Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 929
Filtrar
1.
World Neurosurg ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33418117

RESUMO

OBJECTIVE: This study aims to evaluate the performance of convolutional neural networks (CNN) trained with resting-state functional MRI (rfMRI) latency data in the classification of patients with pediatric epilepsy from healthy controls. METHODS: Preoperative rfMRI and anatomical MRI scans were obtained from 63 pediatric patients with refractory epilepsy and 259 pediatric healthy controls. Latency maps of the temporal difference between rfMRI and the global mean signal were calculated using voxel-wise cross-covariance. Healthy control and epilepsy latency z-score maps were pseudorandomized and partitioned into training data (60%), validation data (20%) and test data (20%). Healthy control and epilepsy patients were labeled as negative and positive, respectively. CNN models were then trained with the designated training data. Model hyperparameters were evaluated with a grid-search method. The model with the highest sensitivity was evaluated using unseen test data. Accuracy, sensitivity, specificity, F1-score and AUC were used to evaluate the model's ability to classify epilepsy in the test data set. RESULTS: The model with the highest validation sensitivity, correctly classified 74% of unseen test patients with 85% sensitivity, 71% specificity, F1-score of 0.56 and an AUC of 0.86. CONCLUSION: Using rfMRI latency data, we trained a CNN model to classify pediatric epilepsy patients from healthy controls with good performance. CNN could serve as an adjunct in the diagnosis of pediatric epilepsy. Identification of pediatric epilepsy earlier in the disease course could decrease time to referral to specialized epilepsy centers, and thus improve prognosis in this population.

2.
Biol Sex Differ ; 12(1): 8, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413673

RESUMO

BACKGROUND: Sex differences in stroke have been attributed to the neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation for stroke prevention have failed. The contribution of sex hormones to stroke outcome remains a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests aromatase activity increases in response to brain injury, and increased aromatase expression is seen in the ischemic penumbra in animal models. The objective of this study was to examine the levels of endogenous sex steroids after acute ischemic stroke and determine if levels of sex steroids were associated with acute stroke outcomes. METHODS: Peripheral blood from ischemic stroke patients and controls was collected under an approved IRB within 24 h of symptom onset. 17ß-estradiol, testosterone, and aromatase levels were measured in the serum of both men and women using ELISA. Hormone levels were compared in men vs. women in stroke and control groups and correlated with outcomes (NIHSS and change in the modified Rankin Scale (mRS), defined as the difference of premorbid and discharge mRS) using multivariate regression. RESULTS: We found no significant difference in estradiol levels 24 h after stroke in men (p = 0.86) or women (p = 0.10). In men, testosterone significantly decreased after stroke as compared with controls (1.83 ± 0.12 vs. 2.86 ± 0.65, p = 0.01). Aromatase levels were significantly increased in women after stroke as compared with controls (2.27 ± 0.22 vs. 0.97 ± 0.22, p = 0.002), but not in men (p = 0.84). Estradiol levels positively correlated with change in mRS in both women (r = 0.38, p = 0.02) and men (r = 0.3, p = 0.04). CONCLUSIONS: Estradiol levels correlated with functional outcomes (change in mRS) in both men and women, at least in the acute phase (24 h) of stroke. However, no significant difference in estradiol levels is seen 24 h post-stroke in men or women. Testosterone levels decrease at 24 h after stroke in men. As seen in animal models, aromatase levels increase after acute ischemic stroke, but this was only true for women. These indicate an active aromatization process in post-menopausal women after acute ischemic stroke.

3.
Med Biol Eng Comput ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33432508

RESUMO

The objective of this study is to investigate the effect of hyperthermia-induced improvement of hydraulic conductivity and lymphatic function on both tumoral IFP reduction and nanoparticle delivery to PC3 tumors. We developed a theoretical model for nanoparticle transport in a tumor incorporating Starling's law, Darcy's law, transient convection, and diffusion of chemical species in porous media, and nanoparticle accumulation in tumors. Results have shown that both mechanisms were effective to decrease the IFP at the tumor center from 1600 Pa in the control without heating to 800 Pa in tumors with whole body heating. IFP reductions not only elevate the nanoparticle concentration in the tumor, but also result in a more uniform nanoparticle concentration in the tumor than that in the control without heating. Due to the IFP reductions at the tumor center and/or local blood perfusion increases, the final amount of accumulated nanoparticles in the tumor increased by more than 35-95% when compared to the control without heating. We conclude that increases in the hydraulic conductivity and recovery of lymphatic functions are possible mechanisms that lead to IFP reductions and enhancement in nanoparticle deposition in PC3 tumors observed in our in vivo experimental studies.

