Detecting groundwater level changes related to the 2016 Kumamoto Earthquake.

This study presented the first attempt to detect precursory changes in groundwater level before the 2016 Kumamoto Earthquake. This detection was achieved by accurately determining the relationship between long-term groundwater level fluctuation and crustal deformation over 16 years through analysis of groundwater level time-series data acquired at 17 sites within the study area. Here, we show that the observed groundwater levels were lower than the modelled levels in aquifers composed of porous strata (Togawa lava and part of the pre-Aso volcanic rocks), and that there were larger differences until 2014, which diminished until the occurrence of the Kumamoto Earthquake. The initial reduction in the modelled groundwater level and the latter recovery were most likely caused by crustal strain relaxation associated with the large 2011 earthquake off the Pacific coast of Tohoku (Mw 9.0) and the strain accumulation prior to the 2016 Kumamoto Earthquake.

Thoracoscopic esophagectomy with subcarinal lymph node dissection in the prone position for esophageal cancer with a right top pulmonary vein.

The right top pulmonary vein (RTPV), a rare pulmonary vein (PV) variant draining the right upper lobe, arises independently from the right superior PV, travels posterior to the right bronchial tree and drains directly into the left atrium (LA) or another PV. We report an RTPV discovered on preoperative computed tomography (CT) scanning in a 60-y-old man who subsequently underwent prone thoracoscopic esophagectomy and subcarinal lymph node dissection. The preoperative CT scan showed an anomalous vessel 7.8 mm in diameter arising from the right upper lobe, running posterior to the right main bronchus (RMB), and draining directly into the LA. To our best knowledge, this is the largest reported RTPV (7.8 mm in diameter) and is an extremely rare variant, passing posterior to the RMB and draining into the LA.

Early-onset Marfan syndrome with a novel missense mutation: A case report.

Early-onset Marfan syndrome (eoMFS) progresses rapidly, starting during the neonatal period, causes severe clinical disease, and has a poor prognosis. The genetic abnormality associated with eoMFS is located in a so-called critical neonatal region in exons 25-26 of the fibrillin-1 (FBN1) gene. A female neonate was delivered by emergency cesarean section at 37 weeks gestation due to fetal distress with bradycardia, cyanosis, and no spontaneous breathing. On examination, the patient had multiple musculoskeletal deformities, including loose redundant skin, arachnodactyly, flat soles, and joint contractures. Echocardiography showed poor cardiac contractility with multiple valvular abnormalities. She died 13 h after birth. We identified a novel missense variant c.3218A>G (p.Glu1073Gly) in exon 26 of the FBN1 gene by targeted next-generation sequencing. A literature review revealed that arachnodactyly and aortic root dilatation in the fetus are predictive of eoMFS. However, the predictive potential of ultrasonography alone is limited. Genetic testing of the FBN1 gene restriction region associated with short life expectancy and characteristic fetal ultrasound findings could be important for prenatal diagnosis of eoMFS, postnatal management, and parental preparedness. Learning objective: We identified a novel missense mutation located in exons 25-26 of the Fibrillin-1 gene in a neonate with early-onset Marfan syndrome (eoMFS) who died of severe early heart failure shortly after birth. This mutation was located in a narrowly defined critical neonatal region, recently reported to cause eoMFS, and its clinical profile was consistent with early-onset severe heart failure. In addition to ultrasonography, genetic analysis of this region is important for predicting prognosis in eoMFS.

Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4+, CD8+, and Foxp3+ Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis.

Chemokines and cytokines in the tumor microenvironment influence immune cell infiltration and activation. To elucidate their role in immune cell recruitment during oral cancer development, we generated a mouse tongue cancer model using the carcinogen 4-nitroquinoline 1-oxide (4NQO) and investigated the carcinogenetic process and chemokine/cytokine gene expression kinetics in the mouse tongue. C57/BL6 mice were administered 4NQO in drinking water, after which tongues were dissected at 16 and 28 weeks and subjected to analysis using the RT2 Profiler PCR Array, qRT-PCR, and pathologic and immunohistochemical analyses. We found that Th1-associated chemokine/cytokine (Cxcl9, Cxcl10, Ccl5, and Ifng) and Treg-associated chemokine/cytokine (Ccl17, Ccl22, and Il10) mRNA levels were simultaneously increased in premalignant lesions of 4NQO-treated mice at 16 weeks. Additionally, although levels of Gata3, a Th2 marker, were not upregulated, those of Cxcr3, Ccr4, and Foxp3 were upregulated in the tongue tissue. Furthermore, immunohistochemical analysis confirmed the infiltration of CD4+, CD8+, and Foxp3+ cells in the tongue tissue of 4NQO-treated mice, as well as significant correlations between Th1- or Treg-associated chemokine/cytokine mRNA expression and T cell infiltration. These results indicate that CD4+, CD8+, and Foxp3+ cells were simultaneously recruited through the expression of Th1- and Treg-associated chemokines in premalignant lesions of 4NQO-induced mouse tongue tissue.

