bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitumor effect of berberine against primary effusion lymphoma via inhibition of NF‐κB pathway
Authors: Goto Hiroki , Kariya Ryusho , Shimamoto Masako , Kudo Eriko , Taura Manabu , Katano Harutaka , Okada Seiji
Published: February 2012

Primary effusion lymphoma (PEL) is an infrequent and distinct entity among the aggressive non‐Hodgkin B cell lymphomas that occurs predominantly in patients with advanced AIDS. It shows serous lymphomatous effusion in body cavities, and is resistant to conventional chemotherapy with a poor prognosis. Thus, the optimal treatment for PEL is not well defined and there is a need for novel agents. PEL has been recognized as the tumor caused by Kaposi sarcoma‐associated herpes virus/human herpes virus‐8 (KSHV/HHV‐8), and nuclear factor (NF)‐κB activation plays a critical role in the survival and growth of PEL cells. In this study, we assessed the antitumor effect of berberine, a naturally occurring isoquinoline alkaloid, on this pathway. The methylthiotetrazole assay showed that cell proliferation in the PEL cell lines was inhibited by berberine. Berberine also induced caspase‐dependent apoptosis and suppressed NF‐κB activity by inhibiting IκB kinase (IKK) phosphorylation, IκB phosphorylation and IκB degradation, upstream targets of the NF‐κB pathway, in PEL cells. In a xenograft mouse model that showed ascites and diffuse organ invasion of PEL cells, treatment with berberine inhibited the growth and invasion of PEL cells significantly compared with untreated mice. These results show that the suppression of NF‐κB is a molecular target for treating PEL, and berberine is a potential antitumor agent for PEL. (Cancer Sci 2012; 103: 775–781)
Adenovirus‐mediated gene transfer of tissue factor pathway inhibitor‐2 inhibits gallbladder carcinoma growth in vitro and in vivo
Authors: Qin Yiyu , Zhang Shenglai , Gong Wei , Li Jiyu , Jia Jianguang , Quan Zhiwei
Published: February 2012

Tissue factor pathway inhibitor‐2 (TFPI‐2) has been identified as a tumor suppressor gene in several types of cancers, but its role in gallbladder carcinoma (GBC) is yet to be determined. In the present study, TFPI‐2 expression in GBC tissues was examined, and its inhibitory activities against GBC growth were evaluated in vitro and in vivo after adenovirus‐mediated gene transfer of TFPI‐2 (Ad5‐TFPI‐2) was constructed to restore the expression of TFPI‐2 in GBC cell lines (GBC‐SD, SGC‐996, NOZ) and xenograft tumors. Immunohistochemical staining showed that TFPI‐2 was significantly downregulated in GBC tissue specimens. Ad5‐TFPI‐2 could significantly inhibit GBC growth both in vitro and in vivo. Apoptosis analysis and western blotting assay demonstrated that Ad5‐TFPI‐2 could induce the apoptosis of both GBC cell lines and tissues by promoting the activities of cytochrome c, Bax, caspase‐3 and ‐9 and suppressing Bcl‐2 activity. These data indicated that TFPI‐2 acts as a tumor suppressor in GBC, and may have a potential role in gene therapy for GBC. (Cancer Sci 2012; 103: 723–730)
Dickkopf‐1 inhibits epithelial‐mesenchymal transition of colon cancer cells and contributes to colon cancer suppression
Authors: Qi Lisha , Sun Baocun , Liu Zhiyong , Li Hui , Gao Jun , Leng Xue
Published: February 2012

This study aimed to determine the expression pattern of dickkopf‐1 (Dkk1), a potent inhibitor of Wnt signaling, in colon cancer and to assess the function and mechanism of Dkk1 in tumor progression in vitro and in vivo. We detected the protein expression of Dkk1 and some epithelial‐mesenchymal transition (EMT)‐associated markers (E‐cadherin, vimentin and β‐catenin) in 217 tissue samples of human colon cancer, upregulated Dkk1 expression in HCT116 colon cancer cells, and established a nude mouse xenograft model. Dkk1 protein overexpression was inversely related to tumor grade and the presence of metastasis and recurrence of colon cancer. Notably, the expression of Dkk1 was concomitant with reduced immunohistochemical features of EMT (e.g. increased expression of epithelial marker E‐cadherin, decreased expression of mesenchymal marker vimentin, and cytoplasmic distribution of β‐catenin). Furthermore, Dkk1 overexpression resulted in restoration of the epithelial phenotype, decreased expression of EMT transcription factors Snail and Twist, and decreased expression of markers suggestive of intestinal stem cells (e.g. cluster of differentiation 133 [CD133] and leucine‐rich‐repeat‐containing G‐protein‐coupled receptor 5 [Lgr5]). Functional analysis showed overexpression of Dkk1 reduced proliferation, migration, and invasion of colon cancer cells. Moreover, upregulation of Dkk1 led to decreased tumor‐initiating ability and suppressed colon tumor growth in nude mice. Our findings indicate that Dkk1 can suppress the progression of colon cancer, possibly through EMT inhibition, and could therefore serve as a target for tumor therapy. (Cancer Sci 2012; 103: 828–835)
Epidermal growth factor receptor R521K polymorphism shows favorable outcomes in KRAS wild‐type colorectal cancer patients treated with cetuximab‐based chemotherapy
Authors: Hsieh Yao‐Yu , Tzeng Cheng‐Hwai , Chen Ming‐Huang , Chen Po‐Min , Wang Wei‐Shu
Published: February 2012

