Optical Biopsies Using Probe-Based Confocal Laser Endomicroscopy for Autoimmune Pulmonary Alveolar Proteinosis.

INTRODUCTION: Increasing numbers of cases of mild asymptomatic pulmonary alveolar proteinosis (PAP) are being reported with the recent increase in chest computed tomography (CT). Bronchoscopic diagnosis of mild PAP is challenging because of the patchy distribution of lesions, which makes it difficult to obtain sufficient biopsy samples. Additionally, the pathological findings of mild PAP, particularly those that differ from severe PAP, have not been fully elucidated. This study aimed to clarify the pathological findings of mild PAP and the usefulness of optical biopsy using probe-based confocal laser endomicroscopy (pCLE). METHODS: We performed bronchoscopic optical biopsy using pCLE and tissue biopsy in 5 consecutive patients with PAP (three with mild PAP and two with severe PAP). We compared the pCLE images of mild PAP with those of severe PAP by integrating clinical findings, tissue pathology, and chest CT images. RESULTS: pCLE images of PAP showed giant cells with strong fluorescence, amorphous substances, and thin alveolar walls. Images of affected lesions in mild PAP were equivalent to those obtained in arbitrary lung lesions in severe cases. All 3 patients with mild PAP spontaneously improved or remained stable after ≥3 years of follow-up. Serum autoantibodies to granulocyte-macrophage colony-stimulating factor were detected in all 5 cases. CONCLUSION: Optical biopsy using pCLE can yield specific diagnostic findings, even in patients with mild PAP. pCLE images of affected areas in mild and severe PAP showed similar findings, indicating that the dysfunction level of pathogenic alveolar macrophages in affected areas is similar between both disease intensities.

Effectiveness of remdesivir-based therapy for moderate COVID-19: comparison of Omicron and other variant phases.

Remdesivir is an antiviral drug for the treatment of coronavirus disease 2019 (COVID-19), and the sustained antiviral activity against Omicron variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been reported. In this single-center retrospective study, we first compared the clinical effectiveness of remdesivir-based therapy between Omicron and other variant phases of moderate COVID-19 in a real-world setting. Between Dec 2020 and July 2022, a total of 406 patients with COVID-19 pneumonia were treated with remdesivir-based therapy on admission. The oxygen deterioration rate after initiation of treatment significantly decreased in the Omicron variant phase compared to the alpha and delta variant phases. In an adjusted multivariate Cox proportional hazards model, Omicron variant phase was significantly associated with delayed oxygen deterioration and early recovery from hypoxia. These favorable outcomes during the Omicron variant phase, compared to previous variant phases, might be due to the attenuation and the popularization of vaccination.

Availability of Home sleep apnea test equipment LS-140 on a comparison with Polysomnography.

OBJECTIVE: The prevalence of obstructive sleep apnea (OSA) in Japan is 9% among males and 3% among females. Up to 2.5 million patients are estimated to suffer from the disease, but limited number of facilities are capable of carrying out polysomnography (PSG), leaving more than 80% of these individuals are undiagnosed. In recent years, the development of new portable sleep monitoring (PMs) devices has been remarkable. We evaluate the correlation between the results of the LS-140 PMs device (Fukuda Denshi Tech Co. Ltd.), released in 2017, and those of PSG. METHODS: We obtained contemporaneous data from the same patients by equipping 58 patients with PMs (LS-140) devices while they underwent PSG. Our primary outcome was Case 2 of the intraclass correlation coefficient (ICC), i.e., the ICC (2.1). And we used a Bland-Altman analysis to compare the apnea-hypopnea index (AHI) given by PSG and the respiratory event index (REI) given by LS-140 and examined the sensitivity and specificity of the REI relative to the AHI in the diagnosis of OSA. We also carried out the same comparison but in terms of the presence or absence of periodic limb movements (PLMs). RESULTS: The ICC (2.1) between The REI and the AHI was 0.944, a rather high value (p<0.0001). The mean difference between AHI and REI values was -3.6 (p<0.0001), indicating a negative fixed bias. Sensitivity may decrease in groups with PLMs. CONCLUSION: The REI and the AHI are highly correlated, giving LS-140 sufficient diagnostic sensitivity and specificity to screen for OSA.

Predictive risk factors for pneumothorax after transbronchial biopsy using endobronchial ultrasonography with a guide sheath.

