Caesarean Section Frequency among Immigrants, Second- and Third-Generation Women, and Non-Immigrants: Prospective Study in Berlin/Germany.
The frequency of caesarean section delivery varies between countries and social groups. Among other factors, it is determined by the quality of obstetrics care. Rates of elective (planned) and emergency (in-labor) caesareans may also vary between immigrants (first generation), their offspring (second- and third-generation women), and non-immigrants because of access and language barriers. Other important points to be considered are whether caesarean section indications and the neonatal outcomes differ in babies delivered by caesarean between immigrants, their offspring, and non-immigrants. A standardized interview on admission to delivery wards at three Berlin obstetric hospitals was performed in a 12-month period in 2011/2012. Questions on socio-demographic and care aspects and on migration (immigrated herself vs. second- and third-generation women vs. non-immigrant) and acculturation status were included. Data was linked with information from the expectant mothers' antenatal records and with perinatal data routinely documented in the hospital. Regression modeling was used to adjust for age, parity and socio-economic status. The caesarean section rates for immigrants, second- and third-generation women, and non-immigrant women were similar. Neither indications for caesarean section delivery nor neonatal outcomes showed statistically significant differences. The only difference found was a somewhat higher rate of crash caesarean sections per 100 births among first generation immigrants compared to non-immigrants. Unlike earlier German studies and current studies from other European countries, this study did not find an increased rate of caesarean sections among immigrants, as well as second- and third-generation women, with the possible exception of a small high-risk group. This indicates an equally high quality of perinatal care for women with and without a migration history.


Association of Hair Loss With Health Utility Measurements Before and After Hair Transplant Surgery in Men and Women.
Androgenetic alopecia is a highly prevalent condition across both sexes and can be surgically corrected through hair transplant. Health utility scores, which represent quantitative estimates of individual preferences for a given state of health, are a measure of health-related quality of life. The health utility scores for sex-specific alopecia and the posttransplant state have not previously been quantified. To obtain health utility measurements for the objective assessment of sex-specific alopecia and hair transplant surgery and to analyze layperson perception of alopecia compared with other chronic health conditions. A prospective clinical study was conducted from August 1 to December 31, 2017, at the Harvard Decision Science Laboratory. Adult casual observers (n = 308) completed an internet-based health utility questionnaire. Health states were presented using still patient images and a description of 5 health states, including monocular blindness, binocular blindness, male alopecia, female alopecia, and male posttransplant state. Health utility measures of sex-specific alopecia, posttransplant state, and monocular and binocular blindness were measured by visual analog scale (VAS), standard gamble (SG), and time trade-off (TTO) in quality-adjusted life-years (QALYs). Groups were analyzed with 1-way analysis of variance and post hoc Tukey pairwise comparison. The 308 participants included 157 (51.0%) women with a mean (SD) age of 30.8 (13.5) years. Mean (SD) health utility measures included 0.85 (0.18) QALYs for the VAS, 0.93 (0.17) QALYs for the SG, and 0.93 (0.17) QALYs for the TTO in male alopecia; 0.83 (0.19) QALYs for the VAS, 0.92 (0.17) QALYs for the SG, and 0.91 (0.18) QALYs for the TTO in female alopecia; and 0.93 (0.11) QALYs for the VAS, 0.95 (0.15) QALYs for the SG, and 0.95 (0.16) QALYs for the TTO in a man in the posttransplant state. The mean (SD) health utility of monocular blindness was 0.76 (0.17) QALYs for the VAS, 0.87 (0.21) QALYs for the SG, and 0.86 (0.20) QALYs for the TTO. The health utility score for the posttransplant state was significantly improved compared with the health utility score for alopecia in both sexes (female VAS: +0.10 [95% CI, 0.06-0.14; P < .001]; male VAS, +0.08 [95% CI, 0.04-0.12; P < .001]). Hair loss in women and men demonstrated significantly lower QALYs on the VAS compared with the posttransplant state (female: -0.10 [95% CI, -0.14 to -0.06; P < .001]; male: -0.08 [95% CI, -0.12 to -0.04; P < .001]). Alopecia has a meaningful negative influence on health utility measures in both sexes. Hair transplant surgery significantly increases health utility measures compared with untreated alopecia in both sexes as rated among layperson observers. NA.


Mechanisms of allergen immunotherapy supporting its disease-modifying effect.
Allergen immunotherapy (AIT) is considered the only disease-modifying treatment available at present for allergic disorders. Its main benefits include improvement of symptoms, decreased need for pharmacotherapy, prevention of new sensitizations and sustained effect after AIT completion. The key pillars of AIT-induced tolerance include a shift from Th2 to Th1 response, an increase of regulatory T and B cells, pro-inflammatory effector cell downregulation and IgE suppression, in addition to IgG4, IgA and IgD induction. AIT may also induce trained immunity, characterized by a durable decrease in group 2 of innate lymphoid cells (ILCs) and increased ILC1 and ILC3s. Understanding the immune mechanisms of AIT is essential for validating biomarkers for the prediction of AIT response and for achieving AIT success.


Mechanism for Reducing the Horizontal Transfer Risk of the Airborne Antibiotic-Resistant Genes of Escherichia coli Species through Microwave or UV Irradiation.
Antibiotic-resistant bacteria (ARBs) and antibiotic-resistant genes (ARGs) as new types of contaminants are discharged into the environment, increasing the risk of horizontal gene transfer (HGT). However, few researchers have examined the impacts of airborne ARB deactivation on HGT risk. The deactivation of airborne Escherichia coli 10667 (carrying sul genes) and the emission and removal of ARGs were mainly investigated in this study. Moreover, the potential mechanisms of HGT and transfer frequencies under microwave (MW) and ultraviolet (UV) irradiation were investigated using the nonresistant E. coli GMCC 13373 and E. coli DH5α with plasmid RP4 as the recipient and donor, respectively. E. coli CICC 10667 and E. coli DH5α with RP4 plasmid achieve log inactivation values as high as 5.5-log and 5.0-log, respectively, which were quite different from the antibiotic-sensitive strain E. coli CGMCC 13373 (3.4-log) subjected to MW irradiation. For UV disinfection, E. coli DH5α with the RP4 plasmid was reduced at 4.4-log, E. coli CGMCC 13373 was reduced at 2.3-log, and E. coli CICC 10667 was inactivated at 2.1-log. The removal rates of ARGs and HGT frequencies under MW irradiation were compared with those under UV irradiation. The ARGs removal efficiency (85.5%) obtained by MW was higher than that obtained by UV (48.2%). Consequently, the HGT frequency (0.008) of airborne ARGs released to the recipient (forward transfer) decreased and was lower than that under UV irradiation (0.014). Moreover, the plasmid RP4 was transferred from the donor to the surviving damaged E. coli 10667 as cell permeability (reverse transfer) was increased at a high HGT frequency (0.003) by MW, which was close to the value by UV (0.002). Additionally, sul1 and sul2 genes were confirmed to be more resistant to MW than the sul3 gene. These findings reveal the mechanism of HGT between damaged E. coli 10667 and surrounding environmental microbes. Microwave is a promising technology for disinfecting airborne microbes and preventing the spread of antibiotic resistance.


TIMELESS is a key gene mediating thrombogenesis in COVID-19 and antiphospholipid syndrome.
Abnormal coagulation and increased risk of thrombosis are some of the symptoms associated with COVID-19 severity. Anti-phospholipid antibodies (aPLs) present in critically ill COVID-19 patients contribute to systemic thrombosis. The aim of this study was to identify key common genes to characterize genetic crosstalk between COVID-19 and antiphospholipid syndrome (APS) using bioinformatics analysis and explore novel mechanisms of immune-mediated thrombosis in critically ill COVID-19 patients. The transcriptome data of mononuclear cells from severe COVID-19 patients and APS patients were evaluated to obtain the common genes. The protein-protein interaction network and cytoHubba module analysis in Cytoscape software were used to find the associated hinge genes and hub genes. Among the common differentially expressed genes, TIMELESS depletion was identified only in patients with severe COVID-19 and not in patients with mild COVID-19, and it was validated with the GSE159678 dataset. Functional analyses using gene ontology terms and the Kyoto Encyclopedia of Genes and Genomes pathway suggested that TIMELESS might contribute to the production of antiphospholipid antibody and thrombosis in both COVID-19 and APS patients. The potential role of TIMELESS and autophagy genes in momonuclear cells were further investigated, and GSK3B was found to be associated with TIMELESS. Autophagy targeting agents have a therapeutic potential against COVID-19 and thrombogenesis in APS, which may be related to the role of autophagy genes in the modification of circadian clock proteins. Interference with TIMELESS and other genes associated with it to regulate autoantibody expression may be a potential strategy for immunotherapy against thrombogenesis in severe COVID-19 patients.


Violent delinquency in a Brazilian birth cohort: the roles of breast feeding, early poverty and demographic factors.
We investigated the association between breast feeding, economic factors and conviction for violent delinquency by age 25 years among subjects of the 1982 Birth Cohort from Pelotas, Southern Brazil. Information on breast-feeding pattern and duration was collected in childhood, during the 1983, 1984 and 1986 follow-ups. Information on socio-economic and family characteristics was also obtained between 1982 and 1996. Of the 5914 livebirths enrolled in the cohort, 5228 had obtained an identification document within the state of Rio Grande do Sul, and could thus be identified in judiciary databases. The outcome studied was conviction due to a violent act between ages 12 and 25 years. A total of 106 young people had been convicted at least once (3.0% of men and 1.0% of women). Subjects born to black or mixed mothers and coming from low-income families were at higher risk of having been convicted. Neither crude nor adjusted analyses showed any association between breast feeding and conviction for violent delinquency. Violent delinquency apparently depends more on social factors than on individual factors such as breast feeding.


