Subtype-Based Microbial Analysis in Non-small Cell Lung Cancer / 결핵및호흡기질환

Background@#The human lung serves as a niche for a unique and dynamic bacterial community related to the development and aggravation of multiple respiratory diseases. Therefore, identifying the microbiome status is crucial to maintaining the microecological balance and maximizing the therapeutic effect on lung diseases. Therefore, we investigated the histological type-based differences in the lung microbiomes of patients with lung cancer. @*Methods@#We performed 16S rRNA sequencing to evaluate the respiratory tract microbiome present in bronchoalveolar lavage fluid. Patients with non-small cell lung cancer were stratified based on two main subtypes of lung cancer: adenocarcinoma and squamous cell carcinoma (SqCC). @*Results@#Among the 84 patients analyzed, 64 (76.2%) had adenocarcinoma, and 20 (23.8%) had SqCC. The α- and β-diversities showed significant differences between the two groups (p=0.004 for Chao1, p=0.001 for Simpson index, and p=0.011 for PERMANOVA). Actinomyces graevenitzii was dominant in the SqCC group (linear discriminant analysis [LDA] score, 2.46); the populations of Haemophilus parainfluenza (LDA score, 4.08), Neisseria subflava (LDA score, 4.07), Porphyromonas endodontalis (LDA score, 3.88), and Fusobacterium nucleatum (LDA score, 3.72) were significantly higher in the adenocarcinoma group. @*Conclusion@#Microbiome diversity is crucial for maintaining homeostasis in the lung environment, and dysbiosis may be related to the development and prognosis of lung cancer. The mortality rate was high, and the microbiome was not diverse in SqCC. Further large-scale studies are required to investigate the role of the microbiome in the development of different lung cancer types.

A 35-month-old boy who ingested laundry detergent pods and underwent veno-pulmonary extracorporeal membrane oxygenation support

Laundry detergent pod (LDP) exposure has been reported to be fatal in children younger than 2 years, leading to respiratory or central nervous system depression. While gastrointestinal irritation is the most common symptom, there are reported cases of severe acidosis with respiratory depression or pneumonia, resulting in mortality. To our best knowledge, there is no report on a case of LDP exposure presenting with acute respiratory distress syndrome requiring extracorporeal membrane oxygenation support. Here, we present a case of a child with severe acute respiratory distress syndrome following LDP exposure, who was successfully treated with veno-pulmonary extracorporeal membrane oxygenation and steroids.

Properties of Pleural Mesothelial Cells in Idiopathic Pulmonary Fibrosis and Cryptogenic Organizing Pneumonia

Background@#Profibrotic properties of pleural mesothelial cells may play an important role in the fibrosis activity in idiopathic pulmonary fibrosis (IPF). The purpose of this study was to compare the expression of pleural mesothelial cell markers in IPF and cryptogenic organizing pneumonia (COP), with an assumption that increased expression implies increase in fibrosis. @*Methods@#Twenty IPF lung samples were stained by immunohistochemistry for the pleural mesothelial cell markers: leucine rich repeat neuronal 4 (LRRN4), uroplakin 3B, CCchemokine ligand 18, and laminin-5. Nine COP lung samples were used as controls. A semiquantitative analysis was performed to compare markers expression in IPF and COP. @*Results@#LRRN4 expression was found in epithelial lining cells along the honeycombing and fibroblastic foci in IPF, but not in the fibrotic interstitial lesion and airspace filling fibrous tufts in COP. We found a significant decrease in baseline forced vital capacity when LRRN4 expression was increased in honeycombing epithelial cells and fibroblastic foci. @*Conclusion@#LRRN4 expression patterns in IPF are distinct from those in COP. Our findings suggest that mesothelial cell profibrotic property may be an important player in IPF pathogenesis and may be a clue in the irreversibility of fibrosis in IPF.

