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1.
BMJ Ment Health ; 27(1)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39353685

RESUMO

BACKGROUND: Personal and family history of psychiatric disorders are key risk factors for postpartum depression (PPD), yet their combined contribution has been understudied. OBJECTIVE: To examine personal and family psychiatric history, alone and combined, and their effect on absolute risk and relative risk (RR) of mild/moderate or severe PPD. METHODS: In this cohort study, we used data from 142 064 childbirths with PPD screenings from 2015 to 2021 merged with population registers. Exposures were personal and family psychiatric history defined as a psychiatric hospital contact or psychotropic prescription fills by index mothers and their parents prior to delivery. Outcomes were mild/moderate PPD (Edinburgh Postnatal Depression Scale, cut-off: ≥11 within 12 weeks post partum) and severe PPD (antidepressant fill or depression diagnosis within 6 months post partum). We calculated absolute risks and RRs using Poisson regression models adjusted for parity, education, maternal age, and calendar year. FINDINGS: Of the 142 064 participants, 23.4% had no psychiatric history, 47.4% had only family history, 6.0% had only personal history, and 23.2% had both. The latter group had the highest risk of PPD: absolute risk of mild/moderate PPD was 11.7% (95% CI 11.5%; 11.8%), and adjusted RR: 2.35 (95% CI 2.22; 2.49). Alone, personal psychiatric history was the most potent risk factor. Dose-response relationship based on severity of personal and family psychiatric history was found. DISCUSSION: Our study documents a substantial association between personal and family psychiatric history and PPD risk. CLINICAL IMPLICATIONS: Evaluating combinations of risk factors is important to improve risk assessment.


Assuntos
Depressão Pós-Parto , Humanos , Feminino , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/diagnóstico , Fatores de Risco , Adulto , Estudos de Coortes , Diagnóstico Precoce , Adulto Jovem , Gravidez , Mães/psicologia
2.
J Clin Med ; 13(19)2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39407833

RESUMO

Background: Brain magnetic resonance imaging (MRI) of infants with congenital heart disease (CHD) shows brain immaturity assessed via a cortical-based semi-quantitative score. Our primary aim was to develop an infant paralimbic-related subcortical-based semi-quantitative dysmaturation score, termed brain dysplasia score (BDS), to detect abnormalities in CHD infants compared to healthy controls and secondarily to predict clinical outcomes. We also validated our BDS in a preclinical mouse model of hypoplastic left heart syndrome. Methods: A paralimbic-related subcortical BDS, derived from structural MRIs of infants with CHD, was compared to healthy controls and correlated with clinical risk factors, regional cerebral volumes, feeding, and 18-month neurodevelopmental outcomes. The BDS was validated in a known CHD mouse model named Ohia with two disease-causing genes, Sap130 and Pchda9. To relate clinical findings, RNA-Seq was completed on Ohia animals. Findings: BDS showed high incidence of paralimbic-related subcortical abnormalities (including olfactory, cerebellar, and hippocampal abnormalities) in CHD infants (n = 215) compared to healthy controls (n = 92). BDS correlated with reduced cortical maturation, developmental delay, poor language and feeding outcomes, and increased length of stay. Ohia animals (n = 63) showed similar BDS findings, and RNA-Seq analysis showed altered neurodevelopmental and feeding pathways. Sap130 mutants correlated with a more severe BDS, whereas Pcdha9 correlated with a milder phenotype. Conclusions: Our BDS is sensitive to dysmaturational differences between CHD and healthy controls and predictive of poor outcomes. A similar spectrum of paralimbic and subcortical abnormalities exists between human and Ohia mutants, suggesting a common genetic mechanistic etiology.

