bluuebunny/crossref_metadata_2025 huggingface dataset:
Why should addiction medicine be an attractive field for young physicians?
Authors: Soyka Michael , Gorelick David A.
Published: September 2008

Aims  The clinical practice and science of addiction are increasingly active fields, which are attracting professionals from diverse disciplines such as psychology and neurobiology. Our scientific knowledge of the pathophysiology of addiction is rapidly growing, along with the variety of effective treatments available to clinicians. Yet, we believe that the medical specialties of addiction medicine/psychiatry are not attracting the interest and enthusiasm of young physicians. What can be done?

Methods  We offer the opinions of two experience addiction psychiatrists.

Results  In the US, there has been a decline in the number of psychiatrists seeking training or board certification in addiction psychiatry; about one‐third of graduates with such training are not practicing in an addiction psychiatry setting. There is widespread neglect of addiction medicine/psychiatry among the medical profession, academia and national health authorities. This neglect is unfortunate, given the enormous societal costs of addiction (3–5% of the gross domestic product in some developed countries), the substantial unmet need for addiction treatment, and the highly favourable benefit to cost yield (at least 7:1) from treatment.

Conclusions  We believe that addiction medicine/psychiatry can be made more attractive for young physicians. Helpful steps include widening acceptance as a medical specialty or subspecialty, reducing the social stigma against people with substance use disorders, expanding insurance coverage and increasing the low rates of reimbursement for physicians. These steps would be easier to take with broader societal (and political) recognition of substance use disorders as a major cause of premature death, morbidity and economic burden.
Development of a full‐genome cDNA clone of Citrus leaf blotch virus and infection of citrus plants
Authors: VIVES MARÍA CARMEN , MARTÍN SUSANA , AMBRÓS SILVIA , RENOVELL ÁGUEDA , NAVARRO LUIS , PINA JOSE ANTONIO , MORENO PEDRO , GUERRI JOSÉ
Published: September 2008

Citrus leaf blotch virus (CLBV), a member of the family Flexiviridae, has a ~9‐kb single‐stranded, positive‐sense genomic RNA encapsidated by a 41‐kDa coat protein. CLBV isolates are associated with symptom production in citrus including leaf blotching of Dweet tangor and stem pitting in Etrog citron (Dweet mottle disease), and some isolates are associated with bud union crease on trifoliate rootstocks, but Koch's postulates for this virus were not fulfilled. A full‐genome cDNA of CLBV isolate SRA‐153, which induces bud union crease, was placed under the T7 promoter (clone T7‐CLBV), or between the 35S promoter and the Nos‐t terminator, with or without a ribozyme sequence downstream of the CLBV sequence (clones 35SRbz‐CLBV and 35S‐CLBV). RNA transcripts from T7‐CLBV failed to infect Etrog citron and Nicotiana occidentalis and N. benthamiana plants, whereas agro‐inoculation with binary vectors carrying 35SRbz‐CLBV or 35S‐CLBV, and the p19 silencing suppressor, caused systemic infection and production of normal CLBV virions. Virus accumulation was similar in citron plants directly agro‐infiltrated, or mechanically inoculated with wild‐type or 35SRbz‐CLBV‐derived virions from Nicotiana, and the three sources incited the symptoms characteristic of Dweet mottle disease, but not bud union crease. Our results show that (1) virions derived from an infectious clone show the same replication, movement and pathogenicity characteristics as the wild‐type CLBV; (2) CLBV is the causal agent of Dweet mottle disease but not of the bud union crease syndrome; and (3) for the first time an RNA virus could be successfully agro‐inoculated on citrus plants. This infectious clone may become a useful viral vector for citrus genomic studies.
Maize food allergy: a double‐blind placebo‐controlled study
Authors: Scibilia J. , Pastorello E. A. , Zisa G. , Ottolenghi A. , Ballmer‐Weber B. , Pravettoni V. , Scovena E. , Robino A. , Ortolani C.
Published: September 2008

Background
Maize allergy is not very common especially in Europe. The number of studies that address IgE mediated maize allergy is all too few.

Objective
Evaluate subjects with a history of maize allergy by double‐blind, placebo‐controlled food challenge; identify the spectrum of symptoms manifested during challenge; determine the lowest provocation dose (PD) during challenge; determine the performance characteristics of maize skin prick test and specific IgE.

Methods
Twenty‐seven patients with a history of maize allergy were enrolled to be evaluated by skin test, specific IgE and double‐blind placebo‐controlled maize challenge.

Results
Forty‐eight percent of the patients were challenge positive. PD range was 0.1–25 g. Fifty‐four percent of the maize allergic subjects had a PD that was 2.5 g; two subjects reacted to 100 mg of maize. Comparison of maize specific IgE levels and skin test results to the challenge results revealed the following (specific IgE level/skin testing): sensitivity 1.00/0.846, specificity 0.077/0.384, positive predictive value 0.520/0.579, and negative predictive value 1.00/0.714.

Conclusion
Maize is a cause of IgE‐mediated allergic reactions to foods in adults and children. Nearly half of the subjects recruited were confirmed by challenge to be allergic to maize. Twenty‐three percent of the positive challenge patients manifested symptoms that involved two organ systems, thus fulfilling the criteria for maize induced anaphylaxis. Maize is allergenic and can pose a risk for symptomatic food allergy at a dose of 100 mg.
Maternal tolerance achieved during pregnancy is transferred to the offspring via breast milk and persistently protects the offspring from allergic asthma
Authors: Polte T. , Hansen G.
Published: September 2008

Background
Maternal, more than paternal, asthma is a risk factor for the development of asthma in children. Recently, epidemiologic studies have shown that environmental exposures during pregnancy might influence the development of childhood asthma and allergies.

