Multi-trait association mapping for phosphorous efficiency reveals flexible root architectures in sorghum.

BACKGROUND: On tropical regions, phosphorus (P) fixation onto aluminum and iron oxides in soil clays restricts P diffusion from the soil to the root surface, limiting crop yields. While increased root surface area favors P uptake under low-P availability, the relationship between the three-dimensional arrangement of the root system and P efficiency remains elusive. Here, we simultaneously assessed allelic effects of loci associated with a variety of root and P efficiency traits, in addition to grain yield under low-P availability, using multi-trait genome-wide association. We also set out to establish the relationship between root architectural traits assessed in hydroponics and in a low-P soil. Our goal was to better understand the influence of root morphology and architecture in sorghum performance under low-P availability. RESULT: In general, the same alleles of associated SNPs increased root and P efficiency traits including grain yield in a low-P soil. We found that sorghum P efficiency relies on pleiotropic loci affecting root traits, which enhance grain yield under low-P availability. Root systems with enhanced surface area stemming from lateral root proliferation mostly up to 40 cm soil depth are important for sorghum adaptation to low-P soils, indicating that differences in root morphology leading to enhanced P uptake occur exactly in the soil layer where P is found at the highest concentration. CONCLUSION: Integrated QTLs detected in different mapping populations now provide a comprehensive molecular genetic framework for P efficiency studies in sorghum. This indicated extensive conservation of P efficiency QTL across populations and emphasized the terminal portion of chromosome 3 as an important region for P efficiency in sorghum. Increases in root surface area via enhancement of lateral root development is a relevant trait for sorghum low-P soil adaptation, impacting the overall architecture of the sorghum root system. In turn, particularly concerning the critical trait for water and nutrient uptake, root surface area, root system development in deeper soil layers does not occur at the expense of shallow rooting, which may be a key reason leading to the distinctive sorghum adaptation to tropical soils with multiple abiotic stresses including low P availability and drought.

Genomic prediction in multi-environment trials in maize using statistical and machine learning methods.

In the context of multi-environment trials (MET), genomic prediction is proposed as a tool that allows the prediction of the phenotype of single cross hybrids that were not tested in field trials. This approach saves time and costs compared to traditional breeding methods. Thus, this study aimed to evaluate the genomic prediction of single cross maize hybrids not tested in MET, grain yield and female flowering time. We also aimed to propose an application of machine learning methodologies in MET in the prediction of hybrids and compare their performance with Genomic best linear unbiased prediction (GBLUP) with non-additive effects. Our results highlight that both methodologies are efficient and can be used in maize breeding programs to accurately predict the performance of hybrids in specific environments. The best methodology is case-dependent, specifically, to explore the potential of GBLUP, it is important to perform accurate modeling of the variance components to optimize the prediction of new hybrids. On the other hand, machine learning methodologies can capture non-additive effects without making any assumptions at the outset of the model. Overall, predicting the performance of new hybrids that were not evaluated in any field trials was more challenging than predicting hybrids in sparse test designs.

Treatment patterns and outcomes associated with sequential and non-sequential use of CDK4 & 6 inhibitors in patients with HR+, HER2- MBC in the real world.

PURPOSE: Cyclin Dependent Kinase 4 & 6 inhibitors (CDK4 & 6i) have transformed the management of HR+, HER2- metastatic breast cancer (MBC); however, the optimal sequence of these treatments and other systemic therapies for MBC remains unclear. METHODS: This study analyzed electronic medical records from the ConcertAI Oncology Dataset. US patients who received abemaciclib and at least one other systemic line of therapy (LOT) for HR+, HER2- MBC were eligible. Treatment sequences were grouped, and data for two pairs of groups are presented herein (N = 397): Group 1 (1L CDK4 & 6i to 2L CDK4 & 6i) vs. Group 2 (1L CDK4 & 6i to 2L non-CDK4 & 6i), and Group 3 (2L CDK4 & 6i to 3L CDK4 & 6i) vs. Group 4 (2L CDK4 & 6i to 3L non-CDK4 & 6i). Time-to-event outcomes (PFS and PFS-2) were analyzed using Kaplan-Meier method and Cox proportional hazard regression. RESULTS: In the total cohort of 690 patients, the most prevalent sequence was 1L CDK4 & 6i to 2L CDK4 & 6i (n = 165). For the 397 patients across Groups 1-4, sequential CDK4 & 6i demonstrated numerically longer PFS and PFS-2 versus non-sequential CDK4 & 6i. Adjusted results demonstrate that patients in Group 1 demonstrated significantly longer PFS (p = 0.05) versus Group 2. CONCLUSIONS: Although retrospective and hypothesis-generating, these data demonstrate numerically longer outcomes in the subsequent LOT associated with sequential CDK4 & 6i treatment.

Clinical and Genomic Characteristics of Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Following Progression on Cyclin-Dependent Kinase 4 and 6 Inhibitors.

