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Whole-genome sequencing was used to identify a dominant inherited NLRP12 c.1382dup mutation in refractory familial Crohn's disease (CD) patients. Additionally, we observed a T insertion at position 1382 in the third exon of NLRP12, leading to a frameshift mutation. Isolation of peripheral blood from mutation carriers and subsequent experiments demonstrated increased interleukin (IL)-1ß in CD patients with the NLRP12 c.1382dup mutation. However, the mechanisms by which the NLRP12 c.1382dup mutation mediates IL-1ß remain unclear. Our research findings reveal a close correlation between elevated p-ERK levels and increased expression of NLRP3 and IL-1ß in the presence of the NLRP12 c.1382dup mutation. Further experiments demonstrate that inhibiting p-ERK with PD98059 effectively reduces the production of NLRP3 and IL-1ß. This discovery provides new insights into the pathogenesis of CD, highlighting the significant role of the ERK/NLRP3/IL-1ß pathway in the progression of CD. Not only does this offer novel therapeutic targets for treating CD, but it also lays the groundwork for the development of treatment strategies targeting this pathway.
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Cement solidification is a commonly used pre-treatment method for municipal solid waste incineration fly ash (MSWIFA) prior to sanitary landfill. However, the long-term environmental risk of cement-solidified MSWIFA blocks in the exposed scenario of zoning sanitary landfill remains unclear. In this study, the leaching characteristics of different heavy metals in cement-solidified MSWIFA blocks under deionized water and acid rain scenarios were firstly investigated. The leaching control mechanisms of heavy metals were also explored and applied to established mechanical models for the estimation of long-term environmental risk. Results revealed that Pb leaching from cement-solidified MSWIFA blocks was controlled by diffusion; Cu, Cr and As leaching was mainly controlled by surface wash-off and diffusion; and Ni leaching was mainly controlled by diffusion and dissolution. Additionally, the established bulk diffusion, first-order reaction/diffusion and diffusion/dissolution models could accurately fit the abovementioned three types of heavy metals with different leaching control mechanisms (R2 > 0.95). Under acid rain scenariosï¼ according to the prediction results of the calibrated models, the cumulative leaching amount of Pb in 718 d was higher than the limit in GB16889-2008, the cumulative leaching amount of Cu, Cr, As and Ni did not exceed the limit in GB 16889-2008 even in 50 years. Therefore, the long-term environmental risk was relatively high for Pb but was low for Cu, Cr, As and Ni in cement-solidified MSWIFA blocks. This finding could be attributed to the strong alkali environment of cement-solidified MSWIFA blocks (pH > 12) that induced Pb salts (e.g. Pb(OH)2 and PbSO4) dissolution. Therefore, the removal of partially soluble Pb salts from freshly made cement-solidified MSWIFA blocks by water or natural rainwater (e.g. without final cover system) washing in the initial landfilling stage (e.g. the leachate drainage system remains functional) is an effective countermeasure to reduce the environmental risks in zoning sanitary landfill.
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Lluvia Ácida , Metales Pesados , Eliminación de Residuos , Carbono , Ceniza del Carbón/análisis , Incineración , Plomo , Metales Pesados/análisis , Material Particulado , Medición de Riesgo , Sales (Química) , Residuos Sólidos/análisis , Instalaciones de Eliminación de Residuos , AguaRESUMEN
Pavement marking in daylight with poor quality cannot provide a reference for drivers to specify their own position relative to nearby vehicles. Luminance and Correlated color temperature (CCT) of sunlight is of importance for daytime visibility of in-service pavement markings, which lacks detailed consideration. This paper aims to explore the daytime visibility requirements of in-service pavement markings considering the influence of natural light characteristics. Based on analyzing the mechanism and impact factors of daytime visibility of pavement markings, a subjective scale of pavement markings state in the drivers' field of view was proposed and a short and bold line was recommended as the standard state. Thirty-six tested drivers were randomly selected to detect white and yellow markings of both 15 cm and 20 cm width under 2000 to 23,000 lx and 5500 to 8500 K for outdoor natural light environment. The luminance contrast of the pavement marking to the surrounding road surface ranged from 0 to 10. The result indicated that the natural light with 2000 to 3000 lx and 7500 to 8500 K is the most unfavorable light environment for drivers to recognize pavement markings during daytime. The detection distance is becoming longer with the increase of luminance contrast. The detection distance does not increase with the increase of luminance contrast when the luminance contrast of white markings is greater than 4 and that of yellow markings is greater than 3. The model was established expressing the relationship between luminance contrast and Qd contrast. The preview time 3.65 s was selected to calculate the minimum requirements of Qd at speeds of 60, 80, 100 km/h, respectively, for different types of markings. The results can provide scientific evidence for quality evaluation and maintenance management of pavement markings in service for daytime visibility.