The R521K polymorphism of epidermal growth factor receptor has attenuated affinity in ligand binding and proto‐oncogene induction, which may affect the efficacy of cetuximab. We analyzed the effect of this polymorphism on the outcome of 112 patients with KRAS wild‐type metastatic colorectal carcinoma treated with first‐line cetuximab plus FOLFOX‐4. The associations of this polymorphism with vascular endothelial growth factor (VEGF) expression and clinicopathologic characteristics were also examined. The results showed that the frequencies of the G/G, G/A, and A/A genotypes were 32.1% (n = 36), 42.9% (n = 48), and 25.0% (n = 28), respectively. A marked decrease in VEGF expression levels (66.7% vs 28.9%, P < 0.01) was observed in patients with 521A allele variants (Arg/Lys or Lys/Lys), which were associated with a decreased tumor size (55.6% vs 31.6%, P = 0.02), good histological differentiation (63.9% vs 85.5%, P = 0.01), decreased lymphovascular invasion (69.4% vs 39.5%, P < 0.01), and a higher response rate to cetuximab plus FOLFOX treatment (55.6% vs 78.9%, P = 0.01). In addition, this polymorphism was associated with a longer progression‐free period (P = 0.001) and overall survival (P = 0.001). By multivariate analysis, this polymorphism was also identified as an independent prognostic factor. These data suggest that the R521K polymorphism of epidermal growth factor receptor, by reducing its activation and a consequential downregulation of its target genes, including VEGF, could be a key determinant of an increased response to cetuximab‐based chemotherapy and a longer survival for KRAS wild‐type colorectal carcinoma patients. (Cancer Sci 2012; 103: 791–796)
Ability of non‐invasive intermittent blood pressure monitoring and a continuous non‐invasive arterial pressure monitor (CNAP™) to provide new readings in each 1‐min interval during elective caesarean section under spinal anaesthesia
Authors: McCarthy T. , Telec N. , Dennis A. , Griffiths J. , Buettner A.
Published: February 2012

We compared the ability of automated non‐invasive intermittent oscillometric blood pressure monitoring with a new device, CNAPTM (continuous non‐invasive arterial pressure) to provide a new blood pressure reading in each 1‐min interval between spinal anaesthesia and delivery during caesarean section. We also compared the accuracy of continuous non‐invasive arterial pressure readings with non‐invasive blood pressure measurements before spinal anaesthesia. Fifty‐nine women participated. The non‐invasive and continuous non‐invasive monitors displayed new blood pressure readings in a mean of 82% (11%) and 83% (13%) (p = 0.97) of the one‐minute intervals between spinal anaesthesia and delivery, respectively. Continuous non‐invasive arterial pressure was more likely to fail on two or more consecutive minutes (p = 0.001). From the pre‐spinal readings, the mean bias, defined as non‐invasive – continuous non‐invasive arterial pressure, and limits of agreement (±2SD mean bias) for systolic, diastolic and mean blood pressure respectively were +1.3 (±26.0), −2.9 (±21.8) and +2.6 (±20.4) mmHg. The new monitor has disadvantages compared with conventional non‐invasive intermittent blood pressure monitoring.
Investigation of the haemodynamic effects of exenatide in healthy male subjects
Authors: Mendis Buddhike , Simpson Elizabeth , MacDonald Ian , Mansell Peter
Published: February 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Large clinical trials show that chronic use of GLP‐1 agonists cause a fall in blood pressure independent of weight loss. Animal studies have shown acute haemodynamic and vasodilator effects of these drugs. The exact mechanism of the blood pressure drop and acute cardiovascular effects has not been studied in humans.

WHAT THIS STUDY ADDS

• This study shows that exenatide also has acute haemodynamic effects in humans. This study demonstrates direct vascular effects and potentially direct cardiac effects. This will enable future studies to look at GLP‐1 agonists as aids in the treatment of cardiovascular disease in type 2 diabetes.

AIMS In clinical studies of glucagon‐like peptide‐1 (GLP‐1) agonists used in the management of patients with type 2 diabetes, there is often a small accompanying fall in blood pressure. The mechanism underlying this effect is not known, although exenatide, a GLP‐1 mimetic, has acute regional vasodilator properties in rats. We have therefore studied the haemodynamic effects of exenatide in healthy male volunteers.

METHODS We compared the effects of a single 10 µg subcutaneous injection of exenatide with placebo in a double‐blind, randomized, crossover study. For 2 h after dosing, haemodynamic measurements were made using a Finometer, venous occlusion plethysmography and Doppler ultrasound. The urine sodium : creatinine excretion ratio was determined.

RESULTS At the end of the study when exenatide was compared with placebo, heart rate had risen by a mean of 8.2 (95% CI 4.2, 12.2, P < 0.01) beats min−1, cardiac output by a mean of 1.2 (95% CI 0.42, 20.3, P < 0.05) l min−1 and total peripheral resistance had fallen by 120 (95% CI −8, −233, P < 0.05) dyn s cm−5.There were no differences in blood pressure. The urinary sodium : creatinine ratio was increased by mean 12.4 (95% CI 4.6, 20.2, P < 0.05) mmol mmol−1 when exenatide was compared with placebo.

CONCLUSIONS Exenatide has significant haemodynamic effects in healthy volunteers. The results of this study are consistent with exenatide having both vasodilator and natriuretic properties. The vascular changes may contribute to the hypotensive effect of exenatide when used chronically in patients with diabetes.
Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma
Authors: Huang Congfa , Sun Zhijun , Sun Yan , Chen Xinming , Zhu Xiaojie , Fan Chengchao , Liu Bing , Zhao Yifang , Zhang Wenfeng
Published: February 2012

Huang C, Sun Z, Sun Y, Chen X, Zhu X, Fan C, Liu B, Zhao Y & Zhang W  (2012) Histopathology 60, 793–803

Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma

Aims:  We evaluated the association of ligand cyclophilin A (CypA) and receptor CD147 with hypoxia, angiogenesis, lymph node metastasis and prognosis of patients with tongue squamous cell carcinoma (TSCC).