PURPOSE: We explored the clinical and genomic characteristics of hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC) after progression on cyclin-dependent kinase 4 and 6 inhibitors (CDK4 and 6i) ± endocrine therapy (ET) to understand potential resistance mechanisms that may aid in identifying treatment options. EXPERIMENTAL DESIGN: Patients in the United States with HR+, HER2- MBC had tumor biopsies collected from a metastatic site during routine care following progression on a CDK4 and 6i ± ET (CohortPost) or prior to initiating CDK4 and 6i treatment (CohortPre) and analyzed using a targeted mutation panel and RNA-sequencing. Clinical and genomic characteristics were described. RESULTS: The mean age at MBC diagnosis was 59 years in CohortPre (n = 133) and 56 years in CohortPost (n = 223); 14% and 45% of patients had prior chemotherapy/ET, and 35% and 26% had de novo stage IV MBC, respectively. The most common biopsy site was liver (CohortPre, 23%; CohortPost, 56%). CohortPost had significantly higher tumor mutational burden (TMB; median 3.16 vs. 1.67 Mut/Mb, P < 0.0001), ESR1 alteration frequency (mutations: 37% vs. 10%, FDR < 0.0001; fusions: 9% vs. 2%, P = 0.0176), and higher copy-number amplification of genes on chr12q15, including MDM2, FRS2, and YEATS4 versus patients in the CohortPre group. In addition, CDK4 copy-number gain on chr12q13 was significantly higher in CohortPost versus CohortPre (27% vs. 11%, P = 0.0005). CONCLUSIONS: Distinct mechanisms potentially associated with resistance to CDK4 and 6i ± ET, including alterations in ESR1 and amplification of chr12q15 and CDK4 copy-number gain, were identified.

Genome-Wide Association Study for Root Morphology and Phosphorus Acquisition Efficiency in Diverse Maize Panels.

Maximizing soil exploration through modifications of the root system is a strategy for plants to overcome phosphorus (P) deficiency. Genome-wide association with 561 tropical maize inbred lines from Embrapa and DTMA panels was undertaken for root morphology and P acquisition traits under low- and high-P concentrations, with 353,540 SNPs. P supply modified root morphology traits, biomass and P content in the global maize panel, but root length and root surface area changed differentially in Embrapa and DTMA panels. This suggests that different root plasticity mechanisms exist for maize adaptation to low-P conditions. A total of 87 SNPs were associated to phenotypic traits in both P conditions at -log10(p-value) ≥ 5, whereas only seven SNPs reached the Bonferroni significance. Among these SNPs, S9_137746077, which is located upstream of the gene GRMZM2G378852 that encodes a MAPKKK protein kinase, was significantly associated with total seedling dry weight, with the same allele increasing root length and root surface area under P deficiency. The C allele of S8_88600375, mapped within GRMZM2G044531 that encodes an AGC kinase, significantly enhanced root length under low P, positively affecting root surface area and seedling weight. The broad genetic diversity evaluated in this panel suggests that candidate genes and favorable alleles could be exploited to improve P efficiency in maize breeding programs of Africa and Latin America.

Repercussões da insuficiência renal crônica no contexto biopsicossocial de pessoa em tratamento hemodialítico / Repercussions of chronic kidney failure on the biopsychosocial context of patients in hemodialytic treatment

Introdução: a insuficiência renal crônica é considerada um importante problema de saúde pública, uma vez que tanto a doença quanto o tratamento provocam impactos profundos em todo o contexto de vida da pessoa acometida. Objetivo: compreender as repercussões da insuficiência renal crônica no contexto biopsicossocial de pacientes em tratamento hemodialítico. Metodologia: trata-se de um estudo descritivo, qualitativo, desenvolvido em um hospital referência regional para o tratamento de hemodiálise no Estado da Bahia, Brasil. Participaram do estudo 20 pessoas com insuficiência renal crônica, com idade superior a 18 anos, em tratamento hemodialítico. A coleta dos dados foi realizada durante o mês de dezembro de 2019 através de uma entrevista semiestruturada. Posteriormente, os dados foram sistematizados através da Análise de Conteúdo. Resultados: evidenciou-se que a insuficiência renal traz repercussões multidimensionais para os pacientes, devido às dificuldades de inserção no mundo do trabalho, dificuldades relacionadas às restrições alimentares e hídricas, limitações relacionadas ao lazer e a prática de atividade física e impactos no exercício da sexualidade. Entretanto, apesar das limitações provocadas pela doença, os pacientes mostraram-se resilientes ao destacarem a importância do tratamento para garantia de sua qualidade de vida. Conclusão: o estudo aponta para necessidade de construção de políticas específicas voltadas para redução dos impactos provocados pela Insuficiência Renal Crônica, uma vez que se trata de uma doença crônica e irreversível, com necessidade de tratamento permanente. Além disso, os achados ratificam a necessidade de avaliação individualizada e oferta de uma assistência holística e humanizada por parte dos profissionais de saúde como forma de minimizar os impactos do adoecimento.

