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1.
Glob Epidemiol ; 7: 100134, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38259323

RESUMO

Background: Diverse representation in clinical trials is an important goal in the testing of a medical, diagnostic, or therapeutic intervention. To date, the desired level of trial equity and inclusivity has been unevenly achieved. Methods: Employing the US National Library of Medicine's Clinicaltrials.gov registry, we examined 481 clinical trials conducted - at least in part - in the state of New Jersey. These trials were initiated after the FDA-mandated Common Rule changes, i.e., between January 2017 and October 2022, were enacted, and had their results posted. We analyzed sex/race/ethnicity reporting as well as applicable enrollment. Using meta-analysis, we estimated group participation proportions of a subset of the 481 identified trials; specifically, the 229 studies that were conducted solely within the US (i.e., without international sites) and compared them to US census data. Findings: Within the 481 clinical trials analyzed, over 97% reported on the race and/or ethnicity of their enrollees; all included information on sex. Reporting was not affected by funding source or therapeutic area. Based on the 229 solely US-based studies, the participants overall were 76.7% White; 14.1% Black; 2.7% Asian; and 15% Hispanic. Inclusion of Black participants did not differ from the 2020 US census data; in contrast, the levels of Asian and Hispanic participation were below the corresponding census percentages. Interpretation: The past five years have seen an overall uptick in the equity of race/ethnicity reporting and inclusivity of clinical trials, as compared to previously reported data, presaging the potential acquisition of ever more powerful and meaningful results of such interventional studies going forward. Funding: Support for this study comes from the Hackensack Meridian Health Research Institute and the Hackensack Meridian School of Medicine. Research in context: Evidence before this studyClinical trials are a critical part of determining whether or not a medical (drug/device/biologic) or socio-behavioral intervention is safe and truly effective. Through their use, scientific understanding is advanced and, ideally, human health is improved. To gain the most impactful information from a clinical trial, it should be sufficiently representative, that is, should enroll an adequate number of participants, and include a diverse population. Without such inclusion, the study is of only limited generalizability. Efforts are underway by funders, sites, and other stakeholders, to enhance reporting and promote inclusive enrollment. The extent to which such attempts are yielding results - at least for clinical trials in the state of New Jersey - is the focus of this data-driven analysis. The ClinicalTrials.gov registry database was carefully mined for the information contained in this report.Added value of this studyOur analysis of clinical trials initiated in the state of New Jersey and conducted there or elsewhere in the US reveals several positive trends. Our 5-year snapshot reveals that a very large percentage of trials report on race/ethnicity - and inclusivity is improving. While there is still some way to go to have the demographic numbers in these trials match US census values, our results suggest that recent efforts are having an effect.Implications of all the available evidenceFor myriad reasons, clinical trials have not enjoyed the public's universal trust over the years. In many ways, medicine moves at the speed of trust - without it, the promise of modern healthcare is brought into question. Clinical trials must include a commitment to diverse enrollment pools and equitable reporting under the law. Creating a legacy of trust - through greater inclusivity in clinical trials and more transparent reporting of results - will begin to heal the divide and engender faith in modern medicine and today's healthcare system. It would also allow for the desired far-reaching generalizability of results across patient populations. To better appreciate what needs to be done going forward, we must truly understand the state of clinical trials reporting and demographic inclusion. This report initiates such an analysis, by carefully documenting how New Jersey's clinical trials are performing. By virtue of its location (e.g., proximity to the cities of New York and Philadelphia) the state is part of a large biopharma cluster and healthcare nexus; it is critical that it performs well with respect to adopting/adhering to updated clinical trial guideline mandates. This report provides a glimpse - an important first look - into the state of clinical trials in New Jersey - from 2017 through 2022.

2.
Pathogens ; 13(1)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38251360

RESUMO

Plant viruses depend on host cellular factors for their replication and movement. There are cellular proteins that change their localization and/or expression and have a proviral role or antiviral activity and interact with or target viral proteins. Identification of those proteins and their roles during infection is crucial for understanding plant-virus interactions and to design antiviral resistance in crops. Important host proteins have been identified using approaches such as tag-dependent immunoprecipitation or yeast two hybridization that require cloning individual proteins or the entire virus. However, the number of possible interactions between host and viral proteins is immense. Therefore, an alternative method is needed for proteome-wide identification of host proteins involved in host-virus interactions. Here, we present cell fractionation coupled with mass spectrometry as an option to identify protein-protein interactions between viruses and their hosts. This approach involves separating subcellular organelles using differential and/or gradient centrifugation from virus-free and virus-infected cells (1) followed by comparative analysis of the proteomic profiles obtained for each subcellular organelle via mass spectrometry (2). After biological validation, prospect host proteins with proviral or antiviral roles can be subject to fundamental studies in the context of basic biology to shed light on both virus replication and cellular processes. They can also be targeted via gene editing to develop virus-resistant crops.

