Hepatitis C virus point-of-care microelimination approach in a vulnerable population in the South of Spain.

Background: Since the introduction of direct-acting antivirals, thousands of chronic hepatitis C patients have been successfully treated. However, vulnerable populations have a higher prevalence of hepatitis C virus (HCV) infection and face barriers that impede their access to antivirals. We carried out an HCV microelimination program focused on vulnerable population groups in Malaga. Methods: People in drug addiction treatment centers and homeless shelters in Malaga who participated in the program between October 2020 and October 2021 were included. After providing participants with educational information on HCV, a dry drop test (DDT) was used to collect blood for subsequent screening for HCV infection. The participants who were diagnosed with HCV infection were scheduled for comprehensive healthcare assessments, including blood tests, ultrasonography, elastography, and the prescription of antivirals, all conducted in a single hospital visit. Sustained viral response (SVR) was analysed 12 weeks after end of treatment. Results: Of the 417 persons invited to participate, 271 (65%) agreed to participate in the program. These participants were screened for HCV infection and 28 of them were diagnosed with HCV infection (10%). These hepatitis C-infected patients had a mean age of 53 ± 9 years; 86% were males and 93% were or had been drug users. Among 23 patients with HCV infection, HCV genotype 1a predominated (74%). Medical exams showed that 19% (4/21) had advanced fibrosis (F3-4), and 5% (1/21) had portal hypertension. Finally, 23 infected patients received treatment with glecaprevir/pibrentasvir or sofosbuvir/velpatasvir and SVR was confirmed in 22 patients (96%). Conclusions: Drug users and homeless people have a higher prevalence of HCV infection than the general population. The microelimination program with educational activity and screening tools achieved a high participation rate, easy healthcare access, and a high rate of SVR despite the SARS-CoV-2 pandemic.

Sellar xanthogranuloma as a diagnostic challenge: a report on five cases.

Xanthogranulomas are considered rare tumors, with their sellar and non-sellar frequency ranging from 1.6 to 7% among intracranial lesions, and described as a separate entity by the World Health Organization in 2000. The diagnosis of sellar xanthogranulomas is challenging, given their uncertain origin and clinical course. In addition, the limited reporting of sellar xanthogranuloma cases and the absence of characteristic images make these entities difficult to distinguish from other cystic lesions of the sellar region, such as adamantinomatous craniopharyngiomas, Rathke's cleft cysts, pituitary tumors, arachnoid cysts, epidermoid cysts, and dermoid cysts. Here, we describe the clinical presentation, radiological findings, immunohistochemical/histopathological analysis, and the ultrastructural examination by transmission electron microscopy of five sellar xanthogranulomas cases reported in two care centers in Cordoba, Argentina. Two males and three females between 37 and 73 years of age (average 51.8 years) presented with persistent headaches, generalized endocrine defects, and visual problems. MRI revealed cystic formations in the sellar region, which usually projected into adjacent tissues such as the suprasellar region or cavernous sinuses, and compressed other structures such as the optic chiasm, pituitary gland, and cranial nerves. All patients underwent surgical intervention to remove the tumor tissue. The histopathological analysis of the samples showed cellular tissue with a xanthogranulomatous appearance, inflammatory cellular infiltrate (mainly lymphocytes and macrophages), fibroblasts, abundant collagen fibers, and hemorrhages. An ultrastructural analysis helped to identify cellular infiltrates and granules resulting from tumor cell activity. The data support the hypothesis that sellar xanthogranulomas could occur as an inflammatory reaction secondary to the rupture and hemorrhage of a previous cystic process, thereby generating an expansion of the tumor body toward adjacent tissues. The information obtained from these cases contributes to the current knowledge about this disease's origin and clinical and histological evolution. However, the scarcity of patients and the observed phenotypic heterogeneity make its diagnosis still challenging. Undoubtedly, more investigations are needed to provide additional information in order to be able to achieve a more accurate diagnosis and effective treatment of this rare disease.

Phase transitions and topological defects in discotic liquid crystal droplets with planar anchoring: a Monte Carlo simulation study.

