bluuebunny/crossref_metadata_2025 huggingface dataset:
Tobacco smoking habits among a cross‐section of rural physicians in China
Authors: Smith Derek R. , Wei Ning , Zhang Yi‐Jie , Wang Rui‐Sheng
Published: March 2006

Objective:  To investigate the prevalence and distribution of tobacco smoking among rural Chinese physicians.

Design:  A self‐reporting survey adapted from previous international studies.

Setting:  A teaching hospital in Hebei Province, China.

Subjects:  A complete cross‐section of 361 physicians working in all hospital departments.

Results:  The overall response rate was 79.2%, among whom 15.7% (95% confidence interval (CI) 12.0–20.4) were current smokers and 1.0% ex‐smokers (95% CI 0.4–3.1). There were no female smokers when stratified by sex, although the prevalence rate among male physicians was 31.9% (95% CI 24.8–40.0). The prevalence of smoking varied widely by hospital department, ranging from zero in the obstetrics and gynaecology department, to 32.6% in the surgical unit. Smoking rates also varied by age, with physicians younger than 25 years having the lowest prevalence (6.3%). Although they only accounted for 7.1% of the entire group by number, the highest smoking prevalence was seen among physicians aged 50–54 years (31.6%).

Conclusions:  Although our study suggests that smoking is an important health issue for rural Chinese physicians, the distribution of risk is not uniform. Future preventive measures will, therefore, need to consider the individual situation of physicians who smoke, particularly those in the older age groups.
Utilisation and clinical efficacy of echocardiography in a regional hospital
Authors: McLean Rick , Malek Sharafat , Corish John , Sienkiewicz Garry
Published: March 2006

Objective:  To determine utilisation and clinical efficacy of echocardiography in a regional setting.

Design:  Consecutive patients referred for echocardiography studied prospectively using a pro‐forma to be completed before and after echocardiography.

Setting:  Regional hospital in New South Wales.

Participants:  A total of 103 consecutive patients.

Main outcome measures:  Utilisation and clinical efficacy of echocardiography.

Results:  No significant abnormalities were detected in 41.7% of patients, but unexpected abnormalities were found in 31.1%. For 60% of pretest diagnoses there was a clinically important change in diagnostic certainty following the test and changes to treatment occurred in 30.1% of patients. A total of 19 patients with neurological events underwent echocardiography but none had cardiac thrombus demonstrated although thrombus was demonstrated in additional seven.

Conclusions:  Echocardiography appears to be used appropriately in our regional setting, resulting in major changes to diagnostic certainty and leading to alterations to treatments in almost one‐third of patients. Education in relation to the use of echocardiography in patients with neurological events is warranted.
Mental health referral role of rural financial counsellors
Authors: Fuller Jeffrey , Broadbent Jessica
Published: March 2006

Objective:  To quantify the proportion of rural financial counsellors’ (RFC) clients requiring social, emotional and stress‐related (SESR) assistance and the referral of these clients to other services.

Design:  Survey of all Australian RFCs.

Setting:  Rural and remote agricultural locations in Australia.

Participants:  Australian RFCs employed over the months of November and December 2004.

Main outcome measures:  The proportion of counsellors’ clients who required assistance with SESR problems and the proportion of these who were referred. Counsellors’ usual referral networks, rating of referral difficulty and ranking of strategies to improve referrals.

Results:  Counsellors reported that on average 20% of their clients required SESR assistance and half of the counsellors referred more than 75% of these clients. Referrals were mainly to GPs, mental health teams, personal counselling and health and welfare organisations. Almost half (49%) reported that referrals were difficult because of rural clients’ reluctance to acknowledge such problems and use mental health services, as well as the lack of these services. Counsellors were placed in a practical role dilemma when clients raised personal issues that were beyond the counsellors’ role but were linked to the financial reason for presentation. Strategies identified to improve referrals were to network with mental health and personal counsellors in the region, training and a referral guide.

Conclusions:  Because RFCs are a first contact for rural people in crisis, they could be brought into a local counselling network. This network could improve the process of referrals and build local mental health system capacity.
PI3K and ERK 1‐2 regulate early stages during head regeneration in hydra
Authors: Manuel Gema C. , Reynoso Rosalia , Gee Lydia , Salgado Luis M. , Bode Hans R.
Published: March 2006

Different signaling systems coordinate and regulate the development of a multicellular organism. In hydra, the canonical Wnt pathway and the signal transduction pathways mediated by PKC and Src regulate early stages of head formation. In this paper, we present evidence for the participation of a third pathway, the PI3K‐PKB pathway, involved in this process. The data presented here are consistent with the participation of ERK 1‐2 as a point of convergence for the transduction pathways mediated by PKC, Src and PI3K for the regulation of the regeneration of the head in hydra. The specific developmental point regulated by them appears to be the commitment of tissue at the apical end of the regenerate to form the head organizer.
Postembryonic epigenesis of Vasa‐positive germ cells from aggregated hemoblasts in the colonial ascidian, Botryllus primigenus
Authors: Sunanaga Takeshi , Saito Yasunori , Kawamura Kazuo
Published: March 2006

