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The liver is the main gateway from the gut, and the unidirectional sinusoidal flow from portal to central veins constitutes heterogenous zones, including the periportal vein (PV) and the pericentral vein zones1-5. However, functional differences in the immune system in each zone remain poorly understood. Here intravital imaging revealed that inflammatory responses are suppressed in PV zones. Zone-specific single-cell transcriptomics detected a subset of immunosuppressive macrophages enriched in PV zones that express high levels of interleukin-10 and Marco, a scavenger receptor that sequesters pro-inflammatory pathogen-associated molecular patterns and damage-associated molecular patterns, and consequently suppress immune responses. Induction of Marco+ immunosuppressive macrophages depended on gut microbiota. In particular, a specific bacterial family, Odoribacteraceae, was identified to induce this macrophage subset through its postbiotic isoallolithocholic acid. Intestinal barrier leakage resulted in inflammation in PV zones, which was markedly augmented in Marco-deficient conditions. Chronic liver inflammatory diseases such as primary sclerosing cholangitis (PSC) and non-alcoholic steatohepatitis (NASH) showed decreased numbers of Marco+ macrophages. Functional ablation of Marco+ macrophages led to PSC-like inflammatory phenotypes related to colitis and exacerbated steatosis in NASH in animal experimental models. Collectively, commensal bacteria induce Marco+ immunosuppressive macrophages, which consequently limit excessive inflammation at the gateway of the liver. Failure of this self-limiting system promotes hepatic inflammatory disorders such as PSC and NASH.
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Colangite Esclerosante , Microbioma Gastrointestinal , Inflamação , Fígado , Macrófagos , Hepatopatia Gordurosa não Alcoólica , Simbiose , Animais , Feminino , Humanos , Masculino , Camundongos , Bacteroidetes/metabolismo , Colangite Esclerosante/imunologia , Colangite Esclerosante/microbiologia , Colangite Esclerosante/patologia , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Perfilação da Expressão Gênica , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia , Interleucina-10/imunologia , Interleucina-10/metabolismo , Fígado/imunologia , Fígado/patologia , Fígado/microbiologia , Macrófagos/citologia , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Veia Porta , Receptores Imunológicos/deficiência , Receptores Imunológicos/metabolismo , Análise de Célula Única , Simbiose/imunologiaRESUMO
BACKGROUND: Clinical practice guidelines assist healthcare professionals in providing evidence-based care. However, pharmaceutical companies' financial interests often influence guideline content. This study aimed to elucidate the magnitude of financial ties among Japanese gastroenterology guideline authors and the pharmaceutical industry. METHODS: Using pharmaceutical company disclosed payment data, we evaluated financial conflicts of interest (COI) among Japanese Society of Gastroenterology guideline authors between 2016 and 2021. Additionally, we assessed the evidence quality supporting guideline recommendations and associations with financial COI. Finally, we evaluated author COI management during guideline development against global standards. RESULTS: Overall, 88.2% (231/262) of guideline authors received a median of $12 968 (interquartile range [IQR]: $1839-$70 374) in payments between 2016 and 2019 for lectures, writings, and consulting. Chairpersons received significantly higher payments (median: $86 444 [IQR: $15 455-$165 679]). Notably, 41 (15.6%) authors had undeclared payments exceeding declaration requirements. Low or very low-quality evidence supported 41.0% of recommendations. There was a negative association between the median 4-year payment per author and the proportion of recommendations based on low-quality evidence (odds ratio: 0.966 [95% confidence interval [95% CI]: 0.945-0.987], P = 0.002) and positive association with moderate-quality evidence (odds ratio: 1.018 [95% CI: 1.011-1.025], P < 0.001). Still, the Japanese Society of Gastroenterology guideline development process remains less transparent, with insufficient COI policies relative to global standards. CONCLUSION: There were extensive financial COI between pharmaceutical companies and guideline authors, and more than 40% of recommendations were based on low-quality evidence. More rigorous and transparent COI policies for guideline development adhering to global standards are warranted.