3.
Mol Plant Pathol ; 24(10): 1347-1356, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37438989

RESUMO

Gene silencing is a conserved mechanism in eukaryotes that dynamically regulates gene expression. In plants, gene silencing is critical for development and for maintenance of genome integrity. Additionally, it is a critical component of antiviral defence in plants, nematodes, insects, and fungi. To overcome gene silencing, viruses encode effectors that suppress gene silencing. A growing body of evidence shows that gene silencing and suppression of silencing are also used by plants during their interaction with nonviral pathogens such as fungi, oomycetes, and bacteria. Plant-pathogen interactions involve trans-kingdom movement of small RNAs into the pathogens to alter the function of genes required for their development and virulence. In turn, plant-associated pathogenic and nonpathogenic microbes also produce small RNAs that move trans-kingdom into host plants to disrupt pathogen defence through silencing of plant genes. The mechanisms by which these small RNAs move from the microbe to the plant remain poorly understood. In this review, we examine the roles of trans-kingdom small RNAs and silencing suppressors produced by nonviral microbes in inducing and suppressing gene silencing in plants. The emerging model is that gene silencing and suppression of silencing play critical roles in the interactions between plants and their associated nonviral microbes.


Assuntos
Inativação Gênica , Plantas , Plantas/microbiologia , Virulência , Fungos/metabolismo , Antivirais , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Interações Hospedeiro-Patógeno/genética
4.
Horiz. sanitario (en linea) ; 22(1): 27-33, Jan.-Apr. 2023. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1528684

RESUMO

Resumen: Objetivo: Determinar la prevalencia del uso complementario de la herbolaria en pacientes de oncología. Materiales y Métodos: El presente estudio fue de tipo observacional, transversal, descriptivo y prolectivo. Se llevó a cabo un muestreo no probabilístico. En el estudio se incluyeron a 100 pacientes que acudieron al área de oncología del Hospital de Alta Especialidad de Ciudad Victoria "Bicentenario 2010" (HRAEV) durante el periodo del estudio y que cumplieron con los criterios de selección señalados para esta investigación. Resultados: Se realizaron 100 encuestas a pacientes oncológicos, de los cuales el 55% fue de sexo femenino. Dicha población presenta una edad promedio de 48.2 años. Respecto al origen de los pacientes, el 67% radica en Cd. Victoria. El rango de nivel educativo entre los entrevistados osciló entre preparatoria y secundaria. Los cuales pertenecen a clase media. Existe una prevalencia del 82% en el uso de tratamientos alternativos para tratar la patología, de los cuales el 76% emplea el uso de la herbolaria como coadyuvante en las diferentes enfermedades que se tratan en el hospital. Las principales plantas empleadas son: la Mariguana (Cannabis sativa) en un 45%, el 23% Noni (Morinda citrifolia) y el 12% Bardana (Arctium lappa). Conclusión: El uso de la medicina alternativa complementaria es frecuente en pacientes oncológicos, destacando la herbolaria. Por lo anterior, el comprender la dinámica de la implementación de terapias alternativas como lo es la herbolaria, permitirá comprender y guiar al paciente en su proceso de ciclos oncológicos y minimizar los efectos secundarios.


Abstract: Objective: To determine the prevalence of the complementary use of herbal medicine in oncology patients. Materials and methods: This study was observational, cross-sectional, descriptive and prolective. A non-probabilistic sampling was carried out. The study included 100 patients who attended the oncology area of the Hospital de Alta Especialidad de Ciudad Victoria "Bicentenario 2010" (HRAEV) during the study period and who met the selection criteria indicated for this research. Results: 100 surveys were carried out on cancer patients, of which 55% were female. This population has an average age of 48.2 years. Regarding the origin of the patients, 67% reside in Cd. Victoria. The range of educational level among the interviewees oscillated between high school and middle school. who belong to the middle class. There is a prevalence of 82% in the use of alternative treatments to treat the pathology, of which 76% employ the use of herbal medicine as an adjuvant in the different diseases that are treated in the hospital. The main plants used are: 45% Marijuana (Cannabis sativa), 23% Noni (Morinda citrifolia) and 12% Burdock (Arctium lappa). Conclusion: The use of complementary alternative medicine is common in cancer patients, highlighting herbal medicine. Due to the above, understanding the dynamics of the implementation of alternative therapies such as herbalism, will allow understanding and guiding the patient in their oncological cycle process and minimizing side effects. KEY WORDS: naturopathy; oncology; alternative medicine.