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BACKGROUND: Brucellosis is a common zoonotic disease that is prevalent in many areas worldwide. This infectious disease can occasionally affect the central nervous system but intracranial arteries are rarely involved. CASE PRESENTATION: A 17-year-old female who had a history of recurrent fever for 1 month was admitted for subarachnoid hemorrhage due to cerebral aneurysm rupture. Surgery was performed to fix the aneurysm, but the patient had persistent fever after the surgery. Cerebrospinal fluid testing showed a high white blood cell count and elevated protein level but no pathogen was identified in the first two tests. Brucella melitensis was identified in the third cerebrospinal fluid culture, and a diagnosis of brucellosis was finally rendered. The patient was subsequently treated with anti-Brucella medications and her symptoms improved significantly at the last follow-up. CONCLUSION: Although extremely rare, Brucella-induced cerebral aneurysms can occur and this should be considered in the differential diagnosis of cerebrovascular accidents, especially in Brucella epidemic areas.
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Brucella melitensis , Brucelosis , Aneurisma Intracraneal , Hemorragia Subaracnoidea , Adolescente , Animales , Brucelosis/complicaciones , Brucelosis/diagnóstico , Brucelosis/tratamiento farmacológico , Femenino , Humanos , Aneurisma Intracraneal/complicaciones , Hemorragia Subaracnoidea/etiología , ZoonosisRESUMEN
To investigate the clinical value of transabdominal ultrasound combined with pulse index continuous cardiac output (PICCO) in fluid resuscitation of septic shock patients, and to analyze the predictive value of survival outcomes, 68 patients with septic shock were randomly divided into the ultrasound + PICCO group and PICCO group. Compared with before treatment, blood lactic acid (BLA) was cleared, and central venous pressure (CVP) and oxygenation index were significantly increased in all patients. The oxygen binding index, central venous oxygen saturation (ScVO2), and CVP in the ultrasound + PICCO group were increased compared with the PICCO group, while BLA, mechanical ventilation time, total fluid resuscitation input and hospitalization were significantly reduced. The extravascular lung water index and shape change index were positively correlated with sequential organ failure assessment. The combination of extravascular lung water index and shape change index had higher clinical value than each alone in predicting the death of patients with septic shock. The combination of transabdominal ultrasound with PICCO is better at guiding fluid resuscitation in patients with septic shock and has a certain predictive value with respect to the survival outcome of septic shock patients.
