Primary Foci Research Articles

EFFECTS OF LEVETINOL ON EPILEPTIFORM ACTIVITY OF THE BRAIN IN RATS WITH COBALT-INDUCED EPILEPSY

The aim of this study was to evaluate the anti-seizure effect of Levetinol tablet (Geropharm) on the cobalt-induced chronic epilepsy. Materials and methods . A model of cobalt-induced epilepsy was created by applying cobalt powder to the sensorimotor zone of the rat cortex. The effects of Levetinol were studied at the early stage of the epileptic system (ES) formation (on day 2 after the cobalt application), and then at the stage of fully developed ES (on day 6 after the cobalt application). Results . The present study showed that at the early stage of ES development, Levetinol at doses of 50 and 200 mg/kg had no statistically significant effect on the development of paroxysmal activity in both primary and secondary epileptic foci: in the ipsi- and contralateral cortex, hypothalamus and hippocampus. On day 6 of the cobalt-induced epilepsy, a significant suppression of paroxysmal activity in the above structures of the brain was observed with the administration of Levetinol at a dose of 200 mg/kg. The most pronounced anti-seizure effect was found in the hippocampus; that was expressed in normalization of the bioelectrical activity and appearance of the regular theta rhythm. Conclusion . The effects of Levetinol are largely manifested in the hippocampal foci of epileptiform activity and, to a lesser extent, in the cortical foci.

Endogenous Endophthalmitis: Epidemiology, Clinic, Therapy and Visual Outcome

Endogenous endophthalmitis is a rare and severe inflammation of the eye in the context of a systemic infectious disease, which can lead to the loss of the affected eye in the worst case. In a 5-year period, 20 eyes were treated for endogenous endophthalmitis and evaluated retrospectively. Evaluation parameters were epidemiological data, causes, concomitant diseases, assessment of the pathogen spectrum, therapy and visual acuity. 13.2% (n = 20/152; 20 eyes of 17 patients) of all endophthalmitis cases were of endogenous origin. In 15% (n = 3/20) of the cases, bilateral endogenous endophthalmitis was present. The cause for the endophthalmitis was generalised sepsis in 9 of 17 cases, an infection of the urogenital tract in 2 of 17 cases and endocarditis and liver abscess in 1 of 17cases, respectively. In 4 of 17 cases, no primary foci were detected. Eight of 17 patients suffered from diabetes mellitus, 6 of 17 from renal insufficiency and 2 of 17 from malignancies, pneumonia or rheumatism. Two of 17 patients had had an organ transplantation, 15 of 17 suffered from cardiovascular diseases, 3 of 17 were immunosuppressed and 2 of 17 reported drug abuse. Four of 17 infections were caused by streptococci, 3 of 17 by Candida, 2 of 17 by herpes viruses and 1 of 17 by Staphylococcus aureus and Bacillus cereus. No pathogen could be found in 5 cases. The time interval between the onset of symptoms and diagnosis and the beginning of the therapy was 4 days (min.: 1 day; max.: 39 days). This was significantly longer in comparison with other causes of endophthalmitis (p < 0.001). Median visual acuity (VA) was 2.0 logMAR (n = 19/20) at the first presentation. One month and three months after initiation of the therapy VA was 1.3 logMAR (both n = 15/20), VA was 0.1 logMAR (n = 9/20) at the one year follow-up. Retinal detachment occurred in 2of 20 eyes and recurrence of the endophthalmitis in 1 of 20eyes within the one year follow-up, 5 of 17 patients died. Enucleation was never necessary. Endogenous endophthalmitis is often misdiagnosed due to a severe underlying non-ophthalmological disease. Delayed presentation with consequent late initiation of therapy is an unresolved problem, because colleagues from other fields are often unexperienced in diagnosing the ocular infection. This is also a cause of the already poor visual prognosis. Ophthalmologists can usually only influence the choice of the proper therapy.