Association of Multiple Gene Polymorphisms Including Homozygous NUDT15 R139C With Thiopurine Intolerance During the Treatment of Acute Lymphoblastic Leukemia.

Although thiopurine is a crucial drug for treating acute lymphoblastic leukemia, individual variations in intolerance are observed due to gene polymorphisms. A 3-year-old boy with B-cell precursor acute lymphoblastic leukemia who was administered thiopurine developed mucositis, sepsis, and hemophagocytic lymphohistiocytosis due to prolonged hematologic toxicity, chronic disseminated candidiasis, and infective endocarditis that triggered multiple brain infarctions. The patient was found to harbor 3 gene polymorphisms associated with thiopurine intolerance including homozygous NUDT15 R139C, heterozygous ITPA C94A, and homozygous MTHFR C677T and heterozygous RFC1 G80A. Thus, the combined effect of intolerance via multiple gene polymorphisms should be considered in case of unexpected adverse reactions.

[Anesthetic management in a patient with arrhythmogenic right ventricular cardiomyopathy and an implantable cardioverter defibrillator: a case report]. / Anestesia para paciente com cardiomiopatia arritmogênica do ventrículo direito portador de cardioversor desfibrilador implantável: descrição de caso.

BACKGROUND AND OBJECTIVES: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiomyopathy characterized by potentially lethal ventricular tachycardia. Here we describe a patient with ARVC and an Implantable Cardioverter Defibrillator (ICD) in whom maxillary sinus surgery was performed under general anesthesia. CASE REPORT: The patient was a 59 year-old man who was scheduled to undergo maxillary sinus surgery under general anesthesia. He had been diagnosed as having ARVC 15 years earlier and had undergone implantation of an ICD in the same year. Electrocardiography showed an epsilon wave in leads II, aVR, and V1-V3. Cardiac function was within normal range on transthoracic echocardiography. The ICD was temporarily deactivated after the patient arrived in the operating room and an intravenous line was secured. An external defibrillator was kept on hand for immediate defibrillation if any electrocardiographic abnormality was detected. Remifentanil 0.3 µg/kg/min, fentanyl 0.1 mg, propofol 154 mg, and rocuronium 46 mg were administered for induction of anesthesia. Tracheal intubation was performed orally. Anesthesia was maintained oxygen 1.0 L.min-1, air 2.0 L.min-1, propofol 5.0-7.0 mg.kg-1.h-1, and remifentanil 0.1-0.25 µg.kg-1.min-1. The surgery was completed as scheduled and the ICD was reactivated. The patient was then extubated after administration of sugammadex 200 mg. CONCLUSION: We report the successful management of anesthesia without lethal arrhythmia in a patient with ARVC and an ICD. An adequate amount of analgesia should be administered during general anesthesia to maintain adequate anesthetic depth and to avoid stress and pain.

Anesthetic management in a patient with arrhythmogenic right ventricular cardiomyopathy and an implantable cardioverter defibrillator: a case report / Anestesia para paciente com cardiomiopatia arritmogênica do ventrículo direito portador de cardioversor desfibrilador implantável: descrição de caso

