bluuebunny/crossref_metadata_2025 huggingface dataset:
Hedgehog Signaling Pathway Regulates Autophagy in Human Hepatocellular Carcinoma Cells
Authors: Wang Ying , Han Chang , Lu Lu , Magliato Susan , Wu Tong
Published: March 2013

Hedgehog (Hh) signaling plays an important role in embryonic development and in the regulation of a variety of cellular functions. Aberrant activation of Hh signaling has been implicated in several human cancers including hepatocellular carcinoma (HCC). In this study we examined the pathobiological functions and molecular mechanisms of the Hh signaling pathway in HCC cells. Treatment of cultured human HCC cells (Huh7, Hep3B, and HepG2) with the Hh signaling ligand (recombinant Shh) or agonist, SAG and purmorphamine, prevented the induction of autophagy. In contrast, GANT61 (a small molecule inhibitor of Gli1 and Gli2) induced autophagy, as determined by immunoblotting for microtubule-associated protein light chain 3 (LC3) and p62, GFP-LC3 puncta, monodansylcadaverine (MDC) staining, and transmission electron microscopy. Hh inhibition-induced autophagy was associated with up-regulation of Bnip3, as determined by immunoblotting and real-time polymerase chain reaction (PCR) assay. Knockdown of Bnip3 by RNAi impaired GANT61-induced autophagy. Additionally, Hh inhibition-induced autophagy was associated with Bnip3-mediated displacement of Bcl-2 from Beclin-1, as determined by immunoblotting and immunoprecipitation assays. Furthermore, inhibition of Hh signaling increased HCC cell apoptosis and decreased cell viability, as determined by caspase and WST-1 assays. Pharmacological or genetic inhibition of autophagy by 3-methyladenine (3-MA) or Beclin-1 small interfering RNA (siRNA) partially suppressed GANT61-induced cell apoptosis and cytotoxicity. In a tumor xenograft model using SCID mice inoculated with Huh7 cells, administration of GANT61 inhibited tumor formation and decreased tumor volume; this effect was partially blocked by the autophagy inhibitor, 3-MA. Conclusion: These findings provide novel evidence that Hh inhibition induces autophagy through up-regulation of Bnip3 and that this mechanism contributes to apoptosis. Therefore, the status of autophagy is a key factor that determines the therapeutic response to Hh-targeted therapies. (Hepatology 2013;53:995–1010)
Suppression of Actopaxin Impairs Hepatocellular Carcinoma Metastasis Through Modulation of Cell Migration and Invasion
Authors: Ng Lui , Tung-Ping Poon Ronnie , Yau Simon , Chow Ariel , Lam Colin , Li Hung-Sing , Chung-Cheung Yau Thomas , Law Wai-Lun , Pang Roberta
Published: March 2013

Early reports suggested that actopaxin, a member of the focal adhesion proteins, regulates cell migration. Here we investigated whether actopaxin is involved in hepatocellular carcinoma (HCC) progression and metastasis. We examined actopaxin expression in human HCC samples using immunohistochemistry and western blotting. The functional and molecular effect of actopaxin was studied

in vitro

by overexpression in a nonmetastatic HCC cell line, as well as repression in a metastatic cell line. The

in vivo

effect of actopaxin repression was studied in nonobese diabetic and severe combined immunodeficient mice. We found that actopaxin was frequently overexpressed in human HCC patients and its overexpression positively correlated with tumor size, stage, and metastasis. Actopaxin expression also correlated with the metastatic potential of HCC cell lines. Actopaxin overexpression induced the invasion and migration ability of nonmetastatic HCC cells, whereas down-regulation of actopaxin reverted the invasive phenotypes and metastatic potential of metastatic HCC cells through regulating the protein expression of certain focal adhesion proteins including ILK, PINCH, paxillin, and cdc42, as well as regulating the epithelial-mesenchymal transition pathway. Furthermore, there was a close association between actopaxin and CD29. HCC cells with stronger CD29 expression showed a higher actopaxin level, whereas actopaxin repression attenuated CD29 activity. Finally, actopaxin down-regulation enhanced the chemosensitivity of HCC cells towards oxaliplatin treatment by way of a collective result of suppression of survivin protein, β-catenin, and mammalian target of rapamycin pathways and up-regulation of p53.

Conclusion

: This study provides concrete evidence of a significant role of actopaxin in HCC progression and metastasis, by way of regulation of cell invasiveness and motility, an epithelial-mesenchymal transition process, and chemosensitivity to cytotoxic drugs. (Hepatology 2013;58:667-679)
Excess S-adenosylmethionine reroutes phosphatidylethanolamine towards phosphatidylcholine and triglyceride synthesis
Authors: Martínez-Uña Maite , Varela-Rey Marta , Cano Ainara , Fernández-Ares Larraitz , Beraza Naiara , Aurrekoetxea Igor , Martínez-Arranz Ibon , García-Rodríguez Juan L. , Buqué Xabier , Mestre Daniela , Luka Zigmund , Wagner Conrad , Alonso Cristina , Finnell Richard H. , Lu Shelly C. , Martínez-Chantar Luz M. , Aspichueta Patricia , Mato José M.
Published: March 2013

Methionine adenosyltransferase 1A (

MAT1A

) and glycine

N

-methyltransferase (

GNMT

) are the primary genes involved in hepatic S-adenosylmethionine (SAMe) synthesis and degradation, respectively.

Mat1a

ablation in mice induces a decrease in hepatic SAMe, activation of lipogenesis, inhibition of triglyceride (TG) release, and steatosis.

Gnmt

-deficient mice, despite showing a large increase in hepatic SAMe, also develop steatosis. We hypothesized that as an adaptive response to hepatic SAMe accumulation, phosphatidylcholine (PC) synthesis by way of the phosphatidylethanolamine (PE)

N

-methyltransferase (PEMT) pathway is stimulated in

Gnmt−/−

mice. We also propose that the excess PC thus generated is catabolized, leading to TG synthesis and steatosis by way of diglyceride (DG) generation. We observed that

Gnmt−/−

mice present with normal hepatic lipogenesis and increased TG release. We also observed that the flux from PE to PC is stimulated in the liver of

Gnmt−/−

mice and that this results in a reduction in PE content and a marked increase in DG and TG. Conversely, reduction of hepatic SAMe following the administration of a methionine-deficient diet reverted the flux from PE to PC of

Gnmt−/−

mice to that of wildtype animals and normalized DG and TG content preventing the development of steatosis.

Gnmt−/−

mice with an additional deletion of perilipin2, the predominant lipid droplet protein, maintain high SAMe levels, with a concurrent increased flux from PE to PC, but do not develop liver steatosis.

Conclusion

: These findings indicate that excess SAMe reroutes PE towards PC and TG synthesis and lipid sequestration. (Hepatology 2013;58:1296–1305)
Winner of the 2013 young investigator award for the society for biomaterials annual meeting and exposition, April 10–13, 2013, Boston, Massachusetts
Authors: Thibault Richard A. , Mikos Antonios G. , Kasper F. Kurtis
Published: March 2013

Devitalization and demineralization processing of biodegradable polymer and extracellular matrix (ECM) hybrid constructs was explored for the effect on the retention of ECM components and construct osteogenicity. Hybrid constructs were generated by seeding osteogenically predifferentiated rat mesenchymal stem cells (MSCs) onto electrospun poly(ε‐caprolactone) fiber meshes and culturing in osteogenic medium for 12 or 16 days within a flow perfusion bioreactor to create an ECM coating. The resulting constructs were then either devitalized (using a freeze‐thaw or a detergent technique), devitalized and demineralized, or left untreated, and subsequently characterized for DNA, glycosaminoglycan, collagen, and calcium content. The osteogenicity of each construct was investigated by culturing MSCs on the hybrid constructs within a flow perfusion bioreactor for 4, 8, and 12 days in osteogenic medium. Histological staining demonstrated that devitalization via the freeze–thaw method retained the thickest coating of ECM components within the constructs. Demineralization and devitalization processing of ECM coated constructs resulted in a decrease in their osteogenicity. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Evaluation of the bulk platelet response and fibrinogen interaction to elastin‐like polypeptide coatings
Authors: Srokowski Elizabeth M. , Woodhouse Kimberly A.
Published: March 2013

In this work, we expand on our understanding of the thrombogenicity of coatings prepared with three different recombinant elastin‐like polypeptides (ELPs). The bulk platelet response of the ELP coatings was characterized following whole blood contact under physiological shear flow (300 s−1) using flow cytometry. Prolonged exposure to shear flow (1‐h) indicated that materials coated with the longer ELP coatings (ELP2 and ELP4) had less bulk platelet activation and microparticle formation than materials coated with the shorter ELP1. Quartz crystal microbalance with dissipation (QCM‐D) was used to monitor the binding of the platelet membrane receptor GPIIb/IIIa to ELP‐adsorbed fibrinogen (Fg) surfaces. Compared to the shorter ELPs, a lower amount of Fg adsorbed to the ELP4 coated material and ELP4 appeared to form a softer, more structurally flexible coating layer. When Fg was adsorbed to the ELP coated surface it demonstrated an altered binding for GPIIb/IIIa that was inhibited in the presence of an AGDV‐containing peptide but not an RGD‐containing peptide. Conversely, on the shorter ELP coatings, binding of GPIIb/IIIa to an adsorbed Fg layer was partially inhibited in the presence of an RGD‐containing peptide. These results indicate that both the quantity and conformational state of Fg varies when adsorbed to surfaces coated with ELPs of varying sequence length, which may be mediating their platelet response. Collectively, the findings reinforce the applicability of the ELPs as potential thromboresistant coatings, especially with the use of the longer polypeptide—ELP4. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 540–551, 2014.
Investigating surface topology and cyclic‐RGD peptide functionalization on vascular endothelialization
Authors: McNichols Colton , Wilkins Justin , Kubota Atsutoshi , Shiu Yan T. , Aouadi Samir M. , Kohli Punit
Published: March 2013

The advantages of endothelialization of a stent surface in comparison with the bare metal and drug‐eluting stents used today include reduced late‐stent restenosis and in‐stent thrombosis. In this article, we study the effect of surface topology and functionalization of tantalum (Ta) with cyclic‐(arginine‐glycine‐aspartic acid‐d‐phenylalanine‐lysine) (cRGDfK) on the attachment, spreading, and growth of vascular endothelial cells. Self‐assembled nanodimpling on Ta surfaces was performed using a one‐step electropolishing technique. Next, cRGDfK was covalently bonded onto the surface using silane chemistry. Our results suggest that nanotexturing alone was sufficient to enhance cell spreading, but the combination of a nanodimpled surfaces along with the cRGDfK peptide may produce a better endothelialization coating on the surface in terms of higher cell density, better cell spreading, and more cell–cell interactions, when compared to using cRGDfK peptide functionalization alone or nanotexturing alone. We believe that future research should look into how to implement both modifications (topographic and chemical modifications) to optimize the stent surface for endothelialization. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 532–539, 2014.
Sonographic predictors of ovarian malignancy
Authors: Barroilhet Lisa , Vitonis Allison , Shipp Thomas , Muto Michael , Benacerraf Beryl
Published: March 2013

Purpose

To identify a combination of sonographic features that best predicts ovarian malignancy.

Methods

Subjects included 249 women who had a transvaginal sonogram for a pelvic mass at Brigham and Women's Hospital between December 2005 and February 2010. Subjects underwent surgery for removal of the mass and pathologic diagnosis was available. Images were reviewed retrospectively by one sonologist blinded to diagnosis and clinical information. Twelve sonographic features were scored for each mass. The dataset was divided into training (n = 149) and testing (n = 100) sets. Within the training set, a stepwise logistic regression was used to weigh each variable and combination of features to identify those associated with malignancies. Using the results from the logistic regression analyses, we created a three‐level risk stratification that was applied to the sonograms of subjects in the testing set to assess its ability to distinguish benign lesions from invasive and borderline cancers.

Results

High risk lesions included all masses with internal vascularity. In our testing set, this feature was present in 9 out of 12 (75%) invasive cancers, 1 out of 6 (16.7%) borderline lesions, and 9 out of 82 (11%) benign masses. The intermediate risk level included lesions with a thick wall or thick septa without internal blood flow. This combination of features identified one additional invasive cancer and 5 out of 6 (83.3%) borderline tumors. Masses with low risk features had a 2/49 (4.0%) incidence of malignancy.

Conclusions

In the absence of high or intermediate risk sonographic features, the risk of malignancy is low. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound, 41:269–274, 2013
Measurements of the lower uterine segment during gestation
Authors: Ginsberg Yuval , Goldstein Israel , Lowenstein Lior , Weiner Zeev
Published: March 2013

Purpose:

To establish normal values for the lower uterine segment (LUS) thickness and to recognize factors that may affect these values.

Methods:

In this cross‐sectional study, we measured the LUS thickness in women between 11 and 41 weeks gestation. Women with placental abnormalities and fetal anomalies were excluded. Fetal weight, location of placental implantation, and cervical length were estimated. The LUS was examined to identify the thinnest zone and evaluated using the transvaginal approach with an empty urinary bladder. Full LUS thickness was measured with a caliper at the inner surface of the posterior bladder wall and another caliper at the interface between the amniotic fluid and the decidua. The myometrium was measured with the first caliper at the interface between the amniotic fluid and the deciduas and the second between the bladder wall and the myometrium. Normal values for the LUS were established throughout gestation, and correlations between the LUS gestational age, fetal weight, previous cesarean section, and other parameters were examined.

Results:

Overall, 350 women were included in our study. Median parity was 1 (0–6) and the majority (62%, 218/350) of women have not had a previous cesarean section. The LUS thickness inversely correlated with gestational week (Pearson's r = −0.11, p < 0.03). When stratifying the linear regression model to women with and without a history of a previous cesarean section, it was demonstrated that gestational age was moderately correlated with LUS only in the second group of patients (Pearson's r = −0.16, p = 0.1 and Pearson's r = −0.47, p < 0.0001, respectively). During the post term period, patients who had had a previous cesarean section had significantly thinner LUS compared with patients who had not had a previous cesarean section (46 mm ± 20 versus 59 mm ± 20, p = 0.002, respectively). Neither parity nor the number of previous cesarean sections were found to correlate with the thickness of the LUS (p > 0.05). Multivariate linear regression (R2 = 0.215, F(2, 63) = 9.021, p < 0.001) demonstrated that both gestational week (β = −0.13, p < 0.04) and cesarean section (β = −0.01, p < 0.0001) were independent factors associated with the thickness of the LUS; for every 1 week increase in gestational week, there was a 1.3 mm decrease in the total thickness of the LUS

Conclusions:

We have established reference ranges for LUS thickness throughout gestation. The LUS thickness decreases throughout gestation in singleton pregnancies and is significantly thinner in postterm period pregnant women with a previous cesarean section. © 2013 Wiley Periodicals, Inc., J Clin Ultrasound, 2013
Ultrasound measurement of the transverse diameter of the fetal thymus in pregnancies complicated by the preterm prelabor rupture of membranes
Authors: Musilova Ivana , Hornychova Helena , Kostal Milan , Jacobsson Bo , Kacerovsky Marian
Published: March 2013

Purpose

To determine whether the measurement of the transverse diameter of the fetal thymus is of value in the identification of either histologic chorioamnionitis or funisitis in pregnancies complicated by preterm prelabor rupture of membranes (PPROM).

Methods

The transverse diameter of the fetal thymus was measured in 216 fetuses from PPROM pregnancies. A small thymus was defined as a transverse thymic diameter below the fifth percentile according to a previously published nomogram. The placenta, the fetal membranes, and the umbilical cord were assessed for the presence of inflammation.

Results

A small thymus was identified in 69% (150/216) of fetuses. A small thymus was present in 80% (106/133) and 88% (36/41) of women with histologic chorioamnionitis or funisitis, respectively. The presence of a small thymus had a sensitivity of 79%, specificity of 47%, positive predictive value of 71%, negative predictive value of 59% for the identification of chorioamnionitis (p < 0.0001; odds ratio 3.5) and a sensitivity of 88%, specificity of 35%, positive predictive value of 24%, and negative predictive value of 92% in the identification of funisitis (p = 0.004; odds ratio 4.4).

Conclusions

The sonographic finding of a small thymus is a sensitive indicator of histologic chorioamnionitis or funisitis; low specificity excludes it as a possible clinical implication in the management of PPROM pregnancies. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound 41:283–289, 2013
Isolated torsion of the fallopian tube with hydrosalpinx mimicking a multiloculated ovarian cyst: Whirlpool sign on preoperative sonography and MRI
Authors: Aydin Ramazan , Bildircin Devran , Polat Ahmet Veysel
Published: March 2013

Isolated torsion of the fallopian tube is a rare case of lower abdominal pain. Early diagnosis of such cases is crucial because it allows for the possibility of salvage surgery and the prevention of irreversible vascular damage. However, diagnosis is rarely made before surgery due to nonspecific clinical and imaging features. We report a case of isolated tubal torsion with specific imaging findings on preoperative ultrasonography, color Doppler ultrasonography, and magnetic resonance imaging that was misdiagnosed as a multiloculated ovarian cyst at a local hospital. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound 42:45–48, 2014
Relationship between idiopathic sudden sensorineural hearing loss and subsequent stroke
Authors: Chang Chia‐Fan , Kuo Yen‐Ling , Chen Shih‐Pin , Wang Mao‐Che , Liao Wen‐Huei , Tu Tzong‐Yang , Shiao An‐Suey
Published: March 2013

Objectives/Hypothesis:

The correlation between idiopathic sudden sensorineural hearing loss and subsequent stroke is unclear. This study aimed to review stroke incidence after idiopathic sudden sensorineural hearing loss among patients admitted to a tertiary referral center and aimed to compare the characteristics of patients with and without stroke.

Study Design:

Individual retrospective cohort study.

Methods:

Between January 2000 and April 2004, a total of 349 patients diagnosed with idiopathic sudden sensorineural hearing loss were admitted to Taipei Veterans General Hospital and followed up until May 31, 2009. The patients were divided into two groups: a stroke group and a nonstroke group. Cox proportional hazards regression was used for analysis after adjusting for age, sex, hypertension, diabetes mellitus, coronary artery disease, and prior stroke history.

Results:

The average follow‐up duration was 81.7 ± 15.0 months, and the average annual stroke incidence rate was 0.6%. The number of patients with older age, hypertension, coronary artery disease, and prior stroke history was significantly higher in the stroke group than in the nonstroke group. Prior stroke history was the most important risk factor for stroke after idiopathic sudden sensorineural hearing loss.

Conclusions:

Idiopathic sudden sensorineural hearing loss did not increase stroke risk. The average annual stroke incidence rate after idiopathic sudden sensorineural hearing loss was comparable with that in the general Taiwanese population. The study patients experienced stroke because they carried the risk factors for stroke. In patients with modified risk factors for stroke, efforts should be made to prevent stroke rather than idiopathic sudden sensorineural hearing loss.
Divergent and sex‐dimorphic expression of the paralogs of the Sox9‐Amh‐Cyp19a1 regulatory cascade in developing and adult atlantic cod (Gadus morhua L.)
Authors: Johnsen Hanne , Tveiten Helge , Torgersen Jacob S. , Andersen Øivind
Published: March 2013

The factors of the Sox9‐Amh‐Cyp19a1 cascade play a crucial role in the complex process of sex differentiation in mammals. The involvement of Sox9 and Cyp19a1 paralogs and the single Amh ortholog in sex differentiation and development of the gonads and the brain in Atlantic cod was examined by analyzing bimodal and sex‐dimorphic gene expression patterns, respectively, during early stages and in maturing males and females. Expression of sox9a and sox9b were initiated at blastulation, and both paralogs were expressed in chondrogenic tissue in the hatched larvae. The male‐specific expression of sox9a in the adult gonads supports a conserved role in testis function, while sox9b was expressed in the maturing testes and ovaries at similar levels. Amh was expressed at low, but variable, levels from late gastrulation prior to the onset of cyp19a1a and cyp19a1b expression. Male‐biased amh expression was found in the maturing gonads, but the increased ovarian levels during maturation suggest a role also in females. The larval expression of cyp19a1a and cyp19a1b increased at the expected time of sex differentiation, but showed large individual variation. The ovarian expression of cyp19a1a and amh increased concomitant with increased plasma estradiol levels during vitellogenesis. The testis‐specific cyp19a1b expression supports the importance of estrogen in the spermatogenesis, while abundant expression in the male and female brain is probably related to the continuous neurogenesis in fish. These divergent and sex‐dimorphic expression patterns of the cod sox9 and cyp19a1 paralogs demonstrate the complexity of the genetic network regulating sexual development in fish. Mol. Reprod. Dev. 80: 358–370, 2013. © 2013 Wiley Periodicals, Inc.
Direct coronary motion extraction from a 2D fat image navigator for prospectively gated coronary MR angiography
Authors: Kawaji Keigo , Spincemaille Pascal , Nguyen Thanh D. , Thimmappa Nandadeepa , Cooper Mitchell A. , Prince Martin R. , Wang Yi
Published: March 2013

Purpose

Direct 2D tracking of cardiac motion may provide superior respiratory navigator gating for coronary magnetic resonance angiography compared to conventional liver‐diaphragm navigators. However, additional 2D processing for motion extraction is unsuitable for real‐time prospective gating. In this work, a 2D fat‐selective image navigator, which delineates the epicardial fat surrounding coronary arteries, is developed to directly monitor epicardial fat motion at every heartbeat in real‐time for prospective gating.

Methods

The proposed navigator is incorporated into a real‐time interactive software that allows rapid setup and efficient motion extraction, and runs on standard clinical hardware without any additional dedicated components for processing. The proposed 2D cardiac fat image navigator was compared with the conventional 1D diaphragm navigator in free‐breathing b‐SSFP coronary MRAs in 12 healthy volunteers at 1.5T.

Results

Real‐time motion extraction from 2D cardiac fat navigator images was feasible within 20 ms, enabling successful prospectively gated coronary magnetic resonance angiographies in all subjects. Compared to 1D diaphragmatic navigator, 2D fat image navigator reduced scan time by 38% (P < 0.0005), and significantly improved vessel sharpness, myocardial suppression, and image quality (P < 0.05).

Conclusion

This demonstrates the feasibility of a 3D SSFP coronary magnetic resonance angiography sequence using a 2D epicardial fat image as a navigator for real‐time prospective motion tracking. Magn Reson Med 71:599–607, 2014. © 2013 Wiley Periodicals, Inc.
Relationship between perceptions about neighborhood environment and prevalent obesity: data from the dallas heart study
Authors: Powell‐Wiley Tiffany M. , Ayers Colby R. , de Lemos James A. , Lakoski Susan G. , Vega Gloria L. , Grundy Scott , Das Sandeep R. , Banks‐Richard Kamakki , Albert Michelle A.
Published: March 2013

Objectives:

Although psychosocial stress can result in adverse health outcomes, little is known about how perceptions of neighborhood conditions, a measure of environment‐derived stress, may impact obesity. The association between perceptions of neighborhood environment and obesity (defined as body mass index [BMI] ≥ 30 kg/m2) among 5,907 participants in the Dallas Heart Study, a multi‐ethnic, probability‐based sample of Dallas County residents was examined.

Design and Methods:

Participants were asked to respond to 18 questions about perceptions of their neighborhood. Factor analysis was used to identify three factors associated with neighborhood perceptions: neighborhood violence, physical environment, and social cohesion. Logistic regression analyses were performed to determine the relationship between each factor (higher quintile = more unfavorable perceptions) and the odds of obesity.

Results:

Decreasing age, income, and education associated with unfavorable overall neighborhood perceptions and unfavorable perceptions about specific neighborhood factors (P trend <0.05 for all). Increasing BMI was associated with unfavorable perceptions about physical environment (P trend <0.05) but not violence or social cohesion. After adjustment for race, age, sex, income, education, and length of residence, physical environment perception score in the highest quintile remained associated with a 25% greater odds of obesity (OR 1.25, [95% CI 1.03‐1.50]). Predictors of obesity related to environmental perceptions included heavy traffic (OR 1.39, [1.17‐1.64]), trash/litter in neighborhood (OR 1.27, [1.01‐1.46]), lack of recreational areas (OR 1.21, [1.01‐1.46]), and lack of sidewalks (OR 1.25, [95% CI 1.04‐1.51]).

Conclusions:

Thus, unfavorable perceptions of environmental physical conditions are related to increased obesity. Efforts to improve the physical characteristics of neighborhoods, or the perceptions of those characteristics, may assist in the prevention of obesity in this community.
A retinoic acid receptor agonist tamibarotene suppresses iron accumulation in the liver
Authors: Yoshikawa Osamu , Ebata Yu , Tsuchiya Hiroyuki , Kawahara Arisa , Kojima Chihiro , Ikeda Yoshito , Hama Susumu , Kogure Kentaro , Shudo Koichi , Shiota Goshi
Published: March 2013

Objective:

Hepatic iron overload (HIO) and iron‐induced oxidative stress have recently emerged as an important factor for the development and progression of insulin resistance. The aim of this study was to evaluate the effect of tamibarotene, a selective retinoic acid receptor α/β agonist, on hepatic iron metabolism, based on our previous findings that retinoids suppress hepatic iron accumulation by increasing hepatic iron efflux through the regulation of hemojuvelin and ferroportin expression.

Design and Methods:

We quantitated the non‐heme iron content and iron metabolism‐related gene expression in the liver, and serum lipid and blood glucose levels in KK‐Ay mice after dietary administration of tamibarotene.

Results:

It was demonstrated that tamibarotene significantly reduced blood glucose and hepatic iron, but not serum lipids, and that hemojuvelin expression significantly decreased while ferroportin increased, as observed previously.

Conclusions:

These results suggest that tamibarotene is a promising alternative for the treatment of insulin resistance associated with HIO.
Racial/ethnic differences in the prevalence of gestational diabetes mellitus and maternal overweight and obesity, by Nativity, Florida, 2004‐2007
Authors: Kim Shin Y. , Sappenfield William , Sharma Andrea J. , Wilson Hoyt G. , Bish Connie L. , Salihu Hamisu M. , England Lucinda J.
Published: March 2013

Objective:

We examined the risk of gestational diabetes mellitus (GDM) among foreign‐born and U.S.‐born mothers by race/ethnicity and BMI category.

Design and Method:

We used 2004‐2007 linked birth certificate and maternal hospital discharge data of live, singleton deliveries in Florida to compare GDM risk among foreign‐born and U.S.‐born mothers by race/ethnicity and BMI category. We examined maternal BMI and controlled for maternal age, parity, and height.

Results:

Overall, 22.4% of the women in our study were foreign born. The relative risk (RR) of GDM among women who were overweight or obese (BMI ≥ 25.0 kg m−2) was higher than among women with normal BMI (18.5‐24.9 kg m−2) regardless of nativity, ranging from 1.3 (95% confidence interval (CI) = 1.0, 1.9) to 3.8 (95% CI = 2.1, 7.2).Foreign‐born women also had a higher GDM risk than U.S.‐born women, with RR ranging from 1.1 (95% CI = 1.1, 1.2) to 2.1 (95% CI = 1.4, 3.1). This finding was independent of BMI, age, parity, and height for all racial/ethnicity groups.

Conclusions:

Although we found differences in age, parity, and height by nativity, these differences did not substantially reduce the increased risk of GDM among foreign‐born mothers. Health practitioners should be aware of and have a better understanding of how race/ethnicity and nativity can affect women with a high risk of GDM. Although BMI is a major risk factor for GDM, it does not appear to be associated with race/ethnicity or nativity.
Midlife obesity and dementia: Meta‐analysis and adjusted forecast of dementia prevalence in the united states and china
Authors: Loef Martin , Walach Harald
Published: March 2013

Objective:

Obesity is a risk factor of dementia. Current forecasts of dementia prevalence fail to take the rising obesity prevalence into account.

Design and Methods:

Embase and Medline were searched for observational studies on the association between overweight (BMI 25‐30 kg/m2) or obesity (BMI > 30 kg/m2) and dementia and pooled the effect sizes by meta‐analysis. The population attributable risk (PAR) was calculated for different time points and adjusted them for confounders. Based on current prevalence rates of dementia and demographic forecasts, patient numbers were calculated and adjusted by the growth rates of PAR.

Results:

Compared to normal weight, midlife obesity increases the risk of dementia later in life (BMI 25‐30: RR = 1.34 [95% CI 1.08, 1.66], BMI > 30: RR = 1.91 [1.4, 2.62]). If obesity is included into forecast models, the prevalence of dementia is estimated to be 7.1 million (6.9, 7.3) and 11.3 million (10.9, 11.7) for the United States in 2030 and 2050, respectively. In China, the estimate is 13.1 million (12.8, 13.3) in 2030 and 26.2 million (25.1, 27.4) in 2050. These figures are 9% and 19% higher for the United States and China, respectively, than forecasts that rely solely on the demographic change.

Conclusion:

The past and ongoing increase in midlife obesity prevalence will contribute significantly to the future prevalence of dementia and public health measures to reduce midlife obesity are simultaneously primary prevention measures to reduce the risk of dementia.
Diurnal salivary cortisol is associated with body mass index and waist circumference: The multiethnic study of atherosclerosis
Authors: Champaneri Shivam , Xu Xiaoqiang , Carnethon Mercedes R. , Bertoni Alain G. , Seeman Teresa , DeSantis Amy S. , Roux Ana Diez , Shrager Sandi , Golden Sherita Hill
Published: March 2013

Objective:

Neuroendocrine abnormalities, such as activation of the hypothalamic‐pituitary‐adrenal (HPA) axis, are associated with obesity; however, few large‐scale population‐based studies have examined HPA axis and markers of obesity. We examined the cross‐sectional association of the cortisol awakening response (CAR) and diurnal salivary cortisol curve with obesity.

Design and Methods:

The Multiethnic Study of Atherosclerosis Stress Study includes 1,002 White, Hispanic, and Black men and women (mean age 65 ± 9.8 years) who collected up to 18 salivary cortisol samples over 3 days. Cortisol profiles were modeled using regression spline models that incorporated random parameters for subject‐specific effects. Cortisol curve measures included awakening cortisol, CAR (awakening to 30‐min postawakening), early decline (30 min to 2‐h postawakening), late decline (2‐h postawakening to bedtime), and the corresponding areas under the curve (AUC). Body mass index (BMI) and waist circumference (WC) were used to estimate adiposity.

Results:

For the entire cohort, both BMI and WC were negatively correlated with awakening cortisol (P < 0.05), AUC during awakening rise, and early decline and positively correlated to the early decline slope (P < 0.05) after adjustments for age, race/ethnicity, gender, diabetes status, socioeconomic status, β‐blockers, steroids, hormone replacement therapy, and smoking status. No heterogeneities of effects were observed by gender, age, and race/ethnicity.

Conclusions:

Higher BMI and WC are associated with neuroendocrine dysregulation, which is present in a large population sample, and only partially explained by other covariates.
Skinfolds and coronary heart disease risk factors are more strongly associated with BMI than with the body adiposity index
Authors: Freedman David S. , Ogden Cynthia L. , Goodman Alyson B. , Blanck Heidi M.
Published: March 2013

Objective:

A recent, cross‐sectional analysis of adults found that the hip circumference divided by height1.5 minus 18 (the body adiposity index, BAI) was strongly correlated (r = 0.79) with percent body fat determined by dual energy X‐ray absorptiometry. The BAI was proposed as a more accurate index of body fatness than BMI. We examined whether BAI was more strongly related, than was BMI and waist circumference, to skinfold thicknesses and levels of various risk factors for coronary heart disease.

Design and Methods:

Cross‐sectional analyses of adults (n = 14,263 for skinfold thickness; n=6291 for fasting lipid levels) in the National Health and Nutrition Examination Survey (NHANES) III, 1988‐1994.

Results:

As compared with BMI and waist circumference, we found that BAI was less strongly associated with the skinfold sum and with risk factor levels. For example, correlations with the skinfold sum were r = 0.79 (BMI) vs. r = 0.70 (BAI) among men, and r = 0.86 (BMI) vs. r = 0.79 (BAI) among women; p < 0.001 for the difference between each pair of correlations. An overall index of the 7 risk factors was also more strongly associated with BMI and waist circumference than BAI in analyses stratified by sex, race‐ethnicity and age. Multivariable analyses indicated that if BMI was known, BAI provided little additional information on risk factor levels.

Conclusions:

Based on the observed associations with risk factor levels and skinfold thicknesses, we conclude that BAI is unlikely to be a better index of adiposity than BMI.
Effects of BMI on the risk and frequency of AIS 3+ injuries in motor‐vehicle crashes
Authors: Rupp Jonathan D. , Flannagan Carol A.C. , Leslie Andrew J. , Hoff Carrie N. , Reed Matthew P. , Cunningham Rebecca M.
Published: March 2013

Objective: Determine the effects of BMI on the risk of serious‐to‐fatal injury (Abbreviated Injury Scale ≥ 3 or AIS 3+) to different body regions for adults in frontal, nearside, farside, and rollover crashes.

Design and Methods: Multivariate logistic regression analysis was applied to a probability sample of adult occupants involved in crashes generated by combining the National Automotive Sampling System (NASS‐CDS) with a pseudoweighted version of the Crash Injury Research and Engineering Network database. Logistic regression models were applied to weighted data to estimate the change in the number of occupants with AIS 3+ injuries if no occupants were obese.

Results: Increasing BMI increased risk of lower‐extremity injury in frontal crashes, decreased risk of lower‐extremity injury in nearside impacts, increased risk of upper‐extremity injury in frontal and nearside crashes, and increased risk of spine injury in frontal crashes. Several of these findings were affected by interactions with gender and vehicle type. If no occupants in frontal crashes were obese, 7% fewer occupants would sustain AIS 3+ upper‐extremity injuries, 8% fewer occupants would sustain AIS 3+ lower‐extremity injuries, and 28% fewer occupants would sustain AIS 3+ spine injuries.

Conclusions: Results of this study have implications on the design and evaluation of vehicle safety systems.
Patterning of children's sedentary time at and away from school
Authors: Abbott Rebecca A. , Straker Leon M. , Erik Mathiassen Svend
Published: March 2013

Objective:

Sedentary behavior in children is positively associated with an increased risk of both obesity and insulin resistance. Children spend a considerable portion of their awake time in sedentary behavior; however, the pattern of accumulation is not known. Thus the objective of this study was to describe the patterning of sedentary behavior of children at and away from school.

Design and Methods:

The patterns of sedentary time in a sample of 53 children (28 girls) aged 10‐12 years during school‐term time were examined. Children wore an accelerometer for 1 week. Total sedentary time, prolonged sequences (bouts) of sedentary time, and frequency of active interruptions to sedentary were examined on school days and weekends and within school time and non‐school time on school days.

Results:

The data did not support our hypothesis that children accumulated more sedentary time on school days when compared with weekend days (mean [SD]: 64.4% [5.3] vs. 64.9% [9.0], P = 0.686). However, when comparing school time with non‐school time on school days, children accumulated more sedentary time at school (66.8% [7.3] vs. 62.4% [5.2], P < 0.001) and spent more time at school in sustained sedentary sequences, that is, uninterrupted sedentary time for 30 min or more (75.6 min [45.8] vs. 45.0 min [26.8], P < 0.002). The children also recorded less breaks per sedentary hour within school time when compared with non‐school time (8.9 h−1 vs. 10.2 h−1, P < 0.001).

Conclusion:

Reducing total sedentary time spent both in and out of school remains an important challenge. Interrupting sedentary time more often in the “working” (school) day could also reap important musculoskeletal and metabolic health rewards for children.
Precision of a new tool to measure visceral adipose tissue (VAT) using dual‐energy X‐Ray absorptiometry (DXA)
Authors: Rothney Megan P. , Xia Yi , Wacker Wynn K. , Martin Francois‐Pierre , Beaumont Maurice , Rezzi Serge , Giusti Vittorio , Ergun David L.
Published: March 2013

Objective:

A new tool to quantify visceral adipose tissue (VAT) over the android region of a total body dual‐energy x‐ray absorptiometry (DXA) scan has recently been reported. The measurement, CoreScan, is currently available on Lunar iDXA densitometers. The purpose of the study was to determine the precision of the CoreScan VAT measurement, which is critical for understanding the utility of this measure in longitudinal trials.

Design and Methods:

VAT precision was characterized in both an anthropomorphic imaging phantom (measured on 10 Lunar iDXA systems) and a clinical population consisting of obese women (n = 32).

Results:

The intrascanner precision for the VAT phantom across 9 quantities of VAT mass (0–1,800 g) ranged from 28.4 to 38.0 g. The interscanner precision ranged from 24.7 to 38.4 g. There was no statistical dependence on the quantity of VAT for either the inter‐ or intrascanner precision result (p = 0.670). Combining inter‐ and intrascanner precision yielded a total phantom precision estimate of 47.6 g for VAT mass, which corresponds to a 4.8% coefficient of variance (CV) for a 1 kg VAT mass. Our clinical population, who completed replicate total body scans with repositioning between scans, showed a precision of 56.8 g on an average VAT mass of 1110.4 g. This corresponds to a 5.1% CV. Hence, the in vivo precision result was similar to the phantom precision result.

Conclusions:

The study suggests that CoreScan has a relatively low precision error in both phantoms and obese women and therefore may be a useful addition to clinical trials where interventions are targeted towards changes in visceral adiposity.
Obesity‐related hypertension: Pathogenesis, cardiovascular risk, and treatment—A position paper of the The Obesity Society and the American Society of Hypertension
Authors: Landsberg Lewis , Aronne Louis J. , Beilin Lawrence J. , Burke Valerie , Igel Leon I. , Lloyd‐Jones Donald , Sowers James
Published: March 2013

In light of the worldwide epidemic of obesity, and in recognition of hypertension as a major factor in the cardiovascular morbidity and mortality associated with obesity, The Obesity Society and The American Society of Hypertension agreed to jointly sponsor a position paper on obesity‐related hypertension to be published jointly in the journals of each society. The purpose is to inform the members of both societies, as well as practicing clinicians, with a timely review of the association between obesity and high blood pressure, the risk that this association entails, and the options for rational, evidenced‐based treatment. The position paper is divided into six sections plus a summary as follows: pathophysiology, epidemiology and cardiovascular risk, the metabolic syndrome, lifestyle management in prevention and treatment, pharmacologic treatment of hypertension in the obese, and the medical and surgical treatment of obesity in obese hypertensive patients. Obesity (2012)
Using facebook and text messaging to deliver a weight loss program to college students
Authors: Napolitano Melissa A. , Hayes Sharon , Bennett Gary G. , Ives Allison K. , Foster Gary D.
Published: March 2013

Objective:

Between 31 and 35% of the college‐aged population is overweight or obese, yet few weight loss trials for this population have been conducted. This study examined the feasibility, acceptability, and initial efficacy of a technology‐based 8‐week weight loss intervention among college students.

Design and Methods:

Students (N = 52) were randomly assigned to one of the three arms: Facebook (n = 17); Facebook Plus text messaging and personalized feedback (n = 18); Waiting List control (n = 17), with assessments at 4 weeks and 8 weeks (post‐treatment). Participants were 20.47 ± 2.19 years old, 86.45 ± 17.11 kg, with a body mass index of 31.36 ± 5.3 kg/m2. Participants were primarily female (86.5%), and the sample was racially diverse (57.7% Caucasian, 30.8% African American, 5.8% Hispanic, and 5.7% other races).

Results:

The primary outcome was weight loss after 8 weeks (post‐treatment); 96.0% of the participants completed this assessment. At 8 weeks, the Facebook Plus group had significantly greater weight loss (−2.4 ± 2.5 kg) than the Facebook (−0.63 ± 2.4 kg) and Waiting List (−0.24 ± 2.6 kg) (both Ps < 0.05). Weight change at 8 weeks was not significantly different between the Facebook and Waiting List groups.

Conclusions:

Results show preliminary efficacy and acceptability of the two active intervention arms (97.0% found the program helpful, 81.3% found the videos/handouts helpful, and 100% would recommend the program to others). Results indicate the potential for an innovative weight loss intervention that uses technology platforms (Facebook and text messaging) that are frequently used and already integrated into the cultural life of college students.
Central adiposity and other anthropometric factors in relation to risk of macrosomia in an african american population
Authors: Li Se , Rosenberg Lynn , Palmer Julie R. , Phillips Ghasi S. , Heffner Linda J. , Wise Lauren A.
Published: March 2013

Objective:

Previous studies have consistently identified maternal obesity and gestational weight gain (GWG) as risk factors for macrosomia, but little is known about the effects of central adiposity and body fat distribution. Using self‐reported data from the Black Women's Health Study (BWHS), a large follow‐up study of US black women, we examined the risk of macrosomia in relation to prepregnancy waist circumference, prepregnancy waist‐to‐hip ratio (WHR), prepregnancy BMI, and GWG.

Design and Methods:

During 1995–2003, BWHS participants ages 21–44 years delivered 6,687 full‐term singleton births (gestational age >37 weeks). We compared mothers of 691 infants weighing ≥4,000 g with mothers of 5,996 infants weighing <4,000 g. Generalized estimating equation models (GEE) that accounted for more than one birth per mother were used to estimate multivariable odds ratios (OR) and 95% confidence intervals (CI).

Results:

Independent of prepregnancy BMI, prepregnancy waist circumference was positively associated with risk of macrosomia (OR = 1.58, 95% CI: 1.07–2.32, for ≥35.0 vs. <27.0 inches (≥88.9 vs. <68.6 cm); P trend = 0.04). As expected, prepregnancy BMI was also positively associated with macrosomia (OR = 1.74, 95% CI: 1.25–2.41 for BMI ≥35.0 vs. 18.5–24.9 kg m−2). GWG above the amount recommended by the 2009 Institute of Medicine report was associated with an increased risk of macrosomia and the association was present in each category of prepregnancy BMI (18.5–24.9, 25.0–29.9, and ≥30.0 kg m−2; P trend <0.001).

Conclusions:

Our data suggest that overall obesity, high GWG, and high waist circumference are independent risk factors for macrosomia among US black women.
High‐normal tsh values in obesity: Is it insulin resistance or adipose tissue's guilt?
Authors: Muscogiuri Giovanna , Sorice Gian P. , Mezza Teresa , Prioletta Annamaria , Lassandro Anna P. , Pirronti Tommaso , Della Casa Silvia , Pontecorvi Alfredo , Giaccari Andrea
Published: March 2013

Objective:

Clinical evidences reported subclinical alterations of thyroid function in obesity, although the relationship between thyroid status and obesity remains unclear. We cross‐sectionally investigated the influence of metabolic features on hypothalamic–pituitary–thyroid axis in obesity.

Design and Methods:

We enrolled 60 euthyroid subjects with no history of type 2 diabetes mellitus and assessed the relationship of thyroid function with insulin resistance, measured using euglycemic clamp, and abdominal fat volume, quantified by computed tomography scan (CT scan). Thyroid stimulating hormone (TSH) correlated with BMI (r = 0.46; P = 0.02), both visceral (r = 0.58; P = 0.02) and subcutaneous adipose tissue volumes (r = 0.43; P = 0.03) and insulin resistance (inverse relationship with insulin sensitivity–glucose uptake: r = −0.40; P = 0.04).

Results:

After performing multivariate regression, visceral adipose tissue volume was found to be the most powerful predictor of TSH (β = 3.05; P = 0.01), whereas glucose uptake, high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, subcutaneous adipose tissue volume, and triglycerides were not. To further confirm the hypothesis that high‐normal TSH values could be dependent on adipose tissue, and not on insulin resistance, we restricted our analyses to moderately obese subjects' BMI ranging 30‐35 kg/m2. This subgroup was then divided as insulin resistant and insulin sensitive according to the glucose uptake (≤ or >5 mg·kg−1·min−1, respectively). We did not find any statistical difference in TSH (insulin resistant: 1.62 ± 0.65 µU/ml vs. insulin sensitive: 1.46 ± 0.48; P = not significant) and BMI (insulin resistant: 32.2 ± 1.6 kg/m2 vs. insulin sensitive: 32.4 ± 1.4; P = not significant), thus confirming absence of correlation between thyroid function and insulin sensitivity per se.

Conclusion:

Our study suggests that the increase in visceral adipose tissue is the best predictor of TSH concentration in obesity, independently from the eventual concurrent presence of insulin resistance.