bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cerebrovascular Pathology in Alzheimer's Disease and Its Influence on Clinical Variables
Authors: Modrego Pedro J. , Rios Consuelo , Pérez Trullen José M. , Errea José M. , García-Gómara Maria J. , Sanchez Sara
Published: February 2008

Vascular pathology is frequently found in the brains of patients with Alzheimer's disease (AD). The aim of this study is to assess the frequency of vascular pathology in the brain in AD patients in a systematic manner and its clinical significance at presentation. A series of 51 patients with mild to moderate AD were consecutively enrolled. At baseline, every patient underwent the following clinical scales: Mini-Mental, Clinical Dementia Rating Scale, Ischemic Scale, Blessed Dementia Rating Scale, Alzheimer's Disease Assessment Scale Cognitive Subscale, Neuropsychiatric Inventory, and an Activities of Daily Living Scale (Disability Assessment for Dementia). We also carried out magnetic resonance imaging of the brain and color echo Doppler of carotids to measure the intima-media thickness. White matter hyperintensities were quantitatively evaluated with the Wahlund scale. We did not find correlation between intima-media thicknesses of carotids and clinical scales and between the Wahlund scale and clinical scales. The presence or absence of both microinfarctions and hypertension had no influence in the scores of the clinical scales. We conclude that the vascular component is common in AD but only as coincident pathology.
Does a Wander Garden Influence Inappropriate Behaviors in Dementia Residents?
Authors: Detweiler Mark B. , Murphy Pamela F. , Myers Laura C. , Kim Kye Y.
Published: February 2008

Background: The effect on resident behaviors of adding a wander garden to an existing dementia facility was investigated. Methods: 34 male residents were observed for 12 months before and after opening the garden. Behaviors were assessed using the Cohen-Mansfield Agitation Inventory Short Form (CMAI), incident reports, as needed medications (pro re nata [PRN]), and surveys of staff and residents' family members as indices of affect. Results: Final CMAI scores and total PRNs employed were lower than baseline values with a trend for residents who used the garden more often to have less agitated behavior. Verbal inappropriate behaviors did not change significantly whereas physical incidents increased. Staff and family members felt that the wander garden decreased inappropriate behaviors and improved mood and quality of life of the dementia residents. Conclusions: Study design characteristics and garden management may have affected behaviors both positively and negatively. Additional studies are needed to explore the benefits of wander gardens for dementia residents.
Neuritic Pathology as a Correlate of Synaptic Loss in Dementia With Lewy Bodies
Authors: Revuelta Gonzalo J. , Rosso Andrea , Lippa Carol F.
Published: February 2008

Synaptic loss is present in Alzheimer's disease and correlates with the severity of dementia. Loss of synapses in dementia with Lewy bodies (DLB) does not correlate as clearly with cognitive status and its cause is unclear. To begin to understand the relationship between cognition and synaptic loss in DLB, we assessed immunoreactivity for the synaptic-terminal specific protein, synaptophysin, in the hippocampus in 14 DLB cases. Quantitative synaptic data were obtained using an Image-Pro semiautomated analysis system. We determined Braak stage, β-amyloid, Lewy bodies (LBs), and Lewy neurites (LN). We found significant correlations ( r = 0.617, P < .01) between Braak stage and synaptophysin score and marginal correlation between LN score and synaptophysin loss ( r = 0.694, P < .06). Correlations of β-amyloid and of LB density with synaptophysin score were unimpressive. These data support the hypothesis that synaptic loss in DLB is related to neuritic degeneration.
The Prevalence of Dementia in an Urban Turkish Population
Authors: Gurvit H. , Emre M. , Tinaz S. , Bilgic B. , Hanagasi H. , Sahin H. , Gurol E. , Kvaloy J.T. , Harmanci H.
Published: February 2008

A cross-sectional, population-based, 2-stage prevalence study was conducted in a sample of 1019 community-dwelling persons over the age of 70 years living in Istanbul. In the first phase, participants were screened with the Mini-Mental State Examination for evidence of cognitive impairment. In the second phase, 79% of those who screened positive (n = 322) and 9% of screen-negatives (n = 63) underwent a standardized diagnostic workup. Diagnosis of dementia and Alzheimer's disease (AD) was made according to established criteria. Ninety-three cases of dementia were identified, 58 of whom were diagnosed with probable AD. Based on these numbers, the prevalence rates of probable AD and dementia were calculated to be 11.0% (95% CI, 7.0% to 15.0%) and 20.0% (95% CI, 14.0% to 26.0%), respectively, in this population. Prevalence rates of dementia and AD in Istanbul, Turkey, are comparable with those seen in the Western world.
Nutrition Education Needs and Resources for Dementia Care in the Community
Authors: Keller Heather H. , Smith Dana , Kasdorf Cara , Dupuis Sherry , Schindel Martin Lori , Edward Gayle , Cook Carly , Genoe Rebecca
Published: February 2008

Nutrition problems and specificly weight loss are common in older adults with dementia living in the community. Study 1 involved interviews with 14 formal providers to identify the range of nutrition concerns they had experienced. In study 2, 74 Canadian Alzheimer Society chapters were surveyed by e-mail (23% participation rate) to determine nutrition concerns and education resources provided to clients. In all, 26 of these nutrition pamphlets or handouts were rated on content and format by 2 independent researchers using a standardized rating system. Common nutrition concerns identified in older adults with dementia living in the community include safety, weight loss, forgetting or refusing to eat, appetite, dysphagia, and unfavorable eating behaviors. Most resources provided to clients were considered low quality and did not match the nutrition concerns expressed by formal providers. Currently, there is a considerable knowledge translation gap around nutrition and dementia, and this study provides a basis for the future development of nutrition education resources.
Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours
Authors: Lunt Sarah Jane , Kalliomaki Tuula MK , Brown Allison , Yang Victor X , Milosevic Michael , Hill Richard P
Published: February 2008

Background

High tumour interstitial fluid pressure (IFP) has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m) or orthotopically and analysed their relationship to tumour vascularity and metastatic spread.

