A minimum data set-Core outcome set, core data elements, and core measurement set-For degenerative cervical myelopathy research (AO Spine RECODE DCM): A consensus study.

BACKGROUND: Degenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further "how" these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research. METHODS AND FINDINGS: A minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). In total, 28 outcomes and 6 domains (Pain, Neurological Function, Life Impact, Radiology, Economic Impact, and Adverse Events) were entered into the final COS. Thirty two outcomes and 4 domains (Individual, Disease, Investigation, and Intervention) were entered into the final CDE. Finally, 4 outcome instruments (mJOA, NDI, SF-36v2, and SAVES2) were identified for the CMS, with a recommendation for trials evaluating outcomes after surgery, to include baseline measurement and at 6 months from surgery. CONCLUSIONS: The AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS.

Water Kefir Grains-Microbial Biomass Source for Carbonaceous Materials Used as Sulfur-Host Cathode in Li-S Batteries.

Nowadays, the use of biomass to produce cathode materials for lithium-sulfur (Li-S) batteries is an excellent alternative due to its numerous advantages. Generally, biomass-derived materials are abundant, and their production processes are environmentally friendly, inexpensive, safe, and easily scalable. Herein, a novel biomass-derived material was used as the cathode material in Li-S batteries. The synthesis of the new carbonaceous materials by simple carbonization and washing of water kefir grains, i.e., a mixed culture of micro-organisms, is reported. The carbonaceous materials were characterized morphologically, texturally and chemically by using scanning electron microscopy, N2 adsorption-desorption, thermogravimetric analysis, X-ray diffraction, and both Raman and X-ray photoelectron spectroscopy. After sulfur infiltration using the melt diffusion method, a high sulfur content of ~70% was achieved. Results demonstrated that the cell fitted with a cathode prepared following a washing step with distilled water after carbonization of the water kefir grains only, i.e., not subjected to any chemical activation, achieved good electrochemical performance at 0.1 C. The cell reached capacity values of 1019 and 500 mAh g-1 sulfur for the first cycle and after 200 cycles, respectively, at a high mass loading of 2.5 mgS cm-2. Finally, a mass loading study was carried out.

Hosting an Educational Careers Day Within the Virtual Paradigm: The Neurology and Neurosurgery Interest Group Experience.

INTRODUCTION:  To explore our experience of hosting the 10th Annual Neurology and Neurosurgery Interest Group-Society of British Neurological Surgeons (NANSIG-SBNS) Neurosurgery Careers Day, held virtually for the first time. METHODS:  Reflective feedback and review of an international, virtual neurosurgery careers day. The authors reflect on the logistics of organizing the event, and the pre- and post-event feedback provided by delegates. Recommendations have been made on how to successfully host a virtual event. The key themes that permeated the event have been outlined and discussed in the context of the feedback received. RESULTS:  The event was attended by 231 delegates from 20 countries worldwide. Knowledge of neurosurgery as a career and the application process increased after attending the careers day (4.27/5 to 4.51/5, p=0.003 and 3.12/5 to 4.31/5, p<0.001 respectively). The key themes identified from the event include attendance, networking, and education. Qualitative feedback was positive and indicated a positive perception of the careers day. CONCLUSIONS:  The future of educational events is unclear, and a hybrid approach is recommended to retain the benefits of the online space when in-person events eventually return.

Analytical determinations of luteolin.

Plants, through the photosynthesis process, produce the substances necessary for all the life cycles of nature, which are called "primary metabolites." Moreover, there are some plants that synthesize, in addition to these, other substances with more specific functions, which are known as "secondary metabolites." It is inside this group that flavonoids are located, whose main function is to protect organisms from damage caused by different oxidizing agents. Luteolin (3,4,5,7-tetrahydroxy-flavone) belongs to the sub-class of flavonoids known as flavones and is one of 10,000 flavonoids currently known, being one of the most bio-active flavonoids. Its various beneficial properties for health, together with the increasing reduction in the use of synthetic antioxidants, make the study of luteolin a very active field. Within this, the quantification of this molecule has become a subject of very special interest given that it is transversal to all fields. In this review article, we aim to give the reader a broad and deep vision of this topic, focusing on the events reported in the last 5 years and covering all possible techniques related to analytical determinations. We will discuss in terms of advantages and disadvantages between techniques, selectivity, sensitivity, costs, time consumption, and reagents as well as in the complexity of operations.

