Criteria for efficient prevention of dissemination and successful eradication of Erwinia amylovora (the cause of fire blight) in Aragon, Spain

Erwinia amylovora was detected on pome fruits in the Aragon region (North-Eastern Spain), in a ca. 5 km radius area located in the mid Jalon river (mid Ebro Valley) in the province of Zaragoza, during 2000-2003. Eight years have now passed since this pathogen was last detected, without new infections being reported in the same area. The bases for surveys and rapid eradication performed have been analyzed in detail to understand the reasons for the success in removing fireblight. The results demonstrate that intensive surveillance, risk assessment, plant analyses using accurate identification methods, and, especially, rapid total or selective eradication of infected trees in the plots have been very effective in preventing the generalized spread of fireblight and in delaying economic losses associated with this disease. Eradication and compensation to growers, estimated to cost approx. (sic) 467,000, were clearly counterbalanced by the economic value of apple and pear production in the 2000-2003 period (approx. (sic) 368 million). Fire blight risk-assessment, using the MARYBLYT system, showed that climatic conditions in the studied area were favourable to infections during the analyzed period (1997-2006). Molecular characterization of E. amylovora strains had revealed their homogeneity, suggesting that these fire blight episodes could have been caused by just one inoculum source, supporting the hypothesis that there was a unique introduction of E. amylovora in the studied area. Spatial spread of E. amylovora to trees was analyzed within six orchards, indicating an aggregated distribution model. This Spanish experience demonstrates the success of scientifically-based prevention methods that lead to the deployment of a fast and strict containment strategy, useful for other Mediterranean areas

Criteria for efficient prevention of dissemination and successful eradication of Erwinia amylovora (the cause of fire blight) in Aragon, Spain

Erwinia amylovora was detected on pome fruits in the Aragon region (North-Eastern Spain), in a ca. 5 km radius area located in the mid Jalon river (mid Ebro Valley) in the province of Zaragoza, during 2000-2003. Eight years have now passed since this pathogen was last detected, without new infections being reported in the same area. The bases for surveys and rapid eradication performed have been analyzed in detail to understand the reasons for the success in removing fireblight. The results demonstrate that intensive surveillance, risk assessment, plant analyses using accurate identification methods, and, especially, rapid total or selective eradication of infected trees in the plots have been very effective in preventing the generalized spread of fireblight and in delaying economic losses associated with this disease. Eradication and compensation to growers, estimated to cost approx. (sic) 467,000, were clearly counterbalanced by the economic value of apple and pear production in the 2000-2003 period (approx. (sic) 368 million). Fire blight risk-assessment, using the MARYBLYT system, showed that climatic conditions in the studied area were favourable to infections during the analyzed period (1997-2006). Molecular characterization of E. amylovora strains had revealed their homogeneity, suggesting that these fire blight episodes could have been caused by just one inoculum source, supporting the hypothesis that there was a unique introduction of E. amylovora in the studied area. Spatial spread of E. amylovora to trees was analyzed within six orchards, indicating an aggregated distribution model. This Spanish experience demonstrates the success of scientifically-based prevention methods that lead to the deployment of a fast and strict containment strategy, useful for other Mediterranean areas

Use of simple noninvasive biomarkers to predict liver fibrosis in HIV/HCV coinfection in routine clinical practice

