Proteomics Profiling of Chikungunya-Infected Aedes albopictus C6/36 Cells Reveal Important Mosquito Cell Factors in Virus Replication

10.1371/journal.pntd.0003544PLoS Neglected Tropical Diseases93e000354

Assessment of fibrosis and vascularization of bone marrow stroma of chronic myeloid Leukemia patients treated with imatinib mesylate and their relationship with the cytogenetic response

Chronic Myeloid Leukemia (CML) is a myeloproliferative disease characterized by the presence of the Philadelphia chromosome (translocation between chromosomes 9 and 22), resulting in the formation of the hybrid BCR-ABL protein. Currently, the treatment of CML patients is performed with imatinib mesylate (IM), which promotes the elimination of leukemic cells by inhibiting the kinase activity of BCR-ABL. This study evaluated the effectiveness of IM by monitoring 22 CML patients in a chronic phase treated at the CEPON/SC with IM for a minimum follow-up period of two years. Cytogenetic Response (CR) and bone marrow biopsies (BMB) were evaluated before and after IM treatment. BMB were evaluated by detection of reticulin degree and vascularization. The results were correlated to the CR. Mean time to achieve CR was 9 months and was attained by 77.27% of the patients. The results from the initial BMB analysis showed that 59.09% presented reticulin of between 2+ and 4+ whereas after treatment, only 27.17% presented this degree. With regard to vascularization of the initial sample, 90.91% were graded between II and IV, whereas after treatment, 40.91% had this degree. The results suggest a positive correlation of degree of reticulin and vascularization with CR.A Leucemia Mielóide Crônica (LMC) é uma doença mieloproliferativa caracterizada pela presença do cromossomo Filadélfia (translocação entre os cromossomos 9 e 22), que resulta na formação da proteína híbrida BCR-ABL. Atualmente o tratamento de pacientes com LMC é realizado com mesilato de imatinibe (MI), o qual promove a eliminação das células leucêmicas pela inibição da atividade quinase de BCR-ABL. O presente estudo avaliou a eficácia do MI por meio do acompanhamento de pacientes portadores de LMC em fase crônica, atendidos no CEPON/SC tratados com MI pelo tempo mínimo de dois anos. Foram avaliadas a Resposta Citogenética (RC) e as biópsias de medula óssea (BMO) antes e após o tratamento com MI. As BMO foram avaliadas quanto ao grau de reticulina e vascularização. Os resultados correlacionaram-se com a RC cujo tempo médio para obtenção da RC foi de 9 meses, sendo atingida por 77.27% dos pacientes. Na primeira BMO, 59.09% dos pacientes apresentaram grau de reticulina entre 2+ e 4+ e após o tratamento, apenas 27.17% apresentaram esta graduação. Quanto à vascularização da primeira amostra, 90.91% foram graduadas entre II e IV e após o tratamento, 40.91% apresentaram esta graduação. Os resultados sugerem uma correlação diretamente proporcional entre os graus de reticulina e vascularização com a RC

