A ß-Carboline Derivate PAD4 Inhibitor Reshapes Neutrophil Phenotype and Improves the Tumor Immune Microenvironment against Triple-Negative Breast Cancer.

Triple-negative breast cancer is a highly aggressive and heterogeneous breast cancer subtype characterized by early metastasis, poor prognosis, and high recurrence. Targeting histone citrullination-mediated chromatin dysregulation to induce epigenetic alterations shows great promise in TNBC therapy. We report the synthesis, optimization, and evaluation of a novel series of ß-carboline-derived peptidyl arginine deiminase 4 inhibitors that exhibited potent inhibition of TNBC cell proliferation. The most outstanding PAD4 inhibitor, compound 28, hindered the PAD4-H3cit-NET signaling pathway and inhibited the growth of solid tumors and pulmonary metastatic nodules in the 4T1 in situ mouse model. Furthermore, 28 improved the tumor immune microenvironment by reshaping neutrophil phenotype, upregulating the proportions of dendritic cells and M1 macrophages, and reducing the amount of myeloid-derived suppressor cells. In conclusion, our work offered 28 as an efficacious PAD4 inhibitor that exerts a combination of conventional chemotherapy and immune-boosting effects, which represents a potential therapy strategy for TNBC.

Genome Mining Leads to Diverse Sesquiterpenes with Anti-inflammatory Activity from an Arctic-Derived Fungus.

With the advancement of bioinformatics, the integration of genome mining with efficient separation technology enables the discovery of a greater number of novel bioactive compounds. The deletion of the key gene responsible for triterpene cyclase biosynthesis in the polar strain Eutypella sp. D-1 instigated metabolic shunting, resulting in the activation of dormant genes and the subsequent production of detectable, new compounds. Fifteen sesquiterpenes were isolated from the mutant strain, with eight being new compounds. The structural elucidation of these compounds was obtained through a combination of HRESIMS, NMR spectroscopy, and ECD calculations, revealing six distinct skeleton types. Compound 7 possessed a unique skeleton of 5/10 macrocyclic ether structure. Based on the gene functions and newly acquired secondary metabolites, the metabolic shunting pathway in the mutant strain was inferred. Compounds 6, 8, 11, 14, and 15 exhibited anti-inflammatory effects without cytotoxicity through the release of nitric oxide from lipopolysaccharide-stimulated RAW264.7 cells. Notably, acorane-type sesquiterpene 8 inhibited nitric oxide production and modulated the MAPK and NLRP3/caspase-1 signaling pathways. Compound 8 also alleviated the CuSO4-induced systemic neurological inflammation symptoms in a transgenic fluorescent zebrafish model.

PD-L1 targeted peptide demonstrates potent antitumor and immunomodulatory activity in cancer immunotherapy.

Background: In recent years, immunotherapy has been emerging as a promising alternative therapeutic method for cancer patients, offering potential benefits. The expression of PD-L1 by tumors can inhibit the T-cell response to the tumor and allow the tumor to evade immune surveillance. To address this issue, cancer immunotherapy has shown promise in disrupting the interaction between PD-L1 and its ligand PD-1. Methods: We used mirror-image phage display technology in our experiment to screen and determine PD-L1 specific affinity peptides (PPL-C). Using CT26 cells, we established a transplanted mouse tumor model to evaluate the inhibitory effects of PPL-C on tumor growth in vivo. We also demonstrated that PPL-C inhibited the differentiation of T regulatory cells (Tregs) and regulated the production of cytokines. Results: In vitro, PPL-C has a strong affinity for PD-L1, with a binding rate of 0.75 µM. An activation assay using T cells and mixed lymphocytes demonstrated that PPL-C inhibits the interaction between PD-1 and PD-L1. PPL-C or an anti-PD-L1 antibody significantly reduced the rate of tumor mass development in mice compared to those given a control peptide (78% versus 77%, respectively). The results of this study demonstrate that PPL-C prevents or retards tumor growth. Further, immunotherapy with PPL-C enhances lymphocyte cytotoxicity and promotes proliferation in CT26-bearing mice. Conclusion: PPL-C exhibited antitumor and immunoregulatory properties in the colon cancer. Therefore, PPL-C peptides of low molecular weight could serve as effective cancer immunotherapy.

Childhood adversities and caregiving for older parents: Building capacity for a caring society.