Methods

KHT-C murine fibrosarcoma, ME180 and SiHa human cervix carcinoma were grown either intramuscularly (i/m), sub-cutaneously (s/c) or orthotopically. Polyoma middle-T (MMTV-PyMT) transgenic spontaneous mammary tumours were studied either as spontaneous tumours or following orthotopic or i/m transplantation. IFP was measured in all tumours using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. An immunohistochemical analysis of tumour hypoxia, vascular density, lymphatic vascular density and proliferation was carried out in ME180 tumours grown both i/m and orthotopically. Blood flow was also assessed in the ME180 model using high-frequency micro-ultrasound functional imaging.

Results

Tumour IFP was heterogeneous in all the models irrespective of growth site: KHT-C i/m: 2–42 mmHg, s/c: 1–14 mmHg, ME180: i/m 5–68 mmHg, cervix 4–21 mmHg, SiHa: i/m 20–56 mmHg, cervix 2–26 mmHg, MMTV-PyMT: i/m: 13–45 mmHg, spontaneous 2–20 mmHg and transplanted 2–22 mmHg. Additionally, there was significant variation between individual tumours growing in the same mouse, and there was no correlation between donor and recipient tumour IFP values. Metastatic dissemination to the lungs or lymph nodes demonstrated no correlation with tumour IFP. Tumour hypoxia, proliferation, and lymphatic or blood vessel density also showed no relationship with tumour IFP. Speckle variance analysis of ultrasound images showed no differences in vascular perfusion between ME180 tumours grown i/m versus orthotopically despite differences in IFP.

Conclusion

Our studies across a range of different tumour models showed substantial heterogeneity in tumour IFP, suggesting differences in the vascular development and interstitial fluid dynamics in the individual tumours. The results demonstrate a strong stochastic aspect to tumour IFP development, notably the variation apparent between different tumours within the same animal and the lack of correlation between donor and recipient tumours.
Nurse-led implementation of an insulin-infusion protocol in a general intensive care unit: improved glycaemic control with increased costs and risk of hypoglycaemia signals need for algorithm revision
Authors: Alm-Kruse Kristin , Bull Eva M , Laake Jon H
Published: February 2008

Background

Strict glycaemic control (SGC) has become a contentious issue in modern intensive care. Physicians and nurses are concerned about the increased workload due to SGC as well as causing harm through hypoglycaemia. The objective of our study was to evaluate our existing degree of glycaemic control, and to implement SGC safely in our ICU through a nurse-led implementation of an algorithm for intensive insulin-therapy.

Methods

The study took place in the adult general intensive care unit (11 beds) of a 44-bed department of intensive care at a tertiary care university hospital. All patients admitted during the 32 months of the study were enrolled. We retrospectively analysed all arterial blood glucose (BG) results from samples that were obtained over a period of 20 months prior to the implementation of SGC. We then introduced an algorithm for intensive insulin therapy; aiming for arterial blood-glucose at 4.4 – 6.1 mmol/L. Doctors and nurses were trained in the principles and potential benefits and risks of SGC. Consecutive statistical analyses of blood samples over a period of 12 months were used to assess performance, provide feedback and uncover incidences of hypoglycaemia.

Results

Median BG level was 6.6 mmol/L (interquartile range 5.6 to 7.7 mmol/L) during the period prior to implementation of SGC (494 patients), and fell to 5.9 (IQR 5.1 to 7.0) mmol/L following introduction of the new algorithm (448 patients). The percentage of BG samples > 8 mmol/L was reduced from 19.2 % to 13.1 %. Before implementation of SGC, 33 % of samples were between 4.4 to 6.1 mmol/L and 12 patients (2.4 %) had one or more episodes of severe hypoglycaemia (< 2.2 mmol/L). Following implementation of SGC, 45.8 % of samples were between 4.4 to 6.1 mmol/L and 40 patients (8.9 %) had one or more episodes of severe hypoglycaemia. Of theses, ten patients died while still hospitalised (all causes).

Conclusion

The retrospective part of the study indicated ample room for improvement. Through the implementation of SGC the fraction of samples within the new target range increased from 33% to 45.8%. There was also a significant increase in severe hypoglycaemic episodes. There continues to be potential for improved glycaemic control within our ICU. This might be achieved through an improved algorithm and continued efforts to increase nurses' confidence and skills in achieving SGC.
Prescription of respiratory medication without an asthma diagnosis in children: a population based study
Authors: Zuidgeest Mira GP , van Dijk Liset , Smit Henriette A , van der Wouden Johannes C , Brunekreef Bert , Leufkens Hubert GM , Bracke Madelon
Published: February 2008

Background

In pre-school children a diagnosis of asthma is not easily made and only a minority of wheezing children will develop persistent atopic asthma. According to the general consensus a diagnosis of asthma becomes more certain with increasing age. Therefore the congruence between asthma medication use and doctor-diagnosed asthma is expected to increase with age. The aim of this study is to evaluate the relationship between prescribing of asthma medication and doctor-diagnosed asthma in children age 0–17.

