Would you be surprised? Prospective multicenter study of the Surprise Question as a screening tool to predict mortality in trauma patients.

BACKGROUND: The Surprise Question (SQ) ("Would I be surprised if the patient died within the next year?") is a validated tool used to identify patients with limited life expectancy. Because it may have potential to expedite palliative care interventions per American College of Surgeons Trauma Quality Improvement Program Palliative Care Best Practices Guidelines, we sought to determine if trauma team members could use the SQ to accurately predict 1-year mortality in trauma patients. METHODS: A multicenter, prospective, cohort study collected data (August 2020 to February 2021) on trauma team members' responses to the SQ at 24 hours from admission. One-year mortality was obtained via social security death index records. Positive/negative predictive values and accuracy were calculated overall, by provider role and by patient age. RESULTS: Ten Level I/II centers enrolled 1,172 patients (87.9% blunt). The median age was 57 years (interquartile range, 36-74 years), and the median Injury Severity Score was 10 (interquartile range, 5-14 years). Overall 1-year mortality was 13.3%. Positive predictive value was low (30.5%) regardless of role. Mortality prediction minimally improved as age increased (positive predictive value highest between 65 and 74 years old, 34.5%) but consistently trended to overprediction of death, even in younger patients. CONCLUSION: Trauma team members' ability to forecast 1-year mortality using the SQ at 24 hours appears limited perhaps because of overestimation of injury effects, preinjury conditions, and/or team bias. This has implications for the Trauma Quality Improvement Program Guidelines and suggests that more research is needed to determine the optimal time to screen trauma patients with the SQ. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Incidence, outcomes and costs of severe sepsis and septic shock in geriatric trauma patients: Analysis of 2,563,463 hospitalizations at 3,284 hospitals.

BACKGROUND: Severe sepsis/septic shock (sepsis) is a leading cause of death in hospitalized trauma patients. Geriatric trauma patients are an increasing proportion of trauma care but little recent, large-scale, research exists in this high-risk demographic. The objectives of this study are to identify incidence, outcomes and costs of sepsis in geriatric trauma patients. METHODS: Patients at short-term, nonfederal hospitals 65 years or older with ≥1 injury International Classification of Diseases, Tenth Revision, Clinical Modification code were selected from 2016 to 2019 Centers for Medicare & Medicaid Services Medicare Inpatient Standard Analytical Files. Sepsis was defined as International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes R6520 and R6521. A log-linear model was used to examine the association of Sepsis with mortality, adjusting for age, sex, race, Elixhauser score, and Injury Severity Score. Dominance analysis using logistic regression was used to determine the relative importance of individual variables in predicting Sepsis. Institutional review board exemption was granted for this study. RESULTS: There were 2,563,436 hospitalizations from 3,284 hospitals (62.8% female; 90.4% White; 72.7% falls; median ISS, 6.0). Incidence of Sepsis was 2.1%. Sepsis patients had significantly worse outcomes. Mortality risk was significantly higher in septic patients (adjusted risk ratio, 3.98, 95% confidence interval, 3.92-4.04). Elixhauser score contributed the most to the prediction of Sepsis, followed by ISS (McFadden's R2 = 9.7% and 5.8%, respectively). CONCLUSION: Severe sepsis/septic shock occurs infrequently among geriatric trauma patients but is associated with increased mortality and resource utilization. Pre-existing comorbidities influence Sepsis occurrence more than Injury Severity Score or age in this group, identifying a population at high risk. Clinical management of geriatric trauma patients should focus on rapid identification and prompt aggressive action in high-risk patients to minimize the occurrence of sepsis and maximize survival. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Spatial and temporal variations of extreme climate index in the Songhua River Basin during 1961-2020.

