Visual manifestations in giant cell arteritis: identification of risk factors from the ARTESER Registry.

OBJECTIVE: To determine the prevalence and predictive factors of visual manifestations in a large registry of patients with GCA. METHODS: ARTESER is a large Spanish multicentre registry supported by the Spanish Society of Rheumatology. It includes patients with GCA from across the entire country diagnosed between June 2013 and March 2019. The variables collected at diagnosis were demographics, clinical manifestations (including all visual manifestations), laboratory, temporal artery biopsy, and imaging findings (ultrasound, FDG-PET/CT, MRI angiography, CT angiography). Patients with and without visual involvement were compared in a bivariate analysis. Multivariate logistic regression was performed to determine potential predictive factors of visual manifestations. RESULTS: The study population comprised 1636 GCA patients, of whom 599 (36.6%) presented visual manifestations. Anterior ischemic optic neuropathy was the most frequent (n = 274 of 599; 45.7%) ocular complication. The independent predictors that increased the risk (OR; 95% confidence interval) of visual involvement were older age (1.027; 1.009-1.045) and jaw claudication (1.724; 1.325-2.243). The variables associated with a reduced risk were polymyalgia rheumatica (0.541; 0.414-0.708), fever (0.373; 0.264-0.527), longer symptom duration (0.946; 0.909-0.985), and higher erythrocyte sedimentation rate (ESR) (0.992; 0.988-0.997), common features of patients with large vessel-GCA. CONCLUSION: One-third of GCA patients present visual manifestations at diagnosis. Older age and jaw claudication are independent predictors of visual manifestations, whereas polymyalgia rheumatica, fever, longer symptom duration, and high ESR reduce the risk of visual involvement.

New electronic implementation of the timestamps method intended for high resolution comparison of laser wavelengths.

This article describes a new measurement system for the comparison of two electronic signals of different frequencies with application to high resolution comparison of laser wavelengths using a Michelson interferometer. It was built within the framework of research projects made by the University of Vigo and the Laboratorio Oficial de Metroloxía de Galicia (LOMG) in cooperation with Escolas Proval High School. The new hardware is based on a cheap high-speed module for the acquisition of data and a microcontroller module for processing, which can also be used for practical lessons in vocational training. The system has been tested with electronic signal generators. The novel measurement method reduces the uncertainty using multiple consecutive measurements and the fractional part of the fringes and could achieve precisions in the range 10-12 of the wavelength ratios.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

INTRODUCTION: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. METHODS: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. RESULTS: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. CONCLUSION: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

Introduction: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. Methods: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. Results: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. Conclusion: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Introducción: El 14 de marzo de 2020 España declaró el estado de alarma por la pandemia por COVID-19 incluyendo medidas de confinamiento. El objetivo es describir el proceso de desescalada de estas medidas. Métodos: Un plan de transición hacia una nueva normalidad, del 28 de abril, incluía 4 fases secuenciales incrementando progresivamente las actividades socioeconómicas y la movilidad. Concomitantemente, se implementó una nueva estrategia de diagnóstico precoz, vigilancia y control. Se estableció un mecanismo de decisión bilateral entre Gobierno central y comunidades autónomas (CCAA), guiado por un panel de indicadores cualitativos y cuantitativos de la situación epidemiológica y las capacidades básicas. Las unidades territoriales evaluadas comprendían desde zonas básicas de salud hasta CCAA. Resultados: El proceso se extendió del 4 de mayo al 21 de junio y se asoció a planes de refuerzo de las capacidades en las CCAA. La incidencia disminuyó de una mediana inicial de 7,4 por 100.000 en 7 días a 2,5 al final del proceso. La mediana de pruebas PCR aumentó del 53% al 89% de los casos sospechosos, y la capacidad total de 4,5 a 9,8 pruebas semanales por 1.000 habitantes; la positividad disminuyó del 3,5% al 1,8%. La mediana de casos con contactos trazados aumentó del 82% al 100%. Conclusión: La recogida y análisis sistemático de información y el diálogo interterritorial logaron un adecuado control del proceso. La situación epidemiológica mejoró, pero sobre todo, se aumentaron las capacidades, en todo el país y con criterios comunes, cuyo mantenimiento y refuerzo fue clave en olas sucesivas.

