Methodological limitations and recommendations in publications on migrant population health in Spain

El objetivo es describir las limitaciones y las recomendaciones metodológicas identificadas por los autores de artículos originales sobre inmigración y salud en España. Se realizó una revisión bibliográfica de artículos originales publicados en español e inglés entre 1998 y 2012, combinando descriptores de inmigración y salud. Se incluyeron 311 artículos; de ellos, 176 (56,6%) mencionaban limitaciones y 15 (4,8%) emitían recomendaciones. Entre las limitaciones más mencionadas destacan el reducido tamaño de las muestras, problemas de validez interna y representatividad de la muestra con infrarrepresentación o sobrerrepresentación de determinados grupos, problemas de validez de la información recogida y datos faltantes relacionados sobre todo con los instrumentos de medición, y ausencia de variables clave de ajuste o estratificación. En función de los resultados obtenidos, se proponen una serie de recomendaciones para minimizar las limitaciones habituales y avanzar en la calidad de los trabajos científicos sobre inmigración y salud en nuestro ámbito.Our objective was to describe the methodological limitations and recommendations identified by authors of original articles on immigration and health in Spain. A literature review was conducted of original articles published in Spanish or English between 1998 and 2012 combining keywords on immigration and health. A total of 311 articles were included; of these, 176 (56.6%) mentioned limitations, and 15 (4.8%) made recommendations. The most frequently mentioned limitations included the following: reduced sample sizes; internal validity and sample representativeness issues, with under- or overrepresentation of specific groups; problems of validity of the collected information and missing data mostly related to measurement tools; and absence of key variables for adjustment or stratification. Based on these results, a series of recommendations are proposed to minimise common limitations and advance the quality of scientific production on immigration and health in our setting.El Subprograma Inmigración y Salud (SIS) del CIBER de Epidemiología y Salud Pública (CIBERESP) financió la realización de la revisión bibliográfica. La Sociedad Española de Epidemiología (SEE) financió los gastos derivados de la publicación

Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1

Prognostic impact; Mutation; Acute myeloid leukemiaImpacte pronòstic; Mutació; Leucèmia mieloide agudaImpacto pronóstico; Mutación; Leucemia mieloide agudaThe negative prognostic impact of internal tandem duplication of FLT3 (FLT3-ITD) in patients with acute myeloid leukemia with mutated NPM1 (AML-NPM1) is restricted to those with a higher FLT3-ITD allelic ratio (FLT3high; ≥0.5) and considered negligible in those with a wild-type (FLT3WT)/low ITD ratio (FLT3low). Because the comutation of DNMT3A (DNMT3Amut) has been suggested to negatively influence prognosis in AML-NPM1, we analyzed the impact of DNMT3Amut in FLT3-ITD subsets (absent, low, and high ratios). A total of 164 patients diagnosed with AML-NPM1 included in 2 consecutive CETLAM protocols and with DNMT3A and FLT3 status available were studied. Overall, DNMT3Amut status did not have a prognostic impact, with comparable overall survival (P = .2). Prognostic stratification established by FLT3-ITD (FLT3WT = FLT3low > FLT3high) was independent of DNMT3Amut status. Measurable residual disease (MRD) based on NPM1 quantitative polymerase chain reaction was available for 94 patients. DNMT3Amut was associated with a higher number of mutated NPM1 transcripts after induction (P = .012) and first consolidation (C1; P < .001). All DNMT3Amut patients were MRD+ after C1 (P < .001) and exhibited significant MRD persistence after C2 and C3 (MRD+ vs MRD−; P = .027 and P = .001, respectively). Finally, DNMT3Amut patients exhibited a trend toward greater risk of molecular relapse (P = .054). In conclusion, DNMT3Amut did not modify the overall prognosis exerted by FLT3-ITD in AML-NPM1 despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention.This work was supported in part by the Biomedical Research Institute (IIB Sant-Pau) and the José Carreras Leukemia Research Institute as well as grants from the Catalan Government (PERIS SLT002/16/0043 and AGAUR 2017 SGR 139) and the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain (PI17/01246, PI20/01621 and CM20/00061)

Adapting cord blood collection and banking Standard Operating Procedures for HLA-homozygous induced Pluripotent Stem Cells production and banking for clinical application

