RESUMEN
OBJECTIVE: To identify the predictive value of the neutrophil-to-lymphocyte ratio (NLR) on admission for intrapartum maternal fever in parturients undergoing epidural analgesia (EA). METHODS: In this retrospective cohort study, propensity score matching (PSM) was applied to address covariates. Univariate and multivariate regression analyses were implemented in sequence to find out the factors influencing intrapartum fever. The receiver operating characteristics curve was applied to determine the area under the curve (AUC) of NLR for intrapartum fever. RESULTS: NLR and duration of EA were independent risk factors for intrapartum fever. The AUC of the combined indicator (NLR + duration of EA) was higher than that of NLR (AUC = 0.583, 95% confidence interval [CI] 0.53-0.64) and duration of EA (AUC = 0.702, 95% CI 0.66-0.75), reaching 0.715 (95% CI 0.67-0.76; p < 0.001). NLR increased predictive performance for intrapartum fever when added to the duration of EA (net reclassification index 0.076, p = 0.022; integrated discrimination improvement 0.020, p = 0.002). CONCLUSION: NLR has limited predictive power for intrapartum fever. The combination of NLR and duration of epidural analgesia may be considered a promising predictor for intrapartum maternal fever in parturients undergoing epidural analgesia. SYNOPSIS: The neutrophil-to-lymphocyte ratio is an accessible predictor for the early identification of parturients at risk of intrapartum fever.
RESUMEN
Immune checkpoints are essential regulators of immune responses, either by activating or suppressing them. Consequently, they are regarded as pivotal elements in the management of infections, cancer, and autoimmune disorders. In recent years, researchers have identified numerous soluble immune checkpoints that are produced through various mechanisms and demonstrated biological activity. These soluble immune checkpoints can be produced and distributed in the bloodstream and various tissues, with their roles in immune response dysregulation and autoimmunity extensively documented. This review aims to provide a thorough overview of the generation of various soluble immune checkpoints, such as sPD-1, sCTLA-4, sTim-3, s4-1BB, sBTLA, sLAG-3, sCD200, and the B7 family, and their importance as indicators for the diagnosis and prediction of autoimmune conditions. Furthermore, the review will investigate the potential pathological mechanisms of soluble immune checkpoints in autoimmune diseases, emphasizing their association with autoimmune diseases development, prognosis, and treatment.
Asunto(s)
Enfermedades Autoinmunes , Proteínas de Punto de Control Inmunitario , Humanos , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/diagnóstico , Proteínas de Punto de Control Inmunitario/metabolismo , Proteínas de Punto de Control Inmunitario/genética , Biomarcadores , Animales , Autoinmunidad , Pronóstico , Susceptibilidad a Enfermedades/inmunologíaRESUMEN
Anticancer peptides (ACPs) have regarded as a new generation of promising antitumor drugs due to the unique mode of action. The main challenge is to develop potential anticancer peptides with satisfied antitumor activity and low toxicity. Here, a series of new α-helical anticancer peptides were designed and synthesized based on the regular repeat motif KLLK. The optimal peptides 14E and 14Aad were successfully derived from the new short α-helical peptide KL-8. Our results demonstrated that 14E and 14Aad had good antitumor activity and low toxicity, exhibiting excellent selectivity index. This result highlighted that the desirable modification position and appropriate hydrophobic side-chain structure of acidic amino acids played critical roles in regulating the antitumor activity/toxicity of new peptides. Further studies indicated that they could induce tumor cell death via the multiple actions of efficient membrane disruption and intracellular mechanisms, displaying apparent superiority in combination with PTX. In addition, the new peptides 14E and 14Aad showed excellent antitumor efficacy in vivo and low toxicity in mice compared to KL-8 and PTX. Particularly, 14Aad with the longer side chain at the 14th site exhibited the best therapeutic performance. In conclusion, our work provided a new avenue to develop promising anticancer peptides with good selectivity for tumor therapy.
