A Case of Superficial Primary Malignant Melanoma of the Esophagus Detected and Treated at Stage 0.

The patient was a 79-year-old male. At three years and eight months after his initial presentation, upper gastrointestinal endoscopy revealed a black-flattened elevated lesion in the middle third of the esophagus, which was diagnosed as malignant melanoma on biopsy. No lymph node or distant metastasis was found. A diagnosis of cT1bN0M0 Stage I was thus made. We performed a robot-assisted, minimally invasive esophagectomy and D2 dissection. The postoperative diagnosis was pT1a (MM), N0, M0, vascular invasion+, stage 0. The patient was recurrence-free for 14 months after surgery. We presume that an aggressive biopsy diagnosis is important for the early detection of malignant melanoma.

High-Field Nuclear Magnetic Resonance Studies Reveal New Structural Landscape of Sulfur-Vulcanized Natural Rubber.

Despite intensive research efforts over the past 3 decades, the structural analysis of sulfur-vulcanized natural rubber (NR) remains challenging owing to the complexity and low population of its sulfur moieties. Herein, solid vulcanized NR samples and NR samples reacted with sulfur and other reactants in an organic solvent were analyzed by solid-state NMR with fast magic-angle spinning and solution NMR, respectively. The present high-field two-dimensional NMR analysis revealed six novel sulfur moieties in these samples, including cyclic sulfides, cyclic di/polysulfides, and crosslinked structures with a vinylidene group. While previous studies reported a variety of sulfur-crosslinked structures in NR, our analysis identified only two dominant types of crosslinked structures that matched those reported previously. Our NMR assignments for the crosslinked structures were inconsistent to a large extent with those presented in the previous studies; thus, in the current work, the crosslinked structures were reassigned using the new data. Based on quantitative NMR analysis, this study also provides the first tangible evidence that cyclic rather than crosslinked sulfides can be the dominant sulfur moieties in vulcanized NR. These results may drastically alter the previously established structural landscape of sulfur-vulcanized NR.

Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunization Stress-Related Responses With COVID-19 mRNA Vaccine.

BACKGROUND: With the implementation of mass vaccination campaigns against COVID-19, the safety of vaccine needs to be evaluated. OBJECTIVE: We aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunization stress-related responses (ISRR) with the Moderna COVID-19 vaccine. METHODS: This nested case-control study included recipients who received the Moderna vaccine at a mass vaccination center, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1 case: 4 controls) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR. RESULTS: Of the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2478 recipients (cases 2) showed 318 events of IHSR and 2558 events of ISRR, respectively. The incidence rates per million doses were estimated as IHSR: 266 cases, ISRR: 2129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and a history of allergy; for ISRR, the risk factors were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex. CONCLUSION: In the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should be aware of the occurrence of ISRR. Although recipients with risk factors are associated with slightly increased risks of IHSR and ISRR, this is not of sufficient magnitude to warrant special measures regarding their vaccination.

Copper-Nanocoated Ultra-Small Cells in Grain Boundaries Inside an Extinct Vent Chimney.

Chemosynthetic organisms flourish around deep-sea hydrothermal vents where energy-rich fluids are emitted from metal sulfide chimneys. However, microbial life hosted in mineral assemblages in extinct chimneys lacking fluid venting remains largely unknown. The interior of extinct chimneys remains anoxic where the percolation of oxygenated seawater is limited within tightly packed metal sulfide grains. Given the scarcity of photosynthetic organics in deep seawater, anaerobic microbes might inhabit the grain boundaries energetically depending on substrates derived from rock-water interactions. In this study, we reported ultra-small cells directly visualized in grain boundaries of CuFeS2 inside an extinct metal sulfide chimney from the southern Mariana Trough. Nanoscale solid analyses reveal that ultra-small cells are coated with Cu2O nanocrystals in grain boundaries enriched with C, N, and P. In situ spectroscopic and spectrometric characterizations demonstrate the distribution of organics with amide groups and a large molecular organic compound in the grain boundaries. We inferred that the ultra-small cells are anaerobes because of the fast dissolution of Cu2O nanocrystals in oxygenated solution. This Cu2O property also excludes the possibility of microbial contamination from ambient seawater during sampling. It is shown by 16S rRNA gene sequence analysis that the chimney interior is dominated by Pacearchaeota known to have anaerobic metabolisms and ultra-small cells. Our results support the potential existence of photosynthesis-independent microbial ecosystems in grain boundaries in submarine metal sulfides deposits on the early Earth.