OBJECTIVES: This study investigates the relationships between childhood adversities and the provision of informal care for older parents in later life in China. METHOD: The data came from four waves of the China Health and Retirement Longitudinal Study (CHARLS, N = 20,047). Using multilevel logistic regression models, we examined the relationships between adverse experiences in childhood and both the propensity and intensity of caregiving for older parents. Drawing on the regression results, we then estimated the total number of caregivers for older parents in China. RESULTS: Experiencing one additional childhood adversity was associated with a decrease of 8% in the odds of providing informal care (p<0.001). The association between childhood adversity and caregiving remained significant after socio-demographic factors and later life outcomes were controlled for. We estimated that 58.3 million middle-aged adults in China were providing care for parents in 2020. Had people experienced one fewer adversity in their childhood, there would have been 2.2 million more caregivers in 2020. Had they experienced two fewer adversities, there would have been 3.4 million more caregivers. DISCUSSION: The factors associated with informal caregiving can be traced back to early life experiences. To address the shortage of informal care supply, it is crucial to foster a caring culture from the very beginning of human development.

Consensus statement of Chinese experts on exercise prescription (2023).

Exercise prescriptions play a vital role in the prevention and treatment of chronic diseases. A consensus regarding exercise prescription is important for physical health. The "Consensus statement of Chinese experts on exercise prescription" (hereinafter referred to as "Expert Consensus") divides exercise prescription into two categories: fitness exercise prescription and medical exercise prescription. Traditional Chinese fitness exercises, exercise risk, exercise prescription, and basic precautions for exercise prescription are explained.

Trends in temporal and spatial changes of Japanese encephalitis in Chinese mainland, 2004-2019: A population-based surveillance study.

BACKGROUND: Japanese encephalitis (JE) is a serious health concern in China, with approximately 80 % of global infections occurring in China. To develop effective prevention and control strategies, this study explored the epidemiological characteristics of JE in China based on spatiotemporal data, to understand the patterns and trends of JE incidence in different regions and time periods. METHOD: The incidence and mortality rates of JE were extracted from the Public Health Data Center, the official website of the National Health Commission of the People's Republic of China, and the National Notifiable Infectious Disease Surveillance System from 2004 to 2019. Joinpoint regression was applied to examine the spatiotemporal patterns and annual percentage change in incidence and mortality of the JE. RESULTS: From 2004 to 2019, a total of 43,569 cases of JE were diagnosed, including 2081 deaths. The annual incidence rate of JE decreased from 0.4171/100,000 in 2004 to 0.0298/100,000 in 2019, with an annual percentage change (APC) of -13.5 % (P < 0.001). The annual mortality rate of JE showed three stages of change, with inflection points in 2006 and 2014. The incidence and mortality rates of JE have declined in all provinces of China, and more cases were reported in 0-14 years of age, accounting for nearly 80 % of all patients. CONCLUSIONS: The morbidity and mortality rates of JE in China are generally on a downward trend, and emphasis should be placed on strengthening disease surveillance in special areas and populations, popularizing vaccination, and increasing publicity.

Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration.

Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74 000 human single cells were profiled. As results, we found that SPP1+ macrophages, RGCC+ endothelial cells, ACKR1+ endothelial cells and ADAM12+ fibroblasts participated in tendon adhesion formation. Interestingly, despite specific fibrotic clusters in tendon adhesion, FOLR2+ macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells. Furthermore, ACKR1 was verified to regulate FOLR2+ macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26RtdTomato mice to lethally irradiated Ackr1-/- mice (Ackr1-/- chimeras; deficient in ACKR1) and control mice (WT chimeras). Compared with WT chimeras, the decline of FOLR2+ macrophages was also observed, indicating that ACKR1 was specifically involved in FOLR2+ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered a novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.

Organ-Targeted Ionizable Lipid Nanoparticles Facilitate Sequence-Activated Fluorogenic Probe for Precise Imaging of Inflammatory Liver Disease.