5.
Pathogens ; 11(9)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36145471

RESUMO

Virus evolution is the change in the genetic structure of a viral population over time and results in the emergence of new viral variants, strains, and species with novel biological properties, including adaptation to new hosts. There are host, vector, environmental, and viral factors that contribute to virus evolution. To achieve or fine tune compatibility and successfully establish infection, viruses adapt to a particular host species or to a group of species. However, some viruses are better able to adapt to diverse hosts, vectors, and environments. Viruses generate genetic diversity through mutation, reassortment, and recombination. Plant viruses are exposed to genetic drift and selection pressures by host and vector factors, and random variants or those with a competitive advantage are fixed in the population and mediate the emergence of new viral strains or species with novel biological properties. This process creates a footprint in the virus genome evident as the preferential accumulation of substitutions, insertions, or deletions in areas of the genome that function as determinants of host adaptation. Here, with respect to plant viruses, we review the current understanding of the sources of variation, the effect of selection, and its role in virus evolution and host adaptation.

6.
Curr Opin Biotechnol ; 70: 187-195, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34153774

RESUMO

Alternatives to protect crops against diseases are desperately needed to secure world food production and make agriculture more sustainable. Genetic resistance to pathogens utilized so far is mostly based on single dominant resistance genes that mediate specific recognition of invaders and that is often rapidly broken by pathogen variants. Perturbation of plant susceptibility (S) genes offers an alternative providing plants with recessive resistance that is proposed to be more durable. S genes enable the establishment of plant disease, and their inactivation provides opportunities for resistance breeding of crops. However, loss of S gene function can have pleiotropic effects. Developments in genome editing technology promise to provide powerful methods to precisely interfere with crop S gene functions and reduce tradeoffs.


Assuntos
Resistência à Doença , Melhoramento Vegetal , Produtos Agrícolas/genética , Resistência à Doença/genética , Edição de Genes , Engenharia Genética , Doenças das Plantas/genética , Plantas Geneticamente Modificadas/genética
7.
J Virol ; 95(15): e0049621, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34037417

RESUMO

The Severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 originated in bats and adapted to infect humans. Several SARS-CoV-2 strains have been identified. Genetic variation is fundamental to virus evolution and, in response to selection pressure, is manifested as the emergence of new strains and species adapted to different hosts or with novel pathogenicity. The combination of variation and selection forms a genetic footprint on the genome, consisting of the preferential accumulation of mutations in particular areas. Properties of betacoronaviruses contributing to variation and the emergence of new strains and species are beginning to be elucidated. To better understand their variation, we profiled the accumulation of mutations in all species in the genus Betacoronavirus, including SARS-CoV-2 and two other species that infect humans: SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Variation profiles identified both genetically stable and variable areas at homologous locations across species within the genus Betacoronavirus. The S glycoprotein is the most variable part of the genome and is structurally disordered. Other variable parts include proteins 3 and 7 and ORF8, which participate in replication and suppression of antiviral defense. In contrast, replication proteins in ORF1b are the least variable. Collectively, our results show that variation and structural disorder in the S glycoprotein is a general feature of all members of the genus Betacoronavirus, including SARS-CoV-2. These findings highlight the potential for the continual emergence of new species and strains with novel biological properties and indicate that the S glycoprotein has a critical role in host adaptation. IMPORTANCE Natural infection with SARS-CoV-2 and vaccines triggers the formation of antibodies against the S glycoprotein, which are detected by antibody-based diagnostic tests. Our analysis showed that variation in the S glycoprotein is a general feature of all species in the genus Betacoronavirus, including three species that infect humans: SARS-CoV, SARS-CoV-2, and MERS-CoV. The variable nature of the S glycoprotein provides an explanation for the emergence of SARS-CoV-2, the differentiation of SARS-CoV-2 into strains, and the probability of SARS-CoV-2 repeated infections in people. Variation of the S glycoprotein also has important implications for the reliability of SARS-CoV-2 antibody-based diagnostic tests and the design and deployment of vaccines and antiviral drugs. These findings indicate that adjustments to vaccine design and deployment and to antibody-based diagnostic tests are necessary to account for S glycoprotein variation.