Video-based neonatal state assessment method for timing of procedures.

BACKGROUND: Procedures should be performed when an infant is most receptive to disruptions in order to reduce the stress on the infant. However, frequent direct observations place a heavy burden on medical staff. There is therefore a need for a method for quantitatively and automatically evaluating the neonatal state. METHODS: Ten infants in our hospital were enrolled in this study. The states of the infants were assessed by medical staff using the Brazelton Neonatal Behavioral Assessment Scale and were recorded on video at the same time. The recorded states were reclassified as activity levels, a new state classification method that includes middle activity, which is the appropriate time for a procedure. Using image analysis, motions of the infant were quantified as two indices: activity and pause time. Activity and pause time were compared for each activity level. The cutoff values of the indices were calculated, and the sensitivity and specificity of the middle activity were calculated. RESULTS: There was a significant difference between all groups of activity level (P < 0.01). The maximum sensitivity and specificity of middle activity were 71.7% and 51.2%, respectively. CONCLUSIONS: The neonatal state of infants can be quantitatively and automatically evaluated using video cameras, and the activity level can be used to determine an appropriate time for procedures in infants. This will reduce the burden on medical staff and lead to less stressful procedures for infants.

Discovery of fossil asteroidal ice in primitive meteorite Acfer 094.

Carbonaceous chondrites are meteorites believed to preserve our planet's source materials, but the precise nature of these materials still remains uncertain. To uncover pristine planetary materials, we performed synchrotron radiation-based x-ray computed nanotomography of a primitive carbonaceous chondrite, Acfer 094, and found ultraporous lithology (UPL) widely distributed in a fine-grained matrix. UPLs are porous aggregates of amorphous and crystalline silicates, Fe─Ni sulfides, and organics. The porous texture must have been formed by removal of ice previously filling pore spaces, suggesting that UPLs represent fossils of primordial ice. The ice-bearing UPLs formed through sintering of fluffy icy dust aggregates around the H2O snow line in the solar nebula and were incorporated into the Acfer 094 parent body, providing new insight into asteroid formation by dust agglomeration.

Cyanobacterial exopolymer properties differentiate microbial carbonate fabrics.

Although environmental changes and evolution of life are potentially recorded via microbial carbonates, including laminated stromatolites and clotted thrombolites, factors controlling their fabric are still a matter of controversy. Herein, we report that the exopolymer properties of different cyanobacterial taxa primarily control the microbial carbonates fabrics in modern examples. This study shows that the calcite encrustation of filamentous Phormidium sp. secreting acidic exopolymers forms the laminated fabric of stromatolites, whereas the encrustation of coccoid Coelosphaeriopsis sp. secreting acidic exopolymers and poor calcification of filamentous Leptolyngbya sp. secreting non-acidic exopolymers form peloids and fenestral structures, respectively, i.e. the clotted fabric of thrombolites. Based on these findings, we suggest that the rise and decline of cyanobacteria possessing different exopolymer properties caused the expansion of thrombolites around the Proterozoic/Cambrian boundary.

Genome-wide screening of transcription factor deletion targets in Escherichia coli for enhanced production of lactate-based polyesters.

Engineered Escherichia coli is a useful platform for production of lactate (LA)-based polyester poly[LA-co-3-hydroxybutyrate (3HB)] from renewable sugars. Here we screened all non-lethal transcription factor deletions of E. coli for efficient production of the polymer. This approach aimed at drawing out the latent potential of the host for efficient polymer production via indirect positive effects. Among 252 mutants from Keio Collection tested, eight mutants (ΔpdhR, ΔcspG, ΔyneJ, ΔchbR, ΔyiaU, ΔcreB, ΔygfI and ΔnanK) accumulated greater amount of polymer (6.2-10.1 g/L) compared to the parent strain E. coli BW25113 (5.1 g/L). The mutants increased polymer production per cell (1.1-1.5-fold) without significant change in cell density. The yield of the polymer from glucose was also higher for the selected mutants (0.34-0.38 g/g) than the parent strain (0.27 g/g). Therefore, the deletions of transcription factors should channel the carbon flux towards polymer production. It should be noted that the screening employed in this study identified beneficial mutants without analyzing causal relationship between the mutation and the enhanced polymer production. This approach, therefore, should be applicable to broad range of fermentation productions.

Indirect positive effects of a sigma factor RpoN deletion on the lactate-based polymer production in Escherichia coli.

The production of bacterial polyesters, polyhydroxyalkanoates (PHAs), has been improved by several rational approaches such as overexpression and/or engineering of the enzymes directly related to PHA biosynthetic pathways. In this study, a new approach at transcription level has been applied to a new category of the copolymer of lactate (LA) and 3-hydroxybutyrate (3HB), P(LA-co-3HB). When the 4 disrupting mutants of sigma factors in Escherichia coli, rpoN, rpoS, fliA, fecI, were used as platforms for production of P(LA-co-3HB), increases in the production level and LA fraction of the copolymer were observed for the mutant strain with rpoN disruption. These positive impacts on the polymer production were caused in an "indirect manner" via changes in the multiple genes governed by RpoN. A genome-wide engineering by sigma factors would be a versatile approach for the production of value-added products of interest and available for combination with the other beneficial tools.

Enhanced cellular content and lactate fraction of the poly(lactate-co-3-hydroxybutyrate) polyester produced in recombinant Escherichia coli by the deletion of σ factor RpoN.

A new approach at the transcriptional level was applied to lactate-based polyester production. Four σ factor disruptants, ΔrpoN, ΔrpoS, ΔfliA and ΔfecI, of Escherichia coli were used as hosts for poly(lactate-co-3-hydroxybutyrate) production from glucose. Among them, ΔrpoN caused dual positive effects of polymer production, enhanced cellular content and lactate fraction.

Evaluation of inner retinal thickness around the optic disc using optical coherence tomography of a rodent model of nonarteritic ischemic optic neuropathy.

PURPOSE: To clarify the usefulness of optical coherence tomography (OCT) for the objective and quantitative evaluation of retinal nerve fiber layer (RNFL) thickness around the optic disc in a rodent model of nonarteritic ischemic optic neuropathy (rNAION). METHODS: Inner retinal thickness was measured using OCT before and after rNAION induction. The thicknesses of the RNFL and the inner plexiform layer (IPL) were measured using a histologic preparation before and 56 days after induction. We compared the inner retinal thickness measured by OCT with that measured by the histologic preparation. RESULTS: The mean inner retinal thickness around the optic disc of normal rats measured using OCT was similar to that measured using a histologic preparation (73.50 ± 4.94 vs. 75.94 ± 5.90 µm). The mean inner retinal thickness of rNAION significantly increased until the 7th day, returned to baseline on the 14th day, and decreased until the 90th day after induction. On the 56th day after rNAION induction, histologic measurements indicated that the mean RNFL thickness had decreased but that the IPL thickness was similar to that at baseline. CONCLUSION: The mean inner retinal thickness measured by OCT correlated with the RNFL thickness of rNAION. OCT is useful for the objective and quantitative evaluation of RNFL thickness around the optic disc in a model of rNAION.

Rodent model of nonarteritic ischemic optic neuropathy and its electrophysiological evaluation.

PURPOSE: Our aim was to establish a rodent model of nonarteritic ischemic optic neuropathy (rNAION). METHODS: To induce rNAION, after administration of Rose Bengal (RB) (2.5 mM), the small vessels of the left optic nerve were photoactivated using a 514-nm argon green laser with about 500-µm spot size for 12 s (RB-laser induction). To evaluate the induction, funduscopic examination, fluorescein angiography (FA), visualization of capillaries within the optic disc, histologic evaluation, and electrophysiological testing were performed. RESULTS: In the RB-laser-induction eyes, the optic disc became swollen on day 3 followed by atrophy on week 8. FA showed filling defects in the choroid and optic disc at an early stage, followed by hyperfluorescence at a late stage. The capillaries within the optic disc were reduced markedly. Histopathologic examination showed acellular nerve fiber layer (NFL) swelling anterior to the optic disc. The morphologic retinal changes were apparent only in the retinal ganglion cell (RGC) layer, with a reduction in the number of cells. Visually evoked potential (VEP) amplitude decreased significantly, but electroretinography (ERG) showed no significant difference. The positive scotopic threshold response (pSTR) was not reduced on the 1st day but was significantly reduced 3 days after induction. CONCLUSIONS: The findings are similar to human NAION. Therefore, RB-laser induction is well suited to establish the presence of rNAION.