Methods

We studied all 74,580 children below 18 years of age, belonging to 95 GP practices within the second Dutch national survey of general practice (DNSGP-2), in which GPs registered all physician-patient contacts during the year 2001. Status on prescribing of asthma medication (at least one prescription for beta2-agonists, inhaled corticosteroids, cromones or montelukast) and doctor-diagnosed asthma (coded according to the International Classification of Primary Care) was determined.

Results

In total 7.5% of children received asthma medication and 4.1% had a diagnosis of asthma. Only 49% of all children receiving asthma medication was diagnosed as an asthmatic. Subgroup analyses on age, gender and therapy groups showed that the Positive Predictive Value (PPV) differs significantly between therapy groups only. The likelihood of having doctor-diagnosed asthma increased when a child received combination therapy of short acting beta2-agonists and inhaled corticosteroids (PPV = 0.64) and with the number of prescriptions (3 prescriptions or more, PPV = 0.66). Both prescribing of asthma medication and doctor-diagnosed asthma declined with age but the congruence between the two measures did not increase with age.

Conclusion

In this study, less than half of all children receiving asthma medication had a registered diagnosis of asthma. Detailed subgroup analyses show that a diagnosis of asthma was present in at most 66%, even in groups of children treated intensively with asthma medication. Although age strongly influences the chance of being treated, remarkably, the congruence between prescribing of asthma medication and doctor-diagnosed asthma does not increase with age.
Chemopreventive effects of celecoxib are limited to hormonally responsive mammary carcinomas in the neu-induced retroviral rat model
Authors: Woditschka Stephan , Haag Jill D , Mau Bob , Lubet Ronald A , Gould Michael N
Published: February 2008

Introduction

While current breast cancer chemoprevention strategies using selective estrogen response modulators and aromatase inhibitors are quite successful, their effects are limited to hormonally responsive breast cancer. Hormonally nonresponsive breast cancer (including estrogen receptor-negative cancer) is associated with poor prognosis for patients, and few chemoprevention agents exist for this type of cancer. The cyclooxygenase-2 inhibitor celecoxib (Celebrex®) is a nonsteroidal anti-inflammatory drug and as such is a potential candidate for the prevention of hormonally nonresponsive breast cancer.

Methods

The chemopreventive effects of celecoxib were evaluated in the neu-induced retroviral rat mammary carcinogenesis model, to assess the efficacy of celecoxib on hormonally responsive and hormonally nonresponsive mammary carcinomas.

Results

Dietary celecoxib at 1,200 mg/kg diet was highly efficacious in the prevention of hormonally responsive mammary carcinomas in intact rats, decreasing tumor multiplicity by 56% (P < 0.0001) and by 74% (P = 0.0002) in two independent experiments. No significant effect was found, however, on hormonally nonresponsive mammary carcinomas of ovariectomized rats. Treatment with a combination diet, consisting of tamoxifen at 2 mg/kg diet and celecoxib at 1,200 mg/kg diet, reduced tumor multiplicity by 72% (P = 0.0002) in intact rats. This reduction was not statistically different from that observed with celecoxib alone. Furthermore, long-term treatment with celecoxib was not associated with reductions in tumor volume in either intact rats or ovariectomized rats. In contrast, tamoxifen treatment and the combination regimen caused significant reductions in tumor volumes in intact rats (P = 0.01 and P = 0.004, respectively). Consistent with these data, decreases in proliferation and increases in apoptosis were detected in tamoxifen-treated and combination diet-treated tumors. No such modulations were observed in celecoxib-treated tumors.

Conclusion

The chemopreventive effects of celecoxib appear to be limited to modulations in multiplicity of hormonally responsive mammary carcinomas. The fact that no synergistic or additive effects were observed in combination diet-treated rats raises the question of whether celecoxib is suitable for the prevention of hormonally nonresponsive breast cancer or for use in combination therapy with selective estrogen response modulators or aromatase inhibitors.
Withholding and withdrawing life-sustaining treatment: a comparative study of the ethical reasoning of physicians and the general public
Authors: Rydvall Anders , Lynöe Niels
Published: February 2008

Background

Our objective was to investigate whether a consensus exists between the general public and health care providers regarding the reasoning and values at stake on the subject of life-sustaining treatment.

Methods

A postal questionnaire was sent to a random sample of members of the adult population (n = 989) and to a random sample of intensive care doctors and neurosurgeons (n = 410) practicing in Sweden in 2004. The questionnaire was based on a case involving a severely ill patient and presented arguments for and against withholding and withdrawing treatment, and providing treatment that might hasten death.

Results

Approximately 70% of the physicians and 51% of the general public responded. A majority of doctors (82.3%) stated that they would withhold treatment, whereas a minority of the general public (40.2%) would do so; the arguments forwarded (for instance, belief that the first task of health care is to save life) and considerations regarding quality of life differed significantly between the two groups. Most physicians (94.1%) and members of the general public (77.7%) were prepared to withdraw treatment, and most (95.1% of physicians and 82% of members of the general public) agreed that sedation should be provided.

