Ni-Xides (B, S, and P) for Alkaline OER: Shedding Light on Reconstruction Processes and Interplay with Incidental Fe Impurities as Synergistic Activity Drivers.

Ni-Xides (X = B, P, or S) exhibit intriguing properties that have endeared them for electrocatalytic water splitting. However, the role of B, P, and S, among others, in tailoring the catalytic performance of the Ni-Xides remains vaguely understood, especially if they are studied in unpurified KOH (Un-KOH) because of the renowned impact of incidental Fe impurities. Therefore, decoupling the effect induced by Fe impurities from inherent material reconstruction processes necessitates investigation of the materials in purified KOH solutions (P-KOH). Herein, studies of the OER on Ni2B, Ni2P, and Ni3S2 in P-KOH and Un-KOH coupled with in situ Raman spectroscopy, ex situ post-electrocatalysis, and online dissolution studies by ICP-OES are used to unveil the distinctive role of Ni-Xide reconstruction and the role of Fe impurities and their interplay on the electrocatalytic behavior of the three Ni-Xide precatalysts during the OER. There was essentially no difference in the OER activity and the electrochemical Ni2+/Ni3+ redox activation fingerprints of the three precatalysts via cyclic voltammetry in P-KOH, whereas their OER activity was considerably higher in Un-KOH with marked differences in the intrinsic activity and evolution of the Ni2+/Ni3+ fingerprint redox peaks. Thus, in the absence of Fe in the electrolyte (P-KOH), neither the nature of the guest element (B, P, and S) nor the underlying reconstruction processes are decisive activity drivers. This underscores the crucial role played by incidental Fe impurities on the OER activity of Ni-Xide precatalysts, which until now has been overlooked. In situ Raman spectroscopy revealed that the nickel hydroxide derived from Ni2B exhibits higher disorder than in the case of Ni2P and Ni3S2, both exhibiting a similar degree of disorder. The guest elements thus influence the degree of disorder of the formed nickel oxyhydroxides, which through their synergistic interaction with incidental Fe impurities concertedly realize high OER performance.

Limited induction of polyfunctional lung-resident memory T cells against SARS-CoV-2 by mRNA vaccination compared to infection.

Resident memory T cells (TRM) present at the respiratory tract may be essential to enhance early SARS-CoV-2 viral clearance, thus limiting viral infection and disease. While long-term antigen-specific TRM are detectable beyond 11 months in the lung of convalescent COVID-19 patients, it is unknown if mRNA vaccination encoding for the SARS-CoV-2 S-protein can induce this frontline protection. Here we show that the frequency of CD4+ T cells secreting IFNγ in response to S-peptides is variable but overall similar in the lung of mRNA-vaccinated patients compared to convalescent-infected patients. However, in vaccinated patients, lung responses present less frequently a TRM phenotype compared to convalescent infected individuals and polyfunctional CD107a+ IFNγ+ TRM are virtually absent in vaccinated patients. These data indicate that mRNA vaccination induces specific T cell responses to SARS-CoV-2 in the lung parenchyma, although to a limited extend. It remains to be determined whether these vaccine-induced responses contribute to overall COVID-19 control.

Transcriptional analysis of nasal polyps fibroblasts reveals a new source of pro-inflammatory signaling in CRSwNP.

BACKGROUND: Fibroblasts and others mesenchymal cells have recently been identified as critical cells triggering tissue-specific inflammatory responses. Persistent activation of fibroblasts inflammatory program has been suggested as an underlying cause of chronic inflammation in a wide range of tissues and pathologies. Nevertheless, the role of fibroblasts in the emergence of chronic inflammation in the upper airway has not been previously addressed. We aimed to elucidate whether fibroblasts could have a role in the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: We performed whole-transcriptome microarray in fibroblast cultured from CRSwNP samples and confirmed our results by qRT-PCR. We selected patients without other associated diseases in upper airway. To investigate shifts in transcriptional profile we used fibroblasts from nasal polyps and uncinate mucosae from patient with CRSwNP, and fibroblasts from uncinate mucosae from healthy subjects as controls. RESULTS: This study exposes activation of a pro-inflammatory and pro-fibrotic transcriptional program in nasal polyps and CRSwNP fibroblasts when compared to controls. Our Gene-set Enrichment Analysis (GSEA) pointed to common up-regulation of several pro-inflammatory pathways in patients-derived fibroblasts, along with higher mRNA expression levels of cytokines, growth factors and extracellular matrix components. CONCLUSIONS: Our work reveals a potential new source of inflammatory signaling in CRSwNP. Furthermore, our results suggest that deregulated inflammatory signaling in tissue-resident fibroblasts could support a Type-2 inflammatory response. Further investigations will be necessary to demonstrate the functionality of these novel results.

