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1.
J Diabetes Complications ; 38(6): 108743, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38688179

ABSTRACT

AIM: This systematic review and meta-analysis aimed to comprehensively evaluate the impact of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in individuals with diabetes mellitus and non-alcoholic fatty liver disease (NAFLD) or obesity. METHODS: A search of PubMed, Embase, and Web of Science until October 2023 identified 13 Randomized Controlled Trials (RCTs) meeting the inclusion criteria. Bias risk was assessed using the Cochrane risk-of-bias instrument. Statistical analysis utilized standard mean differences (SMD) in Review Manager 5.4. Heterogeneity and publication bias were assessed. This study used the protocol registered with the Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY2023110020). RESULTS: GLP-1RA treatment significantly reduced VAT (SMD -0.55, 95 % CI [-0.90, -0.19]), SAT (SMD -0.59, 95 % CI [-0.99, -0.19]), body weight (SMD -1.07, 95 % CI [-1.67, -0.47]), and body mass index (BMI) (SMD -1.10, 95 % CI [-1.74, -0.47]) compared to controls. Heterogeneity was observed for VAT (I2 = 79 %, P < 0.01), SAT (I2 = 73 %, P < 0.01), body weight (I2 = 82 %, P < 0.01), and BMI (I2 = 82 %, P < 0.01). No publication bias was detected for VAT (P = 0.57) and SAT (P = 0.18). GLP-1RA treatment improved fasting blood glucose (FBG), postprandial glucose (PPG), hemoglobin A1c (HbA1c), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and fibrosis-4 (FIB-4). CONCLUSIONS: This meta-analysis highlights GLP-1RAs' potential to reduce fat accumulation, body weight, and BMI and improve glycemic control in individuals with diabetes mellitus and NAFLD or obesity. These findings supported using GLP-1RAs as promising therapeutic agents to address abnormal adipose tissue distribution and metabolic dysfunction.


Subject(s)
Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Non-alcoholic Fatty Liver Disease , Obesity , Randomized Controlled Trials as Topic , Humans , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/metabolism , Glucagon-Like Peptide-1 Receptor/agonists , Obesity/complications , Obesity/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Hypoglycemic Agents/therapeutic use , Intra-Abdominal Fat/drug effects , Intra-Abdominal Fat/metabolism , Adiposity/drug effects , Glucagon-Like Peptide-1 Receptor Agonists
2.
Epidemiol Psychiatr Sci ; 33: e11, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38450478

ABSTRACT

AIMS: To examine the effectiveness of Self-Help Plus (SH+) as an intervention for alleviating stress levels and mental health problems among healthcare workers. METHODS: This was a prospective, two-arm, unblinded, parallel-designed randomised controlled trial. Participants were recruited at all levels of medical facilities within all municipal districts of Guangzhou. Eligible participants were adult healthcare workers experiencing psychological stress (10-item Perceived Stress Scale scores of ≥15) but without serious mental health problems or active suicidal ideation. A self-help psychological intervention developed by the World Health Organization in alleviating psychological stress and preventing the development of mental health problems. The primary outcome was psychological stress, assessed at the 3-month follow-up. Secondary outcomes were depression symptoms, anxiety symptoms, insomnia, positive affect (PA) and self-kindness assessed at the 3-month follow-up. RESULTS: Between November 2021 and April 2022, 270 participants were enrolled and randomly assigned to either SH+ (n = 135) or the control group (n = 135). The SH+ group had significantly lower stress at the 3-month follow-up (b = -1.23, 95% CI = -2.36, -0.10, p = 0.033) compared to the control group. The interaction effect indicated that the intervention effect in reducing stress differed over time (b = -0.89, 95% CI = -1.50, -0.27, p = 0.005). Analysis of the secondary outcomes suggested that SH+ led to statistically significant improvements in most of the secondary outcomes, including depression, insomnia, PA and self-kindness. CONCLUSIONS: This is the first known randomised controlled trial ever conducted to improve stress and mental health problems among healthcare workers experiencing psychological stress in a low-resource setting. SH+ was found to be an effective strategy for alleviating psychological stress and reducing symptoms of common mental problems. SH+ has the potential to be scaled-up as a public health strategy to reduce the burden of mental health problems in healthcare workers exposed to high levels of stress.