Conclusion

There are indeed considerable differences in how physicians and the general public assess and reason in critical care situations, but the more hopelessly ill the patient became the more the groups' assessments tended to converge, although they prioritized different arguments. In order to avoid unnecessary dispute and miscommunication, it is important that health care providers be aware of the public's views, expectations, and preferences.
Recombinant activated factor VIIa for the treatment of bleeding in major abdominal surgery including vascular and urological surgery: a review and meta-analysis of published data
Authors: von Heymann Christian , Jonas Sven , Spies Claudia , Wernecke Klaus-Dieter , Ziemer Sabine , Janssen Detlev , Koscielny Jürgen
Published: February 2008

Background

The purpose of this study was to determine the role of recombinant activated factor VII (rFVIIa) in abdominal, vascular, and urological surgery.

Methods

We conducted meta-analyses of case series and placebo-controlled studies reporting on the treatment or prophylaxis of bleeding with rFVIIa regarding 'reduction or cessation of bleeding', 'mortality', and 'thromboembolism'.

Results

All case reports (n = 15 case reports and 17 patients) documented an effect of rFVIIa in the treatment of bleeding. A meta-analysis of 10 case series revealed a reduction or cessation of bleeding in 39 out of 50 patients after administration of rFVIIa (estimated mean effect 73.2%, 95% confidence interval [CI] 51.0% to 95.4%) and a mean probability of survival of 53.0% (95% CI 26.4% to 79.7%). Among the rFVIIa responders, 19 out of 29 patients (66%) survived versus 1 out of 10 rFVIIa nonresponders (P = 0.003). Six out of 36 patients from the case series had a thromboembolic complication (estimated mean probability 16.5%, 95% CI 1.2% to 31.8%). Compared with a meta-analysis of eight placebo-controlled studies, no increased risk of thromboembolism was seen after administration of rFVIIa.

Conclusion

The meta-analysis of case series showed that, in a mean of 73% patients, rFVIIa achieved at least a reduction of bleeding and that the probability of survival is increased in patients responding to rFVIIa. rFVIIa was not associated with an increased risk of thromboembolism compared with placebo.
Hyperleptinemia without Obesity in Male Mice Lacking Androgen Receptor in Adipose Tissue
Authors: Yu I-Chen , Lin Hung-Yun , Liu Ning-Chun , Wang Ruey-Shen , Sparks Janet D. , Yeh Shuyuan , Chang Chawnshang
Published: February 2008

Insulin resistance occurs through an inadequate response to insulin by insulin target organs such as liver, muscle, and adipose tissue with consequent insufficient glucose uptake. In previous studies we demonstrated that whole body androgen receptor (AR) knockout (AR−/y) mice develop obesity and exhibit insulin and leptin resistance at advanced age. By examining adipose tissue-specific AR knockout (A-AR−/y) mice, we found A-AR−/y mice were hyperleptinemic but showed no leptin resistance, although body weight and adiposity index of A-AR−/y mice were identical with those of male wild-type control mice. Hypotriglyceridemia and hypocholesterolemia found in nonobese A-AR−/y mice suggested a beneficial effect of high leptin levels independent of fat deposition. Further examination showed that androgen-AR signaling in adipose tissue plays a direct regulatory role in leptin expression via enhanced estrogen receptor transactivation activity due to elevated intraadipose estrogens. The present study in A-AR−/y mice suggests a differential tissue-specific role of AR in energy balance control in males.
Epidermal Growth Factor Abrogates Hypoxia-Induced Apoptosis in Cultured Human Trophoblasts through Phosphorylation of BAD Serine 112
Authors: Humphrey Rachel G. , Sonnenberg-Hirche Christina , Smith Steven D. , Hu Chaobin , Barton Aaron , Sadovsky Yoel , Nelson D. Michael
Published: February 2008

We tested the hypothesis that epidermal growth factor (EGF) limits hypoxia-induced apoptosis in cultured human trophoblasts by phosphorylation of the proapoptotic protein Bcl-2-associated death promoter (BAD). Cytotrophoblasts were isolated from placentas of uncomplicated pregnancies at 38–40 wk gestation. Primary trophoblasts or transfected JEG3 trophoblast cells were cultured in less than 1 or 20% oxygen in the presence or absence of EGF and signaling pathway inhibitors. BAD, green fluorescent protein (GFP)-BAD, 14-3-3, Bcl-XL, and neoepitopes formed during apoptotic cleavage of cytokeratin 18 intermediate filaments were quantified using immunoblotting. Cultures immunostained by fluorescent antibodies were analyzed by confocal microscopy for BAD and GFP. Fluorescence resonance energy transfer was used to detect molecular interaction between endogenous BAD and GFP-BAD. We found EGF increased the phosphorylation of BADser112 under standard culture conditions. Whereas hypoxia enhanced apoptosis and increased phosphorylation of both BADser136 and BADser155, hypoxia diminished phosphorylation of BADser112, and this effect was reversible by EGF. Transfected GFP-BAD, which directly interacted with endogenous BAD by colocalization and fluorescence resonance energy transfer, enhanced hypoxia-induced apoptosis in JEG3 cells. EGF reduced apoptosis in hypoxic JEG3 cells that overexpressed GFP-BAD but not in cells overexpressing GFP-BAD that harbored a serine-to-alanine mutation at the 112 site. Coimmunoprecipitation studies showed that EGF reduced the proapoptotic interaction of BAD with Bcl-XL. The effect of EGF on phosphorylation of BADser112 was dependent on the action of p38 MAPK. We conclude that EGF signals via p38 MAPK to increase phosphorylation of BADser112 and thereby limit trophoblast apoptosis.
Relaxation of Androgens on Rat Thoracic Aorta: Testosterone Concentration Dependent Agonist/Antagonist l-Type Ca2+ Channel Activity, and 5β-Dihydrotestosterone Restricted to l-Type Ca2+ Channel Blockade
Authors: Montaño Luis M. , Calixto Eduardo , Figueroa Alejandra , Flores-Soto Edgar , Carbajal Verónica , Perusquía Mercedes
Published: February 2008

