Association of Cough Severity with Asthma Control and Quality of Life in Patients with Severe Asthma.

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.

Synthetic ShK-like Peptide from the Jellyfish Nemopilema nomurai Has Human Voltage-Gated Potassium-Channel-Blocking Activity.

We identified a new human voltage-gated potassium channel blocker, NnK-1, in the jellyfish Nemopilema nomurai based on its genomic information. The gene sequence encoding NnK-1 contains 5408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the fifth peptide, NnK-1, which was chemically synthesized, is an effective blocker of hKv1.3, hKv1.4, and hKv1.5. Multiple-sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that three residues (3Asp, 25Lys, and 34Thr) of NnK-1, together with six cysteine residues, were conserved. Therefore, we hypothesized that these three residues are crucial for the binding of the toxin to voltage-gated potassium channels. This notion was confirmed by an electrophysiological assay with a synthetic peptide (NnK-1 mu) where these three peptides were substituted with 3Glu, 25Arg, and 34Met. In conclusion, we successfully identified and characterized a new voltage-gated potassium channel blocker in jellyfish that interacts with three different voltage-gated potassium channels. A peptide that interacts with multiple voltage-gated potassium channels has many therapeutic applications in various physiological and pathophysiological contexts.

Spillover effects of organizational support for patient and workplace safety on safety outcomes: The mediating role of safety compliance.

AIM(S): To investigate spillover effects of organizational support for patient and workplace safety on safety outcomes and to examine the mediating role of safety compliance in these relationships. DESIGN: A cross-sectional, correlational survey design. METHODS: This study analysed data from 1255 nurses in 34 Korean hospitals. A structured questionnaire was used including items from the Hospital Survey on Patient Safety Culture and Safety Compliance scales. Data were collected between February and June 2022. We employed structural equation modelling (SEM) for analysis with a significance level set at 0.05. RESULTS: Organizational support for patient and workplace safety showed direct impacts on patient and workplace safety outcomes. Findings supported our hypotheses regarding spillover effects, as organizational support for patient safety was related to enhanced workplace safety and organizational support for workplace safety was associated with improved patient safety. SEM analysis showed safety compliance's mediating role. When the distribution of serial indirect effects was examined, three out of eight indirect pathways were statistically significant. CONCLUSION: Improving organizational support for patient safety can lead to better workplace safety outcome, and enhancing support for workplace safety can result in better patient safety outcome. Given this mutually beneficial relationship, healthcare organizations should simultaneously promote safety in both areas rather than focusing on just one. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Study results highlight the need to recognize the interconnected nature of patient and workplace safety in order to achieve better overall safety outcomes. IMPACT: This study shows that organizational safety efforts for patients and workers are interconnected and mutually beneficial. The study's results have both theoretical and practical implications in demonstrating that organizational support for both patient and workplace safety plays a strong role in promoting nurses' safety compliance and improving overall safety outcomes. REPORTING METHOD: STROBE checklist. PATIENT CONTRIBUTION: No patient or public contribution.

Clinical Factors Affecting the Rate of Liver Regeneration in Living Donors after Right Hepatectomy.

Sufficient liver regeneration after a right hepatectomy is important in living donors for preventing postoperative hepatic insufficiency; however, it differs for each living donor so we investigated the clinical factors affecting the rate of liver regeneration after hepatic resection. This retrospective case-control study investigated fifty-four living donors who underwent a right hepatectomy from July 2015 to March 2023. Patients were classified into 2 groups by the remnant/total volume ratio (RTVR): Group A (RTVR < 30%, n = 9) and Group B (RTVR ≥ 30%, n = 45). The peak postoperative level of total bilirubin was more elevated in Group A than in Group B (3.0 ± 1.1 mg/dL vs. 2.3 ± 0.8 mg/dL, p = 0.046); however, no patients had hepatic insufficiency or major complications. The rates of residual liver volume (RLV) growth at Postoperative Week 1 (89.1 ± 26.2% vs. 53.5 ± 23.7%, p < 0.001) were significantly greater in Group A, and its significant predictors were RTVR (ß = -0.478, p < 0.001, variance inflation factor (VIF) = 1.188) and intraoperative blood loss (ß = 0.247, p = 0.038, VIF = 1.182). In conclusion, as the RLV decreases, compensatory liver regeneration after hepatic resection becomes more prominent, resulting in comparable operative outcomes. Further studies are required to investigate the relationship between hematopoiesis and the rate of liver regeneration.

