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BACKGROUND: Chronic atrophic gastritis (CAG) is a prevalent chronic gastritis usually accompanied by precancerous lesions such as intestinal metaplasia and dysplasia. The increasing application of traditional Chinese medicine in CAG treatment has shown promising results with low side effects and significant efficacy. AIM: To investigate the pharmacological effects of Yiqi Jiedu Huayu decoction (YJHD) on precancerous lesions of CAG. METHODS: A CAG rat model was established by Helicobacter pylori bacteria solution combined with N-methyl-N'-nitro-N-nitrosoguanidine. Histopathological measurements were conducted by hematoxylin-eosin and alcian blue and periodic acid-Schiff staining. Serum levels of inflammatory factors and gastric mucosal-related factors were examined using enzyme-linked immunosorbent assay. Protein and mRNA levels were quantified via western blot and quantitative real-time polymerase chain reaction analysis, respectively. Molecular interaction was verified by chromatin immunoprecipitation (ChIP) assay. RESULTS: YJHD greatly attenuated pathological changes in the gastric mucosa and precancerous lesions in CAG rats. Meanwhile, YJHD treatment reduced serum levels of inflammatory factors [interleukin (IL)-6, tumor necrosis factor-α and C-reactive protein] and increased serum levels of gastric mucosal-related factors (gastrin, pepsin, somatostatin and prostaglandin E2) in CAG rats. In addition, YJHD administration suppressed NLRP3 inflammasome-mediated cell pyroptosis, as well as the activation of TLR4/NF-κB and IL-6/STAT3 signaling pathways. Mechanically, ChIP experiments confirmed that NLRP3 transcription was regulated by TLR4/NF-κB and IL-6/STAT3 signaling. CONCLUSION: Taken together, YJHD alleviated NLRP3 inflammasome formation and pyroptosis of epithelial cells in CAG, potentially through the inactivation of TLR4/NF-κB and IL-6/STAT3 pathways.
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BACKGROUND: Acute lung injury (ALI) is a severe clinical condition in the intensive care units, and obesity is a high risk of ALI. Paradoxically, obese ALI patients had better prognosis than non-obese patients, and the mechanism remains largely unknown. METHODS: Mouse models of ALI and diet-induced-obesity (DIO) were used to investigate the effect of exosomes derived from adipose tissue. The adipose-derived exosomes (ADEs) were isolated by ultracentrifugation, and the role of exosomal miRNAs in the ALI was studied. RESULTS: Compared with ADEs of control mice (C-Exo), ADEs of DIO mice (D-Exo) increased survival rate and mitigated pulmonary lesions of ALI mice. GO and KEGG analyses showed that the target genes of 40 differentially expressed miRNAs between D-Exo and C-Exo were mainly involved with inflammation, apoptosis and cell cycle. Furthermore, the D-Exo treatment significantly decreased Ly6G+ cell infiltration, down-regulated levels of pro-inflammatory cytokines (IL-6, IL-12, TNF-α, MCP-1) and chemokines (IL-8 and MIP-2), reduced pulmonary apoptosis and arrest at G0G1 phase (P < 0.01). And the protective effects of D-Exo were better than those of C-Exo (P < 0.05). Compared with the C-Exo mice, the levels of miR-16-5p and miR-335-3p in the D-Exo mice were significantly up-regulated (P < 0.05), and the expressions of IKBKB and TNFSF10, respective target of miR-16-5p and miR-335-3p by bioinformatic analysis, were significantly down-regulated in the D-Exo mice (P < 0.05). CONCLUSIONS: Exosomes derived from adipose tissue of DIO mice are potent to attenuate LPS-induced ALI, which could be contributed by exosome-carried miRNAs. Our data shed light on the interaction between obesity and ALI.
