SARS-CoV-2 Variants and Age-Dependent Infection Rates among Household and Nonhousehold Contacts.

To determine the effects of age and variants of concern on transmission of SARS-CoV-2, we analyzed infection rates among close contacts over 4 periods in Toyama Prefecture, Japan. Among household contacts, odds of infection were 6.2 times higher during the period of the Omicron variant than during previous periods, particularly among children and adolescents.

Impact of the angiotensin receptor-neprilysin inhibitor in clinical diabetes management: Potential benefits and pitfalls.

The possible mechanism of increased urinary C-peptide due to neprilysin inhibitors is investigated. Neprilysin inhibition blocks degradation of natriuretic peptides, and elicits a natriuretic and antihypertensive effect. Neprilysin inhibition might similarly block degradation of C-peptides in the kidney and thus increase the urinary C-peptide level.

Transverse and longitudinal right ventricular fractional parameters derived from four-chamber cine MRI are associated with right ventricular dysfunction etiology.

Studies of the usefulness of transverse right ventricular (RV) shortening are limited. We retrospectively analyzed the CMR images of 67 patients (age: 50.8 ± 19.0 years; men: 53.7%; Control: n = 20, Overloaded RV (atrial septal defect): n = 15, Constricted RV (pericarditis): n = 17, Degenerated RV (arrhythmogenic right ventricular cardiomyopathy): n = 15) (all enrolled consecutively for each disease) in a single center. We defined RV longitudinal (fractional longitudinal change: FLC) and transverse (fractional transverse change: FTC) contraction parameters. We assessed the FTC/FLC (T/L) ratio on four-chamber cine CMR views and compared the four groups regarding the fractional parameters. FTC had a stronger correlation (R2 = 0.650; p < 0.001) with RV ejection fraction than that with FLC (R2 = 0.211; p < 0.001) in the linear regression analysis. Both FLC and FTC were significantly lower in the Degenerated RV and Constricted RV groups compared with those in the Control and Overloaded RV groups. The T/L ratio was significantly lower in the Degenerated RV group (p = 0.008), while the Overloaded RV (p = 0.986) and Constricted RV (p = 0.582) groups had preserved T/L ratios, compared with the Control group. Transverse shortening contributes to RV function more significantly compared with longitudinal contraction. Impaired T/L ratios may reflect RV myocardial degeneration. RV fractional parameters may help precisely understand RV dysfunction.

Near-Complete Genome Sequences of Three Foot-and-Mouth Disease Virus O/ME-SA/Ind-2001e Isolates Obtained from Cattle and Pigs in Thailand in 2016.

Here, we report near-complete genome sequences of three foot-and-mouth disease viruses isolated in 2016 from bovine and porcine epithelial tissue samples collected in Nonthaburi, Songkhla, and Ratchaburi provinces, Thailand. These viruses were classified as serotype O, topotype ME-SA, and sublineage Ind-2001e.

Visualization of Amyloid Oligomers in the Brain of Patients with Alzheimer's Disease.

In the pathogenesis of Alzheimer's disease (AD), highly neurotoxic amyloid-ß (Aß) oligomers appear early, they are thus considered to be deeply involved in the onset of Alzheimer's disease. However, Aß oligomer visualization is challenging in human tissues due to their multiple forms (e.g., low- and high-molecular-weight oligomers, including protofibrils) as well as their tendency to rapidly change forms and aggregate. In this review, we present two visualization approaches for Aß oligomers in tissues: an immunohistochemical (using the monoclonal antibody TxCo1 against toxic Aß oligomer conformers) and imaging mass spectrometry using the small chemical Shiga-Y51 that specifically binds Aß oligomers. TxCo1 immunohistochemistry revealed Aß oligomer distributions in postmortem human brains with AD. Using Shiga-Y51, imaging mass spectrometry revealed Aß oligomer distributions in the brain of a transgenic mouse model for AD. These two methods would potentially contribute to elucidating the pathological mechanisms underlying AD.

An analysis of intestinal morphology and incretin-producing cells using tissue optical clearing and 3-D imaging.