In this work we present the results of Monte Carlo (MC) simulations at the isothermal-isobaric ensemble for a discotic liquid crystal (DLC) droplet whose surface promotes edge-on (planar) anchoring. For a given pressure, we simulate an annealing process that enables observation of phase transitions within the spherical droplet. In particular, we report a first order isotropic-nematic transition as well as a nematic-columnar transition at the center of the droplet. We found the appearance of topological defects consisting of two disclination lines with ends at the surface of the sphere. We also observed that both transitions, isotropic-nematic and nematic-columnar, occur at lower temperatures as compared to the unconfined system.

Evaluation of diagnostic and prognostic candidate biomarkers in drug-induced liver injury vs. other forms of acute liver damage.

AIMS: Detection and characterization of idiosyncratic drug-induced liver injury (DILI) currently rely on standard liver tests, which are suboptimal in terms of specificity, sensitivity and prognosis. Therefore, DILI diagnosis can be delayed, with important consequences for the patient. In this study, we aimed to evaluate the potential of osteopontin, cytokeratin-18 (caspase-cleaved: ccK18 and total: K18), α-glutathione-S-transferase and microRNA-122 as new DILI biomarkers. METHODS: Serial blood samples were collected from 32 DILI and 34 non-DILI acute liver injury (ALI) cases and a single sample from 43 population controls without liver injury (HLC) and analysed using enzyme-linked immunosorbent assay (ELISA) or single-molecule arrays. RESULTS: All biomarkers differentiated DILI and ALI from HLC with an area under receiver operator characteristic curve (AUC) value of >0.75 but were less efficient in distinguishing DILI from ALI, with ccK18 (0.79) and K18 (0.76) demonstrating highest potential. However, the AUC improved considerably (0.98) for ccK18 when comparing DILI and a subgroup of autoimmune hepatitis cases. Cytokeratin-18, microRNA-122 and α-glutathione-S-transferase correlated well with traditional transaminases, while osteopontin correlated most strongly with the international normalized ratio (INR). CONCLUSIONS: ccK18 appears promising in distinguishing DILI from autoimmune hepatitis but less so from other forms of acute liver injury. Osteopontin demonstrates prognostic potential with higher levels detected in more severe cases regardless of aetiology.

Structural properties and ring defect formation in discotic liquid crystal nanodroplets.

In this work, we performedNpTMonte Carlo simulations of a Gay-Berne discotic liquid crystal confined in a spherical droplet under face-on anchoring and fixed pressure. We find that, in contrast to the unbounded system, a plot of the order parameter as function of temperature does not show a clear evidence of a first-order isotropic-nematic transition. We also find that the impossibility of simultaneously satisfy the uniform director field requirement of a nematic phase with the radial boundary conditions, results in the appearance of a ring disclination line as a stress release mechanism in the interior of the droplet. Under further cooling, a columnar phase appears at the center of the droplet.

Is Tumor Budding a New Predictor for Early Cystectomy in pT1 High-Grade Bladder Cancer?

Background & Objectives: We aimed to evaluate the risk of progression in high-grade T1 (HGT1) tumors using tumor budding (TB) and other standard clinical and histological features. TB is defined as an isolated cancer cell or a cluster composed of fewer than 5 cells scattered in the stroma and is usually used as a strong predictor of lymph node metastasis in T1 colorectal cancer. METHODS: This is an observational longitudinal cohort study involving 168 consecutive patients with HGT1 between 2013 and 2016. Cox regression was performed to analyze the relationship between the clinical and histological features and progression. All slides were blindly assessed by 2 genitourinary pathologists. Budding was determined to be positive when the number of buds was equal to or greater than 6. RESULTS: The median age was 75 years; 152 (90.5%) patients were men, and 49 (29.2%) were positive for TB. At a median follow-up time of 35 months, 33 patients (19.6%) showed progression. Progression was observed in 32.7% of the patients positive for TB and in only 14.3% of those who were negative (p = 0.006). TB was significantly associated with the endoscopic tumor pattern (TP) (papillary/solid) and lymphovascular invasion (LVI). Univariate analysis showed that TB, carcinoma in situ (CIS), TP, LVI, sub-staging, and BCG induction predict progression. The multivariate analysis showed that TB (p = 0.032, hazard ratio 2.1), CIS, TP, and lack of BCG induction were significant for progression. CONCLUSIONS: TB is a new and significant pathological variable for predicting progression in HGT1 tumors and can be easily introduced in clinical practice. Its inclusion in the TNM system should be carefully considered, as it may aid early cystectomy decisions.

