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1.
Am J Respir Cell Mol Biol ; 70(3): 215-225, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38061028

RESUMO

The function of type 2 immunity and mechanisms underlying the initiation of type 2 immunity after sepsis-induced lung injury remain unclear. Sphingosine-1-phosphate receptor 2 (S1PR2) has been demonstrated to modulate type 2 immunity in the context of asthma and pulmonary fibrosis. Thus, this study aims to investigate the role of type 2 immunity and whether and how S1PR2 regulates type 2 immunity in sepsis. Peripheral type 2 immune responses in patients with sepsis and healthy control subjects were assessed. The impact of S1PR2 on type 2 immunity in patients with sepsis and in a murine model of sepsis was further investigated. The type 2 innate immune responses were significantly increased in the circulation of patients 24 hours after sepsis, which was positively related to clinical complications and negatively correlated with S1PR2 mRNA expression. Animal studies showed that genetic deletion or pharmacological inhibition of S1PR2 induced type 2 innate immunity accumulation in the post-septic lungs. Mechanistically, S1PR2 deficiency promoted macrophage-derived interleukin (IL)-33 increase and the associated type 2 response in the lung. Furthermore, S1PR2-regulated IL-33 from macrophages mitigated lung injury after sepsis in mice. In conclusion, a lack of S1PR2 modulates the type 2 immune response by upregulating IL-33 release from macrophages and alleviates sepsis-induced lung injury. Targeting S1PR2 may have potential therapeutic value for sepsis treatment.


Assuntos
Lesão Pulmonar , Sepse , Animais , Humanos , Camundongos , Interleucina-33 , Macrófagos , Sepse/complicações , Receptores de Esfingosina-1-Fosfato
2.
Anal Chem ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959297

RESUMO

Mitochondria (MT) and the endoplasmic reticulum (ER) maintain lipid and calcium homeostasis through membrane contacts, particularly MT-ER contacts (MERCs), spanning distances from 10 to 50 nm. However, the variation of different distance ranges and the metabolic factors influencing this variation remain poorly understood. This study employed microfluidic chip-based super-resolution microscopy in conjunction with a Moore-Neighbor tracing-incorporated organelle proximity analysis algorithm. This approach enabled precise three-dimensional localization of single-fluorescence protein molecules within narrow and irregular membrane proximities. It achieved lateral localization precision of less than 20 nm, resulting in a minimum MERC distance of approximately 8 nm in spatial and mean distances across multiple threshold ranges. Additionally, we demonstrated that the MERC distance variation was correlated with MT size rather than ER width. The proportion of each distance range varied significantly after the stimuli. Free cholesterol showed a negative correlation with various distances, while distances of 10-30 nm were associated with glucose, glutamine, and pyruvic acid. Furthermore, the 30-40 nm range was influenced by citric acid. These results underscore the role of advanced subcellular organelle analysis in elucidating the single-molecule behavior and organelle morphology in single-cell studies.

3.
Anal Chem ; 96(11): 4430-4436, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38447029

RESUMO

Traditional single-molecule fluorescence in situ hybridization (smFISH) methods for RNA detection often face sensitivity challenges due to the low fluorescence intensity of the probe. Also, short-lived autofluorescence complicates obtaining clear signals from tissue sections. In response, we have developed an smFISH probe using highly grafted lanthanide complexes to address both concentration quenching and autofluorescence background. Our approach involves an oligo PCR incorporating azide-dUTP, enabling conjugation with lanthanide complexes. This method has proven to be stable, convenient, and cost-effective. Notably, for the mRNA detection in SKBR3 cells, the lanthanide probe group exhibited 2.5 times higher luminescence intensity and detected 3 times more signal points in cells compared with the Cy3 group. Furthermore, we successfully applied the probe to image HER2 mRNA molecules in breast cancer FFPE tissue sections, achieving a 2.7-fold improvement in sensitivity compared to Cy3-based probes. These results emphasize the potential of time-resolved smFISH as a highly sensitive method for nucleic acid detection, free of background fluorescence interference.


Assuntos
Elementos da Série dos Lantanídeos , Hibridização in Situ Fluorescente/métodos , RNA/análise , RNA Mensageiro/genética , Diagnóstico por Imagem
4.
Eur J Immunol ; 53(10): e2250226, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37389889

RESUMO

Protein arginine methyltransferase 5 (Prmt5) is essential for normal B-cell development; however, the roles of Prmt5 in tumor-infiltrating B cells in tumor therapy have not been well elucidated. Here, we revealed that CD19-cre-Prmt5fl/fl (Prmt5cko) mice showed smaller tumor weights and volumes in the colorectal cancer mouse model; B cells expressed higher levels of Ccl22 and Il12a, which attracted T cells to the tumor site. Furthermore, we used direct RNA sequencing to comprehensively profile RNA processes in Prmt5 deletion B cells to explore underline mechanisms. We found significantly differentially expressed isoforms, mRNA splicing, poly(A) tail lengths, and m6A modification changes between the Prmt5cko and control groups. Cd74 isoform expressions might be regulated by mRNA splicing; the expression of two novel Cd74 isoforms was decreased, while one isoform was elevated in the Prmt5cko group, but the Cd74 gene expression showed no changes. We observed Ccl22, Ighg1, and Il12a expression was significantly increased in the Prmt5cko group, whereas Jak3 and Stat5b expression was decreased. Ccl22 and Ighg1 expression might be associated with poly(A) tail length, Jak3, Stat5b, and Il12a expression might be modulated by m6A modification. Our study demonstrated that Prmt5 regulates B-cell function through different mechanisms and supported the development of Prmt5-targeted antitumor treatments.


Assuntos
Neoplasias Colorretais , Proteína-Arginina N-Metiltransferases , Animais , Camundongos , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Isoformas de Proteínas/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Processamento Pós-Transcricional do RNA , RNA Mensageiro
5.
Small ; 20(24): e2306725, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38287726

RESUMO

Droplet microfluidics are extensively utilized to generate monodisperse cell-laden microgels in biomedical applications. However, maintaining cell viability is still challenging due to overexposure to harsh conditions in subsequent procedures that recover the microgels from the oil phase. Here, a gravity-oriented microfluidic device for end-to-end fabrication of cell-laden microgels is reported, which integrates dispersion, gelation, and extraction into a continuous workflow. This innovative on-chip extraction, driven by native buoyancy and kinetically facilitated by pseudosurfactant, exhibits 100% retrieval efficiency for microgels with a wide range of sizes and stiffnesses. The viability of encapsulated cells is perfectly maintained at ≈98% with minimal variations within and between batches. The end-to-end fabrication remarkably enhances the biocompatibility and practicality of microfluidics-based cell encapsulation and is promising to be compatible with various applications ranging from single-cell analysis to clinical therapy.


Assuntos
Materiais Biocompatíveis , Células , Dispositivos Lab-On-A-Chip , Microgéis , Microgéis/química , Dispositivos Lab-On-A-Chip/normas , Gravitação , Células/química
6.
Small ; 20(27): e2308565, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38339770

RESUMO

Cuproptosis is an emerging programmed cell death, displaying great potential in cancer treatment. However, intracellular copper content to induce cuproptosis is unmet, which mainly ascribes to the intracellular pumping out equilibrium mechanism by copper exporter ATP7A and ATP7B. Therefore, it is necessary to break such export balance mechanisms for desired cuproptosis. Mediated by diethyldithiocarbamate (DTC) coordination, herein a strategy to efficiently assemble copper ions into polydopamine nanostructure (PDA-DTC/Cu) for reprogramming copper metabolism of tumor is developed. The deposited Cu2+ can effectively trigger the aggregation of lipoylated proteins to induce cuproptosis of tumor cells. Beyond elevating intracellular copper accumulation, PDA-DTC/Cu enables to break the balance of copper metabolism by disrupting mitochondrial function and restricting the adenosine triphosphate (ATP) energy supply, thus catalytically inhibiting the expressions of ATP7A and ATP7B of tumor cells to enhance cuproptosis. Meanwhile, the killed tumor cells can induce immunogenic cell death (ICD) to stimulate the immune response. Besides, PDA-DTC/Cu NPs can promote the repolarization of tumor-associated macrophages (TAMs ) to relieve the tumor immunosuppressive microenvironment (TIME). Collectively, PDA-DTC/Cu presented a promising "one stone two birds" strategy to realize copper accumulation and inhibit copper export simultaneously to enhance cuproptosis for 4T1 murine breast cancer immunotherapy.


Assuntos
Cobre , Imunoterapia , Indóis , Nanoestruturas , Polímeros , Cobre/química , Polímeros/química , Animais , Imunoterapia/métodos , Indóis/química , Indóis/farmacologia , Camundongos , Nanoestruturas/química , Linhagem Celular Tumoral , Humanos , Catálise , Feminino , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
7.
Am J Geriatr Psychiatry ; 32(5): 586-595, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38184422

RESUMO

OBJECTIVES: Collaborative care (CC) has demonstrated effectiveness for improving late-life depression in primary care, but clinics offering this service can find it challenging to address unmet social needs that may be contributing to their patients' depression. Clinics may benefit from better coordination and communication with community-based organizations (CBO) to strengthen depression treatment and to address unmet social needs. We evaluated the feasibility of adding a CBO to enhance standard collaborative care and the impact of such partnered care on older adults. DESIGN: Multisite, prepost evaluation. SETTING: Eight (n = 8) partnerships between primary care clinics and community-based organizations in California. PARTICIPANTS: A total of 707 depressed older adults (60 years or older) as evidenced by having a score of 10 or more on the Patient Health Questionnaire (PHQ-9) received care under the Care Partners project. INTERVENTION: A CBO partner was added to augment CC for late-life depression in primary care. MEASUREMENTS: The PHQ-9 was used to identify depressed older adults and to monitor depression symptom severity during a course of care. RESULTS: At baseline, the average PHQ-9 depression score across the partnerships was 15, indicating moderate depression severity. Participating patients saw an average 7-point reduction in their PHQ-9 score, baseline to last score assessed, with nearly half of all participants (48.4%) experiencing a 50% or greater improvement from their baseline score. CONCLUSIONS: Our findings suggest that partnering with a community-based organization is a feasible and effective way for primary care clinics to address late-life depression in their patients.


Assuntos
Depressão , Transtorno Depressivo , Humanos , Idoso , Depressão/terapia , Cuidadores , Melhoria de Qualidade , Transtorno Depressivo/terapia
8.
Pharm Res ; 41(6): 1257-1270, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38844745

RESUMO

PURPOSE: Cinchoninze hydrochloride solves the problem of the low solubility of cinchonine, but it is unstable and susceptible to deliquescence. In this study, we designed and prepared cinchonine cocrystal salts or cinchonine salts with better stability, solubility and antioxidant activity than cinchonine. METHOD: We successfully synthesized and characterized three cinchonine salts, namely, cinchonine-fumaric acid, cinchonine-isoferulic acid, and cinchonine-malic acid. The high humidity (92.5% RH) and high temperature (60°C) tests were conducted to determine the physical stability and hygroscopicity of cinchonine hydrochloride, cinchonine and three cinchonine salts. And the ultraviolet spectrophotometry was conducted to determine the equilibrium solubility and intrinsic dissolution rate of cinchonine and salts. Moreover, the DPPH, ABTS, and FRAP assays determined the antioxidant activity of cinchonine and salts. RESULT: Compared with cinchonine hydrochloride and cinchonine, all three cinchonine salts exhibited good physical stability over 15 days under high humidity (92.5% RH) and high temperature (60°C) conditions. While cinchonine and cinchonine hydrochloride are categorized as hygroscopic and deliquescent, respectively, three cinchonine salts are classified as slightly hygroscopic, meaning that they have a lower hygroscopicity than cinchonine and cinchonine hydrochloride. And three cinchonine salts had higher equilibrium solubility, faster intrinsic dissolution rates, and higher antioxidant activity in comparison to cinchonine. Moreover, they showed a "spring and parachute" pattern in the phosphate buffer (pH = 6.8). CONCLUSION: Cocrystallization technology is a viable option for improving cinchonine's poor physicochemical qualities.


Assuntos
Antioxidantes , Cristalização , Estabilidade de Medicamentos , Solubilidade , Antioxidantes/química , Antioxidantes/farmacologia , Molhabilidade , Química Farmacêutica/métodos , Umidade , Sais/química
9.
BMC Med Res Methodol ; 24(1): 125, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831262

RESUMO

BACKGROUND: Mediation analysis is a powerful tool to identify factors mediating the causal pathway of exposure to health outcomes. Mediation analysis has been extended to study a large number of potential mediators in high-dimensional data settings. The presence of confounding in observational studies is inevitable. Hence, it's an essential part of high-dimensional mediation analysis (HDMA) to adjust for the potential confounders. Although the propensity score (PS) related method such as propensity score regression adjustment (PSR) and inverse probability weighting (IPW) has been proposed to tackle this problem, the characteristics with extreme propensity score distribution of the PS-based method would result in the biased estimation. METHODS: In this article, we integrated the overlapping weighting (OW) technique into HDMA workflow and proposed a concise and powerful high-dimensional mediation analysis procedure consisting of OW confounding adjustment, sure independence screening (SIS), de-biased Lasso penalization, and joint-significance testing underlying the mixture null distribution. We compared the proposed method with the existing method consisting of PS-based confounding adjustment, SIS, minimax concave penalty (MCP) variable selection, and classical joint-significance testing. RESULTS: Simulation studies demonstrate the proposed procedure has the best performance in mediator selection and estimation. The proposed procedure yielded the highest true positive rate, acceptable false discovery proportion level, and lower mean square error. In the empirical study based on the GSE117859 dataset in the Gene Expression Omnibus database using the proposed method, we found that smoking history may lead to the estimated natural killer (NK) cell level reduction through the mediation effect of some methylation markers, mainly including methylation sites cg13917614 in CNP gene and cg16893868 in LILRA2 gene. CONCLUSIONS: The proposed method has higher power, sufficient false discovery rate control, and precise mediation effect estimation. Meanwhile, it is feasible to be implemented with the presence of confounders. Hence, our method is worth considering in HDMA studies.


Assuntos
Análise de Mediação , Pontuação de Propensão , Humanos , Estudos Observacionais como Assunto/métodos , Fatores de Confusão Epidemiológicos , Epigenômica/métodos , Simulação por Computador , Algoritmos
10.
J Immunol ; 208(2): 501-513, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34911774

RESUMO

Protein arginine methyltransferase 5 (PRMT5) participates in the symmetric dimethylation of arginine residues of proteins and contributes to a wide range of biological processes. However, how PRMT5 affects the transcriptional and epigenetic programs involved in the establishment and maintenance of T cell subset differentiation and roles in antitumor immunity is still incompletely understood. In this study, using single-cell RNA and chromatin immunoprecipitation sequencing, we found that mouse T cell-specific deletion of PRMT5 had greater effects on CD8+ than CD4+ T cell development, enforcing CD8+ T cell differentiation into Klrg1+ terminal effector cells. Mechanistically, T cell deficiency of PRMT5 activated Prdm1 by decreasing H4R3me2s and H3R8me2s deposition on its loci, which promoted the differentiation of Klrg1+CD8+ T cells. Furthermore, effector CD8+ T cells that transited to memory precursor cells were decreased in PRMT5-deficient T cells, thus causing dramatic CD8+ T cell death. In addition, in a mouse lung cancer cell line-transplanted tumor mouse model, the percentage of CD8+ T cells from T cell-specific deletion of PRMT5 mice was dramatically lost, but CD8+Foxp3+ and CD8+PDL1+ regulatory T cells were increased compared with the control group, thus accelerating tumor progression. We further verified these results in a mouse colon cancer cell line-transplanted tumor mouse model. Our study validated the importance of targeting PRMT5 in tumor treatment, because PRMT5 deficiency enforced Klrg1+ terminal CD8+ T cell development and eliminated antitumor activity.


Assuntos
Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Carcinogênese/genética , Lectinas Tipo C/metabolismo , Proteína-Arginina N-Metiltransferases/deficiência , Receptores Imunológicos/metabolismo , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Hematopoese/fisiologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Ativação Linfocitária/imunologia , Masculino , Metilação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Proteína-Arginina N-Metiltransferases/genética , RNA-Seq , Transdução de Sinais/genética , Análise de Célula Única
11.
Int J Cancer ; 152(3): 436-446, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36214796

RESUMO

Esophageal cancer (EC) is a main cause of cancer-related deaths. However, genomic alterations and the clinical value of next-generation sequencing (NGS) in advanced or metastatic EC for precision therapy remain largely unclear. Herein, we performed comprehensive analyses on a cohort of 47 individuals with advanced or metastatic EC who underwent NGS between May 2017 and February 2020. Eventually, 227 mutated genes were identified in the cohort. TP53, NQO1, DPYD, GSTM1, XRCC1 and ERCC1 were the most mutated genes and associated with immune cell infiltration, autophagy and hypoxia. Patients who received NGS-guided treatments exhibited better objective remission rate (ORR) (72.22%), disease control rate (DCR) (88.89%), overall survival (OS) (P = .0019) and progression-free survival (PFS) (P = .0077) than those not receiving NGS-guided therapies. The multivariate analyses further demonstrated that the NGS-guided therapy was an independently prognostic factor (OS: hazard radio [HR] 0.31, 95% coincidence interval [CI] 0.1-0.97, P = .04). In conclusion, we depicted a comprehensive mutational landscape of 47 patients with locally advanced or metastatic EC and illustrated the utility of NGS testing to guide clinical management in improving ORR, DCR, OS and PFS.


Assuntos
Neoplasias Esofágicas , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Genômica , Intervalo Livre de Progressão , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética
12.
J Neuroinflammation ; 20(1): 183, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37533053

RESUMO

BACKGROUND: Protein arginine methyltransferase 5 (Prmt5) is the main type II methyltransferase, catalyzes protein arginine residue symmetric dimethylation, and modulates normal cellular physiology and disease progression. Prmt5 inhibition or deletion in CD4+ T cells has been reported to ameliorate experimental autoimmune encephalomyelitis (EAE), but the detailed molecular mechanisms have not yet been elucidated. METHODS: EAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG35-55) in T cells Prmt5 conditional knockout (CD4-cre-Prmt5fl/fl, Prmt5cko) and Prmt5fl/fl (WT) mice. Flow cytometry, single-cell RNA sequencing, ATAC sequencing and chromatin immunoprecipitation assay (ChIP) approaches were used to explore the detail mechanisms. RESULTS: We find that Prmt5cko mice are resistant to EAE; infiltrating inflammatory CD4+ T cells in the central nervous system (CNS) are greatly reduced. However, in Prmt5cko mice, T cells in the spleen show much more proliferation and activation properties, the total number of CD4+ T cells in the spleen is not reduced, and the percentage of Rora+ CD4+ T cells is elevated. Also, CD4+ T cells express lower levels of S1pr1 and Klf2 than WT mice, which may influence pathogenic CD4+ T-cell egress from the spleen and migration to the CNS. Moreover, the single-cell ATAC sequence and ChIP assay reveal that the transcription factor Klf2 is enriched at the S1pr1 promoter and that Klf2 motif activity is reduced in Prmt5cko mice. CONCLUSIONS: Our study delineates the undiscovered role of Prmt5 in T-cell biology in which Prmt5 may inhibit Klf2-S1pr1 pathway to ameliorate EAE disease. Controlling T-cell Prmt5 expression may be helpful for the treatment of autoimmune diseases.


Assuntos
Encefalomielite Autoimune Experimental , Proteína-Arginina N-Metiltransferases , Animais , Camundongos , Linfócitos T CD4-Positivos , Sistema Nervoso Central/patologia , Encefalomielite Autoimune Experimental/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito/toxicidade , Fatores de Transcrição/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo
13.
J Org Chem ; 88(9): 5348-5358, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37011379

RESUMO

A facile access to isocoumarins has been established via rhodium(III)-catalyzed C-H bond activation and intramolecular C-C cascade annulation of enaminones and cyclic 1,3-dicarbonyl compounds. The synthetic protocol features a wide range of substrates with high functional group tolerance, mild reaction conditions, and the selective cleavage of the enaminone C-C bond. Notably, the cyclic 1,3-dicarbonyl compounds can in situ-generate iodonium ylide as a carbene precursor to prepare polycyclic scaffolds by reacting with PhI(OAc)2. The application of this method to prepare useful synthetic precursors and bioactive skeletons is also exemplified.

14.
Inorg Chem ; 62(5): 2228-2235, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36689703

RESUMO

Commercial polyketone materials are generally produced by palladium-catalyzed terpolymerization of ethylene and α-olefin with carbon monoxide (CO), and rare examples were reported regarding the incorporation of propylene into an ethylene/CO copolymer chain using a cost-effective nickel catalyst. In this study, we have developed a series of [P,O]-type cationic Pd and Ni complexes supported by a diphosphazane monoxide (PNPO) platform, and the electronic and steric effect on phosphine, amine, and phosphine oxide moieties is systematically investigated for terpolymerization in terms of activity, propylene/CO (C3) incorporation, and molecular weight control. It is observed that the melting temperature (Tm) is proportional to the number of C3 incorporations present in the polymer chain, and the incorporated propylene does not affect the degradation temperature substantially, thus broadening the processing temperature window of the resultant polyketones. Notably, in comparison with dppp-type catalysts, PNPO catalysts exhibited a higher preference for propylene consumption, which is of great importance for making more efficient use of α-olefin resources.

15.
Appl Opt ; 62(36): 9446-9453, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38108768

RESUMO

A dual aspheric integrated beam shaper suitable for a high-power laser situation has been designed and realized. The model for this lens was derived theoretically and the performance was evaluated using a detailed simulation. The ultrasonic vibration assisted cutting and the high-precision grinding and polishing technology were used for the processing. The surface accuracy was less than 200 nm measured with a profiler, and the roughness was smaller than 20 nm with the help of the white light interferometer. Shaping experiments were carried out, which verified that the Gaussian beam has uniform intensity distribution with a uniformity of 85.13% in the near field and converges to a point in the far field, which is exactly as expected. It thus provides an actual selection for high-power laser shaping.

16.
J Trauma Stress ; 36(6): 1102-1114, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37845820

RESUMO

The PTSD Checklist for DSM-5 (PCL-5) is a measure of posttraumatic stress disorder (PTSD) symptom severity that is widely used for clinical and research purposes. Although previous work has examined metrics of minimal important difference (MID) of the PCL-5 in veteran samples, no work has identified PCL-5 MID metrics among adults in primary care in the United States. In this secondary analysis, data were evaluated from primary care patients (N = 971) who screened positive for PTSD and participated in a large clinical trial in federally qualified health centers in three U.S. states. Participants primarily self-identified as women (70.2%) and White (70.3%). We calculated test-retest reliability using clinic registry data and multiple distribution- and anchor-based metrics of MID using baseline and follow-up survey data. Test-retest reliability (Pearson's r, Spearman's ρ, intraclass correlation coefficient) ranged from adequate to excellent (.79-.94), with the shortest time lag demonstrating the highest reliability estimate. The MID for the PCL-5 was estimated using multiple approaches. Distribution-based approaches indicated an MID range of 8.5-12.5, and anchor-based approaches indicated an MID range of 9.8-11.7. Taken together, the MID metrics indicate that PCL-5 change scores of 9-12 likely reflect real change in PTSD symptoms and indicate at least an MID for patients, whereas PCL-5 change scores of 5 or less likely are not reliable. These findings can help inform clinicians using the PCL-5 in similar populations to track patient responses to treatment and help researchers interpret PCL-5 score changes in clinical trials.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Adulto , Humanos , Feminino , Estados Unidos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Lista de Checagem , Reprodutibilidade dos Testes , Psicometria , Atenção Primária à Saúde
17.
BMC Musculoskelet Disord ; 24(1): 301, 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37069521

RESUMO

BACKGROUND: The mutual compensatory relationship between the upper cervical sagittal alignment and the lower cervical sagittal alignment has been repeatedly reported. However, the evaluation of the upper cervical sagittal parameters are varied in previous studies. This retrospective study was performed to compare three methods for measuring the upper cervical sagittal parameters. METHODS: A total of 263 individuals with standing neutral lateral cervical radiographs were included in this study. The Frankfort horizontal line (FHL), foramen magnum line (FML), and McGregor line (ML) were separately used as the reference lines for measuring the C0-1 angle and C0-2 angle. Intraclass correlation (ICC) values were used to compare the consistency and repeatability of the three methods. Pearson's correlation analysis was used to analyze the correlation between the sagittal parameters of the upper and lower cervical spine. RESULTS: The interobserver and intraobserver ICC values obtained from using the ML to measure the C0-1 angle and C0-2 angle were both higher than those obtained from using the FML or FHL. The C0-1 angle and C0-2 angle measured by the three methods were negatively correlated with the C2-7 angle. The upper sagittal parameters measured by the FHL were the most correlated with the C2-7 angle. The correlation between the C0-1 angle measured by the three methods and the C0-2 angle measured with the FHL or ML and the C2-7 angle increased with aging. CONCLUSION: Use of the ML to measure the C0-1 angle and C0-2 angle has higher reliability. Use of the FHL to measure the sagittal alignment of the upper cervical spine is more suitable for evaluating the compensation mechanism between the upper and the lower cervical spine.


Assuntos
Fluormetolona , Lordose , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Vértebras Cervicais/diagnóstico por imagem , Pescoço
18.
J Med Internet Res ; 25: e46052, 2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37384392

RESUMO

BACKGROUND: Despite the high prevalence of major depressive disorder and the related societal burden, access to effective traditional face-to-face or video-based psychotherapy is a challenge. An alternative that offers mental health care in a flexible setting is asynchronous messaging therapy. To date, no study has evaluated its efficacy and acceptability in a randomized controlled trial for depression. OBJECTIVE: The aim of this study was to compare the efficacy and acceptability of message-based psychotherapy for depression to once-weekly video-based psychotherapy. METHODS: In this 2-armed randomized controlled trial, individuals (N=83) with depressive symptomatology (Patient Health Questionnaire-9 ≥10) were recruited on the internet and randomly assigned to either a message-based intervention group (n=46) or a once-weekly video-based intervention group (n=37). Patients in the message-based treatment condition exchanged asynchronous messages with their therapist following an agreed-upon schedule. Patients in the video-based treatment condition met with their therapist once each week for a 45-minute video teletherapy session. Self-report data for depression, anxiety, and functional impairment were collected at pretreatment, weekly during treatment, at posttreatment, and at a 6-month follow-up. Self-reported treatment expectancy and credibility for the assigned intervention were assessed at pretreatment and therapeutic alliance at posttreatment. RESULTS: Findings from multilevel modeling indicated significant, medium-to-large improvements in depression (d=1.04; 95% CI 0.60-1.46), anxiety (d=0.61; 95% CI 0.22-0.99), and functional impairment (d=0.66; 95% CI 0.27-1.05) for patients in the message-based treatment condition. Changes in depression (d=0.11; 95% CI -0.43 to 0.66), anxiety (d=-0.01; 95% CI -0.56 to 0.53), and functional impairment (d=0.25; 95% CI -0.30 to 0.80) in the message-based treatment condition were noninferior to those in the video-based treatment condition. There were no significant differences in treatment credibility (d=-0.09; 95% CI -0.64 to 0.45), therapeutic alliance (d=-0.15; 95% CI -0.75 to 0.44), or engagement (d=0.24; 95% CI -0.20 to 0.67) between the 2 treatment conditions. CONCLUSIONS: Message-based psychotherapy could present an effective and accessible alternative treatment modality for patients who might not be able to engage in traditional scheduled services such as face-to-face or video-based psychotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT05467787; https://www.clinicaltrials.gov/ct2/show/NCT05467787.


Assuntos
Transtorno Depressivo Maior , Aliança Terapêutica , Humanos , Depressão/terapia , Psicoterapia , Ansiedade
19.
J Adv Nurs ; 79(1): 215-222, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36317455

RESUMO

AIM: To examine (1) the mediating role of self-efficacy between resilience and self-management behaviours and (2) the moderating role of diabetes distress on the relationship between self-efficacy and self-management behaviours in patients newly diagnosed with type 2 diabetes. DESIGN: Cross-sectional design. METHODS: Totally, 195 patients newly diagnosed with type 2 diabetes for more than 5 months but less than 18 months were recruited from three endocrine clinics in Taiwan through convenience sampling. Self-reported questionnaires including demographic and disease characteristics, resilience, self-efficacy and self-management behaviours were used to collect data from October 2020 to May 2021. Moderated mediation analysis was performed by Hayes's PROCESS macro. RESULT: According to bootstrapping results, the indirect effect of resilience on self-management was significant, although the direct effect of resilience on self-management was not. Participants were categorized into with and without diabetes distress groups. The results of moderated mediation analysis indicated self-efficacy significantly correlated with self-management behaviours in participants without diabetes distress, although self-efficacy did not significantly correlate with self-management in participants with diabetes distress. CONCLUSION: The association of resilience with self-management behaviours was fully mediated through self-efficacy with diabetes distress moderating the relationship between self-efficacy and self-management behaviours in patients newly diagnosed with type 2 diabetes. IMPACT: Improving resilience could enhance self-efficacy leading to possible improvement in self-management behaviour, although improving self-efficacy might not benefit self-management behaviours for those with high levels of diabetes distress. Healthcare providers need to first assess and address the diabetes distress before intervening to improve self-efficacy to enhance self-management behaviours in patients newly diagnosed with type 2 diabetes. PATIENT OR PUBLIC CONTRIBUTION: When designing this study, two patients newly diagnosed with diabetes were consulted about the importance of self-management behaviours for them personally.


Assuntos
Diabetes Mellitus Tipo 2 , Autogestão , Humanos , Autoeficácia , Diabetes Mellitus Tipo 2/terapia , Análise de Mediação , Estudos Transversais
20.
J Adv Nurs ; 79(10): 4034-4043, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37259482

RESUMO

AIMS: To develop and psychometrically test Character Strengths Use in Diabetes Self-management Scale in people with type 2 diabetes. DESIGN: Cross-sectional design. METHODS: Based on literature reviews and examination by experts, a 20-item scale was developed and administered to 350 participants with type 2 diabetes who were enrolled from two endocrine clinics by convenience sampling in Taiwan. Item analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), concurrent and predictive validity as well as reliability were used to examine the psychometric characteristics of the scale. Data were collected from November 2021 to March 2022. RESULTS: EFA and CFA supported a 12-item scale with three factors, namely learning proactively, taking on challenges and thinking positively, fit the data well. The total score of the 12-item scale significantly and positively correlated with diabetes-specific quality of life, and significantly and negatively correlated with baseline and 9-month haemoglobin A1c levels. Cronbach's α for overall scale and subscales ranged between .78 and .91. CONCLUSION: The 12-item Character Strengths Use in Diabetes Self-management Scale demonstrated satisfactory validity and reliability in people with type 2 diabetes. IMPACT: Nurses could apply this new scale to identify the degree of using character strengths in self-management in people with type 2 diabetes; accordingly, character strength-based interventions could be provided to improve self-management in such patients with diabetes. Furthermore, the 12-item Character Strengths Use in Diabetes Self-management Scale has the potential to be used to measure the effectiveness of strength-based interventions in people with Type 2 diabetes. PATIENT OR PUBLIC CONTRIBUTION: Five patients with type 2 diabetes were invited to take the original 20-item scale to evaluate the clarity, readability and comprehensiveness of the 20 items.


Assuntos
Diabetes Mellitus Tipo 2 , Autogestão , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Qualidade de Vida , Psicometria , Reprodutibilidade dos Testes , Estudos Transversais , Análise Fatorial , Inquéritos e Questionários
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