Using a novel hemostatic peptide solution to prevent bleeding after endoscopic submucosal dissection of a gastric tumor.

BACKGROUND: Endoscopic mucosal dissection has become the standard treatment for early gastric cancer. However, post-endoscopic submucosal dissection (ESD) ulcer occurs in 4.4% of patients. This study hypothesized whether applying PuraStat, a novel hemostatic peptide solution, prevents post-ESD bleeding. AIM: To investigate the preventive potential of PuraStat, a hemostatic formulation, against bleeding in post-ESD gastric ulcers. METHODS: Between May 2022 and March 2023, 101 patients (Group P) underwent ESD for gastric diseases at our hospital and received PuraStat (2 mL) for post-ESD ulcers. We retrospectively compared this group with a control group (Group C) comprising 297 patients who underwent ESD for gastric diseases at our hospital between April 2017 and March 2021. P values < 0.05 on two-sided tests indicated significance. RESULTS: Post-ESD bleeding occurred in 6 (5.9%) (95%CI: 2.8-12.4) and 20 (6.7%) (95%CI: 4.4-10.2) patients in Groups P and C, respectively, with no significant between-group difference. The relative risk was 1.01 (95%CI: 0.95-1.07). The lesser curvature or anterior wall was the bleeding site in all 6 patients who experienced postoperative bleeding in Group P. In multivariate analysis, the odds ratios for resection diameter ≥ 50 mm and oral anticoagulant use were 6.63 (95%CI: 2.52-14.47; P = 0.0001) and 4.04 (1.26-0.69; P = 0.0164), respectively. The adjusted odds ratio of post-ESD bleeding and PuraStat was 1.28 (95%CI: 0.28-2.15). CONCLUSION: PuraStat application is not associated with post-ESD bleeding. However, the study suggests that gravitational forces may affect the effectiveness of applied PuraStat.

One-step embedding method for maintaining orientation of pathological tissue specimens using agar thin films.

Pathological histology examination involves handling a variety of specimens that are cut according to regulations and placed in cassettes. Tissue fragments in the cassettes are then diagnosed after processing, embedding, thin sectioning, staining and other procedures using a processing machine. Maintaining tissue fragment order and orientation during these processes is important for accurate diagnosis. In this study, we present a method of maintaining tissue fragment order and orientation using a thin film of ultra-high-strength agar and evaluate its usefulness during tissue sectioning.Cassettes were prepared, each containing three pieces of porcine liver, and compared embedding time with and without agar thin films (ATFs). Embedding was performed by three medical laboratory scientists with different levels of experience.To enable one-step tissue sample embedding, ATFs were integrated with samples in the cassettes. This resulted in an average reduction of 6.22 s of embedding time per cassette compared with traditional embedding methods.Through the use of ATFs, tissue fragment order and orientation is maintained, and embedding process time shortened. Additionally, ATFs are easily prepared and stored in 10% neutral buffered formalin over extended periods, allowing for immediate use during sectioning. This method is ideal to implement in busy pathology laboratories.

Online SFE-SFC-MS/MS colony screening: A high-throughput approach for optimizing (-)-limonene production.

Conventional analysis of microbial bioproducers requires the extraction of metabolites from liquid cultures, where the culturing steps are time consuming and greatly limit throughput. To break through this barrier, the current study aims to directly evaluate microbial bioproduction colonies by way of supercritical fluid extraction-supercritical fluid chromatography-triple quadrupole mass spectrometry (SFE-SFC-MS/MS). The online SFE-SFC-MS/MS system offers great potential for high-throughput analysis due to automated metabolite extraction without any need for pretreatment. This is the first report of SFE-SFC-MS/MS as a method for direct colony screening, as demonstrated in the high-throughput screening of (-)-limonene bioproducers. Compared with conventional analysis, the SFE-SFC-MS/MS system enables faster and more convenient screening of highly productive strains.

Factors that affect the development of acute hemorrhagic rectal ulcer syndrome and rebleeding.

