Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection.

Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics.

Postoperative Medial Tilting of the Joint Line and Preoperative Kinematics Influence Postoperative Medial Pivot Pattern Reproduction in Total Knee Arthroplasty.

Background: Reproducing the medial pivot pattern after total knee arthroplasty (TKA) is known to improve patient satisfaction. However, the factors affecting the postoperative medial pivot pattern in TKA are controversial. The purpose of this study was to examine the factors affecting the postoperative medial pivot pattern in posterior-stabilized TKA. Methods: This study involved 30 cases with knee osteoarthritis who underwent primary posterior-stabilized TKA. The preoperative and postoperative kinematics were measured using a computed tomography-free navigation system, and the patients were divided into the following 2 groups: the medial pivot pattern (MP) group and non-medial pivot pattern (non-MP) group. In addition, we measured each of the following angles on X-ray films (preoperative and postoperative femorotibial angle, hip-knee-ankle angle, mechanical lateral distal femoral angle, medial proximal tibial angle). We examine the factors affecting the postoperative medial pivot pattern. Results: There were 14 cases in the MP group and 16 cases in the non-MP group at the preoperative knee kinematic assessment and 17 cases in the MP group and 13 cases in the non-MP group at the postoperative knee kinematic assessment. The preoperative kinematic pattern was conserved after the surgery at a rate of 76.7%. The postoperative MP-group showed a significantly smaller preoperative femorotibial angle and hip-knee-ankle and a significantly smaller postoperative mechanical lateral distal femoral angle and medial proximal tibial angle in comparison to the postoperative non-MP group. Conclusions: Preoperative kinematics and postoperative mechanical lateral distal femoral angle and medial proximal tibial angle may be important factors that affect the postoperative medial pivot pattern.

Saturation time of exposure interval for cross-neutralization response to SARS-CoV-2: Implications for vaccine dose interval.

Evaluating the serum cross-neutralization responses after breakthrough infection with various SARS-CoV-2 variants provides valuable insight for developing variant-proof COVID-19 booster vaccines. However, fairly comparing the impact of breakthrough infections with distinct epidemic timing on cross-neutralization responses, influenced by the exposure interval between vaccination and infection, is challenging. To compare the impact of pre-Omicron to Omicron breakthrough infection, we estimated the effects on cross-neutralizing responses by the exposure interval using Bayesian hierarchical modeling. The saturation time required to generate saturated cross-neutralization responses differed by variant, with variants more antigenically distant from the ancestral strain requiring longer intervals of 2-4 months. The breadths of saturated cross-neutralization responses to Omicron lineages were comparable in pre-Omicron and Omicron breakthrough infections. Our results highlight the importance of vaccine dosage intervals of 4 months or longer, regardless of the antigenicity of the exposed antigen, to maximize the breadth of serum cross-neutralization covering SARS-CoV-2 Omicron lineages.

Non-Omicron breakthrough infection with higher viral load and longer vaccination-infection interval improves SARS-CoV-2 BA.4/5 neutralization.

The immune responses to SARS-CoV-2 variants in COVID-19 cases are influenced by various factors including pre-existing immunity via vaccination and prior infection. Elucidating the drivers for upgrading neutralizing activity to SARS-CoV-2 in COVID-19 cases with pre-existing immunity will aid in improving COVID-19 booster vaccines with enhanced cross-protection against antigenically distinct variants, including the Omicron sub-lineage BA.4/5. This study revealed that the magnitude and breadth of neutralization activity to SARS-CoV-2 variants after breakthrough infections are determined primarily by upper respiratory viral load and vaccination-infection time interval. Extensive neutralizing breadth, covering even the most antigenically distant BA.4/5, was observed in cases with higher viral load and longer time intervals. Antigenic cartography depicted a critical role of the time interval in expanding the breadth of neutralization to SARS-CoV-2 variants. Our results illustrate the importance of dosing interval optimization as well as antigen design in developing variant-proof booster vaccines.

Intranasal vaccination induced cross-protective secretory IgA antibodies against SARS-CoV-2 variants with reducing the potential risk of lung eosinophilic immunopathology.