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Choque Séptico , Gasto Cardíaco , Agua Pulmonar Extravascular , Fluidoterapia , Humanos , Saturación de Oxígeno , Choque Séptico/diagnóstico por imagen , Choque Séptico/terapiaRESUMEN
BACKGROUND: Acute febrile illness is one of the main reasons for outpatient hospital visits worldwide. However, differential diagnosis between bacterial and viral causes is challenging and misdiagnosis can result in antimicrobial overuse and hinder prompt treatment. We aimed to build and validate a diagnostic model to discriminate bacterial from viral infection in acute febrile illness by evaluating the expression of potential classifier host genes. METHODS: In this multicentre discovery and validation study, we included patients aged 14-85 years with acute febrile illness (fever for ≤14 days, axillary temperature of ≥38°C, and confirmed bacterial infection, viral infection, or non-infectious inflammatory disease), and healthy control participants (no significant medical history and no fever within the past 90 days) from four hospitals in Shandong province, China. Patients from the first hospital were divided into the screening, discovery, and internal validation groups, and patients from the three other hospitals comprised the external validation group. We measured expression of candidate genes in peripheral blood by RT-PCR, and patients for whom a successful RT-PCT result was recorded were included in the next-step analysis. For patients from the first hospital, those enrolled during the early phase of the study were assigned to the screening group, which was used to identify the optimal transcripts (IFI44L and PI3) for discrimination between bacterial and viral infections by screening four candidate genes (FAM89A, IFI44L, PI3, and ITGB2) by RT-PCR. The remaining patients were then randomly assigned (1:1) to discovery and internal validation groups by time of admission and blood drawing via the equidistant random sampling method. A logistic regression model integrating the mRNA levels of IFI44L and PI3 was built by use of the discovery group, and the diagnostic performance of the model was evaluated in the internal and external validation groups using area under the receiver operating curve (AUC), sensitivity, and specificity. FINDINGS: Between March 1, 2018, and Aug 31, 2019, we assessed 1658 individuals for inclusion in the study. After exclusion of ineligible participants, 458 participants were enrolled (178 patients with acute febrile illness caused by bacterial infection, 212 with acute febrile illness caused by viral infection, 38 with non-infectious inflammatory diseases, and 30 healthy controls). The 390 patients with bacterial or viral infections were assigned to one of four groups: screening (n=64, 33 with bacterial infections and 31 with viral infections), discovery (n=124, 55 with bacterial infections and 69 with viral infections), internal validation (n=124, 55 with bacterial infections and 69 with viral infections), and external validation (n=78, 35 with bacterial infections and 43 with viral infections). Of the four candidate host genes (FAM89A, IFI44L, PI3, and ITGB2), IFI44L and PI3 showed the most discriminative expression pattern and were used to build the logistic regression model. We established the optimal cutoff of the bacterial infection likelihood score to be 0·547598. With the diagnostic result from the gold standard tests (culture and PCR) as the reference, the two-transcript classifier model had an AUC of 0·969 (95% CI 0·937-1·000), sensitivity of 0·891 (0·782-0·949), and specificity of 0·971 (0·900-0·992) to discriminate bacterial and viral infections in the internal validation group. The model showed similar results in the external validation group (AUC 0·986, 95% CI 0·968-1·000; sensitivity 0·857, 0·706-0·937; and specificity 0·954, 0·845-0·987). INTERPRETATION: IFI44L and PI3 transcripts, measured by RT-PCR, are robust classifiers to discriminate bacterial from viral infection in acute febrile illness. This two-transcript biomarker has the potential to be transformed into a commercial panel and applied universally. FUNDING: None.
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Bacterias , Infecciones Bacterianas/diagnóstico , Fiebre/diagnóstico , Tamizaje Masivo/métodos , Modelos Biológicos , Virosis/diagnóstico , Virus , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Bacterias/crecimiento & desarrollo , Infecciones Bacterianas/metabolismo , Infecciones Bacterianas/microbiología , Biomarcadores/metabolismo , China , Diagnóstico Diferencial , Femenino , Fiebre/metabolismo , Fiebre/microbiología , Fiebre/virología , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Reproducibilidad de los Resultados , Virosis/metabolismo , Virosis/virología , Virus/crecimiento & desarrollo , Adulto JovenRESUMEN
With the increasing number of reports on aristolochic acid I (AAI), more and more toxic and side effects have been discovered successively. The main recognized carcinogenic mechanism is that AAI is metabolized into aristololactam I (AAT) in the body by nitroreductases, ultimately forming AAT-DNA adducts that cause disease. However, the carcinogenic mechanism is still not well understood by currently reported indirect method, there has always been a great demand to develop a direct method for real-time monitoring such process. In this work, surface-enhanced Raman spectroscopy (SERS) was used for the first time to monitor the process of AAI under the action of reducing agent sodium borohydride and catalyst Raney nickel to form AAT. We first found the abundant intermediate product-amino derivative of AAI, which was never reported before by other methods. The AAT was then obtained by a one-step dehydration reaction from the amino derivative of AAI under such reduction conditions. The product of amino derivative of AAI and AAT were further verified by thin-layer chromatography, H nuclear magnetic resonance spectra, mass spectrometry, and ultra-high performance liquid chromatography. Furthermore, a density functional theory-supported in-depth vibrational characterization of AAI and AAT was performed. The monitoring of the AAI reduction process by SERS can be of great significance for further exploration of its pathogenic mechanism, prevention, and monitoring of "nephropathy" and other diseases caused by AAI.
