bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testing biogeographical hypotheses in space and time: faunal relationships of the putative ancient Lake Egˇirdir in Asia Minor
Authors: Wilke Thomas , Albrecht Christian , Anistratenko Vitaliy V. , Sahin Serap Kosal , Yildirim Mehmet Zeki 
Published: May 2007

AbstractAim The aims of this study are to establish a multi‐locus phylogeny‐based hypothesis for the biogeographical relationship of gastropods from the putative ancient Lake Egˇirdir, to test the respective null hypothesis, to estimate the timing of biogeographical events based on independent molecular clock approaches, and to interpret the data with respect to the putative ancient character of Lake Egˇirdir.Location Lake Egˇirdir, western Taurus Lake District, Turkey.Methods DNA sequences from the putatively only extant endemic taxon of Lake Egˇirdir,Falsipyrgula pfeiferi, as well as representatives of other pyrgulinid genera from Europe and western Asia are used for phylogenetic analyses based on Bayesian inference. The respective null hypothesis is tested utilizing parametric bootstrapping. The timing of evolutionary events is estimated based on two independent molecular clock approaches, which involve the modelling of judicious errors associated with branch‐length calculations and calibration points.Results Bayesian inference indicates a very close relationship between the Lake Egˇirdir and Ponto‐Caspian taxa. Parametric bootstrapping rejects the null hypothesis that these taxa are not monophyletic (P ≤ 0.01). The alternative hypothesis, namely monophyly of the Ponto‐Caspian and Egˇirdir taxa, can therefore be accepted. The two independent molecular clock approaches show diversion times for the Ponto‐Caspian/Egˇirdir taxa of 0.42 ± 0.18 and 0.43 ± 0.63 Ma.Main conclusions The present study shows that there is no close biogeographical affiliation between the probably only remaining endemic taxon of Lake Egˇirdir and taxa from central Europe or the Balkan region. Instead, there is a very close and relatively young (i.e. late Pleistocene) biogeographical relationship with the Ponto‐Caspian pyrgulinids. However, fossil and comparative data from other invertebrates indicate that biogeographical connections between Lake Egˇirdir and the Ponto‐Caspian region existed during various time periods, i.e. the Miocene/Pliocene, early Pleistocene, and late Pleistocene. Acknowledging the still‐restricted knowledge of the evolutionary history of the lake, the data presented here do not reject the putative ancient status of Lake Egˇirdir. Future studies utilizing endemic taxa of other lakes in the region need to show whether the western Taurus Lake District represents a melting pot of Pleistocene refuge biodiversity from different regions, and whether the admixture of divergent lineages has created a genetically distinct set of taxa that would warrant the designation of the area as a unique biogeographical subregion.
Factors influencing change in health‐related quality of life after liver transplantation
Authors: Estraviz Begoña , Quintana José M. , Valdivieso Andrés , Bilbao Amaia , Padierna Angel , De Urbina Jorge Ortiz , Sarabia Sebastian 
Published: May 2007

Abstract: Objective: To assess health‐related quality of life (HRQoL) in patients following liver transplantation and the factors associated with HRQoL variation.Methods and Materials: Sociodemographic and clinical data were collected for 60 consecutive patients activated for liver transplantation in a single hospital. Patients were classified according to the severity of the cirrhosis (Child–Pugh class) and disease etiology (alcoholic cirrhosis, viral cirrhosis, cholestatic diseases, and hepatocarcinoma). HRQoL was assessed by three different questionnaires: the Health Survey Short Form 36 (SF‐36), the Hospital Anxiety and Depression Scale (HAD), and a specific‐symptom questionnaire. Questionnaires were completed during the pre‐operative period and six months after transplantation.Results: In the pre‐operative period, patients with Child A had higher mean levels of HRQoL than did those in other groups. At six months following transplantation, there were no significant differences among the groups, largely because gains obtained by patients with Child B and C were much greater than those attained by patients with Child A. Across the four etiological groups, there were significant differences in all domains of the three questionnaires, except SF‐36‐bodily pain and HAD‐anxiety, prior to transplantation, because patients with hepatocarcinoma had much better HRQoL. After transplantation, there were no differences because patients with viral and alcohol‐induced cirrhosis achieved greater gains with respect to the neoplastic group. During the pre‐operative period, the scores for all areas of the SF‐36 and for all groups were below the general population normalized score of 50 (except for patients with Child class A and those affected with hepatocarcinoma). Six‐months post‐transplantation, the scores on most of the domains remained below 50, except for certain mental areas in which higher scores were attained.Conclusions: Health‐related quality of life is influenced by the severity and etiology of cirrhosis—patients with Child class C and those with alcoholic or viral cirrhosis have the poorest quality of life. There were no differences observed among the groups after the transplantation, as the patients with the lowest HRQoLs prior to surgery demonstrated greater gains in HRQoL associated with liver transplantation.
Can a rural community‐based work‐related activity program make a difference for chronic pain‐disabled injured workers?
Authors: Dunstan Debra A. , Covic Tanya 
Published: May 2007

