Reliable Control Applications with Wireless Communication Technologies: Application to Robotic Systems.

The nature of wireless propagation may reduce the QoS of the applications, such that some packages can be delayed or lost. For this reason, the design of wireless control applications must be faced in a holistic way to avoid degrading the performance of the control algorithms. This paper is aimed at improving the reliability of wireless control applications in the event of communication degradation or temporary loss at the wireless links. Two controller levels are used: sophisticated algorithms providing better performance are executed in a central node, whereas local independent controllers, implemented as back-up controllers, are executed next to the process in case of QoS degradation. This work presents a reliable strategy for switching between central and local controllers avoiding that plants may become uncontrolled. For validation purposes, the presented approach was used to control a planar robot. A Fuzzy Logic control algorithm was implemented as a main controller at a high performance computing platform. A back-up controller was implemented on an edge device. This approach avoids the robot becoming uncontrolled in case of communication failure. Although a planar robot was chosen in this work, the presented approach may be extended to other processes. XBee 900 MHz communication technology was selected for control tasks, leaving the 2.4 GHz band for integration with cloud services. Several experiments are presented to analyze the behavior of the control application under different circumstances. The results proved that our approach allows the use of wireless communications, even in critical control applications.

Towards an Open Medical School without Checkerboards during the COVID-19 Pandemic: How to Flexibly Self-Manage General Surgery Practices in Hospitals?

BACKGROUND: Can we create a technological solution to flexibly self-manage undergraduate General Surgery practices within hospitals? Before the pandemic, the management of clerkships was starting to depend less on checkerboards. This study aims to explore undergraduates' perceptions of doing rotations in teaching hospitals using different teaching styles and elicit their views regarding the options of managing practices to design a mobile app that substitutes for checkerboards. METHODS: In this sequential exploratory mixed methods study, 38 semi-structured interviews at a teaching hospital were conducted. The data was used to survey 124 students doing their rotations in four teaching hospitals during the first wave of COVID-19. RESULTS: 21 themes highlighted concerns related to the practices, the teacher involvement in the students' education, and the students' adaptation to clinical culture. The students reported positive perceptions concerning self-managing and organizing practices via a mobile application. However, problems emerged regarding transparency, the lack of feedback, and the need for new tools. Regarding the teaching styles, the facilitator and personal models were perceived as optimal, but the personal style had no effect on using or not using a tool. CONCLUSIONS: A mobile-learning application designed like an educational opportunities' manager tool can probably promote self-directed learning, flexible teaching, and bidirectional assessments. However, teachers who employ a personal teaching style may not need either checkerboards or a tool. This solution supports teaching at hospitals in pandemic times without checkerboards.

Cisplatin resistance involves a metabolic reprogramming through ROS and PGC-1α in NSCLC which can be overcome by OXPHOS inhibition.

BACKGROUND: Platinum-based chemotherapy remains the standard of care for most lung cancer cases. However chemoresistance is often developed during the treatment, limiting clinical utility of this drug. Recently, the ability of tumor cells to adapt their metabolism has been associated to resistance to therapies. In this study, we first described the metabolic reprogramming of Non-Small Cell Lung Cancer (NSCLC) in response to cisplatin treatment. METHODS: Cisplatin-resistant versions of the A549, H1299, and H460 cell lines were generated by continuous drug exposure. The long-term metabolic changes, as well as, the early response to cisplatin treatment were analyzed in both, parental and cisplatin-resistant cell lines. In addition, four Patient-derived xenograft models treated with cisplatin along with paired pre- and post-treatment biopsies from patients were studied. Furthermore, metabolic targeting of these changes in cell lines was performed downregulating PGC-1α expression through siRNA or using OXPHOS inhibitors (metformin and rotenone). RESULTS: Two out of three cisplatin-resistant cell lines showed a stable increase in mitochondrial function, PGC1-α and mitochondrial mass with reduced glycolisis, that did not affect the cell cycle. This phenomenon was confirmed in vivo. Post-treatment NSCLC tumors showed an increase in mitochondrial mass, PGC-1α, and a decrease in the GAPDH/MT-CO1 ratio. In addition, we demonstrated how a ROS-mediated metabolism reprogramming, involving PGC-1α and increased mitochondrial mass, is induced during short-time cisplatin exposure. Moreover, we tested how cells with increased PGC-1a induced by ZLN005 treatment, showed reduced cisplatin-driven apoptosis. Remarkably, the long-term metabolic changes, as well as the metabolic reprogramming during short-time cisplatin exposure can be exploited as an Achilles' heel of NSCLC cells, as demonstrated by the increased sensitivity to PGC-1α interference or OXPHOS inhibition using metformin or rotenone. CONCLUSION: These results describe a new cisplatin resistance mechanism in NSCLC based on a metabolic reprogramming that is therapeutically exploitable through PGC-1α downregulation or OXPHOS inhibitors.

