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Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) crucial for the detection of infections and activation of downstream signaling pathways that lead to the production of pro-inflammatory cytokines and interferons. The TLR pathway is an attractive actively studied target pathway. Because of their strong immunostimulatory activity, TLRs are thought to be a "double-edged sword" for systemic treatment, even in the cancer field. To solve this, we have developed dextran-based TAM targeting activating conjugate (D-TAC) technology, which successfully uses tumor-associated macrophages (TAMs) to deliver the TLR7 agonist DSP-0509. We used low molecular weight dextran to target CD206 high M2-type macrophages, activate them, and induce a change in phenotype to antitumor M1-type macrophages with rapid clearance from the body and astonishing antitumor activity. We also demonstrated that the antitumor effect of our best drug candidate 5DEX-0509R is dependent on the abundance of TAMs, which is consistent with their mechanism of action. We believe that 5DEX-0509R generated by D-TAC technology can be a clinically applicable immunotherapy targeting the TLR signaling pathway.
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PURPOSE: To evaluate improvement in local vascular perfusion of the lower limbs on intravoxel incoherent motion (IVIM) imaging after endovascular therapy (EVT). MATERIALS AND METHODS: IVIM imaging was performed on 20 lower limbs of 16 patients with lower extremity arterial diseases before and after EVT. To estimate IVIM, diffusion-weighted lower-limb axial images (number of slices = 25 and slice thickness = 3.5 mm) were acquired using different b values (0, 300, and 1000 s/mm2). IVIM imaging with the simplified IVIM techniques was performed. The perfusion-related coefficient (D* [10-3 mm2/s]), perfusion fraction (f [%]), and D*f product (10-3 mm2/s %) were calculated before and 2-3 days after EVT. The ankle brachial index (ABI), mean D* (10-3 mm2/s), mean f (%), and mean D*f product (10-3 mm2/s %) before and after EVT were compared. RESULTS: Successful revascularization was achieved in all cases. After EVT, the mean ABI significantly increased from 0.59 ± 0.19 to 0.87 ± 0.15 (p < 0.001, paired t test). The mean D* (10-3 mm2/s) (22.08 ± 3.26 versus 24.87 ± 2.65, p = 0.005, paired t test), and D*f product (10-3 mm2/s%) (551.03 ± 79.02 versus 634.55 ± 76.96, p = 0.002, paired t-test) of the lower limbs significantly increased after EVT, whereas f (%) (25.00 ± 1.28 versus 25.52 ± 1.61, p = 0.261, paired t-test) did not significantly increased after EVT. CONCLUSION: D* (10-3 mm2/s) and D*f product (10-3 mm2/s %) on IVIM imaging could evaluate improvement in local vascular perfusion of the lower limbs after EVT. LEVEL OF EVIDENCE: Level 4, Case Series.
Subject(s)
Diffusion Magnetic Resonance Imaging , Endovascular Procedures , Humans , Diffusion Magnetic Resonance Imaging/methods , Motion , Perfusion , Lower Extremity/diagnostic imagingABSTRACT
The Health Enhancement Lifestyle Profile (HELP) was an assessment instrument for health-related behaviors and was translated into Japanese (HELP-J) using subjective rating scales. This study investigated the internal validity of the HELP-J using a Rasch analysis. Snowball and purposive sampling were used for data collection. The data obtained from the 109 respondents were subjected to Rasch analysis to assess their internal validity. The rating scale analysis supported a 3-category scale; five of the seven subscales showed unidimensionality. Thus, this study presents essential information on the possibility of translating the original HELP into Japanese and converting it into a unidimensional scale.
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Fabry disease (FD) is a multi-organ disorder caused by a deficiency of alpha-galactosidase (α-GLA) or reduced activity of the enzyme due to mutations in the GLA gene on the X chromosome, making it an X-linked hereditary disease. A 37-year-old man previously diagnosed with sudden deafness and cardiac hypertrophy was referred to our department after an abnormal urine finding during a public health checkup. A renal biopsy revealed characteristic findings, and he was diagnosed with FD with a novel GLA abnormality (c.714dupT (p.I239Yfs*11)). We are currently administering enzyme replacement therapy (ERT) with agalsidase α. This case shows that a novel genetic abnormality in FD can be overlooked for 37 years, even in the presence of typical symptoms. The significance of a renal biopsy in diagnosing FD is emphasized, highlighting the crucial role of nephrologists. DOI: 10.52547/ijkd.7595.