Objective
The aim of the present study was to investigate whether the induction of tolerance against a specific antigen during pregnancy prevents in the offspring the development of allergic asthma in response to this antigen.

Methods
Balb/c mice were orally tolerized with ovalbumin (OVA) during pregnancy. The offspring of tolerized and naïve mothers were immunized with OVA at 6 weeks and 4 months of age and analysed in our murine asthma model.

Results
While the offspring of naïve mice developed increased AHR, eosinophilic airway inflammation, T‐helper type 2 cytokine production and high serum IgE levels in response to OVA sensitization, the offspring of tolerized mice were almost completely protected from asthma, even when immunized as late as 4 months after birth. Breastfeeding was crucial for protection because tolerance was only observed when the offspring were nursed by their own mothers and not when nursed by naïve wet‐nurses. Allergen‐specific IgG1 antibodies were exclusively increased in the breast milk of tolerant mothers and serum of protected pups, indirectly supporting its important role in tolerance transfer from the mother to the offspring. Sensitization of the F1 generation from OVA‐tolerized mothers with a heterologous allergen enhanced the immune response to this antigen.

Conclusion
Our results demonstrate that mucosal allergen contact during pregnancy modifies the asthma and allergy risk of the offspring mediated via breast milk. This observation may suggest that the time window for primary prevention strategies starts even before early childhood during pregnancy.
Important roles of tachykinins in the development of allergic nasal hyperresponsiveness in guinea‐pigs
Authors: Nabe T. , Tsuzuike N. , Ohtani Y. , Mizutani N. , Watanabe S. , Fujii M. , Yoshimura M. , Nagasawa M. , Kohno S.
Published: September 2008

Background
Although it has been suggested that the use of tachykinin receptor antagonists might prove to be an effective treatment for allergic rhinitis (AR), they are not used clinically. Therefore, we decided to examine the effects of tachykinin receptor antagonists on AR symptoms in an appropriate experimental model.

Objective
To evaluate newly developed tachykinin receptor antagonists in a Japanese cedar pollen‐induced AR model and to determine their effect on allergen‐induced sneezing, nasal blockage, and nasal hyperresponsiveness (NHR).

Methods
Sensitized guinea‐pigs were challenged by forced inhalation of pollen once every week. Sneezing and nasal blockage were observed after pollen challenges. NHR (nasal blockage) to an intranasal application of leukotriene D4 was assessed 2 days after an antigen challenge. We also evaluated whether intranasal dosing with a tachykinin causes NHR. NK1 and NK2 receptor antagonists were administered before an intranasal treatment with antigen or tachykinin. Amounts of tachykinins present in nasal cavity lavage fluid were measured by an enzyme immunoassay.

Results
Although an NK1 and NK2 receptor dual antagonist showed no effect on pollen‐induced sneezing and biphasic nasal blockage, it did completely suppress the development of NHR. Experiments using specific NK1 or NK2 receptor antagonists revealed that NK2 receptor activation was preferentially involved in the development of hyperresponsiveness. Increases in the levels of substance P (SP) and neurokinin A (NKA) in the nasal tissue were noted 20 min–1 h after the challenge. Intranasal instillation of either SP or NKA‐induced NHR, which was almost completely inhibited by NK2 receptor antagonists and partially inhibited by NK1 receptor antagonists.

Conclusions
SP and NKA, which are released early after the challenge, mediate the development of NHR by preferentially activating NK2 receptors. Therefore, NK2 receptor antagonists might prove to be effective treatment of AR.
Gene flow and genetic structure of the aquatic macrophyte Sparganium emersum in a linear unidirectional river
Authors: POLLUX B. J. A. , LUTEIJN A. , VAN GROENENDAEL J. M. , OUBORG N. J.
Published: September 2008

1. River systems offer special environments for the dispersal of aquatic plants because of the unidirectional (downstream) flow and linear arrangement of suitable habitats.

2. To examine the effect of this flow on microevolutionary processes in the unbranched bur‐reed (Sparganium emersum) we studied the genetic variation within and among nine (sub)populations along a 103 km stretch of the Niers River (Germany–The Netherlands), using amplified fragment length polymorphisms.

3. Genetic diversity in S. emersum populations increased significantly downstream, suggesting an effect of flow on the pattern of intrapopulation genetic diversity.

4. Gene flow in the Niers River is asymmetrically bidirectional, with gene flow being approximately 3.5 times higher in a downstream direction. The observed asymmetry is probably caused by frequent hydrochoric dispersal towards downstream locations on the one hand, and sporadic zoochoric dispersal in an upstream direction on the other. The spread of vegetative propagules (leaf and stem fragments) is probably not an important mode of dispersal for S. emersum, suggesting that gene flow is mainly via seed dispersal. Realized dispersal distances exceeded 60 km, revealing a potential for long‐distance dispersal in S. emersum.

5. There was no correlation between geographical and genetic distances among the nine S. emersum populations (i.e. no isolation by distance), which may be due to the occurrence of long‐distance dispersal and/or colonization and extinction dynamics in the Niers River.