Asunto(s)
Antineoplásicos , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Péptidos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Animales , Humanos , Ratones , Péptidos/química , Péptidos/farmacología , Péptidos/síntesis química , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Estructura Molecular , Línea Celular Tumoral , Ratones Endogámicos BALB C , Apoptosis/efectos de los fármacos , FemeninoRESUMEN
Neonatal epilepsy is a common emergency phenomenon in neonatal intensive care units (NICUs), which requires timely attention, early identification, and treatment. Traditional detection methods mostly use supervised learning with enormous labeled data. Hence, this study offers a semi-supervised hybrid architecture for detecting seizures, which combines the extracted electroencephalogram (EEG) feature dataset and convolutional autoencoder, called Fd-CAE. First, various features in the time domain and entropy domain are extracted to characterize the EEG signal, which helps distinguish epileptic seizures subsequently. Then, the unlabeled EEG features are fed into the convolutional autoencoder (CAE) for training, which effectively represents EEG features by optimizing the loss between the input and output features. This unsupervised feature learning process can better combine and optimize EEG features from unlabeled data. After that, the pre-trained encoder part of the model is used for further feature learning of labeled data to obtain its low-dimensional feature representation and achieve classification. This model is performed on the neonatal EEG dataset collected at the University of Helsinki Hospital, which has a high discriminative ability to detect seizures, with an accuracy of 92.34%, precision of 93.61%, recall rate of 98.74%, and F1-score of 95.77%, respectively. The results show that unsupervised learning by CAE is beneficial to the characterization of EEG signals, and the proposed Fd-CAE method significantly improves classification performance.
Asunto(s)
Electroencefalografía , Convulsiones , Humanos , Electroencefalografía/métodos , Recién Nacido , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Procesamiento de Señales Asistido por Computador , Aprendizaje Profundo , Aprendizaje Automático no Supervisado , Redes Neurales de la ComputaciónRESUMEN
Honokiol (HNK) is a typical natural biphenyl polyphenol compound. It has been proven to have a wide range of biological activities, including pharmacological effects such as anti-cancer, anti-inflammatory, neuroprotective, and antimicrobial. However, due to the poor stability, water solubility, and bioavailability of HNK, HNK has not been used in clinical treatment. This article reviews the latest research on the pharmacological activity of HNK and summarizes the HNK derivatives designed and improved by several researchers. Reviewing these contents could promote the research process of HNK and guide the design of better HNK derivatives for clinical application in the future.
Asunto(s)
Compuestos de Bifenilo , Lignanos , Lignanos/farmacología , Lignanos/química , Lignanos/síntesis química , Compuestos de Bifenilo/farmacología , Compuestos de Bifenilo/antagonistas & inhibidores , Compuestos de Bifenilo/química , Humanos , Relación Estructura-Actividad , Animales , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/síntesis química , Estructura Molecular , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/síntesis química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/síntesis química , Compuestos Alílicos , FenolesRESUMEN
Mutant isocitrate dehydrogenases (IDHs) produce R-2-hydroxyglutarate (R-2HG), which inhibits the growth of most acute myeloid leukemia (AML) cells. Here, we showed that necroptosis, a form of programmed cell death, contributed to the antileukemia activity of R-2HG. Mechanistically, R-2HG competitively inhibited the activity of lysine demethylase 2B (KDM2B), an α-ketoglutarate-dependent dioxygenase. KDM2B inhibition increased histone 3 lysine 4 trimethylation levels and promoted the expression of receptor-interacting protein kinase 1 (RIPK1), which consequently caused necroptosis in AML cells. The expression of RIPK3 was silenced because of DNA methylation in IDH-mutant (mIDH) AML cells, resulting in R-2HG resistance. Decitabine up-regulated RIPK3 expression and repaired endogenous R-2HG-induced necroptosis pathway in mIDH AML cells. Together, R-2HG induced RIPK1-dependent necroptosis via KDM2B inhibition in AML cells. The loss of RIPK3 protected mIDH AML cells from necroptosis. Restoring RIPK3 expression to exert R-2HG's intrinsic antileukemia effect will be a potential therapeutic strategy in patients with AML.
