Hypothermia for encephalopathy in low and middle-income countries (HELIX): Study protocol for a randomised controlled trial

BACKGROUND: Therapeutic hypothermia reduces death and disability after moderate or severe neonatal encephalopathy in high-income countries and is used as standard therapy in these settings. However, the safety and efficacy of cooling therapy in low- and middle-income countries (LMICs), where 99% of the disease burden occurs, remains unclear. We will examine whether whole body cooling reduces death or neurodisability at 18-22 months after neonatal encephalopathy, in LMICs. METHODS: We will randomly allocate 408 term or near-term babies (aged ≤ 6 h) with moderate or severe neonatal encephalopathy admitted to public sector neonatal units in LMIC countries (India, Bangladesh or Sri Lanka), to either usual care alone or whole-body cooling with usual care. Babies allocated to the cooling arm will have core body temperature maintained at 33.5 °C using a servo-controlled cooling device for 72 h, followed by re-warming at 0.5 °C per hour. All babies will have detailed infection screening at the time of recruitment and 3 Telsa cerebral magnetic resonance imaging and spectroscopy at 1-2 weeks after birth. Our primary endpoint is death or moderate or severe disability at the age of 18 months. DISCUSSION: Upon completion, HELIX will be the largest cooling trial in neonatal encephalopathy and will provide a definitive answer regarding the safety and efficacy of cooling therapy for neonatal encephalopathy in LMICs. The trial will also provide important data about the influence of co-existent perinatal infection on the efficacy of hypothermic neuroprotection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02387385. Registered on 27 February 2015

Fatores associados ao equilíbrio funcional e à mobilidade em idosos diabéticos ambulatoriais

OBJECTIVES: To characterize balance and mobility among diabetic elderly outpatients and to estimate the extent to which functional balance and mobility abnormalities can be influenced by sociodemographic, clinical and other functional factors in a cross-sectional study. METHODS: Ninety-one elderly (65+ years) outpatients were assessed. Mobility was evaluated by the Timed Up and Go Test (TUGT) and the balance, by the Berg Balance Scale (BS). RESULTS: TUGT mean score was 15.65 ± 5.9 seconds and BS mean score was 49.31 ± 7.3 points. Using linear regression analysis (α < 0.05), significant and independent positive relationships were obtained between TUGT and age, daily activities (ADL/IADL), step strategy, and proprioceptive sensitivity. Factors negatively associated with BS were: ADL/IADL, step strategy, proprioceptive sensitivity, orthostatic hypotension (OH) and conflictive sensory conditions. CONCLUSION: Elderly diabetic outpatients show abnormal balance and mobility related mainly to advanced age, disability, absence of step strategy, absence of proprioceptive sensitivity and presence of OH.OBJETIVOS: Caracterizar o equilíbrio e a mobilidade de idosos diabéticos ambulatoriais e estimar o quanto suas anormalidades podem ser influenciadas por fatores sociodemográficos, clínicos e funcionais globais em um estudo transversal. MÉTODOS: 91 idosos (65 + anos) ambulatoriais foram avaliados quanto à mobilidade pelo Timed Up and Go Test (TUGT) e ao equilíbrio, pela Berg Balance Scale (BS). RESULTADOS: A média dos escores do TUGT foi de 15,65 ± 5,9 segundos e da BS, de 49,31 ± 7,3 pontos. Empregando-se análise de regressão linear (α < 0,05), associações significantes positivas e independentes foram obtidas entre o TUGT e idade, atividades cotidianas, estratégia do passo atrás e sensibilidade proprioceptiva. Os fatores associados negativamente à BS foram: atividades cotidianas, estratégia do passo, sensibilidade proprioceptiva, hipotensão ortostática (HO) e condições sensoriais conflituosas. CONCLUSÃO: Idosos diabéticos ambulatoriais apresentam equilíbrio e mobilidade prejudicados, relacionados principalmente à idade avançada, limitação para atividades diárias, ausência de estratégia de equilíbrio, prejuízo na sensibilidade proprioceptiva e a presença de HO.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Departamento de Medicina PreventivaUniversidade Cidade de São PauloUNIFESP Departamento de MedicinaUNIFESP, Depto. de Medicina PreventivaUNIFESP, Depto. de MedicinaSciEL

The evidence base for circulating tumour DNA blood-based biomarkers for the early detection of cancer: a systematic mapping review

