Information-seeking behaviour of community pharmacists during the COVID-19 pandemic: an ecological study

[Objective] To evaluate the information-seeking behaviour of pharmacists during the COVID-19 pandemic and its relation to COVID-19 and related infections and deaths within the local prefecture. [Design] Ecological study. [Setting] Japan—47 prefectures. [Methods] The number of accesses to a Japanese web page established by the Pharmacy Informatics Group to disseminate information about infection control and the number of infections and deaths in 47 prefectures were investigated from 6 April to 30 September 2020 using the access information on the web page and publicly available information. [Results] During the first 6 months of the COVID-19 pandemic, the total number of accesses was 226 130 (range: 10 984–138 898 per month), the total number of infections was 78 761 (1738–31 857) and the total number of deaths was 1470 (39–436). The correlation between the total number of accesses and that of infections per 100 000 individuals in 47 prefectures was r=0.72 (95% CI 0.55 to 0.83, p<0.001), and between the total number of accesses and deaths per 100 000 individuals in 47 prefectures was r=0.44 (95% CI 0.17 to 0.65, p=0.002). [Conclusions] The information-seeking behaviour of community pharmacists correlated positively with infection status within the community

Energy of Liposome Patch Adhesion to the Pipet Glass Determined by Confocal Fluorescence Microscopy.

The formation of the gigaseal in the patch clamp technique is dependent on the adhesion between the cell or liposome membrane and the glass pipet. The adhesion results in a capillary force causing creep of the patch membrane up the pipet. The membrane can be immobilized by counteracting the capillary force by positive pressure applied to the patch pipet. We use this phenomenon to develop a method for static measurement of the adhesion free energy of the lipid bilayer to the glass. Confocal fluorescent microscopy is used to track the bilayer creep inside the pipet and measure the immobilization pressure at various salt concentrations and pH. The adhesion energy is simply related to this pressure. For the studied phospholipid bilayers, its values were in the 0.3-0.7 mJ/m2 range, increased with salt concentration, and had a maximum as a function of pH. This method offers a way to measure bilayer-glass adhesion energy in patch clamp experiments that is more precise than dynamic methods

Binding of fullerenes and nanotubes to MscL

Multi-drug resistance is becoming an increasing problem in the treatment of bacterial infections and diseases. The mechanosensitive channel of large conductance (MscL) is highly conserved among prokaryotes. Evidence suggests that a pharmacological agent that can affect the gating of, or block the current through, MscL has significant potential as a new class of antimicrobial compound capable of targeting a range of pathogenic bacteria with minimal side-effects to infected patients. Using molecular dynamics we examine the binding of fullerenes and nanotubes to MscL and demonstrate that both are stable within the MscL pore. We predict that fullerenes will attenuate the flow of ions through MscL by reducing the pore volume available to water and ions, but nanotubes will prevent pore closure resulting in a permanently open pore. Moreover, we confirm experimentally that it is possible to attenuate the flow of ions through MscL using a C60-γ 3 cyclodextrin complex

Biophysical implications of lipid bilayer rheometry for mechanosensitive channels

The lipid bilayer plays a crucial role in gating of mechanosensitive (MS) channels. Hence it is imperative to elucidate the rheological properties of lipid membranes. Herein we introduce a framework to characterize the mechanical properties of lipid bilayers by combining micropipette aspiration (MA) with theoretical modeling. Our results reveal that excised liposome patch fluorometry is superior to traditional cell-attached MA for measuring the intrinsic mechanical properties of lipid bilayers. The computational results also indicate that unlike the uniform bilayer tension estimated by Laplace's law, bilayer tension is not uniform across the membrane patch area. Instead, the highest tension is seen at the apex of the patch and the lowest tension is encountered near the pipette wall. More importantly, there is only a negligible difference between the stress profiles of the outer and inner monolayers in the cellattached configuration, whereas a substantial difference (~30%) is observed in the excised configuration. Our results have farreaching consequences for the biophysical studies of MS channels and ion channels in general, using the patch-clamp technique, and begin to unravel the difference in activity seen between MS channels in different experimental paradigms

Stable Iodine Distribution among Children after the 2011 Fukushima Nuclear Disaster in Japan: An Observational Study

福島第一原発事故後の安定ヨウ素剤配布後の実態調査を実施 --安定ヨウ素剤の情報提供・内服指示に関する課題が浮き彫りに--. 京都大学プレスリリース. 2019-01-10.Context: Intake of stable iodine helps prevent childhood thyroid cancer in nuclear emergencies but there is limited case information. Objective: We identified the intake rate and the factors associated with no intake among children who did not take stable iodine after the Fukushima disaster. Design: Retrospective observational study. Setting: Data were obtained from thyroid cancer screening performed in August–November 2017. Participants: Children in Miharu Town, Fukushima, Japan. Intervention: No intervention. Main Outcome Measures: We performed multilevel logistic regression analysis at the regional and individual levels. We qualitatively examined the reasons for no intake of stable iodine based on closed- and open-ended questions. Results: The rate of distribution was 94.9%, but the intake rate was only 63.5%. Intake was lower in those aged 0–2 years compared with those aged ≥3 years: odds ratio (OR), 0.21 [95% confidence interval (CI), 0.11–0.36]. Parents’ intake was positively associated with their children’s intake [OR, 61.0 (95% CI, 37.9–102.9)]. The variance partition coefficient for regions was 0.021, suggesting that the intake of stable iodine was more likely affected by individual than by regional factors. The main reasons for avoiding intake were concern about safety, issues related to distribution, drug information sharing, and instructions for intake. There were no claimed adverse effects. Conclusions: The distribution and consumption of stable iodine occurred without claims of adverse effects after the Fukushima disaster. To prepare for future nuclear emergencies, it is important to explain to both children and parents the need for intake of stable iodine, particularly among young children

Improved electrical conductance through self-assembly of bioinspired peptides into nanoscale fibers

We investigated the electrical conductance of films consisting of bio-inspired peptide molecules and of their extended form, self-assembled nanoscale fibers. Here, the entirely natural and novel peptide sequence, GFPRFAGFP, was designed based on naturally occurring fibrous proteins. To attain electrical conductance, we implemented phenylalanine residues in the sequence such that the aromatic rings are present along face of the molecule. We confirmed self-assembly of nanoscale fibers in pure water after incubating the peptides at 37 °C by AFM. The morphology and conformation of the incubated peptide fibers were studied using AFM, fluorescence spectroscopy and circular dichroism spectroscopy. It was shown that very thin fibers with a single-molecule-level diameter form. The helical feature of the peptide backbone and enhanced stacking of aromatic residues were also investigated. This aromatic stacking is important to our electrical measurements as, even in vacuum environment, films of non-incubated GFPRFAGFP sometimes show apparent conductance while those containing self-assembled nanoscale fibers show stable and improved conductance. We propose that this effect may be due to extended stacking of aromatic residues providing π - π conjugation along the fiber

Internet-Based Inquiries From Users With the Intention to Overdose With Over-the-Counter Drugs: Qualitative Analysis of Yahoo! Chiebukuro

市販薬乱用に関して投稿された質問の分析 --Yahoo!知恵袋内テキストデータの定性分析--. 京都大学プレスリリース. 2023-12-05.[Background:] Public concern with regard to over-the-counter (OTC) drug abuse is growing rapidly across countries. OTC drug abuse has serious effects on the mind and body, such as poisoning symptoms, and often requires specialized treatments. In contrast, there is concern about people who potentially abuse OTC drugs whose symptoms are not serious enough to consult medical institutions or drug addiction rehabilitation centers yet are at high risk of becoming drug dependent in the future. [Objective:] Consumer-generated media (CGM), which allows users to disseminate information, is being used by people who abuse (and those who are trying to abuse) OTC drugs to obtain information about OTC drug abuse. This study aims to analyze the content of CGM to explore the questions of people who potentially abuse OTC drugs. [Methods:] The subject of this research was Yahoo! Chiebukuro, the largest question and answer website in Japan. A search was performed using the names of drugs commonly used in OTC drug abuse and the keywords overdose and OD, and the number of questions posted on the content of OTC drug abuse was counted. Furthermore, a thematic analysis was conducted by extracting text data on the most abused antitussive and expectorant drug, BRON. [Results:] The number of questions about the content of overdose medications containing the keyword BRON has increased sharply as compared with other product names. Furthermore, 467 items of question data that met the eligibility criteria were obtained from 528 items of text data on BRON; 26 codes, 6 categories, and 3 themes were generated from the 578 questions contained in these items. Questions were asked about the effects they would gain from abusing OTC drugs and the information they needed to obtain the effects they sought, as well as about the effects of abuse on their bodies. Moreover, there were questions on how to stop abusing and what is needed when seeking help from a health care provider if they become dependent. It has become clear that people who abuse OTC drugs have difficulty in consulting face-to-face with others, and CGM is used as a means to obtain the necessary information anonymously. [Conclusions:] On CGM, people who abused or tried to abuse OTC drugs were asking questions about their abuse expectations and anxieties. In addition, when they became dependent, they sought advice to quit their abuse. CGM was used to exchange information about OTC drug abuse, and many questions on anxieties and hesitations were posted. This study suggests that it is necessary to produce and disseminate information on OTC drug abuse, considering the situation of those who abuse or are willing to abuse OTC drugs. Support from pharmacies and drugstores would also be essential to reduce opportunities for OTC drug abuse

Knowledge and self-efficacy among healthcare providers towards novel tobacco products in Japan

Several new tobacco products, including e-cigarettes and heated tobacco products (HTPs), have become highly prevalent in Japan. As safety data continues to evolve, healthcare providers are considered important sources for product use, yet little is known about provider knowledge or self-efficacy to counsel patient about novel tobacco product use. This cross-sectional study used data from a Japanese Association of Smoking Control Science (JASCS) online survey of physicians, pharmacists, nurses, and public health practitioners (N = 277) to assess provider knowledge of novel tobacco products and self-efficacy to counsel patients about product use. Correlates of knowledge and self-efficacy were also assessed. More than half the sample had received previous training in treating tobacco use, but 62% of respondents had no knowledge of HTPs; 80% of respondents indicated that they occasionally or always provide smoking cessation support. Overall knowledge of HTPs was low (41.4% correct) with higher knowledge for HTPs containing nicotine (89% correct) vs. HTPs emitting no carbon monoxide (25%). Self-efficacy to counsel patients about novel tobacco products was low on a scale ranging from 10 to 70 (Mean = 31.2; Standard Deviation = 16.7). Greater knowledge of HTPs was associated with male gender, higher rates of training at JASCS and previous learning about HTPs at JASCS. (p < 0.05). The results suggested that healthcare providers' knowledge and self-efficacy regarding novel tobacco products remains low in Japan, but additional training may improve it

Degradation of Phosphorylated p53 by Viral Protein-ECS E3 Ligase Complex

p53-signaling is modulated by viruses to establish a host cellular environment advantageous for their propagation. The Epstein-Barr virus (EBV) lytic program induces phosphorylation of p53, which prevents interaction with MDM2. Here, we show that induction of EBV lytic program leads to degradation of p53 via an ubiquitin-proteasome pathway independent of MDM2. The BZLF1 protein directly functions as an adaptor component of the ECS (Elongin B/C-Cul2/5-SOCS-box protein) ubiquitin ligase complex targeting p53 for degradation. Intringuingly, C-terminal phosphorylation of p53 resulting from activated DNA damage response by viral lytic replication enhances its binding to BZLF1 protein. Purified BZLF1 protein-associated ECS could be shown to catalyze ubiquitination of phospho-mimetic p53 more efficiently than the wild-type in vitro. The compensation of p53 at middle and late stages of the lytic infection inhibits viral DNA replication and production during lytic infection, suggesting that the degradation of p53 is required for efficient viral propagation. Taken together, these findings demonstrate a role for the BZLF1 protein-associated ECS ligase complex in regulation of p53 phosphorylated by activated DNA damage signaling during viral lytic infection

Efficient production of infectious viruses requires enzymatic activity of Epstein-Barr virus protein kinase

AbstractThe Epstein-Barr virus (EBV) BGLF4 gene product is the only protein kinase encoded by the virus genome. In order to elucidate its physiological roles in viral productive replication, we here established a BGLF4-knockout mutant and a revertant virus. While the levels of viral DNA replication of the deficient mutant were equivalent to those of the wild-type and the revertant, virus production was significantly impaired. Expression of the BGLF4 protein in trans fully complemented the low yield of the mutant virus, while expression of a kinase-dead (K102I) form of the protein failed to restore the virus titer. These results demonstrate that BGLF4 plays a significant role in production of infectious viruses and that the kinase activity is crucial