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1.
Mol Psychiatry ; 28(3): 1383-1395, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36481932

RESUMEN

In response to stressful events, the hypothalamic-pituitary-adrenal (HPA) axis is activated, and consequently glucocorticoids are released by the adrenal gland into the blood circulation. A large body of research has illustrated that excessive glucocorticoids in the hippocampus exerts negative feedback regulation of the HPA axis through glucocorticoid receptor (GR), which is critical for the homeostasis of the HPA axis. Maternal prenatal stress causes dysfunction of the HPA axis feedback mechanism in their offspring in adulthood. Here we report that telomerase reverse transcriptase (TERT) gene knockout causes hyperactivity of the HPA axis without hippocampal GR deficiency. We found that the level of TERT in the dentate gyrus (DG) of the hippocampus during the developmental stage determines the responses of the HPA axis to stressful events in adulthood through modulating the excitability of the dentate granular cells (DGCs) rather than the expression of GR. Our study also suggests that the prenatal high level of glucocorticoids exposure-induced hypomethylation at Chr13:73764526 in the first exon of mouse Tert gene accounted for TERT deficiency in the DG and HPA axis abnormality in the adult offspring. This study reveals a novel GR-independent mechanism underlying prenatal stress-associated HPA axis impairment, providing a new angle for understanding the mechanisms for maintaining HPA axis homeostasis.


Asunto(s)
Sistema Hipotálamo-Hipofisario , Receptores de Glucocorticoides , Femenino , Embarazo , Animales , Ratones , Sistema Hipotálamo-Hipofisario/metabolismo , Receptores de Glucocorticoides/metabolismo , Glucocorticoides/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Homeostasis
2.
Arch Toxicol ; 98(5): 1399-1413, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38460002

RESUMEN

Pulmonary fibrosis involves destruction of the lung parenchyma and extracellular matrix deposition. Effective treatments for pulmonary fibrosis are lacking and its pathogenesis is still unclear. Studies have found that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AECs) plays an important role in progression of pulmonary fibrosis. Thus, an in-depth exploration of its mechanism might identify new therapeutic targets. In this study, we revealed that a novel circular RNA, MKLN1 (circMKLN1), was significantly elevated in two pulmonary fibrosis models (intraperitoneally with PQ, 50 mg/kg for 7 days, and intratracheally with BLM, 5 mg/kg for 28 days). Additionally, circMKLN1 was positively correlated with the severity of pulmonary fibrosis. Inhibition of circMKLN1 expression significantly reduced collagen deposition and inhibited EMT in AECs. EMT was aggravated after circMKLN1 overexpression in AECs. MiR-26a-5p/miR-26b-5p (miR-26a/b), the targets of circMKLN1, were confirmed by luciferase reporter assays. CircMKLN1 inhibition elevated miR-26a/b expression. Significantly decreased expression of CDK8 (one of the miR-26a/b targets) was observed after inhibition of circMKLN1. EMT was exacerbated again, and CDK8 expression was significantly increased after circMKLN1 inhibition and cotransfection of miR-26a/b inhibitors in AECs. Our research indicated that circMKLN1 promoted CDK8 expression through sponge adsorption of miR-26a/b, which regulates EMT and pulmonary fibrosis. This study provides a theoretical basis for finding new targets or biomarkers in pulmonary fibrosis.


Asunto(s)
MicroARNs , Fibrosis Pulmonar , Humanos , Ratones , Animales , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/genética , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , Células Epiteliales Alveolares , Transición Epitelial-Mesenquimal/genética , Quinasa 8 Dependiente de Ciclina/metabolismo , Moléculas de Adhesión Celular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo
3.
Respiration ; 103(2): 95-99, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38272003

