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BACKGROUND: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. PATIENTS AND METHODS: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors. RESULTS: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1-2 or 3-4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001). CONCLUSIONS: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy.
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Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Adjuvantes Imunológicos , Platina , Estudos RetrospectivosRESUMO
To describe the clinical outcomes and risk factors for 90-day mortality in patients with solid tumours (ST) and coronavirus disease 2019 (COVID-19) during the first outbreak in Catalonia. This is a multicentre retrospective study including adults with ST and COVID-19 confirmed by real time reverse transcription polymerase chain reaction between 13 March and 30 April 2020. Clinical and survival data were collected. Follow-up ended on 30 July 2020. Multivariate and survival analysis were performed. A hundred and fifteen patients were included. In all, 42.6% had advanced disease and were receiving anticancer treatment; 7% were admitted to the ICU and 22.6% died during hospitalisation. Thirty-day mortality was 27.8%, which increased to 33.9% at 90 days. Ninety-day mortality was associated with current smoker status (hazard ratio [HR]: 2.91, 95% CI [confidence interval]: 1.03-8.33, P = .044), baseline ECOG-PS 2 to 3 (HR: 3.88, 95% CI: 1.77-8.46, P < .001]), dyspnoea (HR: 3.02, 95% CI: 1.31-6.96, P = .009), a respiratory rate ≥ 24 (HR: 2.24, 95% CI: 1.02-4.92, P = .046) and sepsis (HR: 3.97, 95% CI: 1.78-8.88, P < .001). Of the 76 survivors, 73.6% had a follow-up visit. Of those, 33.9% had their cancer controlled and 23.2% had progressed. Thirty-five survivors were receiving anticancer treatment before COVID-19 diagnosis though 14 had to discontinue the treatment. Eight survivors without previous anticancer therapy started therapy. The median time to start anticancer therapy after COVID-19 was 45 days (interquartile range: 28-61). In conclusion, 90-day mortality in patients with ST and COVID-19 was 33.9%; current smoker status, poor ECOG-PS, dyspnoea, respiratory rate ≥24 and sepsis were independent risk factors for mortality; and survivors did not restart their anticancer treatment until 1.5 months after COVID-19 diagnosis.
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COVID-19/epidemiologia , COVID-19/mortalidade , Neoplasias/epidemiologia , Neoplasias/mortalidade , Idoso , Surtos de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Pandemias , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Espanha , Resultado do TratamentoRESUMO
BACKGROUND: Most anticancer drugs are approved by regulatory agencies based on surrogate measures. This article explores the variables associated with overall survival (OS), quality of life (QoL), and substantial clinical benefit among anticancer drugs at the time of approval and in the postmarketing period. METHODS: Anticancer drugs approved by the FDA between January 2006 and December 2015 and with postmarketing follow-up until April 2019 were identified. We evaluated trial-level data supporting approval and any updated OS and/or QoL data. We applied the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the ASCO Value Framework (ASCO-VF) to initial and follow-up studies. RESULTS: We found that 58 drugs were approved for 96 indications based on 96 trials. At registration, approval was based on improved OS in 39 trials (41%) and improved QoL in 16 of 45 indications (36%). Postmarketing data showed an improvement in OS for 28 of 59 trials (47%) and in QoL for 22 of 48 indications (46%). At the time of approval, 25 of 94 (27%) and 26 of 80 scorable trials (33%) met substantial benefit thresholds using the ESMO-MCBS and ASCO-VF, respectively. In the postmarketing period, 37 of 69 (54%) and 35 of 65 (54%) trials met the substantial benefit thresholds. Drugs with companion diagnostics and immune checkpoint inhibitors were associated significantly with substantial clinical benefit. CONCLUSIONS: Compared with the time of approval, more anticancer drugs showed improved OS and QoL and met the ESMO-MCBS or ASCO-VF thresholds for substantial benefit over the course of postmarketing time. However, only approximately half of the trials met the threshold for substantial benefit. Companion diagnostic drugs and immunotherapy seemed to be associated with greater clinical benefit.
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BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.