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Ácidos Aristolóquicos , Técnicas Biosensibles , Enfermedades Renales , Aductos de ADN , Humanos , Espectrometría RamanRESUMEN
To evaluate the associations of inflammatory factors and serological test results with complicated brucellosis, we recruited 285 patients with a diagnosis of brucellosis between May 2016 and September 2019. The patients were subsequently classified into two groups according to the presence of complications. We collected demographic and clinical information and routine laboratory test results in addition to anti-Brucella IgG and IgM levels. Anti-Brucella IgG and IgM were uniformly tested using enzyme-linked immunosorbent assays (ELISAs) in this study. Among the 285 patients with brucellosis, 111 (38.95%) had complicated brucellosis. Osteoarthritis occurred more often in the subacute and chronic stages than in the acute stage (P = 0.002). Genital infection occurred more frequently in the acute stage than in the other stages (P = 0.023). Fever was not frequently observed in complicated cases (P < 0.001). The erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP) and anti-Brucella IgM and IgG levels were higher in complicated-brucellosis patients than in uncomplicated-brucellosis patients (P < 0.001). Anti-Brucella IgG, with an area under the curve of 0.885 (95% confidence interval [CI], 0.847 to 0.924), was the most robust indicator of complicated brucellosis. Positive culture, anti-Brucella IgM, the ESR, and CRP could be considered indicators, but their efficacy was weaker than that of IgG. In conclusion, a high ESR, high CRP, high anti-Brucella IgM and IgG levels, and positive culture were indicators of complicated brucellosis; among these, anti-Brucella IgG was the most robust biomarker.
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Brucella , Brucelosis , Pruebas de Aglutinación , Anticuerpos Antibacterianos , Brucelosis/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina G , Inmunoglobulina MRESUMEN
OBJECTIVE: To compare the efficacy and safety of standard-dose (SD) daptomycin with those of high-dose (HD) daptomycin in complicated skin and soft tissue infections (cSSTIs) in an Asian population. MATERIALS AND METHODS: Patients from three medical centers diagnosed with cSSTIs were screened in the clinical information system. Patients included in the analysis were divided into two groups: those who received daptomycin at doses ≥ 6 mg/kg (HD group) and those receiving 4 mg/kg (SD group). The demographics and clinical treatment information were analyzed. RESULTS: Overall, 155 patients were recruited, including 108 patients in the SD group and 47 patients in the HD group. The rate of healthcare-associated infections was higher in the HD group (61.70% vs. 37.04%), demonstrating a statistically significant difference (P = 0.005). Compared with the SD group, the HD group had statistically significant early clinical stabilization (72.34% vs 52.78%, P = 0.023). The results of the multivariate analysis indicated that HD daptomycin was an independent effector for early clinical stabilization (HR=0.394, P < 0.001). The rate of drug-related adverse events was equally distributed in the HD and SD groups (36.17% vs. 26.85%, P = 0.243). CONCLUSION: Compared with SD daptomycin, HD daptomycin increased the rate of early clinical stabilization in Asian patients with cSSTIs, whereas the incidence of adverse events did not increase.
