Changes in cerebrovascular disease-related deaths and their location during the COVID-19 pandemic in Japan.

OBJECTIVE: The COVID-19 pandemic placed an enormous strain on healthcare systems and raised concerns for delays in the management of patients with acute cerebrovascular events. In this study, we investigated cerebrovascular excess deaths in Japan. STUDY DESIGN: Vital mortality statistics from January 2012 to May 2022 were obtained from the Japanese Ministry of Health, Labour and Welfare. METHODS: Using quasi-Poisson regression models, we estimated the expected weekly number of cerebrovascular deaths in Japan from January 2020 through May 2022 by place of death. Estimates were calculated for deaths in all locations, as well as for deaths in hospitals, in geriatric health service facilities, and at home. The age subgroups of ≥75 and <75 years were also considered. Weeks with a statistically significant excess of cerebrovascular deaths were determined when the weekly number of observed deaths exceeded the upper bound of 97.5% prediction interval. RESULTS: Excess deaths were noted in June 2021 and became more pronounced from February 2022 onward. The trend was notable among those aged ≥75 years and for those who died in hospitals. With respect to the location of deaths, the excess was significant in geriatric health services facilities from April 2020 to June 2021, whereas no evidence of excess hospital deaths was observed during the same period. CONCLUSIONS: Beginning in the late 2021, excess cerebrovascular deaths coincided with the spread of the Omicron variant and may be associated with increased healthcare burden. In 2020, COVID-19 altered the geography of cerebrovascular deaths, with fewer people dying in hospitals and more dying in geriatric health service facilities and at home.

Excess deaths from COVID-19 in Japan and 47 prefectures from January through June 2021.

OBJECTIVES: In Japan, several studies have reported no excess all-cause deaths (the difference between the observed and expected number of deaths) during the coronavirus disease 2019 (COVID-19) pandemic in 2020. This study aimed to estimate the weekly excess deaths in Japan's 47 prefectures for 2021 until June 27. STUDY DESIGN: Vital statistical data on deaths were obtained from the Ministry of Health, Labour and Welfare of Japan. For this analysis, we used data from January 2012 to June 2021. METHODS: A quasi-Poisson regression was used to estimate the expected weekly number of deaths. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the one-sided prediction interval. RESULTS: Since January 2021, excess deaths were observed for the first time in the week corresponding to April 12-18 and have continued through mid-June, with the highest excess percentage occurring in the week corresponding to May 31-June 6 (excess deaths: 1431-2587; excess percentage: 5.95-10.77%). Similarly, excess deaths were observed in consecutive weeks from April to June 2021 in 18 of 47 prefectures. CONCLUSIONS: For the first time since February 2020, when the first COVID-19 death was reported in Japan, excess deaths possibly related to COVID-19 were observed in April 2021 in Japan, during the fourth wave. This may reflect the deaths of non-infected people owing to the disruption that the pandemic has caused.

The relationship between fever rate and telework implementation as a social distancing measure against the COVID-19 pandemic in Japan.

OBJECTIVES: On March 28, the Japanese government decided on the "Basic Policies for Novel Coronavirus Disease Control" and called on the public to thoroughly implement social distancing measures (i.e., behavioral restrictions to limit the frequency and intensity of human contact), especially telework. METHODS: We used population-level questionnaire data from a social networking service (SNS), with 275,560 respondents from March 5 to April 6, to evaluate the relationship between telework implementation and the presence of a fever (body temperature higher than 37.5 °C) within 1 month as a surrogate indicator of COVID-19 infection, by occupation type and age-group. RESULTS: Among company employees, statistical significance was identified in the 15- to 29-year and 30- to 59-year age-groups, showing higher fever rates in the non-teleworker group (for the 15- to 29-year age-group, non-teleworkers: 7.64%; teleworkers: 6.45%; P = 0.02; for the 30- to 59-year age-group, non-teleworkers: 3.46%; teleworkers: 3.14%; P = 0.02). CONCLUSIONS: Telework remains a controversial topic in Japan as the government called for emergency measures. Although caution is warranted in interpreting our findings because our data are limited to the voluntary SNS users, they will be essential to push forward with more measures to promote social distancing measures in the midst of Japan's current tense political climate.