3.
BMC Nephrol ; 25(1): 360, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39420277

RESUMO

OBJECTIVES: To explore the influencing factors and relationships associated with decisional conflict of dialysis modality in End-stage kidney disease (ESKD) patients. METHODS: This study was a survey-based cross-sectional investigation conducted on 150 ESKD patients in a third-class hospital in Wuhan. The general information questionnaire, decisional conflict scale, Montreal cognitive assessment, frail scale, perceived social support scale, and brief health literacy screen were used for investigation. SPSS 25.0 was used to compare the differences between the decisional and non-decisional conflict groups, and AMOS 23.0 was used to construct a structural equation model to explore the influencing factors. RESULTS: The incidence of decisional conflict in 150 ESKD patients was 33.3% (50/150). Binary logistic regression analysis showed that the independent risk factors for decisional conflict of dialysis modality in ESKD patients included monthly household income (OR = 0.184), cognitive function (OR = 7.0), social support (OR = 0.891), health literacy (OR = 0.608), the level of eGFR (OR = 1.488), and the level of cTnI (OR = 9.558). The constructed path analysis model had a good fit (x2/df = 1.499, GFI = 0.957, AGFI = 0.911, NFI = 0.906, CFI = 0.967, RMSEA = 0.055). The path analysis showed that health literacy (0.577) had the greatest impact on the decisional conflict, with a direct effect of 0.480 and an indirect effect of 0.097 through cognitive function and monthly household income. Next was social support, with an effect value of 0.434. CONCLUSIONS: In clinical practice, it is important to enhance the health literacy of patients and their families and to provide advanced education on dialysis plans. Additionally, in managing and planning chronic kidney disease progression and dialysis, it is recommended to regularly and systematically assess cognitive function, particularly before the patient's cognitive impairment worsens or the severity of the disease progresses. Advanced care planning can be established through collaboration between healthcare professionals and patients to ensure appropriate decision-making and management. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: This paper finds that the factors that influence and relate to dialysis methods in end-stage renal disease patients help nurses exercise autonomy better, assist patients in reducing their decisional conflict, and improve clinical outcomes. PATIENT OR PUBLIC CONTRIBUTION: Patients received a relevant questionnaire survey, and caregivers assisted in conducting the study.


Assuntos
Conflito Psicológico , Letramento em Saúde , Falência Renal Crônica , Diálise Renal , Apoio Social , Humanos , Falência Renal Crônica/terapia , Falência Renal Crônica/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Diálise Renal/psicologia , China/epidemiologia , Estudos Transversais , Tomada de Decisões , Idoso , Análise de Classes Latentes , Adulto , Taxa de Filtração Glomerular
4.
Fam Syst Health ; 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39432363

RESUMO

BACKGROUND: China's recent policy initiatives and dedication of resources to heighten the public's awareness of cancer risks have led to increased cervical cancer screening and testing for human papillomavirus (HPV) which has resulted in a greater number of people diagnosed with HPV. The psychological stress experienced by women of childbearing age who are infected with HPV is also felt by their spouses, as the close relationship between spouses results in intertwined psychological distress and health statuses. Therefore, this study aimed to explore the dyadic coping experience of HPV-infected patients of childbearing age and their spouses in China and to provide a research basis for marital interventions for the disease. METHOD: From July 2022 to January 2023, we used a purposive sampling method to select 11 pairs of HPV-infected patients of childbearing age and their spouses from a tertiary hospital. We conducted in-depth interviews with the patients and their spouses and analyzed the data using Colaizzi's seven-step method. RESULTS: We identified three main themes and eight subthemes: (a) stress perception (including negative psychological reactions, emotional relationship deterioration, and family social role imbalance), (b) stress communication (including enhancing communication awareness and changing communication methods), and (c) stress adjustment (including supporting each other emotionally, facing the disease together, and seeking social support). CONCLUSION: Health care professionals should assess the stress experienced by patients and their spouses. Moreover, they should encourage them to better cope with the disease as a team. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

5.
Br J Psychiatry ; : 1-8, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39376122

RESUMO

BACKGROUND: Previous studies have indicated associations between maternal mental disorders and adverse birth outcomes; however, these studies mainly focus on certain types of mental disorders, rather than the whole spectrum. AIMS: We aimed to conduct a broad study examining all maternal mental disorder types and adverse neonatal outcomes which is needed to provide a more complete understanding of the associations. METHOD: We included 1 132 757 liveborn singletons born between 1997 and 2015 in Denmark. We compared children of mothers with a past (>2 years prior to conception; n = 48 646), recent (2 years prior to conception and during pregnancy; n = 15 899) or persistent (both past and recent; n = 10 905) diagnosis of any mental disorder, with children of mothers with no mental disorder diagnosis before the index delivery (n = 1 057 307). We also considered different types of mental disorders. We calculated odds ratios and 95% CIs of low birthweight, preterm birth, small for gestational age, low Apgar score, Caesarean delivery and neonatal death. RESULTS: Odds ratios for children exposed to past, recent and persistent maternal mental disorders suggested an increased risk for almost all adverse neonatal outcomes. Estimates were highest for children in the 'persistent' group for all outcomes, with the exception of the association between persistent maternal mental disorders and neonatal death (odds ratio 0.96, 0.62-1.48). CONCLUSIONS: Our study provides evidence for increased risk of multiple adverse neonatal outcomes among children of mothers with mental disorders, highlighting the need for close monitoring and support for women with mental disorders.