Pandrug-resistant Acinetobacter baumannii from different clones and regions in Mexico have a similar plasmid carrying the blaOXA-72 gene.

Background: Multidrug-resistant Acinetobacter baumannii is a common hospital-acquired pathogen. The increase in antibiotic resistance is commonly due to the acquisition of mobile genetic elements carrying antibiotic resistance genes. To comprehend this, we analyzed the resistome and virulome of Mexican A. baumannii multidrug-resistant isolates. Methods: Six clinical strains of A. baumannii from three Mexican hospitals were sequenced using the Illumina platform, the genomes were assembled with SPAdes and annotated with Prokka. Plasmid SPAdes and MobRecon were used to identify the potential plasmid sequences. Sequence Type (ST) assignation under the MLST Oxford scheme was performed using the PubMLST database. Homologous gene search for known virulent factors was performed using the virulence factor database VFDB and an in silico prediction of the resistome was conducted via the ResFinder databases. Results: The six strains studied belong to different STs and clonal complexes (CC): two strains were ST208 and one was ST369; these two STs belong to the same lineage CC92, which is part of the international clone (IC) 2. Another two strains were ST758 and one was ST1054, both STs belonging to the same lineage CC636, which is within IC5. The resistome analysis of the six strains identified between 7 to 14 antibiotic resistance genes to different families of drugs, including beta-lactams, aminoglycosides, fluoroquinolones and carbapenems. We detected between 1 to 4 plasmids per strain with sizes from 1,800 bp to 111,044 bp. Two strains from hospitals in Mexico City and Guadalajara had a plasmid each of 10,012 bp pAba78r and pAba79f, respectively, which contained the bla OXA-72 gene. The structure of this plasmid showed the same 13 genes in both strains, but 4 of them were inverted in one of the strains. Finally, the six strains contain 49 identical virulence genes related to immune response evasion, quorum-sensing, and secretion systems, among others. Conclusion: Resistance to carbapenems due to pAba78r and pAba79f plasmids in Aba pandrug-resistant strains from different geographic areas of Mexico and different clones was detected. Our results provide further evidence that plasmids are highly relevant for the horizontal transfer of antibiotic resistance genes between different clones of A. baumannii.

Emergence of New SARS-CoV2 Omicron Variants after the Change of Surveillance and Control Strategy.

In January 2022, there was a global and rapid surge of the Omicron variant of SARS-CoV-2 related to more transmission. This coincided with an increase in the incidence in Asturias, a region where rapid diagnosis and containment measures had limited the circulation of variants. METHODS: From January to June 2022, 34,591 variants were determined by the SNP method. From them, 445 were characterized by the WGS method and classified following pangolin program and phylogenic analysis. RESULTS: The Omicron variant went from being detected in 2438 (78%) samples in the first week of January 2021 to 4074 (98%) in the third week, according to the SNP method. Using the WGS method, 159 BA.1 (35.7%), 256 BA.2 (57.6%), 1 BA.4 (0.2%) and 10 BA.5 (2.2%) Omicron variants were found. Phylogenetic analysis detected that three new sub-clades, BA.2,3.5, BA.2.56 and BF1, were circulating. CONCLUSIONS: The increase in the incidence of SARS-CoV2 caused the circulation of new emerging variants. Viral evolution calls for continuous genomic surveillance.

Validation of Content for an App for Caregivers of Stroke Patients through the Delphi Method.

The aim of this study was to reach a consensus among experts (using the Delphi technique) to validate the informative content that should be included in an App to be used by informal caregivers of stroke patients in order to improve their quality of life, facilitating access to the health care system and involving them in their own health. This technique was developed between June and December 2021. The group of experts was selected on the basis of previously established criteria, and the coefficient of variation (v) was used as a measure of consensus. In addition, the concordance index was calculated to determine the stability of the different rounds. In the first round, the preliminary content, previously elaborated by the research group, was evaluated as very appropriate for the objectives set (N-P < 1.07). In addition, averages of 4.5 out of five and a coefficient of variation of less than 0.5 were obtained, confirming the consensus. In the second round, suggestions were made by the experts on how to improve the content of the information, obtaining 100% agreement with the results obtained in the first round. The results obtained allow a positive evaluation of the use of the Delphi method for the elaboration of the information to be housed in an App.

