Optimal vaccine allocation strategy: Theory and application to the early stage of COVID-19 in Japan.

In this paper, we construct an age-structured epidemic model to analyze the optimal vaccine allocation strategy in an epidemic. We focus on two topics: the first one is the optimal vaccination interval between the first and second doses, and the second one is the optimal vaccine allocation ratio between young and elderly people. On the first topic, we show that the optimal interval tends to become longer as the relative efficacy of the first dose to the second dose (RE) increases. On the second topic, we show that the heterogeneity in the age-dependent susceptibility (HS) affects the optimal allocation ratio between young and elderly people, whereas the heterogeneity in the contact frequency among different age groups (HC) tends to affect the effectiveness of the vaccination campaign. A counterfactual simulation suggests that the epidemic wave in the summer of 2021 in Japan could have been greatly mitigated if the optimal vaccine allocation strategy had been taken.

Heterogeneous risk attitudes and waves of infection.

Many countries have experienced multiple waves of infection during the COVID-19 pandemic. We propose a novel but parsimonious extension of the SIR model, a CSIR model, that can endogenously generate waves. In the model, cautious individuals take appropriate prevention measures against the virus and are not exposed to infection risk. Incautious individuals do not take any measures and are susceptible to the risk of infection. Depending on the size of incautious and susceptible population, some cautious people lower their guard and become incautious-thus susceptible to the virus. When the virus spreads sufficiently, the population reaches "temporary" herd immunity and infection subsides thereafter. Yet, the inflow from the cautious to the susceptible eventually expands the susceptible population and leads to the next wave. We also show that the CSIR model is isomorphic to the SIR model with time-varying parameters.

Effect of in-patient cardiac rehabilitation at rehabilitation hospital for cardiology patients: two-center trial.

The effectiveness of cardiac rehabilitation (CR) in patients with cardiovascular disease requiring continuous CR from an acute care hospital to a convalescent rehabilitation hospital is unknown. Therefore, we compared the effect of CR in a rehabilitation hospital for patients with cardiovascular disease with that of those who underwent cardiovascular surgery. Sixty-nine consecutive patients were admitted to two rehabilitation hospitals for CR. Patients were classified by primary disease into two groups: patients with cardiovascular disease (cardiology group, 26 patients) and patients who underwent cardiovascular surgery (surgery group, 43 patients). Clinical information, physical function, cognitive function, activities of daily living (ADL), quality of life (QOL), amount of CR, and length of hospital stay were compared between the two groups. Compared with clinical features, age was significantly higher in the cardiology group (P < 0.001), and the preadmission Barthel index was significantly lower in the cardiology group (P = 0.025). Physical function at the time of transfer was significantly lower in the cardiology group than in the surgery group for the short physical performance battery (P < 0.001), gait speed (P = 0.005), and 6-min walking distance (P = 0.042). No significant difference was found in the amount of CR performed or the length of hospital stay, and no interaction effects were observed in improvements in physical function, exercise tolerance, or QOL. In conclusion, in rehabilitation hospitals, patients with cardiovascular disease were older, had lower preadmission ADL, and had lower a physical function at transfer than those who underwent cardiovascular surgery, but CR improved physical function and QOL to the same extent. The results suggest that the recovery of patients with cardiovascular disease may be similar to those who undergo cardiovascular surgery.

Safety monitoring of COVID-19 vaccines in Japan.

The assessment of the efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines in actual practice is extremely important, and monitoring efforts are being implemented worldwide. In Japan, a joint council in the Ministry of Health, Labour and Welfare is held every two to three weeks to summarise information on the adverse events following COVID-19 vaccination, with careful assessment of individual case safety reports and comparison with background incidence rates. In 2021, the joint council mainly reviewed anaphylaxis, death, myocarditis/pericarditis, and thrombosis with thrombocytopenia syndrome. These activities resulted in several safety-related regulatory actions, including the revision of vaccine package inserts with warnings about myocarditis/pericarditis. International sharing of vaccine safety information, as well as details of the evaluation systems, is important for international discussion and decision-making on better safety monitoring of COVID-19 vaccines.

Correction to: COVID­19 and output in Japan.

[This corrects the article DOI: 10.1007/s42973-021-00098-4.].

COVID-19 and output in Japan.

We build a tractable SIR-macro-model with time-varying parameters and use it to explore various policy questions such as when to lift the state of emergency (SOE). An earlier departure from the SOE results in smaller output loss and more deaths in the short run. However, if the SOE is lifted too early, the number of new cases will surge and another SOE may need to be issued in the future, possibly resulting in both larger output loss and more deaths. That is, the tradeoff between output and infection that exists in the short run does not necessarily exist in the long run. Our model-based analysis-updated weekly since January 2021, frequently reported by media, and presented to policymakers on many occasions-has played a unique role in the policy response to the COVID-19 crisis in Japan.

