p-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 p-conjugated compounds. Here we demonstrate a strategy for mechanoresponsive luminescent materials by imparting amphiphilic and dipolar characteristics to a luminescent p-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 p-system. Consequently, these metastable solid structures can be transformed through mechanical stimulation to a more stable structure, from a p-p stacked aggregate to a liquid crystal and further to a crystalline phase with variable luminescence.
A recently synthesized alpha 1-blocker, (R)(-)-5-[2-[[2-(o-ethoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzenesulfonamide hydrochloride (YM617), was evaluated in 270 patients with benign prostatic hypertrophy in a double-blind study. After 2 weeks on placebo the patients were assigned at random to 4 groups: group P--placebo, group L--0.1 mg., group M--0.2 mg. and group H--0.4 mg. of YM617. Comparing the placebo to the treatment period, subjective symptoms, such as nocturia and urgency, were significantly decreased in group H (p less than 0.01). The sensation of incomplete voiding was significantly improved in groups M and H (p less than 0.01). However, the differences among the groups were statistically insignificant. Residual urine volume was significantly decreased in groups L, M and H after instillation of saline into the bladder (p less than 0.01) but not in group P. The maximum and average flow rates were significantly increased in groups L, M and H (p less than 0.01) but not in group P. Average flow rate showed significant differences between groups M or H versus group P. Neither orthostatic hypotension nor a decrease in blood pressure was noted. Adverse side effects and changes in laboratory data were all slight and disappeared when the second tests were performed. In summary, the irritative and obstructive symptoms caused by benign prostatic hypertrophy were decreased and urodynamic studies were markedly improved by the alpha 1-blocker, YM617. The drug seems to be useful in the treatment of patients with benign prostatic hypertrophy.
Background
The immune profile against 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 the Omicron in individuals with various immune histories.
Methods
The neutralization susceptibility of the variants including the Omicron and their ancestor 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 by the Alpha/Delta with multiple time intervals following vaccination.
Findings
The Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against the Omicron were 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 the 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 the Omicron and future variants.
Funding
This study was supported by grants from the Japan Agency for Medical Research and Development (AMED).
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