Background: The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to those interested in early cancer detection, as well as to those wishing to monitor tumour progression or diagnose the presence of activating mutations to guide treatment. In 2014, the UK Early Cancer Detection Consortium undertook a systematic mapping review of the literature to identify blood-based biomarkers with potential for the development of a non-invasive blood test for cancer screening, and which identified this as a major area of interest. This review builds on the mapping review to expand the ctDNA dataset to examine the best options for the detection of multiple cancer types. Methods: The original mapping review was based on comprehensive searches of the electronic databases Medline, Embase, CINAHL, the Cochrane library, and Biosis to obtain relevant literature on blood-based biomarkers for cancer detection in humans (PROSPERO no. CRD42014010827). The abstracts for each paper were reviewed to determine whether validation data were reported, and then examined in full. Publications concentrating on monitoring of disease burden or mutations were excluded. Results: The search identified 94 ctDNA studies meeting the criteria for review. All but 5 studies examined one cancer type, with breast, colorectal and lung cancers representing 60% of studies. The size and design of the studies varied widely. Controls were included in 77% of publications. The largest study included 640 patients, but the median study size was 65 cases and 35 controls, and the bulk of studies (71%) included less than 100 patients. Studies either estimated cfDNA levels non-specifically or tested for cancer-specific mutations or methylation changes (the majority using PCR-based methods). Conclusion: We have systematically reviewed ctDNA blood biomarkers for the early detection of cancer. Pre-analytical, analytical, and post-analytical considerations were identified which need to be addressed before such biomarkers enter clinical practice. The value of small studies with no comparison between methods, or even the inclusion of controls is highly questionable, and larger validation studies will be required before such methods can be considered for early cancer detection

Stakeholder involvement in Multi-Criteria Decision Analysis

This brief perspective highlights the importance of decision maker buy-in and ownership through stakeholder engagement in the co-construction of the multi-criteria decision analysis (MCDA) model. A brief historical overview of MCDA is presented before outlining the importance of bridging the gap (and to gain trust) between the tool developers and users. The issues with the current MCDA tool development and testing efforts are highlighted, and the ownership and routine adoption of the MCDA process is discussed

Sinocurculigo, a New Genus of Hypoxidaceae from China Based on Molecular and Morphological Evidence

, with eight species are distributed in China. Recently, we have found a hypoxid-like plant in China that is quite different in floral structure from any of the three genera and even of the known taxa in Hypoxidaceae. regions of 59 taxa in Hypoxidaceae and its alliance. Findings of the molecular investigation is consistent with those of the morphological analysis.

Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for Hepatocellular Carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across TNM stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types

Adult Neurogenesis Transiently Generates Oxidative Stress

An increasing body of evidence suggests that alterations in neurogenesis and oxidative stress are associated with a wide variety of CNS diseases, including Alzheimer’s disease, schizophrenia and Parkinson’s disease, as well as routine loss of function accompanying aging. Interestingly, the association between neurogenesis and the production of reactive oxidative species (ROS) remains largely unexamined. The adult CNS harbors two regions of persistent lifelong neurogenesis: the subventricular zone and the dentate gyrus (DG). These regions contain populations of quiescent neural stem cells (NSCs) that generate mature progeny via rapidly-dividing progenitor cells. We hypothesized that the energetic demands of highly proliferative progenitors generates localized oxidative stress that contributes to ROS-mediated damage within the neuropoietic microenvironment. In vivo examination of germinal niches in adult rodents revealed increases in oxidized DNA and lipid markers, particularly in the subgranular zone (SGZ) of the dentate gyrus. To further pinpoint the cell types responsible for oxidative stress, we employed an in vitro cell culture model allowing for the synchronous terminal differentiation of primary hippocampal NSCs. Inducing differentiation in primary NSCs resulted in an immediate increase in total mitochondria number and overall ROS production, suggesting oxidative stress is generated during a transient window of elevated neurogenesis accompanying normal neurogenesis. To confirm these findings in vivo, we identified a set of oxidation-responsive genes, which respond to antioxidant administration and are significantly elevated in genetic- and exercise-induced model of hyperactive hippocampal neurogenesis. While no direct evidence exists coupling neurogenesis-associated stress to CNS disease, our data suggest that oxidative stress is produced as a result of routine adult neurogenesis

Micropropagation and conservation of selected endangered anticancer medicinal plants from the Western Ghats of India

Globally, cancer is a constant battle which severely affects the human population. The major limitations of the anticancer drugs are the deleterious side effects on the quality of life. Plants play a vital role in curing many diseases with minimal or no side effects. Phytocompounds derived from various medicinal plants serve as the best source of drugs to treat cancer. The global demand for phytomedicines is mostly reached by the medicinal herbs from the tropical nations of the world even though many plant species are threatened with extinction. India is one of the mega diverse countries of the world due to its ecological habitats, latitudinal variation, and diverse climatic range. Western Ghats of India is one of the most important depositories of endemic herbs. It is found along the stretch of south western part of India and constitutes rain forest with more than 4000 diverse medicinal plant species. In recent times, many of these therapeutically valued herbs have become endangered and are being included under the red-listed plant category in this region. Due to a sharp rise in the demand for plant-based products, this rich collection is diminishing at an alarming rate that eventually triggered dangerous to biodiversity. Thus, conservation of the endangered medicinal plants has become a matter of importance. The conservation by using only in situ approaches may not be sufficient enough to safeguard such a huge bio-resource of endangered medicinal plants. Hence, the use of biotechnological methods would be vital to complement the ex vitro protection programs and help to reestablish endangered plant species. In this backdrop, the key tools of biotechnology that could assist plant conservation were developed in terms of in vitro regeneration, seed banking, DNA storage, pollen storage, germplasm storage, gene bank (field gene banking), tissue bank, and cryopreservation. In this chapter, an attempt has been made to critically review major endangered medicinal plants that possess anticancer compounds and their conservation aspects by integrating various biotechnological tool