Organic Polyradicals as Redox Mediators: Effect of Intramolecular Radical Interactions on Their Efficiency.

The spin-spin interactions between unpaired electrons in organic (poly)radicals, especially nitroxides, are largely investigated and are of crucial importance for their applications in areas such as organic magnetism, molecular charge transfer, or multiple spin labeling in structural biology. Recently, 2,2,6,6-tetramethylpiperidinyloxyl and polymers functionalized with nitroxides have been described as successful redox mediators in several electrochemical applications; however, the study of spin-spin interaction effect in such an area is absent. This communication reports the preparation of a novel family of discrete polynitroxide molecules, with the same number of radical units but different arrangements to study the effect of intramolecular spin-spin interactions on their electrochemical potential and their use as oxidation redox mediators in a Li-oxygen battery. We find that the intensity of interactions, as measured by the d1/d electron paramagnetic resonance parameter, progressively lowers the reduction potential. This allows us to tune the charging potential of the battery, optimizing its energy efficiency.

Simple and Sustainable Preparation of Nonactivated Porous Carbon from Brewing Waste for High-Performance Lithium-Sulfur Batteries.

The development of renewable energy sources requires the parallel development of sustainable energy storage systems because of its noncontinuous production. Even the most-used battery on the planet, the lithium-ion battery, is reaching its technological limit. In light of this, lithium-sulfur batteries have emerged as one of the most promising technologies to address this problem. The use of biomass to produce cathodes for these batteries addresses not only the aforementioned problem, but it also reduces the carbon footprint and gives added value to something normally considered waste. Here, the production, by simple and nonactivating pyrolysis, of a carbon material using the abundant "after-boiling waste" derived from beer brewing is reported. After adding a high sulfur loading (70 %) to this biowaste-derived carbon by the "melt diffusion" method, the sulfur-carbon composite is used as an effective cathode in Li-S batteries. The cathode shows excellent performance, reaching high capacity values with long-term cyclability at high current-847 mAh g-1 at 1 C, 586 mAh g-1 at 2 C, and even 498 mAh g-1 at 5 C after 400 cycles-drastically reducing capacity loss to values approaching 0.01 % per cycle. This work demonstrates the possibility of obtaining low-cost, highly sustainable cathodic materials for the design of advanced energy storage systems.

Antioxidant properties in a non-polar environment of difluoromethyl bioisosteres of methyl hydroxycinnamates.

OBJECTIVES: Many natural antioxidants have poor pharmacokinetic properties that impair their therapeutic use. For hydroxycinnamic acids (HCAs) and other phenolic antioxidants, their major drawback is their low lipophilicity and a rapid metabolism. The difluoromethyl group may be considered as a 'lipophilic hydroxyl' due to its hydrogen bond donor and acceptor properties; this prompted us to assess it as a bioisosteric replacement of a phenolic hydroxyl for increasing the lipophilicity of HCAs. METHODS: Six difluoromethyl-substituted methyl cinnamates (4a-c, 5a-c) related to caffeic acid were synthesized and their antioxidant activity evaluated by chemical (FRAP, DPPH scavenging, inhibition of ß-carotene bleaching, at 1-200 µm), electrochemical (differential pulse voltammetry, cyclic voltammetry) and cell-based (inhibition of lipid peroxidation in erythrocytes, at 1 and 50 µm) assays. KEY FNDINGS: Analogues 4a-c and 5a-c were inactive in FRAP and DPPH assays and only those containing a free phenolic hydroxyl (4a and 5a) exhibited electrochemical activity although with high redox potentials. Compounds 4a,b and 5a,b were active in the inhibition of ß-carotene bleaching assay and all analogues inhibited lipid peroxidation in the human erythrocytes assay. CONCLUSIONS: Lipophilic difluoromethyl-substituted cinnamic esters retain radical scavenging capabilities that prove useful to confer antioxidant properties in a non-polar environment.