Methods and results:  We studied the expression of CypA, CD147, hypoxia‐inducible factor 1α (HIF‐1α), vascular endothelial growth factor A and C (VEGF‐A and VEGF‐C) protein by immunohistochemistry in 80 specimens of TSCC. CypA, CD147, HIF‐1α, VEGF‐A and VEGF‐C were overexpressed in TSCCs, and were significantly higher than those in normal oral mucosa tissues (P < 0.01). Increased ligand CypA and receptor CD147 correlated significantly with expression of HIF‐1α, VEGF‐A and VEGF‐C. A significant relationship between VEGF‐A and VEGF‐C was also detected (P < 0.01). Patients with overexpression of CypA, CD147, HIF‐1α and VEGF‐C had significantly worse overall survival (P < 0.05) using Kaplan–Meier analysis. Multivariate Cox regression analysis showed that HIF‐1α, recurrence and distant metastasis were independent prognostic factors on overall survival in TSCC patients.

Conclusions:  The association of expression of ligand CypA and receptor CD147 with carcinogenesis, hypoxia, angiogenesis, metastasis and prognosis of TSCC suggests that ligand CypA and receptor CD147 may have prognostic value and could be regarded as potential therapeutic targets in TSCC.
Distinctive characteristics of bronchial reticular basement membrane and vessel remodelling in chronic obstructive pulmonary disease (COPD) and in asthma: they are not the same disease
Authors: Soltani Amir , Muller Hans Konrad , Sohal Sukhwinder S , Reid David W , Weston Steve , Wood‐Baker Richard , Walters Eugene Haydn
Published: February 2012

Soltani A, Muller H K, Sohal S S, Reid D W, Weston S, Wood‐Baker R & Walters E H  (2012) Histopathology 60, 964–970

Distinctive characteristics of bronchial reticular basement membrane and vessel remodelling in chronic obstructive pulmonary disease (COPD) and in asthma: they are not the same disease

Aims:  This study compared reticular basement membrane (Rbm) and vascular remodelling within the bronchial mucosa of subjects with chronic obstructive pulmonary disease (COPD) with those from patients with asthma, to test the ‘Dutch hypothesis’ of whether these are essentially the same or different pathological conditions.

Methods and results:  Bronchoscopic biopsies were stained with anti‐collagen IV antibody; 18 current smoking COPD, 10 symptomatic asthmatics and 13 healthy non‐smoking controls were studied. The Rbm in COPD was fragmented, non‐homogeneous, variable in thickness and hypervascular, whereas in asthma the Rbm was compact and homogeneous with no evidence of increased vascularity compared to controls. Length of Rbm splitting presented as percentage of Rbm length was used to measure fragmentation; it was greater in COPD than in controls and asthmatics [median (range) 20.7% (0.4–68.5) versus 5.3% (0.0–21.7) versus 1.5% (0.0–15.1), P < 0.001]. The number of Rbm vessels/mm Rbm [median (range) 10.1 (1.6–23.0) versus 4.5 (0.0–26.4) versus 4.4 (0.4–8.1), P < 0.01] and area of Rbm vessels, μm2/mm Rbm [median (range) 953 (115–2456) versus 462 (0–3263) versus 426 (32–2216), P < 0.05] was also increased in COPD compared to normal subjects and asthmatics.

Conclusions:  The characteristics of Rbm remodelling are quite different in asthma and COPD.
Bcl‐2 and BLIMP‐1 expression predict worse prognosis in gastric diffuse large B cell lymphoma (DLCBL) while other markers for nodal DLBCL are not useful
Authors: Martin‐Arruti Maialen , Vaquero Manuel , Díaz de Otazu Ramón , Zabalza Iñaki , Ballesteros Javier , Roncador Giovanna , García‐Orad Africa
Published: February 2012

Martin‐Arruti M, Vaquero M, Díaz de Otazu R, Zabalza I, Ballesteros J, Roncador G & García‐Orad A  (2012) Histopathology 60, 785–792

Bcl‐2 and BLIMP‐1 expression predict worse prognosis in gastric diffuse large B cell lymphoma (DLCBL) while other markers for nodal DLBCL are not useful

Aims:  Previous studies have identified clinicopathological and immunohistochemical differences among diffuse large B cell lymphomas (DLBCL) as a function of disease location. Nevertheless, there is a continuing tendency to generalize the prognostic value of various identified markers without taking into account tumour site. Accordingly, we analysed the prognostic value of several of the immunohistochemical markers that have been proposed for nodal DLBCL in a group of patients with gastric DLBCL.

Methods and results:  Using histochemical methods, CD10, Bcl‐6, Gcet1, MUM‐1, Bcl‐2 and BLIMP‐1 expression was investigated in 43 cases of gastric DBLCL. As in nodal DLBCLs, expression of BLIMP‐1, and of Bcl‐2 in non‐germinal centre B cell‐like (non‐GCB) patients, was associated with a worse prognosis. However, unlike nodal DBLCL, there was no significant association of prognosis with expression of CD10, Bcl‐6, Gcet1 or MUM‐1, or with categorization according to Hans or Muris algorithms.