In this article, we will discuss the main aspects to be considered to define standard operation procedures (SOPs) for the creation of an induced pluripotent stem cell (iPSC) bank using cord blood (CB)-or similar cell type-bank guidelines for clinical aims. To do this, we adapt the pre-existing SOP for CB banking that can be complementary for iPSCs. Some aspects of iPSC manufacturing and the particular nature of these cells call for special attention, such as the potential multiple applications of the cells, proper explanation to the donor for consent of use, the genomic stability and the risk of genetic privacy disclosure. Some aspects of the iPSC SOP are solidly established by CB banking procedures, other procedures have good consensus in the scientific and medical community, while others still need to be further debated and settled. Given the international sharing vocation of iPSC banking, there is an urgent need by scientists, clinicians and regulators internationally to harmonize standards and allow future sample interchange between many iPSC bank initiatives that are springing up worldwide

Control of Therapeutic Levels of Anticoagulation and Associated Factors: A Prospective Cohort Study

Teràpia anticoagulant; Vitamin K; Estudis de cohortsTerapia anticoagulante; Vitamin K; Estudios de cohortesAnticoagulant therapy; Vitamin K; Cohort StudiesMaintaining therapeutic levels of anticoagulation is essential to avoid health complications in people who take vitamin K antagonists. This study aimed to analyze the influence of people’s characteristics and the presence of changes in their lives in the control of therapeutic levels of anticoagulation. A longitudinal multicenter study with a 1-year follow-up of a cohort of 199 people receiving anticoagulant therapy was performed. The effect of biological, clinical, social, lifestyle, and changes in life on the international normalized ratio (INR) was analyzed. During the follow-up, 46.7% of participants presented good INR control. At baseline, a diagnosis of atrial fibrillation (P = .00), the lack of comorbidities (P = .03), absence of depression (P = .04), and not following a pharmacological treatment with hypoglycemia drugs (P = .01) were associated with good INR control. During the follow-up, the variable of making changes to the usual diet was associated with poor INR control (P = .05). In the binary multiple regression model, factors associated with poor control were taking hypoglycemia drugs (P = .02) and the presence of depression (P = .04), and only the diagnosis of atrial fibrillation was associated with good control (P = .03). People with a diagnosis of atrial fibrillation had good INR control. Having comorbidities, suffering depression, taking hypoglycemia drugs, and making changes to the diet have a negative effect on INR control

Dendritic Cells From the Cervical Mucosa Capture and Transfer HIV-1 via Siglec-1

HIV-1; Siglec-1; CervixVIH-1; Siglec-1; CèrvixVIH-1; Siglec-1; CérvixAntigen presenting cells from the cervical mucosa are thought to amplify incoming HIV-1 and spread infection systemically without being productively infected. Yet, the molecular mechanism at the cervical mucosa underlying this viral transmission pathway remains unknown. Here we identified a subset of HLA-DR+ CD14+ CD11c+ cervical DCs at the lamina propria of the ectocervix and the endocervix that expressed the type-I interferon inducible lectin Siglec-1 (CD169), which promoted viral uptake. In the cervical biopsy of a viremic HIV-1+ patient, Siglec-1+ cells harbored HIV-1-containing compartments, demonstrating that in vivo, these cells trap viruses. Ex vivo, a type-I interferon antiviral environment enhanced viral capture and trans-infection via Siglec-1. Nonetheless, HIV-1 transfer via cervical DCs was effectively prevented with antibodies against Siglec-1. Our findings contribute to decipher how cervical DCs may boost HIV-1 replication and promote systemic viral spread from the cervical mucosa, and highlight the importance of including inhibitors against Siglec-1 in microbicidal strategies

Development of a full-genome cDNA clone of Citrus leaf blotch virus and infection of citrus plants

Citrus leaf blotch virus (CLBV), a member of the family Flexiviridae, has a similar to 9-kb single-stranded, positive-sense genomic RNA encapsidated by a 41-kDa coat protein. CLBV isolates are associated with symptom production in citrus including leaf blotching of Dweet tangor and stem pitting in Etrog citron (Dweet mottle disease), and some isolates are associated with bud union crease on trifoliate rootstocks, but Koch&#39;s postulates for this virus were not fulfilled. A full-genome cDNA of CLBV isolate SRA-153, which induces bud union crease, was placed under the T7 promoter (clone T7-CLBV), or between the 35S promoter and the Nos-t terminator, with or without a ribozyme sequence downstream of the CLBV sequence (clones 35SRbz-CLBV and 35S-CLBV). RNA transcripts from T7-CLBV failed to infect Etrog citron and Nicotiana occidentalis and N. benthamiana plants, whereas agro-inoculation with binary vectors carrying 35SRbz-CLBV or 35S-CLBV, and the p19 silencing suppressor, caused systemic infection and production of normal CLBV virions. Virus accumulation was similar in citron plants directly agro-infiltrated, or mechanically inoculated with wild-type or 35SRbz-CLBV-derived virions from Nicotiana, and the three sources incited the symptoms characteristic of Dweet mottle disease, but not bud union crease. Our results show that (1) virions derived from an infectious clone show the same replication, movement and pathogenicity characteristics as the wild-type CLBV; (2) CLBV is the causal agent of Dweet mottle disease but not of the bud union crease syndrome; and (3) for the first time an RNA virus could be successfully agro-inoculated on citrus plants. This infectious clone may become a useful viral vector for citrus genomic studies

Citrus leaf blotch virus invades meristematic regions in Nicotiana benthamiana and citrus.

To invade systemically host plants, viruses need to replicate in the infected cells, spread to neighbouring cells through plasmodesmata and move to distal parts of the plant via sieve tubes to start new infection foci. To monitor the infection of Nicotiana benthamiana plants by Citrus leaf blotch virus (CLBV), leaves were agroinoculated with an infectious cDNA clone of the CLBV genomic RNA expressing green fluorescent protein (GFP) under the transcriptional control of a duplicate promoter of the coat protein subgenomic RNA. Fluorescent spots first appeared in agroinfiltrated leaves 11-12 days after infiltration, indicating CLBV replication. Then, after entering the phloem vascular system, CLBV was unloaded in the upper parts of the plant and invaded all tissues, including flower organs and meristems. GFP fluorescence was not visible in citrus plants infected with CLBV-GFP. Therefore, to detect CLBV in meristematic regions, Mexican lime (Citrus aurantifolia) plants were graft inoculated with CLBV, with Citrus tristeza virus (CTV), a virus readily eliminated by shoot-tip grafting invitro, or with both simultaneously. Although CLBV was detected by hybridization and real-time reverse transcription-polymerase chain reaction (RT-PCR) in 0.2-mm shoot tips in all CLBV-inoculated plants, CTV was not detected. These results explain the difficulty in eliminating CLBV by shoot-tip grafting invitro

Bone Marrow Clonogenic Myeloid Progenitors from NPM1-Mutated AML Patients Do Not Harbor the NPM1 Mutation: Implication for the Cell-Of-Origin of NPM1+ AML

The cell-of-origin of NPM1- and FLT3-mutated acute myeloid leukemia (AML) is still a matter of debate. Here, we combined in vitro clonogenic assays with targeted sequencing to gain further insights into the cell-of-origin of NPM1 and FLT3-ITD-mutated AML in diagnostic bone marrow (BM) from nine NPM1+/FLT3-ITD (+/-) AMLs. We reasoned that individually plucked colony forming units (CFUs) are clonal and reflect the progeny of a single stem/progenitor cell. NPM1 and FLT3-ITD mutations seen in the diagnostic blasts were found in only 2/95 and 1/57 individually plucked CFUs, suggesting that BM clonogenic myeloid progenitors in NPM1-mutated and NPM1/FLT3-ITD-mutated AML patients do not harbor such molecular lesions. This supports previous studies on NPM1 mutations as secondary mutations in AML, likely acquired in an expanded pool of committed myeloid progenitors, perhaps CD34-, in line with the CD34-/low phenotype of NPM1-mutated AMLs. This study has important implications on the cell-of-origin of NPM1+ AML, and reinforces that therapeutic targeting of either NPM1 or FLT3-ITD mutations might only have a transient clinical benefit in debulking the leukemia, but is unlikely to be curative since will not target the AML-initiating/preleukemic cells. The absence of NPM1 and FLT3-ITD mutations in normal clonogenic myeloid progenitors is in line with their absence in clonal hematopoiesis of indeterminate potential.We thank CERCA/Generalitat de Catalunya and Fundació Josep Carreras-Obra Social la Caixa for their institutional support. Financial support for this work was obtained from the Generalitat de Catalunya (SGR330) to P.M., the Spanish Ministry of Economy and Competitiveness (SAF2016-80481-R to P.M. and SAF2016-76758-R to I.V.), the Fundación Uno entre Cienmil, the Obra Social La Caixa (ID 100010434, under agreement LCF/PR/HR19/52160011), the Josep Carreras Foundation, the Leo Messi Foundation, and the Banco Santander Foundation to P.M.; and the Spanish Association against cancer (AECC-CI-2015) to C.B. E.A. acknowledges support form “Fundación Hay Esperanza”. P.M. is an investigator of the Spanish Cell Therapy cooperative network (TERCEL)