P047 The Crohn's Disease-Health Index (CD-HI): Development and Validation of a Novel, Disease-Specific Patient Reported Outcome Measure for Clinical Trials.
In preparation for upcoming clinical trials involving patients with Crohn's disease (CD), we examine the validity, reliability and usability of the Crohn's Disease-Health Index (CD-HI). The CD-HI is a multifaceted, disease-specific patient reported outcome measure (PROM) designed to measure CD symptomatic disease burden during clinical trials. As promising therapeutic interventions are being tested among CD patients, there is a clear need for researchers to have access to a valid, sensitive, and reliable patient reported outcome tool to track disease burden. This research describes the development and validation of the CD-HI as an efficient mechanism to quantify how CD patients both feel and function. We conducted semi-structured, qualitative interviews with CD patients to identify potential symptoms of importance in CD. We then conducted a large, cross-sectional survey study with CD patients to identify the prevalence and importance of symptoms identified during the prior interviews. Symptom questions in the first version of the CD-HI were selected based on overall frequency and impact in a large population of CD patients, generalizability, and potential to respond to therapeutic intervention. Questions which measured a similar concept were grouped into subscales using factor analysis. The first version of the CD-HI was beta tested to explore the usability and relevance of the instrument to patients. We then performed test-retest reliability of each question and subscale. Lastly, we determined the internal consistency for each subscale and the overall instrument. The CD-HI is now finalized and available for use in upcoming clinical trials. Sixteen adults with CD participated in semi-structured qualitative interviews, providing 792 quotes regarding the symptomatic burden of CD. Four hundred and three adults with CD completed an online survey to determine the prevalence and relative importance of 148 patient identified symptoms. Questions were selected for the CD-HI based on their prevalence and relative importance to CD patients. Sixteen adults with CD participated in beta interview testing to address the usability and relevance of the instrument. Patients found the CD-HI to be clear, highly relevant, and easy to use. Test-retest reliability was conducted with twenty-three adults with CD, where participants completed the CD-HI at baseline and fourteen days later. One question was removed to optimize the overall reliability of the instrument. The final version of the CD-HI contains subscales that measure the following granular areas of CD health: 1) fatigue; 2) dietary restrictions; 3) gastrointestinal health; 4) sleep and daytime sleepiness; 5) bowel and bladder function; 6) emotional health; 7) joint health; 8) pain; 9) neck and back health; 10) activity participation; 11) social health; and 12) skin health. Total CD disease burden is measured using a weighted composite of these subscale scores. This research successfully demonstrates the ability of the CD-HI to report valid, reliable, and patient-relevant data as a disease-specific PROM. The CD-HI provides researchers and clinicians with an optimal mechanism to record relevant changes in CD health using the patient's perspective.


Bovine papillomavirus transcriptional regulation: localization of the E2-responsive elements of the long control region.
The long control region (LCR) of the bovine papillomavirus type 1 genome can function as a conditional transcriptional enhancer which can be specifically trans-activated by the viral E2 gene product. To precisely map the target(s) of this trans-activation, BAL 31 exonuclease was used to generate two overlapping series of deleted DNA segments through the LCR. These fragments were assayed for their ability to activate transcription from the enhancer-deleted simian virus 40 early promoter of pA10CAT in the presence or absence of the viral E2 gene product. Two different E2-responsive elements were localized within the LCR. The major target for E2 trans-activation (E2-responsive element 1) was mapped to a 196-base-pair fragment between nucleotides 7611 and 7806, just upstream from promoters P7940 and P89. Further deletions which destroyed or impaired enhancer function revealed that the ACCN6GGT sequence motifs at each end of E2-responsive element 1 are critical components of this element. Primer extension analysis of RNA extracted from acute transfections with plasmids containing the bovine papillomavirus type 1 LCR driving the CAT gene revealed that each of the P7940 and P89 promoters is responsive to E2 trans-activation.


The economics of vein disease.
The management of cosmetic vein problems requires a very different approach than that for the majority of most other vascular disorders that occur in a vascular surgery practice. This article focuses on the business aspects of a cosmetic vein practice, with particular attention to the uniqueness of these issues. Managing patient expectations is critical to the success of a cosmetic vein practice. Maneuvering within the insurance can be difficult and frustrating for both the patient and the practice. Practices should use cost accounting principles to evaluate the success of their vein work. Vein surgery--especially if performed within the office--can undergo an accurate break-even analysis to determine its profitability.


California Residents' Perceptions of Gene Drive Systems to Control Mosquito-Borne Disease.
Scientists developing gene drive mosquitoes for vector control must understand how residents of affected areas regard both the problem of mosquito-borne disease and the potential solutions offered by gene drive. This study represents an experiment in public engagement at an early stage of technology development, intended to inform lab scientists about public attitudes toward their research and inspire consideration and conversation about the social ramifications of creating mosquitoes with gene drive. Online focus groups with California residents explored views on mosquito-borne disease risk, current mosquito control methods, and the proposed development and use of different classes of gene drives to control Ae. aegypti. Rather than a dogmatic rejection of genetic engineering or gene drive, many participants expressed pragmatic concerns with cost, control, the ability to narrowly target specific species, and the challenges of mistrust and institutional cooperation. Work like this can inform the alignment of community priorities and the professional priorities of scientists and vector control specialists.


Prostatic arterial embolization for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.
A variety of minimally invasive surgical approaches are available as an alternative to transurethral resection of the prostate (TURP) for management of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Prostatic arterial embolization (PAE) is a relatively new, minimally invasive treatment approach. To assess the effects of PAE compared to other procedures for treatment of LUTS in men with BPH. We performed a comprehensive search the Cochrane Library, MEDLINE, Embase, three other databases, trials registries, other sources of grey literature, and conference proceedings with no restrictions on language of publication or publication status, up to 8 November 2021. We included parallel-group randomized controlled trials (RCTs), as well as non-randomized studies (NRS, limited to prospective cohort studies with concurrent comparison groups) enrolling men over the age of 40 years with LUTS attributed to BPH undergoing PAE versus TURP or other surgical interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies for inclusion or exclusion and abstracted data from the included studies. We performed statistical analyses by using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE guidance to rate the certainty of evidence of RCTs and NRSs. MAIN RESULTS: We found data to inform two comparisons: PAE versus TURP (six RCTs and two NRSs), and PAE versus sham (one RCT). Mean age was 66 years, International Prostate Symptom Score (IPSS) was 22.8, and prostate volume of participants was 72.8 mL. This abstract focuses on the comparison of PAE versus TURP as the primary topic of interest. Prostatic arterial embolization versus transurethral resection of the prostate We included six RCTs and two NRSs with short-term (up to 12 months) follow-up, and two RCTs and one NRS with long-term follow-up (13 to 24 months). Short-term follow-up: based on RCT evidence, there may be little to no difference in urologic symptom score improvement measured by the International Prostatic Symptom Score (IPSS) on a scale from 0 to 35, with higher scores indicating worse symptoms (mean difference [MD] 1.72, 95% confidence interval [CI] -0.37 to 3.81; 6 RCTs, 360 participants; I² = 78%; low-certainty evidence). There may be little to no difference in quality of life as measured by the IPSS-quality of life question on a scale from 0 to 6, with higher scores indicating worse quality of life between PAE and TURP, respectively (MD 0.28, 95% CI -0.28 to 0.84; 5 RCTs, 300 participants; I² = 63%; low-certainty evidence). While we are very uncertain about the effects of PAE on major adverse events (risk ratio [RR] 0.75, 95% CI 0.19 to 2.97; 4 RCTs, 250 participants; I² = 24%; very low-certainty evidence), PAE likely increases retreatments (RR 3.20, 95% CI 1.41 to 7.27; 4 RCTs, 303 participants; I² = 0%; moderate-certainty evidence). PAE may make little to no difference in erectile function measured by the International Index of Erectile Function-5 on a scale from 1 to 25, with higher scores indicating better function (MD -0.50 points, 95% CI -5.88 to 4.88; 2 RCTs, 120 participants; I² = 68%; low-certainty evidence). Based on NRS evidence, PAE may reduce the occurrence of ejaculatory disorders (RR 0.51, 95% CI 0.35 to 0.73; 1 NRS, 260 participants; low-certainty evidence). Long-term follow-up: based on RCT evidence, PAE may result in little to no difference in urologic symptom scores (MD 2.58 points, 95% CI -1.54 to 6.71; 2 RCTs, 176 participants; I² = 73%; low-certainty evidence) and quality of life (MD 0.50 points, 95% CI -0.03 to 1.04; 2 RCTs, 176 participants; I² = 29%; low-certainty evidence). We are very uncertain about major adverse events (RR 0.91, 95% CI 0.20 to 4.05; 2 RCTs, 206 participants; I² = 72%; very low-certainty evidence). PAE likely increases retreatments (RR 3.80, 95% CI 1.32 to 10.93; 1 RCT, 81 participants; moderate-certainty evidence). While PAE may result in little to no difference in erectile function (MD 3.09 points, 95% CI -0.76 to 6.94; 1 RCT, 81 participants; low-certainty evidence), PAE may reduce the occurrence of ejaculatory disorders (RR 0.67, 95% CI 0.45 to 0.98; 1 RCT, 50 participants; low-certainty evidence). Compared to TURP, PAE may provide similar improvement in urologic symptom scores and quality of life. While we are very uncertain about major adverse events, PAE likely increases retreatment rates. While erectile function may be similar, PAE may reduce ejaculatory disorders. Certainty of evidence for the outcomes of this review was low or very low except for retreatment (moderate-certainty evidence), signaling that our confidence in the reported effect size is limited or very limited, and that this topic should be better informed by future research.


A plane-grating monochromator beamline for the PTB undulators at BESSY II.
At the BESSY II storage ring, the Physikalisch-Technische Bundesanstalt (PTB) will operate insertion devices dedicated to radiometric use. One branch of the appendant beamline system will be equipped with a grazing-incidence monochromator, described here. The monochromator concept is based on a plane grating operated in parallel light; therefore exact focusing is maintained for all photon energies irrespective of the angular setting at the grating. The monochromator has been optimized for small higher-order transmittance and high power throughput, as required by radiometric applications in the wide photon energy range from 20 eV to 1900 eV.