Objectives: Acute hemorrhagic rectal ulcer syndrome (AHRUS) causes massive bleeding and often recurrent rebleeding from rectal ulcers that form immediately above the dentate line. This study aimed to determine the clinical background and risk factors contributing to rebleeding in patients with AHRUS and the most appropriate method of hemostasis treatment. Methods: This retrospective study included 93 patients diagnosed with AHRUS at Showa University Fujigaoka Hospital, Japan, between April 2009 and November 2018. Information on clinical background factors, endoscopic findings, and hemostasis was obtained from medical records. The relationship with episodes of rebleeding was analyzed by multivariate logistic regression analysis. Results: The median age was 79 years, and 84 patients (90%) had a performance status of grade 2 or higher. The patients had multiple background factors, with a median number of 5 per patient. The background factors could be classified into two major factors: those related to arteriosclerosis and those related to delayed wound healing.In the multivariate analysis, significantly more rebleeding occurred in patients with active bleeding during the initial endoscopy (odds ratio 4.88, 95% confidence interval 1.80-14.46, p = 0.003); significantly less rebleeding occurred in patients for whom hemostasis was first performed by clipping (odds ratio 0.30, 95% confidence interval 0.09-0.88, p = 0.035). Conclusions: In bedridden older individuals with poor general health, multiple combinations of arteriosclerosis-related factors and protracted wound healing factors can induce AHRUS. We strongly recommend performing hemostasis via the clipping method on suspected bleeding points, including active bleeding sites, in AHRUS.

Anti programmed death-ligand 1 antibody-related cholangitis without bile duct dilation or stenosis.

Cholangitis has been reported as an immune-related adverse event, although it rarely occurs. Here we report a case of cholangitis due to atezolizumab in a 77-year-old woman who had been treated with atezolizumab and nab-paclitaxel for breast cancer and lung metastasis. On the seventh cycle, she presented with fever and epigastric pain, and computed tomography and endoscopic ultrasound showed slight wall thickening of the common bile duct, and transpapillary bile duct biopsy was performed. Pathologically, CD8+ T cells predominant infiltration was detected in the subepithelium of the bile duct, resulting in the diagnosis of atezolizumab-related cholangitis. The patient's symptoms were resolved immediately after discontinuing atezolizumab. Hepatobiliary enzymes returned to normal 21 days after onset, and bile duct wall thickening disappeared. Cholangitis should be included as the differential diagnosis of liver dysfunction in patients receiving immune checkpoint inhibitors.

Multiple myeloma with esophageal involvement: A rare case.

A 77-year-old man presented with a spinal cord tumor at the cervical 7/thoracic 1 level and pain and weakness in the right hand. Blood tests revealed anemia, renal dysfunction, and hyperproteinemia. Immunoelectrophoresis revealed the M-protein component of immunoglobulin G gamma globulin. Bone marrow aspirate contained an increased number of atypical plasma cells. He was diagnosed with symptomatic myeloma and treated with radiation therapy, chemotherapy, and extradural tumor resection. Upper gastrointestinal endoscopy, performed because of anemia progression, revealed a 5-mm submucosal tumor-like elevated lesion in the upper thoracic esophagus. On white light observation, the lesion appeared whitish with a central redness. Our patient was diagnosed with extramedullary multiple myeloma. Extramedullary lesions are rare in the gastrointestinal tract. To our knowledge, this case is the first of multiple myeloma with esophageal involvement.

Diphyllobothrium stemmacephalum (Cestoda: Diphyllobothriidae) found from a harbor porpoise in northern Japan, with comments on a geographical gap with human infection cases in southern Japan.

Even though the cetacean tapeworm Diphyllobothrium stemmacephalum occurs in both cold and warm waters, human infections and final host occurrences have been confined to temperate areas in and near Japan. We recently obtained a strobila of this cestode that was excreted from a harbor porpoise accidentally caught offshore of Hokkaido of northern Japan. Genetic analysis of 28S rDNA and cox1 genes confirmed that the cestode was D. stemmacephalum. Our finding sets the northernmost record of D. stemmacephalum in the western Pacific, suggesting that the risk of human infections by this parasite in northern Japan deserves further attention.

Immunogenicity and safety of AZD1222 (ChAdOx1 nCoV-19) against SARS-CoV-2 in Japan: a double-blind, randomized controlled phase 1/2 trial.