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Lesão Pulmonar Aguda , Tecido Adiposo , Apoptose , Citocinas , Exossomos , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , MicroRNAs , Obesidade , Animais , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/induzido quimicamente , Exossomos/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Tecido Adiposo/metabolismo , Camundongos , Masculino , Citocinas/metabolismo , Inflamação , Modelos Animais de Doenças , Pulmão/patologia , Pulmão/imunologia , Humanos , Camundongos Obesos , Dieta Hiperlipídica/efeitos adversosRESUMO
Proteins can misfold into fibrillar or amorphous aggregates and molecular chaperones act as crucial guardians against these undesirable processes. The BRICHOS chaperone domain, found in several otherwise unrelated proproteins that contain amyloidogenic regions, effectively inhibits amyloid formation and toxicity but can in some cases also prevent non-fibrillar, amorphous protein aggregation. Here, we elucidate the molecular basis behind the multifaceted chaperone activities of the BRICHOS domain from the Bri2 proprotein. High-confidence AlphaFold2 and RoseTTAFold predictions suggest that the intramolecular amyloidogenic region (Bri23) is part of the hydrophobic core of the proprotein, where it occupies the proposed amyloid binding site, explaining the markedly reduced ability of the proprotein to prevent an exogenous amyloidogenic peptide from aggregating. However, the BRICHOS-Bri23 complex maintains its ability to form large polydisperse oligomers that prevent amorphous protein aggregation. A cryo-EM-derived model of the Bri2 BRICHOS oligomer is compatible with surface-exposed hydrophobic motifs that get exposed and come together during oligomerization, explaining its effects against amorphous aggregation. These findings provide a molecular basis for the BRICHOS chaperone domain function, where distinct surfaces are employed against different forms of protein aggregation.
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Chaperonas Moleculares , Domínios Proteicos , Chaperonas Moleculares/química , Chaperonas Moleculares/metabolismo , Sítios de Ligação , Humanos , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Modelos Moleculares , Interações Hidrofóbicas e HidrofílicasRESUMO
BACKGROUND: The COVID-19 pandemic disrupted how primary care patients with chronic pain received care. Our study sought to understand how long-term opioid therapy (LtOT) for chronic pain changed over the course of the pandemic overall and for different demographic subgroups. METHODS: We used data from electronic health records of 64 primary care clinics across Washington state and Idaho to identify patients who had a chronic pain diagnosis and were receiving long-term opioid therapy. We defined 10-month periods in 2019 to 2021 as prepandemic, early pandemic and late pandemic and used generalized estimating equations analysis to compare across these time periods and demographic characteristics. RESULTS: We found a proportional decrease in LtOT for chronic pain in the early months of the pandemic (OR = 0.94, P = .007) followed by an increase late pandemic (OR = 1.08, P = .002). Comparing late pandemic to prepandemic, identifying as Asian or Black, having fewer comorbidities, or living in an urban area were associated with higher likelihood of being prescribed LtOT. DISCUSSION: The use of LtOT for chronic pain in primary care has increased from before to after the COVID-19 pandemic with racial/ethnic and geographic disparities. Future research is needed to understand these disparities in LtOT and their effect on patient outcomes.