Limited induction of lung-resident memory T cell responses against SARS-CoV-2 by mRNA vaccination

Resident memory T cells (TRM) present at the respiratory tract may be essential to enhance early SARS-CoV-2 viral clearance, thus limiting viral infection and disease. While long-term antigen (Ag)-specific TRM are detectable beyond 11 months in the lung of convalescent COVID-19 patients after mild and severe infection, it is unknown if mRNA vaccination encoding for the SARS-CoV-2 S-protein can induce this frontline protection. We found that the frequency of CD4+ T cells secreting interferon (IFN){gamma} in response to S-peptides was variable but overall similar in the lung of mRNA-vaccinated patients compared to convalescent-infected patients. However, in vaccinated patients, lung responses presented less frequently a TRM phenotype compared to convalescent infected individuals and polyfunctional CD107a+ IFN{gamma}+ TRM were virtually absent. Thus, a robust and broad TRM response established in convalescent-infected individuals may be advantageous in limiting disease if the virus is not blocked by initial mechanisms of protection, such as neutralization. Still, mRNA vaccines might induce responses within the lung parenchyma, potentially contributing to the overall disease control.

Post-COVID Complications after Pressure Ulcer Surgery in Patients with Spinal Cord Injury Associate with Creatine Kinase Upregulation in Adipose Tissue.

The risk of complications following surgical procedures is significantly increased in patients with SARS-CoV-2 infection. However, the mechanisms underlying these correlations are not fully known. Spinal cord injury (SCI) patients who underwent reconstructive surgery for pressure ulcers (PUs) before and during the COVID-19 pandemic were included in this study. The patient's postoperative progression was registered, and the subcutaneous white adipose tissue (s-WAT) surrounding the ulcers was analyzed by proteomic and immunohistochemical assays to identify the molecular/cellular signatures of impaired recovery. Patients with SCI and a COVID-19-positive diagnosis showed worse recovery and severe postoperative complications, requiring reintervention. Several proteins were upregulated in the adipose tissue of these patients. Among them, CKMT2 and CKM stood out, and CKM increased for up to 60 days after the COVID-19 diagnosis. Moreover, CKMT2 and CKM were largely found in MGCs within the s-WAT of COVID patients. Some of these proteins presented post-translational modifications and were targeted by autoantibodies in the serum of COVID patients. Overall, our results indicate that CKMT2, CKM, and the presence of MGCs in the adipose tissue surrounding PUs in post-COVID patients could be predictive biomarkers of postsurgical complications. These results suggest that the inflammatory response in adipose tissue may underlie the defective repair seen after surgery.

[Adverse events and essential actions for patient safety]. / Eventos adversos y acciones esenciales para la seguridad del paciente.

