Establishment of an Adult Medaka Fatty Liver Model by Administration of a Gubra-Amylin-Nonalcoholic Steatohepatitis Diet Containing High Levels of Palmitic Acid and Fructose.

Among lifestyle-related diseases, fatty liver is the most common liver disease. To date, mammalian models have been used to develop methods for inhibiting fatty liver progression; however, new, more efficient models are expected. This study investigated the creation of a new model to produce fatty liver more efficiently than the high-fat diet medaka model that has been used to date. We compared the GAN (Gubra-Amylin nonalcoholic steatohepatitis) diet, which has been used in recent years to induce fatty liver in mice, and the high-fat diet (HFD). Following administration of the diets for three months, enlarged livers and pronounced fat accumulation was noted. The GAN group had large fat vacuoles and lesions, including ballooning, compared to the HFD group. The GAN group had a higher incidence of lesions. When fenofibrate was administered to the fatty liver model created via GAN administration and liver steatosis was assessed, a reduction in liver fat deposition was observed, and this model was shown to be useful in drug evaluations involving fatty liver. The medaka fatty liver model administered with GAN will be useful in future fatty liver research.

Development of a dynamic blood vessel phantom for evaluation of moving images.

In coronary angiography (CAG) and percutaneous coronary intervention (PCI), it is important for radiological technologists to optimize the balance between radiation dose and image quality for physicians to be able to perform CAG and PCI most effectively. Evaluation of image processing is necessary to ensure that technologists can optimally adjust image quality for clinical use to the extent that physicians require. However, few phantoms are available for evaluating fluoroscopic image processing, and this makes it necessary to adjust image quality in clinical settings while utilizing the image processing according to the manufacturer's recommendations. In this study, we developed a dynamic phantom that mimics a pulsating coronary artery for use in image quality analysis of moving images. We also examined whether processed images (image lag) can be physically analyzed. Two issues require special attention in creating a new phantom: establishing the exact position of the simulated blood vessel in the phantom, and providing good reproducibility. The study used the rotational motion of a disk to generate images, with a circular simulated blood vessel on the rotating acrylic disk, with the center of the simulated blood vessel shifted from the center of the acrylic disk. This enabled the reproduction of translational motion of the simulated blood vessel. As a result, because this phantom has signals and afterimages at the same position (of a simulated blood vessel), a quantitative evaluation of the afterimages became possible. In the evaluation of the image processing with the angiograph, it was shown that evaluations of image lag which are typically performed in clinical settings can be performed with the dynamic blood vessel phantom.

Two-dimensional beam-steering device using a doubly periodic Si photonic-crystal waveguide.

We demonstrate a nonmechanical, on-chip optical beam-steering device using a photonic-crystal waveguide with a doubly periodic structure that repeats the increase and decrease of the hole diameter. We fabricated the device using a complementary metal-oxide-semiconductor process. We obtained a beam-deflection angle of 24° in the longitudinal direction, while maintaining a divergence angle of 0.3°. Four such waveguides were integrated, and one was selected by a Mach-Zehnder optical switch. We obtained lateral beam steering by placing a cylindrical lens above these waveguides. By combining the lateral and longitudinal beam steering, we were able to scan the collimated beam in two dimensions, with 80 × 4 resolution points.

High-performance on-chip autocorrelator using a rib waveguide loaded with two-photon absorption diodes.

We report an on-chip autocorrelator comprising a Si rib waveguide and two-photon-absorption photodiodes in which two pulses simultaneously propagate in opposite directions, and their correlation is acquired. The rib waveguide's broadband guiding mode and moderately low group index allow the device to operate over a wide wavelength range with high resolution. We confirm that the waveguide has a transmission band of at least 1300-1630 nm and observed correlation waveforms for pulses of the order of several hundred femtoseconds to several picoseconds, with a range of at least the entire C band region.

Refractory hypotension due to Nivolumab-induced adrenal insufficiency.