We investigated whether Vasa was a germline‐specific marker in the colonial ascidian Botryllus primigenus, and whether it was inducible epigenetically in the adult life span. We cloned a Botryllus Vasa homologue (BpVas). The deduced open reading frame encoded 687 amino acid residues. It was expressed specifically by germline cells such as the loose cell mass, oogonia and juvenile oocytes in the ovary, and the primordial testis (compact cell mass), spermatogonia and juvenile spermatocytes in the testis. The loose cell mass, the most primitive germline cells, showed an ultrastructure of undifferentiated cells known as hemoblasts. The hemoblasts did not contain electron‐dense materials or a mitochondrial assembly in the cytoplasm. These organelles appeared later in the oogonia and oocytes. When the loose cell mass and developing germ cells were eliminated by extirpating all zooids and buds from the colonies, BpVas transcripts disappeared completely from the vascularized colonies. After 14 days, when the colonies regenerated by vascular budding, BpVas‐positive cells reappeared in some cases, and in 30 day colonies, BpVas‐positive germ cells were observed in all the regenerated colonies. These results show that in B. primigenus, germ cells are inducible de novo from the Vasa‐negative cells even at postembryonic stages.
Generation of new human embryonic stem cell lines with diploid and triploid karyotypes
Authors: Baharvand Hossein , Ashtiani Saeid Kazemi , Taee Adeleh , Massumi Mohammad , Valojerdi Mojtaba R. , Yazdi Poopak E. , Moradi Shabnam Z. , Farrokhi Ali
Published: March 2006

Human pluripotent embryonic stem cells (hESC) have great promise for research into human developmental biology and the development of cell therapies for the treatment of diseases. To meet the increased demand for characterized hESC lines, we present the derivation and characterization of five hESC lines on mouse embryonic fibroblast cells. Our stem cell lines are characterized by morphology, long‐term expansion, and expression profiles of a number of specific markers, including TRA‐1‐60, TRA‐1‐81, alkaline phosphatase, connexin 43, OCT‐4, NANOG, CXCR4, NODAL, LEFTY2, THY‐1, TDGF1, PAX6, FOXD3, SOX2, EPHA2, FGF4, TAL1, AC133 and REX‐1. The pluripotency of the cell line was confirmed by spontaneous differentiation under in vitro conditions. Whereas all of the cell lines expressed all the characteristics of undifferentiated pluripotent hESC, two of the cell lines carried a triploid karyotype.
Clinicopathologic features of patients with intrahepatic cholangiocarcinoma who are seropositive for α‐fetoprotein‐L3 and those with combined hepatocellular and cholangiocarcinoma
Authors: Okuda Hiroaki , Shiratori Keiko , Yamamoto Masakazu , Takasaki Ken , Nakano Masayuki
Published: March 2006

Background:  Some patients who are seropositive for lectin‐reactive α‐fetoprotein (AFP‐L3) have intrahepatic cholangiocarcinoma (ICC). There have been no studies regarding the features of ICC patients seropositive for AFP‐L3. Thus, the purpose of the present paper was to compare the features of ICC patients from the viewpoint of two different tumor markers, AFP‐L3 and carbohydrate antigen (CA) 19‐9.

Methods:  The ICC patients who underwent hepatectomy (n = 51) were divided into three groups, and their clinicopathologic features were compared: (i) group A, seropositive for AFP‐L3 ≥ 15%; (ii) group B, seropositive for CA 19‐9 ≥ 37 U/mL; and (iii) group C, seronegative for both AFP‐L3 and CA 19‐9. The features of combined hepatocellular and cholangiocarcinoma (n = 11) were also studied.

Results:  Group A had a higher positivity rate for hepatitis viruses than group B (60%vs 20%, P < 0.05). More patients in group A were misdiagnosed as having hepatocellular carcinoma (HCC) at surgery (70%vs 5.7%, P < 0.001) who also had chronic liver disease (80%vs 25.7%, P < 0.01) than in group B. Seven, 10 and 11 of the 11 patients with combined hepatocellular and cholangiocarcinoma were seropositive for AFP‐L3, CA 19‐9 and hepatitis viruses, respectively. Ten were diagnosed as having HCC at surgery and nine had chronic liver disease.

Conclusions:  Patients with ICC seropositive for AFP‐L3 and those with combined hepatocellular and cholangiocarcinoma have features close to HCC. The present study has, for the first time, identified a subgroup of ICC patients, seropositive for AFP‐L3, having features close to HCC that are very different from those of the classical ICC patients seropositive for CA 19‐9.
Hepatitis B core antigen expression pattern reflects the response to anti‐viral treatment
Authors: Uzun Yusuf , Bozkaya Hakan , Erden Esra , Cinar Kubilay , Idilman Ramazan , Yurdaydin Cihan , Uzunalimoglu Ozden
Published: March 2006

Background:  In hepatitis B early antigen (HBeAg)‐negative patients, response predictors to current treatment regimens are not well known. Hepatocyte cell cycle may influence hepatitis B virus (HBV) replication and hepatitis B core antigen (HBcAg) expression, which is a major target for antiviral immune response. The aim of the present paper was to evaluate the role of HBcAg expression in liver tissue and the rate of hepatocyte proliferation in response to antiviral treatment in chronic hepatitis B.

Methods:  A total of 33 chronic hepatitis B patients (nine HBeAg positive, 24 HBeAg negative) treated with either lamivudine and interferon combined or lamivudine alone were included. Liver expressions of proliferating cell nuclear antigen (PCNA) and HBcAg were immunohistochemically determined. The HBV‐DNA levels were measured by a hybride capture assay. Complete response was defined as alanine aminotransferase (ALT) normalization and HBV‐DNA negativity.

