bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of mast cells in eosinophilic esophagitis
Authors: Lucendo Alfredo J. , Bellón Teresa , Lucendo Baltasar
Published: August 2008

Eosinophilic esophagitis (EE) is a chronic inflammatory disease of the esophagus which is characterized by the presence of dense infiltrate of eosinophilic leukocytes restricted to this organ mucosa. Accumulating published evidence suggests a strong role of mast cells in the inflammatory infiltrate in the physiopathology of EE. We have reviewed published articles with relevant information about the presence and possible role of mast cells in EE. Although mast cells have been studied indirectly in EE, reported data allow us to confirm that the number of mast cells infiltrating the esophageal epithelium in adult and child patients with EE is higher with respect to the normal state and in gastroesophageal reflux disease. Mast cells linked to IgE, which are not found in other conditions, have been identified in EE. Despite that fact, an anaphylactic reaction history after exposure to allergens is not common in these patients. Therefore, the mast cells’ function in EE could be dependent on T lymphocytes, as suggested by a mast cell gene expression analysis. Bi‐directional crosstalk is established between mast cells and eosinophils, hence establishing interesting hypotheses regarding their relationship to EE physiopathology. Mast cells’ function as an immune response leader seems to substitute for their effector functions in EE, while at the same time opening new research pathways for consideration of these cells as a therapeutic target in EE. However, the inefficiency of therapies that inhibit mast cell functions while they are effective in other respiratory tract diseases results in the need for specific studies to identify the real function of such complex cells in the physiopathology of EE. There is indirect proof of the role of mast cells in EE, while many doubts exist about their activation mechanism, which does not seem to be IgE‐mediated. Specific approach studies are needed to clarify the function of these cells in the physiopathology of EE, which could be a possible therapeutic target.
Modifying effects of phenotypic plasticity on interactions among natural selection, adaptation and gene flow
Authors: CRISPO E.
Published: August 2008

Divergent natural selection, adaptive divergence and gene flow may interact in a number of ways. Recent studies have focused on the balance between selection and gene flow in natural populations, and empirical work has shown that gene flow can constrain adaptive divergence, and that divergent selection can constrain gene flow. A caveat is that phenotypic diversification may be under the direct influence of environmental factors (i.e. it may be due to phenotypic plasticity), in addition to partial genetic influence. In this case,phenotypicdivergence may occur between populations despite high gene flow that imposes a constraint ongeneticdivergence. Plasticity may dampen the effects of natural selection by allowing individuals to rapidly adaptphenotypicallyto new conditions, thus slowing adaptive genetic divergence. On the other hand, plasticity may promote future adaptive divergence by allowing populations to persist in novel environments. Plasticity may promote gene flow between selective regimes by allowing dispersers to adapt to alternate conditions, or high gene flow may result in the selection for increased plasticity. Here I expand frameworks for understanding relationships among selection, adaptation and gene flow to include the effects of phenotypic plasticity in natural populations, and highlight its importance in evolutionary diversification.
Sexual conflict is not counterbalanced by good genes in the laboratory Drosophila melanogaster model system
Authors: STEWART A. D. , HANNES A. M. , MIRZATUNY A. , RICE W. R.
Published: August 2008

Sexual conflict theory is based on the observation that females of many species are harmed through their interactions with males. Direct harm to females, however, can potentially be counterbalanced by indirect genetic benefits, where females make up for a reduction in offspring quantity by an increase in offspring quality through a generic increase in offspring fitness (good genes) and/or one restricted to the context of sexual selection (sexy sons). Here, we quantify the magnitude of the good genes mechanism of indirect benefits in a laboratory‐adapted population of Drosophila melanogaster. We find that despite high‐standing genetic variance for fitness, females gain at most only a modest benefit through the good genes form of indirect benefits – far too little to counterbalance the direct cost of male‐induced harm.
Greek nursing students' immunization coverage: Data from central continental Greece
Authors: Noula Maria , Raftopoulos Vasilios , Gesouli Eftihia , Tsaprounis Taxiarchis , Deltsidou Anna
Published: August 2008

Abstract  Nursing students are at risk of acquiring vaccine‐preventable diseases. To estimate the vaccination rates for nursing students, a cross‐sectional survey was conducted in a major district of central continental Greece with an anonymous and self‐administered questionnaire in a sample of 432 nursing students (the response rate was 97%). The eligible nursing students completed the questionnaire after informed consent was obtained. The vaccination rates of the nursing students ranged from 65.2% for the oral polio (SABIN) vaccine and 65.7% for the hepatitis B virus vaccine to 74.6% for the diphtheria‐tetanus‐pertussis (DTP) vaccine. The parents' level of education did not correlate with the students' underimmunization. The t‐test showed that the senior students were more knowledgeable about the compulsory vaccines. Almost half of the nursing students were somewhat satisfied with the available information on vaccination, while 9.5% were not at all satisfied and 38.5% were underimmunized. The proportion of male students who had completed the SABIN and DTP vaccination schedules was higher compared to the female students. More health education programs could increase the vaccination rates among nursing students.
Fathers in situational crisis: A comparison of Asian and Western cultures
Authors: Tseng Yun‐Shan , Verklan M. Terese
Published: August 2008

Abstract  The purpose of this synthesis was to compare the difference between Asian and Western fathers’ perceptions of their roles when confronted with situational crises involving their children. Twenty‐two studies were reviewed and assigned to one of two categories: the father experiencing a situational crisis related to his child's illness or cultural influences on the paternal role. The results indicated that Asian and Western fathers’ perceptions of crises do not differ greatly. It was concluded that there exists a gap in the literature with respect to the knowledge of Asian fathers’ situational crisis surrounding their child's illness, their coping strategies when faced with their child's illness, as well as their emotional reactions toward family health. Future research should investigate the single or same‐gender father's perceptions and emotional reactions in both Asian and Western cultures.
Health literacy: A concept/dimensional analysis
Authors: Mancuso Josephine M.
Published: August 2008

Abstract  The terms “health” and “literacy” form a powerful concept that has evolved from the 1970s to one that has garnered the attention of a wide range of disciplines; most notably, education and health care, but also library science, public health, and the mental health arena. There are many definitions of health literacy, but none that encompass the totality by which the concept is constructed. This paper presents an analysis of the concept of health literacy using the technique of concept/dimensional analysis. A clear understanding of the concept is essential as health literacy has implications that are far‐reaching and impact both the individual and society.
Factors related to cognitive status among elders in southern Thailand
Authors: Taboonpong Sunuttra , Chailungka Pachariya , Aassanangkornchai Sawitree
Published: August 2008

Abstract  This study examined the prevalence of and risk factors predicting cognitive impairment among elders in southern Thailand. Four‐hundred Thai elders were administered five interview‐based questionnaires that assessed demographic characteristics, cognitive function, depression, independent activities of daily living, and social connections. Although most of the elders had normal cognitive function, ∼ 15% experienced cognitive impairment. Though nine of the 10 risk factors examined were identified as being associated with cognitive impairment, only a lack of formal education, female gender, depression, and physical inactivity were found to be significant predictors of cognitive impairment. The results suggested that elders with risk factors should be assessed for cognitive impairment. Depression, and deficits in activities of daily living and educational activities should be addressed and corrected to improve elders' cognitive abilities.
Development and testing of the Resilience Factors Scale for Thai adolescents
Authors: Takviriyanun Nidtaya
Published: August 2008

Abstract The growing body of knowledge related to resilience supported the need for the development of an instrument that can be used to assess resilience factors, that is, individual protective factors, but to date, no established instrument for Thai adolescents exists. The purposes of this study were to develop and test the psychometric properties of the Resilience Factors Scale for Thai adolescents. Derived from the resilience theory of Grotberg and a literature review, 27 items compose the scale. The content validity was evaluated by five experts. The construct, contrast‐group, and predictive validity, as well as the internal reliability, were evaluated with a multistage random sample of 638 tenth‐to‐twelfth graders in four high schools in Bangkok, Thailand. An exploratory factor analysis in the final step indicated that the scale consists of six components with 25 items. Evidence of validity and reliability was obtained. This scale has demonstrated good psychometric properties and has provided an objective tool for assessing the resilience factors of Thai adolescents.
Satisfaction with services among people with progressive neurological illnesses and their carers in Australia
Authors: McCabe Marita P. , Roberts Candice , Firth Lucy
Published: August 2008

Abstract  The current study investigated the types of support networks and services accessed by people with progressive neurological illness, as well as the assessment of the usefulness of these services. The participants were 25 people with multiple sclerosis, 15 people with motor neurone disease, 23 people with Parkinson's disease, and six people with Huntington's disease. Twenty‐eight professionals who worked with people with these illnesses and 41 carers of people with these illnesses also were interviewed. The results demonstrate that all of the groups of respondents indicated a strong need for basic services (e.g. home help), as well as specialized services (e.g. support groups). These two services also were identified as the most useful services by all of the groups of respondents. The similarities and differences between the groups, as well as the patients and carers, are examined. These findings demonstrate the importance of providing basic services for people with progressive neurological illnesses.
The contribution of nursing to public health practice in the prevention of depression
Authors: Wood Stephen
Published: August 2008

Abstract Depression is perceived worldwide as an important public health issue. Its prevalence has increased over the past 50 years. The reasons for the increase might be related, in part, to improved recognition and a greater willingness to label unhappiness or dysphoria as depression. Severe depression might be less amenable to prevention, although the identification of the stressors likely to trigger an episode in vulnerable individuals might prevent some recurrences. There is the potential, however, for the prevention of mild‐to‐moderate depression through action at the individual, community, and structural levels. This paper argues that nursing can make an important contribution to this prevention. At the individual level, this might be best accomplished through the development of the role of non‐mental health nurses in primary care and workplace settings. At the community and structural levels, nursing as a profession can play an important role in influencing the commissioning of health care and the development of healthy public policy.
Successful pregnancy after artificial insemination in a case of human seminal plasma allergy
Authors: MAKINO AIKO , SATO TAKESHI , HATTORI YUKIO , SAITO CHIEKO , SUGIURA‐OGASAWARA MAYUMI , SAITO CHIYO , SHINTANI YOICHI
Published: August 2008

Human seminal plasma allergy in women is uncommon, but causes a variety of serious reactions, including urticaria, dyspnea and vomiting, in those that are affected. Semen barriers, such as condoms, are the most widely advocated method for avoiding these reactions. However, this is not acceptable to couples who wish to have children. We present a case of a woman with human seminal plasma allergy who became pregnant after the eighth cycle of artificial insemination using washed sperm from her spouse. (Reprod Med Biol 2008; 7: 119–122)
The present status of artificial oocyte activation in assisted reproductive technology
Authors: YANAGIDA KAORU , FUJIKURA YOKO , KATAYOSE HARUO
Published: August 2008

Intracytoplasmic sperm injection (ICSI) is the most effective treatment for achieving fertilization in assisted reproductive technology (ART). However, fertilization failure occurs. The incidence of fertilization failure after ICSI is 1–5%. Approximately 50% of fertilization failure cases could be attributed to the abnormality of sperm factor. As the fertilization fails after ICSI using mature sperm, round spermatids and globozoospermia, artificial oocyte activation may provide a means of improving fertilization rates in such cases. The oocyte activation treatments used in clinical research include calcium (Ca) ionophore treatment, electrostimulation and strontium treatment. In terms of the efficiency of oocyte activation, electrostimulation and Ca ionophore gave better outcomes than strontium treatment. Strontium treatment causes Ca2+ oscillations in mice, so it has been viewed favorably. However, in human oocytes calcium oscillation has not been observed. The fertilization rate after ICSI was low in the case of globozoospermia and wiht round spermatids. Some cases of pregnancy were achieved by ICSI alone and oocyte activation methods were not essential in these cases. Among the various oocyte activation methods currently used, it should be noted that issues of genetic safety have not been addressed for the combined use of these oocyte activation methods. (Reprod Med Biol 2008; 7: 133–142)
Novel methylotrophic bacteria isolated from the River Thames (London, UK)
Authors: Boden Rich , Thomas Elizabeth , Savani Parita , Kelly Donovan P. , Wood Ann P.
Published: August 2008

Enrichment and elective culture for methylotrophs from sediment of the River Thames in central London yielded a diversity of pure cultures representing several genera of Gram‐negative and Gram‐positive bacteria, which were mainly of organisms not generally regarded as typically methylotrophic. Substrates leading to successful isolations included methanol, monomethylamine, dimethylamine, trimethylamine, methanesulfonate and dimethylsulfone. Several isolates were studied in detail and shown by their biochemical and morphological properties and 16S rRNA gene sequencing to be Sphingomonas melonis strain ET35, Mycobacterium fluoranthenivorans strain DSQ3, Rhodococcus erythropolis strain DSQ4, Brevibacterium casei strain MSQ5, Klebsiella oxytoca strains MMA/F and MMA/1, Pseudomonas mendocina strain TSQ4, and Flavobacterium sp. strains MSA/1 and MMA/2. The results show that facultative methylotrophy is present across a wide range of Bacteria, suggesting that turnover of diverse C1‐compounds is of much greater microbiological and environmental significance than is generally thought. The origins of the genes encoding the enzymes of methylotrophy in diverse heterotrophs need further study, and could further our understanding of the phylogeny and antiquity of methylotrophic systems.
SHOULD WE WORRY ABOUT THE FAILURE OF THE HOTELLING RULE?
Authors: Kronenberg Tobias
Published: August 2008

Abstract The continuing dependence of the global economy on fossil fuels is worrying because it imposes limits on growth due to the non‐renewable nature of these resources and also contributes to global climate change. Resource optimists believe that this is no reason to worry, because the economy will always find a way to overcome these constraints. Their arguments, however, require that resource prices reflect the scarcity of non‐renewable resources, which implies that they must obey the Hotelling rule. Empirical analyses, however, show that the Hotelling rule does not hold in reality, which raises the question: does the failure of the Hotelling rule imply that social optimality is not achieved? This paper argues that the answer depends on the reason for the failure. If extraction and exploration costs, or technological progress in these activities, are the reasons for the failure, a market failure is not implied, and optimality may still be achieved. But if the Hotelling rule fails due to uncertain property rights or strategic interaction, the market will surely fail to provide an optimal solution. A market failure is likely to speed up resource consumption compared to the social optimum.
INCOME INEQUALITY WITHIN EUROPEAN REGIONS: DETERMINANTS AND EFFECTS ON GROWTH
Authors: Perugini Cristiano , Martino Gaetano
Published: August 2008

Economic inequality across Europe has been largely investigated by analyzing the determinants and dynamics of the disparities between countries and regions. Similarly, many studies have focused on inequality within European countries. So far, less attention has been devoted to economic inequality within European regions, mainly due to data shortages. The aim of this paper is to shed some light on this level of analysis. After the introductory section, the first part of the paper presents the conceptual bases of the study, examining relevant theoretical and empirical arguments about (i) the determinants of economic inequality, (ii) the relationship between economic inequality and growth, and (iii) the desirability and specificity of regional analysis. The second part of the paper, using various econometric approaches, provides evidence of the centrality of labor market qualitative and quantitative aspects and of some country‐level institutional settings for regional inequality levels. As regards the effects of inequality on growth, the results suggest a positive relationship.
RESOURCE BOOMS, INEQUALITY, AND POVERTY: THE CASE OF GAS IN BOLIVIA
Authors: Lay Jann , Thiele Rainer , Wiebelt Manfred
Published: August 2008

This paper addresses the question of whether the Bolivian gas boom of the 1990s has bypassed large parts of the poor population, thereby leading to increasing inequalities in an already unequal society. Using a Computable General Equilibrium model that is sequentially linked to a microsimulation model, we examine the transmission channels through which the large resource inflows related to the gas boom, both initial foreign investment in the sector and the subsequent export earnings, as well as large public transfer programs affect the distribution of income. Our focus is on labor market impacts, in particular on shifts between formal and informal employment and changes in relative factor prices. Our simulation results suggest that the gas boom induces a combination of unequalizing and equalizing forces, which tend to offset each other. As net distributional change is limited, growth generated by the boom reduces poverty despite increasing informality.
MEASUREMENT ERROR IN THE BANK OF ITALY'S SURVEY OF HOUSEHOLD INCOME AND WEALTH
Authors: Biancotti Claudia , D'Alessio Giovanni , Neri Andrea
Published: August 2008

This paper is aimed at evaluating the incidence of measurement error in the Bank of Italy's Survey of Household Income and Wealth (SHIW). In the case of time‐invariant variables, we assess the degree of inconsistency of answers given by panel households in subsequent survey waves. For quantities that vary with time, we estimate the incidence of measurement error by decomposing observed variability into true dynamics and error‐induced noise. We apply the Heise model or the latent Markov model, depending on whether the data are continuous or categorical. We also present regression models that explain the error‐generating process. Our results are relevant to researchers who use SHIW data for economic analysis, but also to data producers involved in similar income and wealth surveys. The methods we describe and test can be employed in a number of contexts to gain better understanding of data‐related problems and plans for survey improvement.
Endemism and Regional Color and Genetic Differences in Five Putatively Cosmopolitan Reef Fishes
Authors: DREW JOSHUA , ALLEN GERALD R. , KAUFMAN LES , BARBER PAUL H.
Published: August 2008

Abstract: Endemism is thought to be relatively rare in marine systems due to the lack of allopatric barriers and the potential for long‐distance colonization via pelagic larval dispersal. Although many species of coral reef fishes exhibit regionally restricted color variants that are suggestive of regional endemism, such variation is typically ascribed to intraspecific variation. We examined the genetic structure in 5 putatively monospecific fishes from the Indo‐West Pacific (Amphiprion melanopus,Chrysiptera talboti, andPomacentrus moluccensis[Pomacentridae] andCirrhilabrus punctatus, andLabroides dimidiatus[Labridae]) that express regional color variation unique to this area. Mitochondrial‐control‐region sequence analysis showed shallow to deep genetic divergence in all 5 species (sequence divergence 2–17%), with clades concordant with regional color variation. These results were partially supported by nuclear RAG2 data. An analysis of molecular variation (AMOVA) mirrored the phylogenetic results; ΦSTvalues ranged from 0.91 to 0.7, indicating high levels of geographic partitioning of genetic variation. Concordance of genetics and phenotype demonstrate the genetic uniqueness of southwestern Pacific color variants, indicating that these populations are at a minimum distinct evolutionarily significant units and perhaps distinct regionally endemic species. Our results indicate that the alpha biodiversity of the southwestern Pacific is likely underestimated even in well‐studied groups, such as reef fishes, and that regional endemism may be more common in tropical marine systems than previously thought.
Some Limitations of Frequency as a Component of Risk: An Expository Note
Authors: Cox, Jr. Louis Anthony (Tony)
Published: August 2008

Students of risk analysis are often taught that “risk is frequency times consequence” or, more generally, that risk is determined by the frequency and severity of adverse consequences. But is it? This expository note reviews the concepts of frequency as average annual occurrence rate and as the reciprocal of mean time to failure (MTTF) or mean time between failures (MTBF) in a renewal process. It points out that if two risks (represented as two (frequency, severity) pairs for adverse consequences) have identical values for severity but different values of frequency, then it is not necessarily true that the one with the smaller value of frequency is preferable—and this is true no matter how frequency is defined. In general, there is not necessarily an increasing relation between the reciprocal of the mean time until an event occurs, its long‐run average occurrences per year, and other criteria, such as the probability or expected number of times that it will happen over a specific interval of interest, such as the design life of a system. Risk depends on more than frequency and severity of consequences. It also depends on other information about the probability distribution for the time of a risk event that can become lost in simple measures of event “frequency.” More flexible descriptions of risky processes, such as point process models can avoid these limitations.
An Investigation Into the Diversification–Performance Relationship in the U.S. Property–Liability Insurance Industry
Authors: Elango B. , Ma Yu‐Luen , Pope Nat
Published: August 2008

Abstract

This article investigates the relationship between product diversification and firm performance in the U.S. property–liability insurance industry using data over the 1994 through 2002 time period. Using various measures of product diversification and firm performance, we find that the extent of product diversification shares a complex and nonlinear relationship with firm performance. Our findings suggest that performance benefits associated with product diversification are contingent upon an insurer's degree of geographic diversification. Robustness tests using subsamples and market returns for public firms show consistent results.
Issues in Claims Reserving and Credibility: A Semiparametric Approach With Mixed Models
Authors: Antonio Katrien , Beirlant Jan
Published: August 2008

Abstract

Using the statistical methodology of semi‐parametric regression and its connection with mixed models, this article revisits smoothing models for loss reserving and credibility. Apart from the flexibility inherent to all semiparametric methods, advantages of the semiparametric approach developed here are threefold. First, a Bayesian implementation of these smoothing models is relatively straightforward and allows simulation from the full predictive distribution of quantities of interest. Second, because the constructed models have an interpretation as (generalized) linear mixed models ((G)LMMs), standard statistical theory and software for (G)LMMs can be used. Third, more complicated data sets, dealing, for example, with quarterly development in a reserving context, heavy tails, semi‐continuous data, or extensive longitudinal data, can be modeled within this framework.
Racial Differences in the Demand for Life Insurance
Authors: Gutter Michael S. , Hatcher Charles B.
Published: August 2008

Abstract

The objective of this article is to measure racial differences in the proportion of human capital that households protect with life insurance. Using the 2004 Survey of Consumer Finances data, racial differences in two stages of the process are tested, where it is assumed that households must decide both whether or not to purchase life insurance and how much of their human capital to insure (if they decide to purchase). Among married and cohabitating households, we find that, controlling for demographics and other factors, there is little difference in life insurance ownership between black and white households but that white households insure a larger proportion of their human capital than black households.
Assessing the Risk Potential of Premium Payment Options in Participating Life Insurance Contracts
Authors: Gatzert Nadine , Schmeiser Hato
Published: August 2008

Abstract

Most life insurance contracts embed the right to stop premium payments during the term of the contract (paid‐up option). Thereby, the contract is not terminated but continues with reduced benefits and often provides the right to resume premium payments later, thus increasing the previously reduced benefits (resumption option). In our analysis, we start with a basic contract with two standard options, namely, an interest rate guarantee and annual surplus participation. Next, in addition to the features of the basic contract, a paid‐up and resumption option is included in the framework. The valuation process is not based on assumptions about a particular policyholders' exercise strategy but instead assesses the risk potential from the insurer's viewpoint by providing an upper bound for any possible exercise behavior. This approach provides important information to the insurer about the potential hazard of offering the paid‐up and resumption option. Further, the approach allows an analysis of the impact of guaranteed interest rate, annual surplus participation, and investment volatility on the values of the premium payment options.
Survival Analysis of a Household Portfolio of Insurance Policies: How Much Time Do You Have to Stop Total Customer Defection?
Authors: Brockett Patrick L. , Golden Linda L. , Guillen Montserrat , Nielsen Jens Perch , Parner Jan , Perez‐Marin Ana Maria
Published: August 2008

Abstract

Customer‐side influences on insurance have been relatively ignored in the literature. Using the household as the unit of analysis, this article focuses on the behavior of households having multiple policies of different types with the same insurance company, and who cancel their first policy. How long after the household's cancellation of the first policy does the insurer have to retain the customer and avoid customer defection on all policies to the competition? And, what customer characteristics are associated with customer loyalty? Using logistic regression and survival analysis techniques, an assessment is made of the probability of total customer withdrawal, and the length of time between first cancellation and subsequent customer withdrawal. Using a European database spanning 54 months of household multiple policyholder behavior, the results show that cancellation of one policy is a very strong indicator that other household policies will be canceled. Further, the insurer can have time to react to retain the customer after the first cancellation, however, this time is significantly dependent on the method used to contact the company, household demographics, and the nature of the household's insurance policy portfolio. Surprisingly, core customers having three or more policies in addition to the canceled policy are more vulnerable to total defection on all policies than noncore customers. Further, the potential customer repelling effects of premium increases seem to wear out after 12 months. Strategic implications of the results are presented.
Income Drawdown Schemes for a Defined‐Contribution Pension Plan
Authors: Emms Paul , Haberman Steven
Published: August 2008

Abstract

In retirement a pensioner must often decide how much money to withdraw from a pension fund, how to invest the remaining funds, and whether to purchase an annuity. These decisions are addressed here by introducing a number of income drawdown schemes, which are relevant to a defined‐contribution personal pension plan. The optimal asset allocation is defined so that it minimizes the expected loss of the pensioner as measured by the performance of the pension fund against a benchmark. Two benchmarks are considered: a risk‐free investment and the price of an annuity. The fair‐value income drawdown rate is defined so that the fund performance is a martingale under the objective measure. Annuitization is recommended if the expected fair‐value drawdown rate falls below the annuity rate available at retirement. As an illustration, the annuitization age is calculated for a Gompertz mortality distribution function and a power law loss function.
Rates and predictors of remission and recovery during 3 years in 392 never‐treated patients with schizophrenia
Authors: Lambert M. , Naber D. , Schacht A. , Wagner T. , Hundemer H.‐P. , Karow A. , Huber C. G. , Suarez D. , Haro J. M. , Novick D. , Dittmann R. W. , Schimmelmann B. G.
Published: August 2008

Objective:  Few studies have prospectively examined remission and recovery as well as their predictors in schizophrenia simultaneously. Aims of the study were to identify remission and recovery rates as well as their predictors in schizophrenia.

Method:  392 never‐treated patients with schizophrenia were assessed over 3 years. Combined remission and recovery required concurrent achievement of symptomatic and functional remission as well as adequate quality of life for at least 6 and 24 months respectively. Predictors were analysed using stepwise logistic regression models.

Results:  At 3 years, remission rates for symptoms, functioning and subjective wellbeing were 60.3%, 45.4% and 57.0%; recovery rates were 51.7%, 35.0% and 44.3%. Of those, 28.1% were in combined remission and 17.1% in combined recovery. Predictors mainly included the baseline functional status and early remission within the first 3 months.

Conclusion:  The proportion of patients who met combined remission or recovery criteria is low. Early treatment adaptations in case of early non‐remission are mandatory.
Major psychoses with mixed psychotic and mood symptoms: are mixed psychoses associated with different neurobiological markers?
Authors: Bora E. , Yucel M. , Fornito A. , Berk M. , Pantelis C.
Published: August 2008

Objective:  Evidence related to overlapping clinical and genetic risk factors in schizophrenia and bipolar disorder (BD) have raised concerns about the validity of ‘Kraepelinian dichotomy’. As controversies mainly arise in mixed psychoses that occupy the intermediate zone between schizophrenia and BD, investigating neurobiological markers of mixed psychoses may be relevant to understanding the nature of psychotic disorders.

Method:  In this article, we review studies comparing magnetic resonance imaging, neuropsychological and electrophysiological findings in mixed psychoses with each other, as well as with more prototypical cases of schizophrenia and BD.

Results:  The evidence reviewed suggests that mixed psychoses may be associated with different genetic and neurobiological markers compared with prototypical forms of schizophrenia and BD.

Conclusion:  These findings may be compatible with more sophisticated versions of dimensional and continuum models or, alternatively, they may suggest that there is an intermediate third category between prototypical schizophrenia and BD.
A 12‐month follow‐up study of treating overweight schizophrenic patients with aripiprazole
Authors: Schorr S. G. , Slooff C. J. , Postema R. , Van Oven W. , Schilthuis M. , Bruggeman R. , Taxis K.
Published: August 2008

Objective:  To investigate the feasibility of switching overweight schizophrenic patients to aripiprazole and to assess the impact of 12 months of aripiprazole treatment on weight in routine practice.

Method:  This was a non‐controlled cohort study in overweight schizophrenic patients. Data were collected before treatment with aripiprazole was started and at 12‐month follow‐up.

Results:  A total of 53 patients were included; of these 55% continued using aripiprazole for 12 months. Aripiprazole treatment for 12 months (P = 0.027) and stopping clozapine or olanzapine treatment (P = 0.038) predicted weight loss (≥3 kg). Patients receiving aripiprazole monotherapy (n = 16, mean −3.0 kg) had similar weight loss than patients receiving aripiprazole in addition to another antipsychotic drug (n = 13, mean −4.4 kg).

Conclusion:  In routine practice once aripiprazole treatment was started, more than half of the patients remained on aripiprazole and most of them lost weight. Adding aripiprazole to clozapine gave similar weight loss as monotherapy with aripiprazole.
Atypical lymphocytic lobular panniculitis: a clonal subcutaneous T‐cell dyscrasia
Authors: Magro Cynthia M. , Schaefer Jochen T. , Morrison Carl , Porcu Pierluigi
Published: August 2008

Background:  Atypical lymphocytic lobular panniculitis (ALLP) is a recently described entity characterized by waxing and waning plaques. A morphologic and biologic continuum with subcutaneous panniculitis‐like T‐cell lymphoma has been suggested.

Methods:  Between 2003 and 2007, we encountered five patients with ALLP. Comprehensive phenotypic and molecular studies were performed using multiplex polymerase chain reaction.

Results:  The patient population comprised four women, one man and two boys, age range of 6–42 years. All patients had a similar clinical presentation, being one of the recurrent infiltrative plaque‐like lesions. All cases showed a permeation of the interstitial spaces of the subcutis by well‐differentiated lymphocytes unaccompanied by significant fat necrosis. Molecular studies showed a clonal and/or oligoclonal profile in all cases. In all cases in which multiple biopsies were obtained, there was preservation of the identical T‐cell clonotypes at different biopsy sites and over time. No patient progressed to lymphoma. One patient achieved remission with isotrentinoin.

Conclusions:  ALLP represents a form of cutaneous lymphoid dyscrasia given the relatively self‐limited nature of the eruption, albeit in the context of clinical recurrence.
Foxp3 expression in cutaneous T‐cell lymphocytic infiltrates
Authors: Solomon Garron J. , Magro Cynthia M.
Published: August 2008

Background:  The primary function of regulatory T cells (Treg cells) is to regulate the function and proliferation of immunologically responsive T cells; the transcription factor Foxp3 is expressed by this cell populace and is held to be the standard marker for Treg cells.

Design:  A variety of cutaneous T‐cell lymphocytic infiltrates were evaluated for Foxp3 expression.

Results:  Of the 95 cases, 33 (35%) were reactive, 40 (42%) were prelymphomatous cutaneous T‐cell dyscrasia and 22 were (23%) T‐cell lymphoma. The reactive category included dermatomyositis, lupus erythematosus, hypersensitivity reactions and graft‐vs.‐host disease. The prelymphomatous dyscrasia category was represented chiefly by pityriasis lichenoides chronica (PLC) and pigmented purpuric dermatosis (PPD). The Foxp3 reactivity was less than 10% for cases of dermatomyositis and lupus erythematosus, 23% for hypersensitivity cases, 0% for graft‐vs.‐host disease, 16% for the dyscrasias and 11% for the lymphomas. Intermediate grade and aggressive lymphomas had very few Foxp3+ cells (< 5%). There were fewer numbers of Foxp3+ T cells in the monoclonal variants of PLC and PPD.

Conclusions:  T‐reg cells may play a role in controlling the extent of T‐cell proliferations in the skin with a lack of T‐regulatory function permissive to the development of various T‐cell disorders.
Platelet‐rich plasma suppresses osteoclastogenesis by promoting the secretion of osteoprotegerin
Authors: Ogino Y. , Ayukawa Y. , Kukita T. , Atsuta I. , Koyano K.
Published: August 2008

Background and Objective:  Platelet‐rich plasma is characterized by containing fundamental protein growth factors. Although many in vitro studies have documented the capability of platelet‐rich plasma to induce the growth of osteoblasts or osteoblast‐like cells, the effect of platelet‐rich plasma on osteoclastogenesis has not yet been studied. The aim of the present study was to evaluate the effects of platelet‐rich plasma and platelet‐poor plasma on osteoclastogenesis with rat bone marrow cell culture.

Material and Methods:  Platelet‐rich plasma and platelet‐poor plasma were produced from the whole blood of rat. For cell culture, rat bone marrow cells were isolated from rat tibiae and then treated with 1,25α dihydroxy vitamin D3 and with different concentrations of platelet‐rich plasma or platelet‐poor plasma. After 4 d of culture, rat bone marrow cells were stained with tartrate‐resistant acid phosphatase (TRAP), and TRAP‐positive cells that had more than three nuclei (TRAP‐positive multinucleated cells) were counted as osteoclast‐like cells. Osteoprotegerin, known as an osteoclastogenesis‐related factor, cells was quantified using an enzyme‐linked immunosorbent assay (ELISA).

Results:  Although platelet‐poor plasma had no effect on the formation of TRAP‐positive multinucleated cells, platelet‐rich plasma decreased the number of TRAP‐positive multinucleated cells in a dose‐dependent manner. The amount of osteoprotegerin produced from rat bone marrow cells and from MC3T3‐E1 cells was enhanced in platelet‐rich plasma‐treated groups.

Conclusion:  Under our experimental conditions, platelet‐rich plasma decreased the formation of TRAP‐positive multinucleated cells and increased the secretion of osteoprotegerin. This study suggests that platelet‐rich plasma suppresses osteoclastogenesis, therefore inhibiting bone resorption. In addition we also demonstrated that platelet‐rich plasma increased the secretion of osteoprotegerin, an inhibitor for osteoclast formation, thus suggesting that the enhancement of osteoprotegerin secretion induces this inhibitory effect.
Loss of the Batten Disease Gene CLN3 Prevents Exit from the TGN of the Mannose 6‐Phosphate Receptor
Authors: Metcalf Daniel J , Calvi Alessandra A , Seaman Matthew NJ , Mitchison Hannah M , Cutler Daniel F
Published: August 2008

The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are a group of inherited childhood‐onset neurodegenerative disorders characterized by the lysosomal accumulation of undigested material within cells. To understand this dysfunction, we analysed trafficking of the cation‐independent mannose 6‐phosphate receptor (CI‐MPR), which delivers the digestive enzymes to lysosomes. A common form of NCL is caused by mutations in CLN3, a multipass transmembrane protein of unknown function. We report that ablation of CLN3 causes accumulation of CI‐MPR in the trans Golgi network, reflecting a 50% reduction in exit. This CI‐MPR trafficking defect is accompanied by a fall in maturation and cellular activity of lysosomal cathepsins. CLN3 is therefore essential for trafficking along the route needed for delivery of lysosomal enzymes, and its loss thereby contributes to and may explain the lysosomal dysfunction underlying Batten disease.
Modulation of Host Cell Endocytosis by the Type III Cytotoxin, Pseudomonas ExoS
Authors: Deng Qing , Barbieri Joseph T.
Published: August 2008

Pseudomonas aeruginosa ExoS is a bifunctional type III cytotoxin that possesses Rho GTPase‐activating protein (RhoGAP) and ADP‐ribosyltransferase (ADPr) activities. In the current study, the RhoGAP and ADPr activities of ExoS were tested for the ability to disrupt mammalian epithelial cell physiology. RhoGAP, but not ADPr, inhibited internalization/phagocytosis of bacteria, while ADPr, but not RhoGAP, inhibited vesicle trafficking, both general fluid‐phase uptake and EGF‐activated EGF receptor (EGFR) degradation. In ADPr‐intoxicated cells, upon EGF activation, EGFR co‐localized with clathrin‐coated vesicles (CCV), which did not mature into Rab5‐positive early endosomes. Constitutively, active Rab5 recruited EGFR from CCV to early endosomes. Consistent with the inhibition of Rab5 function by ADPr, several Rab proteins including Rab5 and 9, but not Rab4, were ADP ribosylated by ExoS. Thus, the two enzymatic activities of ExoS have different effects on epithelial cells with RhoGAP inhibiting bacterial internalization and ADPr interfering with CCV maturation. The ability ADPr to inhibit mammalian vesicle trafficking provides a new mechanism for bacterial toxin‐mediated virulence.
Kinesin‐3 is an Organelle Motor in the Squid Giant Axon
Authors: DeGiorgis Joseph A. , Petukhova Tatyana A. , Evans Teresa A. , Reese Thomas S.
Published: August 2008

Conventional kinesin (Kinesin‐1), the founding member of the kinesin family, was discovered in the squid giant axon, where it is thought to move organelles on microtubules. In this study, we identify a second squid kinesin by searching an expressed sequence tag database derived from the ganglia that give rise to the axon. The full‐length open reading frame encodes a 1753 amino acid sequence that classifies this protein as a Kinesin‐3. Immunoblots demonstrate that this kinesin, unlike Kinesin‐1, is highly enriched in chaotropically stripped axoplasmic organelles, and immunogold electron microscopy (EM) demonstrates that Kinesin‐3 is tightly bound to the surfaces of these organelles. Video microscopy shows that movements of purified organelles on microtubules are blocked, but organelles remain attached, in the presence Kinesin‐3 antibody. Immunogold EM of axoplasmic spreads with antibody to Kinesin‐3 decorates discrete sites on many, but not all, free organelles and localizes Kinesin‐3 to organelle/microtubule interfaces. In contrast, label for Kinesin‐1 decorates microtubules but not organelles. The presence of Kinesin‐3 on purified organelles, the ability of an antibody to block their movements along microtubules, the tight association of Kinesin‐3 with motile organelles and its distribution at the interface between native organelles and microtubules suggest that Kinesin‐3 is a dominant motor in the axon for unidirectional movement of organelles along microtubules.
A randomized, open trial evaluating the effect of Saccharomyces boulardii on the eradication rate of Helicobacter pylori infection in children
Authors: Hurduc Victoria , Plesca Doina , Dragomir Dimitrie , Sajin Maria , Vandenplas Yvan
Published: August 2008

Aim: The failure rate of Helicobacter pylori (H. pylori) eradication imposes the assessment of new options.

Subjects and methods: A prospective open study was performed in 90 symptomatic children (range 3–18 years) with H. pylori infection, randomized in two groups: control (42 patients) and intervention group (48 patients). Both groups were treated with the standard triple eradication therapy (omeprazole/esomeprazole, amoxicillin and clarithromycin) for 7–10 days. The intervention group was also treated with Saccharomyces boulardii (S. boulardii), 250 mg b.i.d., for 4 weeks. The eradication rate of H. pylori was assessed by the same methods (urease test and histology) 4–6 weeks after treatment. Adverse events and compliance were evaluated after 7 and 28 days of treatment. The Chi‐square test was used for statistical evaluation (p < 0.05).

Results: H. pylori infection was identified in 90 of 145 children (62%) and it correlated positively with age (p < 0.002) and inversely with socioeconomic status (p < 0.005). All infected children had chronic gastritis, with antral nodularity in 76.7%. Overall, H. pylori eradication rate was 87.7% (control 80.9%, S. boulardii group 93.3%) (p = 0.750). The incidence of side effects was reduced in the S. boulardii group: 30.9% in the control versus 8.3% in the probiotic group (p = 0.047).

Conclusion: The addition of S. boulardii to the standard eradication treatment confers a 12% nonsignificant enhanced therapeutic benefit on H. pylori eradication and reduces significantly the incidence of side effects.
Inter‐flavin electron transfer in cytochrome P450 reductase – effects of solvent and pH identify hidden complexity in mechanism
Authors: Brenner Sibylle , Hay Sam , Munro Andrew W. , Scrutton Nigel S.
Published: August 2008

This study on human cytochrome P450 reductase (CPR) presents a comprehensive analysis of the thermodynamic and kinetic effects of pH and solvent on two‐ and four‐electron reduction in this diflavin enzyme. pH‐dependent redox potentiometry revealed that the thermodynamic equilibrium between various two‐electron reduced enzyme species (FMNH•,FADH•; FMN,FADH2; FMNH2,FAD) is independent of pH. No shift from the blue, neutral di‐semiquinone (FMNH•,FADH•) towards the red, anionic species is observed upon increasing the pH from 6.5 to 8.5. Spectrophotometric analysis of events following the mixing of oxidized CPR and NADPH (1 to 1) in a stopped‐flow instrument demonstrates that the establishment of this thermodynamic equilibrium becomes a very slow process at elevated pH, indicative of a pH‐gating mechanism. The final level of blue di‐semiquinone formation is found to be pH independent. Stopped‐flow experiments using excess NADPH over CPR provide evidence that both pH and solvent significantly influence the kinetic exposure of the blue di‐semiquinone intermediate, yet the observed rate constants are essentially pH independent. Thus, the kinetic pH‐gating mechanism under stoichiometric conditions is of no significant kinetic relevance for four‐electron reduction, but rather modulates the observed semiquinone absorbance at 600 nm in a pH‐dependent manner. The use of proton inventory experiments and primary kinetic isotope effects are described as kinetic tools to disentangle the intricate pH‐dependent kinetic mechanism in CPR. Our analysis of the pH and isotope dependence in human CPR reveals previously hidden complexity in the mechanism of electron transfer in this complex flavoprotein.