Asunto(s)
Glutaratos , Leucemia Mieloide Aguda , Lisina , Humanos , Necroptosis , Leucemia Mieloide Aguda/tratamiento farmacológico , Apoptosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
BACKGROUND: Pneumonia has a high incidence in traumatic brain injury (TBI) patients and lacks effective treatments. Early mobilization (EM) may be a potentially effective treatment. AIM: To explore the impact of EM on TBI-related pneumonia in the neurosurgical intensive care unit (NICU). METHOD: This study was a historical control study. 100 TBI patients who received EM intervention were prospectively included as the experimental group (EM cohort), and 250 TBI patients were retrospectively included as the control group. The propensity score matching (PSM) method was employed to balance baseline and minimize potential bias. The relationship between EM and TBI-related pneumonia was investigated by univariate and multivariate logistic regression, then further determined by subgroup analysis. The influence of other variables was excluded by interaction analyses. Finally, the effect of EM on the prognosis of TBI patients was analysed by comparing the Glasgow Coma Scale (GCS) and the hospital stay. RESULTS: After screening, 86 patients were included in the EM cohort and 199 patients were included in the control cohort. There were obvious differences between the two cohorts at baseline, and these differences were eliminated after PSM, when the incidence of pneumonia was significantly lower in the EM cohort than in the control cohort (35.0% vs. 61.9%, p < .001). Multivariate logistic regression showed that EM was an independent risk factor for TBI-related pneumonia and was significantly associated with a decreased incidence of pneumonia. This correlation was present in most subgroups and was not affected by other variables (p for interaction >.05). Patients in the EM cohort had shorter length of ICU stay (6 vs. 7 days, p = .017) and higher GCS at discharge (12 vs. 11, p = .010). CONCLUSION: EM is a safe and effective treatment for TBI patients in NICU, which can reduce the incidence of pneumonia, help to improve prognosis and shorten the length of ICU stay. RELEVANCE TO CLINICAL PRACTICE: Although the utilization rate of EM is low in TBI patients for various reasons, EM is still an effective method to prevent complications. Our study confirms that a scientific and detailed EM strategy can effectively reduce the incidence of pneumonia while ensuring the safety of TBI patients, which is worthy of further research and clinical application.
RESUMEN
Background: Chronic obstructive pulmonary disease (COPD) is closely associated with frailty, and prevention of acute exacerbations is important for disease management. Moreover, COPD patients with frailty experience a higher risk of acute exacerbations. However, the frailty instruments that can better predict acute exacerbations remain unclear. Purpose: (1) To explore the factors influencing frailty and acute exacerbations in stable COPD patients, and (2) quantify the ability of multidimensional frailty instruments to predict acute exacerbations within 1 year. Patients and methods: In this retrospective longitudinal study, stable COPD patients were recruited from the outpatient department of Sichuan Provincial People's Hospital from July 2022 to June 2023. COPD patients reviewed their frailty one year ago and their acute exacerbations within one year using face-to-face interviews with a self-developed frailty questionnaire. Frailty status was assessed using the Frailty Index (FI), frailty questionnaire (FRAIL), and Clinical Frailty Scale (CFS). One-way logistic regression was used to explore the factors influencing frailty and acute exacerbations. Multivariate logistic regression was used to establish a prediction model for acute exacerbations, and the accuracy of the three frailty instruments was compared by measuring the area under the receiver operating characteristic curve (AUC). Results: A total of 120 individuals were included. Frailty incidence estimates using FI, FRAIL, and CFS were 23.3%, 11.7%, and 15.8%, respectively. The three frailty instruments showed consistency in COPD assessments (P<0.05). After adjusting for covariates, frailty reflected by the FI and CFS score remained an independent risk factor for acute exacerbations. The CFS score was the best predictor of acute exacerbations (AUC, 0.764 (0.663-0.866); sensitivity, 57.9%; specificity, 80.0%). Moreover, the combination of CFS plus FRAIL scores was a better predictor of acute exacerbations (AUC, 0.792 (0.693-0.891); sensitivity, 86.3%; specificity, 60.0%). Conclusion: Multidimensional frailty assessments could improve the identification of COPD patients at high risk of acute exacerbations and facilitate targeted interventions to reduce acute exacerbations in these patients.
Asunto(s)
Fragilidad , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Estudios Longitudinales , Fragilidad/diagnóstico , Fragilidad/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
[This retracts the article DOI: 10.3892/ol.2016.5230.].