Revisiting the impact of clinicopathologic characteristics in PD-L1 profile in a large cohort of non-small cell lung cancer.

Background: Immunotherapies using anti-programmed cell death ligand-1 (PD-L1) agents have recently shown remarkable outcomes in patients with non-small cell lung cancer (NSCLC). However, there was a poor correlation between PD-L1 expression and treatment response. Many researchers have focused on the clinicopathological factors associated with prognosis, but the results are conflicting. In the present study, we investigated the clinicopathological significance of PD-L1 overexpression in NSCLC cells. Methods: In total, 344 NSCLC cases with PD-L1 assays were retrospectively analyzed. PD-L1 expression was evaluated via immunohistochemical staining using antibodies against SP263 and SP142. The correlation between clinicopathological factors and PD-L1 expression was analyzed for various clinicopathological features. Results: PD-L1 expression significantly correlated with several poor clinicopathological factors, including the solid component of adenocarcinoma, lymphatic invasion, and recurrence. Squamous cell carcinoma, older age, and male sex were also associated with PD-L1 expression. However, we could not observe correlation between PD-L1 expression and disease-free survival (DFS). A novel finding was that lower metastasis was associated with high PD-L1 expression of SP142 in tumor-infiltrating immune cells (ICs). Conclusions: PD-L1 expression in NSCLC is associated with adverse clinicopathological features and recurrence; therefore, it could be utilized to predict poor prognosis. Furthermore, the high PD-L1 expression of SP142 in tumor-infiltrating ICs could be a potential marker for low metastasis.

Practice guidelines for managing extrahepatic biliary tract cancers.

Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Selective omission of sentinel lymph node biopsy in mastectomy for ductal carcinoma in situ: identifying eligible candidates.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited. METHODS: We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis. RESULTS: Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18-137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06-41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7-2.3%) experienced axillary lymph node metastasis. CONCLUSIONS: Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.

Effects of workplace incivility and workload on nurses' work attitude: The mediating effect of burnout.

AIM: The study's aim was to examine how workplace incivility and workload influence nurses' work attitudes (turnover intention, job satisfaction, and organizational commitment) using the stress-strain-outcome framework. BACKGROUND: There is a lack of comprehensive research on the combined effects of workplace incivility and workload on nurses' work attitudes. INTRODUCTION: Two workplace stressors, incivility and workload, were hypothesized to lead to burnout, which in turn influences nurses' work attitudes. METHODS: A cross-sectional, descriptive correlational study was conducted. Survey data were collected from 1,255 direct care nurses with a minimum of 6 months' nursing experiences in 34 general hospitals across Korea. Structural equation modeling was used to test the hypothesized model. This study is reported using the STROBE checklist. RESULTS: As hypothesized, both workplace incivility and workload increased burnout. Heightened burnout correlated with increased turnover intention, lowered job satisfaction, and reduced organizational commitment. While workplace incivility impacted these outcomes both directly and indirectly via its effect on burnout, workload influenced the outcomes solely through burnout. CONCLUSION: The study's findings are based on one, nonrandomized sample of nurses working at South Korean hospitals. Despite such study limitations, the study findings support the adverse impact of two workplace stressors on burnout and nurses' work attitudes. IMPLICATIONS FOR NURSING: Evidence-informed interventions for both workplace stressors include training programs, clear policy guidelines, open communication channels, and supportive work environments. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Zero tolerance and equity, diversity and inclusivity policies to promote workplace civility must be enforced. Workload needs to be patient-centered, ensuring a "fit" between patient needs and nurse staffing.

Effects of nurse managers' inclusive leadership on nurses' psychological safety and innovative work behavior: The moderating role of collectivism.