EXPRESSION OF MMP-9 AS A PROGNOSTIC FACTOR OF UTERINE SARCOMA

Uterine sarcoma is a highly aggressive mesenchymal neoplasm with an extremely unfavorable prognosis. Up today there are still relevant issues concerning search for clinical-morphological and biomolecular criteria for prognosis relapse-free survival of uterine sarcoma patients. It is well-known, the increase of the expression level of MMP-9 in primary tumor or metastatic foci correlates with a low differentiation of tumor cells, high ability for invasiveness, high metastatic activity, and shortened life expectancy. It’s still unknown, whether it is possible to consider the expression of MMP-9 in uterine sarcoma cells as a convincing prognostic factor. For many types of epithelial malignant neoplasms, high metastatic rate is associated with an increase level of MMP-9 both in plasma and in tumor tissue. The purpose of this study is to investigate the features of MMP-9 expression in uterine sarcoma cells for development of the model for individual prediction of the disease course. The study of the surgical material of selected 54 cases of uterine sarcoma of stage I-II (according to FIGO criteria) with a known prognosis of the disease, which were distributed depending on the morphological type done: leiomyosarcoma (LMS) – 18 cases, endometrial stromal sarcoma (ESS) - 22 cases, undifferentiated sarcoma (US) – 14 (according to the classification of tumors of the uterus of the WHO). For histological examination, pieces of tissue were cut from different parts of the tumor nodes – central, peripheral, parts of the adjacent intact tissue of myometrium (total of 6-8 bits). The tumor cell phenotype was determined using low molecular weight cytokeratins (Cytokeratin PAN, AE1 / AE3), smooth muscle actin (Smooth Muscle Actin, 1A4), myogenin (Myogenin (F5D)), CD 10 and vimentin (Vimentin, V9). The histochemical label was evaluated in two parameters: the degree of prevalence and intensity of coloration. To assess the color intensity, a qualitative scale was used: 0 – no reaction, 1+ – weak cytoplasmic coloration to 30.0% of tumor cells, 2+ – moderate reaction, 30.0 to 60.0% of stained cells, 3+ – pronounced cytoplasmic reaction in 60,0-100,0% of tumor cells. Statistical processing of the data was performed using the “STATISTICA 10.0” program package. The conducted study has showed, the negative (0) and weak (1+) expression of matrix metalloproteinase-9 were observed in the most part of ESS and only partially in US. Despite the stage of the disease, with such a status of MMP-9, there was observed no signs of relapsed disease. The moderate (2+) and high (3+) expression of MMP-9 was detected in 44.5 % of uterine sarcoma, in the most part in LMS patients. However, if in LMS cases the progressive disease was observed only in one third of them (4 of 12 cases), in case of ESS and US, in all the patients with such tumors status there was observed relapsed disease. Such a reaction may be indicative for invasive and metastatic potential of ESS and US and cause of the hematogenous metastases.

ULTRASTRUCTURAL FEATURES OF THE MAIN CLINICAL VARIANTS OF BASAL CELL CARCINOMA, AS A FACTOR DETERMINING THE BIOLOGICAL BEHAVIOR OF THE TUMOR

Histological variants of basal cell carcinoma (BСС) are characterized by a variety of structures depending on the location of the original tumor cells, their differentiation, the reaction of the surrounding tissue, the age of the patient, which causes a large number of histological classifications of the tumor. To evaluate the prognosis of the effectiveness of different treatment methods and the biological behavior of the ВCC, the clinical form and the corresponding histomorphological type of tumor are of great importance. Most of the primary foci of the ВCC are surface and micronodular (syn.: nodular) forms, rarely there is a scleroderm-like variant and extremely rarely fibroepithelioma of Pincus. Surface and micronodular forms of ВCC corresponding to the T1N0M0 characteristic (up to 2 cm in diameter) with a simple histological type of structure (multicentric, solidly compact) are regarded as tumors with a low risk of recurrence and progression. Materials and methods. Studying the features of the pathomorphological characteristics of the tumor and the frequency of various variants on the basis of an analysis of 223 ВCC biopsy specimens, we found that most often (54.7%) there was a solid type of tumor, less often -- superficial (12.7%), morphea (4.9% ), adenoid (10.9%), as well as ВCC with a piloidal (3.1%) and sebaceous (4.4%) differentiation. Among the biopsies analyzed in 6.8% of cases metatypic cancer was found. Conclusions: The histological structure of the tumor can determine its biological behavior and have prognostic significance. Thus, pronounced primitive angiogenesis, infiltrating growth and active stroma formation testify to tumor aggressiveness and clinically most correspond to the recurring macronodular and infiltrative clinical forms of BCC. The tumor is most aggressive in its basosquamous transformation, manifested in the emergence of two components of the tumor complex in the area of dyskeratosis and pseudoepitheliomatous hyperplasia of the epidermis: basal cell carcinoma and highly differentiated cancer, which corresponds to the formation of metatype skin cancer.

Mutational landscape of metastatic colorectal cancer: Aggregate insights from a molecular tumor board.

