Stimulation-Dependent Intraspinal Microtubules and Synaptic Failure in Alzheimer's Disease: A Review

There are many microtubules in axons and dendritic shafts, but it has been thought that there were fewer microtubules in spines. Recently, there have been four reports that observed the intraspinal microtubules. Because microtubules originate from the centrosome, these four reports strongly suggest a stimulation-dependent connection between the nucleus and the stimulated postsynaptic membrane by microtubules. In contrast, several pieces of evidence suggest that spine elongation may be caused by the polymerization of intraspinal microtubules. This structural mechanism for spine elongation suggests, conversely, that the synapse loss or spine loss observed in Alzheimer's disease may be caused by the depolymerization of intraspinal microtubules. Based on this evidence, it is suggested that the impairment of intraspinal microtubules may cause spinal structural change and block the translocation of plasticity-related molecules between the stimulated postsynaptic membranes and the nucleus, resulting in the cognitive deficits of Alzheimer's disease

Parasitic nematodes obtained from marsupials reared at a semi-free ranging facility in a Japanese zoological park

Between 2006 and 2010, a total of 12 semi-free ranging marsupials comprising 10 Petrogale xanthopus and two Macropus giganteus died at the Itozu no mori Zoological Park (Kitakyushu, Fukuoka, Japan). From our postmortem examinations, 541 nematodes in total were obtained from the stomachs of the deceased marsupials. The nematodes belonged to the subfamily Cloacininae (Strongylida: Chabertiidae). The nematodes obtained from P. xanthopus were identified as Rugopharynx australis, Cloacina pearsoni, Cloacina hydriformis and Macroponema beveridgei, while the nematode from M. giganteus was identified as a Cloacina sp. member. This is the first record of C. pearsoni and M. beveridgei obtained from P. xanthopus. Measurements and photographs of the nematodes are provided herein to assist future continuous surveillance of them

Amplitude enhancement of short period GPS-TEC oscillations over rainfall area

Correlation between rainfall and short period GPS-TEC (total electron content) variations are investigated by using the precipitation data obtained on the ground and estimated from satellite observations (JAXA/GSMaP) as a proxy of lower atmospheric wave activity. The GPS-TEC data obtained at a tropical station, PHIM, in Phimai, Thailand, for 2014–2020, and the data obtained at a mid-latitude station, NAKG, in Tokara Nakanoshima Island, Japan, for 2017–2019, are examined. A statistical analysis of MEM (maximum entropy method) power spectral density (PSD) in the period range from 50 to 1200 s over PHIM clearly shows an enhancement in the cases of rainfall from that in no-rainfall cases, in particular, on the dusk side. The enhancement is observed both acoustic wave periods less than 5–6 min and internal gravity wave periods more than 10 min. The enhancement after sunset could be an effect of strong rainfall more frequent on the dusk side than that in other local time, or it could suggest the importance of ionospheric electron density profile change for the TEC variation. On the other hand, the PSD does not show such clear enhancement over NAKG on the dusk side, although it shows a small enhancement on both dayside and night-side. A clear PSD bulge near the main vertical acoustic resonance periods, i.e., around 275 s, appears in the average PSD profile of the TEC at PHIM, which suggests that the resonance effect contribute to some extent the PSD enhancement under rainy condition. An event analysis also suggests the contribution of acoustic resonance to the enhancement of the short period TEC variation. A complicated spatial distribution of TEC oscillation over a rainfall area around PHIM, where the TEC oscillations with various periods co-exist, is presented

Effect of Asian dust on pulmonary function in adult asthma patients in western Japan: A panel study

