COVID-19-associated pulmonary aspergillosis in a Japanese man: A case report.

CAPA (COVID-19 associated pulmonary aspergillosis) is an important complication of COVID-19. It has been reported that the incidence of CAPA is as high as 19%-33% worldwide. However, its onset has not been reported in Japan. A 72-year-old Japanese man was diagnosed with COVID-19 and was transferred to our hospital due to deterioration of respiratory condition. Treatment with remdesivir, dexamethasone (DEXA), and antibiotics was performed under mechanical ventilation. Although the condition improved temporarily, a new shadow appeared in the lung, and Aspergillus fumigatus was cultured from sputum. The patient was clinically diagnosed with CAPA and treated with voriconazole. However, his progress deteriorated and he died. High-risk COVID-19 patients should be tested for Aspergillus to ensure early diagnosis of CAPA.

Simultaneous enzymatic saccharification and comminution for the valorization of lignocellulosic biomass toward natural products.

BACKGROUND: Large-scale processing of lignocellulosics for glucose production generally relies on high temperature and acidic or alkaline conditions. However, extreme conditions produce chemical contaminants that complicate downstream processing. A method that mainly rely on mechanical and enzymatic reaction completely averts such problem and generates unmodified lignin. Products from this process could find novel applications in the chemicals, feed and food industry. But a large-scale system suitable for this purpose is yet to be developed. In this study we applied simultaneous enzymatic saccharification and communition (SESC) for the pre-treatment of a representative lignocellulosic biomass, cedar softwood, under both laboratory and large-scale conditions. RESULTS: Laboratory-scale comminution achieved a maximum saccharification efficiency of 80% at the optimum pH of 6. It was possible to recycle the supernatant to concentrate the glucose without affecting the efficiency. During the direct alcohol fermentation of SESC slurry, a high yield of ethanol was attained. The mild reaction conditions prevented the generation of undesired chemical inhibitors. Large-scale SESC treatment using a commercial beads mill system achieved a saccharification efficiency of 60% at an energy consumption of 50 MJ/kg biomass. CONCLUSION: SESC is very promising for the mild and clean processing of lignocellulose to generate glucose and unmodified lignin in a large scale. Economic feasibility is highly dependent on its potential to generate high value natural products for energy, specialty chemicals, feed and food application.

Discovery of novel 5-hydroxy-4-pyridone-3-carboxy acids as potent inhibitors of influenza Cap-dependent endonuclease.

We report the discovery of a novel series of influenza Cap-dependent EndoNuclease (CEN) inhibitors based on the 4-pyridone-carboxylic acid (PYXA) scaffold, which were found from our chelate library. Our SAR research revealed the lipophilic domain to be the key to CEN inhibition. In particular, the position between the chelate and the lipophilic domain in the derivatives was essential for enhancing the potency. Our study, based on virtual modeling, led to the identification of 2y as a potent CEN inhibitor with an IC50 of 5.12nM.

A Multicenter, Randomized, Open-Label Trial: Efficacy of Once-Daily Versus Twice-Daily Double-Dose Rabeprazole on Refractory Gastroesophageal Reflux Disease-Related Symptoms and Quality of Life.

BACKGROUND: Approximately 20% to 40% of patients with gastroesophageal reflux disease (GERD) are refractory to standard-dose proton-pump inhibitor (PPI) treatment. OBJECTIVE: We compared the efficacy and quality-of-life effects of 20 mg once daily (QD) versus 10 mg twice daily (BID) rabeprazole (RPZ) in patients with refractory GERD-related symptoms and sleep disturbances. METHODS: This multicenter, prospective, randomized, open-label study included patients in whom PPI treatment >4 weeks was ineffective. According to the Global Overall Symptom (GOS) scale, PPI-refractory GERD was defined as ≥1 category with >3 points among 10 specific upper gastrointestinal symptoms. Seventy-eight patients were randomly assigned to 20 mg QD and 10 mg BID RPZ groups for 8 weeks. Efficacy was evaluated using self-reported questionnaires, including the GOS scale and Pittsburg Sleep Quality Index (PSQI), whereas quality of life was assessed using the Short-Form 8 Health Survey (SF-8), at 4 and 8 weeks. Patients showing improvement at 8 weeks received follow-up every 4 to 8 weeks. RESULTS: GOS scale scores were significantly improved at 8 weeks in both groups, with no significant intergroup differences. Although SF-8 scores showed an increasing trend over 8 weeks in both groups, the physical component summaries in the 10 mg BID group significantly improved. The mental component summaries clearly improved in the 10 mg BID group. Of the 74 cases (4 missing), 51 (68.9%) had PSQI scores ≥5.5. PSQI scores remained unchanged during follow-up in both groups. The recurrence rate was not significantly different (46.1% vs 47.1% in the 20 mg QD and 10 mg BID groups, respectively) during the follow-up period at median (interquartile range) 24.0 (30.5) months. CONCLUSIONS: In patients with refractory GERD, there was no significant difference in GOS scale score, PSQI, or recurrence rate between the groups. With regard to subscores of the SF-8, the 10 mg BID group might be potentially effective.