Activatable near-infrared (NIR) fluorogenic probes offer a potent tool for real-time, in situ detection of hepatic biomarkers, significantly advancing the precision in diagnosing inflammatory liver disease (ILD). However, the limited distribution of small molecule fluorogenic probes in the liver and their rapid clearance impair the accuracy of fluorescence imaging and in ILD diagnosis. In this study, an effective utilization of ionizable lipid nanoparticles (iLNPs) is presented as liver-targeted carriers for efficient delivery of fluorogenic probes, aiming to overcome biodistribution barriers and achieve accurate detection of hepatic biomarkers. Based on this strategy, a liver-targeted NIR fluorogenic nanoprobe hCy-H2O2@iLNP is prepared using hCy-H2O2 as a small molecule reporter for visualizing the over-produced hydrogen peroxide (H2O2) in situ of liver. Notably, iLNPs not only significantly enhance probe accumulation in the liver, but also enable sequence activation of fluorescent nanoprobes. This response is achieved through primary liposome-dissociation release and secondary hCy-H2O2 response with pathological H2O2, enabling high-precision detection of oxidative stress in hepatocytes. These distinctive features facilitate accurate early diagnosis of acetaminophen (APAP)-induced inflammatory liver injury as well as lipopolysaccharide (LPS)-induced hepatitis. Therefore, the organ-targeted nanoprobe design strategy showcasts great potential for early and accurate diagnosis of lesions in situ in different organs.

Monitoring fatigue cracks in riveted plates using a sideband intensity based nonlinear ultrasonic technique.

Aluminum structures are routinely used in aircraft due to their lightweight and corrosion resistance properties. Multi-layered aluminum plates are generally joined by rivets forming regions which are prone to fatigue crack formation in an aircraft. Therefore, the detection and monitoring of fatigue cracks at rivet joints in aluminum structures are crucial for ensuring flight safety. In this study, piezoelectric sensors were utilized to generate and detect Lamb waves on aluminum plates with rivet joints to investigate the feasibility of a newly developed Sideband Peak Count (SPC) technique for detecting fatigue cracks around these joints. To overcome the limitations of existing SPC-I (Sideband Peak Count - Index) and SPI (Sideband Peak Intensity) techniques in capturing harmonic and modulating wave frequencies due to material nonlinearity, a comprehensive index, the Sideband Intensity Index (SII) is introduced. Comparative analysis with existing SPC-I and SPI techniques confirm the effectiveness of the SII technique. This investigation shows that the SII technique significantly improves the detection capability of initial fatigue cracks around rivet joints on aluminum plates. This study offers a more efficient method for detecting critical fatigue cracks in rivet joints.

A Case Report of Mycoplasma pneumoniae-induced fulminant myocarditis in a 15-year-old male leading to cardiogenic shock and electrical storm.

Mycoplasma pneumoniae (M. pneumoniae) is a well-recognized pathogen primarily associated with respiratory tract infections. However, in rare instances, it can lead to extrapulmonary manifestations, including myocarditis. We present a case of a 15-year-old male who developed fulminant myocarditis, cardiogenic shock, and cardiac electrical storm attributed to M. pneumoniae infection. He underwent a combination of intra-aortic balloon pump (IABP) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiac support, ultimately surviving despite the intracardiac thrombus formation and embolic stroke. Following comprehensive treatment and rehabilitation, he was discharged in stable condition. This case underscores the importance of considering atypical pathogens as potential etiological factors in patients presenting with cardiac complications, especially in the adolescents. It also emphasizes the need for clinical vigilance and effective support for potential cardiac complications arising from M. pneumoniae infection.

Safety and Immunogenicity of an mRNA-Based hMPV/PIV3 Combination Vaccine in Seropositive Children.

OBJECTIVES: Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) are common respiratory illnesses in children. The safety and immunogenicity of an investigational mRNA-based vaccine, mRNA-1653, encoding membrane-anchored fusion proteins of hMPV and PIV3, was evaluated in hMPV/PIV3-seropositive children. METHODS: In this phase 1b randomized, observer-blind, placebo-controlled, dose-ranging study, hMPV/PIV3-seropositive children were enrolled sequentially into 2 dose levels of mRNA-1653 administered 2 months apart; children aged 12 to 36 months were randomized (1:1) to receive 10-µg of mRNA-1653 or placebo and children aged 12 to 59 months were randomized (3:1) to receive 30-µg of mRNA-1653 or placebo. RESULTS: Overall, 27 participants aged 18 to 55 months were randomized; 15 participants received 10-µg of mRNA-1653 (n = 8) or placebo (n = 7), whereas 12 participants received 30-µg of mRNA-1653 (n = 9) or placebo (n = 3). mRNA-1653 was well-tolerated at both dose levels. The only reported solicited local adverse reaction was tenderness at injection site; solicited systemic adverse reactions included grade 1 or 2 chills, irritability, loss of appetite, and sleepiness. A single 10-µg or 30-µg mRNA-1653 injection increased hMPV and PIV3 neutralizing antibody titers (geometric mean fold-rise ratio over baseline: hMPV-A = 2.9-6.1; hMPV-B = 6.2-13.2; PIV3 = 2.8-3.0) and preF and postF binding antibody concentrations (geometric mean fold-rise ratio: hMPV preF = 5.3-6.1; postF = 4.6-6.5 and PIV3 preF = 13.9-14.2; postF = 11.0-12.1); a second injection did not further increase antibody levels in these seropositive children. Binding antibody responses were generally preF biased. CONCLUSIONS: mRNA-1653 was well-tolerated and boosted hMPV and PIV3 antibody levels in seropositive children aged 12 to 59 months, supporting the continued development of mRNA-1653 or its components for the prevention of hMPV and PIV3.

