bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of food properties and body position on swallowing‐related muscle activity amplitude
Authors: INAGAKI D. , MIYAOKA Y. , ASHIDA I. , YAMADA Y.
Published: February 2009

Summary  This study was designed to examine the effect of different food properties and body positions on electromyographic amplitudes of the anterior tongue (AT) and suprahyoid (SH) muscles during swallowing in normal subjects (six men and three women; 21–30 years old). Each subject was asked to swallow three foods (consisting of 2·0%, 5·7% or 9·1% of a thickening agent dissolved in water) with different textural properties in one of four body positions: upright, inclined at 60° or 30°, or supine. Surface electromyograms (EMG) were recorded from the anterior tongue and SH muscles, and the integrated and cumulated EMG were used to evaluate the amplitude changes. The increases in food hardness and adhesiveness elevated the integrated and cumulated EMGs of both the AT and SH muscles during swallowing in a stepwise manner (P < 0·0001, one‐way anova) that was independent of the body position. There was a linear relationship between the concentrations of the thickening agent and the logarithmic values of the food hardness. There was also a parallel relationship between the logarithmic hardness values and the final logarithmic values of the cumulated muscle activity during swallowing. Unlike these simple amplitude responses of the AT and SH muscles to the different food properties, our previous studies have shown that the durational responses of these muscle activities to different food properties are more complicated. Possible neural mechanisms responsible for the amplitude responses observed are discussed.
Polyphosphoric acid treatment promotes bone regeneration around titanium implants
Authors: MAEKAWA K. , SHIMONO K. , OSHIMA M. , YOSHIDA Y. , VAN MEERBEEK B. , SUZUKI K. , KUBOKI T.
Published: February 2009

Summary  This study was conducted to evaluate the effect of polyphosphoric acid (PPA) treatment on bone regeneration around titanium (Ti) implants in vivo. Adsorption of PPA by Ti was achieved by immersing Ti implants (2 mm in diameter, 4 mm in length) in different concentrations of PPA solution (0, 1 and 10 wt%) for 24 h at 37 °C after proper Ti surface cleaning. The treated Ti implants were implanted on 8‐week‐old‐male rat (n = 30) tibiae. Two or four weeks after implantation, all animals were deeply anaesthetized and underwent perfusion fixation. Ten specimens in each condition were further immersed in the same fixative for 1 week and eventually embedded in polyester resin. Afterwards, undecalcified sections were ground to a thickness of approximately 70 μm parallel to the long axis of the implant. The sections were stained with basic fuchsine and methylene blue and then examined by light microscopy. For quantitative evaluation of bone regeneration around the implants, the bone‐implant contact ratio (BICR) was determined. Polyphosphoric acid treatment of the Ti implant surface significantly enhanced direct bone contact to the Ti surface. Especially, the BICRs of the 1 wt% PPA‐treated Ti implants were significantly higher than those of the control untreated Ti implants, both 2 and 4 weeks after implantation. At 4 weeks, 10 wt% PPA‐treated implants also significantly increased the BICR as compared to that of the untreated Ti implants. These results suggest that PPA treatment promotes osteoconductivity of Ti in vivo.
Associations between ward atmosphere, patient satisfaction and outcome
Authors: JÖRGENSEN K. N. , RÖMMA V. , RUNDMO T.
Published: February 2009

Previous studies have found important associations between the ward atmosphere and patient satisfaction. However, fewer studies have examined the relationship between ward atmosphere and outcome of treatment. The aim of the study was to examine whether or not differences in ward atmosphere were associated with differences in satisfaction and outcome. Eighty patients at three different ward units responded to a questionnaire at admission and by the time of discharge from the hospital. The questionnaire comprised the ward atmosphere scale, a five‐item index of patient satisfaction, the Generalized Self‐Efficacy Scale, an index of life satisfaction and the symptom checklist SCL‐90R. The results showed that differences in the treatment environment between the ward units were associated with differences in patient satisfaction. There was mixed evidence for associations between ward atmosphere and outcome, while no associations were found between ward atmosphere and self‐efficacy and life satisfaction. The results may suggest that the relationship between ward atmosphere and outcomes of treatment may be of a more indirect character than the relationship between ward atmosphere and satisfaction.
Evaluation of a community‐based mental health drug and alcohol nurse in the care of people living with HIV/AIDS
Authors: ALLEN J. , HAMILTON A. , NUNN R. , CROCK L. , FRECKER J. , BURK N.
Published: February 2009

There is a growing need for advanced practice mental health and drug and alcohol nursing roles in the care of people living with HIV/AIDS; however, limited publications address these domains. This study evaluated a community‐based mental health drug and alcohol nurse role caring for people living with HIV/AIDS (Mental Health D&A Nurse) in a large not‐for‐profit district nursing organization providing care to people living with HIV/AIDS in an Australian city. Outcomes from a client assessment and 6–8‐week follow‐up by the Mental Health D&A Nurse are presented as captured by the Depression Anxiety Stress Scales (DASS 21), Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), Health of the Nation Outcome Scales (HONOS) and WHOQoL BREF. Mean scores and caseness were analysed, and significant differences were found on the ‘impairment’ and ‘social problems’ subscales of the HONOS. Results of semi‐structured interviews with clients describe effective and supportive mental health care and health‐promoting education following visits by the Mental Health D&A Nurse. These positive findings support continuing implementation of the role within this community setting and indicate that even greater benefits will ensue as the role develops further. Findings are of interest to clinicians and policy makers seeking to implement similar roles in community‐based HIV/AIDS care.
The competence of certified nurse assistants caring for persons with dementia diseases in residential facilities
Authors: FURÅKER C. , NILSSON A.
Published: February 2009

