bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring species richness on sandy beach transects: extrapolative estimators and their implications for sampling effort
Authors: Schoeman David S , Nel Ronel , Goulart Soares Alexandre
Published: June 2008

Species richness is a measure that is fundamental to many studies in ecology, and it is particularly important on sandy beaches, where it underlies patterns described by the broadly accepted swash exclusion hypothesis. However, its estimation in practice is problematic. This has led ecologists in other fields to adopt extrapolative estimators of species richness, which project the total number of species present in a habitat by adjusting upward the number of species observed by an amount related to the number of rare species encountered in the samples. In so doing, the species richness can be estimated, with confidence intervals, at any level of sampling effort. Despite the availability and advantages of these methods, beach ecologists have continued to use the observed species richness as a point estimate of biodiversity for beaches. Here, we employ a Monte Carlo resampling approach over a range of routine transect designs used to sample sandy beaches, and evaluate the performance of seven non‐parametric extrapolative estimators for species richness relative to that of the more conventionally used observed species richness. We find that the first‐order Jackknife estimator (Jack 1) is the least biased, most accurate and most consistent across sites. Employing this estimator would allow accurate estimation of species richness on short (tens of metres) stretches of beach without exceeding the acceptable levels of sampling effort (4–5 m2). Spreading this effort evenly over three across‐shore transects, each with a minimum of 13 equally spaced levels seems appropriately efficient. Although a greater number of research studies is required to ascertain the generality of these results beyond the beaches we sampled, we tentatively recommend the application of our results in biodiversity surveys on sandy beaches.
Brain responses during the first desire to void: A positron emission tomography study
Authors: Takao Tetsuya , Tsujimura Akira , Miyagawa Yasushi , Kiuchi Hiroshi , Ueda Tomohiro , Hirai Toshiaki , Komori Kazuhiko , Takada Shingo , Nonomura Norio , Osaki Yasuhiro , Enomoto Keisuke , Hatazawa Jun , Okuyama Akihiko
Published: June 2008

Objectives:  First desire to void (FDV) is defined as the first feeling that would lead the patient to pass urine. The aim of the present study is to identify the brain regions activated during FDV.

Methods:  Six healthy right‐handed male volunteers, aged 31–40 years, agreed to participate in this study. Rather than inserting a urethral catheter, we used a urinary volume monitoring unit and a self‐adhesive external condom catheter for this study. Positron emission tomography (PET) scans obtained in the FDV and post‐voiding (absence of urge to void) (REST) states were analyzed and compared.

Results:  First desire to void state was associated with increased blood flow in the right and left cerebellum, right parahippocampal gyrus (Brodmann area [BA] 30), left superior frontal gyrus (BA9), and left cingulate gyrus (BA32). Rest state was associated with decreased blood flow in the right superior temporal gyrus (BA22), right uncus (BA28), right cingulate gyrus (BA32), left middle temporal gyrus (BA21), and left medial frontal gyrus (BA25). According to region of interest analysis, regional cerebral blood flow of the periaqueductal grey and pons was significantly increased at FDV as opposed to REST.

Conclusions:  We located possible brain activity associated with the FDV sensation. Combined activation of the right and left cerebellum, parahippocampal gyrus, superior frontal gyrus, and left cingulate gyrus could be associated with FDV.
An artificial neural network for five different assay systems of prostate‐specific antigen in prostate cancer diagnostics
Authors: Stephan Carsten , Cammann Henning , Meyer Hellmuth‐Alexander , Müller Christian , Deger Serdar , Lein Michael , Jung Klaus
Published: June 2008

OBJECTIVE

To compare separate prostate‐specific antigen (PSA) assay‐specific artificial neural networks (ANN) for discrimination between patients with prostate cancer (PCa) and no evidence of malignancy (NEM).

PATIENTS AND METHODS

In 780 patients (455 with PCa, 325 with NEM) we measured total PSA (tPSA) and free PSA (fPSA) with five different assays: from Abbott (AxSYM), Beckman Coulter (Access), DPC (Immulite 2000), and Roche (Elecsys 2010) and with tPSA and complexed PSA (cPSA) assays from Bayer (ADVIA Centaur). ANN models were developed with five input factors: tPSA, percentage free/total PSA (%fPSA), age, prostate volume and digital rectal examination status for each assay separately to examine two tPSA ranges of 0–10 and 10–27 ng/mL.

RESULTS

Compared with the median tPSA concentrations (range from 4.9 [Bayer] to 6.11 ng/mL [DPC]) and especially the median %fPSA values (range from 11.2 [DPC] to 17.4%[Abbott], for tPSA 0–10 ng/mL), the areas under the receiver operating characteristic curves (AUC) for all calculated ANN models did not significantly differ from each other. The AUC were: 0.894 (Abbott), 0.89 (Bayer), 0.895 (Beckman), 0.882 (DPC) and 0.892 (Roche). At 95% sensitivity the specificities were without significant differences, whereas the individual absolute ANN outputs differed markedly.

CONCLUSIONS

Despite only slight differences, PSA assay‐specific ANN models should be used to optimize the ANN outcome to reduce the number of unnecessary prostate biopsies. We further developed the ANN named ‘ProstataClass’ to provide clinicians with an easy to use tool in making their decision about follow‐up testing.
Elective endoscopic management of transitional cell carcinoma first diagnosed in the upper urinary tract
Authors: Thompson R. Houston , Krambeck Amy E. , Lohse Christine M. , Elliott Daniel S. , Patterson David E. , Blute Michael L.
Published: June 2008

OBJECTIVE

To report our experience using ureteroscopic or percutaneous management of upper urinary tract (UUT) transitional cell carcinoma (TCC) in patients with no history of bladder TCC.

