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Importance: Prior trials showed that dual antiplatelet therapy could reduce the risk of early new stroke in patients with acute mild ischemic stroke or transient ischemic attack (TIA) within 24 hours of symptom onset. However, it is currently uncertain whether dual antiplatelet therapy can reduce the risk of early new stroke in patients with a more delayed initiation time window. Objective: To evaluate the efficacy and safety of clopidogrel and aspirin among patients with mild ischemic stroke or TIA when initiated within 24 hours, from more than 24 hours to 48 hours, and from more than 48 hours to 72 hours. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis randomized clinical trial was a double-blind, placebo-controlled, multicenter, 2-by-2 factorial randomized clinical trial conducted at 222 hospitals in China from September 17, 2018, to October 15, 2022. All patients with acute mild ischemic stroke and TIA were included in this subgroup analysis and categorized into 3 groups according to time from symptom onset to randomization (group 1: ≤24 hours; group 2: >24 to ≤48 hours; and group 3: >48 to 72 hours). Patients were followed up for 90 days. Interventions: All patients received clopidogrel combined with aspirin (clopidogrel 300 mg loading dose on day 1, followed by 75 mg daily on days 2 to 90, and aspirin 100 to 300 mg on the first day and then 100 mg daily for days 2 to 90) or aspirin alone (100 to 300 mg on day 1 and then 100 mg daily for days 2 to 90) within 72 hours after symptom onset. Main Outcomes and Measures: The primary outcome was new stroke (ischemic or hemorrhagic) within 90 days. The primary safety outcome was moderate-to-severe bleeding, according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria. Results: This analysis included a total of 6100 patients (3050 in the clopidogrel-aspirin group and 3050 in the aspirin group). The median age was 65 years (IQR, 57-71 years), and 3915 patients (64.2%) were male. In the population with time to randomization of 24 hours or less, stroke occurred in the next 90 days in 97 of 783 patients (12.4%); among those randomized from more than 24 hours to 48 hours, in 211 of 2552 patients (8.3%) among those randomized from more than 24 hours to 48 hours, and in 193 of 2765 patients (7.0%). The clopidogrel-aspirin group had a lower risk of new stroke within 90 days compared with the aspirin alone group both in patients with time to randomization of from 48 to 72 hours (5.8% vs 8.2%; hazard ratio [HR], 0.70 [95% CI, 0.53-0.94]), of more than 24 to 48 hours (7.6% vs 8.9%; HR, 0.85 [95% CI, 0.65-1.12]), and of 24 hours or less (11.5% vs 13.4%; HR, 0.83 [95% CI, 0.55-1.25]) (P = .38 for interaction). Among those with time to randomization of more than 48 to 72 hours, moderate-to-severe bleeding occurred in 12 patients (0.9%) in the clopidogrel-aspirin group and in 6 patients (0.4%) in the aspirin-alone group (HR, 2.00 [95% CI, 0.73-5.43]), while moderate-to-severe bleeding in those with time to randomization of more than 24 hours to 48 hours occurred in 9 patients (0.7%) in the clopidogrel-aspirin group and in 4 patients (0.3%) in the aspirin-alone group (HR, 2.25 [95% CI, 0.68-7.39]) and in those with time to randomization of within 24 hours, occurred in 6 patients (1.5%) in the clopidogrel-aspirin group and in 3 patients (0.8%) in the aspirin-alone group (HR, 1.57 [95% CI, 0.36-6.83]) (P = .92 for interaction). Conclusions and Relevance: In this randomized clinical trial of antiplatelet therapy in China, patients with mild ischemic stroke or TIA had consistent benefit from dual antiplatelet therapy with clopidogrel and aspirin vs aspirin alone when initiated within 72 hours after symptom onset, with a similar increase in the risk of moderate-to-severe bleeding. Patients should receive dual antiplatelet therapy with clopidogrel and aspirin within 72 hours after symptom onset. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.