Abstract Background and objectives: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiomyopathy characterized by potentially lethal ventricular tachycardia. Here we describe a patient with ARVC and an Implantable Cardioverter Defibrillator (ICD) in whom maxillary sinus surgery was performed under general anesthesia. Case report: The patient was a 59 year-old man who was scheduled to undergo maxillary sinus surgery under general anesthesia. He had been diagnosed as having ARVC 15 years earlier and had undergone implantation of an ICD in the same year. Electrocardiography showed an epsilon wave in leads II, aVR, and V1-V3. Cardiac function was within normal range on transthoracic echocardiography. The ICD was temporarily deactivated after the patient arrived in the operating room and an intravenous line was secured. An external defibrillator was kept on hand for immediate defibrillation if any electrocardiographic abnormality was detected. Remifentanil 0.3 µg/kg/min, fentanyl 0.1 mg, propofol 154 mg, and rocuronium 46 mg were administered for induction of anesthesia. Tracheal intubation was performed orally. Anesthesia was maintained oxygen 1.0 L.min−1, air 2.0 L.min−1, propofol 5.0-7.0 mg.kg−1.h−1, and remifentanil 0.1-0.25 µg.kg−1.min−1. The surgery was completed as scheduled and the ICD was reactivated. The patient was then extubated after administration of sugammadex 200 mg. Conclusion: We report the successful management of anesthesia without lethal arrhythmia in a patient with ARVC and an ICD. An adequate amount of analgesia should be administered during general anesthesia to maintain adequate anesthetic depth and to avoid stress and pain.

Resumo Introdução e objetivo: A Cardiomiopatia Arritmogênica do Ventrículo Direito (CAVD) é uma cardiomiopatia genética caracterizada por taquicardia ventricular potencialmente letal. Descrevemos um paciente com CAVD com Cardioversor Desfibrilador Implantável (CDI) submetido a anestesia geral para cirurgia de seio maxilar. Relato do caso: Paciente masculino, 59 anos, a ser submetido a anestesia geral para cirurgia de seio maxilar. O paciente foi diagnosticado com CAVD há 15 anos, momento em que foi submetido a implante de CDI. A eletrocardiografia mostrou onda épsilon nas derivações II, aVR e V1-V3. O ecocardiograma transtorácico revelou função cardíaca normal. Após a entrada do paciente na sala de cirurgia, o CDI foi temporariamente desativado e uma via intravenosa foi instalada. Um desfibrilador externo foi mantido próximo ao paciente caso fosse detectada alguma anormalidade eletrocardiográfica que indicasse desfibrilação do paciente. Foram administrados 0,3 mg/kg/min de remifentanil, 0,1 mg de fentanil, 154 mg de propofol e 46 mg de rocurônio para indução da anestesia. A intubação traqueal foi realizada por via oral. A anestesia foi mantida com 1 L/min de oxigênio, 2 L/min de ar, 5-7 mg/kg/h de propofol e 0,1-0,25 µg/kg/min de remifentanil. O procedimento cirúrgico proposto foi concluído e o CDI foi reativado. O tubo traqueal foi retirado após administração de 200 mg de sugamadex. Conclusão: Descrevemos técnica de anestesia bem sucedida sem arritmia letal em paciente com CAVD e CDI. Analgesia adequada deve ser administrada durante a anestesia geral para manter profundidade anestésica correta e evitar estresse e dor.

Does TMJ Function and Imaging Tools Help Differentiate Between Condylar Resorption and Mandibular Hypoplasia?

PURPOSE: Differentiating between bilateral condylar resorption (CR) and mandibular hypoplasia (MH) can be challenging owing to the difficulty in chronological observation and establishing standardized measurements. The purpose of the present study was to assess whether temporomandibular joint (TMJ) function can distinguish between CR and MH and clarify the essential diagnostic imaging tools for CR. MATERIALS AND METHODS: We performed a cross-sectional study of patients with mandibular retrognathia. The primary predictor variables were a clinical dysfunction score for the TMJ, mandibular plane angle (MPA), SNA angle, SNB angle, and cortical erosion score in the condylar heads. The demographic variables were age, anterior disc displacement, and previous orthodontic treatment. The anatomic variable was the condylar height (CH). The primary outcome variable was the disease status (CR or MH). The patients were divided into the CR group and MH group. The patients with CR were selected on the basis of a CH value of less than 22 mm. TMJ function was assessed using the Helkimo clinical dysfunction index. The CH on panoramic radiographs was measured using the Kjellberg method. The MPA, SNA angle, and SNB angle were analyzed using cephalometric analysis. Cortical erosion in the condylar head was assessed using computed tomography and magnetic resonance imaging. RESULTS: A total of 23 female participants were enrolled in the present study. The average clinical dysfunction score for the TMJ was 4.4 in the CR group and 0.4 in the MH group (P < .05). The average MPA was 41.2° in the CR group and 35.5° in the MH group (P < .05). CONCLUSIONS: The present investigation has shown that assessing TMJ function and analyzing MPA using a cephalometric radiograph can differentiate CR from MH.