Conclusions:  Although most markers of prognosis in nodal DLBCL are not useful indicators for gastric DLBCL, Bcl‐2 or BLIMP‐1 expression does correlate with worse prognosis. These data support the notion that clinicopathological features in DLBCL vary according to the disease location.
Cumulative risk assessment of phthalate exposure of Danish children and adolescents using the hazard index approach
Authors: Søeborg T. , Frederiksen H. , Andersson A. M.
Published: February 2012

Human risk assessment of chemicals is traditionally presented as the ratio between the actual level of exposure and an acceptable level of exposure, with the acceptable level of exposure most often being estimated by appropriate authorities. This approach is generally sound when assessing the risk of individual chemicals. However, several chemicals may concurrently target the same receptor, work through the same mechanism or in other ways induce the same effect(s) in the body. In these cases, cumulative risk assessment should be applied. The present study uses biomonitoring data from 129 Danish children and adolescents and resulting estimated daily intakes of four different phthalates. These daily intake estimates are used for a cumulative risk assessment with anti‐androgenic effects as the endpoint using Tolerable Daily Intake (TDI) values determined by the European Food Safety Authorities (EFSA) or Reference Doses for Anti‐Androgenicity (RfD AA) determined by Kortenkamp and Faust [Int J Androl 33 (2010) 463] as acceptable levels of exposure. United States Environmental Protection Agency Reference Doses (US EPA RfD) could not be used as none of them identifies anti‐androgenic effects as the most sensitive endpoint for the phthalates included in this article. Using the EFSA TDI values, 12 children exceeded the hazard quotient for the sum of di‐n‐butyl phthalate and di‐iso‐butyl phthalate (∑DBP(i+n)) and one child exceeded the hazard quotient for di‐(2‐ethylhexyl)phthalate (DEHP). Nineteen children exceeded the cumulated hazard index for three phthalates. Using the RfD AA values, one child exceeded the hazard quotient for DEHP and the same child exceeded the cumulated hazard index for four phthalates. The EFSA TDI approach thus is more restrictive and identifies ∑DBP(i+n) as the compound(s) associated with the greatest risk, while DEHP is the compound associated with the greatest risk when using the RfD AA approach.
Effect of fermentation on the nutritive value of maize
Authors: Cui Li , Li Da‐jing , Liu Chun‐quan
Published: February 2012

The effects of fermentation on protein, in vitro protein digestibility (IVPD), amino acid, total phenolics, phytic acid and colour values of four maize cultivars (two bi‐colour waxy corn and two super sweet corn), namely Jing Tian Zi Hua Nuo NO. 2, Jing Tian NO. 3, Bright Jean and Su Ke Hua Nuo 2008, were determined and compared with those of their unfermented counterparts. Results showed that fermentation caused significant increase in protein (43.5% largest increase), most kind of amino acid (131.5% largest increase in lysine content) and total phenolic content (23.4% largest increase), but significant reduction in phytic acid content (24.3% largest reduction) of four maize cultivars. The IVPD of four maize cultivars, except Suke2008, did not change significantly. Colour values of two waxy corn were resulted in the increase in a‐values and reduction in L‐values.
Effect of different thermal treatments and freezing on the antioxidant constituents and activity of two Bahraini date cultivars (Phoenix dactylifera L.)
Authors: Allaith Abdulameer A. , Ahmed Safa H. , Jafer Fatima
Published: February 2012

Effect of several thermal treatments and freezing on the antioxidant properties of fresh dates of two cultivars (namely Khalas and Khunaizi) was investigated. Levels of phenolics, total flavonoids and anthocyanins were estimated. Antioxidant activity was measured by ferric reducing ability of plasma (FRAP), diphenylpicrylhydrazyl (DPPH) and deoxyribose assays. Results indicate differential effects of the treatments on the phenolic constituents. Generally, mild treatments and freezing significantly increased the level of total phenolics in both cultivars by 80–180%. All treatments increased in the level of free phenolics in Khalas (between 10% and 540%). In khunaizi, the level of bound phenolic increased in all treatments (9–250%). The level of total flavonoids increased by almost all treatments in both cultivars (33–500%). Most treatments increased the FRAP value in khalas (up to 80%). Significant differences were noticed among the various treatments with regard to DPPH and OH radicals quenching capacities. Results may find applications in food science, food technology and nutrition.
Management of ‘double teeth’ in children and adolescents
Authors: SHAH PURVI , CHANDER JUNE M. L. , NOAR JOSEPH , ASHLEY PAUL F.
Published: February 2012

International Journal of Paediatric Dentistry 2012; 22: 419–426

Background.  Abnormally, large teeth are often referred to as ‘double teeth’. These can pose numerous challenges for the clinician. There is no published protocol on the management of double teeth.

Aim.  To review the published literature and also patients managed at the Eastman Dental Hospital (EDH) and to develop a clinical protocol for the management of double teeth in children and adolescents.

Design.  Literature was searched (Medline and Embase) and data collated. Patient notes of cases managed at the EDH were reviewed.

Results.  Eighty‐one teeth from 53 papers and 22 patients were included in the review. Success criteria were only reported in 32 papers and were variable. Twenty‐three papers had no follow‐up period. The main factor in determining the management of a double tooth was root and root canal system morphology. The treatment of choice in teeth with separate roots was hemisection and in those with a single root was crown modification or extraction.

