International union of basic and clinical pharmacology. XCI. structure, function, and pharmacology of acid-sensing ion channels and the epithelial Na+ channel.

The epithelial Na(+) channel (ENaC) and the acid-sensing ion channels (ASICs) form subfamilies within the ENaC/degenerin family of Na(+) channels. ENaC mediates transepithelial Na(+) transport, thereby contributing to Na(+) homeostasis and the maintenance of blood pressure and the airway surface liquid level. ASICs are H(+)-activated channels found in central and peripheral neurons, where their activation induces neuronal depolarization. ASICs are involved in pain sensation, the expression of fear, and neurodegeneration after ischemia, making them potentially interesting drug targets. This review summarizes the biophysical properties, cellular functions, and physiologic and pathologic roles of the ASIC and ENaC subfamilies. The analysis of the homologies between ENaC and ASICs and the relation between functional and structural information shows many parallels between these channels, suggesting that some mechanisms that control channel activity are shared between ASICs and ENaC. The available crystal structures and the discovery of animal toxins acting on ASICs provide a unique opportunity to address the molecular mechanisms of ENaC and ASIC function to identify novel strategies for the modulation of these channels by pharmacologic ligands.

What can we learn from international comparisons of costs by DRG ?

OBJECTIVES: The objective of this study was to compare costs data by diagnosis related group (DRG) between Belgium and Switzerland. Our hypotheses were that differences between countries can probably be explained by methodological differences in cost calculations, by differences in medical practices and by differences in cost structures within the two countries. METHODS: Classifications of DRG used in the two countries differ (AP-DRGs version 1.7 in Switzerland and APR-DRGs version 15.0 in Belgium). The first step of this study was to transform Belgian summaries into Swiss AP-DRGs. Belgian and Swiss data were calculated with a clinical costing methodology (full costing). Belgian and Swiss costs were converted into US$ PPP (purchasing power parity) in order to neutralize differences in purchasing power between countries. RESULTS: The results of this study showed higher costs in Switzerland despite standardization of cost data according to PPP. The difference is not explained by the case-mix index because this was similar for inliers between the two countries. The length of stay (LOS) was also quite similar for inliers between the two countries. The case-mix index was, however, higher for high outliers in Belgium, as reflected in a higher LOS for these patients. Higher costs in Switzerland are thus probably explained mainly by the higher number of agency staff by service in this country or because of differences in medical practices. CONCLUSIONS: It is possible to make international comparisons but only if there is standardization of the case-mix between countries and only if comparable accountancy methodologies are used. Harmonization of DRGs groups, nomenclature and accountancy is thus required.

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 4: seminal vesicles and lymph nodes.

The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the infiltration of tumor into the seminal vesicles and regional lymph nodes were coordinated by working group 4. There was a consensus that complete blocking of the seminal vesicles was not necessary, although sampling of the junction of the seminal vesicles and prostate was mandatory. There was consensus that sampling of the vas deferens margins was not obligatory. There was also consensus that muscular wall invasion of the extraprostatic seminal vesicle only should be regarded as seminal vesicle invasion. Categorization into types of seminal vesicle spread was agreed by consensus to be not necessary. For examination of lymph nodes, there was consensus that special techniques such as frozen sectioning were of use only in high-risk cases. There was no consensus on the optimal sampling method for pelvic lymph node dissection specimens, although there was consensus that all lymph nodes should be completely blocked as a minimum. There was also a consensus that a count of the number of lymph nodes harvested should be attempted. In view of recent evidence, there was consensus that the diameter of the largest lymph node metastasis should be measured. These consensus decisions will hopefully clarify the difficult areas of pathological assessment in radical prostatectomy evaluation and improve the concordance of research series to allow more accurate assessment of patient prognosis.

International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors.

The three peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear hormone receptor superfamily. They share a high degree of structural homology with all members of the superfamily, particularly in the DNA-binding domain and ligand- and cofactor-binding domain. Many cellular and systemic roles have been attributed to these receptors, reaching far beyond the stimulation of peroxisome proliferation in rodents after which they were initially named. PPARs exhibit broad, isotype-specific tissue expression patterns. PPARalpha is expressed at high levels in organs with significant catabolism of fatty acids. PPARbeta/delta has the broadest expression pattern, and the levels of expression in certain tissues depend on the extent of cell proliferation and differentiation. PPARgamma is expressed as two isoforms, of which PPARgamma2 is found at high levels in the adipose tissues, whereas PPARgamma1 has a broader expression pattern. Transcriptional regulation by PPARs requires heterodimerization with the retinoid X receptor (RXR). When activated by a ligand, the dimer modulates transcription via binding to a specific DNA sequence element called a peroxisome proliferator response element (PPRE) in the promoter region of target genes. A wide variety of natural or synthetic compounds was identified as PPAR ligands. Among the synthetic ligands, the lipid-lowering drugs, fibrates, and the insulin sensitizers, thiazolidinediones, are PPARalpha and PPARgamma agonists, respectively, which underscores the important role of PPARs as therapeutic targets. Transcriptional control by PPAR/RXR heterodimers also requires interaction with coregulator complexes. Thus, selective action of PPARs in vivo results from the interplay at a given time point between expression levels of each of the three PPAR and RXR isotypes, affinity for a specific promoter PPRE, and ligand and cofactor availabilities.

