bluuebunny/crossref_metadata_2025 huggingface dataset:
Mineralocorticoid receptor activation in myocardial infarction and failure: recent advances
Authors: Galuppo Paolo , Bauersachs Johann
Published: March 2012

Eur J Clin Invest 2012; 42 (10): 1112–1120

The classical view of aldosterone actions via the mineralocorticoid receptor (MR) limited to control of fluid balance and blood pressure homoeostasis has been progressively overcome by clinical and experimental evidence emphasizing the pleiotropic role of MR activation in the pathogenesis of cardiovascular disease. Clinical studies have shown the benefit of MR blockade in patients with left ventricular dysfunction and heart failure after myocardial infarction (MI), hypertension or diabetic nephropathy. Deleterious effects of MR activation include cardiac structural and electrical remodelling, cardiovascular fibrosis, inflammation and oxidative stress. Complexity of pathophysiological role of MR derives from the presence of circulating glucocorticoids at higher concentrations than aldosterone and the equal affinity of the MR for aldosterone, cortisol and corticosterone. Recent experimental studies using different animal models and genetic tools have deeply explored the cell‐specific functional role of MR in cardiovascular pathology. This review addresses emerging preclinical studies as well as ongoing clinical trials regarding MR activation in MI and failure.
Microvascular endoglin (CD105) expression correlates with tissue markers for atherosclerotic plaque vulnerability in an ageing population with multivessel coronary artery disease
Authors: Li Xiaofei , van der Meer Jelger J , van der Loos Chris M , Ploegmakers Hanneke J P , de Boer Onno J , de Winter Rob J , van der Wal Allard C
Published: March 2012

Li X, van der Meer J J, van der Loos C M, Ploegmakers H J P, de Boer O J, de Winter R J & van der Wal A C  (2012) Histopathology 61, 88–97

Microvascular endoglin (CD105) expression correlates with tissue markers for atherosclerotic plaque vulnerability in an ageing population with multivessel coronary artery disease

Aims:  Vulnerable atherosclerotic plaques are lesions with a high propensity to develop plaque disruption and superimposed thrombosis. No systematic studies have been carried out on tissue markers for plaque vulnerability throughout the entire coronary artery system at the end stages of coronary atherosclerosis.

Methods and results:  Nine autopsied patients (mean age 77 years) with angiographically severe trivascular coronary atherosclerosis were selected for this study. All visible lesions in postmortem coronary angiograms (n = 125) were histologically and immunohistochemically screened for the presence of intraplaque haemorrhages (activated) microvessels and inflammatory infiltrates. Intraplaque haemorrhages were observed in 76/125 plaques (61%). Chronic inflammation was found superficially in 59/125 plaques (47%) and deeply inside the plaque tissue in 103/125 plaques (83%). Microvessels were found in 100/125 lesions (80%), of which 58% showed endothelial expression of the vascular activation marker CD105. Moreover, microvascular CD105 positivity correlated positively with plaque haemorrhage and deeply seated plaque inflammation.

Conclusions:  Plaque inflammation and haemorrhages can be found at a high frequency throughout the coronary artery system of elderly patients with multivessel coronary atherosclerosis. Microvascular expression of endoglin (CD105), which correlates positively with both of these features of plaque vulnerability, can serve as a marker of the risk of developing coronary thrombotic complications.
High level of Ets‐related gene expression has high specificity for prostate cancer: a tissue microarray study of 11 483 cancers
Authors: Minner Sarah , Luebke Andreas M , Kluth Martina , Bokemeyer Carsten , Jänicke Fritz , Izbicki Jakob , Schlomm Thorsten , Sauter Guido , Wilczak Waldemar
Published: March 2012

Minner S, Luebke A M, Kluth M, Bokemeyer C, Jänicke F, Izbicki J, Schlomm T, Sauter G & Wilczak W  (2012) Histopathology 61, 445–453

High level of Ets‐related gene expression has high specificity for prostate cancer: a tissue microarray study of 11 483 cancers

Aims:  TMPRSS2–ERG fusion resulting in strong Ets‐related gene (ERG) overexpression occurs in about 50% of prostate cancers. This study was undertaken to determine the prevalence of ERG overexpression in other tumour types as well as in normal tissues.

Methods and results:  A total of 11 483 tumours and 72 different normal tissue types were analysed in a tissue microarray format. Strong nuclear ERG overexpression was found in 36.7% of prostate carcinomas as well as in various vascular tumours, including Kaposi sarcomas (91.7%), angiosarcomas (100%) and haemangiomas (90.9%). Moderate to strong nuclear ERG immunostaining was also observed in thymoma (6.1%). Weak to moderate ERG staining was found in a small number of squamous cell carcinomas of the skin, squamous carcinomas of the lung, malignant mesotheliomas, carcinosarcomas of the uterus, gastrointestinal stromal tumours, hepatocellular carcinomas, teratomas of the testis, anaplastic carcinomas of the thyroid, giant cell tumours of the tendon sheath and benign fibrous histiocytomas of the skin. ERG overexpression was not seen in 8886 samples from 132 other tumour types and subtypes. Within normal tissues, immunohistochemically detectable ERG overexpression was restricted to endothelial cells and subsets of lymphocytes.