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Antibacterianos/administración & dosificación , Daptomicina/administración & dosificación , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , China/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Daptomicina/efectos adversos , Daptomicina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
To fight against diabetes mellitus, from which more than 400 million people suffer in the world, the patients have to puncture their fingers 4-5 times a day for the blood glucose level checks when using a glucometer, causing invasive pain and the risk of infection. Therefore, non-invasive method has been urged for blood glucose monitoring, among which the mid-infrared spectroscopy (Mid-IR) response of interstitial fluid was found to be promising. However, despite the prolonged effort, the accuracy still falls below the FDA's requirement. To break this barrier which lasted for almost three decades, we discovered the finger contact pressure playing a critical role during the measurement, where the Mid-IR reading could be affected significantly by a small change of the finger posture. In addition, the Mid-IR absorption level was also found to be highly associated with individual, revealing the necessity of adjusting the calibration correlation for each patient. By imposing a certain contact pressure monitored by a pressure transducer, we were able to achieve over 95% certainty from the Mid-IR measurement of glucose concentration and 100% comparability to the "true" glucose concentration for the first time, which was mainly attributed to the morphological change of finger tissue under pressure. The previous works resulted in only about 70% accuracy on average, barely hitting 80â¯+â¯%, whereas ours reaches 95%, finally exceeding the requirement of FDA.
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Automonitorización de la Glucosa Sanguínea , Glucemia/análisis , Diabetes Mellitus/diagnóstico , Humanos , Presión , Espectrofotometría InfrarrojaRESUMEN
Introduction: Nicotine acts as an agonist at presynaptic nicotinic acetylcholine receptors and to facilitate synaptic release of several neurotransmitters including dopamine and glutamate. The thalamus has the highest density of nicotinic acetylcholine receptors in the brain, which may make this area more vulnerable to the addictive effects of nicotine. However, the volume of thalamus abnormalities and the association with smoking behaviors in young smokers remains unknown. Methods: Thirty-six young male smokers and 36 age-, gender- and education-matched nonsmokers participated in the current study. The nicotine dependence severity and cumulative effect were assessed with the Fagerström test for nicotine dependence (FTND) and pack-years. We used subcortical volume analyses method in FreeSurfer to investigate the thalamus volume differences between young smokers and nonsmokers. Correlation analysis was used to investigate the relationship between thalamus volume and smoking behaviors (pack-years and FTND) in young smokers. Results and Conclusions: Relative to nonsmokers, the young smokers showed reduced volume of bilateral thalamus. In addition, the left thalamus volume was correlated with FTND in young smokers. It is hoped that our findings can shed new insights into the neurobiology of young smokers. Implications: In this article, we investigated the changes of thalamus volume in young male smokers compared with nonsmokers. Reduced left thalamus volume was correlated with FTND in young smokers, which may reflect nicotine severity in young male smokers.
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Índice de Severidad de la Enfermedad , Fumadores , Tálamo/diagnóstico por imagen , Tabaquismo/diagnóstico por imagen , Adolescente , Estudios Transversales , Humanos , Masculino , Nicotina/administración & dosificación , Nicotina/metabolismo , Tamaño de los Órganos , Receptores Nicotínicos/metabolismo , Fumar/epidemiología , Fumar/metabolismo , Fumar/psicología , Fumar Tabaco/epidemiología , Fumar Tabaco/metabolismo , Fumar Tabaco/psicología , Tabaquismo/metabolismo , Tabaquismo/psicología , Adulto JovenRESUMEN
With the help of advanced neuroimaging approaches, previous studies revealed structural and functional brain changes in smokers compared with healthy non-smokers. Homotopic resting-state functional connectivity between the corresponding regions in cerebral hemispheres may help us to deduce the changes of functional coordination in the whole brain of young male smokers. Functional homotopy reflects an essential aspect of brain function and communication between the left and right cerebral hemispheres, which is important for the integrity of brain function. However, few studies used voxel mirrored homotopic connectivity (VMHC) method to investigate the changes of homotopic connectivity in young male smokers. Twenty-seven young male smokers and 27 matched healthy male non-smokers were recruited in our study. Compared with healthy male non-smokers, young male smokers showed decreased VMHC values in the insula and putamen, and increased VMHC values in the prefrontal cortex. Correlation analysis demonstrated that there were significant positive correlations between the average VMHC values of the prefrontal cortex and pack-years in young male smokers. In addition, significant negative correlation was found between the average VMHC values in the insula and pack-years. Our results revealed the disrupted homotopic resting-state functional connectivity in young male smokers. The novel findings may extend our understanding of smoking.