The promiscuous and highly mobile resistome of Acinetobacter baumannii.

Antimicrobial resistance (AR) is a major global threat to public health. Understanding the population dynamics of AR is critical to restrain and control this issue. However, no study has provided a global picture of the whole resistome of Acinetobacter baumannii, a very important nosocomial pathogen. Here we analyse 1450+ genomes (covering >40 countries and >4 decades) to infer the global population dynamics of the resistome of this species. We show that gene flow and horizontal transfer have driven the dissemination of AR genes in A. baumannii. We found considerable variation in AR gene content across lineages. Although the individual AR gene histories have been affected by recombination, the AR gene content has been shaped by the phylogeny. Furthermore, many AR genes have been transferred to other well-known pathogens, such as Pseudomonas aeruginosa or Klebsiella pneumoniae. Despite using this massive data set, we were not able to sample the whole diversity of AR genes, which suggests that this species has an open resistome. Our results highlight the high mobilization risk of AR genes between important pathogens. On a broader perspective, this study gives a framework for an emerging perspective (resistome-centric) on the genomic epidemiology (and surveillance) of bacterial pathogens.

Racial/Ethnic Disparities in Parent Activation: Implications for Developing Interventions Addressing Early Childhood Obesity.

OBJECTIVE: Examine racial/ethnic differences in parent activation and associations with child obesity risk behaviors in low-income families. METHODS: Cross-sectional survey study of 300 low-income Black, Latinx, and White parents of patients aged 2 to 5 years receiving primary care within 2 health care systems (Systems 1 & 2). In-person and phone surveys were conducted. Parent activation, defined as parents' knowledge, confidence, and willingness to act concerning their child's health, was measured using the standardized 13-item Parent Patient Activation Measure (P-PAM). Differences in parent activation by race/ethnicity were assessed using analysis of variance. Multivariate regression analyses were used to test associations between parent activation and child obesity risk behaviors. RESULTS: In pooled unadjusted analyses, Latinx parents had significantly lower activation compared to Black parents (P = .023), but these differences were no longer statistically significant after adjusting for other sociodemographic characteristics (P = .06). Higher activation was associated with slightly greater odds of consuming ≥ 5 daily servings of fruits and vegetables for System 2 only (odds ratio: 1.04, 95% confidence interval: 1.01, 1.07). Associations between parental activation and child screen time or physical activity were not significant. CONCLUSIONS: Findings highlight potential measurement limitations of the P-PAM including the inability of the measure to capture barriers to health system navigation and cultural and linguistic considerations. Further attention to the nuanced interplay between parental activation and contextual and sociodemographic risk factors (eg, food availability, immigrant status, economic opportunity, language proficiency) should be considered in the development of early childhood obesity interventions in primary care settings.

e-Health as a tool to improve the quality of life of informal caregivers dealing with stroke patients: Systematic review with meta-analysis.

OBJECTIVE: The objective of this review was to elucidate the evidence related to utilizing e-Health as a tool in improving the quality of life of informal caregivers of dependent patients due to cerebrovascular accident (CVA). METHODS: This systematic review with meta-analysis includes 13 studies. For these studies, seven databases were searched between 2009 and 2019. A random-effects model was adopted for overall estimation and to explain the heterogeneity. RESULTS: A random-effects model was adopted for overall estimation and to explain heterogeneity. The results did not demonstrate statistical significance (p<0.05) and low heterogeneity (I2  = 0). CONCLUSIONS: There is a tendency toward improvement in psychological health, solving care-related problems, as well as better prevention of problems arising from the burden. Therefore, new studies with larger sample size and primarily to conduct them for more than 6 months for the accuracy. CLINICAL RELEVANCE: This study reflects a trend toward improving psychological health, solving care-related problems, as well as improved the prevention of problems arising from the burden.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

INTRODUCTION: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. METHODS: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. RESULTS: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. CONCLUSION: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Comparative Performance of High-Yielding European Wheat Cultivars Under Contrasting Mediterranean Conditions.

