Performance of machine-learning approach for prediction of pre-eclampsia in a middle-income country.

OBJECTIVE: Pre-eclampsia (PE) is a serious complication of pregnancy associated with maternal and fetal morbidity and mortality. As current prediction models have limitations and may not be applicable in resource-limited settings, we aimed to develop a machine-learning (ML) algorithm that offers a potential solution for developing accurate and efficient first-trimester prediction of PE. METHODS: We conducted a prospective cohort study in Mexico City, Mexico to develop a first-trimester prediction model for preterm PE (pPE) using ML. Maternal characteristics and locally derived multiples of the median (MoM) values for mean arterial pressure, uterine artery pulsatility index and serum placental growth factor were used for variable selection. The dataset was split into training, validation and test sets. An elastic-net method was employed for predictor selection, and model performance was evaluated using area under the receiver-operating-characteristics curve (AUC) and detection rates (DR) at 10% false-positive rates (FPR). RESULTS: The final analysis included 3050 pregnant women, of whom 124 (4.07%) developed PE. The ML model showed good performance, with AUCs of 0.897, 0.963 and 0.778 for pPE, early-onset PE (ePE) and any type of PE (all-PE), respectively. The DRs at 10% FPR were 76.5%, 88.2% and 50.1% for pPE, ePE and all-PE, respectively. CONCLUSIONS: Our ML model demonstrated high accuracy in predicting pPE and ePE using first-trimester maternal characteristics and locally derived MoM. The model may provide an efficient and accessible tool for early prediction of PE, facilitating timely intervention and improved maternal and fetal outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Eficiencia de un enfoque de aprendizaje automático para la predicción de la preeclampsia en un país de ingresos medios OBJETIVO: La preeclampsia (PE) es una complicación grave del embarazo asociada a morbilidad y mortalidad materna y del feto. Dado que los modelos de predicción actuales tienen limitaciones y pueden no ser aplicables en situaciones con recursos limitados, se propuso desarrollar un algoritmo de aprendizaje automático (AA) que ofrezca una solución con potencial para desarrollar una predicción precisa y eficiente de la PE en el primer trimestre. MÉTODOS: Se realizó un estudio de cohorte prospectivo en Ciudad de México para desarrollar un modelo de predicción de la PE pretérmino (PEp) en el primer trimestre utilizando AA. Para la selección de variables se utilizaron las características maternas y los múltiplos de la mediana (MdM) obtenidos localmente para la presión arterial media, el índice de pulsatilidad de la arteria uterina y el factor de crecimiento placentario sérico. El conjunto de datos se dividió en subconjuntos de datos de entrenamiento, de validación y de test estadístico. Se empleó un método de red elástica para la selección de predictores, y el rendimiento del modelo se evaluó mediante el área bajo la curva de características operativas del receptor (ABC) y las tasas de detección (TD) con tasas de falsos positivos (TFP) del 10%. RESULTADOS: El análisis final incluyó a 3050 mujeres embarazadas, de las cuales 124 (4,07%) desarrollaron PE. El modelo de AA mostró una buena eficiencia, con un ABC de 0,897, 0,963 y 0,778 para la PEp, la PE de aparición temprana (PEat) y cualquier tipo de PE (todas las PE), respectivamente. Las TD con TFP del 10% fueron del 76,5%, 88,2% y 50,1% para la PEp, PEat y todas las PE, respectivamente. CONCLUSIONES: Nuestro modelo de AA demostró una alta precisión en la predicción de la PEp y la PEat utilizando características maternas del primer trimestre y MdM calculados localmente. El modelo puede proporcionar una herramienta eficiente y accesible para la predicción temprana de la PE, facilitando la intervención oportuna y la mejora de los resultados maternos y del feto.

Comorbidity, poverty and social vulnerability as risk factors for mortality in pregnant women with confirmed SARS-CoV-2 infection: analysis of 13 062 positive pregnancies including 176 maternal deaths in Mexico.

