bluuebunny/crossref_metadata_2025 huggingface dataset:
What would menthol smokers do if menthol in cigarettes were banned? Behavioral intentions and simulated demand
Authors: O'Connor Richard J. , Bansal‐Travers Maansi , Carter Lawrence P. , Cummings K. Michael
Published: April 2012

Aims  The US Food and Drug Administration must consider whether to ban the use of menthol in cigarettes. This study examines how current smokers might respond to such a ban on menthol cigarettes.

Design  Convenience sample of adolescent and adult smokers recruited from an online survey panel.

Setting  United States, 2010.

Participants  A total of 471 adolescent and adult current cigarette smokers.

Measurements  Respondents were asked a series of questions about how they might react if menthol cigarettes were banned. In addition, participants completed a simulation purchase task to estimate the demand for menthol and non‐menthol cigarettes across a range of prices.

Findings  Overall, 36.1% of respondents said they always (18.9%) or usually (17.2%) smoked menthol cigarettes. When asked how they might respond to a ban on menthol cigarettes, 35% of current menthol smokers said they would stop smoking, and 25% said they would ‘find a way to buy a menthol brand’. Those who reported they might quit tended to have greater current intentions to quit [odds ratio (OR) = 4.47], while those who reported that they might seek illicit menthol cigarettes were far less likely to report current intentions to quit (OR = 0.06). Estimates for demand elasticity for preferred cigarette type were similar for menthol (α = 0.0051) and non‐menthol (α = 0.0049) smokers. Demand elasticity and peak consumption were related to usual cigarette type and cigarettes smoked per day, but did not appear to differ by race, gender or age.

Conclusions  Preliminary evidence suggests that a significant minority of smokers of menthol cigarettes in the United States would try to stop smoking altogether if such cigarettes were banned.
Transdimensional tomography with unknown data noise
Authors: Bodin Thomas , Sambridge Malcolm , Rawlinson Nick , Arroucau Pierre
Published: April 2012

A meaningful interpretation of seismic measurements requires a rigorous quantification of the uncertainty. In an inverse problem, the data noise determines how accurately observations should be fit, and ultimately the level of detail contained in the recovered model. A common problem in seismic tomography is the difficulty in quantifying data uncertainties, and thus the required level of data fit. Traditionally, the complexity of the solution model (defined by both the number of basis functions and the regularization) is defined arbitrarily by the user prior to inversion with only limited use of data errors. In the context of multiscale problems, dealing with multiple data sets that are characterized by different noise variances and that span the Earth at different scales is a major challenge. Practitioners are usually required to arbitrarily weigh the contribution of each data type into the final solution. Furthermore, the basis functions are usually spatially uniform across the velocity field and regularization procedures are global, which prevents the solution model from accounting for the uneven spatial distribution of information. In this work we propose to address these issues with a Hierarchical Bayesian inversion. The new algorithm represents an extension of the transdimensional tomography to account for uncertainties in data noise. This approach has the advantage of treating the level of noise in each data set, as well as the number of model parameters, as unknowns in the inversion. It provides a parsimonious solution that fully represents the degree of knowledge one has about seismic structure (i.e. constraints, resolution and trade-offs). Rather than being forced to make decisions on parametrization, level of data fit and weights between data types in advance, as is often the case in an optimization framework, these choices are relaxed and instead constrained by the data themselves. The new methodology is presented in a synthetic example where both the data density and the underlying structure contain multiple length scales. Three ambient noise data sets that span the Australian continent at different scales are then simultaneously inverted to infer a multiscale tomographic image of Rayleigh wave group velocity for the Australian continent. The procedure turns out to be particularly useful when dealing with multiple data types with different unknown levels of noise as the algorithm is able to naturally adjust the fit to the different data sets and provide a velocity map with a spatial resolution adapted to the spatially variable information present in the data.
Neoplastic spindle cells in nasopharyngeal carcinoma show features of epithelial–mesenchymal transition
Authors: Luo Wei‐Ren , Chen Xiao‐Yi , Li Si‐Yi , Wu Ai‐Bing , Yao Kai‐Tai
Published: April 2012

Luo W‐R, Chen X‐Y, Li S‐Y, Wu A‐B & Yao K‐T  (2012) Histopathology 61, 113–122

Neoplastic spindle cells in nasopharyngeal carcinoma show features of epithelial–mesenchymal transition

Aim:  To investigate whether the neoplastic spindle cells in nasopharyngeal carcinoma (NPC) are associated with the process of epithelial–mesenchymal transition (EMT).

Methods and results:  We used immunohistochemistry to analyse the expression of cytokeratin, E‐cadherin, β‐catenin, vimentin, fibronectin, Snail1, Slug and aldehyde dehydrogenase 1 (ALDH1) in 115 cases of NPC in which there were neoplastic spindle cells; in 47 cases a neoplastic squamous cell component was also present. There was no significant difference in the expression of cytokeratin observed in the neoplastic spindle cells (P = 0.644), compared to the squamous component whereas E‐cadherin expression was reduced. By contrast, the expression of β‐catenin, vimentin, fibronectin, Snail1, Slug and ALDH1 was up‐regulated in the spindle cells (all P = 0.000). Furthermore, E‐cadherin expression was associated negatively with β‐catenin (P < 0.001), vimentin (P < 0.001), fibronectin (P < 0.001), Slug (P < 0.001) and ALDH1 (P < 0.001) in neoplastic spindle cells, but did not correlate with Snail1 expression (P =0.093).

