Predictive value of SUVmax from initial 18F-FDG PET/CT scans for treatment outcomes in endometrial cancer patients undergoing fertility sparing management.

OBJECTIVE: To evaluate whether the maximum standardized uptake value (SUVmax) from initial 18F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) scans could be a predictor of complete response and recurrence in patients with endometrial cancer who are undergoing fertility sparing management. METHODS: We conducted a retrospective review of patients who were diagnosed with endometrial cancer through biopsy and chose to undergo fertility sparing management using progestin at the Asan Medical Center, from January 2011 to December 2020. Of these, 113 patients who had an 18-FDG-PET/CT scan before starting treatment were included in our study. We measured SUVmax and examined its correlation with complete response and time to progression after achieving complete response to progestin therapy. RESULTS: Of 113 patients, 73 (64.6%) achieved a complete response through fertility sparing management. The receiver operating characteristic curve analysis revealed that the optimal cut-off value of SUVmax for predicting complete response was 6.2 (sensitivity 79.5%, specificity 57.5%, p=0.006). After analyzing recurrence in the 73 patients who achieved complete response, we found that patients with an SUVmax value >6.2 had a significantly shorter time to progression compared with those with a value <6.2. (p=0.04). CONCLUSIONS: SUVmax values of PET-CT, along with other clinicopathological parameters, could be used to predict treatment response and recurrence risk in patients with stage I endometrial cancer undergoing fertility sparing management.

The Chronic Toxicity of Endocrine-Disrupting Chemical to Daphnia magna: A Transcriptome and Network Analysis of TNT Exposure.

Endocrine-disrupting chemicals (EDCs) impair growth and development. While EDCs can occur naturally in aquatic ecosystems, they are continuously introduced through anthropogenic activities such as industrial effluents, pharmaceutical production, wastewater, and mining. To elucidate the chronic toxicological effects of endocrine-disrupting chemicals (EDCs) on aquatic organisms, we collected experimental data from a standardized chronic exposure test using Daphnia magna (D. magna), individuals of which were exposed to a potential EDC, trinitrotoluene (TNT). The chronic toxicity effects of this compound were explored through differential gene expression, gene ontology, network construction, and putative adverse outcome pathway (AOP) proposition. Our findings suggest that TNT has detrimental effects on the upstream signaling of Tcf/Lef, potentially adversely impacting oocyte maturation and early development. This study employs diverse bioinformatics approaches to elucidate the gene-level toxicological effects of chronic TNT exposure on aquatic ecosystems. The results provide valuable insights into the molecular mechanisms of the adverse impacts of TNT through network construction and putative AOP proposition.

Intra-Lysosomal Peptide Assembly for the High Selectivity Index against Cancer.

Lysosomes remain powerful organelles and important targets for cancer therapy because cancer cell proliferation is greatly dependent on effective lysosomal function. Recent studies have shown that lysosomal membrane permeabilization induces cell death and is an effective way to treat cancer by bypassing the classical caspase-dependent apoptotic pathway. However, most lysosome-targeted anticancer drugs have very low selectivity for cancer cells. Here, we show intra-lysosomal self-assembly of a peptide amphiphile as a powerful technique to overcome this problem. We designed a peptide amphiphile that localizes in the cancer lysosome and undergoes cathepsin B enzyme-instructed supramolecular assembly. This localized assembly induces lysosomal swelling, membrane permeabilization, and damage to the lysosome, which eventually causes caspase-independent apoptotic death of cancer cells without conventional chemotherapeutic drugs. It has specific anticancer effects and is effective against drug-resistant cancers. Moreover, this peptide amphiphile exhibits high tumor targeting when attached to a tumor-targeting ligand and causes significant inhibition of tumor growth both in cancer and drug-resistant cancer xenograft models.

Protein-Precoated Surface of Metal-Organic Framework Nanoparticles for Targeted Delivery.

Metal-organic framework (MOF) nanoparticles have recently emerged as a promising vehicle for drug delivery with high porosity and feasibility. However, employing a MOF-based drug delivery system remains a challenge due to the difficulty in controlling interfaces of particles in a biological environment. In this paper, protein corona-blocked Zr6 -based MOF (PCN-224) nanoparticles are presented for targeted cancer therapy with high efficiency. The unmodified PCN-224 surface is precoated with glutathione transferase (GST)-fused targetable affibody (GST-Afb) proteins via simple mixing conjugations instead of chemical modifications that can induce the impairment of proteins. GST-Afb proteins are shown to stably protect the surface of PCN-224 particles in a specific orientation with GST adsorbed onto the porous surface and the GST-linked Afb posed outward, minimizing the unwanted interfacial interactions of particles with external biological proteins. The Afb-directed cell-specific targeting ability of particles and consequent induction of cell death is demonstrated both in vitro and in vivo by using two kinds of Afb, which targets the surface membrane receptor, human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR). This study provides insight into the way of regulating the protein-adhesive surface of MOF nanoparticles and designing a more effective MOF-hosted targeted delivery system.

Cystoid macular edema associated with omidenepag isopropyl in a phakic eye with an implantable collamer lens: a case report.

BACKGROUND: Cystoid macular edema is a known complication of omidenepag isopropyl usage. Omidenepag isopropyl is a selective prostanoid EP2 receptor agonist, and its association with macular edema has mainly been identified in pseudophakic eyes. Herein, we report a case of cystoid macular edema caused by omidenepag isopropyl use in a phakic eye with an implantable collamer lens. CASE PRESENTATION: A 38-year-old woman was diagnosed with left eye glaucoma and prescribed omidenepag isopropyl. She had undergone bilateral implantation of implantable collamer lenses approximately 12 years prior to the glaucoma diagnosis. After 9 months of using omidenepag isopropyl, she presented with blurred vision in the left eye; swept source optical coherence tomography revealed cystoid macular edema in this eye. Omidenepag isopropyl usage was discontinued, and bromfenac sodium hydrate was administered twice daily instead. After 2 months, the patient's visual discomfort was completely ameliorated. Additionally, an optical coherence tomography examination confirmed that the macula had normalized. CONCLUSIONS: We report a case of cystoid macular edema development after omidenepag isopropyl use in a patient with glaucoma who had undergone bilateral implantable collamer lens implantation. This case shows that the possibility of cystoid macular edema occurrence should be considered when omidenepag isopropyl is used, even in phakic eyes, after the insertion of implantable collamer lenses.

Adverse Human Health Effects of Chromium by Exposure Route: A Comprehensive Review Based on Toxicogenomic Approach.

Heavy metals are defined as metals with relatively high density and atomic weight, and their various applications have raised serious concerns about the environmental impacts and potential human health effects. Chromium is an important heavy metal that is involved in biological metabolism, but Cr exposure can induce a severe impact on occupational workers or public health. In this study, we explore the toxic effects of Cr exposure through three exposure routes: dermal contact, inhalation, and ingestion. We propose the underlying toxicity mechanisms of Cr exposure based on transcriptomic data and various bioinformatic tools. Our study provides a comprehensive understanding of the toxicity mechanisms of different Cr exposure routes by diverse bioinformatics analyses.

Stimuli-Responsive Adaptive Nanotoxin to Directly Penetrate the Cellular Membrane by Molecular Folding and Unfolding.

Biological nanomachines, including proteins and nucleic acids whose function is activated by conformational changes, are involved in every biological process, in which their dynamic and responsive behaviors are controlled by supramolecular recognition. The development of artificial nanomachines that mimic the biological functions for potential application as therapeutics is emerging; however, it is still limited to the lower hierarchical level of the molecular components. In this work, we report a synthetic machinery nanostructure in which actuatable molecular components are integrated into a hierarchical nanomaterial in response to external stimuli to regulate biological functions. Two nanometers core-sized gold nanoparticles are covered with ligand layers as actuatable components, whose folding/unfolding motional response to the cellular environment enables the direct penetration of the nanoparticles across the cellular membrane to disrupt intracellular organelles. Furthermore, the pH-responsive conformational movements of the molecular components can induce the apoptosis of cancer cells. This strategy based on the mechanical motion of molecular components on a hierarchical nanocluster would be useful to design biomimetic nanotoxins.

Dynamic multimodal holograms of conjugated organogels via dithering mask lithography.

Polymeric materials have been used to realize optical systems that, through periodic variations of their structural or optical properties, interact with light-generating holographic signals. Complex holographic systems can also be dynamically controlled through exposure to external stimuli, yet they usually contain only a single type of holographic mode. Here, we report a conjugated organogel that reversibly displays three modes of holograms in a single architecture. Using dithering mask lithography, we realized two-dimensional patterns with varying cross-linking densities on a conjugated polydiacetylene. In protic solvents, the organogel contracts anisotropically to develop optical and structural heterogeneities along the third dimension, displaying holograms in the form of three-dimensional full parallax signals, both in fluorescence and bright-field microscopy imaging. In aprotic solvents, these heterogeneities diminish as organogels expand, recovering the two-dimensional periodicity to display a third hologram mode based on iridescent structural colours. Our study presents a next-generation hologram manufacturing method for multilevel encryption technologies.

The Relationship between Perioperative Blood Transfusion and Postoperative Delirium in Patients Undergoing Spinal Fusion Surgery: Clinical Data Warehouse Analysis.

Background and Objectives: For preventing postoperative delirium (POD), identifying the risk factors is important. However, the relationship between blood transfusion and POD is still controversial. The aim of this study was to identify the risk factors of POD, to evaluate the impact of blood transfusion in developing POD among people undergoing spinal fusion surgery, and to show the effectiveness of big data analytics using a clinical data warehouse (CDW). Materials and Methods: The medical data of patients who underwent spinal fusion surgery were obtained from the CDW of the five hospitals of Hallym University Medical Center. Clinical features, laboratory findings, perioperative variables, and medication history were compared between patients without POD and with POD. Results: 234 of 3967 patients (5.9%) developed POD. In multivariate logistic regression analysis, the risk factors of POD were as follows: Parkinson's disease (OR 5.54, 95% CI 2.15-14.27; p < 0.001), intensive care unit (OR 3.45 95% CI 2.42-4.91; p < 0.001), anti-psychotics drug (OR 3.35 95% CI 1.91-5.89; p < 0.001), old age (≥70 years) (OR 3.08, 95% CI 2.14-4.43; p < 0.001), depression (OR 2.8 95% CI 1.27-6.2; p < 0.001). The intraoperative transfusion (OR 1.1, 95% CI 0.91-1.34; p = 0.582), and the postoperative transfusion (OR 0.91, 95% CI 0.74-1.12; p = 0.379) had no statistically significant effect on the incidence of POD. Conclusions: There was no relationship between perioperative blood transfusion and the incidence of POD in spinal fusion surgery. Big data analytics using a CDW could be helpful for the comprehensive understanding of the risk factors of POD, and for preventing POD in spinal fusion surgery.

Efficacy and radiographic analysis of oblique lumbar interbody fusion in treating lumbar degenerative spondylolisthesis with sagittal imbalance.

The aim of this study was to evaluate the effectiveness of OLIF (oblique lumbar interbody fusion) in the treatment of lumbar degenerative spondylolisthesis with sagittal imbalance. Fifty-nine patients were included in our analysis. Included patients were divided into 2 groups according to the surgical techniques: PLIF (posterior lumbar interbody fusion) (n = 31) and OLIF + PSF (OLIF combined with posterior spinal fixation) (n = 28). Perioperative radiographic parameters, complications, and clinical outcome from each group were assessed and compared. The operation time for both groups was 165.1 min in the OLIF group and 182.1 min in the PLIF group (P < 0.05). The intraoperative blood loss was 190.6 ml in the OLIF group and 356.3 ml in the PLIF group (P < 0.05). The number of intraoperative and postoperative complications for both groups was 7 in the OLIF group and 11 in the PLIF group. Significant clinical improvement was observed in VAS scores and ODI when comparing preoperative evaluation and final follow-up. The preoperative SVA (the distance from the posterosuperior corner of S1body to the C7 plumb line), PI (pelvic incidence), LL (lumbar lordosis), PI-LL mismatch, DH (disc height), and lumbar Cobb angles of both groups were similar. The postoperative and final follow-up SVA, LL, PI-LL mismatch, and disc height were improved in both groups, and a statistical difference was found between both groups (P < 0.05). An improvement of SVA, LL, PI-LL mismatch, and disc height at the OLIF group was better than that found at the PLIF group. An improvement in radiographic and clinical outcomes for the OLIF group was better than that seen for the PLIF group. Then, OLIF had a more curative effect in lumbar degenerative spondylolisthesis with sagittal imbalance.

Association between Sociodemographic Factors and Diarrhea in Children Under 5 Years in Rwanda.

Diarrheal disease is the second leading cause of mortality and morbidity in children under 5 years old worldwide, and is the most common cause of malnutrition in sub-Saharan Africa. In Rwanda, diarrhea is the third leading cause of death in children under 5 years old. This study examined the association between sociodemographic factors and diarrhea in children under 5 years using the data of 7,474 households in the 2014-2015 Rwanda Demographic and Health Survey. Overall prevalence of diarrhea in this study was 12.7% in children. An increased risk for diarrhea was found for children aged 12-23 months (odds ratio (OR)=4.514), those with a low economic status (OR=1.64), those from the Western province (OR=1.439), those with poorly-educated mothers (OR=5.163), and those with families engaged in agricultural activities (OR=1.624). In conclusion, sociodemographic factors significantly affect the risk of developing diarrhea in children under 5 years in Rwanda. Designing and implementing health education promoting awareness of early interventions and rotavirus vaccination are essential to reduce diarrheal diseases for the Rwandan community.

Effect of post-operative anticoagulation management in patients who have undergone On-X mechanical heart valve replacement surgery on post-discharge warfarin therapy.

WHAT IS KNOWN AND OBJECTIVE: We evaluated the effect of the proportion of time maintained within the target international normalized ratio (INR) postoperatively in hospitalized patients who underwent On-X mechanical heart valve replacement on warfarin therapy after discharge. METHODS: Inclusion was patients who were ≥18 years, received warfarin for a minimum of 10 days without any interruptions during hospitalization and followed by the anticoagulation service (ACS) clinic after discharge between June 2006 and June 2016. Patients were excluded if they had incomplete medical records, INR goal changes, known as warfarin resistance, transferred to another facility or expired during the study. The patients were divided into 3 groups according to the proportion of time maintained within therapeutic INR range (TTR) from day 4 to 10 of warfarin initiation (low: <30%, moderate: ≥30% to <70%, and high: ≥70%). The number of days needed to reach target INR for 2 consecutive measurements after discharge and the number of ACS visits was compared among the groups. RESULTS AND DISCUSSION: Among 539 postoperative patients, 273 were included. The baseline demographics were similar among the 3 groups. The mean time needed to reach target INR for 2 consecutive measurements was 68.6 ± 106.1 days. The low group required time needed to reach target INR for 2 consecutive measurements of 94.0 ± 140.9 days compared with 44.8 ± 57.1 days in the high group (P = .007). Additionally, the low group had more ACS visits than the high group (low, 6.6 ± 5.2 vs high, 4.6 ± 3.9; P = .025). Patient compliance affected the time needed to reach target INR for 2 consecutive measurements (compliant, 42.36 ± 58.5 days vs non-compliant, 132.0 ± 157.1 days, P < .001). WHAT IS NEW AND CONCLUSION: The study implicated that high postoperative TTR would reduce the time to require post-discharge target INR and the number of ACS visits.

Continuous separation of fungal spores in a microfluidic flow focusing device.

The research of fungi is of great importance in a number of fields, such as environmental and healthcare studies. While there are a large number of optical and molecular methods available for characterization and identification of fungi and their spores, their isolation is still conducted using slow and labor-intensive methods. Here, we develop a microfluidic device for the continuous separation of fungal spores from other eukaryotic cells. The spores were separated through the microfluidic device by expanding pinched flow fractionation (PFF) containing the spores, achieving a spatial separation perpendicular to the flow direction according to the spore size. Further branch flow fractionation (BFF) and co-flow of a Newtonian and viscoelastic fluid were used to enhance the separation performance. Using this microfluidic device, we demonstrated the separation of two different types of fungal spores and further separation of fungal spores from eukaryotic cells with a separation efficiency of above 90%. Compared to the existing conventional methods, our microfluidic flow focusing device requires little manual handling and uses small amounts of samples without any pre-treatment steps of the samples.

Chinese liver fluke Clonorchis sinensis infection changes the gut microbiome and increases probiotic Lactobacillus in mice.

Chinese liver fluke Clonorchis sinensis changes the host's immune system. Recently, it has been reported that helminths including C. sinensis can ameliorate immune-related diseases such as allergy. In addition, recent studies showed that helminth infection can alleviate immune-mediated disorders by altering the gut microbiome. However, changes in the gut microbiome due to C. sinensis have not been reported yet. In this study, changes in the gut microbiome of C57BL/6 mice infected with C. sinensis metacercariae were evaluated over time. Stool was analyzed by 16S rRNA amplicon analysis using high-throughput sequencing technology. There was no apparent difference in species richness and diversity between the infected and control groups. However, the composition of the microbiome was different between the infected and control groups at 20 days and 30 days post-infection, and the difference disappeared at 50 days post-infection. In particular, this microbiome alteration was associated with a change in the relative abundance of genus Lactobacillus and the probiotic Lactobacillus species that are known to have an immune-modulation role in immune-mediated diseases.

Rapid and Sensitive Detection of Aspergillus niger Using a Single-Mediator System Combined with Redox Cycling.

Rapid and sensitive mold detection is becoming increasingly important, especially in indoor environments. Common mold detection methods based on double-mediated electron transfer between an electrode and molds are not highly sensitive and reproducible, although they are rapid and simple. Here, we report a sensitive and reproducible detection method specific to Aspergillus niger ( A. niger), based on a single-mediator system combined with electrochemical-chemical (EC) redox cycling. Intracellular NAD(P)H-oxidizing enzymes in molds can convert electro-inactive hydroxy-nitro(so)arenes into electro-active hydroxy-aminoarenes. Since the membrane and wall of A. niger is well permeable to both a substrate (4-nitro-1-naphthol) and a reduced product (4-amino-1-naphthol) in tris buffer (pH 7.5) solution, the electrochemical signal is increased in the presence of A. niger due to two reactions: (i) enzymatic reduction of the substrate to the reduced product and (ii) electrochemical oxidation of the reduced product to an oxidized product. When a reducing agent (NADH) is present in the solution, the oxidized product is reduced back to the reduced product and then electrochemically reoxidized. This EC redox cycling significantly amplifies the electrochemical signal. Moreover, the background level is low and highly reproducible because the substrate and the reducing agent are electro-inactive at an applied potential of 0.20 V. The calculated detection limit for A. niger in a common double-mediator system consisting of Fe(CN)63- and menadione is ∼2 × 104 colony-forming unit (CFU)/mL, but the detection limit in the single-mediator system combined with EC redox cycling is ∼2 × 103 CFU/mL, indicating that the newly developed single-mediator system is more sensitive. Importantly, the detection method requires only an incubation period of 10 min and does not require a washing step, an electrode modification step, or a specific probe.

Natural melanin-loaded nanovesicles for near-infrared mediated tumor ablation by photothermal conversion.

Photothermal therapy requires a biocompatible material to absorb near-infrared (NIR) light and generate sufficient heat. Herein, we suggest natural melanin-loaded nanovesicles (melasicles) as photothermal therapeutic agents (PTA) for NIR mediated cancer therapy in vivo. The mean size of these melasicles was 140 ± 15 nm. They showed excellent colloidal stability. After irradiation from 808 nm NIR laser at 1.5 W cm-2, the melasicles showed good photothermal conversion efficiencies both in vitro and in vivo. In drug release study, laser irradiation increased fluidity of vesicle membrane due to photothermal generation from melanin. Initial drug release in the laser irradiation group was higher than that in the no laser irradiation group. After injecting the melasicles into tail veins of CT-26 bearing mice, tumors were suppressed or eliminated after irradiation at 1.5 W cm-2 for 5 min once or twice. These results suggest that melasicles could be used as attractive PTA for cancer therapy and localized drug release.

Recombinant adenylate kinase 3 from liver fluke Clonorchis sinensis for histochemical analysis and serodiagnosis of clonorchiasis.

Due to the lack of an effective prophylactic intervention and diagnosis, human liver fluke Clonorchis sinensis continues to afflict a large human population, causing a chronic inflammatory bile duct disease. With an aim to identify target antigens for sensitive serodiagnosis, adenylate kinase 3 of C. sinensis (CsAK3) was successfully expressed in soluble form in Escherichia coli by fusion to an RNA-interacting domain derived from human Lys-tRNA synthetase and purified by Ni2+-affinity chromatography. Anti-CsAK3 serum was raised by immunization of mice, and Western blotting confirmed that CsAK3 was expressed in adult-stage C. sinensis. Histochemical analysis showed that CsAK3 was localized to the subtegumental tissue of C. sinensis and was excreted into the bile duct of the host. When tested against sera from various parasite-infected patients by enzyme-linked immunosorbent assay, the recombinant CsAK3 elicited a specific response to C. sinensis-infected sera. The results suggest that CsAK3, either alone or in combination with other antigens, could be used for improving the clinical diagnosis of clonorchiasis.

The incidentally diagnosed adult congenital heart disease during routine medical health checkups in 27,897 Koreans at a single center over seven years.

BACKGROUND: The rate of incidentally diagnosed congenital heart disease (CHD) in adulthood has not been reported. The aim of this study was to investigate the detection rate of CHD in adults by routine, general health checkups. METHODS: Data was acquired from 222,401 patients older than 19 years who participated in general health checkups from January 2010 to December 2016. We excluded persons who did not undergo echocardiography during the general health checkups, who underwent echocardiography prior to the health checkups, and who were previously diagnosed with CHD. RESULTS: Among the 27,897 patients, who were included in the final analysis, 293 cases were newly diagnosed as CHD, and the overall detection rate was 1.05%. The mean age of patients with CHD was 48.7 ± 21.5 years, and most of them were female (n = 187, 63.8%). More than two-thirds were between the third and fifth decade of life, and only six patients (2.04%) were older than 70 years. The most common type was bicuspid aortic valve (n = 155). Interestingly, Ebstein's anomaly that required surgical repair was detected in five persons. CONCLUSIONS: During general health checkup, there were cases of severe CHD that required cardiac surgery upon diagnosis.

Intestinal fluke Metagonimus yokogawai infection increases probiotic Lactobacillus in mouse cecum.

Helminth infection can alleviate immune-mediated disorders such as allergies and autoimmune diseases, by altering the gut microbiome. However, changes in gut microbiome due to intestinal trematodes remain unelucidated. Here, we evaluated the changes in the gut microbiome of ICR mice infected with Metagonimus yokogawai, a hypo-virulent intestinal trematode. Four weeks after infection, mouse cecal content was analyzed by 16S rRNA amplicon analysis. Although there was no apparent difference in species richness and diversity, the microbiome composition was different in the infected and control groups. Furthermore, several Lactobacillus species with known immunomodulatory role in immune-mediated diseases were increased in the infected group.

Oblique retroperitoneal approach for lumbar interbody fusion from L1 to S1 in adult spinal deformity.

In recent years, with advancements in surgical techniques and instrumentation, the lateral lumbar interbody fusion is being used increasingly as an alternative procedure to anterior approach. In this study, we illustrated a oblique retroperitoneal approach for lumbar interbody fusion with one incision site and tilting of the operation table in adult spinal deformity and evaluate the radiographical findings and clinical outcomes of patients treated using this technique. This study included 32 patients scheduled to undergo anterior and posterior long-level fusions for lumbar degenerative kyphosis or degenerative lumbar scoliosis. Data collected included blood loss, operative time, incision size, and perioperative complications. Pre- and postoperative radiographic parameters and clinical outcome measures were assessed. Mean follow-up time was 26.1 months. The mean blood losses were 107.4 and 102.4 ml, and the mean operative times were 116, 97, and 82 min for the patients within five levels (4 cases), four levels (18 cases), and three levels (10 cases). The mean incision sizes were 14.63, 13.82, and 12.5 cm in the patients with five, four, and three levels. The mean pelvic incidence was 50.3°. The mean preoperative sagittal vertical axis (SVA) was + 13.66 cm, and the last follow-up SVA was + 2.94 cm. The preoperative lumbar lordosis (LL) was 5.79°, and the last follow-up LL was 46.54°. The mean correction angle was 41°. The mean Cobb angle decreased from a preoperative value of 21.55° to 9.6°at the last follow-up. An oblique retroperitoneal approach is very safe, allowing reproducible access from L1 to S1 for lumbar interbody fusion in adult spinal deformity.