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Although medical and long-term care expenditures for older adults are closely related, providing rigorous statistical analysis for their dynamic relationship is challenging. In this research, we propose a novel approach using the panel vector autoregression model to reveal the realized patterns of the interdependence. As an empirical application, we analyze monthly panel data on individuals in a city of Japan, where social insurance covers many formal services for long-term care. Our estimation results indicate the existence of intertemporal transition from expensive acute medical care to reasonable at-home medical care, then to at-home long-term care. Under this context, the enhancement of formal long-term care sector in Japan might have played an important role in the suppression of the total care cost in spite for its rapid aging over the past 2 decades. Additionally, we find that daycare plays multiple roles in Japanese long-term care, such as respite and rehabilitation, but there is no considerable transition from outpatient rehabilitation to daycare in the long-term care sector., (© 2023 John Wiley & Sons Ltd.)

Objective: To establish a new rat model of craniofacial myalgia, and to clarify which central nervous system pathways are activated in the model., Background: Craniofacial myalgia, represented by myogenous temporomandibular disorder and tension-type headache with pericranial tenderness, is more common in female patients. The pain is thought to be a type of multifactorial disorder with several coexisting causes. To our knowledge, there are no models of craniofacial muscle hyperalgesia caused by multiple types of stimuli., Methods: We injected nerve growth factor into the trapezius muscle of female and male rats and repeatedly stimulated the masseter muscle (MM) electrically for 10 days. We determined the mechanical head-withdrawal threshold of MM and extent of phosphorylated extracellular signal-related kinase 1/2 (pERK) immunoreactivity in various regions of the lower brainstem. We conducted retrograde tract-tracing to determine the projection of mechanosensitive MM-innervating secondary neurons to the lateral parabrachial nucleus. Finally, we administered morphine in rats to determine whether increases of pERK immunoreactivity were dependent on noxious inputs., Results: In female rats, but not male rats, the mechanical head-withdrawal threshold was decreased significantly from days 9 to 12. The number of pERK-immunoreactive neurons in the brainstem was increased significantly in female rats in the group with both stimuli compared to rats in other groups with a single stimulus. Mechanosensitive MM-innervating neurons in the brainstem projected to the parabrachial nucleus. Morphine administration blocked the increase in the number of pERK-immunoreactive neurons in both the brainstem and parabrachial nucleus., Conclusions: We established a model of craniofacial myalgia by combining trapezius and MM stimuli in female rats. We found mechanical hyperalgesia of the MM and activation of the pain pathway from the brainstem to parabrachial nucleus. The model reflects the characteristics of patients with craniofacial myalgia and might be helpful to clarify the pathogenic mechanisms underlying these disorders., (© 2022 American Headache Society.)

Mycoplasma pneumonia of swine (MPS) is caused by Mycoplasma hyopneumoniae (M.hp) and is a common chronic respiratory disease of pigs. Recently, a genetically selected variant of the Landrace pig (Miyagino L2) has a lower incidence of pulmonary MPS lesions. We investigated the pathological and immunological characteristics of MPS resistance in these pigs (n = 24) by comparing with the normal landrace pig (control: n = 24). The pathological MPS lung lesion score in MPS-selected landrace pigs was significantly lower than in the control. The gene expression of interleukin (IL)-12p40, which acts as a chemoattractant and a component of the bioactive cytokines IL-12 and IL-23, was significantly higher at the hilar lymph nodes, lung, and spleen in MPS-selected landrace pigs than in control landrace pigs, and these were negatively correlated with the macroscopic MPS lung lesion score. In summary, we demonstrate that resistance against MPS in Miyagino L2 pigs is associated with IL-12p40 up-regulation, in comparison with normal landrace pigs without the MPS vaccine. In addition, a comparative study of macroscopic MPS lung lesions and IL-12p40 gene expression in lung and hilar lymph nodes may lead to beneficial selection traits for the genetic selection for MPS resistance in pigs., (© 2020 Japanese Society of Animal Science.)