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Autoria , Conflito de Interesses , Indústria Farmacêutica , Gastroenterologia , Guias de Prática Clínica como Assunto , Humanos , Conflito de Interesses/economia , Apoio Financeiro , Gastroenterologia/economia , Gastroenterologia/ética , Gastroenterologia/normas , Guias de Prática Clínica como Assunto/normas , Indústria Farmacêutica/economia , Indústria Farmacêutica/éticaRESUMO
OBJECTIVE: To evaluate the magnitude and trends in personal payments from pharmaceutical companies to urologists in Japan. METHODS: This cross-sectional study examined the personal payments made to urologists by the major pharmaceutical companies in Japan between 2016 and 2019. Descriptive analyses were performed on the payment data. All urologists board-certified by the Japanese Urological Association as of March 2022 were included in this study. Trends in personal payments were assessed using the population-averaged generalized estimating equations with panel data of per-physician personal payments. RESULTS: Among 7016 active board-certified urologists, 4962 (70.7%) accepted 53,070 payments totaling $36,424,239 for reimbursement of lecturing, writing, and consulting compensations from 66 pharmaceutical companies between 2016 and 2019. The median payments per urologist receiving payments were $1714 [interquartile range(IQR): $700-$4583] in payment amounts and 4.0 (IQR: 2.0-10.0) in the number of payments. Only 1%, 5%, 10%, and 25% of top-paid urologists accepted 36.2%, 64.8%, 75.8%, and 90.1% of overall payments respectively. The payments per urologist and the number of payment contracts had annually increased over this period by 4.1% (95% CI: 2.3%-6.0%, p < 0.001) and 2.4% (95% CI: 1.2%-3.7%, p < 0.001), but there was no significant change in the number of urologists receiving payments, with a relative average annual change of 0.7% (95% CI: -0.15%-1.6%, p = 0.10) between 2016 and 2019. CONCLUSION: Most urologists received personal payments for lecturing, consulting, and writing compensations from pharmaceutical companies in Japan. The payments from pharmaceutical companies had been increasing over the 4-year period. These payments were substantially concentrated on a small number of urologists.
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Indústria Farmacêutica , Urologistas , Humanos , Estados Unidos , Japão , Estudos Transversais , Preparações Farmacêuticas , Conflito de Interesses , RevelaçãoRESUMO
BACKGROUNDS: Given the increasing number of novel and expensive drugs for rheumatoid diseases, the financial relationships between pharmaceutical companies and rheumatologists could be prevalent and substantial. However, little was known about the information in Japan. METHODS: Using payment data publicly disclosed by 92 major pharmaceutical companies, we evaluated the financial relationships between pharmaceutical companies and rheumatologists who were board certified by the Japan College of Rheumatology between 2016 and 2019. The trends in payments were estimated by the generalized estimating equations with 4-year payment data. Differences in payments between general and leading rheumatologists including the board members, clinical practice guideline authors, and medical journal editors were assessed. RESULTS: Of the board-certified rheumatologists, 70.7% (3563 of 5038) received a total of $55,246,485 in personal payments for lecturing, writing, and consulting from 79 pharmaceutical companies between 2016 and 2019. The median payments per rheumatologist receiving payments were $3447 (interquartile range, $1124-$11,974) in payment amounts. There were increasing trends in the payments per rheumatologist and the number of rheumatologists with payments, with average yearly change rates of 5.9% (95% confidence interval, 3.9%-7.9%; p < 0.001) and 1.2% (95% CI, 0.3%-2.0%; p = 0.008). The leading rheumatologists such as the society board members, clinical practice guideline authors, and medical journal editors received much more payments than other rheumatologists. CONCLUSION: Most rheumatologists increasingly received personal payments for lecturing, consulting, and writing reimbursements from pharmaceutical companies in Japan. These payments were significantly concentrated on rheumatologists in authoritative and influential positions.
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Indústria Farmacêutica , Reumatologistas , Humanos , Japão , Conflito de Interesses , Preparações Farmacêuticas , RevelaçãoRESUMO
This cross-sectional study evaluated the magnitude of personal payments made by pharmaceutical companies to pediatric hematologist-oncologists (PHOs) board-certified by the Japanese Society of Pediatric Hematology/Oncology (JSPHO), using publicly disclosed data. Among all 307 PHOs, 215 (70.0%) PHOs received $916 703 personal payments from 54 pharmaceutical companies between 2016 and 2019 in total. Median four-year payments per PHO was $1440 (interquartile range, $523-$4015). Payments per PHO significantly increased during the study period, by 23.8% (95% confidence interval: 15.3%-32.8%, P < 0.001) annually. Furthermore, leading PHOs, including university professors, society board members, and clinical practice guideline authors, received far larger personal payments from the companies.