In Sweden, a majority of elderly persons living in residential facilities have some form of dementia, and caring for them is a demanding and complex task. The formal education level of personnel in residential facilities is low. The aim of this paper is to describe certified nurse assistants' (CNAs) content of competence caring for persons with dementia diseases in residential facilities. Information from 22 diary notes was obtained and 12 CNAs in four residential facilities were interviewed. The diary notes and interviews were transcribed and analysed using conventional content analysis. Three main categories were generated from the diaries: Social and Health Care, Health Care Targeted towards Medicine and, finally, Organization. The same categories were generated from the interviews but with the addition of Knowledge – its use, growth and deficiencies. The results show that competence is mainly based on personal, experienced‐based knowledge and ‘standard routines’. In general, the nurse assistants' interest in developing knowledge is weak. Furthermore, CNAs lack competence in essential theoretical knowledge about dementia diseases. It is notable that CNAs, caring for people with serious dementia, know little about the reasons for the residents' divergent behaviour. Consequently, knowledge related to dementia and mental diseases must be highlighted. Therefore, formal education focused on these diseases is crucial.
Advances in insectivore and rodent systematics due to geometric morphometrics
Authors: BARČIOVÁ LENKA
Published: February 2009

Morphometrics, the study of the variation and change in form amongst organisms, serves as a basic methodological tool in various fields of biological research, including systematics. Because it includes information about spatial relationships amongst anatomical landmarks, geometric morphometrics is more suitable for analyzing morphometric variation than methods based on distance measurements.

Geometric morphometrics allows us to answer general ecological and evolutionary questions about shape.

In this paper, landmark‐based methods are described and illustrated, based on a dataset of measurements from 295 Apodemus mandibles, and the applications of such methods in the systematics of insectivores (Eulipotyphla) and rodents (Rodentia) are summarized.
European rabbit population trends and associated factors: a review of the situation in the Iberian Peninsula
Authors: DELIBES‐MATEOS MIGUEL , FERRERAS PABLO , VILLAFUERTE RAFAEL
Published: February 2009

European rabbits are considered a keystone species in the Iberian Peninsula. Their populations have sharply declined over the past century, mainly due to habitat loss and the arrival of two viral diseases: myxomatosis in the 1950s and rabbit haemorrhagic disease (RHD) at the end of the 1980s. For the conservation of the Iberian Mediterranean ecosystem, it is important to determine whether rabbit populations are recovering two decades after the RHD outbreak, and to identify the factors associated with population recovery.

Here, we review the current knowledge on recent rabbit population trends in the Iberian Peninsula and the factors associated with these trends.

Although most rabbit populations are still declining in the Iberian Peninsula, a few seem to have recovered. In general, positive trends have been recorded in species‐friendly habitats characterized by non‐fragmented landscapes, interspersed patches of Mediterranean scrubland, good pastures and/or crops, soft soils that are suitable for warren construction and a Mediterranean climate with relatively high rainfall. Additionally, rabbits seem to be recovering better in areas where management practices (e.g. low hunting pressure, habitat management and predator control) are applied to increase their numbers.

From these findings, it is possible to identify five broad objectives for rabbit conservation in the Iberian Peninsula. First, it is clearly necessary to establish a long‐term programme for monitoring rabbit abundance and trends on a large scale. Second, the conservation and restoration of open Mediterranean scrubland should be a priority for stabilizing and maintaining existing healthy rabbit populations. Third, despite the lack of experimental evidence, management activities aimed at increasing the quantity and quality of both refuge and food should continue to be implemented. Fourth, legislation on the timing of the hunting season should be revisited following recommendations made by scientists. Finally, experimental approaches are required to investigate whether the control of generalist predators is a successful strategy to allow rabbit populations to recover.
More Vaccine Efficacy Studies on the Recombinant Bacille Calmette‐Guerin Co‐expressing Ag85B, Mpt64190–198 and Mtb8.4
Authors: Qie Y. Q. , Wang J. L. , Liu W. , Shen H. , Chen J. Z. , Zhu B. D. , Xu Y. , Zhang X. L. , Wang H. H.
Published: February 2009

The immunogenicity of the recombinant Bacille Calmette‐Guerin: rBCG‐Ag85B‐Mpt64190–198‐Mtb8.4 (rBCG‐AMM) was evaluated in our previous study. This paper compares the protective efficacy of rBCG‐AMM, rBCG‐A which overexpresses Ag85B and BCG in C57BL/6 mice. There was no significant difference in proliferation characteristics among rBCG‐AMM, rBCG‐A and BCG. The growth characteristics of rBCG‐AMM in host tissue were identical to control BCG, suggesting the improved protective efficacy was directly related to the expression of the Ag85B‐Mpt64190–198‐Mtb8.4 fusion protein. The protective experiment demonstrated that rBCG‐AMM could confer similar or even better protective efficacy against Mycobacterium tuberculosis infection compared with BCG or rBCG‐A as evaluated by bacterial organ loads, lung histopathology and net weight gain or loss. The results suggested that the recombinant BCG: rBCG‐Ag85B‐Mpt64190–198‐Mtb8.4 is a potential vaccine candidate for further study.
Differential Activation of Dendritic Cells by Toll‐like Receptor Agonists Isolated from the Gram‐positive Vaccine Vector Streptococcus gordonii
Authors: Mayer M. L. , Phillips C. M. , Townsend R. A. , Halperin S. A. , Lee S. F.
Published: February 2009