6. Overall, the genetic population structure and regional dispersal patterns of S. emersum in the Niers River are best explained by a linear metapopulation model. Our study shows that flow can exert a strong influence on population genetic processes of plants inhabiting stream systems.
Retinoic acid inhibits in vivo interleukin‐2 gene expression and T‐cell activation in mice
Authors: Ertesvag Aase , Austenaa Liv M. I. , Carlsen Harald , Blomhoff Rune , Blomhoff Heidi Kiil
Published: September 2008

Interleukin‐2 (IL‐2) is an essential cytokine for T‐lymphocyte homeostasis. We have previously reported that all‐trans retinoic acid (atRA) enhances the secretion of IL‐2 from human peripheral blood T cells in vitro, followed by increased proliferation and inhibition of spontaneous cell death. In this study we used a transgenic IL‐2 gene luciferase reporter model to examine the effects of atRA in vivo. In contrast to the observations in human T cells, we found an overall reduction in luciferase‐reported IL‐2 gene expression in mice treated with atRA. Whole‐body luminescence of anti‐CD3‐treated and non‐treated mice was reduced in mice receiving atRA. Accordingly, after 7 hr, IL‐2 gene expression was on average 55% lower in the atRA‐treated mice compared with the control mice. Furthermore, mice fed a vitamin A‐deficient diet had a significantly higher basal level of luciferase activity compared with control mice, demonstrating that vitamin A modulates IL‐2 gene expression in vivo. Importantly, the atRA‐mediated inhibition of IL‐2 gene expression was accompanied by decreased DNA synthesis in murine T cells, suggesting a physiological relevance of the reduced IL‐2 gene expression observed in transgenic reporter mice.
Increased secretion of hyperimmune antibodies following lipopolysaccharide stimulation of CD40‐activated human B cells in vitro
Authors: Dumont Nellie , Aubin Eric , Proulx Dominic P. , Lemieux Réal , Bazin Renée
Published: September 2008

Human B cells can be cultured ex vivo for a few weeks, following stimulation of the CD40 cell surface molecule in the presence of recombinant cytokines such as interleukin‐4 (IL‐4). However, attempts to produce polyclonal antigen‐specific human antibodies by in vitro culture of human B cells obtained from immunized donors have not been successful. It has been shown in mice that lipopolysaccharide (LPS) is a potent mitogen for B cells and plays an important role in the generation of antigen‐specific antibody responses. Although it has long been believed that LPS has no direct effect on human B cells, recent data indicating that IL‐4‐activated human B cells are induced to express Toll‐like receptor‐4, the main LPS receptor, prompted us to study the effects of LPS on the proliferation and antibody secretion of human B cells. Our results showed that LPS caused a reduction in the expansion of CD40‐activated human B cells, accompanied by an increase in antigen‐specific antibody secretion. This result suggested that some, but not all, B cells were able to differentiate into antibody‐secreting cells in response to LPS. This increased differentiation could be explained by the observation that LPS‐stimulated human B cells were induced to secrete higher amounts of IL‐6, a pleiotropic cytokine well‐known for its B‐cell differentiation activity. In vivo, the effect of LPS on cytokine secretion by B cells may not only enhance B‐cell differentiation but also help to sustain a local ongoing immune response to invading Gram‐negative bacteria, until all pathogens have been cleared from the organism.
Dendritic cells: a family portrait at mid‐gestation
Authors: Bizargity Peyman , Bonney Elizabeth A.
Published: September 2008

Recent advances in our understanding of dendritic cells (DCs) and their role in tolerance and immunity has fuelled study of their normal development and function within the reproductive tract. The common hypothesis that pregnancy is a state of immune suppression or deviation now includes the idea that alterations in DC phenotype and function are critical for maternal tolerance. We chose to study DCs in the uterus and lymphoid tissue in non‐pregnant and pregnant mice at mid‐gestation to understand what DC‐related factors may be involved in premature birth. We used a mouse model where the mother’s immune system has been shown to respond to the male antigen H‐Y. Observed differences among DCs in the uterus, uterine draining nodes and spleen, even in non‐pregnant mice, suggest the existence of a specialized uterus‐specific subset of DCs. We further found that, amongst CD45+ CD11c+ cells in the uterus and peripheral lymphoid tissue of pregnant mice, expression of major histocompatibility complex class II (MHC II) and costimulatory molecules (i.e. CD80) was similar to that in the non‐pregnant state. Moreover, there was no pregnancy‐related decrease in the proportion of CD11c+ cells in the uterus or in the uterine node that were CD11b− CD8+. Pregnancy increased the CD11b+ subsets and the expression of chemokine (C‐C motif) ligand 6 (CCL6) in DCs of the uterine draining nodes. Finally, DC subsets showed variable expression, with respect to tissue and pregnancy, of the cytokine interleukin‐15, which is important in lymphoid cell homeostasis. For DCs, pregnancy is not a state of immune paralysis, but of dynamic developmental change.
Poly(ADP‐ribose) polymerase‐1 (Parp‐1)‐deficient mice demonstrate abnormal antibody responses
Authors: Ambrose Helen E. , Willimott Shaun , Beswick Richard W. , Dantzer Françoise , De Murcia Josiane Ménissier , Yelamos José , Wagner Simon D.
Published: September 2008

Poly(ADP‐ribosylation) of acceptor proteins is an epigenetic modification involved in DNA strand break repair, recombination and transcription. Here we provide evidence for the involvement of poly(ADP‐ribose) polymerase‐1 (Parp‐1) in antibody responses. Parp‐1−/− mice had increased numbers of T cells and normal numbers of total B cells. Marginal zone B cells were mildly reduced in number, and numbers of follicular B cells were preserved. There were abnormal levels of basal immunoglobulins, with reduced levels of immunoglobulin G2a (IgG2a) and increased levels of IgA and IgG2b. Analysis of specific antibody responses showed that T cell‐independent responses were normal but T cell‐dependent responses were markedly reduced. Germinal centres were normal in size and number. In vitro purified B cells from Parp‐1−/− mice proliferated normally and showed normal IgM secretion, decreased switching to IgG2a but increased IgA secretion. Collectively our results demonstrate that Parp‐1 has essential roles in normal T cell‐dependent antibody responses and the regulation of isotype expression. We speculate that Parp‐1 forms a component of the protein complex involved in resolving the DNA double‐strand breaks that occur during class switch recombination.
Anti‐ribosomal phosphoprotein autoantibody triggers interleukin‐10 overproduction via phosphatidylinositol 3‐kinase‐dependent signalling pathways in lipopolysaccharide‐activated macrophages
Authors: Lee Tai‐Ping , Leu Shr‐Jeng Jim , Huang Jason C. , Song Ying‐Chyi , Jhou Ren‐Shiang , Tang Shye‐Jye , Sun Kuang‐Hui
Published: September 2008

