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子宮内膜症症例におけるマイクロバイオーム解析； 腹水と卵巣嚢腫内容液にマイクロバイオームは存在するのか？
Get PDFPurpose: To investigate the relationship between the microbiome of the female genital tract and endometriosis.
Methods: This prospective cohort study included 36 women who underwent laparoscopic surgery for ovarian tumor from July 2019 to April 2020. Of them, 18 had endometriosis, and 18 did not have endometriosis. Vaginal secretions, endometrial fluid, peritoneal fluid, and ovarian cystic fluid were collected during surgery. Next-generation sequencing of bacterial 16S rRNA was performed to characterize the microbiome.
Results: Specific microbiomes were not detected in either peritoneal fluid or ovarian cystic fluid regardless of the presence or absence of endometriosis and the type of cyst. When the cutoff value of infectious bacterial abundance in the vagina was set as 64.3%, there were many cases more than a cutoff value in the endometriosis group significantly (p = 0.01). When the cutoff value of infectious bacterial abundance in the endometrium was set as 18.6%, there were many cases more than a cutoff level in the endometriosis cases significantly (p = 0.02).
Conclusion: Peritoneal fluid and ovarian cystic fluid are almost sterile, although dysbiosis may occur in the vaginal and endometrial microbiome in women with endometriosis.博士(医学)琉球大
GRIM-19は結核菌のZn^<2+>メタロプロテアーゼの標的であり、NLRP3インフラマソームの活性化に必須である
Get PDFTuberculosis is a communicable disease caused by Mycobacterium tuberculosis which primarily infects macrophages and establishes intracellular parasitism. A mycobacterial virulence factor Zn^ metalloprotease 1 (Zmp1) is known to suppress interleukin (IL)-1β production by inhibiting caspase-1 resulting in phagosome maturation arrest. However, the molecular mechanism of caspase-1 inhibition by Zmp1 is still elusive. Here, we identified GRIM-19 (also known as NDUFA13), an essential subunit of mitochondrial respiratory chain complex I, as a novel Zmp1-binding protein. Using the CRISPR/Cas9 system, we generated GRIM-19 knockout murine macrophage cell line J774.1 and found that GRIM-19 is essential for IL-1β production during mycobacterial infection as well as in response to NLRP3 inflammasome-activating stimuli such as extracellular ATP or nigericin. We also found that GRIM-19 is required for the generation of mitochondrial reactive oxygen species and NLRP3-dependent activation of caspase-1. Loss of GRIM-19 or forced expression of Zmp1 resulted in a decrease in mitochondrial membrane potential. Our study revealed a previously unrecognized role of GRIM-19 as an essential regulator of NLRP3 inflammasome and a molecular mechanism underlying Zmp1-mediated suppression of IL-1β production during mycobacterial infection.博士(医学)琉球大
タコ類における視覚・触覚間クロスモーダル認知に関する行動学的研究
Get PDFOctopuses, a member,of molluscan class, possess well-developed nervous system such as lens eyes that is anatomically similar to vertebrates, and large brain. Octopuses are also characterized with their highly sensitive sensory receptors, namely, suckers on their eight arms. Due to these biological uniqueness, octopuses have been a target for psychological studies and were reported their advanced abilities for a diversity of learning and memory. All of these findings have come from experiments that tested with single sensory perception (i.e., visual or tactile). On the other hand, it is known in a wide range of organisms, from mammals to insects, they can integrate multiple sensory information and exchange these information between different senses, by which they can vividly image their environments. In this study, we will shed light on an idea for multi modal perception in octopuses, which is based on my studies for visual and tactile perception in tropical octopuses inhabiting the coastal waters of the Ryukyu Archipelago.博士(理学)琉球大
太陽光発電向けの高ゲイン電力変換器に関する研究
Get PDFThe increase in global energy demand and the impending depletion of conventional energy sources, i.e. fossil fuels, has led to increased renewable energy research. Additionally, emissions and by-products of conventional energy sources have led to increased pollution and detrimental effects on the environment. Renewable energy offers a clean, sustainable and viable alternative to fossil fuels. The most popular renewable energy types are wind energy and solar energy. In addition to being renewable, solar energy has no moving parts, is a growing popular energy source for electric vehicles, and is a viable solution for the electrification of rural and remote areas. Despite these advantages, there are some hurdles to overcome for solar energy to become a primary energy supply. In photovoltaic (PV) systems, the voltage obtained from the solar panels is far lower than the utility levels and needs significant power processing before transmission or utilization. This low voltage is also affected by a plethora of external factors such as temperature, angle of irradiation and partial shading. A DC-DC converter interface is essential for the extraction of power from solar panels.