OBJECTIVE: Mortality in pregnancy due to coronavirus disease 2019 (COVID-19) is a current health priority in developing countries. Identification of clinical and sociodemographic risk factors related to mortality in pregnant women with COVID-19 could guide public policy and encourage such women to accept vaccination. We aimed to evaluate the association of comorbidities and socioeconomic determinants with COVID-19-related mortality and severe disease in pregnant women in Mexico. METHODS: This is an ongoing nationwide prospective cohort study that includes all pregnant women with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Mexican National Registry of Coronavirus. The primary outcome was maternal death due to COVID-19. The association of comorbidities and socioeconomic characteristics with maternal death was explored using a log-binomial regression model adjusted for possible confounders. RESULTS: There were 176 (1.35%) maternal deaths due to COVID-19 among 13 062 consecutive SARS-CoV-2-positive pregnant women. Maternal age, as a continuous (adjusted relative risk (aRR), 1.08 (95% CI, 1.05-1.10)) or categorical variable, was associated with maternal death due to COVID-19; women aged 35-39 years (aRR, 3.16 (95% CI, 2.34-4.26)) or 40 years or older (aRR, 4.07 (95% CI, 2.65-6.25)) had a higher risk for mortality, as compared with those aged < 35 years. Other clinical risk factors associated with maternal mortality were pre-existing diabetes (aRR, 2.66 (95% CI, 1.65-4.27)), chronic hypertension (aRR, 1.75 (95% CI, 1.02-3.00)) and obesity (aRR, 2.15 (95% CI, 1.46-3.17)). Very high social vulnerability (aRR, 1.88 (95% CI, 1.26-2.80)) and high social vulnerability (aRR, 1.49 (95% CI, 1.04-2.13)) were associated with an increased risk of maternal mortality, while very low social vulnerability was associated with a reduced risk (aRR, 0.47 (95% CI, 0.30-0.73)). Being poor or extremely poor were also risk factors for maternal mortality (aRR, 1.53 (95% CI, 1.09-2.15) and aRR, 1.83 (95% CI, 1.32-2.53), respectively). CONCLUSION: This study, which comprises the largest prospective consecutive cohort of pregnant women with COVID-19 to date, has confirmed that advanced maternal age, pre-existing diabetes, chronic hypertension, obesity, high social vulnerability and low socioeconomic status are risk factors for COVID-19-related maternal mortality. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Increased levels of soluble fms-like tyrosine kinase-1 are associated with adverse outcome in pregnant women with COVID-19.

OBJECTIVE: In addition to the lungs, the placenta and the endothelium can be affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are markers of endothelial dysfunction and could potentially serve as predictors of severe coronavirus disease 2019 (COVID-19). We aimed to investigate the association of serum concentrations of sFlt-1 and PlGF with the severity of COVID-19 in pregnancy. METHODS: This was a prospective cohort study carried out in a tertiary care hospital in Mexico City, Mexico. Symptomatic pregnant women with a positive reverse-transcription quantitative polymerase chain reaction test for SARS-CoV-2 infection who fulfilled the criteria for hospitalization were included. The primary outcome was severe pneumonia due to COVID-19. Secondary outcomes were intensive care unit (ICU) admission, viral sepsis and maternal death. sFlt-1 levels were expressed as multiples of the median (MoM). The association between sFlt-1 and each adverse outcome was explored by logistic regression analysis, adjusted for gestational age for outcomes occurring in more than five patients, and the predictive performance was assessed by receiver-operating-characteristics-curve analysis. RESULTS: Among 113 pregnant women with COVID-19, higher sFlt-1 MoM was associated with an increased probability of severe pneumonia (adjusted odds ratio (aOR), 1.817 (95% CI, 1.365-2.418)), ICU admission (aOR, 2.195 (95% CI, 1.582-3.047)), viral sepsis (aOR, 2.318 (95% CI, 1.407-3.820)) and maternal death (unadjusted OR, 5.504 (95% CI, 1.079-28.076)). At a 10% false-positive rate, sFlt-1 MoM had detection rates of 45.2%, 66.7%, 83.3% and 100% for severe COVID-19 pneumonia, ICU admission, viral sepsis and maternal death, respectively. PlGF values were similar between women with severe and those with non-severe COVID-19 pneumonia. CONCLUSION: sFlt-1 MoM is higher in pregnant women with severe COVID-19 and has the capability to predict serious adverse pregnancy events, such as severe pneumonia, ICU admission, viral sepsis and maternal death. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Cumplimiento de la dieta mediterránea en el personal sanitario de la provincia de Las Palmas / Adherence to the Mediterranean diet in health personnel from the province of Las Palmas