Conclusions:  Our findings demonstrate for the first time that EMT might play an important role in the development of neoplastic spindle cells in NPC.
Molecular evidence in support of the neoplastic and precursor nature of microglandular adenosis
Authors: Geyer Felipe C , Lacroix‐Triki Magali , Colombo Pierre‐Emmanuel , Patani Neill , Gauthier Arnaud , Natrajan Rachael , Lambros Maryou B K , Khalifeh Ibrahim , Albarracin Constance , Orru Sandra , Marchiò Caterina , Sapino Anna , Mackay Alan , Weigelt Britta , Schmitt Fernando C , Wesseling Jelle , Sneige Nour , Reis‐Filho Jorge S
Published: April 2012

Geyer F C, Lacroix‐Triki M, Colombo P‐E, Patani N, Gauthier A, Natrajan R, Lambros M B K, Khalifeh I, Albarracin C, Orru S, Marchiò C, Sapino A, Mackay A, Weigelt B, Schmitt F C, Wesseling J, Sneige N & Reis‐Filho J S

(2012) Histopathology 60, E115–E130

Molecular evidence in support of the neoplastic and precursor nature of microglandular adenosis

Aims:  Microglandular adenosis (MGA) is a proliferative breast lesion, which has been proposed to be a potential precursor of triple‐negative breast cancers. The aims of this study were to determine whether MGAs harbour genetic alterations and if any such genetic aberrations found in MGAs are similar to those found in matched invasive carcinomas.

Methods and results:  Twelve cases of MGA and/or atypical MGA (AMGA), 10 of which were associated with invasive carcinoma, were evaluated. Immunohistochemical profiling revealed that all invasive carcinomas were of triple‐negative phenotype and expressed S100, cytokeratins 8/18 and ‘basal’ markers. The morphologically distinct components of each case (MGA, AMGA and/or invasive carcinoma) were microdissected and subjected to microarray comparative genomic hybridization. Apart from three typical MGAs, all samples harboured genetic alterations. The percentage of the genome affected by copy number aberrations in MGA/AMGA ranged from 0.5 to 61.9%, indicating varying levels of genetic instability. In three cases, MGA/AMGA displayed copy number aberrations similar to those found in matched invasive components, providing strong circumstantial evidence that MGA may constitute the substrate for the invasive carcinoma development.

Conclusions:  Our results support the contention that MGA can be a clonal lesion and non‐obligate precursor of triple‐negative breast cancer.
RET/PTC rearrangement is prevalent in follicular Hürthle cell carcinomas
Authors: de Vries Margriet M , Celestino Ricardo , Castro Patricia , Eloy Catarina , Máximo Valdemar , van der Wal Jacqueline E , Plukker John T M , Links Thera P , Hofstra Robert M W , Sobrinho‐Simões Manuel , Soares Paula
Published: April 2012

de Vries M M, Celestino R, Castro P, Eloy C, Máximo V, van der Wal J E, Plukker J T M, Links T P, Hofstra R M W, Sobrinho‐Simões M & Soares P  (2012) Histopathology 61, 833–843

RET/PTC rearrangement is prevalent in follicular Hürthle cell carcinomas

Aims:  The molecular alterations underlying follicular Hürthle cell carcinomas (FHCCs) are largely unknown. In an attempt to clarify this issue, we analysed a series of Hürthle cell tumours for the presence of RET/PTC and PAX8/PPARG rearrangements and BRAF, HRAS and NRAS mutations.

Methods and results:  We investigated a series of 20 follicular Hürthle cell tumours [17 FHCCs and three follicular Hürthle cell adenomas (FHCAs)]. RET/PTC rearrangements were found in 33% of FHCAs and in 38% of FHCCs. All RET/PTC‐positive FHCCs had a solid pattern of growth. PAX8/PPARG rearrangement was present in 27% of the FHCCs which displayed, in most cases, a follicular architecture. NRAS mutation was detected in one FHCC. An FHCC with a solid/microfollicular growth pattern scored positive for both RET/PTC and PAX8/PPARG rearrangement.

Conclusions:  Our study has shown a significant association between RET/PTC rearrangements and FHCCs with a solid growth pattern, thus raising the possibility of using tyrosine kinase inhibitors for the treatment of patients with FHCCs, which are often refractory to radioiodine treatment.
IRTA1 is selectively expressed in nodal and extranodal marginal zone lymphomas
Authors: Falini Brunangelo , Agostinelli Claudio , Bigerna Barbara , Pucciarini Alessandra , Pacini Roberta , Tabarrini Alessia , Falcinelli Flavio , Piccioli Milena , Paulli Marco , Gambacorta Marcello , Ponzoni Maurilio , Tiacci Enrico , Ascani Stefano , Martelli Maria Paola , Favera Riccardo Dalla , Stein Harald , Pileri Stefano A
Published: April 2012

Falini B, Agostinelli C, Bigerna B, Pucciarini A, Pacini R, Tabarrini A, Falcinelli F, Piccioli M, Paulli M, Gambacorta M, Ponzoni M, Tiacci E, Ascani S, Martelli M P, Dalla Favera R, Stein H & Pileri S A  (2012) Histopathology 61, 930–941

IRTA1 is selectively expressed in nodal and extranodal marginal zone lymphomas

Aims:  The aim of this study was to search for a molecule selectively expressed by marginal zone (MZ) lymphomas (MZLs), whose diagnosis is currently based on morphological criteria and negativity for markers detectable in other B‐cell lymphomas.