AbstractObjective:  To assess the effectiveness of a clinical guidelines‐informed multidisciplinary work‐related activity program, and to improve the physical, psychological and occupational functioning of chronic pain‐disabled injured workers. Design:  An uncontrolled, repeated‐measures, pilot study was conducted. Setting:  The intervention was delivered in a community setting in regional New South Wales. Participants:  Participants (n = 30), mean age of 41 years, had a compensable musculoskeletal injury: 60% were male, 63% had back injuries; the mean time off work was 13 months.Intervention:  A cognitive‐behavioural, interdisciplinary intervention was delivered using a multi‐contributor provider model (a clinical psychologist and physiotherapist from separate practices, working in liaison with the participant's occupational rehabilitation provider and treating doctor). Groups of six participants attended for one half day per week for six weeks. Main outcome measures:  The outcome measures included: physical functioning, pain intensity and psychological variables, which were assessed pre‐ and post‐program; and medical certification and work participation, which was recorded pre‐program and at six‐month follow up. Results:  Significant gains were made in pain intensity, physical and psychological functioning, and medical certification. The mean effect size of the intervention was medium to large (
d = 0.70). There was no significant change in employment status at six‐month follow up.Conclusions:  The results of this pilot study suggest that independent, rural or community‐based practitioners, working collaboratively using an integrated treatment program, can produce positive outcomes for pain‐disabled injured workers, and achieve results similar to those reported by metropolitan‐based pain clinics.
Australian rural adolescents' experiences of accessing psychological help for a mental health problem
Authors: Boyd Candice , Francis Kristy , Aisbett Damon , Newnham Krystal , Sewell Jessica , Dawes Graham , Nurse Sarah 
Published: May 2007

AbstractObjective:  This study aims to explore Australian rural adolescents' experiences of accessing help for a mental health problem in the context of their rural communities. Design and setting:  A qualitative research design was used whereby university students who had sought help for a mental health problem during their adolescence were interviewed about their experiences. Interviews were conducted face‐to‐face at the university. Main outcome measures:  A semi‐structured interview schedule was designed around the study's main research questions. Audio‐taped interviews were transcribed and thematically coded using a constant comparative method. Participants:  Participants were first‐year undergraduate psychology students between the ages of 17 and 21 years who sought help for a mental health issue during their adolescence and who at that time resided in a rural area. Results:  Participants highlighted various barriers to seeking help for mental health problems in the context of a rural community, including: social visibility, lack of anonymity, a culture of self‐reliance, and social stigma of mental illness. Participants' access to help was primarily school‐based, and participants expressed a preference for supportive counselling over structured interventions. Characteristics of school‐based helpers that made them approachable included: ‘caring’, ‘nonjudgemental’, ‘genuine’, ‘young’, and able to maintain confidentiality. Conclusions:  The findings support previous research that reveals barriers to help seeking for mental health problems that are unique to the culture of rural communities. The study raises questions about the merit of delivery of primary mental health care to young people via GPs alone and suggests that school‐based counsellors be considered as the first step in a young person's access to mental health care.
Depression and remoteness from health services in South Australia
Authors: Goldney Robert D. , Taylor Anne W. , Bain Marcus A. 
Published: May 2007