Antecedentes y objetivos Demostrado efecto protector de la dieta mediterránea, se evaluó su seguimiento y la influencia de distintos factores en el cumplimiento dietético. Material y métodos Se realizó un estudio transversal con encuestas anónimas para obtener datos sobre características demográficas, actividad laboral, antecedentes de factores de riesgo cardiovascular, consumo de alcohol y tabaco, actividad física y consumo de dieta mediterránea. Se evaluó el cumplimiento por medio del cuestionario 14-point Mediterranean Diet Adherence Score (MEDAS) y los factores estadísticamente relacionados con el mismo. Resultados y conclusiones De 922 personas encuestadas (664 mujeres) de edad media 42,61 años (rango: 20 a 69 años), un 61,2% mostró buen cumplimiento. De manera independiente, el consumo de la dieta mediterránea se asoció con la categoría profesional, siendo superior en el personal médico (OR = 1,92; IC 95%: 1,20 a 3,06; p = 0,01) y de enfermería (OR = 1,67; IC 95%: 1,08 a 2,57) comparado con los técnicos auxiliares en cuidados de enfermería. Además, se relacionó con realizar actividad física (OR = 1,78; IC 95%: 1,29 a 2,47; p < 0,001) y cocinar en casa (OR = 1,35; IC 95%: 1,00 a 1,80; p = 0,05). Sin embargo, no se asoció significativamente con la edad, el sexo ni con la presencia de comorbilidades, con las características de la jornada laboral, ni con el consumo de alcohol ni tabaco. Convendría cuantificar el conocimiento sobre la dieta e incrementar los programas educativos, fomentando el ejercicio y el hábito culinario (AU)

Introduction and objectives Given the proven protective effect of the Mediterranean Diet, adherence to it by healthcare personnel and the influence of different factors on dietary compliance were evaluated. Methods A cross-sectional study was conducted on healthcare personnel, obtaining the data through anonymous surveys that collected demographic characteristics, professional activity, history of cardiovascular risk factors, alcohol, and tobacco consumption, physical activity, and adherence to the Mediterranean Diet, using the 14-point Mediterranean Diet Adherence Score (MEDAS). Adherence and related factors were measured. Results and conclusions Of a total of 922 respondents (664 women) mean aged 42.61 years (range 20 to 69), 61.2% showed a good adherence to the Mediterranean Diet. Adherence was significantly associated with the professional categories of physicians (OR = 1.92; 95% CI: 1.20-3.06; p = 0.01) and nurses (OR = 1.67; 95% CI: 1.08-2.57). Furthermore, it was associated with physical exercise (OR = 1.78; 95% CI: 1.29 – 2.47; p < 0.001) and cooking at home (OR = 1.35; 95% CI: 1.00 – 1.80; p = 0.05). However, adherence was not significantly associated with age or sex, comorbidities, working hours, alcohol, or tobacco consumption. Quantifying knowledge of the diet would be useful, as well as increasing educational programs, promoting physical exercise and cooking habits (AU)

Evidence of possible SARS-CoV-2 vertical transmission according to World Health Organization criteria in asymptomatic pregnant women.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vertical transmission has been investigated extensively. Recently, the World Health Organization (WHO) published strict criteria to classify the timing of mother-to-child transmission of SARS-CoV-2 into different categories. The aim of this study was to investigate the possibility of vertical transmission in asymptomatic SARS-CoV-2-positive women. METHODS: Pregnant women attending for delivery at a perinatology center in Mexico City, Mexico, who had a SARS-CoV-2-positive nasopharyngeal swab 24-48 h before delivery, were asymptomatic at the time of the test and had an obstetric indication for Cesarean section were eligible for inclusion in this study. Amniotic fluid was collected during Cesarean delivery, and neonatal oral and rectal swabs were collected at birth and at 24 h after birth. SARS-CoV-2 detection was carried out using real-time reverse-transcription polymerase chain reaction in all samples. Relevant medical information was retrieved from clinical records. The WHO criteria for classifying the timing of mother-to-child transmission of SARS-CoV-2 were applied to the study population. RESULTS: Forty-two SARS-CoV-2-positive asymptomatic pregnant women fulfilled the inclusion criteria. Twenty-five (59%) women developed mild disease after discharge. Neonatal death occurred in three (7%) cases, of which one had a positive SARS-CoV-2 test at birth and none had coronavirus disease 2019-related symptoms. There were five (12%) cases with strong evidence of intrauterine transmission of SARS-CoV-2, according to the WHO criteria, as amniotic fluid samples and neonatal samples at birth and at 24 h after birth were positive for SARS-CoV-2. Our results also showed that 40-60% of infected neonates would have been undetected if only one swab (oral or rectal) was tested. CONCLUSION: This study contributes evidence to reinforce the potential for vertical transmission of SARS-CoV-2 even in asymptomatic women and highlights the importance of testing more than one neonatal sample in order to increase the detection rate of SARS-CoV-2 in affected cases. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A TLR4 agonist improves immune checkpoint blockade treatment by increasing the ratio of effector to regulatory cells within the tumor microenvironment.