6.
Front Pharmacol ; 15: 1455058, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39372209

RESUMO

The rising incidence of fibrosis poses a major threat to global public health, and the continuous exploration of natural products for the effective treatment of fibrotic diseases is crucial. Berberine (BBR), an isoquinoline alkaloid, is widely used clinically for its anti-inflammatory, anti-tumor and anti-fibrotic pharmacological effects. Until now, researchers have worked to explore the mechanisms of BBR for the treatment of fibrosis, and multiple studies have found that BBR attenuates fibrosis through different pathways such as TGF-ß/Smad, AMPK, Nrf2, PPAR-γ, NF-κB, and Notch/snail axis. This review describes the anti-fibrotic mechanism of BBR and its derivatives, and the safety evaluation and toxicity studies of BBR. This provides important therapeutic clues and strategies for exploring new drugs for the treatment of fibrosis. Nevertheless, more studies, especially clinical studies, are still needed. We believe that with the continuous implementation of high-quality studies, significant progress will be made in the treatment of fibrosis.

7.
PLoS One ; 19(9): e0310219, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39259742

RESUMO

Nucleostemin (NS) plays a role in liver regeneration, and aging reduces its expression in the baseline and regenerating livers following 70% partial hepatectomy (PHx). Here we interrogate the mechanism controlling NS expression during liver regeneration and aging. The NS promoter was analyzed by TRANSFAC. Functional studies were performed using cell-based luciferase assay, endogenous NS expression in Hep3B cells, mouse livers with a gain-of-function mutation of C/EBPα (S193D), and mouse livers with C/EBPα knockdown. We found a CAAT box with four C/EBPα binding sites (-1216 to -735) and a GC box with consensus binding sites for c-Myc, E2F1, and p300-associated protein complex (-633 to -1). Age-related changes in NS expression correlated positively with the expression of c-Myc, E2F1, and p300, and negatively with that of C/EBPα and C/EBPß. PHx upregulated NS expression at 1d, coinciding with an increase in E2F1 and a decrease in C/EBPα. C/EBPα bound to the consensus sequences found in the NS promoter in vitro and in vivo, inhibited its transactivational activity in a binding site-dependent manner, and decreased the expression of endogenous NS in Hep3B cells. In vivo activation of C/EBPα by the S193D mutation resulted in a 4th-day post-PHx reduction of NS, a feature shared by 16-m/o livers. Finally, C/EBPα knockdown increased its expression in aged (24-m/o) livers under both baseline and regeneration conditions. This study reports the C/EBPα suppression of NS expression in aged livers, providing a new perspective on the mechanistic orchestration of tissue homeostasis in aging.


Assuntos
Envelhecimento , Proteínas de Ligação ao GTP , Regeneração Hepática , Proteínas Nucleares , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-myc , Animais , Regeneração Hepática/genética , Regeneração Hepática/fisiologia , Camundongos , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Envelhecimento/genética , Humanos , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Fator de Transcrição E2F1/metabolismo , Fator de Transcrição E2F1/genética , Hepatectomia , Sítios de Ligação , Fígado/metabolismo , Proteína p300 Associada a E1A/metabolismo , Regulação da Expressão Gênica , Transcrição Gênica , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Masculino , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Camundongos Endogâmicos C57BL , Linhagem Celular Tumoral , Proteínas de Ligação a RNA
8.
Blood Adv ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39293087