Background: The current randomized, double-blind, phase 2 study assessed the efficacy and safety profile of a single intravenous administration of fosnetupitant, a neurokinin 1 receptor antagonist prodrug, for the prevention of chemotherapy-induced nausea and vomiting in Japanese patients receiving cisplatin-based chemotherapy., Methods: Patients scheduled to receive cisplatin (at a dose of ≥70 mg/m 2 )-based regimens were randomly assigned to receive fosnetupitant at a dose of 81 mg or 235 mg or placebo in combination with palonosetron at a dose of 0.75 mg and dexamethasone. The primary endpoint was complete response (CR; no vomiting and no rescue medication) during the overall phase (0-120 hours). The overall CR rate was compared between each dose of fosnetupitant and the placebo group adjusting for the stratification factors of sex and age class (age <55 years vs age ≥55 years). Safety was assessed, with special attention given to events that potentially were suggestive of infusion site reactions., Results: A total of 594 patients were randomized. Of these, 194 patients, 195 patients, and 195 patients, respectively, in the placebo and fosnetupitant 81-mg and 235-mg dose groups were evaluable for efficacy. The overall CR rate was 54.7% for the placebo group, 63.8% for the fosnetupitant 81-mg dose group (adjusted difference, 9.1%; 95% CI, -0.4% to 18.6% [P = .061]), and 76.8% for the fosnetupitant 235-mg dose group (adjusted difference, 22.0%; 97.5% CI, 11.7% to 32.3% [P < .001]). Safety profiles were comparable between the 3 groups. The incidence of infusion site reactions related to fosnetupitant was ≤1% in each dose group., Conclusions: Fosnetupitant at a dose of 235 mg provided superior prevention of chemotherapy-induced nausea and vomiting among patients receiving cisplatin-based chemotherapy compared with the control group, and with a satisfactory safety profile., (© 2019 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Background: Bevacizumab combined with platinum-based chemotherapy has been established as a standard treatment option in the first-line setting for advanced nonsquamous non-small cell lung cancer (NSCLC). However, there has been no evidence to support the use of bevacizumab beyond disease progression in such patients., Methods: West Japan Oncology Group 5910L was designed as a multicenter, open-label, randomized, phase 2 trial of docetaxel versus docetaxel plus bevacizumab every 3 weeks for patients with recurrent or metastatic nonsquamous NSCLC whose disease had progressed after first-line treatment with bevacizumab plus a platinum-based doublet. The primary endpoint was progression-free survival (PFS)., Results: One hundred patients were randomly assigned to receive docetaxel (n = 50) or docetaxel plus bevacizumab (n = 50), and this yielded median PFS times of 3.4 and 4.4 months, respectively, with a hazard ratio (HR) of 0.71 and a stratified log-rank P value of .058, which met the predefined criterion for statistical significance (P < .2). The median overall survival also tended to be longer in the docetaxel plus bevacizumab group (13.1 months; 95% confidence interval [CI], 10.6-21.4 months) versus the docetaxel group (11.0 months; 95% CI, 7.6-16.1 months) with an HR of 0.74 (95% CI, 0.46-1.19; stratified log-rank P = .11). No unexpected or severe adverse events were recorded., Conclusions: Further evaluation of bevacizumab beyond disease progression is warranted for patients with advanced NSCLC whose disease has progressed after treatment with bevacizumab plus a platinum-based doublet., (© 2016 American Cancer Society.)

Fibroblast growth factor 4 (FGF4) is considered a crucial gene in the proper development of bovine embryos. We recently determined the FGF4 gene sequence in eight cattle derived from three breeds and revealed a common nucleotide sequence of the structural gene encoding FGF4, which leads to the deletion and mutation of amino acid sequences in the mature FGF4 (Pro(32) -Leu(206) ) compared with the sequence previously reported. In the present study, HisbFGF4, a 6× histidine-tagged bovine FGF4 (Pro(32) -Leu(206) ), was produced in Escherichia coli based on the validated nucleotide sequence and purified by heparin column chromatography. In primary bovine fibroblasts, HisbFGF4 showed significant mitogenic activity, whereas, intriguingly, the activity of a commercially available recombinant human FGF4 (Gly(25) -Leu(206) ) produced in E. coli was weaker than that of HisbFGF4. In conclusion, the present study provides a simple method for the production of a bioactive bovine FGF4 derivative in E. coli utilizing its structural gene elucidated by us., (© 2013 Japanese Society of Animal Science.)