Brucella lumazine synthase (BLS) is a homodecameric protein that activates dendritic cells via toll like receptor 4, inducing the secretion of pro-inflammatory cytokines and chemokines. We have previously shown that BLS has a therapeutic effect in B16 melanoma-bearing mice only when administered at early stages of tumor growth. In this work, we study the mechanisms underlying the therapeutic effect of BLS, by analyzing the tumor microenvironment. Administration of BLS at early stages of tumor growth induces high levels of serum IFN-γ, as well as an increment of hematopoietic immune cells within the tumor. Moreover, BLS-treatment increases the ratio of effector to regulatory cells. However, all treated mice eventually succumb to the tumors. Therefore, we combined BLS administration with anti-PD-1 treatment. Combined treatment increases the outcome of both monotherapies. In conclusion, we show that the absence of the therapeutic effect at late stages of tumor growth correlates with low levels of serum IFN-γ and lower infiltration of immune cells in the tumor, both of which are essential to delay tumor growth. Furthermore, the combined treatment of BLS and PD-1 blockade shows that BLS could be exploited as an essential immunomodulator in combination therapy with an immune checkpoint blockade to treat skin cancer.

Adherence to the Mediterranean diet in health personnel from the province of Las Palmas.

INTRODUCTION AND OBJECTIVES: Given the proven protective effect of the Mediterranean Diet, adherence to it by healthcare personnel and the influence of different factors on dietary compliance were evaluated. METHODS: A cross-sectional study was conducted on healthcare personnel, obtaining the data through anonymous surveys that collected demographic characteristics, professional activity, history of cardiovascular risk factors, alcohol, and tobacco consumption, physical activity, and adherence to the Mediterranean Diet, using the 14-point Mediterranean Diet Adherence Score (MEDAS). Adherence and related factors were measured. RESULTS AND CONCLUSIONS: Of a total of 922 respondents (664 women) mean aged 42.61 years (range 20-69), 61.2% showed a good adherence to the Mediterranean Diet. Adherence was significantly associated with the professional categories of physicians (OR = 1.92; 95% CI: 1.20-3.06; p = 0.01) and nurses (OR = 1.67; 95% CI: 1.08-2.57). Furthermore, it was associated with physical exercise (OR = 1.78; 95% CI: 1.29-2.47; p < 0.001) and cooking at home (OR = 1.35; 95% CI: 1.00-1.80; p = 0.05). However, adherence was not significantly associated with age or sex, comorbidities, working hours, alcohol, or tobacco consumption. Quantifying knowledge of the diet would be useful, as well as increasing educational programs, promoting physical exercise and cooking habits.

Neurohormonal activation induces intracellular iron deficiency and mitochondrial dysfunction in cardiac cells.

BACKGROUND: Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, yet its role in the pathophysiology of HF is not well-defined. We sought to determine the consequences of HF neurohormonal activation in iron homeostasis and mitochondrial function in cardiac cells. METHODS: HF was induced in C57BL/6 mice by using isoproterenol osmotic pumps and embryonic rat heart-derived H9c2 cells were subsequently challenged with Angiotensin II and/or Norepinephrine. The expression of several genes and proteins related to intracellular iron metabolism were assessed by Real time-PCR and immunoblotting, respectively. The intracellular iron levels were also determined. Mitochondrial function was analyzed by studying the mitochondrial membrane potential, the accumulation of radical oxygen species (ROS) and the adenosine triphosphate (ATP) production. RESULTS: Hearts from isoproterenol-stimulated mice showed a decreased in both mRNA and protein levels of iron regulatory proteins, transferrin receptor 1, ferroportin 1 and hepcidin compared to control mice. Furthermore, mitoferrin 2 and mitochondrial ferritin were also downregulated in the hearts from HF mice. Similar data regarding these key iron regulatory molecules were found in the H9c2 cells challenged with neurohormonal stimuli. Accordingly, a depletion of intracellular iron levels was found in the stimulated cells compared to non-stimulated cells, as well as in the hearts from the isoproterenol-induced HF mice. Finally, neurohormonal activation impaired mitochondrial function as indicated by the accumulation of ROS, the impaired mitochondrial membrane potential and the decrease in the ATP levels in the cardiac cells. CONCLUSIONS: HF characteristic neurohormonal activation induced changes in the regulation of key molecules involved in iron homeostasis, reduced intracellular iron levels and impaired mitochondrial function. The current results suggest that iron could be involved in the pathophysiology of HF.

MgO surface lattice phonons observation during interstellar ice transition.