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Hansenostáticos/uso terapêutico , Hanseníase Multibacilar/tratamento farmacológico , Hanseníase Paucibacilar/tratamento farmacológico , Minociclina/uso terapêutico , Ofloxacino/uso terapêutico , Rifampina/uso terapêutico , Organização Mundial da Saúde , Adolescente , Adulto , Idoso , Criança , Protocolos Clínicos , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Hansenostáticos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Minociclina/efeitos adversos , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/isolamento & purificação , Doenças Negligenciadas/tratamento farmacológico , Ofloxacino/efeitos adversos , Recidiva , Rifampina/efeitos adversos , Falha de Tratamento , Adulto JovemRESUMO
PURPOSE: We evaluated the prevalence of homologous recombination deficiencies (HRD) to determine the efficacy of different techniques and clinical characteristics of patients. METHODS: This retrospective study included patients with metastatic prostate cancer who underwent molecular testing at our hospital between 2016 and 2022. We used tumor tissue, ctDNA, and lymphocytes for somatic or germline testing. We analyzed the clinical characteristics and survival outcomes. RESULTS: 144 patients were tested (113 somatic, 21 germline, and 10 both). Technical issues prevented the analysis of 23 prostatic samples (18.7%). 12 (8.3%) patients had HRD. BRCA2 was the most frequent mutation (66.7%). Patients with HRD were younger (57.5 years). Patients with BRCA mutations had poorer survival (31.9 vs 56.3 months, p = 0.048). CONCLUSION: In our institution, 8.3% of the patients had HRD. Tumor tissue analysis failed in 18.7% of tests. ctDNA analysis is an alternative detection method. BRCA mutations are correlated with poor prognosis.
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Proteína BRCA2 , Recombinação Homóloga , Neoplasias da Próstata , Humanos , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/mortalidade , Idoso , Proteína BRCA2/genética , Mutação , Prognóstico , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Idoso de 80 Anos ou mais , Mutação em Linhagem Germinativa , Proteína BRCA1/genética , AdultoRESUMO
The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival.
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Anticorpos Monoclonais Humanizados , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Urológicas/patologia , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/terapia , Neoplasias Urológicas/tratamento farmacológico , Radiocirurgia/métodos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Carcinoma de Células de Transição/terapia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/tratamento farmacológico , Resultado do Tratamento , Terapia Combinada , Intervalo Livre de ProgressãoRESUMO
Phytopathogenic bacteria play important roles in plant productivity, and developments in gene editing have potential for enhancing the genetic tools for the identification of critical genes in the pathogenesis process. CRISPR-based genome editing variants have been developed for a wide range of applications in eukaryotes and prokaryotes. However, the unique mechanisms of different hosts restrict the wide adaptation for specific applications. Here, CRISPR-dCas9 (dead Cas9) and nCas9 (Cas9 nickase) deaminase vectors were developed for a broad range of phytopathogenic bacteria. A gene for a dCas9 or nCas9, cytosine deaminase CDA1, and glycosylase inhibitor fusion protein (cytosine base editor, or CBE) was applied to base editing under the control of different promoters. Results showed that the RecA promoter led to nearly 100% modification of the target region. When residing on the broad host range plasmid pHM1, CBERecAp is efficient in creating base edits in strains of Xanthomonas, Pseudomonas, Erwinia and Agrobacterium. CBE based on nCas9 extended the editing window and produced a significantly higher editing rate in Pseudomonas. Strains with nonsynonymous mutations in test genes displayed expected phenotypes. By multiplexing guide RNA genes, the vectors can modify up to four genes in a single round of editing. Whole-genome sequencing of base-edited isolates of Xanthomonas oryzae pv. oryzae revealed guide RNA-independent off-target mutations. Further modifications of the CBE, using a CDA1 variant (CBERecAp-A) reduced off-target effects, providing an improved editing tool for a broad group of phytopathogenic bacteria.
