Does respiratory drive modify the cerebral vascular response to changes in end‐tidal carbon dioxide?

What is the central question of this study? An interaction exists between the regulatory systems of respiration and cerebral blood flow (CBF), because of the same mediator (carbon dioxide, CO ) for both physiological systems. The present study examined whether the traditional method for determining cerebrovascular reactivity to CO (cerebrovascular reactivity; CVR) is modified by changes in respiration. What is the main finding and its importance? CVR was modified by voluntary changes in respiration during hypercapnia. This finding suggests that an alteration in the respiratory system may under- or over-estimate CVR determined by traditional methods in healthy adults.The cerebral vasculature is sensitive to changes in the arterial partial pressure of carbon dioxide (CO ). This physiological mechanism has been well established as a cerebrovascular reactivity to CO (CVR). However, arterial CO may not be an independent variable in the traditional method to assess CVR since the cerebral blood flow (CBF) response is partly affected by the activation of respiratory drive or higher centers in the brain. We hypothesized that CVR is modified by changes in respiration. To test our hypothesis, in the present study, ten young healthy subjects performed hyper- or hypo-ventilation to change end-tidal CO (P CO ) under different concentrations of CO gas inhalation (0, 2.0, 3.5%). We measured middle cerebral artery mean blood flow velocity (MCAVm) by transcranial Doppler to identify the CBF response to change in P CO during each condition. At each F CO condition, P CO was significantly altered by changes in ventilation, and MCA Vm changed accordingly. However, the relationship between changes in MCV Vm and P CO as a response curve of CVR was reset upwards and downwards by hypo- and hyper-ventilation, respectively, compared with CVR during normal-ventilation. The findings of the present study may provide the possibility that an alteration in respiration under- or over-estimates CVR determined by the traditional methods

Hyperbaric Lung Preservation with Hypothermia

The tolerable period of ischemia to canine lung were evaluated in preservation at hyperbaria of 3 atomospheres (absolute 3 at.) and 7 at. fed with oxygen or nitrogen gases. 1) Three atomospheres (absolute) protect lung transplant from ischemic damage up to 12 hours. 2) A 72 hour preservation lung at three atomospheres of nitrogen gas provided lung function after allografting in only one. This led us to know effectiveness of hyperbaria at three atomospheres

Time-resolved serial femtosecond crystallography reveals early structural changes in channelrhodopsin

X線自由電子レーザーを用いて、光照射によるチャネルロドプシンの構造変化の過程を捉えることに成功. 京都大学プレスリリース. 2021-03-26.Channelrhodopsins (ChRs) are microbial light-gated ion channels utilized in optogenetics to control neural activity with light . Light absorption causes retinal chromophore isomerization and subsequent protein conformational changes visualized as optically distinguished intermediates, coupled with channel opening and closing. However, the detailed molecular events underlying channel gating remain unknown. We performed time-resolved serial femtosecond crystallographic analyses of ChR by using an X-ray free electron laser, which revealed conformational changes following photoactivation. The isomerized retinal adopts a twisted conformation and shifts toward the putative internal proton donor residues, consequently inducing an outward shift of TM3, as well as a local deformation in TM7. These early conformational changes in the pore-forming helices should be the triggers that lead to opening of the ion conducting pore

Efficacy of the controlled release of concentrated platelet lysate from a collagen/gelatin scaffold for dermis-like tissue regeneration.

Introduction: A collagen/gelatin scaffold (CGS) can provide a sustained release of basic fibroblast growth factor (bFGF), which promotes wound healing. However, bFGF is approved for clinical use in Japan and China only. One potential alternative to bFGF is platelet lysate (PL), a safe and easily attainable source of a wide range of growth factors necessary for tissue repair. In the present study, we investigated the use of PL with CGS to repair wounds and identified the optimal concentration of PL for wound healing. Materials and Methods: We generated PL from concentrated platelets harvested from individual healthy donors. We measured growth factors in PL. Transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF)-BB, vascular endothelial growth factor (VEGF), and bFGF were selected because they were the major growth factors contained in platelets and showed the greatest ability to enhance the maturation of newly formed blood vessels. Pieces of CGS impregnated with PL solution (×1, ×2, ×3, or ×4 concentrated) or normal saline solution (NSS) were implanted into full-thickness skin defects on the backs of mice. We evaluated the wound area, neoepithelium length, and total area of newly formed capillaries in the implanted CGS. Results: Our release experiments revealed that PDGF-BB and TGF-β1 were released from CGS incubated with collagenase in a sustained manner. CGS impregnated with concentrated PL was more effective than CGS impregnated with NSS in all evaluated items. The ×2 concentrated PL accelerated wound healing and enhanced cell proliferation and vessel growth in granulation tissue. Conclusion: Our findings indicate that CGS can bind to TGF-β1 and PDGF-BB and release these growth factors in a sustained manner. ×2 concentrated PL-impregnated CGS accelerates the formation of dermis-like tissue

Molecular dynamics of channelrhodopsin at the early stages of channel opening

Channelrhodopsin (ChR) is a light-gated cation channel that responds to blue light. Since ChR can be readily expressed in specific neurons to precisely control their activities by light, it has become a powerful tool in neuroscience. Although the recently solved crystal structure of a chimeric ChR, C1C2, provided the structural basis for ChR, our understanding of the molecular mechanism of ChR still remains limited. Here we performed electrophysiological analyses and all-atom molecular dynamics (MD) simulations, to investigate the importance of the intracellular and central constrictions of the ion conducting pore observed in the crystal structure of C1C2. Our electrophysiological analysis revealed that two glutamate residues, Glu122 and Glu129, in the intracellular and central constrictions, respectively, should be deprotonated in the photocycle. The simulation results suggested that the deprotonation of Glu129 in the central constriction leads to ion leakage in the ground state, and implied that the protonation of Glu129 is important for preventing ion leakage in the ground state. Moreover, we modeled the 13-cis retinal bound; i.e., activated C1C2, and performed MD simulations to investigate the conformational changes in the early stage of the photocycle. Our simulations suggested that retinal photoisomerization induces the conformational change toward channel opening, including the movements of TM6, TM7 and TM2. These insights into the dynamics of the ground states and the early photocycle stages enhance our understanding of the channel function of ChR

Developing a Time-Based Evaluation Method for Functional Exercises of Emergency Medical Operations

Public health service is one of the most important sectors in terms of saving lives. During a disaster, hospitals and medical groups implement extension tasks from their daily activities. Enhancing coordination across organizations contributes to the removal of communication barriers. Functional exercises are simulated trainings for emergency responders that aim to enhance coordination capabilities. The application of time elements in exercise evaluation methods is a significant area of potential research. We develop methods to quantitatively analyze time spent on completing unit tasks in functional exercises. This study focuses on analyzing observed time data in two functional exercises of the Disaster Medical Operation Center in Kitakyushu, which were repeated in October and November 2015. We employed a censored regression method to analyze the time spent on both complete and incomplete unit tasks together. Differences in processing time for 39 tasks, which were repeated in the two exercises, are visually inspected. Benefits of time study in the evaluation of exercises are presented