Androgen vasorelaxing action is a subject of recent interest. We investigated the involvement of l-type voltage-operated Ca2+ channels (L-VOCCs), K+ channels, intracellular Ca2+ concentration ([Ca2+]i), and cAMP in the vasorelaxing effect of testosterone and 5β-dihydrotestosterone (5β-DHT) on rat thoracic aorta. Isolated aortic rings were used to study the vasorelaxing potency of testosterone and 5β-DHT on KCl- and noradrenaline-induced contractions. Patch-clamp was used to analyze androgen effects on Ca2+ inward and K+ outward currents. The fluorescence technique was used to evaluate [Ca2+]i in single myocytes; moreover, simultaneous measurements of [Ca2+]i and vascular contraction were evaluated. 5β-DHT was more potent than testosterone to relax KCl-induced contraction, but they were equipotent to relax noradrenaline contraction. l-type Ca2+ currents were blocked by nifedipine, both androgens, and an estrogen in a concentration-dependent manner, and the order of potency was: testosterone > nifedipine > 5β-DHT > 17β-estradiol. We observed that testosterone has different mechanism of action by the concentration range used: at nm concentrations it was a powerful L-VOCCs antagonist, whereas at μm concentrations it was observed that: 1) its Ca2+ antagonist property is reverted by increasing the l-type inward Ca2+ currents (Ca2+ agonist property); and 2) the [Ca2+]i and cAMP production was increased. The total K+ currents were unaffected by testosterone or 5β-DHT. The data show that 5β-DHT-induced vasorelaxation is due to its selective blockade on L-VOCCs (from nm to μm concentrations), but testosterone-induced vasorelaxation involves concentration-dependent additional mechanisms: acting as an L-VOCCs antagonist at low concentrations, and increasing [Ca2+]i and cAMP production at high concentrations.
Growth Hormone Regulation of Insulin-Like Growth Factor-I Gene Expression May Be Mediated by Multiple Distal Signal Transducer and Activator of Transcription 5 Binding Sites
Authors: Eleswarapu Satyanaryana , Gu Zhiliang , Jiang Honglin
Published: February 2008

The transcription factor signal transducer and activator of transcription (STAT)-5 mediates GH stimulation of IGF-I gene expression in the liver. Previous studies suggested that STAT5 might exert this effect by binding to an IGF-I intron 2 region and a distal 5′-flanking region each containing two STAT5 binding sites. Here we report the identification of three additional chromosomal regions containing a total of five putative STAT5 binding sites that may mediate GH-induced STAT5 activation of IGF-I gene expression in the mouse liver. By comparing an 170-kb mouse genomic DNA containing the IGF-I gene with the corresponding human sequence, we identified 19 putative STAT5 binding sites that bear the consensus sequence of STAT5 binding site and are conserved across the two species. Chromatin immunoprecipitation assays indicated that five chromosomal regions containing a total of nine of the 19 putative STAT5 binding sites were bound by STAT5 in the mouse liver in response to GH administration and that these bindings preceded or coincided with GH-increased IGF-I gene transcription. Two of the five chromosomal regions correspond to those previously identified in other species, and the three new chromosomal regions that contain a total of five putative STAT5 binding sites are IGF-I intron 3 regions located at least 26 kb from the transcription start site. Gel-shift assays confirmed the binding of the five new putative STAT5 binding sites as well as three of the four previously identified STAT5 binding sites to GH-activated STAT5 from the mouse liver. Cotransfection analyses indicated that, although each of the five chromosomal regions was able to mediate STAT5 activation of reporter gene expression, together they mediated greater STAT5 activation of reporter gene expression in response to GH. Overall, these results suggest that GH-induced STAT5 activation of IGF-I gene expression in the mouse liver might be collectively mediated by at least eight STAT5 binding sites located in distal intronic and 5′-flanking regions of the IGF-I gene.
Liver-Specific Hepatocyte Nuclear Factor-4α Deficiency: Greater Impact on Gene Expression in Male than in Female Mouse Liver
Authors: Holloway Minita G. , Miles Gregory D. , Dombkowski Alan A. , Waxman David J.
Published: February 2008