To control the coronavirus disease 2019 (COVID-19) pandemic, there is a need to develop vaccines to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. One candidate is a nasal vaccine capable of inducing secretory IgA antibodies in the mucosa of the upper respiratory tract, the initial site of infection. However, regarding the development of COVID-19 vaccines, there is concern about the potential risk of inducing lung eosinophilic immunopathology as a vaccine-associated enhanced respiratory disease as a result of the T helper 2 (Th2)-dominant adaptive immune response. In this study, we investigated the protective effect against virus infection induced by intranasal vaccination of recombinant trimeric spike protein derived from SARS-CoV-2 adjuvanted with CpG oligonucleotides, ODN2006, in mouse model. The intranasal vaccine combined with ODN2006 successfully induced not only systemic spike-specific IgG antibodies, but also secretory IgA antibodies in the nasal mucosa. Secretory IgA antibodies showed high protective ability against SARS-CoV-2 variants (Alpha, Beta and Gamma variants) compared to IgG antibodies in the serum. The nasal vaccine of this formulation induced a high number of IFN-γ-secreting cells in the draining cervical lymph nodes and a lower spike-specific IgG1/IgG2a ratio compared to that of subcutaneous vaccination with alum as a typical Th2 adjuvant. These features are consistent with the induction of the Th1 adaptive immune response. In addition, mice intranasally vaccinated with ODN2006 showed less lung eosinophilic immunopathology after viral challenge than mice subcutaneously vaccinated with alum adjuvant. Our findings indicate that intranasal vaccine adjuvanted with ODN2006 could be a candidate that can prevent the infection of antigenically different variant viruses, reducing the risk of vaccine-associated enhanced respiratory disease.

Vaccination-infection interval determines cross-neutralization potency to SARS-CoV-2 Omicron after breakthrough infection by other variants.

Background: The immune profile against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by Omicron in individuals with various immune histories. Methods: The neutralization susceptibility of the variants, including Omicron and their ancestors, was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections of Alpha/Delta with multiple time intervals following vaccination. Findings: Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against Omicron was induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies. Conclusions: Immune histories with breakthrough infections can overcome the resistance to infection by Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against Omicron and future variants. Funding: This study was supported by grants from the Japan Agency for Medical Research and Development (AMED).

Effect of ganglionated plexi ablation by high-density mapping on long-term suppression of paroxysmal atrial fibrillation - The first clinical survey on ablation of the dorsal right plexusus.

BACKGROUND: Long-term outcomes of suppressing paroxysmal atrial fibrillation (PAF) with additive ganglionated plexus (GP) ablation (GPA) remains unknown. OBJECTIVES: The aim of the study is to assess potential role of additional GPA for PAF suppression. METHODS: This study consisted of 225 patients; 68 (group A: 58 male, aged 60 ± 11 years) underwent pulmonary vein isolation (PVI) alone and 157 (group B: 137 male, aged 61 ± 11 years) GPA followed by PVI. GPA was performed based on the high-density mapping with high-frequency stimulation (HFS) delivered to left atrial (LA) major GP. The latter 85 group B patients (54%) underwent ablation to a posteromedial area within superior vena cava as a part of dorsal right atrial GP (SVC-Ao GP). RESULTS: In group B, HFS was applied to 126 ± 32 sites, with a median of 47 GP sites (40.0%) being ablated. In patients undergoing an SVC-Ao GPA, HFS and the SVC-Ao GPA were applied at a median of 15 and 4 sites (29.4%), respectively. The PVI with a GPA provided higher PAF suppression than a PVI alone during more than 4 years of follow-up (56.7% vs 38.2%, odds ratio: 0.42, 95% confidence interval: 0.23-0.76, P < .05), but the SVC-Ao GPA did not provide further suppressive effects. Multivariate analyses revealed that tachycardia-bradycardia syndrome and non-PV foci were independent predictors of PAF recurrence after PVI with a GPA (P < .01). CONCLUSION: GPA to LA major GP by high-density mapping provides long-term benefits for PAF suppression over 4 years of follow-up, but the effect of an empiric SVC-Ao GPA could not be appreciated, suggesting little effect on suppressing non-PV foci.