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Analgésicos Opioides , COVID-19 , Dor Crônica , Disparidades em Assistência à Saúde , Atenção Primária à Saúde , Humanos , COVID-19/epidemiologia , Dor Crônica/tratamento farmacológico , Dor Crônica/epidemiologia , Masculino , Analgésicos Opioides/uso terapêutico , Feminino , Pessoa de Meia-Idade , Washington/epidemiologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Adulto , Idoso , Idaho/epidemiologia , SARS-CoV-2 , PandemiasRESUMO
Smouldering combustion of oily sludge (OS) was carried out to learn the characteristics of heavy metals (HMs) in ash products. Ash collected from four different height layers of the column reactor was analysed for the chemical speciation and environmental risk of six HMs, including Cr, Ni, Cu, Zn, As, and Pb. The results showed that after smouldering combustion, only 21.3-32.2 % of the total HMs was remained in the ash products. The retention of HMs in ash was closely relevant to the carbonaceous destruction efficiency of OS. Smouldering combustion led to the decrease of HMs in acid-soluble/exchangeable fraction from 21.5-49.3 to 0.8-19.8% and oxidizable fraction from 22.6-49.6 to 5.3-21.3, and the increase of reducible fraction from 13.6-38.0 to 30.5-89.1% and residue fraction from 7.8-27.3 to 24.1-63.6%. Upward migration of HMs during smouldering was evidenced by their occurrence in the top clean sand layer, which was dominated in acid-soluble/exchangeable and reducible fractions, accounting for 89.7-99.1% in total. Toxicity extraction and environmental risk studies indicated that smouldering combustion would effectively reduce the toxicity and pollution risk of HMs; however, attention should be paid to the disposal of the top sand layer after smouldering operation due to its high pollution risk of HMs according to the evaluation of Risk assessment code.
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Metais Pesados , Esgotos , Metais Pesados/análise , Medição de Risco , Esgotos/química , Incineração , Monitoramento Ambiental/métodosRESUMO
BACKGROUND: Primary Sjogren's syndrome (pSS) is a complex autoimmune disease featuring damage to salivary and lacrimal glands, with the possibility of manifestations across multiple organs. Antibody-producing B cells have long been appreciated to play a significant role in pSS pathogenesis, with a number of autoreactive antibody species having been identified to be elevated in pSS patients. While several studies have attempted to characterize the BCR repertoires of peripheral blood B cells in pSS patients, much remains unknown about the repertoire characteristics of gland-infiltrating B cells. METHODS: Through paired scRNAseq and scBCRseq, we profiled the BCR repertoires of both infiltrating and circulating B cells in a small cohort of patients. We further utilize receptor reconstruction analyses to further investigate repertoire characteristics in a wider cohort of pSS patients previously profiled through RNAseq. RESULTS: Via integrated BCR and transcriptome analysis of B cell clones, we generate a trajectory progression pattern for infiltrated memory B cells in pSS. We observe significant differences in BCR repertoires between the peripheral blood and labial gland B cells of pSS patients in terms of relative expansion, isotype usage, and BCR clustering. We further observe significant decreases in IgA2 isotype usage among pSS patient labial and parotid gland B cells these analyses relative to controls as well as a positive correlation between kappa/lambda light chain usage and clinical disease activity. CONCLUSIONS: Through BCR repertoire analysis of pSS patient salivary glands, we identify a number of novel repertoire characteristics that may serve as useful indicators of clinical disease and disease activity. By collecting these BCR repertoires into an accessible database, we hope to also enable comparative analysis of patient repertoires in pSS and potentially other autoimmune disorders.
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Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/genética , Glândulas Salivares/patologia , Glândulas Salivares Menores/patologia , Linfócitos B , Receptores de Antígenos de Linfócitos B/genéticaRESUMO
Purpose: A pragmatic, cluster-randomized controlled trial of a comprehensive practice-level, multi-staged practice transformation intervention aimed to increase behavioral health integration in primary care practices and improve patient outcomes. We examined association between the completion of intervention stages and patient outcomes across a heterogenous national sample of primary care practices. Methods: Forty-two primary care practices across the U.S. with co-located behavioral health and 2,426 patients with multiple chronic medical and behavioral health conditions completed surveys at baseline, midpoint and two year follow-up. Effects of the intervention on patient health and primary care integration outcomes were examined using multilevel mixed-effects models, while controlling for baseline outcome measurements. Results: No differences were found associated with the number of intervention stages completed in patient health outcomes were found for depression, anxiety, fatigue, sleep disturbance, pain, pain interference, social function, patient satisfaction with care or medication adherence. The completion of each intervention stage was associated with increases in Practice Integration Profile (PIP) domain scores and were confirmed with modeling using multiple imputation for: Workflow 3.5 (95% CI: 0.9-6.1), Integration Methods 4.6 (95% CI: 1.5-7.6), Patient Identification 2.9 (95% CI: 0.9-5.0), and Total Integration 2.7 (95% CI: 0.7-4.7). Conclusion: A practice-centric flexible practice transformation intervention improved integration of behavioral health in primary care across heterogenous primary care practices treating patients with multiple chronic conditions. Interventions that allow practices to flexibly improve care have potential to help complex patient populations. Future research is needed to determine how to best target patient health outcomes at a population level.