INTRODUCTION: The adverse events (AE) in hospitalized patients occur with increasing frequency due to the increase in complexity of medical care, which implies a greater risk of committing a human error inherent to the care, constituting a serious threat to the safety of the patient. MATERIAL AND METHODS: Cross-sectional study, including patients older than 16years, with hospital stay longer than 24h and discharge from the general surgery service, patients treated in emergency observation units or other hospital services were not considered. AE were identified, classified by cause according to the essential actions for patient safety (EAPS), and compliance with the EAPS was verified. RESULTS: 352 clinical records were reviewed, 61 (17%) were positive on screening. Of the positives, 66% resulted in AE (47 cases). The prevalence of AE was 13%. The AE were: 40% related to procedures; 39% with infections; 17% with medication; 4% with patient identification. The EAPS with the best rating was EAPS5 and the lowest rating was EAPS4. The night shifts with the greatest opportunity area, only with 40% and 44% correct procedures. CONCLUSIONS: The study shows that the two methodologies used, one to identify AE and the other to establish its causes and classification according to the EAPS, demonstrated usefulness and synergy for patient safety, when detecting AE, as well as determining their causes and evaluate compliance with the EAPS.

Baja incidencia y alta mortalidad por COVID-19 en Cirugía General durante la primera ola de la pandemia / Low incidence and high COVID-19 mortality in a General Surgery during the first wave of the pandemia

Resumen Introducción y objetivo: La infección por coronavirus (COVID-19) en pacientes intervenidos es causa de importante mortalidad posoperatoria, aunque su incidencia es variable. El objetivo primario fue evaluar la incidencia de COVID-19 en los pacientes intervenidos en nuestro Servicio de Cirugía General y Digestiva, durante el máximo impacto de la pandemia en España. El objetivo secundario fue evaluar la mortalidad perioperatoria y determinar los factores de riesgo para la infección por COVID-19. Materiales y Método: Estudio observacional retrospectivo de pacientes consecutivos sometidos a Cirugía General y Digestiva con ingreso superior a 24 h, del 1 de febrero de 2020 al 30 de abril de 2020 en un hospital terciario de Madrid, España. Resultados: Se analizaron 441 pacientes: 423 sin COVID-19 y 18 con COVID-19. Las características preoperatorias y operatorias fueron similares para ambos grupos, salvo por el grado ASA (American Society of Anesthesiologists). La incidencia de COVID-19 en los pacientes intervenidos fue del 4,1%. La mortalidad posoperatoria fue elevada, del 22,2% en pacientes con COVID-19, frente a un 2,8% en pacientes no COVID-19 (p: 0,003). Los factores de riesgo para la infección por COVID-19 en los pacientes intervenidos fueron una estancia hospitalaria prolongada (OR: 1,035 [95% CI: 1,007-1,065]) y la reintervención quirúrgica (OR: 5,025 [95% CI: 1,650-15,311]). Conclusión: Las intervenciones durante la pandemia de COVID-19 causaron una baja tasa de infección con elevada mortalidad posoperatoria. La intervención quirúrgica debe valorarse frente al riesgo adicional para el paciente en contextos de alta transmisión.

The impact of coronavirus disease (COVID-19) in intervened patients seems to cause large postoperative mortality, although its incidence varies among centres. Primary aim was to evaluate the incidence of COVID-19 on the patients intervened in our General and Digestive Surgery Department, during the maximum impact of the pandemia in Spain. Secondary outcomes were evaluating perioperative mortality, and determining the risk factors for COVID-19 infection. Materials and Method: Retrospective single centre study of consecutive patients undergoing general and gastrointestinal surgical procedures with more than 24 hours of inhospital stay, from February 1, 2020 to April 30, 2020 in a tertiary referral centre in Madrid, Spain. Results: A total of 441 patients were analysed: 423 were non-COVID-19 patients while 18 of them had COVID-19. Preoperative and operative characteristics were similar for both groups, unless for the American Society of Anesthesiologists grade. The incidence of COVID-19 in our intervened patients was 4.1%. Postoperative mortality was high among surgical patients with COVID-19, with a mortality rate of 22.2% compared to a 2.8% in non COVID-19 patients. The risk factors for COVID-19 infection were a prolonged postoperative stay (OR: 1.035 [95% CI: 1.007-1.065]) and the need of a reintervention (OR: 5.025 [95% CI: 1.650-15.311]). Conclusion: Surgical interventions during the COVID-19 pandemia resulted in a low infection rate but a high postoperative COVID-19 mortality. The decision to intervene must be carefully balanced against the additional risk for patients in a high transmission setting.