The oral commensal bacterium Streptococcus gordonii has been gathering interest as a candidate live mucosal vaccine delivery vector. S. gordonii has been shown to be capable of activating antigen presenting immune cells in a manner which leads to their activation and maturation, yet the mechanism used by S. gordonii to do so is poorly understood. The aim of this work was to investigate the immunostimulatory components of S. gordonii in inducing murine dendritic cell (DC) activation and maturation. Lipoteichoic acid (LTA), lipoprotein (LP), peptidoglycan (PGN), and DNA were isolated from S. gordonii, and used to stimulate murine DC. Cytokine production and DC surface marker upregulation in response to the bacterial components was quantified by enzyme‐linked immunosorbent assay and flow cytometry respectively. The results were contrasted against data obtained from DC derived from MyD88, TRIF [TIR(Toll/Interleukin‐1 Receptor)‐domain‐containing adapter‐inducing interferon‐beta] or toll‐like receptor‐2 (TLR‐2) knockout mice. The four S. gordonii bacterial components were found to differentially induce cytokine production and surface marker upregulation by murine DC. Activation of DC by both whole S. gordonii cells and the four bacterial components was abrogated in the absence of MyD88, but not in the absence of TRIF. LTA, LP and PGN, but not DNA and whole S. gordonii, required TLR‐2 to induce a DC response. The results collectively indicate that S. gordonii activates DC predominantly through a MyD88‐dependent and TRIF‐independent pathway. This activation can be attributed to multiple immunostimulatory components present within S. gordonii bacterial cells.
Levels of Urinary Complement Factor H in Patients with IgA Nephropathy are Closely Associated with Disease Activity
Authors: Zhang J.‐J. , Jiang L. , Liu G. , Wang S.‐X. , Zou W.‐Z. , Zhang H. , Zhao M.‐H.
Published: February 2009

Factor H plays a key inhibitory role in control of the activation of alternative pathway of complement system. The aim of the study was to investigate the predictive value of factor H as a biomarker of renal injury in IgA nephropathy (IgAN). Urine factor H concentration from 202 patients was measured and compared with that of 60 healthy volunteers. Forty‐eight patients fulfilled Haas‐I or II (group 1), 60 fulfilled Haas‐III (group 2) and 94 fulfilled Haas‐IV or V (group 3). Co‐deposition of factor H and C3b in kidneys were investigated using confocal microscope. The levels of urinary factor H, when expressed as a ratio of urinary creatinine, were significantly higher in groups 3 than group 1 and 2, also significantly higher in group 2 than group 1. In addition, the levels of urinary factor H were significantly higher in those with factor H deposition in the kidney than those without deposition. The levels of urinary factor H may be a useful biomarker to evaluate kidney injury in IgAN.
Protein Tyrosine Phosphatase ε is a Negative Regulator of FcεRI‐mediated Mast Cell Responses
Authors: Akimoto M. , Mishra K. , Lim K.‐T. , Tani N. , Hisanaga S.‐i. , Katagiri T. , Elson A. , Mizuno K. , Yakura H.
Published: February 2009

Modulation of mast‐cell activation may provide novel ways to control allergic diseases. Here, we show that protein tyrosine phosphatase ε (PTPε; Ptpre) plays key regulatory roles during mast‐cell activation mediated by the high‐affinity IgE receptor (FcεRI). Bone marrow‐derived mast cells (BMMC) from Ptpre−/− mice exhibited enhanced FcεRI‐induced Ca2+ mobilization and mitogen‐activated protein kinase (MAPK) (JNK and p38) activation, and showed corresponding enhancement of evoked degranulation and cytokine production, but not leukotriene production. Examination of proteins linking tyrosine kinase activation and Ca2+ mobilization revealed that the absence of PTPε leads to increased phosphorylation of the linker for activation of T cells and SH2 domain‐containing leucocyte phosphoproteins of 76 kDa, but not Grb2‐associated binder‐2 (Gab2). Because Gab2 is considered to be situated downstream of Fyn kinase, we reasoned that Fyn may not be a target of PTPε. In the event, Syk but not Lyn was hyperphosphorylated in PTPε‐deficient BMMC. Thus, PTPε most likely exerts its effects at the level of Syk, inhibiting downstream events including phosphorylation of SLP‐76 and linker of activated T cells and mobilization of Ca2+. Consistent with the in vitro data, antigen‐ and IgE‐mediated passive systemic anaphylactic reactions were augmented in Ptpre−/− mice. Given that the number of mast cells is unchanged in these mice, this observation most likely reflects alterations of mast cell‐autonomous signalling events. These data suggest that PTPε negatively regulates FcεRI‐mediated signalling pathways and thus constitutes a novel target for ameliorating allergic conditions.
Aspects of B‐Cell Non‐Hodgkin’s Lymphoma Development: A Transition from Immune‐Reactivity to Malignancy
Authors: Illes A. , Varoczy L. , Papp G. , Wilson P. C. , Alex P. , Jonsson R. , Kovacs T. , Konttinen Y. T. , Zeher M. , Nakken B. , Szodoray P.
Published: February 2009