Conclusion.  It was not possible to determine the best management strategies because of the variable reporting in the literature. The authors have proposed a protocol for management and a data collection sheet for essential information needed when reporting on double teeth cases.
Estimating Brownian motion dispersal rate, longevity and population density from spatially explicit mark–recapture data on tropical butterflies
Authors: Tufto Jarle , Lande Russell , Ringsby Thor‐Harald , Engen Steinar , Sæther Bernt‐Erik , Walla Thomas R. , DeVries Philip J.
Published: February 2012

1. We develop a Bayesian method for analysing mark–recapture data in continuous habitat using a model in which individuals movement paths are Brownian motions, life spans are exponentially distributed and capture events occur at given instants in time if individuals are within a certain attractive distance of the traps.

2. The joint posterior distribution of the dispersal rate, longevity, trap attraction distances and a number of latent variables representing the unobserved movement paths and time of death of all individuals is computed using Gibbs sampling.

3. An estimate of absolute local population density is obtained simply by dividing the Poisson counts of individuals captured at given points in time by the estimated total attraction area of all traps. Our approach for estimating population density in continuous habitat avoids the need to define an arbitrary effective trapping area that characterized previous mark–recapture methods in continuous habitat.

4. We applied our method to estimate spatial demography parameters in nine species of neotropical butterflies. Path analysis of interspecific variation in demographic parameters and mean wing length revealed a simple network of strong causation. Larger wing length increases dispersal rate, which in turn increases trap attraction distance. However, higher dispersal rate also decreases longevity, thus explaining the surprising observation of a negative correlation between wing length and longevity.
Late Pleistocene lineage divergence among populations ofNeolitsea sericea(Lauraceae) across a deep sea‐barrier in the Ryukyu Islands
Authors: Zhai Sheng‐Nan , Comes Hans Peter , Nakamura Koh , Yan Hai‐Fei , Qiu Ying‐Xiong
Published: February 2012

Aim Our goals were: (1) to assess the population genetic structure and demographic divergence history of a bird‐dispersed tree,Neolitsea sericea, endemic to East Asian land‐bridge islands; and (2) to interpret the results in the light of controversies over the dating and configurations of land bridges through the Japanese Ryukyu Island Arc.

Location Japan–Ryukyu–Taiwan Island Arc and Chinese/Korean offshore islands.

Methods We applied 10 nuclear microsatellites (nSSRs) and one chloroplast (cp) DNA sequence marker (psbA–trnH intergenic spacer) to 31 populations (397 and 326 individuals, respectively) from throughout the species’ range to infer current patterns of genetic diversity and structure, and pollen‐to‐seed migration ratios (r). A coalescent‐based isolation‐with‐migration (IM) model was applied to the combined nSSR/cpDNA data set to estimate lineage divergence times and population demographic parameters.

Results The geographic structure of nSSRs and the distribution of most cpDNA haplotypes revealed two distinct lineages located in areas north and south of the ‘Tokara Gap’, a narrow (c. 37 km wide) but deep (> 1000 m) sea‐strait between the northern and central Ryukyus. Based on the IM analyses, we (1) dated the divergence of these northern and southern lineages toc. 0.07 Ma (90% highest posterior density interval: 0.02–0.38 Ma); (2) estimated a slightly smaller effective population size for the northern compared to the southern lineage; and (3) recovered only trivial signals of post‐divergence gene flow between them.

Main conclusions The estimated divergence time for northern and southern lineages is consistent with geological evidence for the existence of land connections in the Tokara region during cold stages of the latest Pleistocene; it is thus incompatible with an ‘ancient sea‐barrier hypothesis’ for the Ryukyu Arc, where we would have expected much older divergences related to the initial formation of the Tokara and Kerama tectonic straits during the Pliocene. Multiple factors are likely to have had a role in the divergence ofN. sericea, including not only land‐bridge submergence, but also island configuration, and/or constraints on adaptation along a latitudinal temperature gradient.
Feeding difficulties in children with inherited metabolic disorders: a pilot study
Authors: Evans S. , Alroqaiba N. , Daly A. , Neville C. , Davies P. , MacDonald A.
Published: February 2012

How to cite this article: Evans S., Alroqaiba N., Daly A., Neville C., Davies P. & MacDonald A. (2012) Feeding difficulties in children with inherited metabolic disorders (IMD): a pilot study. J Hum Nutr Diet. 25, 209–216

Background:  In children with inherited metabolic disorders (IMD), feeding difficulties are often assumed to be inherent, although there is little evidence describing their frequency or severity. The present study aimed to describe feeding patterns/difficulties among children with IMD on protein‐restricted diets from one centre.

Methods:  Data from an observational, pilot study of 20 IMD children, nine females (median age, 2.7 years; range, 1–6 years) were compared with data obtained from a retrospective historical group of 15 healthy children (HC), 12 females, aged 1–5 years (median 3.0 years). Caregivers completed a feeding assessment questionnaire, and three separate video recordings were taken of each child eating at home.

Results:  The main feeding problems identified by the caregivers’ questionnaire in the IMD group (compared to HC) were: poor appetite (55% versus 7%; P = 0.004), limited food variety (55% versus 27%; P = 0.04) and lengthy mealtimes (70% versus 20%; P = 0.006). During mealtimes, children from the IMD group were more likely to vomit, exhibit negative behaviour, get distracted and self‐feed less often. From video recordings of meals, although the median meal duration was similar for the two groups (18 min IMD versus 16 min HC), the HC ate twice the quantity of food (3.4 mouthfuls min−1 versus 1.5 mouthfuls min−1; P < 0.001). During mealtimes, IMD caregivers were less likely to talk to their children (median parent to child communications: IMD group, seven in 10 min; HC, 17 in 10 min). Eighty‐three percent of IMD children regularly ate alone.