Nivolumab, a new immune checkpoint inhibitor that has been found to improve outcomes for patients with some advanced cancers, is being increasingly used. Immune checkpoint inhibitors can cause immune-related adverse events, including dermatitis, enterocolitis, hepatitis and hypophysitis, but adrenal insufficiency rarely occurs. We present a case of Nivolumab-induced adrenal insufficiency in a man who complained of refractory hypotension. A 52-year-old man with non-small cell lung cancer visited our emergency department complaining of fatigue and diarrhea. He had received Nivolumab every 2 weeks as third-line therapy for a total of 10 times. On arrival, his vital signs revealed shock: blood pressure, 68/48 mmHg; heart rate, 141 beats per minutes. Laboratory examination showed severe hemoconcentration with a hemoglobin level of 19.9 g/dL, normal electrolyte levels and hyperglycemia. We started intravenous infusion of 4.5 L of extracellular fluid, but his vital signs remained unstable. After admission, endocrine examination revealed abnormally low values of serum cortisol (4.86 µg/dL) and ACTH (<1.0 pg/mL), which had been normal at 2 months before admission (21.14 µg/dL and 20.1 pg/mL, respectively). We therefore made a diagnosis of adrenal insufficiency induced by Nivolumab and administered 100 mg hydrocortisone succinate sodium intravenously. He recovered soon after hydrocortisone replacement therapy. Nivolumab is a new immune checkpoint inhibitor and general physicians are not familiar with it. However, adverse events caused by Nivolumab, especially adrenal insufficiency, can lead to serious adverse outcomes if overlooked. We should recognize Nivolumab-induced adrenal insufficiency and administer a glucocorticoid immediately in cancer patients treated with immune checkpoint inhibitors.

Full C-band Si photonic crystal waveguide modulator.

The slow-light effect in silicon lattice-shifted photonic crystal waveguide (LSPCW) Mach-Zehnder modulators allows compact phase shifters, while limiting the working spectrum Δλ. We optimized the structural parameters of the LSPCW and extended Δλ to cover the full C-band in exchange for moderately decreasing the group index ng. We obtained Δλ=42 nm with ng=8-9 in a fabricated device and observed 25 Gbps eye opening in the 200 µm modulator in the full C-band.

Optimized optical coupling to silica-clad photonic crystal waveguides.

Silica-clad silicon photonic crystal waveguides (PCWs) are promising components for various applications because of their simple fabrication and generation of slow light. However, an optical loss higher than 4 dB occurs when they are simply coupled to input/output silicon wire waveguides. To reduce the optical loss, we proposed a junction structure in which light in the waveguide is first coupled to a high-group-velocity radiation mode at an expanded core and subsequently converted to the slow-light mode in a tapered core of the PCW. The coupling loss at a junction is calculated to be 0.28 dB at its minimum and less than 0.5 dB for the wavelength range of 12 nm. We measured a coupling loss of 0.46 dB for the device fabricated by the silicon photonics process. This low-loss junction well supports the practical use of PCWs.

Fan-beam steering device using a photonic crystal slow-light waveguide with surface diffraction grating.

Compact non-mechanical beam steering devices are desired not only for current common applications, but also for advanced applications such as light detection and ranging. We use a Si photonic crystal slow-light waveguide with a diffraction grating, which radiates the guided mode to free space and steers a fan beam by sweeping the wavelength. Due to its large angular dispersion, slow light enhances the steering range without degrading the beam quality, resulting in more resolution points. We fabricated 600 µm devices and observed a 23° steering range and a beam divergence of 0.23°, which resulted in 100 resolution points.

Trousseau's syndrome: cancer-associated thrombosis.

