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PURPOSE: Patients who were administered radiopharmaceuticals can be a source of radiation exposure to sonographers. This study aimed to identify factors associated with radiation exposure to breast sonographers from patients administered radiopharmaceuticals for bone scanning. METHODS: The exposure dose of six sonographers was measured during breast sonography in 59 patients administered 99mTc-HMDP. We predicted the following factors to be related to exposure dose: time interval between administration and sonography, sonography examination time, estimated radioactivity at sonography, sonographer's years of experience, and patients' clinical data (age, renal function and surgical procedure). Spearman's rank correlation coefficient was used to examine the relationship between radiation dose and the aforementioned factors. RESULTS: The mean±standard deviation of the exposure dose for the sonographers was 9.3±3.8 µSv. The time interval between administering the radiopharmaceutical agent and sonography, the sonography examination time and estimated radioactivity at sonography were found to be factors related to the exposure of the sonographer. The exposure dose increased as a function of the shorter time interval, longer examination time and higher estimated radioactivity at sonography. CONCLUSION: The time interval between drug administration and sonography, sonography examination time and estimated radioactivity at sonography contributed to the increased dose to breast sonographers. Although we considered that the exposure dose of sonographers would not possibly exceed the dose limit in the present study, we suggested that radiological technologists need to educate the physicians requesting sonography, and the sonographers about the radiation exposure in nuclear medicine.
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Aim: Pelvic ring fractures (PRFs) due to high-energy trauma often result in severe bleeding and high mortality. Pelvic circumferential compression devices (PCCD) are widely used to stabilize PRF and decrease bleeding. However, evidence supporting their effectiveness is still inconclusive. Methods: We conducted an observational study using the Japan Trauma Data Bank (JTDB) from 2019 to 2021. Patients with blunt lower body trauma aged 15 years or older were included. We used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) to evaluate the association of PCCD and mortality. Results: Of the 74,393 patients in the database, 235 PCCD group and 23,429 control group were analyzed. After PSM, 231 patients in both groups were enrolled. Crude analysis indicated significantly higher in-hospital mortality in the PCCD group (odds ratio (OR) = 3.8 [95% CI = 2.51-5.75]). However, PSM and IPTW analysis indicated that PCCD was associated with decreased in-hospital mortality (PSM: OR = 0.79 [0.43-1.42]; IPTW: OR = 0.73 [0.62-0.86]). In a subgroup analysis of the IPTW analysis, PCCD fitting resulted in increased in-hospital mortality in the group without PRF (OR = 2.08 [1.91-2.27]), a decrease in stable PRF (OR = 0.74 [0.6-0.91]), and a further decrease in unstable PRF (OR = 0.18 [0.12-0.27]). Additional factors, such as a fall from a height, a fall downstairs, and pre-hospital PCCD placement also influenced the treatment effect. Conclusion: The present, large, registry-based study found that PCCD reduced mortality in patients with a lower body injury, especially those with an unstable PRF.
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Assembly of coordination networks from Cd(II) and a multi-interactive hexaazaphenalene-based ligand was successfully modulated using magnetic fields and thermodynamic control. A relatively weak field of only 320 mT was able to perturb the orientational distribution of the ligand in solution nudging the reaction down a different path. The underlying mechanism involved alignment of the ligands along the field lines, which was supported by DFT calculations. This crystallization technique could be extended to the synthesis of other networks and facilitate a deeper exploration of the reaction landscapes.
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The BIS value may decrease by cerebral hypoperfusion. We report a case in which the BIS value suddenly decreased during cervical spine surgery, which led us to find cervical screws compressing the vertebral arteries. In a 79-year-old man undergoing cervical spine surgery, the BIS suddenly decreased from about 40 to 10-20, about 4 h after the start of surgery. Intraoperative 3-dementional computed tomography indicated that both the two tips of cervical screws inserted in the 6th cervical vertebra were within bilateral transverse foramens. These cervical screws were removed, and the BIS increased immediately. The cervical screws were re-inserted again thorough the same vertebra into the bilateral transverse foramens, and the BIS decreased immediately. Postoperatively, cerebral hypoperfusion due to compression of bilateral vertebral arteries by two cervical screws was identified. The BIS may be a useful to detect cerebral hypoperfusion due to compression of the vertebral artery by a cervical screw.