Understanding climate change and extreme climate is of great significance for ensuring food security and socio-economic development of the Songhua River Basin. Based on the daily precipitation, maximum temperature and minimum temperature data during 1961-2020 from 69 meteorological stations in and around the Songhua River Basin, we analyzed the temporal and spatial variations of extreme temperature and precipitation in the Songhua River Basin using 27 extreme climate indices recommended by the World Meteorological Organization, and linear trend method, Mann-Kendall trend test and ordinary Kriging interpolation methodology. The results showed that, from 1961 to 2020, except for cold speel duration, the extreme cold index in the study area showed a downward trend, while the extreme warm index, extreme value index and other temperature indices showed an upward trend. The increasing trend of the minimum temperature was greater than that of the maximum temperature. Icing days, cold speel duration and warm speel duration showed an increasing trend from south to north, while the minimum value of maximum temperature and that of minimum temperature showed opposite spatial characteristics. The high value areas of summer days and tropical nights were mainly distributed in the southwestern region, while there was no obvious spatial variations of cool days, warm nights, and warm days. Overall, except for cold speel duration, other extreme cold indices had a rapid decreasing trend in the north and west of the Songhua River Basin. In the warm index, summer days, warm nights, warm days, and warm speel duration had a rapid upward trend in the north and west, and tropical nights had the fastest rise in the southwest. In the extreme value index, the maximum of temperature rose fastest in the northwest, while the minimum rose fastest in the northeast. Except for consecutive dry days, the rest of precipitation indices showed an increasing trend, and the fastest rising areas were mainly in the north-central part of the Nenjiang River Basin, while some areas in the south of the Nenjiang River Basin became dry. Heavy precipitation days, very heavy precipitation days, heaviest precipitation days, consecutive wet days, very wet day precipitation, extremely wet day precipitation, and annual precipitation showed a gradual decreasing pattern from southeast to northwest. Overall, the Songhua River Basin was warming and wetting, but there were some differences among different regions, especially the northern and southern parts of the Nenjiang River Basin.

Comparative analysis of prevalence, evaluation, management, and rehabilitation outcome of spontaneous isolated visceral artery dissection: a systematic review and meta-analysis of 80 reports.

BACKGROUND: Because of relatively little data for management and evaluation surrounding spontaneous isolated visceral artery dissection (IVAD), existing studies have failed to provide comprehensive analysis for the management, evaluation, prevalence, as well as natural course of the disease. Therefore, we collected and analyzed current evidence on spontaneous IVAD with the aim of providing quantitative pooled data for the natural course and treatment standardization of the disease. METHODS: A systematic search of PubMed, Embase, the Cochrane Library, and Web of Science up to 1 June 2022, was conducted for relevant studies that investigating the natural course, treatment, classification, and outcomes of IVAD. The primary outcomes were to determine the difference in prevalence, risk factors, and characteristics between different spontaneous IVAD. Two reviewers assessed the trial quality and extracted the data independently. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2 and Stata 12.0. RESULTS: A total of 80 reports with 1040 patients were identified. The pooled results indicated that in IVAD, isolated superior mesenteric artery dissection (ISMAD) was more prevalent, with a pooled prevalence of 60% (95% CI: 50-71%), followed by isolated celiac artery dissection (ICAD) (prevalence: 37%; 95% CI: 27-46%). IVAD was male predominated with a pooled proportion of 80% (95% CI: 72-89%). Similar results were found in ICAD (prevalence: 73%; 95% CI: 52-93%). More IVAD patients were diagnosed with symptoms than ICAD (64 vs. 59%). Regarding to the risk factors, this pooled analysis found smoking and hypertension were the top two conditions in both spontaneous IVAD and ICAD patients, with proportion of 43, 41, 44, and 32%, respectively. It was observed that ICAD appeared shorter dissection length (mean difference: -3.4 cm; 95% CI: -4.9 to -2.0; P <0.0001), higher prevalence of Sakamoto's classification Π (odds ratio: 5.31; 95% CI: 1.77-15.95; P= 0.003) and late progression (odds ratio: 2.84; 95% CI: 1.02-7.87; P= 0.05) than ISAMD. CONCLUSIONS: Spontaneous IVAD was male predominant and ISMAD was most prevalent followed by ICAD. Smoking and hypertension were the top two conditions in both spontaneous IVAD and ICAD patients. The majority of patients diagnosed with IVAD received observation and conservative treatment and experienced a low proportion of reintervention or progression, especially for ICAD patients. In addition, ICAD and ISMAD had several differences in clinical features and dissection characteristics. Future studies with enough sample size and long follow-up are required to clear the management, long-term outcome, and risk factors of the IVAD prognosis.