RESUMEN

INTRODUCTION: Fibrosing mediastinitis is a benign but fatal disorder characterized by the proliferation of fibrous tissue in the mediastinum, causing encasement of mediastinal organs and extrinsic compression of adjacent bronchovascular structures. FM-associated pulmonary hypertension (FM-PH) is a serious complication of FM, resulting from the external compression of lung vessels. Pathologic assessment is important for etiologic diagnosis and effective treatment of this disease. CASE PRESENTATION: A 59-year-old male patient presented at our hospital and was diagnosed with FM-PH. He declined surgical biopsy that is the reference standard for pathologic assessment, in consideration of the potential risks. Therefore, an endobronchial ultrasound examination was performed, which identified the subcarinal lesion. Under ultrasound guidance, four needle aspirations were carried out, followed by one cryobiopsy. Histopathological examination of transbronchial needle aspiration specimens was inconclusive, while samples from cryobiopsy suggested a diagnosis of idiopathic FM. Further immunophenotyping demonstrated the infiltration of lymphocytes, macrophages, and FOXP3-positive cells in FM-PH. CONCLUSION: Mediastinal cryobiopsy might be a novel and safe option for FM-PH patients who are unwilling or unsuitable for surgical procedure.


Asunto(s)
Hipertensión Pulmonar , Mediastinitis , Hipertensión Arterial Pulmonar , Esclerosis , Masculino , Humanos , Persona de Mediana Edad , Mediastino , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/complicaciones , Mediastinitis/complicaciones , Mediastinitis/diagnóstico , Hipertensión Arterial Pulmonar/patología
4.
BMC Public Health ; 24(1): 1682, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38914970

RESUMEN

BACKGROUND: Falls are common in the elderly and can lead to adverse consequences, like injuries, hospitalization, disability even mortality. Successful ageing emerged in sight to assess physical, psychological and social status of older adults. This study is conducted to explore the association between them in a large Indian community-dwelling population. METHODS: Data were based on the wave 1 survey of the Longitudinal Ageing Study in India (LASI). People aged 60 and above with complete information were included. The elderly met five standards including absence of chronic diseases, freedom from disability, high cognitive ability, free from depressive symptoms and active social engagement, were classified into successful agers. The assessment of falls, fall-related injuries and multiple falls depended on interview. Multivariate logistic regression was conducted to find the associations between falls, fall-injury, multiple falls and successful ageing after adjusting both socio-demographic and biological covariates. The log-likelihood ratio test was calculated interactions in subgroups. RESULTS: 31,345 participants in LASI were finally included in our study. Of them, 20.25% reported fall, and 25% were classified into successful agers. After full adjustment, successful ageing was negatively associated with falls (OR 0.70; 95%CI 0.65-0.76) and multiple falls (OR 0.70; 95%CI 0.63-0.78). And the association did not show the significance in older adults with fall-related injuries (OR 0.86; 95%CI 0.72-1.04). CONCLUSIONS: Successful ageing was negatively associated with falls and multiple falls, but not fall-related injuries in older people in India. Future studies are demanded to explore the causal relationship and to reveal the underlying mechanism.


Asunto(s)
Accidentes por Caídas , Humanos , Accidentes por Caídas/estadística & datos numéricos , India/epidemiología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Transversales , Estudios Longitudinales , Anciano de 80 o más Años , Envejecimiento/fisiología , Factores de Riesgo
5.
J Transl Med ; 21(1): 586, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37658364