Assuntos
Betacoronavirus/genética , Evolução Molecular , Variação Genética , Genoma Viral , Glicoproteína da Espícula de Coronavírus/genética , Estudo de Associação Genômica Ampla , Humanos
8.
Viruses ; 13(4)2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920930

RESUMO

Viruses are dependent on host factors at all parts of the infection cycle, such as translation, genome replication, encapsidation, and cell-to-cell and systemic movement. RNA viruses replicate their genome in compartments associated with the endoplasmic reticulum, chloroplasts, and mitochondria or peroxisome membranes. In contrast, DNA viruses replicate in the nucleus. Viral infection causes changes in plant gene expression and in the subcellular localization of some host proteins. These changes may support or inhibit virus accumulation and spread. Here, we review host proteins that change their subcellular localization in the presence of a plant virus. The most frequent change is the movement of host cytoplasmic proteins into the sites of virus replication through interactions with viral proteins, and the protein contributes to essential viral processes. In contrast, only a small number of studies document changes in the subcellular localization of proteins with antiviral activity. Understanding the changes in the subcellular localization of host proteins during plant virus infection provides novel insights into the mechanisms of plant-virus interactions and may help the identification of targets for designing genetic resistance to plant viruses.


Assuntos
Citoplasma/metabolismo , Interações entre Hospedeiro e Microrganismos , Proteínas de Plantas/análise , Vírus de Plantas/fisiologia , Citoplasma/química , Interações Hospedeiro-Patógeno , Doenças das Plantas/virologia , Plantas/virologia
9.
Virus Evol ; 7(2): veab102, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35299789

RESUMO

The polerovirus (family Solemoviridae, genus Polerovirus) genome consists of single-, positive-strand RNA organized in overlapping open reading frames (ORFs) that, in addition to others, code for protein 0 (P0, a gene silencing suppressor), a coat protein (CP, ORF3), and a read-through domain (ORF5) that is fused to the CP to form a CP-read-through (RT) protein. The genus Polerovirus contains twenty-six virus species that infect a wide variety of plants from cereals to cucurbits, to peppers. Poleroviruses are transmitted by a wide range of aphid species in the genera Rhopalosiphum, Stiobion, Aphis, and Myzus. Aphid transmission is mediated both by the CP and by the CP-RT. In viruses, mutational robustness and structural flexibility are necessary for maintaining functionality in genetically diverse sets of host plants and vectors. Under this scenario, within a virus genome, mutations preferentially accumulate in areas that are determinants of host adaptation or vector transmission. In this study, we profiled genomic variation in poleroviruses. Consistent with their multifunctional nature, single-nucleotide variation and selection analyses showed that ORFs coding for P0 and the read-through domain within the CP-RT are the most variable and contain the highest frequency of sites under positive selection. An order/disorder analysis showed that protein P0 is not disordered. In contrast, proteins CP-RT and virus protein genome-linked (VPg) contain areas of disorder. Disorder is a property of multifunctional proteins with multiple interaction partners. The results described here suggest that using contrasting mechanisms, P0, VPg, and CP-RT mediate adaptation to host plants and to vectors and are contributors to the broad host and vector range of poleroviruses. Profiling genetic variation across the polerovirus genome has practical applications in diagnostics, breeding for resistance, and identification of susceptibility genes and contributes to our understanding of virus interactions with their host, vectors, and environment.

10.
Pathogens ; 9(7)2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32610472

RESUMO

Orthotospoviruses are plant-infecting members of the family Tospoviridae (order Bunyavirales), have a broad host range and are vectored by polyphagous thrips in a circulative-propagative manner. Because diverse hosts and vectors impose heterogeneous selection constraints on viral genomes, the evolutionary arms races between hosts and their pathogens might be manifested as selection for rapid changes in key genes. These observations suggest that orthotospoviruses contain key genetic components that rapidly mutate to mediate host adaptation and vector transmission. Using complete genome sequences, we profiled genomic variation in orthotospoviruses. Results show that the three genomic segments contain hypervariable areas at homologous locations across species. Remarkably, the highest nucleotide variation mapped to the intergenic region of RNA segments S and M, which fold into a hairpin. Secondary structure analyses showed that the hairpin is a dynamic structure with multiple functional shapes formed by stems and loops, contains sites under positive selection and covariable sites. Accumulation and tolerance of mutations in the intergenic region is a general feature of orthotospoviruses and might mediate adaptation to host plants and insect vectors.

