Two cases of intraoperative hemodynamic instability during combined thoracoscopic-laparoscopic surgery for esophagogastric junction carcinoma

Background Intraoperative complications during combined thoracoscopic-laparoscopic surgery for esophagogastric junction (EGJ) carcinoma have not been reported as compared to those during surgery for esophageal carcinoma. We present two cases which had surgery-related hemodynamic instability during laparoscopic proximal gastrectomy and intra-mediastinal valvuloplastic esophagogastrostomy (vEG) with thoracoscopic mediastinal lymphadenectomy for EGJ carcinoma. Case presentation In case 1, the patient fell into hypotension with hypoxemia during laparoscopic vEG due to pneumothorax caused by entry of intraabdominal carbon dioxide. In case 2, ventricular arrythmia and ST elevation occurred during laparoscopic vEG. Pericardium retraction to secure surgical field during reconstruction compressed the coronary artery, which caused coronary malperfusion. These two events were induced by the surgical procedure, characterized by the following: (1) connection of the thoracic and abdominal cavities and (2) cardiac displacement during vEG. Conclusion These cases indicated tension pneumothorax and coronary ischemia are possible intraoperative complications specific to combined thoracoscopic-laparoscopic surgery for EGJ carcinoma

How different are offline and online diplomacy? A comparative analysis of public statements and SNS posts by delegates to the United Nations

IntroductionThis article investigates the evolving landscape of diplomacy in the digital age, focusing on diplomats at the United Nations (UN) Headquarters in New York. The central inquiry revolves around how diplomatic actors use digital tools to complement or augment traditional face-to-face diplomacy.MethodsWe systematically compare a substantial corpus of X posts (tweets) from UN diplomats with their public statements at the United Nations Security Council (UNSC), employing advanced computational social science techniques. This study applies a range of large-scale text analysis methods, including word embedding, topic modeling, and sentiment analysis, to investigate systematic differences between offline and online communication.ResultsOur analysis reveals that, while the essence of diplomacy remains consistent across both domains, there is strategic selectivity in the use of online platforms by diplomats. Online communication emphasizes non-security topics, ceremonial matters, and prominent policy stances, in contrast to the operational issues common in UNSC deliberations. Additionally, online discourse adopts a less confrontational, more public diplomacy-oriented tone, with variations among countries.DiscussionThis study offers one of the first systematic comparisons between offline and online diplomatic messages. It illuminates how diplomats navigate the digital realm to complement traditional roles. The findings indicate that some elements of public diplomacy and nation branding, directed toward a wider audience far beyond the council chamber, have become an integral part of multilateral diplomacy unfolding at the UNSC

Association between oral corticosteroid starting dose and the incidence of pneumonia in Japanese patients with ulcerative colitis: a nation-wide claims database study

Background/Aims A previous study demonstrated that half of patients started oral corticosteroids (OCS) for ulcerative colitis (UC) exacerbations at lower doses than recommended by Japanese treatment guidelines (initial OCS prednisolone equivalent dose, 30–40 mg). This may relate to physician’s concern about infection, especially pneumonia including Pneumocystis jirovecii pneumonia (PJP), from high OCS doses. We assessed whether pneumonia incidence is increased with guideline-recommended OCS initial doses. Methods This retrospective cohort study used the Japan Medical Data Center claims database (2012–2021). The whole cohort consisted of all UC patients who started OCS during the study period meeting the inclusion and exclusion criteria. The matched cohort was created by propensity score matching; the lower (initial OCS dose 40 mg) in a 2:2:1 ratio. Pneumonia incidence in the primary analysis was evaluated in the matched cohort. A Poisson regression model determined pneumonia-related risk factors in the whole cohort. Results After screening, 3,349 patients comprised the whole cohort; 1,775 patients comprised the matched cohort (lower dose, n = 710; guideline-recommended dose, n = 710; higher dose, n = 355). The incidence of any pneumonia was low; no differences were observed in incidence rates across these dose subgroups. In total, 3 PJP cases were found in the whole cohort, but not detected in the matched cohort. Several risk factors for any pneumonia were identified, including age, higher comorbidities index, treatment in large facility and hospitalization. Conclusions The incidence of pneumonia, including PJP, in UC patients was low across initial OCS dose treatment subgroups

Facilitation of Th1-mediated immune response by prostaglandin E receptor EP1

Prostaglandin E2 (PGE2) exerts its actions via four subtypes of the PGE receptor, EP1–4. We show that mice deficient in EP1 exhibited significantly attenuated Th1 response in contact hypersensitivity induced by dinitrofluorobenzene (DNFB). This phenotype was recapitulated in wild-type mice by administration of an EP1-selective antagonist during the sensitization phase, and by adoptive transfer of T cells from sensitized EP1−/− mice. Conversely, an EP1-selective agonist facilitated Th1 differentiation of naive T cells in vitro. Finally, CD11c+ cells containing the inducible form of PGE synthase increased in number in the draining lymph nodes after DNFB application. These results suggest that PGE2 produced by dendritic cells in the lymph nodes acts on EP1 in naive T cells to promote Th1 differentiation

