en recién nacidos prematuros.

INTRODUCTION: In Chile, necrotizing enterocolitis (NEC) mainly affects preterm infants, with an incidence of 0.3 to 2.4 per 1,000 live births, and 8 to 12% in preterm infants weighing less than 1,500 grams. OBJECTIVE: To describe health professionals perceptions on the use of human colostrum as a preventive measu re against necrotizing enterocolitis in preterm newborns. SUBJECTS AND METHOD: Qualitative study, using 18 semi-structured individual interviews of health professionals in three public hospitals of the Valparaíso Region. The interview included 3 topics: Knowledge, Perception of early colostrum supply and Opinion about the extent of the measure, and 6 subtopics, 2 for each topic respectively: Self-perception of knowledge level and Sources of information; Experience: positive aspects/adverse events and Opinion of colostrum as a protective factor for enterocolitis; Facilitating or hindering aspects and Opinion about the measure as national policy. Data were processed through qualitative content analysis. RESULTS: Two of the three high-complexity neonatal units of the Valparaíso Re gion have a protocol for administrating colostrum in premature infants. Participants have a positive opinion about the preventive results of this measure. Even in the third hospital where there is no protocol, they have a favorable perception of its potential benefit and its low cost of implementa tion. However, we observed that this procedure requires more evidence and an application protocol. Other limitations would be the lack of staffing and training and the need for equipment and supplies. CONCLUSIONS: Professionals who have applied a colostrum administration protocol in preterm infants in the Valparaíso Region report good health outcomes and promote team motivation towards this practice. However, it is relevant to the dissemination and discussion of national and international protocols, as well as the development of local research. Given the ongoing experiences in Chile and the international debate, we considered appropriate to address and discuss the topic within the na tional health community.

Validation of Plasmodium falciparum dUTPase as the target of 5'-tritylated deoxyuridine analogues with anti-malarial activity.

BACKGROUND: Malaria remains as a major global problem, being one of the infectious diseases that engender highest mortality across the world. Due to the appearance of resistance and the lack of an effective vaccine, the search of novel anti-malarials is required. Deoxyuridine 5'-triphosphate nucleotido-hydrolase (dUTPase) is responsible for the hydrolysis of dUTP to dUMP within the parasite and has been proposed as an essential step in pyrimidine metabolism by providing dUMP for thymidylate biosynthesis. In this work, efforts to validate dUTPase as a drug target in Plasmodium falciparum are reported. METHODS: To investigate the role of PfdUTPase in cell survival different strategies to generate knockout mutants were used. For validation of PfdUTPase as the intracellular target of four inhibitors of the enzyme, mutants overexpressing PfdUTPase and HsdUTPase were created and the IC50 for each cell line with each compound was determined. The effect of these compounds on dUTP and dTTP levels from P. falciparum was measured using a DNA polymerase assay. Detailed localization studies by indirect immunofluorescence microscopy and live cell imaging were also performed using a cell line overexpressing a Pfdut-GFP fusion protein. RESULTS: Different attempts of disruption of the dut gene of P. falciparum were unsuccessful while a 3' replacement construct could recombine correctly in the locus suggesting that the enzyme is essential. The four 5'-tritylated deoxyuridine analogues described are potent inhibitors of the P. falciparum dUTPase and exhibit antiplasmodial activity. Overexpression of the Plasmodium and human enzymes conferred resistance against selective compounds, providing chemical validation of the target and confirming that indeed dUTPase inhibition is involved in anti-malarial activity. In addition, incubation with these inhibitors was associated with a depletion of the dTTP pool corroborating the central role of dUTPase in dTTP synthesis. PfdUTPase is mainly localized in the cytosol. CONCLUSION: These results strongly confirm the pivotal and essential role of dUTPase in pyrimidine biosynthesis of P. falciparum intraerythrocytic stages.

Maternal copper status and neuropsychological development in infants and preschool children.

