Six new dammarane-type triterpene saponins from the leaves of Panax ginseng.
Six new minor saponins, together with known ginsenosides, were isolated from the leaves of Panax ginseng. The new saponins were named as ginsenoside-Rh5, -Rh6, -Rh7 -Rh8, -Rh9 and -Rg7, and their structures were elucidated on the basis of chemical and physicochemical evidence to be as follows: ginsenoside-Rh5: 3beta,6alpha,12beta,24zeta-tetrahydroxy-dammar-20(22),25-diene 6-O-beta-D-glucopyranoside (1), -Rh6: 3beta,6alpha12beta,20(S)-tetrahydroxy-25-hydroperoxy-dammar-23-ene 20-O-beta-D-glucopyranoside (2), -Rh7: 3beta,7beta,12beta,20(S)-tetrahydroxy-dammar-5,24-diene 20-O-beta-D-glucopyranoside (3), -Rh8: 3beta,6alpha,20(S)-trihydroxy-dammar-24-ene-12-one 20-O-beta-D-glucopyranoside (4), -Rh9: 3beta,6alpha,20(S)-trihydroxy-12beta,23-epoxy-dammar-24-ene 20-O-beta-D-glucopyranoside (5) and -Rg7: 3-O-beta-D-glucopyranosyl 3beta,12beta,20(S),24(R)-tetrahydroxy-dammar-25-ene 20-O-beta-D-glucopyranoside (6).


Transmissibility of variant influenza from Swine to humans: a modeling approach.
Respiratory illness was reported among humans and swine at an agricultural fair in 2011; 3 human infections with an influenza A(H3N2) variant (H3N2v) virus were confirmed. Using epidemiologic investigation data, we sought to estimate H3N2v transmissibility from swine to humans. We developed a model of H3N2v transmission among swine and humans and fit it to data from a cohort of 100 agricultural club members reporting swine contact to estimate transmissibility. A sensitivity analysis was performed varying H3N2v prevalence in the club cohort. Using the best-fit transmission probability, we simulated the number of swine-acquired infections among all fair attendees. We estimated the best-fit probability of swine-to-human H3N2v transmission per minute of swine contact. Applying this probability to 14 910 people with swine contact at the fair, we estimate that there were 80 (95% confidence interval [CI], 40-133) H3N2v infections among persons aged <20 years and 58 (95% CI, 29-96) H3N2v infections among person aged ≥20 years. Using early data from investigation of a new virus with unclear transmission properties, we estimated the transmissibility of H3N2v from swine to humans and the burden of H3N2v among fair attendees. Although the risk of H3N2v virus infection is small for fair attendees with minimal swine contact, large populations attend agricultural events each year, and human cases will likely occur when infected swine are present.


Optical parameters of oxide films typically used in optical coating production.
Wavelength dependencies of refractive indices of thin film materials differ for various deposition conditions, and it is practically impossible to attribute a single refractive index wavelength dependence to any typical thin film material. Besides objective reasons, differences in the optical parameters of thin films may also be connected with nonadequate choices of models and algorithms used for the processing of measurement data. The main goal of this paper is to present reliable wavelength dependencies of refractive indices of the most widely used slightly absorbing oxide thin film materials. These dependencies can be used by other researchers for comparison and verification of their own characterization results.


Inverse regulation of the nuclear factor-kappaB binding to the p53 and interleukin-8 kappaB response elements in lesional psoriatic skin.
Nuclear factor-kappaB (NF-kappaB) is an inducible nuclear transcription factor regulating a range of cellular processes. An imbalance of the DNA binding activity of NF-kappaB may, therefore, be part of the pathophysiological mechanisms in psoriasis. The purpose of this study was to determine the NF-kappaB DNA binding activity in psoriatic skin using three different kappaB sites and to determine how DNA binding activity was modulated by the anti-psoriatic drug calcipotriol. By electrophoretic mobility shift assay, we demonstrated that the NF-kappaB DNA binding to the p53 kappaB site was decreased, whereas the NF-kappaB DNA binding to the interleukin-8 (IL-8) kappaB site was increased in lesional psoriatic skin compared with non-lesional psoriatic skin. No regulation was seen on the NF-kappaB DNA binding to the major histocompatibility complex class I kappaB site. These changes were paralleled by a similar decrease in p53 expression and an increase in IL-8 expression in involved psoriatic skin compared with uninvolved skin as determined by quantitative RT-PCR. The alteration in NF-kappaB DNA binding activity was neither accompanied by any change in the expression of the inhibitor kappaB (IkappaB) kinases, IKKalpha, IKKbeta, and IKKgamma nor in the expression of the NF-kappaB inhibitor proteins, IkappaBalpha and IkappaBbeta. Immunofluorescence analysis revealed that p65 was sequestered in the cytoplasm of keratinocytes, whereas p50 exhibited a cytoplasmic as well as a nuclear localization. Interestingly, this distribution of p50 and p65 was similar in lesional and non-lesional psoriatic skin. Topical application of calcipotriol to lesional psoriatic skin for 4 d resulted in increased NF-kappaB binding to the p53 kappaB site and decreased NF-kappaB binding to the IL-8 kappaB site. Taken together, our data demonstrate that the NF-kappaB DNA binding activity is regulated in a specific manner in psoriatic skin depending on the kappaB sites investigated, and that topical treatment of psoriatic skin normalizes the abnormal NF-kappaB binding activity seen in lesional psoriatic skin.


DNA methylation alterations exhibit intraindividual stability and interindividual heterogeneity in prostate cancer metastases.
Human cancers almost ubiquitously harbor epigenetic alterations. Although such alterations in epigenetic marks, including DNA methylation, are potentially heritable, they can also be dynamically altered. Given this potential for plasticity, the degree to which epigenetic changes can be subject to selection and act as drivers of neoplasia has been questioned. We carried out genome-scale analyses of DNA methylation alterations in lethal metastatic prostate cancer and created DNA methylation "cityscape" plots to visualize these complex data. We show that somatic DNA methylation alterations, despite showing marked interindividual heterogeneity among men with lethal metastatic prostate cancer, were maintained across all metastases within the same individual. The overall extent of maintenance in DNA methylation changes was comparable to that of genetic copy number alterations. Regions that were frequently hypermethylated across individuals were markedly enriched for cancer- and development/differentiation-related genes. Additionally, regions exhibiting high consistency of hypermethylation across metastases within individuals, even if variably hypermethylated across individuals, showed enrichment for cancer-related genes. Whereas some regions showed intraindividual metastatic tumor heterogeneity in promoter methylation, such methylation alterations were generally not correlated with gene expression. This was despite a general tendency for promoter methylation patterns to be strongly correlated with gene expression, particularly at regions that were variably methylated across individuals. These findings suggest that DNA methylation alterations have the potential for producing selectable driver events in carcinogenesis and disease progression and highlight the possibility of targeting such epigenome alterations for development of longitudinal markers and therapeutic strategies.


Circulating haptoglobin is an independent prognostic factor in the sera of patients with epithelial ovarian cancer.
This study was conducted to evaluate the prognostic significance of haptoglobin levels in the overall survival of patients presenting with various stages of epithelial ovarian cancer. We employed an in-house sandwich enzyme-linked immunosorbent assay method to determine the concentrations of preoperative haptoglobin and C-reactive protein (CRP) in sera samples obtained from 66 malignant tumors, 60 benign tumors, and 10 normal healthy women. Levels of serum haptoglobin significantly correlated with tumor type (P < .001) and International Federation of Gynecology and Obstetrics stage (P < .05). A significant correlation was observed between clinical stage and patient survival (r = 5.99, P = .026). Our data also indicated that elevated serum haptoglobin levels were associated with poor outcome for overall survival using both univariate and multivariate analyses (P = .048 and P = .036 respectively). Using Pearson's correlation, we have noted that serum CRP concentrations significantly correlated with haptoglobin levels (r(2) = 0.22, P < .001). Immunohistochemical findings and Western blot analyses were compatible with sera levels of haptoglobin in which a higher intensity of staining occurred in late-stage epithelial ovarian cancers. This study provides evidence that preoperative serum levels of haptoglobin could serve as an independent prognostic factor in patients presenting with epithelial ovarian cancer.


Triage disposition of patients with acute myocardial infarction--ACSIS 2000.
In the emergency department the physician is often confronted with the decision of where to hospitalize a patient presenting with chest pain and a possible acute myocardial infarction--in the cardiac care unit or in the internal medicine ward. To characterize the clinical factors involved in the triage disposition of patients hospitalized with AMI in Israel to either CCUs or IMWs and to determine to what extent the perceived probability of ischemia influenced the disposition decision. During a 2 month nationwide prospective survey in the 26 CCUs and 82 of the 94 IMWs in Israel, we reviewed the charts of 1,648 patients with a discharge diagnosis of AMI. The probability of ischemia at admission was determined retrospectively by the Acute Coronary Ischemia Time-Insensitive Predictive Instrument. Co-morbidity was coded using the Index of Coexistent Diseases. The ACI-TIPI score for patients admitted to CCUs or to IMWs was 76.2% and 57.7% respectively (P < 0.001). Multivariate analysis showed that young patients with a high probability of ischemia and low co-morbidity or functional impairment were more likely to be hospitalized in CCUs than in IMWs. In Israel, the factors that strongly influence the initial triage disposition of AMI patients to CCUs or IMWs are age, perceived probability of ischemia, status of co-morbid conditions and functional impairment.