4.
J Stroke Cerebrovasc Dis ; 30(3): 105602, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33461026

RESUMO

OBJECTIVE: We aim to report intra-arterial thrombectomy transfer metrics for ischemic stroke patients that were transferred to hub hospitals for possible intra-arterial thrombectomy in multiple geographic regions throughout the state of Texas and to identify potential barriers and delays in the intra-arterial thrombectomy transfer process. METHOD: We prospectively collected data from 8 participating Texas comprehensive stroke/thrombectomy capable centers from 7 major regions in the State of Texas. We collected baseline clinical and imaging data related to the pre-transfer evaluation, transfer metrics, and post-transfer clinical and imaging data. RESULTS: A total of 103 acute ischemic stroke patients suspected/confirmed to have large vessel occlusions between December 2016 to May 2019 that were transferred to hubs as possible intra-arterial thrombectomy candidates were enrolled. A total of 56 (54%) patients were sent from the spoke to the hub via ground ambulance with 47 (46%) patients traveling via air ambulance. The median spoke arrival to hub arrival time was 174 min, median spoke arrival to departure from spoke was 131 min, and median travel time was 39 min. The spoke arrival time to transfer initiation was 68 min. CT-perfusion obtained at the spoke and earlier initiation of transfer were statistically associated with shorter transfer times. CONCLUSION: Transfer of intra-arterial thrombectomy patients in Texas may take over 4 h from spoke arrival to hub arrival. This time may be shortened by earlier transfer initiation and acceptance.

5.
Biosens Bioelectron ; 172: 112780, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33157405

RESUMO

The number of CTCs in peripheral blood is of great significance for the early diagnosis, recurrence and prognosis evaluation of tumor patients. Consequently, it is required to develop simple and effective technique to realize the capture and detection of rare number CTCs. Herein, a SiO2, gelatin and biotinylated EpCAM aptamer P1 modified Fe3O4 immunomagnetic nanoparticles (IMNs) were prepared for the specific capture and nondestructive release of trace amounts of CTCs. Then, utilizing the peroxidase-like activity of single-walled carbon nanotubes (SWCNTs) and the effect of non-specific DNA sequences on this activity, a colorimetric probe was constructed by modifying the three DNA sequences (mDNA) onto the IMNs. When target cell was present, due to the specific interaction between cells and P1, the conformational structure of P1 was changed. Consequently, the mDNA linked with P1 on IMNs was replaced by the cell and released from IMNs. In this way, the quantification of captured CTCs could be converted to that of released mDNA. This strategy combined the capture and detection of CTCs as a whole and could detect down to 10 cells with a high selectivity. Finally, we achieved the accurate quantification of CTCs in lysed bloods from 12 clinical tumor patients, which exhibited a great promise for further clinical applications.