Introducción: La insuficiencia renal crónica es considerada un importante problema de salud pública, ya que tanto la enfermedad como el tratamiento tienen profundos impactos en todo el contexto de vida de la persona afectada. Objetivo: Comprender las repercusiones de la insuficiencia renal crónica en el contexto biopsicosocial de personas en hemodiálisis. Metodología: Se trata de un estudio descriptivo, cualitativo, desarrollado en un hospital regional de referencia para el tratamiento de hemodiálisis en el Estado de Bahía, Brasil. En el estudio participaron 20 personas con insuficiencia renal crónica, mayores de 18 años, sometidas a hemodiálisis. La recolección de datos se realizó durante el mes de diciembre de 2019, a través de una entrevista semiestructurada. Posteriormente, los datos fueron sistematizados mediante análisis de contenido. Resultados: Se demostró que la insuficiencia renal trae repercusiones multidimensionales para las personas, debido a las dificultades para ingresar al mundo laboral, dificultades relacionadas con las restricciones alimentarias y hídricas, limitaciones relacionadas con el ocio y la práctica de actividad física e impactos en el ejercicio de la sexualidad. Sin embargo, a pesar de las limitaciones provocadas por la enfermedad, las personas se mostraron resilientes al resaltar la importancia del tratamiento para garantizar su calidad de vida. Conclusión: El estudio apunta a la necesidad de construir políticas específicas orientadas a reducir los impactos provocados por la insuficiencia renal crónica, por ser una enfermedad crónica e irreversible, que necesita tratamiento permanente. Además, los hallazgos confirman la necesidad de una evaluación individualizada y la provisión de atención integral y humanizada por parte de profesionales de la salud que les brindan atención, como una forma de minimizar los impactos de la enfermedad.

Introduction: chronic renal failure is considered an important public health problem since both the disease and the treatment have profound impacts on the entire life context of the affected person. Objective: to understand the repercussions of chronic renal failure in the biopsychosocial context of patients undergoing hemodialysis. Methodology: this is a descriptive, qualitative study developed in a regional reference hospital for the treatment of hemodialysis in the State of Bahia, Brazil. Twenty people with chronic renal failure undergoing hemodialysis took part in the study; all of them were over 18 years old. The data collection was carried out in December 2019 through a semi-structured interview. Subsequently, the data were systematized through Content Analysis. Results: the study showed that renal failure brings multidimensional repercussions to the patients due to the difficulties in entering the world market, difficulties related to food and water restrictions, limitations related to leisure and the physical activity practices, and the impact on sexuality. However, despite the limitations caused by the disease, patients showed themselves resilient in highlighting the importance of the treatment to guarantee their quality of life. Conclusion: the study points to the need of building specific policies aimed at reducing the impact caused by chronic renal failure since it is a chronic and irreversible disease that requires permanent treatment. Furthermore, the findings confirm the need for individualized assessment and the provision of holistic and humanized care by health professionals as a way to minimize the impact of the illness.

Targeting CDK4 and 6 in Cancer Therapy: Emerging Preclinical Insights Related to Abemaciclib.

Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4 and 6) are approved for the treatment of subsets of patients with hormone receptor positive (HR+) breast cancer (BC). In metastatic disease, strategies involving endocrine therapy combined with CDK4 and 6 inhibitors (CDK4 and 6i) improve clinical outcomes in HR+ BCs. CDK4 and 6i prevent retinoblastoma tumor suppressor protein phosphorylation, thereby blocking the transcription of E2F target genes, which in turn inhibits both mitogen and estrogen-mediated cell proliferation. In this review, we summarize preclinical data pertaining to the use of CDK4 and 6i in BC, with a particular focus on several of the unique chemical, pharmacologic, and mechanistic properties of abemaciclib. As research efforts elucidate the novel mechanisms underlying abemaciclib activity, potential new applications are being identified. For example, preclinical studies have demonstrated abemaciclib can exert antitumor activity against multiple tumor types and can cross the blood-brain barrier. Abemaciclib has also demonstrated distinct activity as a monotherapeutic in the treatment of BC. Accordingly, we also discuss how a greater understanding of mechanisms related to CDK4 and 6 blockade highlight abemaciclib's unique in-class properties, and could pave new avenues for enhancing its therapeutic efficacy.

Real world incidence and management of adverse events in patients with HR+, HER2- metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting.