Results of An International Study of Quantitative BCR/ABL Assays Using Defined RNA Samples

Molecular monitoring of BCR/ABL transcripts by real time quantitative reverse transcription PCR (qRT-PCR) is an essential technique for clinical management of patients with BCR/ABL-positive CML and ALL. Though quantitative BCR/ABL assays are performed in hundreds of laboratories worldwide, results among these laboratories cannot be reliably compared due to heterogeneity in test methods, data analysis, reporting, and lack of quantitative standards. Recent efforts towards standardization have been limited in scope. Aliquots of RNA were sent to clinical test centers worldwide in order to evaluate methods and reporting for e1a2, b2a2, and b3a2 transcript levels using their own qRT-PCR assays. Total RNA was isolated from tissue culture cells that expressed each of the different BCR/ABL transcripts. Serial log dilutions were prepared, ranging from 100 to 10-5, in RNA isolated from HL60 cells. Laboratories performed 5 independent qRT-PCR reactions for each sample type at each dilution. In addition, 15 qRT-PCR reactions of the 10-3 b3a2 RNA dilution were run to assess reproducibility within and between laboratories. Participants were asked to run the samples following their standard protocols and to report cycle threshold (Ct), quantitative values for BCR/ABL and housekeeping genes, and ratios of BCR/ABL to housekeeping genes for each sample RNA. Thirty-seven (n=37) participants have submitted qRT-PCR results for analysis (36, 37, and 34 labs generated data for b2a2, b3a2, and e1a2, respectively). The limit of detection for this study was defined as the lowest dilution that a Ct value could be detected for all 5 replicates. For b2a2, 15, 16, 4, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. For b3a2, 20, 13, and 4 labs showed a limit of detection at the 10-5, 10-4, and 10-3 dilutions, respectively. For e1a2, 10, 21, 2, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. Log %BCR/ABL ratio values provided a method for comparing results between the different laboratories for each BCR/ABL dilution series. Linear regression analysis revealed concordance among the majority of participant data over the 10-1 to 10-4 dilutions. The overall slope values showed comparable results among the majority of b2a2 (mean=0.939; median=0.9627; range (0.399 - 1.1872)), b3a2 (mean=0.925; median=0.922; range (0.625 - 1.140)), and e1a2 (mean=0.897; median=0.909; range (0.5174 - 1.138)) laboratory results (Fig. 1-3)). Thirty-four (n=34) out of the 37 laboratories reported Ct values for all 15 replicates and only those with a complete data set were included in the inter-lab calculations. Eleven laboratories either did not report their copy number data or used other reporting units such as nanograms or cell numbers; therefore, only 26 laboratories were included in the overall analysis of copy numbers. The median copy number was 348.4, with a range from 15.6 to 547,000 copies (approximately a 4.5 log difference); the median intra-lab %CV was 19.2% with a range from 4.2% to 82.6%. While our international performance evaluation using serially diluted RNA samples has reinforced the fact that heterogeneity exists among clinical laboratories, it has also demonstrated that performance within a laboratory is overall very consistent. Accordingly, the availability of defined BCR/ABL RNAs may facilitate the validation of all phases of quantitative BCR/ABL analysis and may be extremely useful as a tool for monitoring assay performance. Ongoing analyses of these materials, along with the development of additional control materials, may solidify consensus around their application in routine laboratory testing and possible integration in worldwide efforts to standardize quantitative BCR/ABL testing.