Different algorithms for quantitative analysis of myocardial infarction with DE MRI: comparison with autopsy specimen measurements.
To compare two semiautomated methods for measurement of infarcted myocardium area on delayed contrast enhanced magnetic resonance imaging, with histopathology findings as standard of reference. Percentage area of myocardial infarction was measured in 10 Yorkshire landrace pigs manually and using two semiautomated methods. The first (standard deviation method) used two operator-selected regions of interest (ROIs) and nine different cutoff values (one to nine times the standard deviation of signal intensity in normal myocardium) to identify infarction. The second (threshold method) used threshold values based on percentages of maximum signal intensity to identify infarction. Results were compared with histopathology findings. Difference between percentage area of infarction obtained with standard deviation method and autopsy specimens was in the range: -13.5% to +13.2%. With threshold method (thresholds from 30% to 90% of signal intensity), difference was -15% to +23%. Manual contouring underestimated infarcted area by 2% comparing to autopsy results. The best agreement between histopathology and semi-automated software was achieved for 4 standard deviations with standard deviation method: difference -0.45%, and for a percentage threshold of 70% (difference +0.67%) with threshold method. However, with standard deviation method, there was statistically significant difference between ROIs based on their location in viable myocardium: mean difference 1.7 ± 4%, P < .0001. Semiautomated measurement of myocardial infarcted area on delayed enhanced magnetic resonance images performs well compared to autopsy. The threshold method, based on percentages of maximum signal intensity is preferable over standard deviation method, which is more susceptible to variability from location of ROIs within viable myocardium.


Formation of N-N cross-links in DNA by reaction of radiation-produced DNA base pair diradicals: a DFT study.
This study employs DFT (density functional theory) to investigate the formation of hydrazine-like (N-N) cross-linked structures between DNA base pair diradicals that are likely to result from the interaction of high linear energy transfer (LET) radiation, such as ion-beam radiation, with DNA. In our calculations, we generated the guanine (G), cytosine (C), adenine (A), and thymine (T) radicals by removing one hydrogen atom from an N-H bond involved in the normal base pairing. The radical species formed are those that naturally result from one-electron oxidation of the bases followed by deprotonation. N-N cross-links between G and C or A and T diradicals were studied using the BHandHLYP, B3LYP, M06, and M06-2X density functionals and 6-31G* basis set. From a comparison to several test cases performed with the G3B3 method, which gives thermodynamically reliable values, we found that calculations employing the BHandHLYP/6-31G* method predict the best estimates of bonding energies for hydrazine-like structures. Our study shows that the N-N cross-link formed between guanine radical and a neutral cytosine is endothermic in nature but can form metastable structures. However, the reactions between two DNA base radicals (diradical) to form several N-N cross-linked structures are found to be highly exothermic in nature. The N-N cross-links formed between various G-C, G-G, and C-C diradicals have binding energies in the range of ca. -54 to -68, -41 to -47, and -67 to -75 kcal/mol, respectively, whereas A-T, A-A, and T-T have binding energies of -80, -60, and -98 kcal/mol, respectively. In all purine-pyrimidine N-N cross-linked structures, the highest occupied molecular orbital (HOMO) is found to be localized on the purine moiety and the lowest unoccupied molecular orbital (LUMO) is on the pyrimidine moiety.


Invasive Melanoma in a Patient with Congenital Ichthyosiform Erythroderma.
We describe the case of a 26-year-old woman with a history of congenital ichthyosiform erythroderma (CIE) who initially presented with a stage IIA amelanotic melanoma on her forearm that was surgically excised. We also review the literature on CIE-associated skin cancers and discuss the possible contribution of ichthyosis to the risk of cutaneous malignancies. Our findings emphasize the importance of close lifelong skin cancer screening in individuals with CIE and highlight the unique malignancy risk of these individuals.


The ascendancy of Amblyomma americanum as a vector of pathogens affecting humans in the United States.
Until the 1990s, Amblyomma americanum was regarded primarily as a nuisance species, but a tick of minor importance as a vector of zoonotic pathogens affecting humans. With the recent discoveries of Ehrlichia chaffeensis, Ehrlichia ewingii, and "Borrelia lonestari," the public health relevance of lone star ticks is no longer in question. During the next 25 years, the number of cases of human disease caused by A. americanum-associated pathogens will probably increase. Based on current trajectories and historic precedents, the increase will be primarily driven by biological and environmental factors that alter the geographic distribution and intensity of transmission of zoonotic pathogens. Sociologic and demographic changes that influence the likelihood of highly susceptible humans coming into contact with infected lone star ticks, in addition to advances in diagnostic capabilities and national surveillance efforts, will also contribute to the anticipated increase in the number of recognized cases of disease.


Calculation of provocative concentration causing a 20% fall in FEV(1): comparison of lowest vs highest post-challenge FEV(1).
Considerable, unexamined controversy exists surrounding the use of the highest vs the lowest FEV(1) for calculating the provocative concentration causing a 20% fall in FEV(1) (PC(20)) during direct bronchoprovocation challenges. To compare the PC(20) calculated using the lowest FEV(1) post-diluent and post-histamine/methacholine vs the PC(20) calculated using the highest FEV(1) post-diluent and post-histamine/methacholine. Retrospective analysis of 225 challenges: 75 research methacholine challenges, 75 research histamine challenges, and 75 clinical methacholine challenges. For each test, the PC(20) was calculated twice, first using the lowest post-diluent FEV(1) to the lowest post-histamine/methacholine FEV(1), and then using the highest to the highest. The intraclass correlation coefficients for methacholine research, histamine research, and methacholine clinic challenges were 0.99, 0.98, and 0.95, respectively. The PC(20) calculated using the lowest to lowest FEV(1) was slightly and significantly lower in all three groups (paired t test p < 0.0001). The PC(20) values calculated using the highest FEV(1) are almost identical to the PC(20) values calculated using the lowest FEV(1). The difference, although clinically irrelevant, holds statistical significance.


Interleukin-4 promotes the expansion of skin-infiltrating lymphocytes from atopic dermatitis in vitro.
Functional studies of lymphocytes in atopic dermatitis (AD) have so far focused on peripheral blood mononuclear cells (PBMC), whereas cells at the involved site, the skin, have not been examined. Accordingly, we have developed methods to generate lymphocyte cultures from biopsies of inflammatory skin areas. Skin-infiltrating lymphocytes (SIL) were isolated from skin biopsies of 6 patients with severe AD and expanded in vitro in the presence of interleukin-2 (IL-2) without additional antigens. After 6-10 d in culture, outgrowth of mononuclear cells from biopsy tissue was observed in all cases. Phenotypic analysis of skin-derived cells revealed the predominance of CD4+ T-helper/inducer phenotype in SIL populations. Parallel cultures of SIL and PBMC showed an increase and expansion of CD8+ T cells in cultured PBMC, whereas the CD4+ phenotype was predominant in SIL cultures. As indicated by their expression of HLA-DR and CD25 antigens, most of the SIL were activated and the cells mainly expressed T-cell receptors (TCR) composed of alpha and beta chains. Different strategies for expansion of SIL in vitro were examined. High levels of IL-4 (1,000 U/ml) in combination with IL-2 (50 U/ml or 1,000 U/ml) preferentially promoted growth of SIL derived from AD and were much more effective than IL-2 alone. No cells expanded in cultures with IL-4 alone. SIL grown with high concentrations of IL-4 contained a significant proportion of double-positive CD4+8+ cells. No other marked differences were observed in the distribution of T cell subsets in cultures propagated under different conditions for 21 d. Our results demonstrate the feasibility of growing infiltrating T lymphocytes from inflammatory skin of AD patients. The use of high concentrations of IL-2 in combination with high levels of IL-4 allows a large expansion of these cells and thus represents a useful strategy to expand cells for further functional and molecular biologic studies.


Application of multiple testing procedures for identifying relevant comorbidities, from a large set, in traumatic brain injury for research applications utilizing big health-administrative data.
Multiple testing procedures (MTP) are gaining increasing popularity in various fields of biostatistics, especially in statistical genetics. However, in injury surveillance research utilizing the growing amount and complexity of health-administrative data encoded in the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10), few studies involve MTP and discuss their applications and challenges. We aimed to apply MTP in the population-wide context of comorbidity preceding traumatic brain injury (TBI), one of the most disabling injuries, to find a subset of comorbidity that can be targeted in primary injury prevention. In total, 2,600 ICD-10 codes were used to assess the associations between TBI and comorbidity, with 235,003 TBI patients, on a matched data set of patients without TBI. McNemar tests were conducted on each 2,600 ICD-10 code, and appropriate multiple testing adjustments were applied using the Benjamini-Yekutieli procedure. To study the magnitude and direction of associations, odds ratios with 95% confidence intervals were constructed. Benjamini-Yekutieli procedure captured 684 ICD-10 codes, out of 2,600, as codes positively associated with a TBI event, reducing the effective number of codes for subsequent analysis and comprehension. Our results illustrate the utility of MTP for data mining and dimension reduction in TBI research utilizing big health-administrative data to support injury surveillance research and generate ideas for injury prevention.


Sexually Transmitted Infections: Compelling Case for an Improved Screening Strategy.
Sexually Transmitted Infections: Compelling Case for an Improved Screening Strategy Stephen Hull, MHS, Seán Kelley, MD, MSc, and Janice L. Clarke, RN, BBA Editorial: Sexually Transmitted Infections-A Fixable Problem: David B. Nash, MD, MBA S-3 Introduction S-3 Rising Prevalence of Sexually Transmitted Diseases (STIs) S-4 Current Screening Rates for Chlamydia and Gonorrhea S-4 The Human Toll and Economic Burden of STI-Related Illness S-5 Current Screening Guidelines for Chlamydia and Gonorrhea S-5 Factors Contributing to Inadequate Screening, Diagnosis, and Treatment for STIs S-6 Methods Used to Improve Screening Rates S-7 Benefits of Opt-Out Screening Strategies for STIs S-8 Cost-Effectiveness of Screening for STIs S-8 Discussion S-9 Conclusion S-10.


Total synthesis of aspercyclide C.
The first total synthesis of (+)-aspercyclide C (1) is reported using a kinetically controlled RCM reaction to form the 11-membered, unsaturated lactone ring of this bioactive diaryl ether macrolide.