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BACKGROUND: Congenital heart defects (CHDs) are the most common congenital malformation in the world. Recent studies have found that essential and toxic trace element levels may play a crucial role in the risk of neonatal malformation. However, the relationships between element levels in early pregnancy and CHD risk among humans remain unclear. This study investigates the association between maternal essential element (copper [Cu], zinc [Zn], calcium [Ca], manganese [Mg] and iron [Fe]) and toxic element (lead [Pb] and cadmium [Cd]) levels during early pregnancy and CHDs. METHODS: A hospital-based case-control study was conducted, including 181 cases and 218 controls. Eligible participants underwent antenatal examination during gestational weeks 11-14 and trace element levels were detected by the atomic absorption method. Multi-variable logistic regression was used to examine the associations between the level of maternal trace elements and CHD risks. RESULTS: Higher levels of Ca in early pregnancy were associated with lower risk of ASD/VSD risks. Moreover, higher Fe, Pb, and Cd levels in the first trimester were associated with higher risks of all CHD and the subtypes risks, and the tests for trend were significant (all p < .05). The restricted cubic spline analysis showed that there was a nonlinear inverted u-shaped dose-response relationship between levels of Zn, Pb, and Cd in the first trimester and risk of CHDs (non-linearity test p < .05). CONCLUSIONS: A moderate increase in Zn and Ca levels and a decrease in Pb and Cd levels during early pregnancy are needed to reduce the incidence of CHDs in the Chinese population.
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Permeabilidade do Canal Arterial , Cardiopatias Congênitas , Comunicação Interatrial , Comunicação Interventricular , Oligoelementos , Recém-Nascido , Gravidez , Feminino , Humanos , Oligoelementos/análise , Cádmio , Permeabilidade do Canal Arterial/complicações , Estudos de Casos e Controles , Chumbo , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/etiologia , Cardiopatias Congênitas/diagnóstico , Comunicação Interventricular/complicações , Comunicação Interatrial/complicações , ZincoRESUMO
Peritoneal fibrosis together with increased capillaries is the primary cause of peritoneal dialysis failure. Mesothelial cell loss is an initiating event for peritoneal fibrosis. We find that the elevated glucose concentrations in peritoneal dialysate drive mesothelial cell pyroptosis in a manner dependent on caspase-3 and Gasdermin E, driving downstream inflammatory responses, including the activation of macrophages. Moreover, pyroptosis is associated with elevated vascular endothelial growth factor A and C, two key factors in vascular angiogenesis and lymphatic vessel formation. GSDME deficiency mice are protected from high glucose induced peritoneal fibrosis and ultrafiltration failure. Application of melatonin abrogates mesothelial cell pyroptosis through a MT1R-mediated action, and successfully reduces peritoneal fibrosis and angiogenesis in an animal model while preserving dialysis efficacy. Mechanistically, melatonin treatment maintains mitochondrial integrity in mesothelial cells, meanwhile activating mTOR signaling through an increase in the glycolysis product dihydroxyacetone phosphate. These effects together with quenching free radicals by melatonin help mesothelial cells maintain a relatively stable internal environment in the face of high-glucose stress. Thus, Melatonin treatment holds some promise in preserving mesothelium integrity and in decreasing angiogenesis to protect peritoneum function in patients undergoing peritoneal dialysis.
