Critical Care Experience Shapes Respiratory Therapists' Attitudes toward Death: A Survey Study.

Respiratory therapists (RTs) frequently encounter death in their work with critically ill patients. Healthcare providers' attitudes toward death significantly affect their approach to caring for dying patients; however, there is a lack of knowledge on RTs' attitudes toward death. This study examines how the work environment and personal characteristics of RTs influence their attitudes toward death. Utilizing the Death Attitude Profile-Revised-Chinese questionnaire, a cross-sectional survey compared non-critical care RTs (non-CCRTs, N = 86) to critical care RTs (CCRTs, N = 85). Non-CCRTs displayed significantly lower scores in overall acceptance of death compared to CCRTs (p = 0.015) and a tendency to actively avoid thoughts about death (p = 0.005). CCRTs scored higher in "neutral acceptance" (p = 0.015), and non-CCRTs exhibited higher scores on items reflecting a negative attitude toward death. RTs with shorter professional tenures showed heightened fear of death and avoidance tendencies. Perception of life and death education correlated with higher "fear of death" and "death avoidance" scores (p = 0.001). The findings indicate that CCRTs demonstrate a more neutral acceptance of death. Additionally, experience, sex, mental health status, and life-death education exposure significantly influence RTs' attitudes toward death.

Optimizing intubation technique using a single-use video laryngoscope: A comparative study in a simulation model.

Tracheal intubation poses a high risk of infection to medical staff due to Coronavirus disease 2019 (COVID-19) highly infectious nature. To mitigate this risk, various medical devices, including video laryngoscopy, have been developed to assist intubation. This study compared conventional laryngoscopy (Macintosh) and disposable video laryngoscopes (Medcaptain VS-10s and Honestmc Laryngoscope_LA10000) in terms of their use and operation processes. We designed a questionnaire to assess the operator perception of performing intubation with the devices, and statistical analysis was performed on 50 clinical staff members from 2 hospitals who had performed intubation or had learned intubation techniques. The primary outcomes were time to glottic visualization, intubation time, intubation success rate, distance between the operator and training model, and time from glottic visualization to tube insertion. The secondary outcomes were as follows: overall laryngoscope quality, operative feel, maneuverability, ease of use, and video quality. This study showed that video laryngoscopes were superior to conventional laryngoscopes in terms of quality, operative feel, and ease of use. When LA10000 was employed, the intubation success rate was higher, and the operator risk of infection was lower because of the greater distance from the training model. However, the use of video laryngoscopes requires appropriate education and training use of the devices. This study also demonstrated that when participants viewed a simple operation video prior to using video laryngoscopes, tube insertion time was shorter. Overall, video laryngoscopy can provide a safer and more convenient option for clinical medical personnel during pandemics.

Synthesis of pentameric chlorotin carboxylate clusters for high resolution EUV photoresists under small doses.

This work reports the synthesis and characterization of a novel pentameric tin chloro cluster, (vinylSn)3Sn2Cl5O2(OH)2(t-BuCO2)6 (1), and explores its application as an efficient negative-tone photoresist in a 1 : 2 weight ratio blend with [(n-BuSn)12O14(OH)6](BF4)2 (2). Through e-beam lithography, a small high-resolution pattern (HP = 20 nm) is achieved for the blend photoresist (3) at a dose of 2080 µC cm-2. Additionally, EUV lithography demonstrates the development of a high-resolution pattern (HP = 16 nm) at an EUV dose of 70 mJ cm-2. Mechanistic studies by reflective FTIR indicate a significant decomposition of Sn-carbon and SnO2(t-Bu) moieties starting at J = 35 mJ cm-2, which is accompanied by growth of the Sn-O absorption intensity. A collapse of the cluster frameworks of clusters (1) and (2) is observed at J > 70 mJ cm-2. High-resolution X-ray photoelectron spectroscopy (HRXPS) reveals that low EUV light predominantly decomposes Sn-butyl and Sn-Cl bonds. As EUV doses increase, primary photolytic reactions involve cleavage of Sn-butyl, Sn-O2CBut, and Sn-vinyl bonds. Notably, the photolytic decomposition of Sn-Cl bonds is distinctive, with only two out of five bonds being cleaved, even at high EUV doses, resulting in a break in film growth at J = 27-35 mJ cm-2 in the EUV contrast curve. Moreover, HRXPS analysis suggests that radical propagation on the vinyltin end of the blend is unlikely, providing concise mechanistic insights into the photochemical processes governing the behavior of this advanced photoresist.

Effect of Interrupting Heated Humidification on Nebulized Drug Delivery Efficiency, Temperature, and Absolute Humidity During Mechanical Ventilation: A Multi-Lab In Vitro Study.

Introduction: During mechanical ventilation (MV), inspired gases require heat and humidification. However, such conditions may be associated with reduced aerosol delivery efficiency. The practice of turning off heated humidification before nebulization and the impact of nebulization on humidity in a dry ventilator circuit remain topics of debate. This study aimed to assess the effect of turning off heated humidification on inhaled dose and humidity with nebulizer use during adult MV. Methods: A bronchodilator (albuterol) and two antibiotics (Colistimethate sodium and Amikacin sulfate) were nebulized with a vibrating mesh nebulizer placed at the humidifier inlet and in the inspiratory limb at the Y-piece. Additionally, albuterol was nebulized using a jet nebulizer in both placements. Aerosol particle size distribution was determined through a cascade impactor. Absolute humidity (AH) and temperature of inspired gases were determined with anemometer/hygrometers before, during, and after nebulization, before, during, and up to 60 minutes after interrupting active humidification. Aerosol collected on a filter distal to the endotracheal tube and on impactor stages were eluted and assayed by spectrophotometry. Results: The inhaled dose was greater when both nebulizers were placed at the humidifier inlet than the inspiratory limb at the Y-piece. Irrespective of the nebulizer types and placements, the inhaled dose either decreased or showed no significant change after the humidifier was turned off. The aerosol particle size ranged from 1.1 to 2.7 µm. With interruption of active humidification, humidity of inspired gas quickly dropped below recommended levels, and nebulization in dry ventilator circuit produced an AH between 10 and 20 mgH2O/L, lower than the recommended minimum of 30 mgH2O/L. Conclusion: Interrupting active humidification during MV before nebulization did not improve aerosol delivery efficiency for bronchodilator or antibiotics, but did reduce humidity below recommended levels.

Modified three-layer vesicourethral reconstruction in robot-assisted radical prostatectomy can change cystography pattern and improve early recovery of continence.

BACKGROUND AND OBJECTIVES: To determine early continence outcomes after three-layer vesicourethral reconstruction during robot-assisted radical prostatectomy (RARP) and the role of postoperative cystography pattern. METHODS: Between May 2015 and January 2019, a total of 170 consecutive patients with localized prostate cancer who underwent RARP, were divided into one- and three-layer groups based on the method of vesicourethral reconstruction. Continent status, preoperative, intraoperative, postoperative, clinicopathological variables, and cystography parameters were analyzed. The patients were followed up for at least 12 months. RESULTS: Of the 170 consecutive patients, 85 with one-layer vesicourethral anastomosis, and 85 with three-layer reconstruction. The continence rates immediately after catheter removal, 4, 12, and 24 weeks after RARP were 47.1%, 75.3%, 92.9%, and 98.8% in the three-layer group; compared to 15.3%, 60%, 78.8%, and 90.6% in the one-layer group, respectively. In the multivariate analysis, three-layer reconstruction was the only independent variable with a 42% risk reduction of postprostatectomy incontinence (hazard ratio (HR): 0.58, 95% confidence interval (CI) = 0.42-0.80, p = 0.001). Cystography in the three-layer group revealed less anastomotic leakage, less sharp bladder neck angle, and higher bladder neck level category. CONCLUSIONS: Three-layer anatomical reconstruction demonstrated promising early continence outcomes, and postoperative cystography revealed a specific pattern more associated with continence.

Mitochondrial Dysfunction in Chronic Obstructive Pulmonary Disease: Unraveling the Molecular Nexus.

Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory disorder characterized by persistent airflow limitation and chronic inflammation. In recent years, the role of mitochondrial dysfunction in COPD pathogenesis has emerged as a focal point of investigation. This review endeavors to unravel the molecular nexus between mitochondrial dysfunction and COPD, delving into the intricate interplay of oxidative stress, bioenergetic impairment, mitochondrial genetics, and downstream cellular consequences. Oxidative stress, a consequence of mitochondrial dysfunction, is explored as a driving force behind inflammation, exacerbating the intricate cascade of events leading to COPD progression. Bioenergetic impairment sheds light on the systemic consequences of mitochondrial dysfunction, impacting cellular functions and contributing to the overall energy imbalance observed in COPD patients. This review navigates through the genetic landscape, elucidating the role of mitochondrial DNA mutations, variations, and haplogroups in COPD susceptibility and severity. Cellular consequences, including apoptosis, autophagy, and cellular senescence, are examined, providing insights into the intricate mechanisms by which mitochondrial dysfunction influences COPD pathology. Therapeutic implications, spanning antioxidant strategies, mitochondria-targeted compounds, and lifestyle modifications, are discussed in the context of translational research. Important future directions include identifying novel biomarkers, advancing mitochondria-targeted therapies, and embracing patient-centric approaches to redefine COPD management. This abstract provides a comprehensive overview of our review, offering a roadmap for understanding and addressing the molecular nexus between mitochondrial dysfunction and COPD, with potential implications for precision medicine and improved patient outcomes.

Roles of oxidative stress/JNK/ERK signals in paraquat-triggered hepatic apoptosis.

Paraquat (PQ), a toxic and nonselective bipyridyl herbicide, is one of the most extensively used pesticides in agricultural countries. In addition to pneumotoxicity, the liver is an important target organ for PQ poisoning in humans. However, the mechanism of PQ in hepatotoxicity remains unclear. In this study, we found that exposure of rat hepatic H4IIE cells to PQ (0.1-2 mM) induced significant cytotoxicity and apoptosis, which was accompanied by mitochondria-dependent apoptotic signals, including loss of mitochondrial membrane potential (MMP), cytosolic cytochrome c release, and changes in the Bcl-2/Bax mRNA ratio. Moreover, PQ (0.5 mM) exposure markedly induced JNK and ERK1/2 activation, but not p38-MAPK. Blockade of JNK and ERK1/2 signaling by pretreatment with the specific pharmacological inhibitors SP600125 and PD98059, respectively, effectively prevented PQ-induced cytotoxicity, mitochondrial dysfunction, and apoptotic events. Additionally, PQ exposure stimulated significant oxidative stress-related signals, including reactive oxygen species (ROS) generation and intracellular glutathione (GSH) depletion, which could be reversed by the antioxidant N-Acetylcysteine (NAC). Buffering the oxidative stress response with NAC also effectively abrogated PQ-induced hepatotoxicity, MMP loss, apoptosis, and phosphorylation of JNK and ERK1/2 protein, however, the JNK or ERK inhibitors did not suppress ROS generation in PQ-treated cells. Collectively, these results demonstrate that PQ exposure induces hepatic cell toxicity and death via an oxidative stress-dependent JNK/ERK activation-mediated downstream mitochondria-regulated apoptotic pathway.

The Benefit of Hydrogen Gas as an Adjunctive Therapy for Chronic Obstructive Pulmonary Disease.

Background and Objectives: Recent studies suggest that hydrogen gas possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. This study aimed to explore the therapeutic potential of hydrogen gas and assess its safety and tolerability in individuals with chronic obstructive pulmonary disease (COPD). Materials and Methods: Enrolled COPD patients received standard treatments along with additional hydrogen inhalation for 30 min in the morning, afternoon, and evening over a 30-day period. The assessment included changes in the COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) Dyspnea Scale, lung function, sleep quality, inflammation markers, and oxidative stress markers before and after hydrogen inhalation. Results: Six patients participated in this study. Patients 2, 3, 4, 5, and 6 demonstrated improvements in CAT scores following hydrogen gas intervention, with patients 2, 4, 5, and 6 also showing improvements in mMRC scores. Statistically, this study revealed significant improvements in CAT [15.5 (10.5-19.75) vs. 8.5 (3-13.5); p = 0.043] and mMRC scores [2.5 (1-4) vs. 2 (0-3.25); p = 0.046] before and after intervention, respectively. However, no significant differences were observed in lung function, DLCO, sleep quality, and 6 MWT before and after hydrogen therapy. CBC examination showed a significant difference in platelet count before and after treatment [247 (209.75-298.75) vs. 260 (232.75-314.5); p = 0.043], respectively, while other blood tests, inflammation markers, and oxidative stress markers did not exhibit significant differences before and after hydrogen therapy. All patients experienced no obvious side-effects. Conclusions: Adjuvant therapy with hydrogen gas demonstrated symptom improvements in specific COPD patients, and no significant adverse effects were observed in any of the patients. Hydrogen gas may also exert a modulatory effect on platelet count.

Inhibition of Autophagy Aggravates Arachis hypogaea L. Skin Extracts-Induced Apoptosis in Cancer Cells.

The skin of Arachis hypogaea L. (peanut or groundnut) is a rich source of polyphenols, which have been shown to exhibit a wider spectrum of noteworthy biological activities, including anticancer effects. However, the anticancer activity of peanut skin extracts against melanoma and colorectal cancer (CRC) cells remains elusive. In this study, we systematically investigated the cytotoxic, antiproliferative, pro-apoptotic, and anti-migration effects of peanut skin ethanolic extract and its fractions on melanoma and CRC cells. Cell viability results showed that the ethyl acetate fraction (AHE) of peanut skin ethanolic crude extract and one of the methanolic fractions (AHE-2) from ethyl acetate extraction exhibited the highest cytotoxicity against melanoma and CRC cells but not in nonmalignant human skin fibroblasts. AHE and AHE-2 effectively modulated the cell cycle-related proteins, including the suppression of cyclin-dependent kinase 4 (CDK4), cyclin-dependent kinase 6 (CDK6), phosphorylation of Retinoblastoma (p-Rb), E2F1, Cyclin A, and activation of tumor suppressor p53, which was associated with cell cycle arrest and paralleled their antiproliferative efficacies. AHE and AHE-2 could also induce caspase-dependent apoptosis and inhibit migration activities in melanoma and CRC cells. Moreover, it is noteworthy that autophagy, manifested by microtubule-associated protein light chain 3B (LC3B) conversion and the aggregation of GFP-LC3, was detected after AHE and AHE-2 treatment and provided protective responses in cancer cells. Significantly, inhibition of autophagy enhanced AHE- and AHE-2-induced cytotoxicity and apoptosis. Together, these findings not only elucidate the anticancer potential of peanut skin extracts against melanoma and CRC cells but also provide a new insight into autophagy implicated in peanut skin extracts-induced cancer cell death.

Highly hydroxylated hafnium clusters are accessible to high resolution EUV photoresists under small energy doses.

This work reports the success in accessing high-resolution negative-tone EUV photoresists without radical chain growth in the aggregation mechanism. The synthesis of a highly hydroxylated Hf6O4(OH)8(RCO2)8 cluster 3 (R = s-butyl or s-Bu) is described; its EUV performance enables high resolution patterns HP = 18 nm under only 30 mJ cm-2. This photoresist also achieves high resolution patterns for e-beam lithography. Our new photoresist design to increase hydroxide substitutions of carboxylate ligands in the Hf6O4(OH)4(RCO2)12 clusters improves the EUV resolution and also greatly reduces EUV doses. Mechanistic analysis indicates that EUV light not only enables photolytic decomposition of carboxylate ligands, but also enhances the Hf-OH dehydration. One additional advantage of cluster 3 is a very small loss of film thickness (ca. 13%) after the EUV pattern development.

Smoking cessation and influenza vaccination can reduce the healthcare burden of COPD.

INTRODUCTION: Influenza vaccination (INV) and smoking cessation (SC) have individual positive effects on COPD, but their synergistic impact has yet to be extensively studied. This retrospective study aimed to assess the combined effect of SC and IV on the medical burden of COPD, including medical visits, hospitalization, medical expenses, and the occurrence of respiratory failure. METHODS: Patients with COPD who visited our medical center between January and October 2018 were included in the study. The patients were categorized into four groups: Group I (no SC or INV), Group II (INV only), Group III (SC only), and Group IV (both SC and INV). The outcomes analyzed were emergency utilization, hospital utilization, and occurrence of respiratory failure. Airflow limitation was stratified according to GOLD guidelines, and successful smoking cessation was defined as not smoking for at least one year. RESULTS: A total of 357 patients were included in the study. Group I (119 patients) neither smoking cessation nor influenza vaccination; Group II (66 patients) had only influenza vaccination; Group III (94 patients), had only smoking cessation, Group IV (78 patients), with both smoking cessation and influenza vaccination. Group IV had lower odds of emergency utilization (OR=0.13; 95% CI: 0.07-0.25), hospital utilization (OR=0.13; 95% CI: 0.05-0.30, p<0.001), and occurrence of respiratory failure (OR=0.13; 95% CI: 0.04-0.40, p<0.001). CONCLUSIONS: Combined smoking cessation and influenza vaccination are more effective in reducing the medical burden of COPD compared to either intervention alone or neither. These findings highlight the importance of promoting both smoking cessation and influenza vaccination in the management of COPD.

A human iPSC-derived hepatocyte screen identifies compounds that inhibit production of Apolipoprotein B.

Familial hypercholesterolemia (FH) patients suffer from excessively high levels of Low Density Lipoprotein Cholesterol (LDL-C), which can cause severe cardiovascular disease. Statins, bile acid sequestrants, PCSK9 inhibitors, and cholesterol absorption inhibitors are all inefficient at treating FH patients with homozygous LDLR gene mutations (hoFH). Drugs approved for hoFH treatment control lipoprotein production by regulating steady-state Apolipoprotein B (apoB) levels. Unfortunately, these drugs have side effects including accumulation of liver triglycerides, hepatic steatosis, and elevated liver enzyme levels. To identify safer compounds, we used an iPSC-derived hepatocyte platform to screen a structurally representative set of 10,000 small molecules from a proprietary library of 130,000 compounds. The screen revealed molecules that could reduce the secretion of apoB from cultured hepatocytes and from humanized livers in mice. These small molecules are highly effective, do not cause abnormal lipid accumulation, and share a chemical structure that is distinct from any known cholesterol lowering drug.

Comparison of BODE and ADO Indices in Predicting COPD-Related Medical Costs.

Background and Objectives:The ADO (age, dyspnea, and airflow obstruction) and BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) indices are often used to evaluate the prognoses for chronic obstructive pulmonary disease(COPD); however, an index suitable for predicting medical costs has yet to be developed. Materials and Methods: We investigated the BODE and ADO indices to predict medical costs and compare their predictive power. A total of 396 patients with COPD were retrospectively enrolled. Results: For hospitalization frequencies, BODE was R2 = 0.093 (p < 0.001), and ADO was R2 = 0.065 (p < 0.001); for hospitalization days, BODE was R2 = 0.128 (p < 0.001), and ADO was R2 = 0.071 (p < 0.001); for hospitalization expenses, BODE was R2 = 0.020 (p = 0.047), and ADO was R2 = 0.012 (p = 0.179). BODE and ADO did not differ significantly in the numbers of outpatient visits (BODE, R2 = 0.012, p = 0.179; ADO, R2 = 0.017, p = 0.082); outpatient medical expenses (BODE, R2 = 0.012, p = 0.208; ADO, R2 = 0.008, p = 0.364); and total medical costs (BODE, R2 = 0.018, p = 0.072; ADO, R2 = 0.016, p = 0.098). In conclusion, BODE and ADO indices were correlated with hospitalization frequency and hospitalization days. However, the BODE index exhibits slightly better predictive accuracy than the ADO index in these items.

Clinical Determinants of Extraurinary Tract Recurrence and Survival after Radical Surgery for pT2 Upper Tract Urothelial Carcinoma.

BACKGROUND: Oncologic outcomes for pT2N0M0 upper tract urothelial carcinoma (UTUC) after nephroureterectomy are not well defined, with most previous studies focused on a heterogeneous population. Therefore, we aimed to investigate the clinical determinants of extraurinary tract recurrence and survival after radical surgery in patients with localized UTUC. METHODS: We retrospectively identified 476 patients with pT2N0M0 UTUC who underwent radical nephroureterectomy or ureterectomy between October 2002 and March 2022. To evaluate the prognostic impact, patients were divided into renal pelvic, ureteral, and both-region (renal pelvis plus synchronous ureter) groups based on tumor location. The outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Associations were evaluated using multivariable Cox regression analyses for prognostic factors and Kaplan-Meier analyses for survival curves. RESULTS: The renal pelvic, ureteral, and both-region groups consisted of 151 (31.7%), 314 (66.0%), and 11 (2.3%) patients, respectively. Kaplan-Meier analyses comparing the three tumor types showed significant differences in 5-year RFS (83.6% vs. 73.6% vs. 52.5%, p = 0.013), CSS (88.6% vs. 80.7% vs. 51.0%, p = 0.011), and OS (83.4% vs. 70.1% vs. 45.6%, p = 0.002). Multivariable analyses showed that age >60 years, previous bladder cancer history, ureteral involvement (ureteral and both-regional groups), and positive surgical margins were significant negative prognostic factors for the studied outcomes. CONCLUSIONS: Patients with pT2 UTUC and presence of ureteral involvement had more frequent disease relapse. Subsequent adjuvant therapy regimens and close follow-up in patients with negative prognostic factors are warranted despite complete pathological removal of the tumor.

Chlorpyrifos induces neuronal cell death via both oxidative stress and Akt activation downstream-regulated CHOP-triggered apoptotic pathways.

Chlorpyrifos (CPF) is one of the most abundant and widely used organophosphate pesticides for agricultural, industrial, and household purposes in the world. Epidemiological studies have reported that CPF can induce neurotoxic impairments in mammalian, which is linked to an important risk factor for development of neurodegenerative diseases (NDs). However, limited information is available on CPF-induced neurotoxicity, with the underlying exact mechanism remains unclear. In this study, CPF exposure (10-400 µM) significantly reduced Neuro-2a cell viability and induced apoptotic events, including the increase in caspase-3 activity, apoptotic cell population, and cleavage of caspase-3/-7 and PARP. Exposure of Neuro-2a cells to CPF also triggered CHOP activation. Transfection with CHOP-specific siRNA markedly suppressed the expression of CHOP, and attenuated cytotoxicity and apoptotic events in CPF-exposed Neuro-2a cells. Furthermore, CPF exposure obviously evoked the phosphorylation of Akt as well as ROS generation in a time-dependent manner. Pretreatment with LY294002 (an Akt inhibitor) effectively attenuated the CPF-induced Akt phosphorylation, CHOP activation, and apoptotic events, but not that ROS production. Of note, buffering the ROS generation with antioxidant N-acetylcysteine effectively prevented the CPF-induced ROS generation, CHOP activation, and apoptotic events, but not that the Akt phosphorylation. Collectively, these findings indicate that CPF exposure exerts neuronal cytotoxicity via the independent pathways of ROS generation and Akt activation downstream-regulated CHOP-triggered apoptosis, ultimately leading to neuronal cell death.

Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease.

Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.

Involvement of AMPKα and MAPK-ERK/-JNK Signals in Docetaxel-Induced Human Tongue Squamous Cell Carcinoma Cell Apoptosis.

Cancers of the oral cavity can develop in the anatomic area extending from the lip, gum, tongue, mouth, and to the palate. Histologically, about 85-90% of oral cavity cancers are of the type squamous cells carcinomas (SCCs). The incidence of oral tongue SCC is higher in the tongue than any other anatomic area of the oral cavity. Here, we investigated the therapeutic effects and molecular mechanisms of docetaxel, which is a paclitaxel antitumor agent, on the cell growth of a human tongue SCC-derived SAS cell line. The results showed that docetaxel (10-300 nM) induced cytotoxicity and caspase-3 activity in SAS cells. Moreover, docetaxel (100 nM) promoted the expression of apoptosis-related signaling molecules, including the cleavages of caspase-3, caspase-7, and poly (ADP-ribose) polymerase (PARP). In mitochondria, docetaxel (100 nM) decreased the mitochondrial membrane potential (MMP) and Bcl-2 mRNA and protein expression and increased cytosolic cytochrome c protein expression and Bax mRNA and protein expression. In terms of mitogen-activated protein kinase (MAPK) and adenosine monophosphate-activated protein kinase (AMPK) signaling, docetaxel increased the expression of phosphorylated (p)-extracellular signal-regulated kinase (ERK), p-c-Jun N-terminal kinase (JNK), and p-AMPKα protein expression but not p-p38 protein expression. Moreover, the increase in caspase-3/-7 activity and Bax protein expression and decreased Bcl-2 protein expression and MMP depolarization observed in docetaxel-treated SAS cells could be reversed by treatment with either SP600125 (a JNK inhibitor), PD98059 (an MEK1/2 (mitogen-activated protein kinase kinase 1/2) inhibitor), or compound c (an AMPK inhibitor). The docetaxel-induced increases in p-JNK, p-ERK, and p-AMPKα protein expression could also be reversed by treatment with either SP600125, PD98059, or compound c. These results indicate that docetaxel induces human tongue SCC cell apoptosis via interdependent MAPK-JNK, MAPK-ERK1/2, and AMPKα signaling pathways. Our results show that docetaxel could possibly exert a potent pharmacological effect on human oral tongue SCC cell growth.

How Did the COVID-19 Pandemic Affect Population Mobility in Taiwan?

BACKGROUND: Coronavirus disease (COVID-19) impairs the free movement of human beings. The study aims to determine how the COVID-19 pandemic affected population mobility. METHODS: The study obtained Google COVID-19 population mobility report and e Taiwan COVID-19 pandemic information from Our World in Data. RESULTS: During the Alpha wave, transit decreased the most, with an average difference of >50%, followed by parks, workplaces, groceries, and pharmacies. During the Omicron wave, the average population flow in parks and transit decreased by about 20%. During the pre-existing wave, the average population visits of transit decreased by 10% at the most, followed by parks and workplaces. The peak of daily new confirmed cases per million (7-day rolling average) was 25.02, 6.39, and 0.81 for Alpha, Omicron, and the pre-existing wave, respectively. Daily new confirmed cases per million people correlated with the change in population visits of various places (all p < 0.001). The reproduction rate (7-day rolling average) correlated with the change of population visits of most places, except retail and recreation. We conclude the Alpha variant affected more individuals than Omicron and pre-existing type. Furthermore, changes in population visits in transit were most impacted. This change was consistent with daily new confirmed cases per million people and reproduction rate (7-day rolling average). CONCLUSION: The Alpha variant affected more individuals than the Omicron and pre-existing types. Furthermore, changes in population visits in transit locations were most impacted. This change was consistent with the daily new number of confirmed cases per million people and the 7-day rolling average reproduction rate.

Effect of abdominal weight training with and without cough machine assistance on lung function in the patients with prolonged mechanical ventilation: a randomized trial.

PURPOSE: The patients with prolonged mechanical ventilation (PMV) have the risk of ineffective coughing and infection due to diaphragm weakness. This study aimed to explore the effect of abdominal weight training (AWT) intervention with/without cough machine (CM) assistance on lung function, respiratory muscle strength and cough ability in these patients. METHODS: Forty patients with PMV were randomly assigned to three groups: AWT group (n = 12), AWT + CM group (n = 14) and control group (n = 14). Change of maximum inspiratory pressure (MIP), Maximum expiratory pressure (MEP) and peak cough flow (PCF) between 1 day before and 2 weeks after the intervention were compared among these three groups. RESULTS: MIP before and after intervention in AWT group (30.50 ± 11.73 vs. 36.00 ± 10.79; p < 0.05) and AWT + CM group (29.8 ± 12.14 vs. 36.14 ± 10.42; p < 0.05) compared with control group (28.43 ± 9.74 vs 26.71 ± 10.77; p > 0.05) was significantly improved. MEP before and after intervention in AWT group (30.58 ± 15.19 vs. 41.50 ± 18.33; p < 0.05) and AWT + CM group (27.29 ± 12.76 vs 42.43 ± 16.96; p < 0.05) compared with control group (28.86 ± 10.25 vs. 29.57 ± 14.21; p > 0.05) was significantly improved. PCF before and after intervention in AWT group in AWT group (105.83 ± 16.21 vs. 114.17 ± 15.20; p < 0.05) and AWT + CM group (108.57 ± 18.85 vs. 131.79 ± 38.96; p < 0.05) compared to control group (108.57 ± 19.96 vs. 109.86 ± 17.44; p > 0.05) showed significant improvements. AWT + CM group had significantly greater improvements than control group in MIP and peak cough flow than control group (13.71 ± 11.28 vs 19.64 ± 29.90, p < 0.05). CONCLUSION: AWT can significantly improve lung function, respiratory muscle strength, and cough ability in the PMV patients. AWT + CM can further improve their expiratory muscle strength and cough ability. Trial registration ClinicalTrials.gov registry (registration number: NCT0529538 retrospectively registered on March 3, 2022).