RESUMEN

BACKGROUND: As the most lethal gynecologic cancer, ovarian cancer (OV) holds the potential of being immunotherapy-responsive. However, only modest therapeutic effects have been achieved by immunotherapies such as immune checkpoint blockade. This study aims to propose a generalized stroma-immune prognostic signature (SIPS) to identify OV patients who may benefit from immunotherapy. METHODS: The 2097 OV patients included in the study were significant with high-grade serous ovarian cancer in the III/IV stage. The 470 immune-related signatures were collected and analyzed by the Cox regression and Lasso algorithm to generalize a credible SIPS. Correlations between the SIPS signature and tumor microenvironment were further analyzed. The critical immunosuppressive role of stroma indicated by the SIPS was further validated by targeting the major suppressive stroma component (CAFs, Cancer-associated fibroblasts) in vitro and in vivo. With four machine-learning methods predicting tumor immune subtypes, the stroma-immune signature was upgraded to a 23-gene signature. RESULTS: The SIPS effectively discriminated the high-risk individuals in the training and validating cohorts, where the high SIPS succeeded in predicting worse survival in several immunotherapy cohorts. The SIPS signature was positively correlated with stroma components, especially CAFs and immunosuppressive cells in the tumor microenvironment, indicating the critical suppressive stroma-immune network. The combination of CAFs' marker PDGFRB inhibitors and frontline PARP inhibitors substantially inhibited tumor growth and promoted the survival of OV-bearing mice. The stroma-immune signature was upgraded to a 23-gene signature to improve clinical utility. Several drug types that suppress stroma-immune signatures, such as EGFR inhibitors, could be candidates for potential immunotherapeutic combinations in ovarian cancer. CONCLUSIONS: The stroma-immune signature could efficiently predict the immunotherapeutic sensitivity of OV patients. Immunotherapy and auxiliary drugs targeting stroma could enhance immunotherapeutic efficacy in ovarian cancer.


Asunto(s)
Síndrome de DiGeorge , Neoplasias Ováricas , Femenino , Animales , Ratones , Humanos , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Pronóstico , Neoplasias Ováricas/tratamiento farmacológico , Inmunosupresores , Inmunoterapia , Microambiente Tumoral
6.
Environ Res ; 223: 115417, 2023 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-36738774

RESUMEN

Evapotranspiration (ET) is an essential process of the water cycle through which water is transferred from terrestrial ecosystems to atmosphere. However, in the climate context of increasing CO2 concentration (also called as a CO2-enriched climate), the variation of ET and its main drivers among different ecosystems remain unclear. This study analyzed the output data of the CMCC ESM2 model with a ridge regression method, and proposed the trends and drivers of ET in different ecosystems in a CO2-enriched climate. In particular, the temporal - spatial characteristics of ET and its primary drivers for different periods and wetness levels were revealed. With the rising of CO2 concentration, the atmospheric evapotranspiration demand increases, and the vegetation grows more luxuriantly. ET shows an overall upward trend, especially in the shrub ecosystems (7.41 mm decade-1). Our results show that the thermal conditions are the main driving factors for humid forest and shrub ecosystems whereas relative humidity (RH) is the main driving factor for arid farm and grass ecosystems. In terms of the average contribution in all periods, surface solar radiation contributes 26% and 41% to ET variation in forest and shrub ecosystems, and RH contributes 49% and 32% to ET variation in farm and grass ecosystems, respectively. Notably, with the increase of wetness levels, the contribution of water conditions on ET becomes smaller, while that of thermal conditions becomes larger. Correlation analysis shows that LAI impacts on ET are regulated by environmental factors, which reflects the complexity of ET change mechanism. Overall, these findings further provide a reference for rational planning of ecosystems and efficient utilization of water resources.


Asunto(s)
Dióxido de Carbono , Ecosistema , Dióxido de Carbono/análisis , Poaceae , Granjas , Bosques , Agua , Cambio Climático
7.
Ecotoxicol Environ Saf ; 258: 114955, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37121076