Tissue optical clearing permits detailed evaluation of organ three-dimensional (3-D) structure as well as that of individual cells by tissue staining and autofluorescence. In this study, we evaluated intestinal morphology, intestinal epithelial cells (IECs), and enteroendocrine cells, such as incretin-producing cells, in reporter mice by intestinal 3-D imaging. 3-D intestinal imaging of reporter mice using optical tissue clearing enabled us to evaluate both detailed intestinal morphologies and cell numbers, villus length and crypt depth in the same samples. In disease mouse model of lipopolysaccharide (LPS)-injected mice, the results of 3-D imaging using tissue optical clearing in this study was consistent with those of 2-D imaging in previous reports and could added the new data of intestinal morphology. In analysis of incretin-producing cells of reporter mice, we could elucidate the number, the percentage, and the localization of incretin-producing cells in intestine and the difference of those between L cells and K cells. Thus, we established a novel method of intestinal analysis using tissue optical clearing and 3-D imaging. 3-D evaluation of intestine enabled us to clarify not only detailed intestinal morphology but also the precise number and localization of IECs and incretin-producing cells in the same samples.

Skills Training in Affective and Interpersonal Regulation Narrative Therapy for women with ICD-11 complex PTSD related to childhood abuse in Japan: a pilot study.

Background: Skills Training in Affective and Interpersonal Regulation (STAIR) Narrative Therapy (SNT) has shown efficacy in alleviating symptoms of posttraumatic stress disorder (PTSD) and improving emotion regulation and interpersonal skills among individuals with complex trauma, such as childhood abuse. Although this therapy is expected to be effective for patients with complex PTSD (CPTSD), no study has directly assessed diagnostic and symptom outcomes. Moreover, the potential of therapy to achieve good outcomes in non-Western countries remains unclear. Objective: This pilot study examined the feasibility, safety, and outcomes of SNT for CPTSD among women with a history of childhood abuse in a Japanese clinical setting. Methods: Ten women aged 21-54 years (M = 29.1 years) with childhood-abuse-related ICD-11 CPTSD were enrolled in this study. The International Trauma Interview and International Trauma Questionnaire were administered to diagnose CPTSD and assess its severity. Symptoms of dissociation and depression, difficulties in emotion regulation and interpersonal relationships, quality of life, and negative cognitions were assessed pretreatment, midtreatment (after the STAIR phase), and immediately posttreatment (after the Narrative Therapy phase), in addition to 3 months after treatment. Results: Seven of the 10 participants completed the treatment. The therapists' adherence to the therapy protocol was 96.4%, ranging from 93.6% to 100% across therapists. Serious adverse events were not observed. Among the seven completers, six at posttreatment and all at follow-up no longer met CPTSD diagnosis. Exploratory analyses using the linear mixed-effects model showed significant improvements at posttreatment and follow-up for almost all the variables. Conclusions: The results provide preliminary evidence for the feasibility and safety of SNT for CPTSD in a Japanese clinical setting. This study is the first to report the use of SNT for individuals diagnosed with ICD-11 CPTSD using reliable clinician and self-report measures. HIGHLIGHTS: This study examined the feasibility and safety of STAIR Narrative Therapy for women with ICD-11 CPTSD related to childhood abuse in a Japanese clinical setting.High therapy adherence was observed.No serious adverse events occurred.

Antecedentes: La terapia narrativa (SNT en su sigla en inglés) de Entrenamiento de habilidades en regulación afectiva e interpersonal (STAIR en su sigla en inglés) ha demostrado eficacia en el alivio de los síntomas del trastorno de estrés postraumático (TEPT) y mejorar regulación emocional y las habilidades interpersonales entre individuos con trauma complejo, como el abuso en la infancia. Aunque esta terapia se espera que sea efectiva para pacientes con TEPT complejo (TEPT-C), ningún estudio ha evaluado directamente su estado diagnóstico y síntomas. Además, el potencial de la terapia para alcanzar resultados parecidos en países no Occidentales sigue sin estar claro.Objetivo: Este estudio piloto examinó la viabilidad, seguridad y resultados de la SNT para TEPTC en mujeres con historia de abuso en la infancia en un contexto clínico japonés.Métodos: Se inscribieron en este estudio diez mujeres de edad entre los 21­54 años (M = 29.1) con TEPT-C según la CIE-11 relacionado con abuso infantil. Se aplicó la Entrevista Internacional de Trauma y el Cuestionario Internacional de Trauma para diagnosticar TEPT-C y evaluar su gravedad. Los síntomas de disociación y depresión, dificultades en la regulación emocional y relaciones interpersonales, calidad de vida y cogniciones negativas se evaluaron durante el pretratamiento, a la mitad del tratamiento (después de la fase STAIR) e inmediatamente postratamiento (después de la fase de Terapia Narrativa), además de a los 3 meses después del tratamiento.Resultados: Siete de las 10 participantes completaron el tratamiento. La adherencia de los terapeutas al protocolo de la terapia fue del 96.4%, con una variación del 93.6% al 100% entre terapeutas. No se observaron eventos adversos serios. Entre las siete que completaron el tratamiento, seis en el postratamiento y todas al seguimiento ya no cumplían con el diagnóstico de TEPT-C. Los análisis exploratorios que utilizaron el modelo lineal de efectos mixtos mostraron una mejoría significativa en el postratamiento y seguimiento para casi todas las variables.Conclusiones: Los resultados entregan evidencia preliminar para la viabilidad y seguridad de la SNT para TEPT-C en un contexto clínico japonés. Este estudio es el primero en reportar el uso de la SNT para individuos diagnosticados con TEPT-C según la CIE-11 usando medidas clínicas y de auto-reporte confiables.