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PURPOSE: To identify the countermeasures and current status of disaster power outages in the radiology departments of hospitals. METHODS: A web-based questionnaire survey of 600 hospitals nationwide was conducted. The questionnaire survey covered 34 items, including availability of power in the radiology department in the event of a disaster and the impact of power outages on medical equipment in the radiology department. RESULTS: In all, 242 facilities (40.3%) responded to our survey. During power outages, 55.8%-68.2% of facilities were able to use CT, digital radiography, and angiography systems with their private generators. In 28.1%-40.7% of facilities, medical information systems were not available in all laboratories. In addition, power outages caused equipment malfunctions in 81.4% of facilities' radiology departments. CONCLUSION: We have identified the power supplied by private generators to the radiology department's medical equipment and medical information systems. Many medical equipment have malfunctioned due to power outages. Therefore, drills should be conducted to simulate various situations caused by power outages.
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Serviço Hospitalar de Radiologia , Inquéritos e Questionários , Fontes de Energia Elétrica , Planejamento em Desastres , DesastresRESUMO
AIM: This study aimed to analyze two cases of marked hypo-high-density lipoprotein (HDL) cholesterolemia to identify mutations in ATP-binding cassette transporter A1 (ABCA1) and elucidate the molecular mechanism by which these novel pathological mutations contribute to hypo-HDL cholesterolemia in Tangier disease. METHODS: Wild type and mutant expression plasmids containing a FLAG tag inserted at the C-terminus of the human ABCA1 gene were generated and transfected into HEK293T cells. ABCA1 protein expression and cholesterol efflux were evaluated via Western blotting and efflux assay. The difference in the rate of change in protein expression was evaluated when proteolytic and protein-producing systems were inhibited. RESULTS: In case 1, a 20-year-old woman presented with a chief complaint of gait disturbance. Her HDL-C level was only 6.2 mg/dL. Tangier disease was suspected because of muscle weakness, decreased nerve conduction velocity, and splenomegaly. Whole-exome analysis showed compound heterozygosity for a W484* nonsense mutation and S1343I missense mutation, which confirmed Tangier disease. Cholesterol efflux decreased by a mixture of W484* and S1343I mutations. The S1343I mutation decreased the protein production rate but increased the degradation rate, decreasing the protein levels. This patient also had Krabbe disease. The endogenous ABCA1 protein level of macrophage cell decreased by knocking down its internal galactocerebrosidase.Case 2, a 51-year-old woman who underwent tonsillectomy presented with peripheral neuropathy, corneal opacity, and HDL-C of 3.4 mg/dL. Whole-exome analysis revealed compound heterozygosity for R579* and R1572* nonsense mutations, which confirmed Tangier disease. CONCLUSION: Case 1 is a new ABCA1 mutation with complex pathogenicity, namely, a W484*/S1343I compound heterozygote with marked hypo-HDL cholesterolemia. Analyses of the compound heterozygous mutations indicated that decreases in ABCA1 protein levels and cholesterol efflux activity caused by the novel S1343I mutation combined with loss of W484* protein activity could lead to marked hypo-HDL cholesterolemia. Galactocerebrosidase dysfunction could also be a potential confounding factor for ABCA1 protein function.
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Various miniature Clark-type oxygen electrodes (COEs), which are typically used to measure dissolved oxygen (DO) concentration in cellular respiration, have been developed since the 1980s. Arrays with individually addressable electrodes that constitute the sensor were used for various applications. However, the large number of leads and contact pads required for connecting the electrodes and the external instrument complicate the electrode layout and make the operation of integrated COE arrays challenging. Here, we fabricated closed bipolar electrochemical systems comprising 6 × 8 and 4 × 4 arrays of COEs for imaging and multiplexed detection. The cathodic compartment was sealed with a hydrophobic oxygen-permeable membrane to separate the internal electrolyte solution from the sample solutions. Using the bipolar Clark-type oxygen electrode (BCOE) arrays and electrochemiluminescence (ECL), we measured the DO concentration at each cathode. The results revealed that the ECL intensity changed linearly with the DO concentration. In addition, we used ECL imaging to investigate the respiratory activity of Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) in suspensions with different cell densities. The ECL images showed that the ECL intensity changed noticeably with the bacterial density. The bacterial respiratory activity was then qualitatively analyzed based on the ECL images acquired successively over a time duration. Further, we measured the antibiotic efficacy of piperacillin, oxacillin, gentamicin, and cefmetazole against E. coli and P. aeruginosa using the BCOE. We found that the ECL intensity increased with the antibiotic concentration, thus indicating the suppression of the bacterial respiratory activity.