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Encéfalo/diagnóstico por imagen , Fumadores , Adolescente , Encéfalo/fisiopatología , Estudios de Casos y Controles , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatología , Fumar Cigarrillos/fisiopatología , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Putamen/diagnóstico por imagen , Putamen/fisiopatología , Descanso , Adulto JovenRESUMEN
Previous electroencephalogram (EEG) studies revealed reduced spectral power during the resting state in smokers. However, few studies investigated the changes of global brain networks during the resting state in young smokers by EEG. In the present study, we used minimum spanning tree (MST) to assess the differences of global network efficiency between young smoker (n = 20) and nonsmokers (n = 20). Compared with healthy nonsmokers, young smokers showed decreased leaf fraction, kappa value, increased diameter and eccentricity value in alpha band (r = 0.574, p = 0.008), which suggested the global network efficiency was decreased in young smokers. We also found positive correlation between leaf fraction and onset time of smoking in smokers. These results provided more scientific evidence of the abnormal neural oscillations of young smokers and improved our understanding of smoking addiction.
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The aim of this study was to identify a microRNA (miRNA) expression signature for predicting HCC (hepatocellular carcinoma) survival. A total of 322 HCC patients in The Cancer Genome Atlas (TCGA) database were randomly divided into training and testing set. miRNAs, associated with survival time in the training set, were identified by using univariate Cox regression analysis. The risk score was formulated based on the expression levels of these miRNAs. Then the miRNA signature was validated in testing set through Kaplan-Meier analysis and log-rank test. hsa-miR-301a, hsa-miR-132, hsa-miR-212, hsa-miR-489, and hsa-miR-1468 were identified to formulate risk score in training set and used to calculate the risk score of each patients in testing set. About 161 patients in testing set were segregated into high- and low-risk group according to the median risk score. The survival time of high-risk group was significantly shorter (p = 0.0248) than low-risk group in testing test. The target genes of five miRNAs were significantly enriched in valine, leucine, and isoleucine degradation pathway and PPAR signaling pathway. hsa-miR-1468 had an up-regulated tendency in HCC tissues compared to adjacent tumor tissues. The expression of hsa-miR-301a, hsa-miR-132, hsa-miR-212, hsa-miR-489, and hsa-miR-1468, which might be potential biomarkers to evaluate HCC patients' prognosis.
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Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Perfilación de la Expresión Génica , MicroARNs/análisis , Biomarcadores/análisis , Femenino , Humanos , Masculino , Pronóstico , Análisis de SupervivenciaRESUMEN
Studying the neural correlates of craving to smoke in young adulthood is of great importance to improve treatment outcomes in nicotine dependence. Previous nicotine dependence studies mainly focused on the neural substrates of craving elicited by smoking-related cues. More explicit attention to abstinence-induced craving during resting state in nicotine dependence has the potential to yield valuable information about craving, and characterizing this kind of craving is critical for developing effective interventions. Twenty-five young male smokers were enrolled in the present study. A within-subject experiment design was carried out to compare regional homogeneity (ReHo) between 12-h smoking abstinence and smoking satiety conditions during resting state in young adult smokers. Then, the ReHo changes associated with smoking abstinence (compared with satiety) were further examined for correlations with abstinence-induced changes in subjective craving. We found young adult smokers in abstinence state (compared with satiety) had higher ReHo in brain regions in fronto-striatal circuits including bilateral caudate, anterior cingulate cortex (ACC) and bilateral dorsal lateral prefrontal cortex (DLPFC), as well as brain regions in default mode network (DMN) including posterior cingulate cortex (PCC)/precuneus and angular gyrus. Additionally, we found the ReHo changes of the ACC and the bilateral caudate were positively correlated with the changes in craving induced by abstinence (i.e., abstinence minus satiety) in young adult smokers. The present findings improve the understanding of the effects of acute smoking abstinence on spontaneous brain activity and may contribute new insights into the neural mechanism of abstinence-induced craving in nicotine dependence.