6.
Water Res ; 188: 116569, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33142118

RESUMO

Intimately coupled photocatalysis and biodegradation (ICPB) combining photocatalysis with microbial degradation is an attractive wastewater treatment technology. However, when prepared in conventional ways, the supported-photocatalysts aggregate frequently, detach easily from carriers, and prohibit the colonization of microorganisms inside the carriers. To overcome these challenges, silane coupling agent (SCA)-enhanced TiO2 coating method is developed in this study. The coupling agent γ-glycidoxypropyltrimethoxysilane (KH560) greatly enhanced the adhesion between photocatalysts and the carrier through ether and Ti-O-Si linkages. The dense TiO2 layer was firmly adhered to the carrier outer surface, and the loading amount reached 351.8±8.2 mg/g, over ten times higher than using the powder sintering method (31.5±2.4 mg/g). In the ICPB system constructed with the KH560-enhanced TiO2-supported polyurethane sponge (KH560-TiO2-PU) carriers, removal efficiencies of two model odor substances, 2-methylisoborneol (2-MIB) and geosmin (GSM), reached 88.9±0.3% and 85.0±1.0% in 12 h at an initial concentration of 500 ng/L respectively, which were 17.7±0.6% and 19.4±0.4% greater than those of the ICPB system prepared with the powder sintering method. After 5 operating cycles, the novel ICPB system remained stable with high 2-MIB and GSM removal efficiencies, reaching 89.9±0.8% and 86.1±0.2% respectively after 12h, while TiO2 peeling ratio was as low as 5.0±2.8%. Biofilms attached onto the carrier inner surface were resilient over the operating cycles with the increase of both richness and diversity of microbial communities. Analysis of biofilm microbial community and pollutant degradation pathways revealed the enhanced removal of 2-MIB and GSM in the novel ICPB system might be attributed to multiple factors. First, the alleviated aggregation and increased adhesion of photocatalysts onto carriers improved the overall photocatalysis efficiency. Second, biofilm inside of the carrier was protected and the microbial activity was well remained. Third, photocatalytic intermediate products were efficiently biodegraded by the enriched functional microbial populations, such as Thauera and Flavobacterium, with little concern of excessive oxidation. Collectively, this research provides a new technological solution that synergizes photocatalysis and biodegradation for effective removal of odorous substances in polluted natural water.


Assuntos
Odorantes , Silanos , Biodegradação Ambiental , Titânio
7.
J Phys Chem A ; 125(1): 411-422, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33378187

RESUMO

The OH-initiated photo-oxidation of piperazine and 1-nitropiperazine as well as the photolysis of 1-nitrosopiperazine were investigated in a large atmospheric simulation chamber. The rate coefficient for the reaction of piperazine with OH radicals was determined by the relative rate method to be kOH-piperazine = (2.8 ± 0.6) × 10-10 cm3 molecule-1 s-1 at 307 ± 2 K and 1014 ± 2 hPa. Product studies showed the piperazine + OH reaction to proceed both via C-H and N-H abstraction, resulting in the formation of 1,2,3,6-tetrahydropyrazine as the major product and in 1-nitropiperazine and 1-nitrosopiperazine as minor products. The branching in the piperazinyl radical reactions with NO, NO2, and O2 was obtained from 1-nitrosopiperazine photolysis experiments and employed analyses of the 1-nitropiperazine and 1-nitrosopiperazine temporal profiles observed during piperazine photo-oxidation. The derived initial branching between N-H and C-H abstraction by OH radicals, kN-H/(kN-H + kC-H), was 0.18 ± 0.04. All experiments were accompanied by substantial aerosol formation that was initiated by the reaction of piperazine with nitric acid. Both primary and secondary photo-oxidation products including 1-nitropiperazine and 1,4-dinitropiperazine were detected in the aerosol particles formed. Corroborating atmospheric photo-oxidation schemes for piperazine and 1-nitropiperazine were derived from M06-2X/aug-cc-pVTZ quantum chemistry calculations and master equation modeling of the pivotal reaction steps. The atmospheric chemistry of piperazine is evaluated, and a validated chemical mechanism for implementation in dispersion models is presented.

8.
World J Clin Cases ; 8(21): 5380-5388, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33269273

RESUMO

BACKGROUND: Pancreatic cancer with ovarian metastases is rare and easily misdiagnosed. Most patients are first diagnosed with ovarian cancer. We report a rare case of ovarian metastases secondary to pancreatic adenocarcinoma. We also review the literature to analyze the clinical characteristics of, diagnostic methods for, and perioperative management strategies for this rare malignancy. CASE SUMMARY: A 48-year-old woman with an abdominal mass presented to our hospital. Computed tomography revealed lesions in the pancreas and lower abdomen. Radiological examination and histological investigation of biopsy specimens revealed either an ovarian metastasis from a pancreatic neoplasm or two primary tumors, with metastasis strongly suspected. The patient simultaneously underwent distal pancreatectomy plus splenectomy by a general surgeon and salpingo-oophorectomy with hysterectomy by a gynecologist. Histological examination of the surgical specimen revealed a pancreatic adenocarcinoma (intermediate differentiation, mucinous) and a metastatic mucinous adenocarci-noma in the ovary. CONCLUSION: For this rare tumor, surgical resection is the most effective treatment, and the final diagnosis depends on tumor pathology.