[Sonographic diagnosis of hilar cholangiocarcinomas by the use of contrast agents].
Imaging of hilar cholangiocarcinomas (Klatskin tumour) is very difficult as these tumours spread along the bile ducts and are hardly distinguishable from the surrounding liver parenchyma. Improved imaging techniques are useful for diagnosis and monitoring of new treatment strategies like photodynamic therapy. In a prospective study, we investigated whether contrast-enhanced sonography is useful in the imaging of Klatskin tumours. Between 1997 and 2004, 72 patients with suspected Klatskin tumour were admitted to our clinic. 47 patients with histologically confirmed hilar cholangiocarcinomas (Bismuth III/IV) were included in the study and investigated by standard B-mode sonography. Consecutively, patients were investigated by the use of an echo enhancer. 27 patients were investigated by Levovist (power-Doppler sonography, 2nd harmonic imaging, high MI), 20 patients were investigated by Sonovue (CPS, low MI). By use of baseline sonography, visualisation of a tumour and differentiation from normal liver parenchyma was possible in 17 of 47 (36%) patients. After application of contrast agents, tumours showed defects in comparison to the intense flow signal of the surrounding liver tissue during the portalvenous phase and could be discriminated from normal liver tissue allowing determination of tumour size and infiltration of liver parenchyma in all patients (100%). During the arterial phase, 42/47 (89%) of neoplasms showed hypovascularisation compared to surrounding liver tissue, 5/47 (11%) tumours were hypervascularised. During follow-up, metastatic tumour spread was observed in (20/47) 43% of patients, 25/47 (53%) patients developed ascites. Contrast agents allow improved imaging of hilar cholangiocarcinomas. The majority of hilar cholangiocarcinomas are hypovascularised.


Why healthcare reform may unleash a litigation explosion.
One aspect of healthcare reform that has been largely overlooked is the expansion of antidiscrimination laws far beyond the traditional grounds of race, sex, age, and religion. Added to this is a provision giving individuals the broad right to sue over "government-guaranteed" medical treatment. What are the implications of such sweeping reforms? According to law professor Bradley A. Smith, a new wave of litigation is a real possibility.


Water pollution and diseases in fish (an epizootiologic survey).
Three watersheds, varying from highly polluted or moderately polluted to essentially pollution-free, were surveyed to determine the frequency of fish disease. Over a five year period, it was found that a relationship existed between the level of pollution and frequency of disease. The occurrence rates of microbial and oncogenic diseases increased similarly in relation to increases in pollution in the waters. Since the water systems studied provide recreational opportunities for man, it is suggested that catching and subsequent ingesting of diseased fish from these waters present a health hazard.


Drought Resistance by Engineering Plant Tissue-Specific Responses.
Drought is the primary cause of agricultural loss globally, and represents a major threat to food security. Currently, plant biotechnology stands as one of the most promising fields when it comes to developing crops that are able to produce high yields in water-limited conditions. From studies of Arabidopsis thaliana whole plants, the main response mechanisms to drought stress have been uncovered, and multiple drought resistance genes have already been engineered into crops. So far, most plants with enhanced drought resistance have displayed reduced crop yield, meaning that there is still a need to search for novel approaches that can uncouple drought resistance from plant growth. Our laboratory has recently shown that the receptors of brassinosteroid (BR) hormones use tissue-specific pathways to mediate different developmental responses during root growth. In Arabidopsis, we found that increasing BR receptors in the vascular plant tissues confers resistance to drought without penalizing growth, opening up an exceptional opportunity to investigate the mechanisms that confer drought resistance with cellular specificity in plants. In this review, we provide an overview of the most promising phenotypical drought traits that could be improved biotechnologically to obtain drought-tolerant cereals. In addition, we discuss how current genome editing technologies could help to identify and manipulate novel genes that might grant resistance to drought stress. In the upcoming years, we expect that sustainable solutions for enhancing crop production in water-limited environments will be identified through joint efforts.


Island formation of Er(trensal) single-ion magnets on graphene observed on the micrometer scale.
We have studied the morphology of Er(trensal) single-ion molecular magnets adsorbed on graphene/Ru(0001) using X-ray photoemission electron microscopy (X-PEEM). By exploiting the elemental contrast at the erbium M5 edge we observe the formation of molecular islands of homogeneous height with a lateral size of several micrometers. The graphene/Ru(0001) substrate exhibits two different signal levels in bright-field low-energy electron microscopy (LEEM) and in X-PEEM, which are ascribed to the presence of small-angle rotational domains of the graphene lattice. We find that the Er(trensal) molecules form islands solely on the bright areas, while the remaining dark areas are empty. Our results are important for the growth and study of the molecule-inorganic hybrid approach in spintronics schemes.


Effect of Lanthanum Carbonate on All-Cause Mortality in Patients Receiving Maintenance Hemodialysis: a Meta-Analysis of Randomized Controlled Trials.
Hyperphosphatemia is common in patients on hemodialysis. The efficacy of lanthanum carbonate (LC) in the treatment of hyperphosphatemia in these patients remains controversial. The objective of this meta-analysis was to evaluate the effect of LC on all-cause mortality in patients on maintenance hemodialysis. We electronically searched the PubMed, EMBASE, and Cochrane Library databases for all randomized controlled trials (RCTs) comparing LC with other phosphate binders used in adult hemodialysis patients, including calcium carbonate, calcium acetate, and sevelamer. Nine RCTs involving 2813 patients were suitable for inclusion. Our results showed that all-cause mortality was significantly lower in patients who received LC than in those who received standard therapy (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.32-0.63, P<0.00001). Compared with the controls, patients who received LC had significantly lower serum calcium and higher serum intact parathyroid hormone levels. However, there was no significant difference between the groups in the cardiovascular event rate (OR: 0.58, 95% CI: 0.31-1.06, P=0.07) or in serum phosphorus levels. Compared with standard therapy, LC reduced all-cause mortality in patients on hemodialysis but did not decrease the risk of cardiovascular events. The decrease in serum phosphorus level was similar between LC and the other phosphate binders, but the risk of hypercalcemia was lower in patients who received LC.


Autopsy diagnosis of leptomeningeal carcinomatosis, the first manifestation of gastric adenocarcinoma: a rare case report and review of the literature.
This study aimed to report an unusual presentation of an advanced gastric adenocarcinoma. Leptomeningeal carcinomatosis is a rare event in gastric adenocarcinoma. It is much more uncommon as the primary manifestation in post-mortem evaluation of the cause of death in a patient presenting with headache and neurological signs and symptoms. Herein, we discuss our experience with a case of gastric adenocarcinoma, who was diagnosed after death, presenting with neurological signs and symptoms of leptomeningeal carcinomatosis. A 52-year-old gentleman presented with intractable headache and neck pain as well as vertigo. His physical examination showed only decreased deep tendon reflexes. He died after a short period of coma. Post-mortem evaluation showed numerous signet ring cells in the subarachnoid space as well as gastric malignant ulcer. In patients with intractable headache with no identifiable cause, meningeal involvement and infiltration should be considered as the probable underlying cause. Radiologic findings are not significant; however, lumbar puncture can be diagnostic.


pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1.
The human organic anion transporting polypeptide 2B1 (OATP2B1, SLCO2B1) is ubiquitously expressed and may play an important role in the disposition of xenobiotics. The present study aimed to examine the role of OATP2B1 in the intestinal absorption and tissue uptake of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitors (statins). We first investigated the functional affinity of statins to the transporter as a function of extracellular pH, using OATP2B1-transfeced HEK293 cells. The results indicate that OATP2B1-mediated transport is significant for rosuvastatin, fluvastatin and atorvastatin, at neutral pH. However, OATP2B1 showed broader substrate specificity as well as enhanced transporter activity at acidic pH. Furthermore, uptake at acidic pH was diminished in the presence of proton ionophore, suggesting proton gradient as the driving force for OATP2B1 activity. Notably, passive transport rates are predominant or comparable to active transport rates for statins, except for rosuvastatin and fluvastatin. Second, we studied the effect of OATP modulators on statin uptake. At pH 6.0, OATP2B1-mediated transport of atorvastatin and cerivastatin was not inhibitable, while rosuvastatin transport was inhibited by E-3-S, rifamycin SV and cyclosporine with IC(50) values of 19.7 ± 3.3 μM, 0.53 ± 0.2 μM and 2.2 ± 0.4 μM, respectively. Rifamycin SV inhibited OATP2B1-mediated transport of E-3-S and rosuvastatin with similar IC(50) values at pH 6.0 and 7.4, suggesting that the inhibitor affinity is not pH-dependent. Finally, we noted that OATP2B1-mediated transport of E-3-S, but not rosuvastatin, is pH sensitive in intestinal epithelial (Caco-2) cells. However, uptake of E-3-S and rosuvastatin by Caco-2 cells was diminished in the presence of proton ionophore. The present results indicate that OATP2B1 may be involved in the tissue uptake of rosuvastatin and fluvastatin, while OATP2B1 may play a significant role in the intestinal absorption of several statins due to their transporter affinity at acidic pH.


Preparation of Quantum Dots Hydrogel Nanocomposites with Improved Cytotoxicity.
Nanocomposites are materials with unique properties and a wide range of applications. The combination of different nanostructures with traditional materials gives a variety of possibilities that should be analyzed. Especially, functional fluorescent semiconductor quantum dots (QDs) embedded in polymeric matrices have shown promising fluorescence and biocompatibility properties. These hybrid materials can be used in medical applications such as biodiagnostic and bioimaging. In this study, two hydrogels, one of polyethylene glycol diacrylate (PEGDA) and other of polyacrylamide (PAAm), were prepared with quantum dots of CdTe (4 nm of diameter) and characterized. The aim of this research was to analyze the optical properties of the nanocomposites and their cell viability. QDs nanocomposites were fabricated by a free radical polymerization process. The optical studies showed that the nanocomposites have well defined properties of fluorescence. To study the biocompatibility of the nanocomposites, metastatic B16f10 cell line were used and MTT assay was performed. The nanocomposites had a significant improved cell viability compared with QDs solutions.


A case of sparganosis mimicking a varicose vein.
Recent advances in radiological and serological techniques have enabled easier preoperative diagnosis of sparganosis. However, due to scarcity of cases, sparganosis has been often regarded as a disease of other etiologic origin unless the parasite is confirmed in the lesion. We experienced a case of sparganosis mimicking a varicose vein in terms of clinical manifestations and radiological findings. Sparganosis should be included among the list of differential diagnosis with the varicose vein.