BACKGROUND: Immunogenicity and safety of the AZD1222 (ChAdOx1 nCoV-19) vaccine was evaluated in Japanese adults in an ongoing phase 1/2, randomized, double-blind, parallel-group, placebo-controlled, multi-centre trial (NCT04568031). METHODS: Adults (n=256, age ≥18 years) seronegative for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were stratified by age into 18-55- (n=128), 56-69- (n=86) and ≥70-year-old cohorts (n=42), and randomized 3:1 to receive AZD1222 or placebo (two intramuscular injections 4 weeks apart). Immunogenicity and safety were coprimary endpoints. Data collected up to Day 57 are reported. RESULTS: Positive seroresponses to SARS-CoV-2 spike and receptor-binding domain antigens were seen in all 174 participants who received two doses of AZD1222. Neutralizing antibody seroresponses were seen in 67.5%, 60.3% and 50.0% of participants receiving AZD1222 aged 18-55, 56-69 and ≥70 years, respectively. Solicited adverse events (AEs) were typically mild/moderate in severity and included pain and tenderness at the injection site, malaise, fatigue, muscle pain and headache. Common unsolicited AEs included pain and tenderness at the injection site, fatigue and elevated body temperature. No vaccine-related serious AEs or deaths were reported. CONCLUSIONS: AZD1222 elicited a strong humoral immune response against SARS-CoV-2, and was well tolerated in Japanese participants, including elderly participants.

Increased carvone production in Escherichia coli by balancing limonene conversion enzyme expression via targeted quantification concatamer proteome analysis.

(-)-Carvone is a monoterpenoid with a spearmint flavor. A sustainable biotechnological production process for (-)-carvone is desirable. Although all enzymes in (-)-carvone biosynthesis have been functionally expressed in Escherichia coli independently, the yield was low in previous studies. When cytochrome P450 limonene-6-hydroxylase (P450)/cytochrome P450 reductase (CPR) and carveol dehydrogenase (CDH) were expressed in a single strain, by-product formation (dihydrocarveol and dihydrocarvone) was detected. We hypothesized that P450 and CDH expression levels differ in E. coli. Thus, two strains independently expressing P450/CPR and CDH were mixed with different ratios, confirming increased carvone production and decreased by-product formation when CDH input was reduced. The optimum ratio of enzyme expression to maximize (-)-carvone production was determined using the proteome analysis quantification concatamer (QconCAT) method. Thereafter, a single strain expressing both P450/CPR and CDH was constructed to imitate the optimum expression ratio. The upgraded strain showed a 15-fold improvement compared to the initial strain, showing a 44 ± 6.3 mg/L (-)-carvone production from 100 mg/L (-)-limonene. Our study showed the usefulness of the QconCAT proteome analysis method for strain development in the industrial biotechnology field.

Peroral endoscopy during the COVID-19 pandemic: Efficacy of the acrylic box (Endo-Splash Protective (ESP) box) for preventing droplet transmission.

BACKGROUND AND AIM: Appropriate personal protective equipment should be worn in all clinical settings during the COVID-19 pandemic because anyone could be carrying SARS-CoV-2. Peroral endoscopy is the procedure potentially generating large volumes of aerosols through stimulation of patient coughing. The present study investigated the efficacy of a specially designed acrylic box (Endo-Splash Protective [ESP] box) for preventing droplet transmission as part of droplet precautions for endoscopists and assistants during routine endoscopy for potential asymptomatic carriers or emergent endoscopy for confirmed or suspected COVID-19 patients. METHODS AND RESULTS: ESP box was fabricated for use in peroral endoscopy performed with the patient in either a left lateral or prone position. Circular ports were created, one for scope insertion and one for each of the assistant's hands. Simulated droplets were released inside ESP box, and the number of droplets was counted every 100/3 ms for 5 s pre-release and post-release at the positions of the endoscopist and assistant. The experiment was repeated eight times at the endoscopist and assistant positions, and the median numbers of droplets were calculated and compared. No significant differences were observed between the median number of droplets counted for 5 s prerelease and postrelease at either the endoscopist (P = 0.239) or assistant (P = 0.576) positions. We could block the droplets by using ESP box. CONCLUSIONS: The present findings suggest that use of ESP box during peroral endoscopy may reduce endoscopist and assistant droplet exposure, potentially reducing the risk of droplet transmission to healthcare professionals performing peroral endoscopy during the COVID-19 pandemic.