Variation in hospice use among trauma centers may impact analysis of geriatric trauma outcomes: An analysis of 1,961,228 Centers for Medicare and Medicaid Services hospitalizations from 2,317 facilities.

BACKGROUND: Defining discharges to hospice as "deaths" is vital for properly assessing trauma center outcomes. This is critical with older patients as a higher proportion is discharged to hospice. The goals of this study were to measure rates of hospice use, evaluate hospice discharge rates by trauma center level, and identify variables affecting hospice use in geriatric trauma. METHODS: Patients from the Centers for Medicare and Medicaid Services Inpatient Standard Analytical Files for 2017 to 2019, 65 years or older, with ≥1 injury International Classification of Diseases, Tenth Revision , code, at hospitals with ≥50 trauma patients per year were selected. Total deaths was defined as inpatient deaths plus hospice discharges. Dominance analysis identified the most important contributors to a model of hospice use. RESULTS: A total of 1.96 million hospitalizations from 2,317 hospitals (Level I, 10%; II, 14%; III, 18%; IV, 7%; none, 51%) were included. Level I's had significantly lower raw hospice discharge values compared with Levels II and III (I, 0.030; II, 0.035; III, 0.035; p < 0.05) but not Level IV (0.032) or nontrauma centers (0.030) ( p > 0.05). Adjusted Level I hospice discharge rates were lower than all other facility types (Level I, 0.026; II, 0.031; III, 0.034; IV, 0.033; nontrauma, 0.030; p < 0.05). Hospice discharges as a proportion of total deaths varied by level and were lowest (0.38) at Level I centers. Dominance analysis showed that proportion of patients with Injury Severity Score of >15 contributed most to explaining hospice utilization rates (3.2%) followed by trauma center level (2.3%), proportion White (1.9%), proportion female (1.5%), and urban/rural setting (1.4%). CONCLUSION: In this near population-based geriatric trauma analysis, Level I centers had the lowest hospice discharge rate, but hospice discharge rates varied significantly by trauma level and should be included in mortality assessments of hospital outcomes. As the population ages, accurate assessment of geriatric trauma outcomes becomes more critical. Further studies are needed to evaluate the optimal utilization of hospice in end-of-life decision making for geriatric trauma. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Characteristics and feasibility of ambulatory respiratory assessment of paediatric neuromuscular disease: an observational retrospective study.

PURPOSE: To investigate the characteristics of respiratory involvement in Chinese paediatric neuromuscular disease (NMD) at early stage and to explore convenient monitoring methods. MATERIALS AND METHODS: Children with NMD (age < 18) diagnosed at a multidisciplinary joint NMD clinic at Peking University First Hospital from January 2016 to April 2021 were included. Overnight polysomnography (PSG) and pulmonary function test (PFT) data were analysed, and the characteristics of four groups: congenital muscular dystrophy (CMD), congenital myopathy, spinal muscular atrophy, and Duchenne muscular dystrophy (DMD) were compared. RESULTS: A total of 83 children with NMD were referred for respiratory assessment, of who 80 children underwent PSG; 41 performed spirometry and 38, both. The duration of pulse oxygen saturation (SpO2) <90% over apnoea and hypopnoea index (AHI) was lowest in DMD and significantly different from CMD (p = 0.033). AHI was positively correlated with the oxygen desaturation index (ODI) (r = 0.929, p = 0.000). The peak expiratory flow (PEF) were positively correlated with forced vital capacity (FVC), both as actual values and percent pred, respectively (r = 0.820, 0.719, p = 0.000). ROC derived sensitivity and specificity of prediction of AHI > 15/h or duration of SpO2<90% ≥ 60 min from FVC <51% pred was 75.8% and 85.7%, respectively. CONCLUSIONS: AHI and hypoxia burden were independent factors in children with NMD in PSG and attention needed to be paid in both. FVC might be a daytime predictor for significant sleep-disordered breathing or hypoxia. Nocturnal consecutive oximetry with diurnal peak flow measurement may be convenient and effective for home monitoring at early stage of respiratory involvement.

