Genetic Control of Parthenogenesis in Kentucky Bluegrass: Results from a Sexual x Apomictic Cross

Apomixis, as it exists in Poa pratensis L., permits to combine genotype fixation with propagation by seed. The process of apomictic seed production involves the formation of embryo sacs without meiotic reduction (apospory) and embryos without egg cell fertilization (parthenogenesis). Further information on the genetic control of apomixis was obtained by analyzing aposporous parthenogenesis and the segregation of molecular markers in a progeny resulting from a “sexual” (S) x “apomictic”(A) cross. Data from the 35 F1 plants examined so far have shown that parthenogenesis segregated 1:1, confirming control by a dominant gene, simplex in the parthenogenetic parent. Analysis of variance and regression were used to find single markers from the A and S parents affecting the trait in the 15 parthenogenetic progenies. A minimum of 4 genes from the sexual parent and 1 from the apomictic parent influencing the expression of parthenogenesis appeared to segregate in this cross

Effect of selenium enrichment on metabolism of tomato (Solanum lycopersicum) fruit during post‐harvest ripening

BACKGROUND Selenium (Se) enrichment of plants seems effective in enhancing the health‐related properties of produce, and in delaying plant senescence and fruit ripening. The current study investigated the effects of Se on tomato fruit ripening. Tomato (Solanum lycopersicum L.) plants were grown in hydroponics with different Se‐enriched nutrient solutions. Se, as sodium selenate, was added at rate of 0 mg L‐1 (control), 1 mg L‐1, and 1.5 mg L‐1. RESULTS Selenium was absorbed by roots and translocated to leaves and fruit. Se enrichment did not significantly affect the qualitative parameters of fruit at commercial harvest, instead it delayed ripening by affecting specific ripening‐related processes (respiration, ethylene production, color evolution) during postharvest. In the current experiment 100 g of tomato hydroponically grown with a 1.5 mg Se L‐1 enriched solution provided a total of 23.7 μg Se. Selenium recommended daily intake is 60 μg for women and 70 μg for men, thus the daily consumption of 100 g of enriched tomato would not lead to Se toxicity, but would provide a good Se diet supplementation. CONCLUSIONS The cultivation of tomato plants in a Se‐enriched solution appeared effective in producing tomato fruit with improved performances during storage and postharvest shelf life, and also with greater potential health‐promoting properties

Poor outcome for patients with gastric cancer and lung metastases treated with ramucirumab and paclitaxel

The aim of this report is to investigate the activity of ramucirumab in combination with paclitaxel in patients with metastatic gastric cancer (GC) and lung metastases. We retrospectively reviewed clinical data from patients with GC treated in second line with ramucirumab and paclitaxel according to the presence or not of lung metastases. Thirty-one patients were eligible. Five (16.1%) patients had lung metastases. The median progression-free survival was 156 days in patients without lung metastases compared with 54 days in patients with lung metastases. The median survival also showed a trend in favour of patients without lung metastases. Despite the small number of patients and the retrospective nature of the data, our analysis showed relatively poor efficacy of ramucirumab plus paclitaxel as a second-line treatment in patients with lung metastases from GC. Further studies are required to evaluate novel treatments in this subset of patients

Mending a broken heart by biomimetic 3D printed natural biomaterial-based cardiac patches: a review

: Myocardial infarction is one of the major causes of mortality as well as morbidity around the world. Currently available treatment options face a number of drawbacks, hence cardiac tissue engineering, which aims to bioengineer functional cardiac tissue, for application in tissue repair, patient specific drug screening and disease modeling, is being explored as a viable alternative. To achieve this, an appropriate combination of cells, biomimetic scaffolds mimicking the structure and function of the native tissue, and signals, is necessary. Among scaffold fabrication techniques, three-dimensional printing, which is an additive manufacturing technique that enables to translate computer-aided designs into 3D objects, has emerged as a promising technique to develop cardiac patches with a highly defined architecture. As a further step toward the replication of complex tissues, such as cardiac tissue, more recently 3D bioprinting has emerged as a cutting-edge technology to print not only biomaterials, but also multiple cell types simultaneously. In terms of bioinks, biomaterials isolated from natural sources are advantageous, as they can provide exceptional biocompatibility and bioactivity, thus promoting desired cell responses. An ideal biomimetic cardiac patch should incorporate additional functional properties, which can be achieved by means of appropriate functionalization strategies. These are essential to replicate the native tissue, such as the release of biochemical signals, immunomodulatory properties, conductivity, enhanced vascularization and shape memory effects. The aim of the review is to present an overview of the current state of the art regarding the development of biomimetic 3D printed natural biomaterial-based cardiac patches, describing the 3D printing fabrication methods, the natural-biomaterial based bioinks, the functionalization strategies, as well as the in vitro and in vivo applications