Leukemia in the eastern region of Saudi Arabia: A population-based study (1987-1988).
This is the first population-based data in Saudi Arabia on the incidence of leukemias in the Eastern Region, as conducted by its regional tumor registry. Data on cancer were captured from all health facilities in the region in 1987-1988. Population census was derived from a survey. Data on cancer deaths were obtained from all death registries. Crude, age-specific, age-standardized, and relative age-standardized incidence rates were used as indicators for the incidence of leukemia. There were 124 cases of leukemias registered. The yearly average crude incidence rate was 5.2 and 3.6 per 100,000 for Saudi males and females, respectively. The age-standardized incidence rate was 7.3 and 6.1 per 100,000 per year in Saudi males and females respectively. The relative age-standardized incidence of leukemias in Saudi males and females ranked, respectively, third and second highest on the international scale. Death from leukemia among Saudis was responsible for 8.9% of the total deaths from cancer. Statistical indicators point to a high incidence rate of leukemias in the Eastern Region of Saudi Arabia among Saudis. Leukemia was the third leading cause of death from cancer. The relative age-standardized rate of leukemias among Saudis of either gender rank very high on the international scale.


Single-step synthesis of pyrimidine derivatives.
We describe a single-step conversion of various N-vinyl and N-aryl amides to the corresponding pyrimidine and quinazoline derivatives, respectively. The process involves amide activation with 2-chloropyridine and trifluoromethanesulfonic anhydride followed by nitrile addition into the reactive intermediate and cycloisomerization. In situ nitrile generation from primary amides allows for their use as nitrile surrogates. The use of this chemistry with sensitive N-vinyl amides and epimerizable substrates in addition to a wide range of functional groups is noteworthy.


Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor.
Three forms of basic fibroblast growth factor (bFGF), initiated at an AUG (18 kDa) and two CUG (21 and 22.5 kDa) start codons, were produced following transfection of COS cells with human hepatoma bFGF cDNA. The subcellular localization of the different forms was investigated directly or by using chimeric genes constructed by fusion of the bFGF and chloramphenicol acetyltransferase open reading frames. The AUG-initiated proteins were cytoplasmic, while the CUG-initiated forms were nuclear. The signal sequence responsible for the nuclear localization of bFGF is contained within 37 amino acid residues between the second CUG and the AUG start codons. Alternative initiation of translation regulates the subcellular localization of bFGF and thus could modulate its role in cell growth and differentiation control.


Metacercariae of Strigeidae Parasitizing Amphibians of the Chaco Region in Argentina.
The goal of the present study was to analyze the metacercariae found in adult amphibians collected in the Argentinean Chaco region. A total of 194 frogs, Leptodactylus chaquensis, Leptodactylus latinasus, and Lepidobatrachus laevis was examined for digeneans. Three different larval trematodes of the genus Strigea (Digenea, Strigeidae) were found infecting the liver, mesentery, body cavity, and muscle of frogs. These metacercariae are described and illustrated for the first time and provide new information on the composition of metacercariae in amphibians, thus contributing to the knowledge of larval trematodes biodiversity in the Neotropical region. We also present new information on the morphology and morphometry of strigeid metacercariae.


[Pathophysiology of neuromuscular impairments in the critically ill patient].
to analyze the causes and manifestations of muscle weakness that critically ill patients develop during their staying at the ICU, and literature review. in the early 1980s, a mixed axonal polyneuropathy was described in septic critically ill patients, which clinically manifested by muscle weakness of variable severity, leading to quadriplegia and/or ventilator dependency in its most severe presentation. Almost at the same time, an acute intensive care myopathy was described in asthmatic patients admitted to the ICU for asthma exacerbation. Later on, this myopathy was also observed in transplanted, septic, or burnt patients. Several authors consider acute intensive care myopathy as the main cause of muscle weakness in the ICU. in this article, we describe the clinical presentation, etiopathogenesis, diagnosis, and treatment of polyneuropathy of the critically ill patient and of acute intensive care myopathy. Both clinical pictures may be differentiated, with neurophysiological studies and eventually muscle biopsy being of great help. Although some authors rather include these conditions under the name of polyneuromyopathy, we propose the general denomination of Acute Neuromuscular Syndrome of the Critically Ill Patient, a more descriptive term no presupposing a single mechanism or etiology.


Chemotactic Ligands that Activate G-Protein-Coupled Formylpeptide Receptors.
Leukocyte infiltration is a hallmark of inflammatory responses. This process depends on the bacterial and host tissue-derived chemotactic factors interacting with G-protein-coupled seven-transmembrane receptors (GPCRs) expressed on the cell surface. Formylpeptide receptors (FPRs in human and Fprs in mice) belong to the family of chemoattractant GPCRs that are critical mediators of myeloid cell trafficking in microbial infection, inflammation, immune responses and cancer progression. Both murine Fprs and human FPRs participate in many patho-physiological processes due to their expression on a variety of cell types in addition to myeloid cells. FPR contribution to numerous pathologies is in part due to its capacity to interact with a plethora of structurally diverse chemotactic ligands. One of the murine Fpr members, Fpr2, and its endogenous agonist peptide, Cathelicidin-related antimicrobial peptide (CRAMP), control normal mouse colon epithelial growth, repair and protection against inflammation-associated tumorigenesis. Recent developments in FPR (Fpr) and ligand studies have greatly expanded the scope of these receptors and ligands in host homeostasis and disease conditions, therefore helping to establish these molecules as potential targets for therapeutic intervention.


KRAS mutant allele-specific imbalance in lung adenocarcinoma.
The significance of KRAS mutant allele-specific imbalance (MASI) in lung adenocarcinomas is unknown. KRAS MASI was defined as predominance of the mutant allele over the wild-type allele. We assessed the frequency of KRAS MASI by comparing peak heights of mutant and wild-type alleles on sequencing electropherograms and by KRAS fluorescence in situ hybridization (FISH). A review of sequencing electropherograms of 207 KRAS-mutated lung adenocarcinomas demonstrated 23 (11%) cases with the mutant allele peak higher than the wild-type allele peak and 15 (7%) cases with the mutant allele peak equal to the wild-type allele peak. Of 17 cases with the mutant allele peak higher or equal to the wild-type allele peak, 8 (47%) showed KRAS amplification by FISH. KRAS FISH analysis of 36 KRAS-mutated lung adenocarcinomas with the mutant allele peak lower than the wild-type allele peak, 21 KRAS and EGFR wild-type and 16 EGFR-mutated adenocarcinomas showed no KRAS amplification. KRAS MASI was associated with selective amplification of the KRAS mutant allele (P<0.001). Patients with KRAS MASI showed worse overall survival. The cumulative proportion surviving at 17 months for KRAS MASI group was 35% compared with 84.1% for patients with KRAS mutant allele peak lower than wild-type allele peak (P=0.012). The adverse prognostic significance of KRAS MASI was independent of clinical stage and was maintained among stage I patients. The detection of KRAS MASI in lung adenocarcinomas by sequencing electropherograms may identify patients with more aggressive disease.


Post-hoc analysis on the CD14 C(-260)T promoter polymorphism and coronary heart disease.
Functional C(-260)--> T polymorphism in the promoter of the CD14 gene has been reported to be associated with coronary heart disease (CHD). The functional role of the polymorphism, however, is still a matter of debate, since several studies have not proved its effect on clinical outcomes associated with atherosclerosis. Cardiovascular-related morbidity and mortality was assessed in a post-hoc approach four years after baseline characterization of patients (male/female n = 36/32) with angiographically proven coronary heart disease. CD14 C(-260)--> T promoter genotype was determined at baseline. Seventeen out of 20 CHD patients with non-lethal cardiovascular events carried at least one T-allele. CD14 T-260 allele carriers have a 3.59-fold (95 % confidence interval: 1.11-6.75) increased risk for non-lethal cardiovascular events (Kaplan-Meier plot: log rank test p = 0.029). All patients with lethal outcomes (n = 6) were also T-allele carriers. Multivariate logistic regression analysis among CHD patients including age, established risk factors and the C(-260)--> T polymorphism as covariates and non-lethal events as a dependent variable confirmed the independent prospective effect of the T-allele on cardiovascular outcomes in this subset. Further evidence is provided for the role of CD14 C(-260)--> T promoter polymorphism as a genetic susceptibility marker of atherosclerosis in patients with an advanced clinical course of the disease. Due to the small sample size and post-hoc character of the study large-scale prospective studies that monitor patients with proven CHD are needed to confirm these findings.


New antioxidant lauryl-free herbal shampoo formulation with a Brazilian plant extract.
Sodium lauryl sulfate is the main cleaning ingredient in shampoos, even though it may be potentially damaging to hair. The demand for antioxidant-rich cosmetics, on the other hand, has encouraged green cosmetics research. Brazil has vast biodiversity that can be exploited for the production of these cosmetics. This work aimed to develop a minimalist antioxidant lauryl-free shampoo formulation with leaf extracts from the Brazilian plant Hancornia speciosa Gomes. Two hydroethanolic extracts were prepared using different extraction methods, Soxhlet, and ultrasound. The extracts were characterized by the presence of saponins, polyphenol quantification, and HLPC chemical identification of the compounds. Antioxidant activity was determined using the DPPH method. The antioxidant lauryl-free shampoo was developed using hydroxyethyl cellulose with two concentrations of leaf extract obtained by Soxhlet, 0.125 mg/g (XP1) and 0.250 mg/g (XP2). Along with the antioxidant activity, the physical and chemical properties, cleaning potential, and foam quality were evaluated. The Soxhlet leaf extract revealed a more favorable chemical profile, including a positive result for saponins, as well as a larger quantity of polyphenols and increased antioxidant activity. The XP2 formulation showed better foam height, dirt dispersion, and antioxidant activity. Thus, the use of mangabeira leaf extract appears to be promising for the development of shampoos with antioxidant activity.


Screened butanol-tolerant Enterococcus faecium capable of butanol production.
Due to the complex mechanisms involved in butanol-induced stress response, butanol tolerance phenotype is difficult to engineer even in microorganisms with well-defined genetic backgrounds. We therefore aimed to isolate butanol-tolerant microorganisms from environmental samples as potential alternative hosts for butanol production. Soil samples collected were subjected to butanol stress. A microbial strain capable of 2.5-3 % (w/v) butanol tolerance was isolated and identified as Enterococcus faecium by 16S rDNA analysis. The isolate grew readily under both aerobic and anaerobic conditions and was capable of producing butanol anaerobically. In comparison with the obligate anaerobe Clostridium acetobutylicum, the growth under both aerobic and anaerobic conditions of the isolated strain, together with no detection of butyrate and lack of two-phase fermentation suggests different metabolic networks from the obligate anaerobe C. acetobutylicum. Under anaerobic condition, butanol reached up to 0.4 gl(-1) in a batch culture without heterologous introduction of butanol biosynthetic pathway. Besides butanol tolerance, the isolated E. faecium IB1 showed high tolerance to 10 % (w/v) ethanol and 3 % (w/v) isobutanol. With distinct features including high butanol tolerance and natural butanol production, the isolated E. faecium IB1 with minimum metabolic engineering can be explored as a potential host for butanol production.