Methods and results:  Two thousand one hundred and four peripheral lymphomas of various types were immunostained with a monoclonal antibody against immunoglobulin superfamily receptor translocation‐associated 1 (IRTA1), which recognizes the equivalents of MZ in human lymphoid tissues other than spleen. IRTA1 expression was restricted to extranodal (93%) and nodal MZLs (73%) and to lymphomas with MZ differentiation. Extranodal MZL cells with the strongest IRTA1 expression were usually located adjacent to epithelia, mimicking the IRTA1 expression pattern of normal and acquired mucosa‐associated lymphoid tissue (MALT). The cytological features, growth pattern and IRTA1 positivity in nodal MZLs suggest they may derive from IRTA1+ perifollicular B cells or monocytoid B cells detectable in reactive lymph nodes. Double immunostaining for IRTA1/bcl‐6 tracked the colonization of B‐cell follicles by MZL cells, and showed modulation of their phenotype (e.g. acquisition of bcl‐6) during recirculation through germinal centres. MZL cells differentiating into plasma cells usually lost IRTA1.

Conclusions:  These results further expand our knowledge of the biology of MZLs, and highlight IRTA1 as the first positive marker for MZLs, enabling more accurate diagnosis of these neoplasms.
Root and canal morphology of maxillary first premolars in a Chinese subpopulation evaluated using cone‐beam computed tomography
Authors: Tian Y.‐Y. , Guo B. , Zhang R. , Yu X. , Wang H. , Hu T. , Dummer P. M. H.
Published: April 2012

Tian Y.‐Y, Guo B, Zhang R, Yu X, Wang H, Hu T, Dummer PMH. Root and canal morphology of maxillary first premolars in a Chinese subpopulation evaluated using cone‐beam computed tomography. International Endodontic Journal., 45, 996–1003, 2012.

Aim  To evaluate the external and internal anatomy of maxillary first premolar teeth in a Chinese subpopulation using cone‐beam computed tomography (CBCT).

Methodology  A total of 300 CBCT images involving maxillary first premolar teeth were obtained from 241 patients who underwent CBCT scanning as part of an oral and dental examination for bone mass before placement of implants or to locate impacted teeth before orthodontic therapy. Tooth position, number of roots, canal configuration, number of canals and number of apical foramina per root were investigated. The Fisher’s exact test was used to analyse the correlation between root number and tooth position.

Results  Overall, 66% (n = 198) of teeth had one root and 33% (n = 100) had two roots; the remaining 1% (n = 2) had three roots. This frequency distribution showed no statistical significance between left and right sides. The most frequent canal configuration of these maxillary first premolars was type IV (n = 153; 51%), followed by type II (n = 70; 23%), with only 1% (n = 2) of teeth having type VIII. One‐rooted teeth with canal bifurcations and/or combinations (types II, III, V, VI and VII) accounted for nearly 50% (n = 98) of the sample. Eighty‐five per cent (n = 255) of the teeth examined had two root canals (types II–VII), and 14% (n = 43) had one. Amongst the 59 patients with bilateral teeth, 38 had a symmetrical pattern of tooth anatomy, including the same number of roots and the same types of canal configurations.

Conclusions  There was a high frequency of one‐rooted teeth amongst maxillary first premolars, with most having one root with two canals (types II–VII). The morphology of the canal in one‐rooted teeth was highly variable.
Adults with intellectual disabilities and challenging behaviour: the costs and outcomes of in‐ and out‐of‐area placements
Authors: Perry J. , Allen D. G. , Pimm C. , Meek A. , Lowe K. , Groves S. , Cohen D. , Felce D.
Published: April 2012

Background People with severe challenging behaviour are vulnerable to exclusion from local services and removal to out‐of‐area placements if locally available supported accommodation is insufficient to meet their needs. There are concerns about the high costs and potentially poorer outcomes of out‐of‐area placements but relatively little is known about how costs and outcomes compare with provision for a similar population placed locally.

Methods Costs, quality of care and a wide range of quality of life outcomes for 38 people with intellectual disabilities and challenging behaviour living in‐area and 38 similar people living out‐of‐area were compared. The two groups were matched as far as possible on risk factors for out‐of‐area placement. The out‐of‐area group represented two‐thirds of the total number of people who originated from the territory served by the largest specialist health service in Wales and were placed in residential settings at least 10 miles beyond its boundaries.

Results There was a mixed pattern of quality of care and quality of outcome advantages between the two types of setting, although in‐area placements had a greater number of advantages than out‐of‐area placements. Unexpectedly, out‐of‐area placements had lower total costs, accommodation costs and daytime activity costs.

Conclusions No overall conclusion could be reached about cost‐effectiveness. A number of potential reasons for the differences in cost were identified. Although additional resources may be needed to provide in‐area services for those currently placed out‐of‐area, government policy to provide comprehensively for those who want to live locally, irrespective of their needs, appears to be attainable.
Hypothalamic Gene Expression Rapidly Changes in Response to Photoperiod in Juvenile Siberian Hamsters (Phodopus sungorus)
Authors: Herwig A. , Petri I. , Barrett P.
Published: April 2012

