Multimodal profiling of term human decidua demonstrates immune adaptations with pregravid obesity.

Leukocyte diversity of the first-trimester maternal-fetal interface has been extensively described; however, the immunological landscape of the term decidua remains poorly understood. We therefore profiled human leukocytes from term decidua collected via scheduled cesarean delivery. Relative to the first trimester, our analyses show a shift from NK cells and macrophages to T cells and enhanced immune activation. Although circulating and decidual T cells are phenotypically distinct, they demonstrate significant clonotype sharing. We also report significant diversity within decidual macrophages, the frequency of which positively correlates with pregravid maternal body mass index. Interestingly, the ability of decidual macrophages to respond to bacterial ligands is reduced with pregravid obesity, suggestive of skewing toward immunoregulation as a possible mechanism to safeguard the fetus against excessive maternal inflammation. These findings are a resource for future studies investigating pathological conditions that compromise fetal health and reproductive success.

Biochemical characterization of the cAMP-dependent protein kinase regulatory subunit-like protein from Trypanosoma equiperdum, detection of its inhibitory activity, and identification of potential interacting proteins.

An enriched fraction of an inhibitor of both the catalytic subunit of the cAMP-dependent protein kinase (PKA) from pig heart and a Trypanosoma equiperdum PKA catalytic subunit-like protein (TeqC-like) was obtained from the soluble fraction of T. equiperdum parasites after three consecutive purification steps: sedimentation through a linear 5-20% sucrose gradient, diethylaminoethyl-Sepharose anion-exchange chromatography, and Bio-Sil Sec-400-S size-exclusion high-performance liquid chromatography. The inhibitor was identified as the T. equiperdum PKA regulatory subunit-like protein (TeqR-like) on the basis of Western blot and mass spectrometry analyses, and behaved as an uncompetitive or anti-competitive inhibitor of the parasite TeqC-like protein, with respect to a fluorescently labeled substrate (kemptide, sequence: LRRASLG), showing a Ki of 1.17 µM. The isolated protein possesses a molecular mass of 57.54 kDa, a Stokes radius of 3.64 nm, and a slightly asymmetric shape with a frictional ratio f/fo = 1.43. As revealed during the purification steps and by immunoprecipitation experiments, the TeqR-like and TeqC-like proteins were not associated forming a heterooligomeric complex, differing from traditional PKA subunits. Co-immunoprecipitation results followed by mass spectrometry sequencing identified two isoforms of the parasite heat-shock protein 70, α-tubulin, and ß-tubulin as candidates that interact with the TeqR-like protein in T. equiperdum.

Assessment of blood-brain barrier integrity and neuroinflammation in preeclampsia.

BACKGROUND: Although blood-brain barrier integrity is intact under normal pregnancy conditions, animal studies suggest that blood-brain barrier impairment occurs in preeclampsia. Yet, human data are limited, and the integrity of the blood-brain barrier has not been assessed in women with preeclampsia. OBJECTIVE: We sought to test the hypothesis that the integrity of the blood-brain barrier is impaired and that neuroinflammation is increased in women with preeclampsia. STUDY DESIGN: We performed an observational case-control study in pregnant women >24 weeks gestation who underwent spinal anesthesia for elective cesarean delivery or combined spinal epidural analgesia for labor. Cases were women with preeclampsia, and control subjects were women with either healthy pregnancy, chronic hypertension, or gestational hypertension. Paired samples of blood, urine, and cerebrospinal fluid were collected from each subject before delivery. We measured albumin, C5a, C5b-9, tumor necrosis factor-α, and interleukin-6 concentrations in plasma and cerebrospinal fluid, and albumin, C5a, and C5b-9 concentrations in urine, using colorimetric or enzyme-linked immunosorbent assays. The ratio of albumin in cerebrospinal fluid to plasma (Qalb) was used as a surrogate for maternal blood-brain barrier integrity. Cerebrospinal fluid concentrations of C5a, C5b-9, tumor necrosis factor-α, and interleukin-6 were used as surrogate markers of neuroinflammation. Differences in Qalb and cerebrospinal fluid protein concentrations between groups were assessed by nonparametric test of medians. RESULTS: Forty-eight subjects were enrolled, which included 16 cases with preeclampsia, 16 control subjects with healthy pregnancy, and 16 control subjects with either chronic or gestational hypertension. Qalb values were not increased in preeclampsia cases compared with healthy or hypertensive control subjects (Qalb median, 3.5 [interquartile range, 2.9-5.1] vs 3.9 [interquartile range, 3.0-4.8] vs 3.9 [interquartile range, 3.0-4.8]; P=.78]. Moreover, Qalb values were not increased in the subset of women with preeclampsia with severe features (n=8) compared with those without severe features (n=8; Qalb median, 3.5 [interquartile range, 3.3-4.9] vs 3.7 [interquartile range, 2.3-5.5]; P=.62]. Cerebrospinal fluid concentrations of C5a, C5b-9, tumor necrosis factor-α and interleukin-6 were not increased in cases of preeclampsia, compared with control subjects with either healthy pregnancy, chronic hypertension, or gestational hypertension (P>.05, all comparisons). In contrast to the negative findings in cerebrospinal fluid, plasma concentrations of both C5b-9 and interleukin-6 and urine concentrations of C5a and C5b-9 were increased in cases of preeclampsia. CONCLUSION: Through measurements of albumin, complement proteins, and cytokines in paired samples of blood and cerebrospinal fluid at the time of delivery, we found no evidence of blood-brain barrier impairment or neuroinflammation in preeclampsia. Larger studies that will investigate a wider range of proteins are suggested to validate our findings.

