Retrospective Analysis of Adverse Factors Impacting Medicine Logistics.

Background: Medicine logistics, particularly cryogenic storage, maintains pharmaceutical efficacy and safety. Ensuring seamless transportation and storage prevents spoilage, degradation, or contamination, safeguarding patient health. Objective: This study aimed to analyze the relationships among the components of the medication cold chain logistics system using grey relational analysis (GRA). Additionally, we utilized GRA to construct an adjacency matrix, facilitating a comprehensive understanding of the interdependencies within the system. Methods: Data from pertinent indices spanning 2021 and 2022 were utilized to conduct a quantitative analysis using GRA. This analysis aimed to identify the most influential elements affecting the growth of pharmaceutical cold chain logistics in a specific location. The negative aspects of the medication cold chain logistics system in particular areas were examined by assessing the grey relationship grades between various components and the medicine cold chain logistics system in those regions. Results: The analysis revealed significant insights into the correlated risk factors impacting medicine logistics operations. Through an examination of the financial status and operational processes of medicine logistics assets, four categories of risks were identified, encompassing transportation, storage, distribution, and quality management. These categories were established by analyzing the most significant risk factors across these operational domains. Additionally, GRA was employed to assess the factors influencing medicine logistics. The study found a strong relationship between key parameters, such as transportation risk and site facilities and equipment, and the growth of the pharmaceutical logistics sector. Operation risk emerged as the least influential factor, while site facilities and equipment, transportation risk, and operation risk demonstrated substantial influence on the region's medical logistics sector growth. Conclusion: This study provides important recommendations to improve medicine logistics, aiming to mitigate adverse effects and elevate inventory management. Implementation can enhance efficiency and safety in the medicine supply chain, benefiting patient care and public health.

A methodological study on the identification of ecological security change processes and zoning control strategies -- Based on the perspective of sustainable development.

Ecological security (ES) is a crucial indicator for assessing the sustainable development of a region. Currently, most studies on ES primarily focus on process analysis, and the integration of environmental variability into the development of tailored control strategies for regions with varying ecological quality is overlooked. Therefore, in this study, we identified regional ES change processes, employed an optimized system to calculate the ecological security index (ESI), and identified ecological corridors (ECs) through the Minimum Constrained Resource (MCR) model to determine zoning strategies for typical arid regions, using the Ningxia region in the Yellow River Basin of China as an example. The findings showed that (1) from 2006 to 2020, the ESI values of most regions were between 0.2 and 0.4, with small but consistent increases in the ESI values over the years. (2) The proportion of regions with high ES ratings increased by 9.08 % across all districts and counties, and the center of gravity of ES shifted in a north-south and east-west direction. (3) The ESI exhibited a strong positive spatial correlation, characterized by spatial diffusion and spillover effects in most regions. (4) The ECs were predominantly distributed in a north-south direction, involving a total of 20 districts and counties. Based on the principles of sustainable development, we developed a model for the dynamic identification and zoning control of regional ES, aiming to provide a practical framework for effective ecological restoration and protection measures. Additionally, the strategies and methodologies presented in this study serve as important references for similar regions worldwide to facilitate the zoning control of ES, highlighting the broader significance and applicability of the study.

Comprehensive Summary of Safety Data on Nirsevimab in Infants and Children from All Pivotal Randomized Clinical Trials.