Therapeutic Effect of Three-Dimensional Cultured Adipose-Derived Stem Cell-Conditioned Medium in Renal Ischemia-Reperfusion Injury

Background and Objectives@#We evaluated the effect of adipose-derived stem cell-derived conditioned medium (ADSC-CM) on the renal function of rats with renal ischemia-reperfusion injury (IRI)-induced acute kidney injury. @*Methods@#and Results: Forty male Sprague‐Dawley rats were randomly divided into four groups: sham, nephrectomy control, IRI control, ADSC-CM. The ADSC-CM was prepared using the three-dimensional spheroid culture system and injected into renal parenchyme. The renal function of the rats was evaluated 28 days before and 1, 2, 3, 4, 7, and 14 days after surgical procedures. The rats were sacrificed 14 days after surgical procedures, and kidney tissues were collected for histological examination. The renal parenchymal injection of ADSC-CM significantly reduced the serum blood urea nitrogen and creatinine levels compared with the IRI control group on days 1, 2, 3, and 4 after IRI. The renal parenchymal injection of ADSC-CM significantly increased the level of creatinine clearance compared with the IRI control group 1 day after IRI. Collagen content was significantly lower in the ADSC-CM group than in the IRI control group in the cortex and medulla. Apoptosis was significantly decreased, and proliferation was significantly increased in the ADSC-CM group compared to the IRI control group in the cortex and medulla. The expressions of anti-oxidative makers were higher in the ADSC-CM group than in the IRI control group in the cortex and medulla. @*Conclusions@#The renal function was effectively rescued through the renal parenchymal injection of ADSC-CM prepared using a three-dimensional spheroid culture system.

Digital Breast Tomosynthesis Plus Ultrasound Versus Digital Mammography Plus Ultrasound for Screening Breast Cancer in Women With Dense Breasts

Objective@#To compare the outcomes of digital breast tomosynthesis (DBT) screening combined with ultrasound (US) with those of digital mammography (DM) combined with US in women with dense breasts. @*Materials and Methods@#A retrospective database search identified consecutive asymptomatic women with dense breasts who underwent breast cancer screening with DBT or DM and whole-breast US simultaneously between June 2016 and July 2019. Women who underwent DBT + US (DBT cohort) and DM + US (DM cohort) were matched using 1:2 ratio according to mammographic density, age, menopausal status, hormone replacement therapy, and a family history of breast cancer. The cancer detection rate (CDR) per 1000 screening examinations, abnormal interpretation rate (AIR), sensitivity, and specificity were compared. @*Results@#A total of 863 women in the DBT cohort were matched with 1726 women in the DM cohort (median age, 53 years; interquartile range, 40–78 years) and 26 breast cancers (9 in the DBT cohort and 17 in the DM cohort) were identified. The DBT and DM cohorts showed comparable CDR (10.4 [9 of 863; 95% confidence interval {CI}: 4.8–19.7] vs. 9.8 [17 of 1726;95% CI: 5.7–15.7] per 1000 examinations, respectively; P = 0.889). DBT cohort showed a higher AIR than the DM cohort (31.6% [273 of 863; 95% CI: 28.5%–34.9%] vs. 22.4% [387 of 1726; 95% CI: 20.5%–24.5%]; P < 0.001). The sensitivity for both cohorts was 100%. In women with negative findings on DBT or DM, supplemental US yielded similar CDRs in both DBT and DM cohorts (4.0 vs. 3.3 per 1000 examinations, respectively; P = 0.803) and higher AIR in the DBT cohort (24.8% [188 of 758; 95% CI: 21.8%–28.0%] vs. 16.9% [257 of 1516; 95% CI: 15.1%–18.9%; P < 0.001). @*Conclusion@#DBT screening combined with US showed comparable CDR but lower specificity than DM screening combined with US in women with dense breasts.

Efficacy and Safety of Human Bone Marrow-Derived Mesenchymal Stem Cells according to Injection Route and Dose in a Chronic Kidney Disease Rat Model

Background and Objectives@#We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease. @*Methods@#and Results: A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×10 6 cells), renal artery moderate dose (RA-MD) (1.0×10 6 cells), renal artery high dose (RA-HD) (2.0×10 6 cells), tail vein low dose (TV-LD) (0.5×10 6 cells), tail vein moderate dose (TV-MD) (1.0×10 6 cells), and tail vein high dose (TV-HD) (2.0×10 6 cells). Renal function and mortality of rats were evaluated after hBMSC injection. Serum blood urea nitrogen was significantly lower in the TV-HD group at 2 weeks (p＜0.01), 16 weeks (p＜0.05), and 24 weeks (p＜0.01) than in the TV-C group, as determined by one-way ANOVA. Serum creatinine was significantly lower in the TV-HD group at 24 weeks (p＜0.05). At 8 weeks, creatinine clearance was significantly higher in the TV-MD and TV-HD groups (p＜0.01, p＜0.05) than in the TV-C group. In the safety evaluation, we observed no significant difference among the groups. @*Conclusions@#Our findings confirm the efficacy and safety of high dose (2×10 6 cells) injection of hBMSC via the tail vein.

