Nuclear Glycolytic Enzyme Enolase of Toxoplasma Gondii Functions as a Transcriptional Regulator

Apicomplexan parasites including Toxoplasma gondii have complex life cycles within different hosts and their infectivity relies on their capacity to regulate gene expression. However, little is known about the nuclear factors that regulate gene expression in these pathogens. Here, we report that T. gondii enolase TgENO2 is targeted to the nucleus of actively replicating parasites, where it specifically binds to nuclear chromatin in vivo. Using a ChIP-Seq technique, we provide evidence for TgENO2 enrichment at the 5′ untranslated gene regions containing the putative promoters of 241 nuclear genes. Ectopic expression of HA-tagged TgENO1 or TgENO2 led to changes in transcript levels of numerous gene targets. Targeted disruption of TgENO1 gene results in a decrease in brain cyst burden of chronically infected mice and in changes in transcript levels of several nuclear genes. Complementation of this knockout mutant with ectopic TgENO1-HA fully restored normal transcript levels. Our findings reveal that enolase functions extend beyond glycolytic activity and include a direct role in coordinating gene regulation in T. gondii

Quality of life among cancer inpatients 80 years and older: a systematic review

Objective The aim of this systematic review was to summarize and assess the literature on quality of life (QoL) among cancer patients 80 years and older admitted to hospitals and what QoL instruments have been used. Methods We searched systematically in Medline, Embase and Cinahl. Eligibility criteria included studies with any design measuring QoL among cancer patients 80 years and older hospitalized for treatment (surgery, chemotherapy or radiation therapy). Exclusion criteria: studies not available in English, French, German or Spanish. We screened the titles and abstracts according to a predefined set of inclusion criteria. All the included studies were assessed according to the Critical Appraisal Skills Programme checklists, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement checklist was used to ensure rigor in conducting and reporting. This systematic review was registered in PROSPERO (CRD42017058290). Results We included 17 studies with 2005 participants with various cancer diagnoses and Classification of Malignant Tumors stages (TNM). The included studies used a range of different QoL instruments and had different aims and outcomes. Both cancer-specific and generic instruments were used. Only one of the 17 studies used an age-specific instrument. All the studies included patients 80 years and older in their cohort, but none specifically analyzed QoL outcomes in this particular subgroup. Based on findings in the age-heterogeneous population (age range 20–100 years), QoL seems to be correlated with the type of diagnosed carcinoma, length of stay, depression and severe symptom burden. Conclusion We were unable to find any research directly exploring QoL and its determinants among cancer patients 80 years and older since none of the included studies presented specific analysis of data in this particular age subgroup. This finding represents a major gap in the knowledge base in this patient group. Based on this finding, we strongly recommend future studies that include this increasingly important and challenging patient group to use valid age- and diagnosis-specific QoL instruments.publishedVersio

Timeliness of Clinic Attendance is a good predictor of Virological Response and Resistance to Antiretroviral drugs in HIV-infected patients

Ensuring long-term adherence to therapy is essential for the success of HIV treatment. As access to viral load monitoring and genotyping is poor in resource-limited settings, a simple tool to monitor adherence is needed. We assessed the relationship between an indicator based on timeliness of clinic attendance and virological response and HIV drug resistance

Adaptation and implementation of a mobile phone–based remote symptom monitoring system for people with cancer in Europe

