bluuebunny/crossref_metadata_2025 huggingface dataset:
Off‐hours admission for acute stroke is not associated with worse outcome – a nationwide Israeli stroke project
Authors: Streifler J. Y. , Benderly M. , Molshatzki N. , Bornstein N. , Tanne D.
Published: December 2011

Background and purpose:  Several studies reported worse outcome for stroke patients arriving on weekends. We compared working hours to off‐work hours throughout the week as there is lack of experienced staff and special services during off‐hours.

Methods:  A nationwide stroke survey project on acute stroke was carried out in all acute care hospitals in Israel during 2004, 2007 and 2010 (2‐month each). ‘On‐hours’ were defined as regular Israel working hours and the rest, including holidays, were defined as ‘off‐hours’. The modified Rankin scale (mRS) at discharge was used for the main analysis on outcome.

Results:  A total of 4827 acute strokes patients were analyzed (2139 arrived on‐hours and 2688 during off‐hours). ‘Off‐hours’ patients were 1 year younger (mean 70 vs. 71 years in ‘on‐hours’) had lower rates of prior cardiac interventions, but had higher admission blood pressure levels and had more intracerebral hemorrhages (ICH) (11% vs. 8% in ‘on‐hours’ patients, P < 0.001). Death during hospitalization was recorded in 9% of ‘off‐hours’ vs. 6% of ‘on‐hours’ patient (P = 0.004). Controlling for age, blood pressure, stroke type, pre‐stroke mRS, admission NIHSS, and thrombolysis, the relative odds of poor outcome (i.e. mRS ≥ 2) amongst ‘off‐hours’ admissions compared to on‐hours was 1.09 (95% CI: 0.92–1.30). Odds ratio amongst ischaemic stroke patients was 1.08 (95% CI: 0.88–1.33).

Conclusions:  Off‐hours stroke admissions were associated with higher short‐term mortality rate, probably due to a higher rate of ICH. After controlling for the latter and other potential confounders, ‘off‐hours’ admissions were not different from ‘on‐hours’ with respect to poor outcome.
Biliary tree stem/progenitor cells in glands of extrahepatic and intraheptic bile ducts: an anatomical in situ study yielding evidence of maturational lineages
Authors: Carpino Guido , Cardinale Vincenzo , Onori Paolo , Franchitto Antonio , Berloco Pasquale Bartolomeo , Rossi Massimo , Wang Yunfang , Semeraro Rossella , Anceschi Maurizio , Brunelli Roberto , Alvaro Domenico , Reid Lola M. , Gaudio Eugenio
Published: December 2011

Stem/progenitors have been identified intrahepatically in the canals of Hering and extrahepatically in glands of the biliary tree. Glands of the biliary tree (peribiliary glands) are tubulo‐alveolar glands with mucinous and serous acini, located deep within intrahepatic and extrahepatic bile ducts. We have shown that biliary tree stem/progenitors (BTSCs) are multipotent, giving rise in vitro and in vivo to hepatocytes, cholangiocytes or pancreatic islets. Cells with the phenotype of BTSCs are located at the bottom of the peribiliary glands near the fibromuscular layer. They are phenotypically heterogeneous, expressing transcription factors as well as surface and cytoplasmic markers for stem/progenitors of liver (e.g. SOX9/17), pancreas (e.g. PDX1) and endoderm (e.g. SOX17, EpCAM, NCAM, CXCR4, Lgr5, OCT4) but not for mature markers (e.g. albumin, secretin receptor or insulin). Subpopulations co‐expressing liver and pancreatic markers (e.g. PDX1+/SOX17+) are EpCAM+/−, and are assumed to be the most primitive of the BTSC subpopulations. Their descendants undergo a maturational lineage process from the interior to the surface of ducts and vary in the mature cells generated: pancreatic cells in hepatopancreatic ducts, liver cells in large intrahepatic bile ducts, and bile duct cells along most of the biliary tree. We hypothesize that there is ongoing organogenesis throughout life, with BTSCs giving rise to hepatic stem cells in the canals of Hering and to committed progenitors within the pancreas. The BTSCs are likely to be central to normal tissue turnover and injury repair and to be key elements in the pathophysiology of liver, pancreas and biliary tree diseases, including oncogenesis.
Annual Research Review: The nature and classification of reading disorders – a commentary on proposals for DSM‐5
Authors: Snowling Margaret J. , Hulme Charles
Published: December 2011

This article reviews our understanding of reading disorders in children and relates it to current proposals for their classification in DSM‐5. There are two different, commonly occurring, forms of reading disorder in children which arise from different underlying language difficulties. Dyslexia (as defined in DSM‐5), or decoding difficulty, refers to children who have difficulty in mastering the relationships between the spelling patterns of words and their pronunciations. These children typically read aloud inaccurately and slowly, and experience additional problems with spelling. Dyslexia appears to arise principally from a weakness in phonological (speech sound) skills, and there is good evidence that it can be ameliorated by systematic phonic teaching combined with phonological awareness training. The other major form of reading difficulty is reading comprehension impairment. These children read aloud accurately and fluently, but have difficulty understanding what they have read. Reading comprehension impairment appears to arise from weaknesses in a range of oral language skills including poor vocabulary knowledge, weak grammatical skills and difficulties in oral language comprehension. We suggest that the omission of reading comprehension impairment from DSM‐5 is a serious one that should be remedied. Both dyslexia and reading comprehension impairment are dimensional in nature, and show strong continuities with other disorders of language. We argue that recognizing the continuities between reading and language disorders has important implications for assessment and treatment, and we note that the high rates of comorbidity between reading disorders and other seemingly disparate disorders (including ADHD and motor disorders) raises important challenges for understanding these disorders.
Phospho‐ibuprofen (MDC‐917) incorporated in nanocarriers: anti‐cancer activity in vitro and in vivo
Authors: Nie T , Wong CC , Alston N , Aro P , Constantinides PP , Rigas B
Published: December 2011

BACKGROUND AND PURPOSE

Phospho‐ibuprofen (P‐I; MDC‐917) inhibits the growth of colon cancer in mice. Here, we investigated the use of nanocarriers to improve its pharmacokinetics (PKs) and anti tumour efficacy.