The development of B‐cell lymphomas is an intricate interplay among various pathogenic factors, leading to a multi‐step process, encompassing various stages of B‐cell maturation. Besides genetic abnormalities, a variety of environmental and microbial factors, as well as disproportional immune‐regulatory processes lead to the malignant transformation. Yet, little is known about the exact chain of events, which lead from the physiological polyclonal B‐cell activation as a response to exogenous antigens through oligoclonality to a monoclonal, uncontrolled, malignant B‐cell proliferation. The aim of the present review was to summarize the potential harmful steps in the development of B‐cell lymphomas, according to conventional and novel theories, and to depict therapeutic regimens presently in use as well as to envision future drug developments, beneficial in the battle against this lymphoid malignancy.
United airways again: high prevalence of rhinosinusitis and nasal polyps in bronchiectasis
Authors: Guilemany J. M. , Angrill J. , Alobid I. , Centellas S. , Pujols L. , Bartra J. , Bernal‐Sprekelsen M. , Valero A. , Picado C. , Mullol J.
Published: February 2009

Background:  Although various relationships between the lower and upper airways have been found, the association of bronchiectasis with chronic rhinosinusitis and nasal polyps has not been thoroughly evaluated. This study was undertaken to examine the association of idiopathic and postinfective bronchiectasis with chronic rhinosinusitis and nasal polyposis.

Methods:  In a prospective study, 56 patients with idiopathic and 32 with postinfective bronchiectasis were evaluated for chronic rhinosinusitis and nasal polyposis by using EP3OS criteria and assessing: symptoms score, nasal endoscopy, sinonasal and chest CT scan, nasal and lung function and nasal and exhaled NO.

Results:  Most bronchiectasis patients (77%) satisfied the EP3OS criteria for chronic rhinosinusitis, with anterior (98.5%) and posterior (91%) rhinorrhea and nasal congestion (90%) being the major symptoms. Patients presented maxillary, ethmoidal and ostiomeatal complex occupancy with a total CT score of 8.4 ± 0.4 (0–24). Using endoscopy, nasal polyps with a moderate score of 1.6 ± 0.1 (0–3) were found in 25% of patients. Nasal NO was significantly lower in patients with nasal polyposis (347 ± 62 ppb) than in those without them (683 ± 76 ppb; P < 0.001), and inversely correlated (R = −0.36; P < 0.01) with the ostiomeatal complex occupancy. In the chest CT scan, patients with chronic rhinosinusitis showed a higher bronchiectasis severity score (7.2 ± 0.5; P < 0.001) than patients without (3.7 ± 0.7). The prevalence of chronic rhinosinusitis, nasal polyps and other outcomes were similar in idiopathic and postinfective bronchiectasis.

Conclusions:  The frequent association of chronic rhinosinusitis and nasal polyposis with idiopathic and postinfective BQ supports the united airways concept, and it suggests that the two type of bronchiectasis share common etiopathogenic mechanisms.
Aluminium per se and in the anti‐acid drug sucralfate promotes sensitization via the oral route
Authors: Brunner R. , Wallmann J. , Szalai K. , Karagiannis P. , Altmeppen H. , Riemer A. B. , Jensen‐Jarolim E. , Pali‐Schöll I.
Published: February 2009

Background:  Aluminium (ALUM) is used as experimental and clinical adjuvant for parenteral vaccine formulation. It is also contained in anti‐acid drugs like sucralfate (SUC). These anti‐acids have been shown to cause sensitization to food proteins via elevation of the gastric pH. The aim of this study was to assess the oral adjuvant properties of ALUM, alone or contained in SUC, in a BALB/c mouse model.

Methods:  Mice were fed SUC plus ovalbumin (OVA) and compared with groups where ALUM or proton pump inhibitors (PPI) were applied as adjuvants. The humoral and cellular immune responses were assessed on antigen‐specific antibody and cytokine levels. The in vivo relevance was investigated in skin tests.

Results:  The highest OVA‐specific immunoglobulin G1 (IgG1) and IgE antibody levels were found in mice fed with OVA/SUC, followed by OVA/ALUM‐treated animals, indicating a T helper 2 (Th2) shift in both groups. Antibody levels in other groups revealed lower (OVA/PPI‐group) or baseline levels (control groups). Positive skin tests confirmed an allergic response in anti‐acid or adjuvant‐treated animals.

Conclusions:  Our data show for the first time that ALUM acts as a Th2‐adjuvant via the oral route. This suggests that orally applied SUC leads to an enhanced risk for food allergy, not only by inhibiting peptic digestion but also by acting as a Th2‐adjuvant by its ALUM content.
Reactivity to sodium tetrachloropalladate (Na2[PdCl4]) compared to PdCl2 and NiCl2 in lymphocyte proliferation tests
Authors: Muris J. , Kleverlaan C. J. , Feilzer A. J. , Valentine‐Thon E.
Published: February 2009

Background:  For patch testing, replacement of the commonly used palladium dichloride (PdCl2) by sodium tetrachloropalladate (Na2[PdCl4]) was recently demonstrated to improve test accuracy and show a significant correlation with nickel (Ni), supporting the concept of cross‐reactivity between Pd and Ni. A promising alternative to metal allergy patch testing is the in vitro lymphocyte proliferation test (LTT).

Objectives:  The aim of this study was to test whether Na2[PdCl4] is also more sensitive for diagnosing Pd allergy with a standardized LTT.