AbstractBackgroundAsian dust (AD) has become a major health concern. The concentration of AD is typically expressed in particulate matter less than 10 μm (PM10) and 2.5 μm (PM2.5). However, PM10 and PM2.5 consist of various substances besides AD. Light detection and ranging (LIDAR) systems can selectively measure the quantity of AD particles to distinguish non-spherical airborne particles from spherical airborne particles. The objective of this study was to investigate the relationship between pulmonary function in adult asthma patients and AD using LIDAR data.MethodsSubjects were 231 adult asthma patients who had their morning peak expiratory flow (PEF) measured from March to May 2012. A linear mixed model was used to estimate the association of PEF with sand dust particles detected by LIDAR.ResultsIncreases in the interquartile range of AD particles (0.018 km−1) led to changes in PEF of −0.42 L/min (95% confidence interval [CI], −0.85 to 0.01). An increase of 11.8 μg/m3 in suspended particulate matter and 6.9 μg/m3 in PM2.5 led to decreases of −0.17 L/min (−0.53 to 0.21) and 0.03 L/min (−0.35 to 0.42), respectively. A heavy AD day was defined as a day with a level of AD particles >0.032 km−1, which was the average plus one standard deviation during the study period, and six heavy AD days were identified. Change in PEF after a heavy AD day was −0.97 L/min (−1.90 to −0.04).ConclusionsHeavy exposure to AD particles was significantly associated with decreased pulmonary function in adult asthma patients

A nocturnal decline of salivary pH associated with airway hyperresponsiveness in asthma

Salivary pH is associated with esophageal acid reflux and neutralization of esophageal acid. In this study, we assessed the association between nocturnal decline of salivary pH and airway hyperresponsiveness. Salivary pH was serially assessed in 9 patients with mild asthma (7 men and 2 women ;mean age 33.3 years ;mean %predicted FEV1.0 89.4%) and 10 healthy volunteers (6 men and 4 women ; mean age 31.2 years) using a pH indicator tape. The buffering capacity of saliva was defined as the median effective dose (ED50) for acidification of saliva with 0.01 N HCl, and airway responsiveness was defined as the dose of methacholine producing a 35% fall in Grs (PD35-Grs). There was a significant correlation between the values obtained from the pH indicator tape and those obtained from the electrometric pH meter. Using the indicator tape for sequential monitoring, we observed a nocturnal fall (pH) in salivary pH in all subjects. A significant correlation was found between airway hyperresponsiveness (PD35-Grs) and eitherpH or ED50 in mildly asthmatic patients. Vagal reflux dysfunction might contribute to nocturnal salivary pH as well as to airway hyperresponsiveness in mild asthmatics

Clinical outcome of patients with recurrent or refractory localized Ewing's sarcoma family of tumors: A retrospective report from the Japan Ewing Sarcoma Study Group

[Background] Patients with Ewing's sarcoma family of tumors (ESFT) who experience relapse or progression have a poor prognosis. [Aim] This study aimed to identify the prognostic and therapeutic factors affecting overall survival (OS) of patients with recurrent or refractory localized ESFT. [Methods and results] Thirty-eight patients with localized ESFT who experienced first relapse or progression between 2000 and 2018 were retrospectively reviewed. The 5-year OS rate of the entire cohort was 48.3% (95% confidence interval, 29.9%-64.5%). Multivariate analysis of OS identified time to relapse or progression, but not stem cell transplantation (SCT), as the sole independent risk factor (hazard ratio, 35.8; P = .002). Among 31 patients who received salvage chemotherapy before local treatment, 21 received chemotherapy regimens that are not conventionally used for newly diagnosed ESFT. The objective response rate to first-line salvage chemotherapy was 55.2% in the 29 evaluable patients. Time to relapse or progression was significantly associated with response to first-line salvage chemotherapy (P = .006). [Conclusions] The present study fails to demonstrate significant clinical benefit of SCT for recurrent or refractory localized ESFT. Recently established chemotherapy regimens may increase the survival rate of patients with recurrent or refractory localized ESFT while attenuating the beneficial effect of SCT

Transonic Dislocation Propagation in Diamond

The motion of line defects (dislocations) has been studied for over 60 years but the maximum speed at which they can move is unresolved. Recent models and atomistic simulations predict the existence of a limiting velocity of dislocation motions between the transonic and subsonic ranges at which the self-energy of dislocation diverges, though they do not deny the possibility of the transonic dislocations. We use femtosecond x-ray radiography to track ultrafast dislocation motion in shock-compressed single-crystal diamond. By visualizing stacking faults extending faster than the slowest sound wave speed of diamond, we show the evidence of partial dislocations at their leading edge moving transonically. Understanding the upper limit of dislocation mobility in crystals is essential to accurately model, predict, and control the mechanical properties of materials under extreme conditions