BACKGROUND: Pneumothorax is one complication of transbronchial biopsy (TBB) using endobronchial ultrasonography with a guide sheath (EBUS-GS-TBB). We sought to clarify the risk factors for pneumothorax after EBUS-GS-TBB under fluoroscopic guidance. METHODS: We retrospectively reviewed data from 916 patients who underwent EBUS-GS-TBB at Fujita Health University Hospital. We evaluated the following risk factors for pneumothorax after EBUS-GS-TBB: patient characteristics (sex, age, and pulmonary comorbidities); lesion data (location, size, existence of ground-glass opacities [GGOs], pleural involvement, computed tomography [CT] bronchus sign, visibility on fluoroscopy, and EBUS findings); final diagnosis; years of bronchoscopist experience; and guide sheath size. Univariate and multivariate logistic regression analyses were performed. RESULTS: Among the 916 patients, 30 (3.28%) presented with pneumothorax. With a univariate analysis, factors that independently predisposed to pneumothorax included lesions containing GGOs, lesions in sagittal lung segments on fluoroscopy, lesions that were not visible on fluoroscopy, and infectious lesions. A univariate analysis also showed that lesions in the right upper lobe or left upper division, as well as malignant lesions, were less likely to lead to pneumothorax. Age, underlying pulmonary disease, CT bronchus sign, EBUS findings, bronchoscopist experience, and guide sheath size did not influence the incidence of pneumothorax. A multivariate analysis revealed that only lesions containing GGOs (odds ratio [OR] 6.47; 95% confidence interval [CI] 2.13-19.6, P = 0.001) and lesions in lung segments with a sagittal orientation on fluoroscopy (OR 2.47; 95% CI 1.09-5.58, P = 0.029) were significant risk factors for EBUS-GS-TBB-related pneumothorax. CONCLUSIONS: EBUS-GS-TBB of lesions containing GGOs or lesions located in sagittal lung segments on fluoroscopy correlate with a higher pneumothorax risk.

Chelated bis-N-heterocyclic carbene platinum and palladium units as tunable components of multinuclear complexes.

Heterometallic trinuclear M2M' complexes (M = Rh, Ir; M' = Pt, Pd) containing a platinum or palladium moiety with chelated bis-N-heterocyclic carbene ligands, [(MCp*)2{M'(bisNHC-Cn-R)}(µ3-S)2](BPh4)2 (M = Rh, Ir; M' = Pt, Pd; bisNHC-Cn-R = methylene-, ethylene-, or propylene-bridged bis(N-alkyl-imidazolylidene)), were synthesized by reacting bis(hydrosulfido)platinum(II) or palladium(II) complexs with bisNHC-Cn-R and hydroxo-bridged dinuclear complexes [(MCp*)2(µ-OH)3](BPh4), whose dinuclear structures remained intact during the formation of the trinuclear complexes, which was confirmed by using electrospray mass spectrometry and NMR spectroscopy. The heterometallic trinuclear M2M' complexes with a variety of alkylene bridges in bisNHC-Cn-R showed two reversible reduction waves in the cyclic voltammogram, and the second reduction potentials were affected by the alkylene chain lengths, which caused different dihedral angles between the imidazolylidene rings and the coordination plane of the platinum or palladium center. The M2M' complexes, except for those containing the platinum unit with the ethylene-bridged bisNHC ligands, showed dynamic behavior in solution due to the flapping wing motion of the NHC ligand moieties. Although activation parameters obtained from line-shape analyses on variable-temperature NMR spectra of the complexes suggested that the flapping wing motion occurred without bond cleavage, large negative ΔS(‡) values were obtained for the complexes with the palladium unit with the ethylene-bridged ligand, suggesting that the Pd-Ccarbene bond cleavage, accompanied by coordination of solvent molecules, occurred.

π-back-bonding interaction depending on the bridging chain lengths of chelated N-heterocyclic carbene platinum units in heterometallic trinuclear complexes affecting their electrochemical property.

Newly synthesized heterometallic trinuclear M2Pt complexes (M = Rh, Ir) containing a platinum moiety having a chelated bis-N-heterocyclic carbene (bisNHC) ligand with a variety of alkylene chain lengths of the bridging part showed two reversible reduction waves in cyclic voltammetry. Only the second reduction potentials were affected by the alkyl chain lengths, which afforded different dihedral angles between the imidazolylidene rings and the platinum coordination plane resulting in the variation of π-back-donation from the platinum center to the carbene carbon atoms.

Fixation and accumulation of thermotolerant catalytic competence of a pair of ligase ribozymes through complex formation and cross ligation.