Cancer-associated fibroblasts modify lung cancer metabolism involving ROS and TGF-ß signaling.

Lung cancer is a major public health problem due to its high incidence and mortality rate. The altered metabolism in lung cancer is key for the diagnosis and has implications on both, the prognosis and the response to treatments. Although Cancer-associated fibroblasts (CAFs) are one of the major components of the tumor microenvironment, little is known about their role in lung cancer metabolism. We studied tumor biopsies from a cohort of 12 stage IIIA lung adenocarcinoma patients and saw a positive correlation between the grade of fibrosis and the glycolysis phenotype (Low PGC-1α and High GAPDH/MT-CO1 ratio mRNA levels). These results were confirmed and extended to other metabolism-related genes through the in silico data analysis from 73 stage IIIA lung adenocarcinoma patients available in TCGA. Interestingly, these relationships are not observed with the CAFs marker α-SMA in both cohorts. To characterize the mechanism, in vitro co-culture studies were carried out using two NSCLC cell lines (A549 and H1299 cells) and two different fibroblast cell lines. Our results confirm that a metabolic reprogramming involving ROS and TGF-ß signaling occurs in lung cancer cells and fibroblasts independently of α-SMA induction. Under co-culture conditions, Cancer-Associated fibroblasts increase their glycolytic ability. On the other hand, tumor cells increase their mitochondrial function. Moreover, the differential capability among tumor cells to induce this metabolic shift and also the role of the basal fibroblasts Oxphos Phosphorylation (OXPHOS) function modifying this phenomenon could have implications on both, the diagnosis and prognosis of patients. Further knowledge in the mechanism involved may allow the development of new therapies.

A multicentre observational study of the effectiveness, safety and economic impact of nivolumab on non-small-cell lung cancer in real clinical practice.

Background Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes. Objective The aim of this study was to evaluate the effectiveness, safety and economic cost of nivolumab in real-world clinical practice. Setting Fifteen regional and academic hospitals from Spain participated in this study. Methods This study was a retrospective, multicentre and observational study involving patients who experienced progression after first-line therapy for non-small-cell lung cancer and were treated with nivolumab between January 2016 and July 2017. Effectiveness and safety were evaluated by the oncologist, and the data from the electronic clinical records of the patients were collected by the research team. Economic cost was calculated using the cost of acquiring nivolumab for the public health system. Main outcome measures Effectiveness variables were overall survival (OS) and progression-free survival (PFS). The safety variable was the incidence of adverse events (AEs), and the cost per life-year gained (LYG) was the economic variable. Results A total of 221 patients were enrolled (83.7% men). The mean age was 64.5 years, and 84.6% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0-1. Squamous tumours accounted for 59.7% of the total, and 78.7% of the patients presented a time since platinum therapy (TPT) > 6 months. The mean nivolumab dose was 216 mg (SD 211), and the treatment duration was 7.0 months (95% CI 5.8-8.1). The median PFS was 5.3 months (95% CI 3.2-7.3), and OS was 9.7 months (95% CI 7.6-11.8). The median PFS and OS values were statistically significantly superior for patients with an ECOG score of 0-1 and for patients with a TPT > 6 months. The median OS was also statistically significantly superior for patients with non-squamous histology. Regarding safety, 71% of the patients presented AEs of any grade, and in 18.6%, the nivolumab treatment had to be delayed or discontinued. The cost of nivolumab per patient was €19,910.00 (SD 19,369), and the cost per LYG was €110,026.00 (€77,557.00-€231,171.00). Conclusions This study confirms that the efficacy and safety of nivolumab treatment in a real population are comparable to the results obtained in clinical trials. A greater clinical benefit of nivolumab therapy was observed in patients with an ECOG score of 0-1, a TPT > 6 months or non-squamous histology. Despite the benefit observed, the cost per LYG is above the threshold of efficiency established by public health institutes.