Hepatocyte nuclear factor (HNF)-4α is a liver-enriched transcription factor that regulates numerous liver-expressed genes including several sex-specific cytochrome P450 genes. Presently, a liver-specific HNF4α-deficient mouse model was used to characterize the impact of liver HNF4α deficiency on a global scale using 41,174 feature microarrays. A total of 4994 HNF4α-dependent genes were identified, of which about 1000 fewer genes responded to the loss of HNF4α in female liver as compared with male liver. Sex differences in the impact of liver HNF4α deficiency were even more dramatic when genes showing sex-specific expression were examined. Thus, 372 of the 646 sex-specific genes characterized by a dependence on HNF4α responded to the loss of HNF4α in males only, as compared with only 61 genes that responded in females only. Moreover, in male liver, 78% of 508 male-specific genes were down-regulated and 42% of 356 female-specific genes were up-regulated in response to the loss of HNF4α, with sex specificity lost for 90% of sex-specific genes. This response to HNF4α deficiency is similar to the response of male mice deficient in the GH-activated transcription factor signal transducer and activator of transcription 5b (STAT5b), where 90% of male-specific genes were down-regulated and 61% of female-specific genes were up-regulated, suggesting these two factors cooperatively regulate liver sex specificity by mechanisms that are primarily active in males. Finally, 203 of 648 genes previously shown to bind HNF4α near the transcription start site in mouse hepatocytes were affected by HNF4α deficiency in mouse liver, with the HNF4α-bound gene set showing a 5-fold enrichment for genes positively regulated by HNF4α. Thus, a substantial fraction of the HNF4α-dependent genes reported here are likely to be direct targets of HNF4α.
Maternal antibodies reduce costs of an immune response during development
Authors: Grindstaff Jennifer L.
Published: February 2008

Young vertebrates are dependent primarily on innate immunity and maternally derived antibodies for immune defense. This reliance on innate immunity and the associated inflammatory response often leads to reduced growth rates after antigenic challenge. However, if offspring have maternal antibodies that recognize an antigen, these antibodies should block stimulation of the inflammatory response and reduce growth suppression. To determine whether maternal and/or offspring antigen exposure affect antibody transmission and offspring growth, female Japanese quail (Coturnix japonica) and their newly hatched chicks were immunized. Mothers were immunized with lipopolysaccharide (LPS), killed avian reovirus vaccine (AR), or were given a control, phosphate-buffered saline, injection. Within each family, one-third of offspring were immunized with LPS, one-third were immunized with AR, and one-third were given the control treatment. Maternal immunization significantly affected the specific types of antibodies that were transmitted. In general, immunization depressed offspring growth. However, offspring immunized with the same antigen as their mother exhibited elevated growth in comparison to siblings immunized with a different antigen. This suggests that the growth suppressive effects of antigen exposure during development can be partially ameliorated by the presence of maternal antibodies, but in the absence of specific maternal antibodies, offspring are dependent on more costly innate immune defenses. Together, the results suggest that the local disease environment of mothers prior to reproduction significantly affects maternal antibody transmission and these maternal antibodies may allow offspring to partially maintain growth during infection in addition to providing passive humoral immune defense.
Finding females: pheromone-guided reproductive tracking behavior by male Nereis succinea in the marine environment
Authors: Ram Jeffrey L. , Fei Xubo , Danaher S. Michelle , Lu Shiyong , Breithaupt Thomas , Hardege Jörg D.
Published: February 2008

Pheromones trigger reproductive responses of many marine organisms, but little is known about how pheromones mediate mate-finding behavior in the marine environment. This paper investigates whether the tetrapeptide nereithione (cysteine-glutathione disulfide), known to be released by females of the polychaete Nereis succinea to trigger spawning in male N. succinea, can also be used at lower concentrations to guide males to the females. Low concentrations of pheromone elicited increased swim speed and turning left or right 84% of the time. Animals sometimes weaved back and forth, or in other cases swam straight along the trails an average of 8.1±1.2 cm before veering off. At higher concentrations, the males circled frequently, often encountering 10–20 cm of pheromone trail before swimming away. Male responses to nereithione were modeled by computer simulation, taking into account arousal of swim speed, activation of turning,speed of response and its decay, etc. In the model, low concentrations(<10–8 mol l–1) of pheromone significantly increased the number of encounters with the pheromone trail, an average following of simulated trails of 10.5±3.6 cm, and a significant increase in the frequency of encountering a virtual female on the trail(ANOVA, P<0.001). The model supports the hypothesis that a pheromone can have a dual function, with low concentration pheromone trails being used by male N. succinea to find females and increase their likelihood of mating whereas high concentrations of the same pheromone trigger the spawning behavior itself.
Insulin regulates aging and oxidative stress in Anopheles stephensi
Authors: Kang Mi-Ae , Mott Tiffany M. , Tapley Erin C. , Lewis Edwin E. , Luckhart Shirley
Published: February 2008