LDL uptake-dependent phosphatidylethanolamine translocation to the cell surface promotes fusion of osteoclast-like cells.

Osteoporosis is associated with vessel diseases attributed to hyperlipidemia, and bone resorption by multinucleated osteoclasts is related to lipid metabolism. In this study, we generated low-density lipoprotein receptor (LDLR)/lectin-like oxidized LDL receptor-1 (LOX-1, also known as Olr1) double knockout (dKO) mice. We found that, like LDLR single KO (sKO), LDLR/LOX-1 dKO impaired cell-cell fusion of osteoclast-like cells (OCLs). LDLR/LOX-1 dKO and LDLR sKO preosteoclasts exhibited decreased uptake of LDL. The cell surface cholesterol levels of both LDLR/LOX-1 dKO and LDLR sKO osteoclasts were lower than the levels of wild-type OCLs. Additionally, the amount of phosphatidylethanolamine (PE) on the cell surface was attenuated in LDLR/LOX-1 dKO and LDLR sKO preosteoclasts, whereas the PE distribution in wild-type OCLs was concentrated on the filopodia in contact with neighboring cells. Abrogation of the ATP binding cassette G1 (ABCG1) transporter, which transfers PE to the cell surface, caused decreased PE translocation to the cell surface and subsequent cell-cell fusion. The findings of this study indicate the involvement of a novel cascade (LDLR∼ABCG1∼PE translocation to cell surface∼cell-cell fusion) in multinucleation of OCLs.

Adhesion and Proliferation of Osteoblastic Cells on Hydroxyapatite-dispersed Ti-based Composite Plate.

BACKGROUND/AIM: Biocompatibility of a novel and more stable hydroxyapatite (HA)-dispersed titanium (Ti)-based composite was investigated, using the mouse osteoblast precursor cell line MC3T3-E1. MATERIALS AND METHODS: Surface of powders and plates was observed by scanning electron microscopy. Distribution of calcium and phosphorus on the surface of the composite was evaluated by an electron beam microanalyzer. Crystal structure was analyzed by X-ray diffractometer. Cell viability was determined by WST-1 assay. RESULTS: HA was stable against the compressive force, shearing stress and sintering heat at 800°C, but it slightly decomposed at 1100°C. With the increase of HA in the composites, the adhesion/proliferation of MC3T3-E1 cells was reduced. The growth inhibition by HA does not seem to be due to materials released from the plate, but rather to the contact to the surface of the plate. Sintering of the HA plate at 1100°C increased the number of attached viable cells. On the other hand, culturing on the synthesized calcium phosphate (apatite containing carbonic acid) increased the number of attached cells to a greater extent. CONCLUSION: HA inhibits the growth of osteoblastic cells, but sintering at 1100°C changes the surface properties of the composite so as to stimulate cell growth.

MYH7 mutation identified by next-generation sequencing in three infant siblings with bi-ventricular noncompaction presenting with restrictive hemodynamics: A report of three siblings with a severe phenotype and poor prognosis.

Noncompaction of the ventricular myocardium (NVM) is a genetically heterogeneous cardiomyopathy. Various mutations associated with NVM have been identified in several genes. NVM patients usually present with complications of dilated cardiomyopathy. We identified a missense mutation, c.5740G>A, p.Glu1914Lys of MYH7, by targeted next-generation sequencing in three infant siblings with isolated bi-ventricular noncompaction who presented with restrictive hemodynamics and severe clinical courses. This mutation appears to be associated with a severe phenotype and poor prognosis. Early heart transplantation should be considered in similar cases. .

The polymethoxy flavonoid sudachitin suppresses inflammatory bone destruction by directly inhibiting osteoclastogenesis due to reduced ROS production and MAPK activation in osteoclast precursors.