Subject(s)
COVID-19 , Psychological Tests , Sleep Initiation and Maintenance Disorders , Adult , Humans , Prospective Studies , Psychosocial Intervention , Sleep Initiation and Maintenance Disorders/therapy , China , Health Personnel , Self Report
3.
Quant Imaging Med Surg ; 14(2): 1699-1715, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38415157

ABSTRACT

Background: Evaluation of the tricuspid valve (TV) is crucial for clinical decision making and post-treatment follow-up in pulmonary hypertension (PH) patients. However, little is known about 4-dimensional (4D) TV geometric remodeling in patients with PH. The aim of this study was to examine the 4D geometry of the TV in PH and its correlation with PH severity. Methods: A total of 74 PH patients with mean pulmonary arterial pressure >25 mmHg and 15 age- and gender-matched healthy individuals were consecutively included from September 2017 to December 2018 in National Center for Cardiovascular Diseases, Fuwai Hospital. All participants underwent 2-dimensional (2D) and 4D transthoracic echocardiography and PH patients underwent right heart catheterization (RHC) within 48 hours of echocardiography. TV geometry was analyzed using a dedicated 4D echocardiography from the right ventricular-focused apical view. Results: Compared with controls, PH patients had significantly larger 4D tricuspid annular (TA) and TV tenting sizes except in the 2-chamber diameter. In high-quality image cases, maximal tenting height (MTH), coaptation point height, tenting volume and 4-chamber diameter had good or moderate correlation with PH severity graded according to RHC mean pulmonary artery pressure (r=0.705, r=0.644, r=0.602, r=0.472, respectively; P<0.001 for all). In multivariable linear regression analysis, PH severity was independently associated with coaptation point height (F=18.070, P<0.001 with an R2=0.647) and MTH (F=25.576, P<0.001 with an R2=0.378). Among all 4D TV parameters, MTH had the highest area under the receiver operating characteristic (ROC) curve (AUC) in high-quality image cases [AUC =0.857, 95% confidence interval (CI): 0.743-0.972; P<0.001], comparable to echocardiographic systolic pulmonary arterial pressure (AUC =0.847, 95% CI: 0.733-0.961; P<0.001). Conclusions: In PH, TV geometric remodeling occurs mainly in TA septal-lateral dimension and TV tenting height. Worsening PH is an independent determinant of TV coaptation point height and MTH, not TA size. MTH shows a great diagnostic potential to detect severe PH.

4.
Environ Sci Technol ; 58(4): 2102-2111, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38238255

ABSTRACT

Waste biomass is one of the promising feedstocks to supply syngas that can be used as fuels, chemicals, reductants, etc. However, the relationship between the component of biomass and the constituent of pyrolysis gas remains unclear. Here, we study the pyrolysis behaviors of various biomasses and reveal the relationship between the biomass components and gas compositions. Further, different pyrolysis gases are applied for the reduction of spent lithium cobalt oxide (LiCoO2) below 500 °C. The pyrolysis gas with a higher concentration of CO has a higher reductivity to convert LiCoO2 to CoO and Li2CO3 with a conversion rate close to 100% in 1 h at 500 °C. The biomass rich in cellulose and with a lower content of lignin tends to produce pyrolysis gas with a high concentration of CO, which comes from the deliberate breakdown of carboxyl, carbonyl, ether, and ester linkages. Moreover, LiCoO2 exerts catalytic functions over the deoxygenation and enhancement of oxygenates and single-ring aromatics. Overall, this paper offers a tailored approach to regulating biomass pyrolysis gases, enabling highly efficient battery recycling and syngas production.


Subject(s)
Electric Power Supplies , Pyrolysis , Biomass , Lignin/chemistry , Recycling , Gases
5.
J Hazard Mater ; 466: 133576, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38278070

ABSTRACT

The ocean is the ultimate sink for all pollutants, rivers are important channels for land-based pollutants to enter the oceans. Riverine transport of polycyclic aromatic hydrocarbons (PAHs) to coastal seas in China poses environmental threats. This study examined the spatial and temporal distribution of PAHs in coastal rivers in Yancheng City in Jiangsu Province of China, with the aim of identifying their likely sources, concentrations, and influencing factors. Surface sediments were taken from the Xinyanggang River (XYR) and the Sheyang River (SYR). The concentrations of Æ©16PAHs in river sediments were measured on average 477.05 ng/g dry weight (dw), with values varying from 2.18 to 6351.42 ng/g, indicating a moderate pollution level, with a dominance of high molecular weight (HMW) PAHs. The XYR exhibited significantly higher PAHs concentrations compared to the SYR. The key sources of PAHs were vehicle emissions (47.87%), coal and natural gas combustion (35.07%). Geographically weighted regression and redundancy analysis linked PAHs pollution to distinct land use patterns and socioeconomic indicators, highlighting urban land as the major contributor, driven by high urbanization and industrialization (70.91%). In XYR, industrial activities and transport emissions were major contributors, while in SYR, agricultural activities predominantly influenced PAHs pollution. Urgent mitigation strategies are needed to reduce PAHs pollution in river sediments, mitigating ecological and human risks associated with these contaminants.


