Methylation of HOXA9 and ISL1 predicts patient outcome in high-grade non-invasive bladder cancer

Introduction Inappropriate DNA methylation is frequently associated with human tumour development, and in specific cases, is associated with clinical outcomes. Previous reports of DNA methylation in low/intermediate grade non-muscle invasive bladder cancer (NMIBC) have suggested that specific patterns of DNA methylation may have a role as diagnostic or prognostic biomarkers. In view of the aggressive and clinically unpredictable nature of high-grade (HG) NMIBC, and the current shortage of the preferred treatment option (Bacillus:Calmette-Guerin), novel methylation analyses may similarly reveal biomarkers of disease outcome that could risk-stratify patients and guide clinical management at initial diagnosis. Methods Promoter-associated CpG island methylation was determined in primary tumour tissue of 36 initial presentation high-grade NMIBCs, 12 low/intermediate-grade NMIBCs and 3 normal bladder controls. The genes HOXA9, ISL1, NKX6-2, SPAG6, ZIC1 and ZNF154 were selected for investigation on the basis of previous reports and/or prognostic utility in low/intermediate-grade NMIBC. Methylation was determined by Pyrosequencing of sodium-bisulphite converted DNA, and then correlated with gene expression using RT-qPCR. Methylation was additionally correlated with tumour behaviour, including tumour recurrence and progression to muscle invasive bladder cancer or metastases. Results The ISL1 genes’ promoter-associated island was more frequently methylated in recurrent and progressive high-grade tumours than their non-recurrent counterparts (60.0% vs. 18.2%, p = 0.008). ISL1 and HOXA9 showed significantly higher mean methylation in recurrent and progressive tumours compared to non-recurrent tumours (43.3% vs. 20.9%, p = 0.016 and 34.5% vs 17.6%, p = 0.017, respectively). Concurrent ISL1/HOXA9 methylation in HG-NMIBC reliably predicted tumour recurrence and progression within one year (Positive Predictive Value 91.7%), and was associated with disease-specific mortality (DSM). Conclusions In this study we report methylation differences and similarities between clinical sub-types of high-grade NMIBC. We report the potential ability of methylation biomarkers, at initial diagnosis, to predict tumour recurrence and progression within one year of diagnosis. We found that specific biomarkers reliably predict disease outcome and therefore may help guide patient treatment despite the unpredictable clinical course and heterogeneity of high-grade NMIBC. Further investigation is required, including validation in a larger patient cohort, to confirm the clinical utility of methylation biomarkers in high-grade NMIBC

Conceptualizing pathways linking women's empowerment and prematurity in developing countries.

BackgroundGlobally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity.MethodsThe key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors.ResultsThere is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies.ConclusionsWomen's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed

Host and viral features of human dengue cases shape the population of infected and infectious Aedes aegypti mosquitoes

Dengue is the most prevalent arboviral disease of humans. The host and virus variables associated with dengue virus (DENV) transmission from symptomatic dengue cases (n = 208) to Aedes aegypti mosquitoes during 407 independent exposure events was defined. The 50% mosquito infectious dose for each of DENV-1–4 ranged from 6.29 to 7.52 log10 RNA copies/mL of plasma. Increasing day of illness, declining viremia, and rising antibody titers were independently associated with reduced risk of DENV transmission. High early DENV plasma viremia levels in patients were a marker of the duration of human infectiousness, and blood meals containing high concentrations of DENV were positively associated with the prevalence of infectious mosquitoes 14 d after blood feeding. Ambulatory dengue cases had lower viremia levels compared with hospitalized dengue cases but nonetheless at levels predicted to be infectious to mosquitoes. These data define serotype-specific viremia levels that vaccines or drugs must inhibit to prevent DENV transmission

Modulatory Communication Signal Performance Is Associated with a Distinct Neurogenomic State in Honey Bees

