Development of an Immunochromatographic Assay Kit Using Fluorescent Silica Nanoparticles for Rapid Diagnosis of Acanthamoeba Keratitis

We developed an immunochromatographic assay kit that uses fluorescent silica nanoparticles bound to anti-Acanthamoeba antibodies (fluorescent immunochromatographic assay [FICGA]) and evaluated its efficacy for the detection of Acanthamoeba and diagnosis of Acanthamoeba keratitis (AK). The sensitivity of the FICGA kit was evaluated using samples of Acanthamoeba trophozoites and cysts diluted to various concentrations. A conventional immunochromatographic assay kit with latex labels (LICGA) was also evaluated to determine its sensitivity in detecting Acanthamoeba trophozoites. To check for cross-reactivity, the FICGA was performed by using samples of other common causative pathogens of infectious keratitis, such as Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans. Corneal scrapings from patients with suspected AK were tested with the FICGA kit to detect the presence of Acanthamoeba, and the results were compared with those of real-time PCR. The FICGA kit detected organisms at concentrations as low as 5 trophozoites or 40 cysts per sample. There were no cross-reactivities with other pathogens. The FICGA was approximately 20 times more sensitive than the LICGA for the detection of Acanthamoeba trophozoites. The FICGA kit yielded positive results for all 10 patients, which corresponded well with the real-time PCR results. The FICGA kit demonstrated high sensitivity for the detection of Acanthamoeba and may be useful for the diagnosis of AK.     

Effective high-dose chemotherapy combined with CD34+-selected peripheral blood stem cell transplantation in a patient with cutaneous involvement of nasal NK/T-cell lymphoma

The prognosis of nasal natural killer (NK)/T-cell lymphoma with cutaneous involvement especially is morbid despite intensive chemotherapy and radiotherapy. We treated a 52-yr-old Japanese woman with cutaneous dissemination of nasal NK/T-cell lymphoma. Six cycles of chemotherapy, irradiation to skin lesion were administered and complete remission (CR) was attained. High-dose chemotherapy (HDC; etoposide 750 mg/m(2) x 2 d, cyclophosphamide 60 mg/kg x 2 d, total body irradiation 12 Gy two daily fractions x 3 d) followed by CD34(+)-selected autologous peripheral blood stem cell transplantation (CD34(+)-APBSCT) was then prescribed. Complete remission (CR) was obtained and she has been free of disease for 34 months since CD34(+)-APBSCT. We suggest that marrow-ablative chemotherapy facilitated by autologous stem cell transplantation should be considered part of the primary therapy for subjects with a poor prognosis for nasal NK/T-cell lymphoma with cutaneous involvement.     

Interactions between lithium and renal transport of Krebs cycle intermediates.

The effect of lithium on the renal transport of Krebs cycle intermediates was studied in brush border membrane vesicles isolated from the rabbit renal cortex. The di- and tricarboxylic acids are avidly transported across renal brush border membranes by a sodium cotransport system. Lithium acted as a potent, specific, competitive inhibitor (Ki = 1.2 mM) of succinate/sodium cotransport when added to the uptake medium. Similar effects were observed for citrate but not D-glucose, L-phenylalanine, L-proline, L-alanine, or L-lactate transport. Intravesicular lithium behaved as a noncompetitive inhibitor of succinate transport in the absence of sodium. These results account for the observation that therapeutic doses of lithium increase the renal excretion of Krebs cycle intermediates. The existence of a transport system for alpha-ketoglutarate in synaptosomes suggests a possible target for lithium in the central nervous system.     