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The addition of surface acoustic wave (SAW) technologies to microfluidics has greatly advanced lab-on-a-chip applications due to their unique and powerful attributes, including high-precision manipulation, versatility, integrability, biocompatibility, contactless nature, and rapid actuation. However, the development of SAW microfluidic devices is limited by complex and time-consuming micro/nanofabrication techniques and access to cleanroom facilities for multistep photolithography and vacuum-based processing. To simplify the fabrication of SAW microfluidic devices with customizable dimensions and functions, we utilized the additive manufacturing technique of aerosol jet printing. We successfully fabricated customized SAW microfluidic devices of varying materials, including silver nanowires, graphene, and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). To characterize and compare the acoustic actuation performance of these aerosol jet printed SAW microfluidic devices with their cleanroom-fabricated counterparts, the wave displacements and resonant frequencies of the different fabricated devices were directly measured through scanning laser Doppler vibrometry. Finally, to exhibit the capability of the aerosol jet printed devices for lab-on-a-chip applications, we successfully conducted acoustic streaming and particle concentration experiments. Overall, we demonstrated a novel solution-based, direct-write, single-step, cleanroom-free additive manufacturing technique to rapidly develop SAW microfluidic devices that shows viability for applications in the fields of biology, chemistry, engineering, and medicine.
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Epithelial cells serve as a barrier by tightly adhering to each other and contribute to the homeostasis of living organisms by controlling substance permeation. Therefore, evaluation of the barrier function is important in pharmaceutical development processes. However, the widely used Transwell-based assays require the development of the defect-free epithelial cell monolayer above several tens of mm2, often resulting in low reproducibility and requiring a long incubation time. In addition, the culture surface of cells is far from the bottom of the well plate, making it difficult to observe the cell morphology using an optical microscope. Herein, we propose simple polydimethylsiloxane microfluidic devices for evaluating the barrier function of an epithelial monolayer using a microchamber array. After the formation of the epithelial monolayer over microchambers, the permeation of the marker molecules introduced above resulted in increased fluorescence intensity in microchambers, which was monitored using confocal laser scanning microscopy. We show that using this technique, alteration of the paracellular permeability induced by sodium caprate (C10) and cytochalasin-D, permeation enhancing factors, can be elucidated. Furthermore, by tilting the microchamber device 90 degrees, the vertical cell section and microchambers were imaged in the same focal plane, allowing for live visualization of the passage of fluorescent substances across the cell monolayer. This technique is expected to be useful for investigating the relationship between paracellular permeability and cell morphology, which is unattainable through conventional methods.
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Células Epiteliais , Reprodutibilidade dos Testes , Células Epiteliais/metabolismo , PermeabilidadeRESUMO
OBJECTIVE: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. RESULTS: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. CONCLUSION: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset.
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Antirreumáticos , Artrite Reumatoide , Transtornos Linfoproliferativos , Metotrexato , Inibidores do Fator de Necrose Tumoral , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Transtornos Linfoproliferativos/induzido quimicamente , Masculino , Feminino , Pessoa de Meia-Idade , Metotrexato/uso terapêutico , Idoso , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Japão , Tacrolimo/uso terapêutico , Tacrolimo/efeitos adversos , Quimioterapia Combinada , Infecções por Vírus Epstein-Barr/complicações , AdultoRESUMO
To expand the range of practical applications of artificial cells, it is important to standardize the production process of giant (cell-sized) vesicles that encapsulate reconstituted biochemical reaction systems. For this purpose, a rapidly developing microfluidics-based giant vesicle generation system is a promising approach, similar to the droplet assay systems that are already widespread in the market. In this study, we examined the composition of the solutions used to generate vesicles encapsulating the in vitro transcription-translation (IVTT) system. We show that tuning of the lipid composition and adding poly(vinyl alcohol) to the outer solution improved the stability of the transition process into the lipid membrane so that protein synthesis proceeded in vesicles. The direct integration of α-hemolysin nanopores synthesized in situ was also demonstrated. These protein-synthesizing monodisperse giant vesicles can be prepared by using a simple microfluidic fabrication/operation with a commercial IVTT system.