LC3/FtMt Colocalization Patterns Reveal the Progression of FtMt Accumulation in Nigral Neurons of Patients with Progressive Supranuclear Palsy.

Mitochondrial ferritin (FtMt) is a mitochondrial iron storage protein associated with neurodegenerative diseases. In patients with progressive supranuclear palsy (PSP), FtMt was shown to accumulate in nigral neurons. Here, we investigated FtMt and LC3 in the post-mortem midbrain of PSP patients to reveal novel aspects of the pathology. Immunohistochemistry was used to assess the distribution and abnormal changes in FtMt and LC3 immunoreactivities. Colocalization analysis using double immunofluorescence was performed, and subcellular patterns were examined using 3D imaging and modeling. In the substantia nigra pars compacta (SNc), strong FtMt-IR and LC3-IR were observed in the neurons of PSP patients. In other midbrain regions, such as the superior colliculus, the FtMt-IR and LC3-IR remained unchanged. In the SNc, nigral neurons were categorized into four patterns based on subcellular LC3/FtMt immunofluorescence intensities, degree of colocalization, and subcellular overlapping. This categorization suggested that concomitant accumulation of LC3/FtMt is related to mitophagy processes. Using the LC3-IR to stage neuronal damage, we retraced LC3/FtMt patterns and revealed the progression of FtMt accumulation in nigral neurons. Informed by these findings, we proposed a hypothesis to explain the function of FtMt during PSP progression.

Subgrouping and analysis of relationships between classical swine fever virus identified during the 2018-2020 epidemic in Japan by a novel approach using shared genomic variants.

Classical swine fever (CSF) is a worldwide devastating disease of the pig industry caused by classical swine fever virus (CSFV). In September 2018, an outbreak of CSF occurred in Japan where the disease had been eradicated and was officially designated a CSF-free country since 2015. Following the detection of the first 2018 case on a farm in Gifu Prefecture, the disease spread among both farm pigs and wild boars and still continues. Epigenome analysis using whole-genome information is helpful in identifying the infection route, but the current approaches provide an insufficient resolution. In this study, a novel method of using single-nucleotide variants (SNVs) was employed to identify the associations among 158 isolates (65 from farms and 93 from wild boars). The identified groups of CSFV strains were plotted in different colours on a map, identifying the location where each strain was collected. The lack of an SNV set shared between the index case and the other strains suggested the first infection in Japan during the outbreak occurred in wild boars, not at the index farm. For the Atsumi Peninsula outbreaks, where nine farms were found infected within a 10-km radius area, the farm strains were assembled into three groups, suggesting these outbreaks resulted from at least three different infection events in this area. For the infections in the area around Saitama Prefecture, an area remote from the epicentre, strains from both the farms and wild boars were identified as being in the same group, suggesting they resulted from one viral introduction. Likewise, seven infected farms in Okinawa Prefecture, almost 1,500 km from Gifu Prefecture, were identified as being in a common, but separate group. By demonstrating the variety of transmission routes and possibility of long-distance infection, these results will help improve disease control measures.

Phylogenetic and phylodynamic analysis of a classical swine fever virus outbreak in Japan (2018-2020).

