Pigmentation of soybean seed coats via a mutation that abolishes production of multiple-phased siRNAs of chalcone synthase genes.

Lack of pigmentation in seed coats of soybean is caused by natural RNA silencing of chalcone synthase (CHS) genes. This phenomenon is an evolutionary consequence of structural changes in DNA that resulted in the production of double-stranded RNAs (dsRNAs) that trigger RNA degradation. Here we determined that a mutant with pigmented seed coats derived from a cultivar that lacked the pigmentation had a deletion between DNA regions ICHS1 and a cytochrome P450 gene; the deletion included GmIRCHS, a candidate gene that triggers CHS RNA silencing via production of CHS dsRNAs. We also characterized CHS short interfering RNAs (siRNAs) produced in the wild-type seed coats that had CHS RNA silencing. Phased 21-nt CHS siRNAs were detected in all 21 phases and were widely distributed in exon 2 of CHS7, which indicates commonality in the pattern of RNA degradation in natural CHS RNA silencing between distantly related species. These results with the similarities in the rearrangements found in spontaneous mutants suggest that the structural organization that generates dsRNAs that trigger phased siRNA production is vulnerable to further structural changes, which eventually abolish the induction of RNA silencing.

A nationwide survey of human metapneumovirus-associated encephalitis/encephalopathy in Japan.

BACKGROUND: As there have been no comprehensive reports of human metapneumovirus-associated encephalopathy (hMPVE), this study examined the clinical features of hMPVE in children in Japan. METHOD: A nationwide survey of children with hMPVE was conducted using a structured research form. An initial survey asked pediatricians about children with hMPVE treated between 2014 and 2018. A second survey obtained patient information from hospitals that responded to the initial survey and those identified as having treated cases from a literature search. We collected demographic data, symptoms of hMPV infection, neurological symptoms, laboratory data, treatment, and outcomes. Outcomes were determined using the Pediatric Cerebral Performance Category Score. RESULT: Clinical information was available for 16 children. Their median age was 37 months. Six had preexisting neurological disorders. The interval between the onsets of infection and hMPVE was 4 days. Outcomes were good in 11 patients and poor in 5. There were no significant differences in demographic data, neurological symptoms, or laboratory data between the patients with good and poor outcomes. The encephalopathy subtypes were acute encephalopathy with biphasic seizures and late reduced diffusion in 3, clinically mild encephalitis/encephalopathy with a reversible splenial lesion in 3, hemorrhagic shock and encephalopathy syndrome in 2, and others in 8. CONCLUSION: The outcomes of children with hMPVE were not very different from those of acute encephalopathy due to other viruses. We found no factors associated with poor outcomes.

Impact of the Coronavirus Disease 2019 Pandemic on the Clinical Features of Pediatric Respiratory Syncytial Virus Infection in Japan.

Background: Mitigation measures implemented during the coronavirus disease 2019 (COVID-19) pandemic remarkably reduced the incidence of infectious diseases among children. However, a re-emergence of respiratory syncytial virus (RSV) infection was observed in 2021 in Japan. We compared the clinical characteristics of hospitalized patients with RSV infection before and during COVID-19. Methods: We retrospectively enrolled children aged <6 years who were hospitalized with RSV infection in 18 hospitals and compared their clinical characteristics before (January 2019 to April 2020, 1675 patients) and during COVID-19 (September 2020 to December 2021, 1297 patients). Results: The mean age of patients with RSV infection was significantly higher during COVID-19 than before (17.4 vs 13.7 months, P < .001). Compared with before COVID-19, a 2.6-fold increase in RSV cases in the 2-5 years age group was observed from sentinel surveillance during COVID-19, whereas a 1.2-fold increase was noted in the same age group among hospitalized patients. On average for all patients, consolidation shadows obtained on radiography were less frequently observed (26.1 vs 29.6%, P = .04), and reduced respiratory assistance (42.2% vs 48.7%, P < .001) and hospitalization stay (5.7 vs 6.0 days, P < .001) was required in patients with RSV infection during COVID-19. Conclusions: Coronavirus disease 2019 and social activity restriction caused epidemiological changes in pediatric RSV infections, and a majority of patients with RSV infection aged ≥2 years did not develop severe symptoms requiring hospitalization. The RSV symptoms during the COVID-19 outbreak were equivalent to or milder than in the previous seasons.

A Case of Lymphomatoid Granulomatosis Presenting as a Cervical Mass.

An 89-year-old man presented with the chief complaint of a sore throat and a mass in the right side of his neck that tended to increase in size. He displayed the right Horner's sign, and imaging findings showed a 65-mm mass in the right side of the neck, invading the carotid artery. There were no other obvious lesions. The differential diagnosis was carcinoma of an unknown primary or neurogenic tumor. An incisional biopsy was performed, and the pathological diagnosis was lymphomatoid granulomatosis. The patient was started on oral prednisolone, but the disease progressed, and his general condition worsened. Therefore, supportive care was provided. This was a very rare case of a cervical lesion of lymphomatoid granulomatosis.