This study was supported by a grant from Abbott Laboratories. The authors wish to thank the Spanish Health Ministry (ISCIII-RETIC RD06/006) for financial support.Background Simple noninvasive tests to predict fibrosis, as an alternative to liver biopsy (LB), are needed. Of these, the aspartate aminotransferase (AST) to platelet ratio index (APRI) and the Forns index (FI) have been validated in HIV/hepatitis C virus (HCV) coinfection. However, these indexes may have lower diagnostic value in situations other than the circumscribed conditions of validation studies. We therefore examined the value of the APRI and FI in HIV/HCV-coinfected patients for the detection of significant fibrosis in real-life conditions. Patients and methods HIV/HCV-coinfected patients who had participated in a multicentre cross-sectional retrospective study were selected if they had undergone an LB within 24 months before the last visit. The predictive accuracy of the APRI and FI was measured using the areas under receiver-operating-characteristic curves (AUROCs). Diagnostic accuracy was determined using the positive (PPV) and negative (NPV) predictive values. Results A total of 519 coinfected individuals were included in the study. The AUROC [95% confidence interval (95% CI)] of the APRI was 0.67 (0.66–0.71) and that of the FI was 0.67 (0.62–0.71). The PPV of the APRI was 79% and its NPV was 66%. The PPV of the FI was 74% and its NPV was 64%. LB length was available and was ≥15 mm in 120 individuals. In this group, the PPV of the APRI was 85%, and that of the FI was 81%. Using these indexes, 22% of patients could be spared LB. Applying both models sequentially, 30% of patients could be spared LB. Conclusions In HIV/HCV-coinfected patients, the diagnostic accuracy of the APRI in real-life conditions was similar to that in the validation studies. The FI performed less well. However, combining the two indexes to make decisions on anti-HCV therapy may prevent a significant proportion of patients from having to undergo LB.Abbott LaboratoriesSpanish Health Ministry (ISCIII-RETIC RD06/006

Optomechanical devides for mechanobiological fingerprinting

Resumen del trabajo presentado en el Frontiers of Nanomechanical Systems (FSN2021), celebraod de forma virtual del 19 al 21 de enero de 2021Twenty years have passed since the first detection of biomolecular recognition using micromechanical systems[1]. In the last two decades, micro- nanomechanical systems have been refined to achieve amazing detection limits in force and mass that have enabled different schemes for ultrasensitive measurements of biological interactions as well as new ways of biological spectrometry. More recently, these figures of merit have been improved by coupling optical cavities to mechanical systems. In this talk, I will review the use of micro- nanomechanical systems for mechanobiological fingerprinting of biological entities, particularizing in the contributions of our group [2]. An essential core of this topic is the discussion about the mechanical coupling between a biological particle and a mechanical resonator, an issue that it is has been often oversimplified. We show that the biomechanical coupling that emerges between a bioparticle and a mechanical resonator is more complex than previously expect and it can give rise to different interaction regimes, in which the resonator response is dominated by different physical parameters of the analyte [3-4]. In particular, we will show experiments done with a variety of micro- nano- optomechanical systems using different measurement schemes where the mass, the stiffness and even the vibration modes of single biological entities can be measured with high sensitivity. It is now widely appreciated the essential role of mechanics in relevant biological processes and how disease can be revealed as changes in the mechanical properties of biological matter. I am pretty sure that future developments in optomechanical devices will contribute for major understanding of diseases as well as for new avenues in diagnosis and therapy

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Identification of candidate Parkinson disease genes by integrating genome-wide association study, expression, and epigenetic data sets

Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. Objective To investigate what genes and genomic processes underlie the risk of sporadic PD. Design and Setting This genetic association study used the bioinformatic tools Coloc and transcriptome-wide association study (TWAS) to integrate PD case-control GWAS data published in 2017 with expression data (from Braineac, the Genotype-Tissue Expression [GTEx], and CommonMind) and methylation data (derived from UK Parkinson brain samples) to uncover putative gene expression and splicing mechanisms associated with PD GWAS signals. Candidate genes were further characterized using cell-type specificity, weighted gene coexpression networks, and weighted protein-protein interaction networks. Main Outcomes and Measures It was hypothesized a priori that some genes underlying PD loci would alter PD risk through changes to expression, splicing, or methylation. Candidate genes are presented whose change in expression, splicing, or methylation are associated with risk of PD as well as the functional pathways and cell types in which these genes have an important role. Results Gene-level analysis of expression revealed 5 genes (WDR6 [OMIM 606031], CD38 [OMIM 107270], GPNMB [OMIM 604368], RAB29 [OMIM 603949], and TMEM163 [OMIM 618978]) that replicated using both Coloc and TWAS analyses in both the GTEx and Braineac expression data sets. A further 6 genes (ZRANB3 [OMIM 615655], PCGF3 [OMIM 617543], NEK1 [OMIM 604588], NUPL2 [NCBI 11097], GALC [OMIM 606890], and CTSB [OMIM 116810]) showed evidence of disease-associated splicing effects. Cell-type specificity analysis revealed that gene expression was overall more prevalent in glial cell types compared with neurons. The weighted gene coexpression performed on the GTEx data set showed that NUPL2 is a key gene in 3 modules implicated in catabolic processes associated with protein ubiquitination and in the ubiquitin-dependent protein catabolic process in the nucleus accumbens, caudate, and putamen. TMEM163 and ZRANB3 were both important in modules in the frontal cortex and caudate, respectively, indicating regulation of signaling and cell communication. Protein interactor analysis and simulations using random networks demonstrated that the candidate genes interact significantly more with known mendelian PD and parkinsonism proteins than would be expected by chance. Conclusions and Relevance Together, these results suggest that several candidate genes and pathways are associated with the findings observed in PD GWAS studies