Results:  At the end of treatment, 23 patients (67.7%) were responders (12 of 23 were sustained responders), while 10 (33.3%) were non‐responders. Age, sex, ALT, HBV‐DNA levels, HBeAg status, histological activity, fibrosis scores and PCNA labeling index were similar in responders versus non‐responders at baseline. The number of patients with positive HBcAg staining was lower in responders compared to non‐responders at the end of treatment (17.4% vs 80%, respectively, P < 0.001), although a similar number of sustained responders and non‐responders had positive HBcAg staining.

Conclusion:  Absence or a low level of HBcAg expression may predict the end of treatment response to current therapies, especially in HBeAg (–) patients. The PCNA determination does not predict treatment response.
Preliminary study of chemical bile duct embolization to treat hepatolithiasis in rabbits
Authors: Li Fu Yu , Cheng Jing Qiu , Mao Hui , Li Ning , Jiang Li Sheng , He Sheng , Cheng Nan Sheng , Dong Jia Hong
Published: March 2006

Background:  The high recurrence rate of hepatolithiasis is still a problem to be solved. The purpose of the present study was therefore to carry out a preliminary study of the practical value of chemical bile duct embolization (CBDE) to treat hepatolithiasis in rabbits.

Methods:  Chemical bile duct embolization was performed with phenol or absolute ethanol along with N‐butyl‐cyanoacrylate. The feasibility and effectiveness of CBDE for chemical hepatectomy was assessed by investigating histological changes, biochemistry for hydroxyproline and in situ hybridization for collagen I.

Results:  Histologically, the mucosal epithelia of the embolized bile ducts were entirely replaced by collagen fibers, thus effectively eradicating chronic proliferative cholangitis. Also of note, the diseased biliary duct lumens were completely filled with N‐butyl‐cyanoacrylate, thus effectively preventing calculus formation. The hepatocytes also disappeared completely in the periphery of the embolized lobe, demonstrating that the desired effects of chemical hepatectomy were achieved through CBDE. In a further comparison of embolizing agents, the phenol‐cyanoacrylate embolized livers and bile ducts had a higher level of hydroxyproline and collagen I than those embolized with ethanol plus cyanoacrylate.

Conclusion:  Chemical bile duct embolization is a promising approach to prevent the recurrence of hepatolithiasis and to achieve the effect of chemical hepatectomy.
Passive avoidance training decreases synapse density in the hippocampus of the domestic chick
Authors: Nikolakopoulou A. M. , Davies H. A. , Stewart M. G.
Published: March 2006

The bird hippocampus (Hp), although lacking the cellular lamination of the mammalian Hp, possesses comparable roles in spatial orientation and is implicated in passive avoidance learning. As in rodents it can be divided into dorsal and ventral regions based on immunocytochemical, tracing and electrophysiological studies. To study the effects of passive avoidance learning on synapse morphometry in the Hp, spine and shaft synapse densities of 1‐day‐old domestic chicks were determined in dorsal and ventral Hp of each hemisphere by electron microscopy, 6 and 24 h following training to avoid pecking at a bead coated with a bitter‐tasting substance, methyl anthranilate (MeA). The density of asymmetric spine and shaft synapses in MeA‐trained birds at 6 h post‐training was significantly lower in the dorsal and ventral Hp of the right hemisphere relative to control (untrained) chicks, but by 24 h this difference was absent. A hemispheric asymmetry was apparent in the ventral Hp where the water‐trained group showed enhanced shaft and spine synapse density in the left hemisphere, whilst in the MeA‐trained group only asymmetric shaft synapses follow the same pattern in relation to the right hemisphere. There were no differences in asymmetric shaft synapses in the dorsal Hp at 6 h post‐training, but at 24 h post‐training there was a reduction in the density of shaft synapses in the right hemisphere in MeA compared with control birds. These data are discussed in relation to the pruning effects of stress and learning on synapse density in chick Hp.
The development of cortical connections
Authors: Price David J. , Kennedy Henry , Dehay Colette , Zhou Libing , Mercier Marjorie , Jossin Yves , Goffinet André M. , Tissir Fadel , Blakey Daniel , Molnár Zoltán
Published: March 2006

The cortex receives its major sensory input from the thalamus via thalamocortical axons, and cortical neurons are interconnected in complex networks by corticocortical and callosal axons. Our understanding of the mechanisms generating the circuitry that confers functional properties on cortical neurons and networks, although poor, has been advanced significantly by recent research on the molecular mechanisms of thalamocortical axonal guidance and ordering. Here we review recent advances in knowledge of how thalamocortical axons are guided and how they maintain order during that process. Several studies have shown the importance in this process of guidance molecules including Eph receptors and ephrins, members of the Wnt signalling pathway and members of a novel planar cell polarity pathway. Signalling molecules and transcription factors expressed with graded concentrations across the cortex are important in establishing cortical maps of the topography of sensory surfaces. Neural activity, both spontaneous and evoked, plays a role in refining thalamocortical connections but recent work has indicated that neural activity is less important than was previously thought for the development of some early maps. A strategy used widely in the development of corticocortical and callosal connections is the early overproduction of projections followed by selection after contact with the target structure. Here we discuss recent work in primates indicating that elimination of juvenile projections is not a major mechanism in the development of pathways feeding information forward to higher levels of cortical processing, although its use is common to developing feedback pathways.
Endogenous opioids upregulate brain‐derived neurotrophic factor mRNA through δ‐ and µ‐opioid receptors independent of antidepressant‐like effects
Authors: Zhang Huina , Torregrossa Mary M. , Jutkiewicz Emily M. , Shi Yong‐Gong , Rice Kenner C. , Woods James H. , Watson Stanley J. , Holden Ko M. C.
Published: March 2006