Trend change of the transmission route of COVID-19-related symptoms in Japan.

OBJECTIVES: The Japanese prime minister declared a state of emergency on April 7 2020 to combat the outbreak of coronavirus disease 2019 (COVID-19). This declaration was unique in the sense that it was essentially driven by the voluntary restraint of the residents. We examined the change of the infection route by investigating contact experiences with COVID-19-positive cases. STUDY DESIGN: This study is a population-level questionnaire-based study using a social networking service (SNS). METHODS: To assess the impact of the declaration, this study used population-level questionnaire data collected from an SNS with 121,375 respondents (between March 27 and May 5) to assess the change in transmission routes over the study period, which was measured by investigating the association between COVID-19-related symptoms and (self-reported) contact with COVID-19-infected individuals. RESULTS: The results of this study show that the declaration prevented infections in the workplace, but increased domestic infections as people stayed at home. However, after April 24, workplace infections started to increase again, driven by the increase in community-acquired infections. CONCLUSIONS: While careful interpretation is necessary because our data are self-reported from voluntary SNS users, these findings indicate the impact of the declaration on the change in transmission routes of COVID-19 over time in Japan.

Variability and constraint of vertebral formulae and proportions in colugos, tree shrews, and rodents, with special reference to vertebral modification by aerodynamic adaptation.

BACKGROUND: The aim of the present study is to provide the first large data set on vertebral formulae and proportions, and examine their relationship with different locomotive modes in colugos (Dermoptera), tree shrews (Scandentia), and rodents (Rodentia), which have been considered less variable because they were thought to have a plesiomorphic number of 19 thoracolumbar vertebrae. MATERIALS AND METHODS: The data included 33 colugos and 112 tree shrews, which are phylogenetically sister taxa, and 288 additional skeletons from 29 other mammalian species adapted to different locomotive modes, flying, gliding, arboreal, terrestrial, digging, and semi-aquatic habitats. RESULTS: The following results were obtained: (1) intra-/interspecies variability and geographical variation in thoracic, lumbar, and thoracolumbar counts were present in two gliding colugo species and 12 terrestrial/arboreal tree shrew species; (2) in our examined mammals, some aerodynamic mammals, such as colugos, southern flying squirrels, scaly-tailed squirrels, and bats, showed exceptionally high amounts of intraspecific variation of thoracic, lumbar, and thoracolumbar counts, and sugar gliders and some semi-aquatic rodents also showed some variation; (3) longer thoracic and shorter lumbar vertebrae were typically shared traits among the examined mammals, except for flying squirrels (Pteromyini) and scaly-tailed squirrels (Anomaluridae). CONCLUSIONS: Our study reveals that aerodynamic adaptation could potentially lead to strong selection and modification of vertebral formulae and/or proportions based on locomotive mode despite evolutionary and developmental constraints. (Folia Morphol 2018; 77, 1: 44-56) Background: The aim of the present study is to provide the first large data set on vertebral formulae and proportions, and examine their relationship with different locomotive modes in colugos (Dermoptera), tree shrews (Scandentia), and rodents (Rodentia), which have been considered less variable because they were thought to have a plesiomorphic number of 19 thoracolumbar vertebrae. MATERIALS AND METHODS: The data included 33 colugos and 112 tree shrews, which are phylogenetically sister taxa, and 288 additional skeletons from 29 other mammalian species adapted to different locomotive modes, flying, gliding, arboreal, terrestrial, digging, and semi-aquatic habitats. RESULTS: The following results were obtained: (1) intra-/interspecies variability and geographical variation in thoracic, lumbar, and thoracolumbar counts were present in two gliding colugo species and 12 terrestrial/arboreal tree shrew species; (2) in our examined mammals, some aerodynamic mammals, such as colugos, southern flying squirrels, scaly-tailed squirrels, and bats, showed exceptionally high amounts of intraspecific variation of thoracic, lumbar, and thoracolumbar counts, and sugar gliders and some semi-aquatic rodents also showed some variation; (3) longer thoracic and shorter lumbar vertebrae were typically shared traits among the examined mammals, except for flying squirrels (Pteromyini) and scaly-tailed squirrels (Anomaluridae). CONCLUSIONS: Our study reveals that aerodynamic adaptation could potentially lead to strong selection and modification of vertebral formulae and/or proportions based on locomotive mode despite evolutionary and developmental constraints. (Folia Morphol 2018; 77, 1: 44-56).

