Differences in proximal and intimacy-related defense mechanisms among patients with cancer in different psychological stages of dying.

Purpose: This study measured three of the psychological stages of dying in patients with cancer and explored the differences in proximal and intimacy-related defense mechanisms at each stage. Patients and methods: A total of 220 cancer patients were recruited for this study; 168 patients met the inclusion criteria and were included in the data analysis. The participants were divided into three groups using the "Death Attitudes Questionnaire Revised" (1994) and then completed the Death-Thought Accessibility Test, Self-Control Questionnaire, Rumination Reflection Questionnaire, Attachment Type Test, Intimacy Test, External Control Test, and Positive and Negative Affect Scale. Results: In the death avoidance stage, which represents a defense stage without cognitive processes, patients are in an irrational state with the highest level of self-control and the lowest level of external control; they tend to prefer close relationships with many people while experiencing high levels of fear and depression. In the bargaining stage, which represents a biased cognitive defense stage, the level of rationality increases, the level of fear and depression decreases, and patients tend to prefer relationships with many people that do not involve intimacy. In the neutral death acceptance stage, which represents a defense stage without cognitive bias, self-control is lowest, external control is highest, patients tend to prefer intimate relationships with a few people, and experience the lowest levels of fear and depression. Conclusion: Three psychological stages of death exist in cancer patients, with differences in proximal and intimacy-related defense mechanisms in each stage. The findings have theoretical and practical implications for psychological interventions for cancer patients.

Development and validation of a major adverse limb events prediction model for peripheral arterial disease with frailty.

OBJECTIVE: To investigate the risk factors for major limb adverse events (MALE) in peripheral arterial disease (PAD) combined with frailty and to develop and validate a risk prediction model of MALE. METHODS: This prospective study was performed in the vascular surgery department of patients in six hospitals in southwest China. Prospective collection of patients with PAD combined with frailty from February 1 to December 20, 2021, with MALE as the primary outcome, and followed for 1 year. The cohort was divided into a development cohort and a validation cohort. In the development cohort, a multivariate risk prediction model was developed to predict MALE using random forests for variable selection and multivariable Cox regression analysis. The model is represented by a visualized nomogram and a web-based calculator. The model performance was tested with the validation cohort and assessed using the C-statistic and calibration plots. RESULTS: A total of 1179 patients were prospectively enrolled from February 1 to December 20, 2021. Among 816 patients with PAD who were included in the analysis, the median follow-up period for this study was 9 ± 4.07 months, the mean age was 74.64 ± 9.43 years, and 249 (30.5%) were women. Within 1 year, 222 patients (27.2%) developed MALE. Target lesion revascularizations were performed in 99 patients (12.1%), and amputations were performed in 131 patients (16.1%). The mortality rate within the whole cohort was 108 patients (13.2%). After controlling for competing risk events (death), the cumulative risk of developing MALE was not statistically different. Prealbumin (hazard ratio [HR], 0.6; 95% confidence interval [CI], 0.41-0.89; P = .010), percutaneous coronary intervention (HR, 2.31; 95% CI, 1.26-4.21; P = .006), Rutherford classification (HR, 1.77; 95% CI, 1.36-2.31; P < .001), white blood cell (HR, 1.85; 95% CI, 1.20-2.87; P = .005), high altitude area (HR, 3.1; 95% CI, 1.43-6.75; P = .004), endovascular treatment (HR, 10.2; 95% CI, 1.44-72.50; P = .020), and length of stay (HR, 1.01; 95% CI, 1.00-1.03; P = .012) were risk factors for MALE. The MALE prediction model had a C-statistic of 0.76 (95% CI, 0.70-0.79). The C-statistic was 0.68 for internal validation and 0.66 for external validation for the MALE prediction model. The MALE prediction model for PAD presented an interactive nomogram and a web-based network calculator. CONCLUSIONS: In this study, the MALE prediction model has a discriminative ability to predict MALE among patients with PAD in frailty. The MALE model can optimize clinical decision-making for patients with PAD in frailty.

Exacerbation of Pre-Existing Chronic Pain in Older Adults After SARS-CoV-2 Infection: A Single-Center, Cross-Sectional, Observational Study.