The main function of the converter is to boost the panel's output voltage to meaningful levels. There are several topologies to achieve high converter gain. Some popular choices for high gain conversion are isolated or transfonner-based converters, multi-level converters, cascaded converters and hybrid converters which employ one or more of these strategies. But some of the problems faced by these topologies are operation at high duty ratio to deliver the high gain, complicated design with many active element which requires complex control circuitry, usage of several magnetic elements which increase the cost and weight of the converter and discontinuity of the input current which affects the overall performance of the solar panel. The objective is to design a suitable DC-DC converter topology that delivers high gain, at a moderate duty ratio which is simple to design.
This dissertation seeks to investigate the issues mentioned and to develop a viable topology that delivers high gain while minimizing the drawbacks of existing topologies. An in-depth study of the existing literature has led to the development of two unique hybrid topologies. The first topology uses a hybrid switched-capacitor network to achieve high gain and the second topology uses a voltage multiplier network to do the same. Also, an in-depth mathematical analysis of the operation of the proposed converters is presented. The proposed converters are. simulated in PSIM and the obtained results prove the validity of the operation. Suitable hardware prototypes are built and tested and the results are presented to show the validity of the research. The proposed converters are compared against converters presented in the literature to show their effectiveness as a viable alternative to the existing topologies.
Finally, the future scope of this research work has also been detailed.博士（工学）琉球大
Study on the Pacific North Equatorial Countercurrent, its variations, and its responses to the El Niño event
Get PDFThe North Equatorial Countercurrent (NECC) is an eastward zonal current that establishes the low-latitude North Pacific Gyre. The NECC, which flows along the Pacific Ocean, has aroused the curiosity of scientists due to the likelihood that it may play a key role in the El Niño Southern Oscillation's (ENSO) evolution. ENSO has two phases: the warm period, which we call El Nino, and the cold phase, which we call La Nina. To explore the dominant mode of the NECC in each season, an empirical orthogonal function (EOF) approach was used in this study. Using geostrophic current data from altimetric satellites, we found that the NECC strengthened (weakened) during the developing phase of the El Niño (La Niña) event, which occurs mostly in boreal summer. The NECC magnitude decreased significantly as it entered the mature phase of El Nino, which occurs primarily in boreal winter. The movement of the NECC pathway to the north (south) was also seen when the magnitude was strengthening (weakening). In addition, the response of the NECC in the west and east of the dateline to three types of El Nino over 40 years (1978-2017) was carried out to analyze the differences. El Nino events are classified into three types: east pacific (EP), central pacific (CP), and a combination of both EP and CP (MIX). The results of this study showed that during the MIX El Nino period, the NECC was at its strongest in the west and east of the dateline. In the western Pacific Ocean, EP El Nino episodes usually induced a stronger NECC than CP El Nino episodes throughout the development phase, although it is difficult to detect with EOF analysis. In the mature phase, on the other hand, CP El Nino is detected more regularly, resulting in a greater NECC magnitude. Several oddities, such as episodes EP 1986/1987, CP 1987/1988, and CP 2002/2003, were identified during El Nino's unique years. In the east of the dateline, The NECC was considerably stronger during the EP and MIX El Niño than during the CP El Niño for the spring to fall, which are frequently linked with the development phase. In the mature phase, the NECC during the EP El Niño was weaker than the NECC during the CP and MIX El Niño. The movement of the western Pacific NECC to the south occurs in all types of El Nino events. The NECC east of the dateline, on the other hand, shifted northward during the mature phase of the CP and MIX episodes but not during the EP episodes.博士（学術）琉球大学University of the Ryukyu
精神病状態を呈した20歳未満の外来初診患者の精神病理と臨床転帰