BACKGROUND: Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in children aged ≤24 months who remain vulnerable to severe RSV disease through their second RSV season. We summarize a pre-specified analysis of nirsevimab safety data from three randomized controlled trials: Phase 2b (NCT02878330; healthy infants born ≥29 to <35 weeks' gestational age [wGA]); Phase 3 MELODY (NCT03979313; healthy infants born ≥35 wGA); and Phase 2/3 MEDLEY (NCT03959488; infants with congenital heart disease [CHD] and/or chronic lung disease of prematurity [CLD] or born ≤35 wGA). METHODS: Participants (randomized 2:1) received a single intramuscular dose of nirsevimab or comparator (placebo, Phase 2b/MELODY; 5× once-monthly palivizumab, MEDLEY) before their first RSV season (recipients < 5 kg, nirsevimab 50 mg; ≥5 kg, nirsevimab 100 mg). In MEDLEY, children with CHD/CLD continued to a second RSV season: first-season nirsevimab recipients received nirsevimab 200 mg; first-season palivizumab recipients were re-randomized 1:1 to receive nirsevimab 200 mg or 5× once-monthly palivizumab. RESULTS: The incidence, severity, and nature of AEs were similar across treatments (nirsevimab, n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with ≥98% unrelated to treatment. AEs of special interest occurred infrequently (<1%): no anaphylaxis or thrombocytopenia were treatment-related, and no immune complex disease was reported. Deaths (incidence < 1.0%) were all unrelated to treatment. CONCLUSIONS: A single dose per season of nirsevimab for the prevention of RSV disease had a favorable safety profile, irrespective of wGA or comorbidities.

Self-Assessed Educational Needs of Chinese Pediatric Clinicians Regarding Pediatric Palliative Care: A Cross-Sectional Investigation.

BACKGROUND: An important first step in enhancing professional palliative care training is to investigate the educational needs of pediatric clinicians in this field. The aims of this research were to analyze the extent of end-of-life care experience of Chinese pediatric clinicians and identify the differing educational needs of physicians and nurses as well as associated impact factors. METHODS: A cross-sectional descriptive survey via a structural questionnaire was used in this research. RESULTS: In total, 187 clinicians, comprising 52 physicians and 135 nurses, participated in this study. The topics "pain management", "symptom management", and "discussing the prognosis with family members" were the most expressed educational needs among both physicians and nurses. Compared to nurses, physicians placed greater emphasis on the importance of "communication" and "pain and symptom management" (p < 0.05). Clinicians with more extensive end-of-life care experience more strongly felt the importance of learning about pain management and communication regarding end-of-life care (p < 0.05). CONCLUSIONS: Research showed that the education currently provided to pediatric clinicians does not meet their distinctive needs. Future palliative care education must be a continuing multi-level, interdisciplinary program and different education should be provided to physicians and nurses based on their respective needs.

Comparative analysis of corneal parameters in simple myopic anisometropia using Scheimpflug technology.

Purpose: This study aims to investigate the differences in binocular corneal parameters and their interrelation with binocular biometric parameters asymmetry in patients with simple myopic anisometropia, thereby elucidating the influence of myopia process on various corneal parameters. Methods: In this cross-sectional study, 65 patients with anisometropia in monocular myopia were included. They were divided into low anisometropia group: 3.00D<Δ spherical equivalent (SE)≤-1.00D (Δ represents the difference between the two eyes, i.e., myopic data minus emmetropic data) and high anisometropia group: ΔSE ≤ -3.00D. Corneal and ocular biometric parameters were measured using Pentacam, Corvis ST, and IOL Master 700. Statistical analyses focused on the binocular corneal parameters asymmetry, using the contralateral emmetropia as a control. Results: The mean age of participants was 18.5 ± 1.3 years, with the average SE for myopia and emmetropia being -2.93 ± 1.09D and -0.16 ± 0.41D, respectively. The central corneal thickness (CCT), flat keratometry (Kf), keratometry astigmatism (Ka), total corneal aberration (6 mm) (TOA), surface variance index (ISV), vertical asymmetry index (IVA), stress-strain index (SSI), and first applanation stiffness parameter (SPA1) and ambrosia relational thickness-horizontal (ARTh) showed significant differences between anisometropic fellow eyes (p < 0.05). There were significant differences in ΔIVA, Δ the difference between the mean refractive power of the inferior and superior corneas (I-S), Δ deviation value of Belin/Ambrósio enhanced ectasia display (BAD-D), Δ deformation amplitude ratio max (2 mm) (DAR)and Δ tomographic biomechanical index (TBI) (p < 0.05) in two groups. Asymmetry of corneal parameters was correlated with asymmetry of ocular biometric parameters. Anisometropia (ΔSE) was positively correlated with ΔIVA (r = 0.255, p = 0.040), ΔBAD-D (r = 0.360, p = 0.006), and ΔSSI (r = 0.276, p = 0.039) and negatively correlated with ΔDAR (r = -0.329, p = 0.013) in multiple regression analysis. Δ mean keratometry (Km), Δ anterior chamber depth (ACD), and Δ biomechanically corrected intraocular pressure (bIOP) were also associated with binocular corneal differences. Conclusion: Compared to contralateral emmetropia, myopic eyes have thinner corneas and smaller corneal astigmatism. Myopic corneas exhibit relatively more regular surface morphology but are more susceptible to deformation and possess marginally inferior biomechanical properties. In addition, there is a certain correlation between anisometropia and corneal parameter asymmetry, which would be instrumental in predicting the development of myopia.