Bone Targeting Agents in Patients with Prostate Cancer: General Toxicities and Osteonecrosis of the Jaw

Introduction: Bone metastases are the most frequent site of secondary localization of prostate cancer (PCa) and are present in about 90% of cases of advanced disease. Consequently, an ade-quate management of bone involvement is of pivotal importance in the therapeutic approach and skeletal-related events (SREs) need to be closely monitored and promptly assessed and treated. Bone targeting agents (BTAs), consisting in bisphosphonates and denosumab, are an essential part of the treatment of metastatic prostate cancer that accompanies systemic treatments throughout the most part of the history of the disease. Activity and safety of bone targeting agents: These treatments are correlated to better outcomes in terms of reduction of SREs and, in metastatic castration resistant setting, of increased overall survival (OS), but several important adverse events have to be managed and prevented. Of these, osteonecrosis of the jaw (ONJ) is extremely invalidating and should be managed with a special attention. Discussion: The role of BTAs in prostate cancer is pivotal throughout many stages of the disease, but several toxicities should be quickly recognized and treated. We aim at recollecting evidence on clinical benefit of BTAs, common and specific toxicities, and explore the pathophysiology and clinical aspects of osteonecrosis of the jaw. We present a review of the literature to report the role of the different types of bone targeting agents in the management of prostate cancer with bone metastases with a particular focus on common toxicities and ONJ to rec-ollect current evidences on the activity of these compounds and the correct management of their adverse events

Predicting suicides after outpatient mental health visits in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).

The 2013 US Veterans Administration/Department of Defense Clinical Practice Guidelines (VA/DoD CPG) require comprehensive suicide risk assessments for VA/DoD patients with mental disorders but provide minimal guidance on how to carry out these assessments. Given that clinician-based assessments are not known to be strong predictors of suicide, we investigated whether a precision medicine model using administrative data after outpatient mental health specialty visits could be developed to predict suicides among outpatients. We focused on male nondeployed Regular US Army soldiers because they account for the vast majority of such suicides. Four machine learning classifiers (naive Bayes, random forests, support vector regression and elastic net penalized regression) were explored. Of the Army suicides in 2004-2009, 41.5% occurred among 12.0% of soldiers seen as outpatient by mental health specialists, with risk especially high within 26 weeks of visits. An elastic net classifier with 10-14 predictors optimized sensitivity (45.6% of suicide deaths occurring after the 15% of visits with highest predicted risk). Good model stability was found for a model using 2004-2007 data to predict 2008-2009 suicides, although stability decreased in a model using 2008-2009 data to predict 2010-2012 suicides. The 5% of visits with highest risk included only 0.1% of soldiers (1047.1 suicides/100 000 person-years in the 5 weeks after the visit). This is a high enough concentration of risk to have implications for targeting preventive interventions. An even better model might be developed in the future by including the enriched information on clinician-evaluated suicide risk mandated by the VA/DoD CPG to be recorded

Prognostic Factors of Survival for High-Grade Neuroendocrine Neoplasia of the Bladder: A SEER Database Analysis