Get PDFAim: This study aimed to clarify the psychopathology, global functioning and clinical outcome of patients under 20 years old exhibiting a psychotic state. Methods: Forty-five patients (15 males and 30 females) under 20 years old with a diagnostic description of psychosis, schizophrenia, at-risk mental state (ARMS) or psychotic-like experiences, who had first visited our clinic between January 2012 and December 2017 were retrospectively extracted from medical records. Their age at the onset of symptoms; psychiatric diagnoses, including comorbidities; insight of disease; symptomatology (early, positive, negative, catatonic and anxiety-depression symptoms); course of illness; prescribed medication; and final treatment outcome were investigated from various aspects. Results: Prodromal stages of schizophrenia (ARMS and early schizophrenia) were observed in about one-third of the overall patients. Patients with insight of disease had a higher baseline global assessment of functioning and greater number of early schizophrenic symptoms and anxiety-depression symptoms than those without insight of disease. In particular, early schizophrenic symptoms appear to be a discriminating factor for insight of disease. A total of 36.4% of ARMS patients converted to schizophrenia, while 25% of early schizophrenia patients converted to frank schizophrenia. Doses of antipsychotics (chlorpromazine equivalence: mg/day) were lower in ARMS non-converters (100 ± 63) than in ARMS converters (364 ± 44) or schizophrenics (477 ± 337). Among overall patients, 62.3% showed improvement as the final treatment outcome. The global assessment of functioning values were higher at 6 (54.2% ± 17.2%) and 12 months (55.1% ± 18.9%) than that at baseline (34.1% ± 10.3%).
Conclusion: The present study suggests that clinicians need to actively ask about early symptoms or attenuated positive symptoms in patients under 20 years old with a psychotic state who may still have insight of disease and encourage voluntary help-seeking. The first six months might be a critical period for achieving symptomatological remission and functional recovery in these patients.博士(医学)琉球大
超高精細CTにおける気管支自動抽出能の検討： 1024マトリクスと0.25mm スライス厚を用いた画像化による進歩
Get PDFPurpose The aim of this study was to evaluate the advantages of ultra-high-resolution computed tomography (U-HRCT)
for automatic bronchial segmentation.Materials and methods This retrospective study was approved by the Institutional Review Board, and written informed consent
was waived. Thirty-three consecutive patients who underwent chest CT by a U-HRCT scanner were enrolled. In each
patient, CT data were reconstructed by two different protocols: 512 x 512 matrix with 0.5-mm slice thickness (conventional
HRCT mode) and 1024x 1024 matrix with 0.25-mm slice thickness (U-HRCT mode). We used a research workstation to
compare the two CT modes with regard to the numbers and total lengths of the automatically segmented bronchi.Results Significantly greater numbers and longer lengths of peripheral bronchi were segmented in the U-HRCT mode than
in the conventional HRCT mode (P < 0.001, for fifth-to eighth-generation bronchi). For example, the mean numbers and
total lengths of the sixth-generation bronchi were 81 and 1048 mm in the U-HRCT mode and 59 and 538 mm in the conventional
HRCT mode.Conclusions The U-HRCT mode greatly improves automatic airway segmentation for the more peripheral bronchi, compared
with the conventional HRCT mode. This advantage can be applied to routine clinical care, such as virtual bronchoscopy and
automatic lung segmentation.博士(医学)琉球大
慢性腎臓病における尿中アンジオテンシノーゲンと腎細動脈リモデリングとの関連
Get PDFObjective: Renin-angiotensin system (RAS) might be associated with arteriolar remodeling. The present study aimed to explore the hitherto unknown relationship between renal RAS and renal arteriolar remodeling and to elucidate whether altered renal RAS subsequently affects renal function in patients with chronic kidney disease (CKD).
Methods: In this retrospective study, patients with various CKDs not using RAS inhibitors who underwent renal biopsy were included in cross-sectional and longitudinal analyses. Urinary angiotensinogen (UAGT) levels and wall/lumen ratio (WLR) were determined to evaluate renal RAS and renal arteriolar remodeling, respectively. The association between ln(UAGT) and ln(WLR) was cross-sectionally examined using a liner regression model. Furthermore, the association of ln(UAGT) with subsequent changes in estimated glomerular filtration rate (eGFR) per year were longitudinally examined in the largest subgroup of patients who were diagnosed with IgA nephropathy.