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Conflito de Interesses , Oncologistas , Criança , Estudos Transversais , Indústria Farmacêutica , Humanos , Japão , Preparações FarmacêuticasRESUMO
BACKGROUND: 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. 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 number 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 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; p < 0.001) in payments and 1.5% (95% CI: 0.61-2.4; p = 0.001) in number of specialists with payments, respectively. CONCLUSION: 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.
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Conflito de Interesses , Indústria Farmacêutica , Humanos , Japão , Estudos Retrospectivos , Pneumologistas , Preparações FarmacêuticasRESUMO
Previous laboratory studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed that the stability of the virus in the air or on surfaces is sensitive to seasonally relevant environmental conditions. However, the seasonality of the virus in the real world remains unclear because each country adopted various infection control policies. Therefore, we investigated peak dates with regard to new confirmed cases of coronavirus disease 2019 (COVID-19) and an association of these dates with the timing of the lockdown among G20 countries that have four seasons from 1 June 2020 to 18 February 2021. As a result, countries in both hemispheres experienced seasonal peaks in the number of COVID-19 cases both in the middle of warm and cold seasons. In addition, there were no apparent relationships between the peak date and periods with stringent measures. Our study demonstrated that SARS-CoV-2 causes seasonal outbreaks in the winter and possibly summer and thus, countries might need to consider measures to prepare for resurgence of the virus in the middle of 2021.
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In recent years,"the fluorescent imaging techniques"has made rapid advances, it has become possible to observe the dynamics of living cells in individuals or tissues. It has been considered that it is extremely difficult to observe the living bone marrow directly because bone marrow is surrounded by a hard calcareous. But now, we established a method for observing the cells constituting the bone marrow of living mice in real time by the use of the intravital two-photon imaging system. In this article, we show the latest data and the reports about the hematopoietic stem cells and the leukemia cells by using the intravital imaging techniques, and also discuss its further application.
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Medula Óssea/patologia , Osso e Ossos/citologia , Células-Tronco Hematopoéticas/citologia , Microscopia de Fluorescência por Excitação Multifotônica , Imagem Molecular , Osteoclastos/citologia , Animais , Humanos , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Imagem Molecular/métodosRESUMO
In recent years, Japan has faced a significant demographic crisis, which was further exacerbated by the coronavirus disease 2019 (COVID-19) pandemic. By 2022, the country experienced a 1.5% decrease in population, which is in contrast to other G7 nations, and had the highest rate of excess mortality among Organization for Economic Co-operation and Development (OECD) countries. This crisis is mainly attributed to aging population, with Japan's aging rate reaching 29.9%, the highest among its peer countries. The Japanese government, led by Prime Minister Fumio Kishida, has proposed policies aimed at addressing these challenges, focusing on increasing fertility rates. Despite these efforts, an evidence-based policymaking (EBPM) analysis reveals that the anticipated impact on fertility rates is marginal, with financial interventions estimated to yield only a slight population increase by 2060. Furthermore, the analysis highlighted the need for a more comprehensive approach, indicating that addressing societal issues such as gender norms and workplace culture might be crucial for a sustainable solution to Japan's demographic challenges. This emphasizes the need for Japan to consider broader societal changes alongside fiscal policies to effectively combat its demographic decline.