Subject(s)
Fabry Disease , Male , Humans , Adult , Fabry Disease/diagnosis , Fabry Disease/genetics , alpha-Galactosidase/genetics , alpha-Galactosidase/therapeutic use , Phenotype , Mutation , Kidney , BiopsyABSTRACT
PURPOSE: The incidence and risk factors of catheter-related bloodstream infections (CRBSI) in patients with intestinal failure (IF) have not been established, partly because catheter management methods vary from different facilities. This study aimed to identify the risk factors and incidence rate of CRBSIs in patients with IF who were given prophylactic treatment. METHODS: Sixteen patients with IF who required home parenteral nutrition were enrolled in this study. Prophylactic management of CRBSI included monthly ethanol lock therapy and standardized infection prevention education. The outcomes included the incidence and risk factors of CRBSI. RESULTS: The median incidence rate of CRBSI was 1.2 per 1000 catheter days. Univariate analysis showed that the risk of developing CRBSI was significantly associated with short bowel syndrome (< 30 cm) (p = 0.016). Other relevant findings included a significant negative correlation between serum albumin and CRBSI rate (r = - 0.505, p = 0.046), and past history of mixed bacterial infections was significantly associated with increased CRBSI rate (p = 0.013). CONCLUSION: CRBSIs can still develop despite undergoing prophylactic management. Risk factors for CRBSI include the residual intestinal length, nutritional status, and susceptibility to certain microorganisms.
Subject(s)
Bacteremia , Catheter-Related Infections , Central Venous Catheters , Intestinal Failure , Parenteral Nutrition, Home , Humans , Central Venous Catheters/adverse effects , Catheter-Related Infections/prevention & control , Bacteremia/epidemiology , Bacteremia/etiology , Bacteremia/prevention & control , Parenteral Nutrition, Home/adverse effects , Parenteral Nutrition, Home/methods , Risk Factors , Retrospective StudiesABSTRACT
A high-flow steerable microcatheter has been reported to be useful as a triaxial system. Moreover, the benefits of steerable microcatheters in acute-angle bifurcation vessel insertions and a compact coil-packing technique using intentional folding with a bendable catheter tip have been reported. However, research on the usefulness of a high-flow steerable catheter and 0.025-inch guidewire combination (steerable-wire) technique is lacking. Herein, we report a case of balloon-occluded retrograde transvenous obliteration (BRTO) via the femoral venous approach to illustrate the usefulness of the steerable-wire technique. The steerable-wire technique facilitates the selection of the wire into the target vessel. The steerable-wire can be used instead of the 0.035-inch guidewire, which is versatile as other devices can follow the steerable wire.
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INTRODUCTION: Aging, an inevitable physiological process, leads to morphological and histological degenerative changes in the mandibular condylar cartilage (MCC); however, the molecular mechanism has not yet been elucidated, and little information is available on age-related factors. Therefore, this study was designed to identify age-related factors by investigating the age-related differentially expressed genes (DEGs) and localization of their translated protein expression in the mandibular condyle. METHODS: Mandibular condyles were collected from 10- and 50-week-old mice. Total RNA was extracted from the samples and then analyzed using cap analysis of gene expression (CAGE) to identify age-related DEGs. Gene ontology (GO) enrichment analysis was performed to determine which biological processes were most affected by aging in terms of gene expression using Metascape. The mandibular condyle samples were processed for histology to investigate morphological changes caused by aging and for immunohistochemistry to localize the protein expression encoded by age-related genes identified with CAGE. Semi-quantitative immunohistochemistry was performed to assess age-related extracellular matrix (ECM) protein levels in the MCC. The histological sections were also used for Alcian blue histochemistry to detect glycosaminoglycans (GAGs). RESULTS: GO enrichment analysis revealed that the genes related to "extracellular matrix organization," including Acan, Col1a1, Col1a2, Col2a1, Mmp3, Mmp9, and Mmp13, were most differentially expressed in the aged mandibular condyle. Among these seven genes, Mmp3 was upregulated, and the others were downregulated with aging. Histological examination showed the age-related morphological and histological changes in the MCC. Immunohistochemical investigation showed the localization of matrix metalloproteinases (MMPs)-3, -9, and -13 and their substrate proteins, aggrecan, type I collagen, and type II collagen, in the mandibular condyle at 10 and 50 weeks, indicating different localizations between the young and the aged. In the aged MCC, semi-quantitative immunohistochemistry showed a significant decrease in the aggrecan protein level, and Alcian blue histochemistry showed a decrease in GAGs. CONCLUSION: MMP-3, MMP-9, and MMP-13 contribute to the remodeling of the ECM of the MCC and subchondral bone during aging by degrading ECM proteins at specific times and sites under the regulation of their production and secretion.