Understanding the interaction between genotype performance and the target environment is the key to improving genetic gain, particularly in the context of climate change. Wheat production is seriously compromised in agricultural regions affected by water and heat stress, such as the Mediterranean basin. Moreover, wheat production may be also limited by the nitrogen availability in the soil. We have sought to dissect the agronomic and physiological traits related to the performance of 12 high-yield European bread wheat varieties under Mediterranean rainfed conditions and different levels of N fertilization during two contrasting crop seasons. Grain yield was more than two times higher in the first season than the second season and was associated with much greater rainfall and lower temperatures. However, the nitrogen effect was rather minor. Genotypic effects existed for the two seasons. While several of the varieties from central/northern Europe yielded more than those from southern Europe during the optimal season, the opposite trend occurred in the dry season. The varieties from central/northern Europe were associated with delayed phenology and a longer crop cycle, while the varieties from southern Europe were characterized by a shorter crop cycle but comparatively higher duration of the reproductive period, associated with an earlier beginning of stem elongation and a greater number of ears per area. However, some of the cultivars from northern Europe maintained a relatively high yield capacity in both seasons. Thus, KWS Siskin from the UK exhibited intermediate phenology, resulting in a relatively long reproductive period, together with a high green area throughout the crop cycle.

Accessory Genomic Epidemiology of Cocirculating Acinetobacter baumannii Clones.

Acinetobacter baumannii has become one of the most important multidrug-resistant nosocomial pathogens all over the world. Nonetheless, very little is known about the diversity of A. baumannii lineages coexisting in hospital settings. Here, using whole-genome sequencing, epidemiological data, and antimicrobial susceptibility tests, we uncover the transmission dynamics of extensive and multidrug-resistant A. baumannii in a tertiary hospital over a decade. Our core genome phylogeny of almost 300 genomes suggests that there were several introductions of lineages from international clone 2 into the hospital. The molecular dating analysis shows that these introductions happened in 2006, 2007, and 2013. Furthermore, using the accessory genome, we show that these lineages were extensively disseminated across many wards in the hospital. Our results demonstrate that accessory genome variation can be a very powerful tool for conducting genomic epidemiology. We anticipate future studies employing the accessory genome along with the core genome as a powerful phylogenomic strategy to track bacterial transmissions over very short microevolutionary scales. IMPORTANCE Whole-genome sequencing for epidemiological investigations (genomic epidemiology) has been of paramount importance to understand the transmission dynamics of many bacterial (and nonbacterial) pathogens. Commonly, variation in the core genome, single nucleotide polymorphisms (SNPs), is employed to carry out genomic epidemiology. However, at very short periods of time, the core genome might not have accumulated enough variation (sufficient SNPs) to tell apart isolates. In this scenario, gene content variation in the accessory genome can be an option to conduct genomic epidemiology. Here, we used the accessory genome, as well as the core genome, to uncover the transmission dynamics of extensive and multidrug-resistant A. baumannii in a tertiary hospital for a decade. Our study shows that accessory genome variation can be a very powerful tool for conducting genomic epidemiology.

Efectividad de una demostración clínica simulada para elevar los conocimientos sobre RCP-B en el adulto / Effectiveness of a simulated clinical performance to raise the adults' knowledge about Bystander Cardiopulmonary Resuscitation

Introducción: La ejecución de maniobras de reanimación cardiopulmonar por las personas que han presenciado un paro aumenta siete veces las posibilidades de supervivencia. Objetivo: Evaluar la efectividad de una demostración de situación clínica simulada realizada en los domicilios para elevar el nivel de conocimientos sobre reanimación cardiopulmonar básica en el adulto. Métodos: Se realizó un estudio de tipo antes y después sin grupo control entre septiembre y diciembre de 2018. El universo estuvo conformado por 620 pacientes pertenecientes a un consultorio del policlínico 19 de abril de Plaza de la Revolución. Se seleccionó una muestra de 200 pacientes y se les aplicó una encuesta, realizada por los autores, antes y después de la intervención, la cual se sometió a test alfa para la validación interna. Para la evaluación de la demostración se utilizó la prueba t de student, un análisis de varianza (ANOVA) y un análisis post hoc. Resultados: La media de edad fue de 45,45 ± 14,45 años. El sexo femenino predominó con 102 personas (51 por ciento). Hubo 63 (32 por ciento) pacientes con nivel de técnico medio. La diferencia de las medias de puntos antes y después de la demostración fue estadísticamente significativa en todos los grados de escolaridad (p ˂ 0,001). Hubo diferencias en el aumento de puntos después de la demostración entre los universitarios y las personas con sexto grado (p = 0,013). Conclusiones: Realizar una demostración con una situación clínica simulada constituyó una herramienta efectiva para elevar el nivel de conocimiento de la población en estudio, independientemente del nivel de escolaridad(AU)