RESUMO

Non-adherence to direct oral anticoagulants (DOACs) pharmacotherapy may increase the risks of thromboembolism or bleeding, and delayed or missed doses are the most common types of non-adherence. Current recommendations from regulatory agencies or guidelines regarding this issue lack evidence and fail to consider individual differences. The study aims to develop individual remedial dosing strategies when the dose was delayed or missed for DOACs including rivaroxaban, apixaban, edoxaban, and dabigatran etexilate. Remedial dosing regimens based on population pharmacokinetic (PK)-pharmacodynamic (PD) modeling and simulation strategies were developed to expeditiously restore drug concentration or PD biomarkers within the therapeutic range. Population PK-PD characteristics of DOACs were retrieved from previously published literature. The effect of factors which influence PK and PD parameters were assessed for their impact on remedial dosing regimens. A web-based dashboard was established with R-shiny to recommend remedial dosing regimens based on patient traits, dosing schedules, and delay duration. Addressing delayed or missed doses relies on the delay time and specific DOACs involved. Additionally, age, body weight, renal function, and polypharmacy may marginally impact remedial strategies. The proposed remedial dosing strategies surpass current recommendations, with less deviation time beyond the therapeutic range. The online dashboard offers quick and convenient solutions for addressing missed or delayed DOACs. We developed a superior, cost-free tool for managing delayed or missed DOACs doses. Individualized remedial dosing strategies could be approached based on patient characteristics to decrease the risks of bleeding and thrombosis.

9.
J Pharm Sci ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39251067

RESUMO

INTRODUCTION: Roxadustat, an oral inhibitor of hypoxia-inducible factor prolyl hydroxylase domain enzymes, has been approved for the treatment of renal anemia. However, there is a lack of study on its pharmacokinetics in kidney transplant recipients (KTRs) with early posttransplant anemia (PTA). Therefore, the aim of this study is to elucidate the pharmacokinetic characteristics of roxadustat in KTRs with early PTA and optimize the dosing regimen. METHODS: A population pharmacokinetic (PopPK) analysis was performed based on 72-hour full concentration-time profiles collected from 52 Chinese KTRs. Covariates influencing exposure were assessed using stepwise covariate modelling. Monte Carlo simulations were conducted to recommend the dosing regimen for patients with different levels of covariates. RESULTS: PopPK analysis showed that the concentration-time data can be fully described by a two-compartment model. Body weight (BW) and direct bilirubin (DBIL) levels significant affected the apparent clearance of roxadustat. Based on the established model and the estimated exposures of roxadustat by Monte Carlo simulations, a recommended dosing regimen for KTRs with early PTA at varying BW and DBIL levels were developed. Roxadustat at 100 mg three times weekly were suitable for the majority of KTRs with a DBIL level around 3 µmol/L and BW between 50 and 75 kg. The required dose may need to be increased with higher BW and lower DBIL levels, while decreased with lower BW and higher DBIL levels. CONCLUSIONS: It was the first PopPK analysis of roxadustat in KTRs with early PTA, which provide a research basis for optimizing the dosing regimen.

10.
Ann Med ; 56(1): 2408463, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39340288

RESUMO

INTRODUCTION: This study combined the bioinformatics and in vitro experiment-related technologies to analyze the impact of steroid 5 alpha-reductase 3 (SRD5A3) on the prognosis and immune microenvironment of Liver Hepatocellular Carcinoma (LIHC). METHOD: Gene expression and clinical data were obtained from public databases. The prognosis was evaluated using survival, multifactor Cox, enrichment, and mutation analyses. This was then verified through in vitro experiments. RESULTS: The expression level of SRD5A3 in LIHC tissues was significantly higher than that in the adjacent tissues. Kaplan-Meier survival analysis showed that high SRD5A3 expression was associated with poor overall survival (OS) and short progression-free survival in patients with LIHC. Multivariate Cox regression analysis revealed that positive SRD5A3 expression was an independent risk factor for OS in patients with LIHC. Expression of SRD5A3 was negatively correlated with immune cell infiltration of CD4+ T, CD8+ T, and B cells. GO and KEGG enrichment analyses showed that SRD5A3 was significantly enriched in signaling- and tumor metastasis-related pathways. Nomogram and calibration curve showed that the predicted performance of the model was consistent with the actual results. In vitro results confirmed that SRD5A3 knockdown inhibited the migration, invasion, and proliferation of LIHC cells. CONCLUSIONS: SRD5A3 is actively expressed in LIHC, and positive expression of SRD5A3 is an independent risk factor for different prognoses in patients with LIHC. SRD5A3 can promote the proliferation, migration, and invasion of liver cancer cells and is related to short immune infiltration in patients with LIHC.