A Pictorial Review of Radiologic Findings of Foreign Bodies in the Thorax

Thoracic foreign bodies (FBs) are serious and relatively frequent in emergency departments. Thoracic FBs may occur in association with aspiration, ingestion, trauma, or iatrogenic causes. Imaging plays an important role in the identification of FBs and their dimensions, structures, and locations, before the initiation of interventional treatment. To guide proper clinical management, radiologists should be aware of the radiologic presentations and the consequences of thoracic FBs. In this pictorial essay, we reviewed the optimal imaging settings to identify FBs in the thorax, classified thoracic FBs into four types according to their etiology, and reviewed the characteristic imaging features and the possible complications.

Comparison of the Lower Trapezius Muscle Activity during Three Different Shoulder Flexion Exercises in Healthy Subjects

Purpose@#This study investigated the muscle activity of the lower trapezius (LT) during three different shoulder flexion exercises. @*Methods@#Twenty-three subjects between 20 and 25 years of age were enrolled. The subjects were asked to perform three different shoulder flexion exercises: 1) shoulder flexion in prone (SFP), 2) shoulder flexion in push-up with a swiss ball (SFPUS) and 3) shoulder flexion in a quadruped position with a swiss ball (SFQPS) in random order. The muscle activity of LT during each shoulder flexion exercise was measured by using surface electromyography. The muscle activity of LT was compared using one-way analysis of variance (ANOVA) and Bonferroni post hoc test among three different shoulder flexion exercises. The statistical significance level was set at α = 0.01. @*Results@#The muscle activity of LT was significantly different among three different shoulder flexion exercises (SFP, SFPUS, and SFQPS).The LT muscle activity with SFQPS exercise was greater than SFP and SFPUS exercises (p 0.01). @*Conclusion@#The LT muscle activity was greater during SFQPS than SFP and SFPUS. Therefore, SFQPS exercise can be recommended for selectively activation of LT muscle.

Comparison of Tibialis Anterior Muscle Thickness with 4 Different Toe and Ankle Postures: Ultrasonographic Study

Purpose@#Ankle dorsiflexion is an essential element of normal functions, including walking, activities of daily living and sport activities.The tibialis anterior (TA) muscle functioned as a dorsiflexor and as a dynamic stabilizer of the ankle joint during walking and jumping.This study aimed to compare TA muscle thickness using ultrasonography according to the four different toe and ankle postures for the selective TA strengthening exercise. @*Methods@#This study were recruited 26 (males: 15, females: 11) aged 20-30 years, with no injury ankle and calf in the medical history, had normal dorsiflexion and inversion range of motion (ROM). The thickness of the TA muscle was measured by ultrasonography in the four different toe and ankle postures: 1. Ankle dorsiflexion with all toe extension and ankle inversion (ITEDF); 2. Ankle dorsiflexion with all toe flexion and ankle inversion (ITFDF); 3. Ankle dorsiflexion with all toe extension and neutral position (NTEDF); 4. Ankle dorsiflexion with all toe flexion and neutral position (NTFDF). One-way repeated analysis of variance (ANOVA) and Bonferroni correction were used to confirm the significant difference among conditions. The level of statistical significance was set at α = 0.01. @*Results@#TA muscle thickness with ITFDF was significantly greater than in any other ankle positions, including ITEDF, NTFDF, and NTEDF (p < 0.01). @*Conclusion@#Among the four toe and ankle postures, isometric contraction in ITFDF postures showed the greatest increase in thickness of TA rather than ITEDF, NTEDF, and NTFDF postures. Based on these results, ITFDF can be recommended in an efficient way to selectively strengthen TA muscle.