Insulinoma Masquerading as Rapid Eye Movement Sleep Behavior Disorder: Case Series and Literature Review

Insulinoma is a rare endocrine tumor that can cause a wide variety of symptoms, including abnormal nocturnal behavior. We report on 3 patients with insulinoma who presented with abnormal nocturnal behavior and injury during sleep, which simulated rapid eye movement (REM) sleep behavior disorder (RBD). In case 1, the fasting glucose level was 15 mg/dL, and insulin levels were elevated (15 μU/mL). In case 3, when the patient was transferred to the hospital because of a disturbance of consciousness, hypoglycemia (29 mg/dL) was detected. In contrast, in case 2, fasting glucose sampling did not indicate hypoglycemia, but continuous glucose monitoring revealed nocturnal hypoglycemia. The time from initial symptoms to a diagnosis of insulinoma ranged from 7 months to 2 years. All 3 patients had previously received anticonvulsant drugs for suspected epilepsy, but the medications were ineffective. Polysomnography showed no evidence of REM sleep without atonia in any of the 3 patients. No patient remembered any events that occurred during sleep. When a patient manifests abnormal behavior during the night and early morning, glucose monitoring should be performed, especially during the night and early morning. Clinicians should be aware that although insulinomas are rare, they can mimic parasomnias, such as RBD.     

Ultraflexible,large-area,physiological temperature sensors for multipoint measurements

We report a fabrication method for flexible and printable thermal sensors based on composites of semicrystalline acrylate polymers and graphite with a high sensitivity of 20 mK and a high-speed response time of less than 100 ms. These devices exhibit large resistance changes near body temperature under physiological conditions with high repeatability (1,800 times). Device performance is largely unaffected by bending to radii below 700 µm, which allows for conformal application to the surface of living tissue. The sensing temperature can be tuned between 25 °C and 50 °C, which covers all relevant physiological temperatures. Furthermore, we demonstrate flexible active-matrix thermal sensors which can resolve spatial temperature gradients over a large area. With this flexible ultrasensitive temperature sensor we succeeded in the in vivo measurement of cyclic temperatures changes of 0.1 °C in a rat lung during breathing, without interference from constant tissue motion. This result conclusively shows that the lung of a warm-blooded animal maintains surprising temperature stability despite the large difference between core temperature and inhaled air temperature.Temperature control plays a very important role in homeostasis, and body temperature varies both spatially and temporally in an effort to transfer heat between the living body and the environment via skin and respiratory organs. Accurate measurement of localized temperature changes in soft tissue regardless of large-scale motion is important in understanding thermal phenomena of homeostasis and realizing future sophisticated health diagnostics (1–3). Therefore, flexible temperature sensors which softly interface with tissue have been investigated frequently for applications in the medical field. However, these applications require the combination of sensitivity, fast response time, stability in physiological environments, and multipoint measurement. Before this work, to our knowledge, no experiment has simultaneously demonstrated orders-of-magnitude changes in electrical properties (sensitivity) repeatedly at varying physiological temperatures and conditions (stability) in a robust, easy-to-fabricate, flexible temperature sensor (processability).When sensors and electronics are directly attached to the surface of an animal body, the use of soft and flexible electronic devices is expected to reduce mechanical stress induced on the body. From this viewpoint, the field of flexible electronics has attracted much attention recently. The ability to gather information such as pressure and temperature from curvilinear and dynamic surfaces without impairing the movement or usability of the users is unmatched by conventional silicon electronics. There have been reports of the potential application of flexible electrodes on ultrathin substrates (4), flexible sensors that measure biological signals, electrocardiograms, temperature, pressure (5, 6), organic amplifier systems (7), high-sensitivity pressure sensors (8), and ultrathin and imperceptible devices (9, 10).To measure spatial and temporal temperature gradients of the body, multiple temperature sensors have to be attached on the freely curved surface of the body. One practical solution is to apply multiple discrete temperature sensors to the skin such as thermocouples (11), thermistors (12), or resistive temperature detectors (4, 6, 13) with individual wirings for data readout. Indeed, there are many excellent temperature sensors that exhibit fast response, mechanical flexibility, physiological stability, and/or high sensitivity (4, 6, 13). For example, the thermal sensors using metals as resistors exhibit the change of resistivity less than 1% for the thermal change of 5 °C (6, 13), which can be perfectly resolved by a high-precision electronic circuit. To realize scalable designs for multipoint measurements and/or to ensure sufficient accuracy of temperature measurement on dynamically moving objects due to strain-induced performance changes of sensors, however, it is important to significantly increase change of resistivity, ideally up to several orders-of-magnitude change. Although line-of-sight–based techniques including infrared thermographs and thermotropic liquid crystals (14) are capable of spatial temperature mapping, they require separation between the sensor and target object and, therefore, are unsuitable for implanted devices.Alternatively, positive temperature coefficient (PTC) polymers (15) have been used to fabricate mechanically flexible temperature sensors that exhibit orders-of-magnitude changes in resistivity over just a few degrees (16). Extraordinarily large resistivity changes can eliminate the need for per-pixel amplification circuitry, as the output signal of the sensor can be directly multiplexed and fed to external recording equipment, ultimately reducing device complexity and manufacturing costs. The PTC effect in conductive-filled polymers results from an increase in the specific volume as the temperature increases, typically during progression through the melting point of crystalline regions (17, 18). For this reason, resistivity is changed drastically by change in temperature for only a few degrees. However, very few polymer PTC materials with sensitivity near physiological temperatures have been demonstrated, and have yet to be fabricated in highly flexible geometries. Besides flexibility and multipoint measurement requirements, each sensor has to exhibit high sensitivity (<0.1 °C) near body temperatures, fast response time (less than 100 ms), and cyclic repeatability. This work demonstrates a highly tuned polymer composite that changes six orders of magnitude over less than 5 °C near body temperature with high cyclic stability. To the best of the authors’ knowledge, no other temperature sensors, either rigid or flexible, organic or inorganic, simultaneously exhibit these qualities—less than 0.1 °C sensitivity, cyclic stability near 37 °C, easily processable, with low-complexity readout circuitry. These properties will enable a wide range of medical and nonmedical devices. Competing inorganic devices require complex postamplification of low signals, which complicates readout and the device architecture. Specifically, the need for per-pixel amplification limits the proliferation of simple medical sensors that lend themselves to continued miniaturization, low power utilization, and wireless addressability. Competing organic devices suffer in terms of repeatability, commonly exhibiting less than 100 stable thermal cycles (16, 19, 20). This work presents an important step toward the realization of implantable and wearable devices that are sensitive, cyclically stable, and processable.     