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Introduction While prior research showed gender gaps in industry payments for medical professionals in the United States, there are limited data in Japan. So, this study seeks to investigate the potential gender gap in the receipt of pharmaceutical companies (PFCs) across all medical fields in Japan. Based on the results of previous studies, we developed a hypothesis that male doctors get more PFC than female doctors. Materials and methods Data from 92 pharmaceutical companies in Japan, covering 2016 to 2019, were analyzed. The analysis was conducted on professors and associate professors at all national and public medical universities in Japan, with gender as a factor variable and payments as an outcome variable, and variables that may have influenced the factor or outcome variables in previous studies, such as specialization, university type, region, rank and years since graduation, as control variables. Payments were converted to US dollars using the December 31, 2021, rate of 115 yen to the dollar for comparison purposes. Results Out of 1,825 subjects, 1,755 were males and 70 females. Males consistently received higher median payments from pharmaceutical companies (PFCs) than females across categories. In particular, among physicians specializing in internal medicine, the median PFC for men was $25 compared to $8 for women. For physicians affiliated with former imperial universities (the seven former imperial universities founded before World War II), the median PFC for men was $32 compared to $5 for women. Multivariate analysis confirmed significantly higher total benefits for males from 2016 to 2019, with the gender gap widening during this period (incidence rate ratio (IRR) for 2016: 0.51, IRR for 2019: 0.44). Conclusions Japanese male professors and associate professors received significantly higher PFCs than their female counterparts, and this gender gap expanded from 2016 to 2019, highlighting persistent gender inequality in the medical field in Japan, similar to trends observed in the United States.
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Improper mechanical stress may induce side effects during orthodontic treatment. If the roots and alveolar bones are extensively resorbed following excess mechanical stress, unplanned tooth mobility and inflammation can occur. Although multiple factors are believed to contribute to the development of side effects, the cause is still unknown. Sonic hedgehog (Shh), one of the hedgehog signals significantly associated with cell growth and cancer development, promotes osteoclast formation in the jawbone. Shh may be associated with root and bone resorptions during orthodontic treatment. In this study, we investigated the relationships between Shh, RANKL, and IL-6 in human periodontal ligament (hPDL) cells exposed to improper mechanical force. Weights were placed on hPDL cells and human gingival fibroblasts (HGFs) for an optimal orthodontic force group (1.0 g/cm2) and a heavy orthodontic force group (4.0 g/cm2). A group with no orthodontic force was used as a control group. Real-time PCR, SDS-PAGE, and Western blotting were performed to examine the effects of orthodontic forces on the expression of Shh, RANKL, and IL-6 at 2, 4, 6, 8, 12, and 24 h after the addition of pressure. The protein expression of Shh was not clearly induced by orthodontic forces of 1.0 and 4.0 g/cm2 compared with the control in HGFs and hPDL cells. In contrast, RANKL and IL-6 gene and protein expression was significantly induced by 1.0 and 4.0 g/cm2 in hPDL cells for forces lasting 6~24 h. However, neither protein was expressed in HGFs. RANKL and IL-6 expressions in response to orthodontic forces and in the control were clearly inhibited by Shh inhibitor RU-SKI 43. Shh did not directly link to RANKL and IL-6 for root and bone resorptions by orthodontic force but was associated with cell activities to be finally guided by the production of cytokines in hPDL cells.
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OBJECTIVE: There is insufficient data on the financial relationships between Japanese neurologists and pharmaceutical companies prior to the advent of new-generation Alzheimer's disease drugs. The purpose of this study is to evaluate the magnitude, prevalence, and trend of the financial relationship between Japanese neurologists and pharmaceutical companies between 2016 and 2019. METHODS: A cross-sectional study was undertaken to evaluate the financial relationships between all board-certified neurology specialists and pharmaceutical companies in Japan from 2016 and 2019. Descriptive statistics were applied to measure the magnitude and prevalence of payments among specialists, as well as their trends during the study periods. RESULTS: In a four-year analysis, 77 pharmaceutical companies disbursed a total of USD 36,869,204 across 50,050 payments to 2,696 neurologists in Japan, revealing a mean payment of USD 10,809 per specialist. Notably, the Gini index of 0.997 indicated a high inequality in payment distribution, with a minority of specialists receiving a substantial proportion of payments. Trends displayed irregularities, but an overall increase in total payments from 2016 to 2019, with a significant contribution from the top 10 pharmaceutical companies accounting for 74.2% of total payments, with Takeda Pharmaceutical and Eisai Company notably increasing payments in 2019. There were notable geographical variations in neurologist and payment distribution across 47 prefectures. CONCLUSION: Our analysis of neurologist payments from pharmaceutical companies in Japan showed a substantial financial relationship with overall increases, yearly varied increments, and payment inequality. Caution is warranted as financial ties may intensify with the continued development of next-generation Alzheimer's disease drugs.