Fast Heating of Imploded Core with Counterbeam Configuration.

A tailored-pulse-imploded core with a diameter of 70 µm is flashed by counterirradiating 110 fs, 7 TW laser pulses. Photon emission (>40 eV) from the core exceeds the emission from the imploded core by 6 times, even though the heating pulse energies are only one seventh of the implosion energy. The coupling efficiency from the heating laser to the core using counterirradiation is 14% from the enhancement of photon emission. Neutrons are also produced by counterpropagating fast deuterons accelerated by the photon pressure of the heating pulses. A collisional two-dimensional particle-in-cell simulation reveals that the collisionless two counterpropagating fast-electron currents induce mega-Gauss magnetic filaments in the center of the core due to the Weibel instability. The counterpropagating fast-electron currents are absolutely unstable and independent of the core density and resistivity. Fast electrons with energy below a few MeV are trapped by these filaments in the core region, inducing an additional coupling. This might lead to the observed bright photon emissions.

Direct heating of a laser-imploded core by ultraintense laser-driven ions.

A novel direct core heating fusion process is introduced, in which a preimploded core is predominantly heated by energetic ions driven by LFEX, an extremely energetic ultrashort pulse laser. Consequently, we have observed the D(d,n)^{3}He-reacted neutrons (DD beam-fusion neutrons) with the yield of 5×10^{8} n/4π sr. Examination of the beam-fusion neutrons verified that the ions directly collide with the core plasma. While the hot electrons heat the whole core volume, the energetic ions deposit their energies locally in the core, forming hot spots for fuel ignition. As evidenced in the spectrum, the process simultaneously excited thermal neutrons with the yield of 6×10^{7} n/4π sr, raising the local core temperature from 0.8 to 1.8 keV. A one-dimensional hydrocode STAR 1D explains the shell implosion dynamics including the beam fusion and thermal fusion initiated by fast deuterons and carbon ions. A two-dimensional collisional particle-in-cell code predicts the core heating due to resistive processes driven by hot electrons, and also the generation of fast ions, which could be an additional heating source when they reach the core. Since the core density is limited to 2 g/cm^{3} in the current experiment, neither hot electrons nor fast ions can efficiently deposit their energy and the neutron yield remains low. In future work, we will achieve the higher core density (>10 g/cm^{3}); then hot electrons could contribute more to the core heating via drag heating. Together with hot electrons, the ion contribution to fast ignition is indispensable for realizing high-gain fusion. By virtue of its core heating and ignition, the proposed scheme can potentially achieve high gain fusion.

Mania occurring during systemic lupus erythematosus relapse and its amelioration on clinical and neuroimaging follow-up.

Psychiatric manifestations of systemic lupus erythematosus (SLE) that are commonly preceded by organic syndromes include confusional states, anxiety disorder, cognitive dysfunction, mood disorder and psychosis. A 35-year-old woman was admitted to hospital with a relapse of SLE. Laboratory data were exacerbated, with some physical symptoms, and her primary psychiatric symptom was mania. The symptoms were reduced by treatment with prednisolone, methylprednisolone and aripiprazole. Magnetic resonance imaging and single-photon emission computed tomography (SPECT) using (123)I-IMP was then performed and analyzed with three-dimensional stereotactic surface projection. This case emphasizes that SLE can commence with organic syndromes and relapse with predominantly psychiatric symptoms, and that the treatment efficacy may be confirmed using a follow-up of SPECT.

Cost-effective development of highly polymorphic microsatellite in Japanese quail facilitated by next-generation sequencing.