Patients/methods:  After determining optimal nontoxic and nonmitogenic concentrations for Na2[PdCl4], blood samples from 105 patients with clinical suspicion of metal allergy were tested with an LTT called memory lymphocyte immuno stimulation assay for Na2[PdCl4], PdCl2 and NiCl2. Reaction profiles were analysed for concordant positive reactions.

Results:  Using the conventional cut‐off of stimulation index ≥ 3, 74.3% showed a positive reaction to NiCl2, 15.2% to PdCl2 and 28.6% to Na2[PdCl4]. All positive results to PdCl2 were covered by Na2[PdCl4]. From the 30 positive reactions to Na2[PdCl4], 26 (87%) were concordant for NiCl2 reactivity.

Conclusion:  In LTT, the use of Na2[PdCl4] results in more positive reactions in Pd allergy testing which are in concordance with positive reactions to PdCl2 and NiCl2.
Grading quality of evidence and strength of recommendations in clinical practice guidelines
Authors: Brożek J. L. , Akl E. A. , Alonso‐Coello P. , Lang D. , Jaeschke R. , Williams J. W. , Phillips B. , Lelgemann M. , Lethaby A. , Bousquet J. , Guyatt G. H. , Schünemann H. J. ,   for the GRADE Working Group
Published: February 2009

The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach provides guidance to grading the quality of underlying evidence and the strength of recommendations in health care. The GRADE system’s conceptual underpinnings allow for a detailed stepwise process that defines what role the quality of the available evidence plays in the development of health care recommendations. The merit of GRADE is not that it eliminates judgments or disagreements about evidence and recommendations, but rather that it makes them transparent. This first article in a three‐part series describes the GRADE framework in relation to grading the quality of evidence about interventions based on examples from the field of allergy and asthma. In the GRADE system, the quality of evidence reflects the extent to which a guideline panel’s confidence in an estimate of the effect is adequate to support a particular recommendation. The system classifies quality of evidence as high, moderate, low, or very low according to factors that include the study methodology, consistency and precision of the results, and directness of the evidence.
Exposure to pets and the association with sensitization and allergic disease in Belgian schoolchildren
Authors: Van Gysel D. , Govaere E. , Verhamme K. , Doli E. , De Baets F.
Published: February 2009

Prolonged domestic exposure, from birth on, to dog allergen may protect against sensitization.
Asthma symptoms in rural living Tanzanian children; prevalence and the relation to aerobic fitness and body fat
Authors: Berntsen S. , Lødrup Carlsen K. C. , Hageberg R. , Aandstad A. , Mowinckel P. , Anderssen S. A. , Carlsen K.‐H.
Published: February 2009

Objective:  To determine the prevalence of asthma symptoms in children from a rural district in North‐Tanzania, and their relationship to aerobic fitness and body fat.

Methods:  In Manyara region in Tanzania, children (aged 9–10 years) were randomly selected to participate in the present cross‐sectional study. Hundred and seventy two participants completed a video questionnaire showing the symptoms and signs of asthma. Lung function was measured by maximum forced expiratory flow‐volume curves. Aerobic fitness was estimated from a standardized indirect maximal cycle ergometer test and sum of three skinfolds reflected body fat.

Results:  Twenty four per cent reported asthma symptoms last year. Severe wheezing attacks last year were reported in 5% of the participants. Thirty seven per cent of the participants were underweight. Underweight children had significantly lower (P < 0.02) lung function (per cent of predicted). Lower body fat was associated with higher occurrence of asthma symptoms (odds ratio and 95% CI; 0.45 (0.22–0.95; P = 0.04). Aerobic fitness was not associated with asthma symptoms.

Conclusions:  More than every fifth 9–10 year old child from a rural district in North‐Tanzania reported asthma symptoms. Lower body fat was associated with higher occurrence of asthma symptoms, but aerobic fitness was not associated with asthma symptoms.
MELD and other predictors of survival after liver transplantation
Authors: Brandão Ajacio , Fuchs Sandra C. , Gleisner Ana L. , Marroni C. , Zanotelli Maria L. , Cantisani Guido ,   on behalf of the Liver Transplantation Group
Published: February 2009

Abstract:  Background:  This study examined how reliable is the pre‐transplant model for end‐stage liver disease (MELD) score in predicting post‐transplantation survival and analyzed variables associated with patient survival.

Methods:  A cohort study was conducted. Receiver operating characteristic curve c‐statistics were used to determine the ability of MELD score to predict mortality. The Kaplan–Meier (KM) method was used to analyze survival as a function of time regarding the MELD score and Child‐Turcotte‐Pugh (CTP) category. The Cox model was employed to assess the association between baseline risk factors and mortality.

Results:  Recipients and donors were mostly male, with a mean age of 51.6 and 38.5 yr, respectively (n = 436 transplants). The c‐statistic values for three‐month patient mortality were 0.60 and 0.61 for MELD score and CTP category, respectively. KM survival at three, six and 12 months were lower in those who had a MELD score ≥21 or were CTP category C. Multivariate analysis revealed that recipient age ≥65 yr, MELD ≥ 21, CTP C category, bilirubin ≥ 7 mg/dL, creatinine ≥ 1.5 mg/dL, platelet transfusion, hepatocellular carcinoma, and non‐white color donor skin were predictors of mortality.