OBJECTIVE: To examine the real-world incidence and management of select adverse events (AEs) among female patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), receiving a cyclin-dependent kinase 4 and 6 (CDK4 and 6) inhibitor (palbociclib, abemaciclib, or ribociclib). METHODS: This retrospective study analyzed data from the US Oncology Network iKnowMed electronic health record database for 396 patients with an initial MBC diagnosis on/after 1 January 2014 and receipt of first CDK4 and 6 regimen between 1 January 2017 and 31 December 2018. In this descriptive study, the proportion of patients who experienced select AEs and associated dose modifications or discontinuations were reported. The occurrence of select healthcare resource utilization categories was also reported. RESULTS: Median follow-up time was 451, 262, and 355 days for patients in the palbociclib, abemaciclib, and ribociclib cohorts, respectively. The most common AEs were neutropenia (palbociclib, 44.8%; abemaciclib, 10.6%; ribociclib, 36.3%), diarrhea (palbociclib, 8.0%; abemaciclib, 43.0%; ribociclib, 8.8%), and fatigue (palbociclib, 12.9%; abemaciclib, 17.6%; ribociclib, 16.5%). AEs resulted in a treatment hold among 91 (23.0%), a dose reduction among 86 (21.7%), and permanent discontinuation among 48 (12.1%) patients overall. CONCLUSIONS: This real-world study provides insight into the occurrence of AEs which varied by CDK4 and 6 inhibitor. Compared to clinical trials, frequencies of AEs were numerically lower but dose reductions due to AEs were numerically higher. It is possible these differences reflect proactive management of AEs on the part of clinicians to help patients remain on therapy.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4 and 6 inhibitors) have changed the landscape for the treatment of metastatic breast cancer (MBC) among patients who are hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2−). An understanding of the real-world management of adverse events (AEs) will help optimize treatment strategies. Here, data from the US Oncology Network electronic health record database for 396 HR+, HER2−, MBC patients receiving a CDK4 and 6 inhibitor were examined to describe the proportion of patients who experienced select AEs and the associated outcomes of these AEs. Compared to clinical trials, frequencies of AEs were numerically lower but dose reductions due to AEs were numerically higher. It is possible that these differences reflect a proactive management of AEs on the part of clinicians to help patients remain on therapy.

Prognostic Factors in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative (HR+/HER2-) Advanced Breast Cancer: A Systematic Literature Review.

PURPOSE: Advanced breast cancer is a heterogeneous disease with several well-defined subtypes, among which, hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) is most prevalent. Determination of HR and HER2 status influences prognosis and, thus, disease management. Although literature on these prognostic factors exist, especially in the early breast cancer setting, it remains unclear to what extent these factors can guide clinical decision-making in the advanced disease setting. Therefore, we sought to identify the strength and consistency of evidence for prognostic factors in patients with HR+/HER2- advanced breast cancer. METHODS: A systematic literature review (SLR) of the major electronic databases was conducted in November 2018 for primary research studies published since 2010. Endpoints of interest were tumor response, progression-free survival (PFS), overall survival (OS), and breast cancer-specific survival (BCSS). RESULTS: Seventy-nine studies were included wherein all patients were diagnosed with advanced breast cancer and ≥50% of the population were HR+/HER2-. OS was the most commonly assessed endpoint (n=67) followed by PFS (n=33), BCSS (n=5) and tumor response (n=3). The prognostic factors with strongest evidence of association with worse OS were negative progesterone receptor status, higher tumor grade, higher circulating tumor cell (CTC) count and higher Ki67 level, number of metastatic sites (eg multiple vs single) and sites of metastases (eg presence of liver metastases vs absence), shorter time to recurrence or progression to advanced breast cancer, poor performance status, prior therapy attributes in the early or metastatic setting (type of therapy, treatment line, response of prior therapy), and race (black vs white). The prognostic factors that had strongest evidence of association with PFS included CTC count, number and sites of metastases, and absence of prior therapy or higher lines of therapy in the early or metastatic setting. The directionality of association was consistent for all prognostic factors except between lymph node and OS, and de novo metastatic breast cancer and PFS. CONCLUSION: Multiple disease, treatment, and patient-related prognostic factors impact survival, particularly OS, in patients with HR+/HER2- advanced breast cancer. Treatment outcomes can vary considerably due to these factors. Understanding poorer prognostic factors for patients can result in improved clinical decision-making.

Real-world treatment patterns and outcomes of abemaciclib for the treatment of HR+, HER2- metastatic breast cancer.

OBJECTIVE: This retrospective observational study described baseline characteristics, real-world treatment patterns, and outcomes among patients with metastatic breast cancer treated with abemaciclib in the United States. METHODS: De-identified electronic health record-derived data were used to describe patients who began abemaciclib treatment on or after 30 June 2016 and ≥4 months before data cutoff (31 December 2018). Real-world response (rwR) and real-world progression assessments were abstracted from clinical documentation. Descriptive statistics were used to calculate the real-world best response. The Kaplan-Meier method estimated real-world time to first response (rwTTFR) and real-world progression-free survival (rwPFS). RESULTS: The median age of 118 female patients at abemaciclib initiation was 66.5 years (interquartile range, 57.0, 73.0). The breakdown of patients who received abemaciclib in first, second, third, or later lines was 28.8%, 21.2%, 20.3%, and 29.7%, respectively. Patients received abemaciclib as monotherapy (12.7%) or in combination with endocrine therapy: fulvestrant (59.3%); aromatase inhibitor (22.9%); aromatase inhibitor and fulvestrant (5.1%). There were 68 patients (57.6%) with ≥1 rwR assessment: 41.2% with a real-world complete response or real-world partial response. Median rwTTFR was 3.6 months (95% confidence interval, 3.5, 5.2). Twelve-month rwPFS probability was 61.7%. CONCLUSIONS: This study represents utilization and outcomes associated with abemaciclib approximately 1 year following FDA approval. Treatment patterns demonstrated heterogeneity and, as in clinical trials, patients appeared to benefit from abemaciclib treatment in the real world. More research investigating outcomes associated with abemaciclib treatment is needed, with larger samples and longer follow-up to enable closer evaluation by subgroup, regimen, and line of therapy.