Background: There has been an international shift in health care, which has seen an increasing focus and development of technological and personalized at-home interventions that aim to improve health outcomes and patient-clinician communication. However, there is a notable lack of empirical evidence describing the preparatory steps of adapting and implementing technology of this kind across multiple countries and clinical settings. Objective: This study aimed to describe the steps undertaken in the preparation of a multinational, multicenter randomized controlled trial (RCT) to test a mobile phone–based remote symptom monitoring system, that is, Advanced Symptom Management System (ASyMS), designed to enhance management of chemotherapy toxicities among people with cancer receiving adjuvant chemotherapy versus standard cancer center care. Methods: There were 13 cancer centers across 5 European countries (Austria, Greece, Ireland, Norway, and the United Kingdom). Multiple steps were undertaken, including a scoping review of empirical literature and clinical guidelines, translation and linguistic validation of study materials, development of standardized international care procedures, and the integration and evaluation of the technology within each cancer center. Results: The ASyMS was successfully implemented and deployed in clinical practices across 5 European countries. The rigorous and simultaneous steps undertaken by the research team highlighted the strengths of the system in clinical practice, as well as the clinical and technical changes required to meet the diverse needs of its intended users within each country, before the commencement of the RCT. Conclusions: Adapting and implementing this multinational, multicenter system required close attention to diverse considerations and unique challenges primarily related to communication and clinical and technical issues. Success was dependent on collaborative and transparent communication among academics, the technology industry, translation partners, patients, and clinicians as well as a simultaneous and rigorous methodological approach within the 5 relevant countries

Law Professor Comment Letter on Harmonization of Private Offering Rules

Comment letter filed on Sept. 24, 2019. File No. S7-08-19 We are fifteen law professors whose scholarship and teaching focuses on securities regulation. We appreciate the opportunity to comment on the U.S. Securities and Exchange Commission’s (“SEC” or the “Commission”) Concept Release on Harmonization of Securities Offering Exemptions (the “Concept Release”)

The eSMART study protocol : a randomised controlled trial to evaluate electronic symptom management using the advanced symptom management system (ASyMS) remote technology for patients with cancer

Introduction While some evidence exists that real-time remote symptom monitoring devices can decrease morbidity and prevent unplanned admissions in oncology patients, overall, these studies have significant methodological weaknesses. The electronic Symptom Management using the Advanced Symptom Management System (ASyMS) Remote Technology (eSMART) study is designed to specifically address these weaknesses with an appropriately powered, repeated-measures, parallel-group stratified randomised controlled trial of oncology patients. Methods and analysis A total of 1108 patients scheduled to commence first-line chemotherapy (CTX) for breast, colorectal or haematological cancer will be recruited from multiple sites across five European countries.Patients will be randomised (1:1) to the ASyMS intervention (intervention group) or to standard care currently available at each site (control group). Patients in the control and intervention groups will complete a demographic and clinical questionnaire, as well as a set of valid and reliable electronic patient-reported outcome measures at enrolment, after each of their CTX cycles (up to a maximum of six cycles) and at 3, 6, 9 and 12 months after completion of their sixth cycle of CTX. Outcomes that will be assessed include symptom burden (primary outcome), quality of life, supportive care needs, anxiety, self-care self-efficacy, work limitations and cost effectiveness and, from a health professional perspective, changes in clinical practice (secondary outcomes). Ethics and dissemination Ethical approval will be obtained prior to the implementation of all major study amendments. Applications will be submitted to all of the ethics committees that granted initial approval.eSMART received approval from the relevant ethics committees at all of the clinical sites across the five participating countries. In collaboration with the European Cancer Patient Coalition (ECPC), the trial results will be disseminated through publications in scientific journals, presentations at international conferences, and postings on the eSMART website and other relevant clinician and consumer websites; establishment of an eSMART website (www.esmartproject.eu) with publicly accessible general information; creation of an eSMART Twitter Handle, and production of a toolkit for implementing/utilising the ASyMS technology in a variety of clinical practices and other transferable health care contexts. Trial registration number NCT02356081

Primary central nervous system lymphomas:EHA–ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

This EHA-ESMO Clinical Practice Guideline provides key recommendations for managing primary DLBCL of the CNS.The guideline covers clinical, imaging and pathological diagnosis, staging and risk assessment, treatment and follow-up.Algorithms for first-line and salvage treatments are provided.The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe.Recommendations are based on available scientific data and the authors' collective expert opinion