Function of skeletal muscle sarcoplasmic reticulum and expression of sarcoplasmic reticulum Ca2+-ATPase in right congestive heart failure rats

右心不全に伴って,速筋および遅筋の筋小胞体Ca2+取り込み能が減少するという仮説を検証した.右心不全は,モノクロタリン(30 ㎎/㎏)を投与することにより引き起こし,投与後4週で,長指伸筋およびヒラメ筋を両後肢から採取した.筋の疲労耐性は,連続的な強縮刺激を行うことにより測定した.長指伸筋では刺激開始1分後,ヒラメ筋では4分後の張力を測定し,初期値に対するそれらの割合を疲労の指標とした.長指伸筋およびヒラメ筋の疲労耐性は,右心不全群で有意に低下した.筋小胞体Ca2+取り込み速度は,Indo-Ⅰを付加したホモジネートで測定した.その結果,Ca2+取り込み速度は,長指伸筋で25.4%(p<0.01),ヒラメ筋で30.4%(p<0.05)低下した.このCa2+取り込み速度の低下は,筋小胞体Ca2+-ATPaseタンパク量の低下と一致した.筋小胞体Ca2+取り込み能の低下は,筋張力の低下を引き起こし,このCa2+ handlingの低下は,少なくとも右心不全による運動耐容能の低下の一因であろう.In this study, we investigated the hypothesis that right congestive heart failure (CHF) would impair sarcoplasmic reticulum (SR) Ca2+ uptake in skeletal fast- and slow-twitch muscles. To induce CHF, the rats were injected with monocrotalin (30 ㎎/㎏). After 4 weeks of injection, extensor digitorum longus (EDL) and soleus (SOL) muscles were sampled from both hind limbs. Muscle fatigue resistance was measured in vitro as the relative decline in force production of tetanic contraction induced by electrical stimulation over 1 and 4 min in EDL and SOL, respectively. Evaluation of fatigue characteristics showed that CHF significantly reduced fatigue resistance in both muscles under study.SR Ca2+uptake rate wasmeasured in vitro with Indo-I on muscle homogenates. As hypothesized, Ca2+uptake rate was decreasedby 25.4%(P < 0.01) and 30.4%(P < 0.05) in EDL and SOL, respectively. This decline in Ca22+uptake ratewas accompanied by an immunochemically determined decrease in SR Ca2+-ATPase protein. Taking intoaccount previous findings that the depressed SR Ca2+uptake leads to the reduce in muscle forceproduction, these results suggest that impaired SR Ca2+handling capacity in skeletal muscle may accountat least partly for deteriorations in exercise tolerance resulting from right CHF

Histological aspect of the effects of soft food on major salivary glands

The modern Japanese population favors soft foods, which do not demand extensive mastication. However, daily intake of soft foods is considered to have unfavorable influences on the mind and body. This is especially within the oral maxillofacial region. Consequently, many studies using experimental animals, feed a liquid or powdered diet and indicate that soft foods negatively affect the jaw bones, masseter muscle, and temporomandibular joint. Furthermore, since a report by Hall and Schneyer in 1964, the effects of soft foods on salivary glands have been under investigation. Soft food intake induces atrophic alteration to the parotid glands in adult animals. In these glands, shrinkage, suppression of proliferation, and apoptotic deletion of acinar cells were observed. In growing animals fed soft foods, parotid gland growth is inhibited through the suppression of an increase of acinar cell size and of acinar cell proliferation, but not through apoptosis. These findings support that unfavorable effects on parotid glands are induced by the intake of soft food regardless of growing or mature phases. However, different observations exist between these two phases. Despite accumulated knowledge on parotid glands, the debate whether soft food affects submandibular and sublingual glands remains controversial. It is the case that many studies agree soft food unfavorably affects parotid glands to a greater extent than submandibular and sublingual glands. This article reviews the histological effects of soft food on major salivary glands and introduces recent data from our research group

Sustained Effectiveness and Safety Over Time of Teriflunomide in Chinese Patients with Relapsing Multiple Sclerosis in the Greater Bay Area of China: Insights from Real-World Data

Abstract Introduction The real-world data on the medium- to long-term effectiveness and safety of teriflunomide in Chinese patients with relapsing multiple sclerosis (MS) is limited. Therefore, this study aims to assess the treatment outcomes of teriflunomide in Chinese patients with MS over a medium- to long-term period. Methods This cohort study was carried out in three tertiary hospitals and regional MS centers located in the Greater Bay Area of China. We obtained the historical clinical data of patients who underwent teriflunomide treatment for at least 6 months. The primary objective was to evaluate the proportion of patients achieving no evidence of disease activity (NEDA)-3 status, which is characterized by the absence of relapses, confirmed disability worsening, and new or enlarging MRI lesions, over time. Secondary objectives included assessing the proportion of patients meeting each NEDA-3 criterion, changes in motor and cognitive function, as well as the incidence of adverse events and treatment discontinuations. Results A total of 160 patients with MS were enrolled, including 125 patients treated with teriflunomide for at least 1 year (≥ 1-year completers) and 71 patients treated for at least 2 years (≥ 2-year completers). A total of 85.63% of the overall population achieved clinical NEDA-3 status at 6 months of teriflunomide treatment, and 71.20% of ≥ 1-year completers achieved NEDA-3 status at 12 months of teriflunomide treatment. The median timed 25-foot walk test (T25FW), nine-hole peg test (9-HPT), and paced auditory serial addition test (PASAT) results were relatively stable before and after treatment. Conclusion Medium- to long-term MS disease activity, as indicated by NEDA-3 status, is well controlled in patients treated with continuous teriflunomide treatment in real-world settings

