Assistive technologies and aging in place for people with dementia and disabilities: a proof-of-concept study with in-home passive remote monitoring with interactive communication functions.

PURPOSE: Can assistive technologies (ATs) support aging in place for people with dementia and disability? In seeking to go beyond the persistent institutional care delivery paradigm, this proof-of-concept study tested the feasibility of home care delivery using sensors and remote communication devices. This article reports the collaborative efforts among care professionals, care recipients and family caregivers in their private home environment and the impact of in-home passive remote monitoring (PRM) system on the users. The purpose of this study was to investigate the usability and impact of a PRM system combining in-house passive remote monitoring and an interactive communication function. METHODS: In order to realize AT-supported, person-centered aging in place, a new care delivery model was designed, developed and tested for the duration of 12 weeks. The study was conducted with 5 older people (1 with severe disability and 4 with dementia), their primary family carers with 15 care professionals as users. RESULTS: The findings indicate that there were some technical issues. However, the overall assessment of the system performance was positive, and the users expressed favorable views regarding its preventive and interactive nature. The importance of team-based care delivery, adjusted to fit the PRM equipment, was also highlighted. Faced with the challenge of meeting the increasing demand for person-centered care with limited resources, there will be a greater need for better integration of improved ATs. The study indicates ATs' potential for enhancing the quality of life for those involved in caregiving, while stressing the significance of stakeholders' engagement, skills and teamwork.IMPLICATIONS FOR REHABILITATIONThis proof-of-concept study tested the feasibility of a home care delivery system using sensors and remote communication device for those with dementia and disabilities.A home care delivery system was successfully created for 12 weeks by collaborative efforts among care professionals, care recipients and family caregivers in their private home environment.The introduction of in-home passive remote monitoring system increased the possibility of the older adults being able to live independently, and enabled rehabilitation at home.The users had favourable views regarding the system's preventive and interactive nature and highlighted a greater need for better integration of improved assistive technology in long-term care and rehabilitation.

[Factors related to activity satisfaction and activity burden in foster parents: A cross-sectional study].

Objectives　This study aimed to identify the relevant factors related to activity satisfaction (AS) and activity burden (AB) in foster parents on the basis of sex.Methods　A survey was conducted among 2,142 foster parents from 32 local foster parent associations. The inclusion criterion was survey respondents who had experience in raising foster children. The demographics, individual factors, and social support/capital factors were measured individually. The residential populations were examined at the municipal level. Based on previous studies, questions related to AS and AB were created using a four-item method. We performed multiple logistic regression analyses. The parents were divided into two groups based on the median total scores of AS and AB, identified as dependent variables.Results　A total of 1,052 parents responded to the survey (response rate, 49.1%), of whom 752 had no data deficiencies and had experience in fostering children; thus, they were included in the analysis, and were divided by sex into male (n=247, 32.8%) and female (n=505, 67.2%) groups. Among the men, multiple logistic regression analysis revealed that satisfaction with the child guidance center (CGC) was a significant factor related to AS and AB. Among the women, <10 years of experience as a foster parent, experience in caring for an infant, and participation in foster parent meetings were significant factors related to AS. Having a biological child, experience of fostering children with disabilities, satisfaction with the CGC, and participation in community activities were significant factors related to AB.Conclusion　Although factors related to AS and AB differed between men and women, satisfaction with the CGC was an important factor for both groups. This suggests that the CGC plays a crucial role in supporting foster parents. We believe that it is essential for the CGC to provide specialized support to foster parents and maintain close relationships with them.

Validity and reliability of the Integrated Palliative Care Outcome Scale for non-cancer patients.