Neuroimaging with Rotterdam Scoring System and long-term outcomes in severe traumatic brain injury patients.

PURPOSE: The Rotterdam Scoring System (RSS) attempts to prognosticate early mortality and early functional outcome in patients with traumatic brain injury (TBI) based on non-contrast head computed tomography (CT) imaging findings. The purpose of this study was to identify the relationship between RSS scores and long-term outcomes in patients with severe TBI. METHODS: Consecutively treated patients with severe TBI enrolled between 2008 and 2011, in the prospective, observational, Brain Trauma Research Center database were included. The Glasgow Outcome Scale (GOS) was used to measure long-term functional outcomes at three, six, 12, and 24 months. GOS scores were categorized into favorable (GOS = 4-5) and unfavorable (GOS = 1-3) outcomes. RSS scores were calculated at the time of image acquisition. RESULTS: Of the 89 patients included, 74 (83.4%) were male, 81 (91.0%) were Caucasian, and the mean age of the cohort was 41.9 ± 18.5 years old. Patients with an RSS score of 3 and lower were more likely to have a favorable outcome with increased survival rates than patients with RSS scores greater than 3. CONCLUSIONS: The RSS score determined on the head CT scan acquired at admission in a cohort of patients with severe TBI correlated with long-term survival and functional outcomes up to two years following injury.

Depression assessment using integrated multi-featured EEG bands deep neural network models: Leveraging ensemble learning techniques.

Mental Status Assessment (MSA) holds significant importance in psychiatry. In recent years, several studies have leveraged Electroencephalogram (EEG) technology to gauge an individual's mental state or level of depression. This study introduces a novel multi-tier ensemble learning approach to integrate multiple EEG bands for conducting mental state or depression assessments. Initially, the EEG signal is divided into eight sub-bands, and then a Long Short-Term Memory (LSTM)-based Deep Neural Network (DNN) model is trained for each band. Subsequently, the integration of multi-band EEG frequency models and the evaluation of mental state or depression level are facilitated through a two-tier ensemble learning approach based on Multiple Linear Regression (MLR). The authors conducted numerous experiments to validate the performance of the proposed method under different evaluation metrics. For clarity and conciseness, the research employs the simplest commercialized one-channel EEG sensor, positioned at FP1, to collect data from 57 subjects (49 depressed and 18 healthy subjects). The obtained results, including an accuracy of 0.897, F1-score of 0.921, precision of 0.935, negative predictive value of 0.829, recall of 0.908, specificity of 0.875, and AUC of 0.8917, provide evidence of the superior performance of the proposed method compared to other ensemble learning techniques. This method not only proves effective but also holds the potential to significantly enhance the accuracy of depression assessment.

The role of alexithymia in suicide ideation among Taiwanese army military personnel: A serial mediation model investigating the effects of perceived stress and depression.