Inflammatory bone diseases, including rheumatoid arthritis, periodontitis and peri-implantitis, are associated not only with the production of inflammatory cytokines but also with local oxidative status, which is defined by intracellular reactive oxygen species (ROS). Osteoclast differentiation has been reported to be related to increased intracellular ROS levels in osteoclast lineage cells. Sudachitin, which is a polymethoxyflavone derived from Citrus sudachi, possesses antioxidant properties and regulates various functions in mammalian cells. However, the effects of sudachitin on inflammatory bone destruction and osteoclastogenesis remain unknown. In calvaria inflamed by a local lipopolysaccharide (LPS) injection, inflammation-induced bone destruction and the accompanying elevated expression of osteoclastogenesis-related genes were reduced by the co-administration of sudachitin and LPS. Moreover, sudachitin inhibited osteoclast formation in cultures of isolated osteoblasts and osteoclast precursors. However, sudachitin rather increased the expression of receptor activator of NF-κB ligand (RANKL), which is an important molecule triggering osteoclast differentiation, and the mRNA ratio of RANKL/osteoprotegerin that is a decoy receptor for RANKL, in the isolated osteoblasts, suggesting the presence of additional target cells. When osteoclast formation was induced from osteoclast precursors derived from bone marrow cells in the presence of soluble RANKL and macrophage colony-stimulating factor, sudachitin inhibited osteoclastogenesis without influencing cell viability. Consistently, the expression of osteoclast differentiation-related molecules including c-fos, NFATc1, cathepsin K and osteoclast fusion proteins such as DC-STAMP and Atp6v0d2 was reduced by sudachitin. In addition, sudachitin decreased activation of MAPKs such as Erk and JNK and the ROS production evoked by RANKL in osteoclast lineage cells. Our findings suggest that sudachitin is a useful agent for the treatment of anti-inflammatory bone destruction.

Combined SN-38 and gefitinib treatment promotes CD44 degradation in head and neck squamous cell carcinoma cells.

The aim of the present study was to search for an effective regimen among existing chemotherapies for head and neck squamous cell carcinoma (HNSCC). Among the tested drugs, we focused on combined SN-38, which is the active metabolite produced from irinotecan hydrochloride - a type I DNA topoisomerase inhibitor - after it is metabolized by carboxylesterase in the liver and gefitinib, an EGFR tyrosine kinase inhibitor treatment, based on the ability of this combination to inhibit HNSCC cell growth. Contrary to our expectation, in vivo, there was no significant difference in tumor growth suppression between gefitinib-only treatment and gefitinib plus SN-38. However, when tumor measurements were continued after treatment ceased, we found that several tumors showed renewed growth in the gefitinib-only group. The tumors that resumed growing after treatment showed increased CD44 expression compared with tumors from the combined treatment group. Next, we investigated the mechanism whereby SN-38 and gefitinib inhibited CD44 expression in vitro. These studies revealed that the combined treatment promoted lysosomal degradation of CD44. The present study revealed that combined gefitinib and SN-38 treatment inhibits CD44 expression by promoting its lysosomal degradation in HNSCC cells. However, it is still unclear whether inhibition of CD44 expression in HNSCC cells can directly suppress tumor regrowth after therapy. Thus, it may be necessary to elucidate the relationship between the effects of these chemotherapeutic agents on CD44 expression and tumor recurrence/metastasis in future studies.

Phase-dependent activity of neurons in the rostral part of the thalamic reticular nucleus with saccharin intake in a cue-guided lever-manipulation task.

Neurons in the rostral part of the thalamic reticular nucleus (rTRN) receive somatosensory and motor information and regulate neural activities of the thalamic nuclei. Previous studies showed that when activity in visual TRN neurons is suppressed prior to the visual stimuli in a visual detection task, the performance of the task improves. However, little is known about such changes in the rTRN preceding certain events. In the present study, we performed unit recordings in the rTRN in alert rats during a cue-guided lever-manipulation task in which saccharin was provided as a reward. Changes in neural activity during saccharin intake were observed in 56% (51 of 91) of the recorded neurons; the firing rates increased in 21 neurons and decreased in 23 neurons. Seven neurons both increased and decreased their firing rates during saccharin intake. Changes in firing rates during the reward-waiting stage between task termination and saccharin intake were also observed in 73% (37 of 51) of the neurons that responded to saccharin intake. Increased activity during saccharin intake did not correlate with increased activity during lever-manipulation or activity during the reward-waiting stage. However, decreased activity during saccharin intake was correlated with activity during the reward-waiting stage. These results suggest that rTRN neurons have phase-dependent changes in their activity and regulate the thalamic activities. Furthermore, the decreased activity of rTRN neurons before reward may contribute to refine somatosensory and motor information processing in the thalamic nuclei depending on the status of mind such as expectation and attention.

Discovery of a Novel, Orally Efficacious Liver X Receptor (LXR) ß Agonist.