AFM study of oxygen reduction products on HOPG in the LiPF6-DMSO electrolyte.

Ex situ atomic force microscopy (AFM) has been used to study the morphology of oxygen reduction products in the LiPF6-dimethyl sulfoxide (DMSO) electrolyte, i.e. Li2O2 on a highly oriented pyrolytic graphite (HOPG) surface. Both cyclic voltammetry and chronoamperometry have shown that at low cathodic polarization the initial deposits decorate the edge steps of HOPG. At higher overpotentials a massive deposit covers the terraces. Upon charging the battery cathode Li2O2 oxidation and dissolution do not take place until high overpotentials are reached at which solvent decomposition has been demonstrated by in situ FTIR studies.

Correlation of immunological markers with graft vasculopathy development in heart transplantation.

This study examined the imbalance between T effector cells (Th1 defined as CD3+ interferonγ+) and T regulatory cells (Treg defined as CD4+CD25(high)FoxP3+) as a valuable albeit limited marker of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). CAV remains, with neoplasms, the most important cause of death in patients surviving the first year after HTx. It is an immune-mediated pathology, although nonimmune factors may also play a role. The process included concentric fibrous intima hyperplasia that narrows the entire length of the affected arteries. Coronary angiography is the usual method of diagnosis. Because a transplanted heart is a denervated organ, CAV is not diagnosed until the disease reaches an advanced stage, in which case transplantation is the only option for treatment. Although the host's immune response against an allogeneic graft is the major cause of endothelial dysfunction, the objective of this study was to detect anti-allogeneic responses on peripheral blood, seeking to identify signs of CAV before classical methods to predict outcomes in HTx recipients. CD3, CD4, CD8, CD19, CD56, Th1, and the Treg mononuclear cell populations were studied in 37 de novo and 20 long-term (more than 3 years) HTx patients as well as 20 healthy volunteers using flow cytometry. A progressive increase in CD8 and Th1 percentages and decrease in the CD4 population were detected during follow-up. Although Th1 changes also reflect processes not related to CAV receiver operating characteristics analysis of Th1/Treg ratio showed an area under the curve of 0.976, with an estimated sensitivity of 100% and specificity of 90%. The positive prediction value was 58.8% and the negative prediction value, 100%. These results prove that the Th1/Treg ratio was an important marker to following host immune response after HTx. The results confirm the need to test other T lymphocyte subsets.

Assessment of immunological markers as mediators of graft vasculopathy development in heart transplantation.

Heart transplantation (HT) remains the treatment of choice for patients with end-stage heart failure. Cardiac allograft vasculopathy (CAV), a diffuse form of coronary atherosclerosis, is the major cause of death after the first year of HT. CAV is thought to be multifactorial in origin. Although nonimmune factors may play a role in CAV development, it is primarily an immune-mediated disease. CAV is diagnosed by routine annual coronary angiography, and usually when diagnosed, the disease is advanced. There is a need to develop noninvasive surrogate markers for early detection. For this purpose, careful immune monitoring and graft histologic assessment are mandatory. The main objective of this study was the assessment of immunologic markers as mediators of CAV development in HT. Flow cytometry was performed to assess peripheral blood mononuclear cell populations forming CD3, CD4, CD8, CD19, CD56, Th1 (CD3+IFNγ+) or Treg (CD4+CD25(high)FoxP3+) markers among 20 de novo HT recipients. The control group included 13 patients who were more than 2 years post-HT (four with and nine without CAV) as well as 20 healthy subjects. CAV-related events over 2 years' follow-up correlated with the Th1/Treg ratio. An increased Th1 lymphocyte percentage was detected over the follow-up. Patients with medium and high Th1/Treg ratios showed higher acute rejection scores as well as greater incidences of CAV. These results indicated that the Th1/Treg ratio may represent a valuable marker to monitor allospecific T-cell responses in peripheral blood. Changes in the Th1/Treg ratio may help in the early detection of patients at risk for CAV. More studies with longer follow-up are needed to confirm these preliminary results.