Systemic administration of δ‐opioid receptor (DOR) agonists decreases immobility in the forced swim test (FST) and increases brain‐derived neurotrophic factor (BDNF) mRNA expression in rats, indicating that DOR agonists may have antidepressant‐like effects. The aim of this study was to investigate the effects of central administration of endogenous opioid peptides on behavior in the FST and on brain BDNF mRNA expression in rats. Effects of endogenous opioids were compared with those produced by intracerebroventricular administration of a selective non‐peptidic DOR agonist (+)BW373U86. Antidepressant‐like effects were measured by decreased immobility in the FST. BDNF mRNA expression was determined by in situ hybridization. Centrally administered (+)BW373U86 decreased immobility and increased BDNF mRNA expression in the frontal cortex through a DOR‐mediated mechanism, because these effects were blocked by the DOR antagonist naltrindole, but not by the µ‐opioid receptor (MOR) antagonist naltrexone (NTX) or the κ‐opioid receptor antagonist nor‐binaltorphimine. Of all the endogenous opioids tested, only leu‐ and met‐enkephalin produced behavioral effects like those of (+)BW373U86 in the FST. Unlike (+)BW373U86, the enkephalins upregulated BDNF mRNA expression in the hippocampus through DOR‐ and MOR‐mediated mechanisms. β‐Endorphin, endomorphin‐1 and endomorphin‐2 significantly increased BDNF mRNA levels in the frontal cortex, hippocampus and amygdala without reducing immobility; and most of these effects were reversed by NTX. This study is the first to provide evidence that endogenous opioids can upregulate BDNF mRNA expression through the DOR and MOR, and that leu‐ and met‐enkephalin have similar pharmacological profiles to synthetic DOR agonists in producing antidepressant‐like effects.
Dopamine desynchronizes the pace‐making neuronal activity of rat respiratory rhythm generation
Authors: Fujii Morimitsu , Umezawa Kazuo , Arata Akiko
Published: March 2006

In an excised Wistar rat medulla‐spinal cord block preparation we previously found that dopamine slows respiratory rhythm by activation of dopamine D4 receptors [Fujii et al., (2004)Neurosci. Res., 50, 355–359.] In the present paper, we investigated the effect of dopamine on pre‐inspiratory (Pre‐I) and inspiratory (I) neurons using the combination of an optical recording technique with a voltage‐sensitive dye, unit recording and patch‐clamp recording. Optical imaging of the ventral surface of the block preparation disclosed different locations and activity patterns of Pre‐I and I neurons. In addition to slowing the rhythm, dopamine depressed respiratory activity of Pre‐I neurons collectively but not that of I neurons. The dopaminergic suppression of Pre‐I neurons was mimicked by a dopamine D4 receptor agonist, PD168077. Unit recording and patch‐clamp recording demonstrated that dopamine depolarizes Pre‐I neurons, disperses Pre‐I firing and depresses Pre‐I phase postsynaptic potentials (PSPs) of I neurons. Immunohistological investigation revealed that Pre‐I neurons express dopamine D4 receptors. We found that approximately 60% of Pre‐I neurons express dopamine D4 receptors. These results show that dopaminergic respiratory rhythm depression is due to dispersion of synchronized Pre‐I driving of I neurons caused by dopamine D4 receptor stimulation of Pre‐I neurons.
The opioid peptide nociceptin/orphanin FQ mediates prostaglandin E2‐induced allodynia, tactile pain associated with nerve injury
Authors: Okuda‐Ashitaka Emiko , Minami Toshiaki , Matsumura Shinji , Takeshima Hiroshi , Reinscheid Rainer K. , Civelli Olivier , Ito Seiji
Published: March 2006

Pain often outlasts its usefulness as warning and aid in wound healing, and becomes chronic and intractable after tissue damage and nerve injury. Many molecules have been implicated as mediators and modulators in persistent pain such as hyperalgesia and tactile pain (allodynia). We previously showed that prostaglandin (PG) E2, PGF2αor the neuropeptide nociceptin, also called orphanin FQ (N/OFQ) administered intrathecally (i.t.) produced allodynia in conscious mice. In the present study, we examined the relationship of pain responses between PGs and N/OFQ using the N/OFQ receptor (NOP) antagonist,N‐(4‐amino‐2‐methylquinolin‐6‐yl)‐2‐(4‐ethylphenoxy‐methyl)benzamide monohydrochloride (JTC‐801), and in mice lacking the N/OFQ prepropeptide (ppN/OFQ–/–) and the NOP receptor (NOP–/–). JTC‐801 dose‐dependently blocked the N/OFQ‐ and PGE2‐induced allodynia, but not the PGF2α‐induced one. Neither N/OFQ nor PGE2induced allodynia in NOP–/–mice. By contrast, the N/OFQ‐induced allodynia was not affected by inhibition of PG production by a 60‐min pretreatment with the non‐steroidal anti‐inflammatory drug, indomethacin. Among PGE receptor (EP) subtype‐selective agonists, the EP4 agonist, AE1‐329, markedly stimulated the release of N/OFQ from spinal slices and induced allodynia. AE1‐329 also increased nitric oxide production in spinal slices using fluorescent nitric oxide detection, which was blocked by pretreatment with JTC‐801. Conversely, PGE2‐induced allodynia was not observed in ppN/OFQ–/–mice. N/OFQ immunoreactive puncta were colocalized with EP4. Taken together, these results demonstrate that PGE2induced allodynia by stimulation of N/OFQ release in the spinal cord via EP4 receptor subtypes.
Molecular mechanisms of cortical differentiation
Authors: Guillemot Francois , Molnár Zoltán , Tarabykin Victor , Stoykova Anastassia
Published: March 2006