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Encéfalo/fisiopatología , Ansia/fisiología , Fumar/fisiopatología , Fumar/psicología , Adolescente , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Descanso , Fumadores/psicología , Adulto JovenRESUMEN
The insula has been implicated in cognitive control and craving, all of which are critical to the clinical manifestations of nicotine dependence. However, little evidence exists about the abnormalities in resting state functional connectivity (RSFC) of the insula in young smokers, which might improve our understanding of the neural mechanisms of nicotine dependence. Due to the structural and functional heterogeneity of the insula, the RSFC patterns of both left and right anterior (AI) and posterior insula (PI) were investigated in young smokers and non-smokers. Meanwhile, the relationship was assessed between the neuroimaging findings and clinical information (pack-years, FTND, and craving) as well as cognitive control deficits measured by Stroop task performance. Compared with non-smokers, young smokers showed reduced RSFC between right AI and anterior cingulate cortex (ACC), ventromedial prefrontal cortex (VMPFC), amygdala, left dorsolateral prefrontal cortex, and dorsal striatum. Additionally, left AI showed reduced RSFC with ACC. Both left and right PI network differences were not observed between two groups. Moreover, in young smokers, FTND and incongruent errors in the Stroop task were negatively correlated with the RSFC between AI and ACC. Craving scores showed a significantly negative relationship with the RSFC strength between right AI and left VMPFC. These results provide a more thorough network-level understanding the role of insula in cigarette smoking. The findings provide new insights into the roles of AI-ACC circuit in cognitive control deficits and right AI-VMPFC circuit relevant to the craving of nicotine dependence for young smokers.
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Corteza Cerebral/fisiopatología , Ansia , Función Ejecutiva , Fumar/fisiopatología , Fumar/psicología , Adolescente , Mapeo Encefálico , Corteza Cerebral/diagnóstico por imagen , Cognición/fisiología , Ansia/fisiología , Estudios Transversales , Función Ejecutiva/fisiología , Humanos , Inhibición Psicológica , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Descanso , Fumadores/psicología , Test de Stroop , Adulto JovenRESUMEN
Studying the neural correlates of smoking behaviors in young adulthood is of great importance to improve treatment outcomes. In previous addiction studies, the important roles of the salience network (SN) in drug cue processing and cognitive control have been revealed. Unfortunately, few studies focused on the resting-state functional connectivity and structural integrity abnormalities of SN in young adult smokers, and less is known about its association with smoking behaviors and cognitive control deficits. Thirty-one young male adult smokers and 30 age-, education- and gender-matched nonsmokers participated in this study. The structural and functional connectivity differences of SN were investigated between young adult smokers and nonsmokers by using diffusion tensor imaging (DTI) and resting-state functional connectivity (RSFC), which were then correlated with the smoking behavioral assessments (pack-years and Fagerström Test for Nicotine Dependence (FTND)) as well as impaired cognitive control measured by the Stroop task. Within SN, reduced RSFC and increased fractional anisotropy (FA) were found between the anterior cingulate cortex (ACC) and the right insula in young adult smokers relative to nonsmokers. The RSFC between the ACC and right insula was negatively correlated with the number of errors during the incongruent condition of the Stroop task in young adult smokers. Additionally, the right insula-ACC RSFC was negatively correlated with pack-years in young adult smokers. Our results revealed abnormal RSFC and structural integrity within the SN in young adult smokers, which shed new insights into the neural mechanism of nicotine dependence.