Determinants and Consequences of Food Insecurity in Artisanal Fishing Families From the Coastal Community of Sonora, Mexico.

BACKGROUND: Families living from artisanal fisheries are vulnerable to food insecurity. OBJECTIVE: This research aimed to assess the determinants and consequences of food insecurity in artisanal fishing families from the coastal community of Sonora, Mexico, and to understand how these families face food insecurity. METHODS: This was a cross-sectional study with 116 mothers. A socioeconomic, demographic, and nutritional knowledge survey was applied to assess determinants. A survey about food in the community and food security scale were collected to evaluate food insecurity and two 24-hour dietary recalls and anthropometric measures to assess consequences. Field notes about facing food insecurity were collected. RESULTS: Sixty-eight percent of families have food insecurity. Being above the poverty line, higher father education, knowing how many glasses of water should be drunk per day, and how many minutes of physical activity should be done per day were associated with lower food insecurity. Not having medical service and lower mother education were associated with higher food insecurity. Higher food insecurity was associated with buying in a convenience store; higher food insecurity and higher mother education were associated with lower dietary score; and higher father education was associated with higher dietary score. Being below the extreme poverty line by income and number of children were associated with lower waist circumference; lower father education was associated with higher waist circumference of mothers. CONCLUSIONS: Artisanal fishing families residing in the coastal community of Sonora, Mexico, experience high food insecurity associated with social and economic determinants and their dietary quality.

A review on segmentation of knee articular cartilage: from conventional methods towards deep learning.

In this paper, we review the state-of-the-art approaches for knee articular cartilage segmentation from conventional techniques to deep learning (DL) based techniques. Knee articular cartilage segmentation on magnetic resonance (MR) images is of great importance in early diagnosis of osteoarthritis (OA). Besides, segmentation allows estimating the articular cartilage loss rate which is utilised in clinical practice for assessing the disease progression and morphological changes. It has been traditionally applied in quantifying longitudinal knee OA progression pattern to detect and assess the articular cartilage thickness and volume. Topics covered include various image processing algorithms and major features of different segmentation techniques, feature computations and the performance evaluation metrics. This paper is intended to provide researchers with a broad overview of the currently existing methods in the field, as well as to highlight the shortcomings and potential considerations in the application at clinical practice. The survey showed that state-of-the-art techniques based on DL outperform the other segmentation methods. The analysis of the existing methods reveals that integration of DL-based algorithms with other traditional model-based approaches has achieved the best results (mean Dice similarity coefficient (DSC) between 85.8% and 90%).

Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies.

Spinal cord injury (SCI) results in long-term neurological and systemic consequences, including antibody-mediated autoimmunity, which has been related to impaired functional recovery. Here we show that autoantibodies that increase at the subacute phase of human SCI, 1 month after lesion, are already present in healthy subjects and directed against non-native proteins rarely present in the normal spinal cord. The increase of these autoantibodies is a fast phenomenon-their levels are already elevated before 5 days after lesion-characteristic of secondary immune responses, further supporting their origin as natural antibodies. By proteomics studies we have identified that the increased autoantibodies are directed against 16 different nervous system and systemic self-antigens related to changes known to occur after SCI, including alterations in neural cell cytoskeleton, metabolism and bone remodeling. Overall, in the context of previous studies, our results offer an explanation to why autoimmunity develops after SCI and identify novel targets involved in SCI pathology that warrant further investigation.

Antibacterial Activities of Azole Complexes Combined with Silver Nanoparticles.