Tamizaje de enfermedades infecciosas en bancos de sangre, Colombia, 1995

As infectious diseases are the major cause of morbidity in Colombia, the objective of this study was to estimate the prevalence of blood transmitted diseases by screening tests in blood donors. Thus, the data collected from the National Blood-Bank Network as analysed. All records received during 1995 at the National Blood Banks' Coordination Centre from local blood banks al1 over the country were reviewed. Some variables such as: number of blood units obtained, number of blood units analysed and number of blood units reactive to HIV 112, hepatitis B and C viruses, human trophic lymphocyte virus, T pallidumand T cruziwere analysed. Epi lnfo 5.0. was used to analyse the data collected. 370,815 blood units were obtained from 172 blood banks. On average, the percentage of blood units analysed for markers such as HIV, hepatitis B and C viruses and T pallidum was higher than 99%; for other markers such as T cruziand HTLV 112 the percentages were 47% and 15%, respectively. Of the total blood units analysed, 0.3% were reactive to HIV-112, 1.2% to HTLV, 1 .O% to hepatitis C virus, 0.9% to hepatitis B virus, 1.2% to T cruz¡ and 1.4% to T. pallidum. These percentages correspond to national averages from reactive blood units analysed in all banks. Some blood banks reported values for anti-l: cruz; and HBsAg 4 times higher than the national average. The availability of blood units in this country is approximately 11 units per 1,000 inhabitants. 6.08% of screened blood units were reactive to any of the infectious agents described above. Blood screening was shown to be helpful in the prevention of infectious agents' transmission, at least, in the same number of infections per 100 possible transfusions. This analysis showed the need for better donor selection procedures at local blood banks in order to decrease infectious agents'transmission through blood transfusion.Con el fin de estimar la prevalencia de las enfermedades transmitidas por la sangre, mediante las pruebas de tamizaje en los donantes de sangre de los bancos del país, pertenecientes a la red nacional, se analizó la información enviada por los bancos de sangre en 1995 a la Coordinación Nacional de Bancos de Sangre en el Instituto Nacional de Salud. Se definieron como variables de estudio las siguientes: unidades de sangre obtenidas, unidades de sangre analizadas y unidades de sangre reactivas para anticuetpos contra el virus de inmunodeficiencia humana tipos 1 y 2 (VIH 1/2), el virus de hepatitis C (VHC), el virus linfotrópico humano (HTLV), Treponemapallidum (sífilis) y Typanosoma cruzi (enferrnedad de Chagas) y reactivas para el antígeno de superficie de hepatitis B (HBsAg); para el análisis, se utilizó el programa Epi-lnfo 5.1. Durante 1995, en Colombia se recolectaron 370.867 unidades de sangre en 172 bancos. En promedio, el porcentaje de sangre analizada por estos bancos fue superior a 99% para marcadores como VIH 112, HBsAg, VHC y Treponema pallidum; para otros marcadores como T: cruziy HTLV 112 fue de 47,9% y 15,1%, respectivamente. Del total de unidades de sangre analizadas por marcador, 0,3% presentó reactividad para VIH-112; para hepatitis B virus, 0,9%; para hepatitis C virus, 1 ,O%; para T cruz;, 1,2%; para 7: pallidum, 1,4% y para HTLV, 1,2%. Estos porcentajes corresponden a los promedios nacionales de unidades de sangre reactiva en los bancos del país. Los bancos de sangre de algunas seccionales informaron valores hasta cuatro veces superiores al promedio nacional para los marcadores anti-T: cruziy HBsAg. La disponibilidad de sangre en el país es de aproximadamente 11 unidades por cada mil habitantes. El tamizaje en las unidades de sangre detectó 6,08% de unidades de sangre reactivas; es decir que previno, por lo menos, la difusión de igual número de infecciones por cada 100 posibles transfusiones. Ei análisis de la información de los bancos de sangre en las seccionales del país, refleja la necesidad de mejorar los procesos de selección de donantes y brinda una aproximación acercadel comportamiento de estas patologías en la población general

Revisiting the Marrow Metabolic Changes after Chemotherapy in Lymphoma: A Step towards Personalized Care

Purpose. The aims were to correlate individual marrow metabolic changes after chemotherapy with bone marrow biopsy (BMBx) for its potential value of personalized care in lymphoma. Methods. 26 patients (mean age, 58 ± 15 y; 13 female, 13 male) with follicular lymphoma or diffuse large B-cell lymphoma, referred to FDG-PET/CT imaging, who had BMBx from unilateral or bilateral iliac crest(s) before chemotherapy, were studied retrospectively. The maximal standardized uptake value (SUV) was measured from BMBx site over the same area on both initial staging and first available restaging FDG-PET/CT scan. Results. 35 BMBx sites in 26 patients were evaluated. 12 of 35 sites were BMBx positive with interval decrease in SUV in 11 of 12 sites (92%). The remaining 23 of 35 sites were BMBx negative with interval increase in SUV in 21 of 23 sites (91%). The correlation between SUV change over the BMBx site before and after chemotherapy and BMBx result was significant (P < 0.0001). Conclusions. This preliminary result demonstrates a strong correlation between marrow metabolic changes (as determined by FDG PET) after chemotherapy and bone marrow involvement proven by biopsy. This may provide a retrospective means of personalized management of marrow involvement in deciding whether to deliver more extended therapy or closer followup of lymphoma patients

Genetic identification of a common collagen disease in Puerto Ricans via identity-by-descent mapping in a health system

Achieving confidence in the causality of a disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with both elevated genetic relatedness and extreme short stature. We link the gene, COL27A1, with a little-known genetic disease, previously thought to be rare and recessive. We demonstrate that disease manifests in both heterozygotes and homozygotes, indicating a common collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian disease

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping on the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710, C8197/A16565), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combination of the GWAS data was supported in part by the US National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative, grant 1 U19 CA148065-01 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.324

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library (MaStar) accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) survey which publicly releases infra-red spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the sub-survey Time Domain Spectroscopic Survey (TDSS) data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey (SPIDERS) sub-survey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated Value Added Catalogs (VACs). This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper (MWM), Local Volume Mapper (LVM) and Black Hole Mapper (BHM) surveys

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years