Association mapping and genomic selection for sorghum adaptation to tropical soils of Brazil in a sorghum multiparental random mating population.

KEY MESSAGE: A multiparental random mating population used in sorghum breeding is amenable for the detection of QTLs related to tropical soil adaptation, fine mapping of underlying genes and genomic selection approaches. Tropical soils where low phosphorus (P) and aluminum (Al) toxicity limit sorghum [Sorghum bicolor (L.) Moench] production are widespread in the developing world. We report on BRP13R, a multiparental random mating population (MP-RMP), which is commonly used in sorghum recurrent selection targeting tropical soil adaptation. Recombination dissipated much of BRP13R's likely original population structure and average linkage disequilibrium (LD) persisted up to 2.5 Mb, establishing BRP13R as a middle ground between biparental populations and sorghum association panels. Genome-wide association mapping (GWAS) identified conserved QTL from previous studies, such as for root morphology and grain yield under low-P, and indicated the importance of dominance in the genetic architecture of grain yield. By overlapping consensus QTL regions, we mapped two candidate P efficiency genes to a ~ 5 Mb region on chromosomes 6 (ALMT) and 9 (PHO2). Remarkably, we find that only 200 progeny genotyped with ~ 45,000 markers in BRP13R can lead to GWAS-based positional cloning of naturally rare, subpopulation-specific alleles, such as for SbMATE-conditioned Al tolerance. Genomic selection was found to be useful in such MP-RMP, particularly if markers in LD with major genes are fitted as fixed effects into GBLUP models accommodating dominance. Shifts in allele frequencies in progeny contrasting for grain yield indicated that intermediate to minor-effect genes on P efficiency, such as SbPSTOL1 genes, can be employed in pre-breeding via allele mining in the base population. Therefore, MP-RMPs such as BRP13R emerge as multipurpose resources for efficient gene discovery and deployment for breeding sorghum cultivars adapted to tropical soils.

Root Adaptation via Common Genetic Factors Conditioning Tolerance to Multiple Stresses for Crops Cultivated on Acidic Tropical Soils.

Crop tolerance to multiple abiotic stresses has long been pursued as a Holy Grail in plant breeding efforts that target crop adaptation to tropical soils. On tropical, acidic soils, aluminum (Al) toxicity, low phosphorus (P) availability and drought stress are the major limitations to yield stability. Molecular breeding based on a small suite of pleiotropic genes, particularly those with moderate to major phenotypic effects, could help circumvent the need for complex breeding designs and large population sizes aimed at selecting transgressive progeny accumulating favorable alleles controlling polygenic traits. The underlying question is twofold: do common tolerance mechanisms to Al toxicity, P deficiency and drought exist? And if they do, will they be useful in a plant breeding program that targets stress-prone environments. The selective environments in tropical regions are such that multiple, co-existing regulatory networks may drive the fixation of either distinctly different or a smaller number of pleiotropic abiotic stress tolerance genes. Recent studies suggest that genes contributing to crop adaptation to acidic soils, such as the major Arabidopsis Al tolerance protein, AtALMT1, which encodes an aluminum-activated root malate transporter, may influence both Al tolerance and P acquisition via changes in root system morphology and architecture. However, trans-acting elements such as transcription factors (TFs) may be the best option for pleiotropic control of multiple abiotic stress genes, due to their small and often multiple binding sequences in the genome. One such example is the C2H2-type zinc finger, AtSTOP1, which is a transcriptional regulator of a number of Arabidopsis Al tolerance genes, including AtMATE and AtALMT1, and has been shown to activate AtALMT1, not only in response to Al but also low soil P. The large WRKY family of transcription factors are also known to affect a broad spectrum of phenotypes, some of which are related to acidic soil abiotic stress responses. Hence, we focus here on signaling proteins such as TFs and protein kinases to identify, from the literature, evidence for unifying regulatory networks controlling Al tolerance, P efficiency and, also possibly drought tolerance. Particular emphasis will be given to modification of root system morphology and architecture, which could be an important physiological "hub" leading to crop adaptation to multiple soil-based abiotic stress factors.

Fatores associados ao conhecimento de pessoas leigas sobre suporte básico de vida / Factores asociados con el conocimiento de los laicos sobre el soporte vital básico / Factors associated with lay people's knowledge about basic life support

Resumo Analisar os fatores associados ao conhecimento de pessoas leigas acerca do suporte básico de vida. Estudo epidemiológico, descritivo, de corte transversal, desenvolvido com 65 funcionários de um Campus da Universidade do Estado da Bahia. Os dados foram coletados nos meses de fevereiro e março de 2019 e tabulados no software IBM SPSS versão 21.0. A análise foi realizada através de frequências descritivas, teste qui-quadrado de Pearson e Exato de Fisher, adotando um grau de significância de 95% e valor de p <0,05. Observou-se que 67,7% dos participantes não sabem o que é suporte básico de vida, 61,5% não se sentem preparadas para agir em emergência, 58,5% não saberia como facilitar a respiração de uma vítima, 64,7% não sabem a quantidade de compressões realizadas por minuto e 86,2% não sabem a função do desfibrilador externo automático. No que se refere aos fatores associados, o conhecimento sobre suporte básico está associado a ser docente, (p=0,005), sentirse preparado para atuar em situações de emergência (p=0,001), saber como facilitar a respiração da vítima (p=0,000), saber o local de realização das compressões torácicas (p=0,013). O estudo levanta a necessidade de maior capacitação de pessoas leigas acerca do suporte básico de vida para que possam assistir adequadamente as vítimas de parada cardíaca em ambiente extra-hospitalar.