AIM: This study assessed the validity and reliability of the Integrated Palliative Care Outcome Scale for non-cancer patients. METHODS: We recruited 223 non-cancer patients receiving palliative care and their healthcare providers (222) across two home care facilities and two hospitals for a cross-sectional study. We assessed the construct validity and known-group validity of the Integrated Palliative Care Outcome Scale. The weighted kappa and interclass correlation coefficients were assessed to ascertain reliability. RESULTS: The scale scores were significantly higher for the 'non-stable' group (worsening condition group) measured in the palliative care phase than for the 'stable' group (P < 0.001). Regarding validity, Spearman's correlations between similar items on the Integrated Palliative Care Outcome Scale and Edmonton Symptom Assessment System ranged from 0.61 to 0.94. Regarding reliability, the weighted kappa coefficients ranged from 0.53 to 0.81 for patients and from 0.58 to 0.90 for healthcare providers. For inter-rater reliability between patients and healthcare providers, the weighted kappa coefficients for each item ranged from 0.03 to 0.42. CONCLUSION: This study confirmed the validity and reliability of the Integrated Palliative Care Outcome Scale for non-cancer patients requiring palliative care. However, the inter-rater reliability indicates poor agreement between the assessments of patients and healthcare providers. This highlights the discrepancies between both their assessments and the importance of the patient's assessment. Geriatr Gerontol Int 2023; 23: 517-523.

Routine patient assessment and the use of patient-reported outcomes in specialized palliative care in Japan.

BACKGROUND: Discrepancies in symptom assessment between providers and patients are reported in cancer care, and the use of patient-reported outcome measures (PROMs) has been recommended for patients receiving palliative care. However, the status of the routine use of PROMs in palliative care in Japan is presently unclear. Therefore, this study aimed to clarify this complex question. To this end, we administered a questionnaire survey either online or via telephone interviews (questionnaire: sent to 427 designated cancer hospitals, 423 palliative care units [PCUs], and 197 home hospices; interviews: conducted at 13 designated cancer hospitals, nine PCUs, and two home hospices). RESULTS: Questionnaires were returned from 458 institutions (44% response rate). We found that 35 palliative care teams (PCTs, 15%), 66 outpatient palliative care services (29%), 24 PCUs (11%) and one (5%) home hospice routinely used PROMs. The most frequently implemented instrument was the Comprehensive Care Needs Survey questionnaire. Moreover, 99 institutions (92%) that routinely used PROMs responded these instruments as useful in relieving patients' symptoms; and moreover, the response rate in regard to usefulness in symptom management was higher than that of institutions that did not routinely use PROMs (p = 0.002); > 50% of the institutions that routinely used PROMs stated that use of these instruments was influenced by disease progression and patients' cognitive function. Moreover, 24 institutions agreed to be interviewed, and interviews demonstrated the benefits of and the barriers to the implementation of PROMs. Effective methods used in the implementation of PROMs were introduced as efforts to reduce the burden placed on patients and to promote healthcare providers' education in the use of PROMs. CONCLUSIONS: This survey quantified the status of the routine use of PROMs within specialized palliative care in Japan, revealed barriers to wider PROM use, and identified needed innovations. Only 108 institutions (24%) routinely used PROMs within specialized palliative care. Based on the results of the study, it is necessary to carefully consider the usefulness of PROs in clinical palliative care, perform careful selection of PROMs according to the patient's condition, and evaluate how specifically to introduce and operate PROMs.

Summer Hospitalization and Bronchial Asthma Make Treatment of Respiratory Syncytial Virus Infection Difficult: A Retrospective Study in Japan.

In recent years, epidemics of respiratory syncytial virus (RSV) have been seen in the summer in Japan. Patients hospitalized in the summer used a high-flow oxygen administration device more frequently than patients hospitalized in the winter. This study was a retrospective study to examine the variables associated with duration of oxygen therapy and severe cases. Subjects were pediatric patients diagnosed with RSV infection and hospitalized for treatment during the 5 years from April 2014 to March 2019. Data from 292 patients were analyzed. Duration of oxygen therapy was significantly associated with bronchial asthma (partial regression coefficient: 0.897, P = .004). Hospitalization in summer was significantly associated with severe condition (adjusted odds ratio: 4.07, 95% confidence interval: 1.16-14.27). The present study showed that bronchial asthma is a risk factor for prolonged oxygen therapy and infection in summer is a risk factor for progression to severe condition in cases of RSV infection.