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Sistemas CRISPR-Cas , Citosina , Citosina/metabolismo , Edição de Genes/métodos , Bactérias/genética , Bactérias/metabolismo , RNARESUMO
The ARON-2 study (NCT05290038) aimed to assess the real-world efficacy of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. This retrospective analysis reports the outcomes of urothelial carcinoma (UC) patients with bone metastases (BM). Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were reviewed from60 institutions in 20 countries. Patients were assessed for Overall Response Rate (ORR), Progression-Free Survival (PFS), and Overall Survival (OS). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 881 patients were included; of them, 263 (30%) presented BM. Median follow-up time was 22.7 months. Patients with BM showed both shorter median OS (5.9 months vs 13.1 months, p < 0.001) and PFS (3.5 months, vs 7.3 months, p < 0.001) compared to patients without BM. Patients who received bone targeted agents (BTAs) showed a significantly longer median OS (8.5 months vs 4.6 months, p = 0.003) and PFS (6.1 months vs 3.2 months, p = 0.003), while no survival benefits were observed among patients who received radiation therapy for BM during pembrolizumab treatment compared to those who did not. In multivariate analysis, performance status, concomitant liver metastases, and the lack of use of BTAs were significantly associated with worse OS and PFS. Bone involvement in UC patients treated with pembrolizumab predicts inferior survival. Poor performance status and liver metastases may further worsen outcomes, while the use of BTAs is associated with improved outcomes.
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Antineoplásicos , Neoplasias Ósseas , Carcinoma de Células de Transição , Neoplasias Hepáticas , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/radioterapia , Neoplasias da Bexiga Urinária/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
Little is known about the impact of control group therapy on clinical benefit scales such as American Society of Clinical Oncology Value Framework (ASCO-VF), European Society for Medical Oncology Magnitude Clinical Benefit Scale (ESMO-MCBS), National Comprehensive Cancer Network (NCCN) Evidence Blocks and ASCO Cancer Research Committee (ASCO-CRC). We searched Drugs@FDA to identify cancer drugs approved between January 2012 and December 2021 based on randomized trials (RCTs). Definition of substantial clinical benefit was based on recommendations for each scale. Associations between characteristics of control group therapy and clinical benefit were explored using logistic regression. RCTs with a control group of active treatment plus placebo were associated with significantly lower odds of substantial benefit with ESMO-MCBS (OR 0.27, P = 0.003) and ASCO-VF (OR 0.30, P = 0.008) but not with NCCN Evidence Blocks or ASCO-CRC. This effect was attenuated and lost statistical significance without adjustment for quality of life (QoL) and/or toxicity (ESMO-MCBS OR 0.50, P = 0.17; ASCO-VF OR 0.49, P = 0.11). Clinical benefit scales can be sensitive to control group therapy. RCTs with substantial overlap between experimental and control therapy showed lower magnitude of clinical benefit using ESMO-MCBS and ASCO-VF scales; possibly due to differences in the weighting of QoL and toxicity between different frameworks.
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Antineoplásicos , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Grupos Controle , Antineoplásicos/uso terapêutico , Oncologia , Qualidade de VidaRESUMO
The largest family of disease resistance genes in plants are nucleotide-binding site leucine-rich repeat genes (NLRs). The products of these genes are responsible for recognizing avirulence proteins (Avr) of phytopathogens and triggering specific defense responses. Identifying NLRs in plant genomes with standard gene annotation software is challenging due to their multidomain nature, sequence diversity, and clustered genomic distribution. We present the results of a genome-wide scan and comparative analysis of NLR loci in three coffee species (Coffea canephora, Coffea eugenioides and their interspecific hybrid Coffea arabica). A total of 1311 non-redundant NLR loci were identified in C. arabica, 927 in C. canephora, and 1079 in C. eugenioides, of which 809, 562, and 695 are complete loci, respectively. The NLR-Annotator tool used in this study showed extremely high sensitivities and specificities (over 99%) and increased the detection of putative NLRs in the reference coffee genomes. The NLRs loci in coffee are distributed among all chromosomes and are organized mostly in clusters. The C. arabica genome presented a smaller number of NLR loci when compared to the sum of the parental genomes (C. canephora, and C. eugenioides). There are orthologous NLRs (orthogroups) shared between coffee, tomato, potato, and reference NLRs and those that are shared only among coffee species, which provides clues about the functionality and evolutionary history of these orthogroups. Phylogenetic analysis demonstrated orthologous NLRs shared between C. arabica and the parental genomes and those that were possibly lost. The NLR family members in coffee are subdivided into two main groups: TIR-NLR (TNL) and non-TNL. The non-TNLs seem to represent a repertoire of resistance genes that are important in coffee. These results will support functional studies and contribute to a more precise use of these genes for breeding disease-resistant coffee cultivars.