The Role of a Brain-specific Splice Variant of Ryanodine Receptor Type 1

The ryanodine receptor type 1 (RyR1) is capable of homotetrameric assembly to form a Ca2+ release channel at intracellular Ca2+ storage sites such as endoplasmic reticulum (ER). The mRNA transcript encoding full-length RyR1 is approximately 16kb and is mainly distributed in excitable cells. A 2.4-kb mRNA splice variant from the 3\u27-terminal region of the RyR1 gene coexists specifically in brain together with the full-length form, although the functions of this brain-specific splice variant remain unclear. To investigate the short form of RyR1 in intracellular Ca2+ signaling in brain at the cellular level, we established an experimental system whereby the green fluorescent protein (GFP) -tagged brain-specific variant of RyR1 is coexpressed with the full-length protein in the same cell. Both forms of RyR1 were localized in the ER. Caffeine-induced Ca2+-release activities in cells expressing both the brain-specific and full-length RyR1 were reduced compared to cells expressing only the full-length form of RyR1. These results suggested that coexpression of the brain-specific splice variant of RyR1 with its full-length counterpart modulates intracellular Ca2+ signaling by acting as a dominant-negative subunit of the Ca2+ release channel in a tissue-specific fashion

Construction of an All-in-one Double-conditional shRNA Expression Vector

Gene silencing by RNA interference （RNAi） is widely used for assessing gene function. An important advance in the RNAi field was the discovery that plasmid-based RNAi can substitute for synthetic small interfering RNA in vitro and in vivo. However, constitutive and ubiquitous knockdown of gene expression by RNAi in mice can limit the scope of experiments because this process can lead to embryonic lethality, or result in compensatory overexpression of other genes such that no phenotypic abnormalities occur. Either way, analyses of the physiological roles of the gene of interest in adult mice are not possible. To overcome these limitations, we previously constructed a double-conditional short-hairpin RNA （shRNA） expression vector that can regulate shRNA expression in a spatio-temporal manner with a tetracycline-inducible floxed stuffer sequence selectively excised by application of Cre recombinase. In this study, we aimed to modify this vector to create an all-in-one vector that produces double-conditional transgenic mice through a single round of gene transfer to fertilized eggs. We added a coding region for nuclear localizing Cre （NCre） recombinase with a multi-cloning site for a cell-specific promoter into the double-conditional short-hairpin RNA （shRNA） expression vector that we previously constructed. Using Escherichia coli, we confirmed successful construction of the vector. First, we confirmed isopropyl-β-D-thiogalactopyranoside-induced expression of NCre recombinase through the lac operon as a specific promoter by western blotting. Second, we confirmed functional recombination of the floxed sequence of loxP-like TATA-lox by analysing restriction enzyme-digested fragments. This all-in-one double-conditional shRNA expression vector will be useful for reversible in vitro and in vivo knockdown of target gene expression, in target cells via promoter-specific expression of NCre, and at specific times by tetracycline application

Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study

BackgroundThe ORAL Surveillance trial showed a potentially higher incidence of malignancy and major adverse cardiovascular events (MACEs) associated with tofacitinib than those associated with tumor necrosis factor (TNF) inhibitors (TNFis). However, few studies have compared the safety of non-TNFis or other Janus kinase (JAK) inhibitors (JAKis). This study was aimed at comparing the incidence rates (IRs) of malignancies and MACEs in patients with rheumatoid arthritis (RA) treated using interleukin-6 (IL-6) inhibitors (IL-6is) or JAKis.MethodsWe retrospectively analyzed 427 patients with RA who were treated using an IL-6i (n = 273) or a JAKi (n = 154). We determined the IRs of malignancy and MACEs, and the standardized incidence ratio (SIR) of malignancies and investigated factors related to malignancy and MACEs. After adjusting the clinical characteristic imbalance by propensity score matching (PSM), we compared the IRs of adverse events between the JAKi and IL-6i groups.ResultsAfter PSM, the observational period was determined to be 605.27 patient-years (PY), and the median observational period was determined to be 2.28 years. We identified seven cases of malignancy (IR: 2.94 per 100 PY) in the JAKi-treated group and five cases (IR: 1.36 per 100 PY) in the IL-6i-treated group after PSM. The IR of MACEs was 2.56 and 0.83 (per 100 PY) in the JAKi- and IL-6i-treated groups. The IRRs of JAKi-treated patients versus IL-6i-treated patients were 2.13 (95% confidence interval (CI): 0.67–7.42) for malignancy and 3.03 (95% CI: 0.77–15.21) for MACE. There were no significant differences in IRR for malignancy and MACE between both groups after PSM. Univariate and multivariable Cox regression analyses revealed that older age and JAKi use were independent risk factors for malignancy, while older age, hypertension, and JAKi use were independent risk factors for MACEs. The overall malignancy SIR was significantly higher in the JAKi-treated group compared to the general population (2.10/100 PY, 95% CI: 1.23–2.97).ConclusionThe IRs of malignancy and MACE in patients with RA after PSM were comparable between IL-6i-treated and JAKi-treated patients. However, the SIR of malignancy in JAKi treatment was significantly higher than in the general population; therefore, further safety studies comparing JAKi to non-TNFi biologic disease-modifying antirheumatic drugs (bDMARDs) are needed