9.
Int J Mol Sci ; 22(1)2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33374156

RESUMO

Social isolation and loneliness are risk factors for stroke. Elderly women are more likely to be isolated. Census data shows that in homeowners over the age of 65, women are much more likely to live alone. However, the underlying mechanisms of the detrimental effects of isolation have not been well studied in older females. In this study, we hypothesized that isolation impairs post-stroke recovery in aged female mice, leading to dysregulated microRNAs (miRNAs) in the brain, including those previously shown to be involved in response to social isolation (SI). Aged C57BL/6 female mice were subjected to a 60-min middle cerebral artery occlusion and were randomly assigned to either single housing (SI) or continued pair housing (PH) immediately after stroke for 15 days. SI immediately after stroke led to significantly more brain tissue loss after stroke and higher mortality. Furthermore, SI significantly delayed motor and sensory recovery and worsened cognitive function, compared to PH. A decrease in cell proliferation was seen in the dentate gyrus of SI mice assessed by bromodeoxyuridine (BrdU) labeling. miRNAome data analysis revealed changes in several miRNAs in the brain, such as miR-297a-3p and miR-200c-3p, which are known to regulate pathways involved in cell proliferation. In conclusion, our data suggest that SI can lead to a poor post-stroke recovery in aged females and dysregulation of miRNAs and reduced hippocampal cell proliferation.

10.
Bioresour Technol ; 321: 124461, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33302010

RESUMO

In this work, ammonia (NH3) torrefaction pretreatment (ATP) was developed to optimize the nitrogen and oxygen element distribution of microalgae via the N-doping and oxygen removal reaction, which could obviously improve the potential use of microalgae as a feedstock for the production of N-heterocyclic chemicals through fast pyrolysis technology. The nitrogen content increased from 8.3% of raw microalgae to 11.51% at 300 °C of ATP, while the oxygen content decreased from 35.96% to 21.61%, because of the Maillard reactions. In addition, the nitrogen-doping ratio and oxygen removal ratio of ATP was much higher than the conventional nitrogen torrefaction pretreatment (NTP). With the increase of ATP torrefaction temperature or the pyrolysis temperature, the relative content of the N-containing compounds increased, while the O-containing compounds decreased. For the N-heterocyclic chemicals, higher pyrolysis temperature favored the formation of pyrroles, while inhibited the formation of pyridines and indoles.

11.
Stat Med ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33274467

RESUMO

Panel count data occur often in event history studies and in these situations, one observes only incomplete information, the number of events rather than the occurrence times of each event, about the point processes of interest.2 Sometimes one may have to face a more complicated type of panel count data, mixed panel count data in which instead of the number of events, one only knows if there is an occurrence of an event.3 Furthermore, this may depend on the underlying point process of interest or in other words, the point process of interest and the observation type process may be related. To address this, a sieve maximum likelihood estimation approach is proposed with the use of Bernstein polynomials, and for the implementation, an EM algorithm is developed. To assess the finite sample performance of the proposed approach, a simulation study is conducted and suggests that it works well for practical situations. The method is then applied to a motivating example about cancer survivors.

12.
Neurology ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33268557

RESUMO

OBJECTIVE: To analyze the association between peri-ictal brainstem posturing semiologies with post-ictal generalized electroencephalographic suppression (PGES) and breathing dysfunction in generalized convulsive seizures (GCS). METHODS: Prospective, multicenter analysis of GCS. Ictal brainstem semiology was classified as (1) decerebration: bilateral symmetric tonic arm extension, (2) decortication: bilateral symmetric tonic arm flexion only, (3) hemi-decerebration: unilateral tonic arm extension with contralateral flexion and (4) absence of ictal tonic phase. Post-ictal posturing was also assessed. Respiration was monitored using thoraco-abdominal belts, video and pulse oximetry. RESULTS: Two hundred ninety-five seizures (180 patients) were analyzed. Ictal decerebration was observed in 122/295 (41.4%), decortication in 47/295 (15.9%) and hemi-decerebration in 28/295 (9.5%) seizures. Tonic phase was absent in 98/295 (33.2%) seizures. Postictal posturing occurred in 18/295 (6.1%) seizures. PGES risk increased with ictal decerebration (OR 14.79, 95% CI [6.18-35.39], p < 0.001), decortication (OR 11.26, 95% CI [2.96-42.93], p < 0.001), or hemi-decerebration (OR 48.56, 95% CI [6.07-388.78], p < 0.001) Ictal decerebration was associated with longer PGES (p = 0.011). Post-ictal posturing was associated with post-convulsive central apnea (PCCA) (p = 0.004), longer hypoxemia (p < 0.001) and SpO2 recovery (p = 0.035). CONCLUSIONS: Ictal brainstem semiology is associated with increased PGES risk. Ictal decerebration is associated with longer PGES. Post-ictal posturing is associated with a threefold increased risk of PCCA, longer hypoxemia and SpO2 recovery. Peri-ictal brainstem posturing may be surrogate biomarkers for GCS severity identifiable without in-hospital monitoring. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that peri-ictal brainstem posturing is associated with the GCS with more prolonged PGES and more severe breathing dysfunction.