International comparison of Russian food processing industry -Finnish perspective

Työn päätavoitteena on kartoittaa Venäjän elintarviketeollisuutta ulkomaisen investoijan näkökulmasta. Tutkimus arvioi liiketoimintamahdollisuuksia ja kilpailutilannetta Venäjän elintarviketeollisuudessa ja auttaa ulkomaisia yrityksiä toteuttamaan liiketoimintastrategioitaan Venäjällä. Venäjän ja muiden siirtymätalousmaiden markkinatilannevertailujen lisäksi Venäjän alueita verrataan keskenään. Myös mahdollisen WTO jäsenyyden vaikutuksia arvioidaan. Kommunismin perintö vaikuttaa edelleen Venäjän elintarviketeollisuuteen ja maatalouteen. Maatalouden tuottavuus on kaukana länsimaisesta tasosta ja maatiloilta puuttuu rahoitusta. Etenkin maidon- ja lihanjalostajat kärsivät raaka-ainepulasta. Venäjän kriisi vuonna 1998 vahvisti paikallista teollisuustuotantoa mutta aiheutti ongelmia ulkomaisille investoijille ja yrityksille, jotka vievät tuotteitaan Venäjälle. Edut, joita mahdollinen maailmankauppajärjestö WTO:n jäsenyys tuo, ovat merkittävämpiä Venäjälle kuin sen kauppakumppaneille. Venäjän alueet eivät ole yhtäläisesti kehittyneitä ja kuluttajien ostovoima vaihtelee paljon. Itsestään selvin ja houkuttelevin vaihtoehto menestyvien elintarvikeyritysten laajentumiselle löytyy alueilta, joilla ostovoima on suurin. Tähän asti kansainväliset elintarvikeyritykset ovat olleet enemmän kiinnostuneita Itä- ja Keski-Euroopan maista. Käytettävissä olevat tulot ovat Itä- ja Keski-Euroopan maissa suurempia kuin Venäjällä, joten tuottajat pystyvät myymään myös kalliimpia tuotteita. Työvoimakustannukset Venäjällä tulevat olemaan suotuisia vielä muutaman vuosikymmenen ja markkinoiden koko on merkittävä. Siksi kansainvälisillä elintarvikeyrityksillä riittää kiinnostusta tulevaisuudessa investoida myös Venäjälle.

Adjuvant cisplatin-based combined chemotherapy for lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC): a retrospective international study of >1500 patients.

OBJECTIVE: To compare outcomes of patients with lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) treated with or without cisplatin-based combined adjuvant chemotherapy (AC) after radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analysed 1523 patients with LN-positive UCB, who underwent RC with bilateral pelvic LN dissection. All patients had no evidence of disease after RC. AC was administered within 3 months. Competing-risks models were applied to compare UCB-related mortality. RESULTS: Of the 1523 patients, 874 (57.4%) received AC. The cumulative 1-, 2- and 5-year UCB-related mortality rates for all patients were 16%, 36% and 56%, respectively. Administration of AC was associated with an 18% relative reduction in the risk of UCB-related death (subhazard ratio 0.82, P = 0.005). The absolute reduction in mortality was 3.5% at 5 years. The positive effect of AC was detectable in patients aged ≤70 years, in women, in pT3-4 disease, and in those with a higher LN density and lymphovascular invasion. This study is limited by its retrospective and non-randomised design, selection bias, the absence of central pathological review and lack in standardisation of LN dissection and cisplatin-based protocols. CONCLUSION: AC seems to reduce UCB-related mortality in patients with LN-positive UCB after RC. Younger patients, women and those with high-risk features such as pT3-4 disease, a higher LN density and lymphovascular invasion appear to benefit most. Appropriately powered prospective randomised trials are necessary to confirm these findings.

The international epidemiology of child sexual abuse: a continuation of Finkelhor

Objective: The purpose of this paper was to compare the prevalence rates of child sexual abuse reported by [Finkelhor, D. (1994). The international epidemiology of child sexual abuse. Child Abuse & Neglect, 18 (5), 409-417] with those found in recent publications in order to confirm the widespread prevalence of child sexual abuse. Methods: Relevant articles about prevalence of child sexual abuse were identified through searches of computerized databases and a handsearch of Child Abuse & Neglect and the Journal of Child Sexual Abuse. Results: Thirty-eight independent articles were identified, corresponding to 39 prevalence studies; these articles report the prevalence of childhood sexual abuse in 21 different countries, ranging from 0 to 53% for women and 0 to 60% for men. Conclusions: Comparison of the present study with that of [Finkelhor, D. (1994). The international epidemiology of child sexual abuse. Child Abuse & Neglect, 18 (5), 409-417] shows a similarity between prevalence distributions; there appears to be a general pattern that remains more or less constant over the years, especially in women. Practice implications: Twelve years after the first revision study about the international prevalence of child sexual abuse, there is still a need for new data about this topic. The present study shows child sexual abuse is still a widespread problem in the society. In this research, carried out on 38 independent studies, there is new data for 21 countries over the world, being especially relevant the results obtained from other countries different from those pertaining toNorth America or Europe. It is important to point out the high prevalence found in most of the countries, so this information could be a new warning to make society and governments aware of this problem and undertake actions to prevent sexual abuse in childhood.