Maintaining the good mental health of Taiwanese military personnel is crucial, especially in light of incidents such as the Taiwan Strait crisis. Suicide is a leading cause of death among military personnel and alexithymia is a significant risk factor for suicidal ideation. However, the mechanisms linking alexithymia and suicidal ideation in this psychologically burdened population remain poorly understood. In total, 863 voluntary army military personnel from Taiwanese reserve brigades and combined-arms brigades were enroled between May 2020 and February 2021. Structured questionnaires about alexithymia, perceived stress, depression, suicidal ideation, and background characteristics were used. Mediation analyses were conducted to examine the serial mediation roles of perceived stress and depression in the relationship between alexithymia and suicidal ideation. Significant positive correlations were observed between alexithymia, perceived stress, depression, and suicidal ideation in bivariate analyses. Serial mediation analyses revealed that alexithymia significantly predicted higher levels of perceived stress, subsequently leading to depressive symptoms, which were associated with suicidal ideation. Depression served as a significant mediator between alexithymia and suicidal ideation. The strongest mediating effect (71.4%) was observed in the pathway from alexithymia through perceived stress and depression to suicidal ideation. Limitations included the utilization of cross-sectional data and a reliance on retrospective self-report measures. Perceived stress and depression were identified as serial mediators in the association between alexithymia and suicidal ideation. Clinically, it is crucial to prioritise interventions that target emotional regulation skills and assess the presence of alexithymia to effectively reduce suicidal ideation in military personnel.

Textbook oncological outcomes and prognosis after curative gastrectomy in advanced gastric cancer: A multicenter study.

BACKGROUND: The impact of achieving textbook oncological outcome (TOO) as a multimodal therapy quality indicator on the prognosis of advanced gastric cancer (AGC) remains inadequately assessed. METHODS: Patients with AGC who underwent curative gastrectomy between January 2010 and December 2017 at two East Asian medical centers were included. TOO was defined as achieving the textbook outcome (TO) and receiving neoadjuvant and/or adjuvant chemotherapy (NCT or ACT). Cox and logistic regression models were used to identify prognostic and non-TOO-associated risk factors. RESULTS: Among 3626 patients, 57.6% achieved TOO (TOO group), exhibiting significantly better 5-year overall survival (OS) and disease-free survival (DFS) than the non-TOO group (both p < 0.05). Multivariate Cox regression identified TOO as an independent prognostic factor for 5-year OS (HR, 0.67; 95% CI, 0.61-0.74; p < 0.001) and DFS (HR, 0.73; 95% CI, 0.66-0.81; p < 0.001). Multivariate logistic regression showed that open gastrectomy, lack of health insurance, age ≥65 years, ASA score ≥ Ⅲ, and tumor size ≥50 mm are independent risk factors for non-achievement of TOO (all p < 0.05). On a sensitivity analysis of TOO's prognostic value using varying definitions of chemotherapy parameters, a stricter definition of chemotherapy resulted in a decrease in the TOO achievement rate from 57.6 to 22.3%. However, the associated reductions in the risk of death and recurrence fluctuated within the ranges of 33-39% and 28-37%, respectively. CONCLUSIONS: TOO is a reliable and stable metric for favorable prognosis in AGC. Optimizing the surgical approach and improving health insurance status may enhance TOO achievement.

Diurnal variation of cerebral blood flow in healthy humans under normal entrained conditions.