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Células Artificiais , Microfluídica , Células Artificiais/química , Proteínas , LipídeosRESUMO
Vibration-induced flow (VIF), in which a mean flow is induced around a microstructure by applying periodic vibrations, is increasingly used as an active flow-control technique at the microscale. In this study, we have developed a microdevice that actively controls the VIF patterns using elastic membrane protrusions (microballoons) actuated by pneumatic pressure. This device enables on-demand spatial and temporal fluid manipulation using a single device that cannot be achieved using a conventional fixed-structure arrangement. We successfully demonstrated that the device achieved displacements of up to 38 µm using the device within a pressure range of 0 to 30 kPa, indicating the suitability of the device for microfluidic applications. Using this active microballoon array, we demonstrated that the device can actively manipulate the flow field and induce swirling flows. Furthermore, we achieved selective actuation of the microballoon using this system. By applying air pressure from a multi-input channel system through a connection tube, the microballoons corresponding to each air channel can be selectively actuated. This enabled precise control of the flow field and periodic switching of the flow patterns using a single chip. In summary, the proposed microdevice provides active control of VIF patterns and has potential applications in advanced microfluidics, such as fluid mixing and particle manipulation.
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Among various single-cell analysis platforms, hydrodynamic cell trapping systems remain relevant because of their versatility. Among those, deterministic hydrodynamic cell-trapping systems have received significant interest; however, their applications are limited because trapped cells are kept within the closed microchannel, thus prohibiting access to external cell-picking devices. In this study, we develop a hydrodynamic cell-trapping system in an open microfluidics architecture to allow external access to trapped cells. A technique to render only the inside of a polydimethylsiloxane (PDMS) microchannel hydrophilic is developed, which allows the precise confinement of spontaneous capillary flow in the open-type microchannel with a width on the order of several tens of micrometers. Efficient trapping of single beads and single cells is achieved, in which trapped cells can be retrieved via automated robotic pipetting. The present system can facilitate the development of new single-cell analytical systems by bridging between microfluidic devices and macro-scale apparatus used in conventional biology.
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Although ear canal electroencephalogram (EEG) recording has received interest from basic and applied research communities, evidence on how it can be implemented in practice is limited. The present study involving eight male participants including the authors presents the utility of our ear canal electrode and method by demonstrating both comparability of ear canal EEG to those at nearby sites and distinctiveness that ear canal event-related potentials (ERPs) could have. For this purpose, we used the balanced noncephalic electrode reference and an experimental paradigm with an error-feedback sound. Clear auditory ERPs were detected at the ear canal sites with a sufficiently low noise level comparable with those at conventional sites. The N1c, a temporal maximum subcomponent, spread over the bilateral temporal sites, including the ear canals and earlobes. While consecutive signals are generally highly similar between the ear canal and the earlobe, the N1c was larger at the ear canal than the earlobe, as demonstrated by the conventional frequentist and the hierarchical Bayesian modelling approaches. Although an evident caveat is that our sample was limited in terms of size and sex, the general capability indicates that the structure of our ear canal electrode provides EEG measurement that can be used in basic and applied settings. Our experimental method can also be an ERP-based test that conveniently assesses the capability of existing and future ear canal electrodes. The distinctive nature of the ERPs to the error-feedback sound may be utilized to examine the basic aspects of auditory ERPs and to test the processes involved in feedback-guided behaviour of participants.
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Meato Acústico Externo , Potenciais Evocados , Humanos , Masculino , Retroalimentação , Teorema de Bayes , EletrodosAssuntos
Divertículo , Ventilação Monopulmonar , Estenose Traqueal , Humanos , Ventilação Monopulmonar/métodos , Estenose Traqueal/complicações , Estenose Traqueal/diagnóstico por imagem , Brônquios/diagnóstico por imagem , Brônquios/cirurgia , Broncoscopia , Divertículo/complicações , Divertículo/diagnóstico por imagem , Divertículo/cirurgia , Intubação Intratraqueal/métodos , Respiração ArtificialRESUMO
Topological defects, the fundamental entities arising from symmetry-breaking, have captivated the attention of physicists, mathematicians, and materials scientists for decades. Here we propose and demonstrate a novel method for robust control of topological defects in a liquid crystal (LC), an ideal testbed for the investigation of topological defects. A liquid layer is introduced on the LC in microwells in a microfluidic device. The liquid/LC interface facilitates the control of the LC alignment thereby introducing different molecules in the liquid/LC phase. A topological defect is robustly formed in a microwell when the liquid/LC interface and the microwell surface impose planar and homeotropic alignment, respectively. We also demonstrate the formation/disappearance of topological defects by light illumination, realized by dissolving photo-responsive molecules in the LC. Our platform that facilitates the control of LC topological defects by the introduction of different molecules and external stimuli could have potential for sensor applications.