MicroRNA-486 regulates normal erythropoiesis and enhances growth and modulates drug response in CML progenitors.
MicroRNAs (miRNAs) are key regulators of hematopoietic cell differentiation and may contribute to altered growth of leukemic stem cells. Using microarray-based miRNA profiling, we found that miRNA 486 (miR-486) is significantly upregulated in chronic myeloid leukemia (CML) compared with normal CD34(+) cells, particularly in the megakaryocyte-erythroid progenitor population. miR-486-5p expression increased during erythroid differentiation of both CML and normal CD34(+) cells. Ectopic miR-486-5p expression enhanced in vitro erythroid differentiation of normal CD34(+) cells, whereas miR-486-5p inhibition suppressed normal CD34(+) cell growth in vitro and in vivo and inhibited erythroid differentiation and erythroid cell survival. The effects of miR-486-5p on hematopoietic cell growth and survival are mediated at least in part via regulation of AKT signaling and FOXO1 expression. Using gene expression and bioinformatics analysis, together with functional screening, we identified several novel miR-486-5p target genes that may modulate erythroid differentiation. We further show that increased miR-486-5p expression in CML progenitors is related to both kinase-dependent and kinase-independent mechanisms. Inhibition of miR-486-5p reduced CML progenitor growth and enhanced apoptosis following imatinib treatment. In conclusion, our studies reveal a novel role for miR-486-5p in regulating normal hematopoiesis and of BCR-ABL-induced miR-486-5p overexpression in modulating CML progenitor growth, survival, and drug sensitivity.


Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome: A Bridge between Functional Organic Dichotomy.
The pathogenesis of irritable bowel syndrome (IBS), once thought to be largely psychogenic in origin, is now understood to be multifactorial. One of the reasons for this paradigm shift is the realization that gut dysbiosis, including small intestinal bacterial overgrowth (SIBO), causes IBS symptoms. Between 4% and 78% of patients with IBS and 1% and 40% of controls have SIBO; such wide variations in prevalence might result from population differences, IBS diagnostic criteria, and, most importantly, methods to diagnose SIBO. Although quantitative jejunal aspirate culture is considered the gold standard for the diagnosis of SIBO, noninvasive hydrogen breath tests have been popular. Although the glucose hydrogen breath test is highly specific, its sensitivity is low; in contrast, the early-peak criteria in the lactulose hydrogen breath test are highly nonspecific. Female gender, older age, diarrhea-predominant IBS, bloating and flatulence, proton pump inhibitor and narcotic intake, and low hemoglobin are associated with SIBO among IBS patients. Several therapeutic trials targeting gut microbes using antibiotics and probiotics have further demonstrated that not all symptoms in patients with IBS originate in the brain but rather in the gut, providing support for the micro-organic basis of IBS. A recent proof-of-concept study showing the high frequency of symptom improvement in patients with IBS with SIBO further supports this hypothesis.


Laser-induced periodic surface structures on titanium upon single- and two-color femtosecond double-pulse irradiation.
Single- and two-color double-fs-pulse experiments were performed on titanium to study the dynamics of the formation of laser-induced periodic surface structures (LIPSS). A Mach-Zehnder inter-ferometer generated polarization controlled (parallel or cross-polarized) double-pulse sequences in two configurations - either at 800 nm only, or at 400 and 800 nm wavelengths. The inter-pulse delays of the individual 50-fs pulses ranged up to some tens of picoseconds. Multiple of these single- or two-color double-fs-pulse sequences were collinearly focused by a spherical mirror to the sample surface. In both experimental configurations, the peak fluence of each individual pulse was kept below its respective ablation threshold and only the joint action of both pulses lead to the formation of LIPSS. Their resulting characteristics were analyzed by scanning electron microscopy and the periods were quantified by Fourier analyses. The LIPSS periods along with the orientation allow a clear identification of the pulse which dominates the energy coupling to the material. A plasmonic model successfully explains the delay-dependence of the LIPSS on titanium and confirms the importance of the ultrafast energy deposition stage for LIPSS formation.


Altering the N-terminal arms of the polymerase manager protein UmuD modulates protein interactions.
Escherichia coli cells that are exposed to DNA damaging agents invoke the SOS response that involves expression of the umuD gene products, along with more than 50 other genes. Full-length UmuD is expressed as a 139-amino-acid protein, which eventually cleaves its N-terminal 24 amino acids to form UmuD'. The N-terminal arms of UmuD are dynamic and contain recognition sites for multiple partner proteins. Cleavage of UmuD to UmuD' dramatically affects the function of the protein and activates UmuC for translesion synthesis (TLS) by forming DNA Polymerase V. To probe the roles of the N-terminal arms in the cellular functions of the umuD gene products, we constructed additional N-terminal truncated versions of UmuD: UmuD 8 (UmuD Δ1-7) and UmuD 18 (UmuD Δ1-17). We found that the loss of just the N-terminal seven (7) amino acids of UmuD results in changes in conformation of the N-terminal arms, as determined by electron paramagnetic resonance spectroscopy with site-directed spin labeling. UmuD 8 is cleaved as efficiently as full-length UmuD in vitro and in vivo, but expression of a plasmid-borne non-cleavable variant of UmuD 8 causes hypersensitivity to UV irradiation, which we determined is the result of a copy-number effect. UmuD 18 does not cleave to form UmuD', but confers resistance to UV radiation. Moreover, removal of the N-terminal seven residues of UmuD maintained its interactions with the alpha polymerase subunit of DNA polymerase III as well as its ability to disrupt interactions between alpha and the beta processivity clamp, whereas deletion of the N-terminal 17 residues resulted in decreases in binding to alpha and in the ability to disrupt the alpha-beta interaction. We find that UmuD 8 mimics full-length UmuD in many respects, whereas UmuD 18 lacks a number of functions characteristic of UmuD.


Mouse bone marrow-derived IL-3-dependent mast cells and autonomous sublines produce IL-6.
This study deals with the question of whether mouse bone marrow-derived mast cells are able to produce interleukin-6 (IL-6) in vitro. For this purpose, a panel of primary mast cell clones from limiting-dilution microcultures, of permanent IL-3-dependent mast cell lines and autonomous malignant sublines, was screened. All of these lines were found to produce growth factor activity for IL-6-dependent mouse hybridoma cells (7TD1), which could be completely neutralized by the monoclonal anti-IL-6-antibody 6B4. Transcriptional activity of the IL-6 gene was demonstrated in both IL-3-dependent mast cells and autonomous sublines using a mouse IL-6-specific cDNA probe.


Devosia epidermidihirudinis sp. nov. isolated from the surface of a medical leech.
A Gram-negative, rod-shaped organism, isolated from the surface of the medical leech Hirudo verbana was characterized phenotypically and genotypically. The calculated 16S rRNA gene sequence similarities to those of the most closely related species grouped strain E84(T) into the genus Devosia showing the highest similarities to Devosia limi (98.1 %), followed by Devosia psychrophila (97.9 %), Devosia neptuniae (97.3 %), and Devosia glacialis (97.5 %). Chemotaxonomic analyses showed that the major quinone was ubiquinone Q-10. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol and three glycolipids. The major fatty acid profile consisted of C18:1 ω7c 11-methyl, C19:0 cyclo ω8c, and C16:0, C18:0 and C18:1 ω7c with C18:0 3OH as hydroxylated fatty acid. This profile is very similar to those of the patterns reported for the already described Devosia species. The results of DNA-DNA hybridization, physiological and biochemical tests allowed both genotypic and phenotypic differentiation of strain E84(T) from all other Devosia species suggesting a novel species for which the name Devosia epidermidihirudinis sp. nov. is proposed, with the type strain E84(T) (=CIP 110375(T) = LMG 26909(T) = CCM 8398(T)).


Sedation in the emergency department.
Pediatric ED patients now have a wide variety of options to help relieve the pain and apprehension associated with an ED visit. Safe and effective management of these children has become a priority in properly staffed and equipped EDs throughout the country.


Changes in intestinal flora of farm personnel after introduction of a tetracycline-supplemented feed on a farm.
A prospective study was undertaken to determine whether feeding farm animals antibiotics in feed caused changes in the intestinal bacterial flora of farm dwellers and their neighbors. Chickens were fed tetracycline-supplemented feed (tet-feed), and, as expected, within one week their intestinal flora contained almost entirely tetracycline-resistant organisms. Increased numbers of resistant intestinal bacteria also appeared, but more slowly, in farm members, but not their neighbors. Within five and six months, 31.3 per cent of weekly fecal samples from farm dwellers contained greater than 80 per cent tetracycline-resistant bacteria as compared to 6.8 per cent of the samples from the neighbors (P less than 0.001). Seven of the 11 farm members, but only three of the 24 neighbors, had two or more fecal samples containing greater than 80 per cent tetracycline-resistant coliforms (P less than 0.01). These resistant bacteria contained transferable plasmids conferring multiple antibiotic resistances. Selective pressure by tet-feed for antibiotic-resistant bacteria in chickens extends to human beings in contact with chickens and the feed.


Early Stage Graves' Disease is Uniformly Accompanied by Orbital Immune Activity even in Patients who Fail to Develop Orbithopathy during Follow-up.
Graves' orbitopathy (GO) is a complication of Graves' disease (GD), the development of which cannot be predicted at the time of diagnosis of GD. Our aims were (i) to test if orbital 99mTc-labelled diethylenetriamine pentaacetic acid single-photon emission computer tomography (DTPA SPECT) can predict development of GO later during the course of the disease and (ii) to study whether orbital immune activity can be detected in GD patients who do not develop GO during follow-up. Fifty-four orbits of 27 patients with newly diagnosed GD were entered into the case-control study. Individuals showing signs of GO at enrolment were excluded. During the two-year follow-up, eye signs were recorded every 3 months. Orbital DTPA uptakes on SPECT images were measured when entering the study and at the end of the follow-up period, or when clinical signs of GO developed, whichever occurred first. During the follow-up, 6 patients (22%) were diagnosed with GO. There was no significant difference between the initial DTPA uptakes of the patients with or without later developing GO (10.45±1.72 MBq/cm3 vs. 9.18±1.18 MBq/cm3 respectively). However, the DTPA uptakes of both GD groups (ie. with and without GO) were higher than that of the control group (7.45±1.36 MBq/cm3, p<0.05). We have shown that GD is accompanied by moderate orbital immune activity in GD patients without GO, irrespective of later development of GO. Why this orbital autoimmunity remains subclinical in the majority of the cases, and progresses into clinically detectable GO in others, remains unclear.