EXPERIMENTAL APPROACH

The cellular uptake and cytotoxicity of P‐I encapsulated into liposomes and micelles, and its in vitro metabolic stability, were determined in cultures of human colon adenocarcinoma cells. The performance of liposomal P‐I was further evaluated in PK studies in mice, and in a model of colon cancer xenografts in nude mice.

KEY RESULTS

Liposomal P‐I and micellar P‐I showed significantly enhanced cellular uptake in the colon cancer cells. Liposomal P‐I also demonstrated increased cytotoxicity in vitro. Free P‐I was metabolized rapidly to ibuprofen in the presence of purified esterases. In contrast, liposomal P‐I, and to a lesser extent micellar P‐I, was resistant to esterase‐mediated hydrolysis. In mice, liposomal P‐I partially protected P‐I from hydrolysis in the circulation, and improved the biodistribution of intact P‐I and its metabolites compared to free P‐I. Liposomal P‐I was more effective at inhibiting the growth of human colon cancer xenografts in mice, which may be explained on the basis of its improved PK profile compared to free P‐I.

CONCLUSIONS AND IMPLICATIONS

Liposome encapsulation of P‐I partially protected P‐I from esterase‐mediated hydrolysis in mice, enhanced the cytotoxicity and bioavailability of P‐I and increased its efficacy at inhibiting the growth of human colon cancer xenografts. These results indicate that liposomes are suitable nanocarriers for the delivery of P‐I, and that the anti‐tumour potential of liposomal P‐I merits further evaluation.
17β‐Oestradiol inhibits doxorubicin‐induced apoptosis via block of the volume‐sensitive Cl‐ current in rabbit articular chondrocytes
Authors: Kumagai Kousuke , Imai Shinji , Toyoda Futoshi , Okumura Noriaki , Isoya Eiji , Matsuura Hiroshi , Matsusue Yoshitaka
Published: December 2011

BACKGROUND AND PURPOSE Chondrocyte apoptosis contributes to disruption of cartilage integrity in osteoarthritis. Recent evidence suggested that the volume‐sensitive organic osmolyte/anion channel [volume‐sensitive (outwardly rectifying) Cl‐ current (ICl,vol)] plays a functional role in the development of cell shrinkage associated with apoptosis (apoptotic volume decrease) in several cell types. In this study, we investigated the cellular effects of 17β‐oestradiol on doxorubicin‐induced apoptotic responses in rabbit articular chondrocytes.

EXPERIMENTAL APPROACH Whole‐cell membrane currents and cross‐sectional area were measured from chondrocytes using a patch‐clamp method and microscopic cell imaging, respectively. Caspase‐3/7 activity was assayed as an index of apoptosis.

KEY RESULTS Addition of doxorubicin (1 µM) to isosmotic bath solution rapidly activated the Cl‐ current with properties similar to those of ICl,vol in chondrocytes. Doxorubicin also gradually decreased the cross‐sectional area of chondrocytes, followed by enhanced caspase‐3/7 activity; both of these responses were totally abolished by the ICl,vol blocker DCPIB (20 µM). Pretreatment of chondrocytes with 17β‐oestradiol (1 nM) for short (approximately 10 min) and long (24 h) periods almost completely prevented the doxorubicin‐induced activation of ICl,vol and subsequent elevation of caspase‐3/7 activity. These effects of 17β‐oestradiol were significantly attenuated by the oestrogen receptor blocker ICI 182780 (10 µM), as well as the phosphatidyl inositol‐3‐kinase (PI3K) inhibitors wortmannin (100 nM) and LY294002 (20 µM). Testosterone (10 nM) had no effect on the doxorubicin‐induced Cl‐ current.

CONCLUSIONS AND IMPLICATIONS 17β‐Oestradiol prevents the doxorubicin‐induced cell shrinkage mediated through activation of ICl,vol and subsequent induction of apoptosis signals, through a membrane receptor‐dependent PI3K pathway in rabbit articular chondrocytes.
The third extracellular loop of the human calcitonin receptor‐like receptor is crucial for the activation of adrenomedullin signalling
Authors: Kuwasako Kenji , Hay Debbie L , Nagata Sayaka , Hikosaka Tomomi , Kitamura Kazuo , Kato Johji
Published: December 2011

BACKGROUND AND PURPOSE The extracellular loops (ECLs) in Family A GPCRs are important for ligand binding and receptor activation, but little is known about the function of Family B GPCR ECLs, especially ECL3. Calcitonin receptor‐like receptor (CLR), a Family B GPCR, functions as a calcitonin gene‐related peptide (CGRP) and an adrenomedullin (AM) receptor in association with three receptor activity‐modifying proteins (RAMPs). Here, we examined the function of the ECL3 of human CLR within the CGRP and AM receptors.