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Melatonina , Fibrose Peritoneal , Humanos , Animais , Camundongos , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/prevenção & controle , Fibrose Peritoneal/patologia , Melatonina/farmacologia , Melatonina/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Piroptose , Ultrafiltração , Células Epiteliais , Glucose/farmacologia , FibroseRESUMO
Cancer stands as a prominent contributor to global mortality rates, necessitating immediate attention toward the exploration of its treatment options. Extracellular vesicles have been investigated as a potential cancer therapy in recent years. Among them, exosomes, as cell-derived nanovesicles with functions such as immunogenicity and molecular transfer, offer new possibilities for immunotherapy of cancer. However, multiple studies have shown that exosomes of different cellular origins have different therapeutic effects. The immunomodulatory effects of exosomes include but are not limited to inhibiting or promoting the onset of immune responses, regulating the function of molecular signaling pathways, and serving as carriers of antitumor drugs. Therefore, this mini-review attempts to summarize and evaluate the development of strategies for using exosomes to package exogenous cargos to promote immunotherapy in cancer.
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Exossomos , Neoplasias , Humanos , Exossomos/metabolismo , Neoplasias/metabolismo , Imunoterapia , Comunicação CelularRESUMO
Advances in single-cell sequencing and data analysis have made it possible to infer biological trajectories spanning heterogeneous cell populations based on transcriptome variation. These trajectories yield a wealth of novel insights into dynamic processes such as development and differentiation. However, trajectory analysis relies on an assumption of trajectory continuity, and experimental limitations preclude some real-world scenarios from meeting this condition. The current lack of assessment metrics makes it difficult to ascertain if/when a given trajectory deviates from continuity, and what impact such a divergence would have on inference accuracy is unclear. By analyzing simulated breaks introduced into in silico and real single-cell data, we found that discontinuity caused precipitous drops in the accuracy of trajectory inference. We then generate a simple scoring algorithm for assessing trajectory continuity, and found that continuity assessments in real-world cases of intestinal stem cell development and CD8 + T cells differentiation efficiently identifies trajectories consistent with empirical knowledge. This assessment approach can also be used in cases where a priori knowledge is lacking to screen a pool of inferred lineages for their adherence to presumed continuity, and serve as a means for weighing higher likelihood trajectories for validation via empirical studies, as exemplified by our case studies in psoriatic arthritis and acute kidney injury. This tool is freely available through github at qingshanni/scEGRET.
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Algoritmos , Transcriptoma , Diferenciação Celular , Análise de Célula ÚnicaRESUMO
This cross-sectional study compares differences in patient characteristics between those using telehealth vs in-clinic services for medication abortion care.
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Aborto Induzido , Telemedicina , Feminino , Gravidez , HumanosRESUMO
Amyloid fibrils-nanoscale fibrillar aggregates with high levels of order-are pathogenic in some today incurable human diseases; however, there are also many physiologically functioning amyloids in nature. The process of amyloid formation is typically nucleation-elongation-dependent, as exemplified by the pathogenic amyloid-ß peptide (Aß) that is associated with Alzheimer's disease. Spider silk, one of the toughest biomaterials, shares characteristics with amyloid. In this study, it is shown that forming amyloid-like nanofibrils is an inherent property preserved by various spider silk proteins (spidroins). Both spidroins and Aß capped by spidroin N- and C-terminal domains, can assemble into macroscopic spider silk-like fibers that consist of straight nanofibrils parallel to the fiber axis as observed in native spider silk. While Aß forms amyloid nanofibrils through a nucleation-dependent pathway and exhibits strong cytotoxicity and seeding effects, spidroins spontaneously and rapidly form amyloid-like nanofibrils via a non-nucleation-dependent polymerization pathway that involves lateral packing of fibrils. Spidroin nanofibrils share amyloid-like properties but lack strong cytotoxicity and the ability to self-seed or cross-seed human amyloidogenic peptides. These results suggest that spidroins´ unique primary structures have evolved to allow functional properties of amyloid, and at the same time direct their fibrillization pathways to avoid formation of cytotoxic intermediates.
