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Tranexamic acid (TXA) is widely used as a hemostatic agent and for various other indications, including dermatological and inflammatory conditions. However, its association with thromboembolism in the real-world setting remains unclear. In this study, we aimed to evaluate this association. We collected data from the Japan Adverse Drug Event Report database from Q1 2004 to Q3 2020 and performed reporting odds ratio analyses and multivariate logistic regression analysis. Overall, 1,735,923 reports were analyzed. TXA was the suspected causal drug in 54 cases of venous thromboembolism (VTE) and 8 cases of arterial thromboembolism. A significant signal was detected for VTE (reporting odds ratio=6.61; 95% confidence interval=5.03-8.70) but not for arterial thromboembolism. VTE cases involving TXA were more frequently reported in women and individuals with a body mass index of ≥25 than in other groups. TXA may be associated with VTE. The findings highlight the importance of careful patient monitoring during TXA administration, particularly in high-risk populations such as women and individuals who are overweight.

Thrombocytopenia is a serious adverse event observed with intravenous immunoglobulin formulations (IVIg). There have been some individual case reports of such events, but to our knowledge, no epidemiological studies have been reported. In this study, the risk of IVIg-induced thrombocytopenia and factors associated with IVIg-induced thrombocytopenia were examined using the Japanese Adverse Drug Event Report database. Data spanning from April 2004 to August 2024 were used. The association between IVIg and thrombocytopenia was evaluated using the reporting odds ratio (ROR). The reports of IVIg-induced thrombocytopenia events were evaluated by disease and aggregated by disease group. Factors associated with IVIg-induced thrombocytopenia were detected using multiple logistic regression with age, sex, formulation method, and disease group as explanatory variables and adjusted RORs were calculated. The IVIgs examined were significantly associated with thrombocytopenia. Pemphigoid was the most frequently reported disease, followed by Kawasaki disease and polymyositis/dermatomyositis. Immune-mediated skin diseases were the most frequently reported disease group, followed by Kawasaki disease, immune-mediated neurological diseases, and immune-mediated muscular diseases. Multiple logistic regression analysis showed that at age 60 years or older, immune-mediated skin diseases and immune-mediated muscular diseases were independently associated with significantly increased RORs. This study suggests that IVIg can induce thrombocytopenia and that thrombocytopenia should be assessed in patients with immune-mediated skin diseases, immune-mediated muscular diseases and in the elderly.

Topological lasers have been intensively investigated as a strong candidate for robust single-mode lasers. A typical topological laser employs a single-mode topological edge state, which appears deterministically in a designed topological bandgap and exhibits robustness to disorder. These properties seem to be highly attractive in pursuit of high-power lasers capable of single mode operation. In this paper, we theoretically analyze a large-scale single-mode laser based on a topological edge state. We consider a sizable array laser consisting of a few hundreds of site resonators, which support a single topological edge mode broadly distributed among the resonators. We build a basic model describing the laser using the tight binding approximation and evaluate the stability of single mode lasing based on the threshold gain difference Δ between the first-lasing edge mode and the second-lasing competing bulk mode. Our calculations demonstrate that stronger couplings between the cavities and lower losses are advantageous for achieving stable operation of the device. When assuming an average coupling of 100 cm between site resonators and other realistic parameters, the threshold gain difference Δ can reach about 2 cm , which would be sufficient for stable single mode lasing using a conventional semiconductor laser architecture. We also consider the effects of possible disorders and long-range interactions to assess the robustness of the laser under non-ideal situations. These results lay the groundwork for developing single-mode high-power topological lasers.

Apolipoprotein E E4 (APOE4) is a risk factor for cognitive decline. A high blood vitamin C (VC) level reduces APOE4-associated risk of developing cognitive decline in women. In the present study, we aimed to examine the effects of functional variants of VC transporter genes expressed in the brain ( SLC2A1 , SLC2A3 , and SLC23A2 ) on APOE4-associated risk of developing cognitive decline. This case–control study involved 393 Japanese subjects: 252 cognitively normal and 141 cognitively impaired individuals (87 mild cognitive impairment and 54 dementia). Database searches revealed that rs1279683 of SLC23A2 , and rs710218 and rs841851 of SLC2A1 are functional variants that are significantly associated with the altered expression of the respective genes and genotyped as three single nucleotide variants (SNVs). When stratified by SNV genotype, we found a significant association between APOE4 and cognitive decline in minor allele carriers of rs1279683 (odds ratio [OR] 2.02, 95% CI, 1.05–3.87, p = 0.035) but not in the homozygote carriers of the major allele. Significant associations between APOE4 and cognitive decline were also observed in participants with major allele homozygotes of rs710218 (OR 2.35, 95% CI, 1.05–5.23, p = 0.037) and rs841851 (OR 3.2, 95% CI, 1.58–6.46, p = 0.0012), but not in minor allele carriers of the respective SNVs. In contrast, the three functional SNVs showed no significant effect on cognitive decline. Our results imply that functional SNVs of VC transporter genes can affect APOE4-associated risk of developing cognitive decline via altered VC levels in the brain.

Background Hyposalivation is treated using oral cholinergic drugs; however, systemic side effects occasionally lead to discontinuation of treatment. We aimed to investigate the effects of transdermal pilocarpine on the salivary gland skin on saliva secretion and safety in rats. Methods Pilocarpine was administered to rats orally (0.5 mg/kg) or topically on the salivary gland skin (5 mg/body). Saliva volume, the number of sweat dots, and fecal weight were measured along with pilocarpine concentration in plasma and submandibular gland tissues. Results Saliva volume significantly increased 0.5 h after oral administration and 0.5, 3, and 12 h after topical administration. Fecal weight and sweat dots increased significantly 1 h after oral administration; however, no changes were observed after topical application. The pilocarpine concentration in the submandibular gland tissues of the topical group was higher than that in the oral group at 0.5, 3, and 12 h of administration. Conclusions Pilocarpine application to salivary gland skin persistently increased salivary volume in rats without inducing sweating or diarrhea. Transdermal pilocarpine applied to the skin over the salivary glands may be an effective and safe treatment option for hyposalivation.

Apolipoprotein E E4 (APOE4) is a risk factor for cognitive decline. A high blood vitamin C (VC) level reduces APOE4-associated risk of developing cognitive decline in women. In the present study, we aimed to examine the effects of functional variants of VC transporter genes expressed in the brain (SLC2A1, SLC2A3, and SLC23A2) on APOE4-associated risk of developing cognitive decline. This case–control study involved 393 Japanese subjects: 252 cognitively normal and 141 cognitively impaired individuals (87 mild cognitive impairment and 54 dementia). Database searches revealed that rs1279683 of SLC23A2, and rs710218 and rs841851 of SLC2A1 are functional variants that are significantly associated with the altered expression of the respective genes and genotyped as three single nucleotide variants (SNVs). When stratified by SNV genotype, we found a significant association between APOE4 and cognitive decline in minor allele carriers of rs1279683 (odds ratio [OR] 2.02, 95% CI, 1.05–3.87, p = 0.035) but not in the homozygote carriers of the major allele. Significant associations between APOE4 and cognitive decline were also observed in participants with major allele homozygotes of rs710218 (OR 2.35, 95% CI, 1.05–5.23, p = 0.037) and rs841851 (OR 3.2, 95% CI, 1.58–6.46, p = 0.0012), but not in minor allele carriers of the respective SNVs. In contrast, the three functional SNVs showed no significant effect on cognitive decline. Our results imply that functional SNVs of VC transporter genes can affect APOE4-associated risk of developing cognitive decline via altered VC levels in the brain.

Scientific Reports 6: Article number: 25655; published online: 19 May 2016; updated: 02 November 2016

The Jaynes-Cummings model, describing the interaction between a single two-level system and a photonic mode, has been used to describe a large variety of systems, ranging from cavity quantum electrodynamics, trapped ions, to superconducting qubits coupled to resonators. Recently there has been renewed interest in studying the quantum strong-coupling (QSC) regime, where states with photon number greater than one are excited. This regime has been recently achieved in semiconductor nanostructures, where a quantum dot is trapped in a planar microcavity. Here we study the quantum strong-coupling regime by calculating its photoluminescence (PL) properties under a pulsed excitation. We discuss the changes in the PL as the QSC regime is reached, which transitions between a peak around the cavity resonance to a doublet. We particularly examine the variations of the PL in the time domain, under regimes of short and long pulse times relative to the microcavity decay time.

Hyposalivation is treated using oral cholinergic drugs; however, systemic side effects occasionally lead to discontinuation of treatment. We aimed to investigate the effects of transdermal pilocarpine on the salivary gland skin on saliva secretion and safety in rats. Pilocarpine was administered to rats orally (0.5 mg/kg) or topically on the salivary gland skin (5 mg/body). Saliva volume, the number of sweat dots, and fecal weight were measured along with pilocarpine concentration in plasma and submandibular gland tissues. Saliva volume significantly increased 0.5 h after oral administration and 0.5, 3, and 12 h after topical administration. Fecal weight and sweat dots increased significantly 1 h after oral administration; however, no changes were observed after topical application. The pilocarpine concentration in the submandibular gland tissues of the topical group was higher than that in the oral group at 0.5, 3, and 12 h of administration. Pilocarpine application to salivary gland skin persistently increased salivary volume in rats without inducing sweating or diarrhea. Transdermal pilocarpine applied to the skin over the salivary glands may be an effective and safe treatment option for hyposalivation.

In a standard semiconductor laser, electrons and holes recombine via stimulated emission to emit coherent light, in a process that is far from thermal equilibrium. Exciton-polariton condensates–sharing the same basic device structure as a semiconductor laser, consisting of quantum wells coupled to a microcavity–have been investigated primarily at densities far below the Mott density for signatures of Bose-Einstein condensation. At high densities approaching the Mott density, exciton-polariton condensates are generally thought to revert to a standard semiconductor laser, with the loss of strong coupling. Here, we report the observation of a photoluminescence sideband at high densities that cannot be accounted for by conventional semiconductor lasing. This also differs from an upper-polariton peak by the observation of the excitation power dependence in the peak-energy separation. Our interpretation as a persistent coherent electron-hole-photon coupling captures several features of this sideband, although a complete understanding of the experimental data is lacking. A full understanding of the observations should lead to a development in non-equilibrium many-body physics.