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.

[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.

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..

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.

Pericyte-fibroblast transition promotes tumor growth and metastasis.

Vascular pericytes, an important cellular component in the tumor microenvironment, are often associated with tumor vasculatures, and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte-fibroblast transition (PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that PDGF-BB-PDGFRß signaling promotes PFT both in vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF-BB-activated pericytes acquire mesenchymal progenitor features. Pharmacological inhibition and genetic deletion of PDGFRß ablate the PDGF-BB-induced PFT. Genetic tracing of pericytes with two independent mouse strains, TN-AP-CreERT2:R26R-tdTomato and NG2-CreERT2:R26R-tdTomato, shows that PFT cells gain stromal fibroblast and myofibroblast markers in tumors. Importantly, coimplantation of PFT cells with less-invasive tumor cells in mice markedly promotes tumor dissemination and invasion, leading to an increased number of circulating tumor cells and metastasis. Our findings reveal a mechanism of vascular pericytes in PDGF-BB-promoted cancer invasion and metastasis by inducing PFT, and thus targeting PFT may offer a new treatment option of cancer metastasis.

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.

Glioma-Derived Platelet-Derived Growth Factor-BB Recruits Oligodendrocyte Progenitor Cells via Platelet-Derived Growth Factor Receptor-α and Remodels Cancer Stroma.

Glioma is an aggressive and incurable disease, and is frequently accompanied by augmented platelet-derived growth factor (PDGF) signaling. Overexpression of PDGF-B ligand characterizes a specific subclass of glioblastoma multiforme, but the significance of the ligand remains to be elucidated. For this end, we implanted a glioma-cell line transfected with PDGF-BB-overexpressing vector (GL261-PDGF-BB) or control vector (GL261-vector) into wild-type mouse brain, and examined the effect of glioma-derived PDGF on the tumor microenvironment. The volume of GL261-PDGF-BB rapidly increased compared with GL261-vector. Recruitment of many PDGF receptor (PDGFR)-α and Olig2-positive oligodendrocyte precursor cells and frequent hemorrhages were observed in GL261-PDGF-BB but not in GL261-vector. We then implanted GL261-PDGF-BB into the mouse brain with and without Pdgfra gene inactivation, corresponding to PDGFRα-knockout (KO) and Flox mice, respectively. The recruitment of oligodendrocyte precursor cells was largely suppressed in PDGFRα-KO than in Flox, whereas the volume of GL261-PDGF-BB was comparable between the two genotypes. Frequent hemorrhage and increased IgG-leakage were associated with aberrant vascular structures within the area where many recruited oligodendrocyte precursor cells accumulated in Flox. In contrast, these vascular phenotypes were largely normalized in PDGFRα-KO. Increased matrix metalloproteinase-9 in recruited oligodendrocyte precursor cells and decreased claudin-5 in vasculature may underlie the vascular abnormality. Glioma-derived PDGF-B signal induces cancer stroma characteristically seen in high-grade glioma, and should be therapeutically targeted to improve cancer microenvironment.

PDGFR-ß Plays a Key Role in the Ectopic Migration of Neuroblasts in Cerebral Stroke.

The neuroprotective agents and induction of endogenous neurogenesis remain to be the urgent issues to be established for the care of cerebral stroke. Platelet-derived growth factor receptor beta (PDGFR-ß) is mainly expressed in neural stem/progenitor cells (NSPCs), neurons and vascular pericytes of the brain; however, the role in pathological neurogenesis remains elusive. To this end, we examined the role of PDGFR-ß in the migration and proliferation of NSPCs after stroke. A transient middle cerebral-arterial occlusion (MCAO) was introduced into the mice with conditional Pdgfrb-gene inactivation, including N-PRß-KO mice where the Pdgfrb-gene was mostly inactivated in the brain except that in vascular pericytes, and E-PRß-KO mice with tamoxifen-induced systemic Pdgfrb-gene inactivation. The migration of the DCX(+) neuroblasts from the subventricular zone toward the ischemic core was highly increased in N-PRß-KO, but not in E-PRß-KO as compared to Pdgfrb-gene preserving control mice. We showed that CXCL12, a potent chemoattractant for CXCR4-expressing NSPCs, was upregulated in the ischemic lesion of N-PRß-KO mice. Furthermore, integrin α3 intrinsically expressed in NSPCs that critically mediates extracellular matrix-dependent migration, was upregulated in N-PRß-KO after MCAO. NSPCs isolated from N-PRß-KO rapidly migrated on the surface coated with collagen type IV or fibronectin that are abundant in vascular niche and ischemic core. PDGFR-ß was suggested to be critically involved in pathological neurogenesis through the regulation of lesion-derived chemoattractant as well as intrinsic signal of NSPCs, and we believe that a coordinated regulation of these molecular events may be able to improve neurogenesis in injured brain for further functional recovery.

Pathogenetic significance and possibility as a therapeutic target of platelet derived growth factor.