Relevant information on the origins of the solar system and the early evolution of life itself can be derive from systematic and controlled exploration of water ice here on Earth. Therefore, over the last decades, a huge effort on experimental methodologies has been made to study the multiple crystal ice phases, which are observed outside our home-gravitational-potential. By employing (100)-oriented MgO lattice surface as a microcantilever sensor, we conducted the first ever study on the dynamics of the Structural Phase Transition at 185 K in water ice by means of coherent elastic scattering of electron diffraction. We estimate the amount of phonons caused by this transition applying precise quantum computing key tools, and resulting in a maximum value of 1.23 ± 0.02. Further applications of our microcantilever sensor were assessed using unambiguous mapping of the surface stress induced by the c([Formula: see text]) → p([Formula: see text]) Structural Phase Transition of the interstellar ice formulated on the Williamsom-Hall model. This development paves the way and thus establishes an efficient characterization tool of the surface mechanical strains of materials with potential applications arising from interstellar ice inclusive glaciers to the wide spectrum of solid-state physics.

Pregnant women with SARS-CoV-2 infection are at higher risk of death and pneumonia: propensity score matched analysis of a nationwide prospective cohort (COV19Mx).

OBJECTIVE: There are limited, unmatched data reporting low complication rates in pregnant women with coronavirus disease 2019 (COVID-19). The aim of this study was to compare COVID-19-related outcomes between pregnant and non-pregnant women after adjusting for potential risk factors for severe outcomes. METHODS: Data were obtained from the COVID-19 National Data Registry of Mexico, which is an ongoing prospective cohort of people of any age with clinically suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and admitted to 475 monitoring hospitals. This study included pregnant and non-pregnant women of reproductive age (15-45 years) with COVID-19 confirmed by reverse transcription polymerase chain reaction. To adjust for underlying risk factors, propensity score matching was conducted for chronic obstructive pulmonary disease, asthma, smoking, hypertension, cardiovascular disease, obesity, diabetes, chronic renal disease, immunosuppression, age, language, nationality and level of health insurance. The primary outcome was death. Secondary outcomes were pneumonia, intubation and intensive care unit (ICU) admission. RESULTS: The cohort comprised 5183 pregnant and 175 905 non-pregnant women with COVID-19. The crude (unmatched) rates of death, pneumonia, intubation and ICU admission in pregnant compared with non-pregnant women were 1.5% vs 1.5%, 9.9% vs 6.5%, 8.1% vs 9.9% and 13.0% vs 6.9%, respectively. After propensity score matching (5183 pregnant and 5183 non-pregnant matched women), pregnant women had a higher odds of death (odds ratio (OR), 1.84; 95% CI, 1.26-2.69), pneumonia (OR, 1.86; 95% CI, 1.60-2.16) and ICU admission (OR, 1.86; 95% CI, 1.41-2.45) than non-pregnant women, but similar odds of intubation (OR, 0.93; 95% CI, 0.70-1.25). CONCLUSION: After adjusting for background demographic and medical factors, pregnancy is a risk factor for death, pneumonia and ICU admission in SARS-CoV-2-infected women of reproductive age. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Acromegalia y cáncer de tiroides

RESUMEN: Introducción La acromegalia se asocia con un mayor riesgo de morbilidad y mortalidad por cáncer. Sin embargo, los datos respecto de la incidencia de cáncer en acromegalia son controvertidos. Objetivos Describir las características clínicas, bioquímicas e imagenológicas de un grupo de pacientes acromegálicos con carcinoma diferenciado de tiroides (CDT). Analizar las características de riesgo de recurrencia (RR) y respuesta en el seguimiento (RtaSg) y comparar la evolución con la de pacientes con CDT no acromegálicos. Materiales y métodos Se realizó un análisis retrospectivo multicéntrico de pacientes con diagnóstico de acromegalia y CDT. Se realizó un análisis comparativo entre los pacientes de bajo RR inicial acromegálicos con una muestra aleatoria de pacientes no acromegálicos con CDT de bajo RR inicial (1:4). Resultados Se analizaron 16 pacientes con diagnóstico de CDT y acromegalia. En 93,8% se hizo el diagnóstico por ecografía, sólo el 50% tenían un nódulo tiroideo palpable. En el momento del diagnóstico del CDT, los valores de IGF-1 fueron 1,8 ± 1,3 LSN, con 62,5% con acromegalia activa. La histología fue papilar en todos los casos, el 56,3% variedad clásica y el resto papilar variedad folicular. El 75% de los pacientes presentó un Estadio I (12/16), sólo 3 pacientes Estadio II y 1 Estadio IVb. El RR inicial fue bajo en el 87,6% (14/16), intermedio en 1 paciente y alto en 1 paciente. Las respuestas al final del seguimiento fueron: 86,7% (13/15) sin evidencia de enfermedad, 1 paciente bioquímica incompleta y 1 estructural incompleta. La RtaSg no tuvo diferencias con los no acromegálicos. Conclusiones Los pacientes acromegálicos con CDT presentaron predominantemente un bajo RR inicial. Al realizar la comparación con el grupo control, se puede concluir que el CDT en pacientes acromegálicos no presentó una evolución más agresiva.

