An atypical surge in RSV infections among children in Saitama, Japan in 2021.

Background: In 2021, atypical seasonal respiratory syncytial virus (RSV) outbreaks were observed in several countries. However, the peak, duration, and severity of these outbreaks have not been assessed. Methods: Data were collected from almost all facilities with pediatric wards in Saitama Prefecture, Japan. Variables included the weekly number of patients admitted with RSV infection, their age, and the number of patients who required intubation. The average weekly admission rates (number of patients admitted divided by the number of hospitals) were compared by pre-pandemic year (2018 and 2019) and 2021, using analysis of variance. Results: In 2021, 1354 patients were admitted with RSV infection. The median age of the patients was < 12 months. The admission rate peaked around week 30. The slope of the peak in 2021 was markedly steeper than in the previous years. The mean weekly admission rate did not differ significantly between 2018, 2019, and 2021 (p = 0.77). The proportions of intubated patients did not differ significantly over the 4 years (2018-2021, p = 0.68). Conclusion: The overall number of RSV admissions and intubation rate in 2021 were similar to those in pre-pandemic years.

A distinct association of inflammatory molecules with outcomes of COVID-19 in younger versus older adults.

Aging can alter immunity affecting host defense. COVID-19 has the most devastating clinical outcomes in older adults, raising the implication of immune aging in determining its severity and mortality. We investigated biological predictors for clinical outcomes in a dataset of 13,642 ambulatory and hospitalized adult COVID-19 patients, including younger (age < 65, n = 566) and older (age ≥ 65, n = 717) subjects, with in-depth analyses of inflammatory molecules, cytokines and comorbidities. Disease severity and mortality in younger and older adults were associated with discrete immune mechanisms, including predominant T cell activation in younger adults, as measured by increased soluble IL-2 receptor alpha, and increased IL-10 in older adults although both groups also had shared inflammatory processes, including acute phase reactants, contributing to clinical outcomes. These observations suggest that progression to severe disease and death in COVID-19 may proceed by different immunologic mechanisms in younger versus older subjects and introduce the possibility of age-based immune directed therapies.

Potential of circulating tumor DNA as a predictor of therapeutic responses to immune checkpoint blockades in metastatic renal cell carcinoma.

We evaluated the predictive role of circulating tumor DNA (ctDNA) detection by targeted deep sequencing in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint blockades (ICB). To determine the feasibility of ctDNA detection in our panel encompassing 40 genes, we collected 10 ml of blood from 20 patients at the time of radical nephrectomy. We analyzed somatic mutations in primary tumors and ctDNA samples from these patients. We finally collected 10 ml of blood before and after 1 month of treatment, respectively, from four patients with mRCC who received first-line ICB treatment. Variants were detected in primary tumors of 15 patients (75%) and ctDNA was detected in the plasma of 9 patients (45%). We examined the predictive role of ctDNA in four patients who received first-line ICB therapy. In two patients showing partial response, ctDNA levels decreased after 1 month of ICB treatment. However, in one patient who showed disease progression, ctDNA levels increased after 1 month of ICB treatment. Taken together, ctDNA detection in plasma by targeted deep sequencing was feasible in patients with RCC. Moreover, the levels of ctDNA could be an early predictor of treatment response in patients with mRCC who receive ICB therapy.

The survival role of peroxisome proliferator-activated receptor gamma induces odontoblast differentiation against oxidative stress in human dental pulp cells.

INTRODUCTION: Peroxisome proliferator-activated receptor gamma (PPARγ) has well-known anti-inflammatory action in human dental pulp cells (HDPCs). The purpose of this study was to investigate whether the anti-inflammatory action of PPARγ involves in cellular cytoprotection and supports odontoblast differentiation under oxidative stress in HDPCs. METHODS: To simulate long-term oxidative stress, pulp cells were treated with 150 µmol hydrogen peroxide (H(2)O(2)) for 12 days. The replication deficiency adenovirus (adenovirus PPARγ) was introduced for PPARγ overexpression in pulp cells. The cellular cytotoxicity and reactive oxygen species formation by H(2)O(2) were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 2',7'-dichlorodihydrofluorescein diacetate with fluorescence-activated cell sorting assay. To determine the roles of PPARγ, several molecules of odontogenic/osteogenic and signal pathway were analyzed by reverse-transcription polymerase chain reaction and Western hybridization. Dentin mineralization was determined by alizarin red stain and alkaline phosphatase activity assay. RESULTS: Pulp cells treated with long-term H(2)O(2) showed high reactive oxygen species formation, low cell viability, down-expression of antioxidant molecules (Cu/Zn and Mn superoxide dismutase), and odontogenic/osteogenic markers (eg, dentin sialophosphoprotein, dentin matrix protein-1, osteopontin, bone sialoprotein, Runx-2, and bone morphogenetic protein 2 and 7). In addition, pulp cells with oxidative stress underwent the activation of ERK1/2, activator protein-1, and nuclear factor-κB translocation to the nucleus. However, the PPARγ-overexpressed cells gave opposite results although under oxidative stress. Furthermore, PPARγ and its agonist rosiglitazone exhibited an induction of dentin mineralization under oxidative stress. CONCLUSIONS: PPARγ in pulp cells increases cell viability, odontoblastic differentiation, and dentin mineralization under oxidative stress. These results offer new insights into the potential antioxidative activity of PPARγ and its agonist for therapeutic agents for pulp vitality in HDPCs.

Sperm abnormalities in high- and low-dose-rate Gamma-irradiated Korean dark-striped field mice, Apodemus agrarius coreae.

To evaluate the in vivo effects of low-dose-rate (0.7 mGy h(-1)) gamma radiation, abnormal shapes of sperm in the caudal epidydimus of Apodemus agrarius coreae (A. a. coreae) were used. The six categories of abnormal forms (amorphous heads, blunt hooks, excessive hooks, two heads and tails, folded tails and short tails) of sperm were observed eight days after gamma irradiation (0, 0.5, 1 and 2 Gy) with a high dose rate (0.8 Gy min(-1)) and a low dose rate. The frequency of total abnormal sperm gradually increased starting from 0.5 Gy after high-dose-rate radiation. Blunt hooks and short tails shaped sperm, in particular, were gradually increasing in the high-dose-rate irradiated mice. Dose rate reduction effects for the frequency of abnormal sperms in low-dose-rate irradiated mice to high-dose-rate irradiated mice were 1 at 0.5 Gy, 0.7 at 1 Gy and 0.5 at 2 Gy. Our results indicate that low-dose-rate radiation is not detrimental to spermatogenic cells.