bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue‐specific stable isotope ratios of shortfin mako (Isurus oxyrinchus) and white (Carcharodon carcharias) sharks as indicators of size‐based differences in foraging habitat and trophic level
Authors: Malpica‐Cruz Luis , Herzka Sharon Z. , Sosa‐Nishizaki Oscar , Escobedo‐Olvera Miguel A.
Published: July 2013

We evaluated whether the trophic level and feeding grounds (coastal versus offshore) of white and shortfin mako sharks captured in the northern Mexican Pacific varied as a function of size using carbon (δ13C values) and nitrogen (δ15N values) stable isotope analysis of soft tissues. A step increase in δ15N values was observed at approximately 85 cm TL and 150–170 cm TL for shortfin mako and white sharks, respectively, consistent with the dilution of the maternal isotopic signal following the incorporation of exogenous food. Shortfin mako and white shark muscle tissue and whole blood were enriched in 15N as a function of size, which is consistent with increasing trophic level, but this pattern may be confounded by differences in habitat. To infer differences in foraging habitat throughout life, we compared isotope ratios of liver and blood fractions with those of white muscle tissue; these tissues have relatively faster and slower isotope turnover rates, respectively. Whole blood and muscle δ13C values of small white sharks (<200 cm total length) caught near the coast suggested benthic foraging. Very limited differences between δ13C values of muscle tissue and whole blood from small and medium mako (<196 cm TL) and small white sharks indicated equilibrium to local feeding grounds. In contrast, differences in the δ13C values of liver tissue from small and medium mako and small white sharks indicated changes in diet or feeding grounds. The δ13C values of plasma and muscle tissue of large white sharks (>350 cm total length) caught offshore indicate feeding in coastal and oceanic areas and are consistent with recent migration to pelagic feeding grounds. Our study provides insight into size‐based habitat use and migration patterns of two species of migratory sharks for which there is limited information, particularly in their nursery grounds in Mexican waters.
Usefulness of combined application of double‐filtration plasmapheresis and twice‐daily injections of interferon‐β in hemodialysis patients with hepatitis C virus genotype 1b infection and a high viral load
Authors: Zeniya Mikio , Nakano Masanori , Saeki Chisato , Yokoyama Keitaro , Ishikawa Toru , Takaguchi Koichi , Takahashi Hiroki
Published: July 2013

Hepatitis C virus (HCV) infection is common among hemodialysis (HD) patients and has been recognized as an important prognostic factor. Therefore, the aggressive antiviral therapy is necessary for HCV infection in HD patients. However, various treatment limitations exist in HD patients such as the inability to use ribavirin. We have previously reported that HCV RNA can be eradicated by administration of interferon (IFN)‐β during HD in patients with HCV infection caused by genotypes known to be sensitive to IFN therapy and low serum HCV RNA levels. In this case report, we tried to clarify the efficacy of combined application of double‐filtration plasmapheresis (DFPP) and IFN‐β in HD patients with HCV genotype 1b infection and high serum HCV RNA levels. We report two HD patients with HCV genotype 1b infection and high viral loads who were successfully treated by five sessions of DFPP undertaken prior to treatment with IFN‐β (twice‐daily injections for 2 weeks). HCV was eradicated by this combination therapy in both patients. We revealed the efficacy of combined application of DFPP and IFN‐β in HD patients with HCV genotype 1b infection and high serum HCV RNA levels. This combined therapy may be useful for the HD patients who are resistant to conventional IFN monotherapy.
Characteristics and prediction of hepatitis B e‐antigen negative hepatitis following seroconversion in patients with chronic hepatitis B
Authors: Morita Susumu , Matsumoto Akihiro , Umemura Takeji , Shibata Soichiro , Kamijo Nozomi , Ichikawa Yuki , Kimura Takefumi , Joshita Satoru , Komatsu Michiharu , Yoshizawa Kaname , Tanaka Eiji
Published: July 2013

Aim

We analyzed the characteristics of alanine aminotransferase (ALT) abnormality after achieving hepatitis B e‐antigen (HBeAg) seroconversion (SC) and other factors associated with the occurrence of HBeAg negative hepatitis.

Methods

We followed 36 patients with chronic hepatitis B from 3 years prior to at least 3 years after SC (mean, 11.6 years) and examined ALT, hepatitis B virus (HBV) DNA, HB surface antigen, HB core‐related antigen (HBcrAg) levels and mutations related to HBeAg SC.

Results

ALT normalization (<31 IU/L for at least 1 year) was primarily observed until 2 years following SC, after which it became more infrequent. We next divided patients into abnormal (≥31 IU/L, n = 20) and normal (<31 IU/L, n = 16) groups based on integrated ALT level after the time point of 2 years from SC, and considered the former group as having HBeAg negative hepatitis in the present study. Although changes in median levels of ALT and HBcrAg differed significantly between the groups, multivariate analysis showed ALT normalization within 2 years after SC to be the only significant determining factor for this disease (P = 0.001). We then assessed the 19 patients whose ALT was normal at 2 years following SC, four of whom developed HBeAg negative hepatitis. Increased levels of HBV DNA (P = 0.037) and HBcrAg (P = 0.033) were significant factors of potential relevance.

Conclusion

ALT abnormality after 2 years of SC may be evaluated as HBeAg‐negative hepatitis. ALT, HBV DNA and HBcrAg levels may be useful in predicting the outcome of patients who achieve HBeAg SC.
Annexin A10 is an immunohistochemical marker for adenocarcinoma of the upper gastrointestinal tract and pancreatobiliary system
Authors: Lu Su‐Hsi , Yuan Ray‐Hwang , Chen Yu‐Ling , Hsu Hey‐Chi , Jeng Yung‐Ming
Published: July 2013

Aims

Annexin A10 (ANXA10) is a calcium‐ and phospholipid‐binding protein expressed normally in the gastric mucosa. In this study, we evaluated the potential use of ANXA10 as a diagnostic marker.

Methods and results

We observed ANXA10 expression in the gastric mucosa, the Brunner gland of the duodenum and the urothelium, but absence of expression in other normal organs. Following the screening of 1327 primary carcinomas of major organs, we identified ANXA10 expression in 46% of gastric, 72% of ampullary, 78% of pancreatic and 33% of biliary adenocarcinomas. ANXA10 was expressed in 83% of non‐invasive urothelial carcinomas, but was expressed in only 9% of invasive urothelial carcinomas. ANAX10 was rarely expressed in carcinomas of other organs. Of 227 metastatic adenocarcinomas, ANXA10 was expressed in 83% of metastatic pancreatic and 47% of metastatic gastric adenocarcinomas, but was expressed in only 2% of metastatic adenocarcinomas from other organs. In the liver, the sensitivity and specificity for identifying the pancreas as the primary site of metastatic adenocarcinoma were 83 and 95%, respectively.

Conclusion

Our study results indicate that the inclusion of ANXA10 in an immunohistochemical panel will be helpful in the differential diagnosis of adenocarcinoma of an unknown primary site.
Development of analytical method for determination of 1,4‐dioxane in cleansing products
Authors: Tahara M. , Obama T. , Ikarashi Y.
Published: July 2013

Synopsis

Objective

1,4‐Dioxane is a toxic by‐product formed during the synthesis of surfactants used in finished cosmetic products. There are no set permissible levels of toxic impurities in finished cosmetic products in Japan. In this study, we have established a simple and sufficiently precise analytical method to determine the activity of 1,4‐dioxane in finished cosmetic cleansing products.

Methods

This method involves the standard addition approach and headspace‐gas chromatography/mass spectrometry without pre‐conditioning.

Results

Fifteen cleansing products that are sold in the Japanese market, such as shampoo, hand soap, and dishwashing liquid, were analyzed, and 1,4‐dioxane was detected at a concentration of a few micrograms per gram of the product in almost all of them. The concentration of 1,4‐dioxane in two dishwashing liquid products was high. The maximum concentration of 1,4‐dioxane in all of the cleansing products was below 10 μg g−1, which is a limit that is thought to be safe and technically achievable through the application of good manufacturing practices. Since 1,4‐dioxane is formed during the synthesis of polyoxyethylene ether sulfate, it was detected at high concentrations in cleansing products that contained a lot of polyoxyethylene ether sulfate.

Conclusion

Control of the synthesis of polyoxyethylene ether sulfate can be effective in reducing the concentration of 1,4‐dioxane in cleansing products.
Aortic Stiffness Measurement Improves the Prediction of Asymptomatic Coronary Artery Disease in Stroke/Transient Ischemic Attack Patients
Authors: Calvet David , Touzé Emmanuel , Laurent Stéphane , Varenne Olivier , Sablayrolles Jean-Louis , Boutouyrie Pierre , Mas Jean-Louis
Published: July 2013

Background

Aortic stiffness is an independent predictor of coronary events.

Aims

We assessed the predictive value of aortic stiffness for ⩾50% asymptomatic coronary artery disease in a stroke/transient ischemic attack population.

Methods

We enrolled 300 consecutive patients aged 45–75 years with nondisabling, noncardioembolic ischemic stroke or transient ischemic attack, and no prior history of coronary artery disease. Coronary artery disease was assessed with 64-section computed tomography coronary angiography and all patients had a detailed cervicocephalic arterial work-up. Aortic stiffness was determined from carotid-femoral pulse wave velocity with 9·6 m/s as cutoff value. The predictive value of aortic stiffness was assessed by logistic regression and reclassification tables method after adjustment for the Framingham Risk Score and the presence of cervicocephalic stenosis, which were previously shown to be independent predictor of ⩾50% asymptomatic coronary artery disease.

Results

Among the 274 included patients who had computed tomography coronary angiography, 26% (95% CI, 21%–32%) had an increased stiffness (pulse wave velocity > 9·6 m/s) and 18% (14%–23%) had ⩾50% asymptomatic coronary artery disease. Increased aortic stiffness was associated with the presence of ⩾50% asymptomatic coronary artery disease, both in univariate (odds ratio = 3·4 [1·8–6·4]) and multivariate analyses (odds ratio = 2·3 [1·2–4·7]) after adjustment for Framingham Risk Score and presence of cervicocephalic stenosis. After carotid-femoral pulse wave velocity was added to the standard model including Framingham Risk Score and the presence of cervicocephalic stenosis, net reclassification improvement was 12·6% ( P < 0·005), integrated discrimination index was 2·51% ( P = 0·025), and model fit was improved (likelihood ratio = 4·99, P = 0·025).

Conclusions

In stroke/transient ischemic attack patients, aortic pulse wave velocity improves the prediction of ⩾50% asymptomatic coronary artery disease beyond classical risk factors.
Loss of β‐arrestin 2 exacerbates experimental autoimmune encephalomyelitis with reduced number of Foxp3+ CD4+ regulatory T cells
Authors: Zhang Yu , Liu Chang , Wei Bin , Pei Gang
Published: July 2013

β‐Arrestins are well‐known regulators and mediators of G protein‐coupled receptor signalling, and accumulating evidence reveals that they are functionally involved in inflammation and autoimmune diseases. Of the two β‐arrestins, β‐arrestin 1 is documented to play regulatory roles in an animal model of multiple sclerosis (MS), whereas the role of β‐arrestin 2 is less clear. Here, we show that β‐arrestin 2‐deficient mice displayed the exacerbated and sustained symptoms of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. At the cellular level, deficiency of β‐arrestin 2 led to a decreased number of Foxp3+ CD4+ regulatory T (Treg) cells in peripheral lymphoid organs of EAE mice. Consistently, our in vitro observations also revealed that loss of β‐arrestin 2 impaired the conversion of Foxp3− CD4+ T cells into Foxp3+ CD4+ inducible Treg cells. Taken together, our data suggest that β‐arrestin 2 plays a regulatory role in MS, that is opposite to that of β‐arrestin 1, in autoimmune diseases such as MS, which is at least partially through regulation of iTreg cell differentiation.
Influenza and respiratory syncytial virus are the major respiratory viruses detected from prospective testing of pediatric and adult coronial autopsies
Authors: Speers David J. , Moss Daniel M. , Minney‐Smith Cara , Levy Avram , Smith David W.
Published: July 2013

Background

To ascertain the full mortality of influenza and other respiratory viruses, the testing of community autopsy specimens is essential.

Methods

Respiratory virus PCR and culture were performed on 2418 fresh unfrozen respiratory samples collected from 1611 coronial cases where the death was either unknown or infection was suspected, from July 2007 to June 2011, to detect the common respiratory viruses in children and adults, using standardized microbiological testing.

Results

The respiratory virus positive rate was 8·3% (134 cases) with a peak of 28% (42 of 151 cases) in children under 10 years of age. Influenza virus was the commonest respiratory virus (50 cases, 3%), followed by respiratory syncytial virus (RSV) (30 cases, 2%). All tested respiratory viruses were found in children, most commonly adenovirus, enterovirus and RSV, and influenza A and RSV predominated in those over 60 years, but coinfection was uncommon. Almost all influenza cases occurred when influenza was widely circulating in the community but few were diagnosed pre‐mortem. Influenza and RSV detection was associated with bronchitis or bronchiolitis in 7 (9%) of the 80 cases and caused pneumonia in 14 (0·8%) deaths overall.

Conclusions

Our prospective review of respiratory viruses using standardized testing found a single lower respiratory tract autopsy specimen for respiratory virus PCR would detect most community infections at the time of death.
A century of chasing the ice: delayed colonisation of ice‐free sites by ground beetles along glacier forelands in the Alps
Authors: Brambilla Mattia , Gobbi Mauro
Published: July 2013

Climate change is affecting species distribution, composition of biological communities, and species traits. Despite the growing body of knowledge on the reaction of species to climate change, the potentially delayed response of species is still severely understudied.

In this paper we modelled the time needed by ground‐living invertebrates to effectively react to habitat modification induced by climate change in relation to dispersal abilities. We analyzed the occurrence pattern of alpine ground beetles (carabids) along areas recently freed by retreating glaciers in the central‐eastern Italian Alps, to test how the synergic effects of time since deglaciation and environmental factors may affect the colonisation process.

Different times of response to climate change in ground beetles were found. Sites already hosting the land cover type suitable for our study taxon, but ice‐free for less than 100 yr, are mainly colonised by winged carabid beetles (which have high dispersal abilities and are mostly habitat generalists). No, or very few, wingless species (slow colonizers and ecologically specialized) occur within those sites. The overall pattern suggests that within a site, suitable land cover is established prior to colonization, due to a strong joint effect of time since deglaciation and land cover type.

Long‐lasting habitat development at the fine scale is likely to result in a lack of specific resources (e.g. food items, or microhabitat), which is likely to contribute to delayed colonisation, which potentially could be tied also to dispersal abilities. Whatever the reason, the existence of a time‐lag often equal to or greater than 100 yr in species colonisation implies caution in predicting species’ occurrence shifts following climate change.
The Current Status of Angioplasty of Atherosclerotic Renal Artery Stenosis for the Treatment of Hypertension
Authors: Chrysant Steven G.
Published: July 2013

Atherosclerotic renal artery stenosis, a fairly common disease of older persons, is a manifestation of generalized atherosclerosis, and is often associated with coronary artery disease. It is frequently associated with hypertension and impaired renal function, and is perceived by many physicians to be the cause of hypertension and renal failure. For this reason, they believe that hypertension can be cured by performing percutaneous renal artery angioplasty (PTRA) with stent placement. This practice has led to an increase in angioplasties, especially by interventional cardiologists, although the results from several randomized studies comparing interventional therapy with medical therapy have shown no significant difference between the two treatment modalities in blood pressure reduction or change in renal function. Similar results have been found by nonrandomized trials with selective PTRA. For this review, a Medline search of the English literature was conducted from 2006 to 2012, and 13 pertinent studies were selected. These studies with collateral literature will be discussed in this concise review.
The Impact of Central Blood Pressure Levels on the Relationship Between Oscillometric and Central Blood Pressure Measurements: A Multicenter Invasive Study
Authors: Alihanoglu Yusuf I. , Kayrak Mehmet , Ulgen Mehmet S. , Yazici Mehmet , Yazici Mehmet , Yilmaz Remzi , Demir Kenan , Dogan Yildiz , Sizer Murat , Ozhan Hakan , Koc Fatih , Bodur Sait
Published: July 2013

The aim of this study was to investigate impact of central blood pressure (BP) levels and sex on the difference between central and upper arm oscillometric BP values. Oscillometric arterial BP measurements of 675 patients were simultaneously compared with values measured from the ascending aorta. The patients were divided into 3 groups according to systolic BP levels. The upper arm oscillometric device overestimated systolic BP (SBP) at low and medium BP levels but it underestimated SBP at high BP level. As for the effect of sex on differences in central and oscillometric BP, SBP was overestimated to a lesser degree in women than in men at low BP levels, but it was more highly underestimated in women than in men at high BP levels. The difference between oscillometric upper arm BP and aortic BP was directly affected by the patient's central BP level. In addition, the difference between central and oscillometric BP was also affected by sex factor.
Inhibition of checkpoint kinase 2 (CHK2) enhances sensitivity of pancreatic adenocarcinoma cells to gemcitabine
Authors: Duong Hong‐Quan , Hong Young Bin , Kim Jung Soon , Lee Hee‐Seok , Yi Yong Weon , Kim Yeon Jeong , Wang Antai , Zhao Wenjing , Cho Chi Heum , Seong Yeon‐Sun , Bae Insoo
Published: July 2013

Checkpoint kinase 2 (CHK2) plays pivotal function as an effector of cell cycle checkpoint arrest following DNA damage. Recently, we found that co‐treatment of NSC109555 (a potent and selective CHK2 inhibitor) potentiated the cytotoxic effect of gemcitabine (GEM) in pancreatic cancer MIA PaCa‐2 cells. Here, we further examined whether NSC109555 could enhance the antitumour effect of GEM in pancreatic adenocarcinoma cell lines. In this study, the combination treatment of NSC109555 plus GEM demonstrated strong synergistic antitumour effect in four pancreatic cancer cells (MIA PaCa‐2, CFPAC‐1, Panc‐1 and BxPC‐3). In addition, the GEM/NSC109555 combination significantly increased the level of intracellular reactive oxygen species (ROS), accompanied by induction of apoptotic cell death. Inhibition of ROS generation by N‐acetyl cysteine (NAC) significantly reversed the effect of GEM/NSC109555 in apoptosis and cytotoxicity. Furthermore, genetic knockdown of CHK2 by siRNA enhanced GEM‐induced apoptotic cell death. These findings suggest that inhibition of CHK2 would be a beneficial therapeutic approach for pancreatic cancer therapy in clinical treatment.
Cancer, stem cell misplacement and cancer stem cells
Authors: Liao Yong
Published: July 2013

The cell of origin of cancer as well as cancer stem cells is still a mystery. In a recent issue of JCMM, Wang et al. challenged the conventional somatic genetic mutation model of multi‐stage carcinogenesis of breast cancer and proposed that ‘Invasive cancers are not necessary from preformed in situ tumours—an alternative way of carcinogenesis from misplaced stem cells’. If this stem cell misplacement theory could withstand future experimental evaluation, it may provide a paradigm shift in the prevention and management of cancer in the clinic.
Nitric oxide production, systemic inflammation and lipid metabolism in periodontitis patients: possible gender aspect
Authors: Andrukhov Oleh , Haririan Hady , Bertl Kristina , Rausch Wolf‐Dieter , Bantleon Hans‐Peter , Moritz Andreas , Rausch‐Fan Xiaohui
Published: July 2013

Aim

Nitric oxide (NO) plays a crucial role in vascular tone regulation and is involved in pathogenesis of periodontitis. In this cross‐sectional study, we investigated the serum and saliva levels of NO metabolites in periodontal disease and their relationship with serum C‐reactive protein (CRP) levels, lipids metabolism and periodontal disease severity.

Material and Methods

Serum and saliva were collected from non‐smoking patients with generalized severe periodontitis (n = 89) and healthy controls (n = 56). Serum and salivary levels of NO metabolites, serum levels of high density lipoproteins (HDL), low density lipoproteins (LDL), triglycerides, cholesterol and CRP were measured. Data were analysed in whole population and in different gender groups.

Results

Periodontitis patients exhibited significantly lower serum and saliva levels of NO metabolites and significantly higher LDL, cholesterol and CRP levels than control group. Similar findings were observed within male but not within female population. Serum NO metabolites levels exhibited significant negative correlation with CRP in whole population and in male population. Significant positive correlation of serum NO metabolite levels with HDL levels was observed in whole population.

Conclusion

NO production is reduced in periodontitis, especially in male population. Gender might be an important factor in assessing risk of cardiovascular disease in periodontitis.
Vascular biology of the biliary epithelium
Authors: Morell Carola M , Fabris Luca , Strazzabosco Mario
Published: July 2013

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Cholangiocytes are involved in a variety of processes essential for liver pathophysiology. To meet their demanding metabolic and functional needs, bile ducts are nourished by their own arterial supply, the peribiliary plexus. This capillary network originates from the hepatic artery and is strictly arranged around the intrahepatic bile ducts. Biliary and vascular structures are linked by a close anatomic and functional association necessary for liver development, normal organ physiology, and liver repair. This strong association is finely regulated by a range of angiogenic signals, enabling the cross talk between cholangiocytes and the different vascular cell types. This review will briefly illustrate the “vascular” properties of cholangiocytes, their underlying molecular mechanisms and the relevant pathophysiological settings.
Hepatoprotective and anti‐fibrotic functions of interleukin‐22: Therapeutic potential for the treatment of alcoholic liver disease
Authors: Kong Xiaoni , Feng Dechun , Mathews Stephanie , Gao Bin
Published: July 2013

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Interleukin‐22 (IL‐22) plays a key role in promoting antimicrobial immunity and tissue repair at barrier surfaces by binding to the receptors IL‐22R1, which is generally thought to be expressed exclusively in epithelial cells, and IL‐10R2. Our laboratory previously demonstrated that IL‐22 plays an important role in ameliorating liver injury in many rodent models by targeting hepatocytes that express high levels of IL‐22R1 and IL‐10R2. Recently, we have identified high expression levels of IL‐22R1 and IL‐10R2 in liver progenitor cells and hepatic stellate cells (HSCs). Overexpression of IL‐22 in vivo or treatment with IL‐22 in vitro promotes proliferation of liver progenitor cells via a signal transducer and activator of transcription 3 (STAT3)‐dependent mechanism. IL‐22 treatment also prevents HSC apoptosis in vitro and in vivo. Surprisingly, overexpression of IL‐22, via either gene targeting or exogenous administration of adenovirus expressing IL‐22, reduces liver fibrosis and accelerates the resolution of liver fibrosis during recovery. The anti‐fibrotic effects of IL‐22 are mediated via the activation of STAT3 in HSCs and subsequent induction of suppressor of cytokine signaling 3, which induces HSC senescence. Taken together, the hepatoprotective, mitogenic, and anti‐fibrotic effects of IL‐22 are beneficial in ameliorating alcoholic liver injury. Importantly, due to the restricted expression of IL‐22R1, IL‐22 therapy is expected to have few side effects, thus making IL‐22 a potential candidate for treatment of alcoholic liver disease.
Reversal of hepatitis B virus‐induced systemic immune tolerance by intrinsic innate immune stimulation
Authors: Han Qiuju , Lan Peixiang , Zhang Jian , Zhang Cai , Tian Zhigang
Published: July 2013

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Systemic immune tolerance induced by chronic hepatitis B virus (HBV) infection is a significant question, but the mechanism of which remains unclear. In this mini‐review, we summarize the impaired innate and adaptive immune responses involved in immune tolerance in chronic HBV infection. Furthermore, we delineate a novel dual functional small RNA to inhibit HBV replication and stimulate innate immunity against HBV, which proposed a promising immunotherapeutic intervention to interrupt HBV‐induced immunotolerance. A mouse model of HBV persistence was established and used to observe the immune tolerant to HBV vaccination, the cell‐intrinsic immune tolerance of which might be reversed by chemically synthesized dual functional small RNA (3p‐hepatitis B Virus X gene [HBx]‐small interfering RNA) in vitro experiments and by biologically constructed dual functional vector (single‐stranded RNA‐HBx‐ short hairpin RNA) in vivo experiment using HBV‐carrier mice.
Immunocompetent nontransgenic mouse models for studying hepatitis B virus immune responses
Authors: Tzeng Horng‐Tay , Hsu Ping‐Ning , Chen Pei‐Jer
Published: July 2013

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Although the chronicity of hepatitis B virus (HBV) infection is the result of impaired HBV‐specific immune responses that cannot eliminate or clear the infected hepatocytes efficiently, many issues remained unsettled. It is thus crucial to have a suitable laboratory animal to study the immunopathogenesis of HBV infection and the mechanisms of HBV persistence. To meet the requirement of a mouse model resembling natural chronic HBV infection in human, there are several approaches in the development of mouse animal model by using hydrodynamic‐based transfection of HBV DNA, delivery of adenovirus or adeno‐associated viral vectors containing HBV DNA for studying HBV immune responses. These immunocompetent nontransgenic mouse animal models will provide new approaches to investigate the mechanisms of immune pathogenesis in HBV infection.
Liver immune‐pathogenesis and therapy of human liver tropic virus infection in humanized mouse models
Authors: Bility Moses T , Li Feng , Cheng Liang , Su Lishan
Published: July 2013

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Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect and replicate primarily in human hepatocytes. Few reliable and easy accessible animal models are available for studying the immune system's contribution to the liver disease progression during hepatitis virus infection. Humanized mouse models reconstituted with human hematopoietic stem cells (HSCs) have been developed to study human immunology, human immunodeficiency virus 1 infection, and immunopathogenesis. However, a humanized mouse model engrafted with both human immune and human liver cells is needed to study infection and immunopathogenesis of HBV/HCV infection in vivo. We have recently developed the humanized mouse model with both human immune and human liver cells (AFC8‐hu HSC/Hep) to study immunopathogenesis and therapy of HCV infection in vivo. In this review, we summarize the current models of HBV/HCV infection and their limitations in immunopathogenesis. We will then present our recent findings of HCV infection and immunopathogenesis in the AFC8‐hu HSC/Hep mouse, which supports HCV infection, human T‐cell response and associated liver pathogenesis. Inoculation of humanized mice with primary HCV isolates resulted in long‐term HCV infection. HCV infection induced elevated infiltration of human immune cells in the livers of HCV‐infected humanized mice. HCV infection also induced HCV‐specific T‐cell immune response in lymphoid tissues of humanized mice. Additionally, HCV infection induced liver fibrosis in humanized mice. Anti‐human alpha smooth muscle actin (αSMA) staining showed elevated human hepatic stellate cell activation in HCV‐infected humanized mice. We discuss the limitation and future improvements of the AFC8‐hu HSC/Hep mouse model and its application in evaluating novel therapeutics, as well as studying both HCV and HBV infection, human immune responses, and associated human liver fibrosis and cancer.
Bermuda Triangle for the liver: Alcohol, obesity, and viral hepatitis
Authors: Zakhari Samir
Published: July 2013

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Despite major progress in understanding and managing liver disease in the past 30 years, it is now among the top 10 most common causes of death globally. Several risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption, viral infection, gender, immune dysfunction, and medications, acting individually or in concert, are known to precipitate liver damage. Viral hepatitis, excessive alcohol consumption, and obesity are the major factors causing liver injury. Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)‐infected subjects worldwide are staggering (370 and 175 million, respectively), and of the 40 million known human immunodeficiency virus positive subjects, 4 and 5 million are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading causes of end‐stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. In addition, the global obesity epidemic that affects up to 40 million Americans, and 396 million worldwide, is accompanied by an alarming incidence of end‐stage liver disease, a condition exacerbated by alcohol. This article focuses on the interactions between alcohol, viral hepatitis, and obesity (euphemistically described here as the Bermuda Triangle of liver disease), and discusses common mechanisms and synergy.
Update on epidemiology of hepatitis B and C in China
Authors: Cui Yan , Jia Jidong
Published: July 2013

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A high rate of chronic hepatitis B virus (HBV) infection in China is mainly caused by perinatal or early childhood transmission. Administration of universal HBV vaccination in infants has led to a dramatic decrease in HBV epidemiology, with hepatitis B surface antigen (HBsAg) prevalence declining from 9.75% in 1992 to 7.18% in 2006. The major HBV genotypes are B and C, with B being more prevalent in the southern part and C more prevalent in the northern part of China. A national survey carried out in 1992 showed that the hepatitis C virus (HCV) infection rate was 3.20% in general population in China. After implementation of mandatory HCV screening for blood transfusion and other precautions to prevent blood‐borne disease since 1993, the new cases of HCV infection associated with blood or blood product has become very rare. Although the anti‐HCV prevalence would be much higher in high‐risk groups, a survey carried in 2006 showed that the anti‐HCV prevalence rate was only 0.43% in general population. This sharp decline in HCV infection rate was mainly due to stringent administration and monitoring of blood donors and blood products, but may also be related to the remarkably improved specificity of anti‐HCV test. The predominant HCV genotype in China is genotype 1b (60–70%), and the host interleukin‐28b rs12979860 CC genotype is very frequent in Chinese population (over 80%).
Common Sleep Disorders: Management Strategies and Pregnancy Outcomes
Authors: Nodine Priscilla M. , Matthews Ellyn E.
Published: July 2013

Sleep disorders, prevalent in industrialized countries, are associated with adverse health outcomes such as hypertension, diabetes, and obesity. Disturbed sleep during pregnancy is frequently overlooked by health care providers, yet recent studies suggest there is an association between sleep disorders and adverse pregnancy outcomes, including preeclampsia, elevated serum glucose, depression, prolonged labor, and cesarean birth. Growing evidence indicates that the recognition and management of prenatal sleep disorders may minimize adverse pregnancy outcomes and improve maternal and fetal well‐being. This focused review of prenatal sleep disturbance literature suggests there are 3 main sleep disorders of interest: breathing‐related sleep disorders (ie, habitual snoring and obstructive sleep apnea), restless legs syndrome, and insomnia. These sleep disorders are common in pregnancy and have maternal and fetal consequences if left untreated. This article describes sleep disorders of pregnancy, elucidates their relationship with maternal and neonatal outcomes, and presents current evidence regarding diagnostic and management strategies.
In vivo bone strain and finite element modeling of the mandible of Alligator mississippiensis
Authors: Porro Laura B. , Metzger Keith A. , Iriarte‐Diaz Jose , Ross Callum F.
Published: July 2013

Forces experienced during feeding are thought to strongly influence the morphology of the vertebrate mandible; in vivo strain data are the most direct evidence for deformation of the mandible induced by these loading regimes. Although many studies have documented bone strains in the mammalian mandible, no information is available on strain magnitudes, orientations or patterns in the sauropsid lower jaw during feeding. Furthermore, strain gage experiments record the mechanical response of bone at a few locations, not across the entire mandible. In this paper, we present bone strain data recorded at various sites on the lower jaw of Alligator mississippiensis during in vivo feeding experiments. These data are used to understand how changes in loading regime associated with changes in bite location are related to changes in strain regime on the working and balancing sides of the mandible. Our results suggest that the working side mandible is bent dorsoventrally and twisted about its long‐axis during biting, and the balancing side experiences primarily dorsoventral bending. Strain orientations are more variable on the working side than on the balancing side with changes in bite point and between experiments; the balancing side exhibits higher strain magnitudes. In the second part of this paper, we use principal strain orientations and magnitudes recorded in vivo to evaluate a finite element model of the alligator mandible. Our comparison demonstrates that strain orientations and mandibular deformation predicted by the model closely match in vivo results; however, absolute strain magnitudes are lower in the finite element model.
Financial Markets and Investment Externalities
Authors: TITMAN SHERIDAN
Published: July 2013

This address explores the link between financial market shocks, investment choices, and various externalities that can arise from these choices. My analysis, which emphasizes differences between shocks to debt and equity markets, provides insights about some stylized facts from the macro finance literature. These insights are illustrated with a discussion of the technology boom and bust in the late 1990s and early 2000s, and the housing boom and bust in the mid‐2000s.
Alternative surgical approach for the management of uterine prolapse in young women: Preliminary results
Authors: Karatayli Rengin , Balci Osman , Gezginç Kazim , Yildirim Pinar , Karanfil Fikriye , Acar Ali
Published: July 2013

Aim

To demonstrate an alternative surgical approach for the management of uterine prolapse in young women by a technique that was previously defined for post‐hysterectomy vaginal vault suspension in published work and also to demonstrate successful operative results.

Methods

The study population consisted of 12 women aged 28–41 years who had stage 4 uterine prolapse and who were surgically treated by abdominal hysteropexy using autogenous rectus fascia strips. Operative results and postoperative follow‐up Pelvic Organ Prolapse Quantification and Prolapse Quality of Life results were recorded.

Results

Mean age of patients was 35.5 ± 4.1 years (range, 28–41). Mean parity in the study group was 2.6 ± 1.0 (range, 1–5). Mean operation time was 32.0 ± 5.2 min (range, 25–42). All patients were discharged on the postoperative 3rd day and no complications were observed postoperatively. Mean follow‐up period was 20 ± 7.0 months (range, 12–36). All of the patients had complete remission for uterine prolapse and none of the patients had complaints related to the operation.

Conclusion

Abdominal hysteropexy operation using rectus fascia strips provides a safe and alternative approach for the management of uterine prolapse in young women who desire to preserve their uterus. But further analysis is needed to confirm our results.
Spinal cord infarction in diabetic pregnancy: A case report
Authors: Sugihara Takeru , Kido Koichiro , Sasamori Yukifumi , Shiba Masahiro , Ayabe Takuya
Published: July 2013

Spinal cord infarction (SCI) is uncommon as compared to cerebral stroke. Moreover, SCI during pregnancy is rare. Here, we report a case of SCI in diabetic pregnancy, properly diagnosed, promptly treated, and a good prognosis achieved. A 38‐year‐old, pregnant woman, para 1, with type 1 diabetes mellitus on insulin since 14 years of age, was admitted to our hospital for paresthesia and numbness in the lower left side of the body, with movement disturbances. On the basis of the temporal profile of the onset and the multiple resonance imaging scans, SCI was diagnosed. Steroid pulse therapy and low‐dose aspirin administration was initiated. Her symptoms were improved and discharged. A repeat cesarean section was performed at 37 weeks of gestation and her postoperative course was uneventful. Her daily activities were not hindered severely, though she experienced defecation discomfort.
Allen–Masters syndrome: Do the classic risk factors also apply in patients with endometriosis?
Authors: Haas Dietmar , Oppelt Peter , Shebl Omar , Chvatal Radek , Shamiyeh Andreas , Mayer Richard , Binder Helge
Published: July 2013

Aim

To evaluate whether the classic risk factors for Allen–Masters syndrome, such as body mass index (BMI) and spontaneous births, are in fact responsible for the condition in patients with endometriosis.

Methods

A total of 26 women who underwent a laparoscopic procedure due to chronic pelvic pain, Allen–Masters syndrome and endometriosis from 2009–2011 were enrolled in this study from an endometriosis competence center specializing in minimally invasive surgery. This was a retrospective cohort study (Canadian Task Force classification II‐2).

Results

Only eight of the 26 patients (30.77%; 95% confidence interval [CI], 14.33–51.79%) had the classic risk factors (BMI >25 kg/m2 and/or at least one spontaneous birth). The mean age in the study group was 32.08 years (SD ± 5.45). The patients had a mean BMI (kg/m2) of 19.61 (SD ± 3.07). The means for the patients' clinical data were 0.88 (SD ± 1.53) pregnancies, 0.81 (SD ± 1.23) for parity, 0.27 (SD ± 0.60) for cesareans and 0.54 (SD ± 0.99) for spontaneous births. The revised American Society for Reproductive Medicine (rASRM) stage showed a median of grade III. The left side of the posterior compartment was more often affected (73.1% of cases) than the right side in all patients.

Conclusion

In all, 69.23% of the cases (95% CI, 48.21–85.67%) were not explained by the classic risk factors. In view of the absence of other diseases and otherwise unremarkable parameters, we consider mechanical damage of the lesser pelvis not to be solely responsible for AMS. Further observations in patients with AMS, with and without endometriosis, may be able to contribute to research into the actual etiology of the condition.
Toll‐like receptor system and endometriosis
Authors: Khan Khaleque Newaz , Kitajima Michio , Fujishita Akira , Nakashima Masahiro , Masuzaki Hideaki
Published: July 2013

Endometriosis is an estrogen‐dependent chronic inflammatory condition associated with variable degrees of pelvic pain and infertility. Studies have showed that the growth and progression of endometriosis continue even in ovariectomized animals. This indicates that besides ovarian steroid hormones, the growth of endometriosis can be regulated by the innate immune system in the pelvic environment. As a component of innate immune system, increased infiltration of macrophages has been described in the intact tissue and peritoneal fluid of women with endometriosis. Different immune cells and dendritic cells express Toll‐like receptors (TLR) and exhibit functional activity in response to microbial products. In this review article, we discuss the role of the TLR system in endometrium and endometriosis and outline the involvement of cytokines/endotoxin in causing adverse reproductive outcome. In the first part of this review article, the fundamentals of innate immune system, functional characteristics of TLR and signaling pathways of TLR4 are discussed for easy understanding by the readers.
Intergenerational Transmission of Noncommunicable Chronic Diseases
Authors: GOULÃO CATARINA , PÉREZ‐BARAHONA AGUSTÍN
Published: July 2013

We introduce a theoretical framework that contributes to the understanding of noncommunicable chronic diseases (NCDs) epidemics: even if NCDs are noninfectious diseases, they may spread due to the social transmission of unhealthy activities such as unhealthy diet, physical inactivity, and smoking. In particular, we study the intergenerational dimension of this mechanism. We find that, due to the social transmission of NCDs, agents choose lower health conditions and higher unhealthy activities than what is socially optimal. Taxes on unhealthy activities, that may subsidize health investments, can be used to restore the social optimum. Finally, our model is consistent with the existence of regional asymmetries regarding the prevalence of obesity and NCDs.
Optimal Piecewise Linear Income Taxation
Authors: APPS PATRICIA , VAN LONG NGO , REES RAY
Published: July 2013

Given its significance in practice, piecewise linear taxation has received relatively little attention in the literature. This paper offers a simple and transparent analysis of its main characteristics. We fully characterize optimal tax parameters for the cases in which budget sets are convex and nonconvex respectively. A numerical analysis of a discrete version of the model shows the circumstances under which each of these cases will hold as a global optimum. We find that, given plausible parameter values and wage distributions, the globally optimal tax system is convex, and marginal rate progressivity increases with rising inequality.
Factors Influencing Patient Decisions to Initiate and Discontinue Subcutaneous Testosterone Pellets (Testopel) for Treatment of Hypogonadism
Authors: Smith Ryan P. , Khanna Abhinav , Coward Robert M. , Rajanahally Saneal , Kovac Jason R. , Gonzales Marshall A. , Lipshultz Larry I.
Published: July 2013

Introduction

A variety of modalities for testosterone replacement therapy (TRT) are available, including topical gels, injections, and Testopel subcutaneous testosterone pellets (STP). STP are becoming more commonly utilized in the United States; however, patient preferences, expectations, and usage patterns regarding this therapy remain poorly characterized.

Aim

To identify factors influencing patients' decisions to initiate or discontinue STP.

Methods

A total of 175 men from an academic urology clinic who were currently using or who had previously used STP for hypogonadism received a 32-item electronic survey.

Main Outcome Measures

Assessment of the impact of convenience, efficacy, side effects, cost, and symptom relief on initiation and discontinuation of STP.

Results

One hundred and thirteen men (64.6% response rate) of mean age 51.4 years who previously underwent a mean of 2.8 STP implant procedures completed the survey. Fifty-nine (52.2%) and 40 (35.4%) men had switched to STP from topical gel and injection therapy, respectively, whereas 14 (12.4%) men initially started TRT with STP. Convenience (68.8%) was the most important factor in patients' decision to start STP, while cost of the previous form of TRT (14.7%) was least important. At the time of the survey, 32 men (28.3%) had discontinued STP therapy. Cost of therapy (50%) was the primary factor in discontinuing STP. There was no difference in serum testosterone levels between men who continued STP and those who discontinued therapy (642.8 vs. 629.0ng/dL, P =0.83). Overall, 68.1% of patients continued STP therapy at the time of survey completion.

Conclusions

Convenience is the most important factor in a patient's decision to initiate STP; however, physician recommendation also plays a substantial role. Cost was the primary reason for discontinuation. Upon survey completion, greater than two-thirds of respondents elected to continue STP therapy. STP are a viable treatment option for hypogonadal men seeking a convenient and efficacious alternative modality of TRT.
Serum PSA as a Predictor of Testosterone Deficiency
Authors: Rastrelli Giulia , Corona Giovanni , Vignozzi Linda , Maseroli Elisa , Silverii Antonio , Monami Matteo , Mannucci Edoardo , Forti Gianni , Maggi Mario
Published: July 2013

Introduction

The relationship between serum prostate-specific antigen (PSA) and testosterone (T) levels is still controversial. According to the “saturation hypothesis,” a significant relationship is apparent only in the low T range.

Aim

To verify whether, in a large sample of male subjects seeking medical care for sexual dysfunction (SD), PSA might represent a reliable marker of T levels.

Methods

A consecutive series of 3,156 patients attending our unit for SD was studied. Among them, only subjects without history of prostate disease and with PSA levels <4 ng/mL (N = 2,967) were analyzed.

Main Outcome Measures

Several hormonal and biochemical parameters were studied, along with structured interview on erectile dysfunction (SIEDY), ANDROTEST, and PsychoANDROTEST.

Results

Receiver operating characteristic curve analysis for predicting severe hypogonadism (T < 8 nmol/L) showed an accuracy of PSA = 0.612 ± 0.022 (P < 0.0001), with the best sensitivity and specificity at PSA < 0.65 ng/mL (65.2% and 55.5%, respectively). In the entire cohort, 254 subjects (8.6%) showed T < 8 nmol/L and, among them, more than half (N = 141, 4.8%) had PSA < 0.65 ng/mL. After adjusting for age, low PSA was associated with hypogonadism-related features (i.e., delayed puberty, lower testis volume) and associated conditions, such as metabolic syndrome (hazard ratio [HR] = 1.506 [1.241–1.827]; P < 0.0001), type 2 diabetes (HR = 2.044 [1.675–2.494]; P < 0.0001), and cardiovascular diseases (HR = 1.275 [1.006–1.617]; P = 0.045). Furthermore, low PSA was associated with impaired sex- and sleep-related erections. The association between low PSA and hypogonadal symptoms and signs as well as with metabolic syndrome was retained even after adjusting for T levels. Sensitivity and positive predictive values of low PSA increased, whereas specificity and negative predictive value decreased as a function of age.

Conclusions

PSA is a marker of T concentrations and it may represent a new tool in confirming hypogonadism. The determination of PSA levels might give insights not only on the circulating levels of total T but also on its active fractions.