Pregnancy outcomes in women with human immunodeficiency virus infection

Resumen Introducción: Desde la aparición de los primeros casos de infección por virus de la inmunodeficiencia humana se ha realizado un gran avance en el tratamiento y el control de la enfermedad, haciendo que pase a ser una enfermedad crónica. Esto también se cumple en el tratamiento y el seguimiento de las mujeres embarazadas que portan el virus, que transmiten cada vez con menos frecuencia la infección a sus hijos. En este estudio se analiza el seguimiento y los resultados de los embarazos de mujeres portadoras de la infección que han sido se guidas en el Hospital Universitario Virgen de las N ieves de Granada. Métodos: Para ello se recogieron las historias clínicas de las mujeres que cumplían estos requisitos y se analizaron las variables que influyen en el control de la infección y en la probabilidad de que la infección se transmita al hijo. Se estudiaron con más profundidad los casos en los que hubo transmisión vertical y los casos correspondientes a mujeres con infección congénita. Resultados: Se observan unos resultados bastante favorables en lo que se refiere al control de la infección de estas pacientes, en especial a partir de la introducción del uso de la zidovudina como profilaxis intraparto. No hay casos de transmisión vertical desde 1997. Conclusiones: Los embarazos en mujeres con infección por virus de la inmunodeficiencia humana se abordaron de manera eficiente con buenos resultados en general, y la mayor parte de las mujeres tuvieron hijos seronegativos.Introduction: Since the appearance of the first cases of human immunodeficiency virus infection, a great improvement in its treatment and control has been achieved, turning it into a chronic disease. This also occurs in the treatment and monitoring of pregnant women who carry the virus, who also pass on the disease to their children less frequently. In this study the monitoring and results of the pregnancy of women who carry the infection and are monitored in the University Hospital Virgen de las Nieves in Granada were analysed. Methods: To this end, the medical records of the women who met these requirements were collected, and the variables that affect the control of the infection and its transmission to the child were studied. The cases with mother-to-child transmission and the ones in which the mother were infected perinatally were studied more thoroughly. Outcomes: The results obtained are favourable when it comes to the control of the HIV infection of these patients, especially after the introduction of the zidovudine as a prophylaxis during labour. There have not been any new cases of mother-to-child transmission since 1997. Conclusions: Pregnancies in women with human immunodeficiency virus infection were managed efficiently with good outcomes in general, and most of the w omen gave birth seronegative children

The Manager’s Vision of CSR in an Emerging Economy: From Implementation to Market Impact

Society in general, and markets in particular, are increasingly sensitive to principles linked to corporate social responsibility (CSR) and sustainability. The literature is prolific in this vein—providing a broad range of research covering the terms’ meaning, implementation processes, drivers and brakes and the impact on variables of interest for business management. Far fewer studies, however, address these phenomena in the context of emerging economies. In response to the growing interest in developing countries in terms of the population and market, this study aims to deepen the vision of large-firm managers in an emerging LATAM economy—namely, Peru—while providing insights into the potential impact of a number of different cross-cultural traits. To this end, we opted for a grounded theory-based approach. Data were collected by way of nine semi-structured interviews with managers at the same number of Peruvian firms. Our findings both coincide with and differ from the extant CSR literature in terms of signification, implementation and intensity, perceived benefits and consumer behavior. Key theoretical and practical implications of our research are discussed in the final section

Effect of monotherapy with darunavir/cobicistat on viral load and semen quality of HIV-1 patients.