Purpose: To identify the prevalence of exacerbation of pre-existing chronic pain after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and investigate the impact of exacerbated previous chronic pain on quality of life, sleep quality, anxiety and depression levels and risk factors associated with exacerbated chronic pain among elderly coronavirus disease of 2019 (COVID-19) survivors. Patients and Methods: In this cross-sectional study, elderly COVID-19 survivors with chronic pain residing in Continuing Care Retirement Community (CCRC) were recruited from April 2023 to June 2023. Eligible individuals were divided into exacerbation and non-exacerbation groups based on the patient-reported worsening symptoms of previous chronic pain after SARS-CoV-2 infection. Baseline information, COVID-19 symptoms, laboratory parameters, characteristics of exacerbated chronic pain, quality of life, anxiety and depression levels were systematically collected. Results: Ninety-five (95/441, 21.5%) older adults suffered from exacerbated chronic pain with a median numerical rating scale (NRS) score of 6 (4-7) on a median duration of 4.9 (4.3-5.6) months after SARS-CoV-2 infection. More participants were not vaccinated against COVID-19 (46.5%, 40/86 vs 26.1%, 86/330, P < 0.001) in exacerbation group. Exacerbation group exhibited poor quality of life (EQ5D index: 0.734 [0.536-0.862] vs 0.837 [0.716-0.942], P < 0.001), more severe anxiety (GAD-7: 2 [0-5] vs 0 [0-3], P < 0.001) and depression (PHQ-9: 4 [2-7] vs 2.5 [0-5], P < 0.001) than non-exacerbation group. Risk factors significantly associated with exacerbation of pre-existing chronic pain were neuropathic pain (aOR 4.81, 95% CI 1.73-13.32, P = 0.003), lymphocyte count (aOR 0.31, 95% CI 0.12-0.78, P = 0.013) and D-dimer levels (aOR 6.46, 95% CI 1.92-21.74, P = 0.003). Conclusion: Our study observed a prevalence of 21.5% exacerbation of pre-existing chronic pain after SARS-CoV-2 infection, with a consequence of poor quality of life, more severe anxiety and depression. Previous chronic neuropathic pain, lower lymphocyte count and higher D-dimer levels were risk factors associated with the development of exacerbated previous chronic pain.

Improving the Quality of Maternity Care: Learning From Malpractice.

OBJECTIVE: This study aimed to depict the characteristics, injury outcomes, and payment of obstetric malpractice lawsuits to better understand the medicolegal burden in obstetrics and categorize the causes of obstetric malpractice lawsuits using The National Health Service Litigation Authority coding taxonomy for further quality improvement in maternity care. METHODS: We reviewed and retrieved key information on court records of legal trials from China Judgment Online between 2013 and 2021. RESULTS: A total of 3441 obstetric malpractice lawsuits successfully claimed were reviewed in this study, with a total indemnity payment of $139,875,375. After peaking in 2017, the number of obstetric malpractice claims begins to decline. Of the 2424 hospitals that were sued, 8.3% (201/2424) were referred to as "repeat defendant" because they were involved in multiple lawsuits. Death and injury were the outcomes in 53.4% and 46.6% of the cases, respectively. The most common outcome type was neonatal death, which made up 29.8% of all cases. The median indemnity payment for death was higher compared with injury ( P < 0.05). In terms of detailed injury outcomes, the major neonatal injury had higher median indemnity payments than neonatal death and fetal death ( P < 0.05). The median indemnity payment of the major maternal injury was higher than that of maternal death ( P < 0.05). The leading causes of obstetric malpractice were the management of birth complications and adverse events (23.3%), management of labor (14.4%), career decision making (13.7%), fetal surveillance (11.0%), and cesarean section management (9.5%). The cause for 8.7% of cases was high payment (≥$100, 000). As indicated by the results of the multivariate analysis, the hospitals in the midland of China (odds ratio [OR], 0.476; 95% confidence interval [CI], 0.348-0.651), the hospitals in the west of China (OR, 0.523; 95% CI, 0.357-0.767), and the secondary hospitals (OR, 0.587; 95% CI, 0.356-0.967) had lower risks of high payment. Hospitals with ultimate liability (OR, 9.695; 95% CI, 4.072-23.803), full liability (OR, 16.442; 95% CI, 6.231-43.391), major neonatal injury (OR, 12.326; 95% CI, 5.836-26.033), major maternal injury (OR, 20.885; 95% CI, 7.929-55.011), maternal death (OR, 18.783; 95% CI, 8.887-39.697), maternal death with child injury (OR, 54.682; 95% CI, 10.900-274.319), maternal injury with child death (OR, 6.935; 95% CI, 2.773-17.344), and deaths of both mother and child (OR, 12.770; 95% CI, 5.136-31.754) had higher risks of high payment. In the causative domain, only anesthetics had a higher risk of high payment (OR, 5.605; 95% CI, 1.347-23.320), but anesthetic-related lawsuits made up just 1.4% of all cases. CONCLUSIONS: The healthcare systems had to pay a significant amount as a result of obstetric malpractice lawsuits. Greater efforts are required to minimize serious injury outcomes and improve obstetric quality in the risky domains.