Trousseau's syndrome (cancer-associated thrombosis) is the second leading cause of death in cancer patients, after death from cancer itself. The risk of a venous thromboembolism is 4- to 7-fold higher in patients with cancer than in those without cancer. The causes of this impaired coagulation are associated with general patient-related risk factors, and other factors that are specific to the particular cancer or treatment. It is important to assess the risk of thrombotic events in cancer patients and administer effective prophylaxis and treatment. Effective prophylaxis and treatment of venous thromboembolism reduces morbidity and mortality, and improves patients' quality of life. Low molecular weight heparin is the first-line treatment for venous thromboembolism, as an effective and safe means for prophylaxis and treatment, according to guidelines released by international scientific societies. Oral anticoagulation therapy with warfarin is preferable to no therapy. However, warfarin has low efficacy and is associated with high rates of recurrence. If low molecular weight heparin is unavailable, some guidelines recommend the use of vitamin K antagonists that have a target international normalized ratio in the range of 2-3, as acceptable alternatives. Novel oral anticoagulants that directly inhibit factor Xa or thrombin are promising for the prophylaxis of high-risk cancer patients and in the long-term treatment of venous thromboembolism. However, to date, there is insufficient evidence to support the use of these new anticoagulants.

Transformation to small-cell lung cancer as a mechanism of acquired resistance to crizotinib and alectinib.

A 56-year-old woman, a never-smoker, had postoperative recurrence of anaplastic lymphoma kinase rearranged lung cancer. She achieved a partial response to treatment with an anaplastic lymphoma kinase tyrosine kinase inhibitor, crizotinib. After the tumor regrowth, crizotinib was switched to alectinib; once again a partial response was observed. At the second recurrence, transbronchial needle aspiration of the right paratracheal node was performed, which revealed cytological findings of small-cell carcinoma. While treatment with cisplatin-irinotecan chemotherapy made reduction of some tumor shadows, including the biopsied mediastinal lymph nodes, new, small, nodular shadows, highly suggestive of pulmonary metastases, were detected in both lung fields. This case may show proof of the transformation to small-cell lung cancer as a mechanism of resistance to anaplastic lymphoma kinase tyrosine kinase inhibitors in anaplastic lymphoma kinase rearranged tumor. However, this transformation may also be only one part of the resistance mechanism of the heterogeneous tumor.

Evaluation of image lag in a flat-panel, detector-equipped cardiovascular X-ray machine using a newly developed dynamic phantom.

We developed a dynamic phantom for use in routine checks. This phantom can be used to physically evaluate image lag that occurs in dynamic images. It has a unique measurement method. ROIs on the target are chosen, and, with the position of ROIs fixed on the image, changes in pixel value are detected physically when the target passes through the ROIs over time and perceived as image lag. Thus, it was possible to physically detect different intensities of image lag lasting less than one second while maintaining the same intensity trends. The checking technique we propose with the dynamic phantom that we developed could be effective for routine checking of fluoroscopy X-ray machines, and could become an established method.

Response to regarding the case image article entitled "A case of angle-closure glaucoma caused by spontaneous lens dislocation" by Kondo et al.

The occurrence of acute angle closure with posterior displacement of the lens is rare compared with that of anterior dislocation; however, several studies have reported its occurrence.

Mechanochemistry enabling highly efficient Birch reduction using sodium lumps and d-(+)-glucose.

In this study, a mechanochemical protocol for highly efficient and ammonia-free sodium-based Birch reduction was developed, leveraging the use of cheap and easy-to-handle sodium lumps. The key to achieving this transformation is the use of d-(+)-glucose as a proton source, which solidifies the reaction mixture in bulk state, enhancing the efficiency of the in situ mechanical activation of sodium lumps through the ball-milling process. Under the developed conditions, a diverse array of aromatic and heteroaromatic compounds were selectively reduced to produce the corresponding 1,4-cyclohexadiene derivatives in high yields within 30 min. Notably, all synthetic operations can be carried out without inert gases or the need for dry or bulk organic solvents. Furthermore, a scaled-up synthesis can be conducted without any yield losses. These results suggest that the present mechanochemical approach offers a more convenient, economically attractive, and sustainable alternative to previously established Birch reduction protocols.

Effectiveness of antibiotic therapy for early recurrence of peritonsillar cellulitis and abscesses: A retrospective cohort study.