Stereoselective Synthesis of Ribofuranoid exo-Glycals by One-Pot Julia Olefination Using Ribofuranosyl Sulfones.

One-pot Julia olefination using ribofuranosyl sulfones is described. The α-anomers of the ribofuranosyl sulfones were synthesized with complete α-selectivity via the glycosylation of heteroarylthiols using ribofuranosyl iodides as glycosyl donors and the subsequent oxidation of the resulting heteroaryl 1-thioribofuranosides with magnesium monoperphthalate (MMPP). The Julia olefination of the α-ribofuranosyl sulfones with aldehydes proceeded smoothly in one pot to afford the thermodynamically less stable (E)-exo-glycals with modest-to-excellent stereoselectivity (up to E/Z = 94:6) under the optimized conditions. The E selectivity was especially high for aromatic aldehydes. In contrast, the (Z)-exo-glycal was obtained as the main product with low stereoselectivity when the corresponding ß-ribofuranosyl sulfone was used (E/Z = 41:59). The remarkable impact of the anomeric configuration of the ribofuranosyl sulfones on the stereoselectivity of the Julia olefination has been rationalized using density functional theory (DFT) calculations. The protected ribose moiety of the resulting exo-glycals induced completely α-selective cyclopropanation on the exocyclic carbon-carbon double bond via the Simmons-Smith-Furukawa reaction. The 2-cyanoethyl group was found to be useful for the protection of the exo-glycals, as it could be removed without affecting the exocyclic C═C bond.

In Silico Ocular Pharmacokinetic Modeling: Delivery of Topical FK962 to Retina.

PURPOSES: To establish the in silico ocular pharmacokinetic modeling for eye drops, and to simulate the dose regimen for FK962 in human choroid/retinal diseases. METHODS: Pharmacokinetics for FK962 in vivo was performed by a single instillation of drops containing 0.1% 14C-FK962 in rabbit eyes. Permeation of FK962 across the cornea, sclera, and choroid/retina was measured in vitro. Neurite elongation by FK962 was measured in cultured rat retinal ganglion cells. Parameters from the experimental data were used in an improved in silico model of ocular pharmacokinetics of FK962 in man. RESULTS: The mean concentration of FK962 in ocular tissues predicted by in silico modeling was consistent with in vivo results, validating the in silico model. FK962 rapidly penetrated into the anterior and posterior segments of the eye and then diffused into the vitreous body. The in silico pharmacokinetic modeling also predicted that a dose regimen of 0.0054% FK962 twice per day would produce biologically effective concentrations of FK962 in the choroid/retina, where FK962 facilitates rat neurite elongation. CONCLUSIONS: Our in silico model for ocular pharmacokinetics is useful (1) for predicting drug concentrations in specific ocular tissues after topical instillation, and (2) for suggesting the optimal dose regimens for eye drops. The pharmacodynamics for FK962 produced by this model may be useful for clinical trials against retinal neuropathy.

RNA silencing in the life cycle of soybean: multiple restriction systems and spatiotemporal variation associated with plant architecture.

The expression of transgenes introduced into a plant genome is sometimes suppressed by RNA silencing. Although local and systemic spread of RNA silencing have been studied, little is known about the mechanisms underlying spatial and temporal variation in transgene silencing between individual plants or between plants of different generations, which occurs seemingly stochastically. Here, we analyzed the occurrence, spread, and transmission of RNA silencing of the green fluorescent protein (GFP) gene over multiple generations of the progeny of a single soybean transformant. Observation of GFP fluorescence in entire plants of the T3-T5 generations indicated that the initiation and subsequent spread of GFP silencing varied between individuals, although this GFP silencing most frequently began in the primary leaves. In addition, GFP silencing could spread into the outer layer of seed coat tissues but was hardly detectable in the embryos. These results are consistent with the notion that transgene silencing involves its reset during reproductive phase, initiation after germination, and systemic spread in each generation. GFP silencing was absent in the pulvinus, suggesting that its cortical cells inhibit cell-to-cell spread or induction of RNA silencing. The extent of GFP silencing could differ between the stem and a petiole or between petiolules, which have limited vascular bundles connecting them and thus deter long-distant movement of silencing. Taken together, these observations indicate that the initiation and/or spread of RNA silencing depend on specific features of the architecture of the plant in addition to the mechanisms that can be conserved in higher plants.

Surgical treatment of substernal goiter: An analysis of 44 cases.

