bluuebunny/crossref_metadata_2025 huggingface dataset:
Decisions about transferring nursing home residents to hospital: highlighting the roles of advance care planning and support from local hospital and community health services
Authors: Shanley Christopher , Whitmore Elizabeth , Conforti David , Masso Janine , Jayasinghe Sanjay , Griffiths Rhonda
Published: May 2011

Aims and objectives.  To explore current practice and opportunities to improve practice in decision‐making about transfer of nursing home residents to hospital.

Background.  Nursing home staff are often faced with the decision of whether to send a resident to hospital for medical treatment. While many residents will benefit from going to hospital, there are also several risks associated with this. This study sought to add to the existing body of research on this issue by seeking the views of nursing home managers, who are the persons most frequently involved in making these decisions.

Design.  Qualitative design using purposive, quota sampling.

Method.  Qualitative interviews with 41 nursing home managers from south‐western Sydney, Australia.

Results.  Factors affecting the decision to transfer a resident to hospital include acuteness of their condition; level and style of medical care available; role of family members; numbers, qualifications and skills mix of staff; and concern about criticism for not transferring to hospital. Two factors that have not featured as strongly in previous research are the roles of advance care planning and support from local hospital and community health services.

Conclusion.  While transferring a nursing home resident to hospital is often necessary, there are many situations where they could be cared for in the nursing home; therefore, avoid complications associated with being in hospital. Apart from a range of factors already identified in the literature, this study has highlighted the important role that advance care planning and support from local health services can play in reducing unnecessary transfers to hospital.

Relevance to clinical practice.  There are several strategies that nursing homes and local health authorities can adopt to promote advance care planning and build better support systems between the two sectors, thereby reducing the numbers of residents who need to be transferred to hospital for their health care.
The impact of antipsychotic side effects on attitudes towards medication in people with schizophrenia and related disorders
Authors: Chiang Yan Ling , Klainin‐Yobas Piyanee , Ignacio Jeanette , Chng Cecilia Mui Lee
Published: May 2011

Aims and objectives. This research aimed to: (i) investigate the prevalence and perceived severity of antipsychotic side effects in people with schizophrenia and related disorders living in communities in Singapore; (ii) examine the relationship between antipsychotic variables (type, dose, route, prescription duration) and side effects; and (iii) examine the relationship between side effects and attitudes towards medication.

Background. Antipsychotics are the mainstay treatment in schizophrenia and other psychotic disorders. However, antipsychotics are associated with a wide range of side effects, which potentially have adverse effects on patients’ functioning. A lack of studies comparing the frequency of side effects and their associated levels of distress across multiple antipsychotics and different medication variables has been noted. Additionally, it is essential to assess patients’ attitudes towards antipsychotics in relation to their experience of side effects.

Design. A cross‐sectional, non‐experimental research design was used.

Method. A convenience sample of 96 adults with schizophrenia and related disorders on antipsychotic treatment and attending the hospital’s outpatient clinic was recruited. Variables collected included antipsychotic type, dose, route, prescription duration and side effects, attitudes towards medication and demographic and clinical variables. They were analysed with descriptive statistics and correlational analyses.

Results. Many participants experienced psychic (80·2%), extrapyramidal (69·8%) and miscellaneous side effects (61·5%). Side effects positively correlated with dose (p = 0·016) and negatively correlated with prescription duration (p = 0·014). Negative attitudes towards medication were positively correlated with side effects in general (p = 0·023), along with hormonal (p = 0·013) and psychic side effects (p = 0·008).

Conclusion. Findings revealed that majority of the participants experienced and were distressed over psychic, extrapyramidal and weight gain, which may be related to high doses and treatment duration. Additionally, patients experiencing psychic and hormonal side effects are at risk of developing negative attitudes towards medication.

Relevance to clinical practice. Findings guide the development of appropriate nursing interventions that aim to alleviate side effects, reduce negative attitudes towards medication and prevent compliance problems.
Comparing the efficacy of aquatic exercises and land‐based exercises for patients with knee osteoarthritis
Authors: Wang Tsae‐Jyy , Lee Shu‐Chiung , Liang Shu‐Yuan , Tung Heng‐Hsin , Wu Shu‐Fang V , Lin Yu‐Ping
Published: May 2011

Aims.  The study aims to compare changes over time among three study groups on the primary outcome, pain, as well as on the secondary outcomes, other symptoms, activities of daily living function, sport and recreation function, knee‐related quality of life, knee range of motions and the six‐minute walk test and to investigate whether aquatic exercises would be superior compared with land exercise on pain reduction.

Background.  Osteoarthritis is a prevalent musculoskeletal disorder. Appropriate exercise may prevent osteoarthritis‐associated disabilities and increase life quality. To date, research that compares the effects of different types of exercise for knee osteoarthritis has been limited.

Design.  The study is a randomised trial.

Methods.  Eighty‐four participants with knee osteoarthritis were recruited from local community centres. Participants were randomly assigned to the control, aquatic or land‐based exercise group. Exercise in both groups ran for 60 minutes, three times a week for 12 weeks. Data were collected at baseline, week 6 and week 12 during 2006–2007. The instruments included the Knee Injury and Osteoarthritis Outcome Score, a standard plastic goniometer and the six‐minute walk test. Generalised estimation equations were used to compare changes over time among groups for key outcomes.

Results.  Results showed statistically significant group‐by‐time interactions in pain, symptoms, sport/recreation and knee‐related quality of life dimensions of Knee Injury and Osteoarthritis Outcome Score, knee range of motions and the six‐minute walk test. However, the aquatic group did not show any significant difference from the land group at both weeks 12 and 6.

Conclusions.  Both aquatic and land‐based exercise programmes are effective in reducing pain, improving knee range of motions, six‐minute walk test and knee‐related quality of life in people with knee osteoarthritis. The aquatic exercise is not superior to land‐based exercise in pain reduction.

Relevance to clinical practice.  Similar outcomes could be possible with the two programmes. Health care professionals may consider suggesting well‐designed aquatic or land‐based exercise classes for patients with osteoarthritis, based on their preferences and convenience.
Characterization of Bacillus subtilis uracil‐DNA glycosylase and its inhibition by phage φ29 protein p56
Authors: Pérez‐Lago Laura , Serrano‐Heras Gemma , Baños Benito , Lázaro José M. , Alcorlo Martín , Villar Laurentino , Salas Margarita
Published: May 2011

Uracil‐DNA glycosylase (UDG) is a conserved DNA repair enzyme involved in uracil excision from DNA. Here, we report the biochemical characterization of UDG encoded by Bacillus subtilis, a model low G+C Gram‐positive organism. The purified enzyme removes uracil preferentially from single‐stranded DNA over double‐stranded DNA, exhibiting higher preference for U:G than U:A mismatches. Furthermore, we have identified key amino acids necessary for B. subtilis UDG activity. Our results showed that Asp‐65 and His‐187 are catalytic residues involved in glycosidic bond cleavage, whereas Phe‐78 would participate in DNA recognition. Recently, it has been reported that B. subtilis phage φ29 encodes an inhibitor of the UDG enzyme, named protein p56, whose role has been proposed to ensure an efficient viral DNA replication, preventing the deleterious effect caused by UDG when it eliminates uracils present in the φ29 genome. In this work, we also show that a φ29‐related phage, GA‐1, encodes a p56‐like protein with UDG inhibition activity. In addition, mutagenesis analysis revealed that residue Phe‐191 of B. subtilis UDG is critical for the interaction with φ29 and GA‐1 p56 proteins, suggesting that both proteins have similar mechanism of inhibition.
Assembly of the Caulobacter cell division machine
Authors: Goley Erin D. , Yeh Yi‐Chun , Hong Sun‐Hae , Fero Michael J. , Abeliuk Eduardo , McAdams Harley H. , Shapiro Lucy
Published: May 2011

Cytokinesis in Gram‐negative bacteria is mediated by a multiprotein machine (the divisome) that invaginates and remodels the inner membrane, peptidoglycan and outer membrane. Understanding the order of divisome assembly would inform models of the interactions among its components and their respective functions. We leveraged the ability to isolate synchronous populations of Caulobacter crescentus cells to investigate assembly of the divisome and place the arrival of each component into functional context. Additionally, we investigated the genetic dependence of localization among divisome proteins and the cell cycle regulation of their transcript and protein levels to gain insight into the control mechanisms underlying their assembly. Our results revealed a picture of divisome assembly with unprecedented temporal resolution. Specifically, we observed (i) initial establishment of the division site, (ii) recruitment of early FtsZ‐binding proteins, (iii) arrival of proteins involved in peptidoglycan remodelling, (iv) arrival of FtsA, (v) assembly of core divisome components, (vi) initiation of envelope invagination, (vii) recruitment of polar markers and cytoplasmic compartmentalization and (viii) cell separation. Our analysis revealed differences in divisome assembly among Caulobacter and other bacteria that establish a framework for identifying aspects of bacterial cytokinesis that are widely conserved from those that are more variable.
A σW‐dependent stress response in Bacillus subtilis that reduces membrane fluidity
Authors: Kingston Anthony W. , Subramanian Chitra , Rock Charles O. , Helmann John D.
Published: May 2011

Bacteria respond to physical and chemical stresses that affect the integrity of the cell wall and membrane by activating an intricate cell envelope stress response. The ability of cells to regulate the biophysical properties of the membrane by adjusting fatty acid composition is known as homeoviscous adaptation. Here, we identify a homeoviscous adaptation mechanism in Bacillus subtilis regulated by the extracytoplasmic function σ factor σW. Cell envelope active compounds, including detergents, activate a sense‐oriented, σW‐dependent promoter within the first gene of the fabHa fabF operon. Activation leads to a decrease in the amount of FabHa coupled with an increase in FabF, the initiation and elongation condensing enzymes of fatty acid biosynthesis respectively. Downregulation of FabHa results in an increased reliance on the FabHb paralogue leading to a greater proportion of straight chain fatty acids in the membrane, and the upregulation of FabF increases the average fatty acid chain length. The net effect is to reduce membrane fluidity. The inactivation of the σW‐dependent promoter within fabHa increased sensitivity to detergents and to antimicrobial compounds produced by other Bacillus spp. Thus, the σW stress response provides a mechanism to conditionally decrease membrane fluidity through the opposed regulation of FabHa and FabF.
The two faces of ToxR: activator of ompU, co‐regulator of toxT in Vibrio cholerae
Authors: Morgan Sarah J. , Felek Suleyman , Gadwal Shilpa , Koropatkin Nicole M. , Perry Jeffrey W. , Bryson Alyson B. , Krukonis Eric S.
Published: May 2011

ToxR of Vibrio cholerae directly activates the ompU promoter, but requires a second activator, TcpP to activate the toxT promoter. ompU encodes a porin, while toxT encodes the transcription factor, ToxT, which activates V. cholerae virulence genes including cholera toxin and the toxin co‐regulated pilus. Using an ompU‐sacB transcriptional fusion, toxR mutant alleles were identified that encode ToxR molecules defective for ompU promoter activation. Many toxR mutants defective for ompU activation affected residues involved in DNA binding. Mutants defective for ompU activation were also tested for activation of the toxT promoter. ToxR‐F69A and ToxR‐V71A, both in the α‐loop of ToxR, were preferentially defective for ompU activation, with ToxR‐V71A nearly completely defective. Six mutants from the ompU‐sacB selection showed more dramatic defects in toxT activation than ompU activation. All but one of the affected residues map to the wing domain of the winged helix–turn–helix of ToxR. Some ToxR mutants preferentially affecting toxT activation had partial DNA‐binding defects, and one mutant, ToxR‐P101L, had altered interactions with TcpP. These data suggest that while certain residues in the α‐loop of ToxR are utilized to activate the ompU promoter, the wing domain of ToxR contributes to both promoter binding and ToxR/TcpP interaction facilitating toxT activation.
The novel Listeria monocytogenes bile sensor BrtA controls expression of the cholic acid efflux pump MdrT
Authors: Quillin Sarah J. , Schwartz Kierstyn T. , Leber Jess H.
Published: May 2011

Mammalian bile has potent anti‐microbial activity, yet bacterial pathogens of the gastrointestinal tract and hepatobiliary system nonetheless persist and replicate within bile‐rich environments. Listeria monocytogenes, a Gram‐positive pathogen, encounters bile at three stages throughout its infectious cycle in vivo: in the gut during initial infection, in the liver where it replicates robustly and in the gallbladder, from which it can return to the intestine and thence to the environment. The mechanisms by which L. monocytogenes senses mammalian bile and counteracts its bactericidal effects are not fully understood. In this report, we have determined the L. monocytogenes bile‐induced transcriptome, finding that many critical virulence factors are regulated by bile. Among these, the multidrug efflux pumps MdrM and MdrT, previously shown to be critical for the bacterial provocation of a pathogenesis‐promoting host innate immune response, are robustly and specifically induced by the bile component cholic acid. This induction is mediated by BrtA, the first identified L. monocytogenes sensor of bile, which loses the ability to bind to and repress the mdrT promoter in the presence of cholic acid. We show that MdrT can export cholic acid, and that ΔmdrT bacteria are significantly attenuated both in vitro when exposed to cholic acid or bile, and in vivo in the gallbladders and livers of infected mice.
Transcription of the plasmid‐encoded toxin gene from Enteroaggregative Escherichia coli is regulated by a novel co‐activation mechanism involving CRP and Fis
Authors: Rossiter Amanda E. , Browning Douglas F. , Leyton Denisse L. , Johnson Matthew D. , Godfrey Rita E. , Wardius Catherine A. , Desvaux Mickael , Cunningham Adam F. , Ruiz‐Perez Fernando , Nataro James P. , Busby Stephen J. W. , Henderson Ian R.
Published: May 2011

Enteroaggregative Escherichia coli (EAEC) is a major cause of diarrhoea in developing countries. EAEC 042 is the prototypical strain. EAEC 042 secretes the functionally well‐characterized Pet autotransporter toxin that contributes to virulence through its cytotoxic effects on intestinal epithelial cells. Following a global transposon mutagenesis screen of EAEC 042, the transcription factors, CRP and Fis, were identified as essential for transcription of the pet gene. Using both in vivo and in vitro techniques, we show that the pet promoter is co‐dependent on CRP and Fis. We present a novel co‐activation mechanism whereby CRP is placed at a non‐optimal position for transcription initiation, creating dependence on Fis for full activation of pet. This study complements previous findings that establish Fis as a key virulence regulator in EAEC 042.
Role for Golgi reassembly and stacking protein (GRASP) in polysaccharide secretion and fungal virulence
Authors: Kmetzsch Lívia , Joffe Luna S. , Staats Charley C. , de Oliveira Débora L. , Fonseca Fernanda L. , Cordero Radames J.B. , Casadevall Arturo , Nimrichter Leonardo , Schrank Augusto , Vainstein Marilene H. , Rodrigues Marcio L.
Published: May 2011

Secretion of virulence factors is a critical mechanism for the establishment of cryptococcosis, a disease caused by the yeast pathogen Cryptococcus neoformans. One key virulence strategy of C. neoformans is the release of glucuronoxylomannan (GXM), a capsule‐associated immune‐modulatory polysaccharide that reaches the extracellular space through secretory vesicles. Golgi reassembly and stacking protein (GRASP) is required for unconventional protein secretion mechanisms in different eukaryotic cells, but its role in polysaccharide secretion is unknown. This study demonstrates that a C. neoformans functional mutant of a GRASP orthologue had attenuated virulence in an animal model of cryptococcosis, in comparison with wild‐type (WT) and reconstituted cells. Mutant cells manifested altered Golgi morphology, failed to produce typical polysaccharide capsules and showed a reduced ability to secrete GXM both in vitro and during animal infection. Isolation of GXM from cultures of WT, reconstituted or mutant strains revealed that the GRASP orthologue mutant produced polysaccharides with reduced dimensions. The mutant was also more efficiently associated to and killed by macrophages than WT and reconstituted cells. These results demonstrate that GRASP, a protein involved in unconventional protein secretion, is also required for polysaccharide secretion and virulence in C. neoformans.
The diguanylate cyclase, Rrp1, regulates critical steps in the enzootic cycle of the Lyme disease spirochetes
Authors: Kostick Jessica L. , Szkotnicki Lee T. , Rogers Elizabeth A. , Bocci Paola , Raffaelli Nadia , Marconi Richard T.
Published: May 2011

Rrp1 is the sole c‐di‐GMP‐producing protein (diguanylate cyclase) of Borrelia burgdorferi. To test the hypothesis that Rrp1 regulates critical processes involved in the transmission of spirochetes between ticks and mammals, an rrp1 deletion mutant (B31‐Δrrp1) and a strain that constitutively produces elevated levels of Rrp1 (B31‐OV) were constructed. The strains were assessed for progression through the enzootic cycle using an Ixodes tick/C3H‐HeJ mouse model and tick immersion feeding methods. B31‐Δrrp1 infected mice as efficiently as wild type but had altered motility, decreased chemotactic responses to N‐acetylglucosamine (NAG) and attenuated ability to disseminate or colonize distal organs. While this strain infected mice, it was not able to survive in ticks. In contrast, B31‐OV displayed normal motility patterns and chemotactic responses but was non‐infectious in mice. Using immersion feeding techniques, we demonstrate that B31‐OV can establish a population in ticks and survive exposure to a natural bloodmeal. The results presented here indicate Rrp1, and by extension, c‐di‐GMP, are not strictly required for murine infection, but are required for the successful establishment of a productive population of B. burgdorferi in ticks. These analyses provide significant new insight into the genetic regulatory mechanisms of the Lyme disease spirochetes.
The oxidative stress response in yeast cells involves changes in the stability of Aft1 regulon mRNAs
Authors: Castells‐Roca Laia , Mühlenhoff Ulrich , Lill Roland , Herrero Enrique , Bellí Gemma
Published: May 2011

Saccharomyces cerevisiae can import iron through a high‐affinity system consisting of the Ftr1/Fet3‐mediated reductive pathway and the siderophore‐mediated non‐reductive one. Expression of components of the high‐affinity system is controlled by the Aft1 transcriptional factor. In this study we show that, upon oxidative stress, Aft1 is transitorily internalized into the nucleus, followed by transcription activation of components of its regulon. In these conditions, the mRNA levels of the genes of the non‐reductive pathway become increased, while those of FTR1 and FET3 remain low because of destabilization of the mRNAs. Consequently, the respective protein levels also remain low. Such mRNA destabilization is mediated by the general 5′–3′ mRNA decay pathway and is independent of the RNA binding protein Cth2. Yeast cells are hypersensitive to peroxides in growth conditions where only the high‐affinity reductive pathway is functional for iron assimilation. On the contrary, peroxide does not affect growth when iron uptake occurs exclusively through the non‐reductive pathway. This reinforces the idea that upon oxidative stress S. cerevisiae cells redirect iron assimilation through the non‐reductive pathway to minimize oxidative damage by the ferrous ions, which are formed during iron import through the Ftr1/Fet3 complexes.
The incidence and risk factors of immediate type food allergy during the first year of life in Korean infants: a birth cohort study
Authors: Kim Jihyun , Chang Eunyoung , Han Youngshin , Ahn Kangmo , Lee Sang‐Il
Published: May 2011

To cite this article: Kim J, Chang E, Han Y, Ahn K, Lee S‐I. The incidence and risk factors of immediate type food allergy during the first year of life in Korean infants: a birth cohort study. Pediatric Allergy Immunology 2011; 22: 715–719.

Objectives:  We conducted this study to determine the incidence of food allergy (FA) in Korean infants and identify the risk factors of FAs during the first year of life in a birth cohort study.

Methods:  Pregnant women ≥34 weeks of gestation were enrolled in this study. Participants were asked to complete questionnaires describing basic demographic information including family history of allergic diseases. Since birth, all the babies were regularly followed up for FA symptoms through telephone interviews at 4, 8, and 12 months of age. FA was defined as a repetitive convincing history of immediate allergic reactions following the ingestion of offending food.

Results & conclusions:  A total of 1177 infants and their parents completed this study. The prevalence of FA was 5.3% in infants. The three leading food allergens were hen’s eggs (33/62), cow’s milk (20/62) and peanut/nuts (8/62). Children with a history of maternal AD showed a significantly higher prevalence of FA (P = 0.012) [aRR = 3.17]. In addition, children who were born during autumn had a higher prevalence than those born during spring (p = 0.005) [aRR = 3.48]. In conclusion, we identified several characteristics that may influence the development of FA in the next generation, including maternal AD and autumn birth.
Partially hydrolyzed cow’s milk formula has a therapeutic effect on the infants with mild to moderate atopic dermatitis: a randomized, double‐blind study
Authors: Jin Ying‐Ying , Cao Rui‐Ming , Chen Ji , Kaku Yoriko , Wu Jian , Cheng Ying , Shimizu Takashi , Takase Mitsunori , Wu Sheng‐Mei , Chen Tong‐Xin
Published: May 2011

To cite this article: Jin Y‐Y, Cao R‐M, Chen J, Kaku Y, Wu J, Cheng Y, Shimizu T, Takase M, Wu S‐M, Chen T‐X. Partially hydrolyzed cow’s milk formula has a therapeutic effect on the infants with mild to moderate atopic dermatitis: a randomized, double‐blind study. Pediatric Allergy Immunology 2011; 22: 688–694.

Objective:  The allergy‐preventing effect of partially hydrolyzed cow’s milk formula (phCMF) in infants at high risk of atopic dermatitis (AD) has been demonstrated in many studies. However, the therapeutic potential of phCMF in treating the infants with AD has not been reported. We sought to assess such therapeutic efficacy of phCMF in infants with mild to moderate AD.

Methods:  From 2006 to 2008, 113 infants <6 months of age with AD were randomized to receive either partially hydrolyzed cow’s milk formula (phCMF) or conventional cow’s milk formula (CMF) in a double‐blind clinical trial. Assessments were made at enrollment and at weeks 4, 8, and 12. The severity of AD was assessed using two scoring systems: Standard guideline for management (diagnosis, severity scoring, and therapy) of AD by the Japanese Dermatological Association Scoring System (JDASS) and the SCORing Atopic Dermatitis (SCORAD). Growth status of the infants was evaluated. Allergy profile was assessed by measuring total blood eosinophils (EOS), total/specific IgE, Th1/Th2 cytokine profiles, and the percentage of regulatory T cells.

Results:  After follow‐up for 12 wk, 27 infants (23.89%) dropped off study. Analysis was performed on 86 infants by the end of 12‐wk observation. The AD severity scores were significantly reduced in the phCMF group (n = 56) compared with CMF group (n = 30) after 12 wk (p < 0.05). The severity scores of phCMF group were significantly reduced at weeks 4, 8, and 12 compared to enrollment (p < 0.05). In contrast, no significant improvement was observed for CMF group at any of those time points (p > 0.05). The number of AD flare‐ups was significantly decreased in the phCMF group (p = 0.002). Th1/Th2 ratio in phCMF was significantly increased compared with CMF group (p = 0.041). The growth rates did not differ significantly between these feeding groups at any assessed time point (p > 0.05) and were in the normal range.

Conclusion:  This study suggests a novel therapeutic effect of phCMF in treating infants with mild to moderate AD during the first 6 months of their life without affecting their nutritional status.
Exploring CCL18, eczema severity and atopy
Authors: Hon Kam Lun , Ching Gary K. , Ng Pak Cheung , Leung Ting Fan
Published: May 2011

To cite this article: Hon KL, Ching GK, Ng PC, Leung TF. Exploring CCL18, eczema severity and atopy. Pediatric Allergy Immunology 2011; 22: 704–707.

Background:  Childhood atopic dermatitis (AD) is a distressing disease associated with pruritus, sleep disturbance, and impaired quality of life. The pathophysiology of AD is complex, and the chemokine CCL18/pulmonary and activation‐regulated chemokine (PARC) may be involved.

Objective:  To evaluate whether CCL18 was associated with disease severity, quality of life, nocturnal scratching, serum eosinophil, and IgE levels.

Patients and methods:  Patients with AD aged 20 yr or younger were recruited. Disease severity was assessed with the SCORing Atopic Dermatitis (SCORAD) index, quality of life with the Children’s Dermatology Life Quality Index (CDLQI), and nocturnal scratching with a wrist motion monitor. Concentrations of plasma CCL18/PARC, serum total IgE, and eosinophil counts were measured in these patients.

Results:  One hundred and eight patients with AD (mean [s.d.] age of 10.5 [4.4] yr) were recruited. The mean (s.d.) plasma concentration of CCL18/PARC was 162.2 (129.0) pg/ml, respectively. CCL18/PARC was significantly correlated with objective SCORAD (r = 0.44, p < 0.001), extent (r = 0.45, p < 0.001), intensity (r = 0.43, p < 0.001), the symptoms of pruritus (r = 0.20, p = 0.04), and sleep loss (r = 0.19, p = 0.049) but not with CDLQI or nocturnal scratching activities. CCL18/PARC levels were also correlated with eosinophil counts (r = 0.37, p < 0.001) and IgElog (r = 0.27, p = 0.005). Positive correlation with SCORAD was present even in patients without bronchial hyper‐reactivity.

Conclusions:  Serum levels of CCL18 correlate with the clinical severity score, serum eosinophil, and IgE levels. CCL18 is associated with AD and atopy.
Maternal dietary patterns during pregnancy and risk of wheeze and eczema in Japanese infants aged 16–24 months: The Osaka Maternal and Child Health Study
Authors: Miyake Yoshihiro , Okubo Hitomi , Sasaki Satoshi , Tanaka Keiko , Hirota Yoshio
Published: May 2011

To cite this article: Miyake Y, Okubo H, Sasaki S, Tanaka K, Hirota Y. Maternal dietary patterns during pregnancy and risk of wheeze and eczema in Japanese infants aged 16–24 months: The Osaka Maternal and Child Health Study. Pediatric Allergy Immunology 2011; 22: 734–741.

Background:  Maternal diet during pregnancy might influence the development of childhood allergic disorders.

Aims:  This prospective study examined the relationship between maternal dietary patterns during pregnancy and the risk of wheeze and eczema in the offspring aged 16–24 months.

Materials & Methods:  Subjects were 763 mother–child pairs. Data on maternal intake during pregnancy were assessed with a diet history questionnaire. Dietary patterns were derived from factor analysis of 33 predefined food groups. Symptoms of wheeze and eczema were based on criteria of the International Study of Asthma and Allergies in Childhood. Adjustment was made for maternal age, gestation, residential municipality, family income, maternal and paternal education, maternal and paternal history of allergic disorders, changes in maternal diet in pregnancy, season at baseline, maternal smoking during pregnancy, baby’s older siblings, sex, birth weight, age at the third survey, household smoking, and breastfeeding duration.

Results:  Three dietary patterns were identified: ‘healthy’, characterized by high intake of green and yellow vegetables, seaweed, mushrooms, white vegetables, pulses, potatoes, fish, sea products, fruit, and shellfish; ‘Western’, characterized by high intake of vegetable oil, salt‐containing seasonings, beef and pork, processed meat, eggs, chicken, and white vegetables; and ‘Japanese’, characterized by high intake of rice, miso soup, sea products, and fish. There was a tendency for an inverse exposure–response relationship between the maternal Western pattern during pregnancy and the risk of childhood wheeze by crude analysis. After adjustment for the confounding factors under study, the inverse relationship was strengthened: the adjusted OR between extreme quartiles was 0.59 (95% CI: 0.35–0.98, p for trend = 0.02). No such inverse association was observed for childhood eczema. Neither the maternal healthy pattern nor the Japanese pattern during pregnancy was related to childhood wheeze or eczema.

Conclusion:  The maternal Western pattern during pregnancy may be preventive against wheeze in the offspring.
Prediction of atopic dermatitis in 2‐yr‐old children by cord blood IgE, genetic polymorphisms in cytokine genes, and maternal mentality during pregnancy
Authors: Wen Hui‐Ju , Wang Ying‐Jan , Lin Ying‐Chu , Chang Chih‐Chin , Shieh Chi‐Chang , Lung For‐Wey , Guo Yue Leon
Published: May 2011

To cite this article: Wen H‐J, Wang Y‐J, Lin Y‐C, Chang C‐C, Shieh C‐C, Lung F‐W, Guo YL. Prediction of atopic dermatitis in 2‐yr‐old children by cord blood IgE, genetic polymorphisms in cytokine genes, and maternal mentality during pregnancy. Pediatric Allergy Immunology 2011; 22: 695–703.

Atopic dermatitis (AD) is the most common skin disease in childhood and the first step of atopic march. This study aimed to investigate whether AD in children could be better predicted by biologic markers (cord blood IgE [cbIgE], LT‐αNcoI alleles, and FcεRI‐β E237G genotypes) and maternal mentality during pregnancy, taking into account gender, socio‐demographic factors, and parental atopy. From 2001 to 2005, 1264 mother–infant pairs were recruited to participate in a birth cohort study. Prenatal questionnaire was used to collect family history, maternal gestational conditions and mentality, and environmental exposures. Cord blood was collected and assayed for genotypes and IgE levels. Phone interviews at 6 months and 2 yrs of age were conducted to inquire children’s health status, including AD occurrence. In addition to the known risk factors such as gender, maternal education, and parental atopy, biomarkers and maternal mentality during pregnancy were screened by logistic regression as candidate predictors of AD. Area‐under‐curve (AUC) statistic from receiver‐operating characteristic (ROC) curve analysis was used to compare two predicting models with and without biomarkers and maternal mentality. A total of 730 pairs completed the prenatal questionnaire and phone interview and were included in final analysis. The prevalence of ever having physician‐diagnosed AD by 2‐yr‐olds was 5.9%. Elevated cbIgE levels (≥0.5 kU/l), LT‐αNcoI alleles, FcεRI‐β E237G genotype, and maternal psychologic stress during pregnancy were significantly associated with AD. Comparison with AUCs of the classic model (including gender, maternal education, and parental atopy), the model adding cbIgE levels, genotypes in cytokine genes, and maternal stress (model 2) showed higher ability to discriminate between children with and without AD (AUC statistics: 0.63 [95% CI = 0.60–0.67] vs. 0.73 [95% CI = 0.70–0.76], respectively; model comparison, p = 0.027). We conclude that elevated cbIgE, LT‐α and FcεRI‐β genotypes, and maternal stress during pregnancy were associated with ever having physician‐diagnosed AD in 2‐yr‐old children and increased the predictive ability for AD after taking into account gender, maternal education, and parental atopic history.
Bateman’s principle and immunity in a sex‐role reversed pipefish
Authors: ROTH O. , SCHARSACK J. P. , KELLER I. , REUSCH T. B. H.
Published: May 2011

In diverse animal species, from insects to mammals, females display a more efficient immune defence than males. Bateman’s principle posits that males maximize their fitness by increasing mating frequency whereas females gain fitness benefits by maximizing their lifespan. As a longer lifespan requires a more efficient immune system, these implications of Bateman’s principle may explain widespread immune dimorphism among animals. Because in most extant animals, the provisioning of eggs and a higher parental investment are attributes of the female sex, sex‐role reversed species provide a unique opportunity to assess whether or not immune dimorphism depends on life history and not on sex per se. In the broad‐nosed pipefish Syngnathus typhle, males brood and nourish the eggs in a ventral pouch and thus invest more into reproduction than females. We found males to have a more active immune response both in field data from four populations and also in an experiment under controlled laboratory conditions. This applied to different measures of immunocompetence using innate as well as adaptive immune system traits. We further determined the specificity of immune response initiation after a fully factorial primary and secondary exposure to a common marine pathogen Vibrio spp. Males not only had a more active but also a more specific immune defence than females. Our results thus indeed suggest that the sex that invests more into the offspring has the stronger immune defence.
Locally asymmetric introgressions between subspecies suggest circular range expansion at theAntirrhinum majusglobal scale
Authors: KHIMOUN A. , BURRUS M. , ANDALO C. , LIU Z.‐L. , VICÉDO‐CAZETTES C. , THÉBAUD C. , PUJOL B.
Published: May 2011

Assessing processes of geographic expansion in contact zones is a crucial step towards an accurate prediction of the evolution of species genetic diversity. The geographic distribution of cytonuclear discordance often reflects genetic introgression patterns across a species geographic range.Antirrhinum majus pseudomajusandA. m. striatumare two interfertile subspecies that occupy nonoverlapping areas but enter in contact in many locations at the margin of their geographic distribution. We found that genetic introgression between both subspecies was asymmetric at the local scale and geographically oriented in opposite directions at both ends of their contact zone perimeter in the Pyrenees. Our results suggest that the geographic expansion ofA. majussubspecies was circular around the perimeter of their contact zone and pinpoint the need to integrate different spatial scales to unravel complex patterns of species geographic expansion.
Adaptation to marginal habitats by evolution of increased phenotypic plasticity
Authors: CHEVIN L.‐M. , LANDE R.
Published: May 2011

In an island population receiving immigrants from a larger continental population, gene flow causes maladaptation, decreasing mean fitness and producing continued directional selection to restore the local mean phenotype to its optimum. We show that this causes higher plasticity to evolve on the island than on the continent at migration‐selection equilibrium, assuming genetic variation of reaction norms is such that phenotypic variance is higher on the island, where phenotypes are not canalized. For a species distributed continuously in space along an environmental gradient, higher plasticity evolves at the edges of the geographic range, and in environments where phenotypes are not canalized. Constant or evolving partially adaptive plasticity also alleviates maladaptation owing to gene flow in a heterogeneous environment and produces higher mean fitness and larger population size in marginal populations, preventing them from becoming sinks and facilitating invasion of new habitats. Our results shed light on the widely observed involvement of partially adaptive plasticity in phenotypic clines, and on the mechanisms causing geographic variation in plasticity.
Genetic and environmental sources of covariance among internal reproductive traits in the yellow dung fly
Authors: THÜLER K. , BUSSIÈRE L. F. , POSTMA E. , WARD P. I. , BLANCKENHORN W. U.
Published: May 2011

Substantial inter‐ and intraspecific variation is found in reproductive traits, but the evolutionary implications of this variation remain unclear. One hypothesis is that natural selection favours female reproductive morphology that allows females to control mating and fertilization and that diverse male reproductive traits arise as counter adaptations to subvert this control. Such co‐evolution predicts the establishment of genetic correlations between male and female reproductive traits that closely interact during mating. Therefore, we measured phenotypic and genetic correlations between male and female reproductive tract characteristics in the yellow dung fly, Scathophaga stercoraria (Diptera: Scathophagidae), using a nested half‐sib breeding experiment. We found significant heritabilities for the size of most reproductive tract traits investigated in both females (spermathecae and their ducts, accessory glands and their ducts) and males (testis size but not sperm length). Within the sexes, phenotypic and genetic correlations were mostly nil or positive, suggesting functional integration of or condition‐dependent investment in internal reproductive traits. Negative intrasexual genetic correlations, potentially suggestive of resource allocation trade‐offs, were not evident. Intersexual genetic correlations were mostly positive, reflecting expected allometries between male and female morphologies. Most interestingly, testis size correlated positively with female accessory gland size and duct length, potentially indicative of a co‐evolutionary arms race. We discuss these and alternative explanations for these patterns of genetic covariance.
A phylogeny of frugivorous hornbills linked to the evolution of Indian plants within Asian rainforests
Authors: VISESHAKUL N. , CHAROENNITIKUL W. , KITAMURA S. , KEMP A. , THONG‐AREE S. , SURAPUNPITAK Y. , POONSWAD P. , PONGLIKITMONGKOL M.
Published: May 2011

Understanding the origin and radiation of modern Asian hornbills and the influential ecological roles they play as seed dispersal agents within Asian rainforests should help reveal the evolution of these roles. We constructed a dated phylogeny of hornbills using mitochondrial DNA sequences of the cytochromebgene and discovered that all clades leading to frugivorous hornbills originated in the mid‐Eocene ∼48 Ma. This ‘explosive’ radiation coincided with a remarkable floral invasion of Asian rainforests from the Indian microcontinent. Analysis of phylogenetic data, in conjunction with palaeontological events, suggests that the invasion of distinctive flora comprised two waves, one during the mid‐Eocene, when India was offshore of the Sunda Shelf, and the other late Eocene, when India collided with the Asian mainland. We propose that frugivorous vertebrates, such as hornbills, were present during the first wave and assisted rapid colonization of the Asian flora.
Pathogenesis of alcohol‐induced liver disease: Classical concepts and recent advances
Authors: Seth Devanshi , Haber Paul S , Syn Wing‐Kin , Diehl Anna Mae , Day Christopher P
Published: May 2011

Alcoholic liver disease (ALD) is a primary consequence of heavy and prolonged drinking. ALD contributes to the bulk of liver disease burden worldwide. Progression of ALD is a multifactorial and multistep process that includes many genetic and environmental risk factors. The molecular pathogenesis of ALD involves alcohol metabolism and secondary mechanisms such as oxidative stress, endotoxin, cytokines and immune regulators. The histopathological manifestation of ALD occurs as an outcome of complex but controlled interactions between hepatic cell types. Hepatic stellate cells (HSCs) are the key drivers of fibrogenesis, but transformation of hepatocytes to myofibroblastoids also implicate parenchymal cells as playing an active role in hepatic fibrogenesis. Recent discoveries indicate that lipogenesis during the early stages of ALD is a risk for advancement to cirrhosis. Other recently identified novel molecules and physiological/cell signaling pathways include fibrinolysis, osteopontin, transforming growth factor‐β‐SMAD and hedgehog signaling, and involvement of novel cytokines in hepatic fibrogenesis. The observation that ALD and non‐alcoholic steatohepatitis share common pathways and genetic polymorphisms suggests operation of parallel pathogenic mechanisms. Future research involving genomics, epigenomics, deep sequencing and non‐coding regulatory elements holds promise to identify novel diagnostic and therapeutic targets for ALD. There is also a need for adequate animal models to study pathogenic mechanisms at the molecular level and targeted therapy.
Emerging management concepts for eosinophilic esophagitis in children
Authors: Heine Ralf G , Nethercote Mark , Rosenbaum Jeremy , Allen Katrina J
Published: May 2011

Eosinophilic esophagitis (EoE) is a newly recognized condition that appears to be increasing in incidence for as yet unknown reasons. It can occur at any age and presents both to gastroenterologists and allergists. Clinical manifestations range from gastrointestinal symptoms (vomiting, feeding difficulties, dysphagia or food bolus impaction) to co‐existing atopic conditions (asthma, allergic rhinitis or eczema). The diagnosis requires demonstration of at least 15 eosinophils per high power field on esophageal histology, usually in the context of resistance to proton pump inhibitor treatment or a normal 24‐h esophageal pH monitoring study. The differential diagnosis between EoE and gastroesophageal reflux disease (GERD) can be problematic as there is significant clinical overlap between both conditions. Although difficult‐to‐manage esophageal strictures are well recognized in patients with long‐standing EoE, little is known about risk factors for the development of this complication. There is a paucity of data on both the natural history and optimal long‐term management of EoE. Current treatment options include food allergen elimination diets, use of topical aerosolized corticosteroids, or a combination of the two. Pediatric case studies have been provided to illustrate the complexity of decision points that often arise in the management of these patients. This paper aims to discuss the various strategies currently available to clinicians in the management of EoE and highlights gaps in the current evidence base that urgently require further research.
Re‐evaluation of melanin bleaching using warm diluted hydrogen peroxide for histopathological analysis
Authors: Momose Masanobu , Ota Hiroyoshi , Hayama Masayoshi
Published: May 2011

Excessive amounts of melanin pigments may hamper histopathological assessments of melanocytic lesions by obscuring cellular morphology and hindering antibody–antigen interactions. To determine the optimal melanin‐bleaching conditions for histopathological examination, heavily pigmented melanomas were treated with warm hydrogen peroxide (H2O2) diluted with various diluents (1% disodium hydrogen phosphate 12H2O ( (Na2 HPO4); phosphate buffer 0.05 M, pH 7.4 (PB); and PBS 0.05 M, pH 7.4) at varying temperatures (50°C, 55°C, and 60°C) and for varying incubation times (0.5, 1, 2, and 3 h). The effect of the sequential order of antigen retrieval and bleaching on preserving tissue morphology was then evaluated. Additionally, the effect of melanin bleaching using warm diluted H2O2 on the antigenicity of melanoma‐related markers (HMB‐45, MART‐1, and S‐100) and other markers used for histopathology was examined in amelanotic melanomas and tonsil tissue. Optimal and complete bleaching was achieved using warm 3% H2O2 in PB treatment at 55°C for 2 h following antigen retrieval with microwaving or digestion with trypsin. Under these conditions, the tissue morphology and antigenicity of various immunohistochemical markers were also well preserved. Bleaching with warm 3% H2O2 PB is a fast and efficient method of bleaching melanin pigments and performing immunohistochemical examination in heavily melanin‐pigmented lesions.
Exhaled nitric oxide and exhaled breath condensate pH as predictors of sputum cell counts in optimally treated asthmatic smokers
Authors: HILLAS GEORGIOS , KOSTIKAS KONSTANTINOS , MANTZOURANIS KONSTANTINOS , BESSA VASSILIKI , KONTOGIANNI KONSTANTINA , PAPADAKI GEORGIA , PAPIRIS SPYROS , ALCHANATIS MANOS , LOUKIDES STELIOS , BAKAKOS PETROS
Published: May 2011

Background and objective:  Smoking is thought to modify the pattern of airway inflammation. Induced sputum provides useful information on cellular phenotype in inflammatory airways disorders; however, it is time‐consuming and difficult to implement in everyday clinical practice. The aim of this study was to determine whether exhaled NO (FeNO) and exhaled breath condensate (EBC) pH differed in asthmatic smokers compared with asthmatic non‐smokers and healthy subjects, and to evaluate the performance of FeNO and EBC pH for predicting the cellular phenotype of induced sputum.

Methods:  Asthmatic smokers (n = 40) and non‐smoking asthmatic patients (n = 43) were recruited for the study. Healthy smoking (n = 30) or non‐smoking (n = 30) subjects served as controls. FeNO and EBC pH were measured and all subjects underwent sputum induction for assessment of cell counts.

Results:  EBC pH was significantly lower in asthmatic smokers compared with non‐smokers (P < 0.01). FeNO levels were also significantly lower in asthmatic smokers compared with non‐smokers (P < 0.001). EBC pH was inversely associated with sputum eosinophils in both asthmatic smokers and non‐smokers (P < 0.001), whereas it was inversely associated with sputum neutrophils only in asthmatic smokers (P < 0.001). FeNO was positively associated with sputum eosinophils both in asthmatic smokers and non‐smokers (P < 0.001) but was not associated with sputum neutrophils. In asthmatic smokers, FeNO was a better predictor of sputum eosinophilia, whereas EBC pH was a better predictor of sputum neutrophilia. A combination of FeNO ≤ 14 ppb together with EBC pH > 7.20 predicted the paucigranulocytic induced sputum phenotype.

Conclusions:  EBC pH and FeNO levels were significantly lower in asthmatic smokers compared with non‐smokers. Combined specific cut‐off levels for FeNO and EBC pH may predict the paucigranulocytic phenotype in asthmatic smokers.