Conclusions:  The high specificity of ERG expression in both normal and neoplastic tissues suggests a very narrow biological role for ERG in highly selected tissues.
Assessment of thymidylate synthase expression in biopsy specimens and corresponding resection specimens of non‐small‐cell lung cancer
Authors: Herpel Esther , Schnabel Philipp A , Steins Martin , Dienemann Hendrik , Herth Felix J F , Thomas Michael , Schirmacher Peter , Warth Arne
Published: March 2012

Herpel E, Schnabel P A, Steins M, Dienemann H, Herth F J F, Thomas M, Schirmacher P & Warth A  (2012) Histopathology 61, 465–472

Assessment of thymidylate synthase expression in biopsy specimens and corresponding resection specimens of non‐small‐cell lung cancer

Aims:  Pemetrexed (Pem) is a potent inhibitor of thymidylate synthase (TS), and has shown efficacy in the treatment of non‐small‐cell lung cancer (NSCLC). TS expression in NSCLC biopsy specimens may correlate with the tumour responses to TS‐inhibiting agents. As TS is not homogeneously expressed, our aim was to test whether TS expression in biopsy specimens may be representative for the whole tumour and can be used for therapeutic assessment.

Methods and results:  We immunohistochemically analysed TS expression in biopsy and corresponding resection specimens of 100 consecutive NSCLCs. The samples were subgrouped according to TS expression levels, and the degree of agreement between the biopsy and the corresponding resection specimen was calculated. TS expression‐based grouping according to one cut‐off criterion (high or low expression) led to concordant results between biopsy and resection specimens. When more than one cut‐off criterion was used, the results were significantly different.

Conclusions:  Thymidylate synthase expression levels in NSCLC biopsy specimens may correspond to TS expression of the whole tumour when robust scoring systems are applied. Further studies are needed to determine whether high or low TS expression in NSCLC biopsy specimens is of predictive value, and whether it may allow the selection of patients who will benefit from Pem treatment.
Stage II colonic adenocarcinoma: a detailed study of pT4N0 with emphasis on peritoneal involvement and the role of tumour budding
Authors: Canney Aoife L , Kevans David , Wang Lai Mun , Hyland John M P , Mulcahy Hugh E , O’Donoghue Diarmuid P , O’Sullivan Jacintha , Geraghty Robert , Sheahan Kieran
Published: March 2012

Canney A L, Kevans D, Wang L M, Hyland J M P, Mulcahy H E, O’Donoghue D P, O’Sullivan J, Geraghty R & Sheahan K  (2012) Histopathology 61, 488–496

Stage II colonic adenocarcinoma: a detailed study of pT4N0 with emphasis on peritoneal involvement and the role of tumour budding

Aims:  Evaluation of peritoneal involvement in colonic cancer (CC) can be difficult. We studied pT4N0 cancers and their association with pathological prognostic markers, including tumour budding.

Method and results:  Tumours were classified as (i) at the peritoneal surface or free in the peritoneal cavity (pT4a subgroup n = 44); (ii) directly invading adjacent organ (pT4b subgroup n = 8); or (iii) showing inflammatory involvement of the peritoneum (pT4I subgroup n = 25). A published pT3N0 cohort was used to compare Stage II subgroups. Standard pathological markers including tumour budding were assessed. Elastin staining was performed in the pT4I subgroup. Seventy‐seven Stage II CCs met inclusion criteria. There was no significant difference in survival across subgroups. pT4b tumours were larger than pT4a tumours (P < 0.001). Over‐represented features in pT4a versus pT4b tumours were tumour budding (P = 0.02) and infiltrative margin (P = 0.02). Tumour budding did not predict survival. Using multivariate analysis, neural invasion was the only parameter predictive of survival (hazard ratio = 2.8; 95% CI 1.2–6.4; P = 0.02).

Conclusion:  Stage II pT4I CCs have a similar outcome to T4a/b tumours. Elastin staining is useful in defining this group. Tumour budding may facilitate peritoneal invasion in pT4a tumours, but does not predict outcome in pT4N0 disease. Only neural invasion independently predicted poor outcome.
Tumorous proliferations of plasmacytoid dendritic cells and Langerhans cells associated with acute myeloid leukaemia
Authors: Song Hsiang‐Lin , Huang Wen‐Ya , Chen Ya‐Ping , Chang Kung‐Chao
Published: March 2012

Song H‐L, Huang W‐Y, Chen Y‐P & Chang K‐C  (2012) Histopathology 61, 974–983

Tumorous proliferations of plasmacytoid dendritic cells and Langerhans cells associated with acute myeloid leukaemia

Aims:  Proliferation of plasmacytoid dendritic cells (PDCs) occurs in both reactive lymphoid hyperplasia and myeloproliferative disorders, especially chronic myelomonocytic leukaemia. PDCs in the former appear reactive, but in the latter are reported to be clonally related to the underlying myeloid neoplasm. Langerhans cells (LCs), another type of dendritic cell, also proliferate in both reactive dermatoses and, rarely, myeloproliferative disorders, such as acute leukaemia.

Methods and results:  We report a rare case of tumorous proliferation of PDCs and LCs in the systemic lymph nodes in a 55‐year‐old man with acute myeloid leukaemia. A microsatellite instability assay showed identical patterns of short tandem repeats in both microdissected PDC and LC components, along with blood blasts.