Preclinical antitumor activity of S-222611, an oral reversible tyrosine kinase inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2.

Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are validated molecular targets in cancer therapy. Dual blockade has been explored and one such agent, lapatinib, is in clinical practice but with modest activity. Through chemical screening, we discovered a novel EGFR and HER2 inhibitor, S-222611, that selectively inhibited both kinases with IC50 s below 10 nmol/L. S-222611 also inhibited intracellular kinase activity and the growth of EGFR-expressing and HER2-expressing cancer cells. In addition, S-222611 showed potent antitumor activity over lapatinib in a variety of xenograft models. In evaluations with two patient-oriented models, the intrafemoral implantation model and the intracranial implantation model, S-222611 exhibited excellent activity and could be effective against bone and brain metastasis. Compared to neratinib and afatinib, irreversible EGFR/HER2 inhibitors, S-222611 showed equivalent or slightly weaker antitumor activity but a safer profile. These results indicated that S-222611 is a potent EGFR and HER2 inhibitor with substantially better antitumor activity than lapatinib at clinically relevant doses. Considering the safer profile than for irreversible inhibitors, S-222611 could be an important option in future cancer therapy.

Factors associated with the outcome of patients with COVID-19 requiring mechanical ventilation: A single-center observational study in Japan.

Aim: Coronavirus disease (COVID-19) spread worldwide, and was declared as a pandemic by the World Health Organization. Despite numerous studies in the last few years, the factors associated with the outcomes of patients with COVID-19 requiring mechanical ventilation remain unclear. The prediction of ventilator weaning and mortality using the data obtained at the time of intubation could be beneficial for establishing appropriate treatment strategies and obtaining informed consent. In this study, we aimed to clarify the association between patient information at the time of intubation and the outcomes of intubated COVID-19 patients. Methods: This retrospective observational study used single-center data from patients with COVID-19. Patients with COVID-19 who were admitted to Osaka Metropolitan University Hospital from April 1, 2020, to March 31, 2022, and under mechanical ventilation were included. The main outcome was defined as the factors related to ventilator weaning; a multivariate analysis was carried out to evaluate the association between patient information at the time of intubation and the outcome. Results: In total, 146 patients were included in this study. The factors significantly associated with ventilator weaning were age (65-74 years old, adjusted odds ratio [OR], 0.168; 75 years and older, adjusted OR, 0.121), vaccination history (adjusted OR, 5.655), and Sequential Organ Failure Assessment (SOFA) respiration score (adjusted OR, 0.007) at the time of intubation. Conclusion: Age, SOFA respiration score, and COVID-19 vaccination history at the time of intubation could be associated with outcomes in patients with COVID-19 requiring mechanical ventilation.

Discovery of novel 5-alkynyl-4-anilinopyrimidines as potent, orally active dual inhibitors of EGFR and Her-2 tyrosine kinases.

5-Alkenyl or 5-alkynyl-4-anilinopyrimidines were prepared and evaluated for in vitro inhibition of EGFR/Her-2 kinase activity and the growth of tumor cell lines (BT474 and N87). Several of these compounds inhibited the growth of BT474 and N87 at concentrations below 200nM. Structure-activity relationship studies revealed a critical role for the 5-alkynyl moieties. The representative compound 19 exhibited significant antitumor potency in a mouse xenograft model.

Synthesis and evaluation of novel pyrimidine-based dual EGFR/Her-2 inhibitors.

