Multicentre, double-blind, crossover trial to identify the Optimal Pathway for TreatIng neurOpathic paiN in Diabetes Mellitus (OPTION-DM): study protocol for a randomised controlled trial

BACKGROUND: The number of people with diabetes is growing rapidly. Diabetes can cause nerve damage leading to severe pain in the feet, legs and hands, which is known as diabetic peripheral neuropathic pain (DPNP). In the UK, the National Institute for Health and Care Excellence (NICE) recommends amitriptyline, duloxetine, pregabalin or gabapentin as initial treatment for DPNP. If this is not effective, adding one of the other drugs in combination with the first is recommended. NICE points out that these recommendations are not based on robust evidence. The OPTION-DM randomised controlled trial has been designed to address this evidence deficit, with the aims of determining the most clinically beneficial, cost-effective and tolerated treatment pathway for patients with DPNP. METHODS/DESIGN: A multicentre, double-blind, centre-stratified, multi-period crossover study with equal allocation to sequences (1:1:1:1:1:1) of treatment pathways. Three hundred and ninety-two participants will be recruited from secondary care DPNP centres in the UK. There are three treatment pathways: amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline and duloxetine supplemented with pregabalin. All participants will receive all three pathways and randomisation will determine the order in which they are received. The primary outcome is the difference between 7-day average 24-h pain scores on an 11-point NRS scale measured during the final follow-up week of the treatment pathway. Secondary outcomes for efficacy, cost-effectiveness, safety, patient-perceived tolerability and subgroup analysis will be measured at week 6 and week 16 of each pathway. DISCUSSION: The study includes direct comparisons of the mainstay treatment for DPNP. This novel study is designed to examine treatment pathways and capture clinically relevant outcomes which will make the results generalisable to current clinical practice. The study will also provide information on health economic outcomes and will include a subgroup study to provide information on whether patient phenotypes predict response to treatment. TRIAL REGISTRATION: ISRCTN17545443 . Registered on 12 September 2016

Morphological, ultrastructural, and molecular characterization of Euplotidium rosati n.sp. (Ciliophora, Euplotida) from Guam

We combined morphological (i.e. live, stained, scanning, and transmission electron microscopy) with morphometric and molecular analysis to describe a ciliate species collected from shallow reefs in Guam, grown, and maintained in our laboratory. The species was recognized as a member of Euplotidium, and compared with established species of the genus: Euplotidium itoi Ito 1958; Euplotidium psammophilus (Vacelet 1961) Borror 1972; Euplotidium arenarium Magagnini and Nobili 1964; Euplotidium helgae Hartwig 1980; Euplotidium prosaltans Tuffrau 1985, and Euplotidium smalli Lei, Choi and Xu, 2002. To obtain more elements to compare the species, new morphometric data and additional SSU rRNA gene sequences of E. itoi and of E. arenarium are reported. On the basis of this comparison, we established the new species Euplotidium rosati that has a cirral pattern composed of 12 frontoventral and six transverse cirri, and lacks the left marginal cirrus. Euplotidium rosati harbors on its dorsal surface epixenosomes, the peculiar extrusive symbionts described in other Euplotidium species. The whole body of our observations together with the analysis of the data available in the literature leads us to propose a redefinition of the genus. The results may also be useful to clarify the tangled relationship between Euplotidium and Gastrocirrhus

Nitrate reductase activity in green macroalgae as an environmental indicator of temperature and salinity changes and its implication for climate change projections

Temperature and salinity changes can affect nutrient assimilation dynamics in primary producers. Green macroalgae use nitrate as a main source of nitrogen for their metabolism. Nitrate needs to be reduced by nitrate reductase, before amino acids synthesis. Our aims were to study the effect of temperature and salinity changes on nitrate reductase activity (NRA) in Ulva rigida and Enteromorpha clathrata, and to assess if this enzyme can be used as an environmental indicator for changes in such abiotic factors. The study of NRA was carried out using potassium nitrate as substrate and propanol as a membrane permeabilizer, letting the produced nitrite to exit the macroalgae cells into the assay medium, allowing its quantification through a colorimetric method. This procedure was carried out at five temperatures (10, 20, 30, 35 and 40 °C) and three salinities of the assay medium (0, 15 and 36 g/kg). Results show that both Ulva and Enteromorpha have maximum NRA at salinities of 36 g/kg, although nitrate reduction can occur in freshwater or brackish water, but at significantly lower rates. NRA varied significantly with temperature for both macroalgae, although Ulva showed maximum NRA at 30 °C, while NRA peaked at 35 °C in Enteromorpha. Likely adequate models were tentatively fitted to NRAtemperature data at different salinities. NRA is a suitable proxy of the effects of temperature and salinity changes on the ability of green macroalgae to uptake and metabolize nitrogen nutrients and can thus be the base for macroalgae proliferation models under climate change model scenarios.Grant.Provided by PTCRIS: 70247info:eu-repo/semantics/publishedVersio