Common genetic variants of the BMP4, BMPR1A, BMPR1B, and ACVR1 genes, left ventricular mass, and other parameters of the heart in newborns.
The members of the family of bone morphogenetic proteins (BMPs) are important regulators in cardiac development. The present study was designed to evaluate the effect of common genetic variants of BMP-4 and its receptors BMPR1A, BMPR1B, and ACVR1 on left ventricular mass (LVM) and other parameters of the heart and blood pressure in newborns. The study included 210 healthy newborns. Two-dimensional M-mode echocardiography was used to assess LVM between days 3 and 4 after birth. Polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism technique. We found lack of associations between LVM, values of blood pressure, and the BMP4, BMPR1A, BMPR1B, and ACVR1 genotypes. A significant association was observed between the 455C allele of BMP4 and increased left ventricular internal diameter systolic (p=0.004) and between 1650T allele of BMPR1B and lower left atrium diameter (p=0.038). Presence of the 455C allele of BMP4 and the 8474T allele of ACVR1 gene was significantly associated with decreased left ventricular ejection fraction (LVEF) (p=0.0004 and p=0.046, respectively). The 455C allele of BMP4 and the 8474T allele of ACVR1 may play a role as significant predictors for decreased LVEF in newborns.


[Multiplex ligation-dependent probe amplification analysis of subtelomeric chromosome rearrangements in children with idiopathic mental retardation].
To study the rate of subtelomeric rearrangements in patients with idiopathic mental retardation (MR) and to search the cause of MR. DNA was extracted and purified from peripheral blood leukocytes of 180 patients with idiopathic MR. DNA was tested using specific subtelomeric multiplex ligation-dependent probe amplification (MLPA) kits P036B/C and P070 according to manufacturer's instructions. The amplification products were separated by capillary electrophoresis using an ABI 3100 automated sequencer and size standard. MLPA data were extracted by GeneScan Analysis software. Data normalization and analysis were performed with the built-in MLPA application in GeneMarker. Among 180 patients with idiopathic MR, 12 had pathological subtelomeric deletions including 3 cases with a 4p deletion, 2 cases with a deletion at 9q and 22q respectively, 1 case with a deletion at 1p, 7p, 8p, 9q and 12q respectively. Subtelomeric rearrangements were responsible for 7% cases of idiopathic mental retardation. Subtelomeric rearrangement is a common cause of idiopathic mental retardation.


[Behavior modification therapy: application in renal nursing].
Kidney patients often suffer numerous comorbidities (e.g., hyperphosphatemia, renal osteodystrophy, and bodyweight gain induced by fluid overload or hypertension), which often impart discomfort and a significantly reduced quality of life. The literatures points to the efficacy of behavior modification therapy in changing inappropriate self-health care behavior in order to improve comorbidity symptoms. This article introduces behavior modification theory and its application as well as clinical strategies related to kidney patient care. The authors hope this article will promote knowledge of behavior modification theory among healthcare professionals and facilitate to the application of this theory in clinical practice to improve nursing care.


Two New Species of Backusella (Mucorales, Mucoromycota) from Soil in an Upland Forest in Northeastern Brazil with an Identification Key of Backusella from the Americas.
During a survey of Mucorales from a forest located in Pernambuco state, Brazil, two new Backusella species were discovered and described based on morphological and molecular data (internal transcribed spacer and large subunit ribosomal DNA sequences). Both species were characterized as unbranched sporangiophores and sporangia with columellae of varied shapes forming. Multispored sporangiola were frequent, whereas unispored sporangiola were rare. URM 8395 forms sporangiophores that may support hyaline, slightly curved or circinate pedicels with multispored sporangiola at their apical portion, and abundant giant cells and chlamydospores. Columellae of sporangia are hyaline, conical (majority), or ellipsoidal with a truncate base, globose to subglobose or subglobose to conical, and, rarely, with slight medial constriction. URM 8427 does not form sporangiola from pedicels, giant cells are not observed, and columellae of sporangia are globose to subglobose, cylindrical with a truncate base, some with a slight constriction, applanate, obovoid, ellipsoidal, or, rarely, conical. Some columellae may have one side more swollen than the other and some are arranged obliquely on the sporangiophores. Sterile sporangia may or may not be formed on short sporophores. The detailed description and illustration of both novel species as well as an identification key for Backusella from the Americas are provided.


[The usefulness of severity scoring systems in elderly intensive care unit (ICU) patients with non-traumatic haemorrhagic shock].
Digestive tract acute haemorrhage has been recognized as one of the major risk factors in mortality of surgical patients. A group of 68 elderly ICU patients with non-traumatic haemorrhagic shock (aged 65-95 yrs) was observed. The patients were evaluated according to commonly used severity-of-illness scoring systems: SAPS2, LODS and POSSUM. A retrospective analysis was based on two groups: a) survivors, and b) nonsurvivors. In both groups there was calculated predicted death rate (PDR): on hospital admittance (in SAPS 2 22.3 in survivors vs 34.8 in non-survivors, in LODS 17.4 vs 30.6, respectively), 2 hrs after surgery (in SAPS 2 25.1 in survivors vs 62.3 in non-survivors, in LODS 21.4 vs 57.2, and in POSSUM 61,6 vs 85.4, respectively), and after the first day of ICU treatment (in SAPS 2 35.0 in survivors vs 70.2 in non-survivors, in LODS 32.5 vs 58.2 respectively); p<001. Similarly, numbers of collected points in Therapeutic Intervention Scoring system (TISS-28) were statistically significant between the groups: 36.1 in survivors vs 47.1 in non-survivors, and in TISS-76: 34.0 vs 45.1, respectively p<0.001. The difference was also noticed during collecting points in severity scoring systems: MODS and SOFA; a number of collected points was twice higher when measured after the surgery, than when comparing the MODS and SOFA values, calculated on hospital admittance in non-survivor group.


Salicylic Acid Enhances Adventitious Root and Aerenchyma Formation in Wheat under Waterlogged Conditions.
The present study investigated the role of salicylic acid (SA) in regulating morpho-anatomical adaptive responses of a wheat plant to waterlogging. Our pharmacological study showed that treatment of waterlogged wheat plants with exogenous SA promotes the formation axile roots and surface adventitious roots that originate from basal stem nodes, but inhibits their elongation, leading to the formation of a shallow root system. The treatment also enhanced axile root formation in non-waterlogged plants but with only slight reductions in their length and branch root formation. Exogenous SA enhanced the formation of root aerenchyma, a key anatomical adaptive response of plants to waterlogging. Consistent with these results, waterlogging enhanced SA content in the root via expression of specific isochorismate synthase (ICS; ICS1 and ICS2) and phenylalanine ammonia lyase (PAL; PAL4, PAL5 and PAL6) genes and in the stem nodes via expression of specific PAL (PAL5 and PAL6) genes. Although not to the same level observed in waterlogged plants, exogenous SA also induced aerenchyma formation in non-waterlogged plants. The findings of this study furthermore indicated that inhibition of ethylene synthesis in SA treated non-waterlogged and waterlogged plants does not have any effect on SA-induced emergence of axile and/or surface adventitious roots but represses SA-mediated induction of aerenchyma formation. These results highlight that the role of SA in promoting the development of axile and surface adventitious roots in waterlogged wheat plants is ethylene independent while the induction of aerenchyma formation by SA requires the presence of ethylene.


Occupational exposure to chlorophenates: toxicology and respiratory effects.
We have identified 71 chlorophenate-exposed sawmill workers as part of a group undergoing an extensive health and environmental evaluation in a pulp mill. We have compared this group with a group (351) with no physical proximity to the area in which chlorophenates were used. We demonstrated a gradient of exposure from 230 ppb in urine and 919 ppb in serum for those directly handling the contaminated wood, to 139 ppb in urine and 354 ppb in serum for those working in the area but not in manual contact as compared with serum levels of 84 ppb in the unexposed group. We noted that the bulk chemical was primarily in the tetrachloro-form but the serum levels contained more pentachlorophenate. The urine proportions were intermediate, approximating the bulk chemical proportions at the lower levels of exposure. We did not find an excess prevalence of respiratory symptoms or spirometric abnormalities which could be explained by the chlorophenate exposure.


[The relationship between German university hospitals and medical schools. Cooperation model versus integration model].
The relationship between German university hospitals and medical schools is mainly based on the cooperation model; in a few cases the integration model is applied. Both models bear characteristic advantages and disadvantages; in the cooperation model, e.g., processes might be slowed down by a multitude of regulatory mechanisms. The integration model supports a close connection of the medical school and university hospital. Currently, legislation concerning university medicine in Germany shows a trend to increase the influence of the government and the university president within the balance of power. Therefore, the cooperation model is still favored. In order that university hospitals remain sustainable for the future, especially in terms of research, site-specific solutions have to be developed and legitimated.


Can nasal continuous positive airway pressure decrease clinic blood pressure in patients with obstructive sleep apnea?
Obstructive sleep apnea (OSA) is commonly associated with systemic hypertension and now recognized as an independent risk factor for daytime hypertension. We aimed to study the short- and long-term effect of nasal continuous positive airway pressure (CPAP) in hypertensive and normotensive patients with OSA. Forty-six patients with moderated to severe OSA were treated with nasal CPAP and followed after one year of treatment. Clinic blood pressure, heart rate, and body weight were taken before and followed up for one year after beginning nasal CPAP. In this study 25 patients with OSA were found to have hypertension (54.3%). The hypertensive group showed a significant reduction in clinic blood pressure after nasal CPAP, whereas the normotensive group showed no changes. The subgroup of hypertensive patients with OSA who had no anti-hypertensive medication revealed a decrease in clinic blood pressure comparable to those with anti-hypertensive drugs. The heart rate was not significantly changed in any patients. There was no significant correlation between the decrease in body weight and the reduction in blood pressure. These results suggest that nasal CPAP alone might have a substantial blood pressure lowering effect in hypertensive patients with OSA. This effect could decrease the morbidity and mortality related to cardiovascular complications in patients with OSA.


