[Impact of border control measures on public health center operations and staffing at international airports during the emergence of the SARS-CoV-2 B.1.1.529 (Omicron) variant of concern].

Objective　Ota City, located in southeastern Tokyo, including Haneda Tokyo International Airport, has numerous scattered lodging facilities. Shortly after the first case of SARS-CoV-2 B.1.1.529 (Omicron) variant was reported abroad, the Japanese government strengthened border control measures, including quarantine procedures and public health official involvement, for incoming travelers. This study aims to propose effective and efficient border control measures to prevent future outbreaks of emerging and re-emerging infectious diseases.Methods　Border control measures implemented between November 2021 and mid-January 2022 were analyzed from three perspectives: chronological changes in government notifications, the situation of in-flight contacts and Omicron cases, and the support system for coronavirus-disease 2019 control department of the Ota City Public Health Center. Additionally, a questionnaire survey was conducted among public health centers with jurisdiction over the top four international airports. This survey aimed to assess the effectiveness of the support system, evaluate cooperation with related organizations, identify common issues faced by public health concerns, and gather suggestions for improvements in future border control measures.Results　The definition and treatment of in-flight contacts of Omicron-positive individuals were initially outlined on November 30, 2021, and underwent frequent revisions until January 14, 2022. Between December 1, 2021, and January 12, 2022, only one Omicron case was identified among the 470 tests conducted on in-flight contacts. However, out of 136 additional domestic specimens collected (including 57 positives for genetic analysis), 40 were confirmed Omicron positive. The results of the questionnaire survey across the four public health centers largely mirrored the issues and suggestions identified by Ota City officials. A significant portion of these issues arose from managing temporary non-Japanese residents staying near international airports.Conclusion　Border control measures should be implemented to delay the domestic spread of the virus. In this reason, it is crucial to avoid placing an undue burden on public health officials responsible for handling domestic infections. Since response policies and target definitions may need to adapt to unknown pathogens, they may be changed frequently, baffling the officials; however, a system for collecting real-time data from frontline sites and making evidence-based decisions is essential. Additionally, deploying liaisons from national and prefectural governments to focal points of emergency response would strengthen the support system by promoting unified instructions and information sharing.

[A case undergoing repeated anaphylactic shock after systemic administration of vinorelbine].

We here describe a 49-year-old man who suffered repeated anaphylactic shock after systemic chemotherapy with vinorelbine for stage IV left lung adenocarcinoma (S1+2). He was treated using a combination of cisplatin and weekly irinotecan (CPT-11) as the first line; however, the regimen was changed to a combination of vinorelbine (VNR) and gemcitabine (GEM) because of his progressive disease. He was admitted to our hospital for examination of the unknown cause of hypotension and loss of consciousness. The second shock occurred after eating pistachios, and the third one at cancerous pain. After pain control, the shock no longer occurred. Anaphylactic shock may show two peaks and late symptoms. In patients with a history of anaphylactic shock, we should pay attention to foods, drugs, and various stresses which might cause anaphylaxis.

Accumulated α-synuclein affects the progression of GM2 gangliosidoses.

The accumulation of α-synuclein (ASyn) has been observed in several lysosomal storage diseases (LSDs) but it remains unclear if ASyn accumulation contributes to LSD pathology. ASyn also accumulates in the neurons of Sandhoff disease (SD) patients and SD model mice (Hexb-/- ASyn+/+ mice). SD is a lysosomal storage disorder caused by the absence of a functional ß-subunit on the ß-hexosaminidase A and B enzymes, which leads to the accumulation of ganglioside in the central nervous system. Here, we explored the role of accumulated ASyn in the progression of Hexb-/- mice by creating a Hexb-/- ASyn-/- double-knockout mice. Our results show that Hexb-/- ASyn-/- mice demonstrated active microglia levels and less dopaminergic neuron loss, without altering the neuronal storage of ganglioside. The autophagy and ubiquitin proteasome pathways are defective in the neurons of Hexb-/- ASyn+/+ mice. In ultrastructural physiological studies, the mitochondria structures look degenerated and dysfunctional. As a result, expression of manganese superoxide dismutase 2 are reduced, and reactive oxygen species-mediated oxidative damage in the neurons of Hexb-/- ASyn+/+ mice. Interestingly, these dysfunctions improved in Hexb-/- ASyn-/- mice. But any clinical improvement were hardly observed in Hexb-/- ASyn-/- mice. Taken together, these findings suggest that ASyn accumulation plays an important role in the pathogenesis of neuropathy in SD and other LSDs, and is therefore a target for novel therapies.

Thymic alterations in GM2 gangliosidoses model mice.

BACKGROUND: Sandhoff disease is a lysosomal storage disorder characterized by the absence of ß-hexosaminidase and storage of GM2 ganglioside and related glycolipids. We have previously found that the progressive neurologic disease induced in Hexb(-/-) mice, an animal model for Sandhoff disease, is associated with the production of pathogenic anti-glycolipid autoantibodies. METHODOLOGY/PRINCIPAL FINDINGS: In our current study, we report on the alterations in the thymus during the development of mild to severe progressive neurologic disease. The thymus from Hexb(-/-) mice of greater than 15 weeks of age showed a marked decrease in the percentage of immature CD4(+)/CD8(+) T cells and a significantly increased number of CD4(+)/CD8(-) T cells. During involution, the levels of both apoptotic thymic cells and IgG deposits to T cells were found to have increased, whilst swollen macrophages were prominently observed, particularly in the cortex. We employed cDNA microarray analysis to monitor gene expression during the involution process and found that genes associated with the immune responses were upregulated, particularly those expressed in macrophages. CXCL13 was one of these upregulated genes and is expressed specifically in the thymus. B1 cells were also found to have increased in the thy mus. It is significant that these alterations in the thymus were reduced in FcRγ additionally disrupted Hexb(-/-) mice. CONCLUSIONS/SIGNIFICANCE: These results suggest that the FcRγ chain may render the usually poorly immunogenic thymus into an organ prone to autoimmune responses, including the chemotaxis of B1 cells toward CXCL13.