Subject(s)
Polycyclic Aromatic Hydrocarbons , Water Pollutants, Chemical , Humans , Geologic Sediments/analysis , Polycyclic Aromatic Hydrocarbons/analysis , Rivers , Anthropogenic Effects , Water Pollutants, Chemical/analysis , Environmental Monitoring , China , Risk Assessment
6.
ESC Heart Fail ; 11(1): 574-580, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37909849

ABSTRACT

Patients with multiple myeloma (MM) are likely to achieve poor therapeutic response when organs are involved. We produced anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells, which are in a trial for patients with relapsed/refractory MM. One enrolled patient developed severe heart failure, highly suspected as light chain cardiac amyloidosis. He exhibited increased N-terminal pro-brain natriuretic peptide with a peak of 32 299 ng/mL and heart failure with an ejection fraction of 30%. Anti-BCMA CAR-T cells were administered following lymphodepletion. The patient achieved cardiac response within 1 week with a decrease in N-terminal pro-brain natriuretic peptide by 80%, an increase in ejection fraction from 30% to 56%, and a haematological response with negative minimal residual disease at 1 month and a complete response at 1 year. To date, this patient has maintained good health without heart failure or haematological relapse. Herein, we show the efficacy of anti-BCMA CAR-T cells in patients with MM and severe heart failure.


Subject(s)
Heart Failure , Multiple Myeloma , Receptors, Chimeric Antigen , Male , Humans , Multiple Myeloma/therapy , Multiple Myeloma/drug therapy , Receptors, Chimeric Antigen/therapeutic use , B-Cell Maturation Antigen/therapeutic use , Natriuretic Peptide, Brain , Neoplasm Recurrence, Local/drug therapy , Heart Failure/therapy , Heart Failure/drug therapy
7.
Alzheimers Dement ; 20(3): 1573-1585, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38041855

ABSTRACT

INTRODUCTION: A wide array of post-translational modifications of the tau protein occurs in Alzheimer's disease (AD) and they are critical to pathogenesis and biomarker development. Several promising tau markers, pT181, pT217, and pT231, rely on increased phosphorylation within a common molecular motif threonine-proline-proline (TPP). METHODS: We validated new and existing antibodies against pT217, pT231, pT175, and pT181, then combined immunohistochemistry (IHC) and immunoassays (ELISA) to broadly examine the phosphorylation of the tau TPP motif in AD brains. RESULTS: The tau burden, as examined by IHC and ELISA, correlates to Braak stages across all TPP sites. Moreover, we observed regional variability across four TPP motif phosphorylation sites in multiple brains of sporadic AD patients. DISCUSSION: We conclude that there is an elevation of TPP tau phosphorylation in AD brains as disease advances. The regional variability of pTPP tau suggests that examining different phosphorylation sites is essential for a comprehensive assessment of tau pathology.


Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/pathology , tau Proteins/metabolism , Phosphorylation , Threonine/metabolism , Brain/pathology , Proline/metabolism
8.
Healthcare (Basel) ; 11(18)2023 Sep 05.
Article in English | MEDLINE | ID: mdl-37761666

ABSTRACT

Nasopharyngeal carcinoma is a common and highly malignant cancer in southern China. It is important to accurately assess the illness perception of nasopharyngeal carcinoma according to the common-sense model of self-regulation. The purpose was to validate the Chinese version of the Revised Illness Perception Questionnaire for patients with Nasopharyngeal carcinoma. A cross-sectional survey of 631 patients with Nasopharyngeal carcinoma was conducted in Guangzhou, China. The reliability of the scale was evaluated using Cronbach's alpha. The factor structure was assessed using exploratory factor analysis (EFA) of each dimension. The EFA revealed that the 29-item self-rated scale has a seven-factor structure consistent with the original scale and explained 67.3% of the variance after extraction and rotation. The scale showed satisfactory reliability. The item-total correlations ranged from -0.16 to 0.64 (p < 0.05). The item-subscale correlations ranged from 0.46 to 0.91 (p < 0.05). The item-other subscale correlations ranged from -0.38 to 0.51 and from -0.21 to 0.56 (p < 0.05). Significant correlations were found between the timeline (acute/chronic) (r = 0.224, r = 0.166), consequences (r = 0.415, r = 0.338), timeline cyclical (r = 0.366, r = 0.284), emotional representations (r = 0.497, r = 0.465), personal control (r = -0.122, r = -0.134), treatment control (r = -0.135, r = -0.148), and illness coherence (r = -0.261, r = -0.213) subscales, and depression, anxiety (p < 0.05). The scale revealed acceptable reliability, factorial validity, and construct validity. It could be used to assess the illness representations of Chinese patients with nasopharyngeal carcinoma.