Homeostasis and systematic ageing as non-equilibrium phase transitions in computational multicellular organizations.

Being a fatal threat to life, the breakdown of homeostasis in tissues is believed to involve multiscale factors ranging from the accumulation of genetic damages to the deregulation of metabolic processes. Here, we present a prototypical multicellular homeostasis model in the form of a two-dimensional stochastic cellular automaton with three cellular states, cell division, cell death and cell cycle arrest, of which the state-updating rules are based on fundamental cell biology. Despite the simplicity, this model illustrates how multicellular organizations can develop into diverse homeostatic patterns with distinct morphologies, turnover rates and lifespans without considering genetic, metabolic or other exogenous variations. Through mean-field analysis and Monte-Carlo simulations, those homeostatic states are found to be classified into extinctive, proliferative and degenerative phases, whereas healthy multicellular organizations evolve from proliferative to degenerative phases over a long time, undergoing a systematic ageing akin to a transition into an absorbing state in non-equilibrium physical systems. It is suggested that the collapse of homeostasis at the multicellular level may originate from the fundamental nature of cell biology regarding the physics of some non-equilibrium processes instead of subcellular details.

Evaluation of an S-system root-finding method for estimating parameters in a metabolic reaction model.

In a mathematical model, estimation of parameters from time-series data of metabolic concentrations in cells is a challenging task. However, it seems that a promising approach for such estimation has not yet been established. Biochemical Systems Theory (BST) is a powerful methodology to construct a power-law type model for a given metabolic reaction system and to then characterize it efficiently. In this paper, we discuss the use of an S-system root-finding method (S-system method) to estimate parameters from time-series data of metabolite concentrations. We demonstrate that the S-system method is superior to the Newton-Raphson method in terms of the convergence region and iteration number. We also investigate the usefulness of a translocation technique and a complex-step differentiation method toward the practical application of the S-system method. The results indicate that the S-system method is useful to construct mathematical models for a variety of metabolic reaction networks.

Characterization of a feruloyl esterase B from Talaromyces cellulolyticus.

A feruloyl esterase catalyzes the hydrolysis of the 4-hydroxy-3-methoxycinnamoyl (feruloyl) group from esterified sugars in plant cell walls. Talaromyces cellulolyticus is a high cellulolytic-enzyme producing fungus. However, there is no report for feruloyl esterase activity of T. cellulolyticus. Analysis of the genome database of T. cellulolyticus identified a gene encoding a putative feruloyl esterase B. The recombinant enzyme was prepared using a T. cellulolyticus homologous expression system and characterized. The purified enzyme exhibited hydrolytic activity toward p-nitrophenyl acetate, p-nitrophenyl trans-ferulate, methyl ferulate, rice husk, and bagasse. HPLC assays showed that the enzyme released ferulic acid and p-coumaric acid from hydrothermal-treated rice husk and bagasse. Trichoderma sp. is well-known high cellulolytic-enzyme producing fungus useful for the lignocellulosic biomass saccharification. Interestingly, no feruloyl esterase has been reported from Trichoderma sp. The results show that this enzyme is expected to be industrially useful for biomass saccharification.

Solvent-dependent strong asymmetric amplification in the catalytic enantioselective Henry reaction using the trans-N,N'-bis-biphenyl-4-ylmethyl-cyclohexane-1,2-diamine-CuCl2 complex.

A strong asymmetric amplification was observed in the enantioselective Henry reaction catalyzed by the (R,R)-trans-N,N'-bis-biphenyl-4-ylmethyl-cyclohexane-1,2-diamine·CuCl2 complex in AcOEt, while no amplification occurred in MeOH.

An Efficient and Very Accurate Method for Calculating Steady-State Sensitivities in Metabolic Reaction Systems.

Stability and sensitivity analyses of biological systems require the ad hocwriting of computer code, which is highly dependent on the particular model and burdensome for large systems. We propose a very accurate strategy to overcome this challenge. Its core concept is the conversion of the model into the format of biochemical systems theory (BST), which greatly facilitates the computation of sensitivities. First, the steady state of interest is determined by integrating the model equations toward the steady state and then using a Newton-Raphson method to fine-tune the result. The second step of conversion into the BST format requires several instances of numerical differentiation. The accuracy of this task is ensured by the use of a complex-variable Taylor scheme for all differentiation steps. The proposed strategy is implemented in a new software program, COSMOS, which automates the stability and sensitivity analysis of essentially arbitrary ODE models in a quick, yet highly accurate manner. The methods underlying the process are theoretically analyzed and illustrated with four representative examples: a simple metabolic reaction model; a model of aspartate-derived amino acid biosynthesis; a TCA-cycle model; and a modified TCA-cycle model. COSMOS has been deposited to https://github.com/BioprocessdesignLab/COSMOS.

Protein fishing using magnetic nanobeads containing calmodulin site-specifically immobilized via an azido group.

We developed a novel method for capturing proteins that interact with a target protein. This method utilizes a protein containing a site-specifically incorporated 3-azidotyrosine (N3-Y) and FG beads for immobilization of the protein via an azido group. Using calmodulin (CaM) as the target protein, we introduced N3-Y at position 72 and conjugated it to FG beads by copper-free click chemistry. From the Ca(2+)/CaM-binding proteins captured from mouse brain cell lysate and analysis by mass spectrometry, we identified six proteins: alpha-enolase (ENOA), glucose-6-phosphate isomerase (GPI), annexin A5 (ANXA5), malate dehydrogenase 1 (MDH1), glyceraldehyde-3-phosphate dehydrogenase and the well-known CaM-binding protein phosphoglycerate kinase 1 (PGK1). The presence of photo-crosslinking products via N3-Y for all the captured proteins except GPI indicated that they bound directly to CaM. In this study, ENOA, ANXA5 and MDH1 were identified as novel CaM-binding proteins, and PGK1 was bound to Ca(2+)/CaM and also Ca(2+)-free CaM. This method should prove useful for capturing novel interacting proteins and serve as a useful tool for proteomic analyses.

Emponzoñamiento ofídico en los Altos Mirandinos enero 1997 a enero 1998 / Envenoming ophidic and in Altos Mirandinos january 1997 a january 1998

Se realizó un estudio retrospectivo de 34 pacientes de enero 1997 a enero 1998, que fueron admitidos en la emergencia del Hospital "Dr. Victorino Santaella R.", con el diagnóstico de emponzoñamiento ofídico por Bothrops y/o Crotalus para clasificar y comparar las características clínicas y epidemiológicas de los pacientes afectados. Se encontró predominio de jóvenes masculinos con empozoñamiento por Bothrops y con época de mayor riesgo entre julio y diciembre que se corresponde con la época de lluvia. Las complicaciones más frecuentes fueron infección local, necrósis, un episodio de insuficiencia renal aguda y prolongación de los tiempos de coagulación. El tratamiento de elección fue suero antíofidico polivalente, analgésicos y antibiótico. No hubo muertes relacionadas con el empozoñamiento

Neumonía postobstructiva a causa de broncolitiasis: reporte de un caso / Postobstructive pneumoniae a cause of broncholitiasis: report of a case

La broncolitiasis es una entidad clínica poco frecuente y el diagnóstico resulta inequívoco cuando, como en nuestro caso el paciente nos enseña los bronquiolitos expulsados al toser, sin embargo, no se debe olvidar que es una causa de infección pulmonar: (Neumonía-Bronconeumonía) asi como de atelectasia, hemoptisis, tos paroxística, sibilancias, disnea, dolor torácico. Finalmente ante la presencia de calcificaciones pulmonares, hiliares o mediastinales que desaparecen o cambian de posición o se acompañan por los síntomas anteriormente mencionados, debe pensarse en la posibilidad de que el origen del cuadro pudiera deberse a la presencia de broncolitiasis. La tomografía del tórax permite la precisa evaluación de la presencia y localización del bronquiolito constituyéndose así en una importante arma diagnóstica