Siberian hamsters are seasonal mammals that survive a winter climate by making adaptations in physiology and behaviour. This includes gonadal atrophy, reduced food intake and body weight. The underlying central mechanisms responsible for the physiological adaptations are not fully established but involve reducing hypothalamic tri‐iodthyronine (T3) levels. Juvenile Siberian hamsters born or raised in short days (SD) respond in a similar manner, although with an inhibition of gonadal development and growth instead of reversing an established long day (LD) phenotype. Using juvenile male hamsters, the present study aimed to investigate whether the central mechanisms are similar before the establishment of the mature LD phenotype. By in situ hybridisation, we examined the response of genes involved in thyroid hormone (Dio2 and Dio3, which determine hypothalamic T3 levels) and glucose/glutamate metabolism in the ependymal layer, histamine H3 receptor and VGF as representatives of the highly responsive dorsomedial posterior arcuate nucleus (dmpARC), and somatostatin, a hypothalamic neuropeptide involved in regulating the growth axis. Differential gene expression of type 2 and type 3 deiodinase in the ependymal layer, histamine H3 receptor in the dmpARC and somatostatin in the ARC was established by the eighth day in SD. These changes are followed by alterations in glucose metabolism related genes in the ependymal layer by day 16 and increased secretogranin expression in the dmpARC by day 32. In conclusion, our data demonstrate similar but rapid and highly responsive changes in gene expression in the brain of juvenile Siberian hamsters in response to a switch from LD to SD. The data also provide a temporal definition of gene expression changes relative to physiological adaptations of body weight and testicular development and highlight the likely importance of thyroid hormone availability as an early event in the adaptation of physiology to a winter climate in juvenile Siberian hamsters.
Overexpression of Cannabinoid CB2 Receptor in the Brain Induces Hyperglycaemia and a Lean Phenotype in Adult Mice
Authors: Romero‐Zerbo S. Y. , Garcia‐Gutierrez M. S. , Suárez J. , Rivera P. , Ruz‐Maldonado I. , Vida M. , Rodriguez de Fonseca F. , Manzanares J. , Bermúdez‐Silva F. Javier
Published: April 2012

It is well known that the endocannabinoid system, through cannabinoid CB1 receptor activation, has an important role in the main aspects of energy balance (i.e. food intake, energy expenditure and glucose and fat metabolism), orchestrating all the machinery involved in body weight control and energy homeostasis. A number of studies have revealed a crucial role of brain CB1 receptors in these processes. However, functional cannabinoid CB2 receptors have also been described in the brain, with no studies addressing their putative role in body weight control and glucose homeostasis. We have tested this hypothesis by analysing fasting‐induced feeding, body weight, some hypothalamic neuropeptides, glucose tolerance and plasma hormones in an animal model specifically overexpressing CB2 receptors in the central nervous system. We found that specific overexpression of CB2 receptors in the brain promoted higher basal glucose levels, decreased fasting‐induced feeding and, eventually, led to a lean phenotype and glucose intolerance. These findings could not be attributed to decreased locomotor activity, increased anxiety or depressive‐like behaviours. The expression of relevant neuropeptides such as pro‐opiomelanocortin and galanin in the arcuate nucleus of the hypothalamus was altered but not those of the CB1 receptor. Indeed, no changes in CB1 expression were found in the liver, skeletal muscle and adipose tissue. However, cannabinoid CB1 and CB2 receptor expression in the endocrine pancreas and glucagon plasma levels were decreased. No changes in plasma adiponectin, leptin, insulin and somatostatin were found. Taken together, these results suggest a role for central cannabinoid CB2 receptors in body weight control and glucose homeostasis.
Protein transport across the cell wall of monoderm Gram‐positive bacteria
Authors: Forster Brian M. , Marquis Hélène
Published: April 2012

In monoderm (single‐membrane) Gram‐positive bacteria, the majority of secreted proteins are first translocated across the cytoplasmic membrane into the inner wall zone. For a subset of these proteins, final destination is within the cell envelope as either membrane‐anchored or cell wall‐anchored proteins, whereas another subset of proteins is destined to be transported across the cell wall into the extracellular milieu. Although the cell wall is a porous structure, there is evidence that, for some proteins, transport is a regulated process. This review aims at describing what is known about the mechanisms that regulate the transport of proteins across the cell wall of monoderm Gram‐positive bacteria.
Linezolid‐induced pure red cell aplasia in a patient with Staphylococcus epidermidis infection after allogeneic stem cell transplantation
Authors: Waki F. , Ohnishi H. , Shintani T. , Uemura M. , Matsumoto K. , Fukumoto T. , Kitanaka A. , Kubota Y. , Tanaka T. , Ishida T. , Matsunaga T.
Published: April 2012

Linezolid (LZD) is the first oxazolidinone antibiotic that is effective against drug‐resistant gram‐positive organisms. Hematological toxicities such as thrombocytopenia, anemia, and leukocytopenia are common in LZD therapy. However, LZD‐induced pure red cell aplasia (PRCA) is very rare. A 56‐year‐old man with myelodysplastic syndrome underwent allogeneic bone marrow transplantation from a human leukocyte antigen‐matched and ABO blood type‐matched unrelated male donor. He had bacteremia caused by Staphylococcus epidermidis after engraftment of neutrophils and red blood cells. We first administered vancomycin, but then changed to intravenous LZD because of kidney damage. Two weeks after LZD therapy, the patient's hemoglobin and reticulocyte levels were 6.8 g/dL and 0.3%, respectively. Bone marrow examination revealed red blood cell aplasia (myeloid/erythroid ratio was 402). The patient showed rapid recovery of normal erythropoiesis within 2 weeks of LZD cessation. It is important to be aware of the hematological effects associated with LZD in the setting of stem cell transplantation,particularly for those with pre‐existing myelosuppression, renal insufficiency, and those receiving concomitant drugs that produce bone marrow suppression. We advocate that a reticulocyte count be performed periodically for detecting bone marrow suppression, including PRCA, during LZD therapy.
Outcome of ICU survivors: a comprehensive review. The role of patient‐reported outcome studies
Authors: GRANJA C. , AMARO A. , DIAS C. , COSTA‐PEREIRA A.
Published: April 2012

Problems survivors face after intensive care unit (ICU) discharge begin while they are still in the ward, where many of their specific problems may run unrecognized, but they assume a heavy weight when they arrive at their homes and face several kind of limitations, from being unable to climb stairs because of weight loss, asthenia, dyspnea or joint stiffness to anxiety, depression or post‐traumatic stress disorder.