Birth Weight Standard Deviation Score is a Significant Determinant of Serum Urotensin-II Levels at Term-Equivalent Age in Preterm Infants.

OBJECTIVE: Urotensin II (U-II) is a potent vasoconstrictor peptide, and increased U-II levels are associated with atherosclerosis and hypertension in adults. Low birth weight (LBW) infants have higher risks of such diseases in the future. A small number of nephrons is one of possible mechanism underlying these risks in LBW infants, while vascular elasticity and cardiac function might be another important factor. The objective of this study is to evaluate U-II levels in preterm LBW infants at an early stage of life and determine perinatal factors associated with U-II levels. STUDY DESIGN: The study population consisted of 57 preterm LBW infants (26 males and 31 females), including 49 appropriate for gestational age (AGA) and 8 small for gestational age (SGA) infants, born at a gestational age of ≤34 weeks with a mean birth weight of 1,589 g. Serum U-II levels were measured at term-equivalent age to evaluate perinatal factors related to serum U-II levels. RESULTS: Preterm SGA infants had significantly higher serum U-II levels than preterm AGA infants at term-equivalent age (p = 0.019). Serum U-II levels in preterm LBW infants at term-equivalent age were inversely correlated with birth weight standard deviation (SD) score in a simple regression analysis (r = - 0.395, p = 0,002) and the correlation was maintained in the multiple regression analysis. CONCLUSION: Our results indicate that birth weight SD score might be associated with serum U-II levels in preterm LBW infants at term-equivalent age. Further studies are required to determine whether U-II levels at an early stage of life might influence the risk of atherosclerosis and hypertension. KEY POINTS: · U-II is a potent vasoconstrictor.. · We evaluated serum U-II levels in preterm infants.. · Fetal growth is negatively related to serum U-II levels..

Dysregulation of Amphiregulin stimulates the pathogenesis of cystic lymphangioma.

Along with blood vessels, lymphatic vessels play an important role in the circulation of body fluid and recruitment of immune cells. Postnatal lymphangiogenesis commonly occurs from preexisting lymphatic vessels by sprouting, which is induced by lymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C). However, the key signals and cell types that stimulate pathological lymphangiogenesis, such as human cystic lymphangioma, are less well known. Here, we found that mouse dermal fibroblasts that infiltrate to sponges subcutaneously implanted express VEGF-D and sushi, Von Willebrand factor type A, EGF, and pentraxin domain containing 1 (SVEP1) in response to PDGFRß signal. In vitro, Pdgfrb knockout (ß-KO) fibroblasts had reduced expression of VEGF-D and SVEP1 and overproduced Amphiregulin. Dysregulation of these three factors was involved in the cyst-like and uneven distribution of lymphatic vessels observed in the ß-KO mice. Similarly, in human cystic lymphangioma, which is one of the intractable diseases and mostly occurs in childhood, fibroblasts surrounding cystic lymphatics highly expressed Amphiregulin. Moreover, fibroblast-derived Amphiregulin could induce the expression of Amphiregulin in lymphatic endothelial cells. The dual source of Amphiregulin activated EGFR expressed on the lymphatic endothelial cells. This exacerbation cascade induced proliferation of lymphatic endothelial cells to form cystic lymphangioma. Ultimately, excessive Amphiregulin produced by fibroblasts surrounding lymphatics and by lymphatic endothelial cells per se results in pathogenesis of cystic lymphangioma and will be a fascinating therapeutic target of cystic lymphangioma.

Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice.