Structure-Guided Creation of an Anti-HA Stalk Antibody F11 Derivative That Neutralizes Both F11-Sensitive and -Resistant Influenza A(H1N1)pdm09 Viruses.

The stalk domain of influenza virus envelope glycoprotein hemagglutinin (HA) constitutes the axis connecting the head and transmembrane domains, and plays pivotal roles in conformational rearrangements of HA for virus infection. Here we characterized molecular interactions between the anti-HA stalk neutralization antibody F11 and influenza A(H1N1)pdm09 HA to understand the structural basis of the actions and modifications of this antibody. In silico structural analyses using a model of the trimeric HA ectodomain indicated that the F11 Fab fragment has physicochemical properties, allowing it to crosslink two HA monomers by binding to a region near the proteolytic cleavage site of the stalk domain. Interestingly, the F11 binding allosterically caused a marked suppression of the structural dynamics of the HA cleavage loop and flanking regions. Structure-guided mutagenesis of the F11 antibody revealed a critical residue in the F11 light chain for the F11-mediated neutralization. Finally, the mutagenesis led to identification of a unique F11 derivative that can neutralize both F11-sensitive and F11-resistant A(H1N1)pdm09 viruses. These results raise the possibility that F11 sterically and physically disturbs proteolytic cleavage of HA for the ordered conformational rearrangements and suggest that in silico guiding experiments can be useful to create anti-HA stalk antibodies with new phenotypes.

Impact of bedrest on cardiovascular events and complications associated with temporary pacemakers in patients waiting for permanent pacemaker implantation.

BACKGROUND: Patients with a temporary pacemaker (TPM) for bradycardias are required to maintain bedrest until permanent pacemakers (PPMs) are implanted because of the development of Adams-Stokes syndrome, worsening heart failure, or complications associated with TPMs is anticipated. However, bedrest may be detrimental in patients because it leads to disuse syndrome. This study examined whether bedrest could decrease the incidence of cardiovascular events or complications associated with TPMs in patients waiting for PPM implantation. METHODS: We conducted a retrospective cohort study on 88 patients who had emergency hospitalization for the treatment of bradycardias, and a TPM was inserted during the waiting period before PPM implantation. We divided patients into two groups according to whether they underwent bedrest (Bedrest Group) or not (Ambulation Group) during the period that patients were supported with TPM. We evaluated whether bedrest was a predictor of adverse events using a logistic regression analysis. RESULTS: Adverse events occurred in 31 patients (35%). In the univariate analysis, there was no significant difference in the incidence of adverse events between the Bedrest and Ambulation Groups (39% vs. 29%). In the logistic regression analysis, bedrest was not a predictor of adverse events (odds ratio, 1.40; 95% confidence interval, 0.53-3.68, P = .497). CONCLUSIONS: In patients with TPMs for bradyarrhythmias during the waiting period for PPM implantations, bedrest might not prevent adverse events, such as cardiovascular events and complications associated with TPMs.

Hallux valgus deformity and postural sway: a cross-sectional study.

BACKGROUND: Hallux valgus deformity has been reported to be associated with increased postural sway. However, the direction and magnitude of postural sway associated with hallux valgus remain inconclusive. We assessed the association between hallux valgus deformity and postural sway using a force plate. METHODS: The subjects were 169 healthy volunteers, > 40 years old (63 males, 106 females, average age: 66.0 ± 12.4 years old), who took part in an annual medical examination. We investigated the photographic hallux valgus angle (°), total trajectory length of the gravity center fluctuation (mm), area of the center of pressure (mm2), mediolateral and anteroposterior postural sway (mm) in a standing position with 2-legged stance and eyes open, hallux pain (Numerical Rating Scale), trunk and lower limb muscle mass (kg). We classified the subjects into a hallux valgus group (n = 44, photographic hallux valgus angle of 1 or both feet ≥ 20°) and a no hallux valgus group (n = 125, photographic hallux valgus angle of both feet < 20°) and analyzed the relationship between hallux valgus and postural sway. RESULTS: The anteroposterior postural sway in the hallux valgus group (6.5 ± 2.8) was significantly greater than in the no hallux valgus group (5.4 ± 2.2, p = 0.014), and the lower limb muscle mass in the hallux valgus group (12.4 ± 2.2) was significantly smaller than in the no hallux valgus group (13.5 ± 3.2, p = 0.016). The total value of the photographic hallux valgus angle on both feet was positively correlated with the anteroposterior postural sway (p = 0.021) and negatively correlated with the lower limb muscle mass (p = 0.038). The presence of hallux valgus (p = 0.024) and photographic hallux valgus angle (p = 0.008) were independently related to the magnitude of anteroposterior postural sway. CONCLUSIONS: Hallux valgus deformity and its severity were positively associated with the magnitude of the anteroposterior postural sway. TRIAL REGISTRATION: 2017 - 135. Registered 22 August 2017.