EXPERIMENTAL APPROACH A CLR ECL3 chimera, in which the ECL3 of CLR was substituted with that of VPAC2 (a Family B GPCR that is unable to interact with RAMPs), and CLR ECL3 point mutants were constructed and transiently transfected into HEK‐293 cells along with each RAMP. Cell‐surface expression of each receptor complex was then measured by flow cytometry; [125I]‐CGRP and [125I]‐AM binding and intracellular cAMP accumulation were also measured.

KEY RESULTS Co‐expression of the CLR ECL3 chimera with RAMP2 or RAMP3 led to significant reductions in the induction of cAMP signalling by AM, but CGRP signalling was barely affected, despite normal cell‐surface expression of the receptors and normal [125I]‐AM binding. The chimera had significantly decreased AM, but not CGRP, responses in the presence of RAMP1. Not all CLR ECL3 mutants supported these findings.

CONCLUSIONS AND IMPLICATIONS The human CLR ECL3 is crucial for AM‐induced cAMP responses via three CLR/RAMP heterodimers, and activation of these heterodimers probably relies on AM‐induced conformational changes. This study provides a clue to the molecular basis of the activation of RAMP‐based Family B GPCRs.

LINKED ARTICLES This article is part of a themed section on Secretin Family (Class B) G Protein‐Coupled Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue‐1
Ethyl pyruvate promotes spinal cord repair by ameliorating the glial microenvironment
Authors: Yuan Yimin , Su Zhida , Pu Yingyan , Liu Xiujie , Chen Jingjing , Zhu Feng , Zhu Yanling , Zhang Han , He Cheng
Published: December 2011

BACKGROUND AND PURPOSE Spinal cord injury (SCI) triggers a series of endogenous processes, including neuroinflammation and reactive astrogliosis, which may contribute to the failure of neural regeneration and functional recovery. In the present study, the effect of ethyl pyruvate on spinal cord repair was explored.

EXPERIMENTAL APPROACH Functional assessment and histological analyses of astrogliosis, neuroinflammation, neuronal survival and axonal regeneration were performed to investigate the effects of ethyl pyruvate (0.086, 0.215, 0.431 or 0.646 mmol·kg−1·day−1) on spinal cord repair in a rat model of SCI. The effect of ethyl pyruvate (5, 10 or 15 mM) on astrocytic activation was also evaluated in an in vitro‘scratch‐wound’ model.

KEY RESULTS Functional assessment showed evident improvement of behavioural functions in the ethyl pyruvate‐treated rats. Reactive astrogliosis was significantly inhibited in vivo, after injection of ethyl pyruvate (0.431 mmol·kg−1day−1), and in vitro‘scratch‐wound’ model in the presence of 10 or 15 mM ethyl pyruvate. The difference between effective concentration in vitro and in vivo suggests that the inhibitory effect of ethyl pyruvate on astrogliosis in damaged spinal cord is indirect. In addition, ethyl pyruvate (0.431 mmol·kg−1day−1) attenuated SCI‐induced neuroinflammation; it decreased the Iba‐1‐, ED‐1‐ and CD11b‐positive cells at the lesion site. Importantly, histological analyses showed a significantly greater number of surviving neurons and regenerative axons in the ethyl pyruvate‐treated rats.

CONCLUSIONS AND IMPLICATIONS Ethyl pyruvate was shown to inhibit astrogliosis and neuroinflammation, promote neuron survival and neural regeneration, and improve the functional recovery of spinal cord, indicating a potential neuroprotective effect of ethyl pyruvate against SCI.
Effects of molecular structure on dyeing performance and colour fastness of yellow dyestuffs applied to polypropylene fibres in supercritical carbon dioxide
Authors: Miyazaki Keisuke , Tabata Isao , Hori Teruo
Published: December 2011

Thirteen dyestuffs of four chemical classes (quinophthalone, anthraquinone, isothiazole‐fused anthrone and pyridone azo) were applied for the dyeing of unmodified polypropylene fibres in supercritical carbon dioxide. From these 13 dyestuffs, three dyestuffs that have a pure yellow hue and good dyeability for polypropylene fibres were found. The results of a dyeability test using the 13 dyestuffs suggested that the affinity for polypropylene fibres requires, in the structural character of the dyestuff molecule, not only extreme hydrophobicity but also high aliphaticity. The isothiazole‐fused anthrone nonanamide dyestuff and two types of N‐butyl substituted pyridone azo dyestuffs were examined for build‐up and colour fastness properties. The light fastness of the dyed fabric was not so good. The ratings of fastness to washing, perspiration and rubbing ranged from excellent to fairly good with the increase of the depth of shade. From the relationship between the build‐up curve and the colour fastness, it was found that the dyestuff of the isothiazole‐fused anthrone nonanamide is suitable for polypropylene dyeing in a pale or medium shade, and that the two types of N‐butyl substituted pyridone azo dyestuffs are suitable in a deep shade.
Alcohol‐Related Effects on Automaticity due to Experimentally Manipulated Conditioning
Authors: Gladwin Thomas E. , Wiers Reinout W.
Published: December 2011

Background:  The use of alcohol is associated with various forms of automatic processing, such as approach tendencies and attentional biases, which may play a role in addictive behavior. The development of such automaticity has generally occurred well before subjects perform tasks designed to detect them. Although it seems plausible that this development involves some form of alcohol‐related conditioning, this process is not usually included in the experimental procedure.