Blood-brain barrier (BBB) dysfunction underlies the pathogenesis of many neurological diseases. Platelet-derived growth factor receptor-alpha (PDGFRα) induces hemorrhagic transformation (HT) downstream of tissue plasminogen activator in thrombolytic therapy of acute stroke. Thus, PDGFs are attractive therapeutic targets for BBB dysfunction. In the present study, we examined the role of PDGF signaling in the process of tissue remodeling after middle cerebral arterial occlusion (MCAO) in mice. Firstly, we found that imatinib increased lesion size after permanent MCAO in wild-type mice. Moreover, imatinib-induced HT only when administrated in the subacute phase of MCAO, but not in the acute phase. Secondly, we generated genetically mutated mice (C-KO mice) that showed decreased expression of perivascular PDGFRα. Additionally, transient MCAO experiments were performed in these mice. We found that the ischemic lesion size was not affected; however, the recruitment of PDGFRα/type I collagen-expressing perivascular cells was significantly downregulated, and HT and IgG leakage was augmented only in the subacute phase of stroke in C-KO mice. In both experiments, we found that the expression of tight junction proteins and PDGFRß-expressing pericyte coverage was not significantly affected in imatinib-treated mice and in C-KO mice. The specific implication of PDGFRα signaling was suggestive of protective effects against BBB dysfunction during the subacute phase of stroke. Vascular TGF-ß1 expression was downregulated in both imatinib-treated and C-KO mice, along with sustained levels of MMP9. Therefore, PDGFRα effects may be mediated by TGF-ß1 which exerts potent protective effects in the BBB.

Temperature-Driven Anchoring Transitions at Liquid Crystal/Water Interfaces.

Controlling the anchoring of liquid crystal molecules at an interface with a water solution influences the entire organization of the underlying liquid crystal phase, which is crucial for many applications. The simplest way to stabilize such interfaces is by fabricating liquid crystal droplets in water; however, a greater sensitivity to interfacial effects can be achieved using liquid crystal shells, that is, spherical films of liquid crystal suspended in water. Anchoring transitions on those systems are traditionally triggered by the adsorption of surfactant molecules onto the interface, which is neither an instantaneous nor a reversible process. In this study, we report the ability to change the anchoring of 4-cyano-4'-pentylbiphenyl (5CB), one of the most widely used liquid crystals, at the interface with dilute water solutions of polyvinyl alcohol (PVA), a polymer commonly used for stabilizing liquid crystal shells, simply by controlling the temperature in the close vicinity of the liquid crystal clearing point. A quasi-static increase in temperature triggers an instantaneous reorientation of the molecules from parallel to perpendicular to the interfaces, owing to the local disordering effect of PVA on 5CB, prior to the phase transition of the bulk 5CB. We study this anchoring transition on both flat suspended films and spherical shells of liquid crystals. Switching anchoring entails a series of structural transformations involving the formation of transient structures in which topological defects are stabilized. The type of defect structure depends on the topology of the film. This method has the ability to influence both interfaces of the film nearly at the same time and can be applied to transform an initially polydisperse group of nematic shells into a monodisperse population of bivalent shells.

Structural transformations in tetravalent nematic shells induced by a magnetic field.

The role of applied fields on the structure of liquid crystals confined to shell geometries has been studied in past theoretical work, providing strategies to produce liquid crystal shells with controlled defect structure or valence. However, the predictions of such studies have not been experimentally explored yet. In this work, we study the structural transformations undergone by tetravalent nematic liquid crystal shells under a strong uniform magnetic field, using both experiments and simulations. We consider two different cases in terms of shell geometry and initial defect symmetry: (i) homogeneous shells with four s = +1/2 defects in a tetrahedral arrangement, and (ii) inhomogeneous shells with four s = +1/2 defects localized in their thinner parts. Consistently with previous theoretical results, we observe that the initial defect structure evolves into a bipolar one, in a process where the defects migrate towards the poles. Interestingly, we find that the defect trajectories and dynamics are controlled by curvature walls that connect the defects by pairs. Based on the angle between Bs, the local projection of the magnetic field on the shell surface, and n+½, a vector describing the defect orientations, we are able to predict the nature and shape of those inversion walls, and therefore, the trajectory and dynamics of the defects. This rule, based on symmetry arguments, is consistent with both experiments and simulations and applies for shells that are either homogeneous or inhomogeneous in thickness. By modifying the angle between Bs and n+½, we are able to induce, in controlled way, complex routes towards the final bipolar state. In the case of inhomogeneous shells, the specific symmetry of the shell allowed us to observe a hybrid splay-bend Helfrich wall for the first time.