Permanent pacemaker implantation and its predictors in patients admitted for complete atrioventricular block: a report from the Tokyo Cardiovascular Care Unit Network multi-center registry.

Little is known about the permanent pacemaker implantation rate and predictors of permanent pacemaker implantation in patients admitted for complete atrioventricular block (cAVB). The present study was a retrospective analysis based on a multicenter cohort of 797 patients with cAVB (mean age: 79.6 ± 10.7 years; males: 48.4%) registered with the Tokyo Cardiovascular Care Unit Network multicenter registry between 2013 and 2016. Secondary cAVB due to acute coronary syndrome was excluded. The permanent pacemaker implantation rate was 82.9%. Multivariable logistic regression analysis revealed that systolic blood pressure (SBP) > 140 mmHg [odds ratio (OR) 2.10; 95% confidence interval (CI) 1.38-3.22; P < 0.001], male gender (OR 1.63; 95% CI 1.07-2.49; P = 0.023), and left ventricular ejection fraction (LVEF) ≥ 50% (OR 2.19; 95% CI 1.16-2.06; P = 0.016) were predictors of permanent pacemaker implantation while pre-admission ß-blocker use (OR 0.28; 95% CI 0.17-0.47; P < 0.001) was associated with a lower risk of permanent pacemaker implantation. Reversible cAVB was not rare in patients admitted for cAVB. Data on SBP on admission, gender, LVEF, and pre-admission ß-blocker use may be important for assessing the requirement for permanent pacemaker implantation in the emergency care setting.

J-PARC H- ion source and space-charge neutralized LEBT for 100-mA high energy and high duty factor LINACs.

In July 2019, a design beam of 8.3 × 1013 protons/pulse, whose 25 Hz operation produced the design beam power of 1 MW, was accelerated for 10.5 h by using the J-PARC 3 GeV rapid cycling synchrotron. During the operation, a J-PARC H- ion source and a 400 MeV linear accelerator (LINAC) were operated with the design beam duty factor (BDF) of 1.25% (0.5 ms × 25 Hz) and ejected beam intensities of 58 mA and 50 mA, respectively. Furthermore, as expected from the transverse emittances measured in an H- ion source test-stand, they were successfully operated with the BDF of 1.5% (0.6 ms × 25 Hz) and ejected beam intensities of 72 mA and 60 mA, respectively. In the operation, the beam pulse accelerated by the J-PARC radio-frequency quadrupole LINAC (RFQ) had a rapid rise-time of about 10 µs and an excellent flatness with a slow variation of ±0.2%. A flat beam pulse was produced by the predicted 100% space-charge neutralization (SCN) in the upstream half of the J-PARC low-energy beam transport (LEBT) with a vacuum pressure of 3.6 × 10-4 Pa and the unpredicted high and almost constant SCN of about 69% in the downstream half of the LEBT with a vacuum pressure of 2.8 × 10-5 Pa. The rapid rise-time was produced by the preformed 100% SCN with a preceding 100 µs 40 keV beam, which was not accelerated by the RFQ due to the low energy outside the RFQ acceptance. In the test-stand operated with the terminal voltage of 62 kV and BDF of 5% (1 ms × 50 Hz), the transverse emittances of a 100-mA beam were also measured to be suitable for the RFQs of high energy LINACs. A 100-mA high energy and high duty factor LINAC could be realized with this source since the transverse emittances were further improved by about 8% with the shortest beam extractor in the test-stand.

