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Introduction: Dolutegravir (DTG), a novel HIV-integrase strand transfer inhibitor (INSTI), is usually used with multiple antiretrovirals (ARVs) for treatment of HIV. DTG is now approved as Tivicay tablets in over 120 countries and Triumeq combination tablets (DTG/abacavir [ABC]/lamivudine [3TC]) in over 90 countries. In Japan, these formulations have been marketed since 2014 and 2015. The post-marketing prospective surveillance has been conducted as part of the HIV-Related Drug (HRD) cooperative survey aimed to collect actual drug use information in all of these DTG-treated patients in accordance with conditions for initial approvals.Methods: The survey has been conducted to evaluate long-term safety and effectiveness of DTG since 2014, for approximately 6 years. The safety was evaluated by incidence of adverse drug reactions (ADRs) and change in body weight. The effectiveness was evaluated by plasma HIV RNA copies/mL and peripheral CD4+ cell counts.Results: Of 2292 patients in 30 Japanese sites, 565 (24.65%) reported ADRs. The most common ADR was blood creatinine increased (4.28%). Incidence of ADRs was statistically significantly higher in patients with severe symptoms (Centers for Disease Control and Prevention [CDC] categories B and C) than those with category A, and in patients with comorbidities than those without comorbidities. Whereas incidence of ADRs was statistically significantly lower in antiretroviral therapy (ART)-experienced patients than that in ART-naïve patients. Incidence of ADRs related to suicide or self-injurious behavior was statistically significantly higher in patients with comorbidities of psychiatric disorders than those without comorbidities. The body weight tended to increase over time and those changes and percentage changes from baseline were greater in ART-naïve patients compared with ART-experienced patients. HIV RNA copies/mL and CD4+ cell counts showed favorable shifts from baseline in both ART-naïve and ART-experienced patients.Conclusion: The results of the survey identified no new safety and effectiveness risks in Japanese patients with HIV/AIDS treated with DTG. [ABSTRACT FROM AUTHOR]

While entanglement is a phenomenon discussed in quantum theory, it can also be found in art. We propose to connect entanglement to art's most fundamental question: what is creativity? For example, Marcel Duchamp found the essence of the creative act in the "art coefficient," the difference and/or gap between the artist's intention and realization which is created. This paper locates the common sense understanding of entanglement in an inseparable whole that ensures difference between the intention and realization. Seeing the artistic act as actively designing entanglement within artistic production, we present examples of this from the work of the Japanese-style painter Nakamura, and present a concrete vision for an answer regarding the question of the nature of creativity. [ABSTRACT FROM AUTHOR]

Free will in intentional consciousness is exposed to skeptics since it was found that subconscious neural activities, what is called readiness potential, precedes the intention to an action. The question of whether free will is an authentic illusion has been argued not only in psychology but physics and philosophy. Most of scientists, however, think that the intentional consciousness who believes to have his/her own free will, is determined by readiness potential in advance, and that free will cannot coexist with determinism. We here point out that knowing to be determined in advance cannot be verified till local event at a local site can be known from a different local site without disturbing the event. That is the assumption of locality. We here show that determinism, free will and locality are three essential elements in consciousness, and show that they constitute trilemma. The fact that one of three elements must be abandoned can lead to three types of consciousness. Absence of free will can constitute type I consciousness which is consistent with symptoms in autism spectrum disorder such as weakened theory of mind. Absence of determinism can constitute type II consciousness which is consistent with symptoms in schizophrenia such as thought insertion, self-other integration. Absence of locality can constitute type III consciousness which is consistent with typical people. We can find the entanglement of intentional consciousness with unconsciousness including readiness potential only in type III consciousness. Finally, we show that sense of agency and free will cannot be established until consciousness as an entanglement is implemented. [ABSTRACT FROM AUTHOR]

Fat-associated lymphoid clusters (FALCs) are a type of lymphoid tissue associated with visceral fat. Here we found that the distribution of FALCs was heterogeneous, with the pericardium containing large numbers of these clusters. FALCs contributed to the retention of B-1 cells in the peritoneal cavity through high expression of the chemokine CXCL13, and they supported B cell proliferation and germinal center differentiation during peritoneal immunological challenges. FALC formation was induced by inflammation, which triggered the recruitment of myeloid cells that expressed tumor-necrosis factor (TNF) necessary for signaling via the TNF receptors in stromal cells. Natural killer T cells (NKT cells) restricted by the antigen-presenting molecule CD1d were likewise required for the inducible formation of FALCs. Thus, FALCs supported and coordinated the activation of innate B cells and T cells during serosal immune responses. [ABSTRACT FROM AUTHOR]

Afferent lymph-borne dendritic cells essentially rely on the chemokine receptor CCR7 for their transition from the subcapsular lymph node sinus into the parenchyma, a migratory step driven by putative gradients of CCR7 ligands. We found that lymph node fringes indeed contained physiological gradients of the chemokine CCL21, which depended on the expression of CCRL1, the atypical receptor for the CCR7 ligands CCL19 and CCL21. Lymphatic endothelial cells lining the ceiling of the subcapsular sinus, but not those lining the floor, expressed CCRL1, which scavenged chemokines from the sinus lumen. This created chemokine gradients across the sinus floor and enabled the emigration of dendritic cells. In vitro live imaging revealed that spatially confined expression of CCRL1 was necessary and sufficient for the creation of functional chemokine gradients. [ABSTRACT FROM AUTHOR]

Endothelial expression of the gap junction proteins, connexin (Cx) 37, Cx40, and Cx43, varies within the vascular network. While previous studies suggest that shear stress may upregulate Cx43, it is not well understood if shear stress affects the expression of all endothelial connexins and to what extent. Endothelial cells on the upstream and downstream surfaces of cardiac valves are subjected to considerably different intensities of shear stress. We therefore reasoned that we could determine the extent hemodynamic forces affect the ex- pression of Cx37, Cx40, and Cx43 by comparing their immunohistochemical distribution on the upstream and downstream surfaces of rat cardiac valves. We found 70- to 200-fold greater expression of Cx43 in the endothelial cells on the upstream than on the downstream surfaces. However, Cx37 was expressed almost equally in the endothelial cells on upstream and downstream surfaces, and Cx40, a major connexin in most vascular endothelial cells, was not detected on either surface. In addition to the heterogeneity in Cx43 expression, endothelial cells on the upstream surface were 35% to 65% smaller than those on the corresponding downstream surface. These results suggest that shear stress may affect endothelial cell size and Cx43 expression but not Cx37 expression. [ABSTRACT FROM AUTHOR]