Conclusions:  In children with IMD on protein restrictions, severe feeding difficulties were common. Caregivers need to focus more attention on the social aspects of feeding. Further larger scale studies are required.
Quality of life and stimulus perception in patients’ rehabilitated with complete denture
Authors: GOIATO M. C. , BANNWART L. C. , MORENO A. , Dos SANTOS D. M. , MARTINI A. P. , PEREIRA L. V.
Published: February 2012

Summary  The objective of this study was to evaluate and correlate quality of life (QoL), and stimulus perception of complete denture users, before and after the insertion of new prostheses. We selected 60 patients using bimaxillary complete conventional dentures who needed to replace their prostheses. During anamnesis, we collected demographic data and applied the Oral Health Impact Profile for Edentulous Patients (OHIP‐EDENT) questionnaire and stimulus perception questionnaire (PERCEPTION). Before installation of new prostheses, the patients responded to OHIP‐EDENT questionnaire, and on the day of installation, they responded to PERCEPTION questionnaire. At the patients’ 3‐month follow‐up, we re‐administered the OHIP‐EDENT and PERCEPTION questionnaires. The Wilcoxon and MacNemar tests were used to compare patient responses between the time points analysed. Most of the OHIP‐EDENT items showed a highly significant impact of the new prostheses on oral health (P ≤ 0·003). The PERCEPTION questionnaire data indicated that the patients experienced significant improvements (P < 0·05) in terms of their sensations with the new prostheses. Cross‐lagged data analysis did not show any causality between the OHIP‐EDENT and PERCEPTION questionnaires (ZPF test, P = 0·772). We concluded that the treatment was effective with respect to the patients’ QoL and their adaptation to the new prostheses.
Retinoic acids and hepatic stellate cells in liver disease
Authors: Lee Young‐Sun , Jeong Won‐Il
Published: February 2012

Quiescent hepatic stellate cells (HSCs) in healthy liver store 80% of total liver retinols and release them depending on the extracellular retinol status. However, HSCs activated by liver injury lose their retinols and produce a considerable amount of extracellular matrix, subsequently leading to liver fibrosis. Emerging evidence suggests that retinols and their metabolites such as retinoic acids (RAs) contribute to liver regeneration, fibrosis and tumor. However, it is not clear yet why HSCs lose retinol, which enzymes are involved in the retinol metabolism of HSCs and what function of retinol metabolites on HSCs upon liver injury. Recently, our group and collaborators have demonstrated that during activation, HSCs not only lose retinols but also metabolize them into RAs by alcohol dehydrogenases and retinaldehyde dehydrogenases. As transcriptional factors, metabolized RAs induce retinoic acid early inducible‐1 and suppressor of cytokine signaling 1 in HSCs, which plays an important role in the interaction between HSCs and natural killer cells. In addition, RAs released from HSCs may induce hepatic cannabinoid receptor 1 expression in alcoholic liver steatosis or regulate immune responses upon liver inflammation. The present review summarizes the role of endogenous metabolized RAs on HSCs themselves and on other liver cells including hepatocytes and immune cells. Moreover, the effects of exogenous retinol and RA treatments on HSCs and liver disease are discussed.
Differential roles of inflammatory cells in pancreatitis
Authors: Mayerle Julia , Dummer Annegret , Sendler Mathias , Malla Sudarshan Ravi , van den Brandt Cindy , Teller Steffen , Aghdassi Ali , Nitsche Claudia , Lerch Markus M
Published: February 2012

The incidence of acute pancreatitis per 100 000 of population ranges from 5 to 80. Patients suffering from hemorrhagic‐necrotizing pancreatitis die in 10–24% of cases. 80% of all cases of acute pancreatitis are etiologically linked to gallstone disease immoderate alcohol consumption. As of today no specific causal treatment for acute pancreatitis exists. Elevated C‐reactive protein levels above 130 mg/L can also predict a severe course of acute pancreatitis. The essential medical treatment for acute pancreatitis is the correction of hypovolemia. Prophylactic antibiotics should be restricted to patients with necrotizing pancreatitis, infected necrosis or other infectious complications. However, as premature intracellular protease activation is known to be the primary event in acute pancreatitis. Severe acute pancreatitis is characterized by an early inflammatory immune response syndrome (SIRS) and a subsequent compensatory anti‐inflammatory response syndrome (CARS) contributing to severity as much as protease activation does. CARS suppresses the immune system and facilitates nosocomial infections including infected pancreatic necrosis, one of the most feared complications of the disease. A number of attempts have been made to suppress the early systemic inflammatory response but even if these mechanisms have been found to be beneficial in animal models they failed in daily clinical practice.
Biological and clinical relevance of stem cells in pancreatic adenocarcinoma
Authors: Rasheed Zeshaan A , Matsui William
Published: February 2012

Cancer stem cells (CSC) have been identified in a growing number of human malignancies. CSC are functionally defined by their ability to self‐renew and recapitulate tumors in the ectopic setting, and a growing number of studies have shown that they display other functional characteristics, such as invasion and drug resistance. These unique functional properties implicate a role for CSC in clinical consequences, such as initial tumor formation, relapse following treatment, metastasis, and resistance, suggesting they are a major factor in directing clinical outcomes. Pancreatic adenocarcinoma is a highly‐aggressive disease with a propensity for early metastasis and drug resistance. Tumorigenic pancreatic cancer cells have been identified using the cell surface antigens CD44, CD24, and CD133, as well as the high expression of aldehyde dehydrogenase (ALDH). In vitro and in vivo studies have shown that ALDH‐ and CD133‐expressing pancreatic CSC have a greater propensity for metastasis, and ALDH‐expressing CSC have been shown to be resistant to conventional chemotherapy. In clinical samples from patients with resected pancreatic adenocarcinoma, the presence of ALDH‐expressing CSC was associated with worse overall survival. The development of CSC‐targeting therapies might be important in changing the clinical outcomes of patients with this disease, and others and we have begun to identify novel compounds that block CSC function. This review will discuss the biological and clinical relevance of CSC in pancreatic cancer, and will discuss novel therapeutic strategies to target them.
Neonatal candidiasis: Results of an 8 year study
Authors: Celebi Solmaz , Hacimustafaoglu Mustafa , Koksal Nilgun , Ozkan Hilal , Cetinkaya Merih , Ener Beyza
Published: February 2012