The presence of a circadian cycle of cerebral blood flow may have implications for the occurrence of daily variations in cerebrovascular events in humans, but how cerebral blood flow varies throughout the day and its mechanism are still unclear. The study aimed to explore the diurnal variation of cerebral blood flow in healthy humans and its possible mechanisms. Arterial spin labelling images were collected at six time-points (09:00 hours, 13:00 hours, 17:00 hours, 21:00 hours, 01:00 hours, 05:00 hours) from 18 healthy participants (22-39 years old; eight females) to analyse diurnal variations in cerebral blood flow. Resting heart rate and blood pressure at six time-points and blood indicators (20-hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acids, prostaglandin E2, noradrenaline and nitric oxide) related to cerebral vascular tone at two time-points (09:00 hours and 21:00 hours) were collected to analyse possible influences on diurnal variations in cerebral blood flow. From 21:00 hours to 05:00 hours, parietal cortical relative cerebral blood flow tended to increase, while frontal cortical and cerebellar relative cerebral blood flow tended to decrease. There was a time-dependent negative correlation between parietal cortical relative cerebral blood flow and resting heart rate, whereas there was a time-dependent positive correlation between cerebellar relative cerebral blood flow and resting heart rate. The change of parietal cortical relative cerebral blood flow was positively correlated with the change of nitric oxide. There was also a time-dependent positive correlation between mean arterial pressure and mean whole-brain cerebral blood flow. The findings indicated that parietal cortical relative cerebral blood flow and frontal cortical/cerebellar relative cerebral blood flow showed roughly opposite trends throughout the day. The diurnal variations in relative cerebral blood flow were regional-specific. Diurnal variation of nitric oxide and neurogenic regulation may be potential mechanisms for diurnal variation in regional relative cerebral blood flow.

A novel gene-trap line reveals the dynamic patterns and essential roles of cysteine and glycine-rich protein 3 in zebrafish heart development and regeneration.

Mutations in cysteine and glycine-rich protein 3 (CSRP3)/muscle LIM protein (MLP), a key regulator of striated muscle function, have been linked to hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in patients. However, the roles of CSRP3 in heart development and regeneration are not completely understood. In this study, we characterized a novel zebrafish gene-trap line, gSAIzGFFM218A, which harbors an insertion in the csrp3 genomic locus, heterozygous fish served as a csrp3 expression reporter line and homozygous fish served as a csrp3 mutant line. We discovered that csrp3 is specifically expressed in larval ventricular cardiomyocytes (CMs) and that csrp3 deficiency leads to excessive trabeculation, a common feature of CSRP3-related HCM and DCM. We further revealed that csrp3 expression increased in response to different cardiac injuries and was regulated by several signaling pathways vital for heart regeneration. Csrp3 deficiency impeded zebrafish heart regeneration by impairing CM dedifferentiation, hindering sarcomere reassembly, and reducing CM proliferation while aggravating apoptosis. Csrp3 overexpression promoted CM proliferation after injury and ameliorated the impairment of ventricle regeneration caused by pharmacological inhibition of multiple signaling pathways. Our study highlights the critical role of Csrp3 in both zebrafish heart development and regeneration, and provides a valuable animal model for further functional exploration that will shed light on the molecular pathogenesis of CSRP3-related human cardiac diseases.

[Multi-scale Driving Mechanism of Urbanization on PM2.5 Concentration in Urban Agglomeration in the Middle Reaches of the Yangtze River].

Exploring the nonlinear effect of urbanization on PM2.5 concentration and its driving mechanism is crucial for controlling urban air pollution. Based on remote sensing data and statistical data from 2002 to 2020, spatial autocorrelation, systematic dynamic panel regression, and spatio-temporal geographical weighted regression models were used to analyze the spatio-temporal evolution of PM2.5 concentration in the urban agglomeration of the middle reaches of the Yangtze River and explore the driving mechanism of urbanization on PM2.5 concentration at different spatial scales. The results showed that:① PM2.5 concentration in the middle reaches of the Yangtze River showed an overall decreasing trend from 2002 to 2020, with a spatial distribution pattern of "high in the north and low in the south." ② Hot spot cities expanded towards the western part of the urban agglomeration, whereas cold spot cities showed enhanced spatial correlation. ③ The relationship between PM2.5 concentration and economic, land, and population urbanization followed N-shaped, U-shaped, and U-shaped curves, respectively. Secondary industry and energy consumption significantly promoted the change in PM2.5 concentration, and precipitation and vegetation helped mitigate PM2.5 pollution. ④ The overall driving effects of all urbanization factors in local areas were transformed, and the main areas of influence were concentrated in the southeast, northwest, and southwest of the study area. Considering the current urban development status and regional characteristics of the urban agglomeration in the middle reaches of the Yangtze River, promoting green industrial transformation, rational planning of urban spatial distribution and population distribution, and enhancing infrastructure construction will facilitate the coordinated development between urbanization and environmental protection.

