Impact of single and combined local air pollution mitigation measures in an urban environment.

Urban air pollution is one of the most important environmental problems for human health and several strategies have been developed for its mitigation. The objective of this study is to assess the impact of single and combined mitigation measures on concentrations of air pollutants emitted by traffic at pedestrian level in the same urban environment. The effectiveness of different scenarios of green infrastructure (GI), the implementation of photocatalytic materials and traffic low emission zones (LEZ) are investigated, as well as several combinations of LEZ and GI. A wide set of scenarios is simulated through Computational Fluid Dynamics (CFD) modelling for two different wind directions (perpendicular (0°) and 45° wind directions). Wind flow for the BASE scenario without any measure implemented was previously evaluated using wind-tunnel measurements. Air pollutant concentrations for this scenario are compared with the results obtained from the different mitigation scenarios. Reduction of traffic emissions through LEZ is found to be the most effective single measure to improve local air quality. However, GI enhances the effects of LEZ, which makes the combination of LEZ + GI a very effective measure. The effectiveness of this combination depends on the GI layout, the intensity of emission reduction in the LEZ and the traffic diversion in streets surrounding the LEZ. These findings, in line with previous literature, suggest that the implementation of GI may increase air pollutant concentrations at pedestrian level for some cases. However, this study highlights that this negative effect on air quality can turn into positive when used in combination with reductions of local traffic emissions.

Estimates of population exposure to atmospheric pollution and health-related externalities in a real city: The impact of spatial resolution on the accuracy of results.

Health impacts of atmospheric pollution is an important issue in urban environments. Its magnitude depends on population exposure which have been frequently estimated by considering different approaches relating pollutant concentration and population exposed to it. However, the uncertainties due to the spatial resolution of the model used to estimate the pollutant concentration or due to the lack of representativeness of urban air quality monitoring station (AQMS) have not been evaluated in detail. In this context, NO2 annual average concentration at pedestrian level in the whole city of Pamplona (Spain) modelled at high spatial resolution (~1 m) by Computational Fluid Dynamic (CFD) simulations is used to estimate the total population exposure and health-related externalities by using different approaches. Air pollutant concentration and population are aggregated at different spatial resolutions ranging from a horizontal grid cell size of 100 m × 100 m to a coarser resolution where the whole city is covered by only one cell (6 km × 5 km). In addition, concentrations at AQMS locations are also extracted to assess the representativeness of those AQMS. The case with a spatial resolution of 100 m × 100 m for both pollutant-concentration distribution and population data is used as a reference (Base case) and compared with those obtained with the other approaches. This study indicates that the spatial resolution of concentration and population distribution in the city should be 1 km × 1 km or finer to obtain appropriate estimates of total population exposure (underestimations <13%) and health-related externalities (underestimations <37%). For the cases with coarser resolutions, a strong underestimation of total population exposure (>31%) and health-related externalities (>76%) was found. On the other hand, the use of AQMS concentrations can induce important errors due to the limited spatial representativeness, in particular in terms of population exposure.

Comparison of oncological outcomes after open and laparoscopic re-resection of incidental gallbladder cancer.