Studies of animal communication systems have revealed that the perception of a salient signal can cause large-scale changes in brain gene expression, but little is known about how communication affects the neurogenomic state of the sender. We explored this issue by studying honey bees that produce a vibratory modulatory signal. We chose this system because it represents an extreme case of animal communication; some bees perform this behavior intensively, effectively acting as communication specialists. We show large differences in patterns of brain gene expression between individuals producing vibratory signal as compared with carefully matched non-senders. Some of the differentially regulated genes have previously been implicated in the performance of other motor activities, including courtship behavior in Drosophila melanogaster and Parkinson's Disease in humans. Our results demonstrate for the first time a neurogenomic brain state associated with sending a communication signal and provide suggestive glimpses of molecular roots for motor control

LIF-Dependent Signaling: New Pieces in the Lego

LIF, a member of the IL6 family of cytokine, displays pleiotropic effects on various cell types and organs. Its critical role in stem cell models (e.g.: murine ES, human mesenchymal cells) and its essential non redundant function during the implantation process of embryos, in eutherian mammals, put this cytokine at the core of many studies aiming to understand its mechanisms of action, which could benefit to medical applications. In addition, its conservation upon evolution raised the challenging question concerning the function of LIF in species in which there is no implantation. We present the recent knowledge about the established and potential functions of LIF in different stem cell models, (embryonic, hematopoietic, mesenchymal, muscle, neural stem cells and iPSC). We will also discuss EVO-DEVO aspects of this multifaceted cytokine

2011 SOSORT guidelines: Orthopaedic and Rehabilitation treatment of idiopathic scoliosis during growth

<p>Abstract</p> <p>Background</p> <p>The International Scientific Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT), that produced its first Guidelines in 2005, felt the need to revise them and increase their scientific quality. The aim is to offer to all professionals and their patients an evidence-based updated review of the actual evidence on conservative treatment of idiopathic scoliosis (CTIS).</p> <p>Methods</p> <p>All types of professionals (specialty physicians, and allied health professionals) engaged in CTIS have been involved together with a methodologist and a patient representative. A review of all the relevant literature and of the existing Guidelines have been performed. Documents, recommendations, and practical approach flow charts have been developed according to a Delphi procedure. A methodological and practical review has been made, and a final Consensus Session was held during the 2011 Barcelona SOSORT Meeting.</p> <p>Results</p> <p>The contents of the document are: methodology; generalities on idiopathic scoliosis; approach to CTIS in different patients, with practical flow-charts; literature review and recommendations on assessment, bracing, physiotherapy, Physiotherapeutic Specific Exercises (PSE) and other CTIS. Sixty-five recommendations have been given, divided in the following topics: Bracing (20 recommendations), PSE to prevent scoliosis progression during growth (8), PSE during brace treatment and surgical therapy (5), Other conservative treatments (3), Respiratory function and exercises (3), Sports activities (6), Assessment (20). No recommendations reached a Strength of Evidence level I; 2 were level II; 7 level III; and 20 level IV; through the Consensus procedure 26 reached level V and 10 level VI. The Strength of Recommendations was Grade A for 13, B for 49 and C for 3; none had grade D.</p> <p>Conclusion</p> <p>These Guidelines have been a big effort of SOSORT to paint the actual situation of CTIS, starting from the evidence, and filling all the gray areas using a scientific method. According to results, it is possible to understand the lack of research in general on CTIS. SOSORT invites researchers to join, and clinicians to develop good research strategies to allow in the future to support or refute these recommendations according to new and stronger evidence.</p