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Both public and academic scrutiny of the financial relationships between the medical device industry and the healthcare society occur less frequently than those involving the pharmaceutical industry, and Japan is no exception to these shortcomings. This paper examines the ethical and legal challenges inherent in Japan's medical device industry through the lens of bribery scandals, placing these issues within the broader context of global healthcare corruption. It aims to derive lessons and suggest universal strategies for ethical and legal enhancements. The discussion includes two notable cases: one involving inappropriate transactions between a cancer center and a biliary stent manufacturer, and another concerning a corrupt donation scheme between a medical device company and a university's anesthesiology department, which was found guilty. In our analysis, we also acknowledge the industry's efforts toward compliance and reform to maintain a balanced perspective. The analysis not only highlights the unique culture and structure of the Japanese medical device industry, such as the exploitation of flexible pricing and opaque financial practices but also contrasts these issues with the tightly regulated pharmaceutical industry. This approach reveals both sector-specific challenges and common corruption drivers, enhancing our understanding of why such scandals occur and persist. We propose ethical and compliance-focused business measures such as centralizing donation decisions, limiting the financial independence of marketing divisions, and increasing transparency, alongside adopting mandatory disclosure practices based on successful models from the United States and Europe. By emphasizing integrity and presenting diverse perspectives, this study aims to elevate ethical and legal standards in the medical device industry and improve patient health outcomes worldwide.
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The in situ behavior of living cells can be visualized by two-photon microscopy. Here, we present a protocol for the live imaging of transferred mouse bone marrow cells by two-photon microscopy. We describe steps for staining and injecting target cells into mice, fixing the skull bone to a head holder and stage, and 4D imaging bone marrow using multi-photon microscopy. We then detail procedures for creating images and analyzing cells. For complete details on the use and execution of this protocol, please refer to Sudo et al. (2021).1.
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Células da Medula Óssea , Microscopia , Animais , Camundongos , Fótons , Crânio , Coloração e RotulagemRESUMO
Introduction: Immune checkpoint inhibitors such as programmed cell death/-ligand 1 inhibitor and cytotoxic T-lymphocyte-associated antigen-4 inhibitors have been widely used for various advanced malignancies. The mechanism of action for these inhibitors is the improvement of antitumor immunity via T-cell modulation. On the contrary, immune-related adverse events such as autoimmune colitis might arise in association with T-cell activation. Upper gastrointestinal adverse events related to pembrolizumab have rarely been reported. Case presentation: A 72-year-old man underwent laparoscopic radical cystectomy for muscle-invasive bladder cancer (pT2N0M0). Multiple lymph node metastases appeared in the paraaortic region. First-line chemotherapy comprising gemcitabine and carboplatin failed to stop disease progression. After the administration of pembrolizumab as second-line treatment, the patient showed symptomatic gastroesophageal reflux disease. Esophagogastroduodenoscopic biopsy of the gastric body showed severe lymphoplasmacytic and neutrophilic infiltration. Conclusion: We present acute gastritis related to pembrolizumab. Early eradication therapy may be able to control immune checkpoint inhibitor-related gastritis.
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OBJECTIVES: Limited evidence is available regarding the financial relationships between gastroenterologists and pharmaceutical companies in Japan. This study analysed the magnitude, prevalence and trends of personal payments made by major pharmaceutical companies to board-certified gastroenterologists in Japan in recent years. DESIGN: Cross-sectional analysis SETTING AND PARTICIPANTS: Using payment data publicly disclosed by 92 major pharmaceutical companies, this study examined the non-research payments made to all board-certified gastroenterologists by the Japanese Society of Gastroenterology. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were payment amounts, the prevalence of gastroenterologists receiving payments, yearly trends in per-gastroenterologist payment values and the number of gastroenterologists with payments. Additionally, we evaluated the differences in payments among influential gastroenterologists, including clinical practice guideline authors, society board member gastroenterologists and other general gastroenterologists. RESULTS: Approximately 52.8% of all board-certified gastroenterologists received a total of US$89 151 253, entailing 134 249 payment contracts as the reimbursement for lecturing, consulting and writing, from 84 pharmaceutical companies between 2016 and 2019. The average and median payments per gastroenterologist were US$7670 (SD: US$26 842) and US$1533 (IQR: US$582-US$4781), respectively. The payment value per gastroenterologist did not significantly change during the study period, while the number of gastroenterologists with payments decreased by -1.01% (95% CI: -1.61% to -0.40%, p<0.001) annually. Board member gastroenterologists (median: US$132 777) and the guideline authoring gastroenterologists (median: US$106 069) received 29.9 times and 17.3 times higher payments, respectively, than general gastroenterologists (median: US$284). CONCLUSION: Most gastroenterologists received personal payments from pharmaceutical companies, but only very few influential gastroenterologists with authority accepted substantial amounts in Japan. There should be transparent and rigorous management strategies for financial conflicts of interest among gastroenterologists working in influential positions.