Background:  The aim of the present study was to evaluate the risk factors, demographic features, treatment and clinical outcome associated with candidemia in a neonatal intensive care unit (NICU) within an 8 year period.

Methods:  The data of infants who were diagnosed as having candidemia, were evaluated.

Results:  Between January 2000 and December 2007, a total of 28 candidemia episodes were identified in 28 infants. A 1.1% candidemia incidence was documented in the neonatal intensive care unit (NICU). The species most frequently causing candidemia were Candida parapsilosis (57.1%), followed by C. albicans (42.9%). The main predisposing factors for candidemia with C. parapsilosis included presence of maternal pre‐eclampsia, prematurity, prolonged mechanical ventilation, prolonged total parenteral nutrition and presence of jaundice. Retinopathy of prematurity and bronchopulmonary dysplasia were the most frequently seen underlying illnesses in infants with C. parapsilosis. In the present study, 13 infants (46.4%) had evidence of organ dissemination. The mortality rate was 42.8% in infants with candidemia. Mean leukocyte counts and mean C‐reactive protein were significantly higher in neonates who died compared with those who survived.

Conclusion:  Candida parapsilosis (57.1%) was the leading causative organism, followed by C. albicans (42.9%) in infants. The rate of organ dissemination in the present cases was high. The mortality rate was 42.8% in infants with candidemia.
Clinical and social characteristics of Korean men with Klinefelter syndrome
Authors: Bak Chong Won , Byun Jae Sang , Lee Jee Han , Park Ji Hye , Lee Kyung‐Ah , Shim Sung Han
Published: February 2012

Objectives:  To investigate the characteristics of Klinefelter syndrome in a consecutive series of men consulting for sexual as well as fertility problems in Korea.

Methods:  A total of 179 men with non‐mosaic 47,XXY Klinefelter syndrome of the 1876 azoospermic males who visited the fertility center of our university hospital between January 2002 and January 2010 were included in this analysis. Their semen characteristics, hormone profiles, size of the prostate gland, and education level were assessed and compared with an age‐matched control group of 218 fertile males. Additionally, a histological evaluation was carried out.

Results:  Prostate size, testicular volume, semen volume and symptom severity showed statistically significant differences in both groups (P < 0.0001). As the severity of signs and symptoms worsened, the education level decreased. Each degree of signs and symptoms was associated with a different level of education, as well as with significant differences in the level of testosterone and testicular volume (P < 0.05). Spearman's correlation coefficient showed the severity of signs and symptoms was associated with testosterone (P < 0.0001).

Conclusions:  Testosterone has the strongest negative association with the severity of signs and symptoms in patients with Klinefelter syndrome. It influences the reproductive capacity, as well as the manifested signs and symptoms of hypogonadism. Furthermore, it is also associated with various aspects of life in these patients.
Perianal necrotizing fasciitis treated with a loose‐seton technique
Authors: Yang B. L. , Lin Q. , Chen H. J. , Gu Y. F. , Zhu P. , Sun X. L. , Shao W. J.
Published: February 2012

Aim  The study evaluated the effect of a loose‐seton technique for perianal necrotizing fasciitis.

Method  The medical records of seven patients with perianal necrotizing fasciitis treated by the loose‐seton technique between December 2005 and June 2010 were reviewed. Age, gender, status of diabetes mellitus, duration of symptoms, the length of hospital stay and number of debridements were investigated.

Results  Five of the patients were men. The mean age was 53 years and the range was 43–79 years. All seven patients had a past history of acute perianal abscess. Six (85.7%) patients had diabetes mellitus. The mean time for removal of the seton was 24 (14–32) days and the mean hospitalization time was 31 (23–45) days. All patients had primary wound healing. There was no mortality. At a median follow‐up 18 (6–60) months one patient required inpatient treatment with cutting‐seton for complex anal fistula after 11 months. All patients had normal faecal continence and none of them required a reconstructive procedure during the follow‐up.

Conclusion  The loose‐seton technique is an effective treatment for perianal necrotizing fasciitis. The advantages include inhibiting the spread of inflammation, reducing the frequency of debridements, decreasing the area of the wound and limiting extensive scar formation.
The pharmacokinetics and pharmacodynamics of rapid‐acting insulin analogues and their clinical consequences
Authors: Home P. D.
Published: February 2012