The burden of geriatric traumatic brain injury on trauma systems: Analysis of 348,800 Medicare inpatient claims.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability in older adults. The aim of this study was to characterize the burden of TBI in older adults by describing demographics, care location, diagnoses, outcomes, and payments in this high-risk group. METHODS: Using 2016-2019 Centers for Medicare & Medicaid Services (CMS) Inpatient Standard Analytical Files (IPSAF), patients >65 years with TBI (>1 injury ICD-10 starting with "S06") were selected. Trauma center levels were linked to the IPSAF file via American Hospital Association Hospital Provider ID and fuzzy-string matching. Patient variables were compared across trauma center levels. RESULTS: Three hundred forty-eight thousand eight hundred inpatients (50.4% female; 87.1% white) from 2963 US hospitals were included. Level I/II trauma centers treated 66.9% of patients; non-trauma centers treated 21.5%. Overall inter-facility transfer rate was 19.2%; in Level I/II trauma centers transfers-in represented 23.3% of admissions. Significant TBI (Head AIS ≥3) was present in 70.0%. Most frequent diagnoses were subdural hemorrhage (56.6%) and subarachnoid hemorrhage (30.6%). Neurosurgical operations were performed in 10.9% of patients and operative rates were similar regardless of center level. Total unadjusted mortality for the sample was 13.9%, with a mortality of 8.1% for those who expired in-hospital, and an additional 5.8% for those discharged to hospice. Medicare payments totaled $4.91B, with the majority (73.4%) going to Level I/II trauma centers. CONCLUSIONS: This study fills a gap in TBI research by demonstrating that although the majority of older adult TBI patients in the United States receive care at Level I/II trauma centers, a substantial percentage are managed at other facilities, despite 1 in 10 requiring neurosurgical operation regardless of level of trauma center. This analysis provides preliminary data on the function of regionalized trauma care for older adult TBI care. Future studies assessing the efficacy of early care guidelines in this population are warranted.

Predictive and Prognostic Assessment Models for Tumor Deposit in Colorectal Cancer Patients With No Distant Metastasis.

BACKGROUND: More and more evidence indicated that tumor deposit (TD) was significantly associated with local recurrence, distant metastasis (DM), and poor prognosis for patients with colorectal cancer (CRC). This study aims to explore the main clinical risk factors for the presence of TD in CRC patients with no DM (CRC-NDM) and the prognostic factors for TD-positive patients after surgery. METHODS: The data of patients with CRC-NDM between 2010 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. A logistic regression model was used to identify risk factors for TD presence. Fine and Gray's competing-risk model was performed to analyze prognostic factors for TD-positive CRC-NDM patients. A predictive nomogram was constructed using the multivariate logistic regression model. The concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and the calibration were used to evaluate the predictive nomogram. Also, a prognostic nomogram was built based on multivariate competing-risk regression. C-index, the calibration, and decision-curve analysis (DCA) were performed to validate the prognostic model. RESULTS: The predictive nomogram to predict the presence of TD had a C-index of 0.785 and AUC of 0.787 and 0.782 in the training and validation sets, respectively. From the competing-risk analysis, chemotherapy (subdistribution hazard ratio (SHR) = 0.542, p < 0.001) can significantly reduce CRC-specific death (CCSD). The prognostic nomogram for the outcome prediction in postoperative CRC-NDM patients with TD had a C-index of 0.727. The 5-year survival of CCSD was 17.16%, 36.20%, and 63.19% in low-, medium-, and high-risk subgroups, respectively (Gray's test, p < 0.001). CONCLUSIONS: We constructed an easily predictive nomogram in identifying the high-risk TD-positive CRC-NDM patients. Besides, a prognostic nomogram was built to help clinicians identify poor-outcome individuals in postoperative CRC-NDM patients with TD. For the high-risk or medium-risk subgroup, additional chemotherapy may be more advantageous for the TD-positive patients rather than radiotherapy.

