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1.
Transl Psychiatry ; 11(1): 609, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34853299

RESUMO

A relationship between the gut microbiome and alcohol use disorder has been suggested. Excessive alcohol use produces changes in the fecal microbiome and metabolome in both rodents and humans. Yet, these changes can be observed only in a subgroup of the studied populations, and reversal does not always occur after abstinence. We aimed to analyze fecal microbial composition and function in a translationally relevant baboon model of chronic heavy drinking that also meets binge criteria (drinking too much, too fast, and too often), i.e., alcohol ~1 g/kg and blood alcohol levels (BALs) ≥ 0.08 g/dL in a 2-hour period, daily, for years. We compared three groups of male baboons (Papio anubis): L = Long-term alcohol drinking group (12.1 years); S = Short-term alcohol drinking group (2.7 years); and C = Control group, drinking a non-alcoholic reinforcer (Tang®) (8.2 years). Fecal collection took place during 3 days of Drinking (D), followed by a short period (3 days) of Abstinence (A). Fecal microbial alpha- and beta-diversity were significantly lower in L vs. S and C (p's < 0.05). Members of the commensal families Lachnospiraceae and Prevotellaceae showed a relative decrease, whereas the opportunistic pathogen Streptococcus genus showed a relative increase in L vs. S and C (p's < 0.05). Microbiota-related metabolites of aromatic amino acids, tricarboxylic acid cycle, and pentose increased in L vs. S and C (FDR-corrected p < 0.01), with the latter two suggesting high energy metabolism and enhanced glycolysis in the gut lumen in response to alcohol. Consistent with the long-term alcohol exposure, mucosal damage and oxidative stress markers (N-acetylated amino acids, 2-hydroxybutyrate, and metabolites of the methionine cycle) increased in L vs. S and C (FDR-corrected p < 0.01). Overall, S showed few differences vs. C, possibly due to the long-term, chronic alcohol exposure needed to alter the normal gut microbiota. In the three groups, the fecal microbiome barely differed between conditions D and A, whereas the metabolome shifted in the transition from condition D to A. In conclusion, changes in the fecal microbiome and metabolome occur after significant long-term excessive drinking and are only partially affected by acute forced abstinence from alcohol. These results provide novel information on the relationship between the fecal microbiome and metabolome in a controlled experimental setting and using a unique non-human primate model of chronic excessive alcohol drinking.

2.
Decis Sci ; 52(2): 393-426, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34732907

RESUMO

A key challenge in information privacy research is how to value personal data with privacy consideration. In this study, we propose an experimental auction approach for valuing personal data. We use the generalized second-price auction to assess the monetary values of individuals' identity, demographic, and private information. We find that individuals' economic valuation of personal data is consistent with their actual self-disclosure behaviors. The economic valuation approach also produces results that are consistent with some well-accepted observations about consumer demographics and privacy. On the other hand, individuals' stated privacy preferences and attitudes are not consistent with their economic valuation. The findings of this study suggest that the proposed approach can be an effective mechanism for measuring personal data privacy. This study also provides important insights into valuing personal information for practical uses with several implications to policy decision makers, corporate executives and managers, data analysts, as well as decision science researchers.

3.
Plant Sci ; 311: 110996, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34482908

RESUMO

Rubus chingii, is widely distributed in many Asian countries and well known for its medicinal and dietary properties. Diversity of fruit color in raspberry has been attributed to the presence of either anthocyanins or carotenoids. In this study, we investigated anthocyanins and carotenoids, and their biosynthesis by LC-MS/MS. Six anthocyanins mainly consisted of flavanol-anthocyanins while five carotenoids mainly consisted of ß-citraurin esters. Flavanol-anthocyanins were produced from an offshoot of the anthocyanin biosynthesis, which started with biosynthesis of flavanols and anthocyanidin by leucoanthocyanidin reductase (LAR)/anthocyanidin reductase (ANR) and anthocyanidin synthase (ANS/LDOX) respectively. ß-citraurin esters were produced from cleavage of zeaxanthin and esterification by organic acid, which was an offshoot of the carotenoid biosynthesis. The offshoot started with biosynthesis of zeaxanthin and ß-citraurin by carotene ß-hydroxylase (CHYB/LUT5) and carotenoid cleavage dioxygenase (CCD) respectively. During fruit ripening, biosynthesis of flavanols and anthocyanins was down-regulated by genes/proteins involved in phenylpropanoid and flavonoid biosynthesis, while biosynthesis of ß-citraurin esters was up-regulated by imbalanced expression of genes/proteins involved in ß,ß-ring and ß, ε-ring hydroxylation. Thus, ß-citraurin esters, instead of anthocyanins imparted reddish color to the ripe fruit. These pigments and their biosynthesis in R. chingii are totally different from what occurs in other raspberry species.


Assuntos
Antocianinas/metabolismo , Carotenoides/metabolismo , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Pigmentação/fisiologia , Rubus/crescimento & desenvolvimento , Rubus/metabolismo , Antocianinas/genética , China , Frutas/anatomia & histologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Pigmentação/genética , Rubus/anatomia & histologia
4.
Plant Cell Rep ; 40(10): 1923-1946, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34333679

RESUMO

KEY MESSAGE: Combined transcriptomic and metabolic analyses reveal that fruit of Rubus chingii Hu launches biosynthesis of phenolic acids and flavonols at beginning of fruit set and then coordinately accumulated or converted to their derivatives. Rubus chingii Hu (Chinese raspberry) is an important dual functional food with nutraceutical and pharmaceutical values. Comprehensively understanding the mechanisms of fruit development and bioactive components synthesis and regulation could accelerate genetic analysis and molecular breeding for the unique species. Combined transcriptomic and metabolic analyses of R. chingii fruits from different developmental stages, including big green, green-to-yellow, yellow-to-orange, and red stages, were conducted. A total of 89,188 unigenes were generated and 57,545 unigenes (64.52%) were annotated. Differential expression genes (DEGs) and differentially accumulated metabolites (DAMs) were mainly involved in the biosynthesis of secondary metabolites. The fruit launched the biosynthesis of phenolic acids and flavonols at the very beginning of fruit set and then coordinately accumulated or converted to their derivatives. This was tightly regulated by expressions of the related genes and MYB and bHLH transcription factors. The core genes products participated in the biosynthesis of ellagic acid (EA) and kaempferol-3-O-rutinoside (K-3-R), such as DAHPS, DQD/SDH, PAL, 4CL, CHS, CHI, F3H, F3'H, FLS, and UGT78D2, and their corresponding metabolites were elaborately characterized. Our research reveals the molecular and chemical mechanisms of the fruit development of R. chingii. The results provide a solid foundation for the genetic analysis, functional genes isolation, fruit quality improvement and modifiable breeding of R. chingii.


Assuntos
Ácido Elágico , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Rubus/crescimento & desenvolvimento , Ácido Elágico/metabolismo , Flavonóis/biossíntese , Flavonóis/genética , Frutas/genética , Perfilação da Expressão Gênica , Hidroxibenzoatos/metabolismo , Quempferóis/genética , Quempferóis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Controle de Qualidade , Rubus/genética , Rubus/metabolismo , Terpenos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
5.
Front Plant Sci ; 12: 706667, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447402

RESUMO

Rubus chingii HU, is a medicinal and nutritious fruit, which is very rich in flavonoids. However, the biosynthesis of its flavonoids is poorly understood. This study examined flavonoids and the genes/proteins at four fruit ripening phases using LC-MS/MS and qPCR. Six major kinds of anthocyanins, primarily consisted of flavanol-anthocyanins, which differed in form or concentration from other Rubus species. In contrast to other known raspberries species, R. chingii had a decline in flavonoids during fruit ripening, which was due to down-regulation of genes and proteins involved in phenylpropanoid and flavonoid biosynthesis. Unexpectedly, anthocyanin also continuously decreased during fruit maturation. This suggests that anthocyanins are not responsible for the fruit's reddish coloration. Flavanol-anthocyanins were derived from the proanthocyanidin pathway, which consumed two flavonoid units both produced through the same upstream pathway. Their presence indicates a reduction in the potential biosynthesis of anthocyanin production. Also, the constantly low expression of RchANS gene resulted in low levels of anthocyanin biosynthesis. The lack of RchF3'5'H gene/protein hindered the production of delphinidin glycosides. Flavonoids primarily comprising of quercetin/kaempferol-glycosides were predominately located at fruit epidermal-hair and placentae. The proportion of receptacle/drupelets changes with the maturity of the fruit and may be related to a decrease in the content of flavonoids per unit mass as the fruit matures. The profile and biosynthesis of R. chingii flavonoids are unique to Rubus. The unique flavonol pathways of R. chingii could be used to broaden the genetic diversity of raspberry cultivars and to improve their fruit quality.

6.
J Bone Miner Res ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34464000

RESUMO

Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) both influence blood phosphate levels by regulating urinary phosphate reabsorption. Clinical data suggest that adequate renal phosphate handling requires the presence of both FGF23 and PTH, but robust evidence is lacking. To investigate whether the phosphaturic effects of PTH and FGF23 are interdependent, 11 patients with hypoparathyroidism, which features high blood phosphate in spite of concomitant FGF23 elevation, and 1 patient with hyperphosphatemic familial tumoral calcinosis (HFTC), characterized by deficient intact FGF23 action and resulting hyperphosphatemia, were treated with synthetic human PTH 1-34 (hPTH 1-34). Biochemical parameters, including blood phosphate, calcium, intact FGF23 (iFGF23), nephrogenic cAMP, 1,25(OH)2 vitamin D (1,25D), and tubular reabsorption of phosphate (TRP), were measured at baseline and after hPTH 1-34 treatment. In patients with hypoparathyroidism, administration of hPTH 1-34 increased nephrogenic cAMP, which resulted in serum phosphate normalization followed by a significant decrease in iFGF23. TRP initially decreased and returned to baseline. In the patient with HFTC, hPTH 1-34 administration also increased nephrogenic cAMP, but this did not produce changes in phosphate or TRP. No changes in calcium were observed in any of the studied patients, although prolonged hPTH 1-34 treatment did induce supraphysiologic 1,25D levels in the patient with HFTC. Our results indicate that PTH and FGF23 effects on phosphate regulation are interdependent and both are required to adequately regulate renal phosphate handling. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.

7.
Sci Rep ; 11(1): 15080, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301985

RESUMO

Blueberry is rich in anthocyanins which accumulate during fruit maturation. Previous studies mostly focus on their translational/transcriptional regulation, but usually underestimate their post-transcriptional regulation, e.g. small RNAs. This study aimed to identify sRNAs and their potential pathways associated with anthocyanin biosynthesis. During three typical phases of fruit maturation (green, pink, and blue), we investigated dynamic changes of sRNA by deep sequencing sRNA and examined the interaction of sRNAs with their target genes by degradome and RLM-PCR. During maturation, up-regulation of VcmiRNA156 and VcmiR393 resulted in down-regulation of VcSPLs and VcTIR1/AFBs, respectively. An important gene of anthocyanin biosynthesis, VcDFR, was substantially down-regulated at both the mRNA and protein levels, and potentially responded to regulation of VcSPLs and VcTIR1/AFBs. Additionally, indole acetic acid (IAA) and abscisic acid (ABA) were involved in the regulation of anthocyanin biosynthesis by interacting with VcmiR393-TIR1/AFBs and VcmiRNA319-VcMYBs respectively. This information provides another insight into blueberry anthocyanin biosynthesis.


Assuntos
Antocianinas/genética , Mirtilos Azuis (Planta)/genética , Frutas/genética , RNA/genética , Ácido Abscísico/metabolismo , Mirtilos Azuis (Planta)/metabolismo , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Plantas/efeitos dos fármacos , Regulação para Cima/genética
8.
J Clin Endocrinol Metab ; 106(10): 3007-3018, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34097071

RESUMO

CONTEXT: Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are frequent accompaniments of depression, and studies have documented the role of stress and stressful life events in the ontogeny of perimenopausal depressions (PMD). Because HPA axis function in women is further modulated both by aging and ovarian steroids, it is possible that a dysregulated HPA axis contributes to the increased risk of PMD. OBJECTIVE: We examined HPA axis function in perimenopausal women with and without depression using the combined dexamethasone-corticotropin-releasing hormone (Dex/CRH) test. METHODS: Dex/CRH tests were performed on 20 women with PMD and 20 women who were also perimenopausal but without current or past depression (control women). Main outcome measures were plasma levels of cortisol and adrenocorticotropin (ACTH) and 24-hour urinary free cortisol (UFC). Five women took chronic stable medications, otherwise all women were medically healthy, and both groups were comparable with respect to reproductive stage and age. Standardized symptom rating scales were administered to each woman prior to Dex/CRH testing. RESULTS: No group differences were present in either baseline or stimulated ACTH and cortisol secretion. Baseline plasma measures of estradiol, progesterone, and 24-hour UFC levels similarly did not differ in PMD and control women. CONCLUSION: Despite reports of increased stress responsiveness in PMD, we observed no abnormalities of HPA axis activity associated with PMD compared with women without depression. These findings suggest that PMD is not uniformly associated with HPA dysregulation and could reflect underlying pathophysiologic processes that are distinct from women with nonreproductive-related depressions.


Assuntos
Hormônio Adrenocorticotrópico/efeitos dos fármacos , Hormônio Liberador da Corticotropina/administração & dosagem , Depressão/fisiopatologia , Dexametasona/administração & dosagem , Hidrocortisona/metabolismo , Perimenopausa/efeitos dos fármacos , Hormônio Adrenocorticotrópico/sangue , Adulto , Estradiol/sangue , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Pessoa de Meia-Idade , Perimenopausa/metabolismo , Perimenopausa/psicologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Progesterona/sangue
9.
J Pediatr ; 238: 249-258.e3, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34144034

RESUMO

OBJECTIVES: To assess the US public's views on whether the potential medical benefits of phase 1 pediatric oncology trials justify the risks. STUDY DESIGN: Online survey of a nationally representative sample of US adults. Participants were presented with a hypothetical scenario in which they have a 10-year-old child with advanced cancer. They were then offered the option of giving their child supportive care or trying one more potential treatment, in the research or clinical care setting, which has the same risks and potential medical benefits as the average phase 1 pediatric oncology trial. We assessed what percentage of respondents thought the potential medical benefits justify the risks. RESULTS: In total, 1658 of the 2508 individuals who were sent the survey participated (response rate = 66.1%). Of those who passed all 3 test questions indicating understanding, 67.1% in the research scenario and 58.5% in the clinical care scenario regarded the potential medical benefits of an average phase 1 pediatric oncology trial as equal to or greater than the risks. In addition, 53.4% of respondents in the research scenario thought it was appropriate for researchers to conduct a study in children with these risks and potential medical benefits, and 46.9% stated they would enroll their own child in such a trial. CONCLUSIONS: A majority of the US public regards the potential medical benefits of average phase 1 pediatric oncology trials as justifying the risks. This finding suggests that these trials are ethically appropriate and approvable in patients who have no more effective treatment options. At the same time, a significant minority thought the potential medical benefits do not justify the risks, suggesting these trials should be approved only when they have significant social value. Moreover, approximately one-half of respondents regarded the trials as inappropriate and would not enroll their own child, underscoring the need for a rigorous informed consent process that accurately educates parents regarding the risks, potential medical benefits, and alternatives, so they can decide whether to enroll their child based on their own preferences and goals.


Assuntos
Ensaios Clínicos Fase I como Assunto , Oncologia/métodos , Neoplasias/tratamento farmacológico , Adulto , Criança , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Consentimento Livre e Esclarecido/psicologia , Masculino , Pessoa de Meia-Idade , Pais/psicologia , Medição de Risco , Inquéritos e Questionários , Estados Unidos
10.
Nat Commun ; 12(1): 3391, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099646

RESUMO

Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled clinical trial of tofacitinib in SLE subjects (ClinicalTrials.gov NCT02535689). In this study, 30 subjects are randomized to tofacitinib (5 mg twice daily) or placebo in 2:1 block. The primary outcome of this study is safety and tolerability of tofacitinib. The secondary outcomes include clinical response and mechanistic studies. The tofacitinib is found to be safe in SLE meeting study's primary endpoint. We also show that tofacitinib improves cardiometabolic and immunologic parameters associated with the premature atherosclerosis in SLE. Tofacitinib improves high-density lipoprotein cholesterol levels (p = 0.0006, CI 95%: 4.12, 13.32) and particle number (p = 0.0008, CI 95%: 1.58, 5.33); lecithin: cholesterol acyltransferase concentration (p = 0.024, CI 95%: 1.1, -26.5), cholesterol efflux capacity (p = 0.08, CI 95%: -0.01, 0.24), improvements in arterial stiffness and endothelium-dependent vasorelaxation and decrease in type I IFN gene signature, low-density granulocytes and circulating NETs. Some of these improvements are more robust in subjects with STAT4 risk allele.


Assuntos
Aterosclerose/prevenção & controle , Inibidores de Janus Quinases/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Piperidinas/administração & dosagem , Pirimidinas/administração & dosagem , Adulto , Idoso , Animais , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/imunologia , HDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Predisposição Genética para Doença , Fatores de Risco de Doenças Cardíacas , Humanos , Inibidores de Janus Quinases/efeitos adversos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Pirimidinas/efeitos adversos , Fator de Transcrição STAT4/genética , Resultado do Tratamento , Rigidez Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Adulto Jovem
12.
Behav Brain Res ; 411: 113389, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34058267

RESUMO

BACKGROUND: Brain development is a prolonged process and it is sensitive to the environment during critical periods. Stress in early life is believed to increase vulnerability to depression, while enriched environment (EE) has beneficial effects on neural plasticity and depression. In this study, we compared the therapeutic effect of EE during different periods on early life stress-induced depression, and investigated the role of brain-derived neurotrophic factor (BDNF) and protein kinase B (AKT) on the effect of EE. Plasma corticosterone level was also detected to evaluate the reactivity of hypothalamic-pituitary-adrenal axis. METHODS: C57BL/6 mice were subjected to a 4-h maternal separation (MS) procedure during postnatal days 2-21. After this separation, the mice were assigned to standard environment groups (SE), EE in the early period groups (3-8 weeks, EEE) and EE in the adult groups (8-13 weeks, EEA). Depression and anxiety behavior were evaluated at 14-weeks of age. The plasma corticosterone was quantified utilizing enzyme-linked immunosorbent assay. Hippocampus BDNF and AKT/p-AKT were detected using Western blotting. RESULTS: The results showed that MS increased depression and anxiety level, while EE in both intervention periods alleviated the symptoms of depression and anxiety. The EEE group showed better effects in terms of anhedonia and anxiety than the EEA group. The difference in despair behavior between the EEE and EEA groups was not significant. MS increased plasma corticosterone level, while EE decreased corticosterone level in both intervention periods. EE increased BDNF and p-AKT expression in the hippocampus, with stronger effects in the EEE group. CONCLUSION: EE during the early development period was more effective in alleviating depression and anxiety induced by early life stress. BDNF and AKT may play a significant role in the effect of EE, and further research is needed to explore the detailed neurobiological mechanisms.

13.
Plant Physiol Biochem ; 163: 76-86, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33819717

RESUMO

Carotenoids are one of the most abundant pigments in raspberries. Rubus chingii Hu, indigenous to China, is traditionally consumed for health benefits. However, the carotenoid composition and pathways of R. chingii have not yet been studied. In this study, the components of carotenoids and genes/proteins involved in their biosynthesis were investigated during four fruit ripening phases via LC-MS/MS. Zeaxanthin, ß-citraurin and its esters, first identified in Rubus, gradually accumulated during fruit maturation. These compounds, rather than anthocyanins, were responsible for the ripe fruit coloration. In carotenoid metabolism, upstream synthesis genes of RcPSY2 (CL1406.Contig2), RcPDS1 (CL7625.Contig2), RcZDS1 (CL590.Contig6) and RcCRTISO1 (CL6919.Contig2) were up-regulated in gene/protein expression to accelerate carotene biosynthesis. Downstream genes of RcLUT5CHYB/CYP97A (CL8884.Contig3) and RcCHYB/BCH (CL7966.Contig1) were up-regulated in gene/protein expression, while RcCHYE/CYP97C (CL9380.Contig1/2) were maintained at low levels. RcLCYE (Unigene19570) was down-regulated while RcLCYB (CL7586.Contig1) was up-regulated and then down-regulated. These differential gene/protein expressions between LCYB and LCYE, and between CHYE and CHYB led to zeaxanthin accumulation by elevating its biosynthetic enzymes and lowering enzymes for lutein biosynthesis. In apocarotenoid biosynthesis, RcCCD (CL1310.Contig3) was up-regulated in gene/protein expression, which raised the content of ß-citraurin and its esters. Additionally, these genes/proteins diverged into different subgroups with distinct pattens of expression, suggesting their difference in function. For example, RcPSY1/3, RcZDS2, and RcCRTISO2/3 genes were expressed at very low levels, suggesting that they may be active in other tissues rather than in fruit. The mechanism of zeaxanthin and ß-citraurin biosynthesis is responsible for fruit coloration, which is completely novel to Rubus.


Assuntos
Rubus , China , Cromatografia Líquida , Frutas/genética , Regulação da Expressão Gênica de Plantas , Espectrometria de Massas em Tandem
14.
Abdom Radiol (NY) ; 46(7): 3301-3308, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33688985

RESUMO

PURPOSE: To assess differences in FDG-PET/CT uptake among four subtypes of renal tumors: clear cell RCC (ccRCC), papillary type I and II RCC (pRCC), and oncocytoma. METHODS: This retrospective study investigated 33 patients with 98 hereditary renal tumors. Lesions greater than 1 cm and patients with a timeframe of less than 18 months between preoperative imaging and surgery were considered. FDG-PET/CT images were independently reviewed by two nuclear medicine physicians, blinded to clinical information. Volumetric lesion SUVmean was measured and used to calculate a target-to-background ratio respective to liver (TBR). The Shrout-Fleiss intra-class correlation coefficient was used to assess reliability between readers. A linear mixed effects model, accounting for within-patient correlations, was used to compare TBR values of primary renal lesions with and without distant metastasis. RESULTS: The time interval between imaging and surgery for all tumors had a median of 77 (Mean: 139; Range: 1-512) days. Intra-class reliability of mean TBR resulted in a mean κ score of 0.93, indicating strong agreement between the readers. The mixed model showed a significant difference in mean TBR among the subtypes (p < 0.0001). Pairwise comparison showed significant differences between pRCC type II and ccRCC (p < 0.0001), pRCC type II and pRCC type I (p = 0.0001), and pRCC type II and oncocytoma (p = 0.0016). Furthermore, a significant difference in FDG uptake was present between primary pRCC type II renal lesions with and without distant metastasis (p = 0.023). CONCLUSION: pRCC type II lesions demonstrated significantly higher FDG activity than ccRCC, pRCC type I, or oncocytoma. These findings indicate that FDG may prove useful in studying the metabolic activity of renal neoplasms, identifying lesions of highest clinical concern, and ultimately optimizing active surveillance, and personalizing management plans.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/genética , Diferenciação Celular , Fluordesoxiglucose F18 , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Reprodutibilidade dos Testes , Estudos Retrospectivos
15.
Complement Ther Clin Pract ; 42: 101302, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33445147

RESUMO

BACKGROUND: and purpose: Preoperative anxiety is an important factor for postoperative complications, and many patients are using aromatherapy to relieve preoperative anxiety. This study aimed to evaluate the effect of aromatherapy on preoperative anxiety in adult patients. METHODS: An electronic search of six databases (Cochrane Library, PubMed, Embase, CINAHL, CNKI, and WanFang Data) was conducted for full-text publications of trials published from the inception of the databases to February 20, 2020. All randomized controlled trials (RCTs) where aromatherapy was used for treatment of preoperative anxiety were included. Interventions included all types of aromatherapy compared to standard care or placebo. The primary outcome was self-rated anxiety and the secondary outcome was adverse effect. Two researchers independently screened and extracted relevant data. A random-effects model was utilized to calculate the effect size as mean difference (MD). RESULTS: Our search retrieved 347 records. Thirteen trials were included for qualitative analysis, of which ten RCTs with 750 patients were included for meta-analysis. Most studies had a high or unclear selection and performance bias. Overall, aromatherapy was found to decrease preoperative anxiety significantly compared to the control group (MD = -3.95, 95%CI [-6.36, -1.53], P = 0.001). According to subgroup analysis, most subgroups showed a significant effect of aromatherapy on preoperative anxiety, except for the no treatment subgroup (MD: 5.40, 95%CI: 7.76 to 0.71) and female subgroup (MD: 3.96, 95%CI: 9.19 to 1.27). CONCLUSION: Aromatherapy may be an effective complementary treatment for preoperative anxiety. Nevertheless, due to methodological limitations of the included trials, further studies with strict control of the research design are required for firm recommendations.


Assuntos
Aromaterapia , Adulto , Ansiedade/terapia , Transtornos de Ansiedade , Feminino , Humanos , Complicações Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Cardiovasc Intervent Radiol ; 44(5): 774-781, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33409547

RESUMO

PURPOSE: To compare needle placement performance using an augmented reality (AR) navigation platform implemented on smartphone or smartglasses devices to that of CBCT-guided fluoroscopy in a phantom. MATERIALS AND METHODS: An AR application was developed to display a planned percutaneous needle trajectory on the smartphone (iPhone7) and smartglasses (HoloLens1) devices in real time. Two AR-guided needle placement systems and CBCT-guided fluoroscopy with navigation software (XperGuide, Philips) were compared using an anthropomorphic phantom (CIRS, Norfolk, VA). Six interventional radiologists each performed 18 independent needle placements using smartphone (n = 6), smartglasses (n = 6), and XperGuide (n = 6) guidance. Placement error was defined as the distance from the needle tip to the target center. Placement time was recorded. For XperGuide, dose-area product (DAP, mGy*cm2) and fluoroscopy time (sec) were recorded. Statistical comparisons were made using a two-way repeated measures ANOVA. RESULTS: The placement error using the smartphone, smartglasses, or XperGuide was similar (3.98 ± 1.68 mm, 5.18 ± 3.84 mm, 4.13 ± 2.38 mm, respectively, p = 0.11). Compared to CBCT-guided fluoroscopy, the smartphone and smartglasses reduced placement time by 38% (p = 0.02) and 55% (p = 0.001), respectively. The DAP for insertion using XperGuide was 3086 ± 2920 mGy*cm2, and no intra-procedural radiation was required for augmented reality. CONCLUSIONS: Smartphone- and smartglasses-based augmented reality reduced needle placement time and radiation exposure while maintaining placement accuracy compared to a clinically validated needle navigation platform.


Assuntos
Fluoroscopia/métodos , Imageamento Tridimensional/métodos , Imagens de Fantasmas , Óculos Inteligentes , Smartphone , Tomografia Computadorizada de Feixe Cônico Espiral/métodos , Cirurgia Assistida por Computador/métodos , Realidade Aumentada , Humanos
17.
IEEE Trans Pattern Anal Mach Intell ; 43(9): 3005-3023, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33166249

RESUMO

Face anti-spoofing (FAS) plays a vital role in securing face recognition systems. Existing methods heavily rely on the expert-designed networks, which may lead to a sub-optimal solution for FAS task. Here we propose the first FAS method based on neural architecture search (NAS), called NAS-FAS, to discover the well-suited task-aware networks. Unlike previous NAS works mainly focus on developing efficient search strategies in generic object classification, we pay more attention to study the search spaces for FAS task. The challenges of utilizing NAS for FAS are in two folds: the networks searched on 1) a specific acquisition condition might perform poorly in unseen conditions, and 2) particular spoofing attacks might generalize badly for unseen attacks. To overcome these two issues, we develop a novel search space consisting of central difference convolution and pooling operators. Moreover, an efficient static-dynamic representation is exploited for fully mining the FAS-aware spatio-temporal discrepancy. Besides, we propose Domain/Type-aware Meta-NAS, which leverages cross-domain/type knowledge for robust searching. Finally, in order to evaluate the NAS transferability for cross datasets and unknown attack types, we release a large-scale 3D mask dataset, namely CASIA-SURF 3DMask, for supporting the new 'cross-dataset cross-type' testing protocol. Experiments demonstrate that the proposed NAS-FAS achieves state-of-the-art performance on nine FAS benchmark datasets with four testing protocols.

18.
Neuropsychobiology ; 80(4): 279-287, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33238265

RESUMO

INTRODUCTION: The interleukin-6/janus kinase 2/signal transducer and activator of transcription 3 (IL-6/JAK2/STAT3) pathway plays an important role in immune function, but little research has focused on this pathway in depression. We sought to examine the relationship between the IL-6/JAK2/STAT3 pathway and depressive-like behavior. METHODS: Using a chronic mild stress (CMS) paradigm, a total of 36 adult male Sprague-Dawley rats were divided into four matched groups: (1) control + vehicle, (2) CMS + vehicle, (3) control + paroxetine, and (4) CMS + paroxetine. We investigated the effects of CMS on depressive-like behavior by using the forced swimming test (FST). Subsequently, the mRNA levels of members of the IL-6/JAK2/STAT3 pathway were assessed by qRT-PCR. RESULTS: We found that rats exposed to CMS displayed a significant increase in immobility time and a decrease in climbing time in the FST. Moreover, mRNA levels of IL-6, JAK2, and STAT3 in the hypothalamus were increased following CMS. We also found that mRNA levels of IL-6, JAK2, and STAT3 were normalized by paroxetine administration, which coincided with normalization of the depressive-like behavior. CONCLUSIONS: The IL-6/JAK2/STAT3 pathway may be activated in depression, and targeting this pathway may provide a novel effective therapeutic approach for the treatment of depression.

19.
Mater Sci Eng C Mater Biol Appl ; 118: 111543, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33255095

RESUMO

The regenerated silk fibroin (RSF)-based microfluidic device has attracted tremendous interests in recent years due to its excellent biocompatibility, mild processing conditions, and all aqueous casting production. However, the need of a micro-fabricated mold in the manufacture process greatly hinder its practical applications. Herein, we introduce an adhesive tape-assisted etching method with LiBr solution as the etchant to prepare RSF microfluidic devices. An engraved adhesive tape is used as the mask to cover on the surface of a RSF film. Then, LiBr solution is dropped on the mask to etch RSF in concentration- and duration-dependent manners. During this process, the LiBr-treated RSF transits from insoluble ß-sheet crystallites to soluble conformations. The as-prepared RSF microfluidic devices possess good chemical resistance and excellent tolerance to mechanical deformation. RSF microfluidic systems with different patterns were fabricated to demonstrate the universality of the approach. A concentration gradient generator and a blood vessel-like channel were manufactured for the preparation of solutions with gradient pHs and the growth of living cells, respectively. The proposed strategy has great potentials in the facile fabrication of low-cost RSF microfluidic devices for tissue engineering and biomedical analysis.


Assuntos
Bombyx , Fibroínas , Animais , Dispositivos Lab-On-A-Chip , Microfluídica , Seda , Engenharia Tecidual , Água
20.
Lancet Infect Dis ; 21(5): 697-710, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33333013

RESUMO

BACKGROUND: Clindamycin is strongly recommended as an adjunctive treatment to ß-lactam antibiotics in patients with severe invasive group A ß-haemolytic streptococcal (iGAS) infections. However, there is little evidence of a benefit in the use of clindamycin in humans, and its role, if any, in treating patients with invasive non-group A/B ß-haemolytic streptococcal (iNABS) infections is unclear. METHODS: For this retrospective multicentre cohort study, we used a dataset from patients in the Cerner Health Facts database, which contains electronic health-based data from 233 US hospitals. We queried the Cerner Health Facts database for inpatients (no age restriction) admitted to hospital in 2000-15, with any clinical cultures positive for ß-haemolytic streptococcal taxa of interest, and who had received ß-lactam antibiotics within 3 days either side of culture sampling. This group of patients was then queried for those who had also received intravenous or oral clindamycin within 3 days either side of culture sampling. Patients were excluded if they had polymicrobial growth or clindamycin non-susceptible isolates, received linezolid, or had missing variable data needed for analysis. Patients were categorised by Lancefield group (iGAS or iNABS); ß-lactam antibiotic-treated patients who had received clindamycin were propensity-matched (1:2) to those who did not receive clindamycin separately for iGAS and iNABS cohorts, and logistic regression was then used to account for residual confounding factors. The primary outcome was the adjusted odds ratio (aOR) of in-hospital mortality in propensity-matched patients treated with adjunctive clindamycin versus those not treated with clindamycin in the iGAS and iNABS infection cohorts. FINDINGS: We identified 1956 inpatients with invasive ß-haemolytic streptococcal infection who had been treated with ß-lactam antibiotics across 118 hospitals (1079 with iGAS infections and 877 with iNABS infections). 459 (23·4%) of these patients had received adjunctive clindamycin treatment (343 [31·7%] patients with iGAS infections and 116 [13·2%] patients with iNABS infections). The effect of adjunctive clindamycin therapy on in-hospital mortality differed significantly and showed the opposite trend in iGAS and iNABS infection cohorts (p=0·013 for an interaction). In the iGAS cohort, in-hospital mortality in propensity-matched patients who received adjunctive clindamycin (18 [6·5%] of 277 patients) was significantly lower than in those who did not (55 [11·0%] of 500 patients; aOR 0·44 [95% CI 0·23-0·81]). This survival benefit was maintained even in patients without shock or necrotising fasciitis (six [2·6%] of 239 patients treated with adjunctive clindamycin vs 27 [6·1%] of 422 patients not treated with adjunctive clindamycin; aOR 0·40 [0·15-0·91]). By contrast, in the iNABS infection cohort, in-hospital mortality in propensity-matched patients who received adjunctive clindamycin (ten [9·8%] of 102) was higher than in those who did not (nine [4·6%] of 193), but this difference was not significant (aOR 2·60 [0·94-7·52]). Several subset analyses found qualitatively similar results. INTERPRETATION: Real-world data suggest that increased use of adjunctive clindamycin for invasive iGAS infections, but not iNABS infections, could improve outcomes, even in patients without shock or necrotising fasciitis. FUNDING: Intramural Research Program of the National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Disease.


Assuntos
Clindamicina/uso terapêutico , Hospitais , Infecções Estreptocócicas/tratamento farmacológico , beta-Lactamas/uso terapêutico , Adulto , Idoso , Antibacterianos/uso terapêutico , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Streptococcus pyogenes/efeitos dos fármacos , Estados Unidos
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