Reporting the whole story: Analysis of the 'out-of-scope' questions from the James Lind Alliance Teenage and Young Adult Cancer Priority Setting Partnership Survey.

OBJECTIVE: We conducted a UK-wide survey to identify the top 10 research questions for young people's cancer. We conducted secondary analysis of questions submitted, which were 'out-of-scope' of the original survey aim. We sought to disseminate these questions, to inform practice, policy and the development of potential interventions to support young people with cancer. DESIGN: James Lind Alliance Priority Setting Partnership. PARTICIPANTS: Young people aged 13-24 with a current/previous cancer diagnosis, their families/friends/partners and professionals who work with this population. METHODS: Eight hundred and fifty-five potential research questions were submitted, and 326 were classified as 'out-of-scope'. These questions, along with 49 'free-text' comments, were analysed using thematic analysis. RESULTS: The 375 out-of-scope questions and comments were submitted by: 68 young people, 81 family members/partners/friends and 42 professionals. Ten overarching themes were identified: diagnostic experience; communication; coordination of care; information needs and lack of information; service provision; long-term effects and aftercare support; family support; financial impact; end-of life care; and research methods and current research. CONCLUSIONS: The need to tailor services, information and communication is a striking thread evidenced across the 'out-of-scope' questions. Gaps in information highlight implications for practice in revisiting information needs throughout the cancer trajectory. We must advocate for specialist care for young people and promote the research priorities and these findings to funding bodies, charities, young people and health and social care policymakers, in order to generate an evidence base to inform effective interventions across the cancer trajectory and improve outcomes. PATIENT/PUBLIC CONTRIBUTIONS: Patients and carers were equal stakeholders throughout.

A Brief Overview of Potential Treatments for Viral Diseases Using Natural Plant Compounds: The Case of SARS-Cov.

The COVID-19 pandemic, as well as the more general global increase in viral diseases, has led researchers to look to the plant kingdom as a potential source for antiviral compounds. Since ancient times, herbal medicines have been extensively applied in the treatment and prevention of various infectious diseases in different traditional systems. The purpose of this review is to highlight the potential antiviral activity of plant compounds as effective and reliable agents against viral infections, especially by viruses from the coronavirus group. Various antiviral mechanisms shown by crude plant extracts and plant-derived bioactive compounds are discussed. The understanding of the action mechanisms of complex plant extract and isolated plant-derived compounds will help pave the way towards the combat of this life-threatening disease. Further, molecular docking studies, in silico analyses of extracted compounds, and future prospects are included. The in vitro production of antiviral chemical compounds from plants using molecular pharming is also considered. Notably, hairy root cultures represent a promising and sustainable way to obtain a range of biologically active compounds that may be applied in the development of novel antiviral agents.

Percutaneous left ventricular assist device support during ablation of ventricular tachycardia: A meta-analysis of current evidence.

INTRODUCTION: Catheter ablation of ventricular tachycardia (VT) can be an effective therapy to reduce VT burden, but often it is limited by the potential for hemodynamic instability. Percutaneous left ventricular assist devices (pLVADs) have been used to maintain hemodynamic support during VT ablation but the evidence regarding its clinical impact has been inconclusive. METHODS AND RESULTS: We sought to assess the clinical impact of pLVAD when used in VT ablation by conducting a meta-analysis of the current evidence. We searched Pubmed and found nine observational studies that compared clinical outcomes of VT ablation in patients with pLVAD support to controls with no pLVAD support. The pooled data did not show a significant difference in mortality between both groups, nor a difference in acute procedural success or in recurrence of VT. There was also no difference in the number of patients receiving a cardiac transplant or being enrolled in the transplant list. Although there was no difference in the ablation time between the groups, patients in the pLVAD group had a longer total procedural time and more procedure-related adverse effects. CONCLUSION: This meta-analysis did not show clinical benefits from using pLVAD support during VT ablation, whereas it was associated with longer procedure times and more complications. This study was, however, limited by the observational nature of the data. In view of these data, the risk and benefit of pLVAD support during VT ablation should be considered on an individual basis.

