Short-chain fatty acid butyrate against TMAO activating endoplasmic-reticulum stress and PERK/IRE1-axis with reducing atrial arrhythmia.

INTRODUCTION: The accumulation of microbiota-derived trimethylamine N-oxide (TMAO) in the atrium is linked to the development and progression of atrial arrhythmia. Butyrate, a major short-chain fatty acid, plays a crucial role in sustaining intestinal homeostasis and alleviating systemic inflammation, which may reduce atrial arrhythmogenesis. OBJECTIVES: This study explored the roles of butyrate in regulating TMAO-mediated atrial remodeling and arrhythmia. METHODS: Whole-cell patch clamp experiments, Western blotting, and immunocytochemistry were used to analyze electrical activity and signaling, respectively, in TMAO-treated HL-1 atrial myocytes with or without sodium butyrate (SB) administration. Telemetry electrocardiographic recording and echocardiography and Masson's trichrome staining and immunohistochemistry were employed to examine atrial function and histopathology, respectively, in mice treated with TMAO with and without SB administration. RESULTS: Compared with control cells, TMAO-treated HL-1 myocytes exhibited reduced action potential duration (APD), elevated sarcoplasmic reticulum (SR) calcium content, larger L-type calcium current (ICa-L), increased Na+/Ca2+ exchanger (NCX) current, and increased potassium current. However, the combination of SB and TMAO resulted in similar APD, SR calcium content, ICa-L, transient outward potassium current (Ito), and ultrarapid delayed rectifier potassium current (IKur) compared with controls. Additionally, TMAO-treated HL-1 myocytes exhibited increased activation of endoplasmic reticulum (ER) stress signaling, along with increased PKR-like ER stress kinase (PERK)/IRE1α axis activation and expression of phospho-IP3R, NCX, and Kv1.5, compared with controls or HL-1 cells treated with the combination of TMAO and SB. TMAO-treated mice exhibited atrial ectopic beats, impaired atrial function, increased atrial fibrosis, and greater activation of ER stress signaling with PERK/IRE1α axis activation compared with controls and mice treated with TMAO combined with SB. CONCLUSION: TMAO administration led to PERK/IRE1α axis activation, which may increase atrial remodeling and arrhythmogenesis. SB treatment mitigated TMAO-elicited ER stress. This finding suggests that SB administration is a valuable strategy for treating TMAO-induced atrial arrhythmia.

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.

Analysis of warpage and reliability of very thin profile fine pitch ball grid array.

With the evolution of advanced integrated circuit (IC) packaging technology, the use of experiments to identify package performance and life expectation will take a significant amount of time and cost to finish the job. To reduce the cost of research and testing, predictive analyses of reliability and performance using simulation tools have become a feasible approach for the IC assembly industry. Therefore, this study utilized Moldex3D molding simulation software to analyze very thin profile fine pitch ball grid array (VFBGA) packages and established a numerical analysis procedure from the molding and curing process, the post-mold cure (PMC) process, to a thermal cycling test (TCT) to predict the amount of package warpage during processing and reliability after TCT. The results showed that the warpage trends of both experiments and simulations during the same temperature ramping process were similar. In the thermal cycling analysis, potential failure locations were found to be at the copper pillars and redistribution layer (RDL), where the maximum Von Mises stress occurred at the lowest temperature (-65 °C). The fatigue life model, Coffin-Manson model, was used to calculate the potential fatigue life at the two locations, resulting in 1689 cycles (copper pillars) and 9706 cycles (RDL L1).

Exploring Nurse Use of Digital Nursing Technology.

Technological developments and nursing shortages have become global trends. To solve the problem of shortage of healthcare professionals, technology may be used as a backup. Nurses constitute the largest working group in the healthcare system. Therefore, nurses are very important to the success of implementing digitization in hospitals. This cross-sectional study used the characteristics and adoption roles of innovation diffusion theory to understand technology use within the organization. Data were collected through structured questionnaires and open-ended questions from March 21 to May 31, 2022, in two hospitals in Taiwan. In total, 159 nurses agreed to participate in the study. The results of this study revealed that observability, simplicity, advantage, trialability, and compatibility positively improved the acceptance of digital nursing technology. In the distribution of users' innovative roles, early adopters had a significant impact on innovation characteristics and technology acceptance. Nurses in acute and critical care units perceived a greater comparative advantage and trial availability of digital nursing technology use than did those in general wards and outpatient clinics. In addition, based on user opinions and suggestions, the development of smart healthcare and the use of digital technology are expected to improve the quality of nursing care.