OBJECTIVE: Short-term recurrence is common in patients with peritonsillar cellulitis and abscesses, leading to socioeconomic problems. Early switching from intravenous to oral antibiotics is feasible for treating certain diseases. However, reports on early switching and total antibiotic administration duration in peritonsillar cellulitis and abscesses are limited. This study aimed to determine the appropriate antibiotic therapy duration and examine the impact of early oral switch therapy on peritonsillar cellulitis and abscesses. METHODS: We retrospectively identified 98,394 patients who received antibiotic therapy during hospitalization for peritonsillar cellulitis and abscesses between July 1, 2010, and December 31, 2019, using the Japanese Diagnosis Procedure Combination database. RESULTS: Propensity score matching analysis revealed no significant between-group difference in the rehospitalization rate (early oral switch therapy and long intravenous therapy: 1.7 % [198 of 11,621] vs. 2.0 % [234 of 11,621], odds ratio [OR] 0.84, 95 % confidence interval [CI] 0.70-1.02). A long total duration of antibiotic therapy (reference: 1-9 days) was associated with a low risk of rehospitalization (10-14 days: OR 0.86, 95 % CI 0.78-0.95; 15+ days: OR 0.51, 95 % CI 0.38-0.66). CONCLUSION: Early oral switch therapy may be a viable option for treating patients with peritonsillar cellulitis and abscesses in good condition who can tolerate oral intake. No less than 10 days of antibiotic therapy is desirable.

Otologic disease trends in Japan post-COVID-19 outbreak: A retrospective time-series analysis.

OBJECTIVE: To evaluate the potential impact of coronavirus disease 2019 (COVID-19) and vaccinations on otologic diseases, including facial nerve paralysis (including Ramsay Hunt syndrome), vestibular neuritis, sudden sensorineural hearing loss, and Meniere's disease. METHODS: In this retrospective study, we conducted a time-series analysis employing a causal impact algorithm on a large-scale inpatient database in Japan. We compared the actual number of hospitalized patients with otologic diseases to two predictions: one without any covariates and another with a covariate accounting for the reduction in the number of hospitalized patients due to lockdown measures. Additionally, we performed Granger causality tests to ensure the robustness of our findings. RESULTS: No significant increase was noted in the number of hospitalized patients with otologic diseases following the onset of the COVID-19 pandemic in the causal impact analysis. Similarly, no notable surge was observed in hospitalizations for these diseases following the introduction of the COVID-19 vaccine. The Granger causality tests results aligned with the causal impact analysis findings. CONCLUSION: Our findings indicate that COVID-19 and vaccinations had minimal discernible effects on hospitalization of patients with otologic diseases, suggesting that otologic diseases may not be significantly impacted by COVID-19 and vaccinations, which could have implications for public health policies and the allocation of healthcare resources during a pandemic. Further research and monitoring of long-term effects are warranted to validate these findings and guide healthcare decision-making.

Diagnostic performance of interferon-gamma release assays in elderly populations in comparison with younger populations.

An understanding of the diagnostic performance of interferon-gamma release assays (in terms of parameters such as specificity, positive predictive value, and likelihood ratio) is important in the diagnosis of active tuberculosis in elderly Japanese patients because the high proportion of a prior history of tuberculosis among these patients can lead to misleading results. To elucidate the diagnostic performance of such assays, we examined the results of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) in 65 patients in a younger group, and 52 patients in an elderly group who were suspected of having active tuberculosis and who had received the QFT-GIT. The median ages of the younger patients and elderly patients were 54 and 78 years, respectively. Among patients with active tuberculosis, the number of those with positive results on the QFT-GIT was similar in the two age groups [15 out of 17 (88.2 %) in the younger patients compared with 7 out of 8 (87.5 %) in the elderly patients]. However, in the patients with other diseases the number of those with positive QFT-GIT results was significantly different in the younger and elderly groups, being 6.3 and 27.3 %, respectively (P = 0.01). Although the sensitivity, negative predictive value, and negative likelihood ratio were similar in the two groups, the specificity, positive predictive value, and positive likelihood ratio were significantly lower in the elderly patients, being 72.7% (95 % confidence interval [CI], 57.2-85.0) compared with 93.8% (95 % CI, 82.8-98.7), 36.8% (95 % CI, 16.3-61.6) compared with 83.8% (95 % CI, 58.6-96.4), and 3.21 (95 % CI, 1.85-5.56) compared with 14.12 (95 % CI, 4.66-42.81), respectively. In the elderly patients with positive results on the test, a comparison of clinical data between those with active tuberculosis and those with other diseases demonstrated that the only clinical parameter showing a significant difference between these two groups was the radiological finding of small nodules in the patients with active tuberculosis (P < 0.01). The QFT-GIT may be less accurate in elderly patients, and radiological findings can be helpful in the clinical evaluation of patients with positive results on the test.