RESUMEN
BACKGROUND: Men who have sex with men (MSM) are disproportionally affected by HIV and drug and alcohol use; however, few effective HIV prevention interventions for MSM who use substances exist. Screening, Brief Intervention, and Referral to Treatment is an early intervention for non-treatment-seeking individuals with problematic substance use and for timely referral to treatment for those with substance use disorders. Electronic screening and brief interventions (e-SBIs) reduce implementation challenges. An e-SBI tailored for MSM at the time of HIV testing might be particularly opportune to strengthen their motivation to reduce substance use and HIV risk behavior. OBJECTIVE: This study aims to develop a tailored e-SBI program to reduce substance use and HIV risk behavior among MSM seeking HIV testing at Nexo Asociación Civil, our community partners in Argentina (primary); assess the feasibility and acceptability of integrating the e-SBI into the Nexo HIV testing program (primary); assess the feasibility and acceptability of implementing an adapted Men's Health Project (MHP) at Nexo (secondary); and finally, explore preliminary findings on substance use and sexual risk reduction outcomes (exploratory). METHODS: This mixed methods study has 2 stages. During stage 1 (development), we will use the User Centered Rapid App Design process consisting of focus groups (n=16), individual interviews (n=24), and a pilot deployment of the e-SBI (n=50) to iteratively develop the e-SBI. Quantitative and qualitative assessments at each step will inform the revision of the e-SBI. Furthermore, we will use the assessment, decision, administration, production, topic experts, integration, training, testing framework to adapt MHP. During stage 2 (pilot randomized controlled trial [RCT]), we will randomize 200 MSM coming to Nexo for HIV testing. They will complete a baseline assessment and then their assigned intervention (e-SBI vs screening only) and will be followed-up for 6 months. We will also conduct in-depth interviews with up to 45 participants: 15 participants from either study condition who entered or completed MHP or other substance abuse treatment and 15 from each arm who met the criteria for MHP but did not request it. RESULTS: The study began recruitment in October 2022, and the stage-1 pilot study is near completion. Preliminary findings from stage 1 show high e-SBI acceptability. Data analysis of the stage-1 pilot is now beginning. The stage-2 pilot RCT will be launched in March 2024, with all data collection completed by May 2025. CONCLUSIONS: This study will allow us to assess the acceptability and feasibility of e-SBI implementation during HIV testing encounters. We will also build the necessary research infrastructure for a subsequent RCT to assess the efficacy of e-SBIs in reducing substance use and HIV sexual risk behavior among MSM in this setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT05542914; https://tinyurl.com/yyjj64dm. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56683.
RESUMEN
RNA-binding proteins (RBPs) are critical regulators for RNA transcription and translation. As a key member of RBPs, ELAV-like family protein 2 (CELF2) has been shown to regulate RNA splicing and embryonic hematopoietic development and was frequently seen dysregulated in acute myeloid leukemia (AML). However, the functional role(s) of CELF2 in hematopoiesis and leukemogenesis has not been fully elucidated. In the current study, we showed that Celf2 deficiency in hematopoietic system led to enhanced HSCs self-renewal and differentiation toward myeloid cells in mice. Loss of Celf2 accelerated myeloid cell transformation and AML development in MLL-AF9-induced AML murine models. Gene expression profiling integrated with RNA immunoprecipitation sequencing (RIP-Seq), together with biochemical experiments revealed that CELF2 deficiency stabilizes FAT10 mRNA, promotes FAT10 translation, thereby increases AKT phosphorylation and mTORC1 signaling pathway activation. Notably, combination therapy with a mTORC1 inhibitor (Rapamycin) and a MA9/DOTL1 inhibitor (EPZ-5676) reduced the leukemia burden in MLL-AF9 mice lacking Celf2 in vivo. Our study elucidated a novel mechanism by which the CELF2/FAT10-AKT/mTORC1 axis regulates the proliferation of normal blood cells and the development of AML, thus providing potential therapeutic targets for myeloid leukemia suppression.