Methods:  The development of automaticity involving alcoholic or nonalcoholic stimuli was experimentally manipulated via a conditioning task. Subjects were presented with pairs of stimuli from a set of 4 stimuli: 2 pictures of alcoholic beverages, and 2 pictures of nonalcoholic beverages. One of the alcoholic and 1 of the nonalcoholic beverages was associated with reward, the other stimuli with punishment. Subjects had to learn to select the rewarded stimuli from pairs of 1 rewarded and 1 punished stimulus. The task, thus experimentally established reward versus punishment stimulus–response–outcome associations, for alcoholic and for nonalcoholic stimuli. Subsequently, a cued reversal task was used to test automaticity involving alcoholic versus nonalcoholic, and rewarded versus punished stimuli.

Results:  An association was found between heavier drinking and an alcohol‐related conditioning bias: heavier drinkers had more difficulty overcoming a conditioned response when it involved selecting a previously punished nonalcoholic stimulus over a previously rewarded alcoholic stimulus.

Conclusions:  The study provided novel information on secondary reinforcement involving alcoholic stimuli: heavier drinkers may more easily develop automaticity related to alcohol‐reward contingencies. This may have implications for interventions and the interpretation of findings concerning alcohol‐related automatic processing.
Religious Environmentalism: Thomas Berry, the Bishnoi, and Satish Kumar
Authors: Chapple Christopher Key
Published: December 2011

Abstract:  This article explores two thinkers and one movement involved with religious environmentalism. Thomas Berry drew from the world's religious traditions and a depth study of science to develop what he refers to as “The New Story,” a narrative that encourages the cultivation of intimacy with nature, leading to an appropriate ethical response. The Bishnoi movement, which originated in fifteenth‐century India, sets forth a pre‐modern paradigm, still widely observed in northern India, for dealing with threats to local eco‐systems. Satish Kumar, a former monk and post‐Gandhian activist, invokes the ideas and practices of Jainism in developing an environmental action plan. These examples demonstrate the interdisciplinary and cross‐cultural aspects of religious environmentalism.
The Future of Theological Education: A Speculative Glimpse at 20321
Authors: Aleshire Daniel O.
Published: December 2011

Abstract:  While the long‐term future is unpredictable, institutions need a way of seeing their work past the present. This article identifies the forces that cause change in theological schools and speculates about the characteristics that theological schools will exhibit in twenty years in light of the most significant forces that will influence them, including denominational and congregational issues, the changing racial/ethnic composition of the American population, the changing character of global Christianity, and the changing practices of American higher education.
Primacy of Information About Means Selection Over Outcome Selection in Goal Attribution by Infants
Authors: Verschoor Stephan , Biro Szilvia
Published: December 2011

It has been shown that, when observing an action, infants can rely on either outcome selection information (i.e., actions that express a choice between potential outcomes) or means selection information (i.e., actions that are causally efficient toward the outcome) in their goal attribution. However, no research has investigated the relationship between these two types of information when they are present simultaneously. In an experiment that addressed this question directly, we found that when outcome selection information could disambiguate the goal of the action (e.g., the action is directed toward one of two potential targets), but means selection information could not (i.e., the action is not efficiently adjusted to the situational constraints), 7‐ and 9‐month‐old infants did not attribute a goal to an observed action. This finding suggests that means selection information takes primacy over outcome selection information. The early presence of this bias sheds light on the nature of the notion of goal in action understanding.
A Rational Analysis of the Acquisition of Multisensory Representations
Authors: Yildirim Ilker , Jacobs Robert A.
Published: December 2011

How do people learn multisensory, or amodal, representations, and what consequences do these representations have for perceptual performance? We address this question by performing a rational analysis of the problem of learning multisensory representations. This analysis makes use of a Bayesian nonparametric model that acquires latent multisensory features that optimally explain the unisensory features arising in individual sensory modalities. The model qualitatively accounts for several important aspects of multisensory perception: (a) it integrates information from multiple sensory sources in such a way that it leads to superior performances in, for example, categorization tasks; (b) its performances suggest that multisensory training leads to better learning than unisensory training, even when testing is conducted in unisensory conditions; (c) its multisensory representations are modality invariant; and (d) it predicts ‘‘missing” sensory representations in modalities when the input to those modalities is absent. Our rational analysis indicates that all of these aspects emerge as part of the optimal solution to the problem of learning to represent complex multisensory environments.
Variation in Parent Use of Information and Communications Technology: Does Quantity Matter?
Authors: Walker Susan K. , Dworkin Jodi , Connell Jessica
Published: December 2011

Although the availability of new information and communication technologies (ICT) may be revolutionizing learning, an understanding of how parents use these innovations is still emerging. Using online survey data from 1,653 parents across the United States, this study identified nine subgroups of parent technology users on dimensions that included their online activity frequency, devices they were using, and their attitude toward technology. Subgroups ranged from those who did a variety of activities daily, used many different devices, and had a positive attitude, to those who infrequently accessed technology, used few types of technology, and had a negative attitude. Further subgroup comparisons reveal few demographic differences characterizing technology use. However, clear differences in constraints and attitude suggest the need for assessing variations in and expanding conceptualizations of technology behavior before designing programs that rely on the Internet for delivery.
iFamily: Internet and Social Media Technology in the Family Context
Authors: Williams Amanda L. , Merten Michael J.
Published: December 2011

The internet has become a major research focus across disciplines and studies report both risks and benefits of use. However, less research explores family technology dynamics from an ecological perspective and how internet use occurring within and outside the family microsystem relates to individual and family well‐being. This study explores parents’ and adolescents’ use of the internet and other technology in terms of family connectedness and parent–child dynamics. Data are derived from the Pew Internet & American Life Project’s Networked Families 2008 surveys (
n
 = 386) and Parents & Teens 2006 (
n
 = 696). Results illustrate how social media technology has the potential to strengthen family bonds. In addition, how parents and adolescents negotiate the role of the internet in their families has implications for adolescent exposure to potential harm from outside the family system. Future directions are offered for exploring families and technology from a dynamic and multisystemic perspective.
Toward a Digital Goods Consumer Competence Index: An Exploratory Study
Authors: Park Hye‐Young , Rha Jong‐Youn , Widdows Richard
Published: December 2011