Ixazomib が奏効している心アミロイドーシス合併多発性骨髄腫

　Ixazomib は，経口のプロテアソーム阻害薬であり，特に非注射薬の組み合わせが選択される多発性骨髄腫患者の再発難治例にとって有用な治療薬である．今回，我々はIxazomib が奏効している心アミロイドーシス合併多発性骨髄腫を経験したため報告する．症例は50歳代女性で，20XX 年10月心不全精査のため当院循環器内科入院となり，精査にて洞不全症候群（type3），心アミロイドーシスと診断された．洞不全症候群（type3）に対して心臓ペースメーカー移植術が施行され，血液検査にてM 蛋白を認めたため当科紹介となった．骨髄検査では形質細胞の増加を認め，AL アミロイドーシス（心臓，消化管）合併多発性骨髄腫（IgG‐λ with BJP）と診断した．20XX 年12月から治療を開始．VRD 療法を１コース施行中に，ペースメーカー波形ではない不整脈が多発し，うっ血性心不全の併発や，心源性脳梗塞による左完全片麻痺を発症した．VRD 療法は継続困難と判断し，elotuzumab 併用RD 療法に変更し治療を施行した．２コースでPD となったため，脳梗塞の発症によるADL の低下があることから，施設入所をふまえて外来通院頻度が少ない治療法として，Ixazomib 併用RD 療法を選択し治療を開始した．治療効果および忍容性は良好で，M 蛋白の順調な低下を認め，心不全の増悪なく経過している．心アミロイドーシス合併多発性骨髄腫は，治療に伴い致死性不整脈や心不全を併発することが多い．プロテアソーム阻害剤であるbortezomib 投与にて，不整脈や心不全の併発症状が出現していたが，経口プロテアソーム阻害剤であるixazomib の投与では，不整脈や心不全を併発させることなく，治療が継続し得た．　Ixazomib is an oral proteasome inhibitor that is useful for the treatment of recurrent refractory cases, particularly when a non-injection combination drug therapy is chosen for the patient. Here, we report a case of cardiac amyloidosis treated with ixazomib in a patient with multiple myeloma. The patient was a 50-year-old woman hospitalized in the cardiovascular medicine department of our hospital in October 20XX for close examination of cardiac failure. On the basis of the test findings, sick sinus syndrome (type 3) and cardiac amyloidosis were diagnosed. A heart pacemaker transplantation was performed for the sick sinus syndrome (type 3), and additional tests indicated M-protein expression; thus, the patient was referred to our department. A bone marrow test revealed increased plasma cells, which led to the diagnosis of immunoglobulin light chain amyloidosis (heart and digestive tract) secondary to multiple myeloma (IgG‐λ with BJP). Treatment was initiated in December 20XX. During the first course of VRD treatment, multiple non-pacemaker waveform arrhythmias and congestive heart failure occurred. Left total hemiplegia due to cardioembolic stroke occurred. We judged it difficult to continue the VRD treatment, so we switched the treatment to concomitant elotuzumab and RD therapy. After 2 courses, the patient became PD. With a decrease in ADL due to the onset of cerebral infarction and considering the possible need for institutionalization, ixazomib combined with RD therapy was initiated as treatment to reduce the frequency of outpatient visits. The treatment efficacy and tolerance were good, the M-protein expression level decreased gradually. Her progress was uneventful with no worsening of cardiac failure. Cardiac amyloidosis secondary to multiple myeloma is commonly associated with treatment-related lifethreatening arrhythmias and cardiac failure. Treatment with the proteasome inhibitor bortezomib is associated with the onset of arrhythmias and cardiac failure. However, treatment with the oral proteasome inhibitor ixazomib can be continued without onset of arrhythmia and cardiac failure