Introduction: Bystander cardiopulmonary resuscitation increases the chances of survival by seven times. Objective: To assess the effectiveness of a simulated clinical situation carried out in homes to raise the level of knowledge about basic cardiopulmonary resuscitation in adults. Methods: A before-and-after study without a control group was carried out between September and December 2018. The universe consisted of 620 patients from a family doctor's office belonging to 19 de Abril Outpatient Polyclinic in Plaza de la Revolución Municipality (Havana, Cuba). A sample of 200 patients was selected and a survey was applied on them, carried out by the authors, before and after the intervention, which was subjected to an alpha test for internal validation. For the assessment of the demonstration, Student's t test, variance analysis (ANOVA) and a post hoc analysis were used. Results: The mean age was 45.45 ± 14.45 years. The female sex predominated, with 102 people (51 percent). There were 63 (32 percent) patients with an associate's degree. The difference in the means of scores before and after the demonstration was statistically significant in all school levels (P˂0.001). There were differences in the increase of scores after the simulated performance between the university students and the people with sixth grade (P=0.013). Conclusions: Performance of a simulated clinical situation was an effective tool to raise the level of knowledge of the population under study, regardless of their level of education(AU)

Optimismo disposicional, ansiedad, depresión y estrés en una muestra del Ecuador. Análisis inter-género y de predicción / Dispositional Optimism, Anxiety, Depression and Stress in a Sample of Ecuador. Inter-gender and Prediction Analysis

Resumen.Objetivo. Determinar las diferencias inter-género del optimismo disposicional, la depresión, la ansiedad, el estrés y el rol predictor sobre estos rasgos patológicos en una muestra de universitarios del Ecuador. Método. Investigación descriptiva, comparativa, predictora y de corte transversal con las pruebas de Orientación Vital y la Escala de Depresión, Ansiedad y Estrés con 288 participantes de una universidad pública de Ambato, Ecuador (63.9% son mujeres y 31% hombres). Con edades entre 17 a 39 años (M = 21.6 años; DT = 2.5). Resultados. Hay diferencias (p < .05) de género en ansiedad y estrés (con mayor presencia en mujeres que en hombres. También, hay correlaciones entre el optimismo disposicional y los rasgos patológicos. Finalmente, el optimismo disposicional explica en la depresión (15.2%), la ansiedad (9.7%) y el estrés (5.5%) los cambios de la varianza. Se concluye que el optimismo disposicional es un predictor de la depresión, la ansiedad y el estrés en estudiantes universitarios.

Abstract.Objective. To determine the inter-gender differences in dispositional optimism, depression, anxiety, and stress; as well as the predictive role of optimism on pathological features in a sample of Ecuadorian university students. Method. This is a descriptive, comparative, predictive and cross-sectional study using the Life Orientation (LOT-R) and Depression, Anxiety and Stress Scale (DASS-21) tests with 288 university students belonging to one university of Ambato; 63.9% women, 31% men aged between 17 to 39 (M = 21.6 years, SD = 2.5). Results. Gender differences were found at the Anxiety and Stress level, with greater presence in women than in men. As regards dispositional optimism and depression, gender is invariant. There were both slight and significant correlations between dispositional optimism and the dimensions evaluated by the DASS 21 test. Dispositional optimism also explains changes in variance in depression (15.2%), anxiety (9.7%) and stress (5.5%). As a conclusion, dispositional optimism is a relevant predictor of depression, as well as anxiety and stress in university students.