Prevalence and predictors of compassion satisfaction, secondary traumatic stress, and burnout among Chinese hospice nurses: A cross-sectional study.

AIM: To explore the prevalence and predictors of compassion satisfaction, secondary traumatic stress, and burnout among Chinese hospice nurses. BACKGROUND: Because of prolonged and continual contact with suffering, deaths, and grief, hospice nurses may be vulnerable to emotional burdens and have difficulty maintaining their professional quality of life. METHODS: A cross-sectional study was conducted. A total of 478 hospice nurses were selected from 24 medical institutions in Sichuan province. Demographic, work-related information and work-related trauma questionnaire, the Chinese version of the Interpersonal Reactivity Index, the Chinese version of the Emotion Regulation Questionnaire, and the Chinese version of the Professional Quality of Life Scale for Nurses were used for collecting data. RESULTS: The mean scores of compassion satisfaction, secondary traumatic stress, and burnout were 34.89 ± 6.21, 26.35 ± 5.24, and 24.49 ± 5.01, respectively. Job satisfaction, perspective-taking, empathic concern, working in tertiary hospitals, and adopting cognitive reappraisal strategy were positively associated with compassion satisfaction, while personal distress was a negative factor, all variables explaining 50.7 % of the variance. Higher burnout was found among nurse who had higher personal distress, worked in secondary or primary hospitals, worked >8 h per day and caring for >10 dying patients last month. In addition, job satisfaction, social support, perspective-taking, empathic concern, and cognitive reappraisal were identified as significant protectors, explaining 50.1 % of the variance. We also found that lower job satisfaction, higher personal distress, higher expressive suppression, lack of social support, senior nurses, and cared for >10 dying patients last month, were positively related to secondary traumatic stress. However, cognitive reappraisal had negative associations. These seven factors explained 32.0 % of the variance. CONCLUSIONS: Hospice care has specific characteristics and hospice nurses may suffer from more work-related stressors compared with other nurses. Our study may provide clues to help nursing administrators identify hospice nurses who are at higher risk of compassion fatigue and design targeted interventions focused on potential risk factors and protectors to improve hospice nurses' compassion satisfaction, while reducing compassion fatigue.

Metabolism of fatty acids in follicular cells, oocytes, and blastocysts.

Fatty acids (FA) are one of the substrates that can be oxidized for energy production. The blood concentration of all types of FA varies according to different nutrition conditions, and follicular fluid levels are generally in line with serum levels. Elevated levels of FA, especially non-esterified fatty acids (NEFA), are commonly found in females with metabolic issues, which are often related to subfertility in many species including humans, pigs, cattle, and mice. Long-time exposure to an excessive quantity of fatty acids impairs the cell structure and functions causing injuries in tissues and organs, resulting in lipotoxicity and eventually hampering health and fertility. High levels of saturated NEFA can have detrimental effects on granulosa cells, oocyte quality, and embryo development. Although the harmful effects of FA are established in reproductive tissues, how granulosa cells and cumulus cells respond and cooperate with oocytes when exposed to NEFA requires further understanding. This review provides a summary of the adverse impacts of exposure to NEFA during in vitro maturation on oocytes, follicular cells, and embryos. A comprehensive understanding of the effects of NEFA on oocytes in vitro would improve our understanding of the impacts of natural exposure in vivo. Lay summary: Exposure to excess FAs affects the health of eggs, early embryos, and children born from these. The way different cell types react to excess FAs has not been studied very extensively, especially in pigs which provide a good model to investigate the impact of nutrition on the ovaries in humans. This review also looks at the way cells surrounding the egg react to FAs to help our understanding of the impact of excess fatty acids on female fertility.