The Influence of Brand Image and Favorability Toward Citizens in a Product's Country of Origin on Product Evaluation: Moderating Effects of Switching Costs.

This study aimed to provide practical implications for South Korean corporations seeking to enter the Chinese market. It explored the influences of brand image and favorability toward citizens in a product's country of origin (FCPCO) on consumers' product evaluation and repurchase intention, in addition to examining the moderating effects of procedural switching costs (economic risk costs, evaluation costs, learning costs, and set-up costs), financial switching costs (benefit loss costs and monetary loss costs), and relational switching costs (personal relationship loss costs and brand relationship loss costs) on the aforementioned influences. Although previous studies have established the relationships between some of the aforementioned variables, further research is required to determine the moderating effects of switching costs in various dimensions. Studies on the relationships of a product's country of origin with product evaluation and repurchase intention have rarely explored FCPCO. Through a questionnaire survey, this study obtained effective data from 302 respondents. Constituted of an exploratory research design, this study adopted PLS-SEM method for empirical analysis. IPMA analysis results indicated that brand image had a stronger influence on product evaluation than FCPCO did and that FCPCO had a stronger influence on repurchase intention than brand image did. Overall, the performance of FCPCO was higher than that of brand image. Moreover, economic risk costs and brand relationship loss costs positively moderated the relationship between brand image and product evaluation; monetary loss costs and brand relationship loss costs negatively moderated the relationship between FCPCO and product evaluation. These study results could help corporations gain competitive edge.

In Vitro Assessment of Hydrolysed Collagen Fermentation Using Domestic Cat (Felis catus) Faecal Inocula.

The gastrointestinal microbiome has a range of roles in the host, including the production of beneficial fermentation end products such as butyrate, which are typically associated with fermentation of plant fibres. However, domestic cats are obligate carnivores and do not require carbohydrates. It has been hypothesised that in the wild, collagenous parts of prey-the so-called animal-derived fermentable substrates (ADFS) such as tendons and cartilage-may be fermented by the cat's gastrointestinal microbiome. However, little research has been conducted on ADFS in the domestic cat. Faecal inoculum was obtained from domestic cats either consuming a high carbohydrate (protein:fat:carbohydrate ratio of 35:20:28 (% dry matter basis)) or high protein (protein:fat:carbohydrate ratio of 75:19:1 (% dry matter basis)) diet. ADFS (hydrolysed collagen, cat hair, and cartilage) were used in a series of static in vitro digestions and fermentations. Concentrations of organic acids and ammonia were measured after 24 h of fermentation, and the culture community of microbes was characterised. The type of inoculum used affected the fermentation profile produced by the ADFS. Butyrate concentrations were highest when hydrolysed collagen was fermented with high protein inoculum (p < 0.05). In contrast, butyrate was not detectable when hydrolysed collagen was fermented in high carbohydrate inoculum (p < 0.05). The microbiome of the domestic cat may be able to ferment ADFS to provide beneficial concentrations of butyrate.

The public health burden of geriatric trauma: Analysis of 2,688,008 hospitalizations from Centers for Medicare and Medicaid Services inpatient claims.