COX-2 Inhibitor Use as an Early Treatment Option for Knee Osteoarthritis Patients in Korea:A Population-Based Cross-Sectional Study

Background@#To investigate the use of cyclooxygenase-2 (COX-2) inhibitors as an initial drug treatment for knee osteoarthritis (OA) patients. @*Methods@#From 2013 to 2015, patients with knee OA were identified from the Korean nationwide claims database. Among them, we extracted incident cases of knee OA to identify the initial drug treatment. Trends in the use of non-steroid anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors were analyzed during the first year after their diagnosis. Associated factors for COX-2 inhibitor use were examined using a multivariate logistic regression model. @*Results@#We identified 2,857,999 incident knee OA patients (955,259 in 2013, 981,314 in 2014, and 921,426 in 2015). The mean ± standard deviation age of patients was 64.2 ± 9.8 years. The frequency of COX-2 inhibitor use as initial treatment increased from 3.5% in 2013 to 7.2% in 2015 (P < 0.01). In patients taking the medication regularly for one year after diagnosis (medication possession ratio ≥ 50%), COX-2 inhibitor use also rapidly increased from 5.5% in 2013 to 11.1% in 2015 (P < 0.01). However, the frequencies of non-selective NSAID and analgesic use did not decrease remarkably. Factors associated with patients using COX-2 inhibitors on initial drug treatment were older age (odds ratio [OR], 1.08), female (OR, 1.24), and comorbidity (OR, 1.03). Type of institution, physician speciality, and insurance type of patients were also associated. @*Conclusion@#In Korea, COX-2 inhibitors have rapidly increased as an initial treatment for knee OA patients, but it has not appeared to reduce the use of non-selective NSAIDs and analgesics.

Radiologically Suspected Organizing Pneumonia in a Patient Recovering from COVID-19: A Case Report / 감염과화학요법

We report a case of coronavirus disease 2019 (COVID-19)-associated radiologically suspected organizing pneumonia with repeated negative Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) results from nasopharyngeal swab and sputum samples, but positive result from bronchoalveolar lavage fluid. Performing SARS-CoV-2 RT-PCR in upper respiratory tract samples only could fail to detect COVID-19-associated pneumonia, and SARS-CoV-2 could be an etiology of radiologically suspected organizing pneumonia.

Recurrent L3 Chordoma Presented as Intradural Extramedullary Mass With Distant Metastasis: A Case Report

Here, we report a rare case of L3 chordoma progressed to an intradural extramedullary (IDEM) mass and distant metastasis to the fascia lata. A 64-year old female patient presented to a local university hospital due to back pain and received excisional biopsy for a L3 destructive bony lesion. Local radiation therapy was initially administered, assuming a malignancy of unknown origin, but she developed cerebrospinal fluid leakage during adjuvant radiation therapy, which was managed by wound revision and lumbar drainage. As the destructive lesion progressed, she visited our hospital for a second opinion 3 months after the biopsy. After review of outside pathology, we diagnosed the lesion to be a chordoma, and performed a L3 corpectomy with cage and plate fixation. One and a half years later, positron emission tomography and computed tomography (PET-CT) revealed a right tensor fascia lata hypermetabolic lesion. Excisional biopsy confirmed a distant metastasis of the chordoma. One year later, she complained of L2 radiating pain. PET-CT and CT myelogram revealed an IDEM lesion. Surgical excision confirmed the transdural invasion of the chordoma. To our knowledge, this is the first report of an iatrogenic IDEM invasion and distant metastasis to the tensor of the fascia lata by a L3 chordoma.

Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group / Journal of the Korean Cancer Association, 대한암학회지

Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

Prescription Patterns for Bipolar Disorder in Asian Countries:Findings from Research on Asian Prescription Pattern-Bipolar Disorder

Objective@#Pharmacotherapy including mood stabilizers and antipsychotics are frequently used in bipolar disorder (BD); however, the lack of consensus regarding the definition of polypharmacy hinders conducting comparative studies across different settings and countries. Research on Asian Prescription Pattern (REAP) is the largest and the longest lasting international collaborative research in psychiatry in Asia. The objective of REAP BD was to investigate the prescription patterns of psychotropic medications across Asian countries. The rates of polypharmacy and psychotropic drug load were also analyzed. @*Methods@#The data collection was web-based. Prescription patterns were categorized as (1) mood stabilizer monotherapy: one mood stabilizer; (2) antipsychotic monotherapy: one antipsychotic; (3) simple polypharmacy: one mood stabilizer and one antipsychotic; and (4) complex polypharmacy: ≥ 2 mood stabilizers or/and antipsychotics. The psychotropic drug load in each patient was calculated using the defined daily dose method. @*Results@#Among 2003 patients with BD (52.1% female, 42.4 years) from 12 countries, 1,619 (80.8%) patients received mood stabilizers, 1,644 (82.14%) received antipsychotics, and 424 (21.2%) received antidepressants, with 14.7% mood stabilizer monotherapy, 13.4% antipsychotic monotherapy, 48.9% simple polypharmacy, 20.3% complex polypharmacy, and 2.6% other therapy. The average psychotropic drug load was 2.05 ± 1.40. Results varied widely between countries. @*Conclusion@#Over 70% of psychotropic regimens involved polypharmacy, which accords with the high prevalence of polypharmacy in BD under a permissive criterion (2 or more core psychotropic drugs) worldwide. Notably, ≥ 80% of our sample received antipsychotics, which may indicate an increasing trend in antipsychotic use for BD treatment.