Consumer spending on digital goods such as e‐books, entertainment, and online services is increasing exponentially. Digitalization of the marketplace is transforming the competencies required by consumers if they are to operate efficiently in the changing marketplace. In this study, an index of digital goods consumer competency was developed to help consumer and family scientists to better understand the new marketplace. Empirical testing of the proposed index was carried out using a sample of Korean consumers. Factor analysis was performed to identify the underlying dimensions of the index. Further analysis showed that consumers face particular difficulties in the prepurchase search and evaluation of digital goods. Cluster analysis showed that there are distinct consumer groups that differ in their level of digital goods consumer competence, suggesting that there may be consumer groups that are more vulnerable in the consumption and use of digital goods. This implies a need for intervention from a consumer policy and education perspective.
2010 Graduate Research Productivity in Family and Consumer Sciences
Authors: Dodor Bernice A. , Woods Barbara A.
Published: December 2011

Family and consumer sciences programs in colleges and universities in the United States submitted 263 titles of graduate research in 2010, a decrease of 68 titles from the previous year. However, nonresponse from 27 of the 48 universities that were contacted suggests the number of theses and dissertations reported in this article does not fully represent all graduate degrees granted in family and consumer sciences in 2010. Factors associated with underreporting need to be further explored. Three categories account for 59% of all reported titles in theses and dissertations. The categories are foods/nutrition/dietetics; child/human development; and family relations/marriage.
Melatonin sensitizes human hepatoma cells to endoplasmic reticulum stress–induced apoptosis
Authors: Zha Lixia , Fan Lulu , Sun Guoping , Wang Hua , Ma Tai , Zhong Fei , Wei Wei
Published: December 2011

Abstract:  Endoplasmic reticulum stress–mediated cell apoptosis is implicated in the development of cancer. Melatonin induces apoptosis in hepatocellular carcinoma (HCC) in experimental studies, but the effects of melatonin on endoplasmic reticulum (ER) stress–induced apoptosis in HCC have not been tested. Differences in ER stress–induced apoptosis in human hepatoma cells and normal human hepatocyte were investigated by exposure to tunicamycin (ER stress inducer). Significant differences were observed in the rate of apoptosis between HepG2 cells (hepatoma cells) and HL‐7702 cells (normal human hepatocyte cells). The expression of cyclooxygenase‐2 (COX‐2) was increased in HepG2 cells but not in HL‐7702 cells. Furthermore, down‐regulation of COX‐2 expression using the COX‐2 inhibitor, celecoxib, increased tunicamycin‐induced apoptosis concomitant with the up‐regulation of pro‐apoptotic transcription factor CHOP (GADD153) and down‐regulation of B‐cell lymphoma 2/Bcl‐2–associated X protein (Bcl‐2/Bax) ratio, suggesting that inhibition of COX‐2 sensitized human hepatoma cells to ER stress–induced apoptosis. Interestingly, co‐treatment with tunicamycin and melatonin also decreased the expression of COX‐2 and significantly increased the rate of apoptosis by elevating the levels of CHOP and reducing the Bcl‐2/Bax ratio. These results demonstrate that melatonin sensitizes human hepatoma cells to ER stress–induced apoptosis by down‐regulating COX‐2 expression, increasing the levels of CHOP and decreasing the Bcl‐2/Bax ratio.
TACI‐Fc gene therapy improves autoimmune sialadenitis but not salivary gland function in non‐obese diabetic mice
Authors: Vosters JL , Roescher N , Illei GG , Chiorini JA , Tak PP
Published: December 2011

Oral Diseases (2012) 18, 365–374

Objective:  Patients with Sjögren’s syndrome (SS) show aberrant expression of the B cell‐related mediators, B cell‐activating factor (BAFF), and a proliferation‐inducing ligand (APRIL) in serum and salivary glands (SGs). We studied the biological effect of neutralizing these cytokines by local gene transfer of the common receptor transmembrane activator and CAML interactor (TACI) in an animal model of SS.

Material and Methods:  A recombinant serotype 2 adeno‐associated virus (rAAV2) encoding TACI‐Fc was constructed, and its efficacy was tested in the SGs of non‐obese diabetic mice. Ten weeks later, SG inflammation was evaluated and serum and SG tissue were analyzed for inflammatory markers including immunoglobulins (Ig) and cytokines.

Results:  AAV2‐TACI‐Fc gene therapy significantly reduced the number of inflammatory foci in the SG, owing to a decrease in IgD+ cells and CD138+ cells. Moreover, IgG and IgM levels, but not IgA levels, were reduced in the SG. Overall expression of mainly proinflammatory cytokines tended to be lower in AAV2‐TACI‐Fc‐treated mice. Salivary flow was unaffected.

Conclusion:  Although local expression of soluble TACI‐Fc reduced inflammation and immunoglobulin levels in the SG, further research will have to prove whether dual blockade of APRIL and BAFF by TACI‐Fc can provide a satisfying treatment for the clinical symptoms of patients.
T‐helper 17 cells mediate the osteo/odontoclastogenesis induced by excessive orthodontic forces
Authors: Hayashi N , Yamaguchi M , Nakajima R , Utsunomiya T , Yamamoto H , Kasai K
Published: December 2011

Oral Diseases (2012) 18, 375–388

Objective:  The aim of this study was to investigate how T‐helper 17 cells (Th17 cells), interleukin (IL)‐17, and interleukin‐6 contribute to root resorption during orthodontic tooth movement.