Oligodendrogenesis and Myelin Formation in the Forebrain Require Platelet-derived Growth Factor Receptor-alpha.

The platelet-derived growth factor receptor-α (PDGFRα) principally mediates growth factor signals in oligodendroglial progenitors and is involved in oligodendrogenesis and myelinogenesis in the developing spinal cord. However, the role of PDGFRα in the developing forebrain remains relatively unknown. We established a conditional knockout mouse for the Pdgfra gene (N-PRα-KO) using a Nestin promoter/enhancer-driven Cre recombinase and examined forebrain development. The expression of PDGFRα was efficiently suppressed in the Olig2+ cells in N-PRα-KO mice. In these mice, Olig2+ cells were slightly decreased during embryonic periods. The decrease was particularly striking during the postnatal period. The commitment of Pdgfra-inactivated Olig2+ cells to Sox10+ oligodendroglial-lineage was largely suppressed. Surviving Olig2+ cells and Sox10+ cells were distributed widely in the N-PRα-KO mouse brain, similarly to those in control mice until the early neonatal period. After that, these cells were drastically depleted in the forebrain during the second postnatal week. The brains of N-PRα-KO mice were severely hypomyelinated, and these mice died on approximately P17 with motor disturbances. Disturbed axonal fibers and extensively aberrant vascular formations appeared in the postnatal N-PRα-KO mouse brains. After the defective PDGFRα signal in the forebrain, these phenotypes were clearly different from those in the spinal cord that showed defective populations expansion and migration of oligodendroglial lineage and premature myelination, as previously described. In contrast, areas of severe hypomyelination were common to both anatomical sites. PDGFRα was critically involved in the myelination of the forebrain and may differently regulate oligodendroglial lineage between the forebrain and spinal cord.

Chronotherapeutic effect of orexin antagonists on glucose metabolism in diabetic mice.

Disrupted sleep is associated with increased risk of type 2 diabetes. Central actions of orexin, mediated by orexin-1 and orexin-2 receptors, play a crucial role in the maintenance of wakefulness; accordingly, excessive activation of the orexin system causes insomnia. Resting-phase administration of dual orexin receptor antagonist (DORA) has been shown to improve sleep abnormalities and glucose intolerance in type 2 diabetic db/db mice, although the mechanism remains unknown. In the present study, to investigate the presence of functional link between sleep and glucose metabolism, the influences of orexin antagonists with or without sleep-promoting effects were compared on glucose metabolism in diabetic mice. In db/db mice, 2-SORA-MK1064 (an orexin-2 receptor antagonist) and DORA-12 (a DORA) acutely improved non-rapid eye movement sleep, whereas 1-SORA-1 (an orexin-1 receptor antagonist) had no effect. Chronic resting-phase administration of these drugs improved glucose intolerance, without affecting body weight, food intake, locomotor activity, and energy expenditure calculated from O2 consumption and CO2 production. The expression levels of pro-inflammatory factors in the liver were reduced by 2-SORA-MK1064 and DORA-12, but not 1-SORA-1, whereas those in the white adipose tissue were reduced by 1-SORA-1 and DORA-12 more efficiently than 2-SORA-MK1064. When administered chronically at awake phase, these drugs caused no effect. In streptozotocin-induced type 1-like diabetic mice, neither abnormality in sleep-wake behavior nor improvement of glucose intolerance by these drugs were observed. These results suggest that both 1-SORA-type (sleep-independent) and 2-SORA-type (possibly sleep-dependent) mechanisms can provide chronotherapeutic effects against type 2 diabetes associated with sleep disturbances in db/db mice.

Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain.