During development, several populations of progenitor cells in the dorsal telencephalon generate a large variety of neurons which acquire distinct morphologies and physiological properties and serve distinct functions in the mammalian cortex. This paper reviews recent work that has identified (i) key molecules involved in the specification and differentiation of cortical neurons, (ii) novel genes which distinguish distinct subsets of cortical progenitors and may be involved in the diversification of cortical neurons present in different cortical layers, and (iii) mechanisms involved in the generation of different projection neuronal subtypes in the well‐studied model of layer 5 of the rodent cortex.
Circulating insulin‐like growth factor I and functional recovery from spinal cord injury under enriched housing conditions
Authors: Koopmans Guido C. , Brans Maike , Gómez‐Pinilla Fernando , Duis Simone , Gispen Willem Hendrick , Torres‐Aleman Ignazio , Joosten Elbert A. J. , Hamers Frank P. T.
Published: March 2006

Voluntary locomotor training as induced by enriched housing of rats stimulates recovery of locomotion after spinal cord injury (SCI). Generally it is thought that spinal neural networks of motor‐ and interneurons located in the ventral and intermediate laminae within the lumbar intumescence of the spinal cord, also referred to as central pattern generators (CPGs), are the ‘producers of locomotion’ and play a pivotal role in the amelioration of locomotor deficits after SCI. It has been suggested that locomotor training provides locomotor‐specific sensory feedback into the CPGs, which stimulates remodeling of central nervous system pathways, including motor systems. Several molecules have been proposed to potentiate this process but the underlying mechanisms are not yet known. To understand these mechanisms, we studied the role of insulin‐like growth factor (IGF) I in functional recovery from SCI under normal and enriched environment (EE) housing conditions. In a first experiment, we discovered that subcutaneous administration of IGF‐I resulted in better locomotor recovery following SCI. In a second experiment, detailed analysis of the observed functional recovery induced by EE revealed full recovery of hindlimb coordination and stability of gait. This EE‐dependent functional recovery was attenuated by alterations in the pre‐synaptic bouton density within the ventral gray matter of the lumbar intumescence or CPG area. Neutralization of circulating IGF‐I significantly blocked the effectiveness of EE housing on functional recovery and diminished the EE‐induced alterations in pre‐synaptic bouton density within the CPG area. These results support the use of IGF‐I as a possible therapeutic aid in early rehabilitation after SCI.
CXCL10‐induced cell death in neurons: role of calcium dysregulation
Authors: Sui Yongjun , Stehno‐Bittel Lisa , Li Shanping , Loganathan Rajprasad , Dhillon Navneet K. , Pinson David , Nath Avindra , Kolson Dennis , Narayan Opendra , Buch Shilpa
Published: March 2006

Chemokines play a key role in the regulation of central nervous system disease. CXCL10 over‐expression has been observed in several neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease and HIV‐associated dementia. More recent studies by others and us have shown that CXCL10 elicits apoptosis in fetal neurons. The mechanism of CXCL10‐mediated neurotoxicity, however, remains unclear. In this study, we provide evidence for the direct role of Ca2+ dysregulation in CXCL10‐mediated apoptosis. We demonstrate that treatment of fetal neuronal cultures with exogenous CXCL10 produced elevations in intracellular Ca2+ and that this effect was modulated via the binding of CXCL10 to its cognate receptor, CXCR3. We further explored the association of intracellular Ca2+ elevations with the caspases that are involved in CXC10‐induced neuronal apoptosis. Our data showed that increased Ca2+, which is available for uptake by the mitochondria, is associated with membrane permeabilization and cytochrome c release from this compartment. The released cytochrome c then activates the initiator active caspase‐9. This initiator caspase sequentially activates the effector caspase‐3, ultimately leading to apoptosis. This study identifies the temporal signaling cascade involved in CXCL10‐mediated neuronal apoptosis and provides putative targets for pharmaceutical intervention of neurological disorders associated with CXCL10 up‐regulation.
Diurnal regulation of the gastrin‐releasing peptide receptor in the mouse circadian clock
Authors: Karatsoreos Ilia N. , Romeo Russell D. , McEwen Bruce S. , Silver Rae
Published: March 2006

