Novel Postoperative Hypofractionated Accelerated Radiation Dose-Painting Approach for Soft Tissue Sarcoma.

Purpose: Hypofractionated radiation therapy (RT) offers benefits in the treatment of soft tissue sarcomas (STS), including exploitation of the lower α/ß, patient convenience, and cost. This study evaluates the acute toxicity of a hypofractionated accelerated RT dose-painting (HARD) approach for postoperative treatment of STS. Methods and Materials: This is a retrospective review of 53 consecutive patients with STS who underwent resection followed by postoperative RT. Standard postoperative RT dosing for R0/R1/gross disease with sequential boost (50 Gy + 14/16/20 Gy in 32-35 fractions) were replaced with dose-painting, which adapts dose based on risk of disease burden, to 50.4 and 63, 64.4, 70 Gy in 28 fractions, respectively. The first 10 patients were replanned with a sequential boost RT approach and dosimetric indices were compared. Time-to-event outcomes, including local control, regional control, distant control, and overall survival, were estimated with Kaplan-Meier analysis. Results: Median follow-up was 25.2 months. Most patients had high-grade (59%) STS of the extremity (63%) who underwent resection with either R1 (40%) or close (36%) margins. Four patients experienced grade 3 acute dermatitis which resolved by the 3-month follow-up visit. The 2-year local control, regional control, distant control, and overall survival were 100%, 92%, 68%, and 86%, respectively. Compared with the sequential boost plan, HARD had a significantly lower field size (total V50 Gy; P = .002), bone V50 (P = .031), and maximum skin dose (P = .008). Overall treatment time was decreased by 4 to 7 fractions, which translated to a decrease in estimated average treatment cost of $3056 (range, $2651-$4335; P < .001). Conclusions: In addition to benefits in cost, convenience, and improved biologic effect in STS, HARD regimen offers a safe treatment approach with dosimetric advantages compared with conventional sequential boost, which may translate to improved long-term toxicity.

Carotid Web as an Embolic Source of Acute Ischemic Stroke.

INTRODUCTION: Carotid webs are shelf-like projections of the carotid bulb lumen associated with ipsilateral ischemic stroke in young patients. Given its rarity, a limited number of studies have evaluated the optimal management of symptomatic carotid webs to prevent further ischemic stroke. CASE REPORT: A 40-year-old Caucasian man presented with a sudden onset of left-sided facial droop, hemiparesis, and dysarthria. Computed tomography angiography revealed occlusion of the distal M1 and proximal M2 segments of the right middle cerebral artery and a small intimal flap at the right internal carotid artery origin. Intravenous alteplase was administered without clinical improvement. The patient underwent successful mechanical thrombectomy with complete revascularization of the middle cerebral artery and no residual neurologic deficits. Magnetic resonance angiography confirmed a curvilinear, shelf-like projection from the right carotid bulb posterior wall, consistent with a carotid web. The patient underwent carotid endarterectomy with no complications and was discharged home with no residual deficits or recurrence of stroke. CONCLUSION: No randomized, controlled prospective studies have compared the efficacy of endarterectomy to carotid artery stenting in patients with symptomatic carotid web. This case emphasizes the importance of considering carotid web as an embolic source of stroke in the young and provides support for revascularization as a safe and effective mean of secondary stroke prevention.

Effects of oyster aquaculture on carbon capture and removal in a tropical mangrove lagoon in southwestern Taiwan.

Blue carbon ecosystems (BCEs) are a promising resource for the mitigation of global warming; however, climate spectrums and anthropogenic activities could influence the fragile balance of BCEs as carbon sinks or sources. We assess how oyster farming affects dissolved inorganic carbon (DIC) and total alkalinity (TA) on CO2 fluxes in a mangrove-dominated lagoon. Water physical, chemical and biological parameters were recorded by in-situ buoys within the lagoon and at its inflow. Structural equation modeling was adopted to clarify the factors/processes controlling the partial pressure of CO2 (pCO2). A three-dimensional environmental model followed by a conceptual DIC model was used to quantify the spatiotemporal patterns of capture and release of DIC and TA by oyster production. The results showed that 49% of TA and DIC released from mangroves was depleted by oyster shell formation. DIC was reduced by algal photosynthesis and algal was served as a food source supporting oyster production. Annual oyster production through phytoplankton photosynthesis accounted for 11% of the atmosphere carbon inflows, suggesting that oyster production served as a significant atmospheric/terrestrial carbon sink in the lagoon. The results indicate that mangroves benefit local oyster production by acting as an important source of DIC and TA, and that the oyster aquaculture contributed to carbon capture in a mangrove-dominated lagoon ecosystem.

The presentation of brain metastases in melanoma, non-small cell lung cancer, and breast cancer and potential implications for screening brain MRIs.