Asunto(s)

Aspirina , Clopidogrel , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Clopidogrel/uso terapéutico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Masculino , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/prevención & control , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Método Doble Ciego , Ataque Isquémico Transitorio/tratamiento farmacológico , China/epidemiología , Tiempo de Tratamiento/estadística & datos numéricos , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

BACKGROUND AND OBJECTIVES: Clopidogrel-aspirin initiated within 72 hours of symptom onset is effective in patients with mild ischemic stroke or transient ischemic attack (TIA) in the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial. Uncertainties remain about the duration of the treatment effect. This study aimed to assess duration of benefit and risk of clopidogrel-aspirin in these patients. METHODS: The INSPIRES trial was a 2*2 factorial placebo-controlled randomized trial conducted in 222 hospitals in China. The 2 treatments did not interact and were evaluated separately. In this study, we performed secondary analyses based on antiplatelet treatment. All patients with mild stroke or TIA of presumed atherosclerotic cause within 72 hours of symptom onset enrolled in the trial were included. Patients were randomly assigned to receive clopidogrel-aspirin on days 1-21 followed by clopidogrel on days 22-90 or aspirin alone for 90 days. The primary efficacy outcome was major ischemic event which included the composite of ischemic stroke and nonhemorrhagic death. The primary safety outcome was moderate-to-severe bleeding. We estimated the risk difference between the 2 treatments for each stratified week. RESULTS: All 6,100 patients in the trial were included (3,050 in each group). The mean age was 65 years, and 3,915 patients (64.2%) were men. Compared with aspirin alone, the reduction of major ischemic events by clopidogrel-aspirin mainly occurred in the first week (absolute risk reduction [ARR] 1.42%, 95% CI 0.53%-2.32%) and remained in the second week (ARR 0.49%, 95% CI 0.09%-0.90%) and the third week (ARR 0.29%, 95% CI -0.05% to 0.62%). Numerical higher risk of moderate-to-severe bleedings in the clopidogrel-aspirin group was observed in the first 3 weeks (absolute risk increase 0.05% [95% CI -0.10% to 0.20%], 0.10% [95% CI -0.09% to 0.29%], and 0.18% [95% CI -0.03% to 0.40%] in the first, second, and third weeks, respectively). CONCLUSIONS: Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low, but ongoing hemorrhagic risk. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03635749. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low but ongoing hemorrhagic risk.

Asunto(s)

Aspirina , Clopidogrel , Terapia Antiplaquetaria Doble , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Masculino , Femenino , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Terapia Antiplaquetaria Doble/métodos , Factores de Tiempo , Quimioterapia Combinada , Resultado del Tratamiento

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The epidermal growth factor receptor (EGFR) plays a pivotal role in tumor progression and is an essential therapeutic target for treating malignant gliomas. Small interfering RNA (siRNA) has the potential to selectively degrade EGFR mRNA, yet its clinical utilization is impeded by various challenges, such as inefficient targeting and limited escape from lysosomes. Our research introduces polyethylene glycol (PEG) and endoplasmic reticulum membrane-coated siEGFR nanoplexes (PEhCv/siEGFR NPs) as an innovative approach to brain glioma therapy by overcoming several obstacles: 1) Tumor-derived endoplasmic reticulum membrane modifications provide a homing effect, facilitating targeted accumulation and cellular uptake; 2) Endoplasmic reticulum membrane proteins mediate a non-degradable "endosome-Golgi-endoplasmic reticulum" transport pathway, circumventing lysosomal degradation. These nanoplexes demonstrated significantly enhanced siEGFR gene silencing in both in vitro and in vivo U87 glioma models. The findings of this study pave the way for the advanced design and effective application of nucleic acid-based therapeutic nanocarriers.

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OBJECTIVE: Accurate diagnoses and personalized treatments in medicine rely on identifying causality. However, existing causal discovery algorithms often yield inconsistent results due to distinct learning mechanisms. To address this challenge, we introduce MINDMerge, a multi-causal investigation and discovery framework designed to synthesize causal graphs from various algorithms. METHODS: MINDMerge integrates five causal models to reconcile inconsistencies arising from different algorithms. Employing credibility weighting and a novel cycle-breaking mechanism in causal networks, we initially developed and tested MINDMerge using three synthetic networks. Subsequently, we validated its effectiveness in discovering risk factors and predicting acute kidney injury (AKI) using two electronic medical records (EMR) datasets, eICU Collaborative Research Database and MIMIC-III Database. Causal reasoning was employed to analyze the relationships between risk factors and AKI. The identified causal risk factors of AKI were used in building a prediction model, and the prediction model was evaluated using the area under the receiver operating characteristics curve (AUC) and recall. RESULTS: Synthetic data experiments demonstrated that our model outperformed significantly in capturing ground-truth network structure compared to other causal models. Application of MINDMerge on real-world data revealed direct connections of pulmonary disease, hypertension, diabetes, x-ray assessment, and BUN with AKI. With the identified variables, AKI risk can be inferred at the individual level based on established BNs and prior information. Compared against existing benchmark models, MINDMerge maintained a higher AUC for AKI prediction in both internal (AUC: 0.832) and external network validations (AUC: 0.861). CONCLUSION: MINDMerge can identify causal risk factors of AKI, serving as a valuable diagnostic tool for clinical decision-making and facilitating effective intervention.