In mammals, circadian rhythms are generated by the suprachiasmatic nuclei (SCN) of the hypothalamus. SCN neurons are heterogeneous and can be classified according to their function, anatomical connections, morphology and/or peptidergic identity. We focus here on gastrin‐releasing peptide‐ (GRP) and on GRP receptor‐ (GRPr) expressing cells of the SCN. Pharmacological application of GRP in vivo or in vitro can shift the phase of circadian rhythms, and GRPr‐deficient mice show blunted photic phase shifting. Given the in vivo and in vitro effects of GRP on circadian behavior and on SCN neuronal activity, we investigated whether the GRPr might be under circadian and/or diurnal control. Using in situ hybridization and autoradiographic receptor binding, we localized the GRPr in the mouse SCN and determined that GRP binding varies with time of day in animals housed in a light–dark cycle but not in conditions of constant darkness. The latter results were confirmed with Western blots of SCN tissue. Together, the present findings reveal that changes in GRPr are light driven and not endogenously organized. Diurnal variation in GRPr activity probably underlies intra‐SCN signaling important for entrainment and phase shifting.
Rpe65 as a modifier gene for inherited retinal degeneration
Authors: Samardzija M. , Wenzel A. , Naash M. , Remé C. E. , Grimm C.
Published: March 2006

Light accelerates progression of retinal degeneration in many animal models of retinitis pigmentosa (RP). A sequence variant in the Rpe65 gene (Rpe65450Leu or Rpe65450Met) can act as a modulator of light‐damage susceptibility in mice by influencing the kinetics of rhodopsin regeneration and thus by modulating the photon absorption. Depending on exposure duration and light intensity applied, white fluorescent light induces photoreceptor apoptosis and retinal degeneration in wild‐type mice by the activation of one of two known molecular pathways. These pathways depend, respectively, on activation of the transcription factor c‐Fos/AP‐1 and on phototransduction activity. Here we tested Rpe65 as a genetic modifier for inherited retinal degeneration and analysed which degenerative pathway is activated in a transgenic mouse model of autosomal dominant RP. We show that retinal degeneration was reduced in mice expressing the Rpe65450Met variant and that these mice retained more visual pigment rhodopsin than did transgenic mice expressing the Rpe65450Leu variant. In addition, lack of phototransduction slowed retinal degeneration whereas ablation of c‐Fos had no effect. We conclude that sequence variations in the Rpe65 gene can act as genetic modifiers in inherited retinal degeneration, presumably by regulating the daily rate of photon absorption through the modulation of rhodopsin regeneration kinetics. Increased absorption of photons and/or light sensitivity appear to accelerate retinal degeneration via an apoptotic cascade which involves phototransduction but not c‐Fos.
PRINCIPLES AND THEORIES OF LOCAL GOVERNMENT
Authors: Watt Peter A.
Published: March 2006

The role of local government is viewed in the context of the overall role of government per se. A particular advantage of local government lies in its ability to arrange for the provision of local public goods in line with local tastes and preferences. A number of arguments suggest that local governments should be assigned adequate powers of local taxation to finance their expenditure responsibilities rather than having to rely on central government grant.
THE FAILURE OF THE POLL TAX AND CLASSICAL LIBERAL POLITICAL ECONOMY: LESSONS FOR THE FUTURE
Authors: Meadowcroft John
Published: March 2006

The failure of the Poll Tax has been claimed to be an indictment of the principles of classical liberal political economy that it was intended to apply to local government finance. This article argues that, on the contrary, the failure of the Poll Tax was entirely predictable from the perspective of classical liberal political economy, and, in particular, public choice economics, because it involved a politically impossible reassignment of the local tax burden, presented local electors with an insurmountable collective action problem and ignored the ‘vote motive’ underlying the actions of national politicians held accountable for the new tax. Finally, the article proposes some lessons for the future of local government reform from the experience of the Poll Tax.
A LOCAL SALES TAX WILL SET THE TOWN HALLS FREE
Authors: Carswell Douglas
Published: March 2006

At a time when the financing of local government is subject to particular scrutiny, this article advocates a radical change to the way local government is financed. It is argued that the Council Tax‐based system of local government finance should be abolished and that local government should be made entirely self‐financing by turning VAT into a Local Sales Tax.
HAYEK, ‘THE INTELLECTUALS AND SOCIALISM’, AND WEIGHTED SCALE‐FREE NETWORKS
Authors: Ormerod Paul
Published: March 2006

In 1949, Hayek attributed the dominant position of planning in the West to the role of intellectuals, by which he meant ‘professional second‐hand dealers in ideas’ such as journalists and commentators. Later in the twentieth century, we saw a similar phenomenon: particular social ideas, although frequently falsified empirically, have come to dominate through the efforts of intellectuals. This paper addresses how a small minority can set so decisively the terms of the debate. Hayek conjectured that this was the case, but did not specify the mechanism by which this can occur. Recent advances in network theory about how ideas can either spread across, or disappear in, a social network of individuals can explain this phenomenon. The implication of Hayek's insight, validated by modern network theory, is that think tanks should seek to influence ‘professional second‐hand dealers in ideas’ rather than adopt the naïve democratic principle of trying to persuade individual voters.
FREE TRADE, ‘PAUPER LABOUR’ AND PROSPERITY: A REPLY TO PROFESSOR MISHAN
Authors: Meadowcroft John
Published: March 2006

In an Economic Viewpoint published in the September 2005 edition of Economic Affairs, ‘Can Globalisation Depress Living Standards in the West?’, Professor E. J. Mishan argued that globalisation may reduce living standards in the West by decreasing the labour–capital ratio in developed countries as firms move production to countries where labour is cheaper and/or migrants to the West from the developing world bid down wage rates. In a reply to Professor Mishan's article, Dr John Meadowcroft argues that this view of globalisation is far too pessimistic and explains why free trade, not protection, will secure the prosperity of developed and developing economies. In a final comment, Professor Mishan responds to this critique of his analysis.
Familiar and environmental factors influencing atopic dermatitis in the childhood
Authors: Sebõk B , Schneider I ,   Primary Care Paediatricians in Baranya County, Harangi F
Published: March 2006

Background  The increase in the incidence of atopic dermatitis (AD) in developed countries has been related to familiar and environmental factors. This survey was undertaken to investigate the family background, birthweight and the home environment of children suffering from AD in order to point out the possible factors that provoke the development of the disease.

Methods  The study uses data collected by means of self‐administered questionnaires and discusses 461 cases of children (age 0–12) with active skin signs of AD. The control group comprised of 343 children (age 0–12) with no skin signs or positive lifetime history of AD. Associations between familiar and various home environmental factors and the risk of AD were calculated by means of odds ratios.

Results  There were statistically significant positive associations between atopic eczema symptoms and higher birthweight, small households, wall‐to‐wall carpets, as well as indoor‐kept pets. Day‐nursery attendance, heating system and indoor smoking, however, did not significantly alter the risk of the disease.

Conclusions  Because of the limitations of a retrospective questionnaire study, further research is needed to confirm these associations and clarify whether they are causative.
β‐Amyloid protein converting enzyme 1 and brain‐specific type II membrane protein BRI3: binding partners processed by furin
Authors: Wickham Louise , Benjannet Suzanne , Marcinkiewicz Edwige , Chretien Michel , Seidah Nabil G.
Published: March 2006

Using a yeast two‐hybrid system, we screened a human brain cDNA library for possible interacting proteins with the C‐terminal cytosolic tail of the β‐secretase β‐amyloid protein converting enzyme (BACE)1. This identified seven potential candidates, including the brain‐specific type II membrane protein BRI3. Co‐localization and co‐immunoprecipitation experiments confirmed that BACE1 and BRI3 co‐localize and interact with each other via the cytosolic tail of BACE1. Furthermore, pulse and pulse‐chase analyses revealed that the pro‐protein convertases furin, and to a lesser extent PC7 and PC5A, process BRI3 into a C‐terminal secreted ∼ 4‐kDa product. Thus, furin efficiently processes both pro‐BACE1 and its novel interacting protein pro‐BRI3.
An orthodoxy of ‘the local’: post‐colonialism, participation and professionalism in northern Thailand
Authors: MCKINNON KATHARINE ISLAY
Published: March 2006

Post‐colonial critiques of development reveal the neo‐colonial potential of the development project, embedded in the imbalances of power in relations between West and East, First World and Third World. One of the core responses to the challenge of such a critique has been to turn to new participatory approaches that privilege local knowledges, locally defined needs and priorities, above the vagaries of aid agencies or the ‘expertise’ of development professionals. In this paper I argue that such a shift in development discourse and method has had a significant impact on the discursive practices of professionalism and professional responsibility. Drawing on ethnographic research with development professionals in northern Thailand, I argue that participation has emerged as a new orthodoxy among development professionals who seek to identify themselves as ethical and moral agents of an emancipatory development project. The rise of such orthodoxy has had clear impacts in terms of fostering the emergence of local organization and advocacy groups. At the same time, however, this paper considers how a ‘pro‐local’ orthodoxy may also be having dis‐enabling effects for the very project of emancipation that professionals wish to carry out.
Bare life as a development/postcolonial problematic
Authors: SYLVESTER CHRISTINE
Published: March 2006

Development studies and postcolonial studies conceptualize and examine the Third World in different ways, yet works associated with the two fields can usefully be combined to illuminate key issues in our time. This article focuses on postcolonial transitions in parts of Africa where the state actively injures or kills a local citizenry, sometimes in the name of development. Using Zimbabwe and Rwanda as very different examples of such transitions, and drawing on selected development and postcolonial writings – fact and ‘fiction’– I argue for framing such cases as examples of the ‘bare life’, ‘camp’ biopolitics articulated by Georgio Agamben. These concepts enable us to see the widening spaces of exception to law that a postcolonial state can create in periods of crisis and defend on the grounds of post‐coloniality, that is, as states always already injured by colonialism and its biopolitical development project. The terrain such states enter might be termed ‘fascism’– a location of political economy that development studies has generally neglected in recent years but that novels depicting postcolonial contexts can make vivid.
From Alcohol Toxicity to Treatment
Authors: Seitz Helmut K. , Salaspuro Mikko , Savolainen Markku , Haber Paul , Ishii Hiromasa , Teschke Rolf , Moshage Hans , Lieber Charles S.
Published: March 2006

This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism in Mannheim, Germany, in October 2004. This symposium was dedicated to Charles S. Lieber in recognition of his contribution in alcohol research over the last 50 years. It was divided into two parts, namely effects of alcohol on the gastrointestinal tract and effects of alcohol on the liver. Major emphasis was given to recent discoveries elucidating mechanisms of alcohol‐associated carcinogenesis. M. Salaspuro (Finland) discussed the role of acetaldehyde in the saliva and in the large intestine with respect to its role in the pathogenesis of alcohol‐associated cancer, and H. K. Seitz (Germany) presented new data identifying individuals homozygous for the ADH1C&1 allele as high on risk for alcohol‐associated upper aerodigestive tract cancer. M. Savolainen (Finland) discussed the role phosphatidylethanol as a bioactive lipid that can mediate beneficial and harmful effects of alcohol drinking. In the second part of the symposium, alcoholic liver disease was discussed. P. Haber (Australia) presented new data on hepatic transcriptome in alcoholic liver disease with the identification of new genes possibly involved in alcohol‐initiated fibrogenesis of the liver, and H. Moshage (The Netherlands) described survival mechanisms of the cholestatic hepatocytes with implications for therapy in cholestatic liver disease. The role of the hepatic microsomal ethanol oxidizing system in the metabolism of alcohol in alcoholic liver disease was summarized by R. Teschke (Germany). H. Ishii (Japan) discussed the current status and treatment of alcoholic hepatitis in Japan. Finally, in a state‐of‐the‐art lecture, Charles S. Lieber (USA) discussed the development of the understanding of the pathophysiology of alcoholic liver disease in the last 50 years. He emphasized the role of pathophysiology as an important prerequisite for better treatment strategies.
The Search for New Ways to Change Implicit Alcohol‐Related Cognitions in Heavy Drinkers
Authors: Wiers Reinout W. , Cox W. Miles , Field Matt , Fadardi Javad S. , Palfai Tibor P. , Schoenmakers Tim , Stacy Alan W.
Published: March 2006

This article summarizes a symposium on new ways to change implicit alcohol‐related cognitions, presented at the 2005 Annual Meeting of the Research Society on Alcoholism in Santa Barbara, California, organized by Wiers and Cox. During the past few years, research has demonstrated that implicit cognitions predict unique variance in prospective alcohol use and preliminary results indicate that they also predict treatment outcomes. The central question in this symposium was how implicit cognitions can be changed and how the changes will influence behavior. Field presented data showing that an attentional bias for alcohol can be altered by attentional training: heavy drinkers who were trained not to attend to alcohol stimuli reported less craving and drank less beer than those trained to attend to alcohol stimuli. Schoenmakers used a similar, clinically relevant attentional retraining (AR) procedure, heavy drinkers were trained not to attend to alcohol pictures or received no training. After the training, the AR group attended less to the alcohol pictures than the control group. Fadardi described the Alcohol Attentional Control Training Program (AACTP), which makes alcohol drinkers aware of the automatic, cognitive determinants of their drinking and aims to help them to gain control over these processes. Data were presented to support the effectiveness of the AACTP. Palfai presented data showing that alcohol drinkers can be taught to use implementation intentions to gain control over their drinking, which may be used to automatically activate self‐control skills in the presence of alcohol cues. In his discussion, Stacy pointed out the importance of recent cognitive theories that integrate attention and memory processes—theories that can help us better understand the mechanisms involved in AR. Together, the studies presented demonstrate that there are promising new ways in which implicit alcohol‐related cognitions and their effects on drinking can be changed. After further refinement, these procedures might be used in clinical interventions that have not previously addressed implicit cognitive processes.
Effect of a Dementia Care Management Intervention on Primary Care Provider Knowledge, Attitudes, and Perceptions of Quality of Care
Authors: Chodosh Joshua , Berry Elise , Lee Martin , Connor Karen , DeMonte Robert , Ganiats Theodore , Heikoff Lisa , Rubenstein Laurence , Mittman Brian , Vickrey Barbara
Published: March 2006

OBJECTIVES: To evaluate the effect of a multicomponent dementia care management program on primary care provider knowledge, attitudes, and perceptions of quality of dementia care.

DESIGN: A clinic‐level randomized, controlled trial of a comprehensive care management program for patients with dementia and their nonprofessional caregivers. The program included provider education and protocols for care managers to communicate with patients' medical providers.

SETTING: Sixteen clinics (eight intervention, eight usual care) in three healthcare systems in San Diego, California.

PARTICIPANTS: Two hundred thirty‐two medical providers; 129 from eight intervention clinics; 103 from eight usual‐care clinics.

MEASUREMENTS: Providers were surveyed 9 months after intervention onset on knowledge (five items on four topics), attitudes about dementia (three items), and perception of quality of dementia care in their practice setting (three items). Multivariable linear and logistic regression models were used to evaluate the differences between intervention and usual‐care providers, adjusting for covariate effects across groups and clustering by clinic.

RESULTS: One hundred sixty‐six of 232 (72%) providers responded. Intervention providers had better knowledge about assessing decision‐making capacity than usual‐care providers (adjusted difference in percentage correct=12%; adjusted odds ratio=2.4, 95% confidence interval=1.2–4.8). Intervention providers viewed dementia patients as more difficult to manage in primary care than usual‐care providers (P=.03). There were no other differences in knowledge, attitudes, or care quality perceptions across intervention and usual‐care providers.

CONCLUSION: A comprehensive dementia care management model resulted in few differences in provider knowledge or attitudes favorable to dementia care, suggesting that this care model's effects on quality were primarily mediated through other components of the care management program.