BACKGROUND: Geriatric trauma care (GTC) represents an increasing proportion of injury care, but associated public health research on outcomes and expenditures is limited. The purpose of this study was to describe GTC characteristics, location, diagnoses, and expenditures. METHODS: Patients at short-term nonfederal hospitals, 65 years or older, with ≥1 injury International Classification of Diseases, Tenth Revision, were selected from 2016 to 2019 Centers for Medicare and Medicaid Services Inpatient Standard Analytical Files. Trauma center levels were linked to Inpatient Standard Analytical Files data via American Hospital Association Hospital ID and fuzzy string matching. Demographics, care location, diagnoses, and expenditures were compared across groups. RESULTS: A total of 2,688,008 hospitalizations (62% female; 90% White; 71% falls; mean Injury Severity Score, 6.5) from 3,286 hospitals were included, comprising 8.5% of all Medicare inpatient hospitalizations. Level I centers encompassed 7.2% of the institutions (n = 236) but 21.2% of hospitalizations, while nontrauma centers represented 58.5% of institutions (n = 1,923) and 37.7% of hospitalizations. Compared with nontrauma centers, patients at Level I centers had higher Elixhauser scores (9.0 vs. 8.8) and Injury Severity Score (7.4 vs. 6.0; p < 0.0001). The most frequent primary diagnosis at all centers was hip/femur fracture (28.3%), followed by traumatic brain injury (10.1%). Expenditures totaled $32.9 billion for trauma-related hospitalizations, or 9.1% of total Medicare hospitalization expenditures and approximately 1.1% of the annual Medicare budget. The overall mortality rate was 3.5%. CONCLUSION: Geriatric trauma care accounts for 8.5% of all inpatient GTC and a similar percentage of expenditures, the most common injury being hip/femur fractures. The largest proportion of GTC occurs at nontrauma centers, emphasizing their vital role in trauma care. Public health prevention programs and GTC guidelines should be implemented by all hospitals, not just trauma centers. Further research is required to determine the optimal role of trauma systems in GTC, establish data-driven triage guidelines, and define the impact of trauma centers and nontrauma centers on GTC mortality. LEVEL OF EVIDENCE: Therapeutic/care management, Level III.

Impact of Monetary Policy Uncertainty on R&D Investment Smoothing Behavior of Pharmaceutical Manufacturing Enterprises: Empirical Research Based on a Threshold Regression Model.

R&D investment is the source of technological innovation of pharmaceutical enterprises, but it will be restricted by the funding level, especially in the context of major public health emergencies occurring more frequently, therefore exploring the impact of monetary policy uncertainty on the R&D investment smoothing behavior of pharmaceutical manufacturing enterprises has important theoretical and practical value. Based on the relevant data of Chinese pharmaceutical manufacturing enterprises from 2012 to 2018, this paper studies the impact of monetary policy uncertainty on R&D investment smoothing behavior of pharmaceutical enterprises, and investigates whether there is a threshold effect. First, our results demonstrate that the empirical test results of this article support the hypothesis of R&D investment smoothing behavior of pharmaceutical manufacturing enterprises. Second, there is a negative correlation between monetary policy uncertainty and R&D investment smoothing behavior, and the shorter the period is, the higher the financing constraints of pharmaceutical enterprises are, and the more obvious the negative correlation is. Third, financing constraints have a single threshold effect on the R&D investment smoothing behavior of pharmaceutical manufacturing enterprises, with a threshold of -13.7693. Moreover, this conclusion can better promote the virtuous circle of the real economy of financial and pharmaceutical manufacturing enterprises. It is recommended that pharmaceutical manufacturing enterprises establish and improve the enterprise R&D reserve system, reduce the risk of R&D investment, play the role of R&D smoothing, and realize the sustainable development of enterprise R&D.

Population pharmacokinetics-pharmacodynamics of ceftazidime in neonates and young infants: Dosing optimization for neonatal sepsis.