Growing antimicrobial resistance is considered a potential threat for human health security by health organizations, such as the WHO, CDC and FDA, pointing to MRSA as an example. New antibacterial drugs and complex derivatives are needed to combat the development of bacterial resistance. Six new copper and cobalt complexes of azole derivatives were synthesized and isolated as air-stable solids and characterized by melting point analyses, elemental analyses, thermogravimetric analyses (TGA), and infrared and ultraviolet/visible spectroscopy. The analyses and spectral data showed that the complexes had 1:1 (M:L) stoichiometries and tetrahedral geometries, the latter being supported by DFT calculations. The antibacterial activities of the metal complexes by themselves and combined with silver nanoparticles (AgNPs; 2 µg mL-1) were assessed in vitro by broth microdilution assays against eight bacterial strains of clinical relevance. The results showed that the complexes alone exhibited moderate antibacterial activities. However, when the metal complexes were combined with AgNPs, their antibacterial activities increased (up to 10-fold in the case of complex 5), while human cell viabilities were maintained. The minimum inhibitory concentration (MIC50) values were in the range of 25-500 µg mL-1. This study thus presents novel approaches for the design of materials for fighting bacterial resistance. The use of azole complexes combined with AgNPs provides a new alternative against bacterial infections, especially when current treatments are associated with the rapid development of antibiotic resistance.

The spectrum of neuropathological changes associated with congenital Zika virus infection.

A major concern associated with ZIKV infection is the increased incidence of microcephaly with frequent calcifications in infants born from infected mothers. To date, postmortem analysis of the central nervous system (CNS) in congenital infection is limited to individual reports or small series. We report a comprehensive neuropathological study in ten newborn babies infected with ZIKV during pregnancy, including the spinal cords and dorsal root ganglia (DRG), and also muscle, pituitaries, eye, systemic organs, and placentas. Using in situ hybridization (ISH) and electron microscopy, we investigated the role of direct viral infection in the pathogenesis of the lesions. Nine women had Zika symptoms between the 4th and 18th and one in the 28th gestational week. Two babies were born at 32, one at 34 and 36 weeks each and six at term. The cephalic perimeter was reduced in four, and normal or enlarged in six patients, although the brain weights were lower than expected. All had arthrogryposis, except the patient infected at 28 weeks gestation. We defined three patterns of CNS lesions, with different patterns of destructive, calcification, hypoplasia, and migration disturbances. Ventriculomegaly was severe in the first pattern due to midbrain damage with aqueduct stenosis/distortion. The second pattern had small brains and mild/moderate (ex-vacuo) ventriculomegaly. The third pattern, a well-formed brain with mild calcification, coincided with late infection. The absence of descending fibres resulted in hypoplastic basis pontis, pyramids, and cortico-spinal tracts. Spinal motor cell loss explained the intrauterine akinesia, arthrogryposis, and neurogenic muscle atrophy. DRG, dorsal nerve roots, and columns were normal. Lympho-histiocytic inflammation was mild. ISH showed meningeal, germinal matrix, and neocortical infection, consistent with neural progenitors death leading to proliferation and migration disorders. A secondary ischemic process may explain the destructive lesions. In conclusion, we characterized the destructive and malformative consequences of ZIKV in the nervous system, as reflected in the topography and severity of lesions, anatomic localization of the virus, and timing of infection during gestation. Our findings indicate a developmental vulnerability of the immature CNS, and shed light on possible mechanisms of brain injury of this newly recognized public health threat.

Synthesis and in vitro safety assessment of magnetic bacterial cellulose with porcine aortic smooth muscle cells.

Bacterial cellulose (BC) has been used as a scaffold for tissue regeneration (TR). Improving functional TR requires highly selective strategies for specific cell attraction. Embedding iron oxide nanoparticles into a BC matrix can drive magnetically labeled cells to specific tissues where they may begin to heal injured tissue. This article focuses on characterization and in vitro toxicity assessment of magnetic BC (MBC). We proposed to detect the production of radical oxygen species (ROS), esterase activity, and apoptosis to study cytotoxic interactions of MBC within its bioenvironment. Morphological characterization was performed using scanning electron microscopy where evidence shows that the diameter of MBC fibers compared to BC fibers was 33% smaller, and the pore areas were 25% bigger. Cytotoxicity assays in porcine aortic smooth muscle cells exposed for 24 hours to BC, MBC, and poly(ethylene glycol)-coated MBC (MBC-PEG) reveals 96% viability and 9% ROS production for MBC-PEG. In contrast, 25% of cells exposed to MBC were apoptotic, suggesting that even when the cells were metabolically active, MBC can induce damage. These outcomes support the need for more integral assessment in the hopes of assessing the potential biosafety and uses of nanocomposites for TR. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2801-2809, 2016.