A structure-activity relationship study of 4-anilinopyrimidines for dual EGFR/Her-2 inhibitor has resulted in the identification of 4-anilino-5-alkenyl or 5-alkynyl-6-methylpyrimidine derivatives that have exhibited effective inhibitory activity against both enzymes. The presence of 5-alkenyl or 5-alkynyl moiety bearing terminal hydrophilic group played important role for inhibition of these enzymes. Selected compounds in the series demonstrated some activity against Her-2 dependent cell line (BT474).

Discrepant Antigen-specific Antibody Responses Causing SARS-CoV-2 Persistence in a Patient Receiving B-cell-targeted Therapy with Rituximab.

A 73-year-old man previously treated with rituximab for his mucosa-associated lymphoid tissue lymphoma suffered a suboptimal humoral immune response against an acquired SARS-CoV-2 infection. A detailed serological description revealed discrepant antigen-specific humoral immune responses. The titer of spike-targeting, "viral-neutralizing" antibodies remained below the detection level, in contrast to the anti-nucleocapsid, "binding" antibody response, which was comparable in both magnitude and kinetics. Accordingly, viral neutralizability and clearance was delayed, leading to prolonged RNAemia and persistent pneumonia. The present case highlights the need to closely monitor this unique population of recipients of B-cell-targeted therapies for their neutralizing antibody responses against SARS-CoV-2.

Combined simultaneous enzymatic saccharification and comminution (SESC) and anaerobic digestion for sustainable biomethane generation from wood lignocellulose and the biochemical characterization of residual sludge solid.

Simultaneous enzymatic saccharification and comminution (SESC) was used for large-scale anaerobic digestion of wood lignocellulose to generate methane and unmodified lignin. During SESC, 10% aqueous mixture of powdered debarked wood from various species was subjected to bead milling with hydrolytic enzymes to generate particles below 1 µm. This slurry was directly used as a cosubstrate for anaerobic digestion in a 500 L stirred-tank reactor. Temperature and hydraulic retention time (HRT) were maintained at 50 °C and 30 days, respectively. At stable operation periods, an average yield of 224 L of methane per kg of cedar was attained. Comparable yields were achieved with red pine, elm, oak, and cedar bark. High-throughput microbial analysis established the presence of a relevant community to support the elevated level of methane production. The stability of the unmodified lignin in anaerobic digestion was also confirmed, allowing for its recovery as an important by-product.

Red LED Light Is Influenced by IL-6 to Promote the Migration Ability of Oral Squamous Cell Carcinoma Cell Line.

AIM: The purpose of this study was to search for the influence of red LED light of oral squamous cell carcinoma cells (OSCC) Material & Methods: HSC-3 was irradiated with red LED light (630 nm/3 J). Proliferative capacity was analyzed using WST-1. Transwell migration assay, real-time PCR, and ELISA method were also used to analyze migratory ability. CONCLUSIONS: HSC-3 cells irradiated with red LED light showed increased migration ability. Interestingly, we clarified that the expression of Interleukin-6 (IL-6), which promotes the migratory ability of cancer cells, is induced.

Clinical Evaluation of CO2 Laser Vaporization Therapy for Oral Lichen Planus: A Single-Arm Intervention Study.

Objective: The purpose of this study is to evaluate the efficacy of CO2 laser vaporization therapy for oral lichen planus (OLP) refractory to conservative treatments. Methods: The study group comprised 16 patients with clinically and histologically diagnosed OLP. They underwent conservative treatment for 3 months using an adrenal cortex hormone ointment and azulene sulfonate sodium hydrate gargle. Patients who showed no improvement with conservative treatment underwent CO2 laser vaporization therapy (3 W, continuous-wave mode). The assessment was performed using the numerical rating scale (NRS) as a subjective indicator and the Thongprasom sign score (TSS) as an objective indicator of OLP. These two scales were recorded during examinations performed before treatment and then at 7 days, 1, 3, and 6 months, and 1 year after irradiation. Differences between preirradiation and each point of time after irradiation were tested by Wilcoxon's signed-rank tests. Results: Laser irradiation was administered to 9 patients with 11 sites. The NRS score and TSS decreased at all 11 sites (100%) and 10 sites (90.9%) at 1 year after irradiation compared with preirradiation scores. The NRS score and TSS were statistically lower (p < 0.05) at 1 and 3 months (short-term) and 6 months and 1 year (mid-long-term) after irradiation than the preirradiation scores. There were no patients with malignant transformation during the study period. Conclusions: These single-arm clinical trial results show the efficacy of CO2 laser vaporization therapy for OLP refractory to conservative treatment.