Occipital Neuralgia: a noninvasive therapeutic approach / Neuralgia Occipital: uma abordagem terapêutica não invasiva / Neuralgia Occipital: un abordaje terapéutico no invasivo

ABSTRACT Objective: to evaluate the application of a noninvasive intervention consisting of a postural modification using personalized models and osteopathy in people with occipital neuralgia. Method: retrospective study of the intervention performed in adult population with occipital neuralgia, consisting of postural modification using personalized plantar orthoses and osteopathy, in a study period of four years. The observed variables were: persistence of headache, alignment of the axes, plantar support, center of gravity and center of mass; medical interview data, visual analogue scale, Win-Track gait analysis system and Kinovea software for video analysis (clinical assessment instruments used). Results: a total of 34 records of people with occipital neuralgia were studied. A fraction of 58.8% of the patients reported improvement after the intervention. The visual analogue scale data were provided for 64.7% of the records and significant differences (p <0.001) between the means before (8.4 ± 1.7) and after the intervention (2.6 ± 2.7) were found. Conclusion: postural modification using personalized orthoses and osteopathy substantially improves the symptomatology of patients with occipital neuralgia.

RESUMO Objetivo: avaliar a aplicação de uma intervenção não invasiva que consiste em uma modificação postural usando modelos personalizados e osteopatia em pessoas com neuralgia occipital. Método: estudo retrospectivo da intervenção realizada em população adulta com neuralgia occipital que consiste de modificação postural empregando órteses plantares personalizadas e osteopatia, em um período de estudo de quatro anos. As variáveis observadas foram: persistência de cefaleia, alinhamento dos eixos, apoio plantar, centro de gravidade e centro de massa; dados da entrevista médica, escala visual analógica, sistema de análise de marcha Win-Track e o software Kinovea para análise de vídeo (instrumentos de avaliação clínica utilizados). Resultados: foram estudados no total 34 registros de pessoas com neuralgia occipital. Uma fração de 58,8% dos pacientes informou apresentar melhoria após a intervenção. Os dados da escala visual analógica foram fornecidos para 64,7% dos registros, encontrando diferenças significativas (p<0,001) entre as médias antes (8,4±1,7) e depois da intervenção (2,6±2,7). Conclusão: a modificação postural empregando órteses personalizadas e osteopatia melhora substancialmente a sintomatologia dos pacientes com neuralgia occipital.

RESUMEN Objetivo: evaluar la aplicación de una intervención no invasiva consistente en una modificación postural empleando plantillas personalizadas y osteopatía en personas con neuralgia occipital. Método: estudio retrospectivo de la intervención llevada a cabo en población adulta con neuralgia occipital, de modificación postural empleando órtesis plantares personalizadas y osteopatía, en un período de estudio de cuatro años. Las variables observadas fueron: persistencia de cefalea, alineación de los ejes, apoyo plantar, centro de gravedad y centro de masa; datos de la entrevista médica, la escala visual análoga, el sistema de análisis de la marcha Win-Track y el software Kinovea para análisis de vídeo (instrumentos de valoración clínica utilizados). Resultados: un total de 34 registros de personas con neuralgia occipital fueron estudiados. Un 58,8% refería presentar mejoría tras la intervención. Los datos de la escala visual análoga eran proporcionados un 64,7% de los registros, encontrándose diferencias significativas (p<0,001) entre las medias previas a la intervención (8,4±1,7) y aquellas posteriores (2,6±2,7). Conclusión: la modificación postural empleando órtesis personalizadas y osteopatía mejora sustancialmente la sintomatología de los pacientes con neuralgia occipital.