Anti‐ribosomal phosphoprotein autoantibodies have been shown to be significantly associated with multiple manifestations of systemic lupus erythematosus (SLE). High levels of interleukin‐10 (IL‐10) have been demonstrated to contribute to lupus susceptibility and severity. In this study, we investigated the molecular mechanisms of anti‐ribosomal phosphoprotein monoclonal antibody (anti‐P mAb)‐induced autoimmune responses. Anti‐P mAb promoted IL‐10 overproduction in a dose‐ and time‐dependent manner in both lipopolysaccharide (LPS)‐activated RAW 264.7 cells and primary human macrophages. Anti‐P mAb enhanced phosphorylation of Akt (PKB; protein kinase B), extracellular signal regulated kinase 1/2 (ERK1/2) and c‐Jun NH2‐terminal kinase 1/2 (JNK1/2), while phosphorylation of p38 remained unaltered. Furthermore, anti‐P mAb decreased glycogen synthase kinase 3 (GSK3) activity and reduced the phosphorylation of IκBα in LPS‐activated macrophages. The Syk, phosphatidylinositol 3‐kinase (PI3K), protein kinase C (PKC), JNK and ERK signalling pathways involved in anti‐P mAb‐triggered IL‐10 secretion were also confirmed using various pharmacological inhibitors. In addition, nuclear factor (NF)‐κB had negative regulatory effects on anti‐P mAb‐triggered IL‐10 secretion. Using reporter plasmids containing the nuclear factor binding sites of NF‐κB, cAMP‐enhanced activation protein 1 (AP‐1), serum response element (SRE) or cyclic AMP response element (CRE), treatment of anti‐P mAb led to activation of the corresponding factors that bind to the AP‐1 site, SRE and CRE in the LPS‐activated macrophages. Furthermore, by transfection with reporter plasmids bearing various lengths of the IL‐10 promoter, the AP‐1 binding site, SRE and CRE were shown to be required for anti‐P mAb‐induced effects. Collectively, our results provide a molecular model for anti‐P mAb‐induced IL‐10 overproduction in LPS‐activated macrophages, which may play a role in the pathogenesis of SLE.
Expansion of CD4+ CD25+ Foxp3+ T cells by bone marrow‐derived dendritic cells
Authors: Marguti Ivo , Yamamoto Guilherme Lopes , da Costa Thaís Boccia , Rizzo Luiz Vicente , de Moraes Luciana Vieira
Published: September 2008

Dendritic cells (DCs) are the most important antigen‐presenting cells of the immune system and have a crucial role in T‐lymphocyte activation and adaptive immunity initiation. However, DCs have also been implicated in maintaining immunological tolerance. In this study, we evaluated changes in the CD4+ CD25+ Foxp3+ T‐cell population after co‐culture of lymph node cells from BALB/c mice with syngeneic bone marrow‐derived DCs. Our results showed an increase in CD4+ CD25+ Foxp3+ T cells after co‐culture which occurred regardless of the activation state of DCs and the presence of allogeneic apoptotic cells; however, it was greater when DCs were immature and were pulsed with the alloantigen. Interestingly, syngeneic apoptotic thymocytes were not as efficient as allogeneic apoptotic cells in expanding the CD4+ CD25+ Foxp3+ T‐cell population. In all experimental settings, DCs produced high amounts of transforming growth factor (TGF)‐β. The presence of allogeneic apoptotic cells induced interleukin (IL)‐2 production in immature and mature DC cultures. This cytokine was also detected in the supernatants under all experimental conditions and enhanced when immature DCs were pulsed with the alloantigen. CD4+ CD25+ Foxp3+ T‐cell expansion during co‐culture of lymph node cells with DCs strongly suggested that the presence of alloantigen enhanced the number of regulatory T cells (Tregs) in vitro. Our data also suggest a role for both TGF‐β and IL‐2 in the augmentation of the CD4+ CD25+ Foxp3+ population.
Using expert knowledge to assess uncertainties in future polar bear populations under climate change
Authors: O’Neill Saffron J. , Osborn Tim J. , Hulme Mike , Lorenzoni Irene , Watkinson Andrew R.
Published: September 2008

Polar bear Ursus maritimus population dynamics under conditions of climate change has become a controversial topic. A survey of expert opinion based on modelled sea‐ice data was performed in order to quantify the trends and variance surrounding possible impacts of climate change on polar bear populations.

Polar bears have become an iconic species in the communication of climate change. Negative impacts of climatic warming on polar bears have been suggested, but cannot be fully quantified as no Arctic‐wide models yet exist to analyse the relationship between polar bear population dynamics and climate change.

Ten polar bear experts participated in an expert opinion survey in early 2007, quantifying the trends and variance surrounding possible impacts of climate change on polar bear populations. The experts were provided with maps and time‐series of sea‐ice extent and duration to 2050, simulated under a mid‐range emissions scenario. Expert projections of future polar bear habitat range and population size across the Arctic, and for population size in five regions, were obtained. Experts were asked to define ‘best conservation practice’, and to re‐evaluate the total Arctic population projection if this best practice was implemented.