Design of RGDS Peptide-Immobilized Self-Assembling ß-Strand Peptide from Barnacle Protein.

We designed three types of RGD-containing barnacle adhesive proteins using self-assembling peptides. In the present study, three types of RGD-containing peptides were synthesized by solid-phase peptide synthesis, and the secondary structures of these peptides were analyzed by CD and FT-IR spectroscopy. The mechanical properties of peptide hydrogels were characterized by a rheometer. We discuss the correlation between the peptide conformation, and cell attachment and cell spreading activity from the viewpoint of developing effective tissue engineering scaffolds. We created a peptide-coated cell culture substrate by coating peptides on a polystyrene plate. They significantly facilitated cell adhesion and spreading compared to a non-coated substrate. When the RGDS sequence was modified at N- or C-terminal of R-Y, it was found that the self-assembling ability was dependent on the strongly affects hydrogel formation and cell adhesion caused by its secondary structure.

Collagenous Alzheimer amyloid plaque component impacts on the compaction of amyloid-ß plaques.

Massive deposition of amyloid ß peptides (Aß) as senile plaques (SP) characterizes the brain pathology of Alzheimer's disease (AD). SPs exhibit a variety of morphologies, although little is known about the SP components that determine their morphology. Collagenous Alzheimer amyloid plaque component (CLAC) is one of the major non-Aß proteinaceous components of SP amyloid in AD brains. Here we show that overexpression of CLAC precursor (CLAC-P) in the brains of APP transgenic mice results in a significant remodeling of amyloid pathology, i.e., reduction in diffuse-type amyloid plaques and an increase in compact plaques laden with thioflavin S-positive amyloid cores. In vivo microdialysis revealed a significant decrease in Aß in the brain interstitial fluid of CLAC-P/APP double transgenic mice compared with APP transgenic mice. These findings implicate CLAC in the compaction of Aß in amyloid plaques and the brain dynamics of Aß.

Synthesis and Photophysical Properties of Two Diazaporphyrin-Porphyrin Hetero Dimers in Polar and Nonpolar Solutions.

Two diazaporphyrin (DAP)-porphyrin hetero dimers, in ß-meso and ß-ß configurations, were prepared to study their photoinduced intramolecular electron transfer properties. The two meso nitrogen atoms in the porphyrin ring of DAP change its redox potential, making DAP more easily reduced, compared to its porphyrin counterpart. A charge-transfer from porphyrin to DAP in both hetero dimers was verified by versatile optical spectroscopic methods. The steady-state fluorescence spectra indicated an efficient intramolecular exciplex formation for both dimers. For the ß-meso dimer, ultrafast time-resolved spectroscopic methods revealed the subpicosecond formation of two types of primary short-living (1-18 ps) intramolecular exciplexes, which relaxed in toluene to form a long-living final exciplex (1.4 ns) followed by a longer-living charge transfer complex (>5 ns). However, in benzonitrile, the lifetime of the final exciplex was longer (660 ps) as was that of the charge transfer complex (180 ps). The ß-ß analogue formed similar short-living exciplexes in both solvents, but the final exciplex and the charge transfer state had significantly shorter lifetimes. The electrochemical redox potential measurements and density functional theory calculations supported the proposed mechanism.

Covalently linked 5,15-diazaporphyrin dimers: promising scaffolds for a highly conjugated azaporphyrin π system.

The first examples of ß-ß directly linked, acetylene-bridged, and butadiyne-bridged 5,15-diazaporphyrin dimers have been prepared by palladium-catalyzed coupling reactions of nickel(II) and copper(II) complexes of 3-bromo-10,20-dimesityl-5,15-diazaporphyrin (mesityl=2,4,6-trimethylphenyl). The effects of the linking modes and meso-nitrogen atoms on the structural, optical, electrochemical, and magnetic properties of the distributed π systems were investigated by using X-ray crystallography, UV/Vis absorption spectroscopy, DFT calculations, cyclic voltammetry, and ESR spectroscopy. Both the electronic and steric effects of the meso-nitrogen atoms play an important role in the highly coplanar geometry of the directly linked dimers. The direct ß-ß linkage produces enhanced π conjugation and electron-spin coupling between the two diazaporphyrin units.

CLAC-P/collagen type XXV is required for the intramuscular innervation of motoneurons during neuromuscular development.

