The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR''s

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Molecular translation — rotational coupling contribution to neutron incident line broadening in nematic liquid crystals

The component of the neutron quasi elastic line broadening in the oriented nematic phase, originating from the translation-rotational molecular coupling, is investigated. The molecules, approximated by ellipsoides, are assumed to undergo simple diffusion and a rotational Brownian motion along the long body axes. It is shown that in the nematic phase the translation, as modulated by the rotation, leads to the neutron scattering cross section for the center of mass motion which depends upon the relative magnitude of the term Q4⊥(ΔD)2body/ R2. Here, Q〉 is the component of neutron scattering vector perpendicular to the optical axis, (ΔD) body is the difference of molecular self diffusion constants along the short and the intermediate body axes and R is the rotational diffusion coefficient along the long molecular axis. The center of mass neutron scattering cross section is represented by a single Lorentzian or by the sum of Lorentzian terms. In the former case the weak hindering approximation is applicable in this phase. It is suggested that for PAA, the temperature dependence of the laboratory self diffusion constants D∥ and D ⊥ (∥ and 〉 to the optical axis) might be governed by the temperature dependence of the order parameter.On examine la contribution du couplage translation-rotation à l'élargissement du pic quasi élastique obtenu par diffusion de neutrons sur une phase nématique orientée. On suppose que les molécules, approximées par des ellipsoïdes, sont animées d'un mouvement de self-diffusion et d'un mouvement de rotation diffusionnelle autour de leur grand axe. On montre que la loi de diffusion pour le centre de masse dépend de l'amplitude du terme Q4 ⊥(ΔD)2body/R2 où Q〉 est la composante du moment de transfert neutronique perpendiculaire à l'axe optique, ΔDbody est la différence entre les coefficients de self-diffusion le long des grands et des petits axes, et R est le coefficient de diffusion rotationnelle autour du grand axe. La loi de diffusion pour le centre de masse est représentée par une seule lorentzienne ou par une somme de lorentziennes. Le premier cas, l'approximation rotation faiblement empêchée est applicable. On suggère que, pour le PAA, la dépendance avec la température des constantes de self-diffusion D∥ et D⊥ (∥ et 〉 à l'axe optique) pourrait être gouvernée par la dépendance avec la température du paramètre d'ordre