Comparative pharmacokinetics between two tablets of tramadol 37.5 mg/acetaminophen 325 mg and one tablet of tramadol 75 mg/acetaminophen 650 mg for extended-release fixed-dose combination

An extended-release (ER) fixed-dose combination (FDC) of tramadol 37.5 mg/acetaminophen 325 mg was developed due to the demand for varying dosages. This study aimed to evaluate the pharmacokinetics (PKs) for two tablets of the new developed tramadol 37.5 mg/acetaminophen 325 mg ER FDC (DW-0920, Wontran Semi ER®) as test formulation compared to one tablet of the tramadol 75 mg/acetaminophen 650 mg ER FDC (DW-0919, Wontran ER®) as reference formulation. A randomized, open-label, 2-way crossover study was conducted in 30 healthy subjects. Subjects were orally administered one of 2 formulations followed by an alternate formulation with a 7-day washout period. Blood samples were collected up to 36 hours post-dose. Plasma concentrations of tramadol and acetaminophen were determined using a validated high-performance liquid chromatography with tandem mass spectrometric method. The geometric mean ratios (GMRs) and their 90% confidence intervals (90% CIs) of test formulation to reference formulation were calculated for the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from zero to the last measurable time point (AUClast). The PK profiles of 2 formulations were comparable. The GMRs (90% CI) of Cmax and AUClast for tramadol were 1.086 (1.047–1.127) and 1.008 (0.975–1.042), respectively. The corresponding values for acetaminophen were 0.956 (0.897–1.019) and 0.986 (0.961–1.011), respectively. All the values were within the bioequivalence range of 0.80–1.25. Two tablets of DW-0920 were comparable to one tablet of DW-0919. The DW-0920 may be used for optimal pharmacotherapy for pain control with a lower dose.

Assessment of the Synergistic Effect of Seven Antimicrobial Combinations on Extensively DrugResistant Acinetobacter baumannii Strains / 대한임상미생물학회지

Background@#To solve the difficulty in determining the appropriate treatment regimen for patients infected with extensively drug-resistant Acinetobacter baumannii (XDRAB), it is necessary to develop various strategies to increase the therapeutic effect of antimicrobial agents. The purpose of this study was to select the treatment combination showing the greatest antimicrobial effect among seven candidate antimicrobial substances. @*Methods@#Seven strains of XDRAB were used in this study. The composition of the treatment consisted of colistin as the base and one of the seven antimicrobial substances, doripenem, minocycline, tigecycline, linezolid, fusidic acid, vancomycin, or alyteserin E4K peptide. The interaction between the drugs in each combination was evaluated by measuring the synergy rates using time-kill analysis. @*Results@#The synergy rates of the seven combinations tested in the time-kill assay in this study were as follows, in descending order from the combination with the highest synergy rate: colistin + minocycline (57.1%), colistin + alyteserin E4K (50.0%), colistin + tigecycline (42.9%), colistin + vancomycin (28.6%), colistin + doripenem (14.3%), colistin + fusidic acid (14.3%), and colistin + linzolid (0%). None of the combinations showed antagonism. The three combinations showing bactericidal activity and the rates of their bactericidal activity were colistin + alyteserin E4K combination (33.3%), colistin + minocycline (14.3%), and colistin + vancomycin (14.3%). @*Conclusion@#The colistin + minocycline and colistin + alyteserin E4K treatment combinations, which showed high synergy rates, can be considered as promising candidates for future in vivo experiments evaluating combination therapies.