Novel Catalysts for Methane Combustion Based on Cobalt-Doped Lanthanum Silicates Having an Apatite-type Structure.

Novel PdO/La10Si6-xCoxO27-δ/γ-Al2O3 catalysts with applications to methane combustion were developed. These materials were based on the use of La10Si6-xCoxO27-δ as a promoter because this compound has an oxide-ion conducting apatite-type structure that allows the smooth migration of active oxygen to the PdO activator. Co3+/2+ ions were also introduced into the original La10Si6O27 lattice to enhance its redox properties. Temperature-programmed reduction measurements revealed that the oxygen supply was facilitated by introducing Co3+/2+, where the reduction was observed at 290 °C for La10Si6-xCoxO27-δ (x = 1.0), whereas no reduction was observed below 460 °C for La10Si6O27. Among the samples synthesized in this work, PdO/La10Si6-xCoxO27-δ/γ-Al2O3 (x = 1.0) exhibited the highest catalytic activity, allowing the complete oxidation of methane at 310 °C, a temperature 80 °C lower than the 390 °C required when employing PdO/La10Si6O27/γ-Al2O3.

Clinical Study of Laser Treatment for Frenectomy of Pediatric Patients.

AIM: To suggest regarding the timing of oral surgery and laser treatment for frenulum abnormalities in the pediatric population. MATERIALS AND METHODS: We investigated the sex, age, frenulum site, reason for consultation, treatment method, and prognosis of 35 patients aged 15 years or younger and who were examined at our hospital for the chief complaint of frenulum abnormality. RESULTS: A total of 21 (mean age, 6.0 years) of the 35 patients underwent frenectomy using a carbon dioxide (CO2) laser. Of these, 7 patients (mean age, 2.8 years) underwent the procedure with general anesthesia and 14 patients (mean age, 7.6 years) underwent the procedure with local anesthesia. The surgical site was the lingual frenulum in 15 patients and the maxillary labial frenulum in 6 patients. No adverse events were intraoperatively reported in any of the patients, and the procedure was quickly and safely performed. The mean postoperative follow-up period was 4.6 months, and readhesion was noted in one patient (4.8%). The most common reason cited for not undergoing frenectomy in the 14 patients (mean age, 3.4 years) was the young age of the child. CONCLUSION: Retrospective study of pediatric patients with frenulum abnormalities demonstrated the usefulness of the CO2 laser in performing frenectomy and offered suggestions regarding the timing of this procedure. CLINICAL SIGNIFICANCE: Frenectomy performed using a CO2 laser for pediatric patients is a useful, simple, and safe treatment method. HOW TO CITE THIS ARTICLE: Komori S, Matsumoto K, Matsuo K, Suzuki H, Komori T. Clinical Study of Laser Treatment for Frenectomy of Pediatric Patients. Int J Clin Pediatr Dent 2017;10(3):272-277.

A Case Series of Fibro-Osseous Lesions of the Jaws.

The aim of this case series was to reveal the difficulties in diagnosing fibro-osseous lesions with radiological and histopathological examinations and quantify the potential risk of infection to fibro-osseous legions. To analyze the concordance between radiological and histopathological diagnoses, this retrospective case series included patients who were clinically diagnosed with fibro-osseous lesions via radiological findings and excluded the patients who did not undergo histopathological examinations. This study also included the patients in whom histopathological results confirmed fibro-osseous legions when preoperative radiological diagnosis did not include fibro-osseous legions. Eleven patients (three men, eight women; median age 24.5 years, range 15-57 years) were enrolled. Although radiological diagnoses of fibrous dysplasia (FD) corresponded with histopathological diagnoses in seven patients, mismatches between radiological findings and histopathological results were found in three patients. In one patient, suspected diagnosis with radiological examinations was malignant lymphoma or FD. In two patients, the histopathological differentiation between FD and ossifying fibroma (OF) was difficult. One patient had lesion recurrence which was suspected to be OF with surgical findings and postoperative course after the initial surgery. In three patients, infections of FD were found. Preoperative diagnosis of OF with radiographic feature of unilocular radiolucency is difficult. In cases in which histopathological differentiation between FD and OF is difficult, operative findings should be used because OF is often found to be well-encapsulated and easily enucleated. Bone in FD showing mixed radiolucent-radiopaque may be vulnerable to infection.