INTRODUCTION: In the rapidly evolving healthcare landscape, the capacity to foster innovative work behavior among nurses is increasingly important. This study examined the dynamics between inclusive leadership, psychological safety, collectivism, and innovative work behavior among nurses. DESIGN: The study used a cross-sectional, correlational design. METHODS: This study utilized data from 730 medical-surgical nurses who provided direct care to patients. Standardized instruments were used to assess key study variables. Statistical analyses, including moderated mediation regressions, were employed to investigate the complex interplay among these variables. RESULTS: We found a positive association between inclusive leadership and innovative work behavior, and psychological safety mediated this relationship. Collectivism moderated inclusive leadership's direct relationship with psychological safety and its indirect relationship with innovative work behavior. The results revealed that nurses with lower levels of collectivism were more responsive to their managers' inclusive behaviors, strengthening the relation between inclusive leadership, psychological safety, and innovative work behavior. CONCLUSION: Our findings suggest that promoting inclusive leadership behaviors among nurse managers to create a psychologically safe environment can motivate nurses to engage in innovative work behavior. However, it is also important to understand that the effectiveness of leadership may differ depending on the collectivist values of individual nurses. CLINICAL RELEVANCE: Nurse managers should adopt inclusive leadership behaviors, such as valuing trust, open communication, and diversity, in order to foster psychological safety and innovative work behavior among nurses.

Glycemic Control and Retinal Microvascular Changes in Type 2 Diabetes Mellitus Patients without Clinical Retinopathy.

Background: To investigate the association of glycemic control and retinal microvascular changes in patients with type 2 diabetes mellitus (T2DM) without diabetic retinopathy (DR). Methods: This retrospective, observational, cohort study included patients with T2DM without DR. The patients were categorized into intensive control (IC; mean glycosylated hemoglobin [HbA1c] ≤7.0%) and moderate control (MC; mean HbA1c >7.0%) groups. Optical coherence tomography (OCT) and swept-source OCT angiography (OCTA) image parameters were compared between three groups, including healthy controls. Results: In total, 259 eyes of 259 participants (88 IC, 81 MC, and 90 controls) were included. The foveal avascular zone area was significantly larger in the MC group than IC and control groups (all P<0.05). The IC group had lower vessel density in the superficial retinal layer and deep retinal layer than the controls (all P<0.05). The choriocapillaris (CC) flow deficit (FD) was significantly greater in the MC group than in the IC and control groups (18.2%, 16.7%, and 14.2%, respectively; all P<0.01). In multivariate regression analysis, CC-FD was associated with the mean HbA1c level (P=0.008). There were no significant differences in OCT parameters among the groups. Conclusion: OCTA revealed that early CC impairment is associated with HbA1c levels; the CC changes precede clinically apparent DR. The OCTA parameters differed among the groups according to the degree of glycemic control. Our results suggest that microvascular changes precede DR and are closely related to glycemic control.

Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study.

PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.

Efficacy of Filter Trocar for Clear Visualization during Laparoscopic Cholecystectomy: A Prospective Randomized Controlled Trial.

Filter trocar designed to eliminate harmful smoke is also regarded as effective for improving surgical visualization. The aim of this study is to evaluate the efficacy of filter trocar in maintaining clear operative view. From 2019 to 2020, 100 patients underwent laparoscopic cholecystectomy and they were randomized to either the control or filter group. The primary end point was a laparoscopic operative view score (1, clear; 2, slightly blurry; 3, completely blurry) during gallbladder dissection from the liver bed when dissection was started (LV1), when dissection was half completed (LV2) and when dissection was completed (LV3). Between the control and filter groups, there were no significant differences in mean LV1 (1.44 vs. 1.40, p = 0.234) and LV3 (1.86 vs. 2.01, p = 0.880). There was no significant difference in the mean duration of suction after dissection (3.82 s vs. 3.67 s, p = 0.097) and the mean number of laparoscope removals from inside to outside the body to clean during gallbladder dissection from the liver bed (0.55 vs. 0.22, p = 0.963) or the mean amount of time required to dissect the gallbladder from the liver bed (221.58 s vs. 177.09 s, p = 0.253). The study demonstrated that filter trocar is not as effective as expected in the maintenance of clear operative view. Further study is needed to develop devices to improve clear surgical visualization.