837 Background: The mutational landscape of metastatic colorectal cancer (CRC) is being elucidated by next-generation sequencing of both primary tumors and metastatic foci. In this study, we examined the results of all stage IV CRC cases submitted to our molecular tumor board (MTB). Methods: We performed a retrospective analysis of all patients who had next-generation sequencing performed between January 2015 and August 2017 on either their primary tumor and/or metastasis. Cases were presented at a MTB convened twice monthly. For the purposes of this study only pathogenic mutations were notated, not variants of unknown significance (VUS). Results: Eighty-seven unique patients had 97 specimens sequenced (28 primary tumors and 69 metastases). The primaries averaged 3 mutations per specimen (range: 1-6) whereas the metastases averaged 4 (range: 1-14, p=.25). The most common anatomic sites of submitted metastatic tissue were the liver (n=35, average mutations=4), followed by the lungs (n=10, average mutations=3) and the omentum/peritoneum (n=8, average mutations=3). Two patients had both a primary tumor and a metastasis sequenced, with a 33% rate of concordance in inter-specimen mutations. Five patients had multiple metastases sequenced, with a 53% rate of concordance in inter-specimen mutations; in every case of longitudinal sequencing, mutational burden increased in metastases over time. The most common mutation was apc (21% of all mutations), followed by p53 (16%) and then kras (13%). Candidacy for EGFR-directed therapy was found in 8 cases, and mismatch repair defects were detected in 5 cases. Conclusions: In stage IV CRC cases sent to our MTB, tissue from metastases was more commonly submitted for analysis than from the primary tumors. There is not necessarily concordance between mutations in primary tumors and metastases, nor among multiple metastases in the same patient. Sequencing at multiple time points in the disease course may allow observation of clonal evolution and dynamic adaptation of therapeutic targets.

Plant and Insect Viruses in Managed and Natural Environments: Novel and Neglected Transmission Pathways.

The capacity to spread by diverse transmission pathways enhances a virus' ability to spread effectively and survive when circumstances change. This review aims to improve understanding of how plant and insect viruses spread through natural and managed environments by drawing attention to 12 novel or neglected virus transmission pathways whose contribution is underestimated. For plant viruses, the pathways reviewed are vertical and horizontal transmission via pollen, and horizontal transmission by parasitic plants, natural root grafts, wind-mediated contact, chewing insects, and contaminated water or soil. For insect viruses, they are transmission by plants serving as passive "vectors," arthropod vectors, and contamination of pollen and nectar. Based on current understanding of the spatiotemporal dynamics of virus spread, the likely roles of each pathway in creating new primary infection foci, enlarging previously existing infection foci, and promoting generalized virus spread are estimated. All pathways except transmission via parasitic plants, root grafts, and wind-mediated contact transmission are likely to produce new primary infection foci. All 12 pathways have the capability to enlarge existing infection foci, but only to a limited extent when spread occurs via virus-contaminated soil or vertical pollen transmission. All pathways except those via parasitic plant, root graft, contaminated soil, and vertical pollen transmission likely contribute to generalized virus spread, but to different extents. For worst-case scenarios, where mixed populations of host species occur under optimal virus spread conditions, the risk that host species jumps or virus emergence events will arise is estimated to be "high" for all four insect virus pathways considered, and, "very high" or "moderate" for plant viruses transmitted by parasitic plant and root graft pathways, respectively. To establish full understanding of virus spread and thereby optimize effective virus disease management, it is important to examine all transmission pathways potentially involved, regardless of whether the virus' ecology is already presumed to be well understood or otherwise.

Utterance of David, the Anointed of the God of Jacob (2 Samuel 23: 1–7)

Building on earlier studies of 2 Sam 23:1–7, I explore unique features of the poem that set it apart from the conceptual framework of Samuel–Kings and reflect a later development in the Davidic traditions. My primary foci are the concept of David the prophet (vv. 1–2) and the link between David and the God of Jacob (vv. 1 and 3), as well as the description of the just and perhaps unidentified ruler (vv. 3–7) and the panorama of divine names throughout. The poem represents the earliest witness to the development of David’s prophetic image in early Judaism and Christianity. Yet the poetry does not merely demonstrate independence and innovation; rather, it draws deeply from earlier traditions, including the Balaam material and imagery from the Prophets and the Psalms. This analysis furthers earlier proposals that, before its inclusion in the appendix of 2 Samuel, the likely context for “David’s last words” was the Psalms.

Developing Care and Socio-Emotional Learning in First Year Doctoral Students: Building Capacity for Success

Aim/Purpose: The purpose of this research is to explore and describe the role of care and socio-emotional learning in the first year of doctoral study. In particular, understanding the nature of the caring relationships doctoral students experience and their development of effective socio-emotional capacity are the primary foci of this study. It may provide institutions with data necessary to add specific supports to graduate orientation programs and/or introductory doctoral courses that will mitigate problems these beginning students face and lead to greater success and quality of life. Background: This study examines the caring relationships of students in two education doctoral programs using the features of socio-emotional learning (SEL), the ethics of care, and learning care to understand the effects of caring relationships on first year doctoral students and to explore how their subsequent use of socio-emotional skills impacts success and quality of life. Methodology: The study used a phenomenological methodology focusing on the initial experiences of returning adult doctoral students in the field of education during the first semester of their studies. A total of seven students from two different cohorts of Ph. D. and Ed. D. programs were interviewed. A deductive process was subsequently pursued, applying the central concepts of care and socio-emotional learning to the data as categories, resulting in the findings of this study. Contribution: As the importance of care is often trivialized, particularly in the most advanced levels of education, it is important for doctoral programs to examine what can be done to enhance relationship-building in order to increase student success and quality of life. This study calls for more attention to care in doctoral study. Findings: Participant responses identified self-awareness as key to how they managed stress, maintained motivation and academic discipline, organized their time in order to accomplish tasks and meet responsibilities, and set goals. Participants attributed their academic discipline and ability to handle stress to perseverance, drive, and work ethic. These doctoral students were very conscious of the decisions they made and the reasons behind these decisions. In their discussion of the relationships that supported them throughout their study, they clearly identified emotions triggered by these relationships, and they discussed how those who cared for them helped them to recognize their own strengths and gain more self-confidence. The presence of caring was clear as participants’ reasons for engaging in doctoral study were often rooted in their care for others in their family and their caring about marginalized populations in society. Recommendations for Practitioners: Examining the nature of the care doctoral students receive and their development of effective socio-emotional abilities may provide institutions with data necessary to add specific supports to graduate orientation programs and/or introductory doctoral courses that will mitigate problems these beginning students face, leading to future success. Recommendation for Researchers: While most research and instruction involving socio-emotional learning has focused on K-12 learners, this study investigates how the experiences of doctoral students reflect the importance of addressing the emotional side of learning at all levels of education. Despite the plethora of extant literature concerning doctoral student experiences related to socialization, the significance of socio-emotional learning, and the importance of care as a facilitator of learning, there are gaps in the literature connecting doctoral students in the first stages of their studies to affective learning. This study will fill that gap and opens the door to future qualitative studies, elaborating the lived experiences of caring relationships and socio-emotional learning. Additionally, these initial qualitative studies provide direction to quantitative researchers looking for ways to measure these concepts. Impact on Society: Elements of care, especially as they relate to socio-emotional learning correlate strongly with successful outcomes in educational contexts. To the extent that doctoral students and doctoral programs experience greater success and increased satisfaction and quality of life, this research will have significant societal impact. Future Research: As a qualitative study using inductive and deductive approaches, it is important for future research to translate the themes and concepts of this study into measurable, quantifiable, and replicable units. This translation will facilitate the generalizability of our findings. The application of the concepts of care and socio-emotional learning to first year doctoral students opens the door to additional qualitative approaches as well, which will greatly increase our understanding of what these concepts mean as they are lived-out.

SPARC inhibits breast cancer bone metastasis and may be a clinical therapeutic target.

Breast cancer is one of the most common types of cancer in females worldwide, and metastasis to bone is an important characteristic of malignancy. The present study aimed to investigate the molecular mechanism of breast cancer to bone metastasis of secreted protein acidic and rich in cysteine (SPARC). Immunohistochemistry was performed to examine the expression of SPARC in primary breast tumors and bone metastatic foci. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect the expression level of SPARC in several types of breast cancer cell. A Transwell filter assay was used to assess the effect of SPARC on breast cancer cell invasion ability, and an osteoblast differentiation assay was employed to analyze the effect of SPARC on the differentiation ability of mesenchymal stem cells. Clinical data revealed that decreased stromal SPARC expression is associated with breast cancer to bone metastasis. Gain- and loss-of-function studies reveal that SPARC inhibits the migration and invasion of breast cancer cells, and suppresses osteoclast activation in the breast cancer microenvironment. SPARC serves an important role in breast cancer bone metastasis and may be a promising therapeutic target for the treatment of breast cancer bone metastasis.

A Review of Contemporary Science and Technology Policy Research: Recent Trends and Future Directions

The societal impacts of scientific and technological advances – whether desirable or undesirable – have been one of the primary foci of contemporary policy research, much of which employs distinct interdisciplinary approaches. In this paper, we seek to characterize the topical, methodological, theoretical, and geographical trends of recent science and technology policy studies. Utilizing reputable scholarly journals within the related subfield of policy science, we review the recent research articles on science and technology policy as they relate to policy development, while paying particular attention to capturing any systemic patterns of trends. We conclude with a discussion of the various ramifications of our findings for future research directions and, in the process, highlight issues including technological innovation and diffusion, science and technology for sustainable energy development, evidence-based decision- making, and information technology and cyber security.

Stem cells in cancer therapy: opportunities and challenges.

Metastatic cancer cells generally cannot be eradicated using traditional surgical or chemoradiotherapeutic strategies, and disease recurrence is extremely common following treatment. On the other hand, therapies employing stem cells are showing increasing promise in the treatment of cancer. Stem cells can function as novel delivery platforms by homing to and targeting both primary and metastatic tumor foci. Stem cells engineered to stably express various cytotoxic agents decrease tumor volumes and extend survival in preclinical animal models. They have also been employed as virus and nanoparticle carriers to enhance primary therapeutic efficacies and relieve treatment side effects. Additionally, stem cells can be applied in regenerative medicine, immunotherapy, cancer stem cell-targeted therapy, and anticancer drug screening applications. However, while using stem cells to treat human cancers appears technically feasible, challenges such as treatment durability and tumorigenesis necessitate further study to improve therapeutic performance and applicability. This review focuses on recent progress toward stem cell-based cancer treatments, and summarizes treatment advantages, opportunities, and shortcomings, potentially helping to refine future trials and facilitate the translation from experimental to clinical studies.

IGF-IEc expression is increased in secondary compared to primary foci in neuroendocrine neoplasms.

Different Insulin-like growth factor-I (IGF-I) mRNA transcripts are produced by alternative splicing and particularly the IGF-IEc isoform has been implicated in the development and/or progression of various types of cancer. In the present study, we examined the potential role of IGF-IEc expression as a new immunohistochemical marker of aggressiveness in neuroendocrine neoplasms (NENs). We utilized immunohistochemical analysis in tissue specimens of 47 patients with NENs, to evaluate the expression of IGF-IEc (%) and Ki-67 proliferation index (%). Specimens from patients with tumors of different tissue origin, of either primary or metastatic lesions and of different grade were examined. Cytoplasmic IGF-IEc staining was found in 23 specimens of NENs or NECs: 10 pancreatic, 4 small bowel, 3 gastric, 1 lung, 1 uterine and 4 poorly differentiated of unknown primary origin. Ki-67 and IGF-IEc expression was positively correlated in all the samples studied (r=0.31, p=0.03). IGF-1Ec expression was more prevalent in specimens originating from metastatic foci with high Ki-67 compared to primary sites with low Ki-67 expression (p=0.036). These findings suggest a possible role of IGF-IEc in NEN tumorigenesis and progression to metastases that could be used as an additional new marker of a more aggressive behavior and a potential drugable target.

68Ga-DOTATOC and 18F-FDG PET/CT for identifying the primary lesions of suspected and metastatic neuroendocrine tumors: Aprospective study in Taiwan.

To investigate the diagnostic accuracy of 68Ga-DOTATOC and 18F-FDG PET/CT to identify the primary foci in Taiwanese patients with clinically suspected neuroendocrine tumors (NET) and NET of unknown primary site. Patients with clinically suspected NET and NET of unknown primary site were eligible. All participants underwent a conventional workup (including CT, MR, endoscopic ultrasound), 68Ga-DOTATOC, and 18F-FDG PET/CT. The results of pathology and findings on clinical follow-up served as the gold standard. Among the 36 patients included in the study, we were able to identify the primary tumor in 17 participants (47.2%). The overall sensitivity values of 68Ga-DOTATOC, 18F-FDG, and conventional workup were 88%, 41%, and 53%, respectively, whereas the specificities were 100%, 100%, 68%, respectively. The areas under curve of 68Ga-DOTATOC, 18F-FDG, and conventional workup were 0.941, 0.706, and 0.607, respectively. 68Ga-DOTATOC was more sensitive than 18F-FDG and more specific than conventional workup. Treatment changes as a result of 68Ga-DOTATOC PET/CT findings occurred in 12 (33.3%) of the 36 study participants. Our data confirm the usefulness of 68Ga-DOTATOC in the identification of NET. In addition, treatment modifications as a result of 68Ga-DOTATOC PET/CT findings were evident in approximately one third of NET patients.

Abstract 2603: A patient driven cancer database to collect information, analyze data, and predict outcomes

Abstract It is widely held that major breakthroughs in cancer treatment will result from properly amassing, analyzing and utilizing existing and emerging “big data.” To date there is no single vehicle that integrates the data available, and of those being developed, none that put patient needs and outcomes as primary foci. CancerBase was released as part of the Cancer Moonshot launch in June 2016. It is a global, real-time data collection tool designed by and for patients. Patients were recruited through social media to share their information, including but not limited to, demographic details, personal cancer data, and history of treatment. Combining open text boxes and drop down preselected response boxes allow for the capture of information in a way that patients understand. In addition to cancer data, Facebook comments demonstrated immediate engagement with the tool and captured the organic community of patients who eagerly shared their stories with others. Personal interviews and a communal Twitter chat have recorded the interests and priorities from patients who were not necessarily familiar with CancerBase. In addition to medical data, general information and questions CancerBase participants wanted to add to the system have been collected. Incorporation of patient-driven deliverables is unique in the space of big data and cancer in that other tools, both existing and still in development, are geared toward the needs of researchers, payors, policy-makers and clinicians. CancerBase is unique in that it adapts to growth. Patient feedback drives improvements via ongoing communication between developers, PIs and participants. Wherever possible, participant recommendations and questions are rapidly incorporated into the website design. The remaining patient recommendations are cataloged and will be incorporated in the forthcoming releases of CancerBase. The initial launch of CancerBase demonstrated patient willingness to share personal, anonymized data and to recruit others. Patients were eager to engage and manipulate the limited data collected in the first release. Moving forward, patient priorities include: How do my treatment decisions compare with others and what can I learn from those who have come before me; What is the likelihood that I will have a recurrence; and, in the case of metastatic patients, how long might I have between progressions, to which organ(s) is progression most likely, and what are my likely survival outcomes. CancerBase is a database tool that resonates with the patient community and is driven by patient needs and interests. As the tool becomes increasingly robust it will grow to support the decision-making needs of clinicians and guide the investigations of researchers. The relaunch of CancerBase in Spring 2017 will address emerging patient concerns, integrate collected data, and utilize existing forecasting databases to add value to patients. Citation Format: Lori Marx-Rubiner, AnneMarie Ciccarella, Vincent An, Jared Bass, Will Berman, Jackson Berry, Chloe Chan, Christopher Han, Louis Harboe, Joshua Lurie, Sara Ma, Parker Malachowsky, Naylee Nagda, Simon Schneider, E. Bircan Çopur, Jorge J. Nieva, Jan Liphardt, Peter Kuhn, Jeremy M. Mason. A patient driven cancer database to collect information, analyze data, and predict outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2603. doi:10.1158/1538-7445.AM2017-2603

Quantitative trait loci in pepper control the effective population size of two RNA viruses at inoculation.

Infection of plants by viruses is a complex process involving several steps: inoculation into plant cells, replication in inoculated cells and plant colonization. The success of the different steps depends, in part, on the viral effective population size (Ne), defined as the number of individuals passing their genes to the next generation. During infection, the virus population will undergo bottlenecks, leading to drastic reductions in Ne and, potentially, to the loss of the fittest variants. Therefore, it is crucial to better understand how plants affect Ne. We aimed to (i) identify the plant genetic factors controlling Ne during inoculation, (ii) understand the mechanisms used by the plant to control Ne and (iii) compare these genetic factors with the genes controlling plant resistance to viruses. Ne was measured in a doubled-haploid population of Capsicum annuum. Plants were inoculated with either a Potato virus Y (PVY) construct expressing the green fluorescent protein or a necrotic variant of Cucumber mosaic virus (CMV). Newas assessed by counting the number of primary infection foci on cotyledons for PVY or the number of necrotic local lesions on leaves for CMV. The number of foci and lesions was correlated (r=0.57) and showed a high heritability (h2=0.93 for PVY and h2=0.98 for CMV). The Ne of the two viruses was controlled by both common quantitative trait loci (QTLs) and virus-specific QTLs, indicating the contribution of general and specific mechanisms. The PVY-specific QTL colocalizes with a QTL that reduces PVY accumulation and the capacity to break down a major-effect resistance gene.

Opportunities and challenges in secondary education for blind/vision-impaired people in the Republic of Ireland

Until comparatively recently blind/vision-impaired young people were generally assigned to particular education settings based on their impairment. Restructuring of the education system commenced in the Republic of Ireland in the 1990s, resulting in significant changes in special education including a language of inclusive education within policy initiatives. In the research upon which this article is based, the educational experiences of blind/vision-impaired people, the factors that impacted on these experiences and how these facilitated or inhibited their future opportunities were the primary foci for the study. This article explores the themes of how the post-primary school curriculum was experienced by blind/vision-impaired students and their future expectations and aspiration. In terms of policy development and practice, it is paramount to ensure both effective curriculum participation and transition opportunities are enabled rather than disabled for these students.

Prognostic significance of glutathione peroxidase 2 in gastric carcinoma.

Increasing evidence suggests that the glutathione peroxidase 2 may actually play important roles in tumorigenesis and progression in various human cancers such as colorectal carcinomas and lung adenocarcinomas. However, the role of glutathione peroxidase 2 in gastric carcinoma remains to be determined. In this study, the expression and prognostic significance of glutathione peroxidase 2 in gastric carcinoma were investigated and the well-known prognostic factor Ki-67 labeling index was also assessed as positive control. Glutathione peroxidase 2 expression levels in the tumor tissue specimens, the matched adjacent normal tissue specimens, and the lymph node metastases of 176 patients with gastric carcinoma were evaluated by quantitative polymerase chain reaction, western blotting, and immunohistochemical staining. The associations between glutathione peroxidase 2 expression levels, as determined by immunohistochemical staining, and multiple clinicopathological characteristics were determined by Pearson's chi-square test and Spearman's correlation analysis. The relationships between glutathione peroxidase 2 expression and other clinicopathological variables and patient prognoses were analyzed further by the Kaplan-Meier method, the log-rank test, and Cox multivariate regression. The quantitative polymerase chain reaction, western blotting, and immunohistochemical staining results showed that glutathione peroxidase 2 expression levels were upregulated in both the primary tumor foci and the lymph node metastases of patients with gastric carcinoma (all p values < 0.05). Furthermore, Pearson's chi-square tests, as well as Spearman's correlation analysis, revealed that glutathione peroxidase 2 expression levels were strongly correlated with the Ki-67 labeling index, differentiation, histological patterns, Lauren classifications, lymph node metastasis, vascular invasion, tumor-node-metastasis stages, Helicobacter pylori infection, and overall survival (all p values < 0.05). Kaplan-Meier analysis, as well as the log-rank test and multivariate Cox regression analysis, showed that multiple clinicopathological risk factors and glutathione peroxidase 2 expression were novel independent prognostic factors for gastric carcinoma (all p values < 0.05). Glutathione peroxidase 2 expression is a novel independent prognostic biomarker for gastric carcinoma that may be used to devise personalized therapeutic regimens and precision treatments for this disease.

The activity of the HDAC inhibitor HBI-8000 (Chidamide) combined with eribulin on 4T1 spontaneous metastasis development.

e14055 Background: In preclinical studies eribulin has shown significant effects on epithelial-mesenchymal transition (EMT) in human breast cancer cells in vitro and in vivo, inducing a switch from mesenchymal to epithelial states, decreasing migration and invasiveness of human breast cancer cells in vitro, as well as experimental metastases in vivo. HBI-8000 is a novel, orally bioavailable Class I selective HDAC inhibitor (HDACi). In addition to its demonstrated positive effects on antitumor immunity, it also exerts significant effects on EMT pathway components, enhancing CDH1 (e-cadherin) expression and inhibiting TGF-β induced metastasis. Methods: The syngeneic, orthotopic 4T1 model is thought to be a close representation of the clinical situation; similar to human mammary carcinoma, the major cause of morbidity and mortality is development of spontaneous metastases. 4T1-implanted mice treated with combinations of eribulin and HBI-8000 were monitored for primary tumor growth inhibition (TGI), survival, and metastatic lung foci. Tumor samples were analyzed by Q-PCR for expression of genes involved in EMT or in the metastatic process. Results: Eribulin alone had no effect on primary TGI. Eribulin combined with HBI-8000 resulted in significant (P &lt; 0.05) reductions in median tumor volume, tumor volume distribution (TMD) and survival (P &lt; 0.005). Single agent HBI-8000 had a similar effect on TGI, TMD (P &lt; 0.05) and survival (P &lt; 0.005). Whereas single agent HBI-8000 or eribulin failed to significantly reduce metastases, the eribulin-HBI-8000 combination produced significant (P &lt; 0.01) and synergistic inhibition of metastases, decreasing the number of lung foci approximately 10-fold. Gene expression analyzed by Q-PCR revealed correlations between metastasis blockade and increases in E-Cadherin, Occludin and Claudin1. There was a strong correlation with inhibition of HMGA2 (High Mobility Group AT-Hook 2) gene expression. Conclusions: Eribulin combined with HBI-8000 inhibited primary tumor growth and inhibited metastasis development and increased survival. This effect was correlated and consistent with changes in genes relevant to EMT, tumor plasticity and stemness.