Ceftazidime is a third-generation cephalosporin with high activity against many pathogens. But the ambiguity and diversity of the dosing regimens in neonates and young infants impair access to effective treatment. Thus, we conducted a population pharmacokinetic study of ceftazidime in this vulnerable population and recommended a model-based dosage regimen to optimize sepsis therapy. Totally 146 neonates and young infants (gestational age (GA): 36-43.4 weeks, postnatal age (PNA): 1-81 days, current weight (CW): 900-4500 g) were enrolled based on inclusion and exclusion criteria. Ceftazidime bloods samples (203) were obtained using the opportunistic sampling strategy and determined by the high-performance liquid chromatography. The population pharmacokinetic-pharmacodynamic analysis was conducted by nonlinear mixed effects model (NONMEM). A one-compartment model with first-order elimination best described the pharmacokinetic data. Covariate analysis showed the significance of GA, PNA, and CW on developmental pharmacokinetics. Monte Carlo simulation was performed based on above covariates and minimum inhibitory concentration (MIC). In the newborns with PNA ≤ 3 days (MIC=8 mg/L), the dose regimen was 25 mg/kg twice daily (BID). For the newborns with PNA > 3 days (MIC=16 mg/L), the optimal dose was 30 mg/kg three times daily (TID) for those with GA ≤ 37 weeks and 40 mg/kg TID for those with GA > 37 weeks. Overall, on the basis of the developmental population pharmacokinetic-pharmacodynamic analysis covering the whole range of neonates and young infants, the evidence-based ceftazidime dosage regimens were proposed to optimize neonatal early-onset and late-onset sepsis therapy.

ADGRA1 negatively regulates energy expenditure and thermogenesis through both sympathetic nervous system and hypothalamus-pituitary-thyroid axis in male mice.

Adhesion G protein-coupled receptor A1 (ADGRA1, also known as GPR123) belongs to the G protein-coupled receptors (GPCRs) family and is well conserved in the vertebrate lineage. However, the structure of ADGRA1 is unique and its physiological function remains unknown. Previous studies have shown that Adgra1 is predominantly expressed in the central nervous system (CNS), indicating its important role in the transduction of neural signals. The aim of this study is to investigate the central function of Adgra1 in vivo and clarify its physiological significance by establishing an Adgra1-deficient mouse (Adgra1-/-) model. The results show that Adgra1-/- male mice exhibit decreased body weight with normal food intake and locomotion, shrinkage of body mass, increased lipolysis, and hypermetabolic activity. Meanwhile, mutant male mice present elevated core temperature coupled with resistance to hypothermia upon cold stimulus. Further studies show that tyrosine hydroxylase (TH) and ß3-adrenergic receptor (ß3-AR), indicators of sympathetic nerve excitability, are activated as well as their downstream molecules including uncoupling protein 1 (UCP1), coactivator 1 alpha (PGC1-α) in brown adipose tissue (BAT), and hormone-sensitive lipase (HSL) in white adipose tissue (WAT). In addition, mutant male mice have higher levels of serum T3, T4, accompanied by increased mRNAs of hypothalamus-pituitary-thyroid axis. Finally, Adgra1-/- male mice present abnormal activation of PI3K/AKT/GSK3ß and MEK/ERK pathways in hypothalamus. Overexpression of ADGRA1 in Neuro2A cell line appears to suppress these two signaling pathways. In contrast, Adgra1-/- female mice show comparable body weight along with normal metabolic process to their sex-matched controls. Collectively, ADGRA1 is a negative regulator of sympathetic nervous system (SNS) and hypothalamus-pituitary-thyroid axis by regulating PI3K/AKT/GSK3ß and MEK/ERK pathways in hypothalamus of male mice, suggesting an important role of ADGRA1 in maintaining metabolic homeostasis including energy expenditure and thermogenic balance.

Reframing the meaning of life and professional values: A theoretical framework of facilitating professional care for terminally ill patients.