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Fibroínas , Aranhas , Humanos , Animais , Seda/química , Fibroínas/química , Polimerização , Amiloide , Peptídeos beta-Amiloides/metabolismo , Aranhas/metabolismoRESUMO
Primary Sjogren's syndrome (pSS) is a complex chronic autoimmune disease in which local tissue damage in exocrine glands are combined with broader systemic involvement across the body in tissues including the skin. These combined manifestations negatively impact patient health and quality of life. While studies have previously reported differences in immune cell composition in the peripheral blood of pSS patients relative to healthy controls, a detailed immune cell landscape of the damaged exocrine glands of these patients remains lacking. Through single-cell transcriptomics and repertoire sequencing of immune cells in paired peripheral blood samples and salivary gland biopsies, we present here a preliminary picture of adaptive immune response in pSS. We characterize a number of points of divergence between circulating and glandular immune responses that have been hitherto underappreciated, and identify a novel population of CD8+CD9+ cells with tissue-residential properties that are highly enriched in the salivary glands of pSS patients. Through comparative analyses with other sequencing data, we also observe a potential connection between these cells and the tissue-resident memory cells found in cutaneous vasculitis lesions. Together, these results indicate a potential role for CD8+CD9+ cells in mediating glandular and systemic effects associated with pSS and other autoimmune disorders.
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BACKGROUND: Suicide is a leading cause of death in adolescents and adults in the US. Follow-up support delivered when patients return home after an emergency department (ED) or primary care encounter can significantly reduce suicidal ideation and attempts. Two follow-up models to augment usual care including the Safety Planning Intervention have high efficacy: Instrumental Support Calls (ISC) and Caring Contacts (CC) two-way text messages, but they have never been compared to assess which works best. This protocol for the Suicide Prevention Among Recipients of Care (SPARC) Trial aims to determine which model is most effective for adolescents and adults with suicide risk. METHODS: The SPARC Trial is a pragmatic randomized controlled trial comparing the effectiveness of ISC versus CC. The sample includes 720 adolescents (12-17 years) and 790 adults (18+ years) who screen positive for suicide risk during an ED or primary care encounter. All participants receive usual care and are randomized 1:1 to ISC or CC. The state suicide hotline delivers both follow-up interventions. The trial is single-masked, with participants unaware of the alternative treatment, and is stratified by adolescents/adults. The primary outcome is suicidal ideation and behavior, measured using the Columbia Suicide Severity Rating Scale (C-SSRS) screener at 6 months. Secondary outcomes include C-SSRS at 12 months, and loneliness, return to crisis care for suicidality, and utilization of outpatient mental health services at 6 and 12 months. DISCUSSION: Directly comparing ISC and CC will determine which follow-up intervention is most effective for suicide prevention in adolescents and adults.
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Suicídio , Envio de Mensagens de Texto , Adolescente , Adulto , Humanos , Serviço Hospitalar de Emergência , Atenção Primária à Saúde , Ideação Suicida , Suicídio/psicologia , Prevenção do Suicídio , Ensaios Clínicos Pragmáticos como AssuntoRESUMO
Colorectal cancer (CRC) is a common malignant gastrointestinal tumor. Long noncoding RNAs (lncRNAs) are revealed to be critically involved in CRC progression, providing new direction for exploring the pathogenesis of CRC. This study aimed to explore the biological functions and regulatory mechanisms of lncRNA AC125257.1 in CRC. Western blotting and reverse-transcription quantitative polymerase chain reaction were used for the measurement of gene expression. Cell counting kit-8 assay and flow cytometry analysis were used to explore the effects of AC125257.1 on CRC cell viability and apoptosis. RNA pull-down and immunoprecipitation assays were performed for validating the binding between AC125257.1 and its potential downstream microRNA. Results showed that lncRNA AC125257.1 expression was upregulated in CRC cells and tumor tissues. AC125257.1 enhanced cell viability and suppressed apoptosis of CRC cells. Moreover, the knockdown of AC125257.1 suppressed CRC progression in vitro and inhibited tumor growth in vivo. miR-133a-3p was revealed to bind with AC125257.1 in CRC cells. CASC5 was proved to be targeted by miR-133a-3p. Moreover, rescue assays indicated that the knockdown of AC125257.1 suppressed the pathogenic overexpression of CASC5. To conclude, AC125257.1 aggravates CRC development via miR-873-5p/CASC5 axis. Our findings might suggest a novel perspective that AC125257.1 may become the target for CRC treatment.