Platelet-derived growth factor (PDGF) is one of the major mitogens and chemoattractants for mesenchymal and glial cells. Nowadays, the expression of PDGFs are recognized widely in our body, and emerging data indicate the relevance of PDGFs in the homeostatic control of systemic connective tissue as well as parenchymal cells such as neurons. Aberrant PDGF signal is primarily tumorigenic, and also regulates tumor microenvironments. The roles of the PDGF signal in tumorigenesis are diverse depending on the type of cancer, and anti-PDGF therapy needs to be carefully designed based on the information of each tumor cell type and the surrounding microenvironment. PDGFs and receptors (PDGFRs) are abundant in neurons and glial cells, and are neuroprotective through the regulation of neurovascular unit. PDGF signal is functionally correlated with neurotransmission, and can be pathogenetically correlated with psychosomatic neurological diseases. Growing genetic information has been unraveling novel connective tissue diseases and vascular abnormalities in which aberrant PDGF signaling is etiologically correlated. Novel therapeutic approaches targeting PDGF signal are beginning to emerge in various diseases.

Significance of Extracellular Vesicles: Pathobiological Roles in Disease.

Over the past decade, many studies have been conducted on extracellular vesicles (EVs) in the fields of basic and clinical research. EVs are small sized membranous vesicles generated from many type of cells upon activation by environmental stresses such as heat, hypoxia, and irradiation. EVs theoretically consist of microparticles/microvesicles, exosomes, and apoptotic bodies by different productive mechanisms. Clinically, EVs are observed in the blood stream of patients suffering from acute and chronic inflammation evoked by various diseases, and number of EVs in blood flow is often dependent on the inflammatory status and severity of the diseases. To date, it has been reported that small molecules such as RNAs and proteins are encapsulated in EVs; however, the functions of EVs are still unclear in the biological, pathological, and clinical aspects. In this review, we summarize and discuss the biogenesis-based classification, expected function, and pathobiological activities of EVs.

A diagnostic marker for superficial urothelial bladder carcinoma: lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression.

BACKGROUND: Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma. METHODS: Seven anti-ATBF1 antibodies were generated to cover the entire ATBF1 sequence. Four human influenza hemagglutinin-derived amino acid sequence-tagged expression vectors with truncated ATBF1 cDNA were constructed to map the functional domains of nuclear localization signals (NLSs) with the consensus sequence KR[X10-12]K. A total of 117 samples from initial TUR of human bladder carcinomas were analyzed. None of the patients had received chemotherapy or radiotherapy before pathological evaluation. RESULTS: ATBF1 nuclear localization was regulated synergistically by three NLSs on ATBF1. The cytoplasmic fragments of ATBF1 lacked NLSs. Patients were divided into two groups according to positive nuclear staining of ATBF1, and significant differences in overall survival (P = 0.021) and intravesical recurrence-free survival (P = 0.013) were detected between ATBF1+ (n = 110) and ATBF1- (n = 7) cases. Multivariate analysis revealed that ATBF1 staining was an independent prognostic factor for intravesical recurrence-free survival after adjusting for cellular grading and pathological staging (P = 0.008). CONCLUSIONS: Cleavage of ATBF1 leads to the cytoplasmic localization of ATBF1 fragments and downregulates nuclear ATBF1. Alterations in the subcellular localization of ATBF1 due to fragmentation of the protein are related to the malignant character of urothelial carcinoma. Pathological evaluation using anti-ATBF1 antibodies enabled the identification of highly malignant cases that had been overlooked at initial TUR. Nuclear localization of ATBF1 indicates better prognosis of urothelial carcinoma.

Metabolism of dextran sulfate sodium by intestinal bacteria in rat cecum is related to induction of colitis.

Ulcerative colitis induced by dextran sulfate sodium (DSS) is one of the most widely used experimental animal models. However, the mechanism responsible for the pathogenesis of the colitis is still unclear. The aim of the present study was to clarify the events occurring after administration of DSS to rats focusing on the relationship between the intestinal bacterial metabolism of DSS and the intestinal mucosal lesions in the model. Within 2 d after DSS administration, severe injury of the cecal mucosa was evident, together with bloody feces and blood in the cecum. However, these lesions were repressed by administration of antibiotics. On the other hand, DSS was found to be metabolized under anaerobic conditions upon incubation with cecal content in vitro, first being desulfated and then undergoing carbohydrate moiety degradation. However, no such metabolic process occurred when cecal content from rats that had been administered antibiotics was employed. These results indicate that the initial step of DSS-induced ulcerative colitis is lesioning of the cecal mucosa, which is related to metabolism of DSS by intestinal bacteria.

Nicotine suppresses acute colitis and colonic tumorigenesis associated with chronic colitis in mice.