Lymphocyte Profile and Immune Checkpoint Expression in Drug-Induced Liver Injury: An Immunophenotyping Study.

The identification of specific HLA risk alleles in drug-induced liver injury (DILI) points toward an important role of the adaptive immune system in DILI development. In this study, we aimed to corroborate the role of an adaptive immune response in DILI through immunophenotyping of leukocyte populations and immune checkpoint expressions. Blood samples were collected from adjudicated DILI (n = 12), acute viral hepatitis (VH; n = 13), acute autoimmune hepatitis (AIH; n = 9), and acute liver injury of unknown etiology (n = 15) at day 1 (recognition), day 7, and day >30. Blood samples from patients with nonalcoholic fatty liver disease (NAFLD; n = 20) and healthy liver controls (HLCs; n = 54) were extracted at one time point. Leukocyte populations and immune checkpoint expressions were determined based on cell surface receptors, except for CTLA-4 that was determined intracellularly, using flow cytometry. At recognition, DILI demonstrated significantly higher levels of activated helper T-cell (P < 0.0001), activated cytotoxic T-cells (P = 0.0003), Th1 (P = 0.0358), intracellular CTLA-4 level in helper T-cells (P = 0.0192), and PD-L1 presenting monocytes (P = 0.0452) than HLC. These levels approached those of HLC over time. No significant differences were found between DILI and VH. However, DILI presented higher level of activated helper T-cells and CTLA-4 than NAFLD and lower PD-L1 level than AIH. Our findings suggest that an adaptive immune response is involved in DILI in which activated CD4+ and CD8+ play an important role. Increased expression of negative immune checkpoints is likely the effect of peripheral tolerance regulation.

Coronavirus (COVID 19) Infection in Pregnancy.

Coronavirus illness 2019 (COVID-19) is an airways infection caused by the new coronavirus (SARS-CoV-2) which has been quickly disseminated all over the world, affecting to the general population including women in pregnancy time. As being a recent infection, the evidence that supports the best practices for the management of the infection during pregnancy is limited, and most of the questions have not been completely solved yet. This publication offers general guidelines focused on decision-making people, managers, and health's teams related to pregnant women attention and newborn babies during COVID-19 pandemic. Its purpose is to promote useful interventions to prevent new infections as well as prompt and adequate attention to avoid serious complications or deaths, trying to be adapted to the different contexts in which attention to expectant mothers is provided. Guidelines are set within a well-scientific evidence and available recommendations up to date.

La enfermedad por coronavirus 2019 (COVID-19) es una infección de las vías respiratorias causada por un nuevo virus (SARS-CoV-2) que se ha diseminado rápidamente en el mundo, afectando a la población general, incluida la población de mujeres cursando un embarazo. Por ser una infección de aparición reciente, la información que soporta las mejores prácticas para el manejo de la infección durante la gestación es escasa y muchas de las preguntas no están completamente resueltas.Esta publicación brinda lineamientos generales orientados a tomadores de decisión, gerentes y equipos de salud en relación con el cuidado de mujeres gestantes y recién nacidos durante la pandemia por COVID 19. Su finalidad es promover intervenciones beneficiosas para prevenir nuevos contagios, y la atención oportuna y adecuada de la gestante para evitar complicaciones graves y/o muertes, adecuándose a los distintos contextos en los que se proporciona atención médica. Los lineamientos se enmarcan en la mejor información científica y las recomendaciones disponibles hasta la fecha.