Using a Mobile Application to Promote Patient Education for Patients With Liver Cirrhosis.

Patient education and self-management are essential for patients with liver cirrhosis. Based on Fisher and Fisher's Information-Motivation-Behavior Skills model, a Cirrhosis Care App was developed to support the education and self-management of these patients. To evaluate the effectiveness of the application, a randomized controlled trial was conducted with patients having liver cirrhosis who were being followed up in the outpatient area of ​​a medical center in Taiwan. The experimental group used the app for 1 month, whereas a control group continued to receive conventional patient education. A pretest and posttest questionnaire was used to evaluate the app's effectiveness in improving the knowledge and practice of self-care. In addition, a questionnaire was developed based on the Technology Acceptance Model to understand satisfaction with the app. Results showed that following the implementation of the Cirrhosis Care App, patients' self-care knowledge and ability to promote self-care practice improved. User satisfaction with the app was measured and reflected in its frequency of use. This study confirmed that the Cirrhosis Care App, based on the Information-Motivation-Behavior Skills model, can improve patient knowledge and self-care practice and be actively promoted to benefit patients with cirrhosis.

Substrate Charge Transfer Induced Ferromagnetism in MnSe/SrTiO3 Ultrathin Films.

The observation of superconductivity in MnSe at 12 GPa motivated us to investigate whether superconductivity could be induced in MnSe at ambient conditions. A strain-induced structural change in the ultrathin film could be one route to the emergence of superconductivity. In this report, we present the physical property of MnSe ultrathin films, which become tetragonal (stretched ab-plane and shortened c-axis) on a (001) SrTiO3 (STO) substrate, prepared by the pulsed laser deposition (PLD) method. The physical properties of the tetragonal MnSe ultrathin films exhibit very different characteristics from those of the thick films and polycrystalline samples. The tetragonal MnSe films show substantial conductivity enhancement, which could be associated with the presence of superparamagnetism. The optical absorption data indicate that the electron transition through the indirect bandgap to the conduction band is significantly enhanced in tetragonal MnSe. Furthermore, the X-ray Mn L-edge absorption results also reveal an increase in unoccupied state valance bands. This theoretical study suggests that charge transfer from the substrate plays an important role in conductivity enhancement and the emergence of a ferromagnetic order that leads to superparamagnetism.

Humic acid changes effect of naturally occurring oxidants on the environmental transformation of molybdenum disulfide nanosheets.

2H-phase molybdenum disulfide (2H-MoS2) has been considered to be a chemically stable two-dimensional (2D) nanomaterial. Nonetheless, the persistence of 2H-MoS2 in the presence of environmental redox-active matrices, such as naturally occurring oxidants (e.g., manganese dioxide (MnO2)) and natural organic matter (NOM), remains largely unknown. Herein, we examined the interplay between 2H-MoS2, MnO2 (a common natural oxidant), and NOM species (i.e., Aldrich humic acid (ALHA) and Suwannee River natural organic matter (SRNOM)). The results show that MnO2 accelerates the oxidative dissolution of 2H-MoS2, regardless of the presence of dissolved oxygen. The effect of NOM on the MnO2-induced fate of 2H-MoS2 was found to depend on its affinity for 2H-MoS2 and the functionality of NOM. ALHA preferentially adsorbed on hydrophobic 2H-MoS2 nanosheets due to the enrichment of reductive polycyclic aromatics and polyphenolic constituents. The preferential ALHA adsorption counteracted the MnO2-triggered oxidative transformation of 2H-MoS2, as revealed by the cathodic response of 2H-MoS2 (i.e., decreased the open circuit potential by 0.0338 V) and the emergence of reductive Mo‒C bonds at 228.8 and 231.9 eV upon the addition of ALHA. This work evaluated the persistence of 2H-MoS2, illustrating its susceptibility to decomposition by naturally occurring oxidants and the influence of NOM on it. These findings are crucial for revealing the fate and transport of MoS2 in aquatic environments and provide guidelines for related applications in natural or engineered systems for MoS2 and potentially other 2D materials.