13.
Protein Sci ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33336515

RESUMO

Focal adhesions (FAs) are integrin-containing protein complexes regulated by a network of hundreds of protein-protein interactions. They are formed in a spatiotemporal manner upon the activation of integrin transmembrane receptors, which is crucial to trigger cell adhesion and many other cellular processes including cell migration, spreading and proliferation. Despite decades of studies, a detailed molecular level understanding on how FAs are organized and function is lacking due to their highly complex and dynamic nature. However, advances have been made on studying key integrin activators, talin and kindlin, and their associated proteins, which are major components of nascent FAs critical for initiating the assembly of mature FAs. This review will discuss the structural and functional findings of talin and kindlin and their immediate interaction network, which will shed light upon the architecture of nascent FAs and how they act as seeds for FA assembly to dynamically regulate diverse adhesion-dependent physiological and pathological responses.

14.
Environ Sci Technol ; 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33381966

RESUMO

Interactions between bacteriophages (phages) and biofilms remain poorly understood despite the broad implications for microbial ecology, water quality, and microbiome engineering. Here, we demonstrate that lytic coliphage PHH01 can hitchhike on carrier bacteria Bacillus cereus to facilitate its infection of host bacteria, Escherichia coli, in biofilms. Specifically, PHH01 could adsorb onto the flagella of B. cereus, and thus phage motility was increased, resulting in 4.36-fold more effective infection of E. coli in biofilm relative to free PHH01 alone. Moreover, phage infection mitigated interspecies competition and enhanced B. cereus colonization; the fraction of B. cereus in the final biofilm increased from 9% without phages to 43% with phages. The mutualistic relationship between the coliphage and carrier bacteria was substantiated by migration tests on an E. coli lawn: the conjugation of PHH01 and B. cereus enhanced B. cereus colonization by 6.54-fold compared to B. cereus alone (6.15 vs 0.94 cm2 in 24 h) and PHH01 migration by 5.15-fold compared to PHH01 alone (10.3 vs 2.0 mm in 24 h). Metagenomic and electron microscopic analysis revealed that the phages of diverse taxonomies and different morphologies could be adsorbed by the flagella of B. cereus, suggesting hitchhiking on flagellated bacteria might be a widespread strategy in aquatic phage populations. Overall, our study highlights that hitchhiking behavior in phages can facilitate phage infection of biofilm bacteria, promote carrier bacteria colonization, and thus significantly influence biofilm composition, which holds promise for mediating biofilm functions and moderating associated risks.

15.
Curr Neurovasc Res ; 2020 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-33319684

RESUMO

BACKGROUND: Haptoglobin (Hp) binds to and facilitates clearance of heme. Compared with HP 1-1 and 1-2 genotypes, HP 2-2 has a weaker binding affinity and has been linked with increased inflammation and vasospasm after aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE: To assess levels of inflammatory cytokines in the context of different HP genotypes. METHODS: Patients were enrolled among those presenting with spontaneous aneurysmal SAH. Blood was drawn at four time points; <24 hours (T1), 24-48 hours (T2), 3-5 days (T3), and 6-8 days (T4). Blood was analyzed for levels of 41 cytokines at each time point, as well as for HP genotypes. These data were analyzed using mixed-effect models to assess the association between HP genotypes and cytokine levels. The modified Rankin Scale (mRS) score was obtained at discharge, 3 months, and 6 months. RESULTS: Fifty-seven patients were enrolled. Compared with HP 1-1 and 1-2, subjects encoding HP 2-2 had elevated levels of the following cytokines at all time points: FLT3L, IFNγ, IL-17A, TGFα, and VEGF-A. Elevations were also seen at some time points for IL-8, CSF2, FGF2, IL-7, IL-12p70, and TNFα. This study was not powered to detect differences in functional outcome; however, there were no significant differences in dichotomized mRS score between patients with HP 1- 1/1-2 or HP 2-2. CONCLUSION: Our findings indicate that HP 2-2 genotype leads to increased proinflammatory cytokine levels compared with HP 1-1/1-2 genotypes. These data may provide guidance for further studies seeking to identify testable markers for functional prognosis or targets for treatment.