11.
Sci Rep ; 10(1): 9540, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32533016

RESUMO

RNA viruses exist as populations of genome variants. Virus-infected plants accumulate 21-24 nucleotide small interfering RNAs (siRNAs) derived from viral RNA (virus-derived siRNAs) through gene silencing. This paper describes the profile of mutations in virus-derived siRNAs for three members of the family Potyviridae: Turnip mosaic virus (TuMV), Papaya ringspot virus (PRSV) and Wheat streak mosaic virus (WSMV). For TuMV in Arabidopsis thaliana, profiles were obtained for mechanically inoculated rosette leaves and systemically infected cauline leaves and inflorescence. Results are consistent with selection pressure on the viral genome imposed by local and systemic movement. By genetically removing gene silencing in the plant and silencing suppression in the virus, our results showed that antiviral gene silencing imposes selection in viral populations. Mutations in siRNAs derived from a PRSV coat protein transgene in the absence of virus replication showed the contribution of cellular RNA-dependent RNA polymerases to the generation of mutations in virus-derived siRNAs. Collectively, results are consistent with two sources of mutations in virus-derived siRNAs: viral RNA-dependent RNA polymerases responsible for virus replication and cellular RNA-dependent RNA polymerases responsible for gene silencing amplification.


Assuntos
Mutação/genética , RNA Interferente Pequeno/genética , RNA Viral/genética , Arabidopsis/virologia , Inativação Gênica/fisiologia , Genoma Viral/genética , Doenças das Plantas/virologia , Vírus de Plantas/genética , Potyviridae/genética , Potyvirus/genética , Interferência de RNA/fisiologia , Proteínas Virais/genética , Replicação Viral/genética
12.
Rev. argent. cir ; 112(3): 274-292, jun. 2020. graf
Artigo em Espanhol | LILACS | ID: biblio-1279741

RESUMO

RESUMEN Introducción: la seguridad de la colonoscopia realizada por cirujanos y el tratamiento de sus complica ciones han sido analizados aisladamente y en escasas publicaciones nacionales. Objetivos: el objetivo principal del estudio fue analizar las colonoscopias realizadas por cirujanos co lorrectales, sus complicaciones y resolución. El objetivo secundario fue comparar los resultados entre un hospital universitario y distintos centros del país dotados de cirujanos colorrectales que habían recibido entrenamiento en una residencia posbásica. Material y métodos: estudio multicéntrico, prospectivo a nivel nacional. Se incluyeron las colonosco pias realizadas entre 2011 y 2016 . Se analizaron como variables las complicaciones, edad, sexo, tipo de endoscopia, diagnóstico, tratamiento, sitio de realización y de entrenamiento del cirujano. Se ex presaron en promedios, porcentajes y rangos. El análisis estadístico consistió en el test exacto ordinal, relaciones y proporciones y exacto de Fisher. Se consideró significancia a p < 0,05. Resultados: de 24 907 procedimientos, 17 283 fueron diagnósticos y 17 202 provenían de centros del interior. Hubo 43 complicaciones (0,17%); 35 específicas: perforaciones (19), hemorragias (8), sín drome pospolipectomía (5) y técnicas (3), diagnosticadas y resueltas por el mismo equipo sin mor bimortalidad. No hubo diferencias en las complicaciones según el centro ni tipo de colonoscopia en incidencia o tratamiento. Todos los cirujanos se entrenaron en residencias de posgrado con programas de entrenamiento en colonoscopia. Conclusiones: existen similares resultados entre cirujanos provenientes de instituciones con residen cia posbásica y centros del interior al realizar colonoscopias. La colonoscopia realizada por cirujanos es un procedimiento seguro y posible de ser adquirido como competencia luego de un entrenamiento formal realizado en una residencia posbásica.