Asunto(s)

Lesión Renal Aguda , Algoritmos , Registros Electrónicos de Salud , Humanos , Lesión Renal Aguda/diagnóstico , Factores de Riesgo , Causalidad , Masculino , Femenino , Curva ROC

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In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.

Asunto(s)

Comprimidos , Comprimidos/química , Tamaño de la Partícula , Composición de Medicamentos , Polvos/química , Ácidos Esteáricos/química , Resistencia a la Tracción , Excipientes/química , Solubilidad

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OBJECTIVE: To investigate the macular morphological and visual outcomes of combined idiopathic epiretinal membrane (iERM) removal with triamcinolone acetonide (TA) injection based on consideration of the ectopic inner foveal layer (EIFL) staging scheme. METHODS: Retrospective case-control study. The clinical data of 84 eyes of 84 patients who underwent vitrectomy for iERM between 2018 and 2022 were reviewed. The enrolled subjects were divided into the TA and non-TA groups. Fifty-one eyes received intravitreal TA injection following vitrectomy and ERM peeling (TA group), and 33 were only treated by standard vitrectomy and ERM peeling (non-TA group). Preoperative and postoperative EIFL stages, central foveal thickness (CFT), and best-corrected visual acuity (BCVA) were compared between both groups. RESULTS: After a mean follow-up of 7.69 ± 3.68 months, both groups exhibited significant improvement in EIFL stages (P < 0.01), with no discernible advantage observed in the TA group. The TA and non-TA groups demonstrated improvement in the EIFL stages in 56.86 and 63.64% of eyes, respectively (P = 0.43). The CFT and BCVA significantly improved in both groups at the final visit (P < 0.01). However, CFT in the non-TA group displayed a more significant reduction during the follow-up (P < 0.03). Subgroup analysis revealed no significant differences in postoperative CFT and BCVA between the two groups in cases with or without continuous EIFL (P > 0.10). CONCLUSION: Our findings indicate that combined intravitreal TA injection following ERM removal conferred no significant benefits in alleviating macular thickening or improving visual acuity in iERM.

Asunto(s)

Membrana Epirretinal , Fóvea Central , Glucocorticoides , Inyecciones Intravítreas , Tomografía de Coherencia Óptica , Triamcinolona Acetonida , Agudeza Visual , Vitrectomía , Humanos , Membrana Epirretinal/diagnóstico , Membrana Epirretinal/cirugía , Estudios Retrospectivos , Masculino , Femenino , Tomografía de Coherencia Óptica/métodos , Glucocorticoides/administración & dosificación , Fóvea Central/patología , Vitrectomía/métodos , Triamcinolona Acetonida/administración & dosificación , Estudios de Casos y Controles , Anciano , Persona de Mediana Edad , Estudios de Seguimiento , Resultado del Tratamiento

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OBJECTIVE: Men's coercive condom use resistance (CUR) with female partners is common and is associated with greater alcohol consumption than men's noncoercive CUR engagement. Prior research indicates that emotion-related factors are relevant to alcohol-involved coercive CUR. Thus, in this alcohol administration study, we examined emotional factors as distal and proximal predictors of alcohol-involved coercive CUR among young men who have sex with women. METHOD: Non-problem drinking young adult men who have sex with women (N = 282) were recruited from the local community, and as part of a larger study, completed a background survey and an in-lab alcohol administration session that included a mood induction and sexual scenario task using a 2 (sober vs. intoxicated) x 2 (positive mood vs. negative mood) experimental design. RESULTS: Path analysis testing a moderated mediation model revealed that for participants in the sober, positive mood, and intoxicated, negative mood conditions, there was a positive association between distal ER difficulties and motives to have sex to cope with negative emotions. Additionally, distal ER difficulties were positively associated with proximal difficulties modulating one's emotions among intoxicated participants. Among those with greater proximal difficulties modulating their emotions, state anger was positively associated with coercive CUR intentions. CONCLUSIONS: Results demonstrate the importance of alcohol intoxication, emotions and emotion regulation, and sexual coping motives in men's coercive CUR likelihood, demonstrating potential malleable targets for prevention efforts.