Background: High-grade neuroendocrine carcinoma (NEC) is a rare and aggressive variant of bladder cancer. Considering its rarity, its therapeutic management is challenging and not standardized. Methods: We analyzed data extracted from the Surveillance, Epidemiology, and End Results (SEER) registry to evaluate prognostic factors for high-grade NEC of the bladder. Results: We extracted data on 1134 patients: 77.6% were small cell NEC, 14.6% were NEC, 5.5% were mixed neuro-endocrine non-neuroendocrine neoplasia, and 2.3% were large cell NEC. The stage at diagnosis was localized for 45% of patients, lymph nodal disease (N+M0) for 9.2% of patients, and metastatic disease for 26.1% of patients. The median overall survival (OS) was 12 months. Multivariate analysis detected that factors associated with worse OS were age being >72 years old (HR 1.94), lymph nodal involvement (HR 2.01), metastatic disease (HR 2.04), and the size of the primary tumor being >44.5 mm (HR 1.80). In the N0M0 populations, the size of the primary tumor being <44.5 mm, age being <72 years old, and major surgery were independently associated with a lower risk of death. In the N+M0 group, the size of the primary lesion was the only factor to retain an association with OS. Conclusions: Our SEER database analysis evidenced prognostic factors for high-grade NEC of the bladder that are of pivotal relevance to guide treatment and the decision-making process

Impact of plastic-related compounds on the gene expression signature of HepG2 cells transfected with CYP3A4

The presence of plastic and microplastic within the oceans as well as in marine flora and fauna have caused a multitude of problems that have been the topic of numerous investigations for many years. However, their impact on human health remains largely unknown. Such plastic and microplastic particles have been detected in blood and placenta, underlining their ability to enter the human body. Plastics also contain other compounds, such as plasticizers, antioxidants, or dyes, whose impact on human health is currently being studied. Critical enzymes within the metabolism of endogenous molecules, especially of xenobiotics, are the cytochrome P450 monooxygenases (CYPs). Although their importance in maintaining cellular balance has been confirmed, their interactions with plastics and related products are poorly understood. In this study, the possible relationship between different plastic-related compounds and CYP3A4 as one of the most important CYPs was analyzed using hepatic cells overexpressing this enzyme. Beginning with virtual compound screening and molecular docking of more than 1000 plastic-related compounds, several candidates were identified to interact with CYP3A4. In a second step, RNA-sequencing was used to study in detail the transcriptome-wide gene expression levels affected by the selected compounds. Three candidate molecules ((2,2′-methylenebis(6-tert-butyl-4-methylphenol), 1,1-bis(3,5-di-tert-butyl-2-hydroxyphenyl)ethane, and 2,2′-methylenebis(6-cyclohexyl-4-methylphenol)) had an excellent binding affinity to CYP3A4 in-silico as well as cytotoxic effects and interactions with several metabolic pathways in-vitro. We identified common pathways influenced by all three selected plastic-related compounds. In particular, the suppression of pathways related to mitosis and ‘DNA-templated DNA replication’ which were confirmed by cell cycle analysis and single-cell gel electrophoresis. Furthermore, several mis-regulated metabolic and inflammation-related pathways were identified, suggesting the induction of hepatotoxicity at different levels. These findings imply that these compounds may cause liver problems subsequently affecting the entire organism

Multidimensional emotional disorders inventory: Reliability and validity in a Spanish clinical sample

Background. The categorical approach to diagnosing mental disorders has been criticized for a number of reasons (e.g., high rates of comorbidity; larger number of diagnostic categories and combination). Diverse alternatives have been proposed using a hybrid or totally dimensional perspective. Despite the evidence supporting use of the Multidimensional Emotional Disorders Inventory (MEDI) for assessing the transdiagnostic dimensions of Emotional Disorders using a dimensional-categorical hybrid approach, no data exist on Spanish clinical samples. The present study explores the validity and reliability of the 49-item MEDI in a clinical sample and provides data for its use. Methods. A total of 280 outpatients with emotional disorders attended in different Spanish public Mental Health Units in Spain filled out all questionnaires during the assessment phase and the MEDI again one week after. The instruments used evaluate four main constructs: personality, mood, anxiety and avoidance. Results. The nine original factors were confirmed and showed adequate reliability (α: 0.66–0.91) and stability (r = 0.76–0.87). No differences in mean scores by sex were presented in any subscale (p ≥ .07). The MEDI subscales correlated significantly with the scales of each of the selected constructs (0.45 < r < 0.76). Limitations. The main limitations of this study were the limited sample size and not being able to count on MEDI scores post-transdiagnostic intervention. Conclusions. The MEDI demonstrates adequate reliability and validity. It allows to assess diverse symptoms efficiently, thus being of interest for clinical studies and practice