Subject(s)
Mandibular Condyle , Matrix Metalloproteinase 3 , Mice , Animals , Matrix Metalloproteinase 3/metabolism , Mandibular Condyle/metabolism , Mandibular Condyle/pathology , Immunohistochemistry , Aggrecans/metabolism , Alcian Blue/metabolism , Gene ExpressionABSTRACT
Matrix-assisted laser desorption/ionization imaging mass spectrometry (IMS) is used to comprehensively visualize the spatial distribution of numerous biomolecules. The present study was designed to investigate the distribution of phospholipids in developing rat teeth by IMS to identify the characteristic phospholipid molecules for tooth development, and to evaluate the suitability of tissue preparation methods. Rats at postnatal day 3 were euthanized, and the resected head specimens were either fixed or not fixed with 4% paraformaldehyde (PFA), and decalcified or not decalcified in 10% ethylenediaminetetraacetic acid (EDTA) before being frozen. Subsequently, sections were prepared and mounted on glass slides coated with indium tin oxide, and analyzed by IMS. The mass spectra showed the highest peaks around m/z 706, 732, and 734 in the region of interest. Characteristic localization of signals in the tooth buds was seen around m/z 706 and 732, and a database search indicated that the corresponding molecules were phosphatidylcholines. The signals were localized to the dental papillae and enamel epithelia in the tooth buds. The PFA-fixed specimens with or without EDTA decalcification showed preserved IMS signals, while the non-fixed specimens showed fewer signals. Thus, PFA fixation with EDTA decalcification appears to be suitable for IMS analysis of calcified tissues.
Subject(s)
Lasers , Phospholipids , Rats , Animals , Edetic Acid , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methodsABSTRACT
A nontraumatic and idiopathic spontaneous subcapsular hepatic hematoma is a rare but often fatal condition. Herein, we report a case of nontraumatic progressive massive subcapsular hepatic hematoma that straddled both liver lobes and was successfully treated by repeated arterial embolization. Following treatment, the hematoma did not progress.
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Mice devoid of matrix metalloproteinase (MMP)-2 due to gene targeting have been reported to show articular cartilage destruction in the knee joint; however, the phenotype of the mandibular condylar cartilage remains unknown. Thus, in the present study, we investigated the mandibular condyle in Mmp2-/- mice. We obtained and bred Mmp2-/- mice from the same source as the previous study, and performed genotyping using genomic DNA extracted from finger snips. The mandibular condyle of Mmp2-/- mice and wild-type (WT) mice was immunohistochemically examined for the localization of extracellular matrix (ECM) proteins (type I and II collagen, and aggrecan), and MMP-9 and MMP-13. No cartilage destruction was observed in the mandibular condyle of Mmp2-/- mice, and no difference was found in the localization of the ECM proteins between the Mmp2-/- mice and WT mice. However, the bone marrow cavity in the subchondral bone of the mandibular condyle was more distinct in Mmp2-/- mice than in WT mice at the age of 50 weeks. Of note, MMP-9 characteristically localized in multinucleated cells in the mandibular condyle in 50-week-old Mmp2-/- mice. MMP-2 may be involved in the regulation of osteoclast differentiation and the formation of the bone marrow cavity in aged mice.