Most experts project a substantial decline in polar bear range and population size across the Arctic and in population size across each region. Expert best estimates for total Arctic polar bear population size lie from no change to a 70% decrease by 2050 relative to today; with half the experts projecting at least a 30% decrease. The median best estimates show the Barents Sea, Hudson Bay and the Chukchi Sea populations experiencing the greatest population decline under this scenario. There is much uncertainty both within and between expert responses, especially in little‐researched regions such as the Chukchi Sea.

Synthesis and applications. Based on projected changes in sea‐ice extent, experts suggest that polar bear populations will undergo significant declines by 2050, even implementing best management practices, under the scenario of climatic warming outlined here. The expert survey approach could be applied to a wide range of species for which there is a lack of available data and considerable uncertainty surrounding all aspects of the problem that prevent quantification with more formal modelling approaches.
Two short‐chain dehydrogenase/reductases, NON‐YELLOW COLORING 1 and NYC1‐LIKE, are required for chlorophyll b and light‐harvesting complex II degradation during senescence in rice
Authors: Sato Yutaka , Morita Ryouhei , Katsuma Susumu , Nishimura Minoru , Tanaka Ayumi , Kusaba Makoto
Published: September 2008

Yellowing, which is related to the degradation of chlorophyll and chlorophyll–protein complexes, is a notable phenomenon during leaf senescence. NON‐YELLOW COLORING1 (NYC1) in rice encodes a membrane‐localized short‐chain dehydrogenase/reductase (SDR) that is thought to represent a chlorophyll b reductase necessary for catalyzing the first step of chlorophyll b degradation. Analysis of the nyc1 mutant, which shows the stay‐green phenotype, revealed that chlorophyll b degradation is required for the degradation of light‐harvesting complex II and thylakoid grana in leaf senescence. Phylogenetic analysis further revealed the existence of NYC1‐LIKE (NOL) as the most closely related protein to NYC1. In the present paper, the nol mutant in rice was also found to show a stay‐green phenotype very similar to that of the nyc1 mutant, i.e. the degradation of chlorophyll b was severely inhibited and light‐harvesting complex II was selectively retained during senescence, resulting in the retention of thylakoid grana even at a late stage of senescence. The nyc1 nol double mutant did not show prominent enhancement of inhibition of chlorophyll degradation. NOL was localized on the stromal side of the thylakoid membrane despite the lack of a transmembrane domain. Immunoprecipitation analysis revealed that NOL and NYC1 interact physically in vitro. These observations suggest that NOL and NYC1 are co‐localized in the thylakoid membrane and act in the form of a complex as a chlorophyll b reductase in rice.
The Regai Dzive Shiri Project: a cluster randomised controlled trial to determine the effectiveness of a multi‐component community‐based HIV prevention intervention for rural youth in Zimbabwe – study design and baseline results
Authors: Cowan Frances M. , Pascoe Sophie J. S. , Langhaug Lisa F. , Dirawo Jeffrey , Chidiya Samson , Jaffar Shabbar , Mbizvo Michael , Stephenson Judith M. , Johnson Anne M. , Power Robert M. , Woelk Godfrey , Hayes Richard J.
Published: September 2008

Objective  To assess the effectiveness of a community‐based HIV prevention intervention for adolescents in terms of its impact on (1) HIV and Herpes simplex virus type 2 (HSV‐2) incidence and on rates of unintended pregnancy and (2) reported sexual behaviour, knowledge and attitudes.

Methods  Cluster randomised trial of a multi‐component HIV prevention intervention for adolescents based in rural Zimbabwe. Thirty communities were selected and randomised in 2003 to early or deferred intervention implementation. A baseline bio‐behavioural survey was conducted among 6791 secondary school pupils (86% of eligibles) prior to intervention implementation.

Results  Baseline prevalences were 0.8% (95% CI: 0.6–1.0) for HIV and 0.2% (95% CI: 0.1–0.3%) for HSV‐2. Four girls (0.12%) were pregnant. There was excellent balance between study arms. Orphans who made up 35% of the cohort were at increased risk of HIV [age–sex adjusted odds ratio 3.4 (95% CI: 1.7–6.5)]. 11.9% of young men and 2.9% of young women reported that they were sexually active (P < 0.001); however, there were inconsistencies in the sexual behaviour data. Girls were less likely to know about reproductive health issues than boys (P < 0.001) and were less likely to have used and to be able to access condoms (P < 0.001).

Conclusion  This is one of the first rigorous evaluations of a community‐based HIV prevention intervention for young people in southern Africa. The low rates of HIV suggest that the intervention was started before this population became sexually active. Inconsistency and under‐reporting of sexual behaviour re‐emphasise the importance of using externally validated measures of sexual risk reduction in behavioural intervention studies.
Sequence‐based typing characterization of the novel HLA‐Cw*0340 allele in a Chinese individual
Authors: Cheng L.‐H. , Li Z. , Jin S.‐Z. , Zou H.‐Y.
Published: September 2008

The novel human leukocyte antigen (HLA)‐Cw*0340 allele was identified by sequence‐based typing in a Chinese individual. This allele shows that the sequences of exons 2–3 of HLA‐Cw*0340 are identical to those of HLA‐Cw*0302, except for a nucleotide substitution that changes CTC to ATC at codon 95, resulting in an amino acid change from Leu to lle in the protein; this allele also shows that the sequences of exons 2–3 of HLA‐Cw*0340 are identical to those of HLA‐Cw*030401 or HLA‐Cw*030403, except for a nucleotide substitution that changes TAC to TCC at codon 116, resulting in an amino acid change from Try to Ser in the protein.
Expression of major histocompatibility complex class I proteins and their antigen processing chaperones in mouse embryonic stem cells from fertilized and parthenogenetic embryos
Authors: Lampton P. W. , Crooker R. J. , Newmark J. A. , Warner C. M.
Published: September 2008