Follow‐up consultations have given us a better understanding of these specific problems, and the information gained has been used to improve intensive care itself and promote a quality service for patients and relatives.

The aim of this article is to provide an overview on adult ICU outcome studies and discuss how they have influenced and improved the delivery of intensive care.

We will explain how we went from real patients to outcome studies and what we have learned concerning the consequences of critical illness and critical care.

Development of outcome studies, what we have learned through them and our own experience will be outlined focusing mainly in four topics: mortality, physical disability, neuropsychological disability and health‐related quality of life.

Interventions to improve outcome on these main topics will be presented, and we will explain how we went from outcome studies to clinical interventions, focusing on the most recent proposals of intervention to improve outcome.
Rapid Detection of Banana Streak Virus by Loop‐mediated Isothermal Amplification Assay in South China
Authors: Peng Jun , Fan Zaifeng , Huang Junsheng
Published: April 2012

Banana streak virus (BSV) is a significant constraint to banana production and genetic improvement. It is necessary to develop and use BSV detection strategies that are both reliable and sensitive for the management of the virus. A loop‐mediated isothermal amplification (LAMP) assay was developed and evaluated for the detection of BSV. Four primers matching a total of six sequences of the conserved ORF III polyprotein genes were synthesized for developing a specific and sensitive LAMP for DNA extracts from field‐infected banana plants. LAMP assay could detect as low as 1 pg/μl template DNA. Test results of all field samples collected from different regions of South China showed that LAMP is more sensitive than PCR. This relatively simple and sensitive technique showed excellent potential with field‐collected samples and for routine screening of tissue culture materials in South China.
Infectivity of Tomato Leaf Curl Hainan Virus in Tomato and Tobacco in China
Authors: Zhang Hui , Tian Shoubo , Wu Xuexia , Liu Longzhou , Liu Na , Zhu Weimin
Published: April 2012

Tomato leaf curl Hainan virus (ToLCHnV) was previously reported as a distinct begomovirus infecting tomato in Hainan, China. To investigate the infectivity of ToLCHnV, an infectious clone of ToLCHnV‐[CN: HaNHK7] was constructed and agro‐inoculated into Solanum lycopersicum, Nicotiana benthamiana, Nicotiana glutinosa, Petunia hybrida, Cucumis sativus, Solanum melongena and Capsicum annuum plants; it induced severe leaf curling and crinkling symptoms in these plant species except C. sativus, S. melongena and C. annuum. The induced symptoms were compared with those induced by Papaya leaf curl China virus.
Micafungin for candidiasis
Authors: Pappas Peter G.
Published: April 2012

Invasive candidiasis and mucosal candidiasis are among the most important health care associated infections; in its invasive form, candidiasis is associated with substantial morbidity and mortality. Among the currently available antifungal agents, the echinocandins are the among the most potent agents against Candida species. As a class, these agents are well tolerated and rapidly fungicidal. Among the echinocandins, micafungin has been studied most extensively. This paper reviews the results from the largest studies of micafungin among patients with invasive and esophageal candidiasis, and supports the use of echinocandins in this increasingly common disorder.
Invasive Candida infections in the ICU
Authors: Eggimann Philippe , Barberini Luc , Calandra Thierry , Marchetti Oscar
Published: April 2012

Invasive candidiasis, including candidemia and deep‐seated Candida infections, is a severe opportunistic infection with an overall mortality in ICU patients comparable to that of severe sepsis/septic shock. With an incidence ranging from 5 to 10 cases per 1000 ICU admissions, invasive candidiasis represents 5–10% of all ICU‐acquired infections. Although a high proportion of critically ill patients is colonised with Candida spp., only 5–40% develop an invasive infection. The occurrence of this complication is difficult to predict and an early diagnosis remains a major challenge. Indeed, blood cultures are positive in a minority of cases and often late in the course of infection. New non‐culture based laboratory techniques may contribute to early diagnosis and management of invasive candidiasis. Recent data suggest that prediction rules based on risk factors, clinical and microbiological parameters or monitoring of Candida colonisation may efficiently identify critically ill patients at high risk of invasive candidiasis who may benefit of preventive or pre‐emptive antifungal therapy. In many cancer centres, exposure to azoles antifungals has been associated with an epidemiological shift from Candida albicans to non‐albicans Candida species with reduced antifungal susceptibility or intrinsic resistance. This trend has not been observed in recent surveys on candidemia in non‐immunocompromised ICU patients. Prophylaxis, pre‐emptive or empirical antifungal treatment are possible approaches for prevention or early management of invasive candidiasis. However, the selection of high‐risk patients remains critical for an efficient management aimed at reducing the number needed to treat and thus avoiding unnecessary treatments associated with the emergence of resistance, drug toxicity and costs.
Follicular Dynamics, Interval to Ovulation and Fertility After AI in Short‐Term Progesterone and PGF2α Oestrous Synchronization Protocol in Sheep
Authors: Cox JF , Allende R , Lara E , Leiva A , Díaz T , Dorado J , Saravia F
Published: April 2012