9.
Adv Healthc Mater ; : e2302502, 2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37616035

ABSTRACT

Human organoids have the potential to revolutionize in vitro disease modeling by providing multicellular architecture and function that are similar to those in vivo. This innovative and evolving technology, however, still suffers from assay throughput and reproducibility to enable high-throughput screening (HTS) of compounds due to cumbersome organoid differentiation processes and difficulty in scale-up and quality control. Using organoids for HTS is further challenged by the lack of easy-to-use fluidic systems that are compatible with relatively large organoids. Here, these challenges are overcome by engineering "microarray three-dimensional (3D) bioprinting" technology and associated pillar and perfusion plates for human organoid culture and analysis. High-precision, high-throughput stem cell printing, and encapsulation techniques are demonstrated on a pillar plate, which is coupled with a complementary deep well plate and a perfusion well plate for static and dynamic organoid culture. Bioprinted cells and spheroids in hydrogels are differentiated into liver and intestine organoids for in situ functional assays. The pillar/perfusion plates are compatible with standard 384-well plates and HTS equipment, and thus may be easily adopted in current drug discovery efforts.

10.
JAMA Netw Open ; 6(6): e2320276, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37368403

ABSTRACT

Importance: Lower neighborhood and household socioeconomic status (SES) are associated with negative health outcomes and altered brain structure in children. It is unclear whether such findings extend to white matter and via what mechanisms. Objective: To assess whether and how neighborhood and household SES are independently associated with children's white matter microstructure and examine whether obesity and cognitive performance (reflecting environmental cognitive and sensory stimulation) are plausible mediators. Design, Setting, and Participants: This cross-sectional study used baseline data from participants in the Adolescent Brain Cognitive Development (ABCD) study. Data were collected at 21 US sites, and school-based recruitment was used to represent the US population. Children aged 9 to 11 years and their parents or caregivers completed assessments between October 1, 2016, and October 31, 2018. After exclusions, 8842 of 11 875 children in the ABCD study were included in the analyses. Data analysis was conducted from July 11 to December 19, 2022. Exposures: Neighborhood disadvantage was derived from area deprivation indices at participants' primary residence. Household SES factors were total income and highest parental educational attainment. Main Outcomes and Measures: A restriction spectrum imaging (RSI) model was used to quantify restricted normalized directional (RND; reflecting oriented myelin organization) and restricted normalized isotropic (RNI; reflecting glial and neuronal cell bodies) diffusion in 31 major white matter tracts. The RSI measurements were scanner harmonized. Obesity was assessed through body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), age- and sex-adjusted BMI z scores, and waist circumference, and cognition was assessed through the National Institutes of Health Toolbox Cognition Battery. Analyses were adjusted for age, sex, pubertal development stage, intracranial volume, mean head motion, and twin or siblingship. Results: Among 8842 children, 4543 (51.4%) were boys, and the mean (SD) age was 9.9 (0.7) years. Linear mixed-effects models revealed that greater neighborhood disadvantage was associated with lower RSI-RND in the left superior longitudinal fasciculus (ß = -0.055; 95% CI, -0.081 to -0.028) and forceps major (ß = -0.040; 95% CI, -0.067 to -0.013). Lower parental educational attainment was associated with lower RSI-RND in the bilateral superior longitudinal fasciculus (eg, right hemisphere: ß = 0.053; 95% CI, 0.025-0.080) and bilateral corticospinal or pyramidal tract (eg, right hemisphere: ß = 0.042; 95% CI, 0.015-0.069). Structural equation models revealed that lower cognitive performance (eg, lower total cognition score and higher neighborhood disadvantage: ß = -0.012; 95% CI, -0.016 to -0.009) and greater obesity (eg, higher BMI and higher neighborhood disadvantage: ß = -0.004; 95% CI, -0.006 to -0.001) partially accounted for the associations between SES and RSI-RND. Lower household income was associated with higher RSI-RNI in most tracts (eg, right inferior longitudinal fasciculus: ß = -0.042 [95% CI, -0.073 to -0.012]; right anterior thalamic radiations: ß = -0.045 [95% CI, -0.075 to -0.014]), and greater neighborhood disadvantage had similar associations in primarily frontolimbic tracts (eg, right fornix: ß = 0.046 [95% CI, 0.019-0.074]; right anterior thalamic radiations: ß = 0.045 [95% CI, 0.018-0.072]). Lower parental educational attainment was associated with higher RSI-RNI in the forceps major (ß = -0.048; 95% CI, -0.077 to -0.020). Greater obesity partially accounted for these SES associations with RSI-RNI (eg, higher BMI and higher neighborhood disadvantage: ß = 0.015; 95% CI, 0.011-0.020). Findings were robust in sensitivity analyses and were corroborated using diffusion tensor imaging. Conclusions and Relevance: In this cross-sectional study, both neighborhood and household contexts were associated with white matter development in children, and findings suggested that obesity and cognitive performance were possible mediators in these associations. Future research on children's brain health may benefit from considering these factors from multiple socioeconomic perspectives.