After 26 years, another classical swine fever virus (CSFV) outbreak in domestic pigs and wild boars occurred in Japan 2018. Herein, we investigated the entry and the spatial dynamics of the CSFV outbreak in Japan using the nearly complete genomes of strains isolated from both wild boars and domestic pigs during this epidemic. Phylogenetic analysis showed that the most recent common ancestor (MRCA) of the Japanese lineage emerged 146 days (95% highest posterior density (HPD): 85-216 days) before the index case was detected. Based on epidemiological analysis, the period for the 95% HPD was 1 month earlier than the time of virus introduction into the index farm. The disease mainly spreads to the adjoining regions during the epidemic, with no spread to the nonadjacent regions. This result indicates that human activities, such as the movement of vehicles, contributed to the infection spread. As cases occurred in nonadjacent regions, the MRCA for the epidemic in the Saitama prefecture was estimated to have emerged 93 days before the date of detection in the initial farm in this region. Similarly, the MRCA for the epidemic in Okinawa prefecture, more than 1,300 km away from the other infected regions, was estimated to have emerged 34 days before the date of detection in the region's primary farm. Therefore, our results indicate that if exotic diseases emerge after a long period of absence or in a disease-free country, a longer period of time will elapse before detection, resulting in further spread. Additionally, subsequent infections occurring in regions distant from the original infected region will require less time for detection than in the original region. This study provides valuable insights into a CSFV outbreak that occurred in a previously CSFV-free country and thus beneficial in enhancing producers' awareness and allow for better preparation for infections.

Thyroid Hormone Plays an Important Role in Cardiac Function: From Bench to Bedside.

Thyroid hormones (THs) are synthesized in the thyroid gland, and they circulate in the blood to regulate cells, tissues, and organs in the body. In particular, they exert several effects on the cardiovascular system. It is well known that THs raise the heart rate and cardiac contractility, improve the systolic and diastolic function of the heart, and decrease systemic vascular resistance. In the past 30 years, some researchers have studied the molecular pathways that mediate the role of TH in the cardiovascular system, to better understand its mechanisms of action. Two types of mechanisms, which are genomic and non-genomic pathways, underlie the effects of THs on cardiomyocytes. In this review, we summarize the current knowledge of the action of THs in the cardiac function, the clinical manifestation and parameters of their hemodynamics, and treatment principles for patients with hyperthyroid- or hypothyroid-associated heart disease. We also describe the cardiovascular drugs that induce thyroid dysfunction and explain the mechanism underlying the thyroid toxicity of amiodarone, which is considered the most effective antiarrhythmic agent. Finally, we discuss the recent reports on the involvement of thyroid hormones in the regulation of myocardial regeneration and metabolism in the adult heart.

Histopathological, Immunohistochemical and In-Situ Hybridization Findings in Suckling Rats Experimentally Infected With Akabane Genogroups â and â ¡, Aino and Peaton Viruses.

Akabane, Aino and Peaton viruses are closely related arthropod-borne viruses in the genus Orthobunyavirus of the family Peribunyaviridae that can cause congenital abnormalities in cattle, sheep and goats. East Asian Akabane virus strains are subdivided into genogroups Ⅰ and Ⅱ, and the former can also cause non-suppurative encephalomyelitis in post-natal animals. Specific detection of the infecting virus in tissues is essential for accurate diagnosis. Immunohistochemistry (IHC) has been used to identify viral antigen but cannot always detect specific viruses due to potential cross-reactivity of the primary antisera. We compared in-situ hybridization (ISH), based on the use of cocktail probe sets targeted at the RNA of each virus, with IHC for the detection of the specific viruses in tissues of suckling rats inoculated intracerebrally with Akabane (KM-1 or OBE-1 strains), Aino or Peaton viruses at 3 or 7 days of age. Most inoculated rats developed severe neurological signs and histopathological brain lesions including necrosis, spongy degeneration and non-suppurative inflammation. A rabbit polyclonal antiserum immunolabelled antigen of all three viruses within the lesions, whereas ISH specifically detected RNA of each individual virus. The distribution of viral RNA was comparable to that of viral antigens, but tended to be more widespread, especially in immature nervous tissue. Viral antigen and RNA were detected in skeletal muscle and heart of the rats infected with the KM-1 strain of Akabane virus but not with any of the other viruses. This study demonstrates the value of ISH detection of these viruses in a rat model and may prove useful for clarification of the pathogenesis of post-natal arbovirus infection.

Medium-chain triglycerides inhibit long-chain triglyceride-induced GIP secretion through GPR120-dependent inhibition of CCK.