An Emerging Role of Micro- and Nanoplastics in Vascular Diseases.

Vascular diseases are the leading causes of death worldwide, and they are attributable to multiple pathologies, such as atherosclerosis, diabetes, and chronic obstructive pulmonary disease. Exposure to various environmental contaminants is associated with the development of various diseases, including vascular diseases. Among environmental contaminants, micro- and nanoplastics have gained attention as global environmental risk factors that threaten human health. Recently, extensive research has been conducted on the effects of micro- and nanoplastics on various human diseases, including vascular diseases. In this review, we highlight the effects of micro- and nanoplastics on vascular diseases.

Monovalent ion-graphene oxide interactions are controlled by carboxylic acid groups: Sum frequency generation spectroscopy studies.

Graphene oxide (GO) is a two-dimensional, mechanically strong, and chemically tunable material for separations. Elucidating GO-ion-water interactions at the molecular scale is highly important for predictive understanding of separation systems. However, direct observations of the nanometer region by GO surfaces under operando conditions are not trivial. Therefore, thin films of GO at the air/water interface can be used as model systems. With this approach, we study the effects of alkali metal ions on water organization near graphene oxide films at the air/water interface using vibrational sum frequency generation (SFG) spectroscopy. We also use an arachidic acid Langmuir monolayer as a benchmark for a pure carboxylic acid surface. Theoretical modeling of the concentration-dependent sum frequency signal from graphene oxide and arachidic acid surfaces reveals that the adsorption of monovalent ions is mainly controlled by the carboxylic acid groups on graphene oxide. An in-depth analysis of sum frequency spectra reveals at least three distinct water populations with different hydrogen bonding strengths. The origin of each population can be identified from concentration dependent variations of their SFG signal. Interestingly, an interfacial water structure seemed mostly insensitive to the character of the alkali cation, in contrast to similar studies conducted at the silica/water interface. However, we observed an ion-specific effect with lithium, whose strong hydration prevented direct interactions with the graphene oxide film.

Chitosan-Based Structural Color Films for Humidity Sensing with Antiviral Effect.

This scientific investigation emphasizes the essential integration of nature's influence in crafting multifunctional surfaces with bio-inspired designs for enhanced functionality and environmental advantages. The study introduces an innovative approach, merging color decoration, humidity sensing, and antiviral properties into a unified surface using chitosan, an organo-biological polymer, to create cost-effective multilayered films through sol-gel deposition and UV photoinduced deposition of metal nanoparticles. The resulting chitosan films showcase diverse structural colors and demonstrate significant antiviral efficiency, with a 50% and 85% virus inhibition rate within a rapid 20 min reaction, validated through fluorescence cell expression and real-time qPCR (polymerase chain reaction) assays. Silver-deposited chitosan films further enhance antiviral activity, achieving remarkable 91% and 95% inhibition in independent assays. These films exhibit humidity-responsive color modifications across a 25-90% relative humidity range, enabling real-time monitoring validated through simulation studies. The proposed three-in-one functional surface can have versatile applications in surface decoration, medicine, air conditioning, and the food industry. It can serve as a real-time humidity sensor for indoor and outdoor surfaces, find use in biomedical devices for continuous humidity monitoring, and offer antiviral protection for frequently handled devices and tools. The customizable colors enhance visual appeal, making it a comprehensive solution for diverse applications.

Current Smoking Status Is Not a Risk Factor for Perioperative Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage Who Underwent Craniotomy Repair.