1. D-Galactosamine (GalN) depletes UTP primarily in the liver, resulting in decreased RNA synthesis in hepatocytes. Co-injection of GalN and lipopolysaccharide (LPS) into mice produces fulminant hepatitis with severe hepatic congestion, resulting in rapid death. Although the underlying mechanism is uncertain, GalN enhances the sensitivity to tumour necrosis factor (TNF). Administration of uridine (a precursor of UTP) prior injection of either LPS itself or interleukin-1 (IL-1) reduces the lethality of GalN+LPS. The present study focused on the effects of these agents on TNF production. 2. Intraperitoneal injection of GalN+LPS into mice greatly elevated serum TNF. Although large doses of LPS alone also greatly elevated serum TNF, LPS itself induced neither hepatic congestion nor rapid death. Administration of a macrophage depletor, liposomes encapsulated with dichloromethylene bisphosphonate, reduced both the TNF production and mortality induced by GalN+LPS. 3. Uridine, when injected 0.5 h after the injection of GalN+LPS, reduced the production of TNF. Prior injection of LPS, but not of IL-1, also reduced this TNF production. 4. Serum from LPS-injected mice reduced the TNF production induced by GalN+LPS, but it was less effective at reducing the lethality. Its ability to reduce TNF production was abolished by heat-treatment. 5. We hypothesize that a factor inhibiting TNF production by macrophages is produced by hepatocytes in response to LPS. Possibly, production of this hepatocyte-derived TNF-down-regulator (TNF-DRh) may be: (i) inhibited by GalN, causing over-production of TNF by macrophages and (ii) stimulated by LPS-pretreatment (and restored by uridine), causing reduced TNF production.

1. Aminobisphosphonates (aminoBPs), potent inhibitors of bone resorption, have been reported to induce inflammatory reactions such as fever and an increase in acute phase proteins in human patients, and to induce the histamine-forming enzyme, histidine decarboxylase, in mice. In the present study, we examined the effect of aminoBP, 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (AHBuBP), on the production of the pro-inflammatory cytokines, IL-1 and TNFalpha, in mice. 2. Intraperitoneal injection of AHBuBP did not itself produce detectable levels of IL-1 (alpha and beta) and TNFalpha in the serum. However, the elevation of serum IL-1 induced by lipopolysaccharide (LPS) was greatly augmented in mice injected with AHBuBP 3 days before the LPS injection, whereas the LPS-induced elevation of serum TNFalpha was almost completely abolished. 3. Spleen and bone marrow cells taken from mice injected with AHBuBP produced IL-1beta in vitro spontaneously, and the production was augmented following the addition of LPS. Cells that accumulated in the peritoneal cavity in response to AHBuBP produced a particularly large amount of IL-1beta. However, AHBuBP treatment of mice did not lead to an impairment of the in vitro production of TNFalpha by these three types of cells. 4. Liposomes encapsulating dichloromethylene bisphosphonate (a non-amino BP) selectively deplete phagocytic macrophages. When an intraperitoneal injection of these liposomes was given 2 days after an injection of AHBuBP, there was a marked decrease in the LPS-induced elevation of serum IL-1 (alpha and beta) (LPS being injected 3 days after the injection of AHBuBP). 5. These results indicate that AHBuBP has contrasting effects on the in vivo LPS-induced production of IL-1 and TNFalpha in mice, enhancing the production of IL-1 by phagocytic macrophages and suppressing the production of TNFalpha, although underling mechanisms remain to be clarified.