Conclusions:  We hypothesize that the combined proliferations of PDCs and LCs derive from the same haematopoietic stem cells, but that they differentiate divergently under the effect of different microenvironments.
Investigation of the expression and functional significance of the novel mouse sperm protein, a disintegrin and metalloprotease with thrombospondin type 1 motifs number 10 (ADAMTS10)
Authors: Dun M. D. , Anderson A. L. , Bromfield E. G. , Asquith K. L. , Emmett B. , McLaughlin E. A. , Aitken R. J. , Nixon B.
Published: March 2012

Fertilization represents the culmination of a series of complex interactions between male and female gametes. Despite advances in our understanding, the precise molecular mechanisms underlying these fundamental interactions remain largely uncharacterized. There is however growing recognition that this process requires the concerted action of multiple sperm receptors that possess affinity for complementary zona pellucida ligands and those that reside on the surface of the oolemma. Among the candidate sperm proteins that have been implicated in fertilization, those belonging to the ADAM (a disintegrin and metalloprotease) family of proteases have received considerable attention. The focus of the studies described herein has been the characterization of a closely related member of this protease family, ADAMTS10 (a disintegrin and metalloprotease with thrombospondin type 1 motifs number 10). We have demonstrated that ADAMTS10 is expressed during the later stages of mouse spermatogenesis and incorporated into the acrosomal domain of developing spermatids. During sperm maturation, the protein appears to be processed before being expressed on the surface of the peri‐acrosomal region of the head. Our collective data suggest that, from this position, ADAMTS10 participates in sperm adhesion to the zona pellucida. Indeed, pre‐incubation of capacitated spermatozoa with either galardin, a broad spectrum inhibitor of metalloprotease activity, or anti‐ADAMTS10 antisera elicited a significant reduction in their ability to engage in zona adhesion. Overall, these studies support the notion that sperm–oocyte interactions involve considerable functional redundancy and identify ADAMTS10 as a novel candidate in the mediation of these fundamentally important events.
Simultaneous renal hypertension and type 2 diabetes exacerbate vascular endothelial dysfunction in rats
Authors: Khalili Azadeh , Nekooeian Ali Akbar , Khosravi Mohammad Bagher , Fakher Shima
Published: March 2012

Despite the high rate of occurrence of both diabetes and hypertension in humans, the cardiovascular effects of the two conditions have not been investigated when they occur simultaneously. Thus this study examined the vascular effects of simultaneous type 2 diabetes and renal hypertension on endothelial function. Serum malondialdehyde and systolic blood pressure (SBP) were measured, glucose tolerance test (GTT) was performed, and concentration‐response to phenylephrine (PE) in the absence and presence of nitro‐l‐arginine methyl ester (l‐NAME), acetylcholine and sodium nitroprusside were conducted on aortic rings from diabetic control, type 2 diabetes, sham‐operated, renal hypertensive, and simultaneous type 2 diabetes plus hypertension rats respectively. Hypertension, diabetes, and simultaneous diabetes and hypertension were associated with either increased or decreased maximal responses (Emax) of PE dependent on in the presence or absence of l‐NAME. There was also increased serum malondialdehyde and decreased Emax of acetylcholine. Thus simultaneous hypertension and diabetes caused a greater decrease in Emax of acetylcholine compared to that seen with either diabetes or hypertension alone higher than that seen in hypertension. The blood glucose during GTT was lower than that seen in diabetes groups. Thus simultaneous type 2 diabetes and the SBP was renal hypertension is associated with improved glucose tolerance, but with further deterioration of endothelial dysfunction compared with either condition alone.
Qualitative survey of fungi isolated from wine‐aging environment
Authors: Ciccarone Claudio , Petruzzi Leonardo , Bevilacqua Antonio , Sinigaglia Milena
Published: March 2012

The main topic of this paper is the study of the qualitative composition of fungal population in some cellar environments: superficial and inner layer of oak barrels, wall surfaces and aging wine. In addition, the influence of age of barrels and winery climatic conditions on fungal populations was evaluated. Two selected types of cellars were studied (a ground level and climate‐controlled cellar‐industrial winery and an unconditioned underground cellar‐family owned winery); 142 different strains were isolated and then identified through a morphology‐based method. Wood inner layer was characterised by the presence of few oak‐specialised endophytes (Trichoderma viride,Acremonium strictumandCladosporium cladosporioides), whereas some strains ofAspergillusspp. andPenicilliumspp. (principallyAspergillus nidulans,Aspergillus oryzae,Penicillium glabrumandPenicillium aurantiogriseum) connected with humidity and pollution were isolated.Aspergillusspp. andPenicilliumspp. were isolated also in wall and barrel surfaces and in aging wine.
Reusing salad from salad bars – simulating the effects on product loss, microbial safety and product quality
Authors: Tromp Seth‐Oscar , Rijgersberg Hajo , Franz Eelco
Published: March 2012

The goal of this study is to model the effects of reusing salad from salad bars to reduce product loss, while keeping microbial safety and product quality at acceptable levels. We, therefore, expand our previously developed simulation model by incorporating reuse strategies and a quality decay model. The expanded model is used to simulate different salad reuse scenarios and to quantify the consequences to product loss, microbial safety and product quality. With this study, we show an application of a generic approach for the integrated modelling of product loss, microbial safety and product quality. The most cautious scenario consists of reusing salad for only 1 day after the first use and only if the salad originates from a package with a valid best‐before date at the time of reuse (‘minimum reuse of salad with the best‐before date criterion’). This scenario decreases product loss at the salad bar considerably from 37% to 29% (−21%). This considerable benefit occurs almost without causing product loss at the cold storage (increase from 0% to 1%), with only a minimal increase in the number of foetal mortality cases because of Listeria monocytogenes (increase from 11.9 to 12.2 cases per year (+3%)) and hardly any decline in product quality.
Inactivation of Lactobacillus fructivorans in physiological saline and unpasteurised sake using CO2 microbubbles at ambient temperature and low pressure
Authors: Kobayashi Fumiyuki , Sugawara Daisuke , Takatomi Tetsuya , Ikeura Hiromi , Odake Sachiko , Tanimoto Shota , Hayata Yasuyoshi
Published: March 2012