Human tNeurons reveal aging-linked proteostasis deficits driving Alzheimer's phenotypes.

Aging is a prominent risk factor for Alzheimer's disease (AD), but the cellular mechanisms underlying neuronal phenotypes remain elusive. Both accumulation of amyloid plaques and neurofibrillary tangles in the brain1 and age-linked organelle deficits2-7 are proposed as causes of AD phenotypes but the relationship between these events is unclear. Here, we address this question using a transdifferentiated neuron (tNeuron) model directly from human dermal fibroblasts. Patient-derived tNeurons retain aging hallmarks and exhibit AD-linked deficits. Quantitative tNeuron proteomic analyses identify aging and AD-linked deficits in proteostasis and organelle homeostasis, particularly affecting endosome-lysosomal components. The proteostasis and lysosomal homeostasis deficits in aged tNeurons are exacerbated in sporadic and familial AD tNeurons, promoting constitutive lysosomal damage and defects in ESCRT-mediated repair. We find deficits in neuronal lysosomal homeostasis lead to inflammatory cytokine secretion, cell death and spontaneous development of Aß and phospho-Tau deposits. These proteotoxic inclusions co-localize with lysosomes and damage markers and resemble inclusions in brain tissue from AD patients and APP-transgenic mice. Supporting the centrality of lysosomal deficits driving AD phenotypes, lysosome-function enhancing compounds reduce AD-associated cytokine secretion and Aß deposits. We conclude that proteostasis and organelle deficits are upstream initiating factors leading to neuronal aging and AD phenotypes.

Patient Preferences for Benefit and Risk Associated With High Intensity Focused Ultrasound for the Ablation of Prostate Tissue in Men With Localized Prostate Cancer.

INTRODUCTION: Food and Drug Administration must make decisions about emerging high intensity focused ultrasound (HIFU) devices that may lack relevant clinical oncologic data but present with known side effects. This study aims to capture patients' perspective by quantifying their preferences regarding the available benefit and important side effects associated with HIFU for localized prostate cancer. MATERIALS AND METHODS: Preferences for HIFU outcomes were examined using a discrete choice experiment survey. Participants were asked to choose a preferred treatment option in 9 choice questions. Each included a pair of hypothetical treatment profiles that have similar attributes/outcomes with varying levels. Outcomes included prostate biopsy outcome and treatment-related risks of erectile dysfunction (ED) and urinary incontinence (UI). We calculated the maximum risk of side effect patients were willing to tolerate in exchange for increased benefit. Preferences were further explored via clinical and demographic data. RESULTS: About 223 subjects with a mean age of 64.8 years completed the survey. Respondents were willing to accept a 1.51%-point increase in new ED risk for a 1%-point increase in favorable biopsy outcome. They were also willing to accept a 0.93%-point increase in new UI risk for a 1%-point increase in biopsy outcome. Subjects who perceived their cancer to be more aggressive had higher risk tolerance for UI. Younger men were willing to tolerate less ED risk than older men. Respondents with greater than college level of education had a lower risk tolerance for ED or UI. CONCLUSIONS: Results may inform development and regulatory evaluation for future HIFU ablation devices by providing supplemental information from the patient perspective.

Polyglutamine-mediated ribotoxicity disrupts proteostasis and stress responses in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat in the Huntingtin (HTT) gene, encoding a homopolymeric polyglutamine (polyQ) tract. Although mutant HTT (mHTT) protein is known to aggregate, the links between aggregation and neurotoxicity remain unclear. Here we show that both translation and aggregation of wild-type HTT and mHTT are regulated by a stress-responsive upstream open reading frame and that polyQ expansions cause abortive translation termination and release of truncated, aggregation-prone mHTT fragments. Notably, we find that mHTT depletes translation elongation factor eIF5A in brains of symptomatic HD mice and cultured HD cells, leading to pervasive ribosome pausing and collisions. Loss of eIF5A disrupts homeostatic controls and impairs recovery from acute stress. Importantly, drugs that inhibit translation initiation reduce premature termination and mitigate this escalating cascade of ribotoxic stress and dysfunction in HD.