Observations from nematodes to mammals indicate that insulin/insulin-like growth factor signaling (IIS) regulates lifespan. As in other organisms, IIS is conserved in mosquitoes and signaling occurs in multiple tissues. During bloodfeeding, mosquitoes ingest human insulin. This simple observation suggested that exogenous insulin could mimic the endogenous hormonal control of aging in mosquitoes, providing a new model to examine this phenomenon at the organismal and cellular levels. To this end, female Anopheles stephensi mosquitoes were maintained on diets containing human insulin provided daily in sucrose or three times weekly by artificial bloodmeal. Regardless of delivery route, mosquitoes provided with insulin at 1.7×10–4 and 1.7×10–3 μmol l–1, doses 0.3-fold and 3.0-fold higher than non-fasting blood levels, died at a faster rate than controls. In mammals, IIS induces the synthesis of reactive oxygen species and downregulates antioxidants, events that increase oxidative stress and that have been associated with reduced lifespan. Insulin treatment of mosquito cells in vitro induced hydrogen peroxide synthesis while dietary supplementation reduced total superoxide dismutase (SOD) activity and manganese SOD activity relative to controls. The effects of insulin on mortality were reversed when diets were supplemented with manganese (III) tetrakis (4-benzoic acid) porphyrin(MnTBAP), a cell-permeable SOD mimetic agent, suggesting that insulin-induced mortality was due to oxidative stress. In addition, dietary insulin activated Akt/protein kinase B and extracellular signal-regulated kinase (ERK) in the mosquito midgut, suggesting that, as observed in Caenorhabditis elegans, the midgut may act as a `signaling center' for mosquito aging.
Thoracic vibrations in stingless bees (Melipona seminigra):resonances of the thorax influence vibrations associated with flight but not those associated with sound production
Authors: Hrncir Michael , Gravel Anne-Isabelle , Schorkopf Dirk Louis P. , Schmidt Veronika M. , Zucchi Ronaldo , Barth Friedrich G.
Published: February 2008

Bees generate thoracic vibrations with their indirect flight muscles in various behavioural contexts. The main frequency component of non-flight vibrations, during which the wings are usually folded over the abdomen, is higher than that of thoracic vibrations that drive the wing movements for flight. So far, this has been concluded from an increase in natural frequency of the oscillating system in association with the wing adduction. In the present study, we measured the thoracic oscillations in stingless bees during stationary flight and during two types of non-flight behaviour, annoyance buzzing and forager communication, using laser vibrometry. As expected, the flight vibrations met all tested assumptions for resonant oscillations: slow build-up and decay of amplitude; increased frequency following reduction of the inertial load; and decreased frequency following an increase of the mass of the oscillating system. Resonances, however, do not play a significant role in the generation of non-flight vibrations. The strong decrease in main frequency at the end of the pulses indicates that these were driven at a frequency higher than the natural frequency of the system. Despite significant differences regarding the main frequency components and their oscillation amplitudes, the mechanism of generation is apparently similar in annoyance buzzing and forager vibrations. Both types of non-flight vibration induced oscillations of the wings and the legs in a similar way. Since these body parts transform thoracic oscillations into airborne sounds and substrate vibrations, annoyance buzzing can also be used to study mechanisms of signal generation and transmission potentially relevant in forager communication under controlled conditions.
The sound field generated by tethered stingless bees (Melipona scutellaris): inferences on its potential as a recruitment mechanism inside the hive
Authors: Hrncir Michael , Schorkopf Dirk Louis P. , Schmidt Veronika M. , Zucchi Ronaldo , Barth Friedrich G.
Published: February 2008

In stingless bees, recruitment of hive bees to food sources involves thoracic vibrations by foragers during trophallaxis. The temporal pattern of these vibrations correlates with the sugar concentration of the collected food. One possible pathway for transfering such information to nestmates is through airborne sound. In the present study, we investigated the transformation of thoracic vibrations into air particle velocity, sound pressure, and jet airflows in the stingless bee Melipona scutellaris. Whereas particle velocity and sound pressure were found all around and above vibrating individuals, there was no evidence for a jet airflow as with honey bees. The largest particle velocities were measured 5 mm above the wings(16.0±4.8 mm s–1). Around a vibrating individual, we found maximum particle velocities of 8.6±3.0 mm s–1(horizontal particle velocity) in front of the bee's head and of 6.0±2.1 mm s–1 (vertical particle velocity) behind its wings. Wing oscillations, which are mainly responsible for air particle movements in honey bees, significantly contributed to vertically oriented particle oscillations only close to the abdomen in M. scutellaris(distances ⩽5 mm). Almost 80% of the hive bees attending trophallactic food transfers stayed within a range of 5 mm from the vibrating foragers. It remains to be shown, however, whether air particle velocity alone is strong enough to be detected by Johnston's organ of the bee antenna. Taking the physiological properties of the honey bee's Johnston's organ as the reference, M. scutellaris hive bees are able to detect the forager vibrations through particle movements at distances of up to 2 cm.
Food intake and fuel deposition in a migratory bird is affected by multiple as well as single-step changes in the magnetic field
Authors: Henshaw Ian , Fransson Thord , Jakobsson Sven , Lind Johan , Vallin Adrian , Kullberg Cecilia
Published: February 2008

Recent studies have shown that migratory thrush nightingales (Luscinia luscinia) experimentally treated with multiple changes of the magnetic field simulating a journey to their target stopover area in northern Egypt,increased fuel deposition as expected in preparation to cross the Sahara desert. To investigate the significance of food intake on the body mass changes observed, in the work described here we analysed food intake of the nightingales under study in those earlier experiments. Furthermore, to study whether a single change in the magnetic field directly to northern Egypt is sufficient to provide information for fuelling decisions, we performed a new experiment, exposing thrush nightingales trapped in Sweden, directly to a magnetic field of northern Egypt. Our results show that an experimentally induced magnetic field of northern Egypt, close to the barrier crossing,triggers the same response in fuel deposition as experiments with multiple changes of the magnetic field simulating a migratory journey from Sweden to Egypt, suggesting that migratory birds do not require successive changes in field parameters to incorporate magnetic information into their migratory program. Furthermore, irrespective of experimental set up (single or multiple changes of the magnetic field parameters) increase in food intake seems to be the major reason for the observed increase in fuelling rate compared with control birds, suggesting that geomagnetic information might trigger hormonal changes in migratory birds enabling appropriate fuelling behaviour during migration.
Is Judicial Proof of Facts a Form of Scientific Explanation? A Preliminary Investigation of ‘Clinical’ Legal Method
Authors: Menashe Doron
Published: February 2008

This article examines the relationship between judicial proof of facts and positivistic explanation in the natural and social sciences. Although these two forms of factual inquiry share evident similarities, it is argued that, on closer analysis, legal fact-finding is not even a proximate model of scientific explanation. Judicial proof more closely resembles clinical deliberations, such as those encountered in a medical context, than classical scientific method. Comparison with clinical practices should therefore promote understanding and serve as a basis for further research, critical appraisal and practical improvement of the processes of judicial proof.
Injustice Perpetuated? The Contribution of the Court of Appeal
Authors: Leigh L. H.
Published: February 2008

This article examines dicta in R v Cottrell pertaining to the extent to which the Criminal Cases Review Commission ought or should have regard to the principles adumbrated by the Court of Appeal in relation to leave to appeal in change of law cases. It concludes that a restatement of the Commission's policy statement to provide that, following R (on the application of the Director of Revenue and Customs Prosecutions) v Criminal Cases Review Commission, the CCRC would not have regard to the Court of Appeal's practice in leave-out-of-time cases was misconceived and wrong. The article further concludes that fears expressed by the Court of Appeal concerning the impact of change of law references on the court's workload were exaggerated because not informed by the practice of the CCRC. It examines critically the standard suggested by the Court of Appeal for referral of such cases, namely substantial injustice, and points to problems which the CCRC may well encounter in applying a formula which, at present, is nebulous.
Community Responses to Local Drug Use
Authors: Mason Mark
Published: February 2008

A number of different approaches have been used in trying to disrupt local drug markets within communities. However, drug use theory and practice have traditionally focused on individuals who misuse drugs, without understanding the context in which they live and how they interact. While this literature is important in preventing and disrupting drug problems, it generally fails to address the actions and behaviours of drug users in their social context. This study sets out to examine what drugs users feel about different styles of intervention and what effect these might have on their drug-use behaviour. Responses indicated a level of ‘entrenched-ness' of drug use among some of the sample, suggesting that very little would deter them from taking drugs in any way. However, there was a noteworthy number of respondents who indicated that they were clearly influenced by local communities. It is suggested that Neighbourhood Policing (NP) presents an opportunity within a framework of police-community liaison to achieve a sustained impact on community drug problems.
Devising Effective Responses to Increased Alcohol and Drug Usage among Students
Authors: Marsal Elizabeth Sharpe , Jackson Mary S. , Harrison Marvin
Published: February 2008

Campus police and university administrators are facing an increased use of alcohol and other drugs by college students. In an effort to address these concerns, campus police are re-examining their policies and adopting flexible community-oriented strategies as well as reassessing methods to deal effectively with alcohol and drug usage. The results of the CORE Institute Center for Alcohol and Drug Studies Survey at a public four-year institution in eastern North Carolina were analysed to determine patterns and trends of alcohol and drug use. Specific recommendations are made for campus police departments to address the increased usage of alcohol and drugs on college campuses based upon the CORE findings and the prevention and intervention strategies utilised by other college and universities.
Combined Newborn Screening for Succinylacetone, Amino Acids, and Acylcarnitines in Dried Blood Spots
Authors: Turgeon Coleman , Magera Mark J , Allard Pierre , Tortorelli Silvia , Gavrilov Dimitar , Oglesbee Devin , Raymond Kimiyo , Rinaldo Piero , Matern Dietrich
Published: February 2008

Background: Tyrosinemia type I (TYR 1) is a disorder causing early death if left untreated. Newborn screening (NBS) for this condition is problematic because determination of the diagnostic marker, succinylacetone (SUAC), requires a separate first-tier or only partially effective second-tier analysis based on tyrosine concentration. To overcome these problems, we developed a new assay that simultaneously determines acylcarnitines (AC), amino acids (AA), and SUAC in dried blood spots (DBS) by flow injection tandem mass spectrometry (MS/MS).

Methods: We extracted 3/16-inch DBS punches with 300 μL methanol containing AA and AC stable isotope-labeled internal standards. This extract was derivatized with butanol-HCl. In parallel, we extracted SUAC from the residual filter paper with 100 μL of a 15 mmol/L hydrazine solution containing the internal standard 13C5-SUAC. We combined the derivatized aliquots in acetonitrile for MS/MS analysis of AC and AA with additional SRM experiments for SUAC (m/z 155–137) and 13C5-SUAC (m/z 160–142). Analysis time was 1.2 min.

Results: SUAC was increased in retrospectively analyzed NBS samples of 11 TYR 1 patients (length of storage, 52 months to 1 week; SUAC range, 13–81 μmol/L), with Tyr concentrations ranging from 65 to 293 μmol/L in the original NBS analysis. The mean concentration of SUAC in 13 521 control DBS was 1.25 μmol/L.

Conclusion: The inclusion of SUAC analysis into routine analysis of AC and AA allows for rapid and cost-effective screening for TYR 1 with no tangible risk of false-negative results.