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Aphids secrete proteins from their stylets that evidence indicates function similar to pathogen effectors for virulence. Here, we describe two small candidate effector gene families of the pea aphid, Acyrthosiphon pisum, that share highly conserved secretory signal peptide coding regions and divergent non-secretory coding sequences derived from miniature exons. The KQY candidate effector family contains eleven members with additional isoforms, generated by alternative splicing. Pairwise comparisons indicate possible four unique KQY families based on coding regions without the secretory signal region. KQY1a, a representative of the family, is encoded by a 968 bp mRNA and a gene that spans 45.7 kbp of the genome. The locus consists of 37 exons, 33 of which are 15 bp or smaller. Additional KQY members, as well as members of the KHI family, share similar features. Differential expression analyses indicate that the genes are expressed preferentially in salivary glands. Proteomic analysis on salivary glands and saliva revealed 11 KQY members in salivary proteins, and KQY1a was detected in an artificial diet solution after aphid feeding. A single KQY locus and two KHI loci were identified in Myzus persicae, the peach aphid. Of the genes that can be anchored to chromosomes, loci are mostly scattered throughout the genome, except a two-gene region (KQY4/KQY6). We propose that the KQY family expanded in A. pisum through combinatorial assemblies of a common secretory signal cassette and novel coding regions, followed by classical gene duplication and divergence.
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During infection, Citrus tristeza virus (CTV) produces a non-coding subgenomic RNA referred to as low-molecular-weight tristeza 1 (LMT1), which for a long time has been considered as a by-product of the complex CTV replication machinery. In this study, we investigated the role of LMT1 in the virus infection cycle using a CTV variant that does not produce LMT1 (CTV-LMT1d). We showed that lack of LMT1 did not halt virus ability to replicate or form proper virions. However, the mutant virus demonstrated significantly reduced invasiveness and systemic spread in Nicotiana benthamiana as well as an inability to establish infection in citrus. Introduction of CTV-LMT1d into the herbaceous host resulted in elevation of the levels of salicylic acid (SA) and SA-responsive pathogenesis-related genes beyond those upon inoculation with wild-type (WT) virus (CTV-WT). Further analysis showed that the LMT1 RNA produced by CTV-WT or via ectopic expression in the N. benthamiana leaves suppressed SA accumulation and up-regulated an alternative oxidase gene, which appeared to mitigate the accumulation of reactive oxygen species. To the best of our knowledge, this is the first report of a plant viral long non-coding RNA being involved in counter-acting host response by subverting the SA-mediated plant defense.
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Closterovirus/genética , Closterovirus/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Vegetal/imunologia , RNA Longo não Codificante/imunologia , RNA Viral/imunologia , Citrus/virologia , Vírus de DNA/genética , Genoma Viral , Interações Hospedeiro-Patógeno/genética , Proteínas Mitocondriais , Oxirredutases , Doenças das Plantas/virologia , Folhas de Planta/virologia , Proteínas de Plantas , RNA Viral/genética , Ácido Salicílico , Nicotiana/virologia , Carga Viral , Replicação ViralRESUMO
Two Streptomyces spp. strains responsible for potato common scab infections in Uruguay which do not produce diketopiperazines were identified through whole-genome sequencing, and the virulence factor produced by one of them was isolated and characterized. Phylogenetic analysis showed that both pathogenic strains can be identified as S. niveiscabiei, and the structure of the phytotoxin was elucidated as that of the polyketide desmethylmensacarcin using MS and NMR methods. The metabolite is produced in yields of â¼200 mg/L of culture media, induces deep necrotic lesions on potato tubers, stuns root and shoot growth in radish seedlings, and is comparatively more aggressive than thaxtomin A. This is the first time that desmethylmensacarcin, a member of a class of compounds known for their antitumor and antibiotic activity, is associated with phytotoxicity. More importantly, it represents the discovery of a new virulence factor related to potato common scab, an economically-important disease affecting potato production worldwide.