Maternal prenatal depression predicts infant negative affect via maternal inflammatory cytokine levels.

Maternal depressive symptoms during pregnancy are associated with risk for offspring emotional and behavioral problems, but the mechanisms by which this association occurs are not known. Infant elevated negative affect (increased crying, irritability, fearfulness, etc.) is a key risk factor for future psychopathology, so understanding its determinants has prevention and early intervention potential. An understudied yet promising hypothesis is that maternal mood affects infant mood via maternal prenatal inflammatory mechanisms, but this has not been prospectively examined in humans. Using data from a pilot study of women followed from the second trimester of pregnancy through six months postpartum (N = 68) our goal was to initiate a prospective study as to whether maternal inflammatory cytokines mediate the association between maternal depressive symptoms and infant offspring negative affect. The study sample was designed to examine a broad range of likely self-regulation and mood-regulation problems in offspring; to that end we over-selected women with a family history or their own history of elevated symptoms of attention-deficit/hyperactivity disorder. Results supported the hypothesis: maternal pro-inflammatory cytokines during the third trimester (indexed using a latent variable that included plasma interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1 concentrations as indicators) mediated the effect, such that higher maternal depressive symptoms were associated with higher maternal inflammation, and this mediated the effect on maternal report of infant negative affect (controlling for maternal affect during the infant period). This is the first human study to demonstrate that maternal inflammatory cytokines mediate the association between prenatal depression and infant outcomes, and the first to demonstrate a biological mechanism through which depressive symptoms impact infant temperament.

Use and attitudes of obstetricians toward 3 high-risk interventions in MFMU Network hospitals.

OBJECTIVE: We sought to evaluate the frequency of, and factors associated with, the use of 3 evidence-based interventions: antenatal corticosteroids for fetal lung maturity, progesterone for prevention of recurrent preterm birth, and magnesium sulfate for fetal neuroprotection. STUDY DESIGN: A self-administered survey was conducted from January through May 2011 among obstetricians from 21 hospitals that included 30 questions regarding their knowledge, attitudes, and practice of the 3 evidence-based interventions and the 14-item short version of the Team Climate for Innovation survey. Frequency of use of each intervention was ascertained from an obstetrical cohort of women between January 2010 and February 2011. RESULTS: A total of 329 obstetricians (74% response rate) who managed 16,946 deliveries within the obstetrical cohort participated in the survey. More than 90% of obstetricians reported that they incorporated each intervention into routine practice. Actual frequency of administration in women eligible for the treatments was 93% for corticosteroids, 39% for progesterone, and 71% for magnesium sulfate. Provider satisfaction with quality of treatment evidence was 97% for corticosteroids, 82% for progesterone, and 57% for magnesium sulfate. Obstetricians perceived that barriers to treatment were most frequent for progesterone (76%), 30% for magnesium sulfate, and 17% for corticosteroids. Progesterone use was more frequent among patients whose provider reported the quality of the evidence was above average to excellent compared with poor to average (42% vs 25%, respectively; P < .001), and they were satisfied with their knowledge of the intervention (41% vs 28%; P = .02), and was less common among patients whose provider reported barriers to hospital or pharmacy drug delivery (31% vs 42%; P = .01). Corticosteroid administration was more common among patients who delivered at hospitals with 24 hours a day-7 days a week maternal-fetal medicine specialist coverage (93% vs 84%; P = .046), CONCLUSION: Obstetricians in Maternal-Fetal Medicine Units Network hospitals frequently use these evidence-based interventions; however, progesterone use was found to be related to their assessment of evidence quality. Neither progesterone nor the other interventions were associated with overall climate of innovation within a hospital as measured by the Team Climate for Innovation. National Institutes of Health Consensus Conference Statements may also have an impact on use; there is such a statement for antenatal corticosteroids but not for progesterone for preterm prevention or magnesium sulfate for fetal neuroprotection.