RESUMEN

The effect of mean flow velocity on phosphorus (P) partitioning between water and sediment has received much attention in recent decades. However, the impact of turbulence on the efficiency and capability of sediment adsorbing and desorbing dissolved inorganic phosphorus (DIP) is still unclear. A series of contrasting experiments on the sediment sorption and desorption of DIP with the flow turbulence kinetic energy (TKE) ranging from 1.95 to 2.93 pa have been conducted. It was found that the adsorbed P onto unit mass of sediment increases with the increase in TKE. It is because an increase in TKE results in a rise in the effective adsorption capacity of sediment (bm) by 20-30% during the adsorption process. The bm shows the maximum rise from 0.18 to 0.25 mg/g when TKE increases from 1.95 to 2.93 pa with a fixed sediment concentration of 0.5 g/L. To account for the direct effect of TKE on P adsorption, the Langmuir model is modified by introducing a newly defined coefficient (fA-TKE). The fA-TKE shows a good linear relationship with TKE. Comparison between the modified model and the classic model shows that the amount of adsorbed P could be overestimated by over 50% if the direct effect of turbulence intensity is ignored. The experimental data show that the increase in TKE also enhances the desorption process, with the degree of P desorption (Ddes) increased by 44%. The relation between Ddes and TKE can be well represented using a logarithmic function to quantify the direct effect of turbulence intensity on desorption of P.


Asunto(s)
Fósforo , Contaminantes Químicos del Agua , Sedimentos Geológicos , Adsorción , Agua , Contaminantes Químicos del Agua/análisis
8.
Pak J Pharm Sci ; 36(5): 1381-1388, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37869913

RESUMEN

A total of 130 patients who underwent percutaneous testicular sperm aspiration from March 2021 to February 2023 were randomly divided into a Dezocine group and a control group. The Dezocine group received a muscle injection of 0.05mg/kg Dezocine 30 minutes before surgery, while the control group received a muscle injection of 0.01ml/kg normal saline. Both groups received 3ml of 2% lidocaine for spermatic cord block anesthesia. The anesthesia onset time, anesthesia duration, numeric rating scale (NRS) score, anesthesia satisfaction rate and incidence of adverse reactions were recorded and compared between the two groups. The statistical results showed that there were significant differences between the two groups in terms of anesthesia onset time, anesthesia duration, anesthesia satisfaction rate, non-steroidal anti-inflammatory drug (NSAID) use within 24 hours after surgery and NRS scores at 15 minutes, 1 hour and 2 hours after surgery. The incidence of adverse reactions in the Dezocine group was lower than that in the control group, but the difference was not statistically significant. The combination of Dezocine and lidocaine for spermatic cord block anesthesia during percutaneous testicular sperm aspiration is safe, effective and associated with fewer adverse reactions. It is suitable for clinical application and promotion in reproductive medicine outpatient surgery.


Asunto(s)
Anestesia Local , Lidocaína , Humanos , Masculino , Lidocaína/efectos adversos , Anestesia Local/efectos adversos , Analgésicos Opioides , Recuperación de la Esperma/efectos adversos , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/etiología , Semen
9.
J Cell Mol Med ; 26(4): 1113-1127, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35014165

RESUMEN

Deep hypothermic circulatory arrest (DHCA) can cause acute lung injury (ALI), and its pathogenesis mimics ischaemia/reperfusion (I/R) injury. Autophagy is also involved in lung I/R injury. The present study aimed to elucidate whether DHCA induces natural autophagy activation and its role in DHCA-mediated lung injury. Here, rats were randomly assigned to the Sham or DHCA group. The sham group (n = 5) only received anaesthesia and air intubation. DHCA group rats underwent cardiopulmonary bypass (CPB) followed by the DHCA procedure. The rats were then sacrificed at 3, 6 and 24 h after the DHCA procedure (n = 5) to measure lung injury and autophagy activity. Chloroquine (CQ) was delivered to evaluate autophagic flux. DHCA caused lung injury, which was prominent 3-6 h after DHCA, as confirmed by histological examination and inflammatory cytokine quantification. Lung injury subsided at 24 h. Autophagy was suppressed 3 h but was exaggerated at 6 h. At both time points, autophagic flux appeared uninterrupted. To further assess the role of autophagy in DHCA-mediated lung injury, the autophagy inducer rapamycin and its inhibitor 3-methyladenine (3-MA) were applied, and lung injury was reassessed. When rapamycin was administered at an early time point, lung injury worsened, whereas administration of 3-MA at a late time point ameliorated lung injury, indicating that autophagy contributed to lung injury after DHCA. Our study presents a time course of lung injury following DHCA. Autophagy showed adaptive yet protective suppression 3 h after DHCA, as induction of autophagy caused worsening of lung tissue. In contrast, autophagy was exaggerated 6 h after DHCA, and autophagy inhibition attenuated DHCA-mediated lung injury.


Asunto(s)
Lesión Pulmonar Aguda , Paro Circulatorio Inducido por Hipotermia Profunda , Lesión Pulmonar Aguda/etiología , Animales , Autofagia , Puente Cardiopulmonar/efectos adversos , Puente Cardiopulmonar/métodos , Paro Circulatorio Inducido por Hipotermia Profunda/efectos adversos , Paro Circulatorio Inducido por Hipotermia Profunda/métodos , Pulmón , Ratas
10.
Clin Gastroenterol Hepatol ; 20(2): e168-e181, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33220526

RESUMEN

BACKGROUND & AIMS: Although current quality indicators of colonoscopy recommend 6 minutes as the minimum standard for withdrawal time (WT), the impact of a WT longer than 6 minutes on neoplasia detection is unclear. METHODS: A multicenter randomized controlled trial involving 1027 patients was conducted from January 2018 to July 2019. Participants were randomly divided into a 9-minute (n = 514) and 6-minute (n = 513) WT group, and a timer was used to adjust the withdrawal speed. The primary outcome was the adenoma detection rate (ADR). RESULTS: Intention-to-treat analysis showed a significantly higher ADR in the 9-minute versus 6-minute WT group (36.6% vs. 27.1%, P = .001). Prolonging WT from 6 to 9 minutes significantly increased ADR of the proximal colon (21.4% vs. 11.9%, P < .001) as well as of the less experienced colonoscopists (36.8% vs. 23.5%, P = .001). Improvements were also observed in the polyp detection rate (58.0% vs. 47.8%, P < .001), and mean number of polyps and adenomas detected per colonoscopy (1.1 vs. 0.9, P = .002; 0.5 vs. 0.4, P = .008, respectively). The higher ADRs in 9-minute WT were also confirmed by the per-protocol (PP) analysis and subgroup analyses, with an increased rate of sessile serrated lesion detection in the 9-minute WT by PP analysis (4.0% vs. 1.3%, P = .04). Multivariate logistic regression demonstrated that the 9-minute WT was independently associated with increased ADR (P = .005). CONCLUSIONS: Prolonging WT from 6 to 9 minutes significantly improved ADR, especially in the proximal colon and for less experienced colonoscopists. A 9-minute WT benchmark should be considered as one of the quality indicators of colonoscopy. ClinicalTrials.gov (identifier, NCT03399045).


Asunto(s)
Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Pólipos , Adenoma/diagnóstico , Pólipos del Colon/diagnóstico , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Humanos
11.
Anal Chem ; 94(49): 17295-17302, 2022 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-36451079

RESUMEN

Photoelectrochemical (PEC) immunoassays with ultrasensitive detection abilities are highly desirable for in vitro PEC diagnosis and biological detection. In this paper, dual Z-scheme PEC immunoassays with hierarchical nanostructures (TiO2@NH2-MIL-125@CdS) are synthesized through epitaxial growth of MOF-on-MOF and further in situ derivatization. The dual Z-scheme configuration not only extends the light absorption range but also increases the redox ability due to the interface structure nanoengineering, which synergistically suppresses bulk carrier recombination and promotes the charge transfer efficiency at the electron level. Furthermore, a smart MOF-derived labeling probe (CuO@ZnO nanocube) is designed to develop a split-type PEC biosensor by using prostate-specific antigen (PSA) as a target biomarker. In the presence of PSA, the Ab2-labeled CuO@ZnO would specifically bond to the dual Z-scheme electrode. Then, the MOF-derived CuO@ZnO is dissolved by hydrochloric acid to release Cu2+, which could replace Cd2+ via an ion-exchange reaction, thus leading to the decrease of the photocurrent due to the destruction of the dual Z-scheme configuration. In typical applications, the split-type PEC immunoassay exhibits an excellent detection performance for PSA with a LOD as low as 0.025 pg·mL-1.


Asunto(s)
Técnicas Biosensibles , Compuestos de Cadmio , Humanos , Masculino , Compuestos de Cadmio/química , Técnicas Electroquímicas , Sulfuros/química , Inmunoensayo , Antígeno Prostático Específico , Límite de Detección
12.
Catheter Cardiovasc Interv ; 100(4): 696-704, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36098330

RESUMEN

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) remains a controversial treatment for uncomplicated chronic type B aortic dissection (cTBAD). This study was performed to investigate the postoperative outcomes of TEVAR, such as survival and reintervention, and the risk factors for prognoses. METHODS: In total, 41 patients with uncomplicated cTBAD who underwent TEVAR from 2014 to 2021 were reviewed. The patients were divided into two groups: those with false lumen complete thrombosis (FLCT) and false lumen partial thrombosis (FLPT) based on computed tomography angiography (CTA) images. Kaplan-Meier analysis was performed to estimate survival and freedom from reintervention. Binary logistic analysis was performed to estimate risk factors for partial thrombosis. RESULTS: During a mean follow-up of 31 (1-78) months, five deaths and six reinterventions had occurred at 5 years. By 1 week, thoracic FLCT had occurred in 23 (56.1%) patients and thoracic FLPT had occurred in 18 (43.9%). The rate of freedom from reintervention was significantly lower in the FLCT than in the FLPT group (p = 0.04). The 5-year survival rate of the two groups was not statistically significant (p = 0.14). Risk factors for thoracic FLPT were the distance between the re-entry site and the graft (p = 0.02) and the proximal oversizing ratio (p = 0.04). CONCLUSIONS: TEVAR is an effective and safe treatment for uncomplicated cTBAD and has a low mortality rate. Thoracic FLCT is associated with less reintervention, but overall survival is not impacted by this difference. Patients treated with TEVAR without certain risk factors can have a good prognosis.


Asunto(s)
Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Trombosis , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/etiología , Disección Aórtica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/etiología , Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Humanos , Estudios Retrospectivos , Factores de Riesgo , Stents , Trombosis/etiología , Factores de Tiempo , Resultado del Tratamiento
13.
Br J Clin Pharmacol ; 88(9): 4092-4099, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35384015

RESUMEN

AIMS: Antithrombotic management initiatives could prevent inappropriate prescribing and improve patient outcomes especially in patients on combined antithrombotic therapy. To investigate this, a multidisciplinary antithrombotic stewardship program (ASP) was implemented in our hospital. The primary aim of this study was to determine the efficacy of this ASP by assessing the number of patients on combined antithrombotic therapy for whom one or more interventions were needed. METHODS: A prospective cohort study in a large teaching hospital was conducted. Hospitalized patients were included who received combined antithrombotic therapy in which an oral anticoagulant was combined with one (double therapy) or two (triple therapy) platelet aggregation inhibitors. The ASP proactively evaluated the appropriateness of this combined antithrombotic therapy. If needed, ASP improved the concerned therapy. Each improvement measurement recommended by the ASP was counted as one intervention. RESULTS: A total of 460 patients were included over a period of 12 months. Of these, 251 (54.6%) patients required at least one intervention from the ASP. The most common interventions were: (1) to define and document the maximum duration of the combined antithrombotic therapy needed instead of lifetime use of the combination (65.5%), (2) to discontinue antithrombotic therapy as the proper indication was lacking (19.4%), and (3) to adjust the dosage (8.1%). CONCLUSION: An intervention was needed in more than half of the patients on combined antithrombotic therapy. Implementation of a dedicated ASP evaluating combined antithrombotic therapy improves the use and safety of antithrombotic medication.


Asunto(s)
Fibrinolíticos , Inhibidores de Agregación Plaquetaria , Anticoagulantes , Humanos , Prescripción Inadecuada/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos
14.
J Org Chem ; 87(18): 12414-12423, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36007244

RESUMEN

An efficient and facile visible-light-mediated tandem difluoromethylation/cyclization of alkenyl aldehydes, with easily accessible and air-stable [Ph3PCF2H]+Br- as the difluoromethylation reagent, has been established. A range of CF2H-substituted chroman-4-one skeletons and their derivatives, such as 2,3-dihydroquinolin-4(1H)-ones, chroman, 3,4-dihydronaphthalen-1(2H)-one, 2,3-dihydrobenzofuran, and 2,3-dihydro-1H-inden-1-one, are efficiently produced in moderate to good yields with excellent chemoselectivity under mild reaction conditions.

15.
Org Biomol Chem ; 20(6): 1196-1199, 2022 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-35072683

RESUMEN

The visible-light-mediated tandem phosphorylation/cyclization of N-arylacrylamides with H-phosphine oxides has been developed for the synthesis of phosphorylated oxindoles. This efficient and facile process was useful for the construction of a C-P bond and triggered the formation of a C-C bond with good compatibility with functional groups undermild reaction conditions.

16.
Org Biomol Chem ; 20(16): 3283-3286, 2022 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-35373792

RESUMEN

The aluminum(III) triflate catalyzed three-component coupling reaction of alkynes, amines and phosphorylated aryl aldehydes to access phosphoryl quinoline derivatives has been developed. The reaction proceeds in a simple system without the use of transition metals, ligands or additives, thus making it attractive for the fast preparation of a variety of new potential N-P bidentate ligands.

17.
Neurol Sci ; 43(12): 6803-6811, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36048377

RESUMEN

INTRODUCTION: The interrelationship between neurocognitive impairments and motor functions was observed in patients with advanced Parkinson's disease (PD). This study was conducted to identify pre-operative neurocognitive and clinical predictors of short-term motor outcome following subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: All consecutive PD patients who were eligible for bilateral STN-DBS from 2009 to 2019 were evaluated before and at 1 year following surgery. Standard motor evaluation and neurocognitive tests including global cognition, memory, executive functions (attention and category fluency), confrontational speech, visuospatial abilities, and mood were conducted at baseline. The post-operative STN-DBS effects were assessed at 1 year following the surgery. Multiple regression analysis was applied to identify baseline independent predictors of post-operative STN-DBS effect. RESULTS: A total of 82 patients were analyzed. It was found that younger age at operation, higher levodopa responsiveness at baseline based on UPDRS-III total score, and better baseline verbal delayed memory and category fluency predicted post-operative motor outcome at 1 year following STN-DBS (F = 9.639, p < 0.001, R2 = .340). CONCLUSION: Our findings demonstrated the role of baseline cognitive burden, especially cognitive processes related to frontostriatal circuits, was significant clinical predictors of short-term motor outcomes following STN-DBS. Profile analysis of neurocognitive functions at baseline is recommended.


Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Humanos , Núcleo Subtalámico/fisiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/psicología , Levodopa , Cognición , Resultado del Tratamiento
18.
Ann Diagn Pathol ; 60: 152021, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35939880

RESUMEN

BACKGROUND: Molecular markers for the detection of lymph node micrometastases of malignant tumors have been extensively investigated. However, epigenetic signatures have rarely been reported for identification of metastatic lymph nodes and disease relapse. Septin 9 is the most frequently reported hypermethylated gene in colorectal cancer (CRC). This study aimed to assess the clinical relevance of Septin 9 methylation in regional lymph nodes in recurrence/metastases of CRC. METHODS: We analyzed Septin 9 methylation of DNA from resected lymph nodes in 75 CRC patients with or without tumor recurrence using quantitative methylation-sensitive PCR (qMS-PCR). RESULTS: Of the 30 histologically negative lymph node CRC patients without recurrence (group 1), methylated Septin 9 was detected in 3 (10 %) cases. The positivity rate of methylated Septin 9 in group 2 containing 30 histologically node-negative CRC patients with recurrence was 30 % (9/30). For group 3, lymphatic invasion as well as tumor recurrence, 11 (73 %) out of 15 subjects had Septin 9 methylation-positive lymph nodes. Moreover, patients in group 3 had a higher level of methylated Septin 9 compared to subjects in group 1 and group 2 (p < 0.05). In addition, CRC patients with Septin 9 methylation in lymph nodes had significantly reduced survival (Log-rank P < 0.0001). CONCLUSION: Our data support the predictive role of Septin 9 methylation analysis of lymph node micrometastases for tumor relapse after surgery.


Asunto(s)
Neoplasias Colorrectales , Micrometástasis de Neoplasia , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Metilación , Micrometástasis de Neoplasia/diagnóstico , Micrometástasis de Neoplasia/patología , Recurrencia Local de Neoplasia/metabolismo , Estadificación de Neoplasias , Pronóstico , Septinas/genética , Septinas/metabolismo
19.
Neuroophthalmology ; 46(4): 264-269, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35859628

RESUMEN

Suprasellar germinomas can present with non-diagnostic, or even normal results on imaging. The spectrum of reported cases ranges from normal imaging, thickened pituitary stalks, to discrete tumour growths. This similar phenomenon is less commonly seen in the pineal region, or bifocal germinomas, and the literature is sparse with only a few case series or reports mentioning a similar presentation of signs and symptoms preceding radiological evidence of diagnosis. We report a case of pineal germinoma presenting with dorsal midbrain syndrome with no evidence of tumour growth on initial imaging despite symptoms. For patients presenting with this clinical radiological latent period, follow-up imaging is useful to identify interval development of germinomas. This applies to patients with dorsal midbrain syndrome, or even other unexplained ophthalmoplegia, as the initial sign of pineal region germinoma, despite normal imaging.

20.
J Orthop Traumatol ; 23(1): 12, 2022 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-35254507

RESUMEN

BACKGROUND: It is still unknown whether tranexamic acid (TXA) is beneficial for the minimally invasive surgical approach to total hip arthroplasty (THA). The aim of this study is to investigate the efficacy and safety of intravenous TXA in primary THA via the direct anterior approach (DAA). MATERIALS AND METHODS: We performed a retrospective analysis of prospectively collected data on 70 patients with nontraumatic avascular necrosis of the femoral head who underwent THA via the DAA between October 2017 and October 2018. Patients were divided into two groups: TXA group (39 patients received 1.5 g TXA intravenously) and control group (31 patients did not receive TXA). Patients were assessed by operative time, postoperative hemoglobin (HB) drop, transfusion rate, postoperative length of hospital stays (LHS), deep vein thrombosis (DVT), and Harris hip score (HHS). RESULTS: Total blood loss, hidden blood loss, and postoperative HB drop in the TXA group were significantly lower than in the control group (p < 0.05). There was no statistical difference between the two groups in terms of intraoperative blood loss, operative time, transfusion rate, postoperative LHS, HHS, or incidence of DVT (p > 0.05). CONCLUSIONS: TXA may reduce perioperative blood loss without increasing complications in THA via the DAA. LEVEL OF EVIDENCE: Level IV, therapeutic study.


Asunto(s)
Antifibrinolíticos , Artroplastia de Reemplazo de Cadera , Ácido Tranexámico , Antifibrinolíticos/uso terapéutico , Artroplastia de Reemplazo de Cadera/efectos adversos , Pérdida de Sangre Quirúrgica/prevención & control , Humanos , Estudios Retrospectivos , Ácido Tranexámico/uso terapéutico
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