Materials and Methods:  Fifteen male 6‐week‐old Wistar rats were subjected to orthodontic force of 10 or 50 g to induce a mesially tipping movement of the upper first molars for 7 days. The expression levels of TRAP, IL‐17, the IL‐17 receptor (IL‐17R), and IL‐6 proteins were determined in periodontal ligament (PDL) by immunohistochemical analysis. Moreover, the fluorescent localization immunoassay was performed to detect Th17 cells. Furthermore, the effects of IL‐17 on IL‐6 release were investigated using human PDL cells in vitro. The effect of IL‐17 on osteoclastogenesis was evaluated by TRAP staining, actin ring staining, and the pit formation assay.

Results:  The immunoreactivity for Th17, IL‐17, IL‐17R, and IL‐6 was detected in PDL tissue subjected to the orthodontic force on day 7. IL‐17 increased the release of IL‐6 from human periodontal ligament cells in a time‐dependent manner. Moreover, IL‐17 stimulated osteoclastogenesis from human osteoclast precursor cells, and these effects were partially suppressed by an anti‐IL‐6 antibody.

Conclusion:  These results suggest that Th17 cells may aggravate the process of orthodontically induced inflammatory root resorption.
Changes in hippocampal gene expression by 7‐nitroindazole in rats submitted to forced swimming stress
Authors: Ferreira F. R. , Oliveira A. M. , Dinarte A. R. , Pinheiro D. G. , Greene L. J. , Silva W. A. , Joca S. R. , Guimarães F. S.
Published: December 2011

Nitric oxide (NO) is an atypical neurotransmitter that has been related to the pathophysiology of major depression disorder. Increased plasma NO levels have been reported in depressed and suicidal patients. Inhibition of neuronial nitric oxide synthase (nNOS), on the other hand, induces antidepressant effects in clinical and pre‐clinical trials. The mechanisms responsible for the antidepressant‐like effects of nNOS inhibitors, however, are not completely understood. In this study, genomic and proteomic analyses were used to investigate the effects of the preferential nNOS inhibitor 7‐nitroindazole (7‐NI) on changes in global gene and protein expression in the hippocampus of rats submitted to forced swimming test (FST). Chronic treatment (14 days, i.p.) with imipramine (15 mg/kg daily) or 7‐NI (60 mg/kg daily) significantly reduced immobility in the FST. Saturation curves for Serial analysis of gene expression libraries showed that the hippocampus of animals submitted to FST presented a lower number of expressed genes compared to non‐FST stressed groups. Imipramine, but not 7‐NI, reverted this effect. GeneGo analyses revealed that genes related to oxidative phosphorylation, apoptosis and survival controlled by HTR1A signaling and cytoskeleton remodeling controlled by Rho GTPases were significantly changed by FST. 7‐NI prevented this effect. In addition, 7‐NI treatment changed the expression of genes related to transcription in the cAMP response element‐binding pathway. Therefore, this study suggests that changes in oxidative stress and neuroplastic processes could be involved in the antidepressant‐like effects induced by nNOS inhibition.
Prevalence of oral mucosal lesions in institutionalized elderly people in Mashhad, Northeast Iran
Authors: Mozafari Pegah M. , Dalirsani Zohreh , Delavarian Zahra , Amirchaghmaghi Maryam , Shakeri Mohammad T. , Esfandyari Abdollah , Falaki Farnaz
Published: December 2011

doi: 10.1111/j.1741‐2358.2011.00588.x
 
Prevalence of oral mucosal lesions in institutionalized elderly people in Mashhad, Northeast Iran

Objective:  The aim of this study was to determine the prevalence of oral mucosal lesions in institutionalized elderly people in Mashhad, northeast of Iran.

Background:  This study was conducted to assess the prevalence of oral lesions in the institutionalized elderly.

Methods:  In this survey, we studied all of the nursing homes in Mashhad; a total of five encompassing 237 residents. The subjects were examined and lesions recorded in a designed checklist. T‐test, chi‐square and Fisher’s exact tests were used for the analysis.

Results:  The mean age of the patients was 79.59 ± 8.88. Ninety‐eight per cent of cases had at least one oral mucosal lesion. The most common lesions were fissured tongue (66.5%), atrophic glossitis (48.8%), sublingual varicosity (42%) and xerostomia (38%). There was no significant difference in the prevalence of denture‐related lesions (DRLs) between men and women (p > 0.05). Xerostomia was more prevalent in 70–79‐year‐old than in 60–69‐year‐old subjects. No case of oral malignant lesion was detected.

Discussion:  These findings revealed a higher prevalence of oral mucosal lesions in Mashhad city compared with other studies conducted in other major cities in Iran and abroad. The results emphasise the necessity of national programmes towards oral health promotion.
Factor H and CFHR1 polymorphisms associated with atypical Haemolytic Uraemic Syndrome (aHUS) are differently expressed in Tunisian and in Caucasian populations
Authors: Leban N. , Abarrategui‐Garrido C. , Fariza‐Requejo E. , Amiñoso‐Carbonero C. , Pinto S. , Chibani J. B. , Khelil A. H. , Sánchez‐Corral P.
Published: December 2011