ABSTRACT Introduction: The safety of colonoscopies performed by surgeons and the management of their com plications has not been analyzed in depth in the low number of national publications. Objective: The primary endpoint of this study was to analyze the outcomes of colonoscopies perfor med by colorectal surgeons, in terms of complications. and their resolution. The secondary endpoint was to compare the results between a university hospital and different centers nationwide staffed with colorectal surgeons who had received formal training during a residency program in the surgical subspecialty. Material and methods: We conducted a multicenter, prospective and consecutive national study. The colonscopies performed between 2011 and 2016 were included. The variables analyzed included complications, age, sex, type of endoscopy, diagnosis, treatment, location were the procedure was performed and surgeon's training. The results were expressed as mean, percentage and range. The statistical analysis was performed using Fisher's exact test. A p value < 0.05 was considered statistically significant. Results: A total of 24,907 procedures were performed, 17,283 corresponded to diagnostic colonosco pies and 17,202 were made in provincial centers. Forty-four complications were recorded (0.17%), of which 35 were procedure-related complications: 19 perforations, 8 bleeding events, 5 post-polypec tomy syndromes and three related with the technique; all were diagnosed and solved by the same team without morbidity and mortality. There were no differences in the incidence of complications and how they were treated according to the center or type of colonoscopy. All the surgeons received colonoscopy training during a residency program in the surgical subspecialty. Conclusions: The results obtained in colonoscopies performed by surgeons trained in institutions with residency programs in surgical subspecialties are similar t Safe colonoscopies can be performed by surgeons who have been trained in institutions with a residency program in a surgical subspecialty and with a formal training program in colonoscopy.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Colonoscopia/efeitos adversos , Cirurgia Colorretal/efeitos adversos , Estudos Prospectivos , Cirurgiões/educação , Hemorragia , Hospitais Universitários , Internato e Residência
13.
Front Plant Sci ; 11: 56, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117392

RESUMO

The terms genome engineering, genome editing, and gene editing, refer to modifications (insertions, deletions, substitutions) in the genome of a living organism. The most widely used approach to genome editing nowadays is based on Clustered Regularly Interspaced Short Palindromic Repeats and associated protein 9 (CRISPR-Cas9). In prokaryotes, CRISPR-Cas9 is an adaptive immune system that naturally protects cells from DNA virus infections. CRISPR-Cas9 has been modified to create a versatile genome editing technology that has a wide diversity of applications in medicine, agriculture, and basic studies of gene functions. CRISPR-Cas9 has been used in a growing number of monocot and dicot plant species to enhance yield, quality, and nutritional value, to introduce or enhance tolerance to biotic and abiotic stresses, among other applications. Although biosafety concerns remain, genome editing is a promising technology with potential to contribute to food production for the benefit of the growing human population. Here, we review the principles, current advances and applications of CRISPR-Cas9-based gene editing in crop improvement. We also address biosafety concerns and show that humans have been exposed to Cas9 protein homologues long before the use of CRISPR-Cas9 in genome editing.

14.
Front Plant Sci ; 10: 1439, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798606

RESUMO

Potyviruses (family Potyviridae, genus Potyvirus) are the result of an initial radiation event that occurred 6,600 years ago. The genus currently consists of 167 species that infect monocots or dicots, including domesticated and wild plants. Potyviruses are transmitted in a non-persistent way by more than 200 species of aphids. As indicated by their wide host range, worldwide distribution, and diversity of their vectors, potyviruses have an outstanding capacity to adapt to new hosts and environments. However, factors that confer adaptability are poorly understood. Viral RNA-dependent RNA polymerases introduce nucleotide substitutions that generate genetic diversity. We hypothesized that selection imposed by hosts and vectors creates a footprint in areas of the genome involved in host adaptation. Here, we profiled genomic and polyprotein variation in all species in the genus Potyvirus. Results showed that the potyviral genome is under strong negative selection. Accordingly, the genome and polyprotein sequence are remarkably stable. However, nucleotide and amino acid substitutions across the potyviral genome are not randomly distributed and are not determined by codon usage. Instead, substitutions preferentially accumulate in hypervariable areas at homologous locations across potyviruses. At a frequency that is higher than that of the rest of the genome, hypervariable areas accumulate non-synonymous nucleotide substitutions and sites under positive selection. Our results show, for the first time, that there is correlation between host range and the frequency of sites under positive selection. Hypervariable areas map to the N terminal part of protein P1, N and C terminal parts of helper component proteinase (HC-Pro), the C terminal part of protein P3, VPg, the C terminal part of NIb (RNA-dependent RNA polymerase), and the N terminal part of the coat protein (CP). Additionally, a hypervariable area at the NIb-CP junction showed that there is variability in the sequence of the NIa protease cleavage sites. Structural alignment showed that the hypervariable area in the CP maps to the N terminal flexible loop and includes the motif required for aphid transmission. Collectively, results described here show that potyviruses contain fixed hypervariable areas in key parts of the genome which provide mutational robustness and are potentially involved in host adaptation.