A controlled, randomised trial comparing single to multiple application lidocaine analgesia in paediatric patients undergoing urethral catheterisation procedures.
The aim of this study was to evaluate if discomfort levels are statistically significant when two different topical and intraurethral precatheterisation analgesia strategies are used. The primary objective of this research project was to examine methods to decrease pain experienced by paediatric cystogram patients. Paediatric patients undergoing urinary catheterisations frequently report discomfort. To alleviate catheterisation discomfort in children, some institutions have either used sedation techniques or topical analgesia strategies. Standardisation of topical anaesthetic application prior to paediatric urinary catheterisation has not been demonstrated in the research literature. A prospective, single-blind, randomised, controlled trial. The trial was performed with infants and children aged two months-eight years. The first group received one application of lidocaine five minutes prior to catheterisation. The control group received two applications, spaced five minutes apart prior to catheterisation. The FLACC pain score, as the primary outcome variable, was assessed at the time of the catheterisation. Secondary outcome variables including pre- and postcatheterisation heart rate and parental perception were also measured. Two hundred children between two months-eight years of age were randomly assigned for study inclusion with 91 patients enrolled into the two application groups and 109 patients into the single application group. No statistically significant differences (p = 0.779) in the mean FLACC pain score at the time of the catheterisation between the intervention (single application) group (mean = 3.30) and the control (two application) group (mean = 3.39), heart rate or parental perceptions were observed. Topical and intraurethral lidocaine analgesia strategies prior to urinary catheterisation provide an important tool in reducing discomfort for paediatric patients undergoing urinary catheterisation procedures. This study confirms that multiple applications of intraurethral lidocaine gel add little additional benefits in reducing discomfort over single intraurethral application techniques.


Crocin inhibits the activation of mouse hepatic stellate cells via the lnc-LFAR1/MTF-1/GDNF pathway.
Crocin is the main monomer of saffron, which is a momentous component of traditional Chinese medicine Lang Qing A Ta. Here, we tried to probe into the role of crocin in liver fibrosis. Hematoxylin-eosin staining and Sirius Red staining were used to observe the pathological changes of liver tissues. After hepatic stellate cells (HSCs) were isolated from liver tissues, lnc-LFAR1, MTF-1, GDNF, and α-SMA expressions were detected by qRT-PCR and western blot. Immunohistochemistry and immunofluorescence were used to detect α-SMA expression. Chromatin immunoprecipitation was used to analyze the binding of MTF-1 to the GDNF promoter. Moreover, the dual-luciferase reporter gene, RNA pull-down, and RNA immunoprecipitation were used to clarify the interaction between MTF-1 and GDNF, lnc-LFAR1 and MTF-1. The degree of liver fibrosis was more severe in the mice from the liver fibrosis model, while the liver fibrosis was alleviated by the injection of crocin. lnc-LFAR1, GDNF, and α-SMA were up-regulated, and MTF-1 was down-regulated in liver fibrosis tissues and cells, while these trends were reversed after the injection of crocin. Besides, lnc-LFAR1 negatively regulated MTF-1 expression, and positively regulated GDNF and α-SMA expressions, and MTF-1 was enriched in the promoter region of GDNF. Furthermore, the cellular direct interactions between MTF-1 and GDNF, lnc-LFAR1 and MTF-1 were verified. In vivo experiments confirmed the relief of crocin on liver fibrosis. Our research expounded that crocin restrained the activation of HSCs through the lnc-LFAR1/MTF-1/GDNF axis, thereby ameliorating liver fibrosis.


Comparison of ileal endogenous amino acid flows in broiler chicks and turkey poults.
Ileal endogenous amino acid (IEAA) and total amino acid (TAA) flow (mg/kg of DM intake) in turkey poults and broiler chicks at 3 ages (5, 15, and 21 d) were compared by feeding a N-free diet (NFD) or graded levels of casein (highly digestible protein, HDP). The semipurified diets contained 0 (NFD), 50, 100, or 150 g of casein/kg of diet as the only source of amino acids. Each diet was fed to 6 replicate cages containing 30 (5 d), 10 (15 d), or 8 (21 d) birds per cage for 5 d prior to the collection of ileal digesta. At d 5, IEAA and TAA flow in poults fed the NFD, 50, and 100 g of casein/kg of diet was higher (P < 0.05) than in chicks. The IEAA flows within and between both species on d 15 and 21 were not different. Similar trends were observed for the HDP diets (50, 100, or 150 g of casein/kg of diet). An interaction (P < 0.05) between species and age was observed for most of the amino acids for all treatments. The results from this study suggest that at d 5, poults have significantly higher concentration of IEAA and TAA output relative to chicks. However, by d 15 and 21, there were no species differences in IEAA or TAA flow. These results also showed that IEAA flow is species and age dependent. The increased IEAA flow observed at d 5 should be taken into consideration when formulating starter diets on a digestible amino acid basis.


Intramedullary pancreatic adenocarcinoma metastasis: The first case in literature.
Pancreatic cancer is a common gastrointestinal malignancy, and is often associated with a poor prognosis. Although liver is generally seen as a distant metastasis point, it has been shown that it can metastasize to any organ, especially the gastrointestinal tract, and approximately 0.3% of metastases are observed in spinal cord. We report a 36-year-old woman with a prior history of pancreatic adenocarcinoma who presented to us with a thoracic intramedullary lesion and recent onset of neurological deficits. She underwent surgery with histological confirmation of a diagnosis of metastatic adenocarcinoma. To our knowledge there is no prior report of pure intramedullary spinal cord metastasis from a pancreatic adenocarcinoma in the literature. We report the present patient in view of the rarity of intramedullary spinal cord metastasis and its clinical significance. Although intramedullary metastases are rare, they should be investigated in every patient with malignancy and progressive neurological deficit. While its general prognosis is poor regardless of the type of treatment, early diagnosis and treatment is important in terms of quality of life and survival.


Variability in tellurite resistance and the ter gene cluster among Shiga toxin-producing Escherichia coli isolated from humans, animals and food.
Tellurite-containing media are widely used for the screening and isolation of Shiga toxin-producing Escherichia coli (STEC) O157:H7, but tellurite resistance among non-O157 STEC is poorly characterized. Therefore, we investigated 202 STEC strains representing 61 different serotypes from humans, animals or food for the presence of ter genes by PCR and their correlation with tellurite resistance, by assessing growth on cefixime-tellurite sorbitol MacConkey agar. All strains were screened for terC, terE and terF as markers for the ter gene cluster. Of the 202 strains, 127 contained terC and terE and were tellurite-resistant, but only 121 of these also contained terF. All 72 non-sorbitol-fermenting O157:H7 and O157:NM (non-motile) strains contained terC, terE and terF and expressed tellurite resistance. In contrast, all eight sorbitol-fermenting STEC O157:NM were terC-, terE- and terF-negative and tellurite-sensitive. Among non-O157 STEC, terC, terE and terF were found in all seven O145:NM, four O111:H8/NM, 17 of 18 O26:H11/NM and in 21 strains of 14 other serotypes. The strong correlation between the presence of ter genes and the ability to grow on tellurite-containing media suggest that the ter genes encode tellurite resistance in the vast majority of these strains. The presence of the ter gene cluster was significantly (P<0.00001) associated with the presence of eae genes. We conclude that the use of tellurite-containing media in screening for STEC will allow the detection of STEC O26, O111, O145 and non-sorbitol-fermenting O157, but most strains (in this study 74.3%) from other serotypes will be missed.


Student-led research team-building program may help junior faculty increase productivity in competitive biomedical research environment.
Interdisciplinary research teams can increase productivity among academic researchers, yet many junior investigators do not have the training or financial resources to build productive teams. We developed and tested the acceptability and feasibility of three low-cost services to help junior faculty build and maintain their own research teams. At an urban academic medical centre, we implemented three types of consultation services: 1) giving talks on evidence-based best practices for building teams; 2) providing easy-to-use team building resources via email; and 3) offering a year-long consultation service-co-led by students-that taught faculty to build and maintain research teams. Our primary outcome was the number of faculty who used each service. For the yearlong consultation service, we asked faculty participants to complete three online self-assessments to rate their leadership confidence, the team's performance, and which of the consultation components were most helpful. We used descriptive statistics to evaluate faculty assessment scores at three timepoints by comparing median scores and interquartile ranges. We gave 31 talks on team building to 328 faculty and postdoctoral fellows from 2014 to 2020. Separately, 26 faculty heard about our research team building expertise and requested materials via email. For the consultation service, we helped build or enhance 45 research teams from 2014 to 2020. By the end of the consultation, 100% of the faculty reported they were still maintaining their team. In the initial survey, the majority of participants (95.7%, n = 22) reported having no or few experiences in building teams. Further, when asked to rate their team's performance at 12-months, faculty highly rated many elements of both teamwork and taskwork, specifically their team's productivity (6/7 points), morale (6/7 points), and motivation (6/7 points). By the end of the program, faculty participants also highly rated two components of the consultation program: recruitment assistance (7/10 points) and provision of team management tools (7/10 points). For participating faculty, our program provided valued guidance on recruitment assistance and team management tools. The high demand for team-building resources suggests that junior faculty urgently need better training on how to develop and manage their own team.


Diagnosis and management of skin and soft-tissue infections (SSTI). A literature review and consensus statement: an update.
Skin and soft-tissue infections (SSTIs) are among the most common bacterial infections, posing considerable diagnostic and therapeutic challenges. Fourteen members of the Italian Society of Infectious Diseases, after a careful review of the most recent literature using Medline database and their own clinical experience, updated a previous paper published in 2011 by preparing a draught manuscript of the statements. The manuscript was successively reviewed by all members and ultimately re-formulated the present manuscript during a full day consensus meeting. The microbiological and clinical aspects together with diagnostic features were considered for necrotizing and not necrotizing SSTIs in the light of the most recent guidelines and evidences published in the last five years. The antimicrobial therapy was considered as well - both empirical and targeted to methicillin-resistant Staphylococcus aureus and/or other pathogens, also taking into account the epidemiological and bacterial resistance data and the availability of new antibacterial agents.


Gastric emptying in early noninsulin-dependent diabetes mellitus.
The aims of this study were to determine in early noninsulin-dependent diabetes mellitus (NIDDM): (a) the prevalence of disordered gastric emptying of glucose; (b) the relationship between the blood glucose response to an oral glucose load and gastric emptying; and (c) the relationship between appetite and gastric emptying. Sixteen patients (ages 39-79 yr) with recently diagnosed NIDDM consumed 350 ml water containing 75 g glucose and 99mTc-sulfur colloid while sitting in front of a gamma camera. Blood glucose concentrations were monitored immediately before and after the drink. Hunger and fullness were evaluated using visual analog scales. The results were compared to those obtained in 13 normal subjects of similar age and body mass index. All patients and control subjects were white and non-Hispanic. Gastric emptying was slightly slower in the NIDDM patients when compared to the control subjects (retention at 180 min 15.9 +/- 2.3% versus 3.8 +/- 1.0%, p < 0.001), but there was no significant difference in the 50% emptying time between the two groups. In the NIDDM patients, there was an inverse relationship between the magnitude of the increase in the blood glucose concentration and gastric emptying, e.g., between the area under the curve for blood glucose from 0-60 min and the intragastric retention of the drink at 60 min (r = -0.60, p < 0.05). In the NIDDM patients, fullness was greater (p < 0.005) both before and after the drink, and the score for hunger at 30 min was inversely related to the rate of gastric emptying (r = -0.52, p < 0.05). In patients with early NIDDM, gastric emptying of 75 g glucose is similar to that of normal subjects and is a significant determinant of the glycemic response.