Several polymorphisms in the complement components factor H and CFHR1 are associated with higher risk to develop atypical Haemolytic Uraemic Syndrome (aHUS) in Caucasians. We have determined the prevalence of these polymorphisms in Tunisian controls by using genetic and immunological techniques. No differences in the frequency of the factor H risk alleles c.−331C>T, c.2089A>G or c.2881G>T between Tunisian and Caucasians were found. On the contrary, the analysis of CFHR1 polymorphism revealed a higher frequency of Tunisian individuals homozygous for the CFHR1*Del (deleted) allele, and of individuals presenting the CFHR1*A phenotype. These results suggest distinct contributions of factor H and CFHR1 polymorphisms to aHUS in Tunisian and Caucasian populations.
Light‐based Regeneration Niches: Evidence from 21 Dipterocarp Species using Size‐specific RGRs
Authors: Philipson Christopher D. , Saner Philippe , Marthews Toby R. , Nilus Reuben , Reynolds Glen , Turnbull Lindsay A. , Hector Andy
Published: December 2011

A continuing challenge in tropical ecology is to explain the coexistence of large numbers of rain forest tree species. One possible coexistence mechanism is partitioning of the highly variable and dynamic forest light environment, in which species that grow better in one light treatment grow worse in another. To test whether species respond differently to the light environment, we estimated growth rates of 21 Dipterocarpaceae species from Malaysian Borneo grown in shade houses for 2 yr in three light treatments (0.3%, 3%, and 18% full sunlight). We made regular measurements of height, diameter, and aboveground biomass, enabling us to calculate growth rates for each response. We estimated size‐specific growth rates using nonlinear mixed‐effects models, as average relative growth rate was strongly size dependent. For all species, the greatest diameter growth rate was achieved in 18 percent full sunlight, whereas for five of the twenty‐one species, the greatest height growth rate was achieved in three percent full sunlight. We investigated correlations among growth rates in different light treatments, but no negative correlations were found, indicating that species growing well in one light treatment did not grow poorly in the others. There were substantial crossovers, however, in species ranks among the three light treatments, indicating that there was no single growth rate hierarchy common to all light treatments. The lack of a single consistent growth hierarchy across light treatments indicates that heterogeneity in the forest light environment could contribute to the maintenance of the diversity of Dipterocarpaceae found in lowland Bornean rain forests via light‐based regeneration niches.
Oxidative stress and redox signaling mechanisms of alcoholic liver disease: Updated experimental and clinical evidence
Authors: ZHU Hong , JIA Zhenquan , MISRA Hara , LI Y Robert
Published: December 2011

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality in the United States and Europe. The spectrum of ALD ranges from fatty liver to alcoholic hepatitis and cirrhosis, which may eventually lead to hepatocellular carcinoma. In developed countries as well as developing nations, ALD is a major cause of end‐stage liver disease that requires liver transplantation. The most effective therapy for ALD is alcohol abstinence; however, for individuals with severe ALD and those in whom alcohol abstinence is not achievable, targeted therapies are absolutely necessary. In this context, advances of our understanding of the pathophysiology of ALD over the past two decades have contributed to the development of therapeutic modalities (e.g., pentoxifylline and corticosteroids) for the disease although the efficacy of the available treatments remains limited. This article is intended to succinctly review the recent experimental and clinical findings of the involvement of oxidative stress and redox signaling in the pathophysiology of ALD and the development of mechanistically based antioxidant modalities targeting oxidative stress and redox signaling mechanisms. The biochemical and cellular sources of reactive oxygen and nitrogen species (ROS/RNS) and dysregulated redox signaling pathways associated with alcohol consumption are particularly discussed to provide insight into the molecular basis of hepatic cell dysfunction and destruction as well as tissue remodeling underlying ALD.
Risk factors and outcomes of massive red blood cell transfusion following living donor liver transplantation
Authors: LI Chuan , MI Kai , WEN Tian Fu , YAN Lu Nan , LI Bo , WEI Yong Gang , YANG Jia Ying , XU Ming Qing , WANG Wen Tao
Published: December 2011

OBJECTIVES:  To identify the factors influencing blood loss and secondary blood transfusion and to investigate the outcomes of patients who underwent a massive blood transfusion (MBT) following living donor liver transplantation (LDLT).

METHODS:  Patients who underwent primary adult‐to‐adult right hepatic lobe LDLT were included in the study, and were divided into the MBT group [≥ 6 red blood cell (RBC) units in 24 h] and the non‐massive blood transfusion (NMBT) group (< 6 RBC units in 24 h). All potential risk factors, length of intensive care unit (ICU) stay and long‐term survival rate of the patients in the two groups were analyzed.

RESULTS:  The data of 181 eligible patients were retrospectively analyzed. A decreased long‐term survival rate, a higher incidence of postoperative infection and prolonged ICU stay were observed in the MBT group. No significant difference was observed in survival rate between patients having platelet transfusion > 2 units and ≤ 2 units. Hemoglobin < 100 g/L, platelet counts < 70 × 109/L, fibrinogen level < 1.5 g/L and history of upper abdominal surgery were found to be independent risk factors.

CONCLUSIONS:  Blood transfusion during LDLT can be predicted using preoperative variables. Massive RBC transfusion may lead to poor long‐term survival, higher postoperative infection rate and prolonged ICU stay. Platelet transfusion may not be a risk factor for long‐term survival.
Retracted: Natural course of nonalcoholic fatty liver disease in southern China: A prospective cohort study
Authors: ZHOU Yong Jian , LI Yu Yuan , NIE Yu Qiang , HUANG Chun Ming , CAO Chuang Yu
Published: December 2011

OBJECTIVE:  Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, the natural course of which has not been well documented. This study aimed to perform a prospective cohort study to investigate NAFLD in a Chinese population.