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Coerced condomless sex is a prevalent form of sexual coercion that is associated with severe negative health consequences. This scoping review addresses the current lack of synthesized qualitative evidence on coerced condomless sex. Our systematic literature search yielded 21 articles that met review eligibility criteria. Themes of coerced condomless sex were organized into three categories (tactics, motives, and sequelae) and presented separately for studies based on whether researchers stipulated pregnancy promotion intent as underlying the behavior. Coerced condomless sex perpetration tactics ranged from verbal pressure to physical assault. Besides pregnancy promotion, perpetration motives included control, dominance, entrapment, enhancing sexual experiences, and avoiding conflict. Following coerced condomless sex, victims reported developing protective strategies. They also reported experiencing various negative emotional, relational, and physical health effects. Interventions that specifically address coerced condomless sex perpetration and provide supportive programs for those who have experienced coercive condomless sex may be beneficial.

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Importance: Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis. Objective: To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed. Interventions: Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90). Main Outcomes and Measures: The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome. Results: A total of 11 431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively. Conclusions and Relevance: Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.

Asunto(s)

Atorvastatina , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Método Doble Ciego , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/prevención & control , Atorvastatina/uso terapéutico , Atorvastatina/administración & dosificación , Ataque Isquémico Transitorio/tratamiento farmacológico , Adulto , Isquemia Encefálica/tratamiento farmacológico , Anciano de 80 o más Años , Prevención Secundaria/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación

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Under the new coronavirus epidemic, the implementation of public health measures has generated some resistance in countries around the world. The essence of examining the human rights claims of those who oppose the epidemic is that they have a too narrow understanding of individual human rights and ignore the obligation implications of human rights itself. From the historical point of view, health and epidemic prevention is the objective necessity of the survival and development of human society; From the ethical point of view, the joint fight against the epidemic is the moral obligation of the coordinated development of individuals and society. From the normative point of view, the management of infectious diseases is the basic consensus established by many international conventions. To correct the narrow understanding of individual human rights concept, the global human rights concept should be established in pandemic governance, and the concept of human health community should be shaped in the pandemic convention to build governance consensus, implement the same health concept to clarify the scope of governance, implement the principle of common but differentiated responsibilities, and strengthen the participation of individuals and communities in public health governance to improve governance paths. To shape a more reasonable and effective pandemic governance order.

RESUMEN

Broomrape (Orobanche cumana) negatively affects sunflower, causing severe yield losses, and thus, there is a need to control O. cumana infestation. Brassinosteroids (BRs) play key roles in plant growth and provide resilience to weed infection. This study aims to evaluate the mechanisms by which BRs ameliorate O. cumana infection in sunflower (Helianthus annuus). Seeds were pretreated with BRs (1, 10, and 100 nM) and O. cumana inoculation for 4 weeks under soil conditions. O. cumana infection significantly reduced plant growth traits, photosynthesis, endogenous BRs and regulated the plant defence (POX, GST), BRs signalling (BAK1, BSK1 to BSK4) and synthesis (BRI1, BR6OX2) genes. O. cumana also elevated the levels of malondialdehyde (MDA), hydroxyl radical (OH-), hydrogen peroxide (H2O2) and superoxide (O2 •-) in leaves/roots by 77/112, 63/103, 56/97 and 54/89%, as well as caused ultrastructural cellular damages in both leaves and roots. In response, plants activated a few enzymes, superoxide dismutase (SOD), peroxidase (POD) and reduced glutathione but were unable to stimulate the activity of ascorbate peroxidase (APX) and catalase (CAT) enzymes. The addition of BRs (especially at 10 nM) notably recovered the ultrastructural cellular damages, lowered the production of oxidative stress, activated the key enzymatic antioxidants and induced the phenolic and lignin contents. The downregulation in the particular genes by BRs is attributed to the increased resilience of sunflower via a susceptible reaction. In a nutshell, BRs notably enhanced the sunflower resistance to O. cumana infection by escalating the plant immunity responses, inducing systemic acquired resistance, reducing oxidative or cellular damages, and modulating the expression of BR synthesis or signalling genes.