Programa de prevención y rehabilitación cardiaca: herramienta útil y necesaria en el tratamiento del ataque cerebrovascular / Prevention and Cardiac Rehabilitation Program: useful and necessary tool in the treatment after stroke

El Observatorio Nacional de Salud del Instituto Nacional de Salud de Colombia, en su Boletín N.◦ 1 de diciembre 9 de 2013, establece que las enfermedades cardiovasculares representan la primera causa de muerte en el país. En el periodo 1998-2011 se registraron 628.630 muertes por enfermedades cardiovasculares, que corresponden al 23,5% del total de las muertes en Colombia. De las defunciones atribuidas al grupo de enfermedad cardiovascular seleccionado, un 56,3% obedece a enfermedad cardiaca isquémica, 30,6% a enfermedad cerebrovascular, 12,4% a enfermedad hipertensiva y 0,5% a enfermedad cardiaca reumática crónica1 . A pesar de estas cifras y del conocido impacto social y económico que generan estas enfermedades, no se presta una atención adecuada a las enfermedades cerebrovasculares, una preocupación que no debe dejarse de lado y que implica una intervención acertada desde diferentes especialidades médicas, así como también una implementación de estrategias que mejoren la carga generada por esta.

Costos ambulatorios y hospitalarios de la falla cardiaca en dos hospitales de Bogotá / Outpatient and inpatient costs of heart failure in two hospitals in Bogotá

Objetivo: realizar una aproximación a la determinación de costos directos de la falla cardiaca (FC) en el país, a través de la evaluación de costos asociados con el cuidado de pacientes atendidos en dos instituciones prestadoras de salud de Bogotá. Métodos: estudio de costos bajo la perspectiva del tercer pagador. La identificación de eventos generadores de costos en atención ambulatoria se realizó mediante revisión de historias clínicas de pacientes atendidos durante 2011 en la consulta externa especializada de una institución. Los costos de interconsultas y paraclínicos se determinaron según los valores del Acuerdo 256 de 2001, con adición de 30%. Los costos de la medicación se determinaron a partir del registro SISMED. La identificación de eventos generadores de costos en hospitalización se realizó mediante revisión de listados y facturas de pacientes atendidos entre 2009 y 2010 en dos instituciones. Los resultados se presentan resumidos por medidas de tendencia central y de dispersión, en pesos colombianos (COP) de 2011. Resultados: el costo mensual promedio del tratamiento ambulatorio de FC fue de 304.318 COP (D.E. 760.876), con una mediana de 45.280 COP (RIC 25.539 - 109.715); los medicamentos representaron la fuente principal de consumo de recursos (55,2%). El costo promedio de la hospitalización por descompensación de FC fue de 6.427.887 COP (D.E. 9.663.176); la estancia hospitalaria representó la mayor proporción del costo (29,1%). Conclusiones: los costos ambulatorios, y especialmente los hospitalarios, asociados con la FC en Colombia son sustanciales. La fuente principal de costos difiere dependiendo de si el manejo es hospitalario (estancia) o ambulatorio (medicamentos). (Acta Med Colomb 2013; 38: 208-212).

Objective: to make an approach to the determination of direct costs of heart failure (HF) in the country through the evaluation of costs associated with the care of patients seen in two health institutions in Bogota. Methods: low cost third-party payer perspective. Identification of cost generating events in ambulatory care was performed by review of medical records of patients seen during 2011 in the specialized outpatient clinic of an institution. Interconsultations and paraclinical costs were determined according to the 256 Agreement of 2001, with addition of 30%. Medication costs were determined from the SISMED register. Identification of events that generate costs in hospitalization was conducted by reviewing lists and bills of patients treated between 2009 and 2010 in two institutions. The results are presented summarized by measures of central tendency and dispersion, in Colombian pesos (COP) of 2011. Results: the average monthly cost for outpatient treatment of HF was 304,318 COP (D.E. 760 876), with a median of 45,280 COP (RIC 25,539-109,715); drugs represented the main source of resource consumption (55.2%). The average cost of hospitalization for decompensated HF was 6,427,887 COP (D.E. 9.663.176); hospital stay accounted for the largest proportion of the cost (29.1%). Conclusions: outpatient costs, and especially the inpatient ones associated with HF in Colombia are substantial. The main source of costs differs depending on whether the management is hospitable (stay) or outpatient (drugs). (Acta Med Colomb 2013; 38: 208-212).