Oligodendrocyte progenitor cells (OPCs) are widely distributed cells of ramified morphology in adult brain that express PDGFRα and NG2. They retain mitotic activities in adulthood and contribute to oligodendrogenesis and myelin turnover; however, the regulatory mechanisms of their cell dynamics in adult brain largely remain unknown. Here, we found that global Pdgfra inactivation in adult mice rapidly led to elimination of OPCs due to synchronous maturation toward oligodendrocytes. Surprisingly, OPC densities were robustly reconstituted by the active expansion of Nestin+ immature cells activated in meninges and brain parenchyma, as well as a few OPCs that escaped from Pdgfra inactivation. The multipotent immature cells were induced in the meninges of Pdgfra-inactivated mice, but not of control mice. Our findings revealed powerful homeostatic control of adult OPCs, engaging dual cellular sources of adult OPC formation. These properties of the adult oligodendrocyte lineage and the alternative OPC source may be exploited in regenerative medicine.

PDGFR-ß restores blood-brain barrier functions in a mouse model of focal cerebral ischemia.

Although platelet-derived growth factor receptor beta (PDGFR-ß) mediates the recruitment of vascular pericytes into ischemic lesion to restore the blood-brain barrier (BBB) dysfunction, its mechanisms still remain elusive. Compared with control PDGFR-ßfloxed/floxed mice (Floxed), postnatally induced systemic PDGFR-ß knockout mice (Esr-KO) not only showed severe brain edema, neurologic functional deficits, decreased expression of tight junction (TJ) proteins, abundant endothelial transcytosis, and deformed TJs in the BBB, but also showed reduced expression of transforming growth factor-ß (TGF-ß) protein after photothrombotic middle cerebral artery occlusion (MCAO). In endothelial-pericyte co-culture, an in vitro model of BBB, the increment in the barrier function of endothelial monolayer induced by pericyte co-culture was completely cancelled by silencing PDGFR-ß gene expression in pericytes, and was additively improved by PDGFR-ß and TGF-ß receptor signals under hypoxia condition. Exogenous PDGF-BB increased the expression of p-Smad2/3, while anti-TGF-ß1 antibody at least partially inhibited the phosphorylation of Smad2/3 after PDGF-BB treatment in vitro. Furthermore, pre-administration of TGF-ß1 partially alleviated edema formation, neurologic dysfunction, and TJs reduction in Esr-KO mice after MCAO. Accordingly, PDGFR-ß signalling, via TGF-ß signalling, may be crucial for restoration of BBB integrity after cerebral ischemia and therefore represents a novel potential therapeutic target.

Different PDGF Receptor Dimers Drive Distinct Migration Modes of the Mouse Skin Fibroblast.

BACKGROUND/AIMS: The migration of mesenchymal cells is a fundamental cellular process that has been implicated in many pathophysiological conditions and is induced by chemoattractants such as platelet-derived growth factors (PDGFs). However, the regulatory mechanisms shaping this migration remain to be elucidated. METHODS: Here, we prepared mouse skin fibroblasts inactivated for different PDGF receptor genes and systematically measured their chemotactic responses within a gradient of different chemoattractants. RESULTS: We found that PDGFRαß and PDGFRßß dimers were strong inducers of random and directionally-persistent migration, respectively, that was sustained for up to 24 h. MAPK and PI3K were necessary to mediate random and directional migration, respectively. Directional migration was accompanied by abundant ventral stress fiber formation and consistent cell shape with less frequent formation of branch-like processes. CONCLUSION: This is the first systematic study that characterized the chemotaxis mediated by three-different types of PDGFR dimers in mesenchymal cell migration. Our data demonstrate that PDGFR dimer formation is the critical step to determine the specific mode of fibroblast chemotaxis, while the accompanying cytoskeletal remodeling might contribute to migration persistence.

The Novel Pathogenesis of Retinopathy Mediated by Multiple RTK Signals is Uncovered in Newly Developed Mouse Model.