Subject(s)
Cartilage, Articular , Matrix Metalloproteinase 2 , Mice , Animals , Aggrecans/genetics , Aggrecans/metabolism , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Chondrocytes/metabolism , Mandibular Condyle/metabolism , Collagen/metabolism , Extracellular Matrix Proteins/metabolism , Cartilage, Articular/physiology , Collagen Type II/metabolismABSTRACT
Febrile seizures are frequently accompanied by stress-induced hyperglycemia. Herein, we report the case of a 1.5-yr-old girl with hyperglycemia during febrile seizures who was subsequently diagnosed with glucokinase (GCK) maturity-onset diabetes of the young (MODY), considering its distinction from stress hyperglycemia. Following the development of febrile seizures owing to adenovirus infection, the patient presented a casual blood glucose level was 185 mg/dL. She had a multigenerational family history of diabetes and a hemoglobin A1c (HbA1c) level of 6.4%. Owing to the persistent glucose intolerance until the age of 5 years, genetic testing was performed, which revealed a heterozygous mutation in GCK, and the patient was diagnosed with GCK-MODY. Precise diagnosis of GCK-MODY individuals is important to avoid administering unnecessary antidiabetic medications. Even during hyperglycemia under stress, multigenerational diabetes and mildly elevated HbA1c levels can suggest GCK-MODY.
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Background Wilms tumor 1 (WT1) is highly expressed in various solid tumors and hematologic malignancies. DSP-7888 (adegramotide/nelatimotide) Emulsion is an investigational therapeutic cancer vaccine comprising three synthetic epitopes derived from WT1. We evaluated the mechanism of action of DSP-7888 Emulsion, which is hypothesized to induce WT1-specific cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs). Methods The ability of nelatimotide and adegramotide to induce WT1-specific CD8+ T cells and CD4+ T cells was assessed in human peripheral blood mononuclear cells (PBMCs). The ability of DSP-7888 Emulsion to induce WT1-specific CTLs in vivo was assessed using human leukocyte antigen-I (HLA-I) transgenic mice. To assess how adegramotide, the helper peptide in DSP-7888 Emulsion, enhances WT1-specific CTLs, HLA-I transgenic mice were administered DSP-7888 or nelatimotide-only Emulsion. Interferon-gamma secretion under antigen stimulation by splenocytes co-cultured with or without tumor cells was then quantified. The effects of combination treatment with DSP-7888 Emulsion and an antiprogrammed cell death protein 1 (PD-1) antibody on tumor volume and the frequency of tumor-infiltrating WT1-specific T cells were assessed in HLA-I transgenic mice implanted with WT1 antigen-positive tumors. Result The peptides in DSP-7888 Emulsion were shown to induce WT1-specific CTLs and HTLs in both human PBMCs and HLA-I transgenic mice. Unlike splenocytes from nelatimotide-only Emulsion-treated mice, splenocytes from DSP-7888 Emulsion-treated mice exhibited high levels of interferon-gamma secretion, including when co-cultured with tumor cells (AU)
Subject(s)
Humans , Animals , Mice , Cancer Vaccines/therapeutic use , Wilms Tumor/drug therapy , Wilms Tumor/metabolism , Peptides/therapeutic use , CD8-Positive T-Lymphocytes , Emulsions/metabolism , Interferon-gamma/metabolism , Leukocytes, Mononuclear/metabolism , Mice, Transgenic , T-Lymphocytes, Cytotoxic , WT1 ProteinsABSTRACT
The assessment of stent lumen patency via non-contrast-enhanced 2-dimensional time-of-flight magnetic resonance angiography (2D TOF MRA) is complex due to stent-related artifacts. However, an imaging technique using the phase-contrast method, which can reduce susceptibility to artifact, is available. Herein, we report the use of 3-dimensional velocity vector image obtained via 4-dimensional flow magnetic resonance imaging (4D flow MRI) for in-stent flow visualization after stent development in the right superficial femoral artery. Hence, instead of 2D TOF MRA, 4D flow MRI using the phase-contrast method can be performed to assess stent lumen patency as it reduces stent-related artifacts.