The ability of carbon dioxide microbubbles (MB‐CO2) to inactivate Lactobacillus fructivorans suspended in physiological saline and unpasteurised sake at ambient temperature and a pressure lower than 2.0 MPa was investigated. The number of L. fructivorans cells in physiological saline solution containing 15% ethanol showed a 6‐log reduction following MB‐CO2 treatment at 40 °C and 2.0 MPa for 50 min. The effectiveness of the treatment increased concomitantly with temperature, pressure and ethanol concentration of the sample solution but was unaffected by the glucose concentration in the sample solution. Furthermore, the number of L. fructivorans cells showed a 5‐log reduction in sake after MB‐CO2 treatment at 40°C and 2.0 MPa for 60 min. Sensory evaluation revealed no significant difference between MB‐CO2‐treated sake and unpasteurised sake. These results indicated that MB‐CO2 treatment was highly effective for the inactivation of L. fructivorans and might become a practical method for pasteurising sake at ambient temperature.
Effects of process variables and addition of polydextrose and whey protein isolate on the properties of barley extrudates
Authors: Kirjoranta Satu , Solala Kari , Suuronen Jussi‐Petteri , Penttilä Paavo , Peura Marko , Serimaa Ritva , Tenkanen Maija , Jouppila Kirsi
Published: March 2012

Extrusion cooking is commonly used in the production of snacks. In the present study, extrudates were prepared using barley flour alone and with the addition of either polydextrose (PD) or whey protein isolate (WPI) and both PD and WPI. Independent process variables were water content of the mass (17%, 20% and 23%), screw speed (200, 350 and 500 rpm) and temperature of section 6 and die (110, 130 and 150 °C). Expansion, hardness, water content, porosity and chemical composition of the extrudates were analysed. Highly porous and expanded snack products with high dietary fibre and protein contents were obtained from barley flour and WPI when water content of mass was 17%, screw speed 500 rpm and temperature of section 6 and die 130 °C. Barley flour alone or with PD resulted in hard and non‐expanded extrudates. Expansion of extrudates was statistically significantly increased with decreasing water content of the mass and increasing screw speed in all trials.
Creating continuity out of the disruption of a diagnosis of HIV during pregnancy
Authors: Kelly Carmel , Alderdice Fiona , Lohan Maria , Spence Dale
Published: March 2012

Aim.  To understand the uniqueness of the experience of testing HIV positive from the perspective of pregnant women.

Background.  As more people learn of their HIV diagnosis through routine screening processes, it is timely to reflect on the impact of receiving an unexpected positive result.

Design.  A prospective qualitative study.

Methods.  This paper draws on the case studies of four women who were participating in a larger prospective qualitative study of reproductive decision‐making, pregnancy and childbirth following HIV diagnosis. Multiple interviews were conducted following diagnosis during pregnancy, and, after the birth of their babies. Thematic data analysis was undertaken.

Results.  Drawing on Becker’s theory of disruption, we document the ‘sudden disjuncture’ of their antenatal diagnosis and the embodied emotional struggle the women engaged in to create continuity in their lives. A diagnosis of HIV disrupted the women’s biographies in terms of their health, relationships and social identity. As pregnant women, the threat of HIV was experienced most significantly in relation to their unborn child. However, their narratives also revealed how a diagnosis of HIV in the context of pregnancy, whilst traumatic, provided a focus for regaining continuity in their lives, as the baby became a metaphor for hope and orientation toward the future.

Conclusions.  As HIV testing becomes more ‘routine’, the findings of this study serve to remind health professionals that a positive diagnosis continues to constitute a major trauma to individuals and families.

Relevance to clinical practice.  We propose that appropriately educated nursing and midwifery staff could facilitate the ‘meaning making’ process that is required for newly diagnosed HIV positive persons to find a subjective sense of well‐being in their lives.
The ceremonial order of public health nursing consultations: an ethnographic study
Authors: Clancy Anne
Published: March 2012

Aims.  To explore public health nursing consultations by providing reflections on the overt interaction between public health nurses, parents and young people during consultations.

Background.  There is limited research on public health nursing strategies and intervention models. There is a need to observe and describe the content of public health nursing work.

Design.  The study has an ethnographic design and this article focuses mainly on the observations.

Methods.  Five consultations at four different child health clinics, six consultations at two health clinics for young people and one consultation at the school public health nurse’s office were observed. The sociological concept of role formats provides the analytical focus for the paper.

Results.  There are differences between the overriding ceremonial order in the public health nursing consultations observed in this study and the dominant role format observed in Sociologist P.M. Strong’s study of medical consultations. Gentility can be a common denominator, yet ease and focus on everyday issues seems consistent with public health nursing consultations. The ‘personal professional format’ seems to be the correct term for the overriding ceremonial order.

Conclusion.  The outward show of behaviour in nursing and medical consultations differs. Despite society’s increased bureaucracy within health care systems, ease and a personal professional approach, not a rigid bureaucratic format, seems to be the dominant ceremonial order in public health nursing consultations.