Construction and validation of a neovascular glaucoma nomogram in patients with diabetic retinopathy after pars plana vitrectomy.

BACKGROUND: Neovascular glaucoma (NVG) is likely to occur after pars plana vitrectomy (PPV) for diabetic retinopathy (DR) in some patients, thus reducing the expected benefit. Understanding the risk factors for NVG occurrence and building effective risk prediction models are currently required for clinical research. AIM: To develop a visual risk profile model to explore factors influencing DR after surgery. METHODS: We retrospectively selected 151 patients with DR undergoing PPV. The patients were divided into the NVG (NVG occurrence) and No-NVG (No NVG occurrence) groups according to the occurrence of NVG within 6 months after surgery. Independent risk factors for postoperative NVG were screened by logistic regression. A nomogram prediction model was established using R software, and the model's prediction accuracy was verified internally and externally, involving the receiver operator characteristic curve and correction curve. RESULTS: After importing the data into a logistic regression model, we concluded that a posterior capsular defect, preoperative vascular endothelial growth factor ≥ 302.90 pg/mL, glycosylated hemoglobin ≥ 9.05%, aqueous fluid interleukin 6 (IL-6) ≥ 53.27 pg/mL, and aqueous fluid IL-10 ≥ 9.11 pg/mL were independent risk factors for postoperative NVG in patients with DR (P < 0.05). A nomogram model was established based on the aforementioned independent risk factors, and a computer simulation repeated sampling method was used to internally and externally verify the nomogram model. The area under the curve (AUC), sensitivity, and specificity of the model were 0.962 [95% confidence interval (95%CI): 0.932-0.991], 91.5%, and 82.3%, respectively. The AUC, sensitivity, and specificity of the external validation were 0.878 (95%CI: 0.746-0.982), 66.7%, and 95.7%, respectively. CONCLUSION: A nomogram constructed based on the risk factors for postoperative NVG in patients with DR has a high prediction accuracy. This study can help formulate relevant preventive and treatment measures.

Influence of trimetazidine on myocardial injury in mice with diabetic cardiomyopathy.