Contents

The study was aimed to assess the influence that short‐term progesterone treatments have on follicular dynamics, oestrus and ovulation in sheep. The treatment was tested thereafter in a field trial to assess its fertility after AI with fresh semen. In a first experiment, 12 ewes without CL were grouped to receive a new (n = 6) or used CIDR (n = 6) for 7 days and blood samples were obtained to follow plasma progesterone profiles. In a second experiment, 39 cycling ewes were synchronized by a 7‐day P4+PGF2α protocol using a new (n = 20) or a 7‐day used CIDR (n = 19). Half of both groups received 400 IU eCG and half remained untreated as controls. Ultrasound ovarian examination and oestrous detection were used to compare follicular dynamics, oestrus and ovulation in both groups. In a third experiment, 288 ewes in 3 farms were synchronized by the short‐term P4+PGF2α+eCG protocol and ewes were AI with fresh semen 24 h after oestrous detection. Lambing performance was used to test the fertility of the treatment. In Experiment 1, ewes with new inserts presented higher P4 concentration than ewes with used inserts throughout the sampling period (p < 0.05) and exhibited a P4 peak at days 1‐2 of the treatment that was not observed in ewes with used inserts. In Experiment 2, ewes treated with new and used inserts show similar ovarian and behavioral traits (p > 0.10). However, ewes treated with eCG show shorter interval to oestrus (p = 0.004) and tend to have larger mature CL (p = 0.06). In Experiment 3, oestrous presentation and lambing performance after AI with fresh semen was considered normal compared to published results. Results suggest that the oestrous synchronization protocol based on P4+PGF2α allows little control of follicular dynamics without compromising fertility after AI with fresh semen provided that eCG is added at the end of the treatment.
Attenuation of cysteamine‐induced duodenal ulcer with Cochinchina momordica seed extract through inhibiting cytoplasmic phospholipase A2/5‐lipoxygenase and activating γ‐glutamylcysteine synthetase
Authors: Choi Ki‐Seok , Kim Eun‐Hee , Hong Hua , Ock Chan Young , Lee Jeong Sang , Kim Joo‐Hyun , Hahm Ki‐Baik
Published: April 2012

Background and Aim:  Cysteamine is a reducing aminothiol used for inducing duodenal ulcer through mechanisms of oxidative stress related to thiol‐derived H2O2 reaction. Cochinchina momordica saponins have been suggested to be protective against various gastric diseases based on their cytoprotective and anti‐inflammatory mechanisms. This study was aimed to document the preventive effects of Cochinchina momordica seed extract against cysteamine‐induced duodenal ulcer as well as the elucidation of its pharmacological mechanisms.

Methods:  Cochinchina momordica seed extract (50, 100, 200 mg/kg) was administrated intragastrically before cysteamine administration, after which the incidence of the duodenal ulcer, ulcer size, serum gastrin level, and the ratio of reduced glutathione (GSH)/ oxidized glutathione disulfide (GSSG) as well as biochemical and molecular measurements of cytoplasmic phospholipase A2 (cPLA2), cyclooxygenase‐2 (COX‐2), 5‐lipoxygenase and the expression of proinflammatory genes including IL‐1β, IL‐6, COX‐2 were measured in rat model. Additional experiments of electron spin resonance measurement and the changes of glutathione were performed.

Results:  Cochinchina momordica seed extract effectively prevented cysteamine‐induced duodenal ulcer in a dose‐dependent manner as reflected with significant decreases in either duodenal ulcerogenesis or perforation accompanied with significantly decreased in serum gastrin in addition to inflammatory mediators including cPLA2, COX‐2, and 5‐lipoxygenase. Cochinchina momordica seed extract induced the expression of γ‐glutamylcysteine synthetase (γ‐GCS)‐related glutathione synthesis as well as significantly reduced the expression of cPLA2. Cochinchina momordica seed extract preserved reduced glutathione through increased expressions of γ‐GCS.

Conclusion:  Cochinchina momordica seed extracts exerted significantly protective effect against cysteamine‐induced duodenal ulcer by either cPLA2 inhibition or glutathione preservation.
Topical application of acetic acid in cytoreduction of gastric cancer. A technical report using mouse model
Authors: Okabe Susumu , Kodama Yosuke , Cao Hailong , Johannessen Helenne , Zhao Chun Mei , Wang Timothy C , Takahashi Rei , Chen Duan
Published: April 2012

Background and Aim:  Application of acetic acid topically to the mucosal or serosal side of the stomach has been well used to create a chronic gastric ulcer model. The aim of the present study was to apply it as a new cytoreductive approach in a mouse model of gastric cancer.

Methods:  A total of 43 genetically engineered mice, the so‐called (INS‐GAS) mice that develop spontaneously gastric cancer at 10–14 months of age, were included. Acetic acid‐induced ulcer method was applied to mice under isofluran anesthesia. The ulcer at the cancer side was made by exposing either the anterior serosal or posterior mucosal side of gastric wall to 0.1 mL of 60% or 100% acetic acid for 30 or 60 s with a cylindrical metal mold (4 mm ID). Route to the serosal side was intra‐abdominal and one to the mucosal side was through a small hole made in the forestomach. The opposite side of gastric wall (no treatment with acetic acid) was used as the corresponding control. After the mice were sacrificed, the stomachs were collected 1, 3, 6 h or 1, 3 and 7 days, postoperatively, and evaluated by visual inspection and histology.