The international epidemiology of child sexual abuse: a continuation of Finkelhor

Objective: The purpose of this paper was to compare the prevalence rates of child sexual abuse reported by [Finkelhor, D. (1994). The international epidemiology of child sexual abuse. Child Abuse & Neglect, 18 (5), 409-417] with those found in recent publications in order to confirm the widespread prevalence of child sexual abuse. Methods: Relevant articles about prevalence of child sexual abuse were identified through searches of computerized databases and a handsearch of Child Abuse & Neglect and the Journal of Child Sexual Abuse. Results: Thirty-eight independent articles were identified, corresponding to 39 prevalence studies; these articles report the prevalence of childhood sexual abuse in 21 different countries, ranging from 0 to 53% for women and 0 to 60% for men. Conclusions: Comparison of the present study with that of [Finkelhor, D. (1994). The international epidemiology of child sexual abuse. Child Abuse & Neglect, 18 (5), 409-417] shows a similarity between prevalence distributions; there appears to be a general pattern that remains more or less constant over the years, especially in women. Practice implications: Twelve years after the first revision study about the international prevalence of child sexual abuse, there is still a need for new data about this topic. The present study shows child sexual abuse is still a widespread problem in the society. In this research, carried out on 38 independent studies, there is new data for 21 countries over the world, being especially relevant the results obtained from other countries different from those pertaining toNorth America or Europe. It is important to point out the high prevalence found in most of the countries, so this information could be a new warning to make society and governments aware of this problem and undertake actions to prevent sexual abuse in childhood.

Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus.

To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.

Clustering and International Competitiveness of Information Technology Industry in the Saint Petersburg Area

The main objective of this study is to assess the potential of the information technology industry in the Saint Petersburg area to become one of the new key industries in the Russian economy. To achieve this objective, the study analyzes especially the international competitiveness of the industry and the conditions for clustering. Russia is currently heavily dependent on its natural resources, which are the main source of its recent economic growth. In order to achieve good long-term economic performance, Russia needs diversification in its well-performing industries in addition to the ones operating in the field of natural resources. The Russian government has acknowledged this and started special initiatives to promote such other industries as information technology and nanotechnology. An interesting industry that is basically less than 20 years old and fast growing in Russia, is information technology. Information technology activities and markets are mainly concentrated in Russia’s two biggest cities, Moscow and Saint Petersburg, and areas around them. The information technology industry in the Saint Petersburg area, although smaller than Moscow, is especially dynamic and is gaining increasing foreign company presence. However, the industry is not yet internationally competitive as it lacks substantial and sustainable competitive advantages. The industry is also merely a potential global information technology cluster, as it lacks the competitive edge and a wide supplier and manufacturing base and other related parts of the whole information technology value system. Alone, the industry will not become a key industry in Russia, but it will, on the other hand, have an important supporting role for the development of other industries. The information technology market in the Saint Petersburg area is already large and if more tightly integrated to Moscow, they will together form a huge and still growing market sufficient for most companies operating in Russia currently and in the future. Therefore, the potential of information technology inside Russia is immense.

Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic valve infective endocarditis: analysis in the International Collaboration of Endocarditis-Prospective Cohort Study.

BACKGROUND: The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. METHODS: Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. RESULTS: EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). CONCLUSIONS: In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

Clustering and international competitiveness of information technology industry in the Saint Petersburg area

The main objective of this study is to assess the potential of the information technology industry in the Saint Petersburg area to become one of the new key industries in the Russian economy. To achieve this objective, the study analyzes especially the international competitiveness of the industry and the conditions for clustering. Russia is currently heavily dependent on its natural resources, which are the main source of its recent economic growth. In order to achieve good long-term economic performance, Russia needs diversification in its well-performing industries in addition to the ones operating in the field of natural resources. The Russian government has acknowledged this and started special initiatives to promote such other industries as information technology and nanotechnology. An interesting industry that is basically less than 20 years old and fast growing in Russia, is information technology. Information technology activities and markets are mainly concentrated in Russia’s two biggest cities, Moscow and Saint Petersburg, and areas around them. The information technology industry in the Saint Petersburg area, although smaller than Moscow, is especially dynamic and is gaining increasing foreign company presence. However, the industry is not yet internationally competitive as it lacks substantial and sustainable competitive advantages. The industry is also merely a potential global information technology cluster, as it lacks the competitive edge and a wide supplier and manufacturing base and other related parts of the whole information technology value system. Alone, the industry will not become a key industry in Russia, but it will, on the other hand, have an important supporting role for the development of other industries. The information technology market in the Saint Petersburg area is already large and if more tightly integrated to Moscow, they will together form a huge and still growing market sufficient for most companies operating in Russia currently and in the future. Therefore, the potential of information technology inside Russia is immense.