PD33-05 TARGETED NEXT GENERATION SEQUENCING TO CHARACTERIZE MAGNETIC RESONANCE IMAGING VISIBLE AND INVISIBLE PROSTATE CANCER: BIOLOGICAL INSIGHTS AND THERAPEUTIC IMPLICATIONS

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I1 Apr 2017PD33-05 TARGETED NEXT GENERATION SEQUENCING TO CHARACTERIZE MAGNETIC RESONANCE IMAGING VISIBLE AND INVISIBLE PROSTATE CANCER: BIOLOGICAL INSIGHTS AND THERAPEUTIC IMPLICATIONS Simpa Salami, Daniel Hovelson, Aaron Udager, Matthew Lee, Nicole Curci, Jeremy Kaplan, Arvin George, Matthew Davenport, Scott Tomlins, and Ganesh Palapattu Simpa SalamiSimpa Salami More articles by this author , Daniel HovelsonDaniel Hovelson More articles by this author , Aaron UdagerAaron Udager More articles by this author , Matthew LeeMatthew Lee More articles by this author , Nicole CurciNicole Curci More articles by this author , Jeremy KaplanJeremy Kaplan More articles by this author , Arvin GeorgeArvin George More articles by this author , Matthew DavenportMatthew Davenport More articles by this author , Scott TomlinsScott Tomlins More articles by this author , and Ganesh PalapattuGanesh Palapattu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3319AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES While multiparametric magnetic resonance imaging (mpMRI) of the prostate has improved disease detection, up to 20% of patients with negative mpMRI harbor high grade prostate cancer (PCa). In this study, we sought to characterize and compare the molecular profiles of mpMRI visible and invisible PCa. METHODS Patients who underwent mpMRI prior to radical prostatectomy were identified for this IRB-approved study. mpMRI for each patient was reviewed by a radiologist with expertise in prostate mpMRI and histopathology reviewed by a genitourinary pathologist. Whole-mount histopathology was co-registered with axial mpMRI images. DNA and RNA were co-isolated from all tumor foci pre-identified on formalin-fixed paraffin-embedded specimens. High depth, targeted DNA and RNA next generation sequencing was performed to characterize the molecular profile of each tumor focus using the Oncomine Comprehensive Panel (DNA sequencing) and a custom targeted RNAseq panel assessing PCa relevant genes. RESULTS A total of 26 primary tumor foci from 10 patients were analyzed. The median number of PCa foci was 3. Of the 14 (54%) invisible lesions on mpMRI, 5 (36%) were Gleason 3+4=7 (Table 1). We detected high-confidence prioritized genetic mutations in 54% (14/26) of tumor foci, 43% (6/14) of which were in mpMRI-invisible lesions. Additionally, 64% (9/14) of lesions exhibiting prioritized mutations were Gleason 7. Notable point mutations were in APC, AR, ARID1B, ATM, ATRX, BRCA2, FAT1, MAP3K1, NF1, SPEN, SPOP, TP53, and a frameshift mutation was detected in SOX2. The expression profile of mpMRI visible and invisible lesions were similar (Figure 1). CONCLUSIONS We found no significant difference in the molecular profile of visible and invisible cancer foci on mpMRI. However, 36% of mpMRI invisible lesions exhibited biologically significant mutations. More work is needed to further characterize the molecular basis for mpMRI prostate cancer visibility. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e595 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Simpa Salami More articles by this author Daniel Hovelson More articles by this author Aaron Udager More articles by this author Matthew Lee More articles by this author Nicole Curci More articles by this author Jeremy Kaplan More articles by this author Arvin George More articles by this author Matthew Davenport More articles by this author Scott Tomlins More articles by this author Ganesh Palapattu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Site Interiography and Geophysical Scanning: Interpreting the Texture and Form of Archaeological Deposits with Ground-Penetrating Radar

The remarkable potential of geophysical scanning—to assess the internal variability of sites in new ways, to highlight important phenomena in the field, to exercise co-creation of interpretation and commitment to minimal destruction of community partners’ resources, and to aid in the practice of due diligence in avoiding desecration of the sacred—continues to be underutilized in archaeology. While archaeological artifacts, features, and strata remain primary foci of archaeological geophysics, these phenomena are perceived quite differently in scans than in visual or tactile exposures. In turn, new registers of site exploration afforded by geophysical prospection may be constrained by the language of site excavation and visual observation, requiring adjustments in the ways of thinking about and describing what the instruments are measuring. The texture and form of site deposits as rendered in ground-penetrating radar scans can be examined in detail prior to making interpretations of cultural features or stratigraphy. Far more than simple “anomalies” demanding our attention for excavation, patterns in geophysical data can be the focus of extensive archaeological analysis prior to, in conjunction with, or independent from excavation.