Persistent ovarian masses and pregnancy outcomes.

OBJECTIVE: To determine if persistent ovarian masses in pregnancy are associated with increased adverse outcomes. METHODS: This is a retrospective cohort of 126 pregnant women with a persistent ovarian mass measuring 5 cm or greater who delivered at two university hospitals between 2001 and 2009. Maternal outcomes included gestational age (GA) at diagnosis, delivery and surgery as well as miscarriage, preterm birth (PTB), ovarian torsion and hospital admission for pain. Neonatal outcomes included birth weight, respiratory distress syndrome (RDS), intra-ventricular hemorrhage (IVH), death and sepsis. RESULTS: A total of 1225 ovarian masses were identified (4.9%) in 24,868 patients. A persistent ovarian mass was found in 0.7%. Average GA at diagnosis was 17.8 weeks. Miscarriage rate was 3.3%. Average GA at delivery was 37.9 weeks. Of the patients, 8.5% had ovarian torsion, 10.3% had admission for pain and 9.3% had PTBs. The mean cesarean delivery rate was 46.3%. The average neonatal weight was 3273 g. There was one neonatal death in this cohort. The rate of RDS was 2.8%, IVH 0.9% and neonatal sepsis 1.9%. The most common surgical pathologic diagnosis was dermoids (37.6%). No overt malignancies were seen. CONCLUSION: A persistent ovarian mass in pregnancy does not confer an increased risk of adverse pregnancy outcomes.

Educación, Bioética y toma de decisiones éticas en unidades de cuidado intensivo / Education, bioehhics and ethical decision making in intensive care units

En el mundo médico, las decisiones del personal de Unidad de Cuidado Intensivo (UCI), Influyen tanto de manera positiva como negativa en el entorno de un paciente y su familia. El personal de salud que está vinculado al cuidado del paciente en UCI, debe ser capaz de resolver y tomar decisiones que son trascendentales para el futuro de una persona que se encuentra entre la vida y la muerte. A pesar de esta obligación moral y profesional, no existe un consenso ampliamente conocido para la toma de decisiones, que facilite al personal afrontar la situación de un paciente en estado crítico. Razón por la cual la educación universitaria en bioética es de vital Importancia, para la formación de profesionales competentes, libre pensadores con responsabilidad social, que actúen como defensores y promotores de la vida.

In the medical world, decisions of staff of Intensive Care Unit, both in a positive and negative way, may affect the patient's environment and family. The health team in charge of the patient care in critical condition should be, able to make decisions important for the future of someone who is between life and death. Despite this moral and professional duty, there is no consensus widely known for decision-making, to provide the staff means to deal this situation, a patient in critical condition. For that reason bioethics education performs vital importance for the training of competent professionals, thinkers open to social responsibility, acting as defenders and promoters of life.

A mucin like gene different from the previously reported members of the mucin like gene families is transcribed in Trypanosoma cruzi but not in Trypanosoma rangeli

Trypanosoma cruzi expresses mucin like glycoproteins encoded by a complex multigene family. In this work, we report the transcription in T. cruzi but not in T. rangeli of a mucin type gene automatically annotated by the T. cruzi genome project. The gene showed no nucleotide similarities with the previously reported T. cruzi mucin like genes, although the computational analysis of the deduced protein showed that it has the characteristic features of mucins: a signal peptide sequence, O-glycosylation sites, and glycosylphosphatidylinositol (GPI) anchor sequence. The presence in this gene of N- terminal and C- terminal coding sequences common to other annotated mucin like genes suggests the existence of a new mucin like gene family.

Muerte violenta relacionada con ingesta de alcohol en Santafé de Bogotá durante diciembre de 1992 / Violent death associated with alcohol abuse

En la historia de la humanidad la violencia ha jugado un papel importante en las diferentes etapas del desarrollo del hombre. Entre los factores más importantes que se asocian están el sexo, la edad, la ocupación, los acontecimientos del momento y la ingesta de alcohol entre otros. En este estudio se escogieron por muestreo aleatorio 151 reportes de personas fallecidas en el mes de Diciembre de 1.992 (tomadas del Instituto de Medicina Legal y Ciencias Forenses de Santafé de Bogotá, D.C). Se analizaron diferentes variables que asocian la muerte violenta con la ingesta de alcohol en un porcentaje del 23.8 por ciento que es ligeramente menor al reportado en el estudio realizado en Diciembre de 1.993 que fue del 36.6 por ciento.