Effects of NEFAs during IVM on pig embryos from granulosa cell-cocultured oocytes.

Circulating levels of nonesterified fatty acids (NEFAs) are elevated in some females, which can impair oocyte maturation and embryo development, and may alter the phenotype of the progeny. However, the effects of NEFAs on human embryo development are not clear due to ethical limitations. Thus, we used pig as the model to investigate the impacts of NEFAs on oocyte and embryo due to their similar reproductive and metabolic physiologies to humans. In this study, porcine cumulus-oocyte complexes were in vitro maturated under a pathologically high concentration of NEFAs (468 µM palmitic acid, 194 µM stearic acid, and 534 µM oleic acid) with the presence of granulosa cell monolayer, in contrast to control without NEFAs. The mature oocytes were fertilized to produce embryos for further analysis of the transcriptome and DNA methylation patterns. The elevated level of NEFAs decreased the blastocyst rate and delayed the blastocyst development. Ingenuity pathway analysis showed that the most affected gene pathways were related mainly to cell activities, metabolism, and inflammation. These findings indicated that oocytes exposed to the exogenous high level of NEFAs during in vitro maturation resulted in altered gene expression and DNA methylation of early embryos, which have detrimental impacts on blastocyst quality.

Cocultured porcine granulosa cells respond to excess non-esterified fatty acids during in vitro maturation.

BACKGROUND: Non-esterified fatty acids (NEFAs) are one of the main lipid components of follicular fluid at concentrations that depend on circulating levels. Elevated levels of NEFAs impair oocyte quality, development potential, and may subsequently influence the metabolism and reproductive fitness of offspring. Granulosa cells (GCs) are the follicular cells that are closely communicating with the oocyte. However, the responses of GCs exposed to high levels of NEFAs when cocultured with cumulus-oocyte complexes (COCs), and how they attenuate the negative effects of NEFAs on oocytes, are unclear. RESULTS: To better understand this protective effect, monolayers of porcine GCs were cocultured with COCs during in vitro maturation (IVM) in the presence of elevated levels of NEFAs. Genomic expression analysis was conducted to explore the responses of the GCs to the elevated levels of NEFAs. After limma algorithm analysis, 1,013 genes were differentially expressed between GCs cultured with and without elevated NEFAs. Among them, 438 genes were upregulated and 575 were downregulated. The differentially expressed genes were enriched in pathways related to metabolism, inflammation, and epithelial-mesenchymal transition. CONCLUSIONS: The pathways and upstream regulators suggested that the cocultured GCs responded to the elevated NEFAs with (1) inhibition of the transition from granulosa to luteal cell, (2) interactions of metabolism change, anti-inflammation, mitochondrial function, and cell transition, (3) intercommunication with cocultured COCs of anti-inflammatory factors.