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BACKGROUND: People of color (POC), especially those who also hold social identities associated with disadvantage (non-English-speaking, female, older, lower socioeconomic level), continue to be underserved in the health system, which can result in poorer care and worsened health outcomes. Most disparity research in traumatic brain injury (TBI) focuses on the impact of single factors, which misses the compounding effect of belonging to multiple historically marginalized groups. OBJECTIVE: To examine the intersectional impact of multiple social identities vulnerable to systemic disadvantage following TBI on mortality, opioid usage during acute hospitalization, and discharge location. METHODS: Retrospective observational design utilizing electronic health records merged with local trauma registry data. Patient groups were defined by race and ethnicity (POC or non-Hispanic White), age, sex, type of insurance, and primary language (English-speaking vs non-English-speaking). Latent class analysis (LCA) was performed to identify clusters of systemic disadvantage. Outcome measures were then assessed across latent classes and tested for differences. RESULTS: Over an 8-year period, 10 809 admissions with TBI occurred (37% POC). LCA identified a 4-class model. Groups with more systemic disadvantage had higher rates of mortality. Classes with older populations had lower rates of opioid administration and were less likely to discharge to inpatient rehabilitation following acute care. Sensitivity analyses examining additional indicators of TBI severity demonstrated that the younger group with more systemic disadvantage had more severe TBI. Controlling for more indicators of TBI severity changed statistical significance in mortality for younger groups. CONCLUSION: Results demonstrate significant health inequities in the mortality and access to inpatient rehabilitation following TBI along with higher rates of severe injury in younger patients with more social disadvantages. While many inequities may be related to systemic racism, our findings suggested an additive, deleterious effect for patients who belonged to multiple historically disadvantaged groups. Further research is needed to understand the role of systemic disadvantage for individuals with TBI within the healthcare system.
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Lesões Encefálicas Traumáticas , Enquadramento Interseccional , Humanos , Feminino , Estudos Retrospectivos , Lesões Encefálicas Traumáticas/terapia , Hospitalização , EtnicidadeRESUMO
20-Hydroxyecdysone (20E) is known to have numerous pharmacological activities and can be used to treat diabetes and cardiovascular diseases. However, the protective effects of 20E against endothelial dysfunction and its targets remain unclear. In the present study, we revealed that 20E treatment could modulate the release of the endothelium-derived vasomotor factors NO, PGI2 and ET-1 and suppress the expression of ACE in TNF-α-induced 3D-cultured HUVECs. In addition, 20E suppressed the expression of CD40 and promoted the expression of SIRT6 in TNF-α-induced 3D-cultured HUVECs. The cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) and molecular docking results demonstrated that 20E binding increased SIRT6 stability, indicating that 20E directly bound to SIRT6 in HUVECs. Further investigation of the underlying mechanism showed that 20E could upregulate SIRT6 levels and that SIRT6 knockdown abolished the regulatory effect of 20E on CD40 in TNF-α-induced HUVECs, while SIRT6 overexpression further improved the effect of 20E. Moreover, we found that 20E could reduce the acetylation of NF-κB p65 (K310) through SIRT6, but the catalytic inactive mutant SIRT6 (H133Y) did not promote the deacetylation of NF-κB p65, suggesting that the inhibitory effect of 20E on NF-κB p65 was dependent on SIRT6 deacetylase activity. Additionally, our results indicated that 20E inhibited NF-κB via SIRT6, and the expression of CD40 was increased in HUVECs treated with SIRT6 siRNA and NF-κB inhibitor. In conclusion, the present study demonstrates that 20E exerts its effect through SIRT6-mediated deacetylation of NF-κB p65 (K310) to inhibit CD40 expression in ECs, and 20E may have therapeutic potential for the treatment of cardiovascular diseases.