Hematological and plasma profiles and ticks and tick-borne pathogens in wild Formosan black bears (Ursus thibetanus formosanus).

BACKGROUND: The endangered Formosan black bear (Ursus thibetanus formosanus) is the largest native carnivorous mammal in Taiwan. Diseases, poor management, illegal hunting, and habitat destruction are serious threats to the survival of bear populations. However, studies on the impact of diseases on bear populations are limited. Therefore, this study aimed to establish a database of the hematological and plasma profiles of free-ranging Formosan black bears and investigate the occurrence of ectoparasites, blood parasites, and vector-borne pathogens. METHODS: Formosan black bears were captured in Yushan National Park (YNP) and Daxueshan Forest Recreation Area (DSY) in Taiwan. Blood samples were collected from each bear for hematological analysis and plasma biochemistry using a hematology analyzer. Parasites and pathogens were detected using a thin blood smear with Wright-Giemsa staining and polymerase chain reaction (PCR) assay. Additionally, macroscopic ectoparasites were collected from bears to detect blood parasites and other pathogens. Moreover, the relationships between the bear variables (sex, age, and occurrence of parasites or pathogens), ectoparasites, and infectious agents were also analyzed. RESULTS: In all, 21 wild bears (14 in YNP and 7 in DSY) were captured and released during the satellite tracking studies. Hematological analysis and plasma biochemistry indicated significant differences in white blood cells (WBC), segments, creatine kinase (CK), and lactate dehydrogenase (LDH) levels between foot snare and culvert-captured bears. Additionally, there were significant differences in total plasma protein (TPP), creatinine, Ca2+, Mg2+, and K+ levels between male and female bears. Moreover, pathogen-infected bears had significantly higher erythrocyte sedimentation rate (ESR; 30 min and 1 h) and globulin levels than uninfected bears. In total, 240 ticks were collected from 13 bears, among which eight adult tick species were identified, including Haemaphysalis flava, Haemaphysalis hystricis, Amblyomma testudinarium, Ixodes ovatus, Dermacentor taiwanensis, Haemaphysalis longicornis, Ixodes acutitarsus, Amblyomma javanense, and nymphs belonging to Haemaphysalis spp. PCR revealed that 13 (61.90%) and 8 (38.10%) bears harbored Hepatozoon ursi and Babesia DNA, respectively. Among the ticks examined, 157 (65.41%) and 128 (53.33%) samples were positive for H. ursi and Babesia, respectively. CONCLUSIONS: To the best of our knowledge, this is the first study to establish a database of the hematological and plasma profiles of wild Formosan black bears and investigate ectoparasite infestation and Hepatozoon and Babesia spp. INFECTION: In conclusion, these findings may serve as a reference for monitoring the health and population of locally endangered bears.

Purification, identification and molecular docking studies of antioxidant and anti-inflammatory peptides from Edible Bird's Nest.

This study investigated antioxidant and anti-inflammatory peptides from Edible Bird's Nest (EBN). The prepared EBN peptides were sequentially separated, purified, and successively identified by ultrafiltration, gel filtration and mass spectrometry techniques. Four potential antioxidant and anti-inflammatory peptides were identified as Peptide 1 (LFWSPSVYLK), Peptide 2 (GWPHLEDNYLDW), Peptide 3 (NPPADLHK) and Peptide 4 (GDLAYLDQGHR). Molecular docking analysis revealed that Peptide 1 and Peptide 2 can competitively interrupt the formation of Keap1-Nrf2 due to the presence of hydrophobic and antioxidant amino acids in their peptide sequences. Peptide 3 and Peptide 4 have a strong effect on interacting with the binding site of IKK-ß due to the interaction of anti-inflammatory amino acids and C-terminal arginine/lysine. The four peptides were synthesised and validated for their antioxidant and anti-inflammatory activities. The results suggest that the four peptides may serve as promising bioactive peptides for preventing oxidative stress and inflammation-related diseases.

Disparities in Visual Field Testing Frequency Among Subjects With Glaucoma.