Diagnostic accuracy of late iodine enhancement on cardiac computed tomography with a denoise filter for the evaluation of myocardial infarction

We evaluated the image quality and diagnostic performance of late iodine enhancement (LIE) in dual-source computed tomography (DSCT) with low kilo-voltage peak (kVp) images and a denoise filter for the detection of acute myocardial infarction (AMI) in comparison with late gadolinium enhancement (LGE) magnetic resonance imaging (MRI). The Hospital Ethics Committee approved the study protocol. Before discharge, 19 patients who received percutaneous coronary intervention after AMI underwent DSCT and 1.5 T MRI. Immediately after coronary computed tomography (CT) angiography, contrast medium was administered at a slow injection rate. LIE-CT scans were acquired via dual-energy CT and reconstructed as 100-, 140-kVp, and mixed images. An iterative three-dimensional edge-preserved smoothing filter was applied to the 100-kVp images to obtain denoised 100-kVp images. The mixed, 140-kVp, 100-kVp, and denoised 100-kVp images were assessed using contrast-to-noise ratio (CNR), and their diagnostic performance in comparison with MRI and infarcted volumes were evaluated. Three hundred four segments of 19 patients were evaluated. Fifty-three segments showed LGE in MRI. The median CNR of the mixed, 140-, 100-kVp and denoised 100-kVp images was 3.49, 1.21, 3.57, and 6.08, respectively. The median CNR was significantly higher in the denoised 100-kVp images than in the other three images (P < 0.05). The denoised 100-kVp images showed the highest diagnostic accuracy and sensitivity. The percentage of myocardium in the four CT image types was significantly correlated with the respective MRI findings. The use of a denoise filter with a low-kVp image can improve CNR, sensitivity, and accuracy in LIE-CT.