Next-generation sequencing technologies permit rapid and cost-effective identification of numerous putative microsatellite loci. Here, from the genome sequences of Japanese quail, we developed microsatellite markers containing dinucleotide repeats and employed these for characterisation of genetic diversity and population structure. A total of 385 individuals from 12 experimental and one wild-derived Japanese quail lines were genotyped with newly developed autosomal markers. The maximum number of alleles, expected heterozygosity and polymorphic information content (PIC) per locus were 10, 0.80 and 0.77 respectively. Approximately half of the markers were highly informative (PIC ≥ 0.50). The mean number of alleles per locus and observed heterozygosity within a line were in the range of 1.3-4.1 and 0.11-0.53 respectively. Compared with the wild-derived line, genetic diversity levels were low in the experimental lines. Genetic differentiation (FST ) between all pairs of the lines ranged from 0.13 to 0.83. Genetic clustering analyses based on multilocus genotypes of individuals showed that most individuals formed clearly defined clusters corresponding to the origins of the lines. These results suggest that Japanese quail experimental lines are highly structured. Microsatellite markers developed in this study may be effective for future genetic studies of Japanese quail.

Ciclosporin A inhibits production of interleukin-12/23p40 and interleukin-23 by the human monocyte cell line, THP-1.

Ciclosporin (Cs)A is an effective treatment for psoriasis. However, to date, the effect of CsA on the production of interleukins (ILs) is unknown. We investigated how CsA affects production of IL-12/23p40 and IL-23 production by the human monocyte cell line, THP-1, which is able to differentiate into macrophage-like cells or normal human keratinocytes (NHKs). THP-1 cells were preincubated with CsA, then stimulated with lipopolysaccharide (LPS), polyinosinic:polycytidylic acid or adenosine triphosphate. The levels of IL-12/23p40 and IL-23 released into the supernatant were assayed by ELISA. CsA significantly reduced both IL-12/23p40 and IL-23 production by LPS-stimulated THP-1 cells, but not in LPS-stimulated macrophage-like differentiated THP-1 cells. None of the stimuli used significantly induced either IL-12/23p40 or IL-23 production in NHKs. CsA inhibits not only IL-12/23p40 and IL-12p70, but also heterodimeric IL-23 production by human monocytes, which may be one possible mechanism for the therapeutic efficacy of CsA in psoriasis.

Fusion using fast heating of a compactly imploded CD core.

A compact fast core heating experiment is described. A 4-J 0.4-ns output of a laser-diode-pumped high-repetition laser HAMA is divided into four beams, two of which counterilluminate double-deuterated polystyrene foils separated by 100 µm for implosion. The remaining two beams, compressed to 110 fs for fast heating, illuminate the same paths. Hot electrons produced by the heating pulses heat the imploded core, emitting x-ray radiations >20 eV and yielding some 10(3) thermal neutrons.

Effects of bosentan on nondigital ulcers in patients with systemic sclerosis.

BACKGROUND: Bosentan is an oral dual endothelin receptor antagonist, which has been shown to be efficacious for preventing new digital ulcers in patients with systemic sclerosis (SSc) in two high-quality randomized controlled trials. However, its efficacy for nondigital ulcers in SSc remains unknown. OBJECTIVES: To evaluate the efficacy of bosentan on nondigital ulcers in patients with SSc. METHODS: Bosentan was administered to five patients with SSc with pulmonary arterial hypertension, who also had nondigital ulcers refractory to conventional treatments. The efficacy of bosentan on nondigital ulcers and its association with clinical features of ulcers were analysed. RESULTS: The nondigital ulcers refractory to conventional treatments were significantly improved by the administration of bosentan in cases surrounded with severe cyanosis. In contrast, nondigital ulcers without cyanosis were still refractory to bosentan therapy. CONCLUSIONS: Bosentan may be efficacious for accelerating the healing of nondigital ulcers with severe cyanosis, suggesting that nondigital ulcers caused by severely impaired peripheral circulation are highly responsive to this treatment.

Serum lipocalin-2 levels are increased in patients with psoriasis.

The protein lipocalin (LCN)-2 is known to be related to insulin resistance, obesity and atherosclerotic diseases. Psoriasis is an inflammatory skin disease related to metabolic syndrome. The aim of this study was to examine the relationship between serum LCN2 levels and indicators for metabolic syndrome and inflammatory cytokine levels in patients with psoriasis. Serum LCN2 levels were measured in patients with psoriasis, atopic dermatitis (AD) or bullous pemphigoid (BP), and compared with those of healthy controls. Serum LCN2 levels were also compared with several indicators for metabolic syndrome, and with serum levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α, two markers of inflammation. Serum LCN2 levels in patients with psoriasis were significantly higher than those of healthy controls, but there was no significant correlation between serum LCN2 and body mass index. Serum LCN2 levels also correlated with serum IL-6 and TNF-α levels in patients with psoriasis. Serum LCN2 levels are a general indicator for increased inflammation in the patients with psoriasis.

A novel Fe(II)/α-ketoglutarate-dependent dioxygenase from Burkholderia ambifaria has ß-hydroxylating activity of N-succinyl l-leucine.

An Fe(II)/α-ketoglutarate-dependent dioxygenase, SadA, was obtained from Burkholderia ambifaria AMMD and heterologously expressed in Escherichia coli. Purified recombinant SadA had catalytic activity towards several N-substituted l-amino acids, which was especially strong with N-succinyl l-leucine. With the NMR and LC-MS analysis, SadA converted N-succinyl l-leucine into N-succinyl l-threo-ß-hydroxyleucine with >99% diastereoselectivity. SadA is the first enzyme catalysing ß-hydroxylation of aliphatic amino acid-related substances and a potent biocatalyst for the preparation of optically active ß-hydroxy amino acids.

Evolutionary transformation of the cervicobrachial plexus in the colugo (Cynocephalidae: Dermoptera) with a comparison to treeshrews (Tupaiidae: Scandentia) and strepsirrhines (Strepsirrhini: Primates).

Four cervicobrachial plexuses from two colugos (Dermoptera), which are gliding mammals with semi-elongated necks, were dissected with imaging analysis and compared with those in its relatives, 12 sides of six treeshrews (Scandentia) and 32 sides of 16 strepsirrhines (Primates), for considering of its evolutionary constraint and functional adaptation. (1) The relative cervical length in the colugos was significantly longer than those in the others, regardless of the number and proportion of vertebrae. (2) In all examined colugos, the cervical plexus exhibited broader cervical root segments comprising the hypoglossal (N. XII) and first to fifth cervical (C1-C5) nerves, whereas the brachial plexus exhibited concentrated segments comprising C6 to the first thoracic nerve (T1) and part of T2. (3) On the other hand, the cervical plexus composed of N. XII and C1-C4 and the brachial plexus composed of C5-T1(2) were formed in all treeshrews (12/12 sides, 100.0%) and most strepsirrhines (27/32 sides, 84.4%) as seen in most terrestrial placental mammals. (4) Similar root segments of broader cervical and concentrated brachial plexuses were found in five sides of three strepsirrhines (15.6%), which are species with somewhat longer necks than the other strepsirrhines and treeshrews. Based on present and previous reports on elongated and shortened neck mammals, the modified root segments of the cervicobrachial plexus in the colugo appears to be related more to neck length than to its ecological habit, specialized locomotion, or any phylogenetic constraint.

Does the phenotypic morphology of the human brachial plexus reflect the theoretical development of concomitant regulation in thoracolumbar spines and nerves?

BACKGROUND: Experimental evidence identified that thoracolumbar mutants caused by Hox genes 7-10 mutants also involve a craniocaudal shift and/or the addition or reduction of segments of the limb plexus roots. This study investigated whether the theoretical concomitant shift of the brachial plexus roots in human different thoracolumbar counts is shared as confirmed in those of the human lumbosacral plexus. MATERIALS AND METHODS: The phenotypic morphology of the brachial plexus and its arterial interaction on 20 sides of 10 atypical human thoracolumbar counts out of the 354 sides of the 177 cadavers, were compared with those of 52 sides of 26 cases in a typical human vertebral formula (7C_12T_5L_5S). RESULTS: Regardless of the course and branching patterns of the axillary artery, our results showed that the main brachial plexus roots were composed of only five segments of the 5th-9th spinal nerves, with small contributions from the 4th and/or 10th nerves. This root composition is identical to a typical human thoracolumbar formula, and therefore, neither a craniocaudal shift nor additional/reduced main roots occurred in our thoracolumbar variants. CONCLUSIONS: Unlike the concomitant shift of the lumbosacral plexus roots, our present cases suggest that the phenotypic morphology of the human brachial plexus may be less likely to show theoretical craniocaudal shifts, further data on the root changes in different vertebral formulae are needed for its accurate validation.

Brain dynein (MAP1C) localizes on both anterogradely and retrogradely transported membranous organelles in vivo.

Brain dynein is a microtubule-activated ATPase considered to be a candidate to function as a molecular motor to transport membranous organelles retrogradely in the axon. To determine whether brain dynein really binds to retrogradely transported organelles in vivo and how it is transported to the nerve terminals, we studied the localization of brain dynein in axons after the ligation of peripheral nerves by light and electron microscopic immunocytochemistry using affinity-purified anti-brain dynein antibodies. Different classes of organelles preferentially accumulated at the regions proximal and distal to the ligated part. Interestingly, brain dynein accumulated both at the regions proximal and distal to the ligation sites and localized not only on retrogradely transported membranous organelles but also on anterogradely transported ones. This is the first evidence to show that brain dynein associates with retrogradely transported organelles in vivo and that brain dynein is transported to the nerve terminal by fast flow. This also suggests that there may be some mechanism that activates brain dynein only for retrograde transport.

[Intraoperative recanalization of type A chronic aortic dissection with a thrombosed false lumen].

A woman of 75 years old urgently admitted to our hospital for type A acute aortic dissection with a thrombosed false lumen, which had ulcer like projection (ULP) on enhanced computed tomography (CT) in the ascending aorta Aortic recanalization occurred in the operating room along with the establishment of extra corporeal circulation. Right axillar arterial perfusion directly struck the intimal tear site equaled to ULP, which caused intraoperative aortic recanalization. Graft replacement of the ascending aorta was successfully performed with the aid of hypothermic circulatory arrest and selective cerebral perfusion.

[Intraoperative graft assessment using fluorescent imaging system (SPY)].

We investigated the efficacy of intraoperative fluorescent imaging system for the assessment of coronary artery bypass grafting (CABG). We used SPY imaging system in 100 CABG (57 off-pump and 43 on-pump CABG), totalling 287 distal anastomoses. The total graft patency rate on postoperative angiography in this series was 96.2% (276/287). Graft revision was done in 10 cases (10.0%) and 13 anastomoses (4.5%) by SPY imaging, which all resulted in good patency at postoperative angiography. On the other hand, 7 distal anastomoses and 1 mammary graft (2.8%) appeared to be successful on intraoperative SPY imaging, but were revealed to be occluded by postoperative angiography. SPY imaging system is useful for graft validation, and may contribute to improvement of coronary bypass graft patency.

Proteoglycan form of macrophage colony-stimulating factor binds low density lipoprotein.

We recently isolated a proteoglycan form of macrophage colony-stimulating factor (PG-M-CSF) that carries a chondroitin sulfate glycosaminoglycan chain. Here, we examined the interaction of PG-M-CSF with low density lipoprotein (LDL). When LDL preincubated with PG-M-CSF was fractionated by molecular size sieving chromatography, it was eluted earlier than untreated LDL. When LDL was preincubated with chondroitin sulfate-free 85-kD M-CSF instead of PG-M-CSF, the elution profile of LDL remained unchanged, indicating specific interaction between PG-M-CSF and LDL. The level of PG-M-CSF binding in the wells of a plastic microtitration plate precoated with LDL was significant, this binding being completely abolished by pretreatment of PG-M-CSF with chondroitinase AC, which degrades chondroitin sulfate. The addition of exogenous chondroitin sulfate or apolipoprotein B inhibited the binding of PG-M-CSF to LDL in a dose-dependent manner, indicating that the interaction between PG-M-CSF and LDL was mediated by the binding of the chondroitin sulfate chain of PG-M-CSF to LDL apolipoprotein B. PG-M-CSF was also demonstrated in the arterial wall, and there were increased amounts of PG-M-CSF in atherosclerotic lesions. The in vitro interaction between PG-M-CSF and LDL thus appears to have physiological significance.