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Doenças das Plantas/microbiologia , Solanum tuberosum/microbiologia , Streptomyces/química , Dicetopiperazinas , Indóis/toxicidade , Estrutura Molecular , Filogenia , Piperazinas/toxicidade , Doenças das Plantas/etiologia , Raphanus/microbiologia , Streptomyces/patogenicidade , Fatores de Virulência/química , Fatores de Virulência/isolamento & purificaçãoRESUMO
The lateral organ boundary domain (LBD) genes encode a group of plant-specific proteins that function as transcription factors in the regulation of plant growth and development. Citrus sinensis lateral organ boundary 1 (CsLOB1) is a member of the LBD family and functions as a disease susceptibility gene in citrus bacterial canker (CBC). Thirty-four LBD members have been identified from the Citrus sinensis genome. We assessed the potential for additional members of LBD genes in citrus to function as surrogates for CsLOB1 in CBC, and compared host gene expression on induction of different LBD genes. Using custom-designed transcription activator-like (TAL) effectors, two members of the same clade as CsLOB1, named CsLOB2 and CsLOB3, were found to be capable of functioning similarly to CsLOB1 in CBC. RNA sequencing and quantitative reverse transcription-polymerase chain reaction analyses revealed a set of cell wall metabolic genes that are associated with CsLOB1, CsLOB2 and CsLOB3 expression and may represent downstream genes involved in CBC.
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Citrus sinensis/metabolismo , Citrus sinensis/microbiologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Citrus sinensis/genética , Suscetibilidade a Doenças , Genoma de Planta/genética , Doenças das Plantas/genética , Proteínas de Plantas/genéticaRESUMO
In 2004, an influential report in The Lancet suggested that open health information for all could be achieved by 2015. Unfortunately, this goal has not yet been accomplished. Despite progress in obtaining quality scientific articles in Latin America, it remains difficult to reliably access new and cutting-edge research. As graduating Peruvian medical students, we have confronted many obstacles in obtaining access to quality and up-to-date information and a constant tension between accessing "what is available" rather than "what we need". As we have learned, these limitations affect not only our own education but also the choices we make in the management of our patients. In the following article, we state our point of view regarding limitations in access to scientific articles in Peru and Latin America.
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Type 2 Diabetes mellitus (DM2) includes a continuum of metabolic disorders characterized by hyperglycemia that causes several chronic long-term complications such as coronary artery disease, peripheral arterial disease, nephropathy, and neuropathy. The hair follicle could reveal signs of early vascular impairment, yet its relationship to early metabolic injuries has been largely ignored. We propose that in earlier stages of the continuum of DM2-related metabolic disorders, a group of susceptible patients who do not yet meet the diagnostic criteria to be considered as persons with DM2 may present chronic vascular impairment and end organ damage, including hair follicle damage, which can be evaluated to identify an early risk marker. This hypothesis is based in the association found between insulin resistance and alopecia in non-diabetic persons, and the hair loss on the lower limbs as a manifestation of long-term peripheral arterial disease among subjects with DM2. In order to test this hypothesis, studies are required to evaluate if hair follicle characteristics are related to and can predict hyperglycemic complications, and if they do so, which feature of the hair follicle, such as hair growth, best characterizes such DM2-related conditions. If this hypothesis were proven to be true, significant advances towards a personalized approach for early prevention strategies and management of DM2 would be made. By focusing on the hair follicles, early stages of metabolic-related organ damage could be identified using non-invasive low-cost techniques. In so doing, this approach could provide early identification of DM2-susceptible individuals and lead to the early initiation of adequate primary prevention strategies to reduce or avoid the onset of large internal organ damage.