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Indústria Farmacêutica , Gastroenterologistas , Humanos , Conflito de Interesses , Estudos Transversais , Revelação , Indústria Farmacêutica/economia , Gastroenterologistas/economia , JapãoRESUMO
OBJECTIVE: There are few valid indicators of oral infection owing to the complexity of pathogenic factors in oral diseases. Salivary markers are very useful for scrutinizing the symptoms of disease. To provide a reliable and useful predictive indicator of infection for opportunistic pathogens in individuals with compromised immune systems, such as those with periodontal diseases and Human Immunodeficiency Virus (HIV), this study examines opportunistic pathogens such as C. albicans and staphylococci and macrophage colony-stimulating factor (M-CSF) and CA125/MUC16 in saliva. The aim was to explore the correlations investigated among these factors. METHODS: Samples were divided into two groups (based on patient sex, the absence and presence of dentures in elderly, or HIV-positive patients and healthy subjects), and the correlation was analyzed in two groups of elderly patients with periodontal disease (64.5 ± 11.2 years old) and HIV-infected patients (41.9 ± 8.4 years old). Healthy subjects (33.8 ± 9.1 years old) were also analyzed as a control. Levels of C. albicans, staphylococci, and M-CSF, which is an immunological factor for the differentiation of macrophage, and CA125/MUC16, which provides a protective lubricating barrier against infection, were investigated. RESULTS: A significant and positive correlation between the levels of M-CSF and staphylococci was found in elderly individuals and HIV-positive patients treated with antiretroviral therapy. A significant and positive correlation between the levels of M-CSF and CD125/MUC16 was also found in both patients. These correlations were enhanced in both patients as compared with healthy subjects. CONCLUSION: Salivary M-CSF might be useful as a new indicator of opportunistic infection caused by staphylococci and a defense against infection in immunocompromised hosts.
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Purpose Transparency in healthcare has led to increased public disclosure of doctors' conflicts of interest, with the "Yen for Docs Database" in Japan emerging as a pivotal source. Nevertheless, there remains ambiguity regarding the backgrounds and influence of highly-searched persons, especially during the COVID-19 pandemic. The primary objective of this study was to examine if the database was utilized for its intended purpose in 2021, a year marked by the introduction of vaccines and treatments, the addition of new COVID-19-related data, and the frequent appearances of expert statements in various media outlets. Methods We conducted a descriptive analysis on the 10 most frequently searched individuals in the "Yen for Docs Database" between August 27 and September 23, 2021, and determined the amount of money they received from pharmaceutical companies and other organizations over the four-year period between 2016 and 2019. To characterize frequently searched individuals' academic profiles and appearances in the mass media, we identified their h-index and affiliation, their activity on Twitter, and the number of TV appearances. Results There were 72,904 searches during the study period, with the top person accounting for 4,905 of those searches. All top 10 were male, mostly affiliated with universities and specialists in infectious diseases or related fields. Their median number of COVID-19 articles was five, and the median h-index was 34. Four of these top 10 had Twitter accounts, with followers ranging from 12,000 to 195,000. The median amount received from pharmaceutical entities over four years was $154,930, ranging from $809 to $705,502. Conclusions In the Yen for Docs Database, a significant portion of searches during the COVID-19 pandemic was concentrated on a selected group of healthcare professionals with considerable payments over the years, and they exhibited prominent academic and media profiles. These observations highlight the need for more transparent conflicts of interest disclosure among physicians with public visibility.