A Case of Pseudohyperaldosteronism Induced by Yokukansan and Shakuyakukanzoto That Resulted in Severe Hypokalemia.

Pseudohyperaldosteronism can be induced by the excessive use of Chinese herbal medicines (Kampo medicines), resulting in serious disorders. We report a case of pseudohyperaldosteronism induced by two Kampo medicines which resulted in severe hypokalemia. A 70-year-old woman was hospitalized for a left calcaneal fracture. She had no subjective symptoms other than trauma. On her admission, blood test results revealed a low serum potassium level of 2.4 mmol/L by chance, as well as low levels of both renin and aldosterone. The patient had been taking 5 g of Yokukansan per day for the past three months. In addition, she was on 5 g Shakuyakukanzoto per day for three months until a month prior to hospitalization. The daily licorice content from the aforementioned herbs was 1.0 g and 4.0 g, respectively. After hospitalization, the administration of the Kampo medicines was discontinued, and 610 mmol of potassium was administered over a period of 13 days, which resulted in the normalization of serum potassium levels. Pre-existing hypertension slowly improved as well. Patients consuming licorice at doses of 2.5 g per day or more, as in our case, are at a high risk of developing pseudohyperaldosteronism. Furthermore, the risk is particularly high with long-term licorice consumption as well as for women and elderly patients. To this end, high-dose potassium supplementation may be necessary for normalizing serum potassium levels. Therefore, awareness regarding the adverse effects of licorice is crucial, even in cases of low dosages of licorice.

Inclusion body myositis in an older patient following a fall.

After experiencing a fall, an 82-year-old woman developed progressive loss of lower limb strength and was diagnosed with inclusion body myositis. Although falls and muscle weakness are often regarded as consequences of aging, inclusion body myositis should be considered in a patient with a history of multiple falls.

Solid-state mechanochemical cross-coupling of insoluble substrates into insoluble products by removable solubilizing silyl groups: uniform synthesis of nonsubstituted linear oligothiophenes.

Conventional solution-based organic reactions that involve insoluble substrates are challenging and inefficient. Furthermore, even if the reaction is successful, the corresponding products are insoluble in most cases, making their isolation and subsequent transformations difficult. Hence, the conversion of insoluble compounds into insoluble products remains a challenge in practical synthetic chemistry. In this study, we showcase a potential solution to address these solubility issues by combining a mechanochemical cross-coupling approach with removable solubilizing silyl groups. Our strategy involves solid-state Suzuki-Miyaura cross-coupling reactions between organoboron nucleophiles bearing a silyl group with long alkyl chains and insoluble polyaromatic halides. The silyl group on the nucleophile can act as a solubilizing group that enables product isolation via silica gel column chromatography and can be easily removed by the addition of fluoride anions to form the desired insoluble coupling products with sufficient purity. Furthermore, we demonstrate that after aromatic electrophilic bromination of the desilylated products, sequential solid-state cross-coupling of the obtained insoluble brominated substrates, followed by desilylation, afforded further π-extended functional molecules. Using this conceptually new protocol, we achieved the first uniform synthesis of the longest nonsubstituted linear insoluble 9-mer oligothiophene.