PURPOSE: This study assessed the presentation and institutional outcomes treating brain metastases (BM) of breast cancer (BC), non-small cell lung cancer (NSCLC), and melanoma origin. METHODS: Patients with brain metastases treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan-Meier method. RESULTS: A total of 959 patients were identified including melanoma (31%), NSCLC (51%), and BC (18%). Patients with BC were younger at BM diagnosis (median age: 57) than NSCLC (65) and melanoma patients (62, p < 0.0001). Breast cancer patients were more likely to present with at least 5 BM (27%) than NSCLC (14%) and melanoma (13%), leptomeningeal disease (23%, 6%, and 6%, p = 0.0004) and receive whole brain radiation therapy (WBRT) (58%, 37%, and 22%, p < 0.0001). There were no differences in surgical resection (24%, 24%, and 29%, p = 0.166). Median OS was shorter for BC patients (9.9, 10.3, and 13.7 months, p = 0.0006). CONCLUSION: Breast cancer patients were more likely to be younger, present with advanced disease, require WBRT, and have poorer OS than NSCLC and melanoma patients. Further investigation is needed to determine which BC patients are at sufficient risk for brain MRI screening.

[Three cases of COVID-19 in elderly patients with delayed release from isolation due to persistent positive polymerase chain reaction findings].

The coronavirus disease 2019 (COVID-19) infection has spread worldwide, with no sign of its control in Japan yet. Eight elderly COVID-19 patients over 90 years of age were treated at our hospital. We herein report three cases with characteristic progression. Case 1 was a 91-year-old female patient diagnosed with bacterial pneumonia previously who did not show improvement with medication; thus, she was transferred to our hospital 16 days after the onset. She was diagnosed with COVID-19 using the SARS-CoV-2 polymerase chain reaction (PCR) test. Favipiravir, methylprednisolone, and unfractionated heparin were administered, but she only tested negative 68 days after the onset, at which point she was discharged. However, she was transferred back to our hospital 80 days after the onset since she tested positive again. She was transferred to another hospital 110 days after the onset without testing negative. Case 2 was a 102-year-old female. Despite being a mild case, it took 32 days to obtain negative PCR findings, leading to a decline in the activities of daily living. Case 3 was a 90-year-old male patient treated with favipiravir, dexamethasone, and unfractionated heparin, but his condition deteriorated. He never tested negative for PCR and ultimately died 20 days after the onset. Reports suggest that PCR positivity does not necessarily indicate infectivity, but there are no clear criteria for lifting a quarantine. Therefore, PCR negativity is often sought for "peace of mind." In the current situation where hospitals are fully occupied, clear criteria for lifting the quarantine should be promptly determined. After the completion of treatment, it is more important to monitor symptoms and take standard precautions, such as daily health monitoring, wearing a mask, and keeping an appropriate distance from others, than to obtain a negative PCR result.

Habitat suitability maps for juvenile tri-spine horseshoe crabs in Japanese intertidal zones: A model approach using unmanned aerial vehicles and the Structure from Motion technique.

The tri-spine horseshoe crab, Tachypleus tridentatus, is a threatened species that inhabits coastal areas from South to East Asia. A Conservation management system is urgently required for managing its nursery habitats, i.e., intertidal flats, especially in Japan. Habitat suitability maps are useful in drafting conservation plans; however, they have rarely been prepared for juvenile T. tridentatus. In this study, we examined the possibility of constructing robust habitat suitability models (HSMs) for juveniles based on topographical data acquired using unmanned aerial vehicles and the Structure from Motion (UAV-SfM) technique. The distribution data of the juveniles in the Tsuyazaki and Imazu intertidal flats from 2017 to 2019 were determined. The data were divided into a training dataset for HSM construction and three test datasets for model evaluation. High accuracy digital surface models were built for each region using the UAV-SfM technique. Normalized elevation was assessed by converting the topographical models that consider the tidal range in each region, and the slope was calculated based on these models. Using the training data, HSMs of the juveniles were constructed with normalized elevation and slope as the predictor variables. The HSMs were evaluated using the test data. The results showed that HSMs exhibited acceptable discrimination performance for each region. Habitat suitability maps were built for the juveniles in each region, and the suitable areas were estimated to be approximately 6.1 ha of the total 19.5 ha in Tuyazaki, and 3.7 ha of the total 7.9 ha area in Imazu. In conclusion, our findings support the usefulness of the UAV-SfM technique in constructing HSMs for juvenile T. tridentatus. The monitoring of suitable habitat areas for the juveniles using the UAV-SfM technique is expected to reduce survey costs, as it can be conducted with fewer investigators over vast intertidal zones within a short period of time.

Gallstone ileus with spontaneous evacuation: A case report.