Conclusions:  Severe pre‐transplant liver disease, age ≥ 65, non‐white skin donor, and hepatocellular carcinoma are associated with poor outcome.
Immunosuppression withdrawal improves long‐term metabolic parameters, cardiovascular risk factors and renal function in liver transplant patients
Authors: Pons Jose A. , Ramírez Pablo , Revilla‐Nuin Beatriz , Pascual Domingo , Baroja‐Mazo Alberto , Robles Ricardo , Sanchez‐Bueno Francisco , Martinez Laura , Parrilla Pascual
Published: February 2009

Abstract:  After liver transplantation, long‐term immunosuppression (IS) administration is commonly complicated by renal dysfunction and cardiovascular complications. Twenty liver transplant patients on cyclosporine (CyA)‐based IS were followed up prospectively after IS withdrawal. They consisted of 10 electively weaned patients and 10 either forcibly or incidentally weaned patients. Liver biochemical tests, blood pressure, serum creatinine, serum urea, serum uric acid, triglycerides, cholesterol and glucose were monitored after the start of weaning. Eight of the 20 patients (40%) were IS therapy free for a mean period of 61 ± 39 months (range: 10–132 months). Of the remaining 12 patients, mild or moderate acute rejection occurred in six patients (30%), and mixed inflammatory portal tract infiltrate was seen in another six patients (30%). At the end of the study, mean (SD) serum creatinine had fallen by 0.28 (0.10) mg/dL (p < 0.001) in operationally tolerant (T) patients whereas the serum creatinine level increased in IS‐dependent patients [+0.35 (0.35) mg/dL] (p = 0.005). In T patients, serum cholesterol, serum uric acid, fasting glucose and diastolic arterial pressure values significantly decreased. IS withdrawal can be achieved in selected liver transplant patients, and can improve not only kidney function, but also other CyA‐associated side effects, such as hypercholesterolemia, hyperuricemia, hypertension and diabetes.
Should the law on anonymity of organ donation be changed? The perception of liver transplant recipients
Authors: Dobbels Fabienne , Van Gelder Frank , Remans Kathleen , Verkinderen Ann , Peeters Jos , Pirenne Jacques , Nevens Frederik
Published: February 2009

Abstract: Background:  Belgian politicians submitted a proposal to rescind the law on anonymity of organ donation and transplantation and facilitate contact between donor families and recipients. It remains uncertain if recipients support this proposal.

Methodology:  One liver transplant patient organization (n = 176/249) answered and provided comments on two questions: (i) how satisfied are you with the current principle of anonymity of the identity of the donor and (ii) the law about anonymity should be changed to allow the donor family and the patient to meet.

Results:  Seventy percent were satisfied/very satisfied with the present law, because of anxiety for emotional involvement or feeling obliged to do something in return, feelings of guilt, and out of mutual respect. Nineteen percent was dissatisfied/very dissatisfied and want to obtain some information about the donor, and directly express their gratitude. Forty‐two percent disagreed with a change, because of anxiety for manipulation, feelings of guilt, respect for the privacy, and worry about the donor having a different background. Thirty‐six percent wanted to change the law out of curiosity, to express their gratitude, or to facilitate their coping process.

Discussion:  Prudence to change the law is warranted, as only a minority of patients are in favor of rescinding the anonymity.
Distribution and evolutionary trends of photoprotective isoprenoids (xanthophylls and tocopherols) within the plant kingdom
Authors: Esteban Raquel , Olano José M , Castresana José , Fernández‐Marín Beatriz , Hernández Antonio , Becerril José M , García‐Plazaola José I
Published: February 2009

The earliest land photosynthesis would have increased the risk of photo‐oxidations and the demand of anti‐oxidative protection. In this work, we aimed to determine the evolutionary trends in photoprotection across a wide representation of the plant kingdom and to verify whether the non‐ubiquitous lutein‐epoxide (Lx) cycle is a polyphyletic or an ancient character. Carotenoids and α‐tocopherol (α‐toc) were analysed by HPLC in 266 species. Phylogenetic analyses of the presence of photoprotective compounds and zeaxanthin‐epoxidase (ZE) sequences were performed. Violaxanthin‐cycle pigments (VAZ) and α‐toc were taxonomically ubiquitous. Ancient groups showed higher contents of VAZ than vascular plants, while α‐toc showed the opposite pattern. Lutein‐epoxide was present in 45% of the species. It showed a remarkable variation across groups but with a clear increasing trend from algae to basal angiosperms. Lutein‐epoxide was also related to woody trait and leaf longevity. No correlation between the presence of Lx and recurrent mutations in ZE sequences, including the duplications, was found. Thus, there is an evolutionary trend to increase the content of α‐toc and to decrease the total amount of VAZ pigments. Absence of Lx in algae discards an ancestral origin. Present results are also inconsistent with a polyphyletic origin of Lx in angiosperms.
Late onset Pneumocystis pneumonia in renal transplantation after long‐term immunosuppression with belatacept
Authors: Haidinger M. , Hecking M. , Memarsadeghi M. , Weichhart T. , Werzowa J. , Hörl W.H. , Säemann M.D.
Published: February 2009

Abstract: Interference with T‐cell function increases the risk of infections, especially during the early post‐transplant period. Belatacept, a costimulation blocker, is currently being tested in phase III clinical trials. Here we report a renal transplant recipient who received belatacept and developed severe Pneumocystis jirovecii pneumonia (PCP) with fatal superinfections 4 years post transplant. Cytomegalovirus infection preceded PCP, which typically occurs in overimmunosuppressed patients, but has not yet been reported under T‐cell costimulation blockade in transplant patients. This case illustrates the possibility of excessive immunosuppression even with a lymphocyte‐specific regimen.
Isolation and characterization of the plant glsA promoter from Alstroemeria
Authors: Igawa T. , Hoshino Y. , Yanagawa Y.
Published: February 2009