High SRD5A3 expression is significantly associated with poor prognosis in patients with LIHC and may help assess tumor progression.Highly expressed SRD5A3 promotes migration, invasion, and proliferation of liver cancer cells.SRD5A3 expression is related to the degree of tumor immune cell infiltration.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase , Carcinoma Hepatocelular , Neoplasias Hepáticas , Microambiente Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Prognóstico , Microambiente Tumoral/imunologia
11.
Pharmaceutics ; 16(9)2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39339182

RESUMO

Micafungin (MFG) is a widely used echinocandin antifungal agent for treating invasive candidiasis, particularly in critically ill patients. However, its pharmacokinetics can be highly variable in this population. This systematic review aims to summarize population pharmacokinetic models and provide recommendations for its use in intensive care unit (ICU) patients. Monte Carlo simulations were implemented to compare pharmacokinetic parameters and probability of target attainment (PTA) against various Candida species. A total of 16 studies were included, of which 6 studies were conducted in adult ICU patients. The key covariates were body size, liver function, and sepsis-related organ failure assessment score (SOFA) score. The median MFG clearance in adult ICU patients was 30-51% higher than in adult non-ICU patients. For infections with C. albican with MIC below 0.016 mg/L, micafungin dosages of 100 and 150 mg/d were recommended for adult non-ICU and ICU patients, respectively. For C. tropicalis and C. glabrata, 200 and 250 mg/d were recommended, respectively. However, for C. krusei and C. parapsilosis, none of the tested dosage regimens achieved assumed PTA criteria within MIC ranges of 0.125-0.25 mg/L and 0.125-2 mg/L, respectively. Therefore, MFG dosage regimens in ICU and non-ICU patients should be tailored based on the Candida spp. and their respective MIC values.

12.
Small ; : e2406621, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39344540

RESUMO

Photo-responsive adsorption has emerged as a vibrant area because it provides a promising route to reduce the energy consumption of the traditional adsorption separation. However, the current methodology to fabricate photo-responsive sorbents is still subject to the photo-deforming molecular units. In this study, a new initiative of photo-dissociated electron-hole pairs is proposed to generate amazing adsorption activity, and prove its feasibility. Employing CuPP [PP = 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin] framework nanosheets compounded with graphene, binary film (BF) sorbents are successfully fabricated. The paradigmatic BF nanostructure brings about efficiently photo-excited electron-hole pairs with durable enough lifetime to meet the needs of microscopic adsorption equilibrium, which ultimately alters the electron density distribution of adsorption surface, and thus markedly modulates the adsorption activity. Therefore, an amazing photo-enhanced adsorption capability for the index gas CO can be gotten. Once exposed to the visible-light at 420 nm, the CO adsorption capacity (0 °C, 1 bar) is risen from 0.23 mmol g-1 in the darkness to 1.66 mmol g-1, changed by + 622%. This is essentially different from majority of current photo-responsive sorbents based on photo-deforming molecular units, of which adsorption capability is only decreased with photo-induction, and the maximum rate of change reported is just -54%.

13.
Respir Res ; 25(1): 313, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39154161

RESUMO

BACKGROUND: Due to a special hemodynamic feature, pulmonary vascular disease in pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) has two stages: reversible and irreversible. So far, the mechanism involved in the transition from reversible to irreversible stage is elusive. Moreover, no recognized and reliable assessments to distinguish these two stages are available. Furthermore, we found that compared with control and reversible PAH, thrombospondin-4 (THBS4) was significantly upregulated in irreversible group by bioinformatic analysis. Hence, we further verify and investigate the expression and role of THBS4 in PAH-CHD. METHODS: We established the monocrotaline plus aorto-cava shunt-induced (MCT-AV) rat model. We measured the expression of THBS4 in lung tissues from MCT-AV rats. Double immunofluorescence staining of lung tissue for THBS4 and α-SMA (biomarker of smooth muscle cells) or vWF (biomarker of endothelial cells) to identify the location of THBS4 in the pulmonary artery. Primary pulmonary artery smooth muscle cells (PASMCs) were cultivated, identified, and used in this study. THBS4 was inhibited and overexpressed by siRNA and plasmid, respectively, to explore the effect of THBS4 on phenotype transformation, proliferation, apoptosis, and migration of PASMCs. The effect of THBS4 on pulmonary vascular remodeling was evaluated in vivo by adeno-associated virus which suppressed THBS4 expression. Circulating level of THBS4 in patients with PAH-CHD was measured by ELISA. RESULTS: THBS4 was upregulated in the lung tissues of MCT-AV rats, and was further upregulated in severe pulmonary vascular lesions. And THBS4 was expressed mainly in PASMCs. When THBS4 was inhibited, contractile markers α-SMA and MYH11 were upregulated, while the proliferative marker PCNA was decreased, the endothelial-mensenchymal transition marker N-cad was downregulated, proapototic marker BAX was increased. Additionally, proliferation and migration of PASMCs was inhibited and apoptosis was increased. Conversely, THBS4 overexpression resulted in opposite effects. And the impact of THBS4 on PASMCs was probably achieved through the regulation of the PI3K/AKT pathway. THBS4 suppression attenuated pulmonary vascular remodeling. Furthermore, compared with patients with simple congenital heart disease and mild PAH-CHD, the circulating level of THBS4 was higher in patients with severe PAH-CHD. CONCLUSIONS: THBS4 is a promising biomarker to distinguish reversible from irreversible PAH-CHD before repairing the shunt. THBS4 is a potential treatment target in PAH-CHD, especially in irreversible stage.