Clinical Study of 19 Cases Resulting in Dental Implant Removal.

Dental implant treatment is a highly anticipated therapy with widespread use. However, various accidental symptoms and complications have been reported, and we may reluctantly have to remove an implant body out of necessity. This study evaluated 19 cases (21 jaws) that resulted in removal after the enforcement of implant treatment in our hospital from January 2003 to August 2013 and clarified the details of the removals clinically for the purpose of improvement of future treatment results. Implants were removed at a higher frequency in elderly patients, particularly those 70 years of age or older. The removal rate regarding the tooth missing style was high in edentulous jaw cases in both the maxilla and mandible, and was low in defective cases of middle teeth. Regarding the duration and cause of removal, approximately half of the implants were removed due to defective primary stability within 6 months; for periods greater than 6 months, all cases except 1 jaw were removed within 30 months and many cases were due to peri-implantitis. Preoperation evaluations, primary stability of the implant body at the time of the operation, long-term observation and maintenance, and patient education are crucial to reduce the frequency of removal.

A sol particle homogeneous immunoassay for measuring serum cystatin C.

OBJECTIVES: We have developed a sol particle immunoassay (SPIA) for measuring serum cystatin C, an endogenous marker of glomerular filtration rate (GFR). DESIGN AND METHODS: We used colloidal gold particles coated with anti-cystatin C antibodies. RESULTS: The assay was linear in the range 0.2 to 8 mg/L and showed good correlation between theoretical and obtained values. The within and between-day coefficients of variation (CV) varied from 1.1 to 1.6% and 0.4 to 1.0%, respectively. Analytical recovery was 95.7 to 103.7%. No interference could be detected from bilirubin (up to 200 mg/L), hemoglobin (up to 3 g/L), chyle (up to 5,000 FTU), rheumatoid factor (up to 1,000 IU/mL) or anticoagulants. Serum samples (n = 101), from which turbidity had been removed, were measured either with our assay or with Dako Cystatin C PET kits, using a Model 7070 Hitachi automatic clinical analyzer. Comparing these two methods, the calculated linear regression equation and the correlation coefficient were y = 0.986 x -0.153 and r = 0.995, respectively. CONCLUSIONS: Our new SPIA assay is a fully automated, homogeneous immunoassay that can readily be used in conjunction with various commercial analyzers that are currently available. The assay is sensitive, precise and suitable for clinical use and appears to offer advantages over other GFR markers such as creatinine.

Purification and characterization of collagenolytic proteases from the hepatopancreas of northern shrimp (Pandalus eous).

Three gelatinolytic proteases (A1, A2, and B) were purified using a synthetic substrate, DNP-Pro-Gln-Gly-Ile-Ala-Gly-Gln-d-Arg, from the hepatopancreas of Northern shrimp (Pandalus eous) by several chromatographic steps involving hydroxyapatite column chromatography, gel filtration on Superdex75, and ion-exchange chromatography on a MonoQ column. Collagenolytic proteases A2 and B, but not protease A1, were demonstrated to digest native porcine type I collagen at 25 degrees C and pH 7.5. Further characterizations of these two collagenolytic proteases showed that the pH optimum of enzyme A2 against DNP-peptide was found to be 11, whereas that of enzyme B was 8.5. The optimum temperature ranged between 40 and 45 degrees C for both enzymes, although enzyme B appeared to be thermally more stable than enzyme A2 at pH 7.5. Both enzymes were strongly inhibited by PMSF and antipain, which suggests that they belong to collagenolytic serine proteases.

New norditerpenoids with trypanocidal activity from Vitex trifolia.

Trypanocidal constituents of the fruits of Vitex trifolia were investigated. Activity-guided isolation of the acetone extract resulted in the isolation of two new norditerpene aldehydes, 1 and 2, together with five known diterpenes: vitexifolin E (3), vitexifolin F (4), vitexilactone (5), 6-acetoxy-9-hydroxy-13(14)-labden-16,15-olide (6), and previtexilactone (7). In vitro minimum lethal concentrations of the isolated compounds against epimastigotes of Trypanosoma cruzi were 11 microM (1), 36 microM (2), 34 microM (3), 34 microM (4), 66 microM (5), 66 microM (6), and >265 microM (7).