Purpose: Prior evidence suggests racial disparities in the utilization of visual field testing (VFT) for the diagnosis and monitoring of glaucoma. In this study, we considered the effect of baseline glaucoma severity and socioeconomic disadvantage along with other potential confounders such as test reliability, ancillary tests, and glaucoma surgeries on racial disparity in the frequency of VFT. Methods: The records of all subjects with a diagnosis of glaucoma who received VFT at an academic, tertiary care facility from January 2018 to December 2021 were accessed. Analysis was performed to compare VFT frequency, the total number of office visits (DoS), and the ratio of VFT frequency to DoS (VFT/DoS) across self-reported races while controlling for sex, age, socioeconomic disadvantage (Area Deprivation Index), VF reliability indicators and baseline mean deviation, optical coherence tomography frequency, and glaucoma surgeries. Results: Among the 2654 subjects (1515 White, 782 Black, and 357 Asian) included in this study, Black subjects had the worst socioeconomic status and disease severity at baseline. They also experienced a 3% lower VFT/DoS ratio compared to White subjects (P = 0.031). Asian subjects had a 5% lower VFT/DoS ratio compared to White subjects (P = 0.015). Discussion: We identified racial disparity in performing VFT in subjects with glaucoma even when multiple confounders were considered. Further investigation is necessary to identify other race-associated factors to work toward reducing racial disparities in VFT. Translational Relevance: Black and Asian subjects with glaucoma receive fewer VFT per visit compared to White subjects even when considering socioeconomic disadvantage and disease severity.

Exploring the Usage Effectiveness of a Nursing Charge System.

The nursing charge system for inpatient accounting has been utilized in healthcare institutions for years. However, the level of its effectiveness in meeting the needs of nursing services, including further development, has not been systematically evaluated. A cross-sectional study based in Delone and McLean's information system success model was applied to explore the level of effective nursing charge system usage across the five dimensions of system quality, information quality, service quality, user satisfaction, and net benefits. We conducted a survey of the inpatient units of a medical center in Taiwan from June 23, 2021, to July 23, 2021. A total of 214 valid questionnaires were collected. Using a 5-point Likert scale, the dimension with the highest score was information quality (3.71), followed by service quality (3.37), user satisfaction (3.36), net benefits (3.31), and system quality (3.23). Older nurses ( r = -0.176) and those with more clinical experience ( r = -0.151) viewed the nursing charge system as having less information quality. The comfort level with using the computer was positively associated with system quality ( r = 0.396), information quality ( r = 0.378), service quality ( r = 0.275), user satisfaction ( r = 0.417), and net benefits ( r = 0.355). The opinions of nurses are vital. User feedback and advice should be investigated regularly to achieve system optimization.

Investigating the Utility of Near-Infrared Reflectance Imaging for Diabetic Retinopathy Screening.

BACKGROUND AND OBJECTIVE: We investigated the reliability of near-infrared reflectance (NIR) imaging as a method of assessing severity of diabetic retinopathy (DR). PATIENTS AND METHODS: One hundred ninety-five NIR images were reviewed by two graders for the number of hyporeflective foci, presence or absence of vascular abnormalities, and presumptive DR stage; these were correlated to fundus photography-defined DR stage. Interrater reliability was confirmed via one-way random effects model of intraclass correlation coefficients. Analysis of variance was used in subgroup analysis, receiver operating characteristic (ROC) curves were created to validate reliability of the model, and logistic regression was used to model foci and vascular abnormalities as predictors for moderate or worse disease. RESULTS: A statistically significant difference in mean number of hyporeflective foci was found between no DR and moderate non-proliferative DR (NPDR; P < 0.0001), no DR and severe NPDR (P < 0.001), no DR and proliferative DR (PDR; P < 0.0001), mild and moderate NPDR (P = 0.008), mild and severe NPDR (P < 0.001), and mild NPDR and PDR (P < 0.001). The area under the ROC curve was 0.849 (CI: 0.792 to 0.905). The threshold for detection of moderate NPDR or worse was 4.75 foci, with a sensitivity of 79.0% and a false positive rate of 20.0%. Multivariate logistic regression model incorporating hyporeflective foci with vascular abnormalities (odds ratio [OR] = 1.592, 95% CI: 1.381 to 1.835; P < 0.001) was able to accurately predict moderate disease or worse, just moderate disease (OR = 1.045, 95% CI: 1.003 to 1.089; P = 0.035), severe disease (OR = 1.050, 95% CI: 1.006 to 1.096; P = 0.027), and proliferative disease (OR = 1.050, 95% CI: 1.008 to 1.095; P = 0.018). CONCLUSIONS: NIR imaging may be an adjunct tool in screening for DR. [Ophthalmic Surg Lasers Imaging Retina 2024;55:318-325.].