Asunto(s)
Proteínas CELF , Leucemia Mieloide Aguda , Diana Mecanicista del Complejo 1 de la Rapamicina , Proteínas del Tejido Nervioso , Proteínas de Unión al ARN , Animales , Humanos , Ratones , Proteínas CELF/genética , Proteínas CELF/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Ratones Noqueados , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal/genéticaRESUMEN
Aberrant lipid metabolism impacts intratumoral T cell-mediated immune response and tumor growth. Fatostatin functions as an inhibitor of sterol regulatory element binding protein (SREBP) activation. However, the complex effects of fatostatin on cholesterol metabolism in the tumor microenvironment (TME) and its influence on T cell anti-tumor immunity remain unclear. In this study, fatostatin effectively suppressed B16 melanoma, MC38 colon cancer, and Lewis lung cancer (LLC) transplanted tumor growth in immunocompetent mice by reducing SREBPs-mediated lipid metabolism, especially cholesterol levels. Mechanistically, fatostatin decreased intracellular cholesterol accumulation and inhibited X-box binding protein 1 (XBP1)-mediated endoplasmic reticulum (ER) stress, reducing Treg cells and alleviating CD8+ T cell exhaustion in the TME, exerting anti-tumor activity. Neverthelessï¼ this effect was impaired in immunodeficient nude mice, suggesting fatostatin's anti-tumor efficacy in transplanted tumors partly relies on T cell-mediated anti-tumor immunity. Our study highlights SREBP2-mediated cholesterol metabolism as a potential strategy for anti-tumor immunotherapy, and confirms fatostatin's promise in tumor immunotherapy.
Asunto(s)
Melanoma Experimental , Piridinas , Tiazoles , Animales , Ratones , Ratones Desnudos , Melanoma Experimental/tratamiento farmacológico , Metabolismo de los Lípidos , Colesterol/metabolismo , Microambiente TumoralRESUMEN
Metallothionein (MTs) can be used in the prevention and treatment of tumors and diabetes due to its antioxidant properties. However, it is necessary to solve its non-transmembrane properties and further improve its antioxidant activity, increase its fluorescence visualization and enhance its stability to meet practical applications in the biomedical field. Here, we report the preparation of a novel metallothionein-AuNP composite material with high transmembrane ability, fluorescence visualization, antioxidant activity, and stability by genetic modification (introducing transduction peptide TAT, fluorescence tag GFP and increasing sulfydryl groups) and immobilization technology (covalently bonding with AuNPs). The transmembrane activity of modified proteins was verified by immunofluorescence. Increasing the sulfhydryl content within a certain range can enhance the antioxidant activity of the protein. In addition, GFP were used to further simplify the imaging of the metallothionein-AuNP composite in cells. XPS results indicated that AuNPs can immobilize metallothionein through AuS covalent bonds. TGA characterization and degradation experiments showed that thermal and degradation stability of the immobilized material was significantly improved. This work provides new ideas to construct metallothionein composites with high transmembrane ability, antioxidant activity, fluorescence visualization and stability to meet novel applications in the biomedical field.
Asunto(s)
Antioxidantes , Nanopartículas del Metal , Metalotioneína/genética , Oro/química , Nanopartículas del Metal/química , PéptidosRESUMEN
Single-molecule toroics are molecular magnets with vortex distribution of magnetic moments. The coupling between magnetic and electric properties such as the magnetodielectric effect will provide potential applications for them. Herein, the observation of significant magnetodielectric effect in a triangular Dy3 crystal with toroidal magnetic moment and multiple magnetic relaxations is reported. The analysis of magnetic and electric properties implies that the magnetodielectric effect is closely related to the strong spin-lattice coupling, magnetic interactions of Dy3+ ions, as well as molecular packing models.
RESUMEN
This trial was a randomized, open-label, single-dose, 2-treatment, 2-period, crossover study to evaluate the pharmacokinetic (PK) profile, bioequivalence, and safety of test formulation and reference formulation of 2-mg dienogest tablets in healthy Chinese participants. Eligible participants were randomly administered a single 2-mg dose of either the test formulation or the reference formulation orally under fed conditions, followed by a 1-week washout period and the administration of the other formulation. Samples of blood were collected until 48 hours following administration. The main PK parameters were calculated using noncompartmental analysis techniques. The main PK parameters included maximum plasma concentration, area under the plasma concentration-time curve (AUC) from time zero to the last quantifiable concentration, and AUC from time zero to infinity. The bioequivalence of test and reference dienogest tablets was determined if the 90% confidence intervals of the geometric mean ratio of the test to reference formulations were within the predefined range of 80%-125%. The safety assessment included incidence of adverse events and serious adverse events and others. Twenty-four healthy Chinese participants were enrolled in this trial. The geometric mean ratios of maximum plasma concentration, AUC from time zero to the last quantifiable concentration, and AUC from time zero to infinity between the 2 formulations, and corresponding 90% confidence intervals, all fell within the range of 80%-125% under fed conditions. The test and reference dienogest tablets were well tolerated, and no severe adverse events were reported in the trial. It was shown that the test and the reference dienogest tablets were bioequivalent and well tolerated under fed conditions in healthy Chinese female participants.
Asunto(s)
Nandrolona/análogos & derivados , Equivalencia Terapéutica , Humanos , Femenino , Disponibilidad Biológica , Estudios Cruzados , ChinaRESUMEN
In Florida, 33% of new HIV infections among men and 21% of new infections among women are among those younger than 29 years of age. We describe the development of a Learning Health Care Community for youth (Y-LHCC) in Orange County, FL. Its core implementation team (iTeam) was composed of representatives from community agencies and academics, whose work was informed by data from the Florida Department of Health (FDOH) and regional research, in-depth interviews (IDIs) with agency representatives, and a pilot implementation of Tailored Motivational Interviewing (TMI) to improve service provision. IDIs revealed limited programming specifically for youth, significant structural challenges providing them with PrEP, and differences in use of evidence-based behavioral interventions to improve HIV services. FDOH provided data on new HIV infections, linkage to care, viral suppression, and PrEP coverage, however, limitations such as minimal data on PrEP referrals and use, agency level data, and inability to generate data quarterly (which would facilitate program improvement) were encountered. Thirty staff members from five agencies serving youth in Orange County participated in TMI training. About half the agency staff (n = 16) completed at least three of the four online training sessions. MI skills improved from pre- (n = 28; M = 1.96) to post TMI training (n = 11; M = 2.48, SD = 0.57); (t(37) = - 3.14, p = 0.0033). The iTeam held seven remote meetings and two in-person half-day meetings at the end of the study, during which they reassessed areas of focus for improving youth services. They also reiterated their commitment to continuing to meet beyond the study period and to engage other agencies in the newly established coalition. Findings highlight the potential of creating a Y-LHCC in Florida as well as some of the challenges that will need to be overcome to achieve ending the HIV Epidemic goals for young people in the region.
RESUMEN: En Florida, el 33% y 21% de las nuevas infecciones del VIH entre hombres y mujeres, respectivamente, fueron entre personas menores de 29 años de edad. Describimos el desarrollo de una Comunidad de Aprendizaje de Atención Médica para jóvenes (Y-LHCC) en el Condado de Orange, FL. Su equipo central de implementación (iTeam) estuvo compuesto de representantes de agencias comunitarias y académicos, cuyo trabajo se basó en datos del Departamento de Salud de Florida (FDOH) e investigaciones regionales, entrevistas en profundidad con representantes de agencias y un programa piloto de implementación de la Entrevista Motivacional a la Medida (TMI) para mejorar la prestación de servicios. Las entrevistas revelaron poca programación específica para los jóvenes, desafíos estructurales significativos para proporcionarles PrEP, y diferencias en el uso de intervenciones conductuales basadas en evidencia para mejorar los servicios de VIH. El FDOH proporcionó datos sobre nuevas infecciones por el VIH, vinculación con la atención médica, supresión viral y cobertura de PrEP. Sin embargo, se encontraron limitaciones en la data, tales como datos limitados sobre derivaciones u uso de PrEP, falta de datos a nivel de agencia, e incapacidad para generar datos trimestrales (lo que facilitaría la mejora de programas en la agencia). Treinta miembros del personal de cinco agencias que atienden a jóvenes en el Condado de Orange participaron en la capacitación de TMI. Aproximadamente la mitad del personal de la agencia (n = 16) completó al menos tres de las cuatro sesiones de capacitación remota. Las habilidades de MI mejoraron desde antes (n = 28; M = 1.96, SD = .042) hasta después del entrenamiento de TMI (n = 11; M = 2.48, SD = 0.57); (t(37) = − 3.14, p = 0.0033). El iTeam realizó siete reuniones remotas y dos reuniones en persona de medio día al final del estudio, durante las cuales reevaluaron las áreas de enfoque para mejorar los servicios para jóvenes. También reiteraron su compromiso de continuar reuniéndose más allá del período de estudio y de involucrar a otras agencias en la coalición recién establecida. Los hallazgos destacan el potencial de crear un Y-LHCC en Florida, así como algunos de los desafíos que deberán superarse para lograr los objetivos de terminar con la epidemia de VIH para los jóvenes de la región.