A study of the clinical characteristics of benign trigeminal sensory neuropathy.
The purpose of this study was to describe the clinical characteristics of a series of patients presenting with benign trigeminal sensory neuropathy. We conducted a retrospective analysis of the clinical and pathologic characteristics of 23 patients presenting with facial numbness of unknown etiology. Patients presented with diverse medical histories but could be grouped into those with a connective tissue disorder, neurologic disease, psychologic problems, or a medical history of unknown significance. The age of the patient, the severity and distribution of the trigeminal neuropathy, and symptoms other than neuropathy closely reflected the patient's medical history. The majority of patients underwent magnetic resonance imaging, but the results did not facilitate the diagnosis of the condition or reflect the extent and severity of the symptoms. In 60% of patients, the symptoms remained unchanged during the course of the study and outcome was not influenced by medical treatment. The diagnosis and management of benign trigeminal sensory neuropathy remain a significant clinical challenge.


Sustained growth hormone (GH) and insulin-like growth factor I responses to prolonged high-dose twice-daily GH-releasing hormone stimulation in middle-aged and older men.
Postulated mechanisms underlying the relative hyposomato-tropism of aging include reduced hypothalamic drive by GHRH. To test this notion, we administered 1 mg (n = 11) vs. 4 mg (n = 11) recombinant human GHRH-1,44-amide s.c. twice daily for 3 months in a double-blind, parallel-cohort design to 22 healthy men (ages, 53-68 yr). After 3 months, GHRH elevated: overnight GH concentrations from 0.71 +/- 0.19 to 1.74 +/- 0.39 microg/liter (P < 0.001; 1 mg) and from 0.80 +/- 0.15 to 5.12 +/- 0.40 microg/liter (P < 0.001; 4 mg) and IGF-I concentrations from 117 +/- 14 to 234 +/- 20 microg/liter (P = 0.007; 1 mg) and from 147 +/- 13 to 286 +/- 22 microg/liter (P < 0.001; 4 mg). Only the higher GHRH dose also increased total body water (tritium space; P = 0.024) and fat-free mass (dual-energy x-ray absorptiometry; P = 0.021), and reduced total abdominal adiposity (computed axial tomography scan; P = 0.042). Both supplementation schedules shortened the time required to walk 30 m and ascend four flights of stairs (P < 0.025 each). Lower extremity strength, aerobic capacity, and bone mineral density did not change. Local injection site reactions were common. We conclude that sc administration of a large dose of GHRH (4 mg) twice daily for 3 months elevates GH and IGF-I concentrations, increases total body water and fat-free mass, reduces total abdominal adiposity, and enhances certain performance measures in healthy aging men but causes local skin reactions.


Isotope partitioning between cow milk and farm water: A tool for verification of milk provenance.
The oxygen and hydrogen isotope compositions of the water component of the milk from nine Italian dairy farms were studied together with the farm water for one year. The aim was to verify the importance of farm water and seasonal temperature variation on milk isotope values and propose mathematical relations as new tools to identify the milk origin. Milk was centrifuged to separate the solids and then distilled under vacuum to separate water. δ(18 O/16 O) and δ(2 H/1 H) analyses of the water molecules were carried out using a water equilibrator online with a mass spectrometer. For oxygen and hydrogen isotope determination, water was equilibrated with pure CO2 for 7.5 h and with pure H2 for 5 h, respectively. The isotope ratio value is indicated with δ (expressed on the VSMOW/SLAP scale) as defined by IUPAC. The average annual isotope value of milk at the different cattle sheds is mostly related to the farm water suggesting that the drinking water is the most important factor influencing the isotopic values of the milk water. The milk/water fractionation factor correlates with the milking time and, thus, the seasonal temperature is best described by a 4th order polynomial regression line. A two-level check model was used to verify the milking provenance. This study shows that it is essential to analyze both milk and farm water to indicate provenance. A two-step verification tool, based on the difference between the measured and calculated δ(18 O/16 O)M values, and the difference between the calculated and estimated milk-water fractionation factors, allowed the source determination of milk. Both conditions must be met if the milk is considered to be from the Parmigiano-Reggiano production region. Although this approach was developed for this region, it can easily be tested and adapted to other dairy production areas.


Analysis of absolute T helper cell number and cellular immune defects in HIV antibody positive and negative homosexual men.
To investigate if serial measurement of T helper (CD4) lymphocyte number in peripheral blood is of prognostic value, we determined lymphocyte function in asymptomatic and symptomatic HIV antibody positive and negative homosexual males and related the results to absolute number of CD4 lymphocytes in peripheral blood. Lymphocyte function was determined by measuring streptolysin O (SLO)-induced proliferative responses of peripheral blood lymphocytes (PBL) and of PBL depleted of CD8 lymphocytes. Phytohemagglutinin (PHA) induced interleukin-2 (IL-2) production was also measured. In all functional tests values were significantly lower in HIV antibody-positive subjects than in HIV antibody-negative subjects. Results lower than the 95% confidence limit in HIV antibody-negative individuals were therefore defined as "decreased." Decreased functional responses were most frequent (83-100%) in individuals with a number of CD4 lymphocytes of less than 400/microliters, and were least frequent (3-21%) in subjects with a CD4 lymphocyte count of greater than 600/microliters. Frequency of decreased functional responses was intermediate in the population with 600-400/microliters CD4 lymphocytes. The magnitude of functional responses differed significantly between groups with less than 400, 400-600, and greater than 600 CD4 lymphocytes per microliter, indicating that T helper cell number decreases with loss of immune function.


The impact of once-nightly versus twice-daily dosing and baseline beliefs about HAART on adherence to efavirenz-based HAART over 48 weeks: the NOCTE study.
To determine the impact of once-nightly versus twice-daily dosing and beliefs about highly active antiretroviral therapy (HAART) on adherence to efavirenz-based HAART in antiretroviral-naive patients. A multicenter, open-label, 48-week, randomized controlled trial. Participants were randomized to receive once nightly didanosine plus lamivudine, or twice-daily combivir (zidovudine plus lamivudine) both in combination with efavirenz. Medication Event Monitoring Systems were used to compile drug-dosing histories. Beliefs about HAART (necessity and concerns) were measured at baseline using validated questionnaires. Perceptions of HAART intrusiveness were assessed after 4 weeks. Eighty-seven patients were randomized (44 once-nightly and 43 twice-daily). Overall adherence was higher among the once-nightly arm (P = 0.0327). Eighty-one percent once-nightly and 62% twice-daily patients persisted with treatment for 48 weeks (P = 0.0559). Regimen execution was similar between both arms. Participants were significantly less likely to persist with HAART if their initial concerns about HAART were high relative to their perceived need for treatment (P = 0.025). The difference in adherence observed between once-nightly and twice-daily dosing was driven by a difference in persistence with treatment. Psychological preparation for starting HAART should address patients' perceptions of necessity for HAART and concerns about adverse effects to maximize persistence with treatment.


Early events in the anoikis program occur in the absence of caspase activation.
Adhesion of many cell types to the extracellular matrix is essential to maintain their survival. In the absence of integrin-mediated signals, normal epithelial cells undergo a form of apoptosis termed anoikis. It has been proposed that the activation of initiator caspases is an early event in anoikis, resulting in Bid cleavage and cytochrome c release from mitochondria. We have previously demonstrated that the loss of integrin signaling in mammary epithelial cells results in apoptosis and that this is dependent upon translocation of Bax from the cytosol to the mitochondria. In this paper, we ask whether caspases are required for Bax activation and the associated changes within mitochondria. We show that Bax activation occurs extremely rapidly, within 15 min after loss of integrin-mediated adhesion to extracellular matrix. The conformational changes associated with Bax activation are independent of caspases including the initiator caspase-8. We also examined downstream events in the apoptosis program and found that cytochrome c release occurs after a delay of at least 1 h, with subsequent activation of the effector caspase-3. This delay is not due to a requirement for new protein synthesis, since cycloheximide has no effect on the kinetics of Bax activation, cytochrome c release, caspase-3 cleavage, or apoptosis. Together, our data indicate that the cellular decision for anoikis in mammary epithelial cells occurs in the absence of caspase activation. Moreover, although the conformational changes in Bax are rapid and synchronous, the subsequent events occur stochastically and with considerable delays.


Outcomes, utilization, and costs among thalassemia and sickle cell disease patients receiving deferoxamine therapy in the United States.
Deferoxamine mesylate (DFO) reduces morbidity and mortality associated with transfusional iron overload. Data on the utilization and costs of care among U.S. patients receiving DFO in typical clinical practice are limited however. This was a retrospective study using a large U.S. health insurance claims database spanning 1/97-12/04 and representing 40 million members in >70 health plans. Study subjects (n = 145 total, 106 sickle cell disease [SCD], 39 thalassemia) included members with a diagnosis of thalassemia or SCD, one or more transfusions (whole blood or red blood cells), and one or more claims for DFO. Mean transfusion episodes were 12 per year. Estimated mean DFO use was 307 g/year. Central venous access devices were required by 20% of patients. Cardiac disease was observed in 16% of patients. Mean total medical costs were $59,233 per year including $10,899 for DFO and $8,722 for administration of chelation therapy. In multivariate analyses, potential complications of iron overload were associated with significantly higher medical care costs. In typical clinical practice, use of DFO in patients with thalassemia and SCD receiving transfusions is low. Administration costs represent a large proportion of the cost of chelation therapy. Potential complications of iron overload are associated with increased costs.


Effect of Furosemide on Urinary Oxygenation in Patients with Septic Shock.
Renal medullary hypoxia precedes the development of acute kidney injury in experimental sepsis and can now be assessed by continuous measurement of urinary oxygen tension (PuO2). We aimed to test if PuO2 measurements in patients with septic shock would be similar to those shown in experimental sepsis and would detect changes induced by the administration of furosemide. Pilot prospective observational cohort study in a tertiary intensive care unit (ICU). Seven adult patients with septic shock admitted to ICU had PuO2 measurements recorded minutely. There were 29 episodes of intravenous furosemide (20 mg n = 19; 40 mg n = 10). The median pre-furosemide PuO2 was low at 21.2 mm Hg (interquartile range [IQR] 17.73-24.86) and increased to 26 mm Hg (IQR 20.27-29.95) at 20 min (p < 0.01), to 27.5 mm Hg (IQR 24.06-33.18) at 40 min (p < 0.01) and to 28.5 mm Hg (IQR 22.65-31.03) at 60 min (p < 0.01). The increase in PuO2 was greater in episodes with a diuretic response >2 mL/kg/h than during episodes without such a response (p < 0.01). PuO2 measurements in patients are reflective of the low values reported in experimental models of sepsis. PuO2 values increased following furosemide administration with a response independently associated with greater diuresis.


[Physical activity level and physical, mental and social factors in community-dwelling elderly people].
This study was conducted to examine the relationship between physical activity level (PAL) and physical, mental and social factors in community-dwelling elderly people. The subjects comprised 428 residents aged 70 or over living in Kusatsu-machi, Gunma, who took part in an interview and tests of physical fitness as part of the "NIKKORI-KENKOSODANJIGYO". Data for 330 out of the 428 residents were adopted for this study. The PAL was evaluated with a questionnaire developed by Naito et al. (2003). Subjects were interviewed on physical, mental and social functioning including the Tokyo Metropolitan Institute of Gerontology (TMIG) Index of Competence and cognitive function (Mini Mental State Examination: MMSE). Physical fitness tests included assessment of handgrip strength, usual and maximal walking speed, and one-leg standing balance with eyes open. Correlations between PAL and the TMIG Index of Competence, physical (e.g. physical fitness), mental (e.g. depression) and social (e.g. roles at home) factors, and smoking status were significant by ANCOVA adjusted for age and sex. Analysis using a general linear model indicated that smoking status, usual walking speed, depression, roles at home, frequency of going outdoors and visual impairment all together explained 13.5% of the PAL variance. The findings indicate that PAL in the community-dwelling elderly aged 70 years or over is associated with physical, mental and social factors.


Regulation of tropomyosin gene expression during myogenesis.
In skeletal muscle, tropomyosin has a critical role in transduction of calcium-induced contraction. Presently, little is known about the regulation of tropomyosin gene expression during myogenesis. In the present study, qualitative and quantitative changes in the nucleic acid populations of differentiating chicken embryo muscle cells in culture have been examined. Total nucleic acid content per nucleus increased about fivefold in fully developed myotubes as compared to mononucleated myoblasts. The contribution of deoxyribonucleic acid to the total nucleic acid population decreased from 24% in myoblasts to 5% of total nucleic acid in myotubes. Concomitant with the decrement in deoxyribonucleic acid contribution to total nucleic acid was an increase in polyadenylated ribonucleic acid (RNA) content per cell which reached levels in myotubes that were 17-fold higher than those of myoblasts. Specific changes in the RNA population during myogenesis were further investigated by quantitation of the synthetic capacity (messenger RNA levels) per cell for alpha- and beta-tropomyosin. Cell-free translation and immunoprecipitation demonstrated an approximately 40-fold increase in messenger RNA levels per nucleus for alpha- and beta-tropomyosin after fusion in the terminally differentiated myotubes. Indirect immunofluorescence with affinity-purified tropomyosin antibodies demonstrated the presence of tropomyosin-containing filaments in cells throughout myogenesis. Thus, the tropomyosin genes are constitutively expressed during muscle differentiation through the production of tropomyosin messenger RNA and translation into tropomyosin protein.


Physical inactivity among older adults across Europe based on the SHARE database.
Regular physical activity is one of the key components of a healthy lifestyle. It is associated with better physical and cognitive functioning in later life and with increased life expectancy. The purpose of this study was to evaluate the prevalence of, and factors related to, physical inactivity among older adults across Europe. In this cross-sectional analysis, we used data from participants aged 55 or older in Wave 4 of the Survey of Health, Ageing, and Retirement in Europe (SHARE) database, a multidisciplinary and cross-national panel database covering health, socioeconomic status, and social and family networks. Individuals included in this study were classified as physically active or physically inactive. Clinical, psychosocial and sociodemographic variables were evaluated for their association with physical inactivity. From the total of 58,489 individuals in SHARE, we selected 19,298 people age 55 or older (mean age 67.8 ± 8.9 years; 11,430 (59.2%) female). The overall prevalence of inactivity among individuals age 55 or older in the 16 included countries was 12.5%. The prevalence of physical inactivity varied between countries, ranging from 4.9% (Sweden) to 29% (Portugal). Increasing age, depression, physical limitations, poor sense of meaning in life, social support and memory loss were significant variables associated with physical inactivity. Physical inactivity can be explained by physical, cognitive and psychological conditions. Interventions aimed at promoting physical activity among older people are needed to address this diversity of factors.


The NHS could learn from inspiring leaders like Barack Obama.
I remember November 2008 like it was yesterday. I was the lead for the NHS Leadership Academy's national Breaking Through programme for black and minority ethnic staff, and recall being at our annual conference bursting with pride at the news that Barack Obama had been elected president of the United States.


Wheat Gluten Amino Acid Analysis by High-Performance Anion-Exchange Chromatography with Integrated Pulsed Amperometric Detection.
The present chapter describes an accurate and user-friendly method for determining amino acid composition of wheat gluten proteins and their gliadin and glutenin fractions. The method consists of hydrolysis of the peptide bonds in 6.0 M hydrochloric acid (HCl) solution at 110 °C for 24 h, followed by evaporation of the acid and separation of the free amino acids by high-performance anion-exchange chromatography with integrated pulsed amperometric detection (HPAEC-IPAD). In contrast to conventional methods, the analysis requires neither pre- or post-column derivatization nor a time-consuming oxidation or derivatization step prior to hydrolysis. Correction factors account for incomplete release of Val and Ile even after hydrolysis for 24 h and for losses of Ser during evaporation. Gradient conditions including an extra eluent allow multiple sequential sample analyses without risk of Glu accumulation on the anion-exchange column which otherwise would result from high Gln levels in gluten proteins.


Nasal and paranasal sinus carcinoma: how can we continue to make progress?
New developments in the nasal and paranasal sinus cancers are reviewed. In addition to woodworking, several risk factors for nasal and paranasal sinus cancers have been identified, most notably smoking. Progress in the differential diagnosis of small round cell nasal and paranasal sinus cancers allows the precise diagnosis of esthesioneuroblastoma. Despite recent improvements, T staging for ethmoid and nasal cavity needs refinement. An association of surgery and radiation therapy remains the best treatment modality. Major developments include endoscopic resection of nasal and paranasal sinus cancers, high-precision radiotherapy techniques such as intensity-modulated radiotherapy, and proton-beam radiotherapy. There is probably no role for chemotherapy in esthesioneuroblastoma. Although chemotherapy is important for aggressive neoplasms, its generalized use for nasal and paranasal sinus cancers awaits the application/development of newer drugs. These drugs might be applied locally since the majority of recurrences remain local. Progress in the treatment of nasal and paranasal sinus cancers could be achieved through better prevention and the developments of more selective treatments such as endoscopic resection, high-precision radiotherapy, and new chemotherapy drugs.


Oesophageal perforation - therapeutic and diagnostics challenge. Retrospective, single-center case report analysis (2009-2015).
Esophageal perforation is a life-threatening condition of a complex etiology. No clear guidelines are available regarding the management of this condition. In this study, we review publications related to esophageal perforation, and analyze patients treated for this condition at our Department of Thoracic, General and Oncological Surgery. The objective of the study was to retrospectively assess and analyze management methods for esophageal perforations of different etiologies. All patients were treated in the Department of Thoracic, General and Oncological Surgery in years 2009-2015. Patients with perforations resulting from post-operational leaks within surgical anastomoses were excluded from the study. Material, methods, results: The analysis involved a total of 16 cases of esophageal ruptures. All cases were treated in years 2009-2015. Patients with perforations resulting from postoperative leaks within surgical anastomoses following elective surgeries for either oncological or non-oncological causes were excluded. The most common reason for esophageal rupture was iatrogenic injury (7 cases, 44%). Other causes included Boerhaave syndrome (5 cases, 31.2%), blunt trauma (2 cases, 12.5%), abscess perforation (1 case, 6.2%), and ulcer perforation (1 case, 6.2%). Ten patients underwent surgery, and the rest underwent esophageal prosthesis placement, of whom 2 cases required drainage of the mediastinum and pleural cavity. The mortality rate in the study group was 9/16 cases (56.2%). Esophageal perforation poses a significant interdisciplinary challenge regarding diagnostic workup, selection of treatment methods, and management of potential postoperative complications. This retrospective study was conducted in a single center. Although the analyzed period was long, we found only 16 cases. In spite of a variety of etiologies present, we found several statistically significant results of potential clinical value. 1. Most perforations that are not diagnosed within 48 hours affected the lower part of the esophagus and presented with unclear symptoms and imaging findings 2. Delaying diagnosis and treatment beyond 24 hours was associated with a higher mortality rate.


Fourier space approach to the classical density functional theory for multi-Yukawa and square-well fluids.
We present a Fourier space density functional approach for hard particles with attractive interactions, which is based on a previously developed two-dimensional approach [S. Hlushak, W. Rżysko, and S. Sokołowski, J. Chem. Phys. 131, 094904 (2009)] for hard-sphere chains. The interactions are incorporated by means of a three-dimensional Fourier image of the direct correlation function that is obtained from the first-order mean-spherical approximation. In order to improve the computational efficiency, we make extensive use of fast Fourier transforms for calculating density convolution integrals. A two-dimensional implementation of the new density functional approach, based on the expansion of the functional around the bulk fluid density, is used to study structure and adsorption of two model fluids in narrow cylindrical pores. We also investigate two methods that improve the accuracy of the theory as compared to the conventional DFT approach, which expands the free energy functional around the bulk fluid density: One a variant of the reference fluid density functional theory used by Gillespie et al. [Phys. Rev. E 68, 031503 (2003)], and the second a weighted density approach with energy route thermodynamics. Results from these two methods are compared to the conventional approach and also to the results of Monte Carlo simulations. We find that the method of Gillespie et al. and the weighted density approach with energy route thermodynamics yield significant improvement over the conventional approach.


Orientation and lever responding in auditory discriminations in squirrel monkeys.
Head orientation during auditory discriminations was studies in squirrel monkeys using a two-lever trial-by-trial procedure. Animals were studied using auditory discriminations based on the position of the sound and on the spectral content differences between a pure tone and a noise. After the percentage of correct responses reached asymptote, head orientation was measured using videotape recordings. Orientation occurred on virtually every trial and was under the control of the position of the sound under all conditions. Lever responding was controlled by the same parameters of the sound under some conditions, and by different parameters in others. Orientation and lever responding were correlated (a level response could be predicted from the direction of orientation) when both responses were under the control of the same parameters of the sound. The two responses were uncorrelated when they were controlled by different parameters of the sound. Orientation and lever responding were not functionally related.


Acute low back pain management in general practice: uncertainty and conflicting certainties.
Low back pain (LBP) is a significant health problem and common reason to visit the GP. Evidence suggests GPs experience difficulty applying evidence-based guidelines. Explore GPs' underlying beliefs about acute LBP and how these influence their clinical management of patients. Eleven GPs from one geographical region within New Zealand were recruited by purposive sampling. Audio recordings of semi-structured qualitative interviews were transcribed verbatim. Data were analysed with an Interpretive Description framework. Four key themes emerged related to the causes of acute LBP, GP confidence, communicating diagnostic uncertainty and encouraging movement and activity. Acute LBP was seen as a direct representation of tissue injury, consequently the assessment and management of patients' attitudes and beliefs was not a priority. Participants' confidence was decreased due to a perceived inability to diagnose or influence the tissue injury. Despite this, diagnoses were provided to patients to provide reassurance and meet expectations. Guideline recommendations regarding activity conflicted with a perceived need to protect damaged tissue, resulting in reported provision of mixed messages about the need to be both active and careful. GPs' initial focus upon tissue injury during acute care, and providing a diagnostic label, may influence patients' subsequent alignment with a biomedical perspective and contribute to consultation conflict and patients' perception of blame when discussion of psychosocial influences is introduced. Demonstrating the relevance of the biopsychosocial model to acute LBP may improve GPs' alignment with guidelines, improve their confidence to manage these patients and ultimately improve outcomes.


Proteins specified by African swine fever virus. II. Analysis of proteins in infected cells and antigenic properties.
Infection of MS cells with African swine fever virus (ASFV) produces inhibition of protein synthesis which is detectable from 4.5 hours after infection. At least 34 viral polypeptides have been indentified with molecular weights ranging between 9500 and 243,000 daltons. Three of these proteins show affinity for the cell nucleus and nine are in both the nuclear and cytoplasmic fractions. Ten early proteins were found, and most of the structural proteins were late proteins. Most of the proteins are synthesized within the first 8 hours after infection. At least nine proteins induced antibodies in the natural infection. Six of these proteins are structural proteins. The antigenic determinants of VP172, VP162, VP146, VP73, VP34, and IP23.5 are in the primary structure of the proteins.


[Application of non-invasive hemodynamic monitoring on high-risk surgical patients in the early stages after emergency admission].
Pulmonary artery (PA) catheterization monitoring (Swan-Ganz) is usually not available to critically high-risk surgical patients before admission to ICU, where action to correct values derived from such monitoring may be too late. To explored the effect of non-invasive monitoring systems that allow hemodynamic monitoring during the early stages after trauma. The early temporal hemodynamic patterns after high-risk trauma with non-invasive monitoring systems were evaluated, and compared these to invasive PA monitoring. The study included 156 patients monitored shortly after admission to the emergency department. The non-invasive impedance cardiac output estimations under extenuating emergency conditions were similar to those of the thermodilution method: r=0.69, r(2)=0.87, P<0.001; bias and precision were (0.62+/-0.38)L. min(-1).m(-2). In ICU, these values improved further to: r=0.84, r(2)=0.93, P<0.001; bias and precision were (0.36+/-0.15) L.min(-1).m(-2). Monitoring revealed episodes of hypotension, low cardiac index, arterial hemoglobin desaturation, low transcutaneous oxygen and high transcutaneous carbon dioxide tension, and low oxygen consumption during initial resuscitation. Low flow and poor tissue perfusion were more pronounced in non-survivors by both METHODS. Multicomponent non-invasive monitoring systems offer continuous on-line, real-time display of hemodynamic data, they allow early recognition of circulatory dysfunction. Such systems provide information similar to that provided by the invasive thermodilution method, and are more effective and safer.


The Role of the Neutrophilic Network in the Pathogenesis of Psoriasis.
One role of neutrophils, the most abundant innate immune sentinels, is neutrophil extracellular trap (NET) formation, which plays a significant role in immune surveillance. However, NET operation is bidirectional. Recent studies report that NETs may contribute to the development of autoimmune diseases such as psoriasis. The participation of neutrophils in the pathogenesis of that disease is dependent on an autoinflammatory feedback loop between neutrophils, lymphocytes, dendritic cells and keratinocytes. Our aim was to clarify the field of NET research in psoriasis and highlight the main factors required for NET generation, which may be a target of new therapies. This article presents a comphrehensive review concerning studies addressing the participation of neutrophils in the pathogenesis of psoriasis. Based on the available English-language literature, we discuss original papers presenting significant research findings which may help to understand and interpret the NET formation process in psoriasis, as well as the newest systematic reviews on PubMed. Next, the comparison, synthesis and summary of reported results were performed to clearly indicate the specific component of the NET which participates in the development of psoriasis.


Phosphoinositides Signaling and Epithelial-to-Mesenchymal Transition: Putative Topic for Basic Toxicological Research.
Ptdlns(4,5)P2 is a key cellular phosphoinositide that localizes in separate and distinctive pools in subcellular membrane and vesicular compartments. In membranes, Ptdlns(4,5)P2 acts as a precursor to second messengers and is itself a main signaling and targeting molecule. Specific subcellular localization of type I PIP kinases directed by interacting with specific targeting module differentiates Ptdlns(4,5)P2 production in a spatial and temporal manner. Several lines of evidences support the idea that Ptdlns(4,5)P2 is generated in very specific pools in a spatial and temporal manner or by feeding Ptdlns(4,5)P2 directly to effectors. In this concept, the interaction of PIPKI isoforms with a specific targeting module to allow precise subcellular targeting modulates highly specific Ptdlns(4,5)P2 synthesis and channeling overall effectors. For instance, localization of PIPKIγ661 to focal adhesions by an interaction with talin results in spatial and temporal production of Ptdlns(4,5)P2, which regulates EGF-stimulated directional cell migration. In addition, Type lγ PIPK is targeted to E-cadherin in cell adherence junction and plays a role in controlling dynamics of cell adherence junction and endocytosis of E-cadherin. Characterizing how PIP kinase isoforms are regulated by interactions with their targeting modules, as well as the mechanisms by which their product, Ptdlns(4,5)P2, exerts its effects on cellular signaling processes, is crucial to understand the harmonized control of numerous cellular signaling pathways. Thus, in this review the roles of the Ptdlns(4)P(5) kinases and Ptdlns(4,5)P2 were described and critically reviewed in terms of regulation of the E-cadherin trafficking, cell migration, and formation of cell adherence junction which is indispensable and is tightly controlled in epithelial-to-mesenchymal transition process.


The business of exploiting induced pluripotent stem cells.
Induced pluripotent stem cells (iPS cells) can be exploited for both research and clinical applications. The first part of this review seeks to provide an understanding of the financial drivers and key elements of a successful business strategy that underpin a company focused on developing iPS-related products and services targeted at the research market. The latter part of the review highlights some of the reasons as to why the reprogramming of somatic cells is currently being used to develop cell-based models to screen for small molecules with drug-like properties rather than to develop cell-based regenerative medicines per se. The latter may be used to repair or replace a patient's damaged cells and thereby have the potential to 'cure' a disease and, in doing so, prevent or delay the onset of associated medical conditions. However, the cost of an expensive regenerative medicine and time to accrue any benefit linked to a decrease in co-morbidity expenditure may not outweigh the benefit for a healthcare community that has finite resources. The implications of this are discussed together with evidence that the UK National Institute for Health and Clinical Excellence (NICE) and the National Health Service (NHS) have established a precedent for a cost-sharing strategy with the pharmaceutical industry.


Estimates of maintenance requirement of growing lambs.
1. Total body energy retention (ER) and metabolizable energy intake (MEI) values from experiments with 231 lambs (Suffolk male x (Border Leicester male x Cheviot female) female) housed indoors and given thirteen forage diets were used to estimate the metabolizable energy (ME) required for maintenance. 2. ER was measured using the comparative slaughter technique, and the lambs were fed at several planes of nutrition above maintenance between 2 and 5 months of age. 3. The daily ER and MEI results were scaled to live weight (kg0.75) and linear regression lines fitted to the values for individual diets. Extrapolation of the fitted lines to zero ER gave estimates of maintenance requirement ranging from 141 to 466 kJ ME/kg0.75 per d and values for the efficiency of utilization of ME for growth and fattening (Kf) of 0.25-0.53 (mean 0.39). 4. An alternative analysis constrained the estimated maintenance requirement to be the same for all diets. An iterative search procedure indicated minimal residual variation at 339 kJ/kg0.75 per d. This common value of ME for maintenance gave Kf values ranging from 0.30 to 0.54 (mean 0.39). 5. The implications of the technique were considered together with some discussion of the variability of the estimate. Allowing the minimum RSD to vary by 10% gave a maintenance requirement of between 231 and 408 kJ/kg0.75 per d.


Emergence of local geometric laws of step flow in homoepitaxial growth.
Below the roughening transition, crystal surfaces exhibit nanoscale line defects, steps, that move by exchanging atoms with their environment. In homoepitaxy, we analytically show how the motion of a step train in vacuum under strong desorption can be approximately described by nonlinear laws that depend on local geometric features such as the curvature of each step, as well as suitably defined effective terrace widths. We assume that each step edge, a free boundary, can be represented by a smooth curve in a fixed reference plane for sufficiently long times. Besides surface diffusion and evaporation, the processes under consideration include kinetic step-step interactions in slowly varying geometries, material deposition on the surface from above, attachment and detachment of atoms at steps, step edge diffusion, and step permeability. Our methodology relies on boundary integral equations for the adatom fluxes responsible for step flow. By applying asymptotics, which effectively treat the diffusive term of the free boundary problem as a singular perturbation, we describe an intimate connection of universal character between step kinetics and local geometry.