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Doenças Cardiovasculares , Sirtuínas , Humanos , NF-kappa B/metabolismo , Ecdisterona/farmacologia , Células Endoteliais/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Simulação de Acoplamento Molecular , Sirtuínas/genética , Sirtuínas/metabolismo , Inflamação/tratamento farmacológicoRESUMO
In this work, zeolite based on coal fly ash was firstly synthesized via wet milling for the adsorption of lead (Pb(II)). The effects of contact time, solid-to-liquid ratio and initial pH of solution on Pb(II) removal were investigated in detail. The experimental data showed that synthesized zeolite has high adsorption capacity of 99.082 mg of Pb(II) per gram of adsorbent. Coal fly ash zeolite synthesized by wet milling has good Pb(II) adsorption performance when the initial pH of the solution is above 5. The adsorption kinetic results demonstrated that removal of Pb(II) via the synthesized zeolite followed pseudo-second-order kinetic model. X-ray photoelectron spectroscopy results directly demonstrated the adsorption between Pb(II) and synthesized zeolite, and a possible reaction pathway was proposed. Specifically, the removing mechanism of Pb(II) from aqueous solution via the synthesized zeolite involves two stages: one is that Pb(II) in aqueous solution is absorbed on the interior of the synthesized zeolite, and the other is chemical precipitation.
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Poluentes Químicos da Água , Zeolitas , Cinza de Carvão/química , Zeolitas/química , Carvão Mineral , Chumbo , Poluentes Químicos da Água/química , Adsorção , CinéticaRESUMO
BACKGROUND: Caring Contacts can effectively reduce suicide ideation, attempts, and death. In published clinical trials, Caring Contacts were sent by someone who knew the recipient. At scale, Caring Contacts programs rarely introduce the recipient and sender. It is not known whether receiving Caring Contacts from someone unknown is as effective as messages from someone the recipient has met. METHODS: Pragmatic randomized controlled trial comparing Caring Contacts with (CC+) versus without an introductory phone call (CC). Recruitment occurred January-July 2021, with outcomes assessed at 6 months. Participants were primary care patients or healthcare providers/staff reporting adverse mental health outcomes on a qualifying survey. Participants were sent 11 standardized caring text messages over 6 months; when participants replied, they received personalized unscripted responses. CC+ calls were semi-structured. The primary outcome was loneliness (NIH Toolkit). RESULTS: Participants included 331 patients (mean [SD] age: 45.5 [16.4], 78.9 % female) and 335 healthcare providers/staff (mean [SD] age: 40.9 [11.8], 86.6 % female). There were no significant differences in loneliness at 6 months by treatment arm in either stratum. In patients, mean (SD) loneliness was 61.9 (10.7) in CC, and 60.8 (10.3) in CC+, adjusted mean difference of -1.0 (95 % CI: -3.0, 1.0); p-value = 0.31. In providers/staff, mean (SD) loneliness was 61.2 (11) in CC, and 61.3 (11.1) in CC+, adjusted mean difference of 0.2 (95 % CI: -1.8, 2.2); p-value = 0.83. LIMITATIONS: Study population was 93 % white which may limit generalizability. CONCLUSIONS: Including an initial phone call added operational complexity without significantly improving the effectiveness of a Caring Contacts program.