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Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Fumar/fisiopatología , Tabaquismo/diagnóstico por imagen , Tabaquismo/fisiopatología , Adolescente , Mapeo Encefálico , Estudios Transversales , Imagen de Difusión Tensora , Función Ejecutiva , Humanos , Inhibición Psicológica , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Descanso , Autocontrol , Índice de Severidad de la Enfermedad , Fumadores/psicología , Fumar/psicología , Test de Stroop , Tabaquismo/psicología , Adulto JovenRESUMEN
Smoking is one of the most prevalent dependence disorders. Previous studies have detected structural and functional deficits in smokers. However, few studies focused on the changes of resting state functional connectivity (RSFC) of the brain regions with structural deficits in young adult smokers. Twenty-six young adult smokers and 26 well-matched healthy non-smokers participated in our study. Voxel-based morphometry (VBM) and RSFC were employed to investigate the structural and functional changes in young adult smokers. Compared with healthy non-smokers, young smokers showed increased gray matter (GM) volume in the left putamen and decreased GM volume in the left anterior cingulate cortex (ACC). Moreover, GM volume in the left ACC has a negative correlation trend with pack-years and GM volume in the left putamen was positively correlated with pack-years. The left ACC and putamen with abnormal volumes were chosen as the regions of interest (ROIs) for the RSFC analysis. We found that smokers showed increased RSFC between the left ACC and right amygdala and between the left putamen and right anterior insula. We revealed structural and functional deficits within the frontostriatal circuits in young smokers, which may shed new insights into the neural mechanisms of smoking.
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Cigarette smoking during young adult may result in serious health issues in later life. Hence, it is extremely necessary to study the smoking neurophysiological mechanisms in this critical transitional period. However, few studies revealed the electrophysiological mechanisms of cognitive processing biases in young adult smokers. In present study, nineteen young smokers with 12h abstinent and 19 matched nonsmokers were recruited. By employing event-related potentials (ERP) measurements during a smoking cue induced craving task, electrophysiological brain responses were compared between the young adult smokers and nonsmokers. The Slow Positive Wave (SPW) amplitude of smoking-related cues was enhanced in young adult smokers compared with nonsmokers. In addition, increased P300/SPW component of smoking-related cues relative to neutral cues were found in young adult smokers. Meanwhile, a positive correlation between Cigarette Per Day (CPD) and the amplitude of ERPs wave (P300/SPW) at anterior (Fz), central (Cz) were observed in young adult smokers. Our findings provided direct electrophysiological evidence for the cognitive processing bias of smoking cue and may shed new insights into the smoking behavior in young adult smokers.
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Corteza Cerebral/fisiopatología , Cognición/fisiología , Ansia/fisiología , Señales (Psicología) , Fumar/fisiopatología , Fumar/psicología , Adulto , Electroencefalografía , Potenciales Relacionados con Evento P300 , Humanos , Masculino , Adulto JovenRESUMEN
The critical roles of frontostriatal circuits had been revealed in addiction. With regard to young smokers, the implication of frontostriatal circuits resting-state functional connectivity (RSFC) in smoking behaviors and cognitive control deficits remains unclear. In this study, the volume of striatum subsets, i.e., caudate, putamen, and nucleus accumbens, and corresponding RSFC differences were investigated between young smokers (n1 = 60) and nonsmokers (n2 = 60), which were then correlated with cigarette smoking measures, such as pack_years-cumulative effect of smoking, Fagerström Test for Nicotine Dependence (FTND)-severity of nicotine addiction, Questionnaire on Smoking Urges (QSU)-craving state, and Stroop task performances. Additionally, mediation analysis was carried out to test whether the frontostriatal RSFC mediates the relationship between striatum morphometry and cognitive control behaviors in young smokers when applicable. We revealed increased volume of right caudate and reduced RSFC between caudate and dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex in young smokers. Significant positive correlation between right caudate volume and QSU as well as negative correlation between anterior cingulate cortex-right caudate RSFC and FTND were detected in young smokers. More importantly, DLPFC-caudate RSFC strength mediated the relationship between caudate volume and incongruent errors during Stroop task in young smokers. Our results demonstrated that young smokers showed abnormal interactions within frontostriatal circuits, which were associated with smoking behaviors and cognitive control impairments. It is hoped that our study focusing on frontostriatal circuits could provide new insights into the neural correlates and potential novel therapeutic targets for treatment of young smokers. Hum Brain Mapp 37:2013-2026, 2016. © 2016 Wiley Periodicals, Inc.