BACKGROUND: The safety and oncological efficacy of laparoscopic re-resection of incidental gallbladder cancer have not been studied. This study aimed to compare laparoscopic with open re-resection of incidentally discovered gallbladder cancer while minimizing selection bias. METHODS: This was a multicentre retrospective observational cohort study of patients with incidental gallbladder cancer who underwent re-resection with curative intent at four centres between 2000 and 2017. Overall survival (OS) and recurrence-free survival (RFS) were analysed by intention to treat. Inverse probability of surgery treatment weighting using propensity scoring was undertaken. RESULTS: A total of 255 patients underwent re-resection (190 open, 65 laparoscopic). Nineteen laparoscopic procedures were converted to open operation. Surgery before 2011 was the only factor associated with conversion. Duration of hospital stay was shorter after laparoscopic re-resection (median 4 versus 6 days; P < 0·001). Three-year OS rates for laparoscopic and open re-resection were 87 and 62 per cent respectively (P = 0·502). Independent predictors of worse OS were residual cancer found at re-resection (hazard ratio (HR) 1·91, 95 per cent c.i. 1·17 to 3·11), blood loss of at least 500 ml (HR 1·83, 1·23 to 2·74) and at least four positive nodes (HR 3·11, 1·46 to 6·65). In competing-risks analysis, the RFS incidence was higher for laparoscopic re-resection (P = 0·038), but OS did not differ between groups. Independent predictors of worse RFS were one to three positive nodes (HR 2·16, 1·29 to 3·60), at least four positive nodes (HR 4·39, 1·96 to 9·82) and residual cancer (HR 2·42, 1·46 to 4·00). CONCLUSION: Laparoscopic re-resection for selected patients with incidental gallbladder cancer is oncologically non-inferior to an open approach. Dissemination of advanced laparoscopic skills and timely referral of patients with incidental gallbladder cancer to specialized centres may allow more patients to benefit from this operation.

ANTECEDENTES: No se conoce la seguridad y la eficacia oncológica de la re-resección laparoscópica del cáncer incidental de vesícula biliar. Este estudio tiene como objetivo comparar las re-resecciones del cáncer incidental de vesícula biliar por vía laparoscópica y vía abierta, minimizando el sesgo de selección. MÉTODOS: Estudio de cohortes observacional, retrospectivo y multicéntrico de pacientes con cáncer incidental de vesícula biliar que se sometieron a una re-resección con intención curativa en 4 centros entre 2000 y 2017. Se analizó la supervivencia global (overall survival, OS) y la supervivencia libre de recidiva (recurrence free survival, RFS) según intención de tratamiento. Se calculó la probabilidad inversa de la ponderación del tratamiento quirúrgico utilizando puntuación de propensión. RESULTADOS: Se incluyeron 255 pacientes con re-resección (190 por vía abierta y 65 por vía laparoscópica). Se convirtieron 19 pacientes del grupo laparoscópico. El único factor relacionado con la conversión fue la realización de la cirugía antes de año 2011. La mediana de la estancia hospitalaria fue más corta tras la re-resección laparoscópica (4 versus 6 días; P < 0,001). La OS a tres años fue del 87% y del 62% (P = 0,502) para las re-resecciones laparoscópicas y abiertas, respectivamente). Los factores predictivos independientes relacionados con una peor OS fueron el hallazgo de cáncer residual en el momento de la re-resección (cociente de riesgos instantáneos, hazard ratio, HR 1,91; i.c. del 95% 1,17-3,11), una pérdida hemática > 500 ml (HR 1,83; i.c. del 95% 1,23-2,74) y la presencia de ≥ 4 ganglios positivos (HR 3,11; i.c. del 95% 1,46-6,65). En el análisis de riesgo competitivo, la RFS fue mayor para la resección laparoscópica (P = 0,038), pero no hubo diferencias en la OS entre ambos grupos. Los factores predictivos independientes de peor RFS fueron la detección de 1-3 ganglios positivos (HR 2,16; i.c. del 95% 1,29-3,60), ≥ 4 ganglio positivos (HR 4,39; i.c. del 95% 1,96-9,82) y el cáncer residual (HR 2,42; i.c. de 95% 1,46-4,0). CONCLUSIÓN: En pacientes seleccionados, los resultados oncológicos de la re-resección laparoscópica de un cáncer incidental de vesícula biliar no son inferiores a los que se obtienen por vía abierta. Una mayor difusión de las técnicas laparoscópicas avanzadas y una oportuna derivación de los pacientes con cáncer de vesícula biliar incidental a centros especializados podrían permitir que un mayor número de pacientes se beneficiaran de este abordaje.

Nitrogen deposition in Spain: modeled patterns and threatened habitats within the Natura 2000 network.