Many patients previously using darunavir/ritonavir (DRV/r) (800/100mg) have switched to darunavir/cobicistat (DRV/C) (800/150 mg) either as part of triple therapy (ART) or as monotherapy with DRV (mDRV). The latter approach continues to be used in some countries for patients receiving long-term treatment. However, to date, the behaviour of DRV/C in the seminal compartment has not been analysed. This study explores how the combination behaves in monotherapy, with respect to the control of viral load and seminal quality. To this end, we studied 20 patients who were treated with mDRV/C after previous treatment with mDRV/r for at least 24 weeks. A viral load control in seminal plasma similar to that published in the literature was observed after 24 weeks of treatment with mDRV/C (viral load positivity in 20% of patients). Similarly, semen quality was confirmed (70% normozoospermic) in patients treated with this formulation, as has previously been reported for ART and mDRV/r. The DRV levels measured in seminal plasma were above EC50, regardless of whether the seminal viral load was positive or negative. We conclude that this mDRV/C co-formulation behaves like mDRV/r in seminal plasma in terms of viral load control and semen quality

Effectiveness of the Quadrivalent HPV Vaccine in Preventing Anal ≥ HSILs in a Spanish Population of HIV+ MSM Aged > 26 Years.

Anal squamous cell carcinoma is the most frequent virus-related non-AIDS-defining neoplasia among HIV-infected individuals, especially MSM. The objectives of this study were to analyze the effectiveness of the quadrivalent HPV (qHPV) vaccine to prevent anal ≥ high-grade squamous intraepithelial lesions (≥HSILs), external ano-genital lesions (EAGLs), and infection by qHPV vaccine genotypes in HIV+ MSM, and to study the immunogenicity of the vaccine and risk factors for ≥ HSILs. This study is nested within a randomized, double-blind, placebo-controlled trial of the qHPV vaccine, which enrolled participants between May 2012 and May 2014, with a 48-month follow-up. A vaccine or placebo was administered at 0, 2, and 6 months, and vaccine antibody titers were evaluated at 7, 12, 24, 36, and 48 months. Data were gathered at 12, 24, 36, and 48 months on sexual habits, CD4/CD8 cell/counts, HIV viral load, and the results of cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope). The study included 129 patients (mean age of 38.8 years, 40 [31%] with a history of AIDS, 119 [92.2%] receiving ART, and 4 [3.3%] with virological failure), 66 (51.2%) in vaccine arm and 63 (48.4%) in placebo arm. The vaccine and placebo groups did not differ in ≥ HSILs (14.1 vs. 13.1%, respectively, p = 0.98) or EAGL (11.1 vs. 6.8%, p = 0.4) rates during follow-up; however, a protective effect against HPV 6 was observed during the first year of follow-up in the vaccine versus placebo group (7.5% vs. 23.4%; p = 0.047). A between-arm difference (p = 0.0001) in antibodies against qHPV vaccine genotypes was observed at 7 months (76.9% in vaccine arm vs. 30.2% in placebo arm), 12 months (68.1% vs. 26.5%), 24 months (75% vs. 32.5%), 36 months (90% vs. 24.4%), and 48 months (87.2% vs. 30%). Finally, the factor associated with the risk of anal ≥ HSIL onset during the four-year follow-up was the receipt of the last dose of the vaccine less than 6 months earlier in comparison to those vaccinated for a longer period (82.4% vs. 17.6% (OR 0.869 [95% CI, 0.825-0.917]). Vaccine and placebo arms did not significantly differ in ≥ HSIL or EAGL rates or in protection against infection by HPV genotype vaccine except for HPV6 at 12 months after the first dose. A long-lasting immune response was observed in almost all the vaccinated men. The main protective factor against ≥ HSIL was to have completed the vaccination regimen more than 6 months earlier