INTRODUCTION: Copper (Cu) is an essential element involved in biological processes; however, excessive Cu could be harmful because of its reactive nature. Very few studies have evaluated its potential neurotoxic effects. We aimed to evaluate the association between maternal Cu levels and children's neuropsychological development. METHODS: Study subjects were mother-child pairs from the Spanish INMA (i.e. Childhood and Environment) Project. Cu was measured by inductively coupled plasma mass spectrometry in serum samples taken at the first trimester of pregnancy (2003-2005). Neuropsychological development was assessed using the Bayley Scales of Infant Development (BSID) at 12 months (n = 651) and the McCarthy Scales of Children's Abilities (MSCA) at 5 years of age (n = 490). Covariates were obtained by questionnaires during pregnancy and childhood. Multivariate linear and non-linear models were built in order to study the association between maternal Cu and child neuropsychological development. RESULTS: The mean ±â€¯standard deviation of maternal Cu concentrations was 1606 ±â€¯272 µg/L. In the multivariate analysis, a negative linear association was found between maternal Cu concentrations and both the BSID mental scale (beta = -0.051; 95% confidence intervals [CI]: -0.102, -0.001) and the MSCA verbal scale (beta = -0.044; 95%CI:-0.094, 0.006). Boys obtained poorer scores than girls, with increasing Cu at 12 months (interaction p-value = 0.040 for the mental scale and 0.074 for the psychomotor scale). This effect modification disappeared at 5 years of age. The association between Cu and the MSCA scores (verbal, perceptive performance, global memory and motor, general cognitive, and executive function scales) was negative for those children with lowest maternal iron concentrations (<938µg/L). CONCLUSION: The Cu concentrations observed in our study were within the reference range established for healthy pregnant women in previous studies. The results of this study contribute to the body of scientific knowledge with important information on the possible neurotoxic capability of Cu during pregnancy.

Discovery of New Compounds Active against Plasmodium falciparum by High Throughput Screening of Microbial Natural Products.

Due to the low structural diversity within the set of antimalarial drugs currently available in the clinic and the increasing number of cases of resistance, there is an urgent need to find new compounds with novel modes of action to treat the disease. Microbial natural products are characterized by their large diversity provided in terms of the chemical complexity of the compounds and the novelty of structures. Microbial natural products extracts have been underexplored in the search for new antiparasitic drugs and even more so in the discovery of new antimalarials. Our objective was to find new druggable natural products with antimalarial properties from the MEDINA natural products collection, one of the largest natural product libraries harboring more than 130,000 microbial extracts. In this work, we describe the optimization process and the results of a phenotypic high throughput screen (HTS) based on measurements of Plasmodium lactate dehydrogenase. A subset of more than 20,000 extracts from the MEDINA microbial products collection has been explored, leading to the discovery of 3 new compounds with antimalarial activity. In addition, we report on the novel antiplasmodial activity of 4 previously described natural products.

Hepatocellular carcinoma in identical twins in Chile: case report.

Liver cancer is the second leading cause of cancer death worldwide, with hepatocellular carcinoma (HCC) being the most common type of primary malignant liver tumour, with a typically poor prognosis, growing incidence and a well-documented relationship with chronic inflammation factors of the liver tissue. Despite the fact that family medical history has been identified as a risk factor for the development of HCC, its significance in terms of etiopathogenesis and prognosis is not well documented. With a view to contributing to this discussion, we will report the clinical case of two identical twins with HCC, both diagnosed within a short period of time, by providing relevant clinical data, and relating this to other medical literature reports that could contribute to a deeper understanding of this illness.

MDN-0104, an antiplasmodial betaine lipid from Heterospora chenopodii.

Bioassay-guided fractionation of the crude fermentation extract of Heterospora chenopodii led to the isolation of a novel monoacylglyceryltrimethylhomoserine (1). The structure of this new betaine lipid was elucidated by detailed spectroscopic analysis using one- and two-dimensional NMR experiments and high-resolution mass spectrometry. Compound 1 displayed moderate in vitro antimalarial activity against Plasmodium falciparum, with an IC50 value of 7 µM. This betaine lipid is the first monoacylglyceryltrimethylhomoserine ever reported in the Fungi, and its acyl moiety also represents a novel natural 3-keto fatty acid. The new compound was isolated during a drug discovery program aimed at the identification of new antimalarial leads from a natural product library of microbial extracts. Interestingly, the related fungus Heterospora dimorphospora was also found to produce compound 1, suggesting that species of this genus may be a promising source of monoacylglyceryltrimethylhomoserines.