Are preventive measures adequate? An evaluation of the implementation of COVID-19 prevention and control measures in nursing homes in China.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic has become a challenge for nursing homes in China. Nursing homes are particularly dangerous places in terms of the spread of COVID-19 given that they house vulnerable, high-risk populations. As such, several useful guidelines for coping with COVID-19 in nursing homes have been provided. However, the actual implementation rates of such guidelines are unknown. This study aims to document the adherence of nursing homes to the Ministry of Civil Affairs guidelines for COVID-19 prevention and control in nursing homes. METHODS: A cross-sectional study was conducted among 484 nursing homes in 136 cities of 28 provinces in China. A self-report questionnaire was created based on the Ministry of Civil Affairs guidelines for COVID-19 prevention and control in nursing homes (first edition). The questionnaire and the Transformational Leadership in the Public Sector Scale were sent to nursing home managers via the Wenjuanxing app online from February 7 to 29, 2020. Ultimately, 461 of 960 nursing homes participated, for a response rate of 48.0%. RESULTS: The average overall implementation rate of COVID-19 prevention and control measures was 80.0% (143.97/180). The average implementation rates for hygienic behaviour management and access management were lower, at 75.3 and 78.7%, respectively. Number of medical staff and transformational leadership score of nursing home's manager were associated with total implementation score (p < 0.05). A total of 69.8% (322/461) of the nursing home managers had serious resource problems, and inadequate protective supplies (72.0%) and staff shortages (47.7%) were the two primary problems. The nursing homes that located in urban, with large nursing home size, had hospital-nursing home cooperation and the transformational leadership score of manager> 60, had a lower risk of having serious resource problems. CONCLUSIONS: Overall, the implementation of prevention and control measures by nursing homes are insufficient during the epidemic in China. More medical staff, adequate resource, cooperation with hospitals, and higher transformational leadership of manager are required to improve the implementation rate. It is urgent for nursing homes to maintain the safety of residents and staff.

Phospholipase C inhibits apoptosis of porcine oocytes cultured in vitro.

Oocyte apoptosis can be used as an indicator of oocyte quality and development competency. Phospholipase C (PLC) is a critical enzyme that participates in phosphoinositide metabolic regulation and performs many functions, including the regulation of reproduction. In this study, we aimed to explore whether PLC participates in the regulation of apoptosis in porcine oocytes and investigated its possible mechanism. In porcine oocytes, 0.5 µM U73122 (the PLC inhibitor) was considered to be the best concentration to facilitate maturation, and 0.5 µM m-3M3FBS (the PLC activator) was regarded as the most appropriate concentration to inhibit maturation. The percentage of cleavage and blastocysts treated with 0.5 µM U73122 was lower than that of the control group. Furthermore, the percentage of cleavage and blastocysts treated with 0.5 µM m-3M3FBS was higher than that of the control group. The relative PLC messenger RNA (mRNA) expression tested by a quantitative real-time polymerase chain reaction was found to be inhibited by 0.5 µM U73122 or activated by 0.5 µM m-3M3FBS. The relative mRNA abundance of BAK, BAX, CASP3, CASP8, and TP53 and protein abundance of Bak, cleaved caspase-3, caspase-8, and P53 was activated by U73122 or inhibited by m-3M3FBS, while the relative mRNA and protein level of BCL6 showed the opposite trend. The intracellular Ca2+ concentration increased and the expression of PLCB1 protein also increased in porcine oocytes when they were cultured with 0.5 µM m-3M3FBS for 44 hours. The abundance of proteins PKCß and CAMKIIα and the expression of several downstream genes (CDC42, NFATc1, NFATc2, NFκB, and NLK) were activated by m-3M3FBS or inhibited by U73122. Our findings indicate that PLC inhibits apoptosis and maturation in porcine oocytes. The intracellular Ca2+ concentration, two Ca2+ -sensitive proteins, and several downstream genes were positively regulated by PLC.

Effect of FH535 on in vitro maturation of porcine oocytes by inhibiting WNT signaling pathway.

Wingless-int (WNT) signaling pathway is vital to modulate life processes, including cell fate determination, cell differentiation, cell proliferation, cell apoptosis and embryogenesis. To demonstrate the uncertain effect of the canonical WNT signaling pathway on oocyte maturation, immature porcine oocytes were collected and cultured in vitro with the WNT/ß-catenin inhibitor FH535. The concentrations of FH535 were selected as 0.00, 0.01, 0.10, 1.00 and 10.00 µmol/L. The results showed that the optimum concentration of FH535 on oocyte maturation was 1.00 µmol/L. In this concentration, the proportion of MII oocytes increased (P < 0.05). The rate of cleavage was the same with the control (P > 0.05), while the rate of blastocysts in the 1.00 µmol/L FH535 treated group was higher than that of control (P < 0.01). Additionally, the average number of nuclei in blastocysts raised significantly (P < 0.05). The inhibition of WNT could regulate expression of maturation-related genes, including Cdc-2, Bmp-15, Gdf-9 and Mos. In the 1.00 µmol/L FH535 treated group, the messenger RNA level of ß-catenin showed no significant change compared to the control (P > 0.05), but the protein abundance was decreased (P < 0.05). This study revealed that the inhibition of FH535 on the WNT signaling pathway could promote the maturation of porcine oocytes and altered gene expressions in vitro.