Results:  Gastric cancer was found in both the anterior and posterior walls of the corpus in all 43 mice. Intraluminal pH value was between 11 and 13. Severe necrosis in the cancer was observed in the side exposing to acetic acid, but not in the control side, shortly after the treatment (i.e. within 30 or 60 min). The muscularis mucosa and muscle layers were less damaged, regardless of the side of the treatment. Ulcer formation in the cancer took place 1, 3 or 7 days later. The ulcer depth was sometimes at the muscularis mucosa and muscle layers. At 3 and 7 days, regeneration of epithelial cells was clearly observed in the ulcer margin in the stomach of mice.

Conclusions:  Topical application of acetic acid either from mucosal or serosal surface promptly caused the necrosis of tumor, suggesting the potential approach of this simple and reliable method as a cytoreductive treatment of gastric cancer in patients through endoscopy or laparoscopy.
Analysis of brain activity during visceral stimulation
Authors: Hojo Mariko , Takahashi Toshimitsu , Nagahara Akihito , Sasaki Hitoshi , Oguro Masako , Asaoka Daisuke , Watanabe Sumio
Published: April 2012

Background and Aim:  Functional magnetic resonance imaging (fMRI) is a useful technology for investigating regional metabolic activity in the brain. Many experiments using fMRI have been performed, but because of variations in protocols and analytic techniques, the results vary. When a priori information of the task is known, a model‐based technique, such as statistical parametric mapping, is often used for analysis. In the case of acid stimulation of the esophagus the task model is unclear, so we analyzed brain activity during an acid or isotonic saline infusion to the esophagus using independent component analysis (ICA), which does not depend on a priori information of the task.

Methods:  Six healthy male volunteers (29–45 years) participated in the study. A multi‐lumen catheter was inserted transnasally and side‐hole infusions ports were approximately 15 cm proximal to the lower esophageal sphincter. The experimental protocol was 5‐min interval, 5‐min saline infusion, 5‐min interval, 5‐min 0.1 N HCl, and a final 5‐min interval. After magnetic resonance scanning, fMRI image data were analyzed using group ICA.

Results:  The cerebral regions activated during the first interval, saline infusion, and HCl infusion were the thalamus, insula, cingulate gyri, temporal pole and some parts of the frontal, parietal, temporal and occipital lobes. Activation of the postcentral and precentral gyri occurred during both infusions, but was not observed during the first interval.

Conclusion:  ICA, which can show the cerebral areas activated in relation to liquid in the esophagus, may be a powerful technique for studying the brain's response to visceral stimulation.
Is the clinical malignant phenotype of prostate cancer a result of a highly proliferative immune‐evasive B7‐H3‐expressing cell population?
Authors: Liu Yishan , Vlatkovic Ljiljana , Sæter Thorstein , Servoll Einar , Waaler Gudmund , Nesland Jahn M , Giercksky Karl‐Erik , Axcrona Karol
Published: April 2012

Objectives:  To assess the expression of the cell surface protein B7‐H3 in prostate cancer, and its association to clinically relevant parameters after radical prostatectomy and to the proliferation marker Ki‐67.

Methods:  Radical prostatectomy specimens from a cohort of 130 patients with a median clinical follow up of 8 years were used for the analysis. The expression of B7‐H3 and the proliferation marker Ki‐67, as well as other standard clinicopathological parameters, were evaluated.

Results:  A high expression of B7‐H3 was associated with pathological stage T3a and T3b, high Gleason score, extraprostatic extension, seminal vesicle invasion and high proliferative activity. Univariable analysis showed that a high expression level of B7‐H3 was also correlated with biochemical failure and clinical relapse, and with the expression of Ki‐67. A high expression level of Ki‐67 was associated with clinical progression and a tendency towards higher rates of prostate‐specific antigen relapse in multivariate analyses.

Conclusions:  Our findings show that a high expression level of B7‐H3 in prostate cancer correlates with the expression of the proliferation marker Ki‐67, biochemical failure and clinical relapse. Thus, expression of the cell surface molecule B7‐H3 adds to the malignant phenotype of prostate cancer cells expressing high levels of Ki‐67. The impact of B7‐H3 function on prostate cancer and its potential role in immunotherapy should be explored further.
Early ileostomy closure: is there a downside?
Authors: Omundsen Mark , Hayes Julian , Collinson Rowan , Merrie Arend , Parry Bryan , Bissett Ian
Published: April 2012

Background:  A loop ileostomy is a common adjunct to formation of a low colorectal anastomosis. However, it is not without significant physical and psychological morbidity, and financial cost. Feasibility of early closure during the index admission has previously been reported. This pilot study examines the safety of early closure compared with traditional timing.

Methods:  A retrospective audit of consecutive ileostomy closures performed in a tertiary colorectal unit from January 2008 to January 2010. Demographic data, treatment data and complications were collected by a single investigator from a prospective clinical audit database and hospital records. Patients undergoing early closure (within 10 days of the index operation) were compared with the traditional timing group.

Results:  A total of 93 patients underwent closure of loop ileostomy during the study period (44 female; 49 male). Median patient age was 61 years. Nineteen patients (20%) underwent early closure. There were six wound infections in the early closure group (32%), and five in the traditional timing group (7%) (P= 0.01). There was no significant difference in other complications between the two groups. There was a significantly shorter overall hospital stay in the early closure group with a median stay of 14 days (range 10–26), and in the traditional timing group a median stay of 17 days (range 7–80) (P= 0.05). Seven patients (9%) in the traditional timing group had ileostomy‐related complications.