Pericyte desorption from retinal blood vessels and subsequent vascular abnormalities are the pathogenesis of diabetic retinopathy (DR). Although the involvement of abnormal signals including platelet-derived growth factor receptor-ß (PDGFRß) and vascular endothelial growth factor-A (VEGF-A) have been hypothesized in DR, the mechanisms that underlie this processes are largely unknown. Here, novel retinopathy mouse model (N-PRß-KO) was developed with conditional Pdgfrb gene deletion by Nestin promoter-driven Cre recombinase (Nestin-Cre) that consistently reproduced through early non-proliferative to late proliferative DR pathologies. Depletion of Nestin-Cre-sensitive PDGFRß+NG2+αSMA- pericytes suppressed pericyte-coverages and induced severe vascular lesion and hemorrhage. Nestin-Cre-insensitive PDGFRß+NG2+αSMA+ pericytes detached from the vascular wall, and subsequently changed into myofibroblasts in proliferative membrane to cause retinal traction. PDGFRα+ astrogliosis was seen in degenerated retina. Expressions of placental growth factor (PlGF), VEGF-A and PDGF-BB were significantly increased in the retina of N-PRß-KO. PDGF-BB may contribute to the pericyte-fibroblast transition and glial scar formation. Since VEGFR1 signal blockade significantly ameliorated the vascular phenotype in N-PRß-KO mice, the augmented VEGFR1 signal by PlGF and VEGF-A was indicated to mediate vascular lesions. In addition to PDGF-BB, PlGF and VEGF-A with their intracellular signals may be the relevant therapeutic targets to protect eyes from DR.

Multiple Synchronous Sporadic Gastrointestinal Stromal Tumors in the Stomach and Jejunum.

A 77-year-old patient was admitted to our hospital for the further examination of melena. A computed tomography scan detected two submucosal tumors (SMTs) in the stomach and jejunum. Double-balloon endoscopy revealed the presence of a delle on the jejunal SMT, suggesting that the SMT was the origin of the gastrointestinal bleeding. Both tumors were surgically resected and subsequently diagnosed via histology as gastrointestinal stromal tumors (GISTs). Furthermore, the two GISTs had different mutations in the c-kit gene, suggesting that they were derived from different clonal origins. This report depicts an extremely rare case of multiple synchronous sporadic GISTs in the stomach and jejunum.

Eplerenone prevented obesity-induced inflammasome activation and glucose intolerance.

Obesity-associated activation of the renin-angiotensin-aldosterone system is implicated in the pathogenesis of insulin resistance; however, influences of mineralocorticoid receptor (MR) inhibition remain unclear. Therefore, we aimed to clarify the anti-inflammatory mechanisms of MR inhibition using eplerenone, a selective MR antagonist, in C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks. Eplerenone prevented excessive body weight gain and fat accumulation, ameliorated glucose intolerance and insulin resistance and enhanced energy metabolism. In the epididymal white adipose tissue (eWAT), eplerenone prevented obesity-induced accumulation of F4/80+CD11c+CD206--M1-adipose tissue macrophage (ATM) and reduction of F4/80+CD11c-CD206+-M2-ATM. Interestingly, M1-macrophage exhibited lower expression levels of MR, compared with M2-macrophage, in the ATM of eWAT and in vitro-polarized bone marrow-derived macrophages (BMDM). Importantly, eplerenone and MR knockdown attenuated the increase in the expression levels of proIl1b, Il6 and Tnfa, in the eWAT and liver of HFD-fed mice and LPS-stimulated BMDM. Moreover, eplerenone suppressed IL1b secretion from eWAT of HFD-fed mice. To reveal the anti-inflammatory mechanism, we investigated the involvement of NLRP3-inflammasome activation, a key process of IL1b overproduction. Eplerenone suppressed the expression of the inflammasome components, Nlrp3 and Caspase1, in the eWAT and liver. Concerning the second triggering factors, ROS production and ATP- and nigericin-induced IL1b secretion were suppressed by eplerenone in the LPS-primed BMDM. These results indicate that eplerenone inhibited both the priming and triggering signals that promote NLRP3-inflammasome activation. Therefore, we consider MR to be a crucial target to prevent metabolic disorders by suppressing inflammasome-mediated chronic inflammation in the adipose tissue and liver under obese conditions.