Relevance to clinical practice.  This study is relevant to clinical nursing practice as it can create awareness of the taken‐for‐granted subtleties in nursing consultations. The findings show the continued need for supportive universal services that focus on the everyday needs of parents, young people and families. The findings also reveal the need for further studies on the moral underpinnings of public health nursing practice.
Psychometric evaluation of a Dutch version of the Mini PAS‐ADD for assessing psychiatric disorders in adults with different levels of intellectual disability
Authors: Janssen R. , Maes B.
Published: March 2012

Background  People with intellectual disabilities (ID) have an increased vulnerability to develop psychiatric problems. Moreover, the early recognition and the accurate diagnosis of psychiatric disorders in the population of persons with ID are challenging.

Method  A Dutch version of the Mini PAS‐ADD, which is a screening instrument for identification of mental health problems in people with ID, was evaluated in terms of internal consistency, interinformant reliability, item grouping and criterion validity based on a large‐scale random sample (n = 377) and a clinical sample (n = 99) of adults with ID.

Results  The Dutch version of the Mini PAS‐ADD showed moderate internal consistency, and moderate concordance among informants. Both aspects of the reliability were comparable for different levels of ID. A factor analysis largely confirmed the scale structure. Concurrent validity with the Reiss Screen for Maladaptive Behavior was high for the Depression, Psychosis and Autism scale. The outcome of the criterion‐validity analysis indicated high specificity. The sensitivity for specific psychiatric disorders by the corresponding scales was moderate, but the general sensitivity for the presence of psychopathology on the basis of any of the scales was satisfying.

Conclusions  The present research reconfirmed the use of the Mini PAS‐ADD as a primary screening device for the identification of mental health problems among people with ID.
Texture of cellulose microfibrils of root hair cell walls of Arabidopsis thaliana, Medicago truncatula, and Vicia sativa
Authors: AKKERMAN M. , FRANSSEN‐VERHEIJEN M.A.W. , IMMERZEEL P. , HOLLANDER L.DEN , SCHEL J.H.N. , EMONS A.M.C.
Published: March 2012

Cellulose is the most abundant biopolymer on earth, and has qualities that make it suitable for biofuel. There are new tools for the visualisation of the cellulose synthase complexes in living cells, but those do not show their product, the cellulose microfibrils (CMFs). In this study we report the characteristics of cell wall textures, i.e. the architectures of the CMFs in the wall, of root hairs of Arabidopsis thaliana, Medicago truncatula and Vicia sativa and compare the different techniques we used to study them. Root hairs of these species have a random primary cell wall deposited at the root hair tip, which covers the outside of the growing and fully grown hair. The secondary wall starts between 10 (Arabidopsis) and 40 (Vicia) μm from the hair tip and the CMFs make a small angle, Z as well as S direction, with the long axis of the root hair. CMFs are 3–4 nm wide in thin sections, indicating that single cellulose synthase complexes make them. Thin sections after extraction of cell wall matrix, leaving only the CMFs, reveal the type of wall texture and the orientation and width of CMFs, but CMF density within a lamella cannot be quantified, and CMF length is always underestimated by this technique. Field emission scanning electron microscopy and surface preparations for transmission electron microscopy reveal the type of wall texture and the orientation of individual CMFs. Only when the orientation of CMFs in subsequent deposited lamellae is different, their density per lamella can be determined. It is impossible to measure CMF length with any of the EM techniques.
Molecular characterization of the Lotus japonicus NRT1(PTR) and NRT2 families
Authors: CRISCUOLO GIUSEPPINA , VALKOV VLADIMIR TOTEV , PARLATI AURORA , ALVES LUDOVICO MARTIN , CHIURAZZI MAURIZIO
Published: March 2012

Nitrate is an essential element for plant growth, both as a primary nutrient in the nitrogen assimilation pathway and as an important signal for plant development. Low‐ and high‐affinity transport systems are involved in the nitrate uptake from the soil and its distribution between different plant tissues. By an in silico search, we identified putative members of both systems in the model legume Lotus japonicus. We investigated, by a time course analysis, the transcripts abundance in root tissues of nine and four genes encoding putative low‐affinity (NRT1) and high‐affinity (NRT2) nitrate transporters, respectively. The genes were sub‐classified as inducible, repressible and constitutive on the basis of their responses to provision of nitrate, auxin or cytokinin. Furthermore, the analysis of the pattern of expression in root and nodule tissues after Mesorhizobium loti inoculation permitted the identification of sequences significantly regulated during the symbiotic interaction. The interpretation of the global regulative networks obtained allowed to postulate roles for nitrate transporters as possible actors in the cross‐talks between different signalling pathways triggered by biotic and abiotic factors.
Mechanisms of hormonal regulation of endosperm cap‐specific gene expression in tomato seeds
Authors: Martínez‐Andújar Cristina , Pluskota Wioletta E. , Bassel George W. , Asahina Masashi , Pupel Piotr , Nguyen Theresa T. , Takeda‐Kamiya Noriko , Toubiana David , Bai Bing , Górecki Ryszard J. , Fait Aaron , Yamaguchi Shinjiro , Nonogaki Hiroyuki
Published: March 2012