The differentiation of a vegetative cell and a generative cell is a critical event during pollen development. The Lilium GlsA is known to localize in pollen and is considered to be involved in development of the generative cell. Here, we cloned a glsA ortholog from Alstroemeria, a commercially important cut flower. The expression of AaglsA (Alstroemeria aurea glsA) transcripts increased gradually after pollen mitosis I (PMI) and reached a significant level when the generative cell started to elongate. Analysis of the promoter of AaglsA suggests that AaglsA expression is controlled by several cis‐regulatory elements during pollen development. This is the first investigation of reproductive factors regulating male gametogenesis in Alstroemeria.
Circuit projection from suprachiasmatic nucleus to ventral tegmental area: a novel circadian output pathway
Authors: Luo Alice H. , Aston‐Jones Gary
Published: February 2009

The suprachiasmatic nucleus (SCN) is a circadian pacemaker that synchronizes a number of vital processes. Although a great deal of research has focused on input pathways to SCN and on the central clock itself, relatively little is known about SCN output signaling pathways. The ventral tegmental area (VTA) has been extensively studied for its influence in motivated learning and, recently, for a potential role in arousal and sleep–wake regulation. Here we present data that SCN indirectly projects to VTA via the medial preoptic nucleus (MPON). Microinjection of the retrograde, transynaptic tracer pseudorabies virus (PRV) in rat VTA consistently labeled SCN neurons at time points indicative of an indirect circuit projection. To specify intermediate relay nuclei between SCN and VTA, putative relays were lesioned 1 week prior to PRV injections in VTA. Unilateral lesions of MPON reduced PRV labeling in SCN by 81.6% in the ipsilateral hemisphere and 75.8% in the contralateral hemisphere. Bilateral lesions of the caudal–dorsal lateral septum, another putative relay nucleus and dorsal injection control, did not significantly reduce PRV labeling in the SCN. Single‐unit extracellular recordings under halothane anesthesia revealed a novel population of VTA neurons that selectively fired during the active circadian phase. These results show that SCN provides an indirect circuit pathway to VTA via MPON, and that VTA neurons exhibit a circadian rhythm in their impulse activity. This pathway may function in the circadian regulation of numerous behavioral processes including arousal and motivation.
Spinal NK‐1 receptor‐expressing neurons and descending pathways support fentanyl‐induced pain hypersensitivity in a rat model of postoperative pain
Authors: Rivat Cyril , Vera‐Portocarrero Louis P. , Ibrahim Mohab M. , Mata Heriberto P. , Stagg Nicola J. , De Felice Milena , Porreca Frank , Malan T. P.
Published: February 2009

The clinically important opioid fentanyl, administered acutely, enhances mechanical hypersensitivity in a model of surgical pain induced by plantar incision. Activity of neurokinin‐1 (NK‐1) receptor‐expressing ascending spinal neurons, descending pathways originating in the rostral ventromedial medulla (RVM), and spinal dynorphin are necessary for the development and maintenance of hyperalgesia during sustained morphine exposure, suggesting that these mechanisms may also be important in opioid enhancement of surgical pain. Therefore, we examined the roles of these mechanisms in sensory hypersensitivity produced by acute fentanyl administration in rats not undergoing surgical incision and in rats undergoing plantar incision. In non‐operated rats, fentanyl induced analgesia followed by immediate and long‐lasting sensory hypersensitivity, as previously described. Fentanyl also enhanced pain sensitivity induced by plantar incision. Ablation of NK‐1‐expressing spinal neurons by pre‐treatment with substance P–Saporin reduced sensory hypersensitivity in fentanyl‐treated rats and, to a lesser extent, in fentanyl‐treated rats with a surgical incision. Microinjection of lidocaine into the RVM completely reversed fentanyl‐induced sensory hypersensitivity and fentanyl enhancement of incision‐induced sensory hypersensitivity. RVM lidocaine injection resulted in a slight reduction of incision‐induced sensory hypersensitivity in the absence of fentanyl pre‐treatment. Spinal dynorphin content increased by 30 ± 7% and 66 ± 17% in fentanyl‐ and fentanyl/incision‐treated rats. Spinal administration of antiserum to dynorphin attenuated sensory hypersensitivity in fentanyl‐treated rats. These data support a partial role of NK‐1 receptor‐containing ascending pathways and a crucial role of descending facilitatory pathways in fentanyl‐induced hyperalgesia and in the enhanced hyperalgesia produced by fentanyl treatment following surgical incision.
Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex
Authors: Lang Simone , Kroll Alexander , Lipinski Slawomira J. , Wessa Michèle , Ridder Stephanie , Christmann Christoph , Schad Lothar R. , Flor Herta
Published: February 2009

Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty‐one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS− was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS− in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context‐specificity of extinction learning.
Geometry and landmark representation by pigeons: evidence for species‐differences in the hemispheric organization of spatial information processing?
Authors: Wilzeck Christiane , Prior Helmut , Kelly Debbie M.
Published: February 2009