Abstract To analyze the factors associated with the knowledge of lay people about basic life support. This is a descriptive cross-sectional epidemiological study, conducted with 65 employees from a Campus at the State University of Bahia. Data were collected in February and March 2019 and tabulated in IBM SPSS version 21.0 software. The analysis was performed using descriptive frequencies, Pearson's chi-square test and Fisher's exact test, adopting a significance level of 95% and p value <0.05. It was observed that 67.7% of participants do not know what is basic life support, 61.5% do not feel prepared to act in emergency, 58.5% would not know how to facilitate the breathing of a victim, 64.7% do not know the amount of compressions performed per minute and 86.2% do not know the function of the automatic external defibrillator. Regarding associated factors, knowledge about basic support is associated with being a teacher (p = 0.005), feeling prepared to act in emergency situations (p = 0.001), knowing how to facilitate the victim's breathing (p = 0.001). = 0.000), know the location of the chest compressions (p = 0.013). The study raises the need for greater training of lay people about basic life support so that they can adequately assist victims of cardiac arrest in an out-of-hospital setting.

Resumen Analizar los factores asociados con el conocimiento de los laicos sobre el soporte vital básico. Este es un estudio epidemiológico descriptivo de corte transversal, realizado con 65 empleados de un campus de la Universidad Estatal de Bahía. Los datos se recopilaron en febrero y marzo de 2019 y se tabularon en el software IBM SPSS versión 21.0. El análisis se realizó utilizando frecuencias descriptivas, la prueba de chi-cuadrado de Pearson y la prueba exacta de Fisher, adoptando un nivel de significación del 95% y un valor de p <0,05. Se observó que el 67.7% de los participantes no sabe qué es el soporte vital básico, el 61.5% no se siente preparado para actuar en caso de emergencia, el 58.5% no sabe cómo facilitar la respiración de una víctima, el 64,7% desconoce la cantidad de compresiones realizadas por minuto y el 86,2% desconoce la función del desfibrilador externo automático. Con respecto a los factores asociados, el conocimiento sobre el apoyo básico se asocia con ser un maestro (p = 0.005), sentirse preparado para actuar en situaciones de emergencia (p = 0.001), saber cómo facilitar la respiración de la víctima (p = 0.001). = 0.000), conoce la ubicación de las compresiones torácicas (p = 0.013). El estudio plantea la necesidad de una mayor capacitación de los laicos sobre el soporte vital básico para que puedan ayudar adecuadamente a las víctimas de un paro cardíaco en un entorno fuera del hospital.

Genomic prediction applied to multiple traits and environments in second season maize hybrids.

Genomic selection has become a reality in plant breeding programs with the reduction in genotyping costs. Especially in maize breeding programs, it emerges as a promising tool for predicting hybrid performance. The dynamics of a commercial breeding program involve the evaluation of several traits simultaneously in a large set of target environments. Therefore, multi-trait multi-environment (MTME) genomic prediction models can leverage these datasets by exploring the correlation between traits and Genotype-by-Environment (G×E) interaction. Herein, we assess predictive abilities of univariate and multivariate genomic prediction models in a maize breeding program. To this end, we used data from 415 maize hybrids evaluated in 4 years of second season field trials for the traits grain yield, number of ears, and grain moisture. Genotypes of these hybrids were inferred in silico based on their parental inbred lines using single nucleotide polymorphisms (SNPs) markers obtained via genotyping-by-sequencing (GBS). Because genotypic information was available for only 257 hybrids, we used the genomic and pedigree relationship matrices to obtain the H matrix for all 415 hybrids. Our results demonstrated that in the single-environment context the use of multi-trait models was always superior in comparison to their univariate counterparts. Besides that, although MTME models were not particularly successful in predicting hybrid performance in untested years, they improved the ability to predict the performance of hybrids that had not been evaluated in any environment. However, the computational requirements of this kind of model could represent a limitation to its practical implementation and further investigation is necessary.

Aluminum tolerance mechanisms in Kenyan maize germplasm are independent from the citrate transporter ZmMATE1.