Exploring the Effectiveness of Nurses' Usage of a Wound-Photography System.

As a result of rapid advancements in health information technology, uploading health-related information and records onto an electronic health record system has become a common practice. Photographs of patients' wounds have been uploaded electronically, but widespread acceptance by nurses has been prevented owing to issues such as file size and equipment. This research explores the attitude and satisfaction toward using an electronic health record for uploading wound photos. Through the integration of the Technology Acceptance Model, Information System Success Model, and other study results, this research aims to explore the impact of the following variables: system quality, information quality, perceived usefulness, perceived ease of use, user attitude, user satisfaction, and net benefits. We also tested nurses' understanding regarding the process of taking photographs and explored the photograph quality and the photography uploading rates. The results revealed that users were satisfied with the wound-photography system, but some believed that the system stability, processing time, and image resolution should be improved. In addition, more than 80% of the nurses correctly answered photo-taking questions, the study photos reached 70% of the quality standards, and the average uploading rate was 74%. The results could serve as guidelines for system design in the future.

Epstein-Barr Virus BRLF1 Induces PD-L1 Expression in Nasopharyngeal Carcinoma Cells.

Nasopharyngeal carcinoma (NPC) is a specific human malignancy with unique geographic distribution and genetic backgrounds. Although early treatment with radio-chemotherapy has been proven effective for NPC therapy, its therapeutic efficacy substantially diminishes in the late stages of this malignancy. In the tumor microenvironment of NPC, PD-L1 has been demonstrated as a critical factor in impairing T cell activation. As an etiological role for NPC development, it is found that Epstein-Barr virus (EBV) latent proteins upregulated PD-L1 expression. However, whether EBV lytic protein affects PD-L1 expression remains unclear. In this study, through monitoring the mRNA expression pattern of lytic genes and PD-L1 in EBV-positive NPC cell line NA, EBV immediately-early gene BRLF1(Rta) was found to have the potential for PD-L1 activation. Furthermore, we identified that Rta expression enhanced PD-L1 expression in mRNA and protein levels through quantitative real-time polymerase chain reaction and western blotting analysis. The luciferase reporter assay revealed that Rta expression enhanced PD-L1 promoter activity. We also demonstrated that Rta-induced PD-L1 expressions could impair interleukin 2 secretion of T cells, and this mechanism may be through ERK activation. These results displayed the importance of EBV Rta in PD-L1 expression in NPC and may give an alternative target for NPC therapy.

Lithium downregulates phosphorylated acetyl­CoA carboxylase 2 and attenuates mitochondrial fatty acid utilization and oxidative stress in cardiomyocytes.

Acetyl-CoA carboxylase 2 plays a crucial role in regulating mitochondrial fatty acid oxidation in cardiomyocytes. Lithium, a monovalent cation known for its cardioprotective potential, has been investigated for its influence on mitochondrial bioenergetics. The present study explored whether lithium modulated acetyl-CoA carboxylase 2 and mitochondrial fatty acid metabolism in cardiomyocytes and the potential therapeutic applications of lithium in alleviating metabolic stress. Mitochondrial bioenergetic function, fatty acid oxidation, reactive oxygen species production, membrane potential and the expression of proteins involved in fatty acid metabolism in H9c2 cardiomyocytes treated with LiCl for 48 h was measured by using a Seahorse extracellular flux analyzer, fluorescence microscopy and western blotting. Small interfering RNA against glucose transporter type 4 was transfected into H9c2 cardiomyocytes for 48 h to induce metabolic stress mimicking insulin resistance. The results revealed that LiCl at a concentration of 0.3 mM (but not at a concentration of 0.1 or 1.0 mM) upregulated the expression of phosphorylated (p-)glycogen synthase kinase-3 beta and downregulated the expression of p-acetyl-CoA carboxylase 2 but did not affect the expression of adenosine monophosphate-activated protein kinase or calcineurin. Cotreatment with TWS119 (8 µM) and LiCl (0.3 mM) downregulated p-acetyl-CoA carboxylase 2 expression to a similar extent as did treatment with TWS119 (8 µM) alone. Moreover, LiCl (0.3 mM) inhibited mitochondrial fatty acid oxidation, improved coupling efficiency and the cellular respiratory control ratio, hindered reactive oxygen species production and proton leakage and restored mitochondrial membrane potential in glucose transporter type 4 knockdown-H9c2 cardiomyocytes. These findings suggested that low therapeutic levels of lithium can downregulate p-acetyl-CoA carboxylase 2, thus reducing mitochondrial fatty acid oxidation and oxidative stress in cardiomyocytes.