16.
Sheng Li Xue Bao ; 72(6): 699-706, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33349826

RESUMO

Systematic integration teaching is a curriculum system focusing on organs and systems, which is an important direction of medical education reform in China. Based on the practice of integrated curriculum teaching in Dalian Medical University for more than 10 years, combined with the experience in 15 medical colleges and universities in China, this paper analyzed the modes of systematic integrated teaching at the basic medicine teaching stage for medical higher education, and specified the purpose and significance of this teaching reform. The results showed that: (1) The systematic integrated teaching is a well-accepted and widely used teaching mode in domestic medical colleges and universities, which mainly includes three types of methodologies, i.e., integration of basic medicine courses, integration of clinical medicine courses and integration of basic and clinical medicine courses. The systematic integrated teaching is carried out by reforming various teaching methods including problem-based learning (PBL), case-based learning (CBL) and team-based learning (TBL). (2) The systematic integration teaching at the basic medicine teaching stage can significantly optimize the transition between basic and clinical courses, promote the cooperation and exchange between basic and clinical teachers, and improve the medical students' knowledge construction and critical thinking, and teachers' teaching ability as well. (3) The systematic integration teaching concept of "Six focuses" and "Five combinations" effectively guides the design and implementation of the integrated curriculum at the basic medical teaching stage of Dalian Medical University. With the deepening and development of medical education system reform in China, giving full play to the respective advantages of the systematic integrated teaching and traditional single-subject teaching at the basic medicine stage, and strengthening the integration of basic and clinical courses will play an important role in optimizing medical education curriculum system with Chinese characteristics.


Assuntos
Educação Médica , Medicina , Grupo com Ancestrais do Continente Asiático , China , Currículo , Humanos
17.
Artigo em Inglês | MEDLINE | ID: mdl-33356996

RESUMO

The arcuate nucleus (ARC) of the hypothalamus comprises two antagonistic neuron populations critical for energy balance: the anorexigenic pro-opiomelanocortin (POMC) and the orexigenic agouti-related peptide (AgRP) neurons, which act as agonists and antagonists for neurons expressing the type IV melanocortin receptor (MC4R). MC4R activation increases energy expenditure and decreases food intake during positive energy balance states to prevent diet-induced obesity (DIO). Work from our group identified aberrant neuronal cell cycle events as both a novel biomarker and druggable target in the ARC for the treatment of DIO, demonstrating pharmacological restoration of retinoblastoma protein function in the ARC using cyclin-dependent kinase 4/6 (CDK4/6) inhibitors could treat DIO in mice by increasing lipid oxidation to selectively decrease fat mass. However, the role of CDK4/6 inhibitors on food intake was not examined. 4-week-old MC4R-loxTB mice were continuously administered high fat diet (60% Kcal fat). At 8 weeks of age, animals were administered 60 mg/kg abemaciclib orally or a saline control and monitored every two weeks for fat mass changes by MRI. At 11 weeks of age, all animals were injected bi-laterally in the paraventricular hypothalamus with AAV8 serotype virus expressing a Cre-mCherry and monitored for another five weeks. Restoration of MC4R expression in the PVN reduced food intake in hyperphagic-obese mice when given CDK4/6 inhibitor therapy. The reduced food intake was responsible for reduced fat mass in mice treated with abemaciclib. These results indicate that targeting POMC neurons could be an effective strategy in treating diet related obesity.