AbstractObjective:  To determine whether the prevalence of depression, its associated quality of life, treatment and mental health literacy about depression varied according to accessibility to health services. Design:  Face‐to‐face interviews with a random and representative sample of the South Australian population (aged ≥ 15 years) were conducted between March and June 2004, with the respondents stratified using the Accessibility and Remoteness Index of Australia into categories of ‘highly accessible’, ‘accessible’, and ‘moderately accessible and remote’.Results:  From 4700 households selected, 3015 participants were interviewed (65.9% response rate). The prevalence of major depression and other depressions was not significantly different between each of the categories, although there was a trend for those from moderately accessible and remote areas to be less depressed overall. A significantly lower proportion of respondents from moderately accessible and remote locations reported that they had family or close friends who had suffered from symptoms consistent with depression, or that they had ever had treatment for those symptoms. However, there was no significant difference between the groups in those who had ever had or who were currently taking antidepressant medication. For those who were depressed, a significantly higher proportion from the accessible, and moderately accessible and remote regions had seen a community or district health service, social worker or other counsellor as compared with those from the highly accessible area. Conclusions:  These findings indicate that depression is no more prevalent in less accessible regions of South Australia, and that when it is present, its treatment, in terms of antidepressants, which can be considered as a proxy marker for the overall management of depression, is similar to treatment in more accessible areas.
Has natural selection in human populations produced two types of metabolic syndrome (with and without fatty liver)?
Authors: Caldwell Stephen H , Ikura Yoshihiro , Iezzoni Julia C , Liu Zhenqi 
Published: May 2007

AbstractFatty liver is closely related to the development of the insulin resistance syndrome that largely results from abnormal insulin signaling in three major organs: (i) skeletal muscle in which insulin sensitivity depends on fat content and metabolic activity (exercise); (ii) adipose tissue, which serves as a reservoir of energy in the form of triglycerides; and (iii) the liver, which variably serves as a source or storage site of carbohydrates and lipids. In many respects, the fatty liver resembles a mixture of brown adipose tissue (microvesicular steatosis) and white adipose tissue (macrovesicular steatosis) including the stages of fatty droplet accumulation, and the expression of uncoupling proteins and perilipin‐like substances. Furthermore, the development of an inflammatory infiltrate and the increased production of cytokines as occurs in adipose tissue, suggest that the liver in some individuals serves as an extension of adipose tissue. Moreover, current evidence indicates that these morphological changes represent altered gene expression similar to that of adipocytes. However, fatty liver does not appear to be a uniform feature of the metabolic syndrome and there is substantial variation in humans in the development of fatty liver independent of insulin resistance. In this regard, the variable development of fatty liver in Palmipedes (migratory fowl) and its close relationship to skeletal muscle utilization of fatty acids, lipoprotein metabolism and thermoregulation are instructive. The predilection to non‐alcoholic fatty liver disease among some varieties of Palmipedes suggests that the development of fatty liver represents an adaptive process, closely integrated with skeletal muscle fat utilization and adipose tissue distribution, and facilitates survival in a very cold, resource‐scarce environment. Variation in human populations with metabolic syndrome likewise suggests that the trait evolved in populations exposed in ancient times to different environmental challenges and, because the liver plays a central role in lipid metabolism, the presence or absence of fatty liver is likely to be integrated with insulin sensitivity in other target organs and with lipoprotein metabolism.
Role of mitochondria in non‐alcoholic fatty liver disease
Authors: Pessayre Dominique 
Published: May 2007

AbstractMitochondrial dysfunction is involved in the three stages of the transition from lack of exercise and excessive food intake to insulin resistance, diabetes and non‐alcoholic steatohepatitis (NASH). In muscle, lack of exercise, a fat‐rich diet, a polymorphism in peroxisome proliferator‐activated receptor γ coactivator‐1 (PGC‐1), and possibly age‐related mitochondrial DNA (mtDNA) mutations may variously combine their effects to decrease PGC‐1 expression, mitochondrial biogenesis and fat oxidation. Together with excessive food intake, insufficient fat oxidation causes fat accumulation and cellular stress in myocytes. The activation of Jun N‐terminal kinase and protein kinase C‐θ triggers the serine phosphorylation and inactivation of the insulin receptor substrate, and hampers the insulin‐mediated translocation of glucose transporter‐4 to the plasma membrane. Initially, the trend for increased blood glucose increases insulin secretion by pancreatic β‐cells. High plasma insulin levels compensate for insulin resistance in muscle and maintain normal blood glucose levels. Eventually, however, increased uncoupling protein‐2 expression and possibly acquired mtDNA mutations in pancreatic β‐cells can blunt glucose‐mediated adenosine triphosphate (ATP) formation and insulin secretion, to cause diabetes in some patients. High plasma glucose and/or insulin levels induce hepatic lipogenesis and cause hepatic steatosis. In fat‐engorged hepatocytes, several vicious cycles involving tumor necrosis factor‐α, reactive oxygen species (ROS), peroxynitrite, and lipid peroxidation products alter respiratory chain polypeptides and mtDNA, thus partially blocking the flow of electrons in the respiratory chain. The overreduction of upstream respiratory chain complexes increases mitochondrial ROS and peroxynitrite formation. Oxidative stress increases the release of lipid peroxidation products and cytokines, which together trigger the liver lesions of NASH.
Role of innate immune response in liver regeneration
Authors: Iimuro Yuji , Seki Ekihiro , Son Gakuhei , Tsutsui Hiroko , Nakanishi Kenji , Fujimoto Jiro 
Published: May 2007

AbstractLiver regeneration following partial hepatectomy (PH) requires several steps including innate immune responses, particularly interleukin‐6 (IL‐6) and tumor necrosis factor‐(TNF‐)α production by Kupffer cells, although the activation processes are still unknown. Toll‐like receptors (TLR) act as innate immune signal sensors and play central roles in host defense. Myeloid differentiation factor (MyD) 88 is a common adaptor molecule required for signaling mediated by TLR. When the receptors are activated, cells bearing TLR produce various pro‐nflammatory cytokines in a MyD88‐dependent manner. The authors investigated whether TLR/MyD88 signaling is critical for induction of innate immune responses after PH. In Myd88‐/‐ mice after PH, induction of expression of immediate early genes involved in hepatocyte replication and phosphorylation of signal transducer and activators of transcription 3 (STAT3) in the liver, and production of TNF‐α/IL‐6 by and activation of NF‐κB in the Kupffer cells were grossly subnormal and were associated with impaired liver regeneration, while TLR2, 4 and 9, which recognize Gram‐negative and ‐positive bacterial products, are not essential for NF‐κB activation and IL‐6 production after PH. In conclusion, the TLR/MyD88 pathway is essential for liver restoration after PH, particularly its early phase.
Role of hepatic stellate cells in fibrogenesis and the reversal of fibrosis
Authors: Kisseleva Tatiana , Brenner David A 
Published: May 2007

AbstractLiver fibrosis is caused by many chronic diseases. Liver injury results in activation of collagen‐producing cells and excessive deposition of extracellular matrix proteins. This process is orchestrated by many cell types. Hepatocytes apoptosis and inflammatory cells trigger secretion of profibrogenic and proinflammatory cytokines, such as transforming growth factor‐β1, angiotensin II, leptin, which in turn activates hepatic stellate cells, the major source of collagen type I. This review is focused on recent progress in the study of the pathogenesis of liver fibrosis.
Molecular mechanisms of hepatic fibrogenesis
Authors: Parsons Christopher J , Takashima Motoki , Rippe Richard A 
Published: May 2007

AbstractLiver fibrosis, a wound‐healing response to a variety of chronic stimuli, is characterized by excessive deposition of extracellular matrix (ECM) proteins, of which type I collagen predominates. This alters the structure of the liver leading to organ dysfunction. The activated hepatic stellate cell (HSC) is primarily responsible for excess collagen deposition during liver fibrosis. Two important aspects are involved in mediating the fibrogenic response: first the HSC becomes directly fibrogenic by synthesizing ECM proteins; second, the activated HSC proliferates, effectively amplifying the fibrogenic response. Although the precise mechanisms responsible for HSC activation remain elusive, substantial insight is being gained into the molecular mechanisms responsible for ECM production and cell proliferation in the HSC. The activated HSC becomes responsive to both proliferative (platelet‐derived growth factor) and fibrogenic (transforming growth factor‐β[TGF‐β]) cytokines. It is becoming clear that these cytokines activate both mitogen‐activated protein kinase (MAPK) signaling, involving p38, and focal adhesion kinase–phosphatidylinositol 3‐kinase–Akt–p70 S6 kinase (FAK‐PI3K‐Akt‐p70S6K) signaling cascades. Together, these regulate the proliferative response, activating cell cycle progression as well as collagen gene expression. In addition, signaling by both TGF‐β, mediated by Smad proteins, and p38 MAPK influence collagen gene expression. Smad and p38 MAPK signaling have been found to independently and additively regulate α1(I) collagen gene expression by transcriptional activation while p38 MAPK, but not Smad signaling, increases α1(I) collagen mRNA stability, leading to increased synthesis and deposition of type I collagen. It is anticipated that by understanding the molecular mechanisms responsible for HSC proliferation and excess ECM production new therapeutic targets will be identified for the treatment of liver fibrosis.
Non‐alcoholic steatohepatitis and hepatocellular carcinoma: Lessons from hepatocyte‐specific phosphatase and tensin homolog (PTEN)‐deficient mice
Authors: Watanabe Sumio , Horie Yasuo , Kataoka Ei , Sato Wataru , Dohmen Takahiro , Ohshima Shigetoshi , Goto Takashi , Suzuki Akira 
Published: May 2007

AbstractNon‐alcoholic steatohepatitis (NASH) is a term used to describe a spectrum of conditions characterized by histological findings of hepatic macrovesicular steatosis with inflammation in individuals who consume little or no alcohol. The NASH patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Hepatocyte‐specific phosphatase and tensin homolog (PTEN)‐deficient mice (PTEN‐deficient mice), which the authors had generated previously, showed massive hepatomegaly and steatohepatitis with triglyceride accumulation followed by liver fibrosis and HCC, a phenotype similar to human NASH. Therefore, it was shown that PTEN deficiency in hepatocytes could induce hepatic steatosis, inflammation, fibrosis and tumors and that PTEN‐deficient mice were a useful animal model for not only the understanding of the pathogenesis of NASH but also the development of treatment for NASH.
Role of apoptosis in acetaminophen hepatotoxicity
Authors: Kon Kazuyoshi , Ikejima Kenichi , Okumura Kyoko , Aoyama Tomonori , Arai Kumiko , Takei Yoshiyuki , Lemasters John J , Sato Nobuhiro 
Published: May 2007

AbstractAcetaminophen overdose causes liver injury by mechanisms involving glutathione depletion, oxidative stress and mitochondrial dysfunction. The role of apoptosis in acetaminophen‐induced cell killing is still controversial. Here, our aim was to evaluate the mitochondrial permeability transition (MPT) as a key factor in acetaminophen‐induced necrotic and apoptotic killing of primary cultured mouse hepatocytes. Acetaminophen (10 μmol/L) induced necrotic killing in approximately 50% of hepatocytes after 6 h and cyclosporin A (CsA), MPT inhibitor, temporarily decreased necrotic killing after 6 h, but cytoprotection was lost after 16 h. Confocal microscopy revealed mitochondrial depolarization and inner membrane permeabilization at approximately 4.5 h after acetaminophen. CsA delayed these changes indicative of the MPT to about 11 h after acetaminophen. TUNEL labeling and caspase 3 activation also increased after acetaminophen. Fructose (20 mmol/L, an ATP‐generating glycolytic substrate) plus glycine (5 mmol/L, a membrane stabilizing amino acid) prevented nearly all necrotic cell killing but paradoxically increased apoptosis. In conclusion, acetaminophen induces the MPT and ATP‐depletion‐dependent necrosis or caspase‐dependent apoptosis as determined, in part, by ATP availability from glycolysis.