Termocoagulación por radiofrecuencia de ganglio de Gasser para el tratamiento de neuralgia trigeminal, resultados de 11 años / Gasser's ganglion radiofrequency thermocoagulation for the treatment of trigeminal neuralgia, 11-year results

Objetivos: Describir resultados de los últimos 11 años en el tratamiento de neuralgia del trigémino con termocoagulación por radiofrecuencia, analizar variables relacionadas a complicaciones y resultados. Material y Métodos: Estudio retrospectivo, descriptivo, longitudinal, comparativo y analítico. Se analizaron los resultados de los últimos 11 años de nuestro servicio evaluando las temperaturas de las lesiones armando dos grupos, de 65°C-70°C y 71°C-75°C para analizar su relación con resultados y complicaciones. Resultados: Se trataron 59 pacientes en los cuales se realizaron 74 procedimientos, la edad media fue 59.22 años (±13,45). Se observó recidiva en 23 procedimientos con una tasa global de 31%. El tiempo medio de recidiva fue de 28,19 meses (±26,21). El tiempo medio de seguimiento fue de 33,10 meses (±33,49). El tiempo medio de evolución del dolor, previo al primer procedimiento, fue de 5,35 años (±4,37). Analizando los grupos se observó que no existía relación significativamente estadística (p = 0,74) entre el grupo de pacientes de 65ºC-70ºC y el grupo de 71ºC-75ºC y recidiva. No se observó relación estadísticamente significativa entre el grupo de 65ºC-70ºC y el grupo de 71ºC-75ºC y tiempo de recidiva (p=0,12). Se observó más pacientes con hipoestesia inmediata en el grupo de pacientes de 65ºC-70ºC, sin significación estadística (p=0,47). Conclusión: La termocoagulación por radiofrecuencia de ganglio de Gasser es un procedimiento accesible, mínimamente invasivo que demostró buenos resultados y buen manejo del dolor con bajo índice de complicaciones.

Objectives: Describe results of the last 11 years in the treatment of trigeminal neuralgia with radiofrequency thermocoagulation, analyze variables related to complications and results. Methods: Retrospective, descriptive, longitudinal, comparative and analytical study. The results of the last 11 years of our service were analyzed by assessing the temperatures of the lesions by assembling two groups, 65° C-70° C and 71 ° C-75° C to analyze their relationship with results and complications. Results: 59 patients were treated in which 74 procedures were performed; the mean age was 59.22 years (± 13.45). Recurrence was observed in 23 procedures with an overall rate of 31%. The average recurrence time was 28.19 months (± 26.21). The average follow-up time was 33.10 months (± 33.49). The average time of pain evolution, prior to the first procedure, was 5.35 years (± 4.37). Analyzing the groups, it was observed that there was no significant statistical relationship (p = 0.74) between the group of patients from 65ºC-70ºC and the group from 71ºC-75ºC and recurrence. No statistically significant relationship was observed between the 65ºC-70ºC group and the 71ºC-75ºC group and recurrence time (p = 0.12). More patients with immediate hypoaesthesia were observed in the group of patients from 65ºC-70ºC, without statistical significance (p = 0.47). Conclusion: Gasser's ganglion radiofrequency thermocoagulation is an accessible, minimally invasive procedure that demonstrated good results and good pain management with a low complication rate

Coronavirus (COVID 19) Infection in Pregnancy / Coronavirus (COVID 19) Infección en el embarazo

Abstract Coronavirus illness 2019 (COVID-19) is an airways infection caused by the new coronavirus (SARS-CoV-2) which has been quickly disseminated all over the world, affecting to the general population including women in pregnancy time. As being a recent infection, the evidence that supports the best practices for the management of the infection during pregnancy is limited, and most of the questions have not been completely solved yet. This publication offers general guidelines focused on decision-making people, managers, and health's teams related to pregnant women attention and newborn babies during COVID-19 pandemic. Its purpose is to promote useful interventions to prevent new infections as well as prompt and adequate attention to avoid serious complications or deaths, trying to be adapted to the different contexts in which attention to expectant mothers is provided. Guidelines are set within a well-scientific evidence and available recommendations up to date.

Resumen La enfermedad por coronavirus 2019 (COVID-19) es una infección de las vías respiratorias causada por un nuevo virus (SARS-CoV-2) que se ha diseminado rápidamente en el mundo, afectando a la población general, incluida la población de mujeres cursando un embarazo. Por ser una infección de aparición reciente, la información que soporta las mejores prácticas para el manejo de la infección durante la gestación es escasa y muchas de las preguntas no están completamente resueltas. Esta publicación brinda lineamientos generales orientados a tomadores de decisión, gerentes y equipos de salud en relación con el cuidado de mujeres gestantes y recién nacidos durante la pandemia por COVID 19. Su finalidad es promover intervenciones beneficiosas para prevenir nuevos contagios, y la atención oportuna y adecuada de la gestante para evitar complicaciones graves y/o muertes, adecuándose a los distintos contextos en los que se proporciona atención médica. Los lineamientos se enmarcan en la mejor información científica y las recomendaciones disponibles hasta la fecha.