Neoplasias malignas en acromegalia / Malignant neoplasms in acromegaly

RESUMEN La asociación entre acromegalia y cáncer ha sido hipotetizada, aunque no existe evidencia clara que defina los mecanismos causales. Los estudios que evaluaron incidencia de cáncer y mortalidad en población acromegálica, aportan información contradictoria. La mayor controversia de la relación entre acromegalia y cáncer es respecto del cáncer colorrectal. Sin embargo, en la actualidad, el cáncer diferenciado de tiroides es el más frecuente en este grupo. Resulta vital el abordaje integral de la acromegalia con el objetivo de lograr control de la enfermedad y de las comorbilidades, que permitan disminuir el impacto en la calidad de la vida y sostener expectativas de vida e incidencia de neoplasias malignas comparables a la población general.

ABSTRACT The association of acromegaly and cancer has been suggested, but there is a lack of evidence of causal mechanisms. Studies that evaluated cancer incidence and mortality in acromegaly, provided contradictory information. The major controversy is about colorectal cancer but thyroid differentiated carcinoma is currently the most frequent. A comprehensive approach is of utmost importance in order to achieve control of the disease and comorbidities, which can reduce the impact on quality of life and sustain life expectancy and incidence of malignancies comparable to the general population.

Clinical guidelines on the diagnosis and treatment of celiac disease in Mexico. / Guía clínica para diagnóstico y tratamiento de la enfermedad celíaca en México.

Celiac disease, celiac sprue, or gluten-sensitive enteropathy, is a generalized autoimmune disease characterized by chronic inflammation and atrophy of the small bowel mucosa. It is caused by dietary exposure to gluten and affects genetically predisposed individuals. In Mexico, at least 800,000 are estimated to possibly have the disease, prompting the Asociación Mexicana de Gastroenterología to summon a multidisciplinary group of experts to develop the "Clinical guidelines on the diagnosis and treatment of celiac disease in Mexico" and establish recommendations for the medical community, its patients, and the general population. The participating medical professionals were divided into three working groups and were given the selected bibliographic material by the coordinators (ART, LUD, JMRT), who proposed the statements that were discussed and voted upon in three sessions: two voting rounds were carried out electronically and one at a face-to-face meeting. Thirty-nine statements were accepted, and once approved, were developed and revised by the coordinators, and their final version was approved by all the participants. It was emphasized in the document that epidemiology and risk factors associated with celiac disease (first-degree relatives, autoimmune diseases, high-risk populations) in Mexico are similar to those described in other parts of the world. Standards for diagnosing the disease and its appropriate treatment in the Mexican patient were established. The guidelines also highlighted the fact that a strict gluten-free diet is essential only in persons with confirmed celiac disease, and that the role of gluten is still a subject of debate in relation to nonceliac, gluten-sensitive patients.

Oxidative modifications of foetal LDL-c and HDL-c lipoproteins in preeclampsia.

BACKGROUND: Oxidative modifications have been observed in lipids and proteins in lipoproteins isolated from women with preeclampsia. Thus, newborns could also be susceptible to this damage directly through their mothers. In this study, we evaluated the oxidative profile of LDL-c and HDL-c lipoproteins isolated from the umbilical cord from newborns born to women with preeclampsia. METHODS: Thirty newborns born to women with preeclampsia and thirty newborns born to women with healthy pregnancies were included. Lipid-damage biomarkers, including conjugated dienes, lipohydroperoxides and malondialdehyde, were measured. The reduction of nitroblue tetrazolium, formation of dityrosines, and carbonylation of proteins were assessed as indicators of protein damage. The protective activity of paraoxonase-I on HDL-c particles was evaluated. The total antioxidant capacity and lipid profiles were quantified in plasma. Data were analysed using Student's t-tests and Pearson correlation coefficients. RESULTS: Compared with the control group, the preeclampsia group had an increase in the percentage of lipid damage in both lipoproteins. There was an increase of 23.3 and 19.9% for conjugated dienes, 82.4 and 21.1% for lipohydroperoxides, and 103.8 and 51.5% for malondialdehyde in LDL-c and HDL-c, respectively. However, these infants did not show evident damage in protein oxidation. The activity of the enzyme paraoxonase-I was decreased by 36.2%; by contrast, the total antioxidant capacity was increased by 40% (protein) and 28.8% (non-protein). CONCLUSIONS: The oxidative modifications that occur in HDL-c and LDL-c isolated from newborns from women with preeclampsia are mainly caused by lipoperoxidation processes related to evident paraoxonase-I inactivation. The absence of protein damage is likely linked to an increase in total antioxidant capacity. Therefore, antioxidant support could be helpful in reducing oxidative stress in mother/newborn dyads.