OBJECTIVE: Substernal goiters are classified as primary or secondary intrathoracic goiters. Here, we report the diagnosis, symptoms, treatment, and postoperative complications of 44 substernal goiters (2 primary mediastinal goiter and 42 secondary mediastinal goiters). METHODS: A retrospective chart review of 351 patients undergoing thyroidectomy at the Department of Otolaryngology-Head and Neck Surgery of the Tokyo Metropolitan Tama Medical Center. Between 2009 and 2015, 44 patients underwent surgery for substernal goiter. RESULTS: The frequency of primary and secondary mediastinal goiters was 0.5% and 11.9%, respectively. The preoperative symptoms were neck mass, dyspnea, and dysphagia. Eight patients were asymptomatic. Thirty-nine patients had benign masses and 5 patients had malignant masses. Most patients were operated on for adenomatous goiters (52.2%). In ten cases beyond the aortic arch, the tumors were benign and there were eight cases of adenomatous goiter. All patients underwent a successful transcervical incision without sternotomy. Even the primary intrathoracic goiters were extracted after total thyroidectomy via the cervical approach without complications. Although one case showed unilateral recurrent nerve paralysis as a postoperative complication, phonetic function improved in 6 postoperative months. No instances of postoperative bleeding or definitive hypoparathyroidism occurred, and tracheostomy was not performed in any of the cases. CONCLUSION: The cervical approach was safely performed in almost all substernal goiters without an extracervical procedure. Selected cases of primary mediastinal goiter may be excised via the cervical approach.

A clinical review of 38 cases of cervical tuberculous lymphadenitis in Japan - The role of neck dissection.

OBJECTIVES: After tuberculous pleurisy, lymphadenitis arising from cervical lesion is the second most common form of extrapulmonary tuberculosis. It is generally treated with antituberculosis agents, but some patients resist chemotherapy. In such cases, surgical resection is often considered as an alternative treatment. This study aims to evaluate the therapeutic outcome of cervical tuberculous lymphadenitis and the future course of treatment of this disease. METHODS: We retrospectively reviewed the clinical charts of patients diagnosed at the Tokyo Metropolitan Tama Medical Center between 2009 and 2015 and identified 38 cases of cervical tuberculous lymphadenitis. Precisely 798 patients were registered for primary tuberculosis at our institution during the same period. RESULTS: Patient ages ranged from 21 to 85 years (average: 58.9 years), and the male-to-female ratio was 1:1.2. The range of tuberculosis progression was as follows: 30 (78.9%) in only the cervical lymph node, 3 in the other (axillary, mediastinal, and abdominal) lymph nodes, 1 in the lung and vertebrae lumbales, 2 in the lung, and 1 in the pleural membrane. All 38 patients were initially treated with antituberculous drugs at the Department of Pulmonary Medicine based on guidelines for tuberculosis cases in Japan. In seven cases, the antituberculous drugs were replaced due to side effects. Four cases involved a single drug-resistant strain, and one case involved a double drug-resistant strain. Thirty-three (86.8%) cases were cured by chemotherapy alone. The three patients resistant to chemotherapy were successfully treated through neck dissection. Thirty-six cases (94.7%) were cured by chemotherapy or chemotherapy and surgery. CONCLUSION: Local therapy could prove effective in cervical tuberculous lymphadenitis patients who exhibit an inadequate response to drugs. The role of neck dissection in cervical tuberculous lymphadenitis remains an important consideration.

Infrared radiation has potential antidepressant and anxiolytic effects in animal model of depression and anxiety.

BACKGROUND: Bright light therapy has been shown to have antidepressant and anxiolytic effects in humans. OBJECTIVE: The antidepressant and anxiolytic effects of infrared radiation were evaluated using an experimental animal model. METHODS: Rats were randomly assigned to either an acutely or chronically exposed infrared radiation group or to a nonexposed control group. Acutely exposed rats were treated with an infrared radiation machine for one session, whereas chronically exposed animals were treated with an infrared radiation for 10 sessions. Control group rats were exposed to the sound of the infrared radiation machine as a sham treatment. After infrared radiation or control exposure, rats underwent behavioral evaluation, including elevated plus maze test, light/dark box, and forced swim test. RESULTS: Chronic infrared radiation exposure decreased indicators of depression- and anxiety-like behavior. No significant effect on general locomotor activity was observed. The number of BrdU-positive cells in CA1 of the hippocampus was significantly increased in both acutely and chronically exposed infrared radiation groups compared with the control group. CONCLUSIONS: These results indicate that chronic infrared radiation might produce antidepressant- and anxiolytic-like effects.

Contact urticaria caused by a fluorescent dye.

A 28-year-old man developed urticaria while he was working in the garage. We suspected contact urticaria, which can be caused by some products used in his field, and we carried out a prick test using his work gloves and shoes. His gloves were orange and black in colour, his shoes were black and white in colour, and the materials they were made of were unknown. The results of the prick test using the gloves and shoes were positive. Gas chromatography/mass spectrometry was applied, and a fluorescent dye was found to be present in his gloves and shoes. The results of a prick test using the fluorescent dye were positive. His urticaria improved after he stopped using these gloves and shoes. This was a rare case of contact urticaria caused by a fluorescent dye in clothing.