Subject(s)
White Matter , Male , Adolescent , Humans , Child , Female , White Matter/diagnostic imaging , Diffusion Tensor Imaging , Cross-Sectional Studies , Obesity , Cognition , Social Class
11.
Neuron ; 111(13): 2012-2020.e4, 2023 07 05.
Article in English | MEDLINE | ID: mdl-37167969

ABSTRACT

Soluble oligomers of amyloid ß-protein (Aß) have been defined as aggregates in supernatants following ultracentrifugation of aqueous extracts from Alzheimer's disease (AD) brains and are believed to be upstream initiators of synaptic dysfunction, but little is known about their structures. We now report the unexpected presence of Aß fibrils in synaptotoxic high-speed supernatants from AD brains extracted by soaking in an aqueous buffer. The fibrils did not appear to form during preparation, and their counts by EM correlated with Aß ELISA quantification. Cryo-EM structures of aqueous Aß fibrils were identical to those from sarkosyl-insoluble homogenates. The fibrils in aqueous extracts were labeled by lecanemab, an Aß aggregate-directed antibody reported to improve AD cognitive outcomes. Lecanemab provided protection against aqueous fibril synaptotoxicity. We conclude that fibrils are abundant in aqueous extracts from AD brains and have the same structures as those from plaques. These findings have implications for AD pathogenesis and drug design.


Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Brain/metabolism , Plaque, Amyloid/pathology
12.
Int J Mol Sci ; 24(8)2023 Apr 13.
Article in English | MEDLINE | ID: mdl-37108399

ABSTRACT

As a starchy and edible tropical plant, cassava (Manihot esculenta Crantz) has been widely used as an industrial raw material and a dietary source. However, the metabolomic and genetic differences in specific germplasms of cassava storage root were unclear. In this study, two specific germplasms, M. esculenta Crantz cv. sugar cassava GPMS0991L and M. esculenta Crantz cv. pink cassava BRA117315, were used as research materials. Results showed that sugar cassava GPMS0991L was rich in glucose and fructose, whereas pink cassava BRA117315 was rich in starch and sucrose. Metabolomic and transcriptomic analysis indicated that sucrose and starch metabolism had significantly changing metabolites enrichment and the highest degree of differential expression genes, respectively. Sugar transport in storage roots may contribute to the activities of sugar, which will eventually be exported to transporters (SWEETs), such as (MeSWEET1a, MeSWEET2b, MeSWEET4, MeSWEET5, MeSWEET10b, and MeSWEET17c), which transport hexose to plant cells. The expression level of genes involved in starch biosynthesis and metabolism were altered, which may result in starch accumulation. These results provide a theoretical basis for sugar transport and starch accumulation and may be useful in improving the quality of tuberous crops and increasing yield.


Subject(s)
Manihot , Starch , Starch/metabolism , Manihot/genetics , Manihot/metabolism , Transcriptome , Plant Roots/genetics , Plant Roots/metabolism , Glucose/metabolism , Sucrose/metabolism
13.
Nat Commun ; 14(1): 1929, 2023 04 06.
Article in English | MEDLINE | ID: mdl-37024491

ABSTRACT

Activating non-inherited mutations in the guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) gene family have been identified in childhood vascular tumors. Patients experience extensive disfigurement, chronic pain and severe complications including a potentially lethal coagulopathy termed Kasabach-Merritt phenomenon. Animal models for this class of vascular tumors do not exist. This has severely hindered the discovery of the molecular consequences of GNAQ mutations in the vasculature and, in turn, the preclinical development of effective targeted therapies. Here we report a mouse model expressing hyperactive mutant GNAQ in endothelial cells. Mutant mice develop vascular and coagulopathy phenotypes similar to those seen in patients. Mechanistically, by transcriptomic analysis we demonstrate increased mitogen activated protein kinase signaling in the mutant endothelial cells. Targeting of this pathway with Trametinib suppresses the tumor growth by reducing vascular cell proliferation and permeability. Trametinib also prevents the development of coagulopathy and improves mouse survival.