15.
Rev. argent. cir ; 111(4): 245-267, dic. 2019. ilus, graf, tab
Artigo em Espanhol | LILACS | ID: biblio-1057368

RESUMO

Antecedentes: la hemicolectomía derecha laparoscópica con abordaje suprapúbico (HDLS) y empleo de tecnología. En los pacientes con cáncer de colon con metástasis hepáticas sincrónicas (CCMHS), la resección completa del tumor primario con las metástasis es la única opción de tratamiento con intención curativa. Se conocen varios informes de series de casos en el mundo; sin embargo, no existe ningún estudio aleatorizado controlado. Objetivo: el objetivo es evaluar la factibilidad y seguridad del abordaje laparoscópico simultáneo de la resección del tumor primario de colon y de la metástasis hepática. Material y métodos: es un estudio retrospectivo; a tal fin se recolectaron todos los pacientes con sospecha de CCMHS abordados por laparoscopia con intención de resección simultánea del tumor primario de colon con las metástasis hepáticas. Se analizaron variables preoperatorias, operatorias, resultados a corto y largo plazo, y anatomopatológicas. Resultados: en el período de estudio se realizaron 89 resecciones hepáticas laparoscópicas (RHL). En 28 pacientes se realizó ‒en forma simultánea con la RHL‒ otro procedimiento, en 21 de los cuales fue una colectomía laparoscópica. El tiempo quirúrgico promedio total de los dos procedimientos llegó a 407 minutos. El promedio de días de estadía hospitalaria fue de 8 días. No hubo mortalidad en la serie, y la morbilidad global fue del 71%, pero un solo caso con morbilidad mayor. La sobrevida global y la sobrevida libre de recurrencia a los 3 años fue de 55,2% y 16,3%, respectivamente. Conclusión: Esta es la primera publicación acerca del tema en nuestro país. Podemos decir que, en casos bien seleccionados, el abordaje laparoscópico simultáneo es factible de realizar, con aceptable morbimortalidad y sin comprometer los resultados oncológicos.


Background: In patients with colorectal cancer with synchronous liver metastases (CLM), complete resection of the primary tumor with the metastases is the only option for curative treatment. Several case series have been reported but no randomized controlled trials have been published. Objective: The aim was to evaluate if the simultaneous laparoscopic resection of the primary colon tumor and liver metastases is feasible and safe. Material and methods: A retrospective study was conducted with patients with suspected CLM scheduled for simultaneous laparoscopic resection of the primary tumor of the colon and liver metastases. The preoperative and operative variables, short- and long-term outcomes and pathological variables were analyzed. Results: A total of 89 laparoscopic liver resections (LLR) were performed during the study period. In 28 patients, LLR was simultaneous with other procedures, 21 of which corresponded to laparoscopic colon resection. Mean surgical time for both procedures was 407 minutes. Mean hospital length of stay was 8 days. None of the patients died and overall morbidity rate was 71% with only one major complication. Overall survival and relapse-free survival at three years was 55.2% and 16.3%, respectively. Conclusion: This is the first publication analyzing this approach in our country. In well selected cases, the simultaneous laparoscopic approach is feasible, with low morbidity and mortality and acceptable oncological results.


Assuntos
Humanos , Morbidade , Colectomia , Colo , Neoplasias do Colo/diagnóstico , Métodos , Neoplasias , Pacientes , Recidiva , Segurança , Sobrevida , Tempo , Indicadores de Morbimortalidade , Estudos Retrospectivos , Neoplasias do Colo , Intenção , Emprego , Duração da Cirurgia , Hospitais , Tempo de Internação , Fígado
16.
Rev. argent. coloproctología ; 30(4): 114-118, dic. 2019. ilus, graf
Artigo em Espanhol | LILACS | ID: biblio-1096800

RESUMO

Los lipomas del colon ocupan el tercer lugar en frecuencia de aparición de tumores benignos. Estos tumores están formados por tejido adiposo bien diferenciado con un estroma fibroso. La gran mayoría de estos lipomas es asintomática, algunos en raras ocasiones presentan complicaciones de urgencia. El fin de esta publicación es presentar un caso de obstrucción de colon por lipoma. (AU)


Benign colonic lesions are infrequent and account for a low percentage of all colonic tumors. Among the benign tumors, lipomas are third in frequency. They are composed of mature adipose tissue with fibrous stroma. Most of them are asymptomatic but in rare instances, they may present as surgical emergencies. We present one case of colonic obstruction caused by lipomas. (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias do Colo/complicações , Intussuscepção/etiologia , Intussuscepção/diagnóstico por imagem , Lipoma/complicações , Endoscopia Gastrointestinal/métodos , Colonoscopia/métodos , Laparoscopia/métodos , Neoplasias do Colo/cirurgia , Intussuscepção/cirurgia , Lipoma/cirurgia
17.
Rev. méd. Chile ; 147(10): 1335-1339, oct. 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1058602