Results: In the overall cohort (n = 54), the median age, blood pressures, eGFR, and WLR were 37 years, 120/73 mmHg, 85 ml/min per 1.73 m2, and 0.93, respectively. Ln(UAGT) was significantly and positively associated with ln(WLR) even after adjusting for classical and nonclassical clinical renal risk factors. In patients with IgA nephropathy, higher ln(UAGT) was associated with higher ln(WLR). Ln(UAGT) also tended to be associated with a greater decline in eGFR per year over a median period of 8.7 years, even after adjusting for potential confounding factors.
Conclusion: In patients with CKD, renal RAS might be associated with renal arteriolar remodeling and future decline in eGFR, independent of potential risk factors.博士(医学)琉球大
心房細動に対するカテーテルアプレーションにおける fluoroscopy image integration module 導入前後の放射線被ばくと手技時間の比較
Get PDFCatheter ablation (ABL) for atrial fibrillation (AF) remains a complex procedure and may require long fluoroscopy time. Further time reduction is necessary. We conducted a retrospective, observational, cross-sectional, single-center study to compare procedure time and radiation exposure before and after fluoroscopy image integration module (IIM) installation for AF between April 2018 and October 2020. We reviewed 236 consecutive patients who underwent ABL at University of the Ryukyus Hospital. We performed ABL for AF for 81 patients (before IIM installation), 67 patients (after IIM installation). We analyzed 68 patients as non-IIM group, 56 patients as IIM group who underwent pulmonary vein isolation (PVI) and cavotricuspid isthmus (CTI) ABL for AF after the exclusion of patients with additional ABL. The procedure time, fluoroscopy time, and radiation dose were considered between both groups. The median PVI procedure time (1.50 [interquartile range {IQR} l.20-l.83]h vs. 1.33 [IQR 0.91-1.SO]h; P<0.05), total fluoroscopy time (36.6 [IQR 24.2-55.8]min vs. 24.0 [IQR 18.0-35.4]min; P<0.05), and radiation dose (125.73 [IQR 73.92-217.04]mGy vs. 77.58 [IQR 48.62-122.90]mGy; P<0.05) in the IIM group were significantly lower than those in the non-IIM group. The use of IIM resulted in shorter procedure time and less radiation exposure in ABL for AF.博士(医学)琉球大
肝転移を伴う膵癌における circulating tumor DNA のバイオマーカーとしての有用性
Get PDFPancreatic cancer is an aggressive, solid tumor, with a grave prognosis. Despite surgical treatment in patients with pancreatic cancer, the rate of recurrence is high. In addition, although tumor biomarkers are frequently used to confirm advanced pancreatic cancer, this is not accurate and the biomarkers currently used cannot indicate prognosis. This study sought to evaluate circulating tumor DNA as a tumor biomarker to prognosticate pancreatic cancer. Patients with advanced pancreatic cancer and liver metastasis (N = 104) were included, and blood samples were collected from all patients. The mutant allele frequency was measured using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with > 240 hot spots. In patients with advanced pancreatic cancer, 50% (N = 52) had detectable ctDNA levels, with TP53 (45%, N = 47) and KRAS (42.3%, N = 44) mutations the most common. Patients with detectable circulating tumor DNA levels also had significantly worse overall survival and progression free survival than ctDNA negative patients (8.4 vs 16 months, P<0.0001 for overall survival; 3.2 vs 7.9 months, P<0.0001 for progression-free survival). In a multivariate analysis, ctDNA status was independently associated with overall survival and progression-free survival (HR = 3.1, 95%CI = 1.9–5.0, P<0.0001; HR 2.6, 95%CI = 1.7–4.0, P<0.0001, respectively). Moreover, circulating tumor DNA significantly correlated with a higher number of liver metastases, the presence of lung and/or peritoneal metastases, tumor burden, and higher carbohydrate antigen 19–9 levels. This study supports the use of circulating tumor DNA as an independent prognostic marker for advanced pancreatic cancer.博士(医学)琉球大