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1.
Am J Gastroenterol ; 114(9): 1531-1538, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31397679

RESUMO

OBJECTIVES: Although low fiber intake has been considered a risk factor for diverticulitis, prospective evidence is limited in women despite having a disproportionate burden of disease, with little known about variation in the protective effects according to food sources. We assessed the associations of intakes of fiber and major food sources of fiber including fruits and vegetables with risk of diverticulitis in a large cohort of women. METHODS: We followed 50,019 women in the Nurses' Health Study (1990-2014) who were aged 43-70 years and free of diverticulitis, cancer, and inflammatory bowel disease at baseline. Incident diverticulitis was identified through self-report with validity confirmed by review of medical records. RESULTS: We documented 4,343 incident cases of diverticulitis, encompassing 1,106,402 person-years of follow-up. Compared with participants in the lowest quintile, the multivariable hazard ratio of diverticulitis in the highest quintile of total fiber intake was 0.86 (95% confidence interval: 0.78-0.95; P-trend = 0.002). Fiber from fruits and cereals, but not vegetables, was associated with a decreased risk of diverticulitis. Furthermore, intake of total whole fruit intake and specific fruits such as apples/pears and prunes were associated with reduced risk of diverticulitis with a multivariable hazard ratio for diverticulitis of 0.95 (0.92-0.98; P-trend < 0.001) for every serving increase of total whole fruit intake per day. DISCUSSION: Higher intake of dietary fiber and fiber from different food sources, except for vegetable fiber, are associated with a lower risk of diverticulitis in women. A greater intake of whole fruit is also associated with reduced risk.

4.
J Acoust Soc Am ; 145(4): EL291, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31046357

RESUMO

Although the acoustic feedback could be alleviated by the neutralization method with a feedback model, an active noise control system could still suffer from being unstable if the feedback path exhibits significant variations. In this letter, a modified Wiener controller is introduced to enhance the robust stability with a fixed feedback neutralization filter. The proposed controller is designed with frequency-weighted penalties, which are adjusted iteratively according to Nyquist stability criterion. Experiment results based on a ventilation duct system shows that the robust stability could be achieved with the proposed method while a relatively good performance could be maintained.

5.
Int J Biochem Cell Biol ; 113: 48-57, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128260

RESUMO

Treatment outcomes for hepatocellular carcinoma (HCC) remain unsatisfactory, and effective new therapeutic methods are urgently needed. Gossypol has been shown to have an anti-HCC effect, but the underlying mechanism requires further study. In this study, we found gossypol inhibited HCC cells in vitro and in vivo. Typical apoptosis was induced in HCC cells. Dilated ER and autophagosomes were observed by electron microscopy, and the activation of the unfolded protein response and autophagy markers suggested that gossypol induced both ER stress and autophagy. C/EBP homologous protein was the key factor that led to apoptotic cell death, whereas inositol-requiring enzyme 1α and eukaryotic initiation factor 2α played a protective role. Autophagy protected the cells from ER stress-related apoptosis. Both in vitro and in vivo studies indicated that inhibition of autophagy enhanced the anti-HCC effect of gossypol. Taken together, ER stress is the molecular mechanism underlying gossypol-induced apoptosis and autophagy. Gossypol exhibits anti-HCC activity primarily through the activation of apoptosis. However, gossypol-induced autophagy protects HCC cells from ER stress. Therefore, a combination therapy of gossypol and autophagy inhibitors may lead to an enhanced anti-HCC effect.

6.
Int J Cancer ; 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31037736

RESUMO

Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.

8.
Int J Cancer ; 145(11): 3040-3051, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31044426

RESUMO

Epidemiologic evidence relating fiber intake to colorectal cancer (CRC) remains inconclusive and data are limited on different food sources of fiber and heterogeneity by tumor subsite and molecular profile. We prospectively followed for CRC incidence 90,869 women from the Nurses' Health Study (1980-2012) and 47,924 men from the Health Professionals Follow-up Study (1986-2012), who completed a validated food frequency questionnaire every 4 years. Cox proportional hazards regression was used to examine the associations with CRC risk for total, cereal, fruit and vegetable fiber and whole grains. We also assessed the associations according to tumor subsites (proximal colon, distal colon and rectum) and molecular markers (microsatellite instability, BRAF mutation, CpG island methylator phenotype and KRAS mutation). We documented 3,178 CRC cases during 3,685,903 person-years of follow-up in the NHS and HPFS. Intake of total dietary fiber was not associated with CRC risk after multivariable adjustment in either women (hazard ratio [HR] comparing extreme deciles, 1.17; 95% CI, 0.92-1.48, ptrend = 0.55) or men (HR, 0.90; 95% CI, 0.67-1.21, ptrend = 0.47). Higher intake of cereal fiber and whole grains was associated with lower CRC risk in men with an HR of 0.75 (95% CI, 0.57-1.00) and 0.72 (95% CI, 0.54-0.96), respectively. No heterogeneity was detected by tumor subsite or molecular markers (pheterogeneity > 0.05). Higher intake of total dietary fiber within the range of a typical American diet is unlikely to substantially reduce CRC risk. The potential benefit of cereal fiber and whole grains in men warrants further confirmation.

9.
Cancer Causes Control ; 30(6): 637-649, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30963391

RESUMO

BACKGROUND: A preventive potential of high calcium intake against colorectal cancer has been indicated for distal colon cancer, which is inversely associated with high-level CpG island methylator phenotype (CIMP), high-level microsatellite instability (MSI), and BRAF and PIK3CA mutations. In addition, BRAF mutation is strongly inversely correlated with KRAS mutation. We hypothesized that the association between calcium intake and colon cancer risk might vary by these molecular features. METHODS: We prospectively followed 88,506 women from the Nurses' Health Study and 47,733 men from the Health Professionals Follow-up Study for up to 30 years. Duplication-method Cox proportional cause-specific hazards regression was used to estimate multivariable hazard ratios (HRs), and 95% confidence intervals (95% CIs) for the associations between calcium intake and the risk of colon cancer subtypes. By Bonferroni correction, the α-level was adjusted to 0.01. RESULTS: Based on 853 colon cancer cases, the inverse association between dietary calcium intake and colon cancer risk differed by CIMP status (pheterogeneity = 0.01). Per each 300 mg/day increase in intake, multivariable HRs were 0.84 (95% CI 0.76-0.94) for CIMP-negative/low and 1.12 (95% CI 0.93-1.34) for CIMP-high. Similar differential associations were suggested for MSI subtypes (pheterogeneity = 0.02), with the corresponding HR being 0.86 (95% CI 0.77-0.95) for non-MSI-high and 1.10 (95% CI 0.92-1.32) for MSI-high. No differential associations were observed by BRAF, KRAS, or PIK3CA mutations. CONCLUSION: The inverse association between dietary calcium intake and colon cancer risk may be specific to CIMP-negative/low and possibly non-MSI-high subtypes.


Assuntos
Cálcio/administração & dosagem , Neoplasias do Colo/patologia , Ilhas de CpG/genética , Proteínas Proto-Oncogênicas B-raf/genética , Idoso , Neoplasias do Colo/genética , Metilação de DNA , Feminino , Seguimentos , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Fenótipo , Modelos de Riscos Proporcionais , Risco
10.
JAMA ; 321(16): 1587-1597, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31012934

RESUMO

Importance: Prolonged sitting, particularly watching television or videos, has been associated with increased risk of multiple diseases and mortality. However, changes in sedentary behaviors over time have not been well described in the United States. Objective: To evaluate patterns and temporal trends in sedentary behaviors and sociodemographic and lifestyle correlates in the US population. Design, Setting, and Participants: A serial, cross-sectional analysis of the US nationally representative data from the National Health and Nutrition Examination Survey (NHANES) among children aged 5 through 11 years (2001-2016); adolescents, 12 through 19 years (2003-2016); and adults, 20 years or older (2003-2016). Exposures: Survey cycle. Main Outcomes and Measures: Prevalence of sitting watching television or videos for 2 h/d or more, computer use outside work or school for 1 h/d or more, and total sitting time (h/d in those aged ≥12 years). Results: Data on 51 896 individuals (mean, 37.2 years [SE, 0.19]; 25 968 [50%] female) were analyzed from 2001-2016 NHANES data, including 10 359 children, 9639 adolescents, and 31 898 adults. The estimated prevalence of sitting watching television or videos for 2 h/d or more was high among all ages (children, 62% [95% CI, 57% to 67%]; adolescents, 59% [95% CI, 54% to 65%]; adults, 65% [95% CI, 61% to 69%]; adults aged 20-64 years, 62% [95% CI, 58% to 66%]; and ≥65 years, 84% [95% CI, 81% to 88%] in the 2015-2016 cycle). From 2001 through 2016, the trends decreased among children over time (difference, -3.4% [95% CI, -11% to 4.5%]; P for trend =.004), driven by non-Hispanic white children; were stable among adolescents (-4.8% [95% CI, -12% to 2.3%]; P for trend =.60) and among adults aged 20 through 64 years (-0.7% [95% CI, -5.6% to 4.1%]; P for trend =.82); but increased among adults aged 65 years or older (difference, 3.5% [95% CI, -1.2% to 8.1%]; P for trend =.03). The estimated prevalence of computer use outside school or work for 1 h/d or more increased in all ages (children, 43% [95% CI, 40% to 46%] to 56% [95% CI, 49% to 63%] from 2001 to 2016; difference, 13% [95% CI, 5.6% to 21%]; P for trend <.001; adolescents, 53% [95% CI, 47% to 58%] to 57% [95% CI, 53% to 62%] from 2003 to 2016, difference, 4.8% [95% CI, -1.8% to 11%]; P for trend =.002; adults, 29% [27% to 32%] to 50% [48% to 53%] from 2003 to 2016, difference, 21% [95% CI, 18% to 25%]; P for trend <.001). From 2007 to 2016, total hours per day of sitting time increased among adolescents (7.0 [95% CI, 6.7 to 7.4] to 8.2 [95% CI, 7.9 to 8.4], difference, 1.1 [95% CI, 0.7 to 1.5]) and adults (5.5 [95% CI, 5.2 to 5.7] to 6.4 [95% CI, 6.2 to 6.6]; difference, 1.0 [95% CI, 0.7 to 1.3]; P for trend <.001 for both). Conclusions and Relevance: In this nationally representative survey of the US population from 2001 through 2016, the estimated prevalence of sitting watching television or videos for at least 2 hours per day generally remained high and stable. The estimated prevalence of computer use during leisure-time increased among all age groups, and the estimated total sitting time increased among adolescents and adults.


Assuntos
Comportamento Sedentário , Televisão , Adolescente , Adulto , Idoso , Peso Corporal , Criança , Grupos de Populações Continentais , Estudos Transversais , Grupos Étnicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Análise de Regressão , Fatores Socioeconômicos , Estados Unidos , Adulto Jovem
11.
Hepatobiliary Pancreat Dis Int ; 18(3): 255-265, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31027910

RESUMO

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury remains a significant problem in clinical practice. Sphingosine kinase 1 (SphK1) phosphorylates sphingosine to sphingosine-1-phosphate (S1P) which participates in multiple bioactive processes. However, little is known about the role of SphK1 in hepatic I/R injury. This study aimed to investigate the effect of SphK1 knockout on liver I/R injury and to explore underlying mechanisms. METHODS: SphK1 knockout and wild type mice were subjected to 70% partial hepatic I/R. Serum alanine aminotransferase was determined to indicate the degree of liver damage. Hematoxylin-eosin staining and TUNEL assay were used to assess histological changes and hepatocellular apoptosis, respectively. Immunohistochemistry was performed to detect the expression and translocation of phosphorylated p65 and signal transducer and activator of transcription 3 (STAT3). Western blotting was used to determine the expression of S1P receptor 1 (S1PR1), phosphorylated p65 and STAT3. Real-time PCR was used to demonstrate the changes of proinflammatory cytokines. Oxidative stress markers were also determined through biochemical assays. RESULTS: SphK1 knockout significantly ameliorated I/R-induced liver damage, mitigated liver tissue necrosis and apoptosis compared with wild type control. I/R associated inflammation was alleviated in SphK1 knockout mice as demonstrated by attenuated expression of S1PR1 and reduced phosphorylation of nuclear factor kappa B p65 and STAT3. The proinflammatory cytokines interleukin-1ß, interleukin-6 and tumor necrosis factor-α were also inhibited by SphK1 genetic deletion. The oxidative stress markers were lower in SphK1 knockout mice after I/R injury than wild type mice. CONCLUSIONS: Knockout of SphK1 significantly alleviated damage after hepatic I/R injury, possibly through inhibiting inflammation and oxidative stress. SphK1 may be a novel and potent target in clinical practice in I/R-related liver injury.

12.
J Proteome Res ; 18(5): 2032-2044, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-30901224

RESUMO

Vascular invasion is considered as the critical risk factor of hepatocellular carcinoma (HCC). To reveal the molecular mechanisms underlying macrovascular invasion (MaVI) in HCC, we performed an iTRAQ based proteomic study to identify notably dysregulated proteins from eight HCC patients with differential vascular invasion and further confirmed them in the other 53 HCC patients. Forty-seven proteins were found significantly down-regulated in HCC with MaVI. More importantly, 30 of them were not changed in HCC without MaVI. Gene ontology analysis of these 47 proteins shows the top three enriched biological processes are urea cycle, gluconeogenesis, and arginine biosynthetic process. We validated nine remarkably dysregulated candidates in HCC patients with MaVI by Western blot including eight down-regulated proteins (CPS1, ASS1, ASL, ARG1, BHMT, DMGDH, Annexin A6, and CES1) and one up-regulated protein (CKAP4). Furthermore, dysregulation of CPS1, ASL, and ARG1, key enzymes involved in urea cycle, together with Annexin A6 and CES1, major proteins in regulating cholesterol homeostasis and fatty acid ester metabolism, was verified using immunohistochemical staining. The significant down-regulation of urea cycle generates clinically relevant proteomic signature in HCC patients with macrovascular invasion, which may provide possible insights into the molecular mechanisms of metastasis and new therapeutic targets of HCC.

13.
Cancer Prev Res (Phila) ; 12(5): 283-294, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30760501

RESUMO

Calcium intake has been associated with a lower risk of colorectal cancer. Calcium signaling may enhance T-cell proliferation and differentiation, and contribute to T-cell-mediated antitumor immunity. In this prospective cohort study, we investigated the association between calcium intake and colorectal cancer risk according to tumor immunity status to provide additional insights into the role of calcium in colorectal carcinogenesis. The densities of tumor-infiltrating T-cell subsets [CD3+, CD8+ , CD45RO (PTPRC) + , or FOXP3+ cell] were assessed using IHC and computer-assisted image analysis in 736 cancer cases that developed among 136,249 individuals in two cohorts. HRs and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. Total calcium intake was associated with a multivariable HR of 0.55 (comparing ≥1,200 vs. <600 mg/day; 95% CI, 0.36-0.84; P trend = 0.002) for CD8+ T-cell-low but not for CD8+ T-cell-high tumors (HR = 1.02; 95% CI, 0.67-1.55; P trend = 0.47). Similarly, the corresponding HRs (95% CIs) for calcium for low versus high T-cell-infiltrated tumors were 0.63 (0.42-0.94; P trend = 0.01) and 0.89 (0.58-1.35; P trend = 0.20) for CD3+ ; 0.58 (0.39-0.87; P trend = 0.006) and 1.04 (0.69-1.58; P trend = 0.54) for CD45RO+ ; and 0.56 (0.36-0.85; P trend = 0.006) and 1.10 (0.72-1.67; P trend = 0.47) for FOXP3+ , although the differences by subtypes defined by T-cell density were not statistically significant. These potential differential associations generally appeared consistent regardless of sex, source of calcium intake, tumor location, and tumor microsatellite instability status. Our findings suggest a possible role of calcium in cancer immunoprevention via modulation of T-cell function.

14.
Am J Gastroenterol ; 114(2): 315-321, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30730324

RESUMO

INTRODUCTION: Diverticulitis is a significant cause of morbidity among older women, and little attention has been paid to understanding its etiology. We have shown that menopausal hormone therapy (MHT) is associated with the risk of inflammatory bowel disease. In this study, we prospectively examined the association between MHT and the risk of incident diverticulitis. METHODS: We studied 65,367 postmenopausal women enrolled in the Nurses' Health Study who provided detailed information on hormone use and other medical and lifestyle factors biennially, and on diet every 4 years. Between 2008 and 2014, participants reported any episodes of diverticulitis that required antibiotics and the date of occurrence. We used Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over 24 years encompassing 1,297,165 person-years of follow-up, we documented 5,425 incident cases of diverticulitis. We observed an increased risk of diverticulitis among both current (HR 1.28; 95% CI 1.18-1.39) and past (HR 1.35; 95% CI 1.25-1.45) MHT users compared to never users. The increased risk was observed among participants using estrogen only (HR 1.30; 95% CI 1.20-1.41) and those using combined estrogen and progesterone (HR 1.31; 95% CI 1.21-1.42) compared to nonusers. The risk did not increase with longer duration of use (P-trend = 0.76). The association between MHT and diverticulitis was not modified by age, body mass index, past oral contraceptive use, or fiber intake (all P-interaction >0.11). CONCLUSIONS: Menopausal hormone therapy was associated with an increased risk of diverticulitis. Further studies are needed to understand the potential mechanisms that may underlie this association.

15.
Br J Pharmacol ; 176(9): 1282-1297, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30767208

RESUMO

BACKGROUND AND PURPOSE: Sleep deprivation compromises learning and memory in both humans and animals, and can be reversed by administration of modafinil, a drug promoting wakefulness. Dysfunctional autophagy increases activation of apoptotic cascades, ultimately leading to increased neuronal death, which can be alleviated by autophagy inhibitors. This study aimed to investigate the alleviative effect and mechanism of modafinil on the excessive autophagy occurring in the hippocampus of mice with deficiency of learning and memory induced by sleep deprivation. EXPERIMENTAL APPROACH: The Morris water maze was used to assess the effects of modafinil on male C57BL/6Slac mice after 48-hr sleep deprivation. The HT-22 hippocampal neuronal cell line was also used. Nissl staining, transmission electron microscope, immunofluorescence, Western blot, transient transfection, and autophagy inducer were used to study the effect and mechanism of modafinil on hippocampal neurons with excessive autophagy and apoptosis. KEY RESULTS: Modafinil improved learning and memory in sleep-deprived mice, associated with the inhibition of excessive autophage and apoptosis and an enhanced activation of the PI3K/Akt/mTOR/P70S6K signalling pathway in hippocampal neurons. These effects of modafinil were abolished by rapamycin. In addition, modafinil suppressed the aberrant autophagy and apoptosis induced by rapamycin and reactivated PI3K/Akt/mTOR/P70S6K signals in HT-22 cells. CONCLUSIONS AND IMPLICATIONS: These results suggested that modafinil alleviated impaired learning and memory of sleep-deprived mice potentially by suppressing excessive autophagy and apoptosis of hippocampal neurons. This novel mechanism may add to our knowledge of modafinil in the clinical treatment of impaired memory caused by sleep loss.

16.
Zhongguo Gu Shang ; 31(12): 1172-1179, 2018 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-30583662

RESUMO

Rotator cuff tear is a common disease that causes shoulder pain and limitation of activity. Rotator cuff repair with arthroscope has become the mainstream method with advance in surgical techniques. In spite of this, the highly rate of retear after surgery mainly because the tendon to bone interface form scar tissue rather than native tissue. Biomechanical of the interface is so poor to retear because of the change of Histological. In recent years, more and more researchers are devoted to the study of biology and biomechanical for improving the process of tendon to bone healing and restoring the original structure at the interface, This article reviews the research progress with four factors(inflammation, slow or limited bone ingrowth into the tendon graft, Mechanical stimulation, scant stem cell) and physiotherapy that affect tendon to bone healing.


Assuntos
Lesões do Manguito Rotador , Traumatismos dos Tendões , Artroplastia , Humanos , Manguito Rotador , Tendões , Cicatrização
17.
J Acoust Soc Am ; 144(4): EL275, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30404506

RESUMO

Decentralized control has great potential to facilitate the implementations of multichannel active noise/vibration control systems. The main drawback, however, is its inherent risk of system instability. In this letter an optimized decentralized adaptive control algorithm subject to periodic disturbances is reported. The algorithm employs the scheme of a decentralized filtered-x least mean square algorithm and utilizes optimized reference filters so that the stability of the control system can be ensured. Simulation results based on a realistic vibration isolation system demonstrate that both the stability and the convergent speed could be significantly improved.

18.
Psychol Res Behav Manag ; 11: 495-502, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425596

RESUMO

Background: This study aimed to determine whether plasma nesfatin-1, cortisol, and inflammatory cytokines could be used as novel noninvasive biomarkers for the diagnosis of moderate and severe depressive disorder (MSDD). Materials and methods: A total of 70 patients with MSDD and 70 healthy subjects were assessed. Patients with MSDD were selected from Hefei Fourth People's Hospital, Anhui Mental Health Center, and subjects in the control group were selected from healthy volunteers. Hamilton Depression Rating Scale-17 (HAMD-17) was used to evaluate the two groups. ELISA was used for the measurement of plasma nesfatin-1, cortisol, IL-6, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) levels. The diagnostic value of plasma nesfatin-1, cortisol, IL-6, CRP, and TNF-α for MSDD was assessed. Results: Compared to healthy controls, the HAMD-17 scores and average nesfatin-1, cortisol, IL-6, and CRP levels in patients with MSDD were significantly increased. Moreover, multivariate linear regression analysis showed that HAMD-17 score was positively associated with plasma nesfatin-1 and cortisol. Furthermore, the results of the receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.985 with 94.3% sensitivity and 97.1% specificity of nesfatin-1, and an AUC of 0.957 with 91.4% sensitivity and 85.7% specificity of cortisol in discriminating patients with MSDD from healthy volunteers. A combined ROC analysis using nesfatin-1 and cortisol revealed an AUC of 0.993 with a sensitivity of 97.1% and a specificity of 98.6% in separating patients with MSDD from healthy volunteers. Conclusion: These results suggest that plasma nesfatin-1 and cortisol might be potential novel biomarkers for the diagnosis of MSDD.

19.
Mol Biol Evol ; 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30445533

RESUMO

Tibetan sheep are the most common and widespread domesticated animals on the Qinghai-Tibetan Plateau (QTP), and have played an essential role in the permanent human occupation of this high-altitude region. However, the precise timing, route and process of sheep pastoralism in the QTP region remain poorly established, and little is known about the underlying genomic changes that occurred during the process. Here, we investigate the genomic variation in Tibetan sheep using whole-genome sequences, SNP arrays, mitochondrial DNA and Y-chromosomal variants in 986 samples throughout their distribution range. We detect strong signatures of selection in genes involved in the hypoxia and ultraviolet signaling pathways (e.g., HIF-1 pathway and HBB and MITF genes) and in genes associated with morphological traits such as horn size and shape (e.g., RXFP2). We identify clear signals of argali (Ovis ammon) introgression into sympatric Tibetan sheep, covering 5.23% - 5.79% of their genomes. The introgressed genomic regions are enriched in genes related to oxygen transportation system, sensory perception and morphological phenotypes, in particular the genes HBB and RXFP2 with strong signs of adaptive introgression. The spatial distribution of genomic diversity and demographic reconstruction of the history of Tibetan sheep shows a stepwise pattern of colonization with their initial spread onto the QTP from its northeastern part c. 3,100 years ago, followed by further southwest expansion to the central QTP c. 1,300 years ago. Together with archeological evidence, the date and route reveals the history of human expansions on the QTP by the Tang-Bo Ancient Road during the late-Holocene. Our findings contribute to a depth understanding of early pastoralism and the local adaptation of Tibetan sheep as well as the late-Holocene human occupation of the QTP.

20.
JAMA Oncol ; 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30326010

RESUMO

Importance: Colorectal cancer (CRC) incidence and mortality among individuals younger than 50 years (early-onset CRC) are increasing. The reasons for such increases are largely unknown, although the increasing prevalence of obesity may be partially responsible. Objective: To investigate prospectively the association between obesity and weight gain since early adulthood with the risk of early-onset CRC. Design, Setting, and Participants: The Nurses' Health Study II is a prospective, ongoing cohort study of US female nurses aged 25 to 42 years at study enrollment (1989). A total of 85 256 women free of cancer and inflammatory bowel disease at enrollment were included in this analysis, with follow-up through December 31, 2011. Validated anthropomorphic measures and lifestyle information were self-reported biennially. Statistical analysis was performed from June 12, 2017, to June 28, 2018. Exposures: Current body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), BMI at 18 years of age, and weight gain since 18 years of age. Main Outcomes and Measures: Relative risk (RR) for incident early-onset CRC. Results: Among the 85 256 women studied, 114 cases of early-onset CRC were documented (median age at diagnosis, 45 years; interquartile range, 41-47 years) during 1 196 452 person-years of follow-up. Compared with women with a BMI of 18.5 to 22.9, the multivariable RR was 1.37 (95% CI, 0.81-2.30) for overweight women (BMI, 25.0-29.9) and 1.93 (95% CI, 1.15-3.25) for obese women (BMI, ≥30.0). The RR for each 5-unit increment in BMI was 1.20 (95% CI, 1.05-1.38; P = .01 for trend). Similar associations were observed among women without a family history of CRC and without lower endoscopy within the past 10 years. Both BMI at 18 years of age and weight gain since 18 years of age contributed to this observation. Compared with women with a BMI of 18.5 to 20.9 at 18 years of age, the RR of early-onset CRC was 1.32 (95% CI, 0.80-2.16) for women with a BMI of 21.0 to 22.9 and 1.63 (95% CI, 1.01-2.61) for women with a BMI of 23.0 or greater at 18 years of age (P = .66 for trend). Compared with women who had gained less than 5.0 kg or had lost weight, the RR of early-onset CRC was 1.65 (95% CI, 0.96-2.81) for women gaining 20.0 to 39.9 kg and 2.15 (95% CI, 1.01-4.55) for women gaining 40.0 kg or more (P = .007 for trend). Conclusions and Relevance: Obesity was associated with an increased risk of early-onset CRC among women. Further investigations among men and to elucidate the underlying biological mechanisms are warranted.

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