Embryonic stem (ES) cells are pluripotent cells with the potential to differentiate into cells or tissues that may be used for transplantation therapy. Parthenogenetic ES (pES) cells have been recently derived from both mouse and human oocytes and hold promise as a cell source that is histocompatible to the oocyte donor. Because of the importance of major histocompatibility complex (MHC) antigens in mediating tissue rejection or acceptance, we examined levels of mRNA and protein expression of MHC class I proteins, as well as several MHC class I antigen processing and presentation chaperones in mouse ES cells derived from both fertilized (fES) and parthenogenetic (pES) embryos. We found that H‐2K, Qa‐2, TAP1, TAP2, and tapasin mRNAs were all expressed at low levels in undifferentiated and differentiating ES cells and were significantly upregulated in response to interferon‐γ (IFN‐γ) treatment following 14 days of differentiation. Likewise, expression of H‐2Kb and H‐2Kk proteins were upregulated to detectable levels by IFN‐γ after 14 days of differentiation, but Qa‐2 protein expression remained low or absent. We also found that MHC class I, TAP1, TAP2, and tapasin mRNAs were all expressed at very low levels in ES cells compared with T cells, suggesting transcriptional regulation of these genes in ES cells. Calnexin, a chaperone molecule involved in other pathways than MHC expression, had mRNA levels that were similar in ES cells and T cells and was not upregulated by IFN‐γ in ES cells. Overall, ES cells derived from fertilized embryos and parthenogenetic embryos displayed remarkably similar patterns of gene expression at the mRNA and protein levels. The similarity between the fES and pES cell lines with regard to expression of MHC class I and antigen‐processing machinery provides evidence for the potential usefulness of pES cells in transplantation therapy.
Monitoring and dispersal of the invading GracillariidaeCameraria ohridella
Authors: Augustin S. , Guichard S. , Heitland W. , Freise J. , Svatoš A. , Gilbert M.
Published: September 2008

The horse‐chestnut leafminerCameraria ohridellais an invasive lepidoptera (Gracillariidae) which has spread throughout Europe over the last two decades. The species can be detected easily because of its noticeable damage to horse‐chestnut trees leaves, which allows the easy collection of large‐scale monitoring data. It is therefore an interesting model species to study invasion processes, and this review summarizes recent progresses in that regard. The date reported here result from monitoring ofC. ohridellapopulation based on pheromone traps and visual observation of damage carried out in Belgium, France, Germany, Switzerland and the UK. The patterns of spread measured using these different monitoring method, and the key factors associated with short‐distance dispersal (within cities), and large‐scale dispersal (across landscapes) are presented and discussed.
CONTRAST‐FREE BALLOON‐ASSISTED UNILATERAL PLASTIC STENTING IN MALIGNANT HILAR BILIARY OBSTRUCTION: A NEW METHOD
Authors: Singh Virendra , Singh Gurpreet , Verma Ganga Ram , Gupta Vikash , Gupta Rajesh , Kapoor Rakesh , Sharma Navneet , Bhalla Ashish
Published: September 2008

Background:  Unilateral endoscopic drainage in unresectable type II malignant hilar biliary obstruction is effective. Contrast injection leads to cholangitis. Recently, contrast‐free unilateral metal stenting in malignant hilar biliary obstruction has shown encouraging results, however, it is costly.

Methods:  We prospectively studied the outcome of unilateral balloon‐assisted plastic stenting in 15 patients with type II malignant hilar biliary obstruction without contrast.

Results:  A successful endoscopic drainage was achieved in 100% (15/15) patients. Cholangitis occurred in none and no patient died within 30 days. Mean patency of stent was 104.8 ± 18.3 days. Mean (±SD) survival of these patients was 129.5 ± 39.2 days. No major complications were observed.

Conclusions:  Unilateral endoscopic contrast‐free balloon‐assisted plastic stenting in type II malignant hilar biliary obstruction is a safe and effective method of palliation. However, a larger study is needed to validate the findings.
REFRACTORY GASTRIC ANTRAL ULCER OF UNKNOWN ETIOLOGY
Authors: Yamane Tateki , Uchiyama Kan , Ishii Takayuki , Omura Mitsuhiro , Fujise Kiyotaka , Tajiri Hisao
Published: September 2008

We report a Helicobacter pylori‐negative patient with multiple gastric antral ulcers of unknown etiology and without a history of taking non‐steroidal anti‐inflammatory drugs (NSAIDs). The patient was a 68‐year‐old woman, and her serum gastrin and pepsinogen levels were within normal limits. The antral ulcers were refractory to treatment with a proton pump inhibitor (PPI) or an H2 receptor antagonist alone. However, since nocturnal gastric acid breakthrough was observed, both drugs were given in combination, which resulted in the healing of the ulcers.
GASTROBILIARY FISTULA FROM A GIANT GASTRIC ULCER
Authors: Shelat Vishal G , Diddapur Ravishankar K
Published: September 2008

Gastrobiliary fistula arising from a gastric ulcer is yet unreported. Biliary lithiasis with its secondary complications is the commonest cause of enterobiliary fistulas. Enterobiliary fistulas are commonly identified incidentally and their discovery can complicate management, especially when identified intraoperatively. Penetration into contiguous organs occurs more frequently with giant (≥3 cm) gastric ulcers.
Comparison of gelatine matrix‐thrombin sealants used during laparoscopic partial nephrectomy
Authors: Nogueira Lucas , Katz Darren , Pinochet Rodrigo , Kurta Jordan M. , Coleman Jonathan A.
Published: September 2008

OBJECTIVE

To compare haemostasis and other outcomes after the use of bovine‐derived or porcine‐derived gelatine matrix‐thrombin sealants (GMTS) in a continuous series of patients during and for 6 months after laparoscopic partial nephrectomy (LPN).