Mortality Effect of ICD in Primary Prevention of Nonischemic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Implantation of an implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death (SCD) is controversial in view of the recent DANISH trial which suggested no benefit with ICD for primary prevention in patients with non-ischemic cardiomyopathy (NICMP). METHODS: We conducted a meta-analysis of randomized control trials studying the role of ICD in primary prevention of SCD in patients with NICMP. Only six studies were identified after the application of inclusion/exclusion criteria. RESULTS: Pooling of these randomized trials showed a statistically significant benefit of using ICDs in patients with NICMP [OR 0.76 (0.64 - 0.91), I2 = 0%]. Sensitivity analysis did not show a statistically significant mortality benefit of ICD in NICMP in trials which had adequate beta blocker, ACE/ARB and aldosterone receptor blocker (ALD-RB) use [OR 0.70 (0.41, 1.19), I2 = 70%]. CONCLUSION: The DANISH trial's failure to show mortality benefit may be due to the significant number of patients who had CRT. Our meta-analysis studied the independent effect of ICDs and showed them to be associated with net mortality benefits in patients who are not on optimal guideline directed medical therapy; especially the patients not on ALD-RB.

Strigolactone biology: genes, functional genomics, epigenetics and applications.

Strigolactones (SLs) represent an important new plant hormone class marked by their multifunctional role in plant and rhizosphere interactions. These compounds stimulate hyphal branching in arbuscular mycorrhizal fungi (AMF) and seed germination of root parasitic plants. In addition, they are involved in the control of plant architecture by inhibiting bud outgrowth as well as many other morphological and developmental processes together with other plant hormones such as auxins and cytokinins. The biosynthetic pathway of SLs that are derived from carotenoids was partially decrypted based on the identification of mutants from a variety of plant species. Only a few SL biosynthetic and regulated genes and related regulatory transcription factors have been identified. However, functional genomics and epigenetic studies started to give first elements on the modality of the regulation of SLs related genes. Since they control plant architecture and plant-rhizosphere interaction, SLs start to be used for agronomical and biotechnological applications. Furthermore, the genes involved in the SL biosynthetic pathway and genes regulated by SL constitute interesting targets for plant breeding. Therefore, it is necessary to decipher and better understand the genetic determinants of their regulation at different levels.

Biotechnological approaches to the production of shikonins: a critical review with recent updates.

Shikonins are commercially important secondary compounds, known for array of biological activities such as antimicrobial, insecticidal, antitumor, antioxidants, etc. These compounds are usually colored and therefore have application in food, textiles and cosmetics. Shikonin and its derivatives, which are commercially most important of the naphthoquinone pigments, are distributed among members of the family Boraginaceae. These include different species of Lithospermum, Arnebia, Alkanna, Anchusa, Echium and Onosma. The growing demand for plant-based natural products has made this group of compounds one of the enthralling targets for their in vitro production. The aim of this review is to highlight the recent progress in production of shikonins by various biotechnological means. Different methods of increasing the levels of shikonins in plant cells such as selection of cell lines, optimization of culture conditions, elicitation, in situ product removal, genetic transformation and metabolic engineering are discussed. The experience of different researchers working worldwide on this aspect is also considered. Further, to meet market demand, the needs for continuous and reliable production systems, as well as future prospects, are included.

Screening and kinetic studies of catharanthine and ajmalicine accumulation and their correlation with growth biomass in Catharanthus roseus hairy roots.

Context Catharanthus roseus (L.) G. Don (Apocynaceae) is still one of the most important sources of terpene indole alkaloids including anticancer and hypertensive drugs as vincristine and vinblastine. These final compounds have complex pathway and many enzymes are involved in their biosynthesis. Indeed, ajmalicine and catharanthine are important precursors their increase can lead to enhance levels of molecules of interest. Objective This study aims at selecting the highest yield of hairy root line(s) and at identifying best times for further treatments. We study kinetics growth and alkaloids (ajmalicine and catharanthine) accumulation of three selected hairy root lines during the culture cycle in order to determine the relationship between biomass production and alkaloids accumulation. Materials and methods Comparative analysis has been carried out on three selected lines of Catharanthus roseus hairy roots (LP10, LP21 and L54) for their kinetics of growth and the accumulation of ajamalicine and catharanthine, throughout a 35-day culture cycle. The methanolic extract for each line in different times during culture cycle is analyzed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Results Maximum accumulation of the alkaloids is recorded for LP10 line in which the peak of ajmalicine and catharanthine accumulation reached to 3.8 and 4.3 mg/g dry weight (DW), respectively. This increase coincides with an exponential growth phase. Discussion and conclusion Our results suggest that the evolution of accumulation of ajmalicine and catharanthine are positively correlated with the development of the biomass growth. Significantly, for LP10 line the most promising line to continue optimizing the production of TIAs. Additionally, the end of exponential phase remains the best period for elicitor stimuli.

Phytometabolites as modulators of breast cancer: a comprehensive review of mechanistic insights.

Breast cancer (BC) is a highly debilitating malignancy affecting females globally and imposing a substantial burden on healthcare systems in both developed and developing nations. Despite the application of conventional therapeutic modalities such as chemotherapy, radiation therapy, and hormonal intervention, BC frequently exhibits resistance, necessitating the urgent development of novel, cost-effective, and accessible treatment strategies. In this context, there is a growing scientific interest in exploring the pharmacological potential of chemical compounds derived from botanical sources, which often exhibit notable biological activity. Extensive in vitro and in vivo investigations have revealed the capacity of these compounds, referred to as phytochemicals, to attenuate the metastatic cascade and reduce the risk of cancer dissemination. These phytochemicals exert their effects through modulation of key molecular and metabolic processes, including regulation of the cell cycle, induction of apoptotic cell death, inhibition of angiogenesis, and suppression of metastatic progression. To shed light on the latest advancements in this field, a comprehensive review of the scientific literature has been conducted, focusing on secondary metabolite agents that have recently been investigated and have demonstrated promising anticancer properties. This review aims to delineate their underlying mechanisms of action and elucidate the associated signaling pathways, thereby contributing to a deeper understanding of their therapeutic potential in the context of BC management.

Tapping the potential of Calotropis procera hairy roots for cardiac glycosides production and their identification using UHPLC/QTOF-MS.

The present work deals with the establishment of hairy root cultures from different explants of C. procera using Agrobacterium rhizogenes strain A4. A high transformation frequency (95%) was obtained from leaves followed by cotyledons (81.6%) and hypocotyls (38.3%). Genetic transformation of hairy roots was confirmed through PCR by amplifying a 400 bp fragment of the rolB gene. Hairy roots were highly branched, possessed plagiotropic and rapid growth on hormone-free ½ B5 medium. Ten cardiac glycosides, including calotropagenin, calotoxin, frugoside, coroglaucigenin, calotropin, calactin, uzarigenin, asclepin, uscharidin, and uscharin, based on their specific masses and fragmentation properties were identified in ethanolic extracts of hairy roots by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry UHPLC/QTOF-MS. This protocol could be used as a powerful tool for large-scale in vitro production of highly valued cardiac glycosides and for further transcriptomics or metabolomics studies.

The Curie temperature: a key playmaker in self-regulated temperature hyperthermia.

The Curie temperature is an important thermo-characteristic of magnetic materials, which causes a phase transition from ferromagnetic to paramagnetic by changing the spontaneous re-arrangement of their spins (intrinsic magnetic mechanism) due to an increase in temperature. The self-control-temperature (SCT) leads to the conversion of ferro/ferrimagnetic materials to paramagnetic materials, which can extend the temperature-based applications of these materials from industrial nanotechnology to the biomedical field. In this case, magnetic induction hyperthermia (MIH) with self-control-temperature has been proposed as a physical thermo-therapeutic method for killing cancer tumors in a biologically safe environment. Specifically, the thermal source of MIH is magnetic nanoparticles (MNPs), and thus their biocompatibility and Curie temperature are two important properties, where the former is required for their clinical application, while the latter acts as a switch to automatically control the temperature of MIH. In this review, we focus on the Curie temperature of magnetic materials and provide a complete overview beginning with basic magnetism and its inevitable relation with Curie's law, theoretical prediction and experimental measurement of the Curie temperature. Furthermore, we discuss the significance, evolution from different types of alloys to ferrites and impact of the shape, size, and concentration of particles on the Curie temperature considering the proposed SCT-based MIH together with their biocompatibility. Also, we highlight the thermal efficiency of MNPs in destroying tumor cells and the significance of a low Curie temperature. Finally, the challenges, concluding remarks, and future perspectives in promoting self-control-temperature based MIH to clinical application are discussed.

Organic extracts from sustainable hybrid poplar hairy root cultures as potential natural antimicrobial and antibiofilm agents.

In order to meet growing consumer demands in terms of naturalness, the pharmaceutical, food, and cosmetic industries are looking for active molecules of plant origin. In this context, hairy roots are considered a promising biotechnological system for the sustainable production of compounds of interest. Poplars (genus Populus, family Salicaceae) are trees of ecological interest in temperate alluvial forests and are also cultivated for their industrial timber. Poplar trees also produce specialized metabolites with a wide range of bioactive properties. The present study aimed to assess the hybrid poplar hairy root extracts for antimicrobial and antibiofilm activities against four main life-threatening strains of Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria. Ethyl acetate extracts from two hairy root lines (HP15-3 and HP A4-12) showed significant antibacterial properties as confirmed by disc diffusion assay. Antibiofilm activities were found to be dose dependent with significant biofilm inhibition (75-95%) recorded at 1000 µg.mL-1 in all the bacterial strains tested. Dose-dependent enhancement in the release of exopolysaccharides was observed in response to treatment with extracts, possibly because of stress and bacterial cell death. Fluorescence microscopy confirmed loss of cell viability of treated bacterial cells concomitant with increased production of reactive oxygen species compared to the untreated control. Overall, this study demonstrates for the first time a high potential of poplar hairy root extracts as a natural and safe platform to produce antimicrobial agents in pharmaceutical, food, industrial water management, or cosmetic industries.

Nanoparticle elicitation: A promising strategy to modulate the production of bioactive compounds in hairy roots.

Hairy root culture is one of the promising biotechnological tools to obtain the stable and sustainable production of specialized metabolites from plants under controlled environment conditions. Various strategies have been adopted to enhance the accumulation of bioactive compounds in hairy roots yet their utilization at the commercial scale is restricted to only a few products. Recently, nanotechnology has been emerged as an active technique that has revolutionized the many sectors in an advantageous way. Elicitation using nanoparticles has been recognized as an effective strategy for enhancing the bioactive compounds of interest in plants. Nanoparticles elicit the activity of defense-related compounds through activation of the specific transcription factors involved in specialized metabolites production. This review discusses the recent progress in using nanoparticles to enhance specialized metabolite biosynthesis using hairy root culture system and the significant achievements in this area of research. Biotic and abiotic elicitors to improve the production of bioactive compounds in hairy roots, different types of nanoparticles as eliciting agents, their properties as dependent on shape, most widely used nanoparticles in plant hairy root systems are described in detail. Further challenges involved in application of nanoparticles, their toxicity in plant cells and risks associated to human health are also envisaged. No doubt, nanoparticle elicitation is a remarkable approach to obtain phytochemicals from hairy roots to be utilized in various sectors including food, medicines, cosmetics or agriculture but it is quite essential to understand the inter-relationships between the nanoparticles and the plant systems in terms of specifics such as type, dosage and time of exposure as well as other important parameters.

Living between two worlds: two-phase culture systems for producing plant secondary metabolites.

The two-phase culture system is an important in vitro strategy to increase the production of secondary metabolites (SMs) by providing an enhanced release of these compounds from plant cells. Whereas the first phase supports cell growth, the second phase provides an additional site or acts as a metabolic sink for the accumulation of SMs and also reduces feedback inhibition. This review is focused on several aspects of the two-phase culture system and aims to show the diverse possibilities of employing this technique for the in vitro production of SMs from plant cells. Depending on the material used in the secondary phase, two-phase culture systems can be broadly categorised as liquid-liquid or liquid-solid. The choice of material for the second phase depends on the type of compound to be recovered and the compatibility with the other phase. Different factors affecting the efficiency of two-phase culture systems include the choice of material for the secondary phase, its concentration, volume, and time of addition. Factors such as cell elicitation, immobilization, and permeabilization, have been suggested as important strategies to make the two-phase culture system practically reliable on a commercial scale. Since there are many possibilities for designing a two-phase system, more detailed studies are needed to broaden the range of secondary phases compatible with the various plant species producing SMs with potential applications, mainly in the food and pharmacology industries.

Use of dried blood blotted on filter paper to detect dengue IgM antibody and dengue NS1 antigen.

A cross sectional study was conducted at the Department of Microbiology, Maulana Azad Medical College, New Delhi, to determine the efficacy of capillary blood samples collected on filter paper compared with serum samples to detect dengue IgM antibody and dengue NS1 antigen. The serum and capillary blood samples were collected from 104 suspected cases of dengue fever at Lok Nayak Hospital, India. The blood eluted from the filter paper and the serum samples were tested for dengue IgM antibody and dengue NS1 antigen by commercial capture ELISA kits. Of the 104 patients, samples from 61 patients tested positive for dengue IgM antibodies with both the serum and filter paper. Samples from 38 patients were negative for both serum and filter paper. Five samples showed discordant results. The filter paper method had sensitivity of 96.8% and specificity of 97.4% for dengue IgM antibody compared to the serum samples. The positive predictive value (PPV) and negative predictive value (NPV) for the filter paper to detect dengue IgM were 95.31% and 95.0%, respectively. The Kappa value (>0.80) showed agreement between the filter paper and serum results for IgM antibody detection. NS1 antigen was detected 28 serum and 28 filter paper samples and was not detected in 72 serum and 72 filter paper samples. Discordant results were seen in 4 samples. The filter paper method had a sensitivity of 96.5% and a specificity of 96.0% compared to the serum for detecting dengue NS1 antigen. The PPV and NPV for the filter paper samples in detecting dengue NS1 antigen were 90.3% and 98.7%, respectively. The Kappa value showed agreement (>0.80) between the serum and filter paper results for detecting dengue NS1 antigen. The results show filter paper samples are a reasonable alternative to serum for detecting dengue infecting.

Efficacy of Artificial Oocyte Activation in Improving the Reproductive Outcome in Poor Responders: A Single Centre Cohort Study.

Objective: Achieving pregnancy in poor ovarian response patients is a challenge. Failed fertilization after ICSI, despite normal semen parameters is due to defects in oocyte activation. In-vitro activation of oocytes using Ca+2 agents can be useful in increasing the fertilization rates in these patients. This study aimed to evaluate the efficacy of artificial oocyte activation by calcium ionophores in poor responders in improving fertilization, cleavage, implantation and clinical pregnancy rates. Materials and methods: This is a prospective, cohort study conducted on 120 patients having poor ovarian response, (POSEIDON criteria) undergoing in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment at Southend Fertility and IVF, New Delhi from 1st August 2019 to 31st March 2020. Exclusion criterion was patients with partners with abnormal semen parameters. After OPU patients were randomized into two groups, study group (n=50) underwent ICSI-AOA (ICSI followed by artificial oocyte activation) using calcium ionophore- GM508 Cult-Active Solution) while the controls (n=57) were subjected to ICSI only. Results: Comparison of ICSI-AOA and ICSI groups showed: (i) number of fertilized oocytes - 2.42 vs. 2.16, p = 0.049 (ii) No. of cleavage stage embryos 2.32 vs. 1.96, p = 0.008 (iii) No. of grade A embryos 1.52 vs. 1.04, p = 0.009 (iv) fertilization rate - 89.00% vs. 83.04%, p = 0.093 (v) cleavage rate - 96.33% vs. 92.55%, p = 0.165 (vi) implantation rate - 27.14% vs. 11.74%, p = 0.098 (vii) clinical pregnancy rate - 34.3% vs. 20.5%, p = 0.167. Conclusion: The number of fertilized oocytes, grade A embryos and cleavage stage embryos formed after ICSI-AOA were statistically significantly more than ICSI. ICSI-AOA has not shown improvement in fertilization, cleavage, implantation and clinical pregnancy rate. From the present study the conclusive evidence cannot be drawn due to small sample size hence further studies are needed on a larger population.

Natural Plant-Derived Compounds in Food and Cosmetics: A Paradigm of Shikonin and Its Derivatives.

Shikonin and its derivatives are the natural naphthoquinone compounds produced in the roots of the Boraginaceae family. These red pigments have been used for a long time in coloring silk, as food colorants, and in the Chinese traditional system of medicines The resurgence of public interest in natural and plant-based products has led to this category of compounds being in high demand due to their wide range of biological activities including antioxidant, antitumor, antifungal, anti-inflammatory ones. Different researchers worldwide have reported various applications of shikonin derivatives in the area of pharmacology. Nevertheless, the use of these compounds in the food and cosmetics fields needs to be explored more in order to make them available for commercial utilization in various food industries as a packaging material and to enhance their shelf life without any side effects. Similarly, the antioxidant properties and skin whitening effects of these bioactive molecules may be used successfully in various cosmetic formulations. The present review delves into the updated knowledge on the various properties of shikonin derivatives in relation to food and cosmetics. The pharmacological effects of these bioactive compounds are also highlighted. Based on various studies, it can be concluded that these natural bioactive molecules have potential to be used in different sectors, including functional food, food additives, skin, health care, and to cure various diseases. Further research is required for the sustainable production of these compounds with minimum disturbances to the environment and in order to make them available in the market at an economic price. Simultaneous studies utilizing recent techniques in computational biology, bioinformatics, molecular docking, and artificial intelligence in laboratory and clinical trials would further help in making these potential candidates promising alternative natural bioactive therapeutics with multiple uses.

What matters to you? Engaging with children in the James Lind Alliance Children's Cancer Priority Setting Partnership.

BACKGROUND: Previous priority setting exercises have sought to involve children, but in the final reporting, it is evident that few children had been engaged through the process. A primary aim in the Children's Cancer Priority Setting Partnership was to find out from children what they want research to focus on. We report on our experience to inform methods of engagement with children in future James Lind Alliance Priority Setting Partnerships and similar exercises. METHODS: We followed the James Lind Alliance process, collecting and shortlisting questions via online surveys with adult survivors of childhood cancer, carers, and professionals, and holding a final workshop. Alongside this, a parallel process to collect and prioritise questions from children was undertaken. We created animations for parents/carers to explain the project and surveys to children, gathered questions via online surveys and held a workshop with children to identify their priorities. RESULTS: Sixty-one children and young people with cancer and 10 siblings, aged 3-21 years, submitted 252 potential questions/topics via the surveys. Submissions were refined into 24 summary questions. These questions were discussed at a workshop with eight children; they also added more questions on topics of importance to them. Workshop participants prioritised the Top 5 questions; top priority was, 'How can we make being in hospital a better experience for children and young people? (like having better food, internet, toys, and open visiting so other family members can be more involved in the child's care)'. The Top 5 also included cancer prevention, treatments closer to home, early diagnosis, and emotional support. These questions were taken to the final workshop at which the Top 10 priorities were decided, all five children's priorities were reflected in the final Top 10. CONCLUSIONS: We have demonstrated that it is possible to successfully involve children directly in setting priorities for future research. Future priority setting exercises on topics relevant to children, should seek to include their views. The Children's Cancer Top 10 priorities reflect the voices of children and should inform the funding of future research.

Priority Setting Partnerships find out what areas of research are important to patients, families, and the professionals who care for them. Few Priority Setting Partnerships have involved children, so what matters to them may not have been well-represented. The Children's Cancer Priority Setting Partnership aimed to find out directly from children what research we should do. We collected questions/topics for research from children using online surveys. We made animations to explain the project and surveys to children. Two-hundred and fifty-two questions were sent in by 61 children and young people with cancer and 10 siblings. We grouped similar questions together into 24 summary questions. Summary questions were discussed at a workshop with eight children. Workshop participants added more questions on topics that mattered to them, and decided their Top 5 questions. The top question was, 'How can we make being in hospital a better experience for children and young people? (like having better food, internet, toys, and open visiting so other family members can be more involved in the child's care)'. The Top 5 questions included: preventing cancer, having treatments nearer home, early diagnosis, and emotional support. These questions were taken to the final project workshop, this was with adults, including childhood cancer survivors, where the Top 10 priorities were decided. All five children's priorities were included in the Top 10. We have shown it is possible to successfully involve children in setting research priorities. Future priority setting exercises on topics that affect children should actively seek and include their views.

Black Poplar (Populus nigra L.) Root Extracellular Trap, Structural and Molecular Remodeling in Response to Osmotic Stress.