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Diabetes Mellitus Tipo 2/diagnóstico , Folículo Piloso/fisiopatologia , Envelhecimento , Alopecia/complicações , Aminoácidos/sangue , Aminoácidos/metabolismo , Doenças Autoimunes/complicações , Diabetes Mellitus Tipo 2/sangue , Progressão da Doença , Etnicidade , Feminino , Cabelo/fisiologia , Humanos , Hiperglicemia/sangue , Resistência à Insulina , Masculino , Modelos Teóricos , Projetos de Pesquisa , Risco , Estações do AnoRESUMO
INTRODUCTION: The inadequate reporting of cross-sectional studies, as in the case of the prevalence of metabolic syndrome, could cause problems in the synthesis of new evidence and lead to errors in the formulation of public policies. OBJECTIVE: To evaluate the reporting quality of the articles regarding metabolic syndrome prevalence in Peruvian adults using the STROBE recommendations. METHODS: We conducted a thorough literature search with the terms "Metabolic Syndrome", "Sindrome Metabolico" and "Peru" in MEDLINE/PubMed, LILACS, SciELO, LIPECS and BVS-Peru until December 2014. We selected those who were population-based observational studies with randomized sampling that reported prevalence of metabolic syndrome in adults aged 18 or more of both sexes. Information was analysed through the STROBE score per item and recommendation. RESULTS: Seventeen articles were included in this study. All articles met the recommendations related to the report of the study's rationale, design, and provision of summary measures. The recommendations with the lowest scores were those related to the sensitivity analysis (8%, n= 1/17), participant flowchart (18%, n= 3/17), missing data analysis (24%, n= 4/17), and number of participants in each study phase (24%, n= 4/17). CONCLUSION: Cross-sectional studies regarding the prevalence of metabolic syndrome in peruvian adults have an inadequate reporting on the methods and results sections. We identified a clear need to improve the quality of such studies.
INTRODUCCIÓN: El reporte inadecuado de estudios transversales, como en el caso de la prevalencia de síndrome metabólico, podría causar problemas en la síntesis de nueva evidencia y generar errores en la formulación de políticas públicas. OBJETIVO: Evaluar la calidad de reporte de estudios transversales sobre la prevalencia de síndrome metabólico en Perú utilizando las recomendaciones de STROBE. MÉTODOS: Se realizó una búsqueda bibliográfica exhaustiva hasta Diciembre 2014 en MEDLINE/PubMed, LILACS, SciELO, LIPECS y BVS-Perú con los términos "Metabolic Syndrome", "Sindrome Metabolico" y "Peru". Se seleccionaron estudios observacionales con base poblacional, muestreo aleatorizado, que reportaran datos de prevalencia en adultos mayores de 18 años de ambos sexos. La información fue analizada a través de STROBE según puntuación por artículo y por recomendación. RESULTADOS: Diecisiete artículos fueron incluidos en este estudio. Todos cumplieron con las recomendaciones relacionadas con el reporte de razones y fundamentos de la investigación, reporte del diseño de estudio y la proporción de medidas de resumen. Las recomendaciones con menor puntaje fueron las relacionadas a la descripción del análisis de sensibilidad (8%, n= 1/13), consideración del uso de diagrama de flujo para los participantes (18%, n= 3/17), explicación del análisis de datos ausentes (24%, n= 4/17) y del número de participantes en cada fase (24%, n= 4/17). CONCLUSIÓN: Los estudios transversales sobre prevalencia de síndrome metabólico en adultos del Perú presentan un inadecuado reporte en las secciones de métodos y resultados. Se identifica una clara necesidad de mejorar la calidad de este tipo de estudios.
Assuntos
Estudos Transversais/normas , Síndrome Metabólica/epidemiologia , Adulto , Guias como Assunto , Humanos , Estudos Observacionais como Assunto/normas , Peru/epidemiologia , Prevalência , Sensibilidade e EspecificidadeAssuntos
Acesso à Informação , Bibliometria , Bases de Dados Bibliográficas/estatística & dados numéricos , Dermatologia/estatística & dados numéricos , Publicações Periódicas como Assunto/estatística & dados numéricos , Indexação e Redação de Resumos , Humanos , América Latina , MEDLINE/estatística & dados numéricosRESUMO
Introduction: The inadequate reporting of cross-sectional studies, as in the case of the prevalence of metabolic syndrome, could cause problems in the synthesis of new evidence and lead to errors in the formulation of public policies. Objective: To evaluate the reporting quality of the articles regarding metabolic syndrome prevalence in Peruvian adults using the STROBE recommendations. Methods: We conducted a thorough literature search with the terms "Metabolic Syndrome", "Sindrome Metabolico" and "Peru" in MEDLINE/PubMed, LILACS, SciELO, LIPECS and BVS-Peru until December 2014. We selected those who were population-based observational studies with randomized sampling that reported prevalence of metabolic syndrome in adults aged 18 or more of both sexes. Information was analysed through the STROBE score per item and recommendation. Results: Seventeen articles were included in this study. All articles met the recommendations related to the report of the study's rationale, design, and provision of summary measures. The recommendations with the lowest scores were those related to the sensitivity analysis (8%, n= 1/17), participant flowchart (18%, n= 3/17), missing data analysis (24%, n= 4/17), and number of participants in each study phase (24%, n= 4/17). Conclusion: Cross-sectional studies regarding the prevalence of metabolic syndrome in peruvian adults have an inadequate reporting on the methods and results sections. We identified a clear need to improve the quality of such studies.
