Kawasaki disease (KD) is a multisystem vasculitis that primarily affects the coronary arteries of young children. The causes of KD remain a mystery. It is suspected that some sort of infectious agent ...is involved because KD has epidemicity and seasonality. That said, the incidence of the disease is high among Japanese people, so it can be speculated that the hosts may have some sort of genetic characteristic that leaves them susceptible to KD. Various theories regarding the etiology have been asserted, such as the infectious vasculitis theory, autoantigen theory, superantigen theory, and RNA virus theory; however, none of them have been able to overcome this epidemicity. Taking into consideration the knowledge gained from previous reports, the best scenario explaining the pathogenesis is "individuals with certain genetic backgrounds are affected by microorganisms which trigger KD." In this article, the pathogenesis of KD is discussed with a focus on the microorganisms mentioned above, along with the previous and current hypotheses as well as my own opinion.
Background:This study determined the current status of the incidence, management, and prognosis of stroke in Japan using a population-based stroke registry.Methods and Results:Shiga Stroke Registry ...is an ongoing population-based registry that covers approximately 1.4 million residents of Shiga Prefecture. Cases of acute stroke were identified using standard definitions through surveillance of both all acute-care hospitals with neurology/neurosurgery facilities and death certificates in 2011. A total of 2,956 stroke cases and 2,176 first-ever stroke cases were identified. The age- and sex-adjusted incidence rate for first-ever stroke using the 2013 European Standard Population as standard was per 100,000 person-years: 91.3 for ischemic stroke, 36.4 for intracerebral hemorrhage, and 13.7 for subarachnoid hemorrhage. It was estimated that approximately 220,000 new strokes occurred in 2011 in Japan. Among the 2,956 cases, most stroke patients underwent neuroimaging, 268 received surgical or endovascular treatment, and 2,158 had rehabilitation therapy; 78 patients received intravenous thrombolysis. A total of 1,846 stroke patients had died or were dependent at hospital discharge, and 390 died within 28 days of onset.Conclusions:Incidence rates of stroke by subtypes were clarified and the total number of new strokes in Japan was estimated. More than half of stroke patients die or become dependent after a stroke. This study re-emphasized the importance of public health measures in reducing the burden of stroke in Japan.
For decades, babies were thought to be born germ-free, but recent evidences suggest that they are already exposed to various bacteria
. However, the data on population levels of such pioneer gut ...bacteria, particularly in context to birth mode, is sparse. We herein aimed to quantify such bacteria from the meconium of 151 healthy term Japanese infants born vaginally or by C-section. Neonatal first meconium was obtained within 24-48 h of delivery; RNA was extracted and subjected to reverse-transcription-quantitative PCR using specific primers for
group,
subgroup,
group,
cluster,
,
,
, Enterobacteriaceae,
,
,
,
, and
. We detected several bacterial groups in both vaginally- and cesarean-born infants.
group, Enterobacteriaceae,
,
, and
were detected in more than 50% of infants, with counts ranging from 10
to 10
cells/g sample. About 30-35% samples harbored
and
(10
-10
cells/g); whereas
group,
subgroup and
were detected in 10-20% infants (10
-10
cells/g). Compared to vaginally-born babies, cesarean-born babies were significantly less often colonized with
genus (6% vs. 37%;
= 0.01) and
subgroup (6% vs. 31%;
= 0.04). Overall, seven
subgroups/species, i.e.,
subgroup,
subgroup,
subgroup,
subgroup,
subgroup,
subgroup, and
were detected in the samples from vaginally-born group, whereas only two members, i.e.,
subgroup and
were detected in the cesarean group. These data corroborate that several bacterial clades may already be present before birth in term infants' gut. Further, lower detection rate of lactobacilli in cesarean-born babies suggests that the primary source of lactobacilli in infant gut is mainly from maternal vaginal and-to a lesser extent-anal microbiota during vaginal delivery, and that the colonization by some important
species is delayed in babies delivered via cesarean-section.
Early-life intestinal microbiota development is crucial for host's long-term health and is influenced by many factors including gestational age, birth and feeding modes, birth environment, ...ethnic/geographical background, etc. However, 'quantitative' data on the actual population levels of gut bacterial communities when these influences are controlled for is relatively rare. Herein, we demonstrate a quantitative perspective of microbiota development in natural and healthy milieus, i.e., in healthy, full-term, vaginally born and breast-fed infants (
= 19) born at same clinic. Fecal microbiota at age 1 and 7 days, 1, 3, and 6 months and 3 years is quantified using highly sensitive reverse-transcription-quantitative-PCR assays targeting bacterial rRNA molecules. At day 1, we detect one or more bacteria in all (100%) of the babies, wherein the microbiota is composed mainly of enterobacteria (35%),
group (23%), enterococci (18%), staphylococci (13%), and bifidobacteria (9%). Altogether, facultative anaerobes predominate during first few weeks whereafter obligate anaerobes including bifidobacteria,
group,
group, and
subgroup gradually start prevailing. At 3 years, the composition is represented almost entirely (99%) by obligate anaerobes including
subgroup (34%), bifidobacteria (22%),
group (21%),
group (17%),
cluster (4%), and
(1%). The overall obligate/facultative proportion is 32/68, 37/63, 54/46, 70/30, 64/36, and 99/1% at 1 and 7 days, 1, 3, and 6 months and 3 years, respectively. However, interestingly, considerable individual-specific variations in the obligate/facultative ratios as well as in the proportions of Firmicutes, Bacteroides, Actinobacteria, and Proteobacteria communities are seen among these babies. This disparity even within this highly homogenous cohort manifests the magnitude of diverse patterns of gut microbiota configuration and hence underpins the importance of considering not only the gestational age, birth, and feeding modes, and ethnic/geographical background but also other potential outstanding factors when investigating the elements shaping the early microbiota development. In summary, the data demonstrate a quantitative bird's-eye view of the ontogenesis of early-life gut microbiota in typically natural and healthy milieus and should be informative and facilitative for future studies exploring various aspects of the human gut microbiota.
Background: While the prevalence of very low birth weight children (VLBWC) experiencing difficulties as a result of developmental coordination disorder (DCD) is increasing, the diagnostic criteria ...for DCD have remained unclear.The objective of this study is to elucidate the current situation and characteristics of DCD in VLBWC.Method: The VLBWC group (n = 14) comprised subjects with a mean birth weight of 986±355 g and a mean gestational age of 26±2.74 weeks. The fine motor skill characteristics of VLBWC were compared to those of the control group using the Movement Assessment Battery for Children-Second Edition (MABC-2). Moreover, the association between the MABC-2 results and the parent-completed child behavior checklists (CBCL) was determined.Result: There was a relatively high percentage of VLBWC with DCD/DCD risk. A significantly low MABC-2 index reported in VLBWC was attributed primarily to manual dexterity. Moreover, VLBWC with DCD frequently experienced daily difficulties as a result of their incompetence.Conclusion: The six-year-old VLBWC were more frequently associated with DCD and had more difficulties with clumsiness in their daily lives compared to the control group.
Background: Molecular biological analysis of the in vitro response of peripheral blood mononuclear cells (PBMCs) from children allergic to ovalbumin could help to elucidate the mechanism of ...IgE-mediated egg allergy in humans.Methods: PBMCs obtained from children with egg allergy who visited our clinic (December 2019 to September 2020) were subjected to in vitro stimulation by ovalbumin for 48 hours. The signal transducer and activator of transcription (STAT) signal and nuclear transcription factor expression were examined using real-time PCR-targeted mRNA of those parameters.Results: We co-cultured PBMCs with ovalbumin from persistent (n = 24), tolerant (n = 12), and control (n = 22) groups, and observed the following. (1) STAT1, STAT4, Foxp3, and STAT3 mRNA expressions fell significantly in the persistence group compared with the control group. (2) STAT4, T-bet, STAT6, GATA3, STAT5, Foxp3, STAT3, and RORγt mRNA expressions increased significantly in the tolerant group compared with the persistent group. (3) T-bet, GATA3, Foxp3, and STAT3 mRNA expressions increased significantly in the tolerant group compared with the control group. (4) PBMCs in the persistent, tolerant, and control groups did not differ significantly in CXCR5 or CD25 mRNA expression.Conclusions: Functional peripheral blood T cells changes may occur at the onset and remission of egg allergy.
Background: Stroke is one of the leading causes of disability and mortality in Japan. The aim of the present analysis was to determine the non-acute survival rate after first-ever stroke using data ...from a large-scale population-based stroke registry in Japan. Methods and Results: Shiga Stroke Registry is an ongoing population-based registry of stroke, which covers approximately 1.4 million residents of Shiga Prefecture in central Japan. A total of 2,176 first-ever stroke patients, who were registered in 2011, were followed up until December 2013. The 2-year cumulative survival rates were estimated using Kaplan-Meier method according to index stroke subtype. Cox proportional hazards models were used to assess predictors of all-cause death. During a 2-year follow-up period, 663 patients (30.5%) died. The 2-year cumulative survival rate after first-ever stroke was 69.5%. There was heterogeneity in 2-year cumulative survival according to stroke subtype: lacunar infarction, 87.2%; large artery infarction, 76.1%; cardioembolic infarction, 55.4%; intracerebral hemorrhage, 65.9%; and subarachnoid hemorrhage, 56.7%. Older age, male sex, medical history, higher Japan coma scale score on admission, and stroke subtype were associated with risk of all-cause death in ≤2 years. Conclusions: In the present population-based stroke registry with a real-world setting in Japan, 2-year cumulative mortality after first-ever stroke is still high (>30%), particularly for cardioembolic infarction, subarachnoid hemorrhage and intracerebral hemorrhage.
Bifidobacteria are important members of human gut microbiota; however, quantitative data on their early-life dynamics is limited. Here, using a sensitive reverse transcription-qPCR approach, we ...demonstrate the carriage of eight signature infant-associated Bifidobacterium species (B. longum, B. breve, B. bifidum, B. catenulatum group, B. infantis, B. adolescentis, B. angulatum and B. dentium) in 76 healthy full-term vaginally-born infants from first day to three years of life. About 21% babies carry bifidobacteria at first day of life (6.2 ± 1.9 log
cells/g feces); and this carriage increases to 64% (8.0 ± 2.2), 79% (8.5 ± 2.1), 97% (9.3 ± 1.8), 99% (9.6 ± 1.6), and 100% (9.7 ± 0.9) at age 7 days, 1, 3 and 6 months, and 3 years, respectively. B. longum, B. breve, B. catenulatum group and B. bifidum are among the earliest and abundant bifidobacterial clades. Interestingly, infants starting formula-feed as early as first week of life have higher bifidobacterial carriage compared to exclusively breast-fed counterparts. Bifidobacteria demonstrate an antagonistic correlation with enterobacteria and enterococci. Further analyses also reveal a relatively lower/ delayed bifidobacterial carriage in cesarean-born babies. The study presents a quantitative perspective of the early-life gut Bifidobacterium colonization and shows how factors such as birth and feeding modes could influence this acquisition even in healthy infants.
Aim: Although renal dysfunction has been identified as a novel risk factor affecting stroke prognosis, few have analyzed the association within large-scale population-based setting, using wide-range ...estimated glomerular filtration rate (eGFR) category. We aimed to determine the association of admission eGFR with acute stroke outcomes using data from a registry established in Shiga Prefecture, Japan.Methods: Following exclusion of patients younger than 18 years, with missing serum creatinine data, and with onset more than 7 days prior to admission, 2,813 acute stroke patients registered in the Shiga Stroke Registry year 2011 were included in the final analysis. The Japanese Society of Nephrology equation was used to estimate GFR. Multivariable logistic regression was performed to analyze the association of eGFR with all-cause in-hospital death (modified Rankin Scale mRS 6), and at-discharge death/disability (mRS 2–6). Separate analyses were conducted within stroke subtypes.Results: Compared to eGFR 60–89 mL/min/1.73 m2, adjusted odds ratios (ORs) and 95% confidence interval 95% CI for in-hospital death (in the order of eGFR ＜45, 45–59, and ≥90 mL/min/1.73 m2) were 1.54 1.04–2.27, 1.07 0.72–1.58, and 1.04 0.67–1.59. Likewise, adjusted ORs 95% CI for at-discharge death/disability were 1.54 1.02–2.32, 0.97 0.73–1.31, and 1.48 1.06–2.05. Similar pattern was further evident in the eGFR ＜45 mL/min/1.73 m2 group for both outcomes within acute ischemic stroke patients.Conclusions: Our study has ascertained that in acute stroke, particularly ischemic stroke, low eGFR was significantly associated with in-hospital death and at-discharge death/disability. Additionally, high eGFR was found to be associated with at-discharge death/disability.
To elucidate the morphological characteristics of spike-wave complexes (SWCs) causing myoclonic seizures (MS) in childhood-onset idiopathic myoclonic epilepsies.
The subjects were 8 patients, ...including 4 with epilepsy with myoclonic-atonic seizures (EMAS), 3 with myoclonic epilepsy in infancy (MEI) and 1 with idiopathic unclassifiable myoclonic epilepsy. Morphometric parameters of the SWCs were compared between those with MS SWC-MS (+) and those without MS SWC-MS (-), and a correlation coefficient analysis was performed between the SWC parameters and the duration of myoclonic electromyogram (EMG) potentials.
A total of 155 SWC-MS (+) (range: 7 ∼ 34) and 80 SWC-MS (-) (10 each as a control) were analyzed. Comparison of the parameters of the SWCs between SWC-MS (+) and SWC-MS (-) demonstrated that the depth and the width of the positive-sharp-components (PSC) in the SWC-MS (+) were significantly deeper in amplitude and longer in duration than those in the SWC-MS (-), respectively, in all 8 patients (P < 0.05), whereas the number of the polyphasic-multiple-spike-components (PMSC) and the height of negative-spike-components (NSC) were not significantly different in most of the patients, respectively. The depth and the width of PSC were also significantly correlated with the duration of myoclonic EMG potentials in all patients except one depth of PSC (n = 7): r = 0.623 ∼ 0.888; width of PSC (n = 8): r = 0.676 ∼ 0.948, P < 0.05.
This study revealed that the depth and width of PSC of the SWC are positively correlated with the MS intensity in childhood-onset idiopathic myoclonic epilepsies and are an important neurophysiological marker to generate MS.
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