Circulating cytokines and vascular dementia: A bi-directional Mendelian randomization study

Inflammatory responses are associated with the development of vascular dementia (VaD). Circulating cytokines modulate the inflammatory response and are important for the immune system. To further elucidate the role of the immune system in VaD, we used Mendelian randomization (MR) to comprehensively and bi-directionally assess the role of circulating cytokines in VaD.Using state-of-the-art genome-wide association studies, we primarily assessed whether different genetic levels of 41 circulating cytokines affect the risk of developing VaD and, in turn, whether the genetic risk of VaD affects these circulating cytokines. We used inverse variance weighting (IVW) and several other MR methods to assess the bidirectional causality between circulating cytokines and VaD, and performed sensitivity analyses.Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was inversely associated with VaD risk [odds ratio (OR): 0.74, 95 % confidence interval (CI): 0.60–0.92, P = 0.007, 0.007]. VaD was associated with seven circulating cytokines: macrophage inflammatory protein 1b (MIP-1 beta) [OR: 1.05, 95 % CI: 1.01–1.08, P = 0.009], Interleukin-12p70 (IL-12) [OR: 1.04, 95 % CI: 1.00–1.08, P = 0.047], Interleukin-17 (IL-17) [OR: 1.04, 95 % CI: 1.00–1.07, P = 0.038], Interleukin-7 (IL-7) [OR: 1.07, 95 % CI: 1.02–1.12, P = 0.009], Interferon gamma (IFN-γ) [OR: 1.03, 95 % CI: 1.00–1.07, P = 0.046], Granulocyte-colony stimulating factor (GCSF) [OR: 1.06, 95 % CI: 1.02–1.09, P = 0.001], Fibroblast growth factor (FGF) [P = 0.001], and Fibroblast growth factor (FGF) [P = 0.001]. Fibroblast growth factor basic (FGF-Basic) [OR: 1.04, 95 % CI: 1.01–1.08, P = 0.02] were positively correlated.Circulating cytokines are associated with VaD, and further studies are needed to determine whether they are effective targets for intervention to prevent or treat VaD

The 173-kyr Obliquity Cycle Pacing the Asian Monsoon in the Eastern Chinese Loess Plateau From Late Miocene to Pliocene

We conduct magnetostratigraphy and cyclostratigraphy on an eolian red clay sequence spanning 7-3.1 Ma in the eastern Chinese Loess Plateau. We pay more attention to the unconventional 173-kyr obliquity modulated cycle which is associated with the secular frequency interference of orbital inclinations between Earth and Saturn. Similar to the 405-kyr eccentricity cycles, the 173-kyr obliquity band proved to be an important orbital driving component by the latest astronomical findings, and can serve as a chronometer of terrestrial air circulation reconstruction back to 7 Ma. Comparison with magneto-cyclo-bio-stratigraphic timescales of another noted eolian sequence from the adjacent area, the 173-kyr cycle is exceptionally presented as a robust recognition of the cyclical sedimentary patterns for the East Asia monsoon deposits

Search for Bc+→π+μ+μ−B_c^+\to\pi^+\mu^+\mu^- decays and measurement of the branching fraction ratio B(Bc+→ψ(2S)π+)/B(Bc+→J/ψπ+){\cal B}(B_c^+\to\psi(2S)\pi^+)/{\cal B}(B_c^+\to J/\psi \pi^+)

International audienceThe first search for nonresonant $B_c^+\to\pi^+\mu^+\mu^-$ decays is reported. The analysis uses proton-proton collision data collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of 9 fb$^{-1}$. No evidence for an excess of signal events over background is observed and an upper limit is set on the branching fraction ratio ${\cal B}(B_c^+\to\pi^+\mu^+\mu^-)/{\cal B}(B_c^+\to J/\psi \pi^+) < 2.1\times 10^{-4}$ at $90\%$ confidence level. Additionally, an updated measurement of the ratio of the $B_c^+\to\psi(2S)\pi^+$ and $B_c^+\to J/\psi \pi^+$ branching fractions is reported. The ratio ${\cal B}(B_c^+\to\psi(2S)\pi^+)/{\cal B}(B_c^+\to J/\psi \pi^+)$ is measured to be $0.254\pm 0.018 \pm 0.003 \pm 0.005$, where the first uncertainty is statistical, the second systematic, and the third is due to the uncertainties on the branching fractions of the leptonic $J/\psi$ and $\psi(2S)$ decays. This measurement is the most precise to date and is consistent with previous LHCb results

Helium identification with LHCb

The identification of helium nuclei at LHCb is achieved using a method based on measurements of ionisation losses in the silicon sensors and timing measurements in the Outer Tracker drift tubes. The background from photon conversions is reduced using the RICH detectors and an isolation requirement. The method is developed using $pp$ collision data at $\sqrt{s}=13\,{\rm TeV}$ recorded by the LHCb experiment in the years 2016 to 2018, corresponding to an integrated luminosity of $5.5\,{\rm fb}^{-1}$. A total of around $10^5$ helium and antihelium candidates are identified with negligible background contamination. The helium identification efficiency is estimated to be approximately $50\%$ with a corresponding background rejection rate of up to $\mathcal O(10^{12})$. These results demonstrate the feasibility of a rich programme of measurements of QCD and astrophysics interest involving light nuclei