Introducción: El reporte inadecuado de estudios transversales, como en el caso de la prevalencia de síndrome metabólico, podría causar problemas en la síntesis de nueva evidencia y generar errores en la formulación de políticas públicas. Objetivo: Evaluar la calidad de reporte de estudios transversales sobre la prevalencia de síndrome metabólico en Perú utilizando las recomendaciones de STROBE. Métodos: Se realizó una búsqueda bibliográfica exhaustiva hasta Diciembre 2014 en MEDLINE/PubMed, LILACS, SciELO, LIPECS y BVS-Perú con los términos "Metabolic Syndrome", "Sindrome Metabolico" y "Peru". Se seleccionaron estudios observacionales con base poblacional, muestreo aleatorizado, que reportaran datos de prevalencia en adultos mayores de 18 años de ambos sexos. La información fue analizada a través de STROBE según puntuación por artículo y por recomendación. Resultados: Diecisiete artículos fueron incluidos en este estudio. Todos cumplieron con las recomendaciones relacionadas con el reporte de razones y fundamentos de la investigación, reporte del diseño de estudio y la proporción de medidas de resumen. Las recomendaciones con menor puntaje fueron las relacionadas a la descripción del análisis de sensibilidad (8%, n= 1/13), consideración del uso de diagrama de flujo para los participantes (18%, n= 3/17), explicación del análisis de datos ausentes (24%, n= 4/17) y del número de participantes en cada fase (24%, n= 4/17). Conclusión: Los estudios transversales sobre prevalencia de síndrome metabólico en adultos del Perú presentan un inadecuado reporte en las secciones de métodos y resultados. Se identifica una clara necesidad de mejorar la calidad de este tipo de estudios.
Assuntos
Adulto , Humanos , Estudos Transversais/normas , Síndrome Metabólica/epidemiologia , Guias como Assunto , Estudos Observacionais como Assunto/normas , Prevalência , Peru/epidemiologia , Sensibilidade e EspecificidadeRESUMO
En el presente estudio se intentó detectar la presencia del gen de toxina en cepas locales de Escherichia Coli serológicamente relacionados a la catergoria enterohemorrágica, caracterizando además un aislamiento reportado como serotipo 0157:H7 procedente de la ciudad de Tacna (cepa Tacna 410), mediante la reacción en cadena de la polimerasa (PCR) y secuenciamiento. Los resultados confirmaron la presencia del gen de la toxina shiga sólo en la cepa Tacna 410, obteniéndose una identidad del 100 por ciento entre la secuencia nucleótida del gen de la copa Tacna 410 y secuencias reportadas de la toxna shiga de tipo II en el Genebank. Asimismo, se detectó en la cepa Tacna 410 propiedades hemolíticas y el gen eae asociado al fenómeno de attaching and effacing, características de una típica cepa de ECEH.
We tried to detect the Shiga gene in local Escherichia Coli strains serologically related the enterohemorragic category. At the same time, using polymerase chain reaction (PCR) and sequencing, we characterized a strain confirmed as E. Coli 0157:H7 serotype, which was isolated in Tacna (a city in southern Peru) (Tacna 410 strain). Our results confirmed the presence of the Shiga toxin gene only in E. coli strain Tacna 410, and we found 100 percentage identify between the sequence from the amplified gene and reference sequence for type II Shiga toxin in the gene bank. We also detected in the Tacna 410 strain hemolytic properties and the eae gene, which is associated to attaching and effacing lesions, typical features of EHEC, strains.