The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis.

Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis.

The role of reduced intracellular concentrations of active drugs in the lack of response to anticancer chemotherapy.

A major difficulty in the treatment of cancers is the poor response of many tumors to pharmacological regimens. This situation can be accounted for by the existence of a variety of complex mechanisms of chemoresistance (MOCs), leading to reduced intracellular concentrations of active agents, changes in the molecular targets of the drugs, enhanced repair of drug-induced modifications in macromolecules, stimulation of anti-apoptotic mechanisms, and inhibition of pro-apoptotic mechanisms. The present review focuses on alterations in the expression and appearance of the genetic variants that affect the genes involved in reducing the amount of active agents inside tumor cells. These alterations can occur through two mechanisms: either by lowering uptake or enhancing efflux (so-called MOC-1a and MOC-1b, respectively), or by decreasing the activation of prodrugs or enhancing inactivation of active agents through their biotransformation (MOC-2). The development of chemosensitizers that are useful in implementing the pharmacological manipulation of these processes constitutes a challenge to modern pharmacology. Nevertheless, the important physiological roles of the most relevant genes involved in MOC-1a, MOC-1b, and MOC-2 make it difficult to prevent the side effects of chemosensitizers. A more attainable goal in this area of pharmacological enquiry is the identification of proteomic profiles that will permit oncologists to accurately predict a lack of response to a given regimen, which would be useful for adapting treatment to the personal situation of each patient.

Novel artemisinin derivatives with potential usefulness against liver/colon cancer and viral hepatitis.

Antitumor and antiviral properties of the antimalaria drug artemisinin from Artemisia annua have been reported. Novel artemisinin derivatives (AD1-AD8) have been synthesized and evaluated using in vitro models of liver/colon cancer and viral hepatitis B and C. Cell viability assays after treating human cell lines from hepatoblastoma (HepG2), hepatocarcinoma (SK-HEP-1), and colon adenocarcinoma (LS174T) with AD1-AD8 for a short (6h) and long (72h) period revealed that AD5 combined low acute toxicity together with high antiproliferative effect (IC50=1-5µM). Since iron-mediated activation of peroxide bond is involved in artemisinin antimalarial activity, the effect of iron(II)-glycine sulfate (ferrosanol) and iron(III)-containing protoporphyrin IX (hemin) was investigated. Ferrosanol, but not hemin, enhanced antiproliferative activity of AD5 if the cells were preloaded with AD5, but not if both compouds were added together. Five derivatives (AD1>AD2>AD7>AD3>AD8) were able to inhibit the cytopathic effect of bovine viral diarrhoea virus (BVDV), a surrogate in vitro model of hepatitis C virus (HCV), used here to evaluate the anti-Flaviviridae activity. Moreover, AD1 and AD2 inhibited the release of BVDV-RNA to the culture medium. Co-treatment with hemin or ferrosanol resulted in enhanced anti-Flaviviridae activity of AD1. In HepG2 cells permanently infected with hepatitis B virus (HBV), AD1 and AD4, at non-toxic concentrations for the host cells were able to reduce the release of HBV-DNA to the medium. In conclusion, high pharmacological interest deserving further evaluation in animal models has been identified for novel artemisinin-related drugs potentially useful for the treatment of liver cancer and viral hepatitis B and C.