Clinical Characteristics and Metabolic Health Status of Obese Korean Children and Adolescents.
This study aimed to determine the prevalence of metabolically healthy and unhealthy obesity (MHO and MUO, respectively) and examine the demographic, anthropometric, and lifestyle predictors of metabolic health status in Korean children and adolescents. This study was based on data collected from the Korean Children-Adolescent Study in 2010. A total of 1,700 children (846 boys and 854 girls) were included in the primary cohort and classified into metabolically healthy and unhealthy groups according to factors related to the metabolic syndrome. Demographic and biochemical features were evaluated in study participants. Logistic regression estimated the odds ratios of having more fat mass among MUO compared with MHO children after adjusting for confounding factors. Mean body mass index was higher in the MUO group than in the MHO group (24.83 vs. 23.02 kg/m(2), respectively). The proportion of obese participants was also higher in the MUO group (59.4%) than in the MHO group (20.7%). MHO children were more likely to have parents with better socioeconomic status and a higher fruit and vegetable intake compared with MUO children. Higher fat mass and percent fat was associated with MUO according to multiple logistic regression analysis. Fat mass and percent fat are associated with metabolically healthy phenotypes of obesity among children and adolescents.


[The use of Doppler in the second half of pregnancy].
The article is a review of the literature on the use and clinical applicability of Doppler examination in the second half of pregnancy Nowadays, despite its accessibility Doppler ultrasound in pregnancy is often contraindicated. At the same time, the is no evidence of clinical utility of Doppler studies in a low-risk pregnancy The main indications for Doppler examinations in pregnancy include intrauterine growth restriction (IUGR), suspicion of fetal anemia, and complications of monochorionic twin pregnancy As far as IUGR is concerned, Doppler allows to diagnose IUGR associated with placental insufficiency and to differentiate IUGR from small for gestational age fetuses (SGA). Doppler is also very useful in making the decision about the time of delivery of IUGR fetuses. The assessment of the peak systolic velocity in the middle cerebral artery (PSV-MVA) reduced the rate of invasive procedures due to fetal anemia by approximately 70%. Complications of the second half of pregnancy which are indications for Doppler ultrasound include selective IUGR, TTTS and TAPS. Similarly to the first trimester, the mid-trimester assessment of the blood flow in the uterine arteries plays an important role in the prediction of preeclampsia and IUGR, especially early-onset forms of these complications.


Evidence-Based Approach of Biologic Therapy in Bronchial Asthma.
The emergence of biologic agents in the treatment of bronchial asthma has a wide impact on improving quality of life, reducing morbidity, and overall health care utilization. These therapies usually work by targeting specific inflammatory pathways involving type 2 inflammation and are particularly effective in severe eosinophilic asthma. Various randomized controlled trials have shown their effectiveness by reducing exacerbation rates and decreasing required glucocorticoid dosages. One of the relatively newer agents, tezepelumab, targets thymic stromal lymphoprotein and has proven its efficacy in patients independent of asthma phenotype and serum biomarker levels. This article reviews the pathophysiologic mechanism behind biologic therapy and offers an evidence-based discussion related to the indication, benefits, and adverse effects of such therapies.


Synchronous malignant phyllodes tumour and invasive lobular carcinoma-case report and review.
Synchronous phyllodes tumour and invasive lobular carcinoma is an extremely rare event. We report these concurrent diagnoses in a patient observed in an ipsilateral breast, suspected due to breast risk factors (family history and lobular carcinoma in situ) and the presence of malignant phyllodes. Screening breast magnetic resonance imaging was able to identify the carcinoma which was occult in other imaging. An understanding of the possibility of dual diagnoses may lead to additional investigations for its identification. Treatment may then be tailored to the individual's pathology.


[Brief Introduction to Regulatory Documents of European and American Drug-Device Combinations and Enlightenment].
This paper briefly introduces the recent regulatory regulations issued by the European Union and the United States on the drug-device combinations. The contents include the definition of drug-device combinations, the attribute definition process, the registration requirements, the review and approval procedures, the management of production systems, and the post-marketing safety supervision. Some inspirations have been obtained from them for reference by the regulatory authorities.


Primate hepatitis B viruses - genetic diversity, geography and evolution.
There are six well characterised genotypes (A-F) of human hepatitis B virus that have distinct geographic ranges which generally relate to chronic HBV infection. A seventh human genotype (G) has recently been described, but there is limited information on ethnic and geographic distribution. Despite the fact that early studies indicated that HBV antigens were present in other primates, the prevailing dogma that HBV was a human disease precluded alternative explanations. Within the past 5 years, hepatitis B viruses have been characterised from all the Old World great apes (orangutan, gibbons, gorillas and chimpanzees) and from a New World woolly monkey. Each group of non-human primates appears to have a distinct strain of hepatitis B virus that can be distinguished from human sequences based upon the nucleotide sequence and selected amino acid changes in the viral proteins. The woolly monkey HBV is most divergent from other primate and human sequences, while the great ape HBV sequences cluster together with separate branches for each group.


Stochastic resonance and the evolution of Daphnia foraging strategy.
Search strategies are currently of great interest, with reports on foraging ranging from albatrosses and spider monkeys to microzooplankton. Here, we investigate the role of noise in optimizing search strategies. We focus on the zooplankton Daphnia, which move in successive sequences consisting of a hop, a pause and a turn through an angle. Recent experiments have shown that their turning angle distributions (TADs) and underlying noise intensities are similar across species and age groups, suggesting an evolutionary origin of this internal noise. We explore this hypothesis further with a digital simulation (EVO) based solely on the three central Darwinian themes: inheritability, variability and survivability. Separate simulations utilizing stochastic resonance (SR) indicate that foraging success, and hence fitness, is maximized at an optimum TAD noise intensity, which is represented by the distribution's characteristic width, sigma. In both the EVO and SR simulations, foraging success is the criterion, and the results are the predicted characteristic widths of the TADs that maximize success. Our results are twofold: (1) the evolving characteristic widths achieve stasis after many generations; (2) as a hop length parameter is changed, variations in the evolved widths generated by EVO parallel those predicted by SR. These findings provide support for the hypotheses that (1) sigma is an evolved quantity and that (2) SR plays a role in evolution.


Physicochemical and sensory quality of yogurt incorporated with pectin from peel of Citrus sinensis.
Industrial by-product like orange peel plays an important role in pectin manufacture. The objective of this article was to extract pectin from peel of Citrus sinensis and to study the effect of its incorporation on the quality of yogurt during the period of fermentation and postacidification. Physicochemical, organoleptic, and rheological properties of yogurt prepared with pectin were studied in order to determine the best preparation depending on the rate of pectin. The extraction pectin yield was estimated to more than 24%. The viscosity and acidity were increased with increasing of the pectin rate. The best viscosity value was obtained with 0.6% of pectin. Furthermore, the effect of the rate of pectin incorporation in the fermented milks was clearly observed on the number of Streptococcus thermophilus and Lactobacillus bulgaricus, the cohesiveness, the adhesiveness, the taste, and the whey exudation.


Design and psychometric evaluation of health system intervention assessment tools for children in floods.
Flood is one of the most frequent disasters in Iran, which has highly affected the population and consequences on the health system. Children as the most vulnerable group too need to receive health services during floods. The aim of the present study was to develop a national tool for evaluating the provision of health services to children in floods. This study is a sequential-exploratory mixed method study that consists of two qualitative and quantitative stages. The qualitative part includes the analysis of documents and panel of experts while the quantitative part includes the design and validation of the tools. In this study, organizations providing health services to children were first identified, and according to their mission the relevant items were extracted and the initial checklist was designed. Then validity and reliability of the tools were done. The content validity ratio and content validity index for the tool were 59 and 98%, respectively. Cronbach's alpha and intraclass correlation coefficient were determined as 0.7 and 0.964, respectively. The final tool was presented with 64 items. The response program, the scope of interventions, service coverage, and the effectiveness of the response after the flood can help reduce the risk of disasters in children. Using the assessment tool of evaluating the health services to children can assist the stakeholder organizations to meet the standards and best quality of services. Assessing the needs of the children affected by floods, identifying the strengths and weaknesses of health services, and proposing corrective strategies according to the information extracted from this tool are other achievements of this study.


Constant and hypervariable regions in conotoxin propeptides.
Conotoxins are small cysteine rich peptides found in the venom of the predatory cone snails (Conus) which have prove to be useful high affinity ligands for various receptors and ion channels. The first cloning data for conotoxins, reported here, were obtained for the King-Kong peptide, a 27 amino acid conotoxin found in the venom of the cloth-of-gold cone, Conus textile. Analysis of cDNA clones of the King-Kong peptide revealed a family of related toxin transcripts. Three different propeptide cDNA sequences were obtained; only one of these encoded sequence for the King-Kong peptide. The other cDNA sequences encoded two different peptides (KK-1 and KK-2). When the predicted propeptide sequences are compared, well defined conserved and hypervariable regions can be identified. The hypervariable regions comprise four regions between Cys residues in the final peptide toxins; the remainder of the propeptide sequences, i.e. the excised N-terminal regions and the disulfide bonded Cys residues, are highly conserved. We suggest that the conserved regions may direct the formation of a specific disulfide configuration in the King-Kong family of conotoxins.


Spectral and temporal cues for perception of material and action categories in impacted sound sources.
In two experiments, similarity ratings and categorization performance with recorded impact sounds representing three material categories (wood, metal, glass) being manipulated by three different categories of action (drop, strike, rattle) were examined. Previous research focusing on single impact sounds suggests that temporal cues related to damping are essential for material discrimination, but spectral cues are potentially more efficient for discriminating materials manipulated by different actions that include multiple impacts (e.g., dropping, rattling). Perceived similarity between material categories across different actions was correlated with the distribution of long-term spectral energy (spectral centroid). Similarity between action categories was described by the temporal distribution of envelope energy (temporal centroid) or by the density of impacts. Moreover, perceptual similarity correlated with the pattern of confusion in categorization judgments. Listeners tended to confuse materials with similar spectral centroids, and actions with similar temporal centroids and onset densities. To confirm the influence of these different features, spectral cues were removed by applying the envelopes of the original sounds to a broadband noise carrier. Without spectral cues, listeners retained sensitivity to action categories but not to material categories. Conversely, listeners recognized material but not action categories after envelope scrambling that preserved long-term spectral content.