METHODS:  Using our previous epidemiological survey, 3543 patients were followed‐up for a median of 4 years (range 3.6–4.8 years). Of these patients, 624 participated in a new survey. Interviews, physical examinations, biochemical tests and abdominal ultrasonography were repeated for these patient.

RESULTS:  The annual incidence of NAFLD was 9.1% (male 7.3% vs female 9.7%, P = 0.047). Among 117 NAFLD patients at baseline, 51 (43.6%) remained unchanged, 26 (22.2%) became worse, and 40 (34.2%) improved. Patients with simultaneous metabolic syndrome (MS) showed accelerated progression (P = 0.026). For the NAFLD patients, both general annual mortality rates and cardiovascular disease deaths (both 0.54%) were significantly higher than those of patients without NAFLD (0.19% and 0.17%, P = 0.005). Age and several variables related to MS were risk factors for NAFLD progression.

CONCLUSIONS:  The incidence of NAFLD in southern China is relatively lower in comparison with that of the developed countries. Patients with NAFLD have a benign prognosis. Variables related to MS are risk factors for NAFLD occurrence and progression.
Optimization of preservation and storage time of sponge tissues to obtain quality mRNA for next‐generation sequencing
Authors: RIESGO ANA , PÉREZ‐PORRO ALICIA R. , CARMONA SUSANA , LEYS SALLY P. , GIRIBET GONZALO
Published: December 2011

Transcriptome sequencing with next‐generation sequencing technologies has the potential for addressing many long‐standing questions about the biology of sponges. Transcriptome sequence quality depends on good cDNA libraries, which requires high‐quality mRNA. Standard protocols for preserving and isolating mRNA often require optimization for unusual tissue types. Our aim was assessing the efficiency of two preservation modes, (i) flash freezing with liquid nitrogen (LN2) and (ii) immersion in RNAlater, for the recovery of high‐quality mRNA from sponge tissues. We also tested whether the long‐term storage of samples at −80 °C affects the quantity and quality of mRNA. We extracted mRNA from nine sponge species and analysed the quantity and quality (A260/230 and A260/280 ratios) of mRNA according to preservation method, storage time, and taxonomy. The quantity and quality of mRNA depended significantly on the preservation method used (LN2 outperforming RNAlater), the sponge species, and the interaction between them. When the preservation was analysed in combination with either storage time or species, the quantity and A260/230 ratio were both significantly higher for LN2‐preserved samples. Interestingly, individual comparisons for each preservation method over time indicated that both methods performed equally efficiently during the first month, but RNAlater lost efficiency in storage times longer than 2 months compared with flash‐frozen samples. In summary, we find that for long‐term preservation of samples, flash freezing is the preferred method. If LN2 is not available, RNAlater can be used, but mRNA extraction during the first month of storage is advised.
Nailfold capillaroscopy by digital microscope in an Indian population with systemic sclerosis
Authors: BHAKUNI Darshan S. , VASDEV Vivek , GARG M.K. , NARAYANAN Krishanan , JAIN Rahul , MULLICK Gautam
Published: December 2011

Aim:  Nailfold capillaroscopy (NFC) is a simple, non‐invasive method with exceptional predictive value for the analysis of microvascular abnormalities, especially in systemic sclerosis (SSc) but remains underutilized due to cost factors of the nailfold videocapillaroscope, lack of expertise and availability issues. The aim of this study was to establish the utility of an inexpensive digital microscope to study NFC changes in SSc in correlation with disease subsets and extent of skin involvement.

Methods:  Twenty‐two diffuse cutaneous SSc (DSS), 20 limited cutaneous SSc (LSS) patients and 42 controls were evaluated with NFC using a digital microscope at 30× and 100× magnification. Digital micrographs were used to study qualitative and quantitative changes in microvasculature.

Results:  The capillary density was significantly less in all cases of SSc as compared to controls (5.3 ± 1.4 vs. 8.7 ± 1.2; P < 0.00001). Disorganized architecture was much more prevalent in DSS versus LSS (86.4%vs. 25%). The vascular deletion score (VDS) was significantly higher in DSS as compared to LSS (P < 0.0001). Scleroderma pattern (SP) was seen in 18 (81.9%) and 15 (75%) of patients with DSS and LSS, respectively. Only 4% of normal subjects showed non‐specific pattern and none showed SP. The mean modified Rodnan skin score (MRSS) was positively correlated with vascular deletion score (r = 0.572; P < 0.001) and negatively with capillary density (r = −0.8; P < 0.001).

Conclusion:  Nailfold capillaroscopy changes in SSc are related to disease subset and MRSS. NFC with digital microscope is a simplified, inexpensive, outpatient procedure with results comparable to previous studies.
The DESTIN: Preservice Teachers' Drawings of the Ideal Elementary Science Teacher
Authors: Mensah Felicia Moore
Published: December 2011

The aim of this study is to report findings from the Drawing‐Elementary‐Science‐Teacher‐Ideal‐Not, or the DESTIN procedure. The study utilizes a simple drawing procedure accompanied by a narrative and discussion for understanding preservice teachers' images of science, science teaching, and the science teacher. Ninety drawings from two sections of an elementary science methods course were analyzed. Looking at the pre‐drawings from the beginning of the semester and post‐drawings done at the end of the semester, the findings relate the value of using drawings in teacher education and the usefulness of this procedure to promote discussions about science teaching, the construction of new images and practices for teaching elementary science, and teacher identity. The DESTIN procedure has potential as a productive activity for teacher education and long‐term professional development by making more explicit teachers' views of science teaching and learning and their past experiences as science learners.