Drug-eluting wound dressings having sustained release of antimicrobial compounds.

Wound healing is a complex and costly public health problem that should be timely addressed to achieve a rapid and adequate tissue repair avoiding or even eliminating potential pathogenic infection. Chronic infected non-healing wounds represent a serious concern for health care systems. Efficient wound dressings with tailored therapy having the best response and highest safety margin for the management of chronic non-healing wounds are still needed. The use of novel wound dressing materials has emerged as a promising tool to fulfil these requirements. In this work, asymmetric electrospun polycaprolactone (PCL)-based nanofibers (NFs) were decorated with electrosprayed poly(lactic-co-glycolic acid) microparticles (PLGA MPs) containing the natural antibacterial compound thymol (THY) in order to obtain drug eluting antimicrobial dressings having sustained release. The synthesized dressings successfully inhibited the in vitro growth of Staphylococcus aureus ATCC 25923, showing also at the same doses cytocompatibility on human dermal fibroblasts and keratinocyte cultures after treatment for 24 h, which was not observed when using free thymol. An in vivo murine excisional wound splinting model, followed by the experimental infection of the wounds with S. aureus and their treatment with the synthesized dressings, pointed to the reduction of the bacterial load in wounds after 7 days, though the total elimination of the infection was not reached. The findings indicated the relevance of the direct contact between the dressings and the bacteria, highlighting the need to tune their design considering the wound surface and the nature of the antimicrobial cargo contained.

Electrospun anti-inflammatory patch loaded with essential oils for wound healing.

Wound healing is a complex process that consists of three overlapping phases: inflammation, proliferation, and remodeling. A bacterial infection can increase inflammation and delay this process. Microorganisms are closely related to the innate immune system, such as macrophages and neutrophils, as they can start an inflammatory cascade. Essential oils play an important role in the inhibition and prevention of bacterial growth due to their ability to reduce antimicrobial resistance. The possibility to find a strategy that combines antimicrobial and anti-inflammatory properties is particularly appealing for wound healing. In this work, we showcase a variety of patches based on electrospun polycaprolactone (PCL) nanofibers loaded with natural compounds derived from essential oils, such as thymol (THY) and tyrosol (TYR), to achieve reduced inflammation. In addition, we compared the effect these essential oils have on activated macrophages when incorporated into the PCL patch. Specifically, we demonstrate that PCL-THY resulted in more efficient down-regulation of pro-inflammatory genes related to the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κb) pathway when compared to PCL-TYR and the combination patch containing TYR and THY (i.e., PCL-TYR-THY). Furthermore, PCL-THY displayed low affinity for cell attachment, which may hinder wound adherence and integration. Overall, our results indicate that THY-loaded patches could serve as promising candidates for the fabrication of dressings that incorporate bactericidal and anti-inflammatory properties while simultaneously avoiding the limitations of traditional antibiotic-loaded devices.

Trends in cancer incidence in Uruguay: 2002 -2015 / Tendencias de la incidencia de cáncer en Uruguay: 2002-2015

Abstract Background: Uruguay is the south American country which has the highest cancer incidence and mortality rates. The National Cancer Registry collects data on cancer cases nationwide since 1989 and has reached high quality standards in the last decades. This is the first report on incidence trends. Methods: Data from the National Cancer Registry of all new cases of invasive cancer from twelve sites diagnosed in 2002-2015 was analyzed. Age-standardized rates were calculated. Trends of incidence rates were analyzed using joinpoint regression models. Results: For both, men and women, incidence rates trends for all cancer sites, colo-rectal and bladder cancer remained stable. Esophageal and gastric cancers descended while thyroid and kidney cancer incidence increased. In men lung cancer decreased; testicular cancer increased, and prostate cancer increased at the beginning of the period and decreased in the final years. In women, lung cancer increased, breast cancer remained stable and cervical cancer presented a significant decline from 2005 to 2010 and reached a plateau since then. Conclusion: Cancer incidence dynamics are complex and affected not only by Public Health policies such as tobacco control, vaccination and screening programs, but also by environmental and life style changes and the attitude of the medical community towards the application of diagnostic and therapeutic tools. The aim of this paper is to analyze cancer incidence time trends in the country and provide possible explanations to them.