Tissue localization and CD8 accessory molecule expression of T gamma delta cells in humans.
In this study, we used TCR isotype-specific antibodies to examine the frequency, phenotype, and histologic localization pattern of T gamma delta cells in humans. The TCR delta 1+ cells comprised an average of 15% of the splenic CD3+ cells and 7% of circulating T cells. The T gamma delta cells in these human tissues, like their avian counterparts, were often not "double-negative" for the CD4 and CD8 accessory molecules. Approximately 50% of the splenic delta+ cells expressed CD8, and 30% of the delta+ cells in blood were CD8+. T cells of both gamma delta and alpha beta TCR isotypes were exceedingly rare in the skin. The T gamma delta cells exhibited preferential homing to the sinusoidal areas (red pulp) of the spleen and into the epithelial layer of the intestine in humans, as had been previously noted in chickens. Although 80% of the T gamma delta cells in the human intestinal mucosa were localized in the epithelial layer, these cells represented only 5 to 10% of all the CD3+ T cells in this microenvironment. We conclude that T gamma delta cells represent a sizeable subpopulation of the T cells in human peripheral tissues. The phylogenetic conservation of the CD8 expression by peripheral T gamma delta cells and of their preferential homing pattern suggests a special role in bodily defense for this T cell subpopulation.


Experimental Trypanosoma evansi infection in the goat. II. Pathology.
Infection of male goats aged 8-10 months with 5000 or 50 000 organisms of a Mindanao strain of Trypanosoma evansi was observed over a period of 90 days. The infection induced clinical disease which was lethal, especially at the higher dose rate. Lesions were more acute in goats that received the higher dose. Gross and microscopical changes were not pathognomonic, except in the presence of demonstrable trypanosomes. At necropsy, a combination of lymphadenopathy, splenomegaly, hepatomegaly, testicular enlargement, anaemic signs and consolidation of the anterior lobes of the lungs was suggestive of surra. Testicular changes, especially aspermia, indicated probable infertility. The cytopathology of the lungs, liver, intestine, kidneys, testes, bone marrow, brain and other organs was immunological in nature, characterized by mononuclear infiltration of interstitial tissues, with minor cellular damage and the presence of trypanosomes. B- and T- cell responses were observed in the lymphatic system, but the findings indicated immunosuppression in the lymph nodes, spleen and bone marrow during the third month after infection. Exudative inflammatory changes were mild. It is suggested that the cytopathology of most haemophilic trypanosomal infections is predominantly an immunological process.


Long-term mitigation of drought changes the functional potential and life-strategies of the forest soil microbiome involved in organic matter decomposition.
Climate change can alter the flow of nutrients and energy through terrestrial ecosystems. Using an inverse climate change field experiment in the central European Alps, we explored how long-term irrigation of a naturally drought-stressed pine forest altered the metabolic potential of the soil microbiome and its ability to decompose lignocellulolytic compounds as a critical ecosystem function. Drought mitigation by a decade of irrigation stimulated profound changes in the functional capacity encoded in the soil microbiome, revealing alterations in carbon and nitrogen metabolism as well as regulatory processes protecting microorganisms from starvation and desiccation. Despite the structural and functional shifts from oligotrophic to copiotrophic microbial lifestyles under irrigation and the observation that different microbial taxa were involved in the degradation of cellulose and lignin as determined by a time-series stable-isotope probing incubation experiment with 13C-labeled substrates, degradation rates of these compounds were not affected by different water availabilities. These findings provide new insights into the impact of precipitation changes on the soil microbiome and associated ecosystem functioning in a drought-prone pine forest and will help to improve our understanding of alterations in biogeochemical cycling under a changing climate.


The frequency of skin diseases among students in a university clinic.
This study was conducted to assess the frequency of dermatologic diseases in Turkish university students. University students who visited two dermatology outpatient clinics within the Ege University Health, Culture and Sports Office were included in the study. Each student was examined by two dermatologists. Questions about demographic data and information about the frequency of using the swimming pool were directed to the patients. All dermatological diseases were recorded. Patients were asked to assess and give a score for the state of their mental wellness using the visual analog scale (0-100) during the past month. Chi-square and Student t tests were used for statistical analyses. A total of 1733 individuals, 750 (43.3%) men and 983 (56.7%) women, were included in the study. The most frequently seen diseases were acne vulgaris (40.1%) and fungal diseases (17.08%), whereas the least frequently seen were parasitic skin diseases (0.46%) and vascular diseases (0.51%). The mean mental wellness score was found to be 61.03 +/- 21.34 (0-100, median: 65.00). It can be concluded that students visit university dermatology outpatient clinics frequently and the most common complaints are acne vulgaris and fungal diseases.


Chronological narratives from smoking initiation through to pregnancy of Indigenous Australian women: A qualitative study.
One in two Indigenous Australian pregnant women smoke, yet little is known about their trajectory of smoking. This study aimed to explore Aboriginal women's narratives from starting smoking through to pregnancy. A female Aboriginal Researcher conducted individual face-to-face interviews with 20 Aboriginal women from New South Wales, Australia. Recruitment, through Aboriginal services and community networks, continued until saturation was reached. Audio-recorded transcripts were independently open coded by two researchers, inductively analysed and reported using a three-dimensional structure of looking backwards, forwards, inwards, outwards and a sense of place, to elucidate the chronology of events, life stages, characters, environments, and turning points of the stories. A chronology emerged from smoking initiation in childhood, coming of age, becoming pregnant, through to attempts at quitting, and relapse post-partum. Several new themes emerged: the role mothers play in women's smoking and quitting; the contribution of nausea to spontaneous quitting; depression as a barrier to quitting; and the hopes of women for their own and their children's future. The epiphany of pregnancy was a key turning point for many - including the interplay of successive pregnancies; and the intensity of expressed regret. Aboriginal women report multiple influences in the progression of early smoking to pregnancy and beyond. Potential opportunities to intervene include: a) childhood, coming of age, pregnancy, post-natal, in-between births; b) key influencers; c) environments, and d) targeting concurrent substance use. Morning sickness appears to be a natural deterrent to continued smoking. Depression, and its relationship to smoking and quitting in Australian Indigenous pregnant women, requires further research.


Effectiveness of UV-based advanced oxidation processes for the remediation of hydrocarbon pollution in the groundwater: a laboratory investigation.
The effectiveness of advanced oxidation processes in a batch and a flow reactor was investigated for the remediation of hydrocarbon pollution in the groundwater underlying a petrochemical industrial site. The main organic contaminants present in the groundwater were MTBE, benzene, alkyl-benzenes and alkyl-naphthalenes. Experimental results with a batch reactor showed that for all the organic contaminants the removal efficiency order is UV/TiO2 approximately UV/H2O2>UV (medium-pressure) in a synthetic aqueous solution, compared to UV/H2O2>UV (medium-pressure)>UV/TiO2 for the real polluted groundwater. The much lower performance of UV/TiO2 with respect to UV/H2O2 was inferred to the matrix of the groundwater, i.e. the salt content, as well as the organic and particulate matter. In fact, it is likely that the salts and dissolved organic matter quench the superoxide anion O2(-) and hydroxyl radicals just formed at the surface of the TiO2 catalyst. MTBE was the hardest compound to remove with each of the investigated treatments. UV and UV/TiO2 treatments were not able to reach a residual concentration of 10 microg/L (set by Italian legislation) even after 180 min. As for the UV/H2O2 process, only the MTBE degradation rate resulted affected by the initial H2O2 concentration, while for other compounds a complete removal was obtained within 20 min even with the lowest H2O2 concentration used (0.13 g/L). Only after 120 min of treatment, with an initial H2O2 concentration of 0.13 g/L, did the residual MTBE concentration fall below the above reported maximum admissible concentration. Instead, by using an initial concentration of 2g/L a residual concentration lower than 5 microg/L was obtained after just 30 min of reaction. The UV/H2O2 process was also investigated with a flow reactor. Results showed that it was more efficient than the batch reactor for removing MTBE, in terms of reaction time and initial H2O2 concentration required. This is consistent with the higher power of the UV lamp and with the different geometry of the flow reactor, which has a much shorter optical path than the batch reactor. By-product characterisation was also performed showing that t-butyl-formate and low molecular weight organic acids are formed as intermediate and final by-products, respectively. Finally, a preliminary evaluation of the operational cost of the UV/H2O2 process showed a value of 1.7 euro/m3 under the optimised condition.


Intrahepatic extramedullary hematopoiesis mimicking a hypervascular hepatic neoplasm on dynamic- and SPIO-enhanced MRI.
We present a rare case of a focal intrahepatic extramedullary hematopoiesis (EMH) that mimicked a hypervascular hepatic neoplasm in a 33-year-old woman with idiopathic myelofibrosis. The lesion showed homogeneous and persistent enhancement on both contrast-enhanced CT and gadolinium-enhanced dynamic MR imaging. The lesion did not demonstrate an apparent signal drop on a T2-weighted sequence following administration of a superparamagnetic iron-oxide agent (SHU 555A). A hepatocellular adenoma was the initial radiological diagnosis. To the best of our knowledge, this is the first report of a histopathologically proven intrahepatic EMH evaluated with dynamic- and SPIO-enhanced MRI.


Cutting the Flesh: Surgery, Autopsy and Cannibalism in the Belgian Congo.
Within the colonial setting of the Belgian Congo, the process of cutting the body, whether living or dead, lent itself to conflation with cannibalism and other fantastic consumption stories by both Congolese and Belgian observers. In part this was due to the instability of the meaning of the human body and the human corpse in the colonial setting. This essay maps out different views of the cadaver and personhood through medical technologies of opening the body in the Belgian Congo. The attempt to impose a specific reading of the human body on the Congolese populations through anatomy and related Western medical disciplines was unsuccessful. Ultimately, practices such as surgery and autopsy were reinterpreted and reshaped in the colonial context, as were the definitions of social and medical death. By examining the conflicts that arose around medical technologies of cutting human flesh, this essay traces multiple parallel narratives on acceptable use and representation of the human body (Congolese or Belgian) beyond its medical assignation.


Poly-epsilon-caprolactone nanoparticles enhance ursolic acid in vivo efficacy against Trypanosoma cruzi infection.
Despite affecting millions of people worldwide, Chagas disease is still neglected by the academia and industry and the therapeutic option available, benznidazole, presents limited efficacy and side effects. Within this context, ursolic acid may serve as an option for treatment, however has low bioavailability, which can be enhanced through the encapsulation in polymeric nanoparticles. Therefore, herein we developed ursolic acid-loaded nanoparticles with poly-ε-caprolactone by the nanoprecipitation method and characterized them for particle size, zeta potential, polydispersity, encapsulation efficiency, morphology by scanning electron microscopy and thermal behavior by differential scanning calorimetry. Results indicated that an appropriate ratio of organic phase/aqueous phase and polymer/drug is necessary to produce smaller particles, with low polydispersity, negative zeta potential and high drug encapsulation efficiency. In vitro studies indicated the safety of the formulation against fibroblast culture and its efficacy in killing T. cruzi. Very importantly, the in vivo study revealed that the ursolic acid-loaded nanoparticle is as potent as the benznidazole group to control parasitemia, which could be attributed to improved bioavailability of the encapsulated drug. Finally, the toxicity evaluation showed that while benznidazole group caused liver toxicity, the nanoparticles were safe, indicating that this formulation is promising for future evaluation.


Increasing Social Support for Breakfast: Project BreakFAST.
High school students in the United States are known to be frequent skippers of breakfast. Social support is one key element needed to encourage adolescents to consume school breakfast. This article presents an analysis of the influence of a school policy and environment change intervention on the social support of adolescents to eat breakfast. The intervention included school policy changes in 16 schools randomized to intervention and delayed-intervention conditions, in order to allow quick and easy access to breakfast as well as to allow breakfast consumption in classrooms and hallways; a School Breakfast Program marketing campaign to address normative and attitudinal beliefs; and increasing social support and role modeling to encourage breakfast eating. The participants in the study completed an online survey at baseline and again postintervention. The final analysis included only students who completed the relevant survey (n = 904) items on both the baseline and follow-up surveys. The students in the intervention group showed a higher level of social support post intervention than the control group with a significant adjusted p of .02. Most of the overall social support change was explained by a change in the "other kids at my school" and "other school staff" categories. The BreakFAST study shows the benefits of school staff and kids other than friends supporting a behavior change to include breakfast consumption in adolescents.


Device simulation of liquid crystal polarization gratings.
Liquid crystal polarization gratings manifest several unique features, such as high diffraction efficiency, polarization selectivity, and fast switching time. However, few works address the chiral-doped liquid crystal alignment issue in such gratings. Here, we develop an improved relaxation method to analyze the liquid crystal director distribution in chiral-doped polarization gratings. Our simulation result agrees well with experimental data on a polarization volume grating. The criteria for forming planar or slanted polarization grating are discussed.


Shortening of Overall Orthodontic Treatment Duration with Low-Intensity Pulsed Ultrasound (LIPUS).
The aim of this retrospective clinical study was to determine if there is a reduction in the overall treatment duration in orthodontic patients using low-intensity pulsed ultrasound (LIPUS) and Invisalign SmartTrack® clear aligners. Data were collected from the first thirty-four patients (9 males, 25 females; average age 41.37 ± 15.02) who finished their orthodontic treatment using an intraoral LIPUS device and Invisalign clear aligners in a private clinic. The LIPUS parameters used by patients at home for 20 min/day were: ultrasonic frequency 1.5 MHz, pulse duration 200µs, pulse repetition rate 1 kHz, and spatial average-temporal average intensity 30mW/cm2. A control group (11 males, 23 females; average age 31.36 ± 14.41) matching for the same malocclusions was randomly selected from finished treatment cases of the same clinician. The date of first Invisalign attachment placement and first use of LIPUS application was recorded as T0, and the date of retainer delivery was recorded as T1. The treatment duration (T1-T0) and treatment reduction percentage with LIPUS device were collected and analyzed using two-sample t-test in Microsoft Excel. Treatment duration was significantly reduced in the LIPUS group (541.44 ± 192.23 days) compared to control group (1061.05 ± 455.64 days) (p < 0.05). The LIPUS group showed on average 49% reduction in the overall treatment time as compared to the control group. The average compliance of the patients using LIPUS was 66.02%. Patients who used LIPUS showed a clinically significant reduction in the overall orthodontic treatment duration compared to the control group who used Invisalign clear aligners only.


Comparison of BTP, NGAL, KIM-1, & ADMA biomarkers in CKD and non-CKD subjects.
New biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin family, and kidney injury molecule-1 (KIM-1) have been utilised in recent years to identify the development of chronic kidney disease (CKD). However, attempts to use them as broad markers to check for renal injury in patients and to pinpoint the kidney injury site have been unsuccessful. Therefore the search for an ideal panel of biomarkers predicting progression of CKD is still ongoing. The present study is designed to evaluate the biomarkers for CKD from NGAL, KIM-1, Beta trace protein (BTP) and Asymmetric dimethylarginine (ADMA). For this case-control study, 100 participants were selected on the basis of inclusion and exclusion criteria at the Index Medical College Hospital and Research Centre, Madhya Pradesh, there were 67 male subjects and 33 female CKD subjects and 100 non-CKD subjects (60 male and 40 female) matched for age and sex were taken from the hospital. Between the CKD and non-CKD participants, the levels of BTP, plasma NGAL, KIM-1, and ADMA were compared and found to be substantially higher than those in the controls. Abnormal renal function is linked to disturbed blood levels of BTP, NGAL, KIM-1, and ADMA. Strong correlations exist between increased blood levels of BTP, NGAL, KIM-1, and ADMA and reduced kidney function. They might thus be used to estimate the decline of renal function and the progression of CKD.


A low-leakage sample plug injection scheme for crossform microfluidic capillary electrophoresis devices incorporating a restricted cross-channel intersection.
This study develops a crossform CE microfluidic device in which a single-circular barrier or a double-circular barrier is introduced at the cross-channel intersection. Utilizing a conventional crossform injection scheme, it is shown that these barriers reduce sample leakage and deliver a compact sample band into the separation channel, thereby ensuring an enhanced detection performance. A series of numerical and experimental investigations are performed to investigate the effects of the barrier type and the barrier ratio on the flow streamlines within the microchannel and to clarify their respective effects on the sample leakage ratio and sample plug variance during the injection process. The results indicate that a single-circular barrier injector with a barrier ratio greater than 20% and a double-circular barrier injector with a barrier ratio greater than 40% minimize the sample leakage ratio and produce a compact sample plug. As a result, both injectors have an excellent potential for use in high-quality, high-throughput chemical analysis procedures and in many other applications throughout the micro-total analysis systems field.


Functional characterization of 12 allelic variants of CYP2C8 by assessment of paclitaxel 6α-hydroxylation and amodiaquine N-deethylation.
Cytochrome P450 2C8 (CYP2C8) is one of the enzymes primarily responsible for the metabolism of many drugs, including paclitaxel and amodiaquine. CYP2C8 genetic variants contribute to interindividual variations in the therapeutic efficacy and toxicity of paclitaxel. Although it is difficult to investigate the enzymatic function of most CYP2C8 variants in vivo, this can be investigated in vitro using recombinant CYP2C8 protein variants. The present study used paclitaxel to evaluate 6α-hydroxylase activity and amodiaquine for the N-deethylase activity of wild-type and 11 CYP2C8 variants resulting in amino acid substitutions in vitro. The wild-type and variant CYP2C8 proteins were heterologously expressed in COS-7 cells. Paclitaxel 6α-hydroxylation and amodiaquine N-deethylation activities were determined by measuring the concentrations of 6α-hydroxypaclitaxel and N-desethylamodiaquine, respectively, and the kinetic parameters were calculated. Compared to the wild-type enzyme (CYP2C8.1), CYP2C8.11 and CYP2C8.14 showed little or no activity with either substrate. In addition, the intrinsic clearance values of CYP2C8.8 and CYP2C8.13 for paclitaxel were 68% and 67% that of CYP2C8.1, respectively. In contrast, the CLint values of CYP2C8.2 and CYP2C8.12 were 1.4 and 1.9 times higher than that of CYP2C8.1. These comprehensive findings could inform for further genotype-phenotype studies on interindividual differences in CYP2C8-mediated drug metabolism.


[Influence of ethinyl estradiol sulfonate on the decreased urinary bladder tonus in the menopause].
In 40 women with hypotonic urinary bladder the influence of 17alpha-Athinyl-3-isopropyl-sulfonyloxy-Ostradiol (Athinylöstradiol) (3 X 15 mug/die without weekend) was examined concerning the intravesical pressure; The cystotonometry has been done just before as well in intervalls of 2 months during half year's period of treatment. The authors used the fill-up-cystotonometry of Hartl. The intra-vesical pressure rose significantly by the influence of Athinylöstradiolsulfonat after 2 months treatment already. In comparison to the hypotonic value before treatment there was an average normotonic urinary bladder after application of Athinylöstradiolsulfonat past 4 and 6 months. Incidence on clinical relevance of these results.


[The resisting patient--interaction problems in daily clinical practice].
Resistance presenting as non-compliance is a challenge for daily medical practice insofar as this behaviour may have serious negative consequences in the medical, health-economic and psycho-hygienic environment of the physician in charge. By means of a concrete case-example possibilities for a therapeutically satisfying handling of resistance are illustrated. Specific difficulties arising during appropriation of conversation technique are pointed out.


Prevalence and pattern of domestic violence against pregnant Nigerian women.
Five hundred and twenty-two pregnant Nigerians attending the antenatal clinic in two private hospitals in Lagos between January and June 2003 were interviewed using a structured questionnaire about their experiences of domestic violence. One hundred and four women declined to participate; a response rate of 80.1% was obtained. Analysis of the completed questionnaire by 418 respondents showed that 197 (47.1%) women reported a history of abuse. Of the 197 women who reported abuse, 23 (11.7%) experienced abuse for the first time during the current pregnancy, 97 (49.2%) experienced abuse prior to and during the current pregnancy and in the remaining 77 (39.1%) abuse predate the current pregnancy. A total of 120 (28.7%) women experienced some form of abuse during current pregnancy. Although all social and ethnic groups were involved, no association could be established between prevalence and pattern of abuse and sociodemographic characteristics. Verbal abuse was the most common type of abuse reported (52.3%), followed by economic deprivation (30%), physical abuse (25%), threat of violence (10.8%) and forced sex in 14.2%. The perpetrators of the abuse were husband and boyfriend (78.7%), in-laws (31.5%) and other relations (6.1%). The majority of abused women (99.0%) were not ready to report the abuse to the police. In conclusion, domestic violence is common in our environment and health-care providers should be alert to the clues in order to protect the women from further abuse.


AGING, DIABETES, AND FALLS.
KEY POINTS Falls are a major health issue for older adults, leading to adverse events and even death. Older persons with type 2 diabetes are at increased risk of falling compared to healthy adults of a similar age. Over 400 factors are associated with falls risk, making identification and targeting of key factors to prevent falls problematic. However, the major risk factors include hypertension, diabetes, pain, and polypharmacy. In addition to age and polypharmacy, diabetes-related loss of strength, sensory perception, and balance secondary to peripheral neuropathy along with decline in cognitive function lead to increased risk of falling. Designing specific interventions to target strength and balance training, reducing polypharmacy to improve cognitive function, relaxation of diabetes management to avoid hypoglycemia and hypotension, and relief of pain will produce the greatest benefit for reducing falls in older persons with diabetes. Abbreviation: DPN = diabetic polyneuropathy.


Use of hamster as a model to study diet-induced atherosclerosis.
Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apoB-100 and intestinal apoB-48 secretion, and uptake of the majority of LDL cholesterol via the LDL receptor pathway. Early work suggested hamsters fed high cholesterol and saturated fat diets responded similarly to humans in terms of lipoprotein metabolism and aortic lesion morphology. Recent work has not consistently replicated these findings. Reviewed was the literature related to controlled hamster feeding studies that assessed the effect of strain, background diet (non-purified, semi-purified) and dietary perturbation (cholesterol and/or fat) on plasma lipoprotein profiles and atherosclerotic lesion formation. F1B hamsters fed a non-purified cholesterol/fat-supplemented diet had more atherogenic lipoprotein profiles (nHDL-C > HDL-C) than other hamster strains or hamsters fed cholesterol/fat-supplemented semi-purified diets. However, fat type; saturated (SFA), monounsaturated or n-6 polyunsaturated (PUFA) had less of an effect on plasma lipoprotein concentrations. Cholesterol- and fish oil-supplemented semi-purified diets yielded highly variable results when compared to SFA or n-6 PUFA, which were antithetical to responses observed in humans. Dietary cholesterol and fat resulted in inconsistent effects on aortic lipid accumulation. No hamster strain was reported to consistently develop lesions regardless of background diet, dietary cholesterol or dietary fat type amount. In conclusion, at this time the Golden-Syrian hamster does not appear to be a useful model to determine the mechanism(s) of diet-induced development of atherosclerotic lesions.


Implementation of a patient-centered mobile shared decision making platform and healthcare workers' evaluation: a case in a medical center.
Shared decision making is a patient-centered clinical decision-making process that allows healthcare workers to share the existing empirical medical outcomes with patients before making critical decisions. This study aims to explore a project in a medical center of developing a mobile SDM in Taiwan. Chi Mei Medical Center developed the mobile SDM platform and conducted a survey of evaluation from healthcare workers. A three-tier platform that based on cloud infrastructure with seven functionalities was developed. The survey revealed that healthcare workers with sufficient SDM knowledge have an antecedent effect on the three perceptive factors of acceptance of mobile SDM. Resistance to change and perceived ease of use show significant effect on behavioral intention. We provided a comprehensive architecture of mobile SDM and observed the implementation in a medical center. The majority of healthcare workers expressed their acceptancem; however, resistance to change still present. It is, therefore, necessary to be eliminated by continuously promoting activities that highlight the advantages of the Mobile SDM platform. In clinical practice, we validated that the mobile SDM provides patients and their families with an easy way to express their concerns to healthcare workers improving significantly their relationship with each other.


Interaction of Phytocompounds of Echinacea purpurea with ABCB1 and ABCG2 Efflux Transporters.
Preparations of Echinacea purpurea (E. purpurea) are widely used for the management of upper respiratory infections, influenza, and common cold, often in combination with other conventional drugs. However, the potential of phytochemical constituents of E. purpurea to cause herb-drug interactions via ABCB1 and ABCG2 efflux transporters remains elusive. The purpose of this study was to investigate the impact of E. purpurea-derived caffeic acid derivatives (cichoric acid and echinacoside) and tetraenes on the mRNA and protein expression levels as well as on transport activity of ABCB1 and ABCG2 in intestinal (Caco-2) and liver (HepG2) cell line models. The safety of these compounds was investigated by estimating EC20 values of cell viability assays in both cell lines. Regulation of ABCB1 and ABCG2 protein in these cell lines were analyzed after 24 h exposure to the compounds at 1, 10, and 50 μg/mL. Bidirectional transport of 0.5 μg/mL Hoechst 33342 and 5 μM rhodamine across Caco-2 monolayer and profiling for intracellular concentrations of the fluorophores in both cell lines were conducted to ascertain inhibition effects of the compounds. Cichoric acid showed no cytotoxic effect, while the EC20 values of tetraenes and echinacoside were 45.0 ± 3.0 and 52.0 ± 4.0 μg/mL in Caco-2 cells and 28.0 ± 4.3 and 62.0 ± 9.9 μg/mL in HepG2 cells, respectively. In general, the compounds showed heterogeneous induction of ABCB1 with the strongest 3.6 ± 1.2-fold increase observed for 10 μg/mL tetraenes in Caco-2 cells (p < 0.001). However, the compounds did not induce ABCG2. None of the phytocompounds inhibited significantly net flux of the fluorophores across Caco-2 monolayers. Overall, tetraenes moderately induced ABCB1 but not ABCG2 in Caco-2 and HepG2 cells while no compound significantly inhibited activity of these transporters at clinically relevant concentration to cause herb-drug interactions.


Evolution of Conspecific Brood Parasitism versus Cooperative Breeding as Alternative Reproductive Tactics.
Cooperative breeding and conspecific brood parasitism can both be favored by ecological saturation of breeding territories or nest sites. Here, we develop a model that links these alternative reproductive tactics by focusing on nonnesting females (S) that either breed cooperatively with a nesting female (N) or parasitize a third, outside host female (H). We find that cooperative breeding is more likely to evolve with increasing relatedness of cooperating females (S or N) to the outside host female (H) and with increasing costs to the hosts for receiving parasitic eggs. Conversely, cooperation is less likely with increasing kinship between the two potentially cooperative nesters (S and N). This is because even the nesting female gains higher inclusive fitness as long as the number of parasitic eggs (of her otherwise potentially cooperating partner) is sufficiently high. We find the relationship between kinship and reproductive skew within cooperative nests can be either positive or negative depending on the fecundity of parasites versus nesting females. We also find that either of the cooperatively nesting females is more likely to tolerate a smaller fraction of group reproduction as kinship with the host female increases and as the host reproduces more (relative to the parasite) in outside nests. Finally, our model predicts that, as the outside option of conspecific brood parasitism becomes more profitable, helping behavior (zero reproduction by one female) is less likely to evolve in cooperatively breeding groups.


Deep Endometriosis of the Terminal Ileum Presenting With Cyclic Recurrent Small Bowel Obstruction.
Here, we discuss a case of a 42-year-old premenopausal female who presented with chronic pelvic pain and recurrent small bowel obstruction during menstruation. The patient reported a nine-year history of pelvic pain and a four-year history of episodic small bowel obstruction requiring multiple prior inpatient admissions. During these admissions, the obstruction was managed conservatively with bowel rest and nasogastric tube placement; however, symptoms would recur with subsequent menstrual cycles. Computed tomography showed diffusely dilated loops of small bowel with a transition point in the central anterior pelvis, and magnetic resonance enterography revealed a mass-like area involving small bowel loops in the mid pelvis. The patient underwent laparoscopic surgical intervention including bowel resection with re-anastomosis, hysterectomy, bilateral salpingectomy, and left oophorectomy. Intraoperative findings included severe distention of the proximal bowel with a discrete deep endometriosis lesion of the terminal ileum which was confirmed on final pathologic examination. This case emphasizes the importance of considering endometriosis as the etiology of recurrent catamenial small bowel obstruction, particularly in premenopausal women.


[Three patients with a fracture during methotrexate use, possibly due to methotrexate osteopathy].
Three female patients, aged 76, 64 and 74 years old, who were treated with low-dose methotrexate due to an inflammatory joint disorder, developed severe pain in a lower extremity. The pain increased on weight bearing and could not be explained by arthritis. Conventional x-ray investigation showed a fracture in the second patient. In the other two patients insufficiency fractures were visualized by MRI and bone scan. Because methotrexate osteopathy was suspected, treatment with methotrexate was stopped. All three patients made a rapid recovery after discontinuation. Methotrexate osteopathy is characterized by pain, osteoporosis and microfractures, and was first reported in children treated with high-dose methotrexate for a malignancy. Similar clinical features are reported in the literature in patients with chronic joint inflammation treated with low-dose methotrexate. The causal relationship between the insufficiency fractures and the use of methotrexate is still under debate. Although the clinical picture fits with methotrexate osteopathy, these patients often also have other risk factors for osteoporotic insufficiency fractures.


Treatment with potassium bromide mitigates ataxia and reduces tremor in lambs with perennial ryegrass toxicosis.
Aims: To assess the use of potassium bromide (KBr) as a therapeutic intervention for perennial ryegrass toxicosis (PRGT) in lambs fed ryegrass seed containing lolitrem B. Methods: Male lambs aged 10-12 months (n = 43) were assigned to receive ryegrass seed containing lolitrem B, at a dose of 0.16 mg/kg/day (Groups 2, 3 and 4), or lucerne chaff and molasses (Groups 1 and 5). Lambs in Groups 2 and 3 were observed for clinical signs and gait changes until defined signs of PGRT were observed, when they were transferred, with lambs in Group 1, to the Testing phase of the trial. Lambs in Group 3 were then treated with a single oral dose of 300 mg/kg bromide. Lambs in Groups 4 and 5 received KBr daily from the start of the trial (540 mg/kg bromide over 3 days then 20 mg/kg daily) and were transferred to the Testing phase after 18 days. Clinical examination and gait assessment, and surface electromyography of the triceps muscle, measuring root-mean-square (RMS) voltages, were carried out on Days 0, 1 and 2 of the Testing phase followed by necropsy, histopathology, measurement of concentrations of bromide in serum and CSF and faecal cortisol metabolites (FCM). Results: In Group 3 lambs, mean composite gait scores decreased between Testing phase Day 0 and Days 1 and 2 (p < 0.001), but increased in lambs in Group 2 between Day 0 and Day 2 (p = 0.015). Scores for lambs in Group 3 on Day 2 were lower than for lambs in Group 2 (p < 0.001). Mean RMS voltages on Day 2 were higher in lambs in Group 2 than Group 3 (p = 0.045). Mean concentrations of bromide in serum were >800 µg/mL in lambs in Groups 3 and 4 on Day 2. Concentrations of FCM were higher in lambs from Group 2 than in Groups 1 or 5, but were similar in Groups 2, 3 and 4. Histopathological findings in the cerebellum of lambs from Groups 2, 3 and 4 were similar, showing pyknosis of neurons within the granular layer of the cerebellum and Purkinje neuron proximal axonal spheroid formation. Conclusions and clinical relevance: A single oral dose of 300 mg/kg bromide in lambs with neurological signs of PRGT resulted in reduced composite gait scores and reduced RMS voltages, indicating a significant improvement in clinical signs of ataxia, movement disorder and muscle tremor associated with the neurotoxic effects of lolitrem B.


Neuroprotective effects of carnosic acid on neuronal cells under ischemic and hypoxic stress.
Ischemia/hypoxia induces oxidative stress which is associated with neurodegenerative diseases. The present study investigated protective mechanism of carnosic acid (CA) on ischemia/reperfusion and hypoxia-induced neuronal cell injury. The results showed that CA reduced 52% of the infarct volume from brains under ischemia/reperfusion in vivo and protected the PC12 cells from hypoxic injury in vitro. CA (1.0 µM) enhanced cell viability, prevented lactic dehydrogenase (LDH) release, scavenged reactive oxygen species (ROS), increased superoxide dismutase activity, and attenuated Ca(2+) release, lipid peroxidation, and prostaglandin E2 production in hypoxic PC12 cells. In addition, CA also reduced nitric oxide (NO) and interleukine (IL)-1 and IL-6 production from activated BV-2 microglia. Furthermore, its effect on hypoxia-induced mitogen-activated protein kinases (MAPKs) signaling pathway and caspase-3 was examined. Extracellular signal-regulated protein kinases, c-jun NH2-terminal kinase, and p38 MAPK were activated during hypoxia. CA inhibited MAPKs, caspase-3, and COX-2 activation and correlated well with the diminished LDH release and apoptosis (TUNEL) in PC12 cells under hypoxia. Taken together, CA protected neuronal cells under ischemia/hypoxia through scavenging or reducing of ROS and NO, inhibiting COX-2 and MAPK pathways by anti-inflammatory and anti-oxidative properties.


Mis-regulation of Zn and Mn homeostasis is a key phenotype of Cu stress in Streptococcus pyogenes.
All bacteria possess homeostastic mechanisms that control the availability of micronutrient metals within the cell. Cross-talks between different metal homeostasis pathways within the same bacterial organism have been reported widely. In addition, there have been previous suggestions that some metal uptake transporters can promote adventitious uptake of the wrong metal. This work describes the cross-talk between Cu and the Zn and Mn homeostasis pathways in Group A Streptococcus (GAS). Using a ∆copA mutant strain that lacks the primary Cu efflux pump and thus traps excess Cu in the cytoplasm, we show that growth in the presence of supplemental Cu promotes downregulation of genes that contribute to Zn or Mn uptake. This effect is not associated with changes in cellular Zn or Mn levels. Co-supplementation of the culture medium with Zn or, to a lesser extent, Mn alleviates key Cu stress phenotypes, namely bacterial growth and secretion of the fermentation end-product lactate. However, neither co-supplemental Zn nor Mn influences cellular Cu levels or Cu availability in Cu-stressed cells. In addition, we provide evidence that the Zn or Mn uptake transporters in GAS do not promote Cu uptake. Together, the results from this study strengthen and extend our previous proposal that mis-regulation of Zn and Mn homeostasis is a key phenotype of Cu stress in GAS.


The Impact of Task Demands on Fixation-Related Brain Potentials during Guided Search.
Recording synchronous data from EEG and eye-tracking provides a unique methodological approach for measuring the sensory and cognitive processes of overt visual search. Using this approach we obtained fixation related potentials (FRPs) during a guided visual search task specifically focusing on the lambda and P3 components. An outstanding question is whether the lambda and P3 FRP components are influenced by concurrent task demands. We addressed this question by obtaining simultaneous eye-movement and electroencephalographic (EEG) measures during a guided visual search task while parametrically modulating working memory load using an auditory N-back task. Participants performed the guided search task alone, while ignoring binaurally presented digits, or while using the auditory information in a 0, 1, or 2-back task. The results showed increased reaction time and decreased accuracy in both the visual search and N-back tasks as a function of auditory load. Moreover, high auditory task demands increased the P3 but not the lambda latency while the amplitude of both lambda and P3 was reduced during high auditory task demands. The results show that both early and late stages of visual processing indexed by FRPs are significantly affected by concurrent task demands imposed by auditory working memory.


The Rombo syndrome: a familial disorder with vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, basal cell carcinomas and peripheral vasodilation with cyanosis.
This hitherto unknown and dominantly inherited disorder is characterized by vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, basal cell carcinomas and peripheral vasodilation with cyanosis. It has been present in the family reported for at least four generations. The lesions become visible in late childhood and are most pronounced on the face. Basal cell carcinomas may develop around the age of 35. Histological observations during the early stage include irregularly distributed and atrophic hair follicles, milia, dilated dermal vessels, lack of elastin or elastin in clumps. After light irradiation a tendency to increased repair activity was observed both in epidermis and in the dermal fibroblasts. On exposure to cold the change in the skin temperature of the hands compared with that in the controls was insignificant. The response to adrenalin iontophoresis was weak.


Wolfram's syndrome and HLA.
A Sicilian family with three siblings affected by Wolfram's syndrome (Ws) is reported. HLA typing was performed in eight individuals from this family through three generations. Two of the three patients were HLA DR2 positive. The results suggest that the gene for Ws is not linked to the HLA region on chromosome 6, but located on some other chromosome, and that the allele HLA DR2 might predispose to the mutation responsible for Ws.


Automated Identification of Fiducial Points on 3D Torso Images.
Breast reconstruction is an important part of the breast cancer treatment process for many women. Recently, 2D and 3D images have been used by plastic surgeons for evaluating surgical outcomes. Distances between different fiducial points are frequently used as quantitative measures for characterizing breast morphology. Fiducial points can be directly marked on subjects for direct anthropometry, or can be manually marked on images. This paper introduces novel algorithms to automate the identification of fiducial points in 3D images. Automating the process will make measurements of breast morphology more reliable, reducing the inter- and intra-observer bias. Algorithms to identify three fiducial points, the nipples, sternal notch, and umbilicus, are described. The algorithms used for localization of these fiducial points are formulated using a combination of surface curvature and 2D color information. Comparison of the 3D co-ordinates of automatically detected fiducial points and those identified manually, and geodesic distances between the fiducial points are used to validate algorithm performance. The algorithms reliably identified the location of all three of the fiducial points. We dedicate this article to our late colleague and friend, Dr. Elisabeth K. Beahm. Elisabeth was both a talented plastic surgeon and physician-scientist; we deeply miss her insight and her fellowship.


GRAM and genfragII: solving and testing the single-digest, partially ordered restriction map problem.
GRAM (Genomic Restriction map AsseMbly) takes as input single-digest restriction fragments for a set of overlapping clones and outputs one or more plausible partially ordered restriction maps. For each restriction map, GRAM shows the corresponding alignment of the input clone fragments. Due to the error and uncertainty in experimental data, this problem is computationally difficult to solve; therefore, the principle objective in the design of GRAM is to facilitate man-machine collaborative problem solving. GRAM quickly approximates a solution, as follows. (i) A clustering algorithm determines a probable set of restriction fragments. (ii) An assembly algorithm permutes the set of restriction fragments such that the maximal number of clone fragments are contiguous. The output of the GRAM algorithm is displayed for the user to query and edit. This paper describes the stochastic assembly algorithm and shows how it works with the interactive graphics to support man-machine problem solving. In order to test and verify the performance of GRAM, we have developed a program called genfragII to simulate the digestion of clones and fragments; this program is described and results are presented. GRAM is also being used for a number of genome mapping projects.


Effect of mouse type I interferon on mouse bone marrow cells and peritoneal exudate cells cultured in vitro.
Type I mouse interferon significantly reduces macrophage colony formation from mouse bone marrow cells or mouse peritoneal exudate cells when cultured in vitro in the presence of colony-stimulating factors (CSF) derived from either pregnant mouse uterus (CSFPMUE or LCM (CSFLCM) (concanavalin-A purified preparation from endotoxin-shocked mouse long-conditioned medium). The effect of interferon on granulocyte (G-CFU) or granulocyte-macrophage-mixed (GM-CFU) colonies depended on the CSF used. G-CFU and GM-CFU were somewhat elevated in interferon-treated cells stimulated by CSFPMUE whereas G-CFU and GM-CFU were slightly inhibited in interferon-treated cells stimulated by CSFLCM. The most dramatic effect of interferon was observed in the macrophage population. We conclude that interferon affects differentiation preferentially at the macrophage progenitor cell level.


Microbial degradation of poly-beta-hydroxyalkanoates.
The search for new materials that are not hazardous to the environment has become a major issue in our society, engaged as it is in the attainment of sustainable development. Poly-beta-hydroxyalkanoates (PHA), produced exclusively by prokaryotes, can be used as thermoplastics and are fully biodegradable and innocuous to the environment. Biodegradability testing has quantified the capacity of microorganisms to degrade such new chemical compounds, particularly polyhydroxyalkanoates. Standardized tests may also discover new microorganisms and environmental conditions that accelerate biodegradation. We evaluate various techniques used to assess the biodegradability of PHA, and which may also be applied to test other kinds of polymers.


Lattice Defects in Sub-Micrometer Spin-Crossover Crystals Studied by Electron Diffraction.
Spin-crossover particles of [Fe(Htrz)2trz](BF4) with sizes of some hundred nanometers are studied by in situ electron microscopy. Despite their high radiation sensitivity, it was possible to analyze the particles by imaging and diffraction so that a detailed analysis of crystallographic defects in individual particles became possible. The presence of one or several tilt boundaries, where the tilt axis is the direction of the polymer chains, is detected in each particle. An in situ exposure of the particles to temperature variations or short laser pulses to induce the spin crossover shows that the defect structure only changes after a high number of transformations between the low-spin and high-spin phases. The observations are explained by the anisotropy of the atomic architecture within the crystals, which facilitates defects between weakly linked crystallographic planes.


Toll-like receptor 3 blockade in rhinovirus-induced experimental asthma exacerbations: A randomized controlled study.
Human rhinoviruses (HRVs) commonly precipitate asthma exacerbations. Toll-like receptor 3, an innate pattern recognition receptor, is triggered by HRV, driving inflammation that can worsen asthma. We sought to evaluate an inhibitory mAb to Toll-like receptor 3, CNTO3157, on experimental HRV-16 inoculation in healthy subjects and asthmatic patients. In this double-blind, multicenter, randomized, parallel-group study in North America and Europe, healthy subjects and patients with mild-to-moderate stable asthma received single or multiple doses of CNTO3157 or placebo, respectively, and were then inoculated with HRV-16 within 72 hours. All subjects were monitored for respiratory symptoms, lung function, and nasal viral load. The primary end point was maximal decrease in FEV1 during 10 days after inoculation. In asthmatic patients (n = 63) CNTO3157 provided no protection against FEV1 decrease (least squares mean: CNTO3157 [n = 30] = -7.08% [SE, 8.15%]; placebo [n = 25] = -5.98% [SE, 8.56%]) or symptoms after inoculation. In healthy subjects (n = 12) CNTO3157 versus placebo significantly attenuated upper (P = .03) and lower (P = .02) airway symptom scores, with area-under-the-curve increases of 9.1 (15.1) versus 34.9 (17.6) and 13.0 (18.4) versus 50.4 (25.9) for the CNTO3157 (n = 8) and placebo (n = 4) groups, respectively, after inoculation. All of the severe and 4 of the nonserious asthma exacerbations occurred while receiving CNTO3157. In summary, CNTO3157 was ineffective in attenuating the effect of HRV-16 challenge on lung function, asthma control, and symptoms in asthmatic patients but suppressed cold symptoms in healthy subjects. Other approaches, including blockade of multiple pathways or antiviral agents, need to be sought for this high unmet medical need.


Perceptions of risk and risk management among 735 women who opted for a home birth.
home birth is not included in the Swedish health-care system and the rate for planned home births is less than one in a thousand. The aim of this study was to describe women's perceptions of risk related to childbirth and the strategies for managing these perceived risks. a nationwide study including all women who had given birth at home in Sweden was conducted between 1 January 1992 and 31 July 2005. a total of 735 women had given birth to 1038 children. Of the 1038 questionnaires sent to the women, 1025 (99%) were returned. two open questions regarding risk related to childbirth and two questions answered using a scale were investigated by content analysis. regarding perceived risks about hospital birth, three categories, all related to loss of autonomy, were identified: (1) being in the hands of strangers; (2) being in the hands of routines and unnecessary interventions; and (3) being in the hands of structural conditions. Perceived risks related to a home birth were associated with a sense of being beyond help: (1) worst-case scenario; and (2) distance to the hospital. The perceived risks were managed by using extrovert activities and introvert behaviour, and by avoiding discussions concerning risks with health-care professionals. women who plan for a home birth in Sweden do consider risks related to childbirth but they avoid talking about the risks with health-care professionals. to understand why women choose to give birth at home, health-care professionals must learn about the perceived beneficial effect of doing so.


(+)-Thalianatriene and (-)-Retigeranin B Catalyzed by Sesterterpene Synthases from Arabidopsis thaliana.
Two GFPPS linked (+)-thalianatriene (1) and (-)-retigeranin B (2) sesterterpene synthase genes were identified from the genome of Arabidopsis thaliana. 1 possesses an unprecedented 11-6-5 tricyclic ring system, while 2 contains a characteristic 5-5-5-6-5 pentacyclic ring system. Their structures were determined by extensive NMR spectroscopy, chemical derivatization, and X-ray crystallography. The variable-temp NMR measurement of 3, a diepoxy-bearing derivative of 1, enables us to completely assign the NMR signals of the two conformers as 3a (67%, UUU) and 3b (33%, UUD). A plausible biosynthesis mechanism of 1 was proposed.


A comparative study on basophil histamine release and skin testing in children with allergic rhinitis.
Skin tests and histamine release from basophils induced by the same allergens in children with allergic rhinitis were compared. A qualitative correlation between these two tests was found. Basophil histamine release either spontaneous or allergen-induced during the period of developed allergic symptoms was markedly higher as compared with that in a period of clinical remission. It is concluded that basophil histamine release might be a valuable diagnostic method for detection of allergen(s) responsible for symptoms of allergic rhinitis.


A new species and a new record of Laccaria (Fungi, Basidiomycota) found in a relict forest of the endangered Fagus grandifolia var. mexicana.
Two species of Laccaria discovered in relicts of Fagus grandifolia var. mexicana forests in eastern Mexico are described based on the macro- and micromorphological features, and their identity supported by molecular analysis of the internal transcribed spacer (ITS) and large subunit (LSU) of the ribosomal RNA gene. The phylogeny obtained here showed that one of the Mexican species is nested in an exclusive clade which in combination with its striking morphological features, infers that it represents a new species, while the other species is placed as a member in the Laccaria trichodermophora clade. This is the first report in Mexico of Laccaria with Fagus grandifolia var. mexicana trees, with which the reported species may form ectomycorrhizal association. Descriptions are accompanied with illustrations of macro- and micromorphological characters and a discussion of related taxa are presented.


Costimulatory molecule CD154 in systemic lupus erythematosus and rheumatoid arthritis. Therapeutic perspectives.
SLE is a systemic autoimmune disease characterized by B cell hyperactivity. Evidence from the last years has shown that B cells play a key role in the development of the immune response. The interaction of CD40 on B cells with its ligand CD154 on activated T cells provides a costimulatory signal that induces T dependent B cell proliferation and differentiation with subsequent antibody production. Moreover, CD154 can act as a cytokine, in addition to its main role to mediate the interactions between T and CD40+ target cells. This review focuses on the multiple roles of CD154 in systemic lupus erythematosus and rheumatoid arthritis and its involvement in the humoral immunity disregulation of patients with these diseases. It also takes in consideration the most recent therapeutic perspectives regarding the use of monoclonal antibodies against CD154, which might be a powerful tool in the treatment of these diseases in the future.


[Unrecognised sexual abuse and abdominal and pelvic complaints].
Sexual abuse is a risk factor for developing various abdominal and pelvic complaints. In this clinical lesson we present one case, highlighting this connection and how it can be missed by different medical professionals. Early identification of the underlying connection with sexual abuse can prevent re-traumatization by medical treatments, reduce the risk of the patient being abused again and raises the opportunity for a more appropriate treatment, such as addition or trauma therapy and/or pelvic physiotherapy.


Thrombus formation patterns in the HeartMate II ventricular assist device: clinical observations can be predicted by numerical simulations.
Postimplant device thrombosis remains a life-threatening complication and limitation of continuous-flow ventricular assist devices (VADs). Using advanced computational fluid dynamic (CFD) simulations, we successfully depicted various flow patterns, recirculation zones, and stagnant platelet trajectories which promote thrombus formation and observed that they matched actual thrombus formation patterns observed in Thoratec HeartMate II VADs explanted from patients with pump thrombosis. Previously, these small eddies could not be captured by either digital particle image velocimetry or CFD due to insufficient resolution. Our study successfully demonstrated the potential capability of advanced CFD to be adopted for device optimization, leading to enhanced safety and efficacy of VADs for long-term destination therapy.


Self-consistent-field calculations of proteinlike incorporations in polyelectrolyte complex micelles.
Self-consistent field theory is applied to model the structure and stability of polyelectrolyte complex micelles with incorporated protein (molten globule) molecules in the core. The electrostatic interactions that drive the micelle formation are mimicked by nearest-neighbor interactions using Flory-Huggins chi parameters. The strong qualitative comparison with experimental data proves that the Flory-Huggins approach is reasonable. The free energy of insertion of a proteinlike molecule into the micelle is nonmonotonic: there is (i) a small repulsion when the protein is inside the corona; the height of the insertion barrier is determined by the local osmotic pressure and the elastic deformation of the core, (ii) a local minimum occurs when the protein molecule is at the core-corona interface; the depth (a few kBT' s) is related to the interfacial tension at the core-corona interface and (iii) a steep repulsion (several kBT ) when part of the protein molecule is dragged into the core. Hence, the protein molecules reside preferentially at the core-corona interface and the absorption as well as the release of the protein molecules has annealed rather than quenched characteristics. Upon an increase of the ionic strength it is possible to reach a critical micellization ionic (CMI) strength. With increasing ionic strength the aggregation numbers decrease strongly and only few proteins remain associated with the micelles near the CMI.


Identification of porins in outer membrane of Proteus, Morganella, and Providencia spp. and their role in outer membrane permeation of beta-lactams.
Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, and Providencia alcalifaciens, which were once classified into the same genus, Proteus, were studied. Cefoxitin-resistant mutants from these species were isolated, and it was confirmed that the resistance was attributed to the lack of an outer membrane protein, resulting in a significant decrease in the penetration of hydrophilic cephalosporins through the outer membrane. Comparison of the mutant strains with their parental strains in the diffusion rates of six monoanionic cephalosporins, a zwitterionic cephalosporin (cephaloridine), and a divalent anionic cephalosporin (cephalosporin C) suggested that each species had only one kind of porin protein, with molecular weights of 40,000 (Proteus mirabilis) or 37,000 (the other four species) and that the porins formed channels with cation selectivity, except for Proteus vulgaris. Porin proteins were purified from all the bacterial species except Providencia alcalifaciens, and the radius of the pores formed by the purified porins was estimated by the use of the liposome swelling assay. The pore radii were estimated to be approximately 0.59 nm (Proteus mirabilis), 0.63 nm (Proteus vulgaris), 0.58 nm (Providencia rettgeri), and 0.60 nm (M. morganii), similar to the size of the pore radius of Escherichia coli porins.