Subject(s)
Melanoma , Uveal Neoplasms , Vascular Neoplasms , Animals , Mice , GTP-Binding Protein alpha Subunits/metabolism , GTP-Binding Protein alpha Subunits, Gq-G11/genetics , GTP-Binding Protein alpha Subunits, Gq-G11/metabolism , Endothelial Cells/metabolism , Apoptosis , Melanoma/genetics , Uveal Neoplasms/genetics , Mutation , Disease Models, Animal , Mitogen-Activated Protein Kinase Kinases/metabolism , Cell Line, Tumor
14.
bioRxiv ; 2023 Mar 13.
Article in English | MEDLINE | ID: mdl-36993405

ABSTRACT

Human organoids have potential to revolutionize in vitro disease modeling by providing multicellular architecture and function that are similar to those in vivo . This innovative and evolving technology, however, still suffers from assay throughput and reproducibility to enable high-throughput screening (HTS) of compounds due to cumbersome organoid differentiation processes and difficulty in scale-up and quality control. Using organoids for HTS is further challenged by lack of easy-to-use fluidic systems that are compatible with relatively large organoids. Here, we overcome these challenges by engineering "microarray three-dimensional (3D) bioprinting" technology and associated pillar and perfusion plates for human organoid culture and analysis. High-precision, high-throughput stem cell printing and encapsulation techniques were demonstrated on a pillar plate, which was coupled with a complementary deep well plate and a perfusion well plate for static and dynamic organoid culture. Bioprinted cells and spheroids in hydrogels were differentiated into liver and intestine organoids for in situ functional assays. The pillar/perfusion plates are compatible with standard 384-well plates and HTS equipment, and thus may be easily adopted in current drug discovery efforts.

15.
Sensors (Basel) ; 23(4)2023 Feb 09.
Article in English | MEDLINE | ID: mdl-36850548

ABSTRACT

Due to the extreme environmental temperature variations, solutions that enable ultra-low thermal sensitivity in a mirror assembly are crucial for high-performance aerial optical imaging sensors (AOIS). Strategies such as the elimination of the coefficient of thermal expansion (CTE) mismatch and the employment of a flexure connection at the interface cannot be simply duplicated for the application involved, demanding specific design constraints. The contributions of support point number to the surface thermal sensitivity reduction and support stiffness improvement have been studied. A synthetic six-point support system that integrates equally spaced multiple ultra-low radial stiffness mirror flexure units and assembly external interface flexure units has been demonstrated on a 260 mm apertured annular mirror that involves significant CTE mismatch and demanding support stiffness constraint. The surface deformation RMS, due to the 35 °C temperature variation, is 16.7 nm.

16.
medRxiv ; 2023 Feb 10.
Article in English | MEDLINE | ID: mdl-36798149

ABSTRACT

Importance: Both neighborhood and household socioeconomic disadvantage relate to negative health outcomes and altered brain structure in children. It is unclear whether such findings extend to white matter development, and via what mechanisms socioeconomic status (SES) influences the brain. Objective: To test independent associations between neighborhood and household SES indicators and white matter microstructure in children, and examine whether body mass index and cognitive function (a proxy of environmental cognitive/sensory stimulation) may plausibly mediate these associations. Design: This cross-sectional study used baseline data from the Adolescent Brain Cognitive Development (ABCD) Study, an ongoing 10-year cohort study tracking child health. Setting: School-based recruitment at 21 U.S. sites. Participants: Children aged 9 to 11 years and their parents/caregivers completed baseline assessments between October 1 st , 2016 and October 31 st , 2018. Data analysis was conducted from July to December 2022. Exposures: Neighborhood disadvantage was derived from area deprivation indices at primary residence. Household SES indicators were total income and the highest parental education attainment. Main Outcomes and Measures: Thirty-one major white matter tracts were segmented from diffusion-weighted images. The Restriction Spectrum Imaging (RSI) model was implemented to measure restricted normalized directional (RND; reflecting oriented myelin organization) and isotropic (RNI; reflecting glial/neuronal cell bodies) diffusion in each tract. Obesity-related measures were body mass index (BMI), BMI z -scores, and waist circumference, and cognitive performance was assessed using the NIH Toolbox Cognition Battery. Linear mixed-effects models tested the associations between SES indicators and scanner-harmonized RSI metrics. Structural equation models examined indirect effects of obesity and cognitive performance in the significant associations between SES and white mater microstructure summary principal components. Analyses were adjusted for age, sex, pubertal development stage, intracranial volume, and head motion. Results: The analytical sample included 8842 children (4299 [48.6%] girls; mean age [SD], 9.9 [0.7] years). Greater neighborhood disadvantage and lower parental education were independently associated with lower RSI-RND in forceps major and corticospinal/pyramidal tracts, and had overlapping associations in the superior longitudinal fasciculus. Lower cognition scores and greater obesity-related measures partially accounted for these SES associations with RSI-RND. Lower household income was related to higher RSI-RNI in almost every tract, and greater neighborhood disadvantage had similar effects in primarily frontolimbic tracts. Lower parental education was uniquely linked to higher RSI-RNI in forceps major. Greater obesity-related measures partially accounted for these SES associations with RSI-RNI. Findings were robust in sensitivity analyses and mostly corroborated using traditional diffusion tensor imaging (DTI). Conclusions and Relevance: These cross-sectional results demonstrate that both neighborhood and household contexts are relevant to white matter development in children, and suggest cognitive performance and obesity as possible pathways of influence. Interventions targeting obesity reduction and improving cognition from multiple socioeconomic angles may ameliorate brain health in low-SES children. Key Points: Question: Are neighborhood and household socioeconomic levels associated with children’s brain white matter microstructure, and if so, do obesity and cognitive performance (reflecting environmental stimulation) mediate the associations?Findings: In a cohort of 8842 children, higher neighborhood disadvantage, lower household income, and lower parental education had independent and overlapping associations with lower restricted directional diffusion and greater restricted isotropic diffusion in white matter. Greater body mass index and poorer cognitive performance partially mediated these associations.Meaning: Both neighborhood and household poverty may contribute to altered white matter development in children. These effects may be partially explained by obesity incidence and poorer cognitive performance.