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The adaptive increase in insulin secretion in early stages of obesity serves as a safeguard mechanism to maintain glucose homeostasis that cannot be sustained, and the eventual decompensation of ß cells is a key event in the pathogenesis of diabetes. Here we describe a crucial system orchestrated by a transcriptional cofactor CtBP2. In cultured ß cells, insulin gene expression is coactivated by CtBP2. Global genomic mapping of CtBP2 binding sites identifies a key interaction between CtBP2 and NEUROD1 through which CtBP2 decompacts chromatin in the insulin gene promoter. CtBP2 expression is diminished in pancreatic islets in multiple mouse models of obesity, as well as human obesity. Pancreatic ß cell-specific CtBP2-deficient mice manifest glucose intolerance with impaired insulin secretion. Our transcriptome analysis highlights an essential role of CtBP2 in the maintenance of ß cell integrity. This system provides clues to the molecular basis in obesity and may be targetable to develop therapeutic approaches.
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Células Secretoras de Insulina , Ilhotas Pancreáticas , Obesidade , Animais , Humanos , Camundongos , Glucose/metabolismo , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Obesidade/metabolismoRESUMO
Krüppel-like transcription factors (Klfs), which are characterized by the three conserved C-terminal zinc fingers, are involved in various biological processes, such as haematopoiesis and angiogenesis. However, how the Klf family of transcription factors cooperate in organogenesis remains elusive. During zebrafish embryogenesis, both klf1 and klf17 are expressed in the intermediate cell mass (ICM), where primitive erythroid cells are produced. Using CRISPR-Cas9 genome editing technology, we established klf1-klf17 double mutant zebrafish to investigate the functionally interactive roles of the klf1 and klf17 genes. The klf1-klf17 mutant exhibited a diminished number of circulating primitive erythroid cells at 2 days postfertilization (dpf), while klf1 or klf17 single mutants and wild-type embryos produced comparable numbers of primitive erythroid cells. Circulating erythroid cells from the klf1-klf17 mutant possessed larger nuclei at 2 dpf than wild-type cells, suggesting the impairment of primitive erythroid cell maturation. The expression of the erythroid cell maturation markers band3 and mitoferrin, but not the haematopoietic progenitor markers c-myb and scl, was decreased in the klf1-klf17 mutant at 1 dpf. Thus, these results illustrate the cooperative function of klf1 and klf17 in the maturation processes of zebrafish primitive erythroid cells.
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Eritropoese , Peixe-Zebra , Animais , Desenvolvimento Embrionário , Eritropoese/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismoRESUMO
Maintenance of metabolic homeostasis is secured by metabolite-sensing systems, which can be overwhelmed by constant macronutrient surplus in obesity. Not only the uptake processes but also the consumption of energy substrates determine the cellular metabolic burden. We herein describe a novel transcriptional system in this context comprised of peroxisome proliferator-activated receptor alpha (PPARα), a master regulator for fatty acid oxidation, and C-terminal binding protein 2 (CtBP2), a metabolite-sensing transcriptional corepressor. CtBP2 interacts with PPARα to repress its activity, and the interaction is enhanced upon binding to malonyl-CoA, a metabolic intermediate increased in tissues in obesity and reported to suppress fatty acid oxidation through inhibition of carnitine palmitoyltransferase 1. In line with our preceding observations that CtBP2 adopts a monomeric configuration upon binding to acyl-CoAs, we determined that mutations in CtBP2 that shift the conformational equilibrium toward monomers increase the interaction between CtBP2 and PPARα. In contrast, metabolic manipulations that reduce malonyl-CoA decreased the formation of the CtBP2-PPARα complex. Consistent with these in vitro findings, we found that the CtBP2-PPARα interaction is accelerated in obese livers while genetic deletion of CtBP2 in the liver causes derepression of PPARα target genes. These findings support our model where CtBP2 exists primarily as a monomer in the metabolic milieu of obesity to repress PPARα, representing a liability in metabolic diseases that can be exploited to develop therapeutic approaches.