PGC-1alpha levels correlate with survival in patients with stage III NSCLC and may define a new biomarker to metabolism-targeted therapy.

Lung cancer remains the leading cause of cancer-related death worldwide, with one-third diagnosed with locally advanced (stage III) disease. Preoperative induction chemo-radiotherapy is key for the treatment of these patients, however conventional cisplatin based approaches has apparently reached a plateau of effectiveness. In the search for new therapies, the targeting of tumor metabolism is revealed as an interesting option to improve the patient's responses. Here we describe the importance of PGC-1alpha and GAPDH/MT-CO1 ratio levels as surrogates of the Warburg effect from a series of 28 stage III NSCLC patients, on PFS, OS and PET uptake. Moreover, our results show a great variability between tumors of different individuals, ranging from very glycolytic to more OXPHOS-dependent tumors, which compromises the success of therapies directed to metabolism. In this sense, using 3 different cell lines, we describe the relevance of Warburg effect on the response to metabolism-targeted therapies. Specifically, we show that the inhibitory effect of metformin on cell viability depends on cell's dependence on the OXPHOS system. The results on cell lines, together with the results of PGC-1alpha and GAPDH/MT-CO1 as biomarkers on patient's biopsies, would point out what type of patients would benefit more from the use of these drugs.

Dabrafenib plus trametinib for compassionate use in metastatic melanoma: A STROBE-compliant retrospective observational postauthorization study.

The main objective of the study was to evaluate the efficacy and safety of dabrafenib alone or combined with trametinib for compassionate use in patients with metastatic melanoma.This retrospective, observational study involved 135 patients with unresectable stage IIIC or stage IV melanoma from an expanded-access program at 30 Spanish centers.Forty-eight patients received dabrafenib monotherapy and 87 received combination dabrafenib and trametinib; 4.4% and 95.6% of the patients had stage IIIC and IV melanoma, respectively. All patients showed BRAF mutations in their primary or metastatic lesions; 3 were positive for V600K while the remainder had V600E or V600+. A positive response to treatment was reported in 89.3% of the patients. Overall survival rates at 12 and 24 months were 59.6% (95% confidence interval [CI], 52.5-68.9%) and 36.4% (95% CI, 27.8-45%), respectively. Progression-free survival rates at 12 and 24 months were 39.3% (95% CI, 31.1-47.5%) and 21.6% (95% CI, 14.5-28.7%), respectively. Fifty-seven patients (42.2%) reported cutaneous toxicity of any type, mainly hyperkeratosis (14.8%) and rash (11.9%). The most frequent adverse events were pyrexia (27.4%), asthenia (19.3%), arthralgia (16.9%), and diarrhoea (13.2%).Our results suggest that both dabrafenib alone or in combination with trametinib are effective for compassionate use in terms of response and/or survival rates. However, differences in patients' prognostic features ought to be considered. No new findings were revealed regarding the safety profiles of either regimen. This is the first study to evaluate the efficacy of these 2 selective BRAF and mitogen-activated extracellular signal-regulated kinase inhibitors in a real-world setting in Spain.

Applicability of Zenith p-branch Standard Fenestrated Endograft in Our Series.

BACKGROUND: In the endovascular treatment of abdominal aortic aneurysm (AAA) with short or absent infrarenal neck, the delay in the availability of fenestrated device and its high cost, have led to the manufacture of standardized models. Another option is the endografts with stents in parallel; however, regulated criteria for their use and long-term studies are lacking. The aim of this study was to assessed whether the AAA treated with fenestrated device or stents in parallel in our department, complied with the characteristics for the placement of the new endograft p-branch(®). Furthermore, the differences between the p-branch and the implanted prosthesis were analyzed. METHODS: Single-center and descriptive study of 41 aneurysms treated consecutively from 2008 to 2015. The anatomic characteristics analyzed were: relative distances between the visceral arteries, time position, diameter in the sealing area and number of fenestrations, and its compatibility with the p-branch. RESULTS: The anatomic compatibility rate with the p-branch options was 73.2% (30 cases). Of the 11 incompatible cases, 6 were due to misalignment of the visceral branches, 2 due to the aortic neck diameter being greater, another because the femoral access was inappropriate, and 2 more due to the fenestration configuration. Of the 30 cases in which compatibility existed, in 12 (40%) the configuration used coincided with the p-branch. In 13 cases, the number of fenestrations was higher than those actually used, with 23 fenestrations carried out and 39 hypothetical fenestrations with the new endograft. In the 5 remaining cases, a fenestration for the celiac trunk was necessary to achieve an adequate seal. CONCLUSIONS: The p-branch could meet the needs of three-quarters of the aortic anatomies of our series, with favorable expectations on cost and waiting time. However, in most cases either a higher number of fenestrations are needed for visceral arteries or the proximal seal was shorter than would be ideal.

The effect of cross-linking on the molecular dynamics of the segmental and ß Johari-Goldstein processes in polyvinylpyrrolidone-based copolymers.

The effect of the cross-link density on the molecular dynamics of copolymers composed of vinylpyrrolidone (VP) and butyl acrylate (BA) was studied using differential scanning calorimetry (DSC) and dielectric relaxation spectroscopy (DRS). A single glass transition was detected by DSC measurements. The dielectric spectra exhibit conductive processes and three dipolar relaxations labeled as α, ß and γ in the decreasing order of temperatures. The cross-linker content affects both α and ß processes, but the fastest γ process is relatively unaffected. An increase of cross-linking produces a typical effect on the α process dynamics: (i) the glass transition temperature is increased, (ii) the dispersion is broadened, (iii) its strength is decreased and (iv) the relaxation times are increased. However, the ß process, which possesses typical features of a pure Johari-Goldstein relaxation, unexpectedly loses the intermolecular character for the highest cross-linker content.

Forced solid-state interactions for the selective "turn-on" fluorescence sensing of aluminum ions in water using a sensory polymer substrate.

Selective and sensitive solid sensory substrates for detecting Al(III) in pure water are reported. The material is a flexible polymer film that can be handled and exhibits gel behavior and membrane performance. The film features a chemically anchored salicylaldehyde benzoylhydrazone derivative as an aluminum ion fluorescence sensor. A novel procedure for measuring Al(III) at the ppb level using a single solution drop in 20 min was developed. In this procedure, a drop was allowed to enter the hydrophilic material for 15 min before a 5 min drying period. The process forced the Al(III) to interact with the sensory motifs within the membrane before measuring the fluorescence of the system. The limit of detection of Al(III) was 22 ppm. Furthermore, a water-soluble sensory polymer containing the same sensory motifs was developed with a limit of detection of Al(III) of 1.5 ppb, which was significantly lower than the Environmental Protection Agency recommendations for drinking water.

Vascular endothelial growth factor A (VEGFA) gene polymorphisms have an impact on survival in a subgroup of indolent patients with chronic lymphocytic leukemia.

Vascular endothelial growth factor (VEGF)-mediated angiogenesis contributes to the pathogenesis of B-cell chronic lymphocytic leukaemia (CLL). We investigated the impact of VEGFA gene diversity on the clinical outcome of patients with this disease. A VEGFA haplotype conformed by positions rs699947 (-1540C>A), rs833061 (-460T>C) and rs2010963 (405C>G) and two additional single-nucleotide polymorphisms (SNPs), rs3025039 (936C>T) and rs25648 (1032C>T), were analysed in 239 patients at the time of their CLL diagnosis. Here, we showed that homozygosity for rs699947/rs833061/rs2010963 ACG haplotype (ACG+/+ genotype) correlated with a reduced survival in CLL patients (ACG+/+ vs other genotypes: HR = 2.3, p = 0.002; recessive model). In multivariate analysis, the ACG+/+ genotype was identified as a novel independent prognostic factor (HR = 2.1, p = 0.005). Moreover, ACG homozygosity subdivided patients with CLL with otherwise indolent parameters into prognostic subgroups with different outcomes. Specifically, patients carrying the ACG+/+ genotype with mutated IgVH, very low and low-risk cytogenetics, initial clinical stage, CD38 negative status or early age at diagnosis showed a shorter survival (ACG+/+ vs other genotypes: HR = 3.5, p = 0.035; HR = 3.4, p = 0.001; HR = 2.2, p = 0.035; HR = 3.4, p = 0.0001 and HR = 3.1, p = 0.009, respectively). In conclusion, VEGFA ACG+/+ genotype confers an adverse effect in overall survival in CLL patients with an indolent course of the disease. These observations support the biological and prognostic implications of VEGFA genetics in CLL.

Different exosome cargo from plasma/bronchoalveolar lavage in non-small-cell lung cancer.

Tumor-derived exosomes mediate tumorigenesis by facilitating tumor growth, metastasis, development of drug resistance, and immunosuppression. However, little is known about the exosomes isolated from bronchoalveolar lavage (BAL) in patients with lung neoplasm. Exosomes isolated in plasma and BAL from 30 and 75 patients with tumor and nontumor pathology were quantified by acetylcholinesterase activity and characterized by Western Blot, Electron Microscopy, and Nanoparticle Tracking Analysis. Differences in exosome cargo were analyzed by miRNA quantitative PCR in pooled samples and validated in a second series of patients. More exosomes were detected in plasma than in BAL in both groups (P < 0.001). The most miRNAs evaluated by PCR array were detected in tumor plasma, tumor BAL, and nontumor BAL pools, but only 56% were detected in the nontumor plasma pool. Comparing the top miRNAs with the highest levels detected in each pool, we found close homology only between the BAL samples of the two pathologies. In tumor plasma, we found a higher percentage of miRNAs with increased levels than in tumor BAL or in nontumor plasma. The data reveal differences between BAL and plasma exosome amount and miRNA content.

Predictors of cervical bleeding after carotid endarterectomy.

BACKGROUND: The aim of this study is to determine the incidence of severe cervical bleeding requiring reintervention after carotid endarterectomy (CEA), to identify its predictive parameters, and to find out the influence of these on major complications. METHODS: This was a retrospective review of 502 CEAs carried out in 455 consecutive patients between 1995-2011 in our institution. The end points were: postoperative cervical bleeding that required reoperation and major postoperative complications (i.e., stroke, myocardial infarction, and death). Patients' demographics, antiplatelet and anticoagulant treatment, anaesthetic technique, surgical details, and perioperative management were registered. The end point predictors were univariate and multivariate analyzed. RESULTS: Neck bleeding after CEA occurred in 42 cases (8.4%), requiring reoperation in 28 cases (5.6%). In the univariate analysis, chronic anticoagulation and anticoagulation 24 hours before surgery were associated with reoperation for bleeding (16.6% vs. 4.8% [P = 0.02] and 17.8% vs. 4.7% [P = 0.014], respectively). The agent used for antiplatelet treatment before surgery was related to reoperation in the univariate analysis and was the only factor with statistical significance in the multivariate analysis: acetylsalicylic acid (ASA) 100 mg (2.4%), ASA 300 mg (1.5%), clopidogrel 75 mg (7.8%), ASA 100 mg associated with clopidogrel (3.3%), triflusal (5.5%), and ticlopidine (2.2%); there was a higher incidence of reoperation only in the group of patients who had taken clopidogrel 24 hours before CEA (4.7% vs. 1.05% [P = 0.06], respectively) but without statistical significance (odds ratio: 2; 95% confidence interval: 0.95-4.84). No reoperations were registered using vein patch compared to prosthetic patch (0% vs. 6.1% [P = 0.028]). Conversion to general anesthesia (22.2% vs. 4.9% [P = 0.014]) and noncontrollable postoperative hypertension (6.9% vs. 2.5% [P = 0.028]) were associated with a higher rate of reoperation. There were no statistically significant differences in the reoperation rates related to bleeding for anesthetic technique (local versus general), surgical procedure (classic endarterectomy versus eversion technique), type of prosthetic patch (Dacron/politetrafluoroethylene), use of shunt, intraoperative dose of heparin, protamine reversal, activated clotting time monitoring, or surgeon qualification level. The combined rate of stroke mortality was 2.6%. Reoperation for bleeding was not associated with an increased rate of thrombosis, stroke, death, or injury of cranial nerves. CONCLUSIONS: Postoperative severe bleeding after carotid surgery in our institution is not an uncommon complication. Its incidence is within the range reported in the literature, but it is not associated with major complications or mortality. Antiplatelet treatment with clopidogrel is the main risk factor associated with reintervention. Other factors, such as coagulation control, postoperative hypertension management, and the use of an autologous patch, could help reduce its incidence.

Endovascular repair of an iliac arteriovenous fistula secondary to perforation from a common iliac aneurysm in a patient with Ehler-Danlos syndrome.

BACKGROUND: Type IV Ehler-Danlos syndrome (EDS) patients are prone to life-threatening vascular complications. Surgical management of those complications is challenging owing to vessel wall fragility, which may result in hemorrhagic events and high mortality rates. Here we report a case of left common iliac aneurysm perforation of the ipsilateral iliac vein repaired using endovascular technique in a patient with EDS. METHOD AND RESULTS: A 54-year-old patient presented with heart failure symptoms that evolved over 1 week in association with left leg edema and steal syndrome due to a perforation of the left iliac vein caused by a left common iliac aneurysm. A thrombosed right common iliac aneurysm and several other visceral and peripheral aneurysms were discovered on computed tomographic scan at admission. An aortouniiliac stent graft was used to seal the fistula. After 18 months of follow-up, the patient remained asymptomatic. CONCLUSIONS: We suggest that endovascular therapy is useful to manage vascular complications in patients with EDS.

Estructura, correlatos y predictores del estrés por aculturación: El caso de personas refugiadas colombianas en Costa Rica / Structure, correlates and predictors of acculturation stress: A case study with colombian refugees in Costa Rica

Cien personas refugiadas colombianas completaron un cuestionario que medía el estrés experimentado durante el proceso de adaptación a la sociedad costarricense, las redes de apoyo construidas en Costa Rica, la frecuencia con que se han visto discriminadas y su nivel de salud mental. Los datos muestran que el estrés por aculturación se estructuran en cuatro dimensiones: el estrés experimentado por los preparativos para la salida, el estrés derivado de su condición de refugiados, el estrés experimentado ante las necesidades económicas y el estrés vivido ante los retos de la adaptación cultural a la sociedad costarricense. Los preparativos para la salida del país son los eventos de mayor estrés reportado. La discriminación percibida y los años de residencia en Costa Rica aparecieron como los principales predictores de los tipos de estrés posinmigración, una vez controlados los efectos de la salud y las redes de apoyo.

One hundred colombian refugees completed a questionnaire measuring the level of stress they have experienced during the process of adaptation to the Costa Rican society; the social networks they have built in Costa Rica; the frequency with which they have been discriminated against; and their mental health. Data show four dimensions for acculturative stress: the stress produced by the arrangements to leave Colombia; the stress derived from their status as refugees; the stress derived from their socioeconomic needs; and the stress resulting from coping with the demands of the social and cultural adaptation to the host society. Participants reported significant higher levels of stress when planning the emigration from Colombia. Perceived discrimination and years of residence in Costa Rica were the principal predictors of acculturative stress in Costa Rica, above and below of the effect of other potential predictors, as social networks and mental health.

The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for proteasome degradation.

The transcription factor SNAIL1 is a master regulator of epithelial to mesenchymal transition. SNAIL1 is a very unstable protein, and its levels are regulated by the E3 ubiquitin ligase beta-TrCP1 that interacts with SNAIL1 upon its phosphorylation by GSK-3beta. Here we show that SNAIL1 polyubiquitylation and degradation may occur in conditions precluding SNAIL1 phosphorylation by GSK-3beta, suggesting that additional E3 ligases participate in the control of SNAIL1 protein stability. In particular, we demonstrate that the F-box E3 ubiquitin ligase FBXl14 interacts with SNAIL1 and promotes its ubiquitylation and proteasome degradation independently of phosphorylation by GSK-3beta. In vivo, inhibition of FBXl14 using short hairpin RNA stabilizes both ectopically expressed and endogenous SNAIL1. Moreover, the expression of FBXl14 is potently down-regulated during hypoxia, a condition that increases the levels of SNAIL1 protein but not SNAIL1 mRNA. FBXL14 mRNA is decreased in tumors with a high expression of two proteins up-regulated in hypoxia, carbonic anhydrase 9 and TWIST1. In addition, Twist1 small interfering RNA prevents hypoxia-induced Fbxl14 down-regulation and SNAIL1 stabilization in NMuMG cells. Altogether, these results demonstrate the existence of an alternative mechanism controlling SNAIL1 protein levels relevant for the induction of SNAIL1 during hypoxia.

Extracellular tumor-related mRNA in plasma of lymphoma patients and survival implications.

BACKGROUND: We studied anomalous extracellular mRNAs in plasma from patients with diffuse large B-cell lymphoma (DLBCL) and their survival implications. mRNAs studied have been reported in the literature as markers of poor (BCL2, CCND2, MYC) and favorable outcome (LMO2, BCL6, FN1) in tumors. These markers were also analyzed in lymphoma tissues to test possible associations with their presence in plasma. METHODOLOGY/PRINCIPAL FINDINGS: mRNA from 42 plasma samples and 12 tumors from patients with DLBCL was analyzed by real-time PCR. Samples post-treatment were studied. The immunohistochemistry of BCL2 and BCL6 was defined. Presence of circulating tumor cells was determined by analyzing the clonality of the immunoglobulin heavy-chain genes by PCR. In DLBCL, MYC mRNA was associated with short overall survival. mRNA targets with unfavorable outcome in tumors were associated with characteristics indicative of poor prognosis, with partial treatment response and with short progression-free survival in patients with complete response. In patients with low IPI score, unfavorable mRNA targets were related to shorter overall survival, partial response, high LDH levels and death. mRNA disappeared in post-treatment samples of patients with complete response, and persisted in those with partial response or death. No associations were found between circulating tumor cells and plasma mRNA. Absence of BCL6 protein in tumors was associated with presence of unfavorable plasma mRNA. CONCLUSIONS/SIGNIFICANCE: Through a non-invasive procedure, tumor-derived mRNAs can be obtained in plasma. mRNA detected in plasma did not proceed from circulating tumor cells. In our study, unfavorable targets in plasma were associated with poor prognosis in B-cell lymphomas, mainly MYC mRNA. Moreover, the unfavorable targets in plasma could help us to classify patients with poor outcome within the good prognosis group according to IPI.

Giant melanoma and depression.

A 29-year-old female patient presented with a giant melanoma on the external side of the left arm and concomitant multiple visceral metastases. The patient also had major depression and had avoided a consultation despite the large size of the lesion, delaying the diagnosis and treatment of her melanoma, which as far as we know is the largest, primary cutaneous melanoma ever reported. Excision of the tumor was performed as a palliative treatment and she died 1 month later. Depression has been identified as a factor that can worsen the course of a disease, although in this case it could have been the direct consequence of the dermatologic process.

Endovascular treatment of a ruptured iliac aneurysm previously excluded.

We report a case of an isolated ruptured iliac artery aneurysm that had previously been treated, 25 months before, with iliac endovascular exclusion. Urgent computed tomographic (CT) scan showed the retroperitoneal hematoma and a type IA endoleak. On an emergency basis, at the operating room, an aortouni-iliac graft and femorofemoral crossover bypass were performed, successfully. This is a very rare but serious complication and requires careful indication and close follow-up with CT. In isolated common iliac artery aneurysms, the common iliac artery and distal aorta may tend to enlarge with failure of the endograft proximal attachment site and migration, thus leading to a late aneurysm rupture. A safe length and width, especially of the proximal sealing zone, should be accurately defined and closely followed up, or otherwise complete exclusion of the aortoiliac arteries should be considered.