bluuebunny/crossref_metadata_2025 huggingface dataset:
Brachioradial pruritus – descriptive analysis of Brazilian case series
Authors: Masuda Paula Y. , Martelli Antonio Carlos Ceribelli , Wachholz Patrick A. , Akumatsu Hélcio T. , Martins Ana L. G. P. , Silva Nathália M.
Published: January 2013

Background

The epidemiology and clinical features of brachioradial pruritus are variably described in the literature. We sought to analyze these features in a large group of Brazilian patients.

Patients and Methods

In a descriptive, observational study, we identified all patients with a final diagnosis of brachioradial pruritus seen over a one‐year period and re‐trospectively reviewed their records. The diagnosis was made after clinical‐laboratory investigation had ruled out other causes of chronic pruritus. Demographic and clinical variables were collected along with pruritus characteristics, and analyzed using des‐criptive statistics.

Results

Forty‐three patients were identified; their mean age was 55.9 years, with predominance of women (81.4%) and Caucasians (86%). In 52%, the pruritus worsened with heat and sun exposure; 58.1% had intermittent complaints; the ice‐pack sign was present only in 20.9%. The arms involving dermatomes C5‐C6‐C7‐C8 (62.8%) were the most affected sites, while psychoactive drugs were the most frequently prescribed therapy.

Conclusions

Although uncommon, brachioradial pruritus should not be neglected in dermatological diagnosis. This case series analysis indicated that Brazilian patients from a tropical climate show characteristics similar to those described in other series from more temperate regions.
Testosterone challenge and androgen receptor activity in relation to UGT2B17 genotypes
Authors: Ekström Lena , Cevenini Luca , Michelini Elisa , Schulze Jenny , Thörngren John‐Olof , Belanger Alain , Guillemette Chantal , Garle Mats , Roda Aldo , Rane Anders
Published: January 2013

Background

We investigated the androgen receptor (AR) bioluminescense response in serum and urine before and after testosterone challenge in different genotypes of the UGT2B17 enzyme, which catalyses testosterone glucuronidation.

Material and methods

The androgen receptor activity was determined using a yeast‐based bioluminescence assay. The androgens were analysed using LC‐MS/MS, and the individuals were genotyped for UGT2B17 deletion polymorphism using real‐time polymerase chain reaction.

Results

The serum concentrations of testosterone and dihydrotestosterone (DHT) were markedly elevated on days 2 and 4 and were still above baseline on day 15 after a dose of 500 mg testosterone enanthate. The androgenic activity in serum increased in parallel and correlated with the hormone concentrations and remained above baseline on day 15. The urinary androgenic activity increased 4–5‐fold and was closely related to the unconjugated testosterone and independent of the UGT2B17 genotype.

Conclusions

The AR assay may serve as a complement to the urinary testosterone/epitestosterone (T/E) doping test, because this is profoundly influenced by the UGT2B17 deletion polymorphism. It may also be useful for detection of other illicit androgens in sports, or in the society, or for monitoring and diagnostics of androgen‐related disorders.
Body size distributions in North American freshwater fish: small‐scale factors and synthesis
Authors: Griffiths David
Published: January 2013

The ecosystem size/trophic structure hypothesis predicts that the shape of body size distributions will change with ecosystem size because of increases in the relative importance of large, predatory, species. I test the hypothesis by examining the statistical moments, as measures of shape, of species body size distributions of North American freshwater fish assemblages in lakes. Species lists, coupled with dietary and body size information, are used to document the patterns. Body size distributions in small lakes are unimodal and right‐skewed, but distributions become more symmetrical and bimodal in large ecosystems. In small lakes, body sizes are generally small and fish trophic levels low, but size and trophic level increase up to lake volumes of about 0.001 km3, and change little in larger lakes. Adding trophic level to the analysis greatly improves the variance explained by the body size–lake size relation. The conclusions of Griffiths (2012, Global Ecology & Biogeography 21: 383‐392), that postglacial recolonisation and evolutionary change are important determinants of body size distributions at regional and larger scales, are combined with those of this study. Mean body size in local assemblages of lake‐dwelling species is larger than in regional and continental ones. Overall, body size distributions are affected by processes operating at a variety of spatial and temporal scales, with the type, size and duration of the ecosystem probably playing a central role by influencing the proportions of vagile and predatory species, the species which dominate the large size mode.
The Timing of Opening Trades and Pricing Errors
Authors: Kim Sukwon Thomas
Published: January 2013

After demonstrating that a zero investment trading strategy that buys stocks with overnight returns below the market average and sells stocks with overnight returns above the market average earns more than 1% monthly profit, I demonstrate that this profit is greater for stocks that start trading more quickly than for other stocks. These results control for trading costs. The resulting pricing errors are a material portion of stock price volatility and suggest that a quick response to overnight information adds non‐information‐based stock volatility to stock prices.
SURgical interventions with FEIBA (SURF): international registry of surgery in haemophilia patients with inhibitory antibodies
Authors: Négrier C. , Lienhart A. , Numerof R. , Stephens D. , Wong W. Y. , Baghaei F. , Yee T. T.
Published: January 2013

Factor VIII Inhibitor Bypassing Activity (FEIBA) can effectively achieve haemostasis in haemophilia patients with inhibitors. Further evaluation of FEIBA in surgical settings is of significant interest considering the relatively limited prospective data published to date. The aim of the study is to evaluate the perioperative efficacy and safety of FEIBA in haemophilia patients with inhibitors. Haemophilia patients with inhibitors who underwent surgical procedures and received FEIBA for perioperative haemostatic control were prospectively enrolled in an open‐label, noninterventional, postauthorization study [SURgical interventions with FEIBA (SURF)]. Outcome measures included haemostatic efficacy, safety, FEIBA exposure and blood loss associated with the perioperative use of FEIBA. Thirty‐five surgical procedures were performed at 19 centres worldwide in patients with congenital haemophilia A, congenital haemophilia B, or acquired haemophilia A. Haemorrhagic risk was severe in 37.1% (13 of 35) of the procedures, moderate in 25.7% (9 of 35) and mild in 37.1% (13 of 35). One moderate risk surgery was excluded from the efficacy analyses because it did not meet all protocol requirements. Haemostasis was judged to be ‘good’ or ‘excellent’ in 91.2% (31 of 34) of surgical procedures and ‘fair’ in 8.8% (3 of 34). Among the 12 adverse events, three were serious adverse events (SAEs), two of which were unrelated to FEIBA therapy; one SAE, a clot in an arteriovenous fistula, was deemed to be possibly related to therapy. This prospective investigation confirms that FEIBA can be safely and effectively used when performing surgical procedures in haemophilia patients with inhibitors.
Gaps in social protection for health care and long‐term care in Europe: Are the elderly faced with financial ruin?
Authors: Scheil‐Adlung Xenia , Bonan Jacopo
Published: January 2013

While public expenditure on health care and long‐term care (LTC) has been monitored for many years in European countries, far less attention has been paid to the financial consequences for older people of private out‐of‐pocket (OOP) expenditure necessary to access such care. Employing representative cross‐sectional data on the elderly populations of 11 European countries in 2004 from the Survey of Health, Ageing and Retirement in Europe (SHARE), we find that OOP payments for health care and LTC are very common among the elderly across European countries and such expenditures impact significantly on disposable income: up to 95 per cent of the elderly make OOP payments for health care and 5 per cent for LTC, resulting in income reductions of between 5 and 10 per cent, respectively. Failure to prevent financial ruin, as a consequence of excessive OOP payments, is evident in 0.7 per cent of elderly households utilizing health care and 0.5 per cent of elderly households utilizing LTC. Those particularly concerned are the poor, women and the very old.
Old‐age protection for women in the Spanish pension system
Authors: Cifre Concha Salvador
Published: January 2013

The example of Spain confirms the common view that contributory pension systems reproduce inequalities between the sexes that result from the nature of labour market structures and the sharing of family responsibilities. In general, women who stay at home are not entitled to their own pensions and are dependent on benefits of lower value such as survivors' pensions (derived entitlements) or non‐contributory pensions. In turn, women who work outside the home accrue lower entitlements than men and, consequently, lower old‐age or disability pensions (personal entitlements). The purpose of this article is to examine the figures for pension distribution by sex in Spain, review some of the pension policies that have been implemented since 2000, and propose direct action for progress in the transition from derived entitlements to personal entitlements. These proposals are designed to promote sex equality, defined as the right to equal well‐being and financial security in old age.
Life with chronic obstructive pulmonary disease: striving for ‘controlled co‐existence’
Authors: Cooney Adeline , Mee Lorraine , Casey Dympna , Murphy Kathy , Kirwan Collette , Burke Eimear , Conway Yvonne , Healy Denise , Mooney Brona , Murphy Jill ,   The PRINCE Team
Published: January 2013

Aims and objectives

To understand the meaning of chronic obstructive pulmonary disease (COPD) for people and their response to this disease.

Background

COPD is a major cause of disability and death. The symptoms of COPD have the potential to impact on every aspect of a person's day‐to‐day life. To date most published qualitative studies have focused on the ‘experience’ of breathlessness and its impact on the person. Few studies have sought to ‘understand’ the meaning of COPD to people and their response to this disease. This study aimed to address this gap.

Design

Straussian grounded theory guided study design. Grounded theory was considered appropriate for this study because of its focus on how people respond to and act on the problems they encounter.

Methods

Data were collected through semi‐structured interviews with 26 people with COPD. Study participants were recruited from general practices on the western seaboard of Ireland.

Results

Two interrelated categories were identified as contributing to ‘co‐existing with COPD’: ‘hiding’ and ‘battling’. ‘Co‐existing with COPD’ was conceptualised as the core category. The potential to ‘co‐exist’ with COPD was influenced by mediating factors.

Conclusion

The Theory of Co‐existing with COPD was generated from the data. This theory explains the delicate balance people with COPD maintain to ‘co‐exist with COPD’. ‘Controlled co‐existence’ enables the person to feel in control and live life to the optimum. This is a fragile balance however and the unpredictability of COPD can tip the person into ‘strained co‐existence’ or ‘uncontrolled co‐existence’.

Relevance to clinical practice

Understanding the experience of living with COPD and the balances involved in ‘co‐existing with COPD’ can help health professionals provide more focused and empowered client care. Enabling people to achieve ‘controlled co‐existence’ with COPD challenges health professionals to educate people with COPD on how to effectively manage their disease.
Acute exogenous lipoid pneumonia caused by accidental kerosene ingestion in an elderly patient with dementia: A case report
Authors: Gotanda Hiroshi , Kameyama Yumi , Yamaguchi Yasuhiro , Ishii Masaki , Hanaoka Yoko , Yamamoto Hiroshi , Ogawa Sumito , Iijima Katsuya , Akishita Masahiro , Ouchi Yasuyoshi
Published: January 2013

Acute exogenous lipoid pneumonia is an uncommon condition caused by aspiration of oil‐based substances, occurring mainly in children. Here, we report the case of an 83‐year‐old patient with Alzheimer's disease who presented with coughing and hypoxia. The diagnosis of acute exogenous lipoid pneumonia caused by accidental kerosene ingestion was made on the basis of the patient's clinical history, and typical radiological and cytological findings. The patient's cognitive impairment and an unsafe environment, in which the patient's 91‐year‐old husband stored kerosene in an old shochu bottle, were responsible for the accidental ingestion. Acute exogenous lipoid pneumonia should be considered in the differential diagnosis for acute respiratory disorders in the rapidly aging population. Geriatr Gerontol Int 2013; 13: 222–225.
Excessive weight gain in women with a normal pre‐pregnancy BMI is associated with increased neonatal adiposity
Authors: Josefson J. L. , Hoffmann J. A. , Metzger B. E.
Published: January 2013

Background

More than 40% of women with a normal pre‐pregnancy body mass index (BMI) exceed the 2009 Institute of Medicine (IOM) guidelines’ recommended weight gain of 25–35 lb. Excessive gestational weight gain is one modifiable factor that may be contributing to childhood overweight and obesity.

Objective

The objective of this study was to evaluate differences in adiposity from neonates born to mothers with a normal pre‐pregnancy BMI who either gained within or above IOM guidelines.

Methods

Neonatal adiposity was measured within 72 h of birth by the method of air displacement plethysmography.

Results

Compared with mothers who gained within IOM guidelines (N = 27), mothers with excessive gestational weight gain (N = 11) (mean 29.0 vs. 45.2 lb) had neonates with 50% more fat mass (348 vs. 525 g) and 3% greater body fat (10.7 vs. 13.9%).

Conclusions

Increased adiposity at birth may predispose these children to increased risk of obesity and highlight the importance that women avoid gaining excessive weight in pregnancy.
Development of a Doula Intervention for Postpartum Depressive Symptoms: Participants' Recommendations
Authors: McComish Judith Fry , Groh Carla J. , Moldenhauer Judith A.
Published: January 2013

Problem

About 10–15% of women experience postpartum depression (PPD). Doulas provide support and education about PPD.

Methods

This qualitative study used focus groups with mothers, doulas, and doula trainers to develop educational materials for doulas to help mothers identify symptoms of depression and seek treatment.

Findings

All participants preferred materials that use simple language and avoid psychiatric jargon. Three themes emerged: someone to talk to, flexibility, and interactivity. Materials developed include tri‐fold brochure and content for an application for smartphones and digital tablets.

Conclusions

Doulas can use these interactive materials to provide supportive, relationship‐based care that complements nursing care.
Research Review: Emanuel Miller Memorial Lecture 2012 – Neuroscientific studies of intervention for language impairment in children: interpretive and methodological problems
Authors: Bishop D. V. M.
Published: January 2013

Background:  Our ability to look at structure and function of a living brain has increased exponentially since the early 1970s. Many studies of developmental disorders now routinely include a brain imaging or electrophysiological component. Amid current enthusiasm for applications of neuroscience to educational interventions, we need to pause to consider what neuroimaging data can tell us. Images of brain activity are seductive, and have been used to give credibility to commercial interventions, yet we have only a limited idea of what the brain bases of language disorders are, let alone how to alter them.

Scope and findings:  A review of six studies of neuroimaging correlates of language intervention found recurring methodological problems: lack of an adequate control group, inadequate power, incomplete reporting of data, no correction for multiple comparisons, data dredging and failure to analyse treatment effects appropriately. In addition, there is a tendency to regard neuroimaging data as more meaningful than behavioural data, even though it is behaviour that interventions aim to alter.

Conclusion:  In our current state of knowledge, it would be better to spend research funds doing well‐designed trials of behavioural treatment to establish which methods are effective, rather than rushing headlong into functional imaging studies of unproven treatments.
Molecular divergence in tropical tree populations occupying environmental mosaics
Authors: Audigeos D. , Brousseau L. , Traissac S. , Scotti‐Saintagne C. , Scotti I.
Published: January 2013

Unveiling the genetic basis of local adaptation to environmental variation is a major goal in molecular ecology. In rugged landscapes characterized by environmental mosaics, living populations and communities can experience steep ecological gradients over very short geographical distances. In lowland tropical forests, interspecific divergence in edaphic specialization (for seasonally flooded bottomlands and seasonally dry terra firme soils) has been proven by ecological studies on adaptive traits. Some species are nevertheless capable of covering the entire span of the gradient; intraspecific variation for adaptation to contrasting conditions may explain the distribution of such ecological generalists. We investigated whether local divergence happens at small spatial scales in two stands of Eperua falcata (Fabaceae), a widespread tree species of the Guiana Shield. We investigated Single Nucleotide Polymorphisms (SNP) and sequence divergence as well as spatial genetic structure (SGS) at four genes putatively involved in stress response and three genes with unknown function. Significant genetic differentiation was observed among sub‐populations within stands, and eight SNP loci showed patterns compatible with disruptive selection. SGS analysis showed genetic turnover along the gradients at three loci, and at least one haplotype was found to be in repulsion with one habitat. Taken together, these results suggest genetic differentiation at small spatial scale in spite of gene flow. We hypothesize that heterogeneous environments may cause molecular divergence, possibly associated to local adaptation in E. falcata.
Effects of within‐colony competition on body size asymmetries and reproductive skew in a social spider
Authors: Grinsted L. , Bilde T.
Published: January 2013

Reproductive partitioning is a key component of social organization in groups of cooperative organisms. In colonies of permanently social spiders of the genus Stegodyphus less than half of the females reproduce, while all females, including nonreproducers, perform suicidal allo‐maternal care. Some theoretical models suggest that reproductive skew is a result of contest competition within colonies, leading to size hierarchies where only the largest females become reproducers. We investigated the effect of competition on within‐group body size variation over six months in S. dumicola, by manipulating food level and colony size. We found no evidence that competition leads to increased size asymmetry within colonies, suggesting that contest competition may not be the proximate explanation for reproductive skew. Within‐colony body size variation was high already in the juvenile stage, and did not increase over the course of the experiment, suggesting that body size variation is shaped at an early stage. This might facilitate task specialization within colonies and ensure colony‐level reproductive output by early allocation of reproductive roles. We suggest that reproductive skew in social spiders may be an adaptation to sociality selected through inclusive fitness benefits of allo‐maternal care as well as colony‐level benefits maximizing colony survival and production.
Anti‐listerial and Anti‐biofilm Activities of Potential Probiotic Lactobacillus Strains Isolated from Tunisian Traditional Fermented Food
Authors: Ben Slama Rihab , Kouidhi Bochra , Zmantar Tarek , Chaieb Kamel , Bakhrouf Amina
Published: January 2013

Three Lactobacilli were isolated from traditional Tunisian fermented food and then characterized for its ability to inhibit Listeria monocytogenes growth. Antagonistic effect of Lactobacillus plantarum on four L. monocytogenes strains was tested in soft artisanal cheese. Anti‐biofilm activity of Lactobacillus extracts was also tested.

Our results demonstrate that the selected lactic acid bacteria (LAB) extract exhibited a good antibacterial effect against L. monocytogenes ATCC 19115 with low MICs values: 8.33 ± 2.1, 20 ± 1.2 and 23.33 ± 1, respectively. L. plantarum also exhibited a stronger inhibitory effect against L. monocytogenes when grown in cheese. Moreover, a potential anti‐biofilm effect of the three LAB extracts with BIC50 values ranging from 5% to 15% for L. monocytogenes ATCC 19115 was demonstrated. Although LAB extracts were able to eradicate significantly a preformed L. monocytogenes biofilm (P < 0.05). Growth inhibition of preformed biofilm was more difficult to achieve. LAB could be used as a bioprotective culture in cheese ripening to prevent Listeria growth.

Practical Applications

A wide range of lactic acid bacteria (LAB) produce bacteriocins, which were essentially active against the food‐borne pathogen Listeria monocytogenes. 2, 3‐bis (2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐5‐[(phenylamino) carbonyl]‐2H‐tetrazolium hydroxide (XTT) reduction method was used to assess the anti‐biofilm and anti‐listerial activity of LAB extract. XTT reduction assay is dependent on the microbial respiratory activity.

Since XTT is used for quantification of the microbial respiratory activity, it was used to quantify viable mature biofilm and to compare LAB activity against planktonic and biofilm cells.
Characterization of electroencephalographic and biochemical responses at 5‐HT promoting drug‐induced onset of serotonin syndrome in rats
Authors: Ma Zhiyuan , Rudacille Mary , Prentice Howard M. , Tao Rui
Published: January 2013

Many psychotropic substances used either for medications or illicit recreational purposes are able to produce an increase in extracellular serotonin (5HT) in the CNS. 5HT is well known to improve mood; however, only when the levels of its release are in an appropriate range. Excessive 5HT is harmful, and will generally result in serotonin syndrome. To date, clinical diagnosis of serotonin syndrome relies exclusively on observation of symptoms because of a lack of available laboratory tests. The goal of this study was to characterize the onset of the syndrome using laboratory settings to determine excessive 5HT‐evoked neurological abnormalities. Experiments were carried out in rats with the syndrome being elicited by three groups of 5HT‐promoting drugs: (i) (±)‐3,4‐methylenedioxymethamphetamine (MDMA); (ii) a combination of the monoamine oxidase inhibitor clorgyline with the 5HT precursor 5‐hydroxytryptophan; (iii) clorgyline combined with the serotonin‐selective reuptake inhibitor paroxetine. The onset of the syndrome was characterized by electroencephalography (EEG), tremor, and brain/plasma 5HT tests. We found that a mild syndrome was associated with reduced EEG amplitudes while a severe syndrome strongly with seizure‐like EEG activity and increased tremor activity. The occurrence of the syndrome was confirmed with microdialysis, showing excessive 5HT efflux in brain dialysate and the increased concentration of unbound 5HT in the plasma. Our findings suggest that the syndrome onset can be revealed with EEG recording, measurements of tremor activity and changes of unbound 5HT concentration in the plasma.
SH2‐Containing Inositol 5′‐Phosphatase 2 Selectively Impairs Hypothalamic Insulin Signalling and Regulation of Food Intake in Mice
Authors: Ichihara Y. , Wada T. , Soeda Y. , Ishii Y. , Sasahara M. , Tsuneki H. , Sasaoka T.
Published: January 2013

SH2‐containing inositol 5′‐phosphatase 2 (SHIP2) is a lipid phosphatase that negatively regulates the metabolic signalling of insulin in peripheral tissues; however, the expression of SHIP2 in the hypothalamus and its functional roles are largely unknown. In the present study, immunohistochemical analysis demonstrated that SHIP2 protein exists in neuronal cells expressing neuropeptide Y and pro‐opiomelanocortin in the arcuate nucleus of the hypothalamus in C57BL/6J mice. Interestingly, the expression levels of SHIP2 in the hypothalamus were elevated in aged C57BL/6J mice and diabetic db/db mice. To clarify the significance of the increased expression of SHIP2 in the hypothalamus, we examined the central effects of insulin and leptin in transgenic mice overexpressing SHIP2 (SHIP2‐Tg). Accumulation of phosphatidylinositol (3,4,5)‐trisphosphate and phosphorylation of Akt in the hypothalamus, induced by i.c.v. injection of insulin, were attenuated in SHIP2‐Tg compared to wild‐type mice, whereas leptin‐induced phosphorylation of signal transducer and activator of transcription 3 in the hypothalamus was comparable between them. The suppression of food intake after i.c.v. administration of insulin (but not leptin) was attenuated consistently in SHIP2‐Tg. In addition, SHIP2‐Tg showed increased food consumption after starvation and become heavier with visceral fat accumulation than wild‐type mice, despite normal levels of oxygen consumption and spontaneous movement. These results suggest that SHIP2 contributes to the regulation of food intake mainly via the attenuation of insulin signalling in the hypothalamus of mice.
Risk factors associated with outcomes of very low birthweight infants in four Asian countries
Authors: Wariki Windy Mariane Virenia , Mori Rintaro , Boo Nem‐Yun , Cheah Irene Guat Sim , Fujimura Masanori , Lee Jiun , Wong Kar Yin
Published: January 2013

Aim

The study aims to determine the risk factors associated with mortality and necrotising enterocolitis (NEC) among very low birthweight infants in 95 neonatal intensive care units in the Asian Network on Maternal and Newborn Health.

Methods

This is a cross‐sectional study using an international collaborative database of 17 595 very low birthweight infants admitted within 28 days of birth between 2003 and 2006 in four Asian countries. Information on the mortality and morbidity of neonates admitted to the neonatal intensive care units was recorded. Factors associated with the death and diseases of infants were estimated using multilevel multivariate logistic regression. Random effects were included to account for the clustering of the observations.

Results

Overall discharge mortality was 15% and it was significantly different by countries and units. The mortality rate was found to be significantly higher in neonates with pulmonary haemorrhage (odds ratio 1.83, 95% confidence interval 1.63–2.04) and air leak syndrome (odds ratio 1.51, 95% confidence interval 1.30–1.72). The incidence of NEC was 4.3% and was strongly associated with other morbidities. Multivariate logistic regression showed that patent ductus arteriosus was the most significant risk factor associated with NEC.

Conclusions

Our analysis has highlighted the great potential that multi‐country, collaborative datasets have in terms of epidemiologic research when it comes to identifying issues in perinatal health that are common throughout Asia, and in relation to particular issues pertaining to specific countries and neonatal units. Establishing collaborative networks, conducting analyses of common datasets and further epidemiologic research are now essential measures to improve newborn health in Asia.
Optimal management of HBV infection during pregnancy
Authors: Piratvisuth Teerha
Published: January 2013

Chronic hepatitis B virus (HBV) infection in pregnancy presents a unique and important challenge. Over 50% of chronicHBVcarriers in endemic areas acquire infection vertically from their mothers. More importantly, over 90% of perinatally acquired infections progress to chronicHBVinfection. Thus, management of chronicHBVduring pregnancy and strategies to prevent mother‐to‐child transmission is an important step in eradicating or reducing the global burden of chronic hepatitis B. In addition, chronicHBVinfection in pregnancy presents a unique clinical challenge because of the complex relationship between the physiological changes of pregnancy and the pathophysiological response toHBV. This review will present the current knowledge and a practical approach to management ofHBVin pregnancy.
Why do I treat HBeAg‐negative chronic hepatitis B patients with pegylated interferon?
Authors: Lampertico Pietro , Viganò Mauro , Colombo Massimo
Published: January 2013

Chronic hepatitis B (CHB) in serum HBeAg negative patients is a difficult to cure, progressive disease leading to end‐stage liver disease and hepatocellular carcinoma. Currently, there are two different treatment strategies for such patients: a finite course of Pegylated interferon (PEG‐IFN) or long‐term administration of the more potent and less resistance‐prone nucleot(s)ide analogues (NUC), i.e. entecavir and tenofovir. Although NUC may ensure persistent viral suppression by preventing disease progression in most patients, they require lifelong administration with the hypothetical disadvantages of cost, lack of long‐term safety data and, most important, the null rates of HBsAg seroclearance. On the other hand, 1 year of PEG‐IFN has the advantage of providing an immune‐mediated control of hepatitis B virus (HBV) infection, with the possibility of achieving a sustained off‐treatment response in 20% of the patients, ultimately leading to HBsAg loss in approximately 50% of these. However, these sustained response rates can be significantly increased by carefully selecting candidates for PEG‐IFN therapy based upon baseline ALT and HBV DNA levels, viral genotype and IL28B polymorphisms, by extending PEG‐IFN therapy beyond 48 weeks and, most importantly, by applying early on‐treatment stopping rules based upon HBsAg kinetics. Overall, PEG‐IFN is an ideal treatment strategy in selected patients with HBeAg‐negative CHB, because of its well‐recognized and predictable safety profile and a unique mechanism of antiviral activity leading to long‐lasting immune control. Because of these features, new therapeutic trials based upon a combination of PEG‐IFN and third generation NUC such as entecavir and tenofovir, in both naïve and NUC‐exposed patients, are ongoing to further increase the rates of HBsAg seroclearance, which remains the ‘ideal end‐point’ in all HBeAg‐negative CHB subjects.
Why do I treat HBeAg‐positive chronic hepatitis B patients with a Nucleoside analogue
Authors: Ma Hong , Jia Jidong
Published: January 2013

Chronic hepatitis B (CHB) is a worldwide public health problem which represents an enormous economic and social burden. Convincing evidence has shown that persistent active viral replication is an independent predictor of disease progression. Therefore, sustained suppression of HBV replication is the cornerstone for preventing the progression of disease and prolonging survival in patients with CHB. Pivotal clinical trials and real‐world studies show that nucleos(t)ide analogues (NAs) are potent suppressors of HBV DNA replication with very good safety profiles. Although 1‐year treatment with NAs only results in a modest rate of HBeAg seroconversion, extended treatment could increase this rate. Profound suppression of HBV DNA can result in histological improvement and a clinical benefit with a decrease in disease progression in patients with compensated or decompensated cirrhosis. Treatment must be begun with a highly potent and low resistant regimen to obtain long‐term suppression of viral replication. An alternative solution may be a roadmap approach in which an inexpensive antiviral drug is started and another drug is added‐on or switched‐to if there is a suboptimal on‐treatment decrease in HBV DNA. Clinical evidence has shown that once HBV DNA is suppressed and long‐term HBeAg seroconversion is achieved, NAs can be stopped. In summary, high antiviral efficacy, excellent tolerance, extensive applicability, clearly proven histological improvement and long‐term clinical benefit all make NAs the preferred choice for the management of CHB in most patients.
How to optimize HCV therapy in genotype 1 patients with cirrhosis
Authors: Bourlière Marc , Wendt Astrid , Fontaine Hélène , Hézode Christophe , Pol Stanislas , Bronowicki Jean Pierre
Published: January 2013

Of all hepatitis C virus patients, those with cirrhosis are most in need of treatment owing to increased morbidity and mortality. Treatment with pegylated interferon and ribavirin (PEG‐IFN/RBV) has clearly shown the benefits of successful treatment by improving fibrosis, causing the regression of cirrhosis and reducing and preventing cirrhosis‐related complications. However, the sustained virological response (SVR) is lower in patients with cirrhosis. First generation protease inhibitors (boceprevir and telaprevir) in combination with PEG‐IFN/RBV are a major advancement in the treatment of both naïve and treatment‐experienced genotype 1 patients. In naïve patients, the SVR rate with the triple regimen with boceprevir increased by 14% in patients with severe fibrosis or cirrhosis compared to PEG‐IFN/RBV compared by 30% in patients with mild or moderate fibrosis. The SVR rate of the triple regimen with telaprevir increased by 10–30% compared to PEG‐IFN/RBV in patients with severe fibrosis or cirrhosis and by nearly 30% in patients with mild or moderate fibrosis. The greatest benefits seem to be found in patients with cirrhosis who have relapsed, and is limited in prior non‐responder patients. Thus, the choice of triple therapy in the latter should be considered in relation to the increase in side effects. There are no data on the efficacy of the triple regimen in patients with decompensated cirrhosis. Results in real‐life settings show that patients with cirrhosis need to be carefully followed‐up during treatment due to the increase in side effects that are greater than in clinical studies. Next generation DAAs and PEG‐IFN/RBV appear to be more effective and have fewer side effects in patients with cirrhosis. Ultimately, an interferon‐free regimen of DAAs combinations will probably provide a SVR in patients with cirrhosis and will probably be proposed in patients with more advanced or decompensated cirrhosis.
New therapeutic strategies in HCV: polymerase inhibitors
Authors: Gerber Ludmila , Welzel Tania M. , Zeuzem Stefan
Published: January 2013

The characterization of the viral life cycle facilitated the development of directly acting antiviral drugs. Among those, several inhibitors of the viral RNA‐dependent RNA polymerase have proven effectiveness in clinical trials. The characteristics of different nucleos(t)ide and non‐nucleoside polymerase inhibitors, as well as their clinical applications and combinations with other classes of directly acting antiviral drugs are reviewed herein.
Optimal treatment with boceprevir for chronic HCV infection
Authors: Maasoumy Benjamin , Manns Michael P.
Published: January 2013

There are 160–170 million people with chronic hepatitis C virus (HCV) infection worldwide. The marketing of protease inhibitors (PIs) has been a milestone in the history of HCV therapy. In phase III studies, up to 75% of the patients achieved a sustained virological response (SVR) after triple therapy with pegylated‐interferon (PEG‐IFN)‐α, ribavirin (RBV) and boceprevir (BOC). However, triple regimens are more expensive and associated with drug–drug interactions (DDIs) and more adverse events (AEs). According to results in ‘real‐world’ settings, safety seems to be limited, in particular in patients with advanced liver disease. To optimize efficacy while minimizing AEs as well as costs, the optimal treatment strategy must be determined for BOC. Optimizing treatment is based on patient selection, the most efficient treatment design, management of side effects and the challenge of DDIs. Therapy‐associated risks, treatment urgency and chances of SVR must all be considered for patient selection. In addition, certain differences between the two approved PIs may help identify the ideal candidates for each HCV PI. Optimal treatment design is based on the results of phase II and III studies, in which different approaches have been tested including ‘lead‐in’ and response‐guided strategies. Treatment regimens and stopping rules recommended by the FDA and EMA should normally be followed. Still, there are some cases in which more personalized strategies may be more promising. Management of side effects is a major challenge and plays a crucial role in ensuring safety and adherence.
Optimal treatment with telaprevir for chronic HCV infection
Authors: Jesudian Arun B. , Jacobson Ira M.
Published: January 2013

Telaprevir is a recently approved direct‐acting antiviral against hepatitis C virus (HCV) that works through inhibition of the NS3/4A serine protease inhibitor.Phase 2b and 3 studies have shown marked increase in sustained virological response rates in both treatment‐ naïve and treatment‐experienced patients with HCV genotype 1 treated with a telaprevir‐containing regimen compared with pegylated interferon (PEG‐IFN) and ribavirin alone. The most commonly observed side effects of telaprevir therapy are anaemia to a greater degree than that observed with PEG‐IFN/ribavirin alone; eczematous rash, which can be severe in a minority of patients; and anorectal discomfort.
HCV therapy in HIV‐infected patients
Authors: Sulkowski Mark S.
Published: January 2013

Hepatitis C virus (HCV) co‐infection is common among HIV‐infected patients. Over the past 15 years, effective HIV treatment has led to dramatic reductions in the incidence of AIDS‐related death; over the same time period, HCV‐related liver disease has emerged as a major cause of morbidity and mortality. Treatment with peginterferon (PEG‐IFN) and ribavirin (RBV) has been recommended for the treatment of HCV infection in HIV‐infected patients at the greatest risk of developing liver disease. However, the effectiveness of this HCV treatment has been low because of limited efficacy in patients infected with HCV genotype 1. More recently, HCV NS3/4A protease inhibitors, telaprevir and boceprevir, in combination with PEG‐IFN/RBV have led to significantly higher sustained viral response rates in HIV‐uninfected patients with HCV genotype 1 infection. The potential use of these agents in patients with HIV/HCV co‐infection is complicated by the potential for drug interactions between antiretroviral drugs and the HCV protease inhibitors and uncertainty regarding the safety and effectiveness of the combination therapy in this population.
Glutamine synthetase expression in activated hepatocyte progenitor cells and loss of hepatocellular expression in congestion and cirrhosis
Authors: Fleming Kirsten E. , Wanless Ian R.
Published: January 2013

Background & Aims

In normal human liver, glutamine synthetase (GS) is expressed in a rim of hepatocytes surrounding hepatic veins. GS expression is decreased in cirrhosis and increased in chronic hepatitis, focal nodular hyperplasia, peritumoural hyperplasia and some hepatocellular neoplasms. For the non‐neoplastic conditions, there is limited information available on histological pattern of altered GS expression and the mechanisms of these changes.

Methods

We examined GS expression in 58 large specimens and 45 needle biopsies with a variety of non‐neoplastic human liver conditions and in 12 normal control livers. Expression was correlated with clinical and histological disease states.

Results

We identified four patterns of GS expression: (i) Loss of normal perivenular expression was seen in states of chronic congestion, severe cirrhosis and zone 3 necrosis. (ii) Diffuse expression was seen in states with active hepatocellular injury and correlated with Ki‐67 expression. (iii) Interface expression was seen in feathery degeneration of chronic cholestasis. (iv) GS expression in activated hepatocyte progenitor cells (HPCs) associated with small ducts and ductules was seen in fulminant hepatic failure and in early and late chronic liver disease and rarely in normal livers.

Conclusions

Glutamine synthetase expression is increased in regenerating hepatocytes and in early HPCs prior to morphological evidence of hepatocellular differentiation. This may be the earliest marker of HPCs yet demonstrated. Loss of expression may be a reflection of disrupted endothelium‐hepatocyte contact in hepatic vein walls caused by congestive injury as found in congestive heart failure and advanced cirrhosis.
Can lightning produce significant levels of mass‐independent oxygen isotopic fractionation in nebular dust?
Authors: Nuth Joseph A. , Paquette John A. , Farquhar Adam
Published: January 2013

Based on recent evidence that oxide grains condensed from a plasma will contain oxygen that is mass‐independently fractionated compared to the initial composition of the vapor, we present a first attempt to evaluate the potential magnitude of this effect on dust in the primitive solar nebula. This assessment relies on previous studies of nebular lightning to provide reasonable ranges of physical parameters to form a very simple model to evaluate the plausibility that lightning could affect a significant fraction of nebular dust and that such effects could cause a significant change in the oxygen isotopic composition of solids in the solar nebula over time. If only a small fraction of the accretion energy is dissipated as lightning over the volume of the inner solar nebula, then a large fraction of nebular dust will be exposed to lightning. If the temperature of such bolts is a few percent of the temperatures measured in terrestrial discharges, then dust will vaporize and recondense in an ionized environment. Finally, if only a small average decrease is assumed in the 16O content of freshly condensed dust, then over the last 5 Myr of nebular accretion the average Δ17O of the dust could increase by more than 30 per mil. We conclude that it is possible that the measured “slope 1” oxygen isotope line measured in meteorites and their components represents a time‐evolution sequence of nebular dust over the last several million years of nebular evolution where 16O‐rich materials formed first, then escaped further processing as the average isotopic composition of the dust gradually became increasingly depleted in 16O.
Effect of sugar beet genotype on the Beet necrotic yellow vein virus P25 pathogenicity factor and evidence for a fitness penalty in resistance‐breaking strains
Authors: Bornemann Kathrin , Varrelmann Mark
Published: January 2013

Beet necrotic yellow vein virus (BNYVV), vectored by Polymyxa betae, causes rhizomania in sugar beet. For disease control, the cultivation of hybrids carrying Rz1 resistance is crucial, but is compromised by resistance‐breaking (RB) strains with specific mutations in the P25 protein at amino acids 67–70 (tetrad). To obtain evidence for P25 variability from soil‐borne populations, where the virus persists for decades, populations with wild‐type (WT) and RB properties were analysed by P25 deep sequencing. The level of P25 variation in the populations analysed did not correlate with RB properties. Remarkably, one WT population contained P25 with RB mutations at a frequency of 11%. To demonstrate selection by Rz1 and the influence of RB mutations on relative fitness, competition experiments between strains were performed. Following a mixture of strains with four RNAs, a shift in tetrad variants was observed, suggesting that strains did not mix or transreplicate. The plant genotype exerted a clear influence on the frequency of RB tetrads. In Rz1 plants, the RB variants outcompeted the WT variants, and mostly vice versa in susceptible plants, demonstrating a relative fitness penalty of RB mutations. The strong genotype effect supports the hypothesized Rz1 RB strain selection with four RNAs, suggesting that a certain tetrad needs to become dominant in a population to influence its properties. Tetrad selection was not observed when an RB strain, with an additional P26 protein encoded by a fifth RNA, competed with a WT strain, supporting its role as a second BNYVV pathogenicity factor and suggesting the reassortment of both types.
Evaluation of hypercoagulability using soluble fibrin monomer complex in sick newborns
Authors: Takahashi Daijiro , Takahashi Yukihiro , Matsui Miyu , Araki Shunsuke , Kubo Kazuyasu , Sato Hiroshi , Shirahata Akira
Published: January 2013

Background

Soluble fibrin monomer complex (SFMC) and fibrin monomer (FM) are well known as markers for hypercoagulability, but such measurements have not been investigated in detail for the neonate. To identify the presence of a hypercoagulable state in sick newborns, the behavior of SFMC with special reference to those of other coagulation tests, and the relationships with other parameters of blood coagulation as well as lactate, which is considered to be the gold standard for assessing tissue hypoxia, were studied.

Methods

Records of 216 sick newborns, who had undergone blood coagulation tests, were retrospectively studied based on their medical records.

Results

SFMC had a significant correlation with d‐dimer in infants with birthweight <1500 g, but no correlation was observed with prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, anti‐thrombin or platelet count. In contrast, in infants with birthweight ≥1500 g, SFMC was correlated with PT, APTT, fibrinogen, and d‐dimer, but no correlation was observed with anti‐thrombin or platelet count. In addition, SFMC was significantly higher in the high lactate group (lactate ≥4 mmol/L), compared with the low lactate group (<4 mmol/L).

Conclusion

Measurement of blood SFMC is useful to monitor hypercoagulable state in sick newborns with hypoxia.
Liver Condition Affects Bovine Oocyte Qualities by Changing the Characteristics of Follicular Fluid and Plasma
Authors: Tanaka H , Shibano K , Monji Y , Kuwayama T , Iwata H
Published: January 2013

Contents

The liver is an important organ that contributes to milk production in dairy cows. The aim of this study was to examine whether liver conditions affect the characteristics of blood plasma and follicular fluid (FF) and whether supplementing in vitro maturation medium with FF from either cows with damaged livers (DL) or those with healthy livers (HL) affects oocyte developmental competence. Biochemical characteristics of FF were significantly correlated with those in plasma. As such, the characteristics of both plasma and FF were similarly affected by liver conditions in that the concentrations of total protein and inorganic phosphorus were higher for the DL cow group than for the HL cow group, whereas the concentrations of albumin, lactate dehydrogenase and calcium were lower for DL cows than for HL cows. In addition, supplementing the medium with DL‐FF retarded the progression of the nuclear maturation of oocytes collected from the HL cows. On culturing oocytes in maturation medium containing HL‐FF, DL‐FF or foetal calf serum, the highest developmental rate to the blastocyst stage was observed in the HL‐FF group, while the lowest developmental ratio was observed in the DL‐FF group. The growth factor array of the FFs revealed that 10 growth factors were significantly downregulated in the DL‐FF compared with those in HL‐FF. In conclusion, the characteristics of plasma and FF are affected by liver conditions in a similar way. Concentrations of several growth factors were low in DL‐FF, as was the ability of DL‐FF to support oocyte maturation compared with that of HL‐FF.