Genetic Association of the Porcine C9 Complement Component with Hemolytic Complement Activity.
The complement system is a part of the natural immune regulation mechanism against invading pathogens. Complement activation from three different pathways (classical, lectin, and alternative) leads to the formation of C5-convertase, an enzyme for cleavage of C5 into C5a and C5b, followed by C6, C7, C8, and C9 in membrane attack complex. The C9 is the last complement component of the terminal lytic pathway, which plays an important role in lysis of the target cells depending on its self-polymerization to form transmembrane channels. To address the association of C9 with traits related to disease resistance, the complete porcine C9 cDNA was comparatively sequenced to detect single nucleotide polymorphisms (SNPs) in pigs of the breeds Hampshire (HS), Duroc (DU), Berlin miniature pig (BMP), German Landrace (LR), Pietrain (PIE), and Muong Khuong (Vietnamese potbelly pig). Genotyping was performed in 417 F2 animals of a resource population (DUMI: DU×BMP) that were vaccinated with Mycoplasma hyopneumoniae, Aujeszky diseases virus and porcine respiratory and reproductive syndrome virus at 6, 14 and 16 weeks of age, respectively. Two SNPs were detected within the third exon. One of them has an amino acid substitution. The European porcine breeds (LR and PIE) show higher allele frequency of these SNPs than Vietnamese porcine breed (MK). Association of the substitution SNP with hemolytic complement activity indicated statistically significant differences between genotypes in the classical pathway but not in the alternative pathway. The interactions between eight time points of measurement of complement activity before and after vaccinations and genotypes were significantly different. The difference in hemolytic complement activity in the both pathways depends on genotype, kind of vaccine, age and the interaction to the other complement components. These results promote the porcine C9 (pC9) as a candidate gene to improve general animal health in the future.


Serum and Liver Tissue Metabonomic Study on Fatty Liver in Rats Induced by High-Fat Diet and Intervention Effects of Traditional Chinese Medicine Qushi Huayu Decoction.
Qushi Huayu Decoction (QSHY), clinically derived, consists of five crude drugs, commonly used in treating fatty liver in a clinical setting. However, little is known about its metabolomics study. Herein, the serum and liver tissue metabolomics approach, based on gas chromatography coupled to spectrometry (GC/MS), was employed to evaluate the efficacy and the mechanism underlying QSHY in a rat model of high-fat diet-induced fatty liver. With pattern recognition analysis of serum and liver tissue metabolite profile, a clear separation of model group and control group was acquired for serum and liver tissue samples, respectively. The QSHY group showed a predisposition towards recovery mimicking the control group, which was in agreement with the biochemical alterations and histological results. 23 candidate biomarkers were identified in the serum and liver tissue samples that were utilized for exploring the underlying mechanism. The present study suggests that QSHY has significant anti-fatty liver effects on high-fat diet-induced fatty liver in rats, which might be attributed to regulating the dysfunction of beta-alanine metabolism, alanine, aspartate, and glutamate metabolism, glycine, serine, and threonine metabolism, pyruvate metabolism, and citrate cycle. Thus, metabolomics is a useful tool in the evaluation of the efficacy and elucidation of the mechanism underlying the complex traditional Chinese medicine prescriptions.


Artifact- and content-specific quality assessment for MRI with image rulers.
In clinical practice MR images are often first seen by radiologists long after the scan. If image quality is inadequate either patients have to return for an additional scan, or a suboptimal interpretation is rendered. An automatic image quality assessment (IQA) would enable real-time remediation. Existing IQA works for MRI give only a general quality score, agnostic to the cause of and solution to low-quality scans. Furthermore, radiologists' image quality requirements vary with the scan type and diagnostic task. Therefore, the same score may have different implications for different scans. We propose a framework with multi-task CNN model trained with calibrated labels and inferenced with image rulers. Labels calibrated by human inputs follow a well-defined and efficient labeling task. Image rulers address varying quality standards and provide a concrete way of interpreting raw scores from the CNN. The model supports assessments of two of the most common artifacts in MRI: noise and motion. It achieves accuracies of around 90%, 6% better than the best previous method examined, and 3% better than human experts on noise assessment. Our experiments show that label calibration, image rulers, and multi-task training improve the model's performance and generalizability.


Nonmuscle myosin IIA with a GFP fused to the N-terminus of the regulatory light chain is regulated normally.
Nonmuscle myosin II plays a crucial role in a variety of cellular processes (e.g., polarity formation, cell motility, and cytokinesis). It is composed of two heavy chains, two regulatory light chains and two essential light chains. The ATPase activity of the myosin II motor domain is regulated through phosphorylation of the regulatory light chain (RLC) by myosin light chain kinase. To study myosin function and localization in cellular processes, GFP-fused RLCs are widely used; however, the exact kinetic properties of myosins with bound GFP-RLC are poorly described. More importantly, it has not been shown that a regulatory light chain fused at its N-terminus with GFP can maintain the normal phosphorylation-dependent regulation of nonmuscle myosin or serve as a substrate for myosin light chain kinase. We coexpressed N-terminal GFP-RLC with a heavy meromyosin (HMM)-like fragment of nonmuscle myosin IIA and essential light chain to characterize the phosphorylation dynamics and in vitro kinetic properties of the resulting HMM. Myosin light chain kinase phosphorylates the GFP-RLC bound to HMM IIA with the same V(max) as it does the wild type RLC bound to HMM IIA, but the K(m) is about two fold higher for the GFP fusion protein, meaning that it is a somewhat poorer substrate. The steady-state actin-activated MgATPase activity of the GFP-RLC HMM is very low in the absence of phosphorylation demonstrating that the GFP moiety does not prevent formation of the off state. The actin-activated MgATPase activity of phosphorylated GFP-RLC-HMM and is about half that of wild type phosphorylated HMM. The ability of phosphorylated GFP-RLC-HMM to move actin filaments in the actin gliding assay is also slightly compromised. These data indicate that despite some kinetic differences the N-terminal GFP fusion to the regulatory light chain is a reasonable model system for studying myosin function in vivo.


Community rehabilitation workers: do they offer hope to disabled people in South Africa's rural areas?
This article outlines the thinking behind the Wits/Tintswalo community rehabilitation worker training programme which is located in South Africa's eastern Transvaal Lowveld. Drawing on a combination of qualitative and quantitative evidence collected during the first eighteen months in which the CRWs were working full-time (January 1993 - June 1994) it suggests that the two year training programme has been successful in providing therapeutic skills. Key issues raised are whether the coverage of disability is adequate in terms of numbers treated or in terms of categories of disability treated.


Does the gut microbiome environment influence response to systemic breast cancer treatment?
The gut microbiome is a novel player in the pathogenesis and treatment of breast cancer. The term "microbiome" is used to describe the diverse community of micro-organisms existing within the gastrointestinal tract. The gut microbiome plays an important role in oestrogen metabolism through its ability to deconjugate oestrogens within the gut resulting in their reabsorption. Therefore, it is not unsurprising that "dysbiosis", the disruption of normal gut microbiota composition, is now thought to play a role in the development of the disease, as women with breast cancer have been shown to have altered gut microbiota and this has been correlated with tumour characteristics. There is emerging evidence to suggest that the gut microbiota may also impact on breast cancer treatment, by mediating both drug efficacy and toxicity. The present review will discuss the influence of the gut microbiota on systemic treatments for breast cancer, including chemotherapy, anti-human epidermal growth factor receptor 2 (HER2) therapy, endocrine therapy and immunotherapy as well as other targeted treatments.


The assessment of genetic risk of breast cancer: a set of GP guidelines.
Assessing a genetic risk for developing breast cancer is not an easy task for a GP. Current expert guidelines for referring and counselling women with a family history positive for breast cancer are complex and difficult to apply in general practice, and have only two strategies (to refer or not to refer for genetic counselling), giving no guidance for the GP on the management of women with a moderately increased risk of familial breast cancer. We aimed to develop a set of simple practical guidelines for use in primary care for assessing risk and advising women with a positive family history in general practice and aimed to explore its performance. Based on a consensus meeting of the Leiden working party of hereditary tumours, the GPs of a university-related health care centre developed a set of GP guidelines to assess risk and advise women with a family history positive for breast cancer in general practice. The GP guidelines include four therapeutic strategies (reassuring, starting surveillance, starting surveillance and contacting a family cancer clinic, referring to a family cancer clinic). Its performance was tested in 67 patients whose pedigrees were available together with the risk assessment of a clinical geneticist using Claus' tables as a gold standard. The gold standard was dichotomized regarding (i) referral to a family cancer clinic and (ii) surveillance. Two existing expert guidelines were similarly compared. Regarding referral to a family cancer clinic, the GP guidelines were very specific, whereas the expert guidelines were more sensitive. Regarding surveillance, the GP guidelines were very sensitive, whereas the expert guidelines were very specific. The total number of misclassified patients was lowest when using the GP guidelines, and higher when using the expert guidelines. The GP guidelines provide a simplification of current guidelines. Before using them on a larger scale, more testing and refining are needed to increase their sensitivity regarding a referral to a family cancer clinic and their specificity regarding surveillance. They incorporate a role for the GP in the care for women with a family history positive for breast cancer with a moderately increased risk.


Characterization and purification of porcine small intestinal mucus receptor for Escherichia coli K88ac fimbrial adhesin.
The objectives of this study were to investigate the nature of, and to purify K88ac fimbrial adhesin-specific receptors in the mucus from the small intestine of piglet. Adhesion was studied by incubating (3)H-labeled Escherichia coli with mucus that were treated with or without pronase, proteinase, trypsin or sodium metaperiodate. The results indicated that treatment with either proteolytic enzymes or sodium metaperiodate (to oxidize sugars) significantly reduced E. coli K88ac or K88+MB adhesion to the mucus, suggesting that the K88ac and K88+MB specific receptors in this preparation were, at least in part, glycoprotein in nature. The K88+MB fimbriae specific receptor was purified using affinity chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified K88+MB specific receptor together with the above data suggested that the receptor from the mucus of the small intestine of the pig was a 80-kDa glycoprotein.


Dietary protein intake is associated with lean body mass in community-dwelling older adults.
Lean body mass (LBM) is important to maintain physical function during aging. We hypothesized that dietary protein intake and leisure-time physical activity are associated with LBM in community-dwelling older adults. To test the hypothesis, participants (n = 237; age, 65-92 years) did 3-day weighed food records and reported physical activity. Body composition was assessed using dual-energy x-ray absorptiometry. Protein intake was 0.98 ± 0.28 and 0.95 ± 0.29 g/kg body weight in male and female participants, respectively. Protein intake (in grams per kilogram of body weight) was associated with LBM (in kilograms); that is, the differences in LBM were 2.3 kg (P < .05) and 2.0 kg (P = .054) between the fourth vs the first and the fourth vs the second quartiles of protein intake, respectively. Only a minor part of this association was explained by increased energy intake, which follows an increased protein intake. Our study shows that dietary protein intake was positively associated with LBM in older adults with a mean protein intake higher than the current recommended daily allowance of 0.8 g/kg per day. Leisure-time physical activity, predominantly consisting of endurance type exercises, was not related to LBM in this group.


Advances in oral anticoagulation therapy - What's in the pipeline?
Approximately 900,000 people are affected by some sort of venous thromboembolic (VTE) event every year in the United States. VTE diagnosis used to mean treatment with medications that required routine lab monitoring for safety and efficacy. Activated factor X (FXa) inhibition has emerged as a convenient pathway for management of VTE and currently three FXa inhibitors are available for anticoagulation management - rivaroxaban, apixaban, and edoxaban. Continued development of medications utilizing this pathway may offer advantages via novel pharmacokinetic or pharmacodynamic properties that may minimize the adverse effects associated with traditional anticoagulant therapy. This review summarizes the available information regarding pharmacokinetic, pharmacodynamic, and early safety and efficacy data for three factor Xa inhibitors being developed - darexaban, betrixaban and nokxaban. The studies reviewed in this article suggests that three newer agents possess the potential for promise based on early phase I and II trials.


The hot hand in the wild.
Streaks of success have always fascinated people and a lot of research has been conducted to identify whether the "hot hand" effect is real. While sports have provided an appropriate platform for studying this phenomenon, the majority of existing literature examines scenarios in a vacuum with results that might or might not be applicable in the wild. In this study, we build on the existing literature and develop an appropriate framework to quantify the extent to which success can come in streaks-beyond the stroke of chance-in a natural environment. Considering in-game basketball game situations, our analysis provides statistical evidence that individual players do indeed exhibit the hot hand in varying degrees, that is, individual players can consistently get in a streak of successful shots beyond random chance. However, as a whole, the average player exhibits shooting regression, that is, after consecutive makes he tends to perform below expectations. Even though our results are based on a sports setting, we believe that our study provides a path towards thinking of the hot hand beyond a laboratory-like, controlled environment. This is crucial if we want to use similar results to enhance our decision making and better understand short and long term outcomes of repeated decisions.


Which linear compartmental systems can be analyzed by spectral analysis of PET output data summed over all compartments?
General linear time-invariant compartmental systems were examined to determine which systems meet the conditions necessary for application of the spectral analysis technique to the sum of the concentrations in all compartments. Spectral analysis can be used to characterize the reversible and irreversible components of the system and to estimate the minimum number of compartments, but it applies only to systems in which the measured data can be expressed as a positively weighted sum of convolution integrals of the input function with an exponential function that has real-valued nonpositive decay constants. The conditions are met by compartmental systems that are strongly connected, have exchange of material with the environment confined to a single compartment, and do not contain cycles, i.e., there is no possibility for material to pass from one compartment through two or more compartments back to the initial compartment. Certain noncyclic systems with traps, systems with cycles that obey a specified loop condition, and noninterconnected collections of such systems also meet the conditions. Dynamic positron emission tomographic data obtained after injection of a radiotracer, the kinetics of which can be described by any model in the class of models identified here, can be appropriately analyzed with the spectral analysis technique.


Emulsion Stability Modulates Gastric Secretion and Its Mixing with Emulsified Fat in Healthy Adults in a Randomized Magnetic Resonance Imaging Study.
Oil-in-water emulsions have recently become of interest to nutritional sciences because of their ability to influence gastrointestinal digestive processes and ultimately benefit human health. MRI offers the potential to noninvasively characterize the interaction between emulsified lipids and gastric secretion within the stomach. We determined noninvasively how emulsion stability modulates volumes of fat and secretion, layering of fat, and the mixing of emulsified fat with secretion within the stomach. This required the development of MRI technology for quantifying fat and secretion concentrations inside the stomach. Twenty-one healthy adults [13 men, mean ± SD age: 22.5 ± 2.5 y, mean ± SD body mass index (in kg/m2): 22.7 ± 1.8] were analyzed in a single-blind, randomized, parallel design. MRI was used to acquire the distributions of fat and secretion in the stomach after ingestion of 2 emulsions: a stable emulsion (E1) or an unstable emulsion (E4) with 20% fat fraction and ∼0.3 mm droplet sizes. Layer, volume, and mixing variables were fitted to the data and compared between the 2 emulsions. The intragastric mixing between fat and secretion was better with the E4 than the E1 [increase in content heterogeneity of 17.1% (95% CI: 12.3%, 21.9%)]. The E4 demonstrated a linear relation [slope 1.57 (95% CI: 0.86, 2.29)] between the degree of layering and mixing. In contrast, no such relation was detected for the E1. Accumulated secretion volume in the stomach was lower with the E4 [decrease in volume variable ks of 2.3 (95% CI: -3.9, -0.7)] and correlated with the degree of layering (r = 0.62, P < 0.001). In healthy adults, intragastric fat layering was influenced mainly by the degree of intragastric mixing, rather than the overall dominance of secretion. The E1 triggered a higher accumulation of gastric secretion, which in turn facilitated homogenization of intragastric content in comparison with its unstable counterpart. This trial was registered at clinicaltrials.gov as NCT02602158.


Exploratory factor analysis of the fear-avoidance beliefs questionnaire in patients with chronic ankle instability.
To perform an exploratory factor analysis of the Fear-Avoidance Beliefs Questionnaire in patients with chronic ankle instability. A cross-sectional survey study was utilized. The Fear-Avoidance Beliefs Questionnaire was administered to patients with chronic ankle instability who met the inclusion criteria. Both an unrestricted and restricted factor analysis with varimax rotation were utilized to explore the factor structure of the instrument. Kaiser-Meyer-Olkin values were used to determine sampling adequacy. Bartlett's test of sphericity was used to justify that the correlations were suitable for the principal component analysis. The restricted two-factor analysis resulted in two factors with acceptable internal consistency values. The Keiser-Meyer-Olkin value was acceptable (0.81), and Bartlett's test of sphericity was significant (χ2 (55) = 515.59, p < 0.001). The ankle-specific Fear-Avoidance Beliefs Questionnaire consists of two stable factors and should be used to further examine fear-avoidance beliefs in people with chronic ankle instability.


Stress and the Mental Health of Populations of Color: Advancing Our Understanding of Race-related Stressors.
This article provides an overview of research on race-related stressors that can affect the mental health of socially disadvantaged racial and ethnic populations. It begins by reviewing the research on self-reported discrimination and mental health. Although discrimination is the most studied aspect of racism, racism can also affect mental health through structural/institutional mechanisms and racism that is deeply embedded in the larger culture. Key priorities for research include more systematic attention to stress proliferation processes due to institutional racism, the assessment of stressful experiences linked to natural or manmade environmental crises, documenting and understanding the health effects of hostility against immigrants and people of color, cataloguing and quantifying protective resources, and enhancing our understanding of the complex association between physical and mental health.


Career satisfaction of women in surgery: perceptions, factors, and strategies.
With the current and projected shortages of general surgeons, more attention is being paid to the increasing pool of women physicians. This study seeks to understand the variables leading to career satisfaction for women surgeons to better recruit, retain, and support them. Eighteen semi-structured interviews of 12 female and 6 male surgeons 2 to 12 years into practice were qualitatively analyzed and converted to coded, categorized data. Significance was derived by Fisher's exact test. Participants were recruited by snowball sampling. Our sample represents a highly satisfied group of female and male surgeons. Although both women and men describe with equal frequency having made career tradeoffs for personal and family time, and vice versa, women far more frequently than men cite reasons related to their personal time, predictable time, and family relationships as why they are currently satisfied with their career (34.1% versus 8.7%; p < 0.05). Both cite being satisfied by career content equally. When describing strategies used in developing a successful surgical career, women most frequently cite social networks as a key to success (88% versus 12% by men; p < 0.05), and men more frequently cite reasons related to training (29% versus 0% by women; p < 0.05) and compensation (24% versus 0% by women; p < 0.05). Although both men and women make tradeoffs of career for family and family for career, women's perception of satisfaction comes from viewing their surgical career within the broader context of their lives. Women might be attracted to a career that acknowledges and values the whole person beyond the surgeon, and could benefit from work infrastructures that enhance networking.


A Mathematical Model of Neutral Lipid Content in terms of Initial Nitrogen Concentration and Validation in Coelastrum sp. HA-1 and Application in Chlorella sorokiniana.
Microalgae are considered to be a potential major biomass feedstock for biofuel due to their high lipid content. However, no correlation equations as a function of initial nitrogen concentration for lipid accumulation have been developed for simplicity to predict lipid production and optimize the lipid production process. In this study, a lipid accumulation model was developed with simple parameters based on the assumption protein synthesis shift to lipid synthesis by a linear function of nitrogen quota. The model predictions fitted well for the growth, lipid content, and nitrogen consumption of Coelastrum sp. HA-1 under various initial nitrogen concentrations. Then the model was applied successfully in Chlorella sorokiniana to predict the lipid content with different light intensities. The quantitative relationship between initial nitrogen concentrations and the final lipid content with sensitivity analysis of the model were also discussed. Based on the model results, the conversion efficiency from protein synthesis to lipid synthesis is higher and higher in microalgae metabolism process as nitrogen decreases; however, the carbohydrate composition content remains basically unchanged neither in HA-1 nor in C. sorokiniana.


Erratum: Tactile Vibrating Toolkit and Driving Simulation Platform for Driving-Related Research.
An erratum was issued for: Tactile Vibrating Toolkit and Driving Simulation Platform for Driving-Related Research. The Authors section was updated. Ao Zhu1 Annebella Tsz Ho Choi1 Ko-Hsuan Ma1 Shi Cao2 Han Yao1 Jian Wu3 Jibo He4,1 1Psychology Department, School of Social Sciences, Tsinghua University 2Department of Systems Design Engineering, University of Waterloo 3Haier Innovation Design Center, Haier Company 4Psychology Department, School of Education and Psychological Sciences, Sichuan University of Science and Engineering to: Ao Zhu1 Annebella Tsz Ho Choi1 Ko-Hsuan Ma1 Shi Cao2 Han Yao1 Jian Wu3 Jibo He1 1Psychology Department, School of Social Sciences, Tsinghua University 2Department of Systems Design Engineering, University of Waterloo 3Haier Innovation Design Center, Haier Company.


A novel phosphotyrosine-binding domain in the N-terminal transforming region of Cbl interacts directly and selectively with ZAP-70 in T cells.
The protooncogene product Cbl has emerged as a novel signal transduction protein downstream of a number of cell surface receptors coupled to tyrosine kinases. Recently, we and others have reported the activation-dependent association of Cbl with the Syk and ZAP-70 tyrosine kinases through presently undefined mechanisms. Potential Src homology 2 and 3 domain binding sites within the C-terminal half of Cbl mediate in vivo interactions with several signaling proteins; however, the N-terminal transforming region (Cbl-N) lacks recognizable catalytic or protein interaction motifs. Here, we show that in vitro Cbl-N (amino acids 1-357) but not Cbl-C (amino acids 358-906) binds to ZAP-70 in a T cell-activation-dependent manner. A point mutation in Cbl-N, G306E, corresponding to a loss-of-function mutation in the Caenorhabditis elegans Cbl homologue, SLI-1, severely compromised Cbl-N/ZAP-70 binding. Cbl-N/ZAP-70 binding was direct and phosphotyrosine-dependent, thus identifying a phosphotyrosine-binding domain within the transforming region of Cbl. In vivo, Cbl-N expressed in T cells selectively associated with the ZAP-70/zeta complex. These results identify a novel mechanism for the direct participation of the N-terminal region of Cbl in ZAP-70 signal transduction, and suggest a biochemical mechanism for the leukemogenicity of the oncogene v-cbl through potential interaction with proliferation-related phosphotyrosyl proteins.


Superoxide production and expression of nox family proteins in human atherosclerosis.
NAD(P)H oxidases are important sources of superoxide in the vasculature, the activity of which is associated with risk factors for human atherosclerosis. This study was designed to investigate the localization of superoxide production and the expression of the Nox family of NAD(P)H oxidase proteins (gp91phox, Nox1, and Nox4) in nonatherosclerotic and atherosclerotic human coronary arteries. In coronary artery segments from explanted human hearts, we examined intracellular superoxide production with dihydroethidium. In nonatherosclerotic coronary arteries, superoxide was present homogenously throughout the intima, media, and adventitia. In atherosclerotic arteries, there was an additional intense area of superoxide in the plaque shoulder, which is rich in macrophages and alpha-actin-positive cells. p22phox colocalized with gp91phox mainly in macrophages, whereas Nox4 was found only in nonphagocytic vascular cells. Expression of gp91phox and p22phox mRNA was associated with the severity of atherosclerosis. gp91phox correlated with the plaque macrophage content, whereas Nox4 correlated with the content of alpha-actin-positive cells. Nox1 expression was low both in human coronary arteries and isolated vascular cells. Several Nox proteins, including gp91phox and Nox4, may contribute to increased intracellular oxidative stress in human coronary atherosclerosis in a cell-specific manner and thus may be involved in the genesis and progression of human coronary atherosclerotic disease.


[Glucocorticoids, adipose metabolism and insulin resistance].
Obesity, insulin resistance, and type 2 diabetes are associated with elevated concentration of circulating free fatty acid (FFA), which is critically governed by the process of triglyceride lipolysis in adipocytes. Endogenous and exogenous glucocorticoids excess could induce insulin resistance and diabetes. Thus, the effects of glucocorticoids stimulating adipose lipolysis and elevating FFA release may contribute to glucocorticoids-induced insulin resistance and diabetes. This review focuses on the regulation and function of glucocorticoids in adipose lipolysis and metabolism.


Dog bites in children less than fourteen years old in Turin.
The purpose of this study was to describe the epidemiology of injuries caused by dog bites treated in the emergency department of OIRM from January 1, 1997 to December 31, 2000. Data on dog's attacks were obtained from declaration forms filled in the emergency department. 253 children were observed: 145 boys and 118 girls. The mean age was 6.4 years. The peak incidence was in children aged 3 to 8 years old. Fifty-six children (22.31%) required admission to the hospital. Thirty-five were younger than 5 years. Injuries to the face (29.48%), hands (14.55%), legs (9.33%) were more common. The prognosis was 5 (18.97%), 7 (21.74%) and 10 (16.6%) days. Twenty-five children had prognosis over fifteen days (9.88%). Children aged 5 or younger presented most face and hand lesions while children aged 6 to 14 years had most hand, legs and arms injuries. Tetanus and rabies prophylaxis were administered only in 4 and 2 cases respectively, while immunoglobulin anti tetanus were administered in 5 children. The great number of attacks occurred during the summer months, with a peak in June and July. More attention should be paid to the prevention of dog bites. Pediatricians should advice parents about the risks of interactions with dogs.


History of myocardial iron loading is a strong risk factor for diabetes mellitus and hypogonadism in adults with β thalassemia major.
Endocrinopathies are common complications of transfusional hemosiderosis among patients with β thalassemia major (TM). Previous studies had shown associations between some endocrinopathies and iron overload of the myocardium, liver and/or endocrine organs as assessed by MRI techniques. This retrospective analysis of 92 patients with TM (median age 36 yr) from a tertiary adult thalassemia unit in UK aimed to determine independent risk factors associated with endocrinopathies among these patients. Unlike previous studies, longitudinal data on routine measurements of iron load [worst myocardial and liver T2* values since 1999, worst LIC by MRI-R2 since 2008 and average 10-yr serum ferritin (SF)] up to April 2010 together with demographic features and age of initiating chelation were analyzed for associations with endocrinopathies. The most common endocrinopathies in this cohort were hypogonadism (67%) and diabetes mellitus (DM) (41%), and these were independently associated with myocardial T2* <20 ms (P < 0.001 and P = 0.008, respectively) and increased age (P = 0.002 and P = 0.016, respectively). DM and hypogonadism were independently associated with average SF >1250 μg/L (P = 0.003) and >2000 μg/L (P = 0.047), respectively. DM was also associated with initial detection of abnormal myocardial T2* at an older age (30 yr vs. 24 yr, P = 0.039). An abnormal myocardial T2* may therefore portend the development of DM and hypogonadism in patients with TM.


Genetic mapping of 262 loci derived from expressed sequences in a murine interspecific cross using single-strand conformational polymorphism analysis.
We have demonstrated previously that noncoding sequences of genes are a robust source of polymorphisms between mouse species when tested using single-strand conformation polymorphism (SSCP) analysis, and that these polymorphisms are useful for genetic mapping. In this report we demonstrate that presumptive 3'-untranslated region sequence obtained from expressed sequence tags (ESTs) can be analyzed in a similar fashion, and we have used this approach to map 262 loci using an interspecific backcross. These results demonstrate SSCP analysis of genes or ESTs is a simple and efficient means for the genetic localization of transcribed sequences, and is furthermore an approach that is applicable to any system for which there is sufficient sequence polymorphism.


[Optimum mode of interventional treatment for hepatocellular carcinoma].
To establish a reasonable protocol for interventional treatment of hepatocellular carcinoma (HCC). The data of 1 000 HCC patients treated by different kinds of interventional treatment were reviewed with their results of biochemistry, imaging, pathology and survival rate evaluated. The value as well as the pros and cons of these various kinds of interventional treatment were compared in order to find an optimum protocol. Segmental-transcatheter oil chemoembolization (S-TOCE) was much effective eradicate the tumor yet inflicting less damage on the noncancerous hepatic tissue and giving much higher survival rate than the conventional transcatheter oil chemoembolization (C-TOCE). Percutaneous ethanol injection (PEI) played an important role in eradicating the residual tumor and improving the survival rate without damaging the noncancerous hepatic tissue. The survival quality or survival rate could be improved by choosing different ways of interventional treatments to cut down the complications. The selection of different interventional treatments should be done according to the size and type of HCC. Active management is indicated for different complications presenting along with HCC.


A Clinical Update on Vasoactive Medication in the Management of Cardiogenic Shock.
This is a focused review looking at the pharmacological support in cardiogenic shock. There are a plethora of data evaluating vasopressors and inotropes in septic shock, but the data are limited for cardiogenic shock. This review article describes in detail the pathophysiology of cardiogenic shock, the mechanism of action of different vasopressors and inotropes emphasizing their indications and potential side effects. This review article incorporates the currently used specific risk-prediction models in cardiogenic shock as well as integrates data from many trials on the use of vasopressors and inotropes. Lastly, this review seeks to discuss the future direction for vasoactive medications in cardiogenic shock.


A new rhodamine-based chemosensor for Cu2+ and the study of its behaviour in living cells.
A new rhodamine-based chemosensor (L1) was synthesized, and it exhibits high sensitivity and selectivity for the copper cation over other commonly coexistent metal ions in aqueous solution. Upon the addition of Cu(2+), the spirolactam ring of L1 was opened and a 1 : 1 metal-ligand complex was formed. Fluorescent imaging of Cu(2+) in living cells is also successfully demonstrated.


Clinical Impact of Delayed Initiation of Adjuvant Chemotherapy Among Patients With Stage II/III Gastric Cancer: Can We Do Better?
Background: To investigate the prognostic effects and risk factors of the omission and delay of postoperative chemotherapy of stage II/III gastric cancer (GC). Methods: The clinicopathological data of 1,520 patients undergoing radical gastrectomy for stage II/III GC were collected and retrospectively analyzed. We defined the chemotherapy delayed until more than 60 days after radical gastrectomy and the complete omission of chemotherapy as unacceptable chemotherapy initiation (UAC), whereas the chemotherapy conducted within 60 days of radical gastrectomy was defined as acceptable chemotherapy initiation (AC). The survival between the two groups was compared, and the trends and risk factors of UAC were analyzed. Results: There were 539 (35.5%) patients with UAC. The overall survival (OS) and disease-free survival of the UAC group patients were significantly inferior to those in the AC group (p < 0.001). Cox multivariate analysis demonstrated that UAC is an independent predictor of OS (p < 0.05). The OS and disease-free survival of the patients in the UAC group were close to those of the patients without chemotherapy (p > 0.05). Logistic analysis showed that female, old age, a self-paid status, a very low social status, high American Society of Anesthesiologists scores, intra-abdominal surgery history, and serious postoperative complications were independent risk factors of UAC (all p < 0.05). The radar chart shows the risk factors of UAC changed with time. Conclusions: UAC after radical gastrectomy is an independent risk factor for the prognosis of stage II/III GC patients. However, no significant decline of UAC has been achieved recently and should call for the attention of both government and clinicians.


Trans-sphenoidal surgery for microprolactinoma: an acceptable alternative to dopamine agonists?
Reported cure rates following trans-sphenoidal surgery for microprolactinoma are variable and recurrence rates in some series are high. We wished to examine the cure rate of trans-sphenoidal surgery for microprolactinoma, and to assess the long-term complications and recurrence rate. A retrospective review of the outcome of trans-sphenoidal surgery for microprolactinoma, performed by a single neurosurgeon at a tertiary referral centre between 1976 and 1997. All thirty-two patients operated on for microprolactinoma were female, with a mean age of 31 years (range 16-49). Indications for surgery were intolerance of dopamine agonists in ten (31%), resistance in six (19%) and resistance and intolerance in four (12.5%). Two patients were from countries where dopamine agonists were unavailable. The mean pre-operative prolactin level was 2933 mU/l (range 1125-6000). All but 1 had amenorrhoea or oligomenorrhoea, with galactorrhoea in 15 (46.9%). Twenty-five (78%) were cured by trans-sphenoidal surgery, as judged by a post-operative serum prolactin in the normal range. During a mean follow-up of 70 months (range 2 months to 16 years) there was one recurrence at 12 years. Post-operatively, one patient became LH deficient, two patients became cortisol deficient and two became TSH deficient. Out of 21 patients tested for post-operative growth hormone deficiency, 6 (28.6%) were deficient. Five patients developed post-operative diabetes insipidus which persisted for greater than 6 months. There were no other complications of surgery. The estimated cost of uncomplicated trans-sphenoidal surgery, and follow-up over 10 years, was similar to that of dopamine agonist therapy. In patients with hyperprolactinaemia due to a pituitary microprolactinoma, transsphenoidal surgery by an experienced pituitary surgeon should be considered as a potentially curative procedure. The cost of treatment over a 10 year period is similar in uncomplicated cases to long-term dopamine agonist therapy.


Dipeptide sulfonamides as endothelin ETA/ETB receptor antagonists.
Endothelin-1 (ET-1) is a potent mitogen and modulator of vascular tone. It is synthesized and released from endothelial cells and acts upon two receptor subtypes designated as ETA and ETB. In this study, a series of potent dipeptide sulfonamide dual-endothelin ETA/ETB receptor antagonists were prepared to investigate their potential benefit in vascular diseases. CGS 31398 inhibited [125I]ET-1 binding to human ETA and ETB receptors expressed in Chinese hamster ovary (CHO) cells (ETA/CHO, ETB/CHO) with respective IC50 values of 0.26 and 0.12 nM. However, in anesthetized rats, this compound markedly potentiated ET-1-induced renal vascular resistance, a response normally observed with selective ETB receptor antagonists. To determine whether species differences account for these results, a direct comparison was made between binding to rat and rabbit aortic membranes versus functional antagonism in isolated rat aortic rings. It was found that CGS 31398 had potent affinity for the ETA receptor in rat and rabbit aorta with IC50 values of 0.87 and 0.79 nM, respectively. Inhibition of ET-1-induced contractions of rat aorta by the compound was considerably weaker than expected (pKB = 6.4), while that of sarafotoxin S6c induced contraction of dog saphenous vein (100% inhibition at 100 nM) was consistent with corresponding binding data. These results suggest that although CGS 31398 is a potent dual inhibitor of ETA/ETB receptor binding, it surprisingly displays potent ETB and weak ETA receptor antagonism in functional assays.


Insights into the effect of soil pH on N(2)O and N(2) emissions and denitrifier community size and activity.
The objective of this study was to investigate how changes in soil pH affect the N(2)O and N(2) emissions, denitrification activity, and size of a denitrifier community. We established a field experiment, situated in a grassland area, which consisted of three treatments which were repeatedly amended with a KOH solution (alkaline soil), an H(2)SO(4) solution (acidic soil), or water (natural pH soil) over 10 months. At the site, we determined field N(2)O and N(2) emissions using the (15)N gas flux method and collected soil samples for the measurement of potential denitrification activity and quantification of the size of the denitrifying community by quantitative PCR of the narG, napA, nirS, nirK, and nosZ denitrification genes. Overall, our results indicate that soil pH is of importance in determining the nature of denitrification end products. Thus, we found that the N(2)O/(N(2)O + N(2)) ratio increased with decreasing pH due to changes in the total denitrification activity, while no changes in N(2)O production were observed. Denitrification activity and N(2)O emissions measured under laboratory conditions were correlated with N fluxes in situ and therefore reflected treatment differences in the field. The size of the denitrifying community was uncoupled from in situ N fluxes, but potential denitrification was correlated with the count of NirS denitrifiers. Significant relationships were observed between nirS, napA, and narG gene copy numbers and the N(2)O/(N(2)O + N(2)) ratio, which are difficult to explain. However, this highlights the need for further studies combining analysis of denitrifier ecology and quantification of denitrification end products for a comprehensive understanding of the regulation of N fluxes by denitrification.


[Cardiac surgery as a significant interference with a patient coagulation status].
Cardiac surgery has been advancing intensively in recent years. However, it is often forgotten that cardiac surgery interventions represent a significant interference with patient's coagulation status. This paper summarizes the main processes in the course cardiac surgery that lead to coagulation disorder. These include: * haemodilution resulting from extracorporeal circuits crystalloid priming and the use of cardioplegic solutions leading to the reduction in coagulation factors concentration and the thrombocytes count * full heparinisation during extracorporeal circulation that represents a significant interference with coagulation that may persist for some time even after all heparin has been bound * contact of the blood with inorganic surface that results in an activation of the coagulation cascade and subsequent consumption of coagulation factors and thrombocytes * surgery-related trauma with activation of the external coagulation pathway leading to activation of the coagulation cascade and subsequent consumption of coagulation factors and thrombocytes * blood re-transfusion from the pericardial cavity and subsequent activation of the external coagulation pathway leading to consumption of coagulation factors and thrombocytes * hypothermia leading to thrombocyte dysfunction and initiation of fibrinolysis * blood loss furthering the haemodilution and reduction in coagulation factors concentration and thrombocytes count. The overview provided suggests that cardiac surgery conducted with the support of extracorporeal circuit represents a significant interference with the coagulation status of the patient. Awareness of the above listed changes is necessary to secure correct post-operative management of coagulation disorders.


Diagnosis and therapy of microscopic colitis with presence of foamy macrophages in children.
We discuss the diagnosis of and efficacy 5-amino-2-hydroxybenzoic acid (5-ASA), Saccharomyces boulardii, or magnesium in therapy of microscopic colitis with presence of foamy macrophages. A basis for diagnosis and inclusion to the analysed group was presence of characteristic foamy macrophages in histopathological examination of hematoxylin and eosin-stained specimens collected from the large intestine, reviewed under ×200 or ×320 magnification. No statistically significant improvement was found following the use of 5-amino-2-dihydroxybenzoic acid in therapy of the disease. The use of Saccharomyces boulardii was associated with statistically significant improvement in clinical, endoscopic, and histopathological condition. Use of magnesium caused a histological, statistically significant improvement but failed to have any effect on the clinical and endoscopic presentation. In the group of children in whom no therapeutic intervention was provided, a statistically significant spontaneous clinical improvement was observed, but no statistically significant changes in endoscopic and microscopic condition were found.


An electrochemical sensor based on a glassy carbon electrode modified with sandwich structured ZIF-67@rGO for bisphenol A measurement.
The low conductivity of metal-organic frameworks seriously impedes their electrocatalytic performance. In this study, we prepared a fabricated sandwich structure composed of a Co-based zeolitic imidazolate framework (ZIF-67) and reduced graphene oxide (rGO) through a facile and simple one-pot hydrothermal reaction. This framework of nanocomposites, which are modified with a glassy carbon electrode, constructed a bisphenol A (BPA) electrochemical sensor for the first time. Operational parameters such as pH, electrolytes, the amount of modifiers, deposition potentials and deposition time were optimised for the sensitive detection of BPA. The performance of electrodes was evaluated by cyclic voltammetry, electrochemical impedance spectroscopy, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction and transmission electron microscopy. With differential pulse voltammetry, the detection concentration of BPA ranged from 0.05 μmol L-1 to 100 μmol L-1. The results revealed that the hierarchical nanocomposites demonstrated better electrocatalytic performance with large electrochemically active surface areas, high sensitivity and a low limit of detection (5.2 nmol L-1), compared with a physical mixture of ZIF-67 and rGO at the same ratio. These impressive features originate from the synergistic effects of ZIF-67 and rGO. This study presents a new strategy using metal-organic framework composite materials for the sensitive detection of BPA.


Differential effects of TNF-alpha and IFN-gamma on gene transcription mediated by NF-kappaB-Stat1 interactions.
Regulation of gene transcription by the cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) involves complex interactions between NF-kappaB and Stat families of transcription factors. The purpose of this study was to identify the spatial promoter requirements that govern cytokine synergy for gene transcription regulated by NF-kappaB and Stat factors. Using a set of transcription reporter-luciferase constructs, we show that the relative orientation of juxtaposed NF-kappaB-Stat (SIE) cis-elements determines the ability of TNF-alpha and IFN- gamma to induce gene transcription. Further, NF-kappaB and Stat1 proteins directly regulate transcription by interacting cooperatively on NF-kappaB-SIE DNA binding in response to TNF-alpha plus IFN-gamma. Coimmunoprecipitation provides evidence for a direct NF-kappaB/Stat1 protein-protein interaction. In contrast, IFN-gamma inhibits TNF-alpha-induced transcription of an NF-kappaB reporter gene in a Stat1-dependent mechanism in 2fTGH fibroblasts. Similarly, Stat1 is inhibitory to NF-kappaB overexpression-induced transcription. IFN-gamma and Stat1-dependent inhibition of NF-kappaB transcription occurs independent of TNF-alpha-induced NF-kappaB DNA binding. Interestingly, IFN-gamma pretreatment of 2fTGH fibroblasts potentiates TNF-alpha induction of Stat1 DNA binding. Further, ChIP analysis was applied to detect cytokine-induced in vivo binding and transcriptional regulation of the human inducible nitric oxide synthase (iNOS) gene by NF-kappaB and Stat1. These data demonstrate complex transcriptional regulatory mechanisms elicited by TNF-alpha and IFN-gamma and have potentially important implications for other genes differentially controlled by cytokines.


Thyroid-specific and cAMP-dependent hypersensitive regions in thyroglobulin gene chromatin.
Two regions hypersensitive to DNase I digestion were found in a 7-kb segment of thyroglobulin gene 5'-flanking sequences in the chromatin from bovine thyroid. The most upstream site (-2000 to -1600 bp relative to the transcriptional start) was found in thyroid chromatin only, but independently of actual expression of the gene. It therefore represents a tissue-specific characteristic which may be associated with the commitment of the thyroglobulin gene to transcriptional activity. The very 5' end of the gene and the proximal promoter sequences (-100 to +60 bp relative to transcriptional start), constitute the second site, the hypersensitive character of which could be directly correlated with transcriptional activity. The structural changes occurring in this region of the chromatin were dependent on cAMP stimulation of the thyroid cells.


Evaluation of Angiogenesis by Using CD105 and CD34 in Sudanese Breast Cancer Patients.
Background and Objective: Angiogenesis is a mechanism by which new blood vessels are developed in healing and tumour tissues, where it is necessary for regeneration growth, tumour cells survival and metastasis. This study aimed to assess the angiogenesis mechanism among Sudanese females with breast cancer using anti-CD34 and anti-CD105 markers. Materials and Methods: Three hundred female representative Formalin-Fixed Paraffin-Embedded (FFPE) breast tissue blocks were included in this study. Of the 300 representative tissue blocks, 200 were breast cancer patient's tissues (confirmed cases) and 100 were normal breast tissues (controls). Their ages mean±SD, 47.3±12.9 years. Results: The results showed the MVD of CD34 significantly increased in malignant lesions as compared to normal breast tissues. The mean of MVD CD34 and MVD CD105 showed statistical differences among different histologic types of breast cancer. Also, a strong positive correlation was detected between the manual and automated MVD counting methods. Also, the current study revealed no significant differences were observed in mean MVD counting for both markers and menopausal status or the age groups of the study population. Conclusion: The MVD is a good tool for assessing prognostic markers. The CD105 marker has a high specificity to the new evolving tumour vessels and is a useful predictor for angiogenesis and breast cancer metastasis.


Gene regulation and molecular toxicology.
Abstract The study of gene expression has become a cornerstone of molecular toxicology and toxicogenomics. From a toxicological standpoint, constitutive expression levels of a gene could be just as important in determining the outcome of toxicity as the inducible expression. There are six distinct steps at which gene expression can be controlled; these are transcription, RNA processing, RNA transport, translation, mRNA degradation, and control of protein activity. While this overall paradigm of gene regulation is still valid, the complexity of genetic regulation begins mostly at the level of transcription and certain post-transcriptional events. A thorough understanding of the complexity and fluidity of gene and genome structure and their regulation is an integral part in the theory and practice of molecular toxicology and toxicogenomics. The present article is an attempt to briefly summarize our understanding of gene regulation beginning from the cistron concept. Relevance of molecular toxicology to gene regulatory mechanisms has been emphasized with examples wherever appropriate.


The influence of early embryo traits on human embryonic stem cell derivation efficiency.
Despite its prognostic value in in vitro fertilization, early embryo morphology is not reported on in the derivation of human embryonic stem cell (hESC) lines. Standard hESC derivation does rely on blastocyst development and its efficiency is highly correlated to inner cell mass (ICM) quality. Poor-quality embryos (PQEs) donated for hESC derivation may have a range of cleavage-stage abnormalities that are known to compromise further development. This study was implemented to determine whether specific PQEs traits influence the efficiency of good-quality ICMs to derive new hESC lines. We found that although the types of PQEs investigated were all able to make blastocysts with good-quality ICMs, the ICMs were unequal in their ability to derive hESCs. Good-quality ICMs from embryos with multiple poor-quality traits were unable to generate hESC lines, in contrast to good-quality ICMs from embryos with a single poor-quality trait. In addition, our data suggest a direct correlation between the number of ICM cells present in the blastocyst and its capacity to derive new hESC lines. This study is the first to demonstrate that ICM quality alone is an incomplete indicator of hESC derivation and that application of in vitro fertilization-based early embryo scoring can help predict hESC derivation efficiency. Experiments aiming to quantify, improve upon, or compare hESC derivation efficiency should thus take into consideration early embryo morphology scoring for the comparison of groups with equal developmental competence.


Doppler-free dual-comb spectroscopy of Rb using optical-optical double resonance technique.
We present a Doppler-free high-resolution dual-comb spectroscopy technique in which a dual-comb system is employed to perform optical-optical double-resonance (OODR) spectroscopy. In our experimental study, Doppler-free high-resolution and high-frequency-accuracy broadband measurements were realized using the proposed OODR dual-comb spectroscopic technique, which does not require high-power-per-mode frequency combs. We observed fully resolved hyperfine spectra of 5P3/2 - 4D5/2, 4D3/2 transitions of Rb at 1530 nm and precisely determined the absolute frequencies of the transitions, with an uncertainty of less than 1 MHz. The variations of the OODR spectral line shapes due to power broadening and alignment and the effects of polarization on the dual-comb OODR spectra were also analyzed. This study provides a widely applicable technique for Doppler-free dual-comb spectroscopy of various gaseous species.


A comparison and verification of computational methods to determine the permeability of vertebral trabecular bone.
Fluid flow in the intertrabecular spaces of vertebral bone has been implicated in a number of physiological phenomena. Despite the potential clinical significance of the flow of various fluids through the intertrabecular cavities, the intrinsic permeability of trabecular bone is not fully characterized or understood. Furthermore, very little is known about the interdependence of permeability and morphological parameters. The main purpose of this study is to characterize computational methods to determine intrinsic bone permeability from three-dimensional computed tomography (CT) image stacks that were, depending on the underlying algorithm of each model, acquired at a spatial resolution ranging from the order of 500 μm (macroscale) up to 10 μm (microscale). A Finite Element formulation of the steady-state Stokes flow and an in house developed pore network modeling approach compute permeability on the microscopic length scale. To approximate the geometry of the trabecular bone network, a cellular model is used to map morphological information into intrinsic permeability by means of a log-linear regression equation. If the image resolution is too low for the quantification of the trabecular bone architecture, permeability is directly derived by fitting a simplified version of the log-linear regression equation to the CT Hounsfield values. Depending on the resolution of the raw image data and the chosen model, permeability value correlations are 0.31 ≤ R(2) ≤ 0.90 compared to the Finite Element method, that is referred to as the baseline for any comparisons in this study. Furthermore, we found no significant dependence of the intrinsic permeability on the trabecular thickness parameter.


[Compliance of dog and cat owners in preventive health care].
Regular preventive health care is an essential part of our pets' health and quality of life. Preventive healthcare appointments can result in the prevention of disease development as well as lead to the detection and subsequent treatment of existing health problems at an early stage. In order to achieve optimal health care, the owners' compliance is of most importance in addition to the veterinary advice. However, dog and cat owners often seem to be unaware of the necessity for preventive health care appointments, often as a result of poor communication by the veterinarian. Educational conversations concerning the necessity of regular preventive health examinations are therefore essential. Communication is one of the key factors in building an owner-veterinarian relationship. Veterinarians are advised to invest sufficient time for communication, be aware of their verbal and non-verbal statements, and enable the owner to participate in treatment decisions. Older animals are presented less often for preventive health care appointments than younger animals, although the prevalence of age-related and chronic diseases increases with age. Owners should therefore be informed on the fact that early detection and treatment of these diseases increases their animals' health and survival. Cats are seen less frequently in preventive health care than dogs; many owners are not aware of the characteristics of cats tending to hide signs of disease. Another reason lies in the fact that many cats are stressed by being captured and transported in addition to the visit in the veterinary practice itself. Veterinarians therefore should educate cat owners concerning stress-reducing transportation measures and design their practice in a more cat-friendly fashion. Compliance can also be influenced positively by appropriate practice management, such as offering monthly instalment payments, establishing annual preventive care plans, as well as regular re-scheduling strategies. In addition to enhancing the animals' health, this can also result in increased owner satisfaction.


Awareness regarding communicable diseases among the patients attending general out-patient department of a tertiary care hospital of Kolkata, India.
Communicable diseases continue to be a major problem in India, a large number of which can be prevented by health education, targeting specially the deficiencies and for which a baseline assessment is essential. This observational study included OPD patients who were selected by random sampling and interviewed. The age range varied from 20 - 50 years. 52.5% resided in rural areas. 80% were literates. Majority had per capita income below Rs 1000 per month. Awareness regarding symptoms, modes of transmission, prevention and management of the studied diseases were not satisfactory. Majority used apparently safe water. Mosquito-net use was more among literates. Media was the main source of information in urban areas, health functionaries in rural areas while relatives, friends and neighbours influenced the residents of both the areas and the finding was statistically significant. An awareness development programme involving a combination of different health education methods is suggested.


Effects of insufficient physical activity on mortality and life expectancy in Jiangxi province of China, 2007-2010.
Physical inactivity remains an under-researched field in terms of studying burden of disease at provincial level, and no studies have examined the effects of inactivity on life expectancy (LE) in China. The purpose of this study was to estimate mortality risk and LE effects associated with insufficient levels of physical activity in Jiangxi province. Prevalence of risk factors and mortality counts were extracted from Chronic Diseases and Risk Factors Surveillance Survey (CDRFSS) and Disease Surveillance Points system (DSP), respectively. Insufficient physical activity (IPA) was defined as less than 150 minutes of moderate-intensity physical activity or 60 minutes of vigorous-intensity physical activity per week, accumulated across work, home, transport and discretionary domains. Population-attributable fractions (PAF) were used to calculate the mortality attributable to risk factors, and life table methods were used to estimate the LE gains and LE shifts. Monte Carlo simulation techniques were used for uncertainty analysis. Overall, 5 885 (95% uncertainly interval (UI), 5 047-6 506) and 8 578 (95% UI, 8 227-9 789) deaths in Jiangxi province were attributable to IPA in 2007 and 2010, respectively. The LE gains for elimination of attributable deaths were 0.68 (95% UI, 0.61-076) in 2007, and increased to 0.91 (95% UI, 0.81-1.10) in 2010. If the prevalence of IPA in 2010 had been decreased by 50% or 30%, 3 678 (95% UI, 3 220-4 229) or 2 090 (95% UI, 1 771-2 533) deaths would be avoided, and 0.40 (95% UI, 0.34-0.53) or 0.23 (95% UI, 0.16-0.31) years of LE gained, respectively. Adults in Jiangxi province of China have a high and increasing prevalence of IPA. Due to the deaths and potential LE gains associated with IPA, there is an urgent need to promote physical activity, one of the most modifiable risk factors, within China's health care reform agenda.


[Management of the Therapy of Pulmonary Sequestration: A Retrospective Multicentre Study].
Pulmonary sequestration is a rare pulmonary malformation whose complex pathogenesis is not completely understood. Extrapulmonary sequestrations are always hereditary malformations and are usually diagnosed during childhood. Some intralobar sequestrations in adults, by contrast, seem to be acquired. The clinical presentation is non-specific and often misinterpreted, which results in delayed diagnosis. Surgical resection continues to be the gold standard. Despite the low incidence, new technologies developed in the past few decades, e.g. preoperative interventional angiology procedures and video-assisted lung resection, have changed the management of the disease. A prospective data collection was performed on adult patients who had undergone surgical resection of a pulmonary sequestration in four different centres during a period of 23 years. These data were retrospectively analysed. A total of 14 patients with intralobar sequestrations (n = 11, 79 % left lower lobe) underwent surgical resection. The male/female ratio was 8/6 (median age 50 years). Non-specific pulmonary symptoms such as recurrent infections had a high prevalence (n = 6, 42 %). Two patients had haemoptysis. Three patients were asymptomatic. All patients had a chest CT, 7 patients had an additional abdominal CT, while 10 underwent angiography. Preoperative embolization was performed in 5 of these patients (branches of the thoracic aorta: in 2 cases, branches of abdominal aorta: in 2 cases, and branches of both: in 1 case). Resection was mostly performed with an open surgical approach (n = 12, 86 %). Most patients had a non-anatomic pulmonary resection (n = 8, 57 %). In 7 patients, a microbiologic examination revealed a superinfection with Streptococcus pneumoniae, while 1 patient had an invasive mycosis with Candida albicans. In patients with non-specific pulmonary symptoms and undetermined lesions, especially in the lower lobes, pulmonary sequestrations must be considered in the differential diagnostic evaluation even in adult and elderly patients. If there are no contraindications, surgical removal is basically recommended and may be minimally-invasive in selected cases. The planning of the resection can be facilitated by preoperative evaluation of the arterial supply (branches of the thoracic or abdominal aorta, or both). In cases with haemoptysis or blood supply over the abdominal aorta, preoperative embolization is indicated.


Occupational health strategy for Great Britain.
The Health and Safety Commission (HSC) recently launched a long term occupational health strategy for England, Scotland, and Wales. Set out in a document entitled Securing health together and on a dedicated website the ten year strategy aims to reduced occupational ill health by a series of five work programmes. This article looks at the background to the document, its content, and likely impact at work.


Modeling the Optimal Conditions for Improved Efficacy and Crosslink Depth of Photo-Initiated Polymerization.
Optimal conditions for maximum efficacy of photoinitiated polymerization are theoretically presented. Analytic formulas are shown for the crosslink time, crosslink depth, and efficacy function. The roles of photoinitiator (PI) concentration, diffusion depth, and light intensity on the polymerization spatial and temporal profiles are presented for both uniform and non-uniform cases. For the type I mechanism, higher intensity may accelerate the polymer action process, but it suffers a lower steady-state efficacy. This may be overcome by a controlled re-supply of PI concentration during the light exposure. In challenging the conventional Beer⁻Lambert law (BLL), a generalized, time-dependent BLL (a Lin-law) is derived. This study, for the first time, presents analytic formulas for curing depth and crosslink time without the assumption of thin-film or spatial average. Various optimal conditions are developed for maximum efficacy based on a numerically-fit A-factor. Experimental data are analyzed for the role of PI concentration and light intensity on the gelation (crosslink) time and efficacy.


High-dose-rate intraluminal brachytherapy for paraneoplastic autoimmune multiorgan syndrome.
Paraneoplastic autoimmune multiorgan syndrome (PAMS), also known as paraneoplasic pemphigus, involves the skin, internal organs and mucosa. PAMS-associated mortality may occur as a result of autoantibody formation against internal tumors and their infiltration into organs other than the skin lesions that characterize PAMS. The most common symptoms of PAMS include pain associated with continuous oral ulceration and resistance to pharmacological treatment. The present study reports the case of a 42-year-old female patient who was admitted with an 8-month history of erosive skin lesions within the trunk region, oral mucosa and vaginal mucosa. The patient was diagnosed with PAMS based on computed tomography scans and histological analyses of the lesions. The lymphoid hyperplasia in the retroperitoneum and lesions in the vaginal mucosa and trunk area were improved following pharmacological treatment and resection of the lymph node showing hyperplasia. However, the oral lesion was treated with intraluminal brachytherapy due to its resistance to long-term pharmacological treatment. The majority of the lesions were improved following treatment, in the absence of any severe side effects. In addition, neither worsening nor progression of the oral lesion was observed during the 4-year follow-up period.


Inhibitors of mammalian melanocyte tyrosinase: in vitro comparisons of alkyl esters of gentisic acid with other putative inhibitors.
To discover safe and effective topical skin-lightening agents, we have evaluated alkyl esters of the natural product gentisic acid (GA), which is related to our lead compound methyl gentisate (MG), and four putative tyrosinase inhibitors, utilizing mammalian melanocyte cell cultures and cell-free extracts. Desirable characteristics include the ability to inhibit melanogenesis in cells (IC50 < 100 microg/mL) without cytotoxicity, preferably due to tyrosinase inhibition. Of the six esters synthesized, the smaller esters (e.g. methyl and ethyl) were more effective enzyme inhibitors (IC50 approximately 11 and 20 microg/mL, respectively). For comparison, hydroquinone (HQ), a commercial skin "bleaching" agent, was a less effective enzyme inhibitor (IC50 approximately 72 microg/mL), and was highly cytotoxic to melanocytes in vitro at concentrations substantially lower than the IC50 for enzymatic inhibition. Kojic acid was a potent inhibitor of the mammalian enzyme (IC50 approximately 6 microg/mL), but did not reduce pigmentation in cells. Both arbutin and magnesium ascorbyl phosphate were ineffective in the cell-free and cell-based assays. MG at 100 microg/mL exhibited a minimal inhibitory effect on DHICA oxidase (TRP 1) and no effect on DOPAchrome tautomerase (TRP-2), suggesting that MG inhibits melanogenesis primarily via tyrosinase inhibition. MG and GA were non-mutagenic at the hprt locus in V79 Chinese hamster cells, whereas HQ was highly mutagenic and cytotoxic. The properties of MG in vitro, including (1) pigmentation inhibition in melanocytes, (2) tyrosinase inhibition and selectivity, (3) reduced cytotoxicity relative to HQ, and (4) lack of mutagenic potential in mammalian cells, establish MG as a superior candidate skin-lightening agent.


Reflecting the thoracic fellowship in Canada as a Japanese thoracic surgeon: is there anything we should follow?
In Japanese surgical society, there have been urgent discussions as to the decrease in the number of junior doctors who want to be surgical specialists. This problem seems to have originated from the loss of attractiveness of surgery. One of the counter-measures to regain the attractiveness of surgical specialties might be a well-organized training system, for which the Japanese Board of General Thoracic Surgery (JBGTS), as well as those of other surgical subspecialties, has struggled. Fortunately, I had an opportunity of general thoracic surgery training in Canada, and had a chance to reflect on the thoracic training programs of both countries. Based on my experience as a thoracic fellow in Canada, I would like to introduce the Canadian way of thoracic surgery training, referring to the differences between each program.


Influence of male rats on the luteinizing hormone-releasing hormone neuronal system in female rats: role of the vomeronasal organ.
Olfactory information processed by the vomeronasal system is reported to influence reproductive functions in a variety of mammals. The present studies were designed to determine if male-associated cues affect the luteinizing hormone-releasing hormone (LHRH) neuronal system, and, if so, to determine the extent to which these cues are processed by the vomeronasal organ (VNO). Ovariectomized rats underwent VNO removal (VNX) or sham surgery (VN-Sham). Forty-eight hours after estrogen priming (5 micrograms), they were subjected to one of the following treatments: repeated mating, repeated exposure to male-soiled bedding or repeated exposure to clean bedding. In animals treated for 180 min, coronal brain sections were double labelled for Fos protein and LHRH. An intense Fos immunoreactivity was induced following mating in the majority of LHRH neurons in the VN-Sham females, whereas removal of the VNO significantly suppressed the mating-induced Fos staining. Exposure of female rats to male-soiled bedding or clean bedding did not induce appreciable Fos immunoreactivity in LHRH neurons. Following 90 min of mating or exposure to bedding, blood samples were assayed for luteinizing hormone (LH). Mating stimulated the release of LH in VN-Sham females, while the removal of the VNO significantly suppressed the mating-induced LH release. Exposure of the females to male-soiled bedding or clean bedding did not induce an LH surge. The present results demonstrate that male-originating sensory cues (i.e. repeated mating) can influence the LHRH neuronal system, as evidenced by the presence of Fos immunoreactivity in LHRH cell bodies, and indicate that this effect is mediated through the VNO to a certain extent.(ABSTRACT TRUNCATED AT 250 WORDS)


Cytogenetic and immunofluorescence analysis of benzo[a]pyrene-DNA adduct formation and chromosome damage in larval brain neuroblasts of Drosophila melanogaster.
Recently we have evaluated the relationship between benzo[a]-pyrene(BaP)-DNA adducts, determined by 32P-postlabelling, and clone frequencies in the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Following that study we proceeded to characterise further the mechanism of induction of genetic damage in vivo by BaP in Drosophila by cytogenetic analysis of larval brain neuroblasts. Third stage larvae were treated with 4 and 10 mM BaP for 24, 48 or 72 h. In all cases, the larvae were killed 72 h after the beginning of treatment, entailing 48, 24 or 0 h post-treatment recovery in BaP-free medium, respectively. At the end of the treatment the following data were collected: (i) the types and levels of chromosome aberrations in neuroblast metaphase and anaphase nuclei; (ii) the distribution and level of BaP-DNA adducts, revealed by indirect immunofluorescence in neuroblast nuclei using an anti-(BaP-DNA) antibody. The results indicate that BaP induces chromosome breaks, deletions and exchanges in this system. In particular, chromosome exchanges decrease as the post-treatment recovery time increases, and the dynamics of breaks and deletions appear to be inversely related to those of the exchanges. This suggests that exchanges may require few preconditions to occur and are thus expressed soon after treatment. Chromosome breaks and deletions could require multiple single events before the actual damage is expressed (even some cell divisions away from the end of treatment). The immunofluorescence analysis suggests that BaP-DNA adducts are more abundant in the heterochromatin of the neuroblast nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)


Self-assembly and generation of complexity.
Supramolecular synthesis, by combining molecules through non-covalent interactions, makes it possible to build up extremely sophisticated supramolecular assemblies in the solid state and offers endless architectural possibilities.


Complexity of alpha thalassemia: growing health problem with new approaches to screening, diagnosis, and therapy.
Alpha thalassemia, the most common genetic disorder of hemoglobin synthesis, affects up to 5% of the world's population. It represents a group of conditions with reduced or absent synthesis of one to all four of alpha globin genes. Deletional or nondeletional mutations occur on chromosome 16. Its severity ranges from asymptomatic to fatal in utero. Hemoglobin H disease, a mutation of three alpha globin genes, is more severe than previously recognized. Anemia, hypersplenism, hemosiderosis, growth failure, and osteoporosis are commonly noted as the patient ages. Alpha thalassemia major, a usually fatal in utero disease, is now recognized to have a complex molecular and phenotypic expression with increasing births being reported. Surviving newborns without intrauterine transfusion often have congenital anomalies and neurocognitive injury. Serious maternal complications often accompany pregnancy. Doppler ultrasonography with intrauterine transfusion ameliorates these complications. The high incidence in many populations mandates population screening and prenatal diagnosis of at-risk couples. Universal newborn screening has been adopted in several regions with DNA confirmatory testing. These advances have resulted in ethical dilemmas for the family and the provider.


LOC102724163 promotes breast cancer cell proliferation and invasion by stimulating MUC19 expression.
Breast cancer (BC) is a malignant disease and the most commonly diagnosed cancer in women. Numerous studies have previously verified the important role of long non-coding RNAs in a number of biological processes in BC. In the present study, analysis of The Cancer Genome Atlas database and reverse transcription-quantitative PCR demonstrated that LOC102724163 expression levels were significantly upregulated in BC tissues compared to matched adjacent normal tissues and were associated with an unfavorable prognosis in patients with BC. Gain or loss of function assays indicated that overexpression of LOC102724163 significantly increased tumorgenicity in vivo and cell migration, proliferation and invasion in vitro. In the mechanistical aspect, LOC102724163 sponged microRNA (miR)-508-5p to elevate MUC19 expression. Additionally, rescue assays ascertained the function of the LOC102724163/miR-508-5p/MUC19 axis in the proliferation and invasion of BC cells. To the best of our knowledge, this is the first study to have demonstrated that LOC102724163 may act as a competing endogenous RNA to control MUC19 expression levels by competitively sponging miR-508-5p to modulate BC progression. Therefore, the present study has provided new insights into BC diagnosis and treatment.


Electroconvulsive therapy, electric field, neuroplasticity, and clinical outcomes.
Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with depressive episodes, but the underlying mechanisms for antidepressant response and procedure-induced cognitive side effects have yet to be elucidated. Such mechanisms may be complex and involve certain ECT parameters and brain regions. Regarding parameters, the electrode placement (right unilateral or bitemporal) determines the geometric shape of the electric field (E-field), and amplitude determines the E-field magnitude in select brain regions (e.g., hippocampus). Here, we aim to determine the relationships between hippocampal E-field strength, hippocampal neuroplasticity, and antidepressant and cognitive outcomes. We used hippocampal E-fields and volumes generated from a randomized clinical trial that compared right unilateral electrode placement with different pulse amplitudes (600, 700, and 800 mA). Hippocampal E-field strength was variable but increased with each amplitude arm. We demonstrated a linear relationship between right hippocampal E-field and right hippocampal neuroplasticity. Right hippocampal neuroplasticity mediated right hippocampal E-field and antidepressant outcomes. In contrast, right hippocampal E-field was directly related to cognitive outcomes as measured by phonemic fluency. We used receiver operating characteristic curves to determine that the maximal right hippocampal E-field associated with cognitive safety was 112.5 V/m. Right hippocampal E-field strength was related to the whole-brain ratio of E-field strength per unit of stimulation current, but this whole-brain ratio was unrelated to antidepressant or cognitive outcomes. We discuss the implications of optimal hippocampal E-field dosing to maximize antidepressant outcomes and cognitive safety with individualized amplitudes.


The Daily Expression of ABCC4 at the BCSFB Affects the Transport of Its Substrate Methotrexate.
The choroid plexuses (CPs), located in the brain ventricles, form an interface between the blood and the cerebrospinal fluid named the blood-cerebrospinal barrier, which, by the presence of tight junctions, detoxification enzymes, and membrane transporters, limits the traffic of molecules into the central nervous system. It has already been shown that sex hormones regulate several CP functions, including the oscillations of its clock genes. However, it is less explored how the circadian rhythm regulates CP functions. This study aimed to evaluate the impact of sex hormones and circadian rhythms on the function of CP membrane transporters. The 24 h transcription profiles of the membrane transporters rAbca1, rAbcb1, rAbcc1, rAbcc4, rAbcg2, rAbcg4, and rOat3 were characterized in the CPs of intact male, intact female, sham-operated female, and gonadectomized rats. We found that rAbcc1 is expressed in a circadian way in the CPs of intact male rats, rAbcg2 in the CPs of intact female rats, and both rAbcc4 and rOat3 mRNA levels were expressed in a circadian way in the CPs of intact male and female rats. Next, using an in vitro model of the human blood-cerebrospinal fluid barrier, we also found that methotrexate (MTX) is transported in a circadian way across this barrier. The circadian pattern of Abcc4 found in the human CP epithelial papilloma cells might be partially responsible for MTX circadian transport across the basal membrane of CP epithelial cells.


The Graduated Embryo Score of Embryos from Infertile Women with and without Peritoneal Endometriosis.
To determine embryo quality (mean graduated embryo score [GES]) in infertile patients with endometriosis undergoing in vitro fertilization with embryo transfer (IVF-ET) compared with infertile patients without endometriosis. A case-control study was performed comparing 706 embryos (162 patients) divided into 2 groups: 472 embryos derived from patients without endometriosis (n = 109, infertile patients with tubal infertility) and 234 embryos from patients in the study group (n = 53, infertile patients with peritoneal endometriosis). All patients were subjected to IVF using an oestradiol-antagonist-recombinant follicle-stimulating hormone (FSH) protocol for ovarian stimulation. The mean GES was performed to evaluate all embryos at 3 points in time: 16 to 18 hours, 25 to 27 hours, and 64 to 67 hours. Embryo evaluation was performed according to the following parameters: fragmentation, nucleolar alignment, polar body apposition, blastomere number/morphology, and symmetry. The primary outcome measure was the mean GES score. We also compared fertilization, implantation, and pregnancy rates. Although the number of embryos transferred was greater in patients with endometriosis than in the control group (2.38 ± 0.66 versus 2.15 ± 0.54; p = 0.001), the mean GES was similar in both groups (71 ± 19.8 versus 71.9 ± 23.5; p = 0.881). Likewise, the fertilization rate was similar in all groups, being 61% in patients with endometriosis and 59% in the control group (p = 0.511). No significant differences were observed in the implantation (21% versus 22%; [p = 0.989]) and pregnancy rates (26.4% versus 28.4%; p = 0.989). Embryo quality measured by the mean GES was not influenced by peritoneal endometriosis. Likewise, the evaluated reproductive outcomes were similar between infertile patients with and without endometriosis.


Self and nonself stimulatory molecules induce preferential expansion of CD5+ B cells or activated T cells of chagasic patients, respectively.
It has previously been demonstrated that Trypanosoma cruzi-derived antigens (TRP) and human parasite-specific antibodies (Id) stimulate proliferation of cells from Chagasic patients. More recently, we have shown that activated T cells and CD5+ B cells are present in elevated levels in the peripheral blood of Chagasic patients. Upon in vitro exposure to these two different types of stimulatory molecules (TRP, Id), we now show that each of these elevated populations respond differentially to TRP or Id. We found that stimulation with TRP led to preferential expansion of activated T cells, while Id preferentially stimulated CD5+ B cells and CD8+ T cells. Moreover, this expansion of CD5+ B cells by Id was even more pronounced in cultures of cells from Chagasic patients with the severe, cardiac form of the disease, as compared to indeterminate patients. CD8+ T cells comprise approximately 50% of the total T cells in cultures stimulated by Id while in TRP-stimulated cultures their frequency is proportionally lower. Since parasite antigens and antiparasite antibodies are always present in the host during the chronic phase of the disease, they may also be involved with differential activation mechanisms of these cell populations in vivo.


[Understanding the advantages and disadvantages of femtosecond laser comprehensive applications in ophthalmology].
The femtosecond (FS) laser is a novel laser technology, and is approved clinical application by FDA in 2000. FS laser initially mainly used in corneal refractive surgery to replace the mechanical microkeratome. Since the accuracy and controllability of the FS laser is very high, it shows superiority in the field of corneal refractive surgery. And with the development of the relative hard and software, FS laser is began to used in other fields of ophthalmology, such as corneal transplants, cataract surgery, as well as assisted diagnosis et al., although still have some limitations, the preliminary clinical results have been shown a very good prospects in the ophthalmology fields. Therefore, we reviewed the alternative applications, challenges and limitations, research direction in the future of FS laser, so that provide a reference and revelations for the peers.


Topographic paracentral corneal thickness with pentacam and orbscan: effect of acoustic factor.
To evaluate the effect of an acoustic factor (AF) on the comparison of central corneal thickness (CCT) and peripheral corneal thickness (PCT) measurements with Orbscan II and Pentacam. The CCT and PCT at 1, 2, and 3 radial distances from the corneal apex were measured using Orbscan II and Pentacam in 22 right eyes of 22 healthy adults (7 men, 15 women). Three measures were obtained from each 1 of the 25 points measured and then compared to gauge the agreement between both devices at the corneal center and anular areas located at 1-, 2-, and 3-mm distances from the central measurement. Orbscan II readings were considered with and without an AF correction. Pentacam provides statistically significant higher values than Orbscan II does at all the 25 locations analyzed (P<0.001). With a few exceptions, the average difference was fairly constant between 20 and 40 μm for all the corneal locations. A high correlation existed between central readings (r(2)=0.927; P<0.001) and average thickness at each one of the annular areas being analyzed (r(2)=0.897 at 1 mm, r(2)=0.876 at 2 mm, and r(2)=0.870 at 3 mm); Pentacam minus Orbscan II value averaged for all the points changed from -28±10 to -22±9 μm after the removal of the AF in Orbscan II. Central and peripheral measurements of the corneal thickness obtained with Orbscan II and Pentacam are significantly different. The removal of the AF in Orbscan II renders lower mean differences but decreases the agreement between both systems and potentially induces an overestimation of CCT and PCT by Orbsan II compared with Pentacam.


Rapid identification of yeast proteins on two-dimensional gels.
This work describes a rapid and sensitive technique for the identification of Saccharomyces cerevisiae proteins on two-dimensional gels based on the determination of their amino acid ratios. Specific double labeling with 3H and 14C or 35S-labeled amino acids, chosen among those that are specifically incorporated into proteins without interconversion, allowed an accurate measurement of different amino acid ratios for 200 proteins. A computer program was developed to screen a yeast data base containing 1700 protein sequences and to identify proteins matching the measured Mr, pI, and amino acid ratios. The method, tested with 45 reference proteins, allowed 79 new identifications corresponding to abundant proteins belonging to a few functional families. Some protein spots correspond to homologs of mammalian proteins or to uncharacterized open reading frames. Remarkably, among identified proteins of similar abundance, the organellar proteins have a markedly lower codon usage bias than the cytosolic ones. The double labeling technique is particularly suited to the analysis, on a single two-dimensional gel, of the influence of physiological or genetic changes on yeast protein content.


Transcriptomic characterization of adult zebrafish infected with Streptococcus agalactiae.
Streptococcus agalactiae is a major aquaculture pathogen infecting various saltwater and freshwater fish. To better understand the mechanism of the immune responses to S. agalactiae in wildtype zebrafish, the transcriptomic profiles of two organs containing mucosal-associated lymphoid tissues from S. agalactiae-infected and non-infected groups were obtained using RNA-seq techniques. In the intestines, 6735 and 12908 differently expressed genes (DEGs) were identified at 24 hpi and 48 hpi, respectively. Among 66 and 116 significantly enriched pathways, 15 and 21 pathways were involved in immune system or signal transduction at 24 hpi and 48 hpi, respectively. A number of genes involved in Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway, NOD-like receptor signaling pathway, T cell receptor signaling pathway, B cell receptor signaling pathway, Antigen processing and presentation, NF-kappa B signaling pathway and PI3K-Akt signaling pathway were significantly downregulated. In the skins, 3113 and 4467 DEGs were identified at 24 hpi and 48 hpi, respectively. Among 24 and 56 significantly enriched pathways, 4 and 13 pathways were involved in immune system or signal transduction at 24 hpi and 48 hpi, respectively. More immune-related signaling pathways including Leukocyte transendothelial migration, Cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, TNF signaling pathway, Complement and coagulation cascades, Hematopoietic cell lineage and Jak-STAT signaling pathway were differently enriched for upregulated DEGs at 48 hpi, which were completely different from that in the intestines. Furthmore, comparative transcriptome analysis revealed that the downregulated 1618 genes and upregulated 1622 genes existed both at 24 hpi and 48 hpi for the intestine samples. In the skins, the downregulated 672 genes and upregulated 428 genes existed both at 24 hpi and 48 hpi. Three pathways related to immune processes were significantly enriched for downregulated DEGs both in the intestines and skins collected at 24 hpi and 48 hpi, which included Antigen processing and presentation, Intestinal immune network for IgA production and Hematopoietic cell lineage. Interaction network analysis of DEGs identified the main DEGs in the sub-network of complement and coagulation cascades both in the intestines and skins. Twenty of DEGs involved in complement and coagulation cascades were further validated by Real-time quantitative PCR. Altogether, the results obtained in this study will provide insight into the immune response of zebrafish against S. agalactiae XQ-1 infection in fatal conditions, and reveal the discrepant expression pattern of complement and coagulation cascades in the intestines and skins.


Genome-wide progesterone receptor binding: cell type-specific and shared mechanisms in T47D breast cancer cells and primary leiomyoma cells.
Progesterone, via its nuclear receptor (PR), exerts an overall tumorigenic effect on both uterine fibroid (leiomyoma) and breast cancer tissues, whereas the antiprogestin RU486 inhibits growth of these tissues through an unknown mechanism. Here, we determined the interaction between common or cell-specific genome-wide binding sites of PR and mRNA expression in RU486-treated uterine leiomyoma and breast cancer cells. ChIP-sequencing revealed 31,457 and 7,034 PR-binding sites in breast cancer and uterine leiomyoma cells, respectively; 1,035 sites overlapped in both cell types. Based on the chromatin-PR interaction in both cell types, we statistically refined the consensus progesterone response element to G•ACA• • •TGT•C. We identified two striking differences between uterine leiomyoma and breast cancer cells. First, the cis-regulatory elements for HSF, TEF-1, and C/EBPα and β were statistically enriched at genomic RU486/PR-targets in uterine leiomyoma, whereas E2F, FOXO1, FOXA1, and FOXF sites were preferentially enriched in breast cancer cells. Second, 51.5% of RU486-regulated genes in breast cancer cells but only 6.6% of RU486-regulated genes in uterine leiomyoma cells contained a PR-binding site within 5 kb from their transcription start sites (TSSs), whereas 75.4% of RU486-regulated genes contained a PR-binding site farther than 50 kb from their TSSs in uterine leiomyoma cells. RU486 regulated only seven mRNAs in both cell types. Among these, adipophilin (PLIN2), a pro-differentiation gene, was induced via RU486 and PR via the same regulatory region in both cell types. Our studies have identified molecular components in a RU486/PR-controlled gene network involved in the regulation of cell growth, cell migration, and extracellular matrix function. Tissue-specific and common patterns of genome-wide PR binding and gene regulation may determine the therapeutic effects of antiprogestins in uterine fibroids and breast cancer.


Early Recognition and Treatment of Acute Disseminated Encephalomyelitis in Pediatrics: A Case Series.
Our aim is to emphasize the varied presentation of acute disseminated encephalomyelitis (ADEM) to help health care professionals improve recognition of the disease in a timely manner, thereby allowing for the selection of an appropriate treatment regimen. Therefore, this may avoid neurocognitive consequences and the ultimate fatality of the patient. This is a retrospective case series involving 7 cases of children presenting to the Pediatric Emergency Department of Hackensack University Medical Center who were ultimately diagnosed with ADEM. In many of the cases, a preceding viral-like illness with nonspecific symptomatology made it difficult to accurately establish an initial diagnosis. Ultimately, the neurologic symptoms spontaneously resolved or improved with administration of high-dose steroids. Children presenting to the emergency department with nonspecific symptoms associated with any neurological deficits should undergo further investigation using magnetic resonance imaging and lumbar puncture to rule out rare yet possibly fatal diseases such as ADEM.


Regulation of dopamine presynaptic markers and receptors in the striatum of DJ-1 and Pink1 knockout rats.
Pathogenic autosomal recessive mutations in the DJ-1 (Park7) or the PTEN-induced putative kinase 1 (Pink1 or PARK6) genes are associated with familial Parkinson's disease (PD). It is not well known regarding the pathological mechanisms involving the DJ-1 and Pink1 mutations. Here we characterized DJ-1 and Pink1 knockout rats both through expression profiling and using quantitative autoradiography to measure the densities of the dopamine D1, D2, D3 receptors, vesicular monoamine transporter type-2 (VMAT2) and dopamine transporter (DAT) in the striatum of transgenic rats and wild type controls. Expression profiling with a commercially available array of 84 genes known to be involved in PD indicated that only the target gene was significantly downregulated in each transgenic rat model. D1 receptor, VMAT2, and DAT were measured using [(3)H]SCH23390, [(3)H]dihydrotetrabenazine, and [(3)H]WIN35428, respectively. No significant changes were observed in the density of DAT in either model. Although the densities of VMAT2 and D1 receptