Transparent reporting of recruitment and informed consent approaches in clinical trials recruiting children with minor parents in sub-Saharan Africa: a secondary analysis based on a systematic review

BACKGROUND: Standardised checklists of items to be addressed in clinical study protocols and publications are promoting transparency in research. However, particular specifications for exceptional cases, such as children with minor parents are missing. This study aimed to examine the level of transparency regarding recruitment and informed consent approaches in publications of clinical trials recruiting children with minor parents in sub-Saharan Africa. We thereby focused particularly on the transparency about consenting persons (i.e. proxy decision-makers) and assessed the need to expand reporting guidelines for such exceptional cases. METHODS: We conducted a secondary analysis of clinical trial publications previously identified through a systematic review. Multiple scientific databases were searched up to March 2019. Clinical trial publications addressing consent and potentially recruiting children with minor parents in sub-Saharan Africa were included. 44 of the in total 4382 screened articles met our inclusion criteria. A descriptive analysis was performed. RESULTS: None of the included articles provided full evidence on whether any recruited children had minor parents and how consent was obtained for them. Four proxy decision-maker types were identified (parents; parents or guardians; guardians; or caregivers), with further descriptions provided rarely and mostly in referenced clinical trial registrations or protocols. Also, terminology describing proxy decision-makers was often used inconsistently. CONCLUSIONS: Reporting the minimum maternal age alongside maternal data provided in baseline demographics can increase transparency on the recruitment of children with minor mothers. The CONSORT checklist should require clinical trial publications to state or reference exceptional informed consent procedures applied for special population groups. A standardized definition of proxy decision-maker types in international clinical trial guidelines would facilitate correct and transparent informed consent for children and children with minor parents. STUDY REGISTRATION: CRD42018074220

BENEFICIALTREATMENTS ON PVX AND PVY INFECTED POTATO(SOLANUM TUBEROSUM L.) PLANTS

This study presents the efficiency of some combined techniques (chemo- and electrotherapy) in decreasing the infection level of PVY and PVX infected plants (cv. Roclas). The infected plantlets were exposed to 100 mA for 5, 10 and 20 minutes (electrotherapy), washed, divided into single node cuttings and multiplied in vitro. Chemotherapy was undertaken with ribavirin (RBV) and oseltamivir (OSMV). Solanum tuberosum L.plantlets regenerated were removed from the culture medium, acclimated in green house. The survivor plants were indexed (DAS ELISA, Bioreba, Switzerland). Distinguished virus elimination rates were obtained for all the material infected, using the most severe variants of electrotherapy (100mA/10minutes; 100mA/20 minutes). The highest values were registered in case of PVX infected material

A four-helix bundle stores copper for methane oxidation

Methane-oxidising bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase (pMMO). Certain methanotrophs are also able to switch to using the iron-containing soluble MMO (sMMO) to catalyse methane oxidation, with this switchover regulated by copper. MMOs are Nature’s primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and MMOs have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. We have discovered and characterised a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for pMMO. Csp1 is a tetramer of 4-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realised. Cytosolic homologues of Csp1 are present in diverse bacteria thus challenging the dogma that such organisms do not use copper in this location

Reaction profiling of a set of acrylamide-based human tissue transglutaminase inhibitors

The major function of the enzyme human tissue transglutaminase (TG2) is the crosslinking of proteins via a transamidation between the γ-carboxamide of a glutamine and the ε-amino group of a lysine. Overexpression of TG2 can lead to undesirable outcomes and has been linked to conditions such as fibrosis, celiac disease and neurodegenerative diseases. Accordingly, TG2 is a tempting drug target. The most effective TG2 inhibitors to date are small-molecule peptidomimetics featuring electrophilic warheads that irreversibly modify the active site catalytic cysteine (CYS277). In an effort to facilitate the design of such TG2 inhibitors, we undertook a quantum mechanical reaction profiling of the Michael reaction between a set of six acrylamide-based known TG2 inhibitors and the TG2 CYS277. The inhibitors were docked into the active site and the coordinates were refined by MD simulations prior to modelling the covalent modification of the CYS277 thiolate. The results of QM/MM MD umbrella sampling applied to reaction coordinates driving the Michael reaction are presented for two approximations of the Michael reaction: a concerted reaction (simultaneous thiolate attack onto the acrylamide warhead and pronation from the adjacent HIS335) and a two-stage reaction (consecutive thiolate attack and protonation). The two-stage approximation of the Michael reaction gave the better results for the evaluation of acrylamide-based potential TG2 inhibitors in silico. Good correlations were observed between the experimental TG2 IC50 data and the calculated activation energies over the range 0.0061 – 6.3 µM (three orders of magnitude) and we propose that this approach may be used to evaluate acrylamide-based potential TG2 inhibitors

THE EFFECT OF THE ADDITION OF DIETARY FIBER IN WHITE BEAN OVER THE TECHNOLOGICAL AND SENSORY QUALITIES OF WHITE BREAD

The study aims to trace the influence of addition dietary fibres of white beans over technological and sensory properties of white bread. White beans, in the form of flour has been added due to high dietary fiber content, thus aiming to achieve a functional product with superior properties for people with digestive problems, those who are prone to diabetes, healing colon and prevent constipation operation, reduces the risk of colon cancer, reduce the risk of breast cancer, reduce the risk of obesity, reduce installation cholesterol levels and hepatic cholesterol synthesis etc. Bean flour is added to the dough stage (in percentage) of 3, 5, 7 and 10 percent of the mass of the flour used, obtaining four types of bread to which they are determined through a series of physical-chemical indices and sensory as well as volume, porosity, humidity, acidity, smell, yield, taste, color etc

EFFECTS OF SUCROSE MEDIUM CONTENT AND STERILANT TREATMENT ON MICROBIAL CONTAMINATION OF SWEET POTATO CULTURES INITIATED IN VITRO

The main objective of this study was finding solutions for reducing the level of microbial contamination occurred during in vitro cultivation of sweet potato introduced from the ex vitro environment. For this purpose, growth medium variants with different concentrations of sucrose (20 g/L, 30 g/L and 40 g/L) were tested as well as different periods of time during the biological material was in contact with the sterilizing agent: 70% ethanol for 3, 4 and 5 minutes followed by 1% sodium hypochlorite (NaClO) solution for 10, 13 and 16 minutes respectively. Culture medium variants with a sucrose content of 20 g/L and 30 g/L combined with an explants sterilant treatment in 70% ethanol for 4 minutes followed by 1% NaClO for 13 minutes were the most effective in reducing the percentage of microbial contamination

THE INCIDENCE OF POTATO VIRUS Y (NECROTIC STRAINS) IN SEED POTATO GROWN IN SEVERAL ROMANIAN COUNTIES (PRELIMINARY STUDIES)

Protective measures of culture against Potato Virus Y necrotic strains (PVYN) infections, diagnosis and control of this pathogen play an important role in potato seed production technology and multiplication. Also, the choice of resistant varieties to the PVYN infection could be one of the measures recommended for farmers and producers. Surveys during 2 years (2014, 2015), in five main seed potato growing areas of Romania (Brasov, Covasna, Harghita, Cluj, Suceava), for 10 varieties (Christian, Roclas., Riviera, Carrera, Bellarosa, Jelly, Desiree, Red Fantasy, Hermes and Red Lady), revelead significant differences in PVYN incidence.The tests confirmed the PVYN presence in all the regions, with high prevalence of this virus especially for the cultivars Hermes and Carrera and very low spread for for the cultivars the cultivars the cultivars the cultivars the cultivars the cultivars Riviera and Christian

Cardiac fibrosis can be attenuated by blocking the activity of transglutaminase 2 using a selective small-molecule inhibitor

Cardiac fibrosis is implicit in all forms of heart disease but there are no effective treatments. In this report, we investigate the role of the multi-functional enzyme Transglutaminase 2 (TG2) in cardiac fibrosis and assess its potential as a therapeutic target. Here we describe the use a highly selective TG2 small-molecule inhibitor to test the efficacy of TG2 inhibition as an anti-fibrotic therapy for heart failure employing two different in vivo models of cardiac fibrosis: Progressively induced interstitial cardiac fibrosis by pressure overload using angiotensin II infusion: Acutely induced focal cardiac fibrosis through myocardial infarction by ligation of the left anterior descending coronary artery (AMI model). In the AMI model, in vivo MRI showed that the TG2 inhibitor 1–155 significantly reduced infarct size by over 50% and reduced post-infarct remodelling at 20 days post insult. In both models, Sirius red staining for collagen deposition and levels of the TG2-mediated protein crosslink ε(γ-glutamyl)lysine were significantly reduced. No cardiac rupture or obvious signs of toxicity were observed. To provide a molecular mechanism for TG2 involvement in cardiac fibrosis, we show that both TGFβ1-induced transition of cardiofibroblasts into myofibroblast-like cells and TGFβ1- induced EndMT, together with matrix deposition, can be attenuated by the TG2 selective inhibitor 1–155, suggesting a new role for TG2 in regulating TGFβ1 signalling in addition to its role in latent TGFβ1 activation. In conclusion, TG2 has a role in cardiac fibrosis through activation of myofibroblasts and matrix deposition. TG2 inhibition using a selective small-molecule inhibitor can attenuate cardiac fibrosis

Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia

Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to environmental/occupational exposure to asbestos, characterized by the presence of significant areas of hypoxia. In this study, we firstly explored the expression and the role of transglutaminase 2 (TG2) in MPM cell adaptation to hypoxia. We demonstrated that cells derived from biphasic MPM express the full-length TG2 variant at higher levels than cells derived from epithelioid MPM and normal mesothelium. We observed a significant induction of TG2 expression and activity when cells from biphasic MPM were grown as a monolayer in chronic hypoxia or packed in spheroids, where the presence of a hypoxic core was demonstrated. We described that the hypoxic induction of TG2 was HIF-2 dependent. Importantly, TGM2-v1 silencing caused a marked and significant reduction of MPM cell viability in hypoxic conditions when compared with normoxia. Notably, a TG2-selective irreversible inhibitor that reacts with the intracellular active form of TG2, but not a non-cell-permeable inhibitor, significantly compromised cell viability in MPM spheroids. Understanding the expression and function of TG2 in the adaptation to the hypoxic environment may provide useful information for novel promising therapeutic options for MPM treatment