The micropylar region of endosperm in a seed, which is adjacent to the radicle tip, is called the ‘endosperm cap’, and is specifically activated before radicle emergence. This activation of the endosperm cap is a widespread phenomenon among species and is a prerequisite for the completion of germination. To understand the mechanisms of endosperm cap‐specific gene expression in tomato seeds, GeneChip analysis was performed. The major groups of endosperm cap‐enriched genes were pathogenesis‐, cell wall‐, and hormone‐associated genes. The promoter regions of endosperm cap‐enriched genes contained DNA motifs recognized by ethylene response factors (ERFs). The tomato ERF1 (TERF1) and its experimentally verified targets were enriched in the endosperm cap, suggesting an involvement of the ethylene response cascade in this process. The known endosperm cap enzyme endo‐β‐mannanase is induced by gibberellin (GA), which is thought to be the major hormone inducing endosperm cap‐specific genes. The mechanism of endo‐β‐mannanase induction by GA was also investigated using isolated, embryoless seeds. Results suggested that GA might act indirectly on the endosperm cap. We propose that endosperm cap activation is caused by the ethylene response of this tissue, as a consequence of mechanosensing of the increase in embryonic growth potential by GA action.
Enhanced midbrain response at 6‐month follow‐up in cocaine addiction, association with reduced drug‐related choice
Authors: Moeller Scott J. , Tomasi Dardo , Woicik Patricia A. , Maloney Thomas , Alia‐Klein Nelly , Honorio Jean , Telang Frank , Wang Gene‐Jack , Wang Ruiliang , Sinha Rajita , Carise Deni , Astone‐Twerell Janetta , Bolger Joy , Volkow Nora D. , Goldstein Rita Z.
Published: March 2012

Drug addiction is characterized by dysregulated dopamine neurotransmission. Although dopamine functioning appears to partially recover with abstinence, the specific regions that recover and potential impact on drug seeking remain to be determined. Here we used functional magnetic resonance imaging (fMRI) to study an ecologically valid sample of 15 treatment‐seeking cocaine addicted individuals at baseline and 6‐month follow‐up. At both study sessions, we collected fMRI scans during performance of a drug Stroop task, clinical self‐report measures of addiction severity and behavioral measures of cocaine seeking (simulated cocaine choice); actual drug use in between the two study sessions was also monitored. At 6‐month follow‐up (compared with baseline), we predicted functional enhancement of dopaminergically innervated brain regions, relevant to the behavioral responsiveness toward salient stimuli. Consistent with predictions, whole‐brain analyses revealed responses in the midbrain (encompassing the ventral tegmental area/substantia nigra complex) and thalamus (encompassing the mediodorsal nucleus) that were higher (and more positively correlated) at follow‐up than baseline. Increased midbrain activity from baseline to follow‐up correlated with reduced simulated cocaine choice, indicating that heightened midbrain activations in this context may be marking lower approach motivation for cocaine. Normalization of midbrain function at follow‐up was also suggested by exploratory comparisons with active cocaine users and healthy controls (who were assessed only at baseline). Enhanced self‐control at follow‐up was suggested by a trend for the commonly hypoactive dorsal anterior cingulate cortex to increase response during a drug‐related context. Together, these results suggest that fMRI could be useful in sensitively tracking follow‐up outcomes in drug addiction.
Differences in regional cerebral blood flow response to a 5HT3 antagonist in early‐ and late‐onset cocaine‐dependent subjects
Authors: Adinoff Bryon , Devous Michael D. , Williams Mark J. , Harris Thomas S. , Best Susan E. , Dong Hongyun , Zielinski Tanya
Published: March 2012

5‐hydroxytryptamine 3 (5HT3) receptors are important modulators of mesostriatal dopaminergic transmission and have been implicated in the pathophysiology of cocaine reward, withdrawal and self‐administration. In addition, the 5HT3 antagonist ondansetron is effective in treating early‐onset, but not late‐onset, alcohol‐dependent subjects. To explore the role of 5HT3 receptor systems in cocaine addiction using functioning imaging, we administered ondansetron to 23 abstinent, treatment‐seeking cocaine‐addicted and 22 sex‐, age‐ and race‐matched healthy control participants. Differences between early‐ (first use before 20 years, n = 10) and late‐onset (first use after 20 years, n = 10) cocaine‐addicted subjects were also assessed. On two separate days, subjects were administered ondansetron (0.15 mg/kg intravenously over 15 minutes) or saline. Regional cerebral blood flow (rCBF) was measured following each infusion with single photon emission computed tomography. No significant rCBF differences between the cocaine‐addicted and control participants were observed following ondansetron relative to saline. Early‐onset subjects, however, showed increased (P < 0.001) right posterior parahippocampal rCBF following ondansetron. In contrast, late‐onset subjects showed decreased rCBF following ondansetron in an overlapping region of the right parahippocampal/hippocampal gyrus. Early‐onset subjects also displayed increased rCBF in the left anterior insula and subthalamic nucleus following ondansetron; late‐onset subjects showed decreased rCBF in the right anterior insula. These findings suggest that the age of drug use onset is associated with serotonergic biosignatures in cocaine‐addicted subjects. Further clarification of these alterations may guide targeted treatment with serotonergic medications similar to those successfully used in alcohol‐dependent patients.
Medications development to treat alcohol dependence: a vision for the next decade
Authors: Litten Raye Z. , Egli Mark , Heilig Markus , Cui Changhai , Fertig Joanne B. , Ryan Megan L. , Falk Daniel E. , Moss Howard , Huebner Robert , Noronha Antonio
Published: March 2012