Assuntos
Cardiopatias Congênitas , Hipertensão Arterial Pulmonar , Ratos Sprague-Dawley , Trombospondinas , Animais , Humanos , Masculino , Ratos , Células Cultivadas , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/complicações , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Trombospondinas/metabolismo , Trombospondinas/biossíntese , Trombospondinas/genética
14.
J Affect Disord ; 364: 279-285, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39137837

RESUMO

BACKGROUND: The interplay between genetic and lifestyle factors in the development of bipolar disorder (BD) remains unclear. METHODS: A cohort study was carried out on 365,517 participants from the UK Biobank. Lifestyle scores, based on smoking, physical activity, diet, alcohol consumption, sedentary behavior, sleep duration, and social contact, were grouped as favorable (scores 6-7), intermediate (scores 4-5), or unfavorable (scores 0-3). The BD polygenic risk score (PRS) was also categorized into high, intermediate, and low-risk groups using PRS tertiles. Cox regression models determined hazard ratios (HRs) and 95 % confidence intervals (CIs) for BD. RESULTS: During the 12.9-year follow-up, 529 individuals developed BD. Comparing those with favorable lifestyles to those with unfavorable participants, the HR of developing BD was 3.28 (95 % CI, 2.76-3.89). Similarly, individuals with a high PRS had a risk of 3.20 (95 % CI, 2.83-3.63) compared to those with a low PRS. Notably, individuals with both a high PRS and an unfavorable lifestyle had a significantly higher risk of BD (HR = 6.31, 95 % CI, 4.14-9.63) compared to those with a low PRS and a favorable lifestyle. Additionally, the interaction between PRS and lifestyle contributed an additional risk, with a relative excess risk of 1.74 (95 % CI, 0.40-3.07) and an attributable proportion due to the interaction of 0.37 (95 % CI, 0.16-0.58). CONCLUSIONS: Our findings suggest that genetic liability for BD, measured as PRS, and lifestyle have an additive effect on the risk of developing BD. A favorable lifestyle was associated with a reduced risk of developing BD.


Assuntos
Consumo de Bebidas Alcoólicas , Bancos de Espécimes Biológicos , Transtorno Bipolar , Estilo de Vida Saudável , Fumar , Humanos , Transtorno Bipolar/genética , Transtorno Bipolar/epidemiologia , Feminino , Masculino , Reino Unido/epidemiologia , Pessoa de Meia-Idade , Consumo de Bebidas Alcoólicas/epidemiologia , Adulto , Fumar/epidemiologia , Estudos de Coortes , Predisposição Genética para Doença , Fatores de Risco , Herança Multifatorial , Idoso , Exercício Físico , Comportamento Sedentário , Dieta/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estilo de Vida , Biobanco do Reino Unido
15.
J Affect Disord ; 366: 91-97, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39187186

RESUMO

BACKGROUND: Little is known about the time trends of postpartum depression (PPD) and whether they differ from time trends of depression among women in general. METHODS: Using Danish health registers, we identified a postpartum population from all women who had a liveborn child from 2000-2022. We sampled a background population by matching five women for each delivery on age and date of childbirth. Depression and PPD were measured as incident depression diagnosis or redeemed antidepressant prescription within 180 days from childbirth/matching. We described incidence rates from 2000-2022 using Poisson regression with a restricted cubic spline. RESULTS: The study population included 1,133,947 postpartum women (669,101 unique), matched to 5,669,735 women (1,165,505 unique). Overall IR per 10,000 person-years of diagnoses was 34.3 (95% CI: 32.8-35.9) for PPD and 18.9 (95% CI: 18.3-19.4) for depression. Both IRs increased similarly over time in the main analyses, but more pronounced for PPD in primiparous and older mothers. Correspondingly, IR for prescriptions was 135.7 (95% CI: 132.7-138.8) for PPD and 209.8 (95% CI: 208.1-211.5) for depression, and both groups had fluctuating time trends. LIMITATIONS: Depression measures were based on women who actively sought and received treatment, expectedly underestimating true disease incidence. CONCLUSIONS: Incidence rates of PPD and depression diagnoses increased over time, especially for PPD among primiparous and older mothers. These findings could suggest either increased vulnerability or increased awareness and detection over time in these groups. Fluctuating trends overserved from prescriptions could likely be driven by external factors and not a reflection of disease trends.


Assuntos
Depressão Pós-Parto , Sistema de Registros , Humanos , Feminino , Depressão Pós-Parto/epidemiologia , Adulto , Incidência , Dinamarca/epidemiologia , Adulto Jovem , Antidepressivos/uso terapêutico , Adolescente , Depressão/epidemiologia , Fatores de Tempo
16.
Eur J Epidemiol ; 39(8): 943-954, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39158818

RESUMO

The HOPE cohort is a Danish nationwide cohort with ongoing follow-up, holding information on postpartum depression (PPD) symptoms and diagnoses on 170,218 childbirths (142,795 unique mothers). These data have been linked with extensive register data on health and socioeconomic information on the mothers, their partners, parents, and children. This cohort profile aimed to provide an overview of the data collection and content, describe characteristics, and evaluate potential selection bias. PPD screenings, using the Edinburgh Postnatal Depression Scale, were collected from 67 of the 98 Danish municipalities, covering the period January 2015 to December 2021. This data was linked with register data on PPD diagnoses (identified through medication prescriptions and hospital contacts) as well as background information. Cohort characteristics were compared to the source population, defined as all childbirths by women residing in Denmark during the same period (452,207 childbirths). Potential selection bias was evaluated by comparing odds ratios of five well-established associations between the cohort and the source population. The HOPE cohort holds information on 170,218 childbirths (38% of the source population) involving 142,795 unique mothers. The HOPE cohort only differed slightly from the source population on most characteristics examined, but larger differences were observed on specific characteristics with an underrepresentation of the youngest and oldest age groups, women with more than three children or twins/triplets, and women born outside Denmark. Similar associations were identified across the two populations within the five well-established associations. There was no indication of selection bias on the five examined associations, and the HOPE cohort is representative of the source population on important perinatal characteristics.


Assuntos
Depressão Pós-Parto , Mães , Humanos , Feminino , Dinamarca/epidemiologia , Viés de Seleção , Adulto , Depressão Pós-Parto/epidemiologia , Estudos de Coortes , Mães/psicologia , Mães/estatística & dados numéricos , Sistema de Registros , Gravidez , Adulto Jovem , Adolescente , Fatores Socioeconômicos
17.
Front Pharmacol ; 15: 1442181, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139645

RESUMO

Fibrosis is a public health issue of great concern characterized by the excessive deposition of extracellular matrix, leading to the destruction of parenchymal tissue and organ dysfunction that places a heavy burden on the global healthcare system due to its high incidence, disability, and mortality. Salvianolic acid B (SalB) has positively affected various human diseases, including fibrosis. In this review, we concentrate on the anti-fibrotic effects of SalB from a molecular perspective while providing information on the safety, adverse effects, and drug interactions of SalB. Additionally, we discuss the innovative SalB formulations, which give some references for further investigation and therapeutic use of SalB's anti-fibrotic qualities. Even with the encouraging preclinical data, additional research is required before relevant clinical trials can be conducted. Therefore, we conclude with recommendations for future studies. It is hoped that this review will provide comprehensive new perspectives on future research and product development related to SalB treatment of fibrosis and promote the efficient development of this field.

18.
Heliyon ; 10(15): e35220, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170282

RESUMO

OBJECTIVE: Paradoxical embolism caused by a patent foramen ovale (PFO) is a rare cause of myocardial infarction (MI) in individuals presenting with normal coronary arteries on angiography; however, the deduction is often made due to the inability to identify the exact thrombus that penetrates the atrial septum. Previous studies using optical coherence tomography (OCT) have reported in situ thrombi attached to PFO tunnel in patients with cryptogenic stroke. However, the presence of such thrombi in patients with cryptogenic MI (without a definite cause) remains uncertain. METHOD: We retrospectively analyzed OCT data collected from February to July 2023 on PFO tunnels in MI adults with normal coronary arteries on angiography. RESULTS: Three patients diagnosed with cryptogenic MI and a PFO underwent OCT examination. These patients exhibited varying OCT findings. White thrombi and endocardial abnormalities in the channel were observed in two patients with MI. No thrombus or anomalous morphology on the endocardial surface was noted in the third patient. PFO closure was performed on all patients, and follow-up was completed by October 1, 2023. None of the patients reported recurrence of chest pain. CONCLUSION: In situ thrombus was identified within the PFO channel in patients with cryptogenic MI, potentially serving as a novel etiological factor for coronary thrombosis.

19.
Int Med Case Rep J ; 17: 647-650, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974881

RESUMO

Neurosyphilis is a central nervous system infection caused by Treponema pallidum that imitates various neurological and mental disorders. Therefore, patients with this disease are prone to misdiagnoses. Here, we report a case of neurosyphilis with a psychotic disorder as the main manifestation. A young girl exhibited mental and behavioural abnormalities after a heartbreak, which manifested as alternating low mood, emotional irritability, and a lack of interest in social relations, followed by memory loss. The cerebrospinal fluid protein - Treponema pallidum particle agglutination test was positive, the toluidine red unheated serum test titre was 1:4, the white blood cell count was 5 × 10^6/L, the cerebrospinal fluid protein level was 0.97 g/L, and the brain CT was abnormal. After admission, the possibility of neurosyphilis was considered and the patient received intravenous penicillin G treatment. The patient's clinical symptom ms improved. This case emphasises that doctors should maintain clinical suspicion of Treponema pallidum infection in adolescent patients with mental abnormalities.

20.
BMC Cancer ; 24(1): 782, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951749

RESUMO

BACKGROUND AND AIMS: The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been identified as a novel predictive marker for the development of cardiovascular illnesses in individuals without pre-existing health conditions. However, it remains unclear whether the levels of SII are linked to cardiotoxicity related to 5-FU. This retrospective study aims to fill this knowledge gap by examining the correlation between SII and cardiotoxicity related to 5-FU in a colorectal cancer cohort. METHODS: The study comprised colorectal cancer patients who received 5-FU-based chemotherapy at the affiliated cancer hospital of Guizhou Medical University between January 1, 2018 and December 31, 2020. After adjustment for confounders and stratification by tertiles of the interactive factor, linear regression analyses, curve fitting and threshold effect analyses were conducted. RESULTS: Of the 754 patients included final analysis, approximately 21% (n = 156) of them ultimately experienced cardiotoxicity related to 5-FU. Monocytes (M) was found as an influential element in the interaction between SII and cardiotoxicity related to 5-FU. In the low tertile of M (T1: M ≤ 0.38 × 109/L), increasing log SII was positively correlated with cardiotoxicity related to 5-FU (Odds Ratio [OR], 8.04; 95% confidence interval [95%CI], 1.68 to 38.56). However, a curvilinear relationship between log SII and cardiotoxicity was observed in the middle tertile of M (T2: 0.38 < M ≤ 0.52 × 109/L). An increase in log SII above 1.37 was shown to be associated with a decreased risk of cardiotoxicity (OR, 0.14; 95%CI, 0.02 to 0.88), indicating a threshold effect. In the high tertile of M (T3: M > 0.52 × 109/L), there was a tendency towards a negative linear correlation between the log SII and cardiotoxicity was observed (OR, 0.85; 95%CI, 0.37 to 1.98). CONCLUSION: Our findings suggest that SII may serve as a potential biomarker for predicting cardiotoxicity related to 5-FU in colorectal cancer patients. SII is an independent risk factor for cardiotoxicity related to 5-FU with low monocytes levels (T1). Conversely, in the middle monocytes levels (T2), SII is a protective factor for cardiotoxicity related to 5-FU but with a threshold effect.


Assuntos
Cardiotoxicidade , Neoplasias Colorretais , Fluoruracila , Humanos , Fluoruracila/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Cardiotoxicidade/etiologia , Estudos Retrospectivos , Idoso , Inflamação , Antimetabólitos Antineoplásicos/efeitos adversos , Monócitos/imunologia , Monócitos/efeitos dos fármacos , Adulto
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