The Mediterranean Basin presents an extraordinary biological richness but very little information is available on the threat that air pollution, and in particular reactive nitrogen (N), can pose to biodiversity and ecosystem functioning. This study represents the first approach to assess the risk of N enrichment effects on Spanish ecosystems. The suitability of EMEP and CHIMERE air quality model systems as tools to identify those areas where effects of atmospheric N deposition could be occurring was tested. For this analysis, wet deposition of NO3(-) and NH4(+) estimated with EMEP and CHIMERE model systems were compared with measured data for the period 2005-2008 obtained from different monitoring networks in Spain. Wet N deposition was acceptably predicted by both models, showing better results for oxidized than for reduced nitrogen, particularly when using CHIMERE. Both models estimated higher wet deposition values in northern and northeastern Spain, and decreasing along a NE-SW axis. Total (wet+dry) nitrogen deposition in 2008 reached maxima values of 19.4 and 23.0 kg N ha(-1) year(-1) using EMEP and CHIMERE models respectively. Total N deposition was used to estimate the exceedance of N empirical critical loads in the Natura 2000 network. Grassland habitats proved to be the most threatened group, particularly in the northern alpine area, pointing out that biodiversity conservation in these protected areas could be endangered by N deposition. Other valuable mountain ecosystems can be also threatened, indicating the need to extend atmospheric deposition monitoring networks to higher altitudes in Spain.

Liver transplantation results for hepatocellular carcinoma in Chile.

UNLABELLED: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Liver transplantation is the best treatment for HCC; it improves survival, cures cirrhosis, and abolishes local recurrence. We describe the outcomes of patients with HCC who underwent liver transplantation in two liver transplantation centers in Chile. METHODS: This study is a clinical series elaborated from the liver transplantation database of Pontificia Universidad Católica and Clínica Alemana between 1993 and 2009. The survival of patients was calculated using the Kaplan-Meier survival analysis. The significant alpha level was defined as <.05. RESULTS: From 250 liver transplantations performed in this period, 29 were due to HCC. At the end of the study, 25 patients (86%) were alive. The mean recurrence-free survival was 30 months (range 5 months to 8 years). The 5-year survival for patients transplanted for HCC was >80%; however, the 5-year overall survival of patients who exceeded the Milan criteria in the explants was 66%. There was no difference in overall survival between patients transplanted for HCC versus other diagnosis (P = .548). CONCLUSION: This series confirmed that liver transplantation is a good treatment for patients with HCC within the Milan criteria.

Bridge therapy in hepatocellular carcinoma before liver transplantation: the experience of two Chilean centers.

BACKGROUND: Orthotopic liver transplantation (OLT) is currently an established therapy for small, early-stage hepatocellular carcinoma (HCC) within the Milan criteria. Long waiting times due to the shortage of donor organs can result in tumor progression and drop-out from OLT candidacy. Therefore a wide variety of procedures are necessary before OLT. The aim of this retrospective study was to review our experience in relation to bridge therapy prior to OLT for HCC. METHODS: This was a retrospective database review of all of the patient who underwent transplantation in our institutions between January 1993 and June 2009. We analyzed patients with a diagnosis of HCC in the explant. RESULTS: Among 29 patients, including 12 who were diagnosed by the explant and 17 prior to transplantation, 88% underwent bridge therapy during a mean waiting time to OLT of 12 months. Among the 23 procedures, namely 1.5 procedures per patient, included most frequently chemoembolization (48%), alcohol ablation (30%), radiofrequency ablation (13%), and surgery (9%). Thirty-three percent of the explants contained lesions within the Milan criteria. In our series the 5-year survival rate for patients transplanted for HCC was 86%; in the bridge therapy group, it was 73%. CONCLUSIONS: The incidence of patients who underwent bridge therapy (52%) was similar to other reported experiences, but the fulfillment of Milan criteria in the explants was lower. Among the bridge therapy group, the survival was slightly lower, probably because this group displayed more advanced disease.

Glycogen synthase kinase-3 and Axin function in a beta-catenin-independent pathway that regulates neurite outgrowth in neuroblastoma cells.

We have sought to determine the roles of beta-catenin and the Wnt signaling pathway in neurite outgrowth using a model cell system, the Neuro-2a neuroblastoma cell line. Activation of the Wnt signaling pathway disrupts a multiprotein complex that includes beta-catenin, Axin, and glycogen synthase kinase-3 (GSK-3), which would otherwise promote the phosphorylation and degradation of beta-catenin. Stabilized beta-catenin accumulates in the cytosol and in the nucleus; in the nucleus it binds to TCF family transcription factors, forming a bipartite transcriptional activator of Wnt target genes. These events can be mimicked by lithium (Li(+)), which inhibits GSK-3 activity. Both Li(+) and the GSK-3 inhibitor SB415286 induced neurite outgrowth of Neuro-2a cells. Li(+)-induced neurite outgrowth did not require beta-catenin-/TCF-dependent transcription, and increasing levels of beta-catenin either by transfection or using Wnt-3A was not sufficient to induce neurite outgrowth. Interestingly, Axin, which is also a substrate for GSK-3, was destabilized by Li(+) and ectopic expression of Axin inhibited Li(+)-induced neurite outgrowth. Deletion analysis of Axin indicated that this inhibition required the GSK-3 binding site, but not the beta-catenin binding site. Our results suggest that a signaling pathway involving Axin and GSK-3, but not beta-catenin, regulates Li(+)-induced neurite outgrowth in Neuro-2a cells.

[Spontaneous bacterial peritonitis and bacteraemia due to Aeromonas hydrophila]. / Peritonitis bacteriana espontánea y bacteriemia por Aeromonas hydrophila.

Bacterial peritonitis is a frequent complication in cirrhotic patients. Amongst the aetiological germs, Aeromonas is very infrequent. We present the clinical case of a cirrhotic patient with peritonitis and bacteraemia due to Aeromonas hydrophila. This micro-organism is a Gram-negative bacillus of the Vibrionaceae family. It very frequently produces gastroenteritis in the human being. Exceptionally it can give rise to extraintestinal infections, especially in immunodepressed patients. Peritonitis due to Aeromonas has been described in association with spontaneous bacterial peritonitis in cirrhotic patients, in patients on peritoneal dialysis and in cases of peritonitis secondary to intestinal perforation.

New approach to the chemistry of polysulfides using diphosphanylmethanide complexes of manganese(I).

The study of the nucleophilic degradation of S8 by the methanide complex [Mn(CO)4[(PPh2)2CH]] (2) has led to the preparation of a unique class of polysulfide derivatives of formula [(CO)4Mn[(PPh2)2C-Sn-C(PPh2)2]-Mn(CO)4]. The structures of 3 (n = 6), 4 (n = 2), and 7 (n = 1) have been determined by X-ray crystallography, whereas those polysulfides with the sulfur chains S7, S5, S4, and S3 have been detected by spectroscopic methods. The polysulfides with n > 2 lose sulfur spontaneously, a process that can be accelerated by treatment with PPh3 or Na/Hg. Complexes 3, 4, and 7 were protonated at the two methanide carbon atoms to give the cationic dinuclear derivatives [(CO)4Mn[(PPh2)2C(H)-Sn-C(H)-(PPh2)2]Mn(CO)4]2+ (8, n=6; 9, n=2; 10, n = 1). The 1H NMR spectrum of 9 suggests the existence of intramolecular C-H...S interactions, in agreement with the X-ray structural determination of this complex. By treatment of 4 and 7 with one equivalent of HBF4 it is possible to selectively protonate just one methanide carbon atom, which allows the isolation of the mixed cationic derivatives R(CO)4Mn[(PPh2)2C(H)-Sn-C(PPh2)2]Mn(CO)4]+ (11, n = 2; 6, n = 1). Additionally, heterometallic complexes containing a bridging disulfide unit, of general formula [(CO)4Mn[(PPh2)2C(AuPPh3)S-SC-(AuPPh3)(PPh2)2]Mn(CO)4]2+ (12) and [(CO)4Mn[(PPh2)2C(H)S-SC(AuPPh3)-(PPh2)2]Mn(CO)4]+ (13), were prepared by reaction of 4 and 11, respectively, with [AuCl(PPh3)] in the presence of TlPF6.

alpha-catenin inhibits beta-catenin signaling by preventing formation of a beta-catenin*T-cell factor*DNA complex.

alpha-Catenin and beta-catenin link cadherins to the cytoskeleton at adherens junctions. beta-Catenin also associates with members of the T-cell factor (Tcf) family of transcription factors, and mutations in beta-catenin lead to activation of Tcf-dependent transcription and increased cell growth. Although the loss of alpha-catenin expression can also promote cell growth, the role of endogenous alpha-catenin in beta-catenin signaling is unclear. Here we show that loss of alpha-catenin expression in a colon cancer cell line correlates with increased Tcf-dependent transcription. The presence of alpha-catenin in colon cancer cell nuclei suggests that it inhibits transcription directly, and, in agreement with this, ectopic expression of alpha-catenin in the nucleus represses Tcf-dependent transcription. Furthermore, recombinant alpha-catenin disrupts the interaction between the beta-catenin.Tcf complex and DNA. We conclude that alpha-catenin inhibits beta-catenin signaling in the nucleus by interfering with the formation of a beta-catenin. Tcf.DNA complex.

Analysis of beta-catenin aggregation and localization using GFP fusion proteins: nuclear import of alpha-catenin by the beta-catenin/Tcf complex.

beta-Catenin plays essential roles in cell adhesion, by associating with cadherins, and as a signaling molecule, by interacting with the Tcf/LEF-1 family of transcription factors. In order to study the protein-protein interactions of beta-catenin in living cells, we fused it to green fluorescent protein (GFP). GFP-beta-catenin was incorporated into cell junctions but also accumulated in the nucleus, where it formed rod-like structures. The carboxyl-terminal armadillo repeats of GFP-beta-catenin were sufficient for nuclear localization, but formation of rods required the armadillo repeats and sequences in both the amino- and the carboxyl-terminal domains. Rod formation was prevented by coexpression of N-cadherin, APC, and Tcf-4, which bind to the armadillo repeats of beta-catenin, but not by coexpression of alpha-catenin, although alpha-catenin expression did prevent accumulation of beta-catenin in the nucleus. Interestingly, when alpha-catenin, beta-catenin, and Tcf-4 were coexpressed they colocalized in the nucleus, and this correlated with a decrease in beta-catenin/Tcf-dependent transcriptional activity. These results indicate that binding of beta-catenin to Tcf-4 overrides the function of alpha-catenin to sequester beta-catenin in the cytoplasm and suggest that alpha-catenin can regulate beta-catenin signaling in the nucleus.

Ciclosporosis: infección por Cyclospora cayetanensis / Cyclosporosis: Cyclospora cayetanensis infection

Cyclospora cayetanensis es un protozo descrito a inicios de siglo, pero detectado como causante de enfermedad humana sólo desde hace 20 años, por lo cual se le considera una infección emergente. Produce una diarrea prolongada pérdida de peso, dolor abdominal y decaimiento en pacientes previamente sanos y en inmunodeprimidos. Se le ha descrito en todo el mundo en personas de todas las edades. Se diagnostica mediante el examen coproparasitoscópico seriado con tinción especial para organismos ácido-alcohol-resistentes de manera específica por no ser de uso rutinario en los laboratorios. Se trata con la combinación de TMP-SMZ, los inmunodeprimidos requieren de profilaxis posterior

A transition in transcriptional activation by the glucocorticoid and retinoic acid receptors at the tumor stage of dermal fibrosarcoma development.

In transgenic mice harboring the bovine papillomavirus genome, fibrosarcomas arise along an experimentally accessible pathway in which normal dermal fibroblasts progress through two pre-neoplastic stages, mild and aggressive fibromatosis, followed by a final transition to the tumor stage. We found that the glucocorticoid receptor (GR) displays only modest transcriptional regulatory activity in cells derived from the three non-tumor stages, whereas it is highly active in fibrosarcoma cells. Upon inoculation into mice, the aggressive fibromatosis cells progress to tumor cells that have high GR activity; thus, the increased transcriptional regulatory activity of GR correlates with the cellular transition to the tumor stage. The intracellular levels of GR, as well as its hormone-dependent nuclear translocation and specific DNA binding activities, are unaltered throughout the progression. Strikingly, the low GR activity observed in the pre-neoplastic stages cannot be overcome by exogenous GR introduced by co-transfection. Moreover, comparisons of primary embryo fibroblasts and their transformed derivatives revealed a similar pattern--modest GR activity, unresponsive to overexpressed GR protein, in the normal cells was strongly increased in the transformed cells. Likewise, the retinoic acid receptor (RAR) displayed similar differential activity in the fibrosarcoma pathway. Thus, the oncogenic transformation of fibroblasts, and likely other cell types, is accompanied by a striking increase in the activities of transcriptional regulators such as GR and RAR. We suggest that normal primary cells have a heretofore unrecognized capability to limit the magnitude of induction of gene expression.

[Study of intestinal microflora in children with acute and persistent diarrhea]. / Estudio de la microflora intestinal en niños con diarrea aguda y persistente.

The etiology and pathogenesis of persistent diarrhoea is usually multifactorial and sometimes can not be identified. It is necessary to define if an alteration of the enteric microflora is a risk factor that influence the duration of the diarrhoea. 30 infants with acute diarrhoea and 30 with persistent diarrhoea were studied. A sample of duodenal content was taken by a double-lumen tube and processed microbiologically in search for enteric microorganisms, anaerobic and Candida. These results were correlated with the nutritional status, the previous use of Metronidazole and the results of the stool culture. The presence of bacterial overgrowth and the identification of the duodenal microflora is an important factor for the persistence of the diarrhoea. There was a quantitative and qualitative alteration of the duodenal flora in both groups of patients.

Study of pro-opiomelanocortin mRNA expression in human postmortem pituitaries.

Complementary oligonucleotide probes specific for the human pro-opiomelanocortin (POMC) mRNA were used to analyze the expression of POMC gene in 56 human postmortem pituitaries by in situ hybridization histochemistry. POMC transcripts were visualized by autoradiography in anterior lobe of the pituitary where their distribution was in a 'patchy-like' pattern. No hybridization could be observed in the posterior lobe of the pituitary. We examined pituitaries from several controls and from patients dying with schizophrenia, Parkinson's disease. Alzheimer's disease, Wernicke's encephalopathy and depressive illness. Computer-assisted microdensitometric semiquantification of POMC mRNA using a complementary oligonucleotide as hybridization standard, revealed no statistically significant effect of postmortem delay (between 2.5 and 66 h), of gender, age (between 22 and 103) or cause of death in 56 human pituitary glands. A large variation in POMC levels was already observed among all 30 control cases. The levels of POMC mRNA observed in pituitaries from different pathologies did not show a significant variation when compared with control cases.

[Bacterial agents most frequently isolated from hospitalized newborns]. / Agentes bacterianos más frecuentes aislados en neonatos hospitalizados

475 samples taken from newborn infants hospitalized at "William Soler" Pediatric Teaching Hospital between January-June 1987 are studied, with the view to determine both localized and generalized sepsis. The total of positive samples was 41.3%. Enterobacteria were the organisms most frequently isolated. The coagulase-negative staphylococcus was the most frequently found in systemic sepsis (25.9%). It was demonstrated that the antibiotics with most effectiveness against enterobacteria were amikacin (97.5%) and Gentamicin (98.2%).