Intra and Inter-Rater Measurement Reliability of Tibialis Anterior Muscle (TA) Thickness using the Ultrasonography Spring Gauge Technique

Purpose@#The purpose of the current study was to determine the intra- and inter-rater reliability of muscle thickness measurement of the TA using ultrasonography (US) conducted at different inward pressures of approximately 0.5 kg, 1.0 kg, and no pressure control. @*Methods@#Twenty healthy subjects were recruited for this study. Two different examiners measured the thicknesses of the dominant TA of each subject randomly to assess the intra- and inter-rater reliability. The measurement values were analyzed using the intra-class correlation coefficient (ICC) with a 95% confidence interval, standard error of measurement, minimal detectable change, and coefficient of variance. @*Results@#All intra-rater reliability ICC values showed high reliability above 0.9. Inter-rater reliability ICC values showed high reliability above 0.9 with 0.5 and 1.0 kg of inward pressure. In contrast, Inter-rater reliability ICC values showed poor reliability (0.23) with no pressure control of inward pressure. @*Conclusion@#The findings showed that maintaining consistent inward pressure is essential for reliable results when the muscle thickness of the TA is measured by different examiners in a clinical setting.

Effect of Sedatives on In-hospital and Long-term Mortality of Critically Ill Patients Requiring Extended Mechanical Ventilation for ≥ 48 Hours

Background@#The purpose of this study was to assess the correlation between sedatives and mortality in critically ill patients who required mechanical ventilation (MV) for ≥ 48 hours from 2008 to 2016. @*Methods@#We conducted a nationwide retrospective cohort study using population-based healthcare reimbursement claims database. Data from adult patients (aged ≥ 18) who underwent MV for ≥ 48 hours between 2008 and 2016 were identified and extracted from the National Health Insurance Service database. The benzodiazepine group consisted of patients who were administered benzodiazepines for sedation during MV. All other patients were assigned to the non-benzodiazepine group. @*Results@#A total of 158,712 patients requiring MV for ≥ 48 hours were admitted in 55 centers in Korea from 2008 to 2016. The benzodiazepine group had significantly higher in-hospital and one-year mortality compared to the non-benzodiazepine group (37.0% vs. 34.3%, 55.0% vs. 54.4%, respectively). Benzodiazepine use decreased from 2008 to 2016, after adjusting for age, sex, and mean Elixhauser comorbidity index in the Poisson regression analysis (incidence rate ratio, 0.968; 95% confident interval, 0.954–0.983; P < 0.001). Benzodiazepine use, older age, lower case volume (≤ 500 cases/year), chronic kidney disease, and higher Elixhauser comorbidity index were common significant risk factors for in-hospital and oneyear mortality. @*Conclusion@#In critically ill patients undergoing MV for ≥ 48 hour, the use of benzodiazepines for sedation, older age, and chronic kidney disease were associated with higher in-hospital mortality and one-year mortality. Further studies are needed to evaluate the impact of benzodiazepines on the mortality in elderly patients with chronic kidney disease requiring MV for ≥ 48 hours.

Nanoparticles: Weighing the Pros and Cons from an Eco-genotoxicological Perspective

The exponential growth of nanotechnology and the industrial production have raised concerns over its impact on human and environmental health and safety (EHS). Although there has been substantial progress in the assessment of pristine nanoparticle toxicities, their EHS impacts require greater clarification. In this review, we discuss studies that have assessed nanoparticle eco-genotoxicity in different test systems and their fate in the environment as well as the considerable confounding factors that may complicate the results. We highlight key mechanisms of nanoparticle-mediated genotoxicity. Then we discuss the reliability of endpoint assays, such as the comet assay, the most favored assessment technique because of its versatility to measure low levels of DNA strand breakage, and the micronucleus assay, which is complementary to the former because of its greater ability to detect chromosomal DNA fragmentation. We also address the current recommendations on experimental design, including environmentally relevant concentrations and suitable exposure duration to avoid false-positive or -negative results. The genotoxicity of nanoparticles depends on their physicochemical features and the presence of co-pollutants. Thus, the effect of environmental processes (e.g., aggregation and agglomeration, adsorption, and transformation of nanoparticles) would account for when determining the actual genotoxicity relevant to environmental systems, and assay procedures must be standardized. Indeed, the engineered nanoparticles offer potential applications in different fields including biomedicine, environment, agriculture, and industry. Toxicological pathways and the potential risk factors related to genotoxic responses in biological organisms and environments need to be clarified before appropriate and sustainable applications of nanoparticles can be established.

Anticancer Activity of Indeno1,2-b-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.