A 65-year-old man was referred to our hospital for abdominal pain. He had a history of enterotomy with stone extraction for gallstone ileus. On abdominal computed tomography, a stone measuring 32 × 28 mm lodged in the jejunum was identified. He was diagnosed with gallstone ileus and treated using a nasal ileus tube. Four days after admission, computed tomography showed that the stone had passed into the rectum. The gallstone was spontaneously evacuated on the same day. A fistula with the gallbladder was found in the duodenal bulb. The patient's condition improved, and he was discharged 9 days after admission.

Time-lapse monitoring of TLR2 ligand internalization with newly developed fluorescent probes.

As a mammalian toll-like receptor family member protein, TLR2 recognizes lipoproteins from bacteria and modulates the immune response by inducing the expression of various cytokines. We have developed fluorescence-labeled TLR2 ligands with either hydrophilic or hydrophobic fluorescence groups. The labeled ligands maintained the inflammatory IL-6 induction activity and enabled us to observe the internalization and colocalization of the TLR2 ligands using live-cell imaging. The time-lapse monitoring in the live-cell imaging of the fluorescence-labeled TLR2 ligand showed that TLR2/CD14 expression in the host cells enhanced the internalization of TLR2 ligand molecules.

LC-MS-based quantification method for Achyranthes root saponins.

A liquid chromatography mass spectrometry (LC-MS) method was developed for simultaneous quantitative analysis of Achyranthes root saponins: chikusetsusaponins IVa (1) and V (2), achyranthosides B (3), C (4), D (5), E (6), and G (7), sulfachyranthosides B (8) and D (9), and betavulgarosides II (10) and IV (11). Satisfactory separation of the saponins was achieved with the use of a volatile ion-pair reagent (dihexyl ammonium acetate) on a phenyl-hexylated silica gel column, and the amounts of saponins extracted under three different conditions were determined. When Achyranthes root was extracted with water at room temperature, achyranthosides B (3) and D (5) were the major saponins, and smaller amounts of other saponins (4, 6-11) were present. However, the amounts of chikusetsusaponins (1 and 2) were negligible. Under the condition to make a standard decoction of a Kampo formula, the major saponins were achyranthosides B (3), C (4), and D (5), and small amounts of chikusetsusaponins IVa (1) and V (2) appeared, whereas prolonged heating largely increased the amounts of chikusetsusaponins. This method can be used for quality control of Achyranthes root.

Changes in cell size and number and in rhizodermal development contribute to root tip swelling of Hyoscyamus albus roots subjected to iron deficiency.

Root tip swelling is a common phenomenon observed when plant roots are subjected to Fe deficiency. We analysed whether an increase in cell number or an enlargement of cell width was involved in this phenomenon. Root tips of Hyoscyamus albus cultured with or without Fe were stained with fluorescent SYTO14 and analysed by confocal laser-scanning microscopy. Time-course and position-based examination revealed that the inhibition of longitudinal cell elongation and acceleration of transverse cell enlargement under Fe deficiency started from the tips and then extended towards the base during the time-course period. An increase in cell number also occurred behind the tips. In addition, the development of rhizodermal protrusions was observed on the surface of roots subjected to Fe deficiency. These results indicated that changes in cell size and number and in root hair development were all involved in root tip swelling.

Characteristics of pemetrexed transport by renal basolateral organic anion transporter hOAT3.

PURPOSE: Pemetrexed transport by human organic anion transporters, hOAT1 (SLC22A6) and hOAT3 (SLC22A8), were characterized in comparison with methotrexate. METHODS: Accumulation of pemetrexed and methotrexate in hOAT1- and hOAT3-expressing cells were evaluated. Pemetrexed and methotrexate were determined by HPLC. Kinetic parameters were calculated by Eadie-Hofstee plot. RESULTS: When HEK-hOAT3 and -hOAT1 cells were incubated with 100 µM pemetrexed for 30 min, pemetrexed was accumulated at 14- and 1.7-fold greater than that in control cells, respectively. Pemetrexed and methotrexate transport by hOAT3 was saturated at high concentrations with apparent Km values 28.2 µM and 76.6 µM, respectively. In addition, intrinsic activity (Vmax/Km) of pemetrexed and methotrexate transport by hOAT3 was 4.82 and 0.42 µl/min/mg protein, respectively, suggesting 11-fold higher transport of pemetrexed than methotrexate by hOAT3. Furthermore, loxoprofen, ibuprofen, pravastatin, and cefazolin, transport substrates of hOAT3, inhibited pemetrexed transport by hOAT3 with IC50 values, 34.2, 27.9, 76.3 and 650 µM, respectively. CONCLUSIONS: Pemetrexed is a superior substrate to methotrexate for hOAT3. Loxoprofen, ibuprofen, and cefazolin could cause drug-drug interactions when attaining high blood concentrations.

Mechanism of the regio- and diastereoselective ring expansion reaction using trimethylsilyldiazomethane.

An equatorial attack of TMS-diazomethane was determined to be the first step of the BF(3)-promoted ring expansion reaction of six-membered ketones using TMS-diazomethane. The migration reaction occurred in a conformation in which the carbonyl oxygen and the TMS group were antiperiplanar to predominantly afford trans-seven-membered ketones.

[Epidemiological analysis of Streptococcus pneumoniae in Gifu prefecture and the northern district of Aichi prefecture--2009].

High pathogenicity and drug resistance of Streptococcus pneumoniae are serious problem in clinical practice. Since 1999, we have conducted epidemiologic analyses of S. pneumoniae in Chubu district. We report the results of the analysis conducted in 2009. Three hundred and eight (308) S. pneumoniae isolates with a gene coding for autolysin lyt-A, which had been isolated from patients at 21 medical institutions in Gifu prefecture and the northern part of Aichi prefecture in 2009, were enrolled in this study. The strains were classified according to their drug resistance based on the presence of the pbp mutation, and examined for the presence of the two macrolide-resistance genes, ermB and mefA. Moreover, they were serotyped using type-specific antisera. The mean age of the patients from whom these S. pneumoniae strains were isolated, was 23.4 +/- 30.1 years old, and children aged 15 years old or less accounted for 66% of all the patients. Genotype penicillin-susceptible S. pneumoniae (gPSSP), genotype penicillin-intermediate S. pneumoniae (gPISP) and genotype penicillin-resistant S. pneumoniae (gPRSP) were 22 (7.1%), 131 (42.5%) and 155 (50.3%), respectively. The strains with mefA positive and ermB negative, mefA negative and ermB positive, and mefA positive and ermB positive were 80 (26.0%), 153 (49.7%), and 47 (15.3%), respectively. The MIC90 values of tebipenem (TBPM) and faropenem were 0.06 microg/mL and 0.5 microg/mL, respectively. TBPM showed the high bactericidal activity against gPRSP. In carbapenems, panipenem and biapenem exhibited higher bactericidal activities. Quinolone-resistant S. pneumoniae (QRSP) were isolated from 10 (3.2%). QRSP dominated 5 (7.9%) and 3 (1.5%) among the elderly (over 65 years old) and children, respectively. (As for the serotype, serotypes 6, 19 and 23 were 60 (19.5%), 62 (20.1%), and 44 (14.3%), respectively. Further epidemiologic studies on S. pneumoniae might be required also in the future, including the relationship between the serotype and drug resistance.

Cooperative regulation of vocal fold morphology and stress by the cricothyroid and thyroarytenoid muscles.

Voice is produced by vibrations of vocal folds that consist of multiple layers. The portion of the vocal fold tissue that vibrates varies depending primarily on laryngeal muscle activity. The effective depth of tissue vibration should significantly influence the vibrational behavior of the tissue and resulting voice quality. However, thus far, the effect of the activation of individual muscles on the effective depth is not well understood. In this study, a three-dimensional finite element analysis is performed to investigate the effect of the activation of two major laryngeal muscles, the cricothyroid (CT) and thyroarytenoid (TA) muscles, on vocal fold morphology and stress distribution in the tissue. Because structures that bear less stress can easily be deformed and involved in vibration, information on the morphology and stress distribution may provide a useful estimate of the effective depth. The results of the analyses indicate that the two muscles perform distinct roles, which allow cooperative control of the morphology and stress. When the CT muscle is activated, the tip region of the vocal folds becomes thinner and curves upward, resulting in the elevation of the stress magnitude all over the tissue to a certain degree that depends on the stiffness of each layer. On the other hand, the TA muscle acts to suppress the morphological change and controls the stress magnitude in a position-dependent manner. Thus, the present analyses demonstrate quantitative relationships between the two muscles in their cooperative regulation of vocal fold morphology and stress.

Aromatic compounds and their antioxidant activity of Acer saccharum.

A new lignan glycoside, 5-(3″,4″-dimethoxy-phenyl)-3-hydroxy-3-(4'-hydroxy-3'-methoxybenzyl)-4-hydroxymethyl-dihydrofuran-2-one 4'-O-α-L: -rhamnopyranoside (1), with seven known compounds, compound 2, koaburside, icariside E(4), cleomiscosin C, cleomiscosin D, scopoletin, and 5'-demethylaquillochin, were isolated from the EtOH extract of the wood of Acer saccharum (Aceraceae). Their structures were determined by 1D and 2D nuclear magnetic resonance (NMR) and mass spectroscopy analysis. All of the isolated compounds, 1-8, were tested for their antioxidant activity in superoxide dismutase (SOD)-like assay.