PATIENTS AND METHODS

Between 1983 and 2004 we identified 22 patients who underwent endoscopic management of TCC first diagnosed in the UUT and in the setting of a normal contralateral kidney. We performed a retrospective chart review and conducted outcome analyses.

RESULTS

The median (range) age at diagnosis was 64 (37–86) years and the median tumour size was 0.8 (0.3–2.6) cm. The tumour grade was 1, 2, or diagnosed as visual low grade in two (9%), seven (32%), and 13 (59%) patients, respectively; no patient had grade 3 TCC at diagnosis. Tumour stage was Ta or visual Ta in all patients. The median follow‐up was 4.9 (0.4–17) years during which 11 (50%) patients developed 21 UUT recurrences and 10 (45%) patients developed bladder TCC. At last follow‐up, seven (32%) patients required a nephroureterectomy for recurrent TCC and two (9%) patients died from TCC. Among 13 patients with a diagnosis based on visual inspection only, three recurred with grade 3 invasive TCC during follow‐up. No patient with pathological confirmation of low‐grade/stage TCC recurred with high‐grade or invasive TCC.

CONCLUSIONS

Recurrence is common after endoscopic management of UUT‐TCC, underscoring the need for strict surveillance. Patients diagnosed visually, without adequate tissue for pathological examination, can recur with high‐grade invasive TCC. No patient with pathological confirmation of low‐grade TCC developed progressive disease during follow‐up.
Destination enlightenment: Branding Buddhism and spiritual tourism in Bodhgaya, Bihar
Authors: Geary David
Published: June 2008

In 2002 the Mahabodhi Temple Complex in Bodhgaya was declared a UNESCO World Heritage site. As the alleged site of Buddha's enlightenment it is one of the most revered and sanctified places for Buddhists around the world. This international designation has also set in motion a series of development proposals and heritage policies that seek to rehabilitate and recreate this centre of world Buddhism that provides glimpses of the land of enlightenment as it used to be in the times of the Buddha. Central to these initiatives are plans on behalf of the Bihar state tourism department to promote Brand Buddhism and spiritual tourism through the establishment of an 18 hole golf course and five‐star hotels. These development proposals along with the recent UNESCO World Heritage designation have brought to the foreground the multiplicity of stakeholders in competition over the site's spiritual capital today. This paper will explore some of the contradictions and entanglements over Bodhgaya's present and uncertain future.
Tamil Tigers: Sacrificial symbolism and ‘dead body politics’
Authors: Roberts Michael
Published: June 2008

This comment criticises the facile manner in which both scholars and journalists have accepted the Tamil Tiger organization's presentation of itself as “secular”; while expressing surprise that some Sri Lankan scholars have also bought into this viewpoint. It focuses on the embodied activities of LTTE personnel and their keen supporters to argue that religious symbolism and metaphors of ash and seeds enable the LTTE to organize rituals and pageants that appeal to Tamil Christians as well as Saivites. Central to their iconography, poetry and rite is the energizing Indic notion of sakti.
Does a Country's Openness to Trade and Capital Accounts Lead to Financial Development? Evidence from Malaysia*
Authors: Law Siong Hook
Published: June 2008

This paper examines the role of trade openness and capital account openness in influencing financial development in Malaysia. The empirical findings using the bounds testing approach demonstrate that trade openness and capital account openness are positively significant determinants of financial development. However, there is no empirical support of the hypothesis that the simultaneous opening of both trade and capital accounts is necessary for financial development to take place. The evidence is valid for three banking sector development and two stock market development indicators.
Is Real Estate Really an Inflation Hedge? Evidence from Taiwan*
Authors: Fang Wen‐Shwo , Wang Kuan‐Min , Nguyen Thanh‐Binh T.
Published: June 2008

This study examines whether Taiwan's housing returns hedge against expected and unexpected inflation. In other words, how well does the rise in housing returns compensate for the costs added as a result of the shrink in wealth and purchasing power? Within the exponential generalized autoregressive conditional heteroskedasticity in mean model framework, we further explore the impact of conditional hetero‐risk on housing return and the influence of asymmetric information on conditional risk. Over the period from 1991 to 2006, the empirical results reveal negative relationships between housing returns and expected as well as unexpected inflation, proving the ineffective inflation hedge of Taiwan's housing investment. The determinant of this phenomenon is the leverage shock between ‘good news’ and ‘bad news’.
How global is the Global Compact?
Authors: Bremer Jennifer Ann
Published: June 2008

Launched by the United Nations in 2000, the Global Compact (GC) promotes private sector compliance with 10 basic principles covering human rights, labour standards, the environment, and anti‐corruption. Its sponsors aim to establish a global corporate social responsibility (CSR) network based on a pledge to observe the 10 principles adopted by companies across the range of company size and regional origin, backed by a modest reporting system and collaborative programmes. The author analyzes the GC's progress toward building a global network from its launch through 2006 and finds that, while the GC's nominal membership base of nearly 3000 companies makes it the largest system among collective action institutions (CAIs) for corporate responsibility, the GC has not reached ‘critical mass’. Deficiencies in its nascent global network include limited market penetration among the largest corporations, a membership heavily weighted toward Western European companies, and major weaknesses in compliance with its reporting system. The author concludes that the GC must improve both penetration and compliance if it is to succeed in building a global standard for CSR.
Individual Heterogeneity in Alcohol Consumption: The Case of Beer, Wine and Spirits in Australia*
Authors: RAMFUL PREETY , ZHAO XUEYAN
Published: June 2008