Effects of bradycardia, hypoxemia and early intubation on bronchopulmonary dysplasia in very preterm infants: An observational study.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common pulmonary complication in preterm infants. OBJECTIVES: The study aimed to explore the effects of bradycardia, hypoxemia, and early intubation on BPD in very preterm infants. METHODS: This is a prospective observational cohort study. Preterm infants with a mean gestational age of 28.67 weeks were recruited from two level III neonatal intensive care units (NICUs) in Taiwan. Continuous electrocardiography was used to monitor heart rates and oxygen saturation (SpO2). Infants were monitored for heart rates of <100 beats per minute and SpO2 levels of <90 % lasting for 30 s. Generalized estimating equations were used to analyze the effects of bradycardia, hypoxemia, and early intubation on BPD in very preterm infants. Model fit was visually assessed using receiver operating characteristic curve analysis. RESULTS: Bradycardia, hypoxemia, and early intubation significantly increased the odds of BPD among the preterm infants (N = 39) during NICU stay; the odds ratios for bradycardia, hypoxemia, and early intubation for BPD versus non-BPD were 1.058, 1.013, and 29.631, respectively (all p < 0.05). A model combining bradycardia, hypoxemia, and early intubation accurately predicted BPD development (area under the curve = 0.919). CONCLUSIONS: Bradycardia, hypoxemia, and early intubation significantly increased the odds of BPD among very preterm infants during NICU stay. The model combining bradycardia, hypoxemia, and early intubation accurately predicted BPD development.

Critical role of FGF21 in diabetic kidney disease: from energy metabolism to innate immunity.

Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease (CKD) on a global scale, with its incidence witnessing a consistent annual rise, thereby imposing a substantial burden on public health. The pathogenesis of DKD is primarily rooted in metabolic disorders and inflammation. Recent years have seen a surge in studies highlighting the regulatory impact of energy metabolism on innate immunity, forging a significant area of research interest. Within this context, fibroblast growth factor 21 (FGF21), recognized as an energy metabolism regulator, assumes a pivotal role. Beyond its role in maintaining glucose and lipid metabolism homeostasis, FGF21 exerts regulatory influence on innate immunity, concurrently inhibiting inflammation and fibrosis. Serving as a nexus between energy metabolism and innate immunity, FGF21 has evolved into a therapeutic target for diabetes, nonalcoholic steatohepatitis, and cardiovascular diseases. While the relationship between FGF21 and DKD has garnered increased attention in recent studies, a comprehensive exploration of this association has yet to be systematically addressed. This paper seeks to fill this gap by summarizing the mechanisms through which FGF21 operates in DKD, encompassing facets of energy metabolism and innate immunity. Additionally, we aim to assess the diagnostic and prognostic value of FGF21 in DKD and explore its potential role as a treatment modality for the condition.

Feedback Intervention for the Control of Glucocorticoid Prescription in Primary Care Institutions: A Cluster Randomized Cross-Over Controlled Trial in Southwest China.