Formation of proper neuromuscular connections is a process coordinated by both motoneuron-intrinsic and target-dependent programs. Under these programs, motoneurons innervate target muscles, escape programmed cell death during fetal development, and form neuromuscular junctions (NMJ). Although a number of studies have revealed molecules involved in axon guidance to target muscles and NMJ formation, little is known about the molecular mechanisms linking intramuscular innervation and target-derived trophic factor-dependent prevention of motoneuron apoptosis. Here we studied the physiological function of CLAC-P/collagen XXV, a transmembrane-type collagen originally identified as a component of senile plaque amyloid of Alzheimer's disease brains, by means of generating Col25a1-deficient (KO) mice. Col25a1 KO mice died immediately after birth of respiratory failure. In Col25a1 KO mice, motor axons projected properly toward the target muscles but failed to elongate and branch within the muscle, followed by degeneration of axons. Failure of muscular innervation in Col25a1 KO mice led to excessive apoptosis during development, resulting in almost complete and exclusive loss of spinal motoneurons and immaturity in skeletal muscle development. Bax deletion in Col25a1 KO mice rescued motoneurons from apoptosis, although motor axons remained halted around the muscle entry site. Furthermore, these motoneurons were positive for phosphorylated c-Jun, an indicator of insufficient supply of target-derived survival signals. Together, these observations indicate that CLAC-P/collagen XXV is a novel essential factor that regulates the initial phase of intramuscular motor innervation, which is required for subsequent target-dependent motoneuron survival and NMJ formation during development.

Identification of serum proteins related to adverse effects induced by docetaxel infusion from protein expression profiles of serum using SELDI ProteinChip system.

BACKGROUND: For the development of quick and easy methods for screening and identifying treatment-responsive proteins, we determined the protein expression profile of the serum after docetaxel infusion using a surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI TOF-MS) system. MATERIALS AND METHODS: Blood from breast cancer patients was collected before and 4, 8, 24 and 48 hours after docetaxel infusion. The protein expression profile was determined by a SELDI TOF-MS system. The relative expression levels of target proteins were compared during the time-course after docetaxel injection. RESULTS: We identified two representative proteins with molecular weights of 7790 Da and 9285 Da. The 7790 Da protein was high molecular weight kininogen, and the 9285 Da protein was apolipoprotein A-II. These two proteins had similar expression patterns in 5 patients, except one patient who experienced severe, acute, adverse effects. CONCLUSION: These results suggest that protein expression profiles determined by SELDI TOF-MS represent useful data for the identification of treatment-responsive proteins.

The ligands of peroxisome proliferator-activated receptor (PPAR) gamma inhibit growth of human esophageal carcinoma cells through induction of apoptosis and cell cycle arrest.

In the present study, we examined the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and the growth-inhibitory effects of Troglitazone and Pioglitazone, selective ligands for PPARgamma, using a series of human esophageal carcinoma cell lines (TE-1, -3, -7, -8, -12 and -13). PPARgamma expression was detected in all six human esophageal carcinoma cell lines. The esophageal carcinoma cell line TE-13 showed marked growth inhibition in response to Troglitazone and Pioglitazone. Flow cytometry performed on TE-13 cells exposed to Troglitazone showed that the cell cycle was arrested at the G1-phase. This result was confirmed by the finding of reduced cyclin D and cyclin E expression by Western blot analysis. DNA ladder formation was also detected, as was the induction of apoptosis-related proteins. Our results suggested that Troglitazone inhibited the growth of human esophageal carcinoma cell lines via G1 arrest and apoptosis and that PPARgamma ligands should be considered as possible target molecules in the treatment of human esophageal carcinomas.

Induction mechanism of apoptosis by troglitazone through peroxisome proliferator-activated receptor-gamma in gastric carcinoma cells.

BACKGROUND: It has been reported recently that the antidiabetic thiazolidinediones not only induce fibroblast differentiation but also inhibit the growth of carcinoma cells. MATERIALS AND METHODS: In the present study, in order to elucidate the further mechanism of growth inhibition by troglitazone, the expression of cell cycle regulators and apoptotic regulators were examined by cDNA microarrays and Western blot analysis by gastric carcinoma cells. RESULTS: Six gastric carcinoma cell lines (TMK-1, MKN-1,7,28,45,74) were treated with 0.1, 1, 10, 100 microM of troglitazone in vitro. The growth of 5 cell lines were inhibited by troglitazone in a time- and dose-dependent manner. Interestingly, the expression of cyclin D mRNA and protein was decreased and that of p27 was increased in TMK-1 cells at 12 hours after troglitazone treatment, suggesting the induction of cell cycle arrest of the cells. On the other hand, DNA ladder formation was observed at 12 hours after treatment. Moreover, the expression of cytochrome C, caspases 3 and 8 and PARP genes was increased after treatment and the gradual reduction of Bcl-XL protein was observed, which indicate that the apoptotic signals were induced after treatment by troglitazone. CONCLUSION: These results suggest that the thiazolidinediones can be a new therapeutic tool for gastric carcinoma via cell cycle regulation and apoptosis.