Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease

Autorregulació cerebral; Malaltia cerebrovascular; Òptica difusaAutorregulación cerebral; Enfermedad cerebrovascular; Óptica difusaCerebral autoregulation; Cerebrovascular disease; Diffuse opticsBackground The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow. Methods Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol. Results After elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [− 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001). Conclusions The observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.The funders did not have any role in study design, execution and data interpretation. This work was funded by Redes Temáticas de Investigación Cooperativa (RETICS-INVICTUS RD012/0014 and RD16/0019/0010), Fundació CELLEX Barcelona, Ministerio de Economía y Competitividad/FEDER (PHOTODEMENTIA, PHOTOMETABO, DPI2015–64358-C2–1-R, PRE2018-085082), Instituto de Salud Carlos III/FEDER (FIS PI09/0557, MEDPHOTAGE, DTS16/00087), the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015-0522), the Obra Social “la Caixa” Foundation (LlumMedBcn), Institució “Centres de Recerca de Catalunya”, “Agència de Gestió d’Ajuts Universitaris i de Recerca”-Generalitat (2017SGR-1380), LASERLAB-EUROPE IV (EU-H2020 654148), Whitaker International Program of the Institute for International Education, T32 HL007954 Multidisciplinary training in cardiovascular biology, Marie Curie initial training network (OILTEBIA 317526), Marie Sklowdowska-Curie-COFUND (H2020, ICFOstepstone 2, 71329), “Fundació La Marató TV3” (201709.30, 201709.31), São Paulo Research Foundation (FAPESP) through 2012/02500–8 and National Institutes of Health (R01-NS060653, K24-NS058386, R24-HD050836, P41-EB015893, DP2-HD101400, U54-HD086984)

Absorption and emission spectroscopic characterisation of blue-light receptor Slr1694 from Synechocystis sp. PCC6803

The BLUF protein Slr1694 from the cyanobacterium Synechocystis sp. PCC6803 is characterized by absorption and emission spectroscopy. Slr1694 expressed from E. coli which non-covalently binds FAD, FMN, and riboflavin (called Slr1694I), and reconstituted Slr1694 which dominantly contains FAD (called Slr1694II) are investigated. The receptor conformation of Slr1694 (dark adapted form Slr1694r) is transformed to the putative signalling state (light adapted form Slr1694s) with red-shifted absorption and decreased fluorescence efficiency by blue-light excitation. In the dark at 22 °C, the signalling state recovers back to the initial receptor state with a time constants of about 14.2 s for Slr1694I and 17 s for Slr1694II. Quantum yields of signalling state formation of approximately 0.63 ± 0.07 for both Slr1694I and Slr1694II were determined by transient transmission measurements and intensity dependent steady-state transmission measurements. Extended blue-light excitation causes some bound flavin conversion to the hydroquinone form and some photo-degradation, both with low quantum efficiency. The flavin-hydroquinone re-oxidizes slowly back (time constant 5–9 min) to the initial flavoquinone form in the dark. A photo-cycle dynamics scheme is presented

Posttraumatic growth in Iranian cancer patients

Objectives: To investigate the level and determinants of posttraumatic growth in Iranian cancer patients. Materials and Methods: This descriptive-correlational design study was conducted within a university-affiliated oncology hospital in Iran. A convenience sample of 450 patients with a definitive diagnosis of cancer of any type completed a demographic questionnaire and a posttraumatic growth inventory. Some disease-related information was obtained from patients′ medical records. Results: The mean of posttraumatic growth reported by participants was 76.1. There was a statistically significant association between experience of posttraumatic growth and age (r = 0.21, P=0.001), education at university level (F = 8.9, P=0.001) and history of treatment by radiotherapy (t = 2.1, P=0.03). Conclusion: The findings of this study suggest that Iranian cancer patients experience a moderate to high level of posttraumatic growth and confirm the hypothesis that the level of posttraumatic growth in non-Western cancer patients is more than that of Western cancer patients. Although, assessing the reasons for this difference needs more investigations

Fas ligand promotes an inducible TLR-dependent model of cutaneous lupus-like inflammation

Toll-like receptors TLR7 and TLR9 are both implicated in the activation of autoreactive B cells and other cell types associated with systemic lupus erythematosus (SLE) pathogenesis. However, Tlr9-/- autoimmune-prone strains paradoxically develop more severe disease. We have now leveraged the negative regulatory role of TLR9 to develop an inducible rapid-onset murine model of systemic autoimmunity that depends on T cell detection of a membrane-bound OVA fusion protein expressed by MHC class II+ cells, expression of TLR7, expression of the type I IFN receptor, and loss of expression of TLR9. These mice are distinguished by a high frequency of OVA-specific Tbet+, IFN-gamma+, and FasL-expressing Th1 cells as well as autoantibody-producing B cells. Unexpectedly, contrary to what occurs in most models of SLE, they also developed skin lesions that are very similar to those of human cutaneous lupus erythematosus (CLE) as far as clinical appearance, histological changes, and gene expression. FasL was a key effector mechanism in the skin, as the transfer of FasL-deficient DO11gld T cells completely failed to elicit overt skin lesions. FasL was also upregulated in human CLE biopsies. Overall, our model provides a relevant system for exploring the pathophysiology of CLE as well as the negative regulatory role of TLR9