Toxic equivalency factors (TEFs) after acute oral exposure of azaspiracid 1, -2 and -3 in mice.

Azaspiracids (AZAs) are marine algal toxins that can be accumulated by edible shellfish to cause a foodborne gastrointestinal poisoning in humans. In the European Union, only AZA1, -2 and -3 are currently regulated and their concentration in shellfish is determined through their toxic equivalency factors (TEFs) derived from the intraperitoneal lethal potency in mice. Nevertheless, considering the potential human exposure by oral route, AZAs TEFs should be calculated by comparative oral toxicity data. Thus, the acute oral toxicity of AZA1, -2 and -3 was investigated in female CD-1 mice treated with different doses (AZA1: 135-1100µg/kg; AZA2 and AZA3: 300-1100µg/kg) and sacrificed after 24h or 14days. TEFs derived from the median lethal doses (LD50) were 1.0, 0.7 and 0.5, respectively for AZA1, -2 and -3. In fact, after 24h from gavage administration, LD50s were 443µg/kg (AZA1; 95% CL: 350-561µg/kg), 626µg/kg (AZA2; 95% CL: 430-911µg/kg) and 875µg/kg (AZA3; 95% CL: 757-1010µg/kg). Mice dead more than 5h after the treatment or those sacrificed after 24h (doses: ≥175µg AZA1/kg, ≥500µg AZA2/kg and ≥600µg AZA3/kg) showed enlarged pale liver, while increased serum markers of liver alteration were recorded even at the lowest doses. Blood chemistry revealed significantly increased serum levels of K+ ions (≥500mg/kg), whereas light microscopy showed tissue changes in the gastrointestinal tract, liver and spleen. No lethality, macroscopic, tissue or haematological changes were recorded two weeks post exposure, indicating reversible toxic effects. LC-MS/MS analysis of the main organs showed a dose-dependency in gastrointestinal absorption of these toxins: at 24h, the highest levels were detected in the stomach and, in descending order, in the intestinal content, liver, small intestine, kidneys, lungs, large intestine, heart as well as detectable traces in the brain. After 14days, AZA1 and AZA2 were still detectable in almost all the organs and intestinal content.

Hemorragia obstétrica manejada con balón de Bakri / Obstetric hemorrhage management with the Bakri SOS balloon

Antecedentes: La Organización Mundial de la Salud reporta que existen en el mundo 536.000 muertes maternas al año, de las cuales 140.000 son originadas por hemorragia obstétrica, representando el 25% del total de dichas muertes. En México, se considera la segunda causa de muerte materna, con una tasa de mortalidad de 14,3 por 100.000 nacidos vivos. Objetivo: Conocer el porcentaje de éxitos de las pacientes con hemorragia obstétrica tratadas con balón de Bakri en el Instituto Nacional de Perinatología. Material y métodos: Se analizó una serie de casos, durante 2 años (2009-2011) en pacientes complicadas con hemorragia obstétrica, las cuales recibieron manejo conservador con balón de Bakri. Se encontró a 19 pacientes y se describieron los antecedentes obstétricos, personales, control prenatal, atención obstétrica, parámetros de laboratorios y desenlace perinatal. Resultados: El porcentaje de éxito con el balón de Bakri fue del 95% y solo el 5% se consideró fallido, ameritando histerectomía obstétrica. La pérdida hemática promedio fue 1.290 cc, con diferencia de 4 g/dl en los controles de hemoglobina pre- y posquirúrgicos. Dos días promedio de estancia en unidad de cuidados intensivos. El peso promedio de los recién nacidos fue 2.580 g y el 63% fue de sexo femenino. No se reportaron complicaciones por el uso del balón de Bakri. Se realizó una fórmula para estimar el llenado de balón en cc = 41 + (11 × semanas de gestación). Conclusión: El uso del balón de Bakri puede ser útil en el manejo conservador ante una hemorragia obstétrica con una tasa considerable de éxito y sin reportes de complicación debida al uso

