Ebola Preparedness and Risk in Latin America

Until today, February 22, 2016, no confirmed Ebola cases have been diagnosed in Americas (except USA, four cases with one death). Confusion, lack of knowledge, and fear have led to quickly misclassify cases as suspected, when in fact most of them are false alarms. Nevertheless, European governments summoned to mobilize resources to attend the Ebola outbreak in West Africa. And also Latin American governments should contribute to halt this humanitarian crisis and to be prepared for the potential arrival of this deadly virus in the Caribbean, Central, and South American mainland. In this chapter, we described the experience of preparedness as well as risk assessment done in Latin America regarding the threat of Ebola for the region

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Capture efficiency of magnetically labeled particles traveling through an intracranial aneurysm

Cell manipulation using external magnetic fields has been proposed to accelerate the neck reendothelization of saccular unruptured stented intracranial aneurysms. This work presents a computational fluid dynamics (CFD) model of a Saccular Brain Aneurysm that incorporates a helicoidal stent. An Eulerian-Lagrangian model implemented in ANSYS-Fluent is used to simulate the hemodynamics in the aneurysm. In silico studies have been conducted to describe the incidence of the magnetic field direction, frequency and amplitude on the blood hemodynamics and particle capture efficiency, when an external magnetic field is used to trap magnetically labeled particles traveling through the aneurysm. It is found that the magnetic field direction affects the particle concentration in the target region. Simulation results show that the highest particle capture efficiency is obtained with a 1T magnetic field amplitude in an open bore MRI scanner, when a permanent magnet is used

Capture Efficiency of Magnetically Labeled Particles Traveling Through an Intracranial Aneurysm

Cell manipulation using external magnetic fields has been proposed to accelerate the neck reendothelization of saccular unruptured stented intracranial aneurysms. This work presents a computational fluid dynamics (CFD) model of a Saccular Brain Aneurysm that incorporates a helicoidal stent. An Eulerian-Lagrangian model implemented in ANSYS-Fluent is used to simulate the hemodynamics in the aneurysm. In silico studies have been conducted to describe the incidence of the magnetic field direction, frequency and amplitude on the blood hemodynamics and particle capture efficiency, when an external magnetic field is used to trap magnetically labeled particles traveling through the aneurysm. It is found that the magnetic field direction affects the particle concentration in the target region. Simulation results show that the highest particle capture efficiency is obtained with a 1T magnetic field amplitude in an open bore MRI scanner, when a permanent magnet is used

Transcriptional signature of TP53 biallelic inactivation identifies a group of multiple myeloma patients without this genetic condition but with dismal outcome

Biallelic inactivation of TP53 has been included in the definition of double-hit (DH) multiple myeloma (MM), which entails an ominous prognosis. However, this condition, or even the presence of high-risk cytogenetic abnormalities, cannot accurately capture the 15%–20% of the MM population with a median overall survival below 24 months. This prompted us to look for other MM patients who might have transcriptional characteristics similar to those with DH-TP53. In the present study, we analysed RNA-seq, whole-genome and whole-exome sequencing data from 660 newly diagnosed MM (NDMM) patients from the MMRF (Multiple Myeloma Research Foundation) CoMMpass study to characterize the transcriptional signature of TP53 double-hit (DH-TP53) MM. We found 78 genes that were exclusively deregulated in DH-TP53 patients. A score based on these genes identified a group of 50 patients who shared the same transcriptional profile (DH-TP53-like group) whose prognosis was particularly unfavourable [median overall survival (OS) < 2 years], despite not harbouring the biallelic inactivation of TP53. The prognostic value of the DH-TP53 score was externally validated using gene expression data from 850 NDMM patients analysed by microarrays. Furthermore, our DH-TP53 score refined the traditional prognostic stratification of MM patients according to the cytogenetic abnormalities and International Staging System (ISS).This work has been supported by grants from the Instituto de Salud Carlos III (ISCIII) co-funded by European Union FEDER funds (projects PI16/01074 and PI19/00674), the Asociación Española Contra el Cáncer (grant PROYE20047GUTI) and the Gerencia Regional de Salud, Junta de Castilla y León (grants GRS 2058/A/19 and GRS 2331/A/21). Cristina De Ramón, Elizabeta A. Rojas and Ignacio J. Cardona-Benavides have been supported by the Asociación Española Contra el Cáncer (CLJUN18010DERA), the Consejería de Educación de Castilla y León and the Instituto de Salud Carlos III (PFIS-2020: FI20/00226), respectively. The authors thank the MMRF for access to the CoMMpass dataset