Professional values reflect nurses' understanding of how to deliver professional care, which might influence nurses' attitudes and caring behaviors during end-of-life care. However, limited research has been conducted to explore nurses' experiences of professional development during end-of-life care, and theoretical explanations are scarce about how nurses enact their professional values during the caring process. This study explored the social process of professional values involved in end-of-life care in the Chinese cultural context by adopting a constructivist grounded theory approach. Twenty semi-structured in-depth interviews with 15 nurses from three hospitals in southeastern China were conducted. A theoretical framework emerged when focusing on the social process of "reframing the meaning of life and professional values" to facilitate professional care for terminally ill patients. Three main categories were sequentially identified as "recognizing the dilemmas when caring for terminally ill patients," "applying strategies to deal with values conflict," and "reconstructing values." This theoretical framework may be applied as a practical framework for equipping nurses with effective strategies to cultivate professional values, including the provision of adequate end-of-life knowledge, and a supportive workplace environment.

Clinical Assessment of Ultrasound-Guided Local Lauromacrogol Injection Combined With Curettage and Hysteroscopy for Cesarean Scar Pregnancy.

Background: To evaluate the efficacy, safeness and cost of ultrasound-guided local lauromacrogol injection (USG-LLI) combined with curettage and hysteroscopy for cesarean scar pregnancy (CSP). Methods: This was a retrospective study included 151 CSP patients diagnosed with CSP from June 2017 to December 2019, and treated by USG-LLI (n = 86) or uterine artery embolization (UAE) (n = 65) combined with curettage and hysteroscopy. Clinical data and outcome were analyzed. Results: There were no significant differences in basic clinical characteristics in the two groups. Two groups showed the similar success rates. USG-LLI group, compared with UAE group had significantly lower complication rates (9.30 vs. 44.62%), lower total costs (both medical and non-medication cost) (p < 0.05). Conclusions: USG-LLI combined with curettage and hysteroscopy is a feasible method to treat CSP with minimal invasion and high efficacy. Moreover, compared with curettage after UAE, USG-LLI exhibited lower complication rate and required fewer expenses.

Probabilistic health risk assessment of nitrosamines in drinking water of Shaoxing, Zhejiang, China.

Nitrosamines (NAms) are potent genotoxic and carcinogenic but widely detected in drinking water. This study aimed to investigate the occurrence of major types of NAms in drinking water in Shaoxing, China, and to conduct multi-pathway probabilistic cancer risk (CR) assessment to residents based on age-dependent adjustment Chinese exposure factors. Results showed that concentrations of NAms in water varied from not detected (ND) to dozens of nanograms per liter level. N-Nitrosodimethylamine (NDMA) was detected most frequently (93.06%), followed by N-nitrosodiethylamine (NDEA) (64.08%)-with the highest cancer risk among NAms. The CR of NAms came mainly through the oral exposure pathway. The 95th percentile of the total CR of five major NAms was 1.06 × 10-4, exceeding the maximum acceptable lifetime CR (1 × 10-4) recommended by US EPA. Exposure to NDEA contributed the highest to the total CR. The CR of the five NAms through ingestion was 2.5 times higher using the Chinese exposure factors than that of the Americans. The most important variables related to CRs were concentrations of NAms in drinking water, exposure duration, drinking water ingestion rate, and exposure time during bathing. Our findings suggest the urgent need to develop and enforce effective regulatory policies to control the contamination of NAms in drinking water in China. Graphical abstract.

Different types of quantum integral inequalities via ( α , m ) -convexity.

In this paper, based on ( α , m ) -convexity, we establish different type inequalities via quantum integrals. These inequalities generalize some results given in the literature.

Life Satisfaction in China and Consumption and Income Inequalities.

This research uses nationally representative data to study how economic resources and inequalities are associated with life satisfaction of Chinese residents. We construct economic resource and inequality measures from expenditure rather than from income, after confirming that expenditure inequality is a better measure in the Chinese context. We find that economic inequalities in general are negatively associated with life satisfaction, and that this association is larger for inequalities in the lower half of the distribution than those in the upper half of the distribution. We further explore the mechanisms under which inequality can be associated with life satisfaction, and find that aspiration is potentially one important channel.