Asunto(s)
Infecciones por VIH , Entrevista Motivacional , Masculino , Humanos , Femenino , Adolescente , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Florida/epidemiología , Atención a la SaludRESUMEN
The cardioprotective effect of microRNAs (miRNAs) on myocardial ischemic-reperfusion (I/R) injury has been documented. Here, we aim to decipher the mechanism of miR-24 delivered by human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSC-EVs) in myocardial I/R injury after dexmedetomidine (DEX) preconditioning. We collected and identified hUC-MSCs and extracted EVs, which were co-cultured with DEX-preconditioned hypoxia/reoxygenation (H/R) cardiomyocyte models or injected into I/R mouse models. The cardiomyocytes and myocardial injury were evaluated by molecular biology experiments. miR-24 was highly expressed in hUC-MSC-EVs. hUC-MSC-EVs could transfer miR-24 into cardiomyocytes where miR-24 augmented cell viability and inhibited cell apoptosis after DEX preconditioning. In the co-culture system of RAW264.7 macrophages with hUC-MSC-EVs, miR-24 promoted M2-type polarization of macrophages and reduced M1-type macrophage polarization. Mechanistically, miR-24 targeted KEAP1 and inhibited its expression, resulting in disruption of the Nrf2/HO-1 signaling. In vivo data confirmed that miR-24 delivered by hUC-MSC-EVs enhanced the suppressing effect of DEX preconditioning on inflammation and apoptosis in rats following myocardial I/R injury. Overall, miR-24 delivered by hUC-MSC-EVs can promote M2 polarization of macrophages and enhance the protective effect of DEX preconditioning on myocardial I/R injury by down-regulating the KEAP1/Nrf2/HO-1 signaling axis.
Asunto(s)
Dexmedetomidina , MicroARNs , Daño por Reperfusión Miocárdica , Ratones , Humanos , Ratas , Animales , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/metabolismo , Dexmedetomidina/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , MicroARNs/metabolismoRESUMEN
OBJECTIVES: To explore the application of 3D printed navigation template technology in severe Hallux valgus surgery. METHODS: Forty-eight patients with severe Hallux valgus were selected. There were 24 cases in the control group underwent hallux valgus osteotomy using traditional methods and fixed with fully threaded hollow screws during the surgery. There were 24 cases in the 3D group who underwent personalized osteotomy using 3D printing navigation template technology. Patients were followed up regularly for six months after surgery. RESULTS: The surgery time of the 3D group was shorter than that of the control group, and the intraoperative bleeding was reduced (P<0.05). Compared with the preoperative data, the HVA and IMA significantly reduced immediately and 1, 3, and 6 months after surgery (P<0.05). The VAS scores decreased significantly, while the AOFAS and SF-36 scores increased (P<0.05). At three months and six months after surgery, the VAS score of the 3D group was lower than that of the control group, while the SF-36 score was higher (P<0.05). During the follow-up period, both groups had no recurrent cases or complications. CONCLUSIONS: The 3D printing navigation template technology improves patients' prognosis, functional recovery, and quality of life.
Asunto(s)
Hallux Valgus , Huesos Metatarsianos , Humanos , Hallux Valgus/diagnóstico por imagen , Hallux Valgus/cirugía , Resultado del Tratamiento , Huesos Metatarsianos/cirugía , Calidad de Vida , Radiografía , Impresión Tridimensional , Estudios RetrospectivosRESUMEN
Electrical control of magnetism in single-molecule magnets with peculiar quantum magnetic behaviours has promise for applications in molecular electronics and quantum computing. Nevertheless, such kind of magnetoelectric effects have not been achieved in such materials. Herein, we report the successful realization of significant magnetoelectric effects by introducing ferroelectricity into a dysprosium-based single-molecule magnet through spatial cooperation between flexible organic ligands and halide ions. The stair-shaped magnetization hysteresis loop, alternating current susceptibility, and magnetic relaxation can be directly modulated by applying a moderate electric field. Conversely, the electric polarization can be modulated by applying a small magnetic field. In addition, a resonant magnetodielectric effect is clearly observed, which enables detection of quantum tunnelling of magnetization by a simple electrical measurement. The integration of ferroelectricity into single-molecule magnets not only broadens the family of single-molecule magnets but also makes electrical detection and modulation of the quantum tunnelling of magnetization a reality.