INTRODUCTION: The prevalence of diabetes mellitus is increasing year by year globally, and diabetic cardiomyopathy (DCM), as the most common complication of type 2 diabetes mellitus, seriously affects the prognosis of patients. Trimetazidine (TMZ), as a drug affecting myocardial energy metabolism, mainly reduces the oxidation rate of ß-oxidation by inhibiting 3-ketoacyl-CoA thiolase (3-KAT), a key enzyme in ß-oxidation of free fatty acid (FFA), so that the energy metabolism substrate of cardiomyocytes preferentially selects glucose rather than fatty acids, increases the content of intracellular adenosine triphosphate (ATP), enhances the contractile function of cardiomyocytes, and improves the state of cellular ischemia and hypoxia. Previous studies have shown that TMZ is closely related to the activation and induction of apoptosis of the MAPK pathway and AMPK pathway, and plays a role in the treatment of diabetic cardiomyopathy, but the specific mechanism is still unclear. OBJECTIVE: This study aims to investigate the impact of TMZ on myocardial damage in mice exhibiting diabetic cardiomyopathy (DCM), and to furnish a laboratory foundation for the clinical treatment of diabetic cardiomyopathy. METHOD: Male db/db mice (6 weeks old, n = 21) and male wild-type (wt) (6 weeks old, n = 20) mice were selected for the study. The wt mice were randomly assigned to the wt group (n = 10) and wt + TMZ group (n = 10), while the remaining db/db mice were randomly allocated to the db/db group (n = 11) and db/db + TMZ group (n = 10). Following 8 weeks of feeding, the wt + TMZ group and db/db + TMZ group received TMZ via gavage, whereas the remaining groups were administered physiological saline. Periodic measurements of blood glucose, blood lipids, and myocardial enzymes were conducted in mice, with samples obtained after the 12th week for subsequent biochemical analysis, myocardial pathology assessment, immunohistochemistry, western blot analysis, and TUNEL staining (TdT-mediated dUTP Nick-End Labeling). RESULT: GLU, TC, TG, LDL-C, and CK-MB levels were significantly higher in db/db mice compared to wt mice (GLU: M ± SD wt 5.94 ± 0.37, db/db 17.63 ± 0.89, p < 0.05, ES = 0.991; TC: M ± SD wt 3.01 ± 0.32, db/db 6.97 ± 0.36, p < 0.05, ES = 0.972; TG: M ± SD wt 0.58 ± 0.2, db/db 1.75 ± 0.14, p < 0.05, ES = 0.920; LDL-C: M ± SD wt 1.59 ± 0.12, db/db 3.87 ± 0.14, p < 0.05, ES = 0.989; CK-MB: M ± SD wt 0.12 ± 0.01, db/db 0.31 ± 0.04, p < 0.05, ES = 0.928). HDL-C levels were significantly lower in db/db mice (M ± SD wt 1.89 ± 0.08, db/db 0.64 ± 0.09, p < 0.05, ES = 0.963). Histopathological analysis confirmed myocardial damage in db/db mice. Treatment with TMZ reduced GLU, TC, TG, LDL-C, and CK-MB levels (p < 0.05, ES > 0.9) and increased HDL-C levels compared to untreated db/db mice. Additionally, TMZ treatment significantly decreased myocardial cell apoptosis (p < 0.05, ES = 0.980). These results demonstrate the efficacy of TMZ in reversing myocardial injury in DCM mice. CONCLUSION: TMZ can mitigate myocardial damage in db/db mice by downregulating the expression of caspase-12, a protein associated with the endoplasmic reticulum stress (ERS) cell apoptosis pathway, consequently diminishing cell apoptosis. This underscores the protective efficacy of TMZ against myocardial damage in mice afflicted with DCM.

Size-resolved water-soluble organic carbon and its significant contribution to aerosol liquid water.

Size-segregated aerosols collected in Beijing from 2021 to 2022 were used to investigate the contribution of organic aerosols to the aerosol liquid water content (ALWC), the influencing factors of ALWC, and the concentrations and size distribution characteristics of water-soluble organic carbon (WSOC) after clean air actions. The results showed that the concentration of WSOC in particulate matter (PM)1.8 was 3.52 ± 2.43 µg/m3 during the sampling period. Obvious changes were observed in the size distribution of WSOC after clean air actions, which may be attributed to the enhancement of atmospheric oxidation capacity and the decrease in PM concentration. The contribution of organic aerosols to the ALWC in fine PM was 18.1 % during the sampling period, which was more significant at lower particles concentration and smaller particle size ranges. The ambient relative humidity (RH) and the ratio of NO3-/SO42- had an apparent influence on ALWC. The continuous increase in the nitrate proportion significantly reduced the deliquescence point of the aerosols, making them prone to hygroscopic growth at lower RH. Analysis of the relation among nitrogen oxidation ratio (sulfur oxidation ratio), ALWC and PM1.8 mass concentrations suggests that organic matter has a significant effect on the formation of secondary inorganic aerosols in the initial phase of pollution formation and plays a crucial role in aerosol pollution formation in Beijing. These results are conducive to understanding the formation mechanism of aerosols and provide scientific data and theoretical support for the formulation of more effective emission-reduction measures.

Liquid-Driven Microinjection System for Precise Fundus Injection.