This article describes the application of Contour to the design and discovery of a novel, potent, orally efficacious liver X receptor ß (LXRß) agonist (17). Contour technology is a structure-based drug design platform that generates molecules using a context perceptive growth algorithm guided by a contact sensitive scoring function. The growth engine uses binding site perception and programmable growth capability to create drug-like molecules by assembling fragments that naturally complement hydrophilic and hydrophobic features of the protein binding site. Starting with a crystal structure of LXRß and a docked 2-(methylsulfonyl)benzyl alcohol fragment (6), Contour was used to design agonists containing a piperazine core. Compound 17 binds to LXRß with high affinity and to LXRα to a lesser extent, and induces the expression of LXR target genes in vitro and in vivo. This molecule served as a starting point for further optimization and generation of a candidate which is currently in human clinical trials for treating atopic dermatitis.

Nitrogen, carbon, and sulfur isotopic change during heterotrophic (Pseudomonas aureofaciens) and autotrophic (Thiobacillus denitrificans) denitrification reactions.

In batch culture experiments, we examined the isotopic change of nitrogen in nitrate (δ(15)NNO3), carbon in dissolved inorganic carbon (δ(13)CDIC), and sulfur in sulfate (δ(34)SSO4) during heterotrophic and autotrophic denitrification of two bacterial strains (Pseudomonas aureofaciens and Thiobacillus denitrificans). Heterotrophic denitrification (HD) experiments were conducted with trisodium citrate as electron donor, and autotrophic denitrification (AD) experiments were carried out with iron disulfide (FeS2) as electron donor. For heterotrophic denitrification experiments, a complete nitrate reduction was accomplished, however bacterial denitrification with T. denitrificans is a slow process in which, after seventy days nitrate was reduced to 40% of the initial concentration by denitrification. In the HD experiment, systematic change of δ(13)CDIC (from -7.7‰ to -12.2‰) with increase of DIC was observed during denitrification (enrichment factor εN was -4.7‰), suggesting the contribution of C of trisodium citrate (δ(13)C=-12.4‰). No SO4(2-) and δ(34)SSO4 changes were observed. In the AD experiment, clear fractionation of δ(13)CDIC during DIC consumption (εC=-7.8‰) and δ(34)SSO4 during sulfur use of FeS2-S (around 2‰), were confirmed through denitrification (εN=-12.5‰). Different pattern in isotopic change between HD and AD obtained on laboratory-scale are useful to recognize the type of denitrification occurring in the field.

Brachial Plexus Involvement of Myeloid Sarcoma Detected by Reconstruction Magnetic Resonance Neurography.

Myeloid sarcoma is a rare hematological disorder that presents as an extramedullary mass of immature myeloid precursors. We herein present the case of a 57-year-old man with a seven-month history of progressive weakness in the right upper extremity. Reconstruction magnetic resonance neurography showed a marked enlargement of the right brachial plexus. Fluorodeoxyglucose positron emission tomography revealed a radioactive lesion in the sacrum, in addition to the right brachial plexus, and a biopsy of the sacrum revealed myeloid sarcoma. The brachial plexus lesion was also regarded as myeloid sarcoma because of the treatment response. Isolated myeloid sarcoma involving the brachial plexus is very rare and its diagnosis is difficult as there was neither a history of leukemia nor bone marrow involvement in this patient. In this case, reconstructed magnetic resonance neurography was useful for detecting the brachial plexus mass lesion which led to an early diagnosis and good recovery.

Tumor-associated macrophages in oral premalignant lesions coexpress CD163 and STAT1 in a Th1-dominated microenvironment.

