Hidden variables with nonlocal time

To relax the apparent tension between nonlocal hidden variables and relativity, we propose that the observable proper time is not the same quantity as the usual proper-time parameter appearing in local relativistic equations. Instead, the two proper times are related by a nonlocal rescaling parameter proportional to |psi|^2, so that they coincide in the classical limit. In this way particle trajectories may obey local relativistic equations of motion in a manner consistent with the appearance of nonlocal quantum correlations. To illustrate the main idea, we first present two simple toy models of local particle trajectories with nonlocal time, which reproduce some nonlocal quantum phenomena. After that, we present a realistic theory with a capacity to reproduce all predictions of quantum theory.Comment: 16 pages, accepted for publication in Found. Phys., misprints corrected, references update

A randomized study of nutritional supplementation in patients with unilateral wet age-related macular degeneration

The purpose of this study is evaluate the efficacy and safety of medicinal products con-taining the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, random-ized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of -1.63 (95% CI -0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Prostate Cancer Susceptibility Loci Identified on Chromosome 12 in African Americans

Prostate cancer (PCa) is a complex disease that disproportionately affects African Americans and other individuals of African descent. A number of regions across the genome have been associated to PCa, most of them with moderate effects. A few studies have reported chromosomal changes on 12p and 12q that occur during the onset and development of PCa but to date no consistent association of the disease with chromosome 12 polymorphic variation has been identified. In order to unravel genetic risk factors that underlie PCa health disparities we investigated chromosome 12 using ancestry informative markers (AIMs), which allow us to distinguish genomic regions of European or West African origin, and tested them for association with PCa. Additional SNPs were genotyped in those areas where significant signals of association were detected. The strongest signal was discovered at the SNP rs12827748, located upstream of the PAWR gene, a tumor suppressor, which is amply expressed in the prostate. The most frequent allele in Europeans was the risk allele among African Americans. We also examined vitamin D related genes, VDR and CYP27B1, and found a significant association of PCa with the TaqI polymorphism (rs731236) in the former. Although our results warrant further investigation we have uncovered a genetic susceptibility factor for PCa in a likely candidate by means of an approach that takes advantage of the differential contribution of parental groups to an admixed population

Optimization of Pathogenicity Tests for Selection of Native Isolates of Entomopathogenic Fungi Isolated from Citrusgrowing Areas of México on Adults ofDiaphorina citriKuwayama (Hemiptera: Liviidae)

Huanglonbing (HLB), es considerado una de las más letales enfermedades de los cítricos alrededor del mundo, y ha alcanzado las principales áreas de producción de limón Mexicano (Citrus latifolia Tanaka) en la costa del pacifico de México. Los productores han iniciado el uso de insecticidas para controlar las poblaciones del psílido asiático de los cítricos, Diaphorina citri Kuwayama (Hemiptera: Liviidae), el vector del patógeno ‘Candidatus Liberibacter asiaticus’ asociado con el HLB. Actualmente los costos de los insecticidas y los efectos secundarios de su uso son las principales preocupaciones, ya que podrían perjudicar la estrategia de manejo contra el vector; y por lo tanto, alternativas ecológicas y económicamente viables a los insecticidas convencionales serian necesarias a corto plazo. Por tanto, el objetivo de este estudio fue evaluar la patogenicidad de 27 aislados nativos y 3 cepas de hongos entomopatógenos para determinar su potencial como agentes de control biológico sobre Diaphorina citri usando 2 diferentes métodos de bioensayo. Los bioensayos fueron realizados bajo condiciones de laboratorio (26 ± 2 °C, 60 ± 5% H.R y 16:8 h L:O) mediante la exposición de insectos adultos a una concentración de 1 × 108 conidios por mililitro utilizando 2 diferentes métodos de aplicación, es decir, por asperjado de esporas en las plántulas de cítricos y por asperjado directo a los psílidos adultos. Los resultados mostraron que para el asperjado directo a los adultos los aislados HIB-24 (B. bassiana) y HIB-32 (I. fumosorosea) mostraron el mayor porcentaje de mortalidad (60.66%). Respecto al asperjado de plántulas el aislado HIB-19 (I. fumosorosea) mostró el mayor porcentaje de mortalidad (62.02%). Los resultados de este estudio demuestran el potencial para el uso de hongos entomopatógenos en el manejo de D. citri en México. ABSTRACT Huanglongbing (HLB), considered one of the most lethal diseases of citrus worldwide, has reached the main areas of Mexican lime (Citrus latifolia Tanaka) fruit production on the Pacific coast of México. Growers have initiated intensive use of insecticides in order to control populations of the Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), the vector of the pathogen, ‘Candidatus Liberibacter asiaticus’ associated with huanglongbing. Presently, costs of insecticides and the side effects of their use are major concerns, because they could impair the management strategy against the vector; and thus, ecologically and economically viable alternatives to conventional insecticides are required in the short term. Therefore the goal of this study was to evaluate the pathogenicity of 27 native isolates and 3 strains of entomopathogenic fungi and determine their potential as biological control agents of D. citri by using 2 different bioassay methods. Bioassays were performed under laboratory conditions (26 ± 2 °C, 60 ± 5% RH and 16:8 h L:D) by exposing adult insects to a concentration of 1 × 108 conidia per milliliter using 2 different application methods, i.e., spraying the spores onto the citrus seedlings and spraying the spores directly onto the adult psyllids. The results showed that by direct spraying the adults, HIB-24 (B. bassiana) and HIB-32 (I. fumosorosea) isolates showed the highest mortality (60.66%). Regarding spraying of the seedlings, HIB-19 (I. fumosorosea) showed the highest percentage of mortality (62.02%). The results from this study demonstrate potential for using entomopathogenic fungi in the management of D. citri in México