Background: The World Health Organization reports that 536,000 maternal deaths occur per year, of which 140,000 are caused by obstetric hemorrhage, representing 25% of all maternal deaths. In Mexico, obstetric hemorrhage is the second cause of maternal death, with a mortality rate of 14.3/100,000 newborns. Objective: To describe the success rate in obstetric hemorrhage patients treated with the Bakri SOS balloon in the National Institute of Perinatology. Material and methods: From 2009- 2011, data were collected from obstetric hemorrhage patients (n = 19) who were treated conservatively with the Bakri SOS balloon in the Institute. Data on obstetric and personal history, prenatal care, obstetric care, laboratory values and perinatal outcomes were obtained. Results: The success rate with the Bakri SOS balloon was 95%, with a failure rate of only 5%; these patients required further hysterectomy. The mean blood loss was 1,290 cc, with a difference of 4 g of hemoglobin before and after surgery. The mean length of stay in the intensive care unit was 2 days. The mean birth weight was 2,580 g, and 63% of the neonates were females. There were no incidents or complications with the use of the Bakri SOS balloon. The formula to estimate balloon filling was cc = 41 + (11 × gestational age). Conclusion: The Bakri SOS balloon can be helpful to treat obstetric hemorrhage and has high success rates and no complications

Repeated oral co-exposure to yessotoxin and okadaic acid: a short term toxicity study in mice.

The polyethers yessotoxin (YTX) and okadaic acid (OA) are two marine algal toxins frequently associated as edible shellfish contaminants. Seafood contamination by these compounds, also at low concentrations and for a long period of time, can increase the possibility of their simultaneous and repeated ingestion, with possible synergistic toxic effects. Thus, in vivo toxicity by repeated oral exposure to a combination of fixed doses of YTX and OA (1 mg YTX/kg and 0.185 mg OA/kg, daily for 7 days) was investigated in mice, in comparison to that of each toxin alone. No mortality, signs of toxicity, diarrhea or hematological changes was induced by the toxins co-administration or by the single toxins. Light microscopy revealed changes at gastric level (multifocal subacute inflammation, erosions and epithelial hyperplasia) in 2/5 mice co-administered with the toxins. In animals dosed only with OA, epithelial hyperplasia of forestomach and slight focal subacute inflammation of its submucosa were noted. No changes were induced by the treatment with YTX. Ultrastructural analysis of the heart revealed some cardiomyocytes with "loose packing" of myofibrils and aggregated rounded mitochondria in mice co-administered with the toxins or with YTX; OA-treated mice showed only occasional mitochondrial assemblage and dilated sarcomeres. Thus, the combined oral doses of YTX (1 mg/kg/day) and OA (0.185 mg/kg/day) did not exert cumulative or additive toxic effects in mice, in comparison to the single toxins.

Treatment of vitiligo with a chimeric monoclonal antibody to CD20: a pilot study.

Five patients with active disseminated vitiligo were given 1g of a chimeric (murine/human) monoclonal antibody to CD20 in a single intravenous infusion and followed-up for 6 months. Three of the patients showed an overt clinical and histological improvement of the disease, one presented slight improvement and the remaining patient showed no changes. Improvement was neither associated with changes in laboratory parameters nor to a specific human leucocyte antigen D-related (HLA-DR) phenotype. We believe that these preliminary results are encouraging, and further clinical trials should be undertaken. An important aim should be the finding of a marker with a good response to this therapeutic approach.

Immunophenotypic characterization of lymphoid cell infiltrates in vitiligo.

The pathogenesis of vitiligo is still controversial. The purpose of this study was to gain insight into the nature of lymphoid cells infiltrating depigmented areas of skin in vitiligo. Immunochemical procedures were carried out in biopsies from 20 patients with active lesions to search for cells expressing CD1a, CD2, CD3, CD4, CD5, CD8, CD20, CD25, CD30, CD56, CD68 and CD79a. Results indicate that early lesions are infiltrated mainly by dendritic cells, whereas older lesions display significantly lower proportions of these cells and increased percentages of mature T cells. This finding might suggest that the autoimmune reactivity towards melanocyte antigens might be T cell-dependent and antigen-driven. It is possible that a non-immune offence of melanocytes is responsible for the exposure of intracellular antigens, while autoreactivity might be a secondary, self-perpetuating mechanism.