18.
Quant Imaging Med Surg ; 10(11): 2125-2132, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33139992

RESUMO

Background: Our study aims to evaluate the anesthetic efficacy of multiparametric magnetic resonance imaging/transrectal ultrasound (mpMRI/TRUS) fusion-guided targeted periprostatic nerve block (PNB) for transperineal template-guided prostate biopsy (TTPB). Methods: The patients who underwent mpMRI/TRUS fusion-guided prostate biopsy from May 2018 to March 2019 were randomized into two groups using a random number table. The intervention group (n=47) and the control group (n=45) received targeted PNB and traditional PNB, respectively. Visual analog scale (VAS) and visual numeric scale (VNS) scores were used to assess the patients' pain and quantify their satisfaction. Results: The total detection rate for prostate cancer was 45.7%, with a comparable positive rate between the intervention group (42.6%) and the control group (48.9%), which meant there was no significant difference between the groups (P=0.542). Patient age, prostate-specific antigen, prostate volume, suspicious lesions on mpMRI, number of cores, operation time, and biopsy time were comparable between the groups. The VAS scores during biopsy were significantly lower in the intervention group than in the control group [2 (1 to 3) vs. 2 (1 to 4), P=0.019]. Conversely, the VNS scores during biopsy were higher in the intervention group [3 (2 to 4) vs. 3 (2 to 3), P=0.015]. There were no significant differences in the pain scores or the satisfaction scores at 30 min after the procedure between the two groups. There were no significant differences between the groups for complications, such as hematuria, urinary retention, infection, hemospermia, and vasovagal reaction (P>0.05). Conclusions: Targeted PNB significantly relieved the pain and did not increase the incidence of complications for patients when compared with traditional PNB.

19.
J Thorac Dis ; 12(10): 5906-5915, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209423

RESUMO

Background: Micropapillary-predominant adenocarcinoma (MPA) of the lung is associated with extensive lymph node involvement and rapid terminal metastasis. However, this subtype has been recognized for only a few years, and there have been few studies of the molecular mechanisms associated with its highly invasive behaviors. Methods: The present study utilized immunohistochemical staining of surgically resected tissue blocks of MPA and lepidic-predominant lung adenocarcinoma to quantify the expression of specific biological markers in the WNT/ß-catenin pathway and evaluate their influence on the lymph nodes invasion of these two types of lung adenocarcinomas. Results: Our findings revealed that disruption of the cell membrane cadherin-catenin complex, which weakens the tumor cell adherence of MPA, was caused by the dissociation of ß-catenin from the cadherin-catenin complex and the subsequent accumulation of ß-catenin in the cytoplasm. This caused abnormal activation of the WNT/ß-catenin pathway. We also found that Wnt-1-specific overexpression and Axin1 inhibition in MPA could explain the redistribution and cytoplasmic retention of ß-catenin. Collectively, these findings suggest that an abnormality in the WNT/ß-catenin pathway could enhance the invasiveness of MPA through the overexpression of Wnt-1 and downregulation of Axin1 molecules. Conclusions: Our data support the need for further research regarding the WNT/ß-catenin pathway and the need to develop novel targeted therapies for restoration of tumor cell adherence and improvement of the prognosis of MPA.

20.
Water Res ; 189: 116586, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33166923

RESUMO

Calcification of anaerobic granular sludge causing the decrease of microbial activity has been focused for several decades, but the mechanism of calcification and deactivation of calcified granule are still lacking. In this study, the calcification process of anaerobic granular sludge was analyzed in the UASB reactor with long-term exposure to a high calcium level of 2 gCa2+L-1. Greyish-white calcified granules with larger size and density first appeared at the bottom of sludge bed. Characterization of granular surface demonstrated that calcified granules had smaller specific surface area and pore volume with the disappearing channels in granules visualized over calcification. The coverage of calcite on granular surface with a thickness of 500-600 µm was observed by a microscope, which is responsible for the blockage of channels for substrate diffusion and transport. The evaluation of mass transfer showed that the 'effectiveness factor' η of calcified granules was higher than 1.23, proving the existence of mass transfer resistance. Furthermore, the interactions between calcium and extracellular polymeric substances (EPS) revealed the possible mechanism of calcite location at the outer layer of anaerobic granular sludge: The bulk calcite directly binds the EPS such as humic acids via charging functional groups, and bulk CO32- could react easily with Ca2+ bound to EPS according to thermodynamic analysis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA