No abstract

The Glu residue in the laminin γ-tail forms a bipartite integrin binding site with three globular domains of the α chain.

Background There are financial relationships between healthcare professionals and pharmaceutical companies, and these relationships have historically caused conflicts of interest and unduly influenced patient care. However, little was known about such relationships and its effect in clinical practice among specialists in respiratory medicine. Methods Based on the retrospective analysis of payment data made available by all 92 pharmaceutical companies in Japan, this study evaluated the magnitude and trend of financial relationships between all board-certified Japanese respiratory specialists and pharmaceutical companies between 2016 and 2019. Magnitude and prevalence of payments for specialists were analyzed descriptively. The payment trends were assessed using the generalized estimating equations for the payment per specialist and the prevalence of specialists with payments. Results Among all 7,114 respiratory specialists certified as of August, 2021, 4,413 (62.0%) received a total of USD($) 53,547,391 and 74,195 cases from 72 (78.3%) pharmaceutical companies between 2016 and 2019. The mean (SD) and median (interquartile range) four-year combined payment values per specialist were $12,134 ($34,045) and $2,210 ($715-$8,178) respectively. At maximum, one specialist received $495,332 personal payments over the four years. Both payments per specialist and prevalence of specialists with payments significantly increased during the four-year period, with 7.8% (95% CI: 5.5-9.8; p<0.001) in payments and 1.5% (95% CI: 0.61-2.4%; p = 0.001) in prevalence of specialists with payments, respectively. Conclusion Majority of respiratory specialists had increasingly received substantial personal payments from pharmaceutical companies for the reimbursement of lecturing, consulting, and writing between 2016 and 2019. These increasing financial relationships with pharmaceutical companies might cause conflicts of interest among respiratory physicians.

Bone metabolism is regulated by the cooperative activity between bone-forming osteoblasts and bone-resorbing osteoclasts. However, the mechanisms mediating the switch between the osteoblastic and osteoclastic phases have not been fully elucidated. Here, we identify a specific subset of mature osteoblast-derived extracellular vesicles that inhibit bone formation and enhance osteoclastogenesis. Intravital imaging reveals that mature osteoblasts secrete and capture extracellular vesicles, referred to as small osteoblast vesicles (SOVs). Co-culture experiments demonstrate that SOVs suppress osteoblast differentiation and enhance the expression of receptor activator of NF-κB ligand, thereby inducing osteoclast differentiation. We also elucidate that the SOV-enriched microRNA miR-143 inhibits Runt-related transcription factor 2, a master regulator of osteoblastogenesis, by targeting the mRNA expression of its dimerization partner, core-binding factor β. In summary, we identify SOVs as a mode of cell-to-cell communication, controlling the dynamic transition from bone-forming to bone-resorbing phases in vivo.

Backgrounds: Conflict of interest with pharmaceutical companies is one of the most concerned issues in infectious diseases. However, there is a lack of whole picture of detailed payments in Japan. Methods: This retrospective study assessed financial relationships between pharmaceutical companies and all infectious disease specialists board-certified by the Japanese Association for Infectious Disease, using publicly disclosed payment data from 92 major pharmaceutical companies. Descriptive analyses were conducted for the payments. Payment trends were examined by the generalized estimating equations. Results: Of 1614 board-certified infection disease specialists, 1055 (65.4%) received a total of $17,784,070 payments, corresponding to 21,680 contracts between 2016 and 2019. The mean ± SD and median (interquartile range: IQR) were $16,857 ± $45,010 and $3183 ($938–$11,250) in payments. All board executive members of Japanese Association of Infectious Disease received higher payments averaging $163,792. There were no significant changes in payments per specialist (annual change rate: −1.4% [95% CI: −4.7–2.3%], p = 0.48) and prevalence of specialists with payments (annual change rate: −1.4% [95% CI: −3.1–0.2%], p = 0.093) over the four years. Conclusion: There were substantial financial relationships between pharmaceutical companies and board-certified infectious disease specialists in Japan. Furthermore, high ranked specialists such as those in the executive board had stronger financial ties with the companies.

Serological evaluation with SARS-CoV-2 specific IgG antibody will be an alternative way to know the pandemic of novel coronavirus disease (COVID-19) if the capacity for diagnostic PCR test is limited. The point-of-care test to detect SARS-CoV-2 specific IgG antibody in peripheral blood (n =202) was performed in two community clinics in Tokyo, Japan. The overall

<b><i>Background:</i></b> Financial relationships between healthcare professionals and pharmaceutical companies have historically caused conflicts of interest and unduly influenced patient care. However, little was known about such relationship and its effect in clinical practice among specialists in respiratory medicine. <b><i>Methods:</i></b> Based on the retrospective analysis of payment data made available by all 92 pharmaceutical companies in Japan, this study evaluated the magnitude and trend of financial relationships between all board-certified Japanese respiratory specialists and pharmaceutical companies between 2016 and 2019. Magnitude and prevalence of payments for specialists were analyzed descriptively. The payment trends were assessed using the generalized estimating equations for the payment per specialist and the number of specialists with payments. <b><i>Results:</i></b> Among all 7,114 respiratory specialists certified as of August 2021, 4,413 (62.0%) received a total of USD 53,547,391 and 74,195 counts from 72 (78.3%) pharmaceutical companies between 2016 and 2019. The median (interquartile range) 4-year combined payment values per specialist were USD 2,210 (USD 715–8,178). At maximum, one specialist received USD 495,332 personal payments over the 4 years. Both payments per specialist and number of specialists with payments significantly increased during the 4-year period, with 7.8% (95% CI: 5.5–9.8; <i>p</i> &#x3c; 0.001) in payments and 1.5% (95% CI: 0.61–2.4; <i>p</i> = 0.001) in number of specialists with payments, respectively. <b><i>Conclusion:</i></b> The majority of respiratory specialists had increasingly received more personal payments from pharmaceutical companies for the reimbursement of lecturing, consulting, and writing between 2016 and 2019. These increasing financial relationships with pharmaceutical companies might cause conflicts of interest among respiratory physicians.

There have been many attempts to visualize the inflamed joints using multiphoton microscopy. However, due to the hypervascular and multilayered structure of the inflamed synovium, intravital imaging of the deep synovial tissue has been difficult. Here, we established original intravital imaging systems to visualize synovial tissue and pathological osteoclasts at the pannus–bone interface using multiphoton microscopy. Combined with fluorescence-labeling of CTLA-4 Ig, a biological agent used for the treatment of rheumatoid arthritis, we identified that CTLA-4 Ig was distributed predominantly within the inflamed synovium and bound to CX 3 CR1 + macrophages and CD140a + fibroblasts 6 h after injection, but not to mature osteoclasts. Intravital imaging of blood and lymphatic vessels in the inflamed synovium further showed that extravasated CTLA-4 Ig was immediately drained through lymphatic vessels under acute arthritic conditions, but the drainage activity was retarded under chronic conditions. These results indicate that this intravital synovial imaging system can serve as a platform for exploring the dynamics of immune cells, osteoclasts, and biological agents within the synovial microenvironment in vivo.