Melatonin modulates the functions of porcine granulosa cells via its membrane receptor MT2 in vitro.

Melatonin (N-acetyl-5-methoxytryptamine) is documented as a hormone involved in the circadian regulation of physiological and neuroendocrine function in mammals. Herein, the effects of melatonin on the functions of porcine granulosa cells in vitro were investigated. Porcine granulosa cells were cultivated with variable concentrations of melatonin (0, 0.001, 0.01, 0.1, 1.0, and 10ng/mL) for 48h. Melatonin receptor agonist (IIK7) and antagonist (Luzindole, 4P-PDOT) were used to further examine the action of melatonin. The results showed optimum cell viability and colony-forming efficiency of porcine granulosa cells at 0.01ng/mL melatonin for 48-h incubation period. The percentage of apoptotic granulosa cells was significantly reduced by 0.01 and 0.1ng/mL melatonin within the 48-h incubation period as compared with the rest of the treatments. Estradiol biosynthesis was significantly stimulated by melatonin supplementation and suppressed for the progesterone secretion; the minimum ratio of progesterone to estradiol was 1.82 in 0.01ng/mL melatonin treatment after 48h of cultivation. Moreover, the expression of BCL-2, CYP17A1, CYP19A1, SOD1, and GPX4 were up-regulated by 0.01ng/mL melatonin or combined with IIK7, but decreased for the mRNA levels of BAX, P53, and CASPASE-3, as compared with control or groups treated with Luzindole or 4P-PDOT in the presence of melatonin. In conclusion, the study demonstrated that melatonin mediated proliferation, apoptosis, and steroidogenesis in porcine granulosa cells predominantly through the activation of melatonin receptor MT2 in vitro, which provided evidence of the beneficial role of melatonin as well as its functional mechanism in porcine granulosa cells in vitro.

Effects of melatonin on follicular atresia and granulosa cell apoptosis in the porcine.

The accumulation of reactive oxygen species is detrimental to the health of the ovarian follicle. The protective, antioxidant properties of melatonin, an endogenous component of porcine follicular fluid, on apoptosis of granulosa cells were evaluated in this study. Porcine granulosa cells from medium-sized (3-5 mm), healthy follicles were cultured in serum-free conditions with melatonin (0, 0.01, 0.1, 1.0, 10, and 100 ng/mL) with or without its receptor antagonist, luzindole, followed by evaluation of apoptotic markers in the treated cells. Results revealed that endogenous, intrafollicular melatonin concentration decreased as follicular atresia progressed, whereas the percentage of apoptotic granulosa cells increased. Spontaneous apoptosis of granulosa cells, triggered by serum deprivation in vitro, was remarkably blocked by melatonin (1.0 ng/mL melatonin, 32.7 ± 0.5%, vs. control, 47.0 ± 1.0%; P < 0.05). Treatment with 1.0 ng/mL of melatonin also significantly elevated MT2, SOD1, and GPX4 while lowering FASL, CHOP, and GRP78 mRNA abundance compared to the untreated control. The anti-apoptotic effect and some changes of apoptotic-relevant genes in granulosa cells invoked by melatonin supplementation were markedly blocked by luzindole, suggesting that melatonin could prevent the apoptosis of porcine granulosa cells during follicular atresia via its membrane receptors and its free-radical-scavenging activity. These findings provide new insights into the regulatory mechanism of melatonin in follicular atresia-related functions. Mol. Reprod. Dev. 83: 692-700, 2016 © 2016 Wiley Periodicals, Inc.