This paper examines the effects of socioeconomic and demographic factors on Australian individuals’ participation in beer, wine and spirits consumption using unit‐record data during 1991–2001. A trivariate probit formulation allows for participation in the three alcoholic beverages to be modelled jointly accounting for correlation via unobserved personal characteristics. Own and cross price elasticities are estimated for both unconditional and conditional participation probabilities. While the three beverages are commonly considered closely related economic goods, we find that they relate to rather heterogenous population groups and the correlations via the unobservable characteristics are low in magnitude.
Happiness Studies: Ways to Improve Comparability and Some Public Policy Implications*
Authors: NG YEW‐KWANG
Published: June 2008

Recent happiness studies by psychologists, sociologists and economists have produced many interesting results. These have important implications, including the need to focus less on purely objective (including economic) variables and more on subjective well‐being. In particular, the focus on GDP should be supplemented (if not replaced) by more acceptable national success indicators such as the environmentally responsible happy nation index. Welfare economics and cost–benefit analysis that are currently based on economic factors (which are in turn based on preferences) should be revised to be based on happiness or welfare. Public spending on areas important for welfare should be preferred over private consumption that is largely no longer important for long‐term welfare at the social level. Public policy should put more emphasis (than suggested by existing economic analysis) on factors more important for happiness than economic production and consumption, including employment, environmental quality, equality, health and safety. Above all, scientific advance in general and in brain stimulation and genetic engineering in particular may offer the real breakthroughs against the biological or psychological limitations on happiness. Some simple ways to improve the accuracy and comparability (including interpersonal) of happiness measurement are suggested: pinning down the level of neutrality, recognising the possible nonlinear scale used in self‐reports, and using the just perceivable increment of pleasure as the interpersonally comparable unit.
Regional dynamics in the globalising wine industry: the case of Marlborough, New Zealand
Authors: HAYWARD DAVID , LEWIS NICK
Published: June 2008

The rapid expansion of the New Zealand wine industry has rested largely on a specific wine commodity form, Marlborough Sauvignon Blanc. Global demand for a specialised product has provided the impetus for substantial development at the regional level, an increasingly complex industry structure, and for the intrusion of international capital. This paper explores the contests and relations within the industry through attention to the commodity's value‐added chain, wherein recent developments are interpreted as a contest over the brand rents. The contemporary situation therefore may be explained through overlapping organisational and geographic framings of these relations: producer versus buyer‐driven dynamics; regional–national and global interests; and inter‐ and intra‐corporate strategies. The commercial contest for control of the region‐varietal commodity reveals some paradoxical outcomes in which the region is reaffirmed as a site of investment in an evidently globalised industry, and the significance of who controls what fraction of the value chain is re‐asserted.
Negotiating partnerships, understanding power: doing action research on Chilean Fairtrade wine value chains
Authors: KLEINE DOROTHEA
Published: June 2008

Sales in Fairtrade wine have been growing rapidly worldwide, and the UK is the most important market. This paper reports on an action research project undertaken with different economic actors along the value chain of a Chilean Fairtrade wine. The aim of the interdisciplinary project was to explore how the internet and tracking and tracing technologies could be used to render value chains more transparent for consumers and producers. An internet interface combined with a barcode‐based data retrieval system could allow actors in the value chain to call up economic, social and environmental information about a product. Early findings from the action research process show that while supermarkets are the lead firms in the Fairtrade wine chain in terms of economic power, the producers and the Fairtrade certification body wield ‘moral power’ over other actors in the value chain. Fairtrade producers and the Fairtrade certification body relate to each other in cycles of mutual recognition, thus underpinning each others’ legitimacy and moral power. The paper argues that action research, in particular the positionality of the researcher team as a collaboration partner, can lead to a better understanding of the nature of linkages and power relations between the economic actors in value chains.
The Impact of Gaps in Health Insurance Coverage on Immunization Status for Young Children
Authors: Blewett Lynn A. , Davidson Gestur , Bramlett Matthew D. , Rodin Holly , Messonnier Mark L.
Published: June 2008

Objective. To examine the impact of full‐year versus intermittent public and private health insurance coverage on the immunization status of children aged 19–35 months.

Data Source. 2001 State and Local Area Integrated Telephone Survey's National Survey of Children with Special Health Care Needs (NS‐CSHCN) and the 2000–2002 National Immunization Survey (NIS).

Study Design. Linked health insurance data from 2001 NS‐CSHCN with verified immunization status from the 2000–2002 NIS for a nationally representative sample of 8,861 nonspecial health care needs children. Estimated adjusted rates of up‐to‐date (UTD) immunization status using multivariate logistic regressions for seven recommended immunizations and three series.

Principal Findings. Children with public full‐year coverage were significantly more likely to be UTD for two series of recommended vaccines, (4:3:1:3) and (4:3:1:3:3), compared with children with private full‐year coverage. For three out of 10 immunizations and series tested, children with private part‐year coverage were significantly less likely to be UTD than children with private full‐year coverage.