La consulta preconcepcional en el Área de Salud de Toledo / Pre-conception consultation in the Toledo healthcare area

Objetivo. Conocer el porcentaje de mujeres que han realizado consulta preconcepcional (CPC), los motivos de dicha consulta y las intervenciones realizadas. Diseño. Estudio observacional descriptivo, basado en entrevistas personales. Emplazamiento. Atención Primaria. Participantes. 465 mujeres con embarazo a término en los últimos doce meses. Mediciones principales. Realización de CPC, motivos, profesionales consultados, consulta privada o pública y actividades realizadas (exploración física, ginecológica, pruebas de laboratorio, citología, estudio genético, vacunaciones, consejo sanitario, quimioprofilaxis). Resultados. El 69,2% de los embarazos fue planificado. El 23,9% de las entrevistadas realizó CPC (IC95% 20,0-27,7). La CPC fue más frecuente en primíparas, mayores de 30 años, españolas y universitarias (p<0,05). El motivo más habitual de CPC fue la prevención de problemas (40,8%). El 63,1% utilizó el sistema público, el 31,1% la privada y el 5,8% ambos. El profesional más consultado fue el médico de familia (60,2%). Las actividades más frecuentemente realizadas fueron: quimioprofilaxis (94,2%), consejo sanitario (82,5%), analítica (68,9%), citología (66,0%), exploración física (55,3%) y ginecológica (44,7%). Sólo hubo un 9,7% de vacunaciones. Existen diferencias entre las actividades realizadas en el sistema público y la medicina privada. Conclusiones. El porcentaje de embarazos planificados es mayor de lo esperado, al igual que el de mujeres que realizaron CPC, probablemente por una mayor concienciación de la mujer. Los motivos son básicamente preventivos, por encima de la existencia de factores de riesgo o enfermedades crónicas. Hay un uso importante de la medicina privada. No existe una actuación homogénea en las actividades realizadas. Tanto la quimioprofilaxis como las vacunaciones son en general bajas (AU)

Objective: Ascertain the percentage of women who have made a pre-conception consultation, the reasons for the consultation and interventions carried out. Design: Observational descriptive-type study based on personal interviews. Location: Primary healthcare. Participants: 465 women with term pregnancies in the last twelve months. Main Surveyed Data: Having pre-conception consultation (PCC), reasons, professionals consulted, private or public practice, activities carried out (physical or gynaecological examination, laboratory tests, pap smear, genetic study, vaccinations, healthcare advice, chemoprophylaxis) Results: 69.2% of pregnancies were planned. 23.9% of those interviewed made a pre-conception consultation (IC95% 20.0-27.7). PCC was most frequent in first-time mothers over 30 years old, of Spanish nationality and with a university degree (p<0.05). The most common reason for a PCC was the prevention of problems (40.8%). 63.1% used public health services, 31.1% private health and 5.8%, both. The most consulted professional was the family doctor (60.2%). The most frequent activities were: chemoprophylaxis (94.2%), healthcare advice (82.5%), analysis (68.9%), pap smear (66.0%), physical examination (55.3%) and gynaecological examination (44.7%). Vaccinations represented only 9.7%. There are differences between activities carried out in public and private health practices. Conclusions: The percentage of planned pregnancies is higher than expected, as was the number of women having PCC, probably due to a greater awareness. The reasons are basically preventive, above the existence of risk factors or chronic illness. There is considerable use of private medicine. There is no unified procedure in activities carried out. Both chemoprophylaxis and vaccination are low (AU)

ABCC2 is involved in the hepatocyte perinuclear barrier for small organic compounds.

Small organic molecules are believed to freely diffuse across nuclear pores but this may not be so if this route is blocked during protein and nucleic acid transfer. Here we have investigated the existence of transport mechanisms across the nuclear envelope (NE) of hepatocytes. Using nuclei isolated from rat liver cells, evidence for the existence of ATP-dependent transporters of organic compounds was found. In rat hepatocyte NE, with negligible contamination by other membranes, the presence of mature and glycosylated ABCC2, but not other ABC export pumps, was detected. ABCC2 was localized in the same membranes as the conjugating enzyme UGT1A1. Human ABCC2 ORF was tagged with V5 and transfected to human hepatoma cells. ABCC2-V5 protein was detected at perinuclear ER vesicles and at the NE. Both compartments expressing ABCC2-V5 were able to exclude calcein. ABCC2 abundance at the NE of rat hepatocytes was modified by treatments able to increase or reduce the expression of canalicular ABCC2. The sensitivity to mitoxantrone was higher for hepatocytes obtained from TR- rats whose NE lacked ABCC2. Incubation with mitoxantrone after depletion of ATP resulted in a marked accumulation of mitoxantrone in the nucleus of wild-type, but not TR-, hepatocytes. In sum, ABCC2 is present at the NE and perinuclear ER where, in combination with the activity of conjugating enzymes, this pump may be involved in the perinuclear barrier for small organic molecules, playing a role in protecting DNA from genotoxic compounds and in the control of intranuclear concentrations of ligands for nuclear receptors.