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BACKGROUND: Wilms' tumor 1 (WT1) is highly expressed in various solid tumors and hematologic malignancies. DSP-7888 (adegramotide/nelatimotide) Emulsion is an investigational therapeutic cancer vaccine comprising three synthetic epitopes derived from WT1. We evaluated the mechanism of action of DSP-7888 Emulsion, which is hypothesized to induce WT1-specific cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs). METHODS: The ability of nelatimotide and adegramotide to induce WT1-specific CD8+ T cells and CD4+ T cells was assessed in human peripheral blood mononuclear cells (PBMCs). The ability of DSP-7888 Emulsion to induce WT1-specific CTLs in vivo was assessed using human leukocyte antigen-I (HLA-I) transgenic mice. To assess how adegramotide, the helper peptide in DSP-7888 Emulsion, enhances WT1-specific CTLs, HLA-I transgenic mice were administered DSP-7888 or nelatimotide-only Emulsion. Interferon-gamma secretion under antigen stimulation by splenocytes co-cultured with or without tumor cells was then quantified. The effects of combination treatment with DSP-7888 Emulsion and an anti-programmed cell death protein 1 (PD-1) antibody on tumor volume and the frequency of tumor-infiltrating WT1-specific T cells were assessed in HLA-I transgenic mice implanted with WT1 antigen-positive tumors. RESULTS: The peptides in DSP-7888 Emulsion were shown to induce WT1-specific CTLs and HTLs in both human PBMCs and HLA-I transgenic mice. Unlike splenocytes from nelatimotide-only Emulsion-treated mice, splenocytes from DSP-7888 Emulsion-treated mice exhibited high levels of interferon-gamma secretion, including when co-cultured with tumor cells; interferon-gamma secretion was further enhanced by concomitant treatment with anti-PD-1. HLA-I transgenic mice administered DSP-7888 Emulsion plus anti-PD-1 experienced significantly greater reductions in tumor size than mice treated with either agent alone. This reduction in tumor volume was accompanied by increased numbers of tumor-infiltrating WT1-specific CTLs. CONCLUSIONS: DSP-7888 Emulsion can promote both cytotoxic and helper T-cell-mediated immune responses against WT1-positive tumors. Adegramotide enhances CTL numbers, and the CTLs induced by treatment with both nelatimotide and adegramotide are capable of functioning within the immunosuppressive tumor microenvironment. The ability of anti-PD-1 to enhance the antitumor activity of DSP-7888 Emulsion in mice implanted with WT1-positive tumors suggests the potential for synergy.
Subject(s)
Cancer Vaccines , Neoplasms , Humans , Mice , Animals , CD8-Positive T-Lymphocytes , Cancer Vaccines/therapeutic use , Interferon-gamma/metabolism , Emulsions/metabolism , Emulsions/pharmacology , Leukocytes, Mononuclear/metabolism , WT1 Proteins , Neoplasms/metabolism , Peptides , T-Lymphocytes, Cytotoxic , Mice, Transgenic , Tumor MicroenvironmentABSTRACT
An accelerating aging society and rise in serious illnesses has led to an increase in deaths and made the demand for palliative care even greater. An integrated review was conducted to identify the impact of interprofessional education (IPE) on palliative/end of life (EOL) care for unlicensed health care students with a multidisciplinary approach. The databases searched included MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Education Resources Information Center (ERIC), PsycINFO, and the Cochrane Library's CENTRAL. Fifteen studies were included. Participants' disciplines included medicine, nursing, pharmacy, physical therapy, occupational therapy, social work, chaplain, public health and psychology. Nine were pre-post design and others were post course evaluations. One research study was an interventional trial with a comparative group. The selected studies included a variety of teaching strategies such as simulation or role play, clinical experience, case study, and TOSCE training. The importance of an interprofessional approach to palliative/EOL care has been highlighted, and our review suggests that combined IPE and palliative/EOL interventions can potentially impact palliative/EOL patient outcomes. More studies are needed to clarify the effectiveness of interprofessional palliative/EOL educational interventions including facilitators, learning outcomes, variable methods or teaching strategy, and the level of students.