Microinjection is usually applied to the treatment of some retinal disorders, such as retinal vein cannulation and displaced submacular hemorrhage. Currently, the microinjection procedure is usually performed by using the viscous fluid control of a standard vitrectomy system, which applies a fixed air pressure through foot pedal activation. The injection process with the fixed pressure is uncontrollable and lacks feedback, the high flow rate of the injected drug may cause damage to the fundus tissue. In this paper, a liquid-driven microinjection system with a flow sensor is designed and developed specifically for fundus injection. In addition, a PID sliding mode control (SMC) method is proposed to achieve precise injection in the injection system. The experimental results of fundus simulation injection demonstrate that the microinjection system meets the requirements of fundus injection and reduces the impact of the injection process on the fundus tissue.

RNA splicing analysis deciphers developmental hierarchies and reveals therapeutic targets in adult glioma.

Widespread alterations in RNA alternative splicing (AS) have been identified in adult gliomas. However, their regulatory mechanism, biological significance, and therapeutic potential remain largely elusive. Here, using a computational approach with both bulk and single cell RNA-sequencing, we uncover a prognostic AS signature linked with neural developmental hierarchies. Using advanced iPSC glioma models driven by glioma driver mutations, we show that this AS signature could be enhanced by EGFRvIII and inhibited by in situ IDH1 mutation. Functional validation of two isoform switching events in CERS5 and MPZL1 shows regulations of sphingolipid metabolism and SHP2 signaling, respectively. Analysis of upstream RNA binding proteins reveals PTBP1 as a key regulator of the AS signature where targeting of PTBP1 suppresses tumor growth and promotes the expression of a neuron marker TUJ1 in glioma stem-like cells. Overall, our data highlights the role of AS in impacting glioma malignance and heterogeneity and its potential as a therapeutic vulnerability for treating adult gliomas.

Unpaid carers of people with dementia and information communication technology: Use, impact and ideas for the future.

OBJECTIVES: Several 100,000s of people living with dementia in the UK are cared for at home by a spouse or relative. Few studies have considered the ICT needs and experiences of unpaid carers. This study explores the types of ICT unpaid carers use, the ways they use ICT, the impact of ICT-use, and their ideas for how ICT could be more supportive of their role as a carer. METHODS: Six focus groups with 32 unpaid carers of people living with dementia discussed their experiences of - and barriers to - using ICT. Transcripts were analysed thematically according to three types of ICT (mainstream, accessible and formal) and five functions (supporting domestic tasks, care management, monitoring, communication and information and education). RESULTS: Participants predominantly used mainstream ICT devices such as laptops and smartphones and internet-enabled applications including videoconferencing and social media platforms to support their daily activities and assist them in their caring role. A few participants discussed using accessible devices such as memory clocks and formal telecare and care-phone services for care management and monitoring functions. Participants' ideas for improvements centred on personalised communication applications that facilitate remote interactions and promote persons living with dementia's independence. Others expressed concerns about the growing need to use ICT to access formal care services and the inadequacy of the ICT infrastructure in some care homes. CONCLUSIONS: Unpaid carers mostly turn to readily available mainstream ICT to support their personal and care activities. Further research is required to understand the social impact of the increasing reliance of ICT across health, social and residential care service sectors. Improved cooperation between unpaid carers, technology developers and care services providers could align ICT development to the needs and experiences of families living with dementia and assist unpaid carers with identifying ICTs that optimally support their personal circumstances.

Reducing decisional conflict in decisions about prenatal genetic testing: the impact of a dyadic intervention at the start of prenatal care.

OBJECTIVES: Decisional conflict and regret about prenatal genetic screening and diagnostic tests may have important consequences in the current pregnancy and for future reproductive decisions. Identifying mechanisms that reduce conflict associated with the decision to use or decline these options is necessary for optimal patient counseling. METHODS: We conducted a cluster-randomized controlled trial of a shared decision-making tool (NEST) at the beginning of prenatal care. Enrolled patients completed follow-up surveys at the time of testing (QTT) and in the second-third trimester (QFF), including the Decision Conflict Scale (DCS). Total DCS scores were analyzed using a multivariate linear mixed-effect model. RESULTS: Of the total number of participants (n=502) enrolled, 449 completed the QTT and QFF surveys. The mean age of participants was 31.6±3.8, with most parous at the time of study participation (n=321; 71.7 %). Both the NEST (the intervention) and control groups had lower median total DCS scores at QFF (NEST 13.3 [1.7, 25.0] vs. control 16.7 [1.7, 25.0]; p=0.24) compared to QTT (NEST 20.8 [5.0, 25.0] vs. control 18.3 [3.3, 26.7]; p=0.89). Participants exposed to NEST had lower decisional conflict at QFF compared to control (ß -3.889; [CI -7.341, -0.437]; p=0.027). CONCLUSIONS: Using a shared decision-making tool at the start of prenatal care decreased decisional conflict regarding prenatal genetic testing. Such interventions have the potential to provide an important form of decision-making support for patients facing the unique type of complex and preference-based choices about the use of prenatal genetic tests.

Changes in ovarian tissue structure and distribution of oestrogen receptors in Huanghuai goats at different ages.

To observe developmental changes in the ovarian tissue structure and distribution characteristics of oestrogen receptors (ERs) in the ovaries of Huanghuai goats at different ages, we selected healthy Huanghuai goats ewes and divided them into five groups (i.e. 3-, 30-, 60-, 90- and 120-day-old groups), with 10 animals in each group. The serum was separated after blood collection through the jugular vein, and the contents of oestrogen (E) and progesterone (P) in the serum of Huanghuai goats at each age were determined. Three goats were randomly selected from each group and sacrificed after anaesthesia, and the ovarian tissue was quickly obtained and placed in 4% paraformaldehyde fixative to prepare the tissue sections. Using HE, oestrogen receptors were immunohistochemically stained and observed. These results showed many primordial follicles and occasional secondary follicles in the ovaries of 3-day-old Huanghuai goats. Ovarian reticular structures were observed in 30-day-old ovarian medulla, with occasional near-mature growing follicles. Mature follicles and corpus luteum were occasionally detected in 60-day-old ovarian cortex. The 90-120-day-old ovarian cortices contained growing and mature follicles, and the number of mature follicles and corpora lutea increased, implying a significant luteal involution period. The E and P contents in the 120-day-old group were significantly higher than those in the 3-, 30-, 60- and 90-day-old groups. The levels of ERα and ERß in the 3- and 30-day-old groups were mainly distributed in the granulosa cells of ovarian reproductive epithelial cells, primordial follicles, atretic follicles, and primary and secondary follicles. The ERα and ERß levels of the 60-, 90- and 120-day-old groups were also distributed in the granulosa cells and luteal cells of mature follicles, especially in the 120-day-old endometrial cells of mature follicles, where ERß was distributed significantly. The overall expression of ERß in the ovary was higher than that of ERα. The results of this study provide basic data on the ovarian development and the specific expression of ERs and PRs in the ovaries of Huanghuai white goats, which play an important role in ovarian development and precocity.

Associations of perceived built environment characteristics using NEWS questionnaires with all-cause mortality and major cardiovascular diseases: The prospective urban rural epidemiology (PURE)-China study.

BACKGROUND: Despite increased literature focusing on the role of the built environment (BE) in health, few cohort studies have quantitatively analyzed neighborhood walkability environment in relation to the risk of death and cardiovascular disease (CVD). This longitudinal study aimed at evaluating the association between perceived BE attributeswith mortality and major CVD based on the Prospective Urban Rural Epidemiology study in China (PURE-China). METHODS: The PURE-China study recruited 47,931 participants aged 35-70 years from 12 provinces of China between 2005 and 2009. The perceived BE information, including land use, street, aesthetics, and safety, was collected using the neighborhood environment walkability scale (NEWS) questionnaire, with higher scores indicating a more favorable rating. Two primary outcomes are all-cause mortality and major CVD event. The Cox frailty model with random intercepts was used to assess the association between the perceived total BE/subscales score and outcomes. RESULTS: Of 32,163 participants included in this study, 19,253 (59.9 %) were women, and the mean (SD) age was 51.0 (9.5) years. After a median follow-up period of 11.7 years (IQR 9.4 - 12.2), we observed that one standard deviation higher of combined BE scores was related to a lower risk of all-cause mortality (HR = 0.85; 95 %CI, 0.80-0.90), and major CVD events (HR = 0.95; 95 %CI, 0.90-0.99). The subscales of perceived BE were related to a lower risk, although a few were not significant. Land use mix-diversity and safety from crime were the two most significant subscales. Stronger risks were observed among urban and female participants. CONCLUSION: Favorable perceived BE characteristics were linked with a lower risk of all-cause mortality and major CVD events in Chinese population, especially in urban areas and females. Our findings can be used by policymakers to take action to mitigate the adverse effect of poor community conditions on health, such as improving local amenities and transport connectivity, providing building paths for walking, running and cycling.