Digital Health Policy and Programs for Hospital Care in Vietnam: Scoping Review

The members of the Vietnam ICU Translational Applications Laboratory (VITAL) group are as follows: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam: An Phuoc Luu, Chanh Quang Ho, Duc Hong Du, Duc Minh Tran, Dung Thi Phuong Nguyen, Giang Thi Nguyen, Hai Bich Ho, Hien Van Ho, Hung Manh Trinh, Huy Quang Nguyen, Khanh Nguyen Quoc Phan, Khoa Dinh Van Le, Kien Trung Dang, Lam Khanh Phung, Lieu Thi Pham, Ngoc Thanh Nguyen, Nhat Tran Huy Phung, Phuong Thanh Le, Quyen Than Ha Nguyen, Thanh Thi Le Nguyen, Thy Bui Xuan Doan, Trieu Trung Huynh, Trinh Huu Khanh Dong, Van Minh Tu Hoang, Van Thi Thanh Ninh, Vuong Lam Nguyen, Yen Minh Lam, Sayem Ahmed, Joseph Donovan, Ronald Geskus, Evelyne Kestelyn, Angela Mcbride, Guy Thwaites, Louise Thwaites, Hugo Turner, Jennifer Ilo Van Nuil, and Sophie Yacoub. Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam: Tam Thi Cao, Thuy Bich Duong, Duong Thi Hai Ha, Nghia Dang Trung Ha, Chau Buu Le, Thu Ngoc Minh Le, Thao Thi Mai Le, Tai Thi Hue Luong, Phu Hoan Nguyen, Viet Quoc Nguyen, Nguyen Thanh Nguyen, Phong Thanh Nguyen, Anh Thi Kim Nguyen, Hao Van Nguyen, Duoc Van Thanh Nguyen, Chau Van Vinh Nguyen, Oanh Kieu Nguyet Pham, Van Thi Hong Phan, Qui Tu Phan, Tho Vinh Phan, and Thao Thi Phuong Truong. University of Oxford, Oxford, United Kingdom: David Clifton, Mike English, Shadi Ghiasi, Heloise Greeff, Jannis Hagenah, Ping Lu, Jacob McKnight, Chris Paton, and Tingting Zhu. Imperial College London, London, United Kingdom: Pantellis Georgiou, Bernard Hernandez Perez, Kerri Hill-Cawthorne, Alison Holmes, Stefan Karolcik, Damien Ming, Nicolas Moser, and Jesus Rodriguez Manzano. King's College London, London, United Kingdom: Alberto Gomez, Hamideh Kerdegari, Marc Modat, and Reza Razavi. ETH Zurich, Zurich, Switzerland: Abhilash Guru Dutt, Walter Karlen, Michaela Verling, and Elias Wicki. The University of Melbourne, Melbourne, Australia: Linda Denehy and Thomas Rollinson.Background: There are a host of emergent technologies with the potential to improve hospital care in low- and middle-income countries such as Vietnam. Wearable monitors and artificial intelligence–based decision support systems could be integrated with hospital-based digital health systems such as electronic health records (EHRs) to provide higher level care at a relatively low cost. However, the appropriate and sustainable application of these innovations in low- and middle-income countries requires an understanding of the local government’s requirements and regulations such as technology specifications, cybersecurity, data-sharing protocols, and interoperability. Objective: This scoping review aims to explore the current state of digital health research and the policies that govern the adoption of digital health systems in Vietnamese hospitals. Methods: We conducted a scoping review using a modification of the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. PubMed and Web of Science were searched for academic publications, and Thư Viện Pháp Luật, a proprietary database of Vietnamese government documents, and the Vietnam Electronic Health Administration website were searched for government documents. Google Scholar and Google Search were used for snowballing searches. The sources were assessed against predefined eligibility criteria through title, abstract, and full-text screening. Relevant information from the included sources was charted and summarized. The review process was primarily undertaken by one researcher and reviewed by another researcher during each step. Results: In total, 11 academic publications and 20 government documents were included in this review. Among the academic studies, 5 reported engineering solutions for information systems in hospitals, 2 assessed readiness for EHR implementation, 1 tested physicians’ performance before and after using clinical decision support software, 1 reported a national laboratory information management system, and 2 reviewed the health system’s capability to implement eHealth and artificial intelligence. Of the 20 government documents, 19 were promulgated from 2013 to 2020. These regulations and guidance cover a wide range of digital health domains, including hospital information management systems, general and interoperability standards, cybersecurity in health organizations, conditions for the provision of health information technology (HIT), electronic health insurance claims, laboratory information systems, HIT maturity, digital health strategies, electronic medical records, EHRs, and eHealth architectural frameworks. Conclusions: Research about hospital-based digital health systems in Vietnam is very limited, particularly implementation studies. Government regulations and guidance for HIT in health care organizations have been released with increasing frequency since 2013, targeting a variety of information systems such as electronic medical records, EHRs, and laboratory information systems. In general, these policies were focused on the basic specifications and standards that digital health systems need to meet. More research is needed in the future to guide the implementation of digital health care systems in the Vietnam hospital setting.This study was supported by the Wellcome Trust United Kingdom WT217650/Z/19/Z