17.
Cardiovasc Ultrasound ; 21(1): 4, 2023 Feb 24.
Article in English | MEDLINE | ID: mdl-36829216

ABSTRACT

BACKGROUND: Intracardiac echocardiography (ICE) provides accurate left atrial (LA) anatomical information in the procedure of atrial fibrillation (AF) ablation but lacks LA functional assessment. LA reservoir strain (LASr) is an excellent marker of LA reservoir function. This study aimed to assess the agreement between LASr derived from ICE and transthoracic echocardiography (TTE) in AF patients and analyze the reproducibility of LASr assessed by ICE combined with speckle tracking imaging. METHODS: This study prospectively enrolled 110 patients with a clinical diagnosis of AF who were ready for AF ablation, including 71 patients with paroxysmal AF and 39 with persistent AF. TTE and ICE examinations were performed on each individual before AF ablation. LASr measurements derived from ICE and TTE images were using dedicated LA-tracking software. Pearson correlation coefficients (r) and Bland-Altman plots were used to evaluate the agreement of LASr between the two modalities. Intraclass correlation coefficients (ICCs) were used to assess intra- and inter-observer reproducibility. RESULTS: The agreement between LASr obtained from ICE and TTE, especially between LASrLPV (LASr derived from LA left pulmonary vein view of ICE) and LASrTTE (LASr derived from TTE) were good in both paroxysmal and persistent AF patients [r = 0.890 (P < 0.001) for overall population; r = 0.815 (P < 0.001) and Bias ± LOA: -0.3 ± 9.9% for paroxysmal AF; r = 0.775 (P < 0.001) and Bias ± LOA: -2.6 ± 3.9% for persistent AF, respectively]. But the values of LASr derived from ICE were slightly lower than those of TTE, especially in patients with persistent AF. The ICCs for LASr derived from ICE were excellent (all ICCs > 0.90). CONCLUSIONS: In patients with AF, LASr derived from ICE demonstrated excellent reproducibility and showed good agreement with LASr obtained from TTE. Obtaining LASr from ICE images may be a supplementary method to evaluate LA reservoir function in AF patients and expands the potential of ICE in the field of cardiac function assessment.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Humans , Reproducibility of Results , Heart Atria/diagnostic imaging , Echocardiography/methods
18.
Mar Pollut Bull ; 187: 114550, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36608478