The use of bubble charts in analyzing second stage cesarean delivery rates.

BACKGROUND: The incidence of second stage cesarean delivery has been rising globally because of the failure or the anticipated difficulty of performing instrumental delivery. Yet, the best way to interpret the figure and its optimal rate remain to be determined. This is because it is strongly influenced by the practice of other 2 modes of birth, namely cesarean delivery performed before reaching the second stage and assisted vaginal birth during the second stage. In this regard, a bubble chart that can display 3-dimensional data through its x-axis, y-axis, and the size of each plot (presented as a bubble) may be a suitable method to evaluate the relationship between the rates of these 3 modes of births. OBJECTIVE: This study aimed to conduct an epidemiologic study on the incidence of second stage cesarean deliveries rates among >300,000 singleton term births in 10 years from 8 obstetrical units and to compare their second stage cesarean delivery rates in relation to their pre-second stage cesarean delivery rates and assisted vaginal birth rates using a bubble chart. STUDY DESIGN: The territory-wide birth data collected between 2009 and 2018 from all 8 public obstetrical units (labelled as A to H) were reviewed. The inclusion criteria were all singleton pregnancies with cephalic presentation that were delivered at term (≥37 weeks' gestation). Pre-second stage cesarean delivery rate was defined as all elective cesarean deliveries and those emergency cesarean deliveries that occurred before full cervical dilatation was achieved as a proportion of the total number of births. The second stage cesarean delivery rate and assisted vaginal birth rate were calculated according to the respective mode of delivery as a proportion of the number of cases that reached full cervical dilatation. The rates of these 3 modes of births were compared among the parity groups and among the 8 units. Using a bubble chart, each unit's second stage cesarean delivery rate (y-axis) was plotted against its pre-second stage cesarean delivery rate (x-axis) as a bubble. Each unit's second stage cesarean delivery to assisted vaginal birth ratio was represented by the size of the bubble. RESULTS: During the study period, a total of 353,434 singleton cephalic presenting term pregnancies were delivered in the 8 units, and 180,496 (51.1%) were from nulliparous mothers. When compared with the multiparous group, the nulliparous group had a significantly lower pre-second stage cesarean delivery rate (18.58% vs 21.26%; P<.001) but a higher second stage cesarean delivery rate (0.79% vs 0.22%; P<.001) and a higher assisted vaginal birth rate (17.61% vs 3.58%; P<.001). Using the bubble of their averages as a reference point in the bubble chart, the 8 units' bubbles were clustered into 5 regions indicating their differences in practice: unit B and unit H were close to the average in the center. Unit A and unit F were at the upper right corner with a higher pre-second stage cesarean delivery rate and second stage cesarean delivery rate. Unit D and unit E were at the opposite end. Unit C was at the upper left corner with a low pre-second stage cesarean delivery rate but a high second stage cesarean delivery rate, whereas unit G was at the opposite end. Unit C and unit G were also in the extremes in terms of pre-second stage cesarean delivery to assisted vaginal birth ratio (0.09 and 0.01, respectively). Although some units seemed to have very similar second stage cesarean delivery rates, their obstetrical practices were differentiated by the bubble chart. CONCLUSION: The second stage cesarean delivery rate must be evaluated in the context of the rates of pre-second stage cesarean delivery and assisted vaginal birth. A bubble chart is a useful method for analyzing the relationship among these 3 variables to differentiate the obstetrical practice between different units.