Long-chain triglycerides (LCTs) intake strongly stimulates GIP secretion from enteroendocrine K cells and induces obesity and insulin resistance partly due to GIP hypersecretion. In this study, we found that medium-chain triglycerides (MCTs) inhibit GIP secretion after single LCT ingestion and clarified the mechanism underlying MCT-induced inhibition of GIP secretion. MCTs reduced the CCK effect after single LCT ingestion in wild-type (WT) mice, and a CCK agonist completely reversed MCT-induced inhibition of GIP secretion. In vitro studies showed that medium-chain fatty acids (MCFAs) inhibit long-chain fatty acid (LCFA)-stimulated CCK secretion and increase in intracellular Ca2+ concentrations through inhibition of GPR120 signaling. Long-term administration of MCTs reduced obesity and insulin resistance in high-LCT diet-fed WT mice, but not in high-LCT diet-fed GIP-knockout mice. Thus, MCT-induced inhibition of GIP hypersecretion reduces obesity and insulin resistance under high-LCT diet feeding condition.

Successful Leadless Pacemaker Implantation in an Elderly Patient With Dextrocardia and Situs Inversus.

Leadless pacemaker is indicated in patients with symptomatic bradycardia as an alternative therapy when transvenous pacemaker implantation is considered difficult or at high risk. The experience of implanting leadless pacemaker in patients with dextrocardia and situs inversus is limited. A 94-year-old male was transferred to our hospital due to advanced atrio-ventricular block with episode of syncope. Chest radiograph and computed tomography revealed dextrocardia with situs inversus. Emergency cardiac catheterization was performed and a temporary pacemaker was inserted, but the patient removed it due to delirium. So, a leadless pacemaker was implanted to him. Shorter time of bed-rest after the implantation and shorter hospital stay would be beneficial of implanting a leadless pacemaker. Precise anatomical evaluation would be important to perform implantation efficiently and safely.

Isolation of epizootic hemorrhagic disease virus serotype 7 from cattle showing fever in Japan in 2016 and improvement of a reverse transcription-polymerase chain reaction assay to detect epizootic hemorrhagic disease virus.

Epizootic hemorrhagic disease (EHD) is an arthropod-borne disease of wild and domestic ruminants caused by the EHD virus (EHDV). To date, seven EHDV serotypes have been identified. In Japan, strain Ibaraki of EHDV serotype 2 has caused outbreaks of Ibaraki disease in cattle. In addition, EHDV serotype 7 (EHDV-7) has caused large-scale EHD epizootics. In mid-September 2016, eight cattle at a breeding farm in Fukuoka Prefecture, Japan developed fever. Since EHDV-7 was detected in sentinel cattle in western Japan in 2016, we suspected that the cause of this fever might be an EHDV-7 infection. In this study, we tested cattle for EHDV-7 and some other viruses. Consequently, EHDV was isolated from washed blood cells collected from three of the eight cattle, and genetic analysis of genome segment 2 revealed that this isolate was EHDV-7. Moreover, all affected cattle tested positive for anti-EHDV-7 neutralizing antibodies. Our results suggest that the fever was caused by EHDV-7 infection. In addition, we modified a conventional reverse transcription polymerase chain reaction assay for the specific detection of EHDV. This modified assay could detect various strains of EHDV isolated in Japan, Australia, and North America. Furthermore, the assay permitted the detection of EHDV-7 in blood cells collected from seven of the eight cattle. We believe that this modified assay will be a useful tool for the diagnosis of EHD.

Immunohistochemical Study of Mitochondrial Ferritin in the Midbrain of Patients with Progressive Supranuclear Palsy.

Mitochondrial ferritin (FtMt) is a novel ferritin that is localized in the mitochondria. FtMt expression is low in the liver and spleen, and high in the heart, testis, and brain. We previously detected FtMt in dopaminergic neurons in the substantia nigra pars compacta (SNc) in human and monkey midbrains. We investigated the localization and expression of FtMt in the midbrain of patients with progressive supranuclear palsy (PSP) and controls using a monoclonal antibody (C65-2) against human FtMt. FtMt immunoreactivity was weakly detected in neuromelanin-containing neurons in the SNc and ventral tegmental area (VTA) of control cases compared with PSP, which exhibited a remarkable increase in FtMt immunoreactivity. Preincubation of C65-2 with the immunizing FtMt peptide significantly reduced the staining, indicating the specificity of C65-2. Several puncta were observed outside the neurons of PSP, in contrast with the control cases. Double immunofluorescence histochemistry for FtMt and tyrosine hydroxylase (TH), glial fibrillary acidic protein, and Iba1 showed localization of FtMt in dopaminergic neurons, microglia, and astrocytes in PSP. Furthermore, FtMt immunoreactivity was detected in a few TH-negative neurons. In the SNc and VTA, FtMt immunoreactivity colocalized with phosphorylated tau immunoreactivity. Our results indicate that FtMt is involved in the pathology of PSP. Clarifying the involvement of FtMt in PSP is of great interest.