Aluminum (Al) toxicity on acid soils adversely affects maize yields, which can be overcome by combining soil amendments with genetic tolerance. In maize, ZmMATE1 confers Al tolerance via Al-activated citrate release, whereby citrate forms non-toxic complexes with Al3+ in the rhizosphere. Here, we investigated Al tolerance mechanisms in maize germplasm originated from Kenya based on quantitative trait loci (QTL) mapping. Five QTLs and four epistatic interactions explained ~51% of the phenotypic variation for Al tolerance. The lack of Al tolerance QTL on chromosome 6 and the much lower expression of ZmMATE1 in both Kenyan lines than in Cateto Al237, which donates the superior allele of ZmMATE1, strongly indicate that this gene does not play a significant role in Al tolerance in neither parent. In turn, maize homologs to genes previously implicated in Al tolerance in other species, ZmNrat1, ZmMATE3, ZmWRKY and ZmART1, co-localized with Al tolerance QTL and were more highly expressed in the parent that donate favorable QTL alleles. However, these candidate genes will require further studies for functional validation on maize Al tolerance. The existence of Al tolerance mechanisms independent from ZmMATE1 suggests it is possible to develop highly Al tolerant cultivars by pyramiding complementary Al tolerance genes in maize.

Prevalence and Factors Associated with Burnout Syndrome among Primary Health Care Nursing Professionals: A Cross-Sectional Study.

The objective of the study was to evaluate the prevalence and factors associated with Burnout Syndrome (BS) in Primary Health Care (PHC) nursing professionals from the state of Bahia, Brazil. A multicentre, cross-sectional population-based study was conducted in a cluster sample among 1125 PHC Nursing professionals during the years 2017 and 2018. We used a questionnaire that included sociodemographic, labor and lifestyle variables and the Maslach Burnout Inventory scale to identify BS. The associations were evaluated using a robust Poisson regression with the hierarchical selection of the independent variables. The prevalence of BS was 18.3% and the associated factors were ethnicity (prevalence ratio (PR) = 0.62, confidence interval (CI) 95% = 0.47-0.83), residence (PR = 2.35, CI 95% = 1.79-3.09), economic situation (PR = 1.40, CI 95% = 1.06-1.86), satisfaction with current occupation (PR = 1.75, CI 95% = 1.31-2.33), (PR = 1.60, CI 95% = 1.23-2.08), rest (PR = 1.83, 95% CI = 1.41-2.37), technical resources and equipment (PR = 1.37, CI 95% = 1.06-1.77), night shift (PR = 1.49, CI 95% = 1.14-1.96), physical activity practice (PR = 1.72; CI 95% = 1.28-2.31), smoking (PR = 1.82, CI 95% = 1.35-2.45), and satisfaction with physical form (PR = 1.34, CI 95% = 1.01-179). Strategies are needed to prevent BS, with an emphasis on implementing worker health programs in the context of PHC.

Clinical findings in congenital infection by Zika virus: a retrospective study in a reference hospital in Central-West Brazil.

BACKGROUND: An increased number of congenital Zika virus infections with neurological and musculoskeletal malformations have been diagnosed worldwide, however, there are still several gaps in the knowledge about this infection, its associated mechanism, timing of transmission, and description of throughout findings of signs and symptoms, which is described in this paper. The purpose of this study is to describe aspects of congenital Zika syndrome (CZS) beyond the central nervous system comprising detailed delineation of all the other clinical findings. METHODS: A retrospective research developed using electronic medical records. We analyzed the files of 69 children with an initial diagnosis of microcephaly by Zika vírus who were born in 2015, 2016 and 2017, treated during the period from 2016 to 2017. RESULTS: The newborns presented several neurological and musculoskeletal malformations, eye damage, hearing impairment and other malformations. CONCLUSIONS: The present study has significant impact for health care teams following lactents with Congenital Zika Syndrome.

The genetic architecture of phosphorus efficiency in sorghum involves pleiotropic QTL for root morphology and grain yield under low phosphorus availability in the soil.

BACKGROUND: Phosphorus (P) fixation on aluminum (Al) and iron (Fe) oxides in soil clays restricts P availability for crops cultivated on highly weathered tropical soils, which are common in developing countries. Hence, P deficiency becomes a major obstacle for global food security. We used multi-trait quantitative trait loci (QTL) mapping to study the genetic architecture of P efficiency and to explore the importance of root traits on sorghum grain yield on a tropical low-P soil. RESULTS: P acquisition efficiency was the most important component of P efficiency, and both traits were highly correlated with grain yield under low P availability. Root surface area was positively associated with grain yield. The guinea parent, SC283, contributed 58% of all favorable alleles detected by single-trait mapping. Multi-trait mapping detected 14 grain yield and/or root morphology QTLs. Tightly linked or pleiotropic QTL underlying the surface area of fine roots (1-2 mm in diameter) and grain yield were detected at positions 1-7 megabase pairs (Mb) and 71 Mb on chromosome 3, respectively, and a root diameter/grain yield QTL was detected at 7 Mb on chromosome 7. All these QTLs were near sorghum homologs of the rice serine/threonine kinase, OsPSTOL1. The SbPSTOL1 genes on chromosome 3, Sb03g006765 at 7 Mb and Sb03g031690 at 60 Mb were more highly expressed in SC283, which donated the favorable alleles at all QTLs found nearby SbPSTOL1 genes. The Al tolerance gene, SbMATE, may also influence a grain yield QTL on chromosome 3. Another PSTOL1-like gene, Sb07g02840, appears to enhance grain yield via small increases in root diameter. Co-localization analyses suggested a role for other genes, such as a sorghum homolog of the Arabidopsis ubiquitin-conjugating E2 enzyme, phosphate 2 (PHO2), on grain yield advantage conferred by the elite parent, BR007 allele. CONCLUSIONS: Genetic determinants conferring higher root surface area and slight increases in fine root diameter may favor P uptake, thereby enhancing grain yield under low-P availability in the soil. Molecular markers for SbPSTOL1 genes and for QTL increasing grain yield by non-root morphology-based mechanisms hold promise in breeding strategies aimed at developing sorghum cultivars adapted to low-P soils.