PATIENTS AND METHODS

Between October 2006 and September 2007, a consecutive sample of 35 patients with renal tumours underwent LPN by a single surgeon at a referral centre. Group 1 (25 patients) received a bovine‐derived GMTS and Group 2 (10 patients) a porcine‐derived GMTS. All patients underwent LPN and received one of the two GMTS, applied to the resected bed before sutured renorrhaphy over oxidized nitrocellulose bolsters. Surgical and pathology variables, including ischaemia time, blood loss, tumour size, and serum creatinine values before and after LPN, were measured. Glomerular filtration rates were calculated before and after LPN. Haemostasis was ascertained by visual examination.

RESULTS

Intraoperative haemostasis was achieved in all cases. No associated complications occurred within 3 weeks of LPN. The two groups were comparable in age (median, 65 vs 69 years, P = 0.62), gender, tumour number and location, median ischaemia time (34 vs 28 min, P = 0.148), and blood loss (200 vs 150 mL, P = 0.518). One patient in Group 1 developed a urinary fistula. One patient in Group 2 experienced self‐limited gross haematuria.

CONCLUSIONS

Both the porcine‐ and bovine‐derived agents provided acceptable haemostasis without adverse events during LPN and in the early postoperative period. Occurrences of delayed haemorrhage and urinary fistula were not likely to be related to the choice of prothrombotic agent.
Radical prostatectomy for prostatic adenocarcinoma: a matched comparison of open retropubic and robot‐assisted techniques
Authors: Krambeck Amy E. , DiMarco David S. , Rangel Laureano J. , Bergstralh Eric J. , Myers Robert P. , Blute Michael L. , Gettman Matthew T.
Published: September 2008

OBJECTIVE

To assess the perioperative complications and early oncological results in a comparative study matching open radical retropubic (RRP) and robot‐assisted radical prostatectomy (RARP) groups.

PATIENTS AND METHODS

From August 2002 to December 2005 we identified 294 patients undergoing RARP for clinically localized prostate cancer. A comparison RRP group of 588 patients from the same period was matched 2:1 for surgical year, age, preoperative prostate‐specific antigen level, clinical stage and biopsy Gleason grade. Perioperative complications were compared. Patients completed a standardized quality‐of‐life questionnaire. Pathological features were assessed and Kaplan‐Meier estimates of biochemical progression‐free survival (PFS) were compared.

RESULTS

There was no significant difference in overall perioperative complications between the RARP and RRP groups (8.0% vs 4.8%, P = 0.064). Wound herniation was more common after RARP (1.0% vs none, P = 0.038), and development of bladder neck contracture was more common after RRP (1.2% vs 4.6%; P < 0.018). The hospital stay was less after RARP (29.3% vs 19.4%, P = 0.004, for a stay of 1 day). At the 1‐year follow‐up there was no significant difference in continence (RARP 91.8%, RRP 93.7%, P = 0.344) or potency (RARP 70.0%, RRP 62.8%, P = 0.081) rates. The biochemical PFS was no different between treatments at 3 years (RARP 92.4%, RRP 92.2%; P = 0.69).

CONCLUSION

There was no significant difference in overall early complication, long‐term continence or potency rates between the RARP and RRP techniques. Furthermore, early oncological outcomes were similar, with equivalent margin positivity and PFS between the groups.
Decreased immunostaining for macrophage scavenger receptor is associated with poor prognosis of prostate cancer
Authors: Takayama Hitoshi , Nonomura Norio , Nishimura Kazuo , Oka Daizo , Shiba Masahiro , Nakai Yasutomo , Nakayama Masashi , Tsujimura Akira , Aozasa Katsuyuki , Okuyama Akihiko
Published: September 2008

OBJECTIVE

The aim of this study is to evaluate the expression of the macrophage scavenger receptor (MSR) in prostate needle biopsy specimens as a possible prognostic factor for prostate cancer. As MSR reportedly has a role in recognizing foreign pathogenic substances, MSR‐positive inflammatory cells are often detected in solid tumours, and there is a correlation between the relative risk of prostate cancer and polymorphism of the MSR gene.

PATIENTS AND METHODS

MSR was evaluated by immunostaining in needle biopsies of the prostate from 135 patients who were confirmed to have prostate cancer. Among these men, 70 were treated by radical prostatectomy or by radiotherapy as definitive therapy; the other 65 were treated by hormonal therapy because of advanced disease or age. Needle‐biopsy specimens were sectioned at 5 µm and immunostained with a monoclonal antibody against MSR. Six microscopic (×400) fields around the cancer foci were selected in each case for analysis.

RESULTS

The median number of MSR‐positive cells (MSR count) in each case was 24. There was an inverse correlation between the MSR count and Gleason score and clinical stage. The MSR count was lower in patients with biochemical (prostate‐specific antigen, PSA) failure than that in those with no PSA failure (P < 0.001). In all patients, the recurrence‐free survival (RFS) rate was significantly higher in those with a high MSR count (≥24) than that in those with low MSR count (<24, P < 0.001). Moreover, for patients treated by definitive or hormonal therapy, the RFS rates in those with a higher MSR count were higher than in those with a lower MSR count (P < 0.001 and 0.014, respectively). Cox multivariate analysis showed that the MSR count was a prognostic factor for prostate cancer in addition to extraprostatic extension and Gleason score (P = 0.002, 0.038 and 0.011, respectively).