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Students, Nursing , Terminal Care , Humans , Interprofessional Education , Delivery of Health Care , Palliative Care , Students, Nursing/psychology , Interprofessional RelationsABSTRACT
Central venous catheterization is a commonly used procedure for disease management. However, the procedure is not without risks of severe morbidity. We herein report hemostasis for accidental venous puncture using thoracoscopy. A 44-year-old man with short bowel syndrome and chronic renal failure required central venous catheterization for nutritional management and hemodialysis. Right internal jugular vein puncture was performed under ultrasonographic guidance, and the guidewire was inserted into the right atrium under fluoroscopic guidance. However, the operator inadvertently perforated the vein, and the thoracic cavity was entered while inserting the introducer. The patient's vital signs were stable; therefore, we performed emergency surgery after computed tomography and achieved hemostasis through thoracoscopic surgery. Sufficient caution should be exercised while inserting central venous catheters through a thrombosed internal jugular vein. In some instances of catheter-induced vessel injury, combined surface and thoracoscopic hemostasis may be a reliable and minimally invasive management option.
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Background: The increasing ratio of functional future liver remnant (functional %FLR) after modified associating liver partition and portal vein ligation/embolization for staged hepatectomy (modified-ALPPS) compared with portal vein embolization (PVE) has not been comprehensively evaluated. Purpose: To compare the increasing ratio of functional %FLR between modified-ALPPS and PVE via technetium-99 m-galactosyl human serum albumin single-photon emission computed tomography (99mTc-GSA SPECT/CT) fusion imaging. Material and Methods: Seven and six patients underwent modified-ALPPS (modified-ALPPS group) and PVE (PVE group) from 2015 to 2019. The functional %FLR on 99 mTc-GSA SPECT/CT fusion imaging was assessed before and 1 week (modified-ALPPS group) and 3 weeks (PVE group) after each procedure. The increasing ratio of functional %FLR (functional %FLR ratio) was calculated and compared between the two groups. Moreover, the hypertrophy ratio of future liver remnant volume (FLRV ratio) and atrophy ratio of embolized liver volume (.ELV ratio) were evaluated. Results: The mean functional %FLR ratios of the modified-ALPPS group (1.47 ± 0.15) and the PVE group (1.49 ± 0.20) were comparable (p > .05). The median FLRV ratio of modified-ALPPS group (1.48) was higher than that of the PVE group (1.16), the median ELV ratio of the PVE group (0.81) was lower than that of the modified-ALPPS group (0.94), and the results significantly differed between the two groups (p < .05). Conclusion: The increasing ratio of functional %FLR was comparable between modified-ALPPS and PVE. Compared with PVE, ALPPS was associated with a higher hypertrophy rate of the remnant liver but a lower atrophy rate of the embolized liver.
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Intravoxel incoherent motion imaging has its improvement-evaluating ability in lower limb perfusion after endovascular therapy in individuals with lower extremity arterial disease. Here, we present a 70-year-old man with intermittent claudication of the left lower limb, whose microperfusion on intravoxel incoherent motion imaging improved after endovascular therapy. The patient underwent intravoxel incoherent motion imaging of the lower extremities pre- and postendovascular therapy. After endovascular therapy, the left ankle brachial index increased from 0.46 to 1.06. The mean perfusion-related coefficient (10-3 mm2/s) of the left lower limb increased from 19.70 ± 3.17 to 24.81 ± 3.41, and mean perfusion fraction (%) of the left lower limb slightly increased from 24.41 ± 0.96% to 25.20 ± 1.89% after endovascular therapy. Therefore, successful revascularization can improve microperfusion on intravoxel incoherent motion imaging in a patient with lower extremity arterial disease.
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Bochdalek hernia is the most common type of congenital diaphragmatic hernia( CDH). Patients with CDH often develop cardiopulmonary dysfunction secondary to pulmonary hypoplasia and pulmonary hypertension, which necessitates emergency surgery. Advanced cardiopulmonary management is essential in such cases;therefore, patients should be treated at a well-facility that is familiar with the treatment of CDH. Respiratory management using gentle ventilation and control of pulmonary hypertension using nitric oxide are necessary for preoperative stabilization of patients. Intraoperatively, the hernia should be cautiously reduced and contents should be returned into the abdominal cavity. Surgery is performed to secure the circumference of the rim and ensure firm closure of the defect. Thoracoscopic surgery may be considered for late-onset cases with a stable general condition.