Conclusion:  Early ileostomy closure appears to be associated with an increased wound infection rate but otherwise appears to be a safe alternative to traditional closure in selected patients and may reduce overall hospital stay.
Queensland Lung Cancer Screening Study: rationale, design and methods
Authors: Marshall H. M. , Bowman R. V. , Crossin J. , Lau M. A. , Slaughter R. E. , Passmore L. H. , McCaul E. M. , Courtney D. A. , Windsor M. N. , Yang I. A. , Smith I. R. , Keir B. J. , Hayes T. J. , Redmond S. J. , Zimmerman P. V. , Fong K. M.
Published: April 2012

Background

Lung cancer is the leading cause of cancer‐related mortality in Australia. Screening using low‐dose computed tomography (LDCT) can reduce lung cancer mortality. The feasibility of screening in Australia is unknown. This paper describes the rationale, design and methods of the Queensland Lung Cancer Screening Study.

Aims

The aim of the study is to describe the methodology for a feasibility study of lung cancer screening by LDCT in Australia.

Methods

The Queensland Lung Cancer Screening Study is an ongoing, prospective observational study of screening by LDCT at a single tertiary institution. Healthy volunteers at high risk of lung cancer (age 60–74 years; smoking history ≥30 pack years, current or quit within 15 years; forced expiratory volume in 1s ≥50% predicted) are recruited from the general public through newspaper advertisement and press release. Participants receive a LDCT scan of the chest at baseline, year 1 and year 2 using a multidetector helical computed tomography scanner and are followed up for a total of 5 years. Feasibility of screening will be assessed by cancer detection rates, lung nodule prevalence, optimal management strategies for lung nodules, economic costs, healthcare utilisation and participant quality of life.

Conclusions

Studying LDCT screening in the Australian setting will help us understand how differences in populations, background diseases and healthcare structures modulate screening effectiveness. This information, together with results from overseas randomised studies, will inform and facilitate local policymaking.
Uncertainty in action‐value estimation affects both action choice and learning rate of the choice behaviors of rats
Authors: Funamizu Akihiro , Ito Makoto , Doya Kenji , Kanzaki Ryohei , Takahashi Hirokazu
Published: April 2012

The estimation of reward outcomes for action candidates is essential for decision making. In this study, we examined whether and how the uncertainty in reward outcome estimation affects the action choice and learning rate. We designed a choice task in which rats selected either the left‐poking or right‐poking hole and received a reward of a food pellet stochastically. The reward probabilities of the left and right holes were chosen from six settings (high, 100% vs. 66%; mid, 66% vs. 33%; low, 33% vs. 0% for the left vs. right holes, and the opposites) in every 20–549 trials. We used Bayesian Q‐learning models to estimate the time course of the probability distribution of action values and tested if they better explain the behaviors of rats than standard Q‐learning models that estimate only the mean of action values. Model comparison by cross‐validation revealed that a Bayesian Q‐learning model with an asymmetric update for reward and non‐reward outcomes fit the choice time course of the rats best. In the action‐choice equation of the Bayesian Q‐learning model, the estimated coefficient for the variance of action value was positive, meaning that rats were uncertainty seeking. Further analysis of the Bayesian Q‐learning model suggested that the uncertainty facilitated the effective learning rate. These results suggest that the rats consider uncertainty in action‐value estimation and that they have an uncertainty‐seeking action policy and uncertainty‐dependent modulation of the effective learning rate.
HbA1c‐based diabetes diagnosis among patients with glucokinase mutation (GCK‐MODY) is affected by a genetic variant of glucose‐6‐phosphatase (G6PC2)
Authors: Borowiec M. , Fendler W. , Dusatkova P. , Antosik K. , Pruhova S. , Cinek O. , Mysliwiec M. , Jarosz‐Chobot P. , Malecki M. T. , Mlynarski W.
Published: April 2012

Aims  Genetic variation at the rs560887 locus of the glucose‐6‐phosphatase, catalytic 2 gene (G6PC2) is known to affect regulation of fasting glycaemia. We determined the rs560887 genotype of patients with monogenic diabetes and glucokinase gene mutations (GCK‐MODY) and correlated the genotypes with HbA1c levels.

Methods  Patients from families with GCK‐MODY were recruited from two large cohorts from Poland (n = 128) and the Czech Republic (n = 154). Genotypes at the rs560887 polymorphic site in G6PC2 were examined using real‐time quantitative polymerase chain reaction. The effect of rs560887 genotype on age at diagnosis of GCK‐MODY and initial HbA1c levels were evaluated separately within both cohorts. Following that, a meta‐analysis of rs560887 genotype–HbA1c associations of both Polish and Czech cohorts was performed to confirm homogeneity of findings and validate cohort‐specific results.

Results  GG homozygosity at rs560887 was associated with marginally elevated HbA1c levels (P = 0.07 in both cohorts). The effects observed in both groups were very homogeneous (Q = 0.18; P = 0.68). Meta‐analysis showed that GG homozygosity at rs560887 was associated with mean HbA1c levels higher by 2.4 mmol/mol (0.24%), 95% CI 0.5–4.4 mmol/mol (0.05–0.44%) than in individuals with other genotypes. Additionally, meta‐analysis of both cohorts showed that GG homozygous individuals had higher odds of reaching the 48 mmol/mol (6.5%) diagnostic threshold of diabetes; (odds ratio 1.90; 95% CI 1.07–3.36; P = 0.03). No such effects were observed for age at diagnosis of diabetes.

Conclusions  Variation at the rs560887 locus of G6PC2 is associated with worse glycated haemoglobin levels in individuals with GCK mutations; GG homozygotes are more likely to meet diagnostic criteria for diabetes based on HbA1c level.