In-Hospital Electrical Storm in Acute Myocardial Infarction　- Clinical Background and Mechanism of the Electrical Instability.

BACKGROUND: Recurrent ventricular tachycardia (VT) and fibrillation (VF), the so-called "electrical storm" (ES) occurs at various stages of acute myocardial infarction (AMI), but its incidence, background, and short-term prognosis remain unclear. Methods and Results: A retrospective observational study was performed using the registry database of the Tokyo CCU Network. The individual data of 6,003 patients with AMI during 2011-2012 was corrected. ES was defined as more than 3 episodes of sustained VT/VF during a 24-h period as first documented after hospitalization. ES occurred in 55 patients after admission (0.9%). The ES(+) group had more severe heart failure (Killip class >III), more extensive MI (peak-CK), greater inflammatory reaction (CRP), history of diabetes, and more frequent application of hemodialysis as compared with the ES(-) group (n=5,865). When the ES patients were divided into Early-ES (n=37: ES occurred ≤48 h after the onset of MI) and Late-ES (n=15 >48 h after onset of MI) groups, logistic regression analysis revealed that Early-ES was associated with severity of MI, whereas Late-ES was related to systemic disorders, including inflammation, renal dysfunction, or diabetes. Late-ES was an independent predictor of in-hospital death. CONCLUSIONS: In-hospital ES was a rare clinical manifestation of AMI. The features and background of the ES varied as time elapsed after admission for MI.

Shoulder Stretching Intervention Reduces the Incidence of Shoulder and Elbow Injuries in High School Baseball Players: a Time-to-Event Analysis.

We prospectively evaluated the effects of a prevention program on the incidence of shoulder and elbow injuries in high school baseball pitchers. Ninety-two pitchers participated in this study and were taught to perform stretching and strength exercises aimed at improving shoulder external rotation strength in the preseason. The pitchers freely chose to participate in one of four groups [SM-group: performed both exercises, S-group: performed stretching exercise only, M-group: performed strength training only, and N-group: performed neither intervention]. Injury was defined as inability to play for ≥8 days because of shoulder/elbow symptoms. Kaplan-Meier survival curves were generated and hazard ratios (HRs) for injury occurrence were calculated using multivariate Cox regression. Log-rank test was used for between-group comparisons of survival distributions. The injuries occurred in 25, 35, and 57% of participants and median times to injury were 89, 92, and 29.5 days in the S- (n = 32), SM- (n = 46), and N- (n = 14) group, respectively. Nobody chose M-group. HRs were 0.36 and 0.47 for the S- and SM-group, respectively, based on the N-group. The incidence of injury was significantly lower in the S-group than in the N-group (p = 0.04). Daily posterior shoulder stretching may reduce the incidence of the injuries in high school baseball pitchers.

Bone turnover markers and the factors associated with atypical femur fractures among Japanese patients.

Many previous reports have indicated that atypical femur fractures (AFFs) are associated with the administration of bisphosphonates (BPs). A number of risk factors and hypotheses regarding the pathogenesis of AFFs have been reported to date. The purpose of the present study was to identify the factors associated with AFFs in Japanese individuals and to elucidate the association between bone metabolism and AFFs by evaluating bone turnover markers (BTMs). We prospectively reviewed all patients with femur fractures and identified the patients with AFFs and typical femur fractures (TFFs). We collected the demographic and clinical data that were relevant to the present study, namely age, gender, affected side, affected site, concomitant medical history, and comorbid conditions, and measured the levels of BTMs within 24h after trauma. Welch's test and Fisher's exact probability test were used for the statistical analyses. A total of 338 patients, including 10 patients with AFFs and 328 patients with TFFs, were analyzed under the inclusion criteria. The use of BPs (p<0.001) and collagen disease and chronic granulomatous disease (CD/CGD) (p=0.025) were more frequently observed in patients with AFFs than in patients with TFFs, while the levels of BTMs, including N-terminal propeptides of type 1 procollagen (P1NP), isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) and undercarboxylated osteocalcin (ucOC) were significantly lower in patients with AFFs than in patients with TFFs. Furthermore, the level of TRACP-5b was found to be significantly lower in patients with atypical subtrochanteric fractures than in atypical diaphyseal fractures (p=0.025). Moreover, the levels of P1NP (p=0.016) and TRACP-5b (p=0.015) were found to be significantly lower in patients with AFFs than in patients with TFFs in a subgroup analysis of BPs users. The use of BPs was considered to be a factor associated with AFFs. Our comparison of the BTMs in patients with AFFs and TFFs indicated that the severe suppression of bone turnover was associated with the pathogenesis of AFFs. The extent of the influence of suppressed turnover on the pathogenesis of AFFs may differ depending on the fracture site.