More than 76 million people world‐wide are estimated to have diagnosable alcohol use disorders (AUDs) (alcohol abuse or dependence), making these disorders a major global health problem. Pharmacotherapy offers promising means for treating AUDs, and significant progress has been made in the past 20 years. The US Food and Drug Administration approved three of the four medications for alcoholism in the last two decades. Unfortunately, these medications do not work for everyone, prompting the need for a personalized approach to optimize clinical benefit or more efficacious medications that can treat a wider range of patients, or both. To promote global health, the potential reorganization of the National Institutes of Health (NIH) must continue to support the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) vision of ensuring the development and delivery of new and more efficacious medications to treat AUDs in the coming decade. To achieve this objective, the NIAAA Medications Development Team has identified three fundamental long‐range goals: (1) to make the drug development process more efficient; (2) to identify more efficacious medications, personalize treatment approaches, or both; and (3) to facilitate the implementation and adaptation of medications in real‐world treatment settings. These goals will be carried out through seven key objectives. This paper describes those objectives in terms of rationale and strategy. Successful implementation of these objectives will result in the development of more efficacious and safe medications, provide a greater selection of therapy options and ultimately lessen the impact of this devastating disorder.
Phenotype in 18 Danish subjects with genetically verified CHARGE syndrome
Authors: Husu E , Hove HD , Farholt S , Bille M , Tranebjærg L , Vogel I , Kreiborg S
Published: March 2012

Husu E, Hove HD, Farholt S, Bille M, Tranebjærg L, Vogel I, Kreiborg S. Phenotype in 18 Danish subjects with genetically verified CHARGE syndrome.

CHARGE (coloboma of the eye, heart defects, choanal atresia, retarded growth and development, genital hypoplasia and ear anomalies and/or hearing loss) syndrome is a rare genetic, multiple‐malformation syndrome. About 80% of patients with a clinical diagnose, have a mutation or a deletion in the gene encoding chromodomain helicase DNA‐binding protein 7 (CHD7). Genotype–phenotype correlation is only partly known. In this nationwide study, phenotypic characteristics of 18 Danish CHD7 mutation positive CHARGE individuals (N = 18) are presented. We studied patient records, clinical photographs, computed tomography, and magnetic resonance imaging (MRI). Information was not available for all traits in all subjects. Therefore, the results are presented as fractions. The following prevalence of cardinal symptoms were found: coloboma, 16/17; heart defects, 14/18; choanal atresia, 7/17; retarded growth and development, 11/13; genital abnormalities, 5/18; ear anomalies, 15/17 and sensorineural hearing loss, 14/15. Vestibular dysfunction (10/13) and swallowing problems (12/15) were other frequent cranial nerve dysfunctions. Three‐dimensional reconstructions of MRI scans showed temporal bone abnormalities in >85%. CHARGE syndrome present a broad phenotypic spectrum, although some clinical features are more frequently occurring than others. Here, we suggest that genetic testing for CHD7 mutation should be considered in neonates with a specific combination of several clinical symptoms.
Anal canal neuroendocrine carcinoma associated with squamous intraepithelial neoplasia: A human papillomavirus 18‐related lesion
Authors: Ohtomo Rie , Sekine Shigeki , Taniguchi Hirokazu , Tsuda Hitoshi , Moriya Yoshihiro , Kushima Ryoji
Published: March 2012

Neuroendocrine carcinoma (NEC) of the anal canal is exceedingly rare and its histogenesis is poorly understood. We present a case of small‐cell NEC of the anal canal in a 70‐year‐old woman. The NEC appeared as a submucosal tumor at the dentate line and was associated with squamous intraepithelial neoplasia (SIN). The NEC was positive for neuroendocrine markers including synaptophysin, chromogranin A and CD56, whereas the SIN component did not express any of these markers. Both components exhibited p16 overexpression. A PCR analysis revealed that both the SIN and NEC components were positive for human papillomavirus (HPV) 18 DNA. Our observations imply that SIN may be a precursor of anal canal NEC and that HPV18 may play an important role in the histogenesis of anal canal NEC, similar to its role in cervical NEC.
Autopsy case of primary myelofibrosis in which myeloid sarcoma was the initial manifestation of tumor progression
Authors: Morita Kohei , Nakamine Hirokazu , Inoue Reina , Takano Masato , Takeda Maiko , Enomoto Yasunori , Kasai Takahiko , Nonomura Akitaka , Tanaka Haruyuki , Amano Itsuto , Morii Takeshi , Kimura Hiroshi
Published: March 2012

Myeloid sarcoma (MyS) is defined as an extramedullary tumor‐forming neoplasm consisting of immature myeloid cells with/without maturation. We experienced a case involving a 68‐year‐old Japanese male patient who had been followed‐up for four years with a diagnosis of chronic idiopathic myelofibrosis/primary myelofibrosis (PMF) and noticed a painful mass in his left axilla. A wedge biopsy characterized the lesion as MyS that displayed megakaryoblastic/megakaryocytic differentiation. As his complete blood count included a few myeloid blasts (1% of WBC) and a bone marrow biopsy detected fibrosis without evidence of acute myelogenous leukemia (AML), a diagnosis of extramedullary blastic transformation of PMF was made, which was confirmed later by V617F mutation in Janus kinase‐2 in both initial bone marrow biopsy and axillary tumor biopsy specimens. The patient died of pneumonia eight months after developing the axillary tumor. At autopsy, multiple MyS masses were detected in his soft tissue, but his bone marrow only contained fibrosis. Although MyS rarely develops before the leukemic transformation of PMF, no evidence of AML could be found in the patient's bone marrow at any point during the course of his disease. Thus, it is possible that the blasts in his peripheral blood were derived from the remaining MyS. Furthermore, the present case indicates that extramedullary blastic transformation, which is occasionally seen in CML, can also occur in PMF. Therefore, it is important to recognize that there is a wide variation in the pathogeneses of MyS and PMF.
Pilot study for evidence‐based nursing management: Improving the levels of job satisfaction, organizational commitment, and intent to leave among nurses in Turkey
Authors: Yurumezoglu Havva Arslan , Kocaman Gulseren
Published: March 2012