RNA sequencing identifies novel regulated IRE1-dependent decay targets that affect multiple myeloma survival and proliferation

[Background]: IRE1 is an unfolded protein response (UPR) sensor with kinase and endonuclease activity. It plays a central role in the endoplasmic reticulum (ER) stress response through unconventional splicing of XBP1 mRNA and regulated IRE1-dependent decay (RIDD). Multiple myeloma (MM) cells are known to exhibit an elevated level of baseline ER stress due to immunoglobulin production, however RIDD activity has not been well studied in this disease. In this study, we aimed to investigate the potential of RNA-sequencing in the identification of novel RIDD targets in MM cells and to analyze the role of these targets in MM cells.[Methods]: In vitro IRE1-cleavage assay was combined with RNA sequencing. The expression level of RIDD targets in MM cell lines was measured by real-time RT-PCR and Western blot.[Results]: Bioinformatic analysis revealed hundreds of putative IRE1 substrates in the in vitro assay, 32 of which were chosen for further validation. Looking into the secondary structure of IRE1 substrates, we found that the consensus sequences of IRF4, PRDM1, IKZF1, KLF13, NOTCH1, ATR, DICER, RICTOR, CDK12, FAM168B, and CENPF mRNAs were accompanied by a stem-loop structure essential for IRE1-mediated cleavage. In fact, we show that mRNA and protein levels corresponding to these targets were attenuated in an IRE1-dependent manner by treatment with ER-stress-inducing agents. In addition, a synergistic effect between IMiDs and ER-stress inducers was found.[Conclusion]: This study, using RNA sequencing, shows that IRE1 RNase has a broad range of mRNA substrates in myeloma cells and demonstrates for the first time that IRE1 is a key regulator of several proteins of importance in MM survival and proliferation.This study was partially supported by the Instituto de Salud Carlos III, co-financed by FEDER, “PI16/01074” and “PI19/00674”; the Gerencia Regional de Salud, Junta de Castilla y León grants “GRS 1833/A/18” and “GRS 2058/A/19″, and the "Asociación Española Contra el Cancer (AECC)”, PROYE20047GUTI. E.A.R. was supported by the Consejería de Educación de Castilla y León and FEDER funds. I.J.C.-B. was supported by a fellowship (contract PFIS-2020: FI20/00226) from the Instituto de Salud Carlos III

Additional file 5 of RNA sequencing identifies novel regulated IRE1-dependent decay targets that affect multiple myeloma survival and proliferation [Dataset]

Additional file 5: Fig. S3. Validation of putative IRE1 substrates. Exon-usage plots of the 28 remaining putative mRNAs, showing the number of reads in mock (red) and IRE1-treated (blue) samples. The black arrows represent the site of primers used in the 5´ region of the putative IRE1-substrates. Red arrows represent the site of primers mapping the predicted cleavage site. Right panel of each exon-usage plot shows the abundance of mRNA in the corresponding target. All results are presented as the means ± SD of three experiments. (*p < 0.05, **p < 0.01, ***p < 0.001).Instituto de Salud Carlos III Gerencia Regional de Salud, Junta de Castilla y León Asociación Española Contra el Cancer (AECC) Consejería de Educación, Junta de Castilla y LeónPeer reviewe