RESUMO

We report a 59-year-old male who, three weeks after a coronary revascularization surgery, reported a sudden intense burning pain in his left upper limb. Two weeks later, he reports a paresis with difficulty to extend his left wrist and fingers. The electromyography showed a severe axonal damage of the radial nerve with distal denervation signs. This clinical picture probably corresponds to a neuralgic amyotrophy, an inflammatory disorder of the brachial plexus known by a number of terms, including Parsonage-Turner syndrome.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neurite do Plexo Braquial/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Neurite do Plexo Braquial/fisiopatologia , Neuropatias do Plexo Braquial/etiologia , Neuropatias do Plexo Braquial/fisiopatologia , Eletromiografia
18.
Mol Plant Pathol ; 20(11): 1588-1601, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31286679

RESUMO

Plant virus genome replication and movement is dependent on host resources and factors. However, plants respond to virus infection through several mechanisms, such as autophagy, ubiquitination, mRNA decay and gene silencing, that target viral components. Viral factors work in synchrony with pro-viral host factors during the infection cycle and are targeted by antiviral responses. Accordingly, establishment of virus infection is genetically determined by the availability of the pro-viral factors necessary for genome replication and movement, and by the balance between plant defence and viral suppression of defence responses. Sequential requirement of pro-viral factors and the antagonistic activity of antiviral factors suggest a two-step model to explain plant-virus interactions. At each step of the infection process, host factors with antiviral activity have been identified. Here we review our current understanding of host factors with antiviral activity against plant viruses.


Assuntos
Interações Hospedeiro-Patógeno , Proteínas de Plantas/metabolismo , Vírus de Plantas/fisiologia , Plantas/virologia , Antivirais/metabolismo , Genes de Plantas , Interações Hospedeiro-Patógeno/genética , Proteínas de Plantas/genética , Vírus de Plantas/patogenicidade , Plantas/genética
19.
Theor Exp Plant Physiol ; 31(1): 227-248, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31355128

RESUMO

Plant viruses are responsible for losses in worldwide production of numerous economically important food and fuel crops. As obligate cellular parasites with very small genomes, viruses rely on their hosts for replication, assembly, intra- and intercellular movement, and attraction of vectors for dispersal. Chloroplasts are photosynthesis and are the site of replication for several viruses. When viruses replicate in chloroplasts, photosynthesis, an essential process in plant physiology, is inhibited. The mechanisms underlying molecular and biochemical changes during compatible and incompatible plants-virus interactions, are only beginning to be elucidated, including changes in proteomic profiles induced by virus infections. In this review, we highlight the importance of proteomic studies to understand plant-virus interactions, especially emphasizing the changes in photosynthesis-related protein accumulation. We focus on: (a) chloroplast proteins that differentially accumulate during viral infection; (b) the significance with respect to chloroplast-virus interaction; and (c) alterations in plant's energetic metabolism and the subsequently the plant defense mechanisms to overcome viral infection.

20.
Front. med. (En línea) ; 14(2): 80-84, abr.-jun. 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1103188

RESUMO

El objetivo de esta guía clínico-quirúrgica es homogeneizar conceptos y conductas para el manejo de la hemorragia digestiva baja (HDB), con el fin de protocolizar y unificar el tratamiento multidisciplinario de dicha patología. Durante el manejo inicial del paciente con HDB, resulta prioritario determinar la estabilidad hemodinámica. Cuando el paciente se presenta hemodinámicamente estable, la videocolonoscopia (VCC) es el método diagnóstico de elección, la cual debe realizarse con preparación colónica y dentro de las 48 horas, mientras que si se trata de un paciente inestable que no responde a la reanimación debe realizarse, de ser posible, angiotomografía para localizar el sitio de sangrado y posteriormente angiografía. Si las condiciones no lo permiten, se procede directamente a la cirugía de urgencia. Si se logra reanimar al paciente, el método diagnóstico de elección es la videoendoscopia digestiva alta (VEDA). Si la VEDA es negativa y el paciente permanece estable, se prosigue con VCC. Por el contrario, si continúa sangrando, el paso siguiente es la angio-TC. En caso de localizar el sitio de sangrado, se realiza angiografía terapéutica. Si falla o la angio-TC es negativa, tiene indicación de cirugía. Esta guía fue consensuada a partir de la bibliografía, guías internacionales y la experiencia de los Servicios de Cirugía General, Coloproctología, Gastroenterología, Diagnóstico por Imágenes y Hemodinamia.(AU)


Assuntos
Hemorragia Gastrointestinal , Terapêutica , Baja
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