Production of HIV Particles Is Regulated by Altering Sub-Cellular Localization and Dynamics of Rev Induced by Double-Strand RNA Binding Protein

Human immunodeficiency virus (HIV)-1 encoded Rev is essential for export from the nucleus to the cytoplasm, of unspliced and singly spliced transcripts coding for structural and nonstructural viral proteins. This process is spatially and temporally coordinated resulting from the interactions between cellular and viral proteins. Here we examined the effects of the sub-cellular localization and dynamics of Rev on the efficiency of nucleocytoplasmic transport of HIV-1 Gag transcripts and virus particle production. Using confocal microscopy and fluorescence recovery after bleaching (FRAP), we report that NF90ctv, a cellular protein involved in Rev function, alters both the sub-cellular localization and dynamics of Rev in vivo, which drastically affects the accumulation of the viral protein p24. The CRM1–dependent nuclear export of Gag mRNA linked to the Rev Response Element (RRE) is dependent on specific domains of the NF90ctv protein. Taken together, our results demonstrate that the appropriate intracellular localization and dynamics of Rev could regulate Gag assembly and HIV-1 replication

Persistent Oxytetracycline Exposure Induces an Inflammatory Process That Improves Regenerative Capacity in Zebrafish Larvae

BACKGROUND: The excessive use of antibiotics in aquaculture can adversely affect not only the environment, but also fish themselves. In this regard, there is evidence that some antibiotics can activate the immune system and reduce their effectiveness. None of those studies consider in detail the adverse inflammatory effect that the antibiotic remaining in the water may cause to the fish. In this work, we use the zebrafish to analyze quantitatively the effects of persistent exposure to oxytetracycline, the most common antibiotic used in fish farming. METHODOLOGY: We developed a quantitative assay in which we exposed zebrafish larvae to oxytetracycline for a period of 24 to 96 hrs. In order to determinate if the exposure causes any inflammation reaction, we evaluated neutrophils infiltration and quantified their total number analyzing the Tg(mpx:GFP)(i114) transgenic line by fluorescence stereoscope, microscope and flow cytometry respectively. On the other hand, we characterized the process at a molecular level by analyzing several immune markers (il-1β, il-10, lysC, mpx, cyp1a) at different time points by qPCR. Finally, we evaluated the influence of the inflammation triggered by oxytetracycline on the regeneration capacity in the lateral line. CONCLUSIONS: Our results suggest that after 48 hours of exposure, the oxytetracycline triggered a widespread inflammation process that persisted until 96 hours of exposure. Interestingly, larvae that developed an inflammation process showed an improved regeneration capacity in the mechanosensory system lateral line

Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy:Results of the EUROCONDOR Clinical Trial

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit

Deep-Sequencing Analysis of the Mouse Transcriptome Response to Infection with Brucella melitensis Strains of Differing Virulence

Brucella melitensis is an important zoonotic pathogen that causes brucellosis, a disease that affects sheep, cattle and occasionally humans. B. melitensis strain M5-90, a live attenuated vaccine cultured from B. melitensis strain M28, has been used as an effective tool in the control of brucellosis in goats and sheep in China. However, the molecular changes leading to attenuated virulence and pathogenicity in B. melitensis remain poorly understood. In this study we employed the Illumina Genome Analyzer platform to perform genome-wide digital gene expression (DGE) analysis of mouse peritoneal macrophage responses to B. melitensis infection. Many parallel changes in gene expression profiles were observed in M28- and M5-90-infected macrophages, suggesting that they employ similar survival strategies, notably the induction of anti-inflammatory and antiapoptotic factors. Moreover, 1019 differentially expressed macrophage transcripts were identified 4 h after infection with the different B. melitensis strains, and these differential transcripts notably identified genes involved in the lysosome and mitogen-activated protein kinase (MAPK) pathways. Further analysis employed gene ontology (GO) analysis: high-enrichment GOs identified endocytosis, inflammatory, apoptosis, and transport pathways. Path-Net and Signal-Net analysis highlighted the MAPK pathway as the key regulatory pathway. Moreover, the key differentially expressed genes of the significant pathways were apoptosis-related. These findings demonstrate previously unrecognized changes in gene transcription that are associated with B. melitensis infection of macrophages, and the central signaling pathways identified here merit further investigation. Our data provide new insights into the molecular attenuation mechanism of strain M5-90 and will facilitate the generation of new attenuated vaccine strains with enhanced efficacy