Staphylococcal enterotoxin B is involved in aggravation and recurrence of murine experimental autoimmune uveoretinitis via Vβ8CD4 T cells

Endogenous uveitis is a common cause of visual disability and blindness. The etiology of uveitis remains largely unknown but reasonable etiologic factors include infections. Superantigens are regarded as one of the leading causes of infectious etiology in autoimmune disease. However, the role of superantigens in uveitis remains unclear. In the present study, we investigated the effect of Staphylococcal enterotoxin B (SEB), a member of the superantigens, using an experimental model of autoimmune uveoretinitis (EAU). C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein (IRBP) peptide, and the severity of EAU disease was scored. Vehicle (PBS) alone or SEB dissolved in PBS was administered by intravenous injection on post-immunization day 10 or on post-immunization day 24. In addition, a systemic immune response study was performed to address the effects of SEB on systemic immunity. EAU was aggravated significantly by the injection of SEB at post-immunization day 10. Furthermore, relapse was induced by the injection of SEB at day 24. On the other hand, SEB injection without IRBP peptide immunization elicited no inflammatory changes in the uvea or retina. Furthermore, SEB enhanced not only the IRBP-specific T-cell proliferative responses but also IFN-γ and IL-17 production. Moreover, the intraocular expression levels of these cytokines was also enhanced by SEB injection. Both anti-CD4 and -Vβ8 Ab administration suppressed disease aggravation and the enhancement of IRBP-specific T-cell responses caused by SEB. These results suggest that SEB is involved significantly in the aggravation or recurrence of endogenous uveitis through activation of autoreactive uveitogenic T cells.     

Efficacy and Safety of a Strategy for Reviewing Intravenous Antibiotics for Hospitalized Japanese Patients with Uncomplicated Diverticulitis: A Single-center Observational Study

Objective Treatment for uncomplicated diverticulitis (UD) is not well established. We evaluated the strategy of reviewing intravenous antibiotics for hospitalized Japanese patients with UD. Methods Treatment was based on the physician''s choice until August 2018; the indications for hospitalization and treatment have been standardized since September 2018. In this study, we monitored the use of intravenous antibiotics administered to patients hospitalized for UD and then reviewed the need for them on hospital day 3. We compared patients'' length of antibiotic use, hospital stay, health care cost, and complications via the review strategy from September 2018 to December 2020 and via the previous physicians'' choice strategy from January 2016 to August 2018. Results Two hundred and forty-seven patients were admitted to our hospital because of acute colonic diverticulitis from January 2016 to December 2020. After excluding complicated cases, 106 individuals were enrolled during the period of physician''s choice; 87 were enrolled when treatment review was employed. There were no significant differences in age, sex, inflammation site, or severity during the first hospital visit. The median duration of antibiotic use was significantly reduced from 5 to 4 days (p=0.0075), with no marked increase in rates of transfer to surgery, mortality, or readmission due to recurrence. A more significant proportion of patients completed 3-day antibiotic treatment with the review strategy than with the physician''s choice strategy (6.6% vs. 25.3%, p=0.0004). However, the length of hospital stay and total medical costs did not decrease. Conclusion The strategy of reviewing treatment on day 3 after hospitalization for UD safety reduced the duration of antibiotic use, but the hospital stay and health care costs did not decrease.     

The interrelationship between three-dimensional foot mobility and bodyweight bearing

[Purpose] To clarify the three-dimensional nature of foot mobility and its interrelationships within the foot due to bodyweight bearing. [Participants and Methods] Data regarding left foot mobility due to body weight bearing were collected from 31 healthy adults. Foot shape differences while sitting and standing, and their interrelationship were examined. The same examiner reapplied the landmark stickers when misaligned during measurement position changes. [Results] The foot length, heel width, forefoot width, hallux valgus angle, and calcaneus eversion angle were significantly larger in the standing than in sitting position. The digitus minimus varus angle was significantly smaller in the standing than in sitting position. The medial and lateral malleoli, navicular, and dorsum of the foot were displaced medially and inferiorly; the other indices, except for the midfoot, were displaced anteriorly. The interrelationships within the foot showed a positive correlation between the calcaneus eversion angle and the medial displacement of the medial and lateral malleoli, navicular, and dorsum of the foot points. There was a negative correlation between the calcaneus eversion angle and inferior displacement of the medial malleolus, navicular, and dorsum of the foot. [Conclusion] The intra-foot coordination relationship in response to bodyweight bearing was clarified.     

Genetically Diverse Highly Pathogenic Avian Influenza A(H5N1/H5N8) Viruses among Wild Waterfowl and Domestic Poultry,Japan, 2021

Genetic analyses of highly pathogenic avian influenza H5 subtype viruses isolated from the Izumi Plain, Japan, revealed cocirculation of 2 genetic groups of clade 2.3.4.4b viruses among migratory waterfowl. Our findings demonstrate that both continuous surveillance and timely information sharing of avian influenza viruses are valuable for rapid risk assessment.     

Effect of long‐term depletion of plasma methionine on the growth and survival of human brain tumor xenografts in athymic mice

Depletion of plasma methionine is expected to inhibit or reverse growth of methionine‐dependent tumors; however, modulation of methionine and other sulfur amino acids is not a trivial task in experimental animals. l‐Methioninase from Pseudomonas putida at 1,000 U/kg causes acute reduction of plasma methionine by 80% in mice, but recovery occurs within 14 hours. Restriction of dietary choline and replacement of dietary methionine with homocystine results in 50% chronic reduction of plasma methionine. A >70% reduction can be accomplished with a diet deficient in methionine, homocystine, and choline, but ultimately this diet is lethal. Plasma methionine can be lowered to a steady state of <5 μM in mice with a combination of dietary restriction of methionine, homocysteine, and choline and synchronous treatments with intraperitoneal injections of 1,000 U/kg L‐methioninase and 25–50 mg/kg homocystine, each administered at 12‐hour intervals. Modulation of plasma methionine by this means causes no weight loss or pathologies in liver or pancreas, and it does not markedly alter levels of cysteine, homocysteine, or glutathione in plasma or in hepatic tissue. When this procedure is applied to athymic mice bearing human medulloblastoma (Daoy) tumors subcutaneously, tumor growth is inhibited. Methionine deprivation arrests mitosis by blocking the cell cycle in G2 and induces apoptosis. Tumor stasis was achieved in 100% of treated animals within 4 days of treatment, and regression was seen in one‐third of animals after a 10‐day period. These data strongly support the use of methionine‐depleting regimens for tumor treatments.