Asunto(s)

Brasinoesteroides , Helianthus , Orobanche , Semillas , Helianthus/efectos de los fármacos , Helianthus/inmunología , Helianthus/fisiología , Brasinoesteroides/farmacología , Brasinoesteroides/metabolismo , Orobanche/fisiología , Orobanche/efectos de los fármacos , Semillas/efectos de los fármacos , Semillas/inmunología , Malezas/efectos de los fármacos , Malezas/fisiología , Enfermedades de las Plantas/parasitología , Enfermedades de las Plantas/inmunología , Inmunidad de la Planta/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Raíces de Plantas/inmunología , Raíces de Plantas/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/inmunología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Malondialdehído/metabolismo

RESUMEN

OBJECTIVE: To identify the risk factors for the development of diabetic retinopathy (DR), diabetic macular edema (DME), and sight-threatening DR (STDR) based on a city-wide diabetes screening program. RESEARCH DESIGN AND METHODS: Diabetic patients were prospectively recruited between June 2016 and December 2022. All patients underwent dilated fundus photography centered on the disc and macula or macular spectral domain optical coherence tomography (SD-OCT) scan. Complete medical history was documented. Systematic examination, blood analysis, and urinalysis were performed. Multivariate logistic regression analysis adjusting for age and sex was conducted. RESULTS: Out of 7274 diabetic patients, 6840 had gradable images, among which 3054 (42.0%) were graded as DR, 1153 (15.9%) as DME, and 1500 (20.6%) as STDR. The factors associated with DR, DME, and STDR included younger age (odds ratio [OR]: 0.96, 0.97, and 0.96 respectively), lower BMI (OR: 0.97, 0.95, and 0.95 respectively), longer duration of diabetes (OR: 1.07, 1.03, and 1.05 respectively) and positive of urinary albumin (OR: 2.22, 2.56, and 2.88 respectively). Other associated factors included elevated blood urea nitrogen (OR: 1.22, 1.28, and 1.27 respectively), higher LDL-cholesterol, lower blood hemoglobin (OR: 0.98, 0.98, and 0.98), insulin intake, presence of diabetic foot pathologies and diabetic peripheral neuropathy. We also identified novel risk factors, including high serum potassium (OR: 1.37, 1.46, and 1.55 respectively), high-serum sodium (OR: 1.02, 1.02, and 1.04 respectively). Better family income was a protective factor for DR, DME, and STDR. Alcohol consumption once a week was also identified as a protective factor for DR. CONCLUSIONS: Similar risk factors for DR, DME, and STDR were found in this study. Our data also indicates high serum sodium, high serum potassium, low blood hemoglobin, and level of family income as novel associated factors for DR, DME, and STDR, which can help with DR monitoring and management.

Asunto(s)

Retinopatía Diabética , Edema Macular , Tomografía de Coherencia Óptica , Humanos , Retinopatía Diabética/epidemiología , Retinopatía Diabética/diagnóstico , Masculino , Factores de Riesgo , Edema Macular/etiología , Edema Macular/epidemiología , Edema Macular/diagnóstico , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía de Coherencia Óptica/métodos , Anciano , Agudeza Visual , Adulto , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología

RESUMEN

BACKGROUND: Myomectomy is the preferred treatment for women with uterine fibroids and fertility requirements. There are three modalities are used in clinical practice for myomectomy: abdominal myomectomy (AM), laparoscopic myomectomy (LM), and robot-assisted laparoscopic myomectomy (RLM). OBJECTIVES: To compare the perioperative and postoperative outcomes of RLM, AM, and LM. SEARCH STRATEGY: We searched PubMed, Web of Science, Embase, and Clinical Trials for relevant literature published between January 2000 and January 2023. SELECTION CRITERIA: We included all studies reporting peri- and postoperative outcomes of myomectomy in patients with uterine myomas. Surgical treatments were classified as RLM, LM, or AM. DATA COLLECTION AND ANALYSIS: Two or more authors selected studies independently, assessed risk of bias, and extracted data. We derived mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CIs) for each outcome, subgrouping trials by the patient characteristics and myoma characteristics. We used the I2 statistic to quantify heterogeneity and the random-effects model for meta-analysis when appropriate. We used the funnel plot to assess the publication bias. MAIN RESULTS: A total of 32 studies with 6357 patients were included, of which 1982 women had undergone RLM. The operating time was significantly longer (MD = 43.58, 95% confidence interval [CI]: 25.22-61.93, P < 0.001), and the incidence of cesarean section after myomectomy was significantly lower (OR = 0.27, 95% CI: 0.10-0.78, P = 0.02) in RLM than in LM. Compared with AM, the operation time, blood loss, blood transfusion rate, complication rate, total cost, length of hospital stay, and pregnancy rate of patients with RLM were significantly different. CONCLUSIONS: The safety and effectiveness of RLM are superior to those of AM but inferior to those of LM.