ABSTRACT

The Xinyanggang River in Yancheng City, one of the essential rivers entering the Yellow sea, has imported abundant pollutants to the coast of Jiangsu Province. Trace elements (Cr, Ni, Cu, Zn, As, Rb, Sr, Mo, Pb, Th, U, Sc, Ga, Se, Zr, Nb, and Sn) in surface sediments in the Xinyanggang River were measured to analyze the spatial distribution, risk assessment, and source appointment. The results showed that the parts of 17 trace elements presented high average values in river sediments, such as Zr (309.19 mg/kg), Sr (182.72 mg/kg), Zn (77.67 mg/kg), and Cr (70.63 mg/kg). Compared with some coastal rivers, the Xinyanggang River was polluted by certain trace elements, such as Cr, Zn, and As. Based on the analysis of the enrichment factor (EF), the contamination factor (CF), the pollution load index (PLI), and the geoaccumulation index (Igeo), trace elements in sediments showed unpolluted to moderate contamination and mild to moderate enrichment. Among them, Zn, Pb, and Sn were highly polluted. The multivariate analysis, the principal component analysis-multiple linear regression (APCS-MLR) model, and the Unmix model identified four contributing trace element sources. Cr, Th, U, Se, Zr, and Nb originated from manufacturing industries and hydrodynamic transport erosion. Ni, Rb, Sc, and Ga were attributed to natural source. Cu, Zn, Mo, Pb, and Sn were contributed from mixed sources including industrial wastewater and transportation emissions. As and Sr were associated mainly with mixed sources of agriculture and combustion. These four sources of metals accounted for 22.5 %, 5.7 %, 15.3 %, and 11.1 % by using the APCS-MLR model, whereas 22.9 %, 39.7 %, 17.5 %, and 19.9 % by using the Unmix model, respectively.


Subject(s)
Metals, Heavy , Trace Elements , Water Pollutants, Chemical , Metals, Heavy/analysis , Trace Elements/analysis , Rivers , Lead , Water Pollutants, Chemical/analysis , Geologic Sediments , Environmental Monitoring/methods , China , Risk Assessment
19.
PLoS One ; 17(12): e0279290, 2022.
Article in English | MEDLINE | ID: mdl-36548282

ABSTRACT

OBJECTIVE: This study examined the reliability and validity of a Shame and Stigma Scale (SSS) and assessed shame and stigma among patients with facial disfigurement from nasopharyngeal carcinoma (NPC). METHODS: Data were collected from 218 patients with NPC through a cross-sectional survey between January 14, 2020, and December 1, 2020. The original SSS is a 20-item scale with four dimensions (i.e., shame with appearance, sense of stigma, regret, and social/speech concern). We used Cronbach's alpha and McDonald's omega to assess reliability and exploratory factor analysis (EFA) to assess the factor structure. We also used Pearson correlation analysis to examine the relationship between each item and total score of scale items and convergent validity. RESULTS: The final 18-item SSS had a Cronbach's alpha coefficient of .89. The EFA revealed that the SSS has a four-factor structure: sense of stigma, social/speech concern, shame with appearance, and regret. These factors showed satisfactory reliability, with McDonald's omega coefficients of .87, .77, .86, and .79, respectively. The scale showed significant relationship between each item and total score of scale items with respect to item-total correlations, item-subscale correlations, and item-other-subscale correlations. Convergent validity was supported by the significant positively correlated with the total scores for depression and anxiety. CONCLUSION: The SSS is valid and reliable in assessing shame and stigma and monitoring treatment compliance among patients with NPC.


Subject(s)
Nasopharyngeal Neoplasms , Social Stigma , Humans , Reproducibility of Results , Nasopharyngeal Carcinoma , Cross-Sectional Studies , East Asian People , Shame , Surveys and Questionnaires , Psychometrics
20.
Article in English | MEDLINE | ID: mdl-36294184

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has posed a profound psychological impact on healthcare workers. However, the role of positive affect in moderating the effect of perceived stress on the psychological states of healthcare workers remains unknown. This study aimed to analyze the moderating effect of positive affect on the association between stress and the mental health of healthcare workers during the COVID-19 pandemic. This cross-sectional study evaluated the relationships between perceived stress (the Perceived Stress Scale), positive affect (the Positive and Negative Affect Schedule), depression (the Patient Health Questionnaire-9), and anxiety (the Generalized Anxiety Disorder 7-item Scale) during the COVID-19 pandemic in 644 Chinese healthcare workers who completed online self-reports. The results revealed a significant negative association between positive affect and psychological problems, including stress, depression, and anxiety. At the total group level, multiple regression analysis showed that positive affect alleviated the influence of perceived stress on depression, but no significant moderating effect was found for anxiety. In the subgroups divided by perceived stress, the moderating effect of positive affect on depression was only significant in healthcare workers with a high level of perceived stress. These results suggested that positive affect played a moderative role in alleviating the effect of stress on depression among healthcare workers, particularly those with a high level of stress, thus emphasizing the importance of positive affect as an intervention strategy for promoting the mental health of healthcare workers in the context of the ongoing COVID-19 pandemic.


Subject(s)
COVID-19 , Pandemics , Humans , COVID-19/epidemiology , Mental Health , Cross-Sectional Studies , SARS-CoV-2 , Depression/epidemiology , Health Personnel/psychology , Anxiety/epidemiology , Stress, Psychological/epidemiology
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