Conclusions. Our findings raise concerns about access to needed immunizations for children with gaps in private health insurance coverage and challenge the prevailing belief that private health insurance represents the gold standard with regard to UTD status for young children.
The Effects of Quality Improvement for Depression in Primary Care at Nine Years: Results from a Randomized, Controlled Group‐Level Trial
Authors: Wells Kenneth B. , Tang Lingqi , Miranda Jeanne , Benjamin Bernadette , Duan Naihua , Sherbourne Cathy D.
Published: June 2008

Objective. To examine 9‐year outcomes of implementation of short‐term quality improvement (QI) programs for depression in primary care.

Data Sources. Depressed primary care patients from six U.S. health care organizations.

Study Design. Group‐level, randomized controlled trial.

Data Collection. Patients were randomly assigned to short‐term QI programs supporting education and resources for medication management (QI‐Meds) or access to evidence‐based psychotherapy (QI‐Therapy); and usual care (UC). Of 1,088 eligible patients, 805 (74 percent) completed 9‐year follow‐up; results were extrapolated to 1,269 initially enrolled and living. Outcomes were psychological well‐being (Mental Health Inventory, five‐item version [MHI5]), unmet need, services use, and intermediate outcomes.

Principal Findings. At 9 years, there were no overall intervention status effects on MHI5 or unmet need (largest F (2,41)=2.34, p=.11), but relative to UC, QI‐Meds worsened MHI5, reduced effectiveness of coping and among whites lowered tangible social support (smallest t(42)=2.02, p=.05). The interventions reduced outpatient visits and increased perceived barriers to care among whites, but reduced attitudinal barriers due to racial discrimination and other factors among minorities (smallest F (2,41)=3.89, p=.03).

Conclusions. Main intervention effects were over but the results suggest some unintended negative consequences at 9 years particularly for the medication‐resource intervention and shifts to greater perceived barriers among whites yet reduced attitudinal barriers among minorities.
Characterization of osteopontin expression and function after status epilepticus
Authors: Borges Karin , Gearing Marla , Rittling Susan , Sorensen Esben S. , Kotloski Robert , Denhardt David T. , Dingledine Raymond
Published: June 2008

Purpose: Osteopontin is a cytokine found in many tissues and plays a role in tissue injury and repair. This study had two goals: to characterize osteopontin expression after status epilepticus (SE), and to test the hypotheses that osteopontin affects the susceptibility to seizures or alters cell death and inflammation after SE.

Methods: Pilocarpine was used to induce SE in OPN−/−and OPN+/+mice to compare seizure susceptibility, neuropathological markers including real time PCR for inflammatory genes, and osteopontin immunohistochemistry. The effect of added osteopontin on excitotoxicity by N‐methyl‐d‐aspartate in neuronal cultures of ONP−/−mice was determined.

Results: Neurons undergoing degeneration showed osteopontin immunoreactivity 2–3  days after SE. After 10 to 31 days degenerating axons in the thalamus were osteopontin‐positive. The susceptibility to seizures of OPN−/−and OPN+/+mice in the pilocarpine, fluorothyl, and maximal electroshock models was similar. There were no significant differences in the extent of neuronal damage after pilocarpine‐induced SE, the expression of several neuropathological markers or the RNA levels of selected inflammatory genes. Recombinant and natural bovine osteopontin did not affect the extent of NMDA‐induced cell death in OPN−/−mouse neuronal cultures.

Conclusion: We demonstrated that osteopontin is up‐regulated in response to SE in distinct temporal sequences in the hippocampus, specifically in dege‐nerating neurons and axons. However, osteopontin did not appear to regulate neurodegeneration or inflammation within the first 3  days after SE.
Altered calcium handling following the recombinant overexpression of protein kinase C isoforms in HaCaT cells
Authors: Gönczi Mónika , Telek Andrea , Czifra Gabriella , Balogh Attila , Blumberg Peter M. , Bíró Tamás , Csernoch László
Published: June 2008

Abstract: Both changes in intracellular calcium concentration ([Ca2+]i) and activation of certain protein kinase C (PKC) isoforms play a crucial role in keratinocyte functions. To better understand the interaction between these two signalling pathways we investigated the resting [Ca2+]iand the extracellular ATP‐induced changes in [Ca2+]ion HaCaT cell clones overexpressing either the classical α or the β PKC isoform. These PKC isoenzymes were previously shown to decrease (α) or increase (β) cell proliferation and augment (α) or suppress (β) cell differentiation. Keratinocyte clones with decreased proliferation rate were found to have unaltered resting [Ca2+]i, but responded with greater calcium transients to the application of 180 μmof ATP. In contrast, clones with increased proliferation rate had elevated resting [Ca2+]iand suppressed calcium responses to ATP. Calcium transients on PKCβ clones displayed a faster falling phase. Each clone had a distinct purinergic receptor expression pattern, some of which paralleled the altered proliferation rate and calcium handling. Keratinocytes overexpressing PKCβ revealed decreased P2X1 and increased P2Y1 receptor expression as compared with the control or PKCα clones. The expression level of P2X7 was significantly increased in keratinocytes overexpressing PKCα. On the other hand neither the P2X2 nor the P2Y2 expression was altered significantly in the cell types investigated. These data indicate that a modified proliferation and differentiation pattern is associated with altered calcium handling in keratinocytes. The observations also suggest that different PKC isoenzymes have different effects on the phosphatidyl–inositol signalling pathway.
Immunophenotyping of the human bulge region: the quest to define useful in situ markers for human epithelial hair follicle stem cells and their niche
Authors: Kloepper Jennifer Elisabeth , Tiede Stephan , Brinckmann Jürgen , Reinhardt Dieter Peter , Meyer Wilfried , Faessler Reinhard , Paus Ralf
Published: June 2008

Abstract:  Since the discovery of epithelial hair follicle stem cells (eHFSCs) in the bulge of human hair follicles (HFs) an important quest has started: to define useful markers. In the current study, we contribute to this by critically evaluating corresponding published immunoreactivity (IR) patterns, and by attempting to identify markers for the in situ identification of human eHFSCs and their niche. For this, human scalp skin cryosections of at least five different individuals were examined, employing standard immunohistology as well as increased sensitivity methods. Defined reference areas were compared by quantitative immunohistochemistry for the relative intensity of their specific IR.

According to our experience, the most useful positive markers for human bulge cells turned out to be cytokeratin 15, cytokeratin 19 and CD200, but were not exclusive, while β1 integrin and Lhx2 IR were not upregulated by human bulge keratinocytes. Absent IR for CD34, connexin43 and nestin on human bulge cells may be exploited as negative markers. α6 integrin, fibronectin, nidogen, fibrillin‐1 and latent transforming growth factor (TGF)‐beta‐binding protein‐1 were expressed throughout the connective tissue sheath of human HFs. On the other hand, tenascin‐C was upregulated in the bulge and may thus constitute a component of the bulge stem cell niche of human HFs.

These immunophenotyping results shed further light on the in situ expression patterns of claimed follicular ‘stem cell markers’ and suggest that not a single marker alone but only the use of a limited corresponding panel of positive and negative markers may offer a reasonable and pragmatic compromise for identifying human bulge stem cells in situ.
The role of the cutaneous cholinergic system in guttate psoriasis
Authors: Dyck W. , Radosa J. , Herbst C. , Schleider B. , Goerdt S. , Kurzen H.
Published: June 2008

In previous studies, high levels of acetylcholine (ACh) have been reported in psoriasis lesions. In addition, patients with guttate psoriasis respond to oral treatment with atropine. We wanted to know how the cutaneous cholinergic system could be involved in this process. Since mast cells (MC) are characteristic components of the inflammatory infiltrate of guttate psoriasis, we compared ACh receptor (AChR) composition and ACh production in both epidermis and mast cells of 10 patients with guttate psoriasis in involved and uninvolved skin on protein level using immunofluorescence and in a MC line (HMC‐1) using PCR. We could confirm the presence of numerous MC in guttate psoriasis lesion. Both in vivo and in vitro, MC lacked expression of cholinacetyltransferase (ChAT), vesicular acetylcholintransorter (VAChT) and cholintransporter‐1 (ChT‐1) but contained high levels of acetylcholinesterase (AChE). In mast cells of both involved and uninvolved skin we found both nicotinic (α3, α5, α7, α9, α10, β2 and β4 subunits) and muscarinic (M1, M3, M4, M5) AChR. In HMC‐1 cells all AChR subunits found in skin where present on mRNA level, except α7 and β2. In lesional epidermis both ACh production and AChR expression was shifted from the basal to the suprabasal layers especially the nicotinic α3, α5, α9, β2 and β4 and the muscarinic M3 and M5 AChR subunits. Our results exclude a role of the cholinergic system in the initiation of keratinocyte proliferation in the basal epidermal layer but point towards a role of epidermal AChR in suprabasal processes, most likely terminal differentiation and barrier formation as has been shown in other systems. Most importantly, mast cells are targets of paracrine and endocrine effects mediated by ACh and choline thus modulating inflammatory processes like guttate psoriasis and explaining the clinical efficacity of anticholinergic drugs like atropine.
1,25‐dihydroxy vitamin D3 regulates cutaneous innate immune function
Authors: Schauber J. , Büchau A. S. , Gallo R. L.
Published: June 2008

Hormonally active vitamin D3 – 1,25‐dihydroxyvitamin D3 (1,25D3) – acts as a signalling molecule in cutaneous immunity. In this study we investigated if Toll‐like‐receptor (TLR) function and antimicrobial peptide (AMP) expression are controlled by 1,25D3 in keratinocytes. The AMP cathelicidin and TLR cofactor CD14 were known to be induced by 1,25D3, and analysis of TLR2 expression revealed this also was increased by 1,25D3. Topical 1,25D3 application to human skin confirmed these results, showing increased cathelicidin, CD14 and TLR2 by immunostaining. Furthermore, the presence of 1,25D3 enabled human keratinocytes to respond to Malp2 (a TLR2/6 ligand) with increased cathelicidin production which was inhibited by neutralizing antibody to TLR2. 1,25D3 also increased the ability of keratinocytes to kill Staphylococcus aureus. Interestingly, keratinocytes surrounding human skin wounds increased expression of CD14 and showed a previously known increase in cathelicidin AMP. Thus, we hypothesized that 1,25D3 was also a signalling molecule during skin injury. Supporting this, we found that CYP27B1, the enzyme that converts 25‐hydroxy vitamin D3 (25D3) to active 1,25D3, was significantly increased in wounds and induced in response to factors in the wound micromilieu such as TGFβ1 or TLR stimulation. Blocking the vitamin D receptor, inhibiting CYP27B1 enzymatic activity, or limiting 25D3 in culture each prevented TGFβ1 from inducing cathelicidin, CD14 or TLR2. Furthermore, mice deficient in CYP27B1 failed to increase CD14 in vivo following injury. Thus, this investigation demonstrates how injury initiates the innate immune response; 25D3 is activated to 1,25D3 by enzymatic conversion, a process triggered by microbial products or host factors such as TGFβ1. The increase in 1,25D3 then directly increases cathelicidin release and enables responsiveness to microbial products through induction of TLR cofactor CD14.
2,3,7,8‐tetrachlorodibenzo‐p‐dioxin alters the differentiation of SZ95 sebocytes in vitro
Authors: Ju Q. , Fimmel S. , Stahlmann R. , Zouboulis C. C.
Published: June 2008

Introduction:  Chloracne is an acneiform skin disease, which is considered to be the most specific and sensitive clinical condition of dioxin intoxication. Sebogenesis is decreased and skin xerosis is one of the most prominent clinical characteristics compared with acne vulgaris. However, the activity of dioxin on the sebaceous glands is still unclear. We studied the effects of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD), which is a representative for a group of dioxins, on sebaceous lipid synthesis and expression of markers related to sebocyte differentiation in vitro.

Materials and Methods:  After pretreatment with and without linoleic acid (LA) 10−4 M for 3 days, SZ95 sebocytes were treated again with TCDD with and without linoleic acid 10−4 M for 3 additional days. Neutral lipids in SZ95 sebocytes were measured by the nile red microassay. Immunohistology and western blotting were used to detect expression of keratin 7 (a marker of undifferentiated sebocytes), EMA (a marker of differentiated sebocytes) and keratin 10 (a marker of keratinocyte differentiation).

Results:  The neutral lipid content of SZ95 sebocytes was markedly inhibited under treatment with TCDD in concentrations of 10−8 M, 10−9 M and 10−10 M (P < 0.001 respectively), in the presence of LA. SZ95 sebocyte lipid content was not affected by TCDD alone. Moreover, expression of keratin 7 and EMA decreased and keratin 10 increased under TCDD treatment.

Conclusions:  Dioxin affects sebaceous gland cell lipogenesis and differentiation in vitro, probably by switching the sebocyte into a kerationocyte lineage. These findings indicate that altered sebaceous gland differentiation is likely to be the major reason of decreased sebogenesis in patients with chloracne.
Review article: Adenosine use in the emergency department
Authors: Innes James A
Published: June 2008

Objective:  To perform a review of the efficacy of adenosine, including its potential role as first‐line treatment in unstable supraventricular tachycardia (SVT) and its use in wide complex tachycardias and diagnosing difficult arrhythmias. The dose and administration, nature and frequency of side‐effects and relevant interactions and dosage adjustments are also discussed.

Methods:  A search of the Medline database from 1950 to 2007 and the Embase Database from 1974 to 2007 was carried out. A manual search was performed of references of each article.

Results:  Adenosine is efficacious at treating stable SVT, but it is no more effective than cheaper alternatives. It has a possible role in the first‐line treatment of unstable SVT and is generally safe and effective when used to treat and/or diagnose wide complex tachycardias. There is a small risk of inducing serious arrhythmias, such as prolonged atrioventricular blockade and ventricular fibrillation. There is evidence that recommended initial doses for infants might be too low, but initial doses for children and adults are adequate. There is evidence that central venous administration requires lower doses, but there are no studies addressing peripheral sites of administration and size of flush. Minor and self‐limiting side‐effects are common. The need for dosage adjustments in the presence of interacting medications is well documented, but no studies have addressed how to rationally effect these adjustments.

Conclusion:  There is extensive evidence showing adenosine to be efficacious at treating SVT, but no more efficacious than cheaper alternatives. More studies are required to investigate other areas of adenosine use.
Evaluation of Sexual Dysfunction Prevalence in Infertile Couples
Authors: Khademi Afsaneh , Alleyassin Ashraf , Amini Mehrnoosh , Ghaemi Marjan
Published: June 2008

Introduction

The physical health and emotional well-being of many individuals and couples of reproductive age are significantly affected by infertility. Sexual function is one of the important components of health and overall quality of life.

Aims

To determine the prevalence of sexual dysfunction in infertile couples.

Methods

In a cross-sectional study, in a tertiary university hospital, sexual dysfunction was assessed in 100 infertile couples. Sexual Function Questionnaire (SFQ) and International Index of Erectile Function (IIEF) questionnaire were administered.

Main Outcome Measures

Prevalence of sexual dysfunction in infertile couples based on the score of the domains of SFQ and IIEF.

Result(s)

The SFQ score was within the normal range in all five domains in only 7% of women. The prevalence of female sexual dysfunction was highest and lowest in arousal-sensation (80.2%) and orgasm (22.8%) domains, respectively. Only 2% of male participants have had severe erectile dysfunction (ED).

Conclusions

The prevalence of dysfunction in arousal-sensation and arousal-lubrication in our study was found to be higher than the results reported from Iranian normal population. The prevalence of any degree of ED in our study was higher than the prevalence reported for normal population and infertile men. The role of demographic factors, relationship parameters, and infertility per se in the prevalence of sexual dysfunction in infertile couples remains to be determined.
Laboratory Forum: Rat as an Animal Model for Male Erectile Function Evaluation in Sexual Medicine Research
Authors: Mehta Neal , Sikka Suresh , Rajasekaran Mahadevan
Published: June 2008

Introduction

Animal models have contributed, to a great extent, to our understanding and advancement in the field of sexual medicine. Many current medical and surgical therapies in sexual medicine are the direct result of the development of such animal models. Over the past 15–20 years, rodents have become the premier models for such studies. In particular, the rat model provided the most valuable and reproducible investigations that significantly contributed to our knowledge of male sexual dysfunction as well as in the development of various treatment modalities. In addition, such in vivo animal models helped us develop the latest biotechnological tools that allowed numerous investigations at the cellular and molecular levels.

Aim

Review the most common laboratory techniques that employ rat model for the evaluation of male erectile function and erectile tissue end-organ analyses.

Methods

Review of peer-reviewed literature.

Main Outcome Measures

Pathophysiology and laboratory research outcome correlation.

Results

The review suggests that rat is a versatile model in sexual medicine research.

Conclusions

This versatile model should help in the further development of research tools, characterize additional signaling target molecules and pathways, and help in our understanding of male sexual dysfunction.
Copper and Quaternary Ammonium Cations Exert Synergistic Bactericidal and Antibiofilm Activity againstPseudomonas aeruginosa
Authors: Harrison Joe J. , Turner Raymond J. , Joo Daniel A. , Stan Michelle A. , Chan Catherine S. , Allan Nick D. , Vrionis Helen A. , Olson Merle E. , Ceri Howard
Published: June 2008

Biofilms are slimy aggregates of microbes that are likely responsible for many chronic infections as well as for contamination of clinical and industrial environments.Pseudomonas aeruginosais a prevalent hospital pathogen that is well known for its ability to form biofilms that are recalcitrant to many different antimicrobial treatments. We have devised a high-throughput method for testing combinations of antimicrobials for synergistic activity against biofilms, including those formed byP. aeruginosa. This approach was used to look for changes in biofilm susceptibility to various biocides when these agents were combined with metal ions. This process identified that Cu2+works synergistically with quaternary ammonium compounds (QACs; specifically benzalkonium chloride, cetalkonium chloride, cetylpyridinium chloride, myristalkonium chloride, and Polycide) to killP. aeruginosabiofilms. In some cases, adding Cu2+to QACs resulted in a 128-fold decrease in the biofilm minimum bactericidal concentration compared to that for single-agent treatments. In combination, these agents retained broad-spectrum antimicrobial activity that also eradicated biofilms ofEscherichia coli,Staphylococcus aureus,Salmonella entericaserovar Cholerasuis, andPseudomonas fluorescens. To investigate the mechanism of action, isothermal titration calorimetry was used to show that Cu2+and QACs do not interact in aqueous solutions, suggesting that each agent exerts microbiological toxicity through independent biochemical routes. Additionally, Cu2+and QACs, both alone and in combination, reduced the activity of nitrate reductases, which are enzymes that are important for normal biofilm growth. Collectively, the results of this study indicate that Cu2+and QACs are effective combinations of antimicrobials that may be used to kill bacterial biofilms.
Mechanism and Fitness Costs of PR-39 Resistance in
Salmonella enterica
Serovar Typhimurium LT2
Authors: Pränting Maria , Negrea Aurel , Rhen Mikael , Andersson Dan I.
Published: June 2008

PR-39 is a porcine antimicrobial peptide that kills bacteria with a mechanism that does not involve cell lysis. Here, we demonstrate that
Salmonella enterica
serovar Typhimurium can rapidly acquire mutations that reduce susceptibility to PR-39. Resistant mutants appeared at a rate of 0.4 × 10
−6
per cell per generation. These mutants were about four times more resistant than the wild type and showed a greatly reduced rate of killing. Genetic analysis revealed mutations in the putative transport protein SbmA as being responsible for the observed resistance. These
sbmA
mutants were as fit as the wild-type parental strain as measured by growth rates in culture medium and mice and by long-term survival in stationary phase. These results suggest that resistance to certain antimicrobial peptides can rapidly develop without an obvious fitness cost for the bacteria and that resistance development could become a threat to the efficacy of antimicrobial peptides if used in a clinical setting.
Susceptibility Testing and Molecular Classification of
Paecilomyces
spp
Authors: Castelli Maria Victoria , Alastruey-Izquierdo Ana , Cuesta Isabel , Monzon Araceli , Mellado Emilia , Rodriguez-Tudela Juan L. , Cuenca-Estrella Manuel
Published: June 2008

In vitro susceptibility profiles of 58
Paecilomyces
clinical isolates are reported. Amphotericin B, itraconazole, and echinocandins showed poor activity against
Paecilomyces lilacinus
, while the new triazoles were active against it.
Paecilomyces variotii
exhibited a different susceptibility pattern, being susceptible to most antifungal agents apart from voriconazole and ravuconazole.
Cooperative Role of Macrophages and Neutrophils in Host Antiprotozoan Resistance in Mice Acutely Infected withCryptosporidium parvum
Authors: Takeuchi Dan , Jones Vickie C. , Kobayashi Makiko , Suzuki Fujio
Published: June 2008

Severe experimental infections withCryptosporidium parvumhave been reported in immunocompromised animals such as SCID mice (mice without functional T cells and B cells). In aC. parvuminfection with 1 × 106oocysts/mouse in SCID beige (SCIDbg) mice (SCID mice lacking functional NK cells), oocyst shedding was first demonstrated 18 days after infection. However, shedding was shown as early as 3 days after the same infection in SCIDbgMN mice. All of the SCIDbgMN mice died within 16 days ofC. parvuminfection, while 100% of the SCIDbg mice exposed to the parasite survived. SCIDbgMN mice are SCIDbg mice depleted of functional macrophages (Mφ) and neutrophils (PMN), suggesting that the severity early afterC. parvuminfection is strongly influenced by the functions of Mφ and PMN. All SCIDbgMN mice orally infected with a lethal dose ofC. parvumsurvived after they were inoculated with Mφ from SCIDbg mice exposed toC. parvum(CP-Mφ) or resident Mφ previously cultured with PMN fromC. parvum-infected SCIDbg mice (CP-PMN). However, all SCIDbgMN mice inoculated with CP-PMN alone or resident Mφ alone died afterC. parvuminfection. CP-Mφ were identified as classically activated Mφ (M1Mφ), and CP-PMN were characterized as PMN-I. In in vitro studies, resident Mφ converted to M1Mφ after transwell cultivation with CP-PMN. These results indicate that the resistance of SCIDbg mice early afterC. parvuminfection is displayed through the function of M1Mφ which are converted from resident Mφ influenced by CP-PMN (PMN-I).
Screening of Highly Expressed Mycobacterial Genes Identifies Rv3615c as a Useful Differential Diagnostic Antigen for theMycobacterium tuberculosisComplex
Authors: Sidders Ben , Pirson Chris , Hogarth Philip J. , Hewinson R. Glyn , Stoker Neil G. , Vordermeier H. Martin , Ewer Katie
Published: June 2008

Tuberculous infections caused by mycobacteria, especially tuberculosis of humans and cattle, are important both clinically and economically. Human populations can be vaccinated withMycobacterium bovisbacille Calmette-Guérin (BCG), and control measures for cattle involving vaccination are now being actively considered. However, diagnostic tests based on tuberculin cannot distinguish between genuine infection and vaccination with BCG. Therefore, identification of differential diagnostic antigens capable of making this distinction is required, and until now sequence-based approaches have been predominant. Here we explored the link between antigenicity and mRNA expression level, as well as the possibility that we may be able to detect differential antigens by analyzing quantified global transcriptional profiles. We generated a list of 14 candidate antigens that are highly expressed inMycobacterium tuberculosisandM. bovisunder a variety of growth conditions. These candidates were screened inM. bovis-infected and naïve cattle for the ability to stimulate a gamma interferon (IFN-γ) response. We identified one antigen, Rv3615c, which stimulated IFN-γ responses in a significant proportion ofM. bovis-infected cattle (11 of 30 cattle [37%] [P< 0.01]) but not in naïve or BCG-vaccinated animals. Importantly, the same antigen stimulated IFN-γ responses in a significant proportion of infected cattle that did not respond to the well-characterized mycobacterial antigens ESAT-6 and CFP-10. Therefore, use of the Rv3615c epitope in combination with previously described differential tests based on ESAT-6 and CFP-10 has the potential to significantly increase diagnostic sensitivity without reducing specificity in BCG-vaccinated populations.
Helicobacter pyloriInfection Stimulates Plasminogen Activator Inhibitor 1 Production by Gastric Epithelial Cells
Authors: Keates A. C. , Tummala S. , Peek R. M. , Csizmadia E. , Kunzli B. , Becker K. , Correa P. , Romero-Gallo J. , Piazuelo M. B. , Sheth S. , Kelly C. P. , Robson S. C. , Keates S.
Published: June 2008

Chronic infection with the gastric pathogenHelicobacter pylorisignificantly increases the risk of developing atrophic gastritis, peptic ulcer disease, and gastric adenocarcinoma.H. pyloristrains that possess thecagpathogenicity island, which translocates CagA into the host cells, augment these risks. The aim of this study was to determine the molecular mechanisms through whichH. pyloriupregulates the expression of plasminogen activator inhibitor 1 (PAI-1), a member of the urokinase activator system that is involved in tumor metastasis and angiogenesis. Levels of PAI-1 mRNA and protein were examined in tissues fromH. pylori-infected patients and in vitro using AGS gastric epithelial cells. In vitro, cells were infected with toxigeniccag-positive or nontoxigeniccag-negative strains ofH. pylorior isogenic mutants. The amount of PAI-1 secretion was measured by enzyme-linked immunosorbent assay, and mRNA levels were determined using real-time PCR. The regulation of PAI-1 was examined using the extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor and small interfering RNA. Analysis of human biopsy samples revealed an increase in both PAI-1 mRNA and protein levels in patients withH. pylorigastritis compared to those of uninfected controls. Infection of AGS cells withH. pylorisignificantly increased PAI-1 mRNA expression and the secretion of PAI-1 protein. Moreover, PAI-1 mRNA and protein production was more pronounced when AGS cells were infected byH. pyloristrains carrying a functionalcagsecretion system than when cells were infected by strains lacking this system. PAI-1 secretion was also reduced when cells were infected with eithercagE-negative orcagA-negative mutants. The ectopic overexpression of CagA significantly increased the levels of PAI-1 mRNA and protein, whereas blockade of the ERK1/2 pathway inhibitedH. pylori-mediated PAI-1 upregulation. These findings suggest that the upregulation of PAI-1 inH. pylori-infected gastric epithelial cells may contribute to the carcinogenic process.