Postprandial glucose excursions can inhibit achievement of good glycaemic control, and possibly have a specific effect on the risk of vascular comorbidities. Rapid‐acting analogues control these excursions better than human insulin because their pharmacokinetic/pharmacodynamic (PK/PD) profile is closer to that of meal‐time endogenous insulin secretion. Review of the findings of PK/PD studies and clinical trials suggests that the three marketed rapid‐acting analogues—insulin lispro, insulin aspart and insulin glulisine—are equally efficacious and safe. In comparison with human insulin when using the same basal insulin, they provide comparable glycaemic control with a reduced risk of hypoglycaemia, although the combination of rapid‐acting and basal analogues reduces glycated haemoglobin (HbA1c) more than human meal‐time insulin combined with neutral protamine Hagedorn (NPH) insulin. Some studies have suggested that insulin glulisine has a slightly faster onset of action compared with insulin lispro or insulin aspart, but this has not been translated into demonstrable clinical benefit. Treatment satisfaction in patients with diabetes has been higher when therapy with a rapid‐acting analogue is used instead of human insulin, perhaps due to differences in advised timing of injection. The largest benefits in efficacy, hypoglycaemia incidence, treatment satisfaction and quality of life have occurred when patients receive an all‐analogue meal‐time plus basal regimen as compared with an all‐human insulin regimen. No new safety issues have been identified with the marketed rapid‐acting analogues, and their insulin‐like growth factor 1receptor affinity and mitogenic activity are comparable to human insulin.
Regional scale speciation reveals multiple invasions of freshwater in Palaemoninae (Decapoda)
Authors: Ashelby Christopher W. , Page Timothy J. , De Grave Sammy , Hughes Jane M. , Johnson Magnus L.
Published: February 2012

Ashelby, C.W., Page, T.J., De Grave, S., Hughes, J.M. & Johnson, M.L. (2012) Regional scale speciation reveals multiple invasions of freshwater in Palaemoninae (Decapoda). —Zoologica Scripta, 41, 293–306.

The generic level, systematic relationship in Palaemoninae was inferred from analyses based on the mitochondrial 16S rDNA and nuclear Histone (H3) genes, primarily focussed on the genera Palaemon and Palaemonetes, as previous morphological and molecular studies indicated potential paraphyly in some genera. Palaemonetes, Exopalaemon, Coutierella and certain Palaemon recover as a strongly supported monophyletic clade, but with the exception of Palaemon concinnus, P. pandaliformis and P. gracilis. Within this clade, six major clades are identified with geographic relationships appearing stronger than generic relationships. The data strongly suggest that Palaemon, Palaemonetes, Exopalaemon and Coutierella are synonymous and that the morphological characters currently used to define these genera require re‐evaluation. Freshwater species are not closely related to each other, but instead group with geographically close marine species, suggesting multiple invasions of freshwater by physiologically plastic ancestors rather than a single colonisation event with subsequent speciation.
Translation and validation of two evidence‐based nursing practice instruments
Authors: Thorsteinsson H. S.
Published: February 2012

THORSTEINSSON H.S. (2012) Translation and validation of two evidence‐based nursing practice instruments. International Nursing Review59, 259–265

Background:  Using existing instruments when assessing nurses' readiness for evidence‐based practice facilitates comparison of research findings and adds to nursing knowledge in a global context.

Aim:  The study aims to: (1) translate the Information Literacy for Evidence Based Nursing Practice© (ILNP©) questionnaire and the Evidence‐based Practice Beliefs Scale© (EBP Beliefs Scale©), (2) assess their appropriateness for use in Iceland, and 3) estimate the psychometric properties of the translated EBP Beliefs Scale [Icelandic‐EBP Beliefs Scale (I‐EBP Beliefs Scale)].

Methods:  The instruments were evaluated for appropriateness and relevancy before translation, and the ILNP© was modified to fit the Icelandic context. Translation followed recommended approaches, including back‐translation. Pilot testing of both instruments ensued. A random sample of 540 nurses answered and returned the questionnaires. Reliability and validity of the I‐EBP Beliefs Scale were tested on 471 complete I‐EBP Beliefs Scale. Data were collected in 2007.

Results:  The translated instruments demonstrated clarity and conciseness; however, the ILNP© needed to be further modified. For the I‐EBP Beliefs Scale, Cronbach's α was 0.86 and Spearman–Brown r was 0.87. Principal components analysis supported the I‐EBP Beliefs Scale's construct validity and unidimensional structure. Criterion validity was established by known‐groups comparison (t‐tests and one‐way analyses of variance).

Conclusions:  The ILNP© and the EBP Beliefs Scale© can be used in contexts other than those for which they were developed. The I‐EBP Scale is a psychometrically sound instrument and its performance supports the validity of the original scale. The instruments can be used to gather valuable information about nurses' readiness for evidence‐based practice.
Construct Validation Theory Applied to the Study of Personality Dysfunction
Authors: Zapolski Tamika C. B. , Guller Leila , Smith Gregory T.
Published: February 2012

The authors review theory validation and construct validation principles as related to the study of personality dysfunction. Historically, personality disorders have been understood to be syndromes of heterogeneous symptoms. The authors argue that the syndrome approach to description results in diagnoses of unclear meaning and constrained validity. The alternative approach of describing personality dysfunction in terms of homogeneous dimensions of functioning avoids the problems of the syndromal approach and has been shown to provide more valid description and diagnosis. The authors further argue that description based on homogeneous dimensions of personality function/dysfunction is more useful because it provides direct connections to validated treatments.
THE MODAL ARGUMENTS AND THE COMPLEXITY OF CONSCIOUSNESS
Authors: DeLancey Craig
Published: February 2012

This paper explores consequences of the claim that phenomenal experiences are physical events of great descriptive complexity. This claim is attractive both because it can explain our most perplexing intuitions about the quality of consciousness and also because it is suggestive of very productive research opportunities. I illustrate the former by showing that two of the most compelling anti‐physicalist arguments about phenomenal experience – the modal argument of Kripke and the conceivability argument of Chalmers – are not sound if this claim is true. I illustrate the latter by showing that significant empirical predictions are a consequence of this claim.