CONCLUSION

The results of immunostaining of MSR in needle‐biopsy specimens is a prognostic factor for prostate cancer.
Reconstruction of urethral erosion in men with a neurogenic bladder
Authors: Meeks Joshua J. , Erickson Bradley A. , Helfand Brian T. , Gonzalez Chris M.
Published: September 2008

OBJECTIVE

To describe the surgical outcomes and operative technique for reconstructing catheter‐induced urethral erosion in men with a neurogenic bladder.

PATIENTS AND METHODS

This was a prospective study of 11 men (median age 45 years, range 26–52) who had elective urethroplasty for urethral erosion between 2004 and 2007 by one surgeon (C.M.G.). All men had a diagnosis of neurogenic bladder and indwelling catheter‐induced urethral erosion. Reconstructive techniques included primary closure in six men, substitution urethroplasty with a penile skin graft in three, penile skin flap in one and a buccal mucosa graft in one. A two‐stage approach was used in one man.

RESULTS

The median (range) length of erosion from the meatus before surgery was 6 (4–10) cm. The repair was successful in seven men at a mean (range) follow‐up of 25 (8–46) months. Of those with recurrence of erosion, the median length of the resultant defect was 2 (2–3) cm. All recurrences were in the first five patients of this series. The median time to recurrence of erosion was 1 month and recurrence did not appear to be related to any particular surgical technique. Urethral catheter traction after surgery appeared to be one of the factors related to repair breakdown.

CONCLUSION

The reconstruction of catheter‐induced urethral erosion in men with a neurogenic bladder is feasible. Primary closure appears to be the best reconstructive method for urethral erosion, and avoiding catheter traction after surgery contributes to successful urethroplasty.
Anin vitrostudy on human ureteric smooth muscle with the α1‐adrenoceptor subtype blocker, tamsulosin
Authors: Rajpathy John , Aswathaman Karthikeyan , Sinha Maneesh , Subramani Sathya , Gopalakrishnan Ganesh , Kekre Nitin S.
Published: September 2008

OBJECTIVE

To study the effects of tamsulosin on ureteric contractions and its effects on the basal tone of human ureteric specimens, as clinical trials with tamsulosin have shown promising results in the spontaneous expulsion of lower ureteric calculus, but the mechanism of action of tamsulosin in the expulsion of ureteric calculus has not been elucidated inin‐vitrostudies on human ureters.

MATERIALS AND METHODS

Human mid‐ureteric specimens were obtained from live kidney donors. The specimen was transported in Krebs’ solution and the isometric contraction of human ureteric smooth muscle was recorded in the presence of tamsulosin. Ureteric rings from 19 kidney donors were studied.

RESULTS

At 100 µmtamsulosin the frequency of ureteric contraction was blocked completely, or the contraction frequency was reduced in 89% of specimens. There was no change in the frequency or in the amplitude of contraction in the remaining specimens. The basal tone of the ureter was reduced in 16% of the specimens.

CONCLUSION

Our results suggest that peristaltic activity in human ureteric smooth muscle is inhibited by tamsulosin. The effect of tamsulosin on basal tone is marginal.
Obesity status and sick leave: a systematic review
Authors: Neovius K. , Johansson K. , Kark M. , Neovius M.
Published: September 2008

This review identified 36 studies on the relation between obesity status and sick leave. Pooling of effect estimates was not possible due to great heterogeneity between studies regarding definition of sick leave (short‐term/long‐term), measure of obesity (body mass index/waist circumference/percentage body fat), definition of obesity status (World Health Organization standards/other), study population (sex/age/occupation/country) and exposure and outcome ascertainment (self‐reported/objectively assessed). Nevertheless, a clear trend towards greater sick leave among obese compared with normal weight workers could be discerned, especially for spells of longer duration. In studies from the USA, which consistently reported about five times lower number of sick leave days per person‐year than European, obese workers had about 1–3 extra days of absence per person‐year compared with their normal weight counterparts. In European studies, the corresponding difference was about 10 d. For overweight workers the data were conflicting, indicating either increased or neutral level of sick leave compared with normal weight. Regarding underweight, the studies were very few and concerns regarding direction of causality were greater. Finally, in all four interventional studies identified substantial weight loss in obese subjects resulted in reduced sick leave, at least temporarily. In conclusion, increasing obesity in children and adults is likely to negatively affect future productivity as obesity increases the risk of sick leave, disability pension and death.
Energy recommendations for normal weight, overweight and obese children and adolescents: are different equations necessary?
Authors: Woodruff S. J. , Hanning R. M. , Barr S. I.
Published: September 2008

In 2002/2005, separate energy requirement equations were generated by the Institute of Medicine's (IOM) Dietary Reference Intake process for normal weight and overweight/obese children and adolescents. The current paper questions the theoretical rationale of having two sets of equations (based solely on body‐weight classification): when body weight is considered, overweight and obese children and adolescents do not seem to differ from their normal weight counterparts in energy expended for basal metabolism or physical activity tasks. However, energy needs for weight maintenance among overweight/obese girls were consistently higher when predicted using the equations for overweight/obese individuals compared with those developed for normal weight individuals. In contrast, among overweight/obese boys, they were consistently lower. Although the differences are within the variability of the estimates, even theoretical support for a higher energy intake (as occurs in girls) seems unwise because of the potential contribution to a higher body mass in children who are already at risk. It is the opinion of the authors that the IOM revisit the use of two separate equations and generate one set that is appropriate for all children and adolescents.