In this study, we investigated how pigeons (Columba livia) represent environmental geometry and landmark information. Birds learned to locate the centre of a square arena by means of geometric cues alone, or by means of both geometric and landmark cues. By manipulating the type of information available at training and testing, we assessed which cues the birds had encoded, and through the use of monocular occlusion we examined how the information was represented by the two brain hemispheres. Our results show that both brain hemispheres encoded geometric and landmark information. During all viewing conditions, the geometric representation was based mainly on an absolute metric for distance. The relative use of geometry and landmarks was experience dependent. With both brain hemispheres available birds relied, to a greater degree, on geometric information and used it in a more integrated way than with either hemisphere alone. Overall, our findings show a different pattern for the hemispheric encoding of geometric and landmark information by the pigeon than that previously reported for the domestic chick. Our results suggest that the organization of spatial information processing in the left and right brain hemispheres of birds may be more diverse than what is currently known.
Steroid hormones and maternal experience interact to induce glial plasticity in the cingulate cortex
Authors: Salmaso N. , Nadeau J. , Woodside B.
Published: February 2009

Neocortical plasticity is not usually associated with changes in reproductive function. However, we have shown a six to 10‐fold increase in the number of astrocytes labeled with glial fibrillary acidic protein (GFAP) and astrocytic basic fibroblast growth factor or FGF‐2 (bFGF) in the cingulate cortex area 2 (Cg2) in postpartum rats, indicative of changes in connectivity in this area. In the present studies, we investigated the necessary and sufficient stimuli for these changes to occur. We show that 3 h of maternal experience combined with a hormonal treatment that mimics late pregnancy induces the astrocytic changes in Cg2 in virgin rats. The extent of these changes was similar to those of postpartum females. Sensitized virgin females did not show any astrocytic changes after 3 h of maternal behavior, suggesting that a similar amount of maternal experience alone is not sufficient to increase astrocytic bFGF‐ and GFAP‐immunoreactivity in Cg2. Consistent with these data, eliminating early maternal experience by removing pups immediately postpartum abolishes the increased bFGF and GFAP protein expression in the cingulate cortex. These results suggest that maternal experience and hormonal state interact to produce astrocytic remodeling in the Cg2. The current results are consistent with a role for the cingulate cortex in maternal responsivity as suggested by early lesion studies in rats and more recent imaging studies in humans.
Impairment of aversive memory reconsolidation by localized intracranial electrical stimulation
Authors: Stehberg Jimmy , Levy Dino , Zangen Abraham
Published: February 2009

Reconsolidation of long‐term memory is blocked in animal models by macromolecular synthesis inhibitors, resulting in item‐specific post‐retrieval amnesia. The induction of such amnesia could ameliorate traumatic memories and phobias. However, this pharmacological approach is of limited value in humans because of toxicity. Here we report that reconsolidation of conditioned taste aversion in the rat is impaired by localized intracranial electrical stimulation. Lasting impairment was obtained only when stimulation was applied during memory reactivation and only to the dysgranular insular cortex bilaterally, which subserves the memory, but not to adjacent brain sites. The ability to learn a new association was not affected. The same method blocked new memory consolidation, but produced anterograde amnesia, reminiscent of the known effect of non‐localized electroconvulsive therapy. Our results suggest that localized electrical microstimulation, such as produced by deep‐brain stimulation or deep transcranial magnetic stimulation, could be used to impair long‐term memory if applied during memory reactivation, and could lead to the development of a novel treatment for intractable post‐traumatic stress disorder.
Sacral nerve modulation and other treatments in patients with faecal incontinence after unsuccessful pelvic floor rehabilitation: a prospective study
Authors: Koch S. M. , Melenhorst J. , Uludağ Ö. , Deutekom M. , Stoker J. , Van Gemert W. G. , Baeten C. G.
Published: February 2009

Objectives  Sacral nerve modulation (SNM) is a minimally invasive technique for the treatment of faecal incontinence. This study investigates the results of SNM after negative outcome of a standardized pelvic floor rehabilitation (PFR) programme for the treatment of faecal incontinence.

Method  A prospective cohort study was performed between December 2001 and August 2007. Consecutive patients who visited the outpatient department for faecal incontinence were included in a multicentre study and treated with standardized PFR. Those with an unsuccessful result who were eligible for SNM were included in the present study. Failures at test stimulation or SNM received another treatment. Clinical outcome, Vaizey scores and Hirschsprung’s disease/anorectal malformation quality‐of‐life (EQ‐5D and HAQL) were assessed during follow‐up in patients with SNM and in patients with other treatments (OT). Adverse events (AE) were documented.

Results  Thirty‐five patients (mean age 59.7 years; 31 females) were included. Twenty‐one had a successful test stimulation and 19 patients proceeded to a SNM implant. Incontinence episodes per week decreased significantly from 11.1 ± 11.7 to 1.9 ± 2.6 during test stimulation (P < 0.0001) and SNM over 24.1 months follow‐up. The overall success rate was 49% (17/35). The patients with unsuccessful test stimulation or SNM received OT. The Vaizey score improved in both SNM (18.2 ± 3.5 vs 13.7 ± 4.8; P = 0.004) and other treatment (18.2 ± 3.5 vs 13.9 ± 6.9; P = 0.019). The HAQL scale improved significantly during SNM in all subscales (P < 0.005), but not in the other treatment group. Eight AE occurred during test stimulation (23%) and six AE after permanent implantation (26%).

Conclusion  Sacral nerve modulation improves disease specific quality of life significantly compared with other treatment.