Asunto(s)

Laparoscopía , Leiomioma , Procedimientos Quirúrgicos Robotizados , Miomectomía Uterina , Neoplasias Uterinas , Humanos , Femenino , Miomectomía Uterina/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Laparoscopía/métodos , Leiomioma/cirugía , Neoplasias Uterinas/cirugía , Embarazo , Complicaciones Posoperatorias/epidemiología , Tempo Operativo

RESUMEN

OBJECTIVE: We used polysomnography (PSG) monitoring and neuropsychological scales to explore the characteristics of coronavirus disease-2019 (COVID-19) patients diagnosed with post-traumatic stress disorder (PTSD) in Wuhan, two years after the onset of the COVID-19 pandemic. METHODS: A total of 42 patients in the Sleep Medicine Center were diagnosed with insomnia between December 2021 and May 2022; they were divided into the PTSD group (patients with PTSD diagnosed with insomnia after COVID-19 infection) and the non-PTSD group (patients with insomnia without PTSD). A healthy control group was simultaneously included. RESULTS: The PTSD group was more significant than the non-PTSD group in partial manifestations of sleep disorders, neuropsychological clinical symptoms, and partial PSG data. Patients with different COVID-19 subtypes showed significant differences in the course of disease, sleep disorders, neuropsychological clinical symptoms, relevant scale scores, and PSG data analysis. CONCLUSION: The emotional anxiety and depression of COVID-19 patients diagnosed with PTSD two years after the COVID-19 pandemic in Wuhan are more significant, and will not be self-alleviated with the passage of time. It is necessary to continue to pay attention to the PTSD symptoms and sleep psychology of COVID-19 infected patients, and take appropriate measures. Patients with severe and critical COVID-19 have more severe sleep and mental disorders, and there is a significant correlation between the duration of the disease and the severity of mental and mental disorders and sleep disorders after recovery.

RESUMEN

BACKGROUND: This study aimed to investigate the functional and anatomical outcomes of subthreshold micropulse laser (SMPL) therapy in eyes with early postoperative macular thickening after idiopathic epiretinal membrane (iERM) removal. METHODS: This was a prospective and interventional study. Forty-eight eyes from 48 patients with macular edema at 1 month after iERM removal were randomly divided into two groups. Patients in the SMPL group (n = 24) received SMPL therapy while no special intervention was used for the observation group (n = 24). Baseline demographic data and clinical findings before and at 1 and 3 months after SMPL treatment or observation, including best-corrected visual acuity (BCVA) and the changes in central subfield thickness (CST) and average macular thickness (AMT), were analyzed. RESULTS: An improvement in BCVA with a decrease in CST and AMT from baseline to the 3-month follow-ups were observed in both SMPL and observation groups. No significant difference in BCVA was observed between the SMPL group and observation group either in the 1-month (0.26 [0.15, 0.52] vs. 0.26 [0.15, 0.39], P = 0.852) or the 3-month (0.15 [0.10, 0.30] vs. 0.23 [0.15, 0.30], P = 0.329) follow-up. There was a greater reduction in CST in the SMPL group versus observation group between baseline and the 3-month follow-up (-77.8 ± 72.3 µm vs. -45.0 ± 46.9 µm, P = 0.049). The alteration in AMT did not differ between the two groups in either 1-month (-16.5 ± 20.1 µm vs. -19.7 ± 16.3 µm, P = 0.547) or 3-month (-36.9 ± 26.9 µm vs. -34.0 ± 20.1 µm, P = 0.678) follow-up. CONCLUSIONS: SMPL therapy led to a significant decrease in CST at the 3-month follow-up while did not significantly improve the visual acuity in patients with postoperative macular thickening following iERM surgery. TRIAL REGISTRATION: The study was registered on Aug 27, 2020 (Trial Registration Number: ChiCTR 2000037227).

Asunto(s)

Membrana Epirretinal , Terapia por Láser , Terapia por Luz de Baja Intensidad , Humanos , Membrana Epirretinal/cirugía , Estudios Prospectivos , Ojo , Trastornos de la Visión

RESUMEN

Temperature is one of the governing factors affecting friction of solids. Undesired high friction state has been generally reported at cryogenic temperatures due to the prohibition of thermally activated processes, following conventional Arrhenius equation. This has brought huge difficulties to lubrication at extremely low temperatures in industry. Here, the study uncovers a hydrogen-correlated sub-Arrhenius friction behavior in hydrogenated amorphous carbon (a-C:H) film at cryogenic temperatures, and a stable ultralow-friction over a wide temperature range (103-348 K) is achieved. This is attributed to hydrogen-transfer-induced mild structural ordering transformation, confirmed by machine-learning-based molecular dynamics simulations. The anomalous sub-Arrhenius temperature dependence of structural ordering transformation rate is well-described by a quantum mechanical tunneling (QMT) modified Arrhenius model, which is correlated with quantum delocalization of hydrogen in tribochemical reactions. This work reveals a hydrogen-correlated friction mechanism overcoming the Arrhenius temperature dependence and provides a new pathway for achieving ultralow friction under cryogenic conditions.

RESUMEN

Sexual aggression (SA) is a significant public health problem, with the majority of SA involving alcohol. The present study examined associations between alcohol expectancies for sexual enhancement, event-level alcohol use, and the likelihood of SA perpetration. Young, adult non-problem drinking men participated in a laboratory session and completed a background survey that included measures of alcohol expectancies. Subsequently, men completed 6-week and 3-month follow-up surveys in which they reported their sexual experiences each day during the intervening 6-week period using Timeline Followback procedures. The analytic sample consisted of the 421 men (Mage = 24.66, SD = 2.69) who reported having sex at least once during the follow-up period. Multilevel models showed a significant alcohol expectancies X alcohol use interaction at the between-person level: Controlling for time and alcohol expectancies for aggression, stronger alcohol expectancies for sexual enhancement were associated with greater SA perpetration likelihood among men who consumed high amounts of alcohol before sexual encounters but not among men who consumed low amounts. Alcohol prevention programs should consider addressing men's alcohol expectancies for sexual enhancement to reduce risk for SA perpetration.

RESUMEN

OBJECTIVE: Victims of sexual violence experience detrimental physical and mental health consequences. Therefore, developing programs to prevent sexual violence is of utmost importance. Our previous work provided preliminary support for the efficacy of brief mindfulness and cognitive restructuring (CR) interventions in reducing sexual violence intentions. Because alcohol use and alcohol expectancies (AE) have been identified as risk factors for sexual violence, this secondary data analysis aimed to examine whether alcohol use and men's expectations that alcohol may affect women's vulnerability of being sexually coerced moderate the usefulness of these two interventions on nonconsensual sex intentions. METHOD: Single, young, heterosexual, heavy episodic drinking men with sexual violence histories were randomly assigned to receive mindfulness or CR skills training, or attention control. Half of the participants in each intervention condition were then randomized to alcohol or sober conditions. All participants read a hypothetical sexual scenario and rated their intention to engage in nonconsensual sex with their hypothetical sexual partner. RESULTS: Mindfulness was effective in lowering nonconsensual sex intentions among sober men with high AE for women's vulnerability and intoxicated men with low AE for women's vulnerability to sexual coercion. CR was effective in lowering nonconsensual sex intentions among intoxicated men with low and moderate AE for women's vulnerability to sexual coercion. CONCLUSIONS: Our results provide preliminary evidence for the efficacy of mindfulness and CR in lowering nonconsensual sex intentions under certain circumstances and highlight men's AE about women's vulnerability to sexual coercion as a critical factor that interacts with alcohol use to influence the efficacy of mindfulness and CR.

Asunto(s)

Intención , Atención Plena , Delitos Sexuales , Humanos , Masculino , Atención Plena/métodos , Adulto Joven , Delitos Sexuales/prevención & control , Delitos Sexuales/psicología , Femenino , Terapia Cognitivo-Conductual/métodos , Adulto , Conducta Sexual/psicología , Consumo de Bebidas Alcohólicas/psicología , Consumo de Bebidas Alcohólicas/prevención & control , Adolescente , Coerción

RESUMEN

We examined healthcare costs at HonorHealth, a community-based academic health center comprised of 5 hospitals and numerous ambulatory care facilities. Patient encounters that resulted in admission in 2019 were included in the study. Mean costs in 2019 for high costs and high needs (HCHN) patients were compared with all remaining patients using a framework developed by the National Academy of Medicine. HCHN patients were older (71 vs 52 years), with a lower percentage of females (41.7% vs 59.8%), more frequently White (90.1% vs 87.5%), less frequently married (52.4% vs 54.5%), with a longer length of stay (6.5 vs 3.0 days) and higher mean charges ($134 743 vs $16 414). The mean cost per patient in the HCHN group decreased by age group ($192, 963, $165 200, $144 584, $134 795, and $108 356) for 0 to 18, 19 to 44, 45 to 64, 65 to 84, and 85+ years, respectively. HCHN patients were more publicly insured (49% vs 38%). Targeted interventions to treat HCHN may lead to lower healthcare costs and improved health outcomes within this system.

Asunto(s)

Hospitalización , Hospitales Comunitarios , Femenino , Humanos , Recién Nacido , Costos de la Atención en Salud , Tiempo de Internación

RESUMEN

We recently showed that riboflavin is a selected substrate of breast cancer resistance protein (BCRP) over P-glycoprotein (P-gp) and demonstrated its prediction performance in preclinical drug-drug interaction (DDI) studies. The aim of this study was to investigate the suitability of riboflavin to assess BCRP inhibition in humans. First, we assessed the substrate potential of riboflavin toward other major drug transporters using established transfected cell systems. Riboflavin is a substrate for organic anion transporter (OAT)1, OAT3, and multidrug and toxin extrusion protein (MATE)2-K, with uptake ratios ranging from 2.69 to 11.6, but riboflavin is not a substrate of organic anion-transporting polypeptide (OATP)1B1, OATP1B3, organic cation transporter (OCT)2, and MATE1. The effects of BMS-986371, a potent in vitro inhibitor of BCRP (IC 50 0.40 µM), on the pharmacokinetics of riboflavin, isobutyryl carnitine, and arginine were then examined in healthy male adults (N = 14 or 16) after oral administration of methotrexate (MTX) (7.5 mg) and enteric-coated (EC) sulfasalazine (SSZ) (1000 mg) alone or in combination with BMS-986371 (150 mg). Oral administration of BMS-986371 increased the area under the plasma concentration-time curves (AUCs) of rosuvastatin and immediate-release (IR) SSZ to 1.38- and 1.51-fold, respectively, and significantly increased AUC(0-4h), AUC(0-24h), and C max of riboflavin by 1.25-, 1.14-, and 1.11-fold (P-values of 0.003, 0.009, and 0.025, respectively) compared with the MTX/SSZ EC alone group. In contrast, BMS-986371 did not significantly influence the AUC(0-24h) and C max values of isobutyryl carnitine and arginine (0.96- to 1.07-fold, respectively; P > 0.05). Overall, these data indicate that plasma riboflavin is a promising biomarker of BCRP that may offer a possibility to assess drug candidate as a BCRP modulator in early drug development. SIGNIFICANCE STATEMENT: Endogenous compounds that serve as biomarkers for clinical inhibition of breast cancer resistance protein (BCRP) are not currently available. This study provides the initial evidence that riboflavin is a promising BCRP biomarker in humans. For the first time, the value of leveraging the substrate of BCRP with acceptable prediction performance in clinical studies is shown. Additional clinical investigations with known BCRP inhibitors are needed to fully validate and showcase the utility of this biomarker.

Asunto(s)

Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Proteínas de Neoplasias , Riboflavina , Humanos , Riboflavina/farmacocinética , Riboflavina/metabolismo , Riboflavina/sangre , Proyectos Piloto , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/antagonistas & inhibidores , Adulto , Masculino , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Biomarcadores/sangre , Biomarcadores/metabolismo , Voluntarios Sanos , Adulto Joven , Metotrexato/farmacocinética , Metotrexato/farmacología , Metotrexato/metabolismo , Metotrexato/sangre , Persona de Mediana Edad