Ulcerative colitis is a chronic inflammatory disease that frequently progresses to colon cancer. The tumor-promoting effect of inflammation is now widely recognized and understood. Recent studies have revealed that treatment with nicotine ameliorates colitis in humans and experimental murine models, whereas the effect of nicotine on colitis-associated colonic tumorigenesis remains unclear. In the present study, we examined the effect of nicotine on the development of acute colitis and colitis-associated cancer (CAC). The acute colitis model was induced by treatment with 3% dextran sulfate sodium (DSS) for 7 days, whereas the CAC model was induced by a combination of azoxymethane and repeated DSS treatment. Nicotine and a selective agonist of the α7-nicotinic acetylcholine receptor (α7-nAChR) reduced the severity of DSS-induced acute colonic inflammation. In addition, the suppressive effect of nicotine on acute colitis was attenuated by an antagonist of α7-nAChR. Furthermore, nicotine inhibited the IL-6 production of CD4 T cells in the DSS-induced inflamed colonic mucosa. We found that nicotine significantly reduced the number and size of colonic tumors in mice with CAC. Nicotine markedly inhibited the elevation of TNF-α and IL-6 mRNA as well as phosphorylated signal transducer and activator of transcription (Stat) 3 expression in the colons of the tumor model mice. These results demonstrate that nicotine suppresses acute colitis and colitis-associated tumorigenesis, and this effect may be associated with the activation of α7-nAChR. Furthermore, it is presumed that nicotine downregulates the expression of inflammatory mediators such as IL-6/Stat3 and TNF-α, thereby reducing the colonic tumorigenesis associated with chronic colitis.

Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP-1c Tg mice fed high-fat and high-fructose diet.

Because the renin-angiotensin-aldosterone system has been implicated in the development of insulin resistance and promotion of fibrosis in some tissues, such as the vasculature, we examined the effect of eplerenone, a selective mineralocorticoid receptor (MR) antagonist, on nonalcoholic steatohepatitis (NASH) and metabolic phenotypes in a mouse model reflecting metabolic syndrome in humans. We adopted liver-specific transgenic (Tg) mice overexpressing the active form of sterol response element binding protein-1c (SREBP-1c) fed a high-fat and fructose diet (HFFD) as the animal model in the present study. When wild-type (WT) C57BL/6 and liver-specific SREBP-1c Tg mice grew while being fed HFFD for 12 wk, body weight and epididymal fat weight increased in both groups with an elevation in blood pressure and dyslipidemia. Glucose intolerance and insulin resistance were also observed. Adipose tissue hypertrophy and macrophage infiltration with crown-like structure formation were also noted in mice fed HFFD. Interestingly, the changes noted in both genotypes fed HFFD were significantly ameliorated with eplerenone. HFFD-fed Tg mice exhibited the histological features of NASH in the liver, including macrovesicular steatosis and fibrosis, whereas HFFD-fed WT mice had hepatic steatosis without apparent fibrotic changes. Eplerenone effectively ameliorated these histological abnormalities. Moreover, the direct suppressive effects of eplerenone on lipopolysaccharide-induced TNFα production in the presence and absence of aldosterone were observed in primary-cultured Kupffer cells and bone marrow-derived macrophages. These results indicated that eplerenone prevented the development of NASH and metabolic abnormalities in mice by inhibiting inflammatory responses in both Kupffer cells and macrophages.

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.

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.

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.

Central versus peripheral impact of estradiol on the impaired glucose metabolism in ovariectomized mice on a high-fat diet.

Age-related loss of ovarian function promotes adiposity and insulin resistance in women. Estrogen (E(2)) directly enhances insulin sensitivity and suppresses lipogenesis in peripheral tissues. Recently, the central actions of E(2) in the regulation of energy homeostasis are becoming clearer; however, the functional relevance and degree of contribution of the central vs. peripheral actions of E(2) are currently unknown. Therefore, we prepared and analyzed four groups of mice. 1) CONTROL: sham-operated mice fed a regular diet, 2) OVX-HF: ovariectomized (OVX) mice fed a 60% high-fat diet (HF), 3) E2-SC: OVX-HF mice subcutaneously treated with E(2), and 4) E2-ICV: OVX-HF mice treated with E(2) intracerebroventricularly. OVX-HF mice showed increased body weight with both visceral and subcutaneous fat volume enlargement, glucose intolerance, and insulin resistance. Both E2-SC and E2-ICV equally ameliorated these abnormalities. Although the size of adipocytes and number of CD11c-positive macrophages in perigonadal fat in OVX-HF were reduced by both E(2) treatments, peripherally administered E(2) decreased the expression of TNFα, lipoprotein lipase, and fatty acid synthase in the white adipose tissue (WAT) of OVX-HF. In contrast, centrally administered E(2) increased hormone-sensitive lipase in WAT, decreased the hepatic expression of gluconeogenic enzymes, and elevated core body temperature and energy expenditure with marked upregulation of uncoupling proteins in the brown adipose tissue. These results suggest that central and peripheral actions of E(2) regulate insulin sensitivity and glucose metabolism via different mechanisms, and their coordinated effects may be important to prevent the development of obesity and insulin resistance in postmenopausal women.