Because of the nursing shortage problem, an important goal for nurse managers is preventing nurses from leaving the organization. This study analyzed the effect of evidence‐based nursing management practices on nurses' levels of job satisfaction, organizational commitment, and intent to leave using the Promoting Action Research Implementation in Health Service framework as a guide. This study employed a single‐group, quasi‐experimental, pretest–post‐test design with repeated measures. Data were collected using the Minnesota Job Satisfaction Questionnaire and the Organizational Commitment Scale. The study was conducted at a 127‐bed private, accredited hospital. The sample was composed of 58 nurses who participated in all three measurements. Data analysis was conducted using repeated‐measures anova and the Cochrane Q‐test. An improvement was observed in the nurses' intrinsic, extrinsic, and total satisfaction levels, and in the degree of normative commitment. Nurse managers stated that they benefited from this study. In order to find effective and long‐lasting solutions to the nursing shortage problem, evidence‐based recommendations should be used in nursing management.
Association between sleep duration and psychological health in overweight and obese children in Korea
Authors: Kim Hee Soon , Ham Ok Kyung , Kim Jong Wook , Park Ji Young
Published: March 2012

This study examined the moderating effects of different body mass index groups on the relationship between sleep duration and psychological variables (i.e. self‐esteem, depression, and perceived obesity stress) among overweight and obese children in Korea. A non‐experimental, cross‐sectional study design was used. Study participants included 424 children residing in one metropolitan city of Korea and participating in weight‐control programs. Self‐reported data collection and physical examinations were performed. An age‐ and sex‐specific reference growth chart was used to produce body mass index for age percentiles, and to classify overweight and obese groups. The results indicated that the main effects of sleep duration and the body mass index group × sleep duration interaction terms were statistically significant for all investigated psychological variables (P < 0.05), indicating that the body mass index group variable moderated the relationship between sleep duration and these psychological variables. This study found that sleep duration < 7 h was particularly detrimental to the investigated psychological variables in overweight, rather than obese, children.
Photoselective vaporization of the prostate using the 180W lithium triborate laser
Authors: Chung Amanda S. J. , Chabert Charles , Yap Hin‐Wai , Lam Jimmy , Awad Nader , Nuwayhid Fadi , Redwig Frank , Rashid Prem , Woo Henry H.
Published: March 2012

Introduction:  Photoselective vaporization of the prostate (PVP) is widely used to treat benign prostatic obstruction (BPO), but there is little experience reported on the new more powerful 180W lithium triborate (LBO) laser. This study evaluates the safety and efficacy of using the 180W LBO laser to treat BPO by examining a multicentre Australian experience.

Methods:  Retrospective review of prospectively collected data on all men treated by 180W LBO laser PVP by eight urologists across six Australian hospitals, from July 2011 to August 2011, was performed. Perioperative and functional outcomes were examined at baseline and 3 months.

Results:  Of the 85 men (median age 70 years, prostate volume 51 cm3) identified, 27% (23/85) were in urinary retention and 44% (37/85) were taking antiplatelet/anticoagulant medication. Median operating time was 46 min, laser time 27 min, energy use 211 kJ, post‐operative duration of catheterization 15 h and hospitalization 22 h. Functional outcomes from baseline to 3 months, respectively, were for IPSS 25–7; QoL 5–2; Qmax 7.7–18.4; and PVR 147–38. All improvements were statistically significant (P < 0.01). Thirty‐eight per cent (32/85) of patients experienced at least one adverse event. Most adverse events were low Clavien–Dindo grade I–II. There were five grade III, two grade IV and no grade V adverse events. Sixty per cent (51/85) of men were able to be discharged home voiding successfully without a catheter within 24‐h post‐PVP.

Conclusions:  Our early multicentre Australian experience indicates the 180W LBO laser PVP is an efficacious and safe treatment for BPO.
Outcomes of patients with appendicitis who present to an outer metropolitan hospital
Authors: Devanathan Raja , Aw Hau Choong , Li Wai Suen Christopher Foong Dhin , Paul Eldho , Rodgers‐Wilson Stephen
Published: March 2012

Background:  The present study investigates patients with acute appendicitis who presented to a hospital with no acute surgical service (group A) and compares the outcomes of these patients with those that presented to a tertiary centre with an acute surgical service within the same health network (group B). All group A patients were transferred to the group B hospital for appendicectomy.

Methods:  During a 10‐month period, 257 patients (80 in group A, 177 in group B) with acute appendicitis were analysed retrospectively. Demographics, emergency department parameters, time to waiting bay, time to surgery, operative time, complications, length of stay and the stage of appendicitis were all noted for each group. A comparison of each of these parameters was made between the two groups of patients.

Results:  There were 80 patients in group A and 177 patients in group B. There was a significant difference between the two groups in the fields of length of stay in the emergency department (P= 0.003), bed availability (P= 0.038), time to waiting bay (P= 0.006) and time to surgery (P= 0.006). There was no significant difference in the total length of stay and complication rates between the two groups (P= 0.58 and 0.78, respectively).

Conclusion:  This study concludes that patients with acute appendicitis presenting to a hospital with no acute surgical services had a greater waiting period prior to surgery. However, this did not translate into greater complication rates or length of stay for these patients. We propose a prospective study to further analyse the outcomes in such patients.