Resumen Introducción: Uruguay es el país de Sudamerica que tiene las mayores tasas de incidencia y mortalidad por cáncer. El Registro Nacional de Cáncer recoge los datos de cáncer de todo el país desde 1989 y en las últimas décadas ha alcanzado los más altos estándares de calidad. Este es el primer reporte de tendencias de incidencia de cáncer de Uruguay. Métodos: Se analizaron los datos de todos los casos de cáncer invasivo diagnosticados entre 2002 y 2015 incluidos en el Registro Nacional de Cáncer y los de once topografías en particular. Se calcularon las tasas de incidencia estandarizada y se analizaron las tendencias utilizando los modelos de regresión de Joinpoint. Resultados: Las tasas de incidencia de cáncer colorrectal, vejiga y todos los sitios reunidos se mantuvieron estables tanto en hombres como en mujeres. La tasa de incidencia de cáncer de estómago y esófago disminuyeron mientras que las de tiroides y riñón aumentaron. En los hombres, el cáncer de pulmón disminuyó, el cáncer de testículo aumentó y el de próstata aumentó en un lapso inicial y decreció en los últimos años. En las mujeres el cáncer de pulmón aumentó y el de mama se mantuvo estable mientras que el cáncer de cérvix presentó un descenso significativo entre 2005 y 2010 alcanzando una meseta desde entonces. Conclusión: La dinámica de la incidencia de cáncer es compleja y está afectada no sólo por las políticas de Salud Pública como las campañas de control de tabaco, vacunación y programas de tamizaje sino por los cambios ambientales y de los estilos de vida y la actitud de los médicos respecto a la aplicación de técnicas diagnósticas y terapéuticas. En este trabajo se analizan las tendencias de incidencia en el país y se plantean posibles explicaciones para los cambios.

Extreme Maternal Morbidity: a tracer event to improve the quality of obstetric care in Latin America / Morbilidad Materna Extrema: evento trazador para mejorar la calidad de la atención obstétrica en América Latina

Abstract This article reviews critical aspects that have had an impact on the implementation of epidemiological surveillance of extreme maternal morbidity, as a tracer event of quality maternal care at population and institutional level; taking into account that maternal mortality has been usually monitored, and its analysis allows interventions to avoid maternal death. Until 2015, very few countries had been able to meet the goals established in the Millennium Development Goals (MDGs), especially MDG 5 - improving maternal health. As of today, it is observed that maternal mortality rate is quite heterogeneous, with rates from 1 case per 100,000 live births in developed countries, to more than 100 cases per 100,000 live births in developing countries. Therefore, complementary strategies such as surveillance of the extreme maternal morbidity could offer a more effective alternative to identify and implement interventions that allow us to prevent mortality and strengthen the quality of obstetric care. In addition, the importance of extreme maternal morbidity as a quality tracer event is that, unlike what is observed with maternal mortality, this is an event that occurs more frequently, is anticipatory of death, and the surviving pregnant woman is the primary source of information.

Resumen Este artículo revisa aspectos críticos que han tenido incidencia en la implementación de la vigilancia epidemiológica de la morbilidad materna extrema, como un evento trazador de calidad del cuidado materno a nivel poblacional e institucional, ya que usualmente se ha monitoreado la mortalidad materna y su análisis permite realizar intervenciones para evitar la muerte materna. Para el año 2015, muy pocos países lograron cumplir las metas establecidas en los Objetivos de Desarrollo del Milenio (ODM), especialmente el ODM 5- mejorar la salud materna. Al día de hoy se observa que la tasa de mortalidad materna es bastante heterogénea con tasas desde 1 caso por 100,000 nacidos vivos en países desarrollados, hasta más de 100 casos por cada 100,000 nacidos vivos en países en vía de desarrollo. Por lo tanto, estrategias complementarias como la vigilancia de la mortalidad materna extrema podrían ofrecer una alternativa más eficaz para identificar e implementar intervenciones que nos permitan prevenir la mortalidad y fortalecer la calidad de atención obstétrica, a partir de información más confiable y sin esperar que ocurra una muerte materna.

Extreme Maternal Morbidity: a tracer event to improve the quality of obstetric care in Latin America.

This article reviews critical aspects that have had an impact on the implementation of epidemiological surveillance of extreme maternal morbidity, as a tracer event of quality maternal care at population and institutional level; taking into account that maternal mortality has been usually monitored, and its analysis allows interventions to avoid maternal death. Until 2015, very few countries had been able to meet the goals established in the Millennium Development Goals (MDGs), especially MDG 5 - improving maternal health. As of today, it is observed that maternal mortality rate is quite heterogeneous, with rates from 1 case per 100,000 live births in developed countries, to more than 100 cases per 100,000 live births in developing countries. Therefore, complementary strategies such as surveillance of the extreme maternal morbidity could offer a more effective alternative to identify and implement interventions that allow us to prevent mortality and strengthen the quality of obstetric care. In addition, the importance of extreme maternal morbidity as a quality tracer event is that, unlike what is observed with maternal mortality, this is an event that occurs more frequently, is anticipatory of death, and the surviving pregnant woman is the primary source of information.

Este artículo revisa aspectos críticos que han tenido incidencia en la implementación de la vigilancia epidemiológica de la morbilidad materna extrema, como un evento trazador de calidad del cuidado materno a nivel poblacional e institucional, ya que usualmente se ha monitoreado la mortalidad materna y su análisis permite realizar intervenciones para evitar la muerte materna. Para el año 2015, muy pocos países lograron cumplir las metas establecidas en los Objetivos de Desarrollo del Milenio (ODM), especialmente el ODM 5- mejorar la salud materna. Al día de hoy se observa que la tasa de mortalidad materna es bastante heterogénea con tasas desde 1 caso por 100,000 nacidos vivos en países desarrollados, hasta más de 100 casos por cada 100,000 nacidos vivos en países en vía de desarrollo. Por lo tanto, estrategias complementarias como la vigilancia de la mortalidad materna extrema podrían ofrecer una alternativa más eficaz para identificar e implementar intervenciones que nos permitan prevenir la mortalidad y fortalecer la calidad de atención obstétrica, a partir de información más confiable y sin esperar que ocurra una muerte materna.

Effect of the anchoring strength on the phase behaviour of discotic liquid crystals under face-on confinement.

In this study we have performed molecular dynamics simulations to study a Gay-Berne discotic fluid confined in a slab geometry for a fixed confinement length. Four different anchoring strengths with a homeotropic (face-on) configuration were studied. We found that changing the anchoring strength changes the normal component of the stress tensor, which in turn changes the density of the system's bulk. This phenomenon leads to a shift in the isotropic-nematic transition temperature. We observe that the temperature regions where the nematic phase is present diminishes as the anchoring strength increases. The anchoring strength also affects the nematic-columnar coexistence temperature-region: it spans over more temperatures at higher anchoring strengths.

Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

Influence of anchoring in the phase behaviour of discotic liquid crystals.

Molecular dynamics simulations were performed for a Gay-Berne discotic fluid confined in a slab geometry for two different anchorings: homeotropic (face-on) and planar (edge-on), and for two different confinement lengths. Our results show that the behaviour of the more confined system in the temperature region of the isotropic-nematic transition is critically influenced by the presence of the walls: the growth of the solid-liquid crystal interface spans over the entire width of the cell, and the character of the transition is changed from first order to continuous. For all the confined systems studied, we observe a higher nematic-columnar transition temperature and a smaller nematic phase region in the phase diagram, as compared with the behaviour of the infinite system.

Cáncer: magnitud del problema en el mundo y en Uruguay, aspectos epidemiológicos / Cancer: magnitude of the problem in the world and in Uruguay, epidemiological aspects / Câncer: magnitude do problema no mundo e no Uruguay, aspectos epidemiológicos

El problema del cáncer es uno de los desafíos más relevantes de nuestra época. Como consecuencia de la transición demográfico-epidemiológica, el cáncer es actualmente una de las principales causas de muerte en el mundo y en Uruguay. Debido a que esta transición está aún en curso y con diferentes dinámicas alrededor del mundo, el problema del cáncer está cambiando en su escala y perfil. Se estima que el número de casos nuevos anuales pasará de alrededor de 14 millones en 2012 a más de 20 millones en 2030, y que casi dos tercios de esos casos ocurrirán en los países menos desarrollados. En tanto que estos últimos no cuentan con recursos similares a aquellos de los países desarrollados para enfrentar la enfermedad, esta situación plantea un desafío dramático para gobiernos y autoridades sanitarias. En Uruguay se diagnostican unos 13000 casos nuevos de cáncer (exceptuando al cáncer de piel distinto al melanoma), y más de 8000 pacientes mueren por esta enfermedad anualmente. Se examina, en particular, la situación epidemiológica de los cuatro tipos de cáncer más importantes: el cáncer de mama femenino, y los de próstata, pulmón y colo-recto, éstos dan cuenta de la mitad del total. Se analizan, además: el cáncer cervico-uterino y el cáncer de esófago. Las tasas estandarizadas por edad de mortalidad por cáncer (todos los sitios reunidos) muestran un descenso sostenido en las últimas décadas. No obstante, Uruguay exhibe en general tasas de incidencia comparables al conjunto de los países desarrollados, pero tasas de mortalidad más elevadas.

The burden of cancer is one of the most relevant challenges of our time. As a consequence of the demographic-epidemiologic transition, cancer is currently one of the leading causes of death, globally and in Uruguay. This transition is still in progress but with different dynamics around the world; therefore, the burden of cancer is changing its scale and profile. The projections indicate that the number of new cases will grow from 14 million in 2012 to more than 20 million in 2030, and that almost two thirds of them will take place in developing countries. Since less developed countries don`t have similar resources as those of developed countries to face the problem, this situation poses a dramatic challenge to governments and health authorities. In Uruguay, a Around 13000 new cancer cases (any sites, except for non-melanoma skin cancer) are diagnosed and more than 8000 patients die due to this cause annually. The epidemiological situation of the four most frequent cancers is analysed in this article as they account for almost half of the total (female breast, prostate, lung and colo-rectum). Cervical and oesophageal cancers are also analysed. Uruguay shows a sustained decline in age- standardized mortality rates for all sites combined during the last two decades. In general, Uruguay exhibits comparable values of incidence rates to more developed countries, but higher values of mortality rates.

O problema do câncer é um dos desafios mais relevantes de nosso tempo. Como consequência da transição demográfico-epidemiológica, o câncer é atualmente uma das principais causas de morte no mundo e no Uruguai. Devido a que essa transição ainda está em desenvolvimento e com diferentes dinâmicas ao redor do mundo, o problema do câncer está mudando na sua escala e no seu perfil. Estima-se que o número anual de novos casos vai aumentar de ao redor de 14 milhões em 2012 para mais de 20 milhões em 2030, e que quase dois terços desses casos ocorrerão nos países menos desenvolvidos. Enquanto esses últimos não contarem com recursos similares àqueles dos países desenvolvidos para enfrentar a doença, essa situação colocará um desafio dramático para os governos e as autoridades sanitárias. No Uruguai, diagnosticam-se aproximadamente 13000 casos novos de câncer (excetuando-se o câncer de pele diferente do melanoma), e mais de 8000 pacientes morren dessa doença anualmente. Examina-se, particularmente, a situação epidemiológica dos quatro tipos de câncer mais importantes: o câncer de mama feminino, e os de próstata, pulmão e colo-reto, estes constituindo a metade do total. Analisam-se, também, o câncer cérvico-uterino e o câncer de esôfago. As taxas padronizadas por idade de mortalidade por câncer (todas as localizações reunidas) mostran uma diminuição persistente nas últimas décadas. Porém, o Uruguai exibe em geral taxas de incidência comparáveis ao conjunto dos países desenvolvidos, embora as taxas de mortalidade sejam mais elevadas.