BACKGROUND: Tumor-associated macrophages (TAMs) are implicated in the growth, invasion and metastasis of various solid tumors. However, the phenotype of TAMs in premalignant lesions of solid tumors has not been clarified. In the present study, we identify the phenotype of TAMs in leukoplakia, an oral premalignant lesion, by immunohistochemical analysis and investigate the involvement of infiltrated T cells that participate in the polarization of TAMs. METHODS: The subjects included 30 patients with oral leukoplakia and 10 individuals with normal mucosa. Hematoxylin and eosin slides were examined for the histological grades, and immunohistochemical analysis was carried out using antibodies against CD68 (pan-MΦ), CD80 (M1 MΦ), CD163 (M2 MΦ), CD4 (helper T cells: Th), CD8 (cytotoxic T cells), CXCR3, CCR5 (Th1), CCR4 (Th2), signal transducer and activator of transcription (STAT1), phosphorylated STAT1 (pSTAT1) and chemokine CXCL9. The differences in the numbers of positively stained cells among the different histological grades were tested for statistical significance using the Kruskal-Wallis test. Correlations between different types of immune cells were determined using Spearman's rank analysis. RESULTS: An increase in the rate of CD163(+) TAM infiltration was observed in mild and moderate epithelial dysplasia, which positively correlated with the rate of intraepithelial CD4(+) Th cell infiltration. Although CCR4(+) cells rarely infiltrated, CXCR3(+) and CCR5(+) cells were observed in these lesions. Cells positive for STAT1 and chemokine CXCL9, interferon- (IFN)-induced gene products, and pSTAT1 were also observed in the same lesions. Double immunofluorescence staining demonstrated that the cells that were positive for CD163 were also positive for STAT1. CONCLUSIONS: CD163(+) TAMs in oral premalignant lesions coexpress CD163 and STAT1, suggesting that the TAMs in oral premalignant lesions possess an M1 phenotype in a Th1-dominated micromilieu.

Efficacy of a half-grip technique using a fine tip LigaSure™, Dolphin Tip Sealer/Divider, on liver dissection in swine model.

BACKGROUND: Recently, a lot of energy devices in the surgical field, especially in the liver surgery, have been developed, and a fine tip LigaSure™, Dolphin Tip Sealer/Divider (DT-SD) also has been used frequently to dissect liver parenchyma as well as ultrasonically activated device (USAD). However, the utility of this instrument for liver dissection (LD) is still unknown. Moreover, to reduce bleeding during LD, a half-grip technique (HGT) was contrived. We herein report an experimental study in swine model to evaluate the feasibility and effectiveness of HGT using DT-SD for LD. METHODS: The swine model experiment was carried out under general anesthesia by veterinarians. LD was performed repeatedly by DT-SD with the HGT (Group A, n = 6), or the conventional clamp-crush technique (CCT) (Group B, n = 6), and by variable mode USAD (Group C, n = 6). The dissection length and depth (cm) as well as bleeding volume (g) were measured carefully, and the dissection area (cm(2)) and speed (cm(2)/min) were calculated precisely. Histological examinations of the dissection surfaces were also executed. Mann-Whitney's U test was used for Statistical analyses with variance at a significance level of 0.05. RESULTS: Among the three groups, the three averages of dissection lengths were unexpectedly equalized to 8.3 cm. The dissection area (cm(2)) was 9.9 ± 5.1 in Group A, 9.8 ± 4.7 in Group B, and 9.9 ± 4.5 in Group C. The mean blood loss during LD was 10.6 ± 14.8 g in Group A, 41.4 ± 39.2 g in Group B, and 34.3 ± 39.2 g in Group C. For Group A, the bleeding rate was the least, 0.9 ± 1.0 g/cm(2), and the average depth of coagulation was the thickest, 1.47 ± 0.29 mm, among the three groups (p < 0.05). The dissection speed in Group A (1.3 ± 0.3 cm(2)/min) was slower, than that in Group C (p < 0.05). CONCLUSIONS: This report indicates firstly that the HGT using DT-SD bring the least blood loss when compared with CCT or USAD. Although the HGT is feasible and useful for LD, to popularize the HGT, further clinical studies will be needed.

Barometric and tidal-induced aquifer water level fluctuation near the Ariake Sea.

Observations of water levels in coastal aquifers and corresponding tides coupled with meteorological variances near the Ariake Sea show that groundwater in this area mainly fluctuates with atmospheric and tidal variations. Tidal effects occur with semi-monthly, diurnal, or semi-diurnal periodicity, whereas the barometric influences commonly act in the low-frequency domain. Tidal and barometric effects in water levels are separable using wavelet techniques and can be evaluated statistically. Results show the following. (1) The tidal coefficients are 0.002-0.154, attenuating roughly exponentially from the seashore. The time lags in water levels increase linearly approximately with increasing inshore distance. Relations between tidal coefficients and time lags and the inshore distance indicate higher hydraulic diffusivity in the south aquifer, which was confirmed by the hydraulic property calibrations in analytical simulations. (2) Water levels related to meteorological phenomena fluctuate inversely according to barometric loading variation with time lags of 2-3 h. The effective barometric efficiencies are 0.022-0.12. Lower barometric influences were found in the south aquifer.