Purpose: The purpose of this study is to assess the effect of glucocorticoid prescription feedback intervention in complex primary care institutions for regulating its inappropriate use. Design Setting and Interventions: A six-month cluster randomized cross-over controlled trial was conducted in primary care institutions. A total of 347 physicians from 69 participating institutions were randomly allocated to either group A or group B. Both groups were given feedback interventions or serve as control. The feedback intervention comprised two components: a real-time pop-up warning of inappropriate glucocorticoid prescriptions based on the Hospital Information System and a high-proportion prescription feedback intervention warning system. Outcome Measures: The primary outcome measure was the 10-day inappropriate glucocorticoid prescription rate, while the 10-day glucocorticoid prescription rate served as secondary outcome measure. Results: At baseline, the 10-day inappropriate glucocorticoid prescription rates were 66.63% and 66.57% in group A and group B, respectively, showing no significant difference (p = 0.140). Following the intervention, group A exhibited a significant reduction in 10-day inappropriate glucocorticoid prescription rate at the crossing point by 13.69% (p < 0.001). In contrast, group B, which served as the control group, experienced an increase of 5.93% (p = 0.037) at the same crossover point. After the crossover point, there was a decrease in 10-day inappropriate glucocorticoid prescription rate for both groups. Group B as the intervention group demonstrated a reduction of 28.22% compared to the crossing point (p < 0.001), whereas group A showed a decrease of 12.20% (p = 0.339). The characteristics of physicians did not significantly influence the inappropriate glucocorticoid prescription rate. Conclusion: The real-time pop-up warning of inappropriate glucocorticoid prescriptions based on the Hospital Information System and high-proportion prescription feedback intervention warning system can effectively regulate the inappropriate glucocorticoid prescribing behavior of physicians. Trial Registration: ISRCTN11747547.

Sense of Coherence as a Mediator Between Functional Status and Health-Related Quality of Life in Patients With Heart Failure.

BACKGROUND: Poor functional status relating to heart failure (HF) negatively affects health-related quality of life (HRQOL). Patients with HF, especially those with New York Heart Association (NYHA) Class III or IV HF, often exhibit poor HRQOL because of physical limitations and HF-related symptoms. Although sense of coherence (SOC) has been reported to be a determinant of HRQOL, its role as a mediator between functional status and HRQOL remains unclear, and few studies have explored the prevalence of HF in patients in NYHA Classes I and II. PURPOSE: This study was designed to investigate SOC as a mediator between different functional status classes and HRQOL in patients with HF. METHODS: A cross-sectional study was conducted on patients with HF recruited from a hospital in northern Taiwan from April 2020 to September 2020. The Minnesota Living with Heart Failure Questionnaire and a questionnaire on sociodemographic characteristics; functional classification in terms of NYHA Classes I, II, and III; and SOC were administered. The PROCESS v3.5 (by Andrew F. Hayes) macro was applied to analyze the effects, and Model 4 was used to examine the mediating role of SOC on the relationship between NYHA functional class and HRQOL. RESULTS: Of the 295 participants, SOC was found to mediate the effects of functional status on HRQOL more significantly in patients in Class II than those in Class III but not more significantly in patients in Class I than those in Class III. A weaker mediating effect of SOC was noted on the relationship between functional status and HRQOL in patients with HF in NYHA Class II than those in Class III. CONCLUSIONS: In patients with HF, poor functional status often reduces HRQOL significantly. SOC mediates the relationship between functional status and HRQOL more significantly in those in NYHA Class II than those in Class III. Nursing staff should work to increase patients' SOC by strengthening their coping capacity and improving their functional status to improve their HRQOL.

Association Between ß-Amyloid Accumulation and Incident Dementia in Individuals 80 Years or Older Without Dementia.

BACKGROUND AND OBJECTIVES: While the highest prevalence of dementia occurs in individuals older than 80 years, most imaging studies focused on younger populations. The rates of ß-amyloid (Aß) accumulation and the effect of Alzheimer disease (AD) pathology on progression to dementia in this age group remain unexplored. In this study, we examined the relationship between changes in Aß deposition over time and incident dementia in nondemented individuals followed during a period of 11 years. METHODS: We examined 94 participants (age 85.9 + 2.8 years) who had up to 5 measurements of Pittsburgh compound-B (PiB)-PET and clinical evaluations from 2009 to 2020. All 94 participants had 2 PiB-PET scans, 76 participants had 3 PiB-PET scans, 18 participants had 4 PiB-PET scans, and 10 participants had 5 PiB-PET scans. The rates of Aß deposition were compared with 120 nondemented individuals younger than 80 years (69.3 ± 5.4 years) from the Australian Imaging, Biomarker, and Lifestyle (AIBL) study who had 3 or more annual PiB-PET assessments. RESULTS: By 2020, 49% of the participants developed dementia and 63% were deceased. There was a gradual increase in Aß deposition in all participants whether they were considered Aß positive or negative at baseline. In a Cox model controlled for age, sex, education level, APOE-4 allele, baseline Mini-Mental State Examination, and mortality, short-term change in Aß deposition was not significantly associated with incident dementia (HR 2.19 (0.41-11.73). However, baseline Aß burden, cortical thickness, and white matter lesions volume were the predictors of incident dementia. Aß accumulation was faster (p = 0.01) in the older cohort (5.6%/year) when compared with AIBL (4.1%/year). In addition, baseline Aß deposition was a predictor of short-term change (mean time 1.88 years). DISCUSSION: There was an accelerated Aß accumulation in cognitively normal individuals older than 80 years. Baseline Aß deposition was a determinant of incident dementia and short-term change in Aß deposition suggesting that an active Aß pathologic process was present when these participants were cognitively normal. Consequently, age may not be a limiting factor for the use of the emergent anti-Aß therapies.

Infants Receiving a Single Dose of Nirsevimab to Prevent RSV Do Not Have Evidence of Enhanced Disease in Their Second RSV Season.

To characterize nirsevimab in the prevention of RSV, children from the Phase 3 MELODY trial were followed through their second RSV season. No increase in medically attended RSV lower respiratory tract infections or evidence of antibody-dependent enhancement of infection or disease severity was found for nirsevimab vs placebo recipients. Clinical Trial Registration: Clinicaltrials.gov, NCT03979313, https://clinicaltrials.gov/ct2/show/NCT03979313.

Glia-derived adenosine in the ventral hippocampus drives pain-related anxiodepression in a mouse model resembling trigeminal neuralgia.

Glial activation and dysregulation of adenosine triphosphate (ATP)/adenosine are involved in the neuropathology of several neuropsychiatric illnesses. The ventral hippocampus (vHPC) has attracted considerable attention in relation to its role in emotional regulation. However, it is not yet clear how vHPC glia and their derived adenosine regulate the anxiodepressive-like consequences of chronic pain. Here, we report that chronic cheek pain elevates vHPC extracellular ATP/adenosine in a mouse model resembling trigeminal neuralgia (rTN), which mediates pain-related anxiodepression, through a mechanism that involves synergistic effects of astrocytes and microglia. We found that rTN resulted in robust activation of astrocytes and microglia in the CA1 area of the vHPC (vCA1). Genetic or pharmacological inhibition of astrocytes and connexin 43, a hemichannel mainly distributed in astrocytes, completely attenuated rTN-induced extracellular ATP/adenosine elevation and anxiodepressive-like behaviors. Moreover, inhibiting microglia and CD39, an enzyme primarily expressed in microglia that degrades ATP into adenosine, significantly suppressed the increase in extracellular adenosine and anxiodepressive-like behaviors. Blockade of the adenosine A2A receptor (A2AR) alleviated rTN-induced anxiodepressive-like behaviors. Furthermore, interleukin (IL)-17A, a pro-inflammatory cytokine probably released by activated microglia, markedly increased intracellular calcium in vCA1 astrocytes and triggered ATP/adenosine release. The astrocytic metabolic inhibitor fluorocitrate and the CD39 inhibitor ARL 67156, attenuated IL-17A-induced increases in extracellular ATP and adenosine, respectively. In addition, astrocytes, microglia, CD39, and A2AR inhibitors all reversed rTN-induced hyperexcitability of pyramidal neurons in the vCA1. Taken together, these findings suggest that activation of astrocytes and microglia in the vCA1 increases extracellular adenosine, which leads to pain-related anxiodepression via A2AR activation. Approaches targeting astrocytes, microglia, and adenosine signaling may serve as novel therapies for pain-related anxiety and depression.