Repeat variants for the SbMATE transporter protect sorghum roots from aluminum toxicity by transcriptional interplay in cis and trans.

Acidic soils, where aluminum (Al) toxicity is a major agricultural constraint, are globally widespread and are prevalent in developing countries. In sorghum, the root citrate transporter SbMATE confers Al tolerance by protecting root apices from toxic Al3+, but can exhibit reduced expression when introgressed into different lines. We show that allele-specific SbMATE transactivation occurs and is caused by factors located away from SbMATE Using expression-QTL mapping and expression genome-wide association mapping, we establish that SbMATE transcription is controlled in a bipartite fashion, primarily in cis but also in trans Multiallelic promoter transactivation and ChIP analyses demonstrated that intermolecular effects on SbMATE expression arise from a WRKY and a zinc finger-DHHC transcription factor (TF) that bind to and trans-activate the SbMATE promoter. A haplotype analysis in sorghum RILs indicates that the TFs influence SbMATE expression and Al tolerance. Variation in SbMATE expression likely results from changes in tandemly repeated cis sequences flanking a transposable element (a miniature inverted repeat transposable element) insertion in the SbMATE promoter, which are recognized by the Al3+-responsive TFs. According to our model, repeat expansion in Al-tolerant genotypes increases TF recruitment and, hence, SbMATE expression, which is, in turn, lower in Al-sensitive genetic backgrounds as a result of lower TF expression and fewer binding sites. We thus show that even dominant cis regulation of an agronomically important gene can be subjected to precise intermolecular fine-tuning. These concerted cis/trans interactions, which allow the plant to sense and respond to environmental cues, such as Al3+ toxicity, can now be used to increase yields and food security on acidic soils.

Perfil de pacientes internados com diagnóstico de síndrome coronariana aguda / Profile of patients admitted to hospital with diagnosis of acute coronary syndrome

OBJETIVO: Descrever o perfil de pacientes internados com diagnóstico de síndrome coronariana aguda. MÉTODOS: Estudo analítico, observacional e transversal, com dados obtidos da análise dos prontuários de cem pacientes internados em um hospital, de fevereiro de 2014 a janeiro de 2015, os quais tiveram diagnóstico de síndrome coronariana aguda e foram regulados para a realização da cineangiocoronariografia. Foi traçado o perfil epidemiológico e fisiopatológico desta população. RESULTADOS: Em nossa amostra, 49 (55,7%) pacientes eram do sexo masculino, com média de idade de 63,88±13,3 anos, sendo 60,2% acima de 60 anos. O quadro clínico mais prevalente foi angina instável (41%). Constatou-se maior prevalência de portadores de hipertensão arterial (88,7%), além de associação positiva entre os pacientes com idade avançada e doença multiarterial. Também foi encontrada obstrução coronariana significativa em cerca de 90% dos pacientes diabéticos. Cineangiocoronariografia sem lesão significativa foi duas vezes mais identificada, em comparação com dados da American College of Cardiology. CONCLUSÃO: Fatores de risco modificáveis devem ser controlados, visando à redução do número de casos de doenças cardiovasculares agudas e daqueles com desfechos desfavoráveis. Sugere-se que a divulgação dos sintomas de infarto seja ampliada, para que os pacientes cheguem à emergência em tempo hábil de receber o tratamento.(AU)

OBJECTIVE: To describe the profile of patients admitted to Hospital with a diagnosis of acute coronary syndrome METHODS: This is an analytical, observational and crosssectional study with data obtained from the analyses of the medical records of 100 patients admitted to a hospital from February/2014 to January / 2015), who were diagnosed with acute coronary syndrome, and were regulated for undergoing coronary angiography. The epidemiological and pathophysiological profile of this population was described. RESULTS: In our sample, there were 49 (55.7 %) male patients with a mean age of 63.88±13.3 years, with 60.2 % being over 60 years. The most prevalent clinical condition was unstable angina (41%). A higher prevalence of patients with hypertension (88.7 %) was found, as well as a positive association of patients with advanced age and multivessel disease. We also find significant coronary obstruction in about 90 % of diabetic patients. Coronary angiographywith no significant lesion was twice as identified if compared with the American College of Cardiology data. CONCLUSION: The modifiable risk factors should be monitored, in order to reduce the number of cases of acute cardiovascular disease and those with unfavorable outcomes. The dissemination of information about infarction should be enhanced for the patients to search for emergent care in a timely manner.(AU)