The root extracellular trap (RET) consists of root-associated, cap-derived cells (root AC-DCs) and their mucilaginous secretions, and forms a structure around the root tip that protects against biotic and abiotic stresses. However, there is little information concerning the changes undergone by the RET during droughts, especially for tree species. Morphological and immunocytochemical approaches were used to study the RET of black poplar (Populus nigra L.) seedlings grown in vitro under optimal conditions (on agar-gelled medium) or when polyethylene glycol-mediated (PEG6000-infused agar-gelled medium) was used to mimic drought conditions through osmotic stress. Under optimal conditions, the root cap released three populations of individual AC-DC morphotypes, with a very low proportion of spherical morphotypes, and equivalent proportions of intermediate and elongated morphotypes. Immunolabeling experiments using anti-glycan antibodies specific to cell wall polysaccharide and arabinogalactan protein (AGP) epitopes revealed the presence of homogalacturonan (HG), galactan chains of rhamnogalacturonan-I (RG-I), and AGPs in root AC-DC cell walls. The data also showed the presence of xylogalacturonan (XGA), xylan, AGPs, and low levels of arabinans in the mucilage. The findings also showed that under osmotic stress conditions, both the number of AC-DCs (spherical and intermediate morphotypes) and the total quantity of mucilage per root tip increased, whereas the mucilage was devoid of the epitopes associated with the polysaccharides RG-I, XGA, xylan, and AGPs. Osmotic stress also led to reduced root growth and increased root expression of the P5CS2 gene, which is involved in proline biosynthesis and cellular osmolarity maintenance (or preservation) in aerial parts. Together, our findings show that the RET is a dynamic structure that undergoes pronounced structural and molecular remodeling, which might contribute to the survival of the root tip under osmotic conditions.

Research priorities for children's cancer: a James Lind Alliance Priority Setting Partnership in the UK.

OBJECTIVES: To engage children who have experienced cancer, childhood cancer survivors, their families and professionals to systematically identify and prioritise research questions about childhood cancer to inform the future research agenda. DESIGN: James Lind Alliance Priority Setting Partnership. SETTING: UK health service and community. METHODS: A steering group oversaw the initiative. Potential research questions were collected in an online survey, then checked to ensure they were unanswered. Shortlisting via a second online survey identified the highest priority questions. A parallel process with children was undertaken. A final consensus workshop was held to determine the Top 10 priorities. PARTICIPANTS: Children and survivors of childhood cancer, diagnosed before age 16, their families, friends and professionals who work with this population. RESULTS: Four hundred and eighty-eight people submitted 1299 potential questions. These were refined into 108 unique questions; 4 were already answered and 3 were under active study, therefore, removed. Three hundred and twenty-seven respondents completed the shortlisting survey. Seventy-one children submitted questions in the children's surveys, eight children attended a workshop to prioritise these questions. The Top 5 questions from children were taken to the final workshop where 23 questions in total were discussed by 25 participants (young adults, carers and professionals). The top priority was 'can we find effective and kinder (less burdensome, more tolerable, with fewer short and long-term effects) treatments for children with cancer, including relapsed cancer?' CONCLUSIONS: We have identified research priorities for children's cancer from the perspectives of children, survivors, their families and the professionals who care for them. Questions reflect the breadth of the cancer experience, including diagnosis, relapse, hospital experience, support during/after treatment and the long-term impact of cancer. These should inform funding of future research as they are the questions that matter most to the people who could benefit from research.

Dengue outbreak in Delhi in 2009: study of laboratory and clinical parameters.

Dengue infection is endemic in India with frequent epidemics of Dengue Fever/Dengue Hemorrhagic Fever. The outbreaks vary in the commonest serotype in circulation during that period, predominant laboratory findings and clinical manifestations. This study was carried during the outbreak of dengue in Delhi in 2009. Clinical assessment and laboratory investigations were performed and severity of the disease with clinical, haematological parameters and serotypes were correlated. Of 107 patients included in the study, 64 (59.8%) were positive by ELISA. These 64 patients were tested by RT-PCR and 7 were found to be positive. DEN-2 and DEN-4 serotypes were isolated. There was a decreasing trend in mean age of patients with severity of infection. The outbreak was milder as compared to earlier ones in regards of number of cases presenting with clinical manifestations of bleeding. A considerable number of patients presented with unusual findings, namely, ascites, pleural effusion, myocarditis, cholecystitis and pancreatitis. There was no statistically significant difference either in platelet count between various groups or comparison of bleeding with severity of thrombocytopenia. This study provides an insight into the clinico-laboratory findings of the outbreak of dengue in 2009.