Time-driven activity-based costing for patients with multiple chronic conditions: a mixed-method study to cost care in a multidisciplinary and integrated care delivery centre at a university-affiliated tertiary teaching hospital in Stockholm, Sweden.

OBJECTIVE: This study can be applied to cost the complex non-standardised processes used to treat patients with multiple chronic conditions. DESIGN: A mixed-method approach to cost analysis, following a modified healthcare-specific version of the seven-step Time-Driven Activity-Based Costing (TDABC) approach. SETTING: A multidisciplinary integrated and person-centred care delivery centre at a university-affiliated tertiary teaching hospital in Stockholm, Sweden, designed to improve care coordination for patients with multiple chronic conditions, specifically diabetes, cardiovascular disease and kidney disease. PARTICIPANTS: 314 patients (248 men and 66 women) fit inclusion criteria. Average age was 80 years. RESULTS: This modified TDABC analysis costed outpatient care for patients with multiple chronic conditions. The approach accounted for the difficulty of conceptualising care cycles. The estimated total cost, stratified by resources, can be reviewed together with existing managerial accounting statements to inform management decisions regarding the multidisciplinary centre. CONCLUSIONS: This article demonstrates that the healthcare-specific seven-step approach to TDABC can be applied to cost care for patients with multiple chronic conditions, where pathways are not yet discernable. It became clear that there was a need for slight methodological adaptations for this particular patient group to make it possible to cost these pathways, stratified by activity and resource. The value of this approach can be discerned from the way management incorporated the results of this analysis into the development of their hospital strategy. In the absence of integrated data infrastructures that can link patients and resources across financial, clinical and process data sets, the scalability of this method will be difficult.

Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs.

Matrix metalloproteinases (MMPs) degrade several ECM components and are crucial modulators of cell invasion and tissue organization. Although much has been reported about their function in remodeling ECM in health and disease, their trafficking across the Golgi apparatus remains poorly understood. Here we report that the cis-Golgi protein nucleobindin-1 (NUCB1) is critical for MMP2 and MT1-MMP trafficking along the Golgi apparatus. This process is Ca2+-dependent and is required for invasive MDA-MB-231 cell migration as well as for gelatin degradation in primary human macrophages. Our findings emphasize the importance of NUCB1 as an essential component of MMP transport and its overall impact on ECM remodeling.

miR-149 Suppresses Breast Cancer Metastasis by Blocking Paracrine Interactions with Macrophages.

Paracrine activation of cells contained in the tumor microenvironment promotes tumor progression and metastasis. In breast cancer, malignant cells recruit and educate macrophages into a M2 tumor-promoting phenotype that supports the metastatic spread of cancer cells. Here, we show that miR-149 functions as a metastasis-suppressing microRNA in breast cancer cells by limiting colony-stimulating factor-1 (CSF1)-dependent recruitment and M2 polarization of macrophages. In lymph node-positive, triple-negative breast cancer (TNBC) tissues, low miR-149 expression correlated with macrophage infiltration and reduced patient survival. By directly targeting CSF1, miR-149 expression in TNBC cell lines (MDA-MB-231 and BT-549) inhibited the recruitment of human monocytic THP-1 cells and primary human macrophages. Furthermore, in macrophages cocultured with MDA-MB-231 cells expressing miR-149, epidermal growth factor (EGF) and amphiregulin expression levels were strongly reduced, resulting in reduced EGF receptor activation in the cancer cells. In vivo, lung metastases developing from orthotopic MDA-MB-231 tumors were reduced by 75% by miR-149 expression, and this was associated with impaired M2 macrophage infiltration of the primary tumors. These data suggest that miR-149 downregulation functionally contributes to breast tumor progression by recruiting macrophages to the tumor and facilitating CSF1 and EGF receptor cross-talk between cancer cells and macrophages. SIGNIFICANCE: These findings contribute to the understanding of tumor-stroma interactions by showing that miR-149 downregulation in TNBC enhances reciprocal growth factor signaling between macrophages and cancer cells, which promotes tumor progression and metastasis. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/6/1330/F1.large.jpg.