In the early stages of the hypothetical RNA world, some primitive RNA catalysts (ribozymes) may have emerged through self-assembly of short RNA oligomers. Although they may be unstable against temperature fluctuations and other environmental changes, ligase ribozymes (ribozymes with RNA strand-joining activity) may resolve structural instability of self-assembling RNAs by converting them to the corresponding unimolecular formats. To investigate this possibility, we constructed a model system using a cross-ligation system composed of a pair of self-assembling ligase ribozymes. Their abilities to act as catalysts, substrates, and a cross-ligation system were analyzed with or without thermal pretreatment before the reactions. A pair of self-assembling ligase ribozymes, each of which can form multiple conformations, demonstrated that thermotolerance was acquired and accumulated through complex-formation that stabilized the active forms of the bimolecular ribozymes and also cross-ligation that produced the unimolecular ribozymes.

Sulfur containing platinum(II) complexes with N-heterocyclic carbene ligands obtained by reactions of a hydrosulfido complex.

A hydrosulfido platinum(ii) complex with a chelated N-heterocyclic carbene (NHC) ligand was oxidised with O(2) in the presence of excess hydrogen sulfide, to give a linear tetrasulfido complex, and without hydrogen sulfide, to give a thiosulfato-bridged dinuclear complex. The hydrosulfido complex also reacted with an acetato complex containing the chelating NHC platinum unit to afford a trinuclear platinum complex with two triply bridging sulfido ligands showing an equilibrium in solution between two isomers based on the arrangement of the chelating NHC ligands.

GNRA/receptor interacting modules: versatile modular units for natural and artificial RNA architectures.

Interactions between GNRA tetraloops and their receptors are found frequently as modular units in various types of naturally occurring structured RNAs. Due to their functional importance, GNRA/receptor interactions have been studied extensively with regard to their 3D structures and biochemical and biophysical properties. Artificial non-natural GNRA/receptor modules have also been generated not only to obtain a better understanding of this class of motifs in natural RNA structures but also for application of these modular units to the design and construction of artificial RNA structures that can be used as platforms to generate functional RNAs applicable for nanobiotechnology. In this review, we present a survey of structures, functions, and analyses as well as artificial generation and application of GNRA/receptor interacting modules.

Trans-acting RNAs as molecular probes for monitoring time-dependent structural change of an RNA complex adapting two structures.

As dynamic structural changes are pivotal for the functions of some classes of RNA molecule, it is important to develop methods to monitor structural changes in RNA in a time-dependent manner without chemical modification. Based on previous reports that trans-acting RNAs can be used as probes for analysis and control of 3D structures of target RNAs, we applied this method to monitor time-dependent structural changes in RNA. We designed and performed a proof-of-principle study using a simple model RNA complex that adopts two different structures as a target. The time-dependent structural changes in the target RNA were successfully monitored using two trans-acting RNAs, which stably form a ternary complex with the bimolecular target RNA and act as a catalyst to join two RNA fragments of the target complex, respectively.

Diurnal rhythms in fetal heart rate baseline and sustained fetal tachycardia in twin pregnancy.

OBJECTIVE: To elucidate the synchronization of phases of diurnal rhythms in fetal heart rate (FHR) baseline between twin fetuses and the occurrence of sustained fetal tachycardia. METHODS: FHR was simultaneously recorded in twins for 24 h in 7 monochorionic diamniotic (MD) and 8 dichorionic diamniotic (DD) twin pregnancies at 35 to 38 weeks of gestation. The diurnal rhythms of the hourly mean FHR baseline were tested in each fetus, and the time of occurrence of sustained fetal tachycardia was compared between twins. The correlation coefficients and phase lags of diurnal rhythms between the hourly mean FHR baselines of twins were calculated in each case. RESULTS: There were significant diurnal rhythms in the hourly mean FHR baselines of all twin fetuses (p<0.01). The patterns of diurnal rhythms were similar for each pair of twins, with the exception of the periods of sustained fetal tachycardia. Sustained fetal tachycardia was not coincident between twins. Analysis in which the periods of sustained fetal tachycardia were excluded demonstrated a significant correlation between the hourly mean FHR baselines of twins in all cases (p<0.01). In the case of DD twins, the phase lag between twins was 0; however, phase lags were observed in 4 cases of MD twins. CONCLUSIONS: The results of this study revealed that the diurnal rhythms in the FHR baseline correlated well between twins, and that the occurrences of sustained fetal tachycardia were completely independent.