Characterization of the role of ABCG2 as a bile acid transporter in liver and placenta.

ABCG2 is involved in epithelial transport/barrier functions. Here, we have investigated its ability to transport bile acids in liver and placenta. Cholylglycylamido fluorescein (CGamF) was exported by WIF-B9/R cells, which do not express the bile salt export pump (BSEP). Sensitivity to typical inhibitors suggested that CGamF export was mainly mediated by ABCG2. In Chinese hamster ovary (CHO cells), coexpression of rat Oatp1a1 and human ABCG2 enhanced the uptake and efflux, respectively, of CGamF, cholic acid (CA), glycoCA (GCA), tauroCA, and taurolithocholic acid-3-sulfate. The ability of ABCG2 to export these bile acids was confirmed by microinjecting them together with inulin in Xenopus laevis oocytes expressing this pump. ABCG2-mediated bile acid transport was inhibited by estradiol 17ß-d-glucuronide and fumitremorgin C. Placental barrier for bile acids accounted for <2-fold increase in fetal cholanemia despite >14-fold increased maternal cholanemia induced by obstructive cholestasis in pregnant rats. In rat placenta, the expression of Abcg2, which was much higher than that of Bsep, was not affected by short-term cholestasis. In pregnant rats, fumitremorgin C did not affect uptake/secretion of GCA by the liver but inhibited its fetal-maternal transfer. Compared with wild-type mice, obstructive cholestasis in pregnant Abcg2(-/-) knockout mice induced similar bile acid accumulation in maternal serum but higher accumulation in placenta, fetal serum, and liver. In conclusion, ABCG2 is able to transport bile acids. The importance of this function depends on the relative expression in the same epithelium of other bile acid exporters. Thus, ABCG2 may play a key role in bile acid transport in placenta, as BSEP does in liver.

[Comparison of real-time polymerase chain reaction and antigenemia assay to detect cytomegalovirus in pediatric transplants]. / Comparación de las técnicas de reacción de polimerasa en cadena en tiempo real y antigenemia para la detección de citomegalovirus en sangre de niños sometidos a trasplantes.

BACKGROUND: Cytomegalovirus (CMV) infections are an important cause of morbidity and mortality in transplant recipient. To date, the antigenemia assay is the most used technique for diagnostic and management of CM V infections. However, quantification of CMV viral load by real time polymerase chain reaction (RT-PCR) has becoming the method of choice to detect CMV in a rapid, sensitive and specific manner. OBJECTIVE: To compare antigenemia and RT-PCR assays in the detection of CMV in blood sample from solid organ and bone marrow transplant (BMT) in children attended at the Dr. Luis Calvo Mackenna Hospital. METHODS: In a prospective study, we detect the presence of CMV in blood sample by RT-PCR and antigenemia assays. RESULTS: We analyzed 219 blood samples from 68 children subjected to kidney, liver and BMT. Out of 219 samples analyzed, 147 were negative and 33 were positive for CMV by both techniques. Thirty-seven samples were positive only by RT-PCR and 2 by antigenemia. Considering the antigenemia as a reference, RT-PCR shows 94%, 80%, 34% and 99% sensitivity, specificity, positive and negative predictive values, respectively. The kappa coefficient between both techniques was 0.528. CONCLUSION: Quantitative determination of CMV viral load by RT-PCR is a sensitive technique with excellent negative predictive valué compared to antigenemia. Our results support the use of RT-PCR as a technique that might facilítate the diagnostic and treatment of active CMV infection in pediatric transplants.