The Genetic Architecture of Emerging Fungicide Resistance in Populations of a Global Wheat Pathogen.
Containing fungal diseases often depends on the application of fungicidal compounds. Fungicides can rapidly lose effectiveness due to the rise of resistant individuals in populations. However, the lack of knowledge about resistance mutations beyond known target genes challenges investigations into pathways to resistance. We used whole-genome sequencing data and association mapping to reveal the multilocus genetic architecture of fungicide resistance in a global panel of 159 isolates of Parastagonospora nodorum, an important fungal pathogen of wheat. We found significant differences in azole resistance among global field populations. The populations evolved distinctive combinations of resistance alleles which can interact when co-occurring in the same genetic background. We identified 34 significantly associated single nucleotide polymorphisms located in close proximity to genes associated with fungicide resistance in other fungi, including a major facilitator superfamily transporter. Using fungal colony growth rates and melanin production at different temperatures as fitness proxies, we found no evidence that resistance was constrained by genetic trade-offs. Our study demonstrates how genome-wide association studies of a global collection of pathogen strains can recapitulate the emergence of fungicide resistance. The distinct complement of resistance mutations found among populations illustrates how the evolutionary trajectory of fungicide adaptation can be complex and challenging to predict.


Gender differences in health-related quality of life of Australian chronically-ill adults: patient and physician characteristics do matter.
The aims of this study were to explore the health-related quality of life (HRQoL) in a large sample of Australian chronically-ill patients (type 2 diabetes and/or hypertension/ischaemic heart disease), to investigate the impact of characteristics of patients and their general practitioners on their HRQoL and to examine clinically significant differences in HRQoL among males and females. This was a cross-sectional study with 193 general practitioners and 2181 of their chronically-ill patients aged 18 years or more using the standard Short Form Health Survey (SF-12) version 2. SF-12 physical component score (PCS-12) and mental component score (MCS-12) were derived using the standard US algorithm. Multilevel regression analysis (patients at level 1 and general practitioners at level 2) was applied to relate PCS-12 and MCS-12 to patient and general practitioner (GP) characteristics. Employment was likely to have a clinically significant larger positive effect on HRQoL of males (regression coefficient (B) (PCS-12) = 7.29, P < 0.001, effect size = 1.23 and B (MCS-12) = 3.40, P < 0.01, effect size = 0.55) than that of females (B(PCS-12) = 4.05, P < 0.001, effect size = 0.78 and B (MCS-12) = 1.16, P > 0.05, effect size = 0.16). There was a clinically significant difference in HRQoL among age groups. Younger men (< 39 years) were likely to have better physical health than older men (> 59 years, B = -5.82, P < 0.05, effect size = 0.66); older women tended to have better mental health (B = 5.62, P < 0.001, effect size = 0.77) than younger women. Chronically-ill women smokers reported clinically significant (B = -3.99, P < 0.001, effect size = 0.66) poorer mental health than women who were non-smokers. Female GPs were more likely to examine female patients than male patients (33% vs. 15%, P < 0.001) and female patients attending female GPs reported better physical health (B = 1.59, P < 0.05, effect size = 0.30). Some of the associations between patient characteristics and SF-12 physical and/or mental component scores were different for men and women. This finding underlines the importance of considering these factors in the management of chronically-ill patients in general practice. The results suggest that chronically ill women attempting to quit smoking may need more psychological support. More quantitative studies are needed to determine the association between GP gender and patient gender in relation to HRQoL.


X chromosome inactivation in nuclear transfer ES cells.
Nuclear transfer ES (ntES) cells are established from cloned blastocysts generated by somatic cell nuclear transfer and are expected to be an important resource for regenerative medicine. However, cloned mammals, generated by similar methods, show various abnormalities, which suggest disordered gene regulation. Random X chromosome inactivation (XCI) has been observed to take place in cloned female mouse embryos, but XCI does not necessarily occur according to Xce strength, a genetic element that determines the likelihood of each X chromosome to be inactivated. This observation suggests incomplete reprogramming of epigenetic marks related to XCI. Here, we investigated XCI in ntES cell lines, which were established using differentiated embryoid bodies that originated from a female mouse ES cell line. We examined Xist RNA localization, histone modifications in the Xist locus, and XCI choice. We did not find substantial differences between the ntES lines and their parental ES line. This suggests that the Xist locus and the epigenetic marks involved in XCI are reprogrammed by nuclear transfer and subsequent ntES cell establishment. In contrast to skewed XCI in cloned mice, our observations indicate that normal XCI choice takes place in ntES cells, which supports the goal of safe therapeutic cloning for clinical use.


Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions.
Inositol phospholipids phosphorylated on D3-position of their inositol rings (3-phosphoinositides) are known to play important roles in various cellular events. Activation of PI (phosphatidylinositol) 3-kinase is essential for aspects of insulin-induced glucose metabolism, including translocation of GLUT4 to the cell surface and glycogen synthesis. The enzyme exists as a heterodimer containing a regulatory subunit and one of two widely-distributed isoforms of the p110 catalytic subunit: p110alpha or p110beta. Activation of PI 3-kinase and its downstream AKT has been demonstrated to be essential for almost all of the insulin-induced glucose and lipid metabolism such as glucose uptake, glycogen synthesis, suppression of glucose output and triglyceride synthesis as well as insulin-induced mitogenesis. Accumulated PI(3,4,5)P(3) activates several serine/threonine kinases containing a PH (pleckstrin homology) domain, including Akt, atypical PKCs, p70S6 kinase and GSK. In the obesity-induced insulin resistant condition, JNK and p70S6K are activated and phosphorylate IRS-proteins, which diminishes the insulin-induced tyrosine phosphorylation of IRS-proteins and thereby impairs the PI 3-kinase/AKT activations. Thus, the drugs which restore the impaired insulin-induced PI 3-kinase/AKT activation, for example, by suppressing JNK or p70S6K, PTEN or SHIP2, could be novel agents to treat diabetes mellitus.


Macrophage-mediated injury and repair after ischemic kidney injury.
Acute ischemic kidney injury is a common complication in hospitalized patients. No treatment is yet available for augmenting kidney repair or preventing progressive kidney fibrosis. Animal models of acute kidney injury demonstrate that activation of the innate immune system plays a major role in the systemic response to ischemia/reperfusion injury. Macrophage depletion studies suggest that macrophages, key participants in the innate immune response, augment the initial injury after reperfusion but also promote tubular repair and contribute to long-term kidney fibrosis after ischemic injury. The distinct functional outcomes seen following macrophage depletion at different time points after ischemia/reperfusion injury suggest heterogeneity in macrophage activation states. Identifying the pathways that regulate the transitions of macrophage activation is thus critical for understanding the mechanisms that govern both macrophage-mediated injury and repair in the postischemic kidney. This review examines our understanding of the complex and intricately controlled pathways that determine monocyte recruitment, macrophage activation, and macrophage effector functions after renal ischemia/reperfusion injury. Careful delineation of repair and resolution pathways could provide therapeutic targets for the development of effective treatments to offer patients with acute kidney injury.


[Effects of tobacco garlic crop rotation and intercropping on tobacco yield and rhizosphere soil phosphorus fractions].
A field plot experiment was conducted to investigate the tobacco yield and different forms of soil phosphorus under tobacco garlic crop rotation and intercropping patterns. The results showed that compared with tobacco monoculture, the tobacco yield and proportion of middle/high class of tobacco leaves to total leaves were significantly increased in tobacco garlic crop rotation and intercropping, and the rhizosphere soil available phosphorus contents were 1.3 and 1.7 times as high as that of tobacco monoculture at mature stage of lower leaf. For the inorganic phosphorus in rhizosphere and non-rhizosphere soil in different treatments, the contents of O-P and Fe-P were the highest, followed by Ca2-P and Al-P, and Ca8-P and Ca10-P were the lowest. Compared with tobacco monoculture and tobacco garlic crop intercropping, the Ca2-P concentration in rhizosphere soil under tobacco garlic crop rotation at mature stage of upper leaf, the Ca8-P concentration at mature stage of lower leaf, and the Ca10-P concentration at mature stage of middle leaf were lowest. The Al-P concentrations under tobacco garlic crop rotation and intercropping were 1.6 and 1.9 times, and 1.2 and 1.9 times as much as that under tobacco monoculture in rhizosphere soil at mature stages of lower leaf and middle leaf, respectively. The O-P concentrations in rhizosphere soil under tobacco garlic crop rotation and intercropping were significantly lower than that under tobacco monoculture. Compared with tobacco garlic crop intercropping, the tobacco garlic crop rotation could better improve tobacco yield and the proportion of high and middle class leaf by activating O-P, Ca10-P and resistant organic phosphorus in soil.


AGAP2-AS1 as a prognostic biomarker in low-risk clear cell renal cell carcinoma patients with progressing disease.
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer and one of the most common cancers. While survival for localized ccRCC is good, the survival of metastatic disease is not, and thirty percent of patients with ccRCC develop metastases during follow-up. Although current scoring methods accurately identify patients at low progression risk, a small subgroup of those patients still experience metastasis. We therefore aimed to identify ccRCC progression biomarkers in "low-risk" patients who were potentially eligible for adjuvant treatments or more intensive follow-up. We assembled a cohort of ccRCC patients (n = 443) and identified all "low-risk" patients who later developed progressing tumors (n = 8). Subsequently, we performed genome-wide expression profiling from formalin-fixed samples obtained at initial surgery from these "low-risk" patients and 16 matched patients not progressing to recurrence with metastasis. The patients were matched for Leibovich sore, creatinine, age, sex, tumor size and tumor stage. Key results were confirmed with qPCR and external data from The Cancer Genome Atlas. Principal component analysis indicated that systematic transcriptomic differences were already detectable at the time of initial surgery. One thousand one hundred sixty-seven genes, mainly associated with cancer and immune-related pathways, were differentially expressed between progressors and nonprogressors. A search for a classifier revealed that overexpression of AGAP2-AS1, an antisense long noncoding RNA, correctly classified 23 of 24 samples, years (4.5 years average) in advance of the discovery of metastasis and without requiring larger gene panels. Subsequently, we confirmed AGAP2-AS1 gene overexpression by qPCR in the same samples (p < 0.05). Additionally, in external data from The Cancer Genome Atlas, overexpression of AGAP2-AS1 is correlated with overall unfavorable survival outcome in ccRCC, irrespective of other prognostic predictors (p = 2.44E-7). AGAP2-AS1 may represent a novel biomarker identifying high-risk ccRCC patients currently classified as "low risk" at the time of surgery.


Vancomycin-intermediate Staphylococcus aureus in Korea.
Recent reports on some methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin have been a major concern in Korea because of the widespread use of vancomycin due to a high prevalence of MRSA in the country. We describe a 45-year-old man with long-standing pelvic abscess due to MRSA. In spite of vancomycin and teicoplanin treatment for a long period of time, the patient died from MRSA sepsis. The blood culture isolate of MRSA exhibited reduced susceptibility to vancomycin (MIC, 8 microg/ml). This is the first report of a vancomycin-intermediate S. aureus case from Korea.


Effect modification by community characteristics on the short-term effects of ozone exposure and mortality in 98 US communities.
Previous research provided evidence of an association between short-term exposure to ozone and mortality risk and of heterogeneity in the risk across communities. The authors investigated whether this heterogeneity can be explained by community-specific characteristics: race, income, education, urbanization, transportation use, particulate matter and ozone levels, number of ozone monitors, weather, and use of air conditioning. Their study included data on 98 US urban communities for 1987 to 2000 from the National Morbidity, Mortality, and Air Pollution Study; US Census; and American Housing Survey. On average across the communities, a 10-ppb increase in the previous week's ozone level was associated with a 0.52% (95% posterior interval: 0.28, 0.77) increase in mortality. The authors found that community-level characteristics modify the relation between ozone and mortality. Higher effect estimates were associated with higher unemployment, fraction of the Black/African-American population, and public transportation use and with lower temperatures or prevalence of central air conditioning. These differences may relate to underlying health status, differences in exposure, or other factors. Results show that some segments of the population may face higher health burdens of ozone pollution.


Mechanical, Fracture, and Microstructural Assessment of Carbon-Fiber-Reinforced Geopolymer Composites Containing Na2O.
For a sustainable environment, geopolymer (GPO) paste can be used in the construction industry instead of Portland cement. Nowadays, sustainable construction and high-efficacy composites are demanding. Therefore, in the present investigation, the mechanical and microstructural efficacy of carbon-fiber-reinforced fly ash-based GPO with different percentages of nano-sodium dioxide (NS) were studied. The investigated percentages of NS were 0%, 1%, 2%, 3%, and 4%. For all the samples, the carbon fiber content was kept the same at 0.5% by weight. Different percentages of NS for all five fabricated GPO composite pastes were assessed with scanning electron microscopy (SEM). Various mechanical parameters of GPO-the compressive strength, toughness modulus, hardness, toughness indices, impact strength, fracture toughness, flexural strength, and elastic modulus-were evaluated. The results revealed that the use of 3% NS was the most effective for ameliorating the mechanical, microstructural, and fracture behavior of GPO. The use of 3% NS in carbon-fiber-reinforced GPO paste showed the maximum improvements of 22%, 46%, 30%, 40%, 14%, 38.4%, 50.2%, 31%, and 64% for the compressive strength, flexural strength, elastic modulus, toughness modulus, hardness, compressive stiffness, bending stiffness, fracture toughness, and impact strength, respectively. The SEM study showed that the inclusion of NS improved the microstructure and delivered a denser GPO paste by improving the interfacial zones and quickening the polymerization reaction.


Real-time analysis of endosomal lipid transport by live cell scintillation proximity assay.
A scintillation proximity assay has been developed to study the endosomal trafficking of radiolabeled cholesterol in living cells. Mouse macrophages were cultured in the presence of tritiated cholesterol and scintillant microspheres. Microspheres were taken up by phagocytosis and stored in phagolysosomes. Absorption of tritium beta particles by the scintillant produces light signals that can be measured in standard scintillation counters. Because of the short range of tritium beta particles and for geometric reasons, scintillant microspheres detect only that fraction of tritiated cholesterol localized inside phagolysosomes or within a distance of approximately 600 nm. By incubating cultures in a temperature-controlled microplate reader, the kinetics of phagocytosis and cholesterol transport could be analyzed in near-real time. Scintillation signals were significantly increased in response to inhibitors of lysosomal cholesterol export. This method should prove a useful new tool for the study of endosomal trafficking of lipids and other molecules.


[Effects of human papilloma virus types on course of juvenile respiratory papillomatosis and effectiveness of interferon therapy in children].
Identification of the type of human papilloma virus (HPV) was done by means of polymerase chain reaction in 40 children with juvenile respiratory papillomatosis (JRP). Adjuvant to surgery interferon treatment was carried out in 18 patients (study group) with severe JRP. The rest 22 patients (control group) with less severe papillomatosis received only surgical treatment. The majority of the patients from both the groups had the virus type 6/11 (72.2 and 77.3% for the study and control groups, respectively). The assessment of a relationship between HPV type and effectiveness of interferon treatment in the study group has shown that the share of patients with effective and uneffective interferon therapy in each category (by HPV type) was about the same, i.e. no correlation exists between HPV type and interferon therapy effectiveness.


Dental hygiene education in Nepal.
This article provides information about the history, recent curriculum changes and the legal status of the dental hygiene education in Nepal. It also intends to show, how, even in a poor developing nation, the personal drive of a native Nepalese citizen with a vision and the proper connections can lead to the establishment of a new profession, until then unknown. Data were obtained from the founder of the first dental hygiene school in Nepal through qualitative interviews, and through personal visits to two Nepalese dental hygiene schools in Kathmandu and in Pokhara. Since 2006, the first author serves as curricular advisor, allowing him access and input to drafts of the development of current curricular changes. In 2000, the first dental hygiene course started in Kathmandu. Since then, dental hygiene education has been going through different stages of development and professionalization. In 2005, the programme was changed to 3 years in length in order for students to obtain an academic Certificate in Dental Hygiene. In 2006, the Nepalese Dental Hygienists Association was founded, resulting in greater recognition of the profession, especially by the powerful Nepalese Dental Association. Obscure rules and legislation results in eclectic specifications governing dental hygiene practice. Future challenges for the schools and the dental hygienists association are issues of quality insurance and scope of practice suitable for a developing country. Currently, Nepal is the only country worldwide with an almost equal gender distribution in the dental hygiene profession.


Protein oligomerization equilibria and kinetics investigated by fluorescence correlation spectroscopy: a mathematical treatment.
Fluorescence correlation spectroscopy (FCS) is a technique that is increasingly being used to investigate protein oligomerization equilibria and dynamics. Each individual FCS decay is characterized by its amplitude and a characteristic diffusion time, both of which are sensitive to the degree of dissociation of the protein. Here, we provide a mathematical treatment that relates these observables with the parameters of interest: the equilibrium constants of the different protein dissociation steps and their corresponding dissociation and association kinetic rate constants. We focused on the two most common types of protein homooligomers (dimers and tetramers) and on the experimental variables relevant for the design of the experiment (protein concentration, fractional concentration of labeled protein). The analysis of the theoretical expectations for proteins with different dissociation constants is a key aspect of experiment design and data analysis and cannot be performed without a physically accurate treatment of the system. In particular, we show that the analysis of FCS data using some commonly used empirical models may result in a serious misinterpretation of the experimental results.


Epigenetic resolution of the 'curse of complexity' in adaptive evolution of complex traits.
The age of most genes exceeds the longevity of their genomic and physiological associations by many orders of magnitude. Such transient contexts modulate the expression of ancient genes to produce currently appropriate and often highly distinct developmental and functional outcomes. The efficacy of such adaptive modulation is diminished by the high dimensionality of complex organisms and associated vast areas of neutrality in their genotypic and developmental networks (and, thus, weak natural selection). Here I explore whether epigenetic effects facilitate adaptive modulation of complex phenotypes by effectively reducing the dimensionality of their deterministic networks and thus delineating their developmental and evolutionary trajectories even under weak selection. Epigenetic effects that link unconnected or widely dispersed elements of genotype space in ecologically relevant time could account for the rapid appearance of functionally integrated adaptive modifications. On an organismal time scale, conceptually similar processes occur during recurrent epigenetic reprogramming of somatic stem cells to produce, recurrently and reversibly, a bewildering array of differentiated and persistent cell lineages, all sharing identical genomic sequences despite strongly distinct phenotypes. I discuss whether close dependency of onset, scope and duration of epigenetic effects on cellular and genomic context in stem cells could provide insights into contingent modulation of conserved genomic material on a much longer evolutionary time scale. I review potential empirical examples of epigenetic bridges that reduce phenotype dimensionality and accomplish rapid adaptive modulation in the evolution of novelties, expression of behavioural types, and stress-induced ossification schedules.


How many markers are needed to robustly determine a cell's type?
Our understanding of cell types has advanced considerably with the publication of single-cell atlases. Marker genes play an essential role for experimental validation and computational analyses such as physiological characterization, annotation, and deconvolution. However, a framework for quantifying marker replicability and selecting replicable markers is currently lacking. Here, using high-quality data from the Brain Initiative Cell Census Network (BICCN), we systematically investigate marker replicability for 85 neuronal cell types. We show that, due to dataset-specific noise, we need to combine 5 datasets to obtain robust differentially expressed (DE) genes, particularly for rare populations and lowly expressed genes. We estimate that 10 to 200 meta-analytic markers provide optimal downstream performance and make available replicable marker lists for the 85 BICCN cell types. Replicable marker lists condense interpretable and generalizable information about cell types, opening avenues for downstream applications, including cell type annotation, selection of gene panels, and bulk data deconvolution.


SHANK3 Co-ordinately Regulates Autophagy and Apoptosis in Myocardial Infarction.
Cardiac remodeling and dysfunction are responsible for the high mortality after myocardial infarction (MI). We assessed the potential for Shank3 to alleviate the post-infarction cardiac dysfunction. The experimental MI mice model was constructed by left anterior descending coronary artery ligation. Shank3 knockout aggravated cardiac dysfunction after MI, while Shank3 overexpression alleviated it. The histological examination showed that the infarct size was significantly increased in the acute phase of MI in the Shank3 knockout group, and the cardiac dysfunction of the Shank3 knockout group was even more severe than the Shank3 overexpression group, revealed by echocardiography analyses. In vitro, cultured neonatal cardiomyocytes were subjected to simulated MI. Shank3 downregulation curbed LC3 expression and autophagosome-lysosome fusion. Furthermore, Shank3 downregulation increased cardiomyocyte apoptosis. In contrast, Shank3 upregulation induced autophagy, and inhibited apoptosis under hypoxia. In vivo, western blot analysis showed decreased levels of Atg7, Beclin1, LC3-II, and Bcl-2 as well as increased expression of p62, cleaved caspase-3, and cleaved caspase-9 in the Shank3 knockout group which suffered from MI. On the other hand, it also revealed that Shank3 overexpression induced autophagy and inhibited apoptosis after MI. Shank3 may serve as a new target for improving cardiac function after MI by inducing autophagy while inhibiting apoptosis.


Intergroup bias and self-evaluation: domain-specific self-esteem, threats to identity and dimensional importance.
Recent theoretical statements argue that two predictions about self-esteem and intergroup bias may be derived from social identity theory. The first suggests that in-group bias enhances self-esteem. The second suggests that threats to self-esteem enhance in-group bias. Previous research has provided little firm evidence for either prediction. Much of this work has, however, tended to ignore realistic groups, domain-specific self-esteem, the assessment of self-esteem prior to and following the display of in-group bias and the importance attached to evaluative dimensions. The current investigation sought to redress these issues. In separate experiments, men and women presented with positive and negative feedback, evaluated in-group and out-group success and failure on dimensions important and unimportant to the in-group. Women displayed out-group bias on dimensions unimportant to their in-group (i.e. physical ability) with respect to evaluations of failure. Women subsequently manifested a decrease in physical self-esteem. Men displayed in-group bias on dimensions unimportant to their in-group (i.e. verbal ability) and, following positive feedback, on dimensions important to the in-group (i.e. physical ability). Men subsequently manifested an increase in verbal and physical self-esteem. Global self-esteem was unaffected in each study. These findings suggest that the relative display of bias can affect domain-specific self-esteem. No support was found for the postulate that low or threatened self-esteem can enhance bias on evaluative dimensions important to the in-group.


Electromagnetic scattering by a uniaxial anisotropic sphere located in an off-axis Bessel beam.
Electromagnetic scattering of a zero-order Bessel beam by an anisotropic spherical particle in the off-axis configuration is investigated. Based on the spherical vector wave functions, the expansion expression of the zero-order Bessel beam is derived, and its convergence is numerically discussed in detail. Utilizing the tangential continuity of the electromagnetic fields, the expressions of scattering coefficients are given. The effects of the conical angle of the wave vector components of the zero-order Bessel beam, the ratio of the radius of the sphere to the central spot radius of the zero-order Bessel beam, the shift of the beam waist center position along both the x and y axes, the permittivity and permeability tensor elements, and the loss of the sphere on the radar cross section (RCS) are numerically analyzed. It is revealed that the maximum RCS appears in the conical direction or neighboring direction when the sphere is illuminated by a zero-order Bessel beam. Furthermore, the RCS will decrease and the symmetry is broken with the shift of the beam waist center.


Inositol 1,4,5-triphosphate-induced granule secretion in platelets. Evidence that the activation of phospholipase C mediated by platelet thromboxane receptors involves a guanine nucleotide binding protein-dependent mechanism distinct from that of thrombin.
Phosphoinositide hydrolysis in platelets stimulated by thrombin is thought to be regulated by a pertussis toxin-sensitive guanine nucleotide binding protein (G protein) referred to as Gp. The present studies examine the role of Gp in platelet responses to the thromboxane A2 analogue U46619 and in the pathway by which the phosphoinositide hydrolysis product inositol 1,4,5-triphosphate (IP3) causes secretion. In permeabilized platelets, U46619 caused phosphatidic acid formation and secretion, which were abolished by the G protein inhibitor, guanosine 5'-O-(2-thiophosphate) (GDP beta S). Unlike thrombin, however, U46619-induced phosphoinositide hydrolysis was unaffected by pertussis toxin, and U46619 was unable to inhibit the [32P]ADP ribosylation of the 42-kD pertussis toxin substrate in platelets. IP3-induced secretion, which is known to depend upon intracellular Ca release and subsequent arachidonic acid metabolism, was also inhibited by GDP beta S, as was Ca-induced secretion. These observations suggest that platelet thromboxane A2 (TxA2) receptors are coupled to a toxin-resistant form of Gp distinct from the one that is coupled to thrombin receptors, and that TxA2-stimulated phosphoinositide hydrolysis may serve as a feedback mechanism by which stimuli for arachidonic acid release, such as IP3 and Ca, amplify responses to agonists.


The diagnostic value of elastography score and strain index for the evaluation of thyroid micronodules
Background/aim: In the general population, the frequency of thyroid micronodules is increasing, and the prevalence of malignancy is higher for such nodules. Ultrasonography findings of these nodules are neither specific nor sensitive. The aim of this study was to investigate the diagnostic value of elastography in patients with thyroid micronodules. Materials and methods: A total of 224 patients with thyroid micronodules were recruited in this prospective study. All patients underwent a thyroid fine-needle aspiration biopsy. Elastography scores (ESs) and strain indexes (SIs) were measured with real-time ultrasound elastography. Results: Malignant micronodules had higher ES and SI values than those of benign micronodules (P < 0.001). When ES was used to diagnose malignancy, scores of >3 showed sensitivity of 79.4% and specificity of 98.1%. The area under the curve (AUC) for ES was 0.888 (P < 0.001). The optimal SI cutoff value that differentiated benign from malignant micronodules was 3.06 (98% sensitivity; 91% specificity). The AUC for SI was 0.970 (P < 0.001). Conclusions: ES and SI are beneficial markers for detecting malignant thyroid micronodules. We showed that SI is better than ES when assessing the malignancy of thyroid micronodules.


[Method of correction of microstomia and deviation of the mouth angles by rotation of trapeziform and triangular flaps of the mouth mucosa].
In the paper, the author suggests an essentially new method of dilation of the oral orifice and elimination of mouth angles deviations basing on the principle of new redistribution of local tissues by means of rotation of a trapeziform graft of the mucosa with its submucous layer from the buccal and adoral region. In this method one uses more adequate tissues, which reserves in case of microstomia are located in the buccal and adoral region. The successful utilization in 60 patients of the suggested method of elimination of microstomia arising due to different causes enabled the author to recommend it widely for reparative surgery.


Temporal and regional changes during focal ischemia in rat brain studied by proton spectroscopic imaging and quantitative diffusion NMR imaging.
The early development of focal ischemia after permanent occlusion of the right middle cerebral artery (MCA) was studied in six rats using interleaved measurements by diffusion-weighted NMR imaging (DWI) of water and two variants of proton spectroscopic imaging (SI), multiecho SI (TE: 136, 272, 408 ms) and short TE SI (TE: 20 ms). Measurements on a 4.7-T NMR imaging system were performed between the control phase and approximately 6 h postocclusion. In the center of the ischemic lesion of all rats, the apparent diffusion coefficient (ADC) decreased rapidly to 84.4 +/- 4.2% (mean +/- SD) of the control values approximately 2 min postocclusion. Approximately 6 h postocclusion, the ADC was reduced to 67.1 +/- 5.9%. In contrast, large differences between the animals were observed for the temporal increase of lactate (Lac) in the ipsilateral hemisphere. The maximum Lac signal was reached in four rats after 0.5-1.5 h, and in two rats was not reached even after 6 h postocclusion. Six h postocclusion, SI spectra measured at a TE of 136 ms revealed a decrease in the CH3 signal of N-acetylaspartate (NAA) to 67 +/- 13% of the control values. Differences were observed between the spatial regions of decreased NAA and increased Lac. In the lesions, a T2 relaxation time of Lac of 292 +/- 40 ms, considering a J-coupling constant of 6.9 Hz, was measured. Furthermore, a prolongation of the T2 of the CH3 signal of creatine/phosphocreatine (Cr/PCr) was observed in the lesion, from 163 +/- 22 ms during control to 211 +/- 41 ms approximately 6 h postocclusion. The experiments proved that DWI and proton SI are valuable tools to provide complementary information on processes associated with brain infarcts.


Soy protein products and heme iron absorption in humans.
Dual radioiron tags were used to measure both heme and nonheme iron absorption simultaneously from meat-containing meals in 76 healthy male volunteers. Partial substitution of beef with soy flour reduced the availability of nonheme iron but improved the percentage absorption of heme iron significantly (27 to 59% rise). In contradistinction three other powerful inhibitors of nonheme iron absorption, bran, tea, and desferrioxamine, had no appreciable effect on heme. Ascorbic acid (100 mg and 1000 mg in separate experiments) improved nonheme iron uptake markedly but also failed to alter the assimilation of heme. These studies demonstrate that the deleterious effects on iron nutrition of substituting soy protein for beef are partially offset by improved availability of the remaining heme iron as well as by an increase in the nonheme iron content of the meal.


Design and Testing of a Smartphone Application for Real-Time Self-Tracking Diabetes Self-Management Behaviors.
Type 1 diabetes (T1D) care requires multiple daily self-management behaviors (SMBs). Preliminary studies on SMBs rely mainly on self-reported survey and interview data. There is little information on adult T1D SMBs, along with corresponding compensation techniques (CTs), gathered in real-time. The article aims to use a patient-centered approach to design iDECIDE, a smartphone application that gathers daily diabetes SMBs and CTs related to meal and alcohol intake and exercise in real-time, and contrast patients' actual behaviors against those self-reported with the app. Two usability studies were used to improve iDECIDE's functionality. These were followed by a 30-day pilot test of the redesigned app. A survey designed to capture diabetes SMBs and CTs was administered prior to the 30-day pilot test. Survey results were compared against iDECIDE logs. Usability studies revealed that participants desired advanced features for self-tracking meals and alcohol intake. Thirteen participants recorded over 1,200 CTs for carbohydrates during the 30-day study. Participants also recorded 76 alcohol and 166 exercise CTs. Comparisons of survey responses and iDECIDE logs showed mean% (standard deviation) concordance of 77% (25) for SMBs related to meals, where concordance of 100% indicates a perfect match. There was low concordance of 35% (35) and 46% (41) for alcohol and exercise events, respectively. The high variability found in SMBs and CTs highlights the need for real-time diabetes self-tracking mechanisms to better understand SMBs and CTs. Future work will use the developed app to collect SMBs and CTs and identify patient-specific diabetes adherence barriers that could be addressed with individualized education interventions.


Caregivers' experiences of having a child with cerebral palsy. A meta-synthesis.
To synthesize qualitative research findings of caregiver experiences and challenges in caring for and raising a child with cerebral palsy. A systematic review and meta-synthesis. Four electronic databases: CINAHL, Embase, OVID Medline, and Cochrane, were systematically searched for qualitative research papers published before December 2022. Two independent reviewers assessed eligibility and further appraised the quality of methodology using the Critical Appraisal Skills Program (CASP) tool for qualitative research. A content thematic analysis approach was used to synthesize the qualitative research findings, construct core subthemes, and synthesize themes. Sixty-seven findings were extracted from the 12 included studies. The findings were grouped into eleven sub-themes and then into five synthesized themes. The synthesized themes are 1. Need for convenient healthcare facilities, therapeutic services, and accessible public places, 2. Need for healthcare information and financial aid, 3. Psychological, and physical constraints, 4. Societal rejection and stigma, and 5. Overwhelming caring burden. Caregivers face many challenges in adjusting their lifestyles to meet the needs of the child with cerebral palsy. Some adjustments reported included giving up full-time jobs and businesses to be full-time caregivers, giving up leisure activities, and confinement to one place.


The cellular growth rate controls overall mRNA turnover, and modulates either transcription or degradation rates of particular gene regulons.
We analyzed 80 different genomic experiments, and found a positive correlation between both RNA polymerase II transcription and mRNA degradation with growth rates in yeast. Thus, in spite of the marked variation in mRNA turnover, the total mRNA concentration remained approximately constant. Some genes, however, regulated their mRNA concentration by uncoupling mRNA stability from the transcription rate. Ribosome-related genes modulated their transcription rates to increase mRNA levels under fast growth. In contrast, mitochondria-related and stress-induced genes lowered mRNA levels by reducing mRNA stability or the transcription rate, respectively. We also detected these regulations within the heterogeneity of a wild-type cell population growing in optimal conditions. The transcriptomic analysis of sorted microcolonies confirmed that the growth rate dictates alternative expression programs by modulating transcription and mRNA decay.The regulation of overall mRNA turnover keeps a constant ratio between mRNA decay and the dilution of [mRNA] caused by cellular growth. This regulation minimizes the indiscriminate transmission of mRNAs from mother to daughter cells, and favors the response capacity of the latter to physiological signals and environmental changes. We also conclude that, by uncoupling mRNA synthesis from decay, cells control the mRNA abundance of those gene regulons that characterize fast and slow growth.


Nonsynonymous single nucleotide polymorphisms of NHE3 differentially decrease NHE3 transporter activity.
Genetic determinants appear to play a role in susceptibility to chronic diarrhea, but the genetic abnormalities involved have only been identified in a few conditions. The Na⁺/H⁺ exchanger 3 (NHE3) accounts for a large fraction of physiologic intestinal Na⁺ absorption. It is highly regulated through effects on its intracellular COOH-terminal regulatory domain. The impact of genetic variation in the NHE3 gene, such as single nucleotide polymorphisms (SNPs), on transporter activity remains unexplored. From a total of 458 SNPs identified in the entire NHE3 gene, we identified three nonsynonymous mutations (R474Q, V567M, and R799C), which were all in the protein's intracellular COOH-terminal domain. Here we evaluated whether these SNPs affect NHE3 activity by expressing them in a mammalian cell line that is null for all plasma membrane NHEs. These variants significantly reduced basal NHE3 transporter activity through a reduction in intrinsic NHE3 function in variant R474Q, abnormal trafficking in variant V567M, or defects in both intrinsic NHE3 function and trafficking in variant R799C. In addition, variants NHE3 R474Q and R799C failed to respond to acute dexamethasone stimulation, suggesting cells with these mutant proteins might be defective in NHE3 function during postprandial stimulation and perhaps under stressful conditions. Finally, variant R474Q was shown to exhibit an aberrant interaction with calcineurin B homologous protein (CHP), an NHE3 regulatory protein required for basal NHE3 activity. Taken together, these results demonstrate decreased transport activity in three SNPs of NHE3 and provide mechanistic insight into how these SNPs impact NHE3 function.


Finding the missing link between diversity and activity using denitrifying bacteria as a model functional community.
The recent development and application of numerous methods mainly based on 16S rDNA analyses have brought insights into the questions of which and how many bacterial populations can be found in a given ecosystem. A new and challenging question for microbial ecologists has emerged from the exploration of this diversity: what is its significance for ecosystem functioning? We propose the denitrifying bacteria as a model microbial community for understanding the relationship between community structure and activity, and have summarized the recent progress in studies of this functional community.


Angiotensin inhibition and longevity: a question of hydration.
With the advancement of medical and investigative science, it is somewhat surprising that although it is possible to stabilise medical patients with hypertension and the associated kidney dysfunction, obesity, diabetes and even cancer, there is still no clear method of significantly reducing these chronic disease pathologies, and thus, extending life expectancy. There is one hormone common to these pathologies, the antagonism of which goes some way to clinical improvements, and this is angiotensin, which is released during hypovolaemia. Angiotensin antagonists are used to treat many of these pathologies, and it has been shown in the obesity literature that angiotensin antagonists decrease weight, but also increase the drinking of water. Increased cellular hydration, and hence, improved mitochondrial metabolism could be one of the mechanisms for the reduction in weight seen in these studies, as well as for reducing the other pathologies, all showing metabolic dysfunction. It appears that the application of straightforward physiological regulation might be an appropriate medical approach to the prevention of hypertension, kidney disease, obesity, diabetes and cancer, and thus, to an increased life expectancy.


An analysis of the chest wall motions using the dynamic MRI in healthy elder subjects.
The objective of this study was to compare respiratory motions of the chest wall in the healthy elder subjects (N = 5; mean age, 71 years old) with those in healthy young subjects (n = 9; mean age, 29 years old). Thirty sequential images (scanning time, 0.4s per image) of dynamic MRI on sagittal and coronal planes were obtained while the subjects were deeply breathing. Lung volume change was simultaneously measured with pneumotachometer. In the elder subjects, dimensions of the middle and posterior parts of the diaphragm were linearly related to instantaneous lung volume. There were poor correlation between motion of the anterior diaphragm and transverse motions of the upper rib-cage and lower rib-cage. The contribution of individual part of the chest wall motion to a unit lung volume change, assessed by slope of the linear regression line, in elder subjects were not significantly different from those in young subjects. Either in the elder or young subjects, the middle and posterior parts of the diaphragm moved coordinately. We conclude that chest wall motion in the healthy elder subjects is not different from that in healthy young people and that middle and posterior parts of the diaphragm act as one functional unit during deep breathing.


Cytosolic phospholipase A2 (PLA2), but not secretory PLA2, potentiates hydrogen peroxide cytotoxicity in kidney epithelial cells.
Phospholipase A2 (PLA2) and reactive oxygen species have been implicated both individually and synergistically in various forms of cellular injury. The form(s) of PLA2 important for cell injury and the implications of enhanced activity of the enzyme, however, have not been discerned. Previous studies reveal an increase in PLA2 activity associated with cell injury, but this association does not establish a causal relationship between the increase in activity and the injury. LLC-PK1 cell lines were created that express either the cytosolic PLA2 or a group II PLA2. The susceptibility of these cells to hydrogen peroxide toxicity was determined in order to evaluate the relative importance of these two forms of PLA2 in oxidant injury. Expression of cytosolic PLA2 in the LLC-cPLA2 cell line was associated with a 50-fold increase in PLA2 activity in the cytosolic fraction, an increase in agonist-stimulated arachidonate release, and immunodetection of the cytosolic PLA2 protein that was undetectable in control cells. Exposure to hydrogen peroxide or menadione, but not mercuric chloride, resulted in significantly greater lactate dehydrogenase release in LLC-cPLA2 cells when compared with control cells. Exogenous arachidonic acid (150 microM) did not enhance hydrogen peroxide-induced injury. The intracellular calcium chelator, 1,2-bis-(o-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid/tetra(acetoxymethyl) ester, protected the cells against injury, but the calcium ionophore, A23187, did not increase injury. Glycine conferred no protective effect against hydrogen peroxide toxicity. By contrast to these results with cytosolic PLA2-expressing cells, secretory PLA2 expression to very high levels did not increase susceptibility to hydrogen peroxide. Thus, cytosolic PLA2 may an be an important mediator of oxidant damage to renal epithelial cells.


Enterobius vermicularis worm granuloma mimicking like a pseudo tumor in the anal canal: An unusual clinical presentation.
Enterobius vermicularis is one of the most common intestinal nematode worldwide. Enterobius rarely causes a symptomatic disease. We report here an unusual case of a 60-year old man who came with a polypoidal growth in the anal canal increasing in size for past 20 years. He had pain and intense itching over the mass. The differential diagnosis of squamous papilloma, fibroma and foreign body granuloma were considered. The mass lesion was excised surgically and sent to the pathology laboratory. The mass turned out to be an "E. vermicularis worm granuloma" by histopathologic examination. Thus, timely reporting and surgical resection of such lesion is necessary to prevent further complications. This case is reported here for the unusual presentation of pinworm as a pseudoneoplasm in the anal canal. Incidence of these cases reflected the poor personal hygiene and improper disposal of human excreta in the rural areas. We insist that health education is the only way to control the spread of helminthic infections that causes a heavy disease burden to our country.


Two approaches for estimating disease prevalence from population-based registries of incidence and total mortality.
Two approaches are described for estimating the prevalence of a disease that may have developed in a previous restricted age interval among persons of a given age at a particular calendar time. The prevalence for all those who ever developed disease is treated as a special case. The counting method (CM) obtains estimates of prevalence by dividing the estimated number of diseased persons by the total population size, taking loss to follow-up into account. The transition rate method (TRM) uses estimates of transition rates and competing risk calculations to estimate prevalence. Variance calculations are described for CM and TRM as well as for a variant of CM, called counting method times 10 (CM10), that is designed to yield more precise estimates than CM. We compare these three estimators in terms of precision and in terms of the underlying assumptions required to justify the methods. CM makes fewer assumptions but is typically ess precise than TRM or CM10. For common diseases such as breast cancer, CM may be preferred because its precision is excellent even though not as high as for TRM or CM10. For less common diseases, such as brain cancer, however, TRM or CM10 and other methods that make stabilizing assumptions may be preferred to CM.


Atypical Bacterial Pathogens and Small-Vessel Leukocytoclastic Vasculitis of the Skin in Children: Systematic Literature Review.
Leukocytoclastic small-vessel vasculitis of the skin (with or without systemic involvement) is often preceded by infections such as common cold, tonsillopharyngitis, or otitis media. Our purpose was to document pediatric (≤18 years) cases preceded by a symptomatic disease caused by an atypical bacterial pathogen. We performed a literature search following the Preferred Reporting of Systematic Reviews and Meta-Analyses guidelines. We retained 19 reports including 22 cases (13 females and 9 males, 1.0 to 17, median 6.3 years of age) associated with a Mycoplasma pneumoniae infection. We did not find any case linked to Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Francisella tularensis, or Legionella pneumophila. Patients with a systemic vasculitis (N = 14) and with a skin-limited (N = 8) vasculitis did not significantly differ with respect to gender and age. The time to recovery was ≤12 weeks in all patients with this information. In conclusion, a cutaneous small-vessel vasculitis with or without systemic involvement may occur in childhood after an infection caused by the atypical bacterial pathogen Mycoplasma pneumoniae. The clinical picture and the course of cases preceded by recognized triggers and by this atypical pathogen are indistinguishable.


Cyanotic congenital heart disease with suspected stroke. Should all patients receive antibiotics?
Two patients with cyanotic congenital heart disease (CHD) and erythremia were seen for abrupt onset of focal neurologic deficits and/or seizure without signs of infection or increased intracranial pressure. Clinical features and initial computed tomography (CT) in both cases suggested stroke. Subsequent CT scans demonstrated cerebral abscess, proved at operation. Review of records of patients with CHD at the University of Rochester (NY) Medical Center from 1965 to 1981 disclosed 12 cases with brain abscess but only two cases with aseptic cerebral infarction. All but one patient with abscess were cyanotic. One third of patients with abscess had a clinical picture suggesting stroke. Clinical or radiologic features of half the cases indicated that cerebral infarction may have led to abscess formation. Diagnosis of brain abscess and immediate antibiotic therapy should be strongly considered in patients with cyanotic CHD who suffer a suspected cerebral infarction.


Induction of apoptosis in hormone refractory breast cancer: horizontal modulation is superior to vertical.
Women with estrogen receptor positive (ER+) breast cancer receive treatment with tamoxifen or aromatase inhibitors as adjuvant hormone therapy, but their tumors frequently exhibit de novo or acquired resistance. Current strategies being developed to overcome resistance involve a combination of growth factor pathway inhibitors in addition to hormone therapy. Unfortunately, prolongation of responses with these new approaches is measured only in months. We reasoned that a pro-apoptotic strategy would be preferable since cell death would abrogate the process of adaptive reprogramming and eliminate the resistant cells rather than inhibiting their growth. Our hypothesis was that combinations of pro-apoptotic agents could be designed that would act synergistically as opposed to a merely additively. We examined two model strategies to determine which would result in the greatest synergy: a vertical approach that involved the targeting of two or more steps in a single pathway and a horizontal one, targeting steps in more than one parallel pathway. We found that combinations involving horizontal activation resulted in greater synergy than vertical. Combination index and isobologram analyses revealed that the horizontal combination of the small molecule 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide (CMH) along with T-DM1 displayed the strongest synergy for inducing apoptosis in hormone refractory breast cancer cells. Both the reprogrammed, hormone resistant cells and the wild type responded to certain combinations with synergistic enhancement of apoptosis. These data suggest that combinations using T-DM1 are promising for further in vivo studies both in xenografts and in patients.


Sexual imprinting leads to speciation in locally adapted populations.
Sexual imprinting is widespread in birds and other species but its existence requires explanation. Our results suggest that sexual imprinting leads to speciation in locally-adapted populations if a neutral mating cue-e.g., novel plumage coloration-arises through mutation. Importantly, the mating cue locus is not linked to adaptation loci. Local adaptation is a necessary precursor to speciation and occurs when evolution results in stable genetic polymorphisms with one allele predominating in some areas while others predominate elsewhere. Here we use a deterministic two-niche population genetic model to map the set of migration and selection rates for which polymorphic evolutionary outcomes, i.e., local adaptations, can occur. Approximate equations for the boundaries of the set of polymorphic evolutionary outcomes were derived by Bulmer (American Naturalist, 106, 254, 1972), but our results, obtained by deterministic simulation of the evolutionary process, show that one of Bulmer's equations is inaccurate except when the level of dominance is 0.5, and fails if one of the alleles is dominant. Having an accurate map of the set of migration and selection rates for which polymorphic evolutionary outcomes can occur, we then show using the model of Sibly et al. (Ecology and Evolution, 9, 13506, 2019) that local adaptation in all analyzed cases leads to speciation if a new neutral mating cue arises by mutation. We finish by considering how genome sequencing makes possible testing our model and its predictions.


Effective dose assessment for participants in the National Lung Screening Trial undergoing posteroanterior chest radiographic examinations.
The National Lung Screening Trial (NLST) is a multicenter randomized controlled trial comparing low-dose helical CT with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer. Recruitment was launched in September 2002 and ended in April 2004, when 53,454 participants had been randomized at 33 screening sites. The objective of this study was to determine the effective radiation dose associated with individual chest radiographic screening examinations. A total of 73,733 chest radiographic examinations were performed with 92 chest imaging systems. The entrance skin air kerma (ESAK) of participants' chest radiographic examinations was estimated and used in this analysis. The effective dose per ESAK for each examination was determined with a Monte Carlo-based program. The examination effective dose was calculated as the product of the examination ESAK and the Monte Carlo estimate of the ratio of effective dose per ESAK. This study showed that the mean effective dose assessed from 66,157 postero-anterior chest examinations was 0.052 mSv. Additional findings were a median effective dose of 0.038 mSv, a 95th percentile value of 0.136 mSv, and a fifth percentile value of 0.013 mSv. The effective dose for participant NLST chest radiographic examinations was determined and is of specific interest in relation to that associated with the previously published NLST low-dose CT examinations conducted during the trial.


Artificial reef design affects benthic secondary productivity and provision of functional habitat.
Novel hard substratum, introduced through offshore developments, can provide habitat for marine species and thereby function as an artificial reef. To predict the ecological consequences of deploying offshore infrastructure, and sustainably manage the installation of new structures, interactions between artificial reefs and marine ecosystem functions and services must be understood. This requires quantitative data on the relationships between secondary productivity and artificial reef design, across all trophic levels. Benthic secondary productivity is, however, one of the least studied processes on artificial reefs.In this study, we show that productivity rates of a common suspension feeder, Flustra foliacea (Linnaeus 1758), were 2.4 times higher on artificial reefs constructed from "complex" blocks than on reefs constructed from "simple" blocks, which had a smaller surface area.Productivity rates were highest on external areas of reefs. Productivity rates decreased by 1.56%, per cm distance into the reef on complex reefs and 2.93% per cm into the reef on simple block reefs. The differences in productivity rates between reefs constructed from simple and complex blocks are assumed to reflect different current regimes and food supply between the external and internal reef areas, according to reef type. Synthesis and applications. Our results show that artificial reef design can affect secondary productivity at low trophic levels. We demonstrate that the incorporation of voids into reef blocks can lead to a greater proportion of the structure serving as functional habitat for benthic species. By including such modifications into the design of artificial reefs, it may be possible to increase the overall productivity capacity of artificial structures.


Pseudoprospective Paraclinical Interaction of Radiology Residents With a Deep Learning System for Prostate Cancer Detection: Experience, Performance, and Identification of the Need for Intermittent Recalibration.
The aim of this study was to estimate the prospective utility of a previously retrospectively validated convolutional neural network (CNN) for prostate cancer (PC) detection on prostate magnetic resonance imaging (MRI). The biparametric (T2-weighted and diffusion-weighted) portion of clinical multiparametric prostate MRI from consecutive men included between November 2019 and September 2020 was fully automatically and individually analyzed by a CNN briefly after image acquisition (pseudoprospective design). Radiology residents performed 2 research Prostate Imaging Reporting and Data System (PI-RADS) assessments of the multiparametric dataset independent from clinical reporting (paraclinical design) before and after review of the CNN results and completed a survey. Presence of clinically significant PC was determined by the presence of an International Society of Urological Pathology grade 2 or higher PC on combined targeted and extended systematic transperineal MRI/transrectal ultrasound fusion biopsy. Sensitivities and specificities on a patient and prostate sextant basis were compared using the McNemar test and compared with the receiver operating characteristic (ROC) curve of CNN. Survey results were summarized as absolute counts and percentages. A total of 201 men were included. The CNN achieved an ROC area under the curve of 0.77 on a patient basis. Using PI-RADS ≥3-emulating probability threshold (c3), CNN had a patient-based sensitivity of 81.8% and specificity of 54.8%, not statistically different from the current clinical routine PI-RADS ≥4 assessment at 90.9% and 54.8%, respectively ( P = 0.30/ P = 1.0). In general, residents achieved similar sensitivity and specificity before and after CNN review. On a prostate sextant basis, clinical assessment possessed the highest ROC area under the curve of 0.82, higher than CNN (AUC = 0.76, P = 0.21) and significantly higher than resident performance before and after CNN review (AUC = 0.76 / 0.76, P ≤ 0.03). The resident survey indicated CNN to be helpful and clinically useful. Pseudoprospective paraclinical integration of fully automated CNN-based detection of suspicious lesions on prostate multiparametric MRI was demonstrated and showed good acceptance among residents, whereas no significant improvement in resident performance was found. General CNN performance was preserved despite an observed shift in CNN calibration, identifying the requirement for continuous quality control and recalibration.


The peroxisome protein translocation machinery is developmentally regulated in the fungus Podospora anserina.
Sexual reproduction allows eukaryotic organisms to produce genetically diverse progeny. This process relies on meiosis, a reductional division that enables ploidy maintenance and genetic recombination. Meiotic differentiation also involves the renewal of cell functioning to promote offspring rejuvenation. Research in the model fungus Podospora anserina has shown that this process involves a complex regulation of the function and dynamics of different organelles, including peroxisomes. These organelles are critical for meiosis induction and play further significant roles in meiotic development. Here we show that PEX13-a key constituent of the protein conduit through which the proteins defining peroxisome function reach into the organelle-is subject to a developmental regulation that almost certainly involves its selective ubiquitination-dependent removal and that modulates its abundance throughout meiotic development and at different sexual differentiation processes. Our results show that meiotic development involves a complex developmental regulation of the peroxisome protein translocation system.


Prevalence of the scuticociliate Orchitophrya stellarum in seastars from the Pacific and Atlantic oceans.
As part of a study to investigate the use of the scuticociliate Orchitophrya stellarum as a biological control for the invasive seastar Asterias amurensis in Australia, we collected prevalence data for O. stellarum from 3 seastar species (A. amurensis, A. rubens, Pisaster ochraceus) between 1996 and 1999 from the Pacific (Australia, Japan, Korea, Canada) and Atlantic (France, Netherlands, Canada) oceans. In the Pacific Ocean, for the first time, we found O. stellarum in male A. amurensis in Korea and female A. amurensis in Japan. The parasite was not detected in the invasive A. amurensis from Australia. There was no significant difference between size of infected and uninfected male seastars, nor a correlation between biased sex ratio and parasite prevalence in populations in the Pacific or Atlantic oceans. Therefore, unlike other studies, we found size and sex ratio in seastar populations in the field are unreliable indicators of parasite impacts. Regular monitoring of infected seastar populations in the field would be useful to better understand how sex ratio varies with parasite prevalence. We recommend laboratory studies under controlled conditions to determine the effect of O. stellarum on seastar populations.


Retinopathy of prematurity in infants with birth weight above 1500 grams.
To identify the rate and prognosis of retinopathy of prematurity (ROP) among newborn infants of birthweight of above 1500 grams, and the possible risk factors associated with the disease. A prospective cohort study. Neonatal unit at Maternity Hospital, Kuwait city, Kuwait. All low birth weight infants were examined for the presence of ROP in the period between January 1996 to December 1997. Prospective collection of data on babies who were above 1500 grams was done to find an association between the disease in these babies and some of the maternal and neonatal risk factors. A total of 68 babies of birth weight above 1500 grams were screened for ROP out of which 13 (19.1%) had different stages of the disease. None of the patients had threshold disease requiring surgery. Among the risk factors chosen, oxygen therapy, presence of hypotension at birth and the non-use of surfactant were the only risk factors to be associated with disease. However, with logistic regression analysis, none of these were independently associated with ROP. ROP may occur in newborn infants of larger birthweight but with good prognosis, and oxygen therapy seems to predispose to the disease.


Diffusive media characterization with laser speckle.
The statistical properties of laser speckle with partially coherent light are related to the scattering characteristics of an optically diffuse material. A diffusion equation model is shown to yield a speckle contrast ratio that agrees well with measurements of opaque plastics of varying thicknesses. We show that partially coherent light can be used to determine material parameters for highly scattering media. Measured data for stratified materials with differing scattering properties indicate that this technique may be useful in detecting inhomogeneities.


Insulin transactivator MafA regulates intrathymic expression of insulin and affects susceptibility to type 1 diabetes.
Tissue-specific self-antigens are ectopically expressed within the thymus and play an important role in the induction of central tolerance. Insulin is expressed in both pancreatic islets and the thymus and is considered to be the primary antigen for type 1 diabetes. Here, we report the role of the insulin transactivator MafA in the expression of insulin in the thymus and susceptibility to type 1 diabetes. The expression profiles of transcriptional factors (Pdx1, NeuroD, Mafa, and Aire) in pancreatic islets and the thymus were examined in nonobese diabetic (NOD) and control mice. Thymic Ins2 expression and serum autoantibodies were examined in Mafa knockout mice. Luciferase reporter assay was performed for newly identified polymorphisms of mouse Mafa and human MAFA. A case-control study was applied for human MAFA polymorphisms. Mafa, Ins2, and Aire expression was detected in the thymus. Mafa expression was lower in NOD thymus than in the control and was correlated with Ins2 expression. Targeted disruption of MafA reduced thymic Ins2 expression and induced autoantibodies against pancreatic islets. Functional polymorphisms of MafA were newly identified in NOD mice and humans, and polymorphisms of human MAFA were associated with susceptibility to type 1 diabetes but not to autoimmune thyroid disease. These data indicate that functional polymorphisms of MafA are associated with reduced expression of insulin in the thymus and susceptibility to type 1 diabetes in the NOD mouse as well as human type 1 diabetes.


Breeding Influenza: The Political Virology of Offshore Farming.
The geographic extent, xenospecificity, and clinical course of influenza A (H5N1), the bird flu strain, suggest the virus is an excellent candidate for a pandemic infection. Much attention has been paid to the virus's virology, pathogenesis and spread. In contrast, little effort has been aimed at identifying influenza's social origins. In this article, I review H5N1's phylogeographic properties, including mechanisms for its evolving virulence. The novel contribution here is the attempt to integrate these with the political economies of agribusiness and global finance. Particular effort is made to explain why H5N1 emerged in southern China in 1997. It appears the region's reservoir of near-human-specific recombinants was subjected to a phase change in opportunity structure brought about by China's newly liberalized economy. Influenza, 200 nm long, seems able to integrate selection pressures imposed by human production across continental distances, an integration any analysis of the virus should assimilate in turn.


The hot breath of the IRS: how trustees can avoid intermediate sanctions.
New regulations from the IRS, called "intermediate sanctions," impose stiff taxes and penalties on members of not-for-profit organizations responsible for "unreasonable" compensation. That means administrators, physicians, trustees, and others must be careful to comply with the letter of the law or risk having the IRS breathing heavily down your neck.


Control of intravascular catheters using an array of active steering coils.
To extend the concept of deflecting the tip of a catheter with the magnetic force created in an MRI system through the use of an array of independently controllable steering coils located in the catheter tip, and to present methods for visualization of the catheter and/or surrounding areas while the catheter is deflected. An array of steering coils made of 42-gauge wire was built over a 2.5 Fr (0.83 mm) fiber braided microcatheter. Two of the coils were 70 turn axial coils separated by 1 cm, and the third was a 15-turn square side coil that was 2 x 4 mm2. Each coil was driven independently by a pulse width modulation (PWM) current source controlled by a microprocessor that received commands from a MATLAB routine that dynamically set current amplitude and direction for each coil. The catheter was immersed in a water phantom containing 1% Gd-DTPA that was placed at the isocenter of a 1.5 T MRI scanner. Deflections of the catheter tip were measured from image-based data obtained with a real-time radio frequency (RF) spoiled gradient echo sequence (GRE). The small local magnetic fields generated by the steering coils were exploited to generate a hyperintense signal at the catheter tip by using a modified GRE sequence that did not include slice-select rewinding gradients. Imaging and excitation modes were implemented by synchronizing the excitation of the steering coil array with the scanner by ensuring that no current was driven through the coils during the data acquisition window; this allowed visualization of the surrounding tissue while not affecting the desired catheter position. Deflections as large as 2.5 cm were measured when exciting the steering coils sequentially with a 100 mA maximum current per coil. When exciting a single axial coil, the deflection was half this value with 30% higher current. A hyperintense catheter tip useful for catheter tracking was obtained by imaging with the modified GRE sequence. Clear visualization of the areas surrounding the catheter was obtained by using the excitation and imaging mode even with a repetition time (TR) as small as 10 ms. A new system for catheter steering is presented that allows large deflections through the use of an integrated array of steering coils. Additionally, two imaging techniques for tracking the catheter tip and visualization of surrounding areas, without interference from the active catheter, were shown. Together the demonstrated steerable catheter, control system and the imaging techniques will ultimately contribute to the development of a steerable system for interventional MRI procedures.


[Challenges on the road to personal recovery in Latin America].
The recovery approach proposes a substantial change towards a more holistic perspective that takes into account social needs in mental health. It is a guiding principle in the development of services and research, a lens through which to look at mental health. This article describes four main challenges on the way to the development of a recovery culture in Latin America: Paying attention to local culture; recognizing and encouraging the contribution of users; reducing the emphasis on the diagnostic classification, and paving the way for social justice. Optimal health services can be achieved by combining the knowledge of professionals and high-quality scientifc research, with local popular knowledge and the experience of users.


[Changes in arylsulphatase activity (EC 3.6.1) in the blood serum and urine in women during the pregnancy and in the course of delivery].
By the determination of arylsulphatase A activity (EC 184.108.40.206) in the blood serum and urine obtained from 66 women using the modified method by Lee-Vaupel and Conzelmann it was noticed the increase in the enzyme activity during the pregnancy comparing to the non-pregnant group. The highest enzyme activity was observed in the III trimester of pregnancy. In the following stages of delivery (I, II, III) it was assumed the increase in enzyme activity in urine. The highest enzyme activity in urine was observed in the stage III, and in the serum--in the stage II. It was compared the enzyme activity in primiparae and multiparae proving, that in the serum nd urine this activity is higher in the stages I and II in multiparae, and in the stage III in primiparae.