Clinical and Electrocardiographic Characteristics of Electrical Storms Due to Monomorphic Ventricular Tachycardia Refractory to Intravenous Amiodarone.

BACKGROUND: Few reports are available on the characteristics of electrical storms of ventricular tachycardia (VT storm) refractory to intravenous (IV) amiodarone. METHODS AND RESULTS: IV-amiodarone was administered to 60 patients with ventricular tachyarrhythmia between 2007 and 2012. VT storms, defined as 3 or more episodes of VT within 24 h, occurred in 30 patients (68±12 years, 7 female), with 12 having ischemic and 18 non-ischemic heart disease. We compared the clinical and electrocardiographic characteristics of the patients with VT storms suppressed by IV-amiodarone (Effective group) to those of patients not affected by the treatment (Refractory group). IV-amiodarone could not control recurrence of VT in 9 patients (30%). The Refractory group comprised 5 patients with acute myocardial infarctions. Although there was no difference in the VT cycle length, the QRS duration of both the VT and premature ventricular contractions (PVCs) followed by VT was narrower in the Refractory group than in the Effective group (140±30 vs. 178±25 ms, P<0.01; 121±14 vs. 179±22 ms, P<0.01). In the Refractory group, additional administration of IV-mexiletine and/or Purkinje potential-guided catheter ablation was effective. CONCLUSIONS: IV-amiodarone-refractory VT exhibited a relatively narrow QRS tachycardia. The narrow triggering PVCs, suggesting a Purkinje fiber origin, may be treated by additional IV-mexiletine and endocardial catheter ablation.

Design amphiphilic dipolar π-systems for stimuli-responsive luminescent materials using metastable states.

π-Conjugated compounds that exhibit tunable luminescence in the solid state under external mechanical stimuli have potential applications in sensors and imaging devices. However, no rational designs have been proposed that impart these mechano-responsive luminescent properties to π-conjugated compounds. Here we demonstrate a strategy for mechano-responsive luminescent materials by imparting amphiphilic and dipolar characteristics to a luminescent π-conjugated system. The oligo(p-phenylenevinylene) luminophore with a didodecylamino group at one end and a tri(ethylene glycol) ester group at the other end yields segregated solid structures by separately aggregating its hydrophobic and hydrophilic moieties. The segregated structures force the molecules to align in the same direction, thereby generating a conflict between the side-chain aggregation and dipolar stabilization of the π-system. Consequently, these metastable solid structures can be transformed through mechanical stimulation to a more stable structure, from a π-π stacked aggregate to a liquid crystal and further to a crystalline phase with variable luminescence.

Cell patterning through inkjet printing of one cell per droplet.

The inkjet ejection technology used in printers has been adopted and research has been conducted on manufacturing artificial tissue by patterning cells through micronozzle ejection of small droplets containing multiple cells. However, stable injection of cells has proven difficult, owing to the frequent occurrence of nozzle clogging. In this paper, a piezoelectric inkjet head constructed with a glass capillary that enabled viewing of the nozzle section was developed, the movement of cells ejected from the nozzle tip was analyzed, and a method for stably ejecting cells was verified. A pull-push ejection method was compared with a push-pull ejection method regarding the voltage waveform applied to the piezoelectric element of the head. The push-pull method was found to be more suitable for stable ejection. Further, ejection of one cell per droplet was realized by detecting the position of the cell in the nozzle section and utilizing these position data. Thus, a method for more precise patterning of viable cells at desired position and number was established. This method is very useful and promising not only for biofabrication, 3D tissue construction, cell printing, but also for a number of biomedical application, such as bioMEMS, lab on a chip research field.