BACKGROUND: Aneurysmal subarachnoid hemorrhage is a rupture leading to blood accumulating in the subarachnoid region. Smoking status is often a risk factor for postoperative complications for vascular procedures. This study aims to retrospectively examine the effect of being a current tobacco smoker on postoperative outcomes in patients with nontraumatic subarachnoid hemorrhage. METHODS: Patients with aneurysmal subarachnoid hemorrhage who underwent craniotomy were identified in the American College of Surgeons-National Surgical Quality Improvement Program database. The 30-day perioperative outcomes of current smokers were compared with those of control individuals, who were patients who had not smoked tobacco in the past year. Postoperative outcomes included death, cardiac complications, stroke, operation time >4 hours, bleeding, and other events. In addition, this study examined the same surgical outcomes in patients older than 65 years. RESULTS: We found no significant difference between these 2 groups across all adverse outcomes analyzed. In patients aged >65 years, we again found no significant differences between these 2 groups across all adverse outcomes analyzed. CONCLUSIONS: This study shows that although current tobacco smoker status is commonly a risk factor for vascular diseases and postoperative complications, it is not a risk factor for the postoperative variables that we analyzed during craniotomy for aneurysmal subarachnoid hemorrhage. Additional research should be conducted to determine if different procedures to treat aneurysmal subarachnoid hemorrhage may have different outcomes among smokers.

PA2G4/EBP1 ubiquitination by PRKN/PARKIN promotes mitophagy protecting neuron death in cerebral ischemia.

Cerebral ischemia induces massive mitochondrial damage, leading to neuronal death. The elimination of damaged mitochondria via mitophagy is critical for neuroprotection. Here we show that the level of PA2G4/EBP1 (proliferation-associated 2G4) was notably increased early during transient middle cerebral artery occlusion and prevented neuronal death by eliciting cerebral ischemia-reperfusion (IR)-induced mitophagy. Neuron-specific knockout of Pa2g4 increased infarct volume and aggravated neuron loss with impaired mitophagy and was rescued by introduction of adeno-associated virus serotype 2 expressing PA2G4/EBP1. We determined that PA2G4/EBP1 is ubiquitinated on lysine 376 by PRKN/PARKIN on the damaged mitochondria and interacts with receptor protein SQSTM1/p62 for mitophagy induction. Thus, our study suggests that PA2G4/EBP1 ubiquitination following cerebral IR-injury promotes mitophagy induction, which may be implicated in neuroprotection.Abbreviations: AAV: adeno-associated virus; ACTB: actin beta; BNIP3L/NIX: BCL2 interacting protein 3 like; CA1: Cornu Ammonis 1; CASP3: caspase 3; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; DMSO: dimethyl sulfoxide; PA2G4/EBP1: proliferation-associated 2G4; FUNDC1: FUN14 domain containing 1; IB: immunoblotting; ICC: immunocytochemistry; IHC: immunohistochemistry; IP: immunoprecipitation; MCAO: middle cerebral artery occlusion; MEF: mouse embryonic fibroblast; OGD: oxygen-glucose deprivation; PRKN/PARKIN: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced kinase 1; RBFOX3/NeuN: RNA binding fox-1 homolog 3; SQSTM1/p62: sequestosome 1; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; TUBB: tubulin beta class I; WT: wild-type.

Piperine improves the quality of porcine oocytes by reducing oxidative stress.

Oxidative stress caused by light and high temperature arises during in vitro maturation (IVM), resulting in low-quality embryos compared with those obtained in vivo. To overcome this problem, we investigated the influence of piperine (PIP) treatment during maturation of porcine oocytes on subsequent embryo development in vitro. Porcine oocytes were cultured in IVM medium supplemented with 0, 50, 100, 200, or 400 µM PIP. After parthenogenetic activation, the blastocyst (BL) formation was significantly higher and the apoptosis rate was significantly lower using 200 µM PIP-treated oocytes (200 PIP). In the 200 PIP group, the level of reactive oxygen species at the metaphase II stage was decreased, accompanied by an increased level of glutathione and increased expression of antioxidant processes (Nrf2, CAT, HO-1, SOD1, and SOD2). Consistently, chromosome misalignment and aberrant spindle organization were alleviated and phosphorylated p44/42 mitogen-activated protein kinase activity was increased in the 200 PIP group. Expression of development-related (CDX2, NANOG, POU5F1, and SOX2), anti-apoptotic (BCL2L1 and BIRC5), and pro-apoptotic (BAK, FAS, and CASP3) processes was altered in the 200 PIP group. Ultimately, embryo development was improved in the 200 PIP group following somatic cell nuclear transfer. These findings suggest that PIP improves the quality of porcine oocytes by reducing oxidative stress, which inevitably arises via IVM. In-depth mechanistic studies of porcine oocytes will improve the efficiencies of assisted reproductive technologies.

Ellagic acid treatment during in vitro maturation of porcine oocytes improves development competence after parthenogenetic activation and somatic cell nuclear transfer.

Ellagic acid (EA) is a natural polyphenol and a free radical scavenger with antioxidant properties. This study investigated the protective effects of EA during in vitro maturation (IVM) of porcine oocytes. To determine the optimal concentration, IVM medium was supplemented with various concentrations of EA. Treatment with 10 µM EA (10 EA) resulted in the highest cleavage rate, blastocyst formation rate, and total cell number per blastocyst and the lowest percentage of apoptotic cell in parthenogenetic blastocysts. In the 10 EA group, abnormal spindle and chromosome misalignment were rescued and the ratio of phosphorylated p44/42 to total p44/42 was increased. Furthermore, the reactive oxygen species and glutathione levels were significantly decreased and increased, respectively, and antioxidant genes (Nrf2, HO-1, CAT, and SOD1) were significantly upregulated in the 10 EA group. mRNA expression of developmental-related (CDX2, POU5F1, and SOX2) and anti-apoptotic (BCL2L1) genes was significantly upregulated in the 10 EA group, while mRNA expression of pro-apoptotic genes (BAK, FAS, and CASP3) was significantly downregulated. Ultimately, following somatic cell nuclear transfer, the blastocyst formation rate was significantly increased and the percentage of apoptotic cell in blastocysts was significantly decreased in the 10 EA group. In conclusion, addition of 10 EA to IVM medium improved oocyte maturation and the subsequent embryo development capacity through antioxidant mechanisms. These findings suggest that EA can enhance the efficiencies of assisted reproductive technologies.

Voice, silence, perceived impact, psychological safety, and burnout among nurses: A structural equation modeling analysis.

BACKGROUND: The organizational studies' literature suggests that employees' expressions of voice and silence may be distinct concepts with different predictors. Organizational researchers also argue that both employees' voice and silence are related to burnout; however, these relationships have not been adequately examined in the healthcare context. OBJECTIVE: This study aimed to investigate the relationships among nurses' perceived impact, psychological safety, voice behaviors, and burnout using a theoretical model. Voice behaviors were conceptualized as voice and silence. DESIGN: A cross-sectional, correlational study design was employed. SETTINGS: Study data were collected in 34 general hospitals in South Korea. PARTICIPANTS: A total of 1255 registered nurses providing direct care to patients were included in this study. METHODS: Using a convenience sampling method, a web-based survey was conducted to obtain data. All variables were measured using standardized instruments. A structural equation modeling analysis was employed to test a hypothesized model positing that perceived impact and psychological safety have both direct and indirect effects on nurse burnout through voice and silence. The response rate was 72.8 %. RESULTS: The findings supported the hypothesized model. Both perceived impact and psychological safety were positively related to expressions of voice, but both were negatively associated with silence. We also found that perceived impact was more strongly associated with voice than with silence, while psychological safety had a stronger impact on silence than on voice. Furthermore, voice reduced burnout, while silence increased it. Finally, perceived impact reduced burnout through voice (ß = -0.10, 95 % confidence interval [-0.143, -0.059]) and silence (ß = -0.04, 95 % confidence interval [-0.058, -0.014]), and psychological safety also decreased burnout through voice (ß = -0.04, 95 % confidence interval [-0.057, -0.016]) and silence (ß = -0.07, 95 % confidence interval [-0.101, -0.033]). Additional analyses revealed that prohibitive voice and silence significantly mediated the associations between psychological safety and burnout and perceived impact and burnout, but the mediating role of promotive voice was not statistically significant. CONCLUSIONS: It is important to recognize that voice and silence are distinct concepts. Moreover, to reduce nurse burnout, nurse managers and hospital administrators should develop separate strategies for promoting nurses' perceived impact and psychological safety, as their influences on voice and silence differ. REGISTRATION: Not applicable. TWEETABLE ABSTRACT: Voice and silence both influence nurse burnout. Separate strategies should be applied to voice and silence, as they are different concepts.