Global expression profiling of CD10 + /CD19 + pre-B lymphoblasts from Hispanic B-ALL patients correlates with comparative TARGET database analysis.

Mexico City has one of the highest incidences of acute lymphoblastic leukemia (ALL) globally, with patients showing low survival, and high relapse rates. To gain more insight into the molecular features of B-ALL in Mexican children, we isolated CD10 + /CD19 + precursor B lymphoblasts from four bone marrow and nine peripheral blood samples of B-ALL patients using a fluorescence-activated cell sorting protocol. The global gene expression profile (BM vs PB) revealed 136 differentially expressed genes; 62 were upregulated (45.6%) and 74 were downregulated (54.4%). Pearson's correlation coefficient was calculated to determine the similarity between pre-B lymphoblast populations. We selected 26 highly significant genes and validated 21 by RT-qPCR (CNN3, STON2, CALN1, RUNX2, GADD45A, CDC45, CDC20, PLK1, AIDA, HCK, LY86, GPR65, PIK3CG, LILRB2, IL7R, TCL1A, DOCK1, HIST1H3G, PTPN14, CD72, and NT5E). The gene set enrichment analysis of the total expression matrix and the ingenuity pathway analysis of the 136 differentially expressed genes showed that the cell cycle was altered in the bone marrow with four overexpressed genes (PLK1, CDC20, CDC45, and GADD45A) and a low expression of IL7R and PIK3CG, which are involved in B cell differentiation. A comparative bioinformatics analysis of 15 bone marrow and 10 peripheral blood samples from Hispanic B-ALL patients collected by the TARGET program, corroborated the genes observed, except for PIK3CG. We conclude the Mexican and the Hispanic B-ALL patients studied present common driver alterations and histotype-specific mutations that could facilitate risk stratification and diagnostic accuracy and serve as potential therapeutic targets.

One-Stage Lengthening and Minimally Invasive Distal Metatarsal Metaphyseal Osteotomy (DMMO) for Brachymetatarsia.

Level of Evidence: Level V.

Woody vegetation dynamics in the tropical and subtropical Andes from 2001 to 2014: Satellite image interpretation and expert validation.

The interactions between climate and land-use change are dictating the distribution of flora and fauna and reshuffling biotic community composition around the world. Tropical mountains are particularly sensitive because they often have a high human population density, a long history of agriculture, range-restricted species, and high-beta diversity due to a steep elevation gradient. Here we evaluated the change in distribution of woody vegetation in the tropical Andes of South America for the period 2001-2014. For the analyses we created annual land-cover/land-use maps using MODIS satellite data at 250 m pixel resolution, calculated the cover of woody vegetation (trees and shrubs) in 9,274 hexagons of 115.47 km2 , and then determined if there was a statistically significant (p < 0.05) 14 year linear trend (positive-forest gain, negative-forest loss) within each hexagon. Of the 1,308 hexagons with significant trends, 36.6% (n = 479) lost forests and 63.4% (n = 829) gained forests. We estimated an overall net gain of ~500,000 ha in woody vegetation. Forest loss dominated the 1,000-1,499 m elevation zone and forest gain dominated above 1,500 m. The most important transitions were forest loss at lower elevations for pastures and croplands, forest gain in abandoned pastures and cropland in mid-elevation areas, and shrub encroachment into highland grasslands. Expert validation confirmed the observed trends, but some areas of apparent forest gain were associated with new shade coffee, pine, or eucalypt plantations. In addition, after controlling for elevation and country, forest gain was associated with a decline in the rural population. Although we document an overall gain in forest cover, the recent reversal of forest gains in Colombia demonstrates that these coupled natural-human systems are highly dynamic and there is an urgent need of a regional real-time land-use, biodiversity, and ecosystem services monitoring network.

Venezuela's humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region.

In the past 5-10 years, Venezuela has faced a severe economic crisis, precipitated by political instability and declining oil revenue. Public health provision has been affected particularly. In this Review, we assess the impact of Venezuela's health-care crisis on vector-borne diseases, and the spillover into neighbouring countries. Between 2000 and 2015, Venezuela witnessed a 359% increase in malaria cases, followed by a 71% increase in 2017 (411 586 cases) compared with 2016 (240 613). Neighbouring countries, such as Brazil, have reported an escalating trend of imported malaria cases from Venezuela, from 1538 in 2014 to 3129 in 2017. In Venezuela, active Chagas disease transmission has been reported, with seroprevalence in children (<10 years), estimated to be as high as 12·5% in one community tested (n=64). Dengue incidence increased by more than four times between 1990 and 2016. The estimated incidence of chikungunya during its epidemic peak is 6975 cases per 100 000 people and that of Zika virus is 2057 cases per 100 000 people. The re-emergence of many vector-borne diseases represents a public health crisis in Venezuela and has the possibility of severely undermining regional disease elimination efforts. National, regional, and global authorities must take action to address these worsening epidemics and prevent their expansion beyond Venezuelan borders.

Gene Expression Profiling of Acute Lymphoblastic Leukemia in Children with Very Early Relapse.

BACKGROUND AND AIMS: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer worldwide. Mexican patients have high mortality rates, low frequency of good prognosis biomarkers (i.e., ETV6-RUNX1) and a high proportion is classified at the time of diagnosis with a high risk to relapse according to clinical features. In addition, very early relapses are more frequently observed than in other populations. The aim of the study was to identify new potential biomarkers associated with very early relapse in Mexican ALL children through transcriptome analysis. METHODS: Microarray gene expression profiling on bone marrow samples of 54 pediatric ALL patients, collected at time of diagnosis and/or at relapse, was performed. Eleven patients presented relapse within the first 18 months after diagnosis. Affymetrix Human Transcriptome Array 2.0 (HTA 2.0) was used to perform gene expression analysis. Annotation and functional enrichment analyses were carried out using Gene Ontology, KEGG pathway analysis and Ingenuity Pathway Analysis tools. RESULTS: BLVRB, ZCCHC7, PAX5, EBF1, TMOD1 and BLNK were differentially expressed (fold-change >2.0 and p value <0.01) between relapsed and non-relapsed patients. Functional analysis of abnormally expressed genes revealed their important role in cellular processes related to the development of hematological diseases, cancer, cell death and survival and in cell-to-cell signaling interaction. CONCLUSIONS: Our data support previous findings showing the relevance of PAX5, EBF1 and ZCCHC7 as potential biomarkers to identify a subgroup of ALL children in high risk to relapse.

Enfermedad de chagas sistémico en fase aguda por transmisión oral: diagnóstico integral de un caso autopsiado / Acute phase of systemic chagas disease due to oral transmission: integral diagnosis of an autopsied case

Se presenta el primer caso autopsiado en Venezuela con enfermedad de Chagas por transmisión oral. Se trata de una joven de 24 años de edad con 8 semanas de embarazo quien contrajo la enfermedad conjuntamente con 71 niños y 14 adultos, la mayoría integrantes de la comunidad escolar “Rómulo Monasterios” en la localidad de Chichiriviche de la costa Vargas, donde ocurrió el segundo brote agudo de enfermedad de Chagas por transmisión oral registrado en Venezuela. El diagnóstico epidemiológico, clínico, serológico y parasitológico en sangre y líquido pleural extraídos en vida, fueron confirmados con los hallazgos histopatológicos y moleculares (PCR) de los tejidos. Se plantearon las características peculiares del caso así como algunos aspectos de la transmisión oral, ampliamente estudiados en nuestro país en animales de experimentación.

This first autopsy case with Chagas disease by oral transmissions in Venezuela is presented. This is a 24 year old girl with 8 weeks of pregnancy who contracted the disease together with 71 and 14 adults, the majority members of the school community “Romulo Monasterios” in the town of Vargas State, where occurred the second acute Chagas disease outbreak by oral transmission in Venezuela.The epidemiological, clinical, serological and parasitological diagnosis in the blood and pleural fluid extracted in life, were confirmed with the histopathology and molecular (PCR) finding in the tissues, Special features of the case are shown, as well as, some aspects of oral transmission widely studied in our country in experimental animals.

Cloning and sequencing of the histidine decarboxylase gene from Photobacterium phosphoreum and its functional expression in Escherichia coli.

The major causative agent of scombroid poisoning is histamine formed by bacterial decarboxylation of histidine. We reported previously that histamine was exclusively formed by the psychrotrophic halophilic bacteria Photobacterium phosphoreum in scombroid fish during storage at or below 10 degrees C. Moreover, histamine-forming ability was affected by two histidine decarboxylases (HDCs): constitutive and inducible enzymes. In this study, the gene encoding P. phosphoreum HDC was cloned into Escherichia coli and sequenced. A sequence analysis of the DNA corresponding to the hdc gene revealed an open reading frame of 1,140 bp coding for a pyridoxal-5'-phosphate-dependent HDC of 380 amino acid residues with a predicted molecular mass of 42.6 kDa. The HDC amino acid sequences formed a phylogenetic clade with strong bootstrap support and revealed high sequence similarities among the P. phosphoreum isolate and species of the family Enterobacteriaceae and a separate phylogenetic branch with the lowest sequence similarity between the isolate and the taxonomically closer Listonella anguillarum. The T7 promoter was used to overexpress the hdc gene in E. coli cells. The recombinant clone, E. coli BL21(DE3), displayed significant levels of HDC activity. The recombinant hdc gene was suggested to code the inducible HDC; therefore, the optimum reaction conditions of the recombinant HDC were similar to those of the inducible HDC in the P. phosphoreum isolate. In addition, a putative catabolite-repressor protein binding site, amino acid permease gene, and histidine-tRNA synthetase gene were found in flanking regions of the hdc gene.

Criterios de cura en la enfermedad de chagas: interpretación de hallazgos parasitológicos serológicos y clínicos / Criterion of cure in chagas disease: interpretation discoveries parasitologicals, serologys and clinical

Uno de los aspectos más compelejos de la enfermedad de chagas es evaluar el efecto del tratamiento etiológico con relación a los resultados de las pruebas parasitológicas y serológicas, donde se necesita un seguimiento prolongado y los resultados obtenidos son en gran parte controversiales. Como criterios de evaluación del tratamiento (criterios de cura), se han empleado los cambios en la serología, la parasitemia y la evaluación clínica; mientras los primeros se pueden observar en meses, la evaluación clínica requiere años de control, hecho que ha desalentado a varios grupos de investigación. Para muchos, aunque no exista correlación clínica que lo confirme, aquellos pacientes tratados que cursan con una parasitemia y serología negativas, se consideran curados. Evidencia reciente muestra que otras técnicas han demostrado la persistencia del parásito en pacientes con chagas crónico y también en pacientes con enfermedad aguda que han recibido drogas contra el typanosoma cruzi. Más aún, el paciente agudo que ha sido tratado, existe poca correlación entre los hallazgos clínicos y la evidencia de daño miocárdico obtenido por biopsias endomiocárdicas y otros estudios, como el ecocardiograma y el cineventriculograma del ventrículo izquierdo. Lo anterior sugiere la necesidad de revaluar los criterios de cura en los pacientes con enfermedad de chagas que reciben tratamiento etiológico o donde se evaluarían nuevas drogas contra el parásito

Efectividad de la amlodipina en tratamiento de la isquemia miocárdica sintomática / Efficacy of amlodipine in the treatment of symptomatic myocardial ischemia

En un estudio abierto y no comparativo de 14 semanas de duración, se evalúa la eficacia y seguridad de un fármaco calcioantagonista, la amlodipina, en el control de los síntomas y mejoría de la calidad de vida en un grupo de pacientes con angina de esfuerzo. A 17 pacientes con criterios clínicos de angina de pecho, donde se documentó enfermedad arterial coronaria por cambios en el ECG y/O la coronariografía, se le administró amlodipina vía oral. En una primera fase (I) de 1 a 2 semanas se indica placebo y a partir de la 3a. semana (fase II) se comienza el uso del medicamento a 5mg/día. Sólo 12 pacientes completaron el seguimiento, a todos se les realizó una prueba de esfuerzo en la fase I y al final del estudio sólo a 9 pacientes. La calidad de vida se evaluó de acuerdo a una escala del 1 (limitado) al 10 (asintomático) y esta mejoró significativamente de 4,47 (I) a 7,9(II) (p>0,01); los episodios de angina promedio semanales disminuyeron de 5,5 (1) a 0,89(II) (P<0,01). El inicio promedio de la angina durante la prueba de esfuerzo en el I fue a los 189 seg. (ñ110) con una duración de 371 seg. (ñ132) y estos se modificaron en II a 346 seg. (ñ163) para el inicio y 172 segundos (ñ137) en la duración, ambos cambios significativos (p<0,05 y 0,01); de igual forma se encuentran cambios en el tiempo del inicio (119 vs 188 seg.) y la máxima depresión del segmento ST (244 vs 188 seg.) durante la prueba siendo la primera altamente significativa (p<0.0006). Sólo 3 pacientes presentaron efectos secundarios (cefalea y edema en miembros) que cedieron espontáneamente. En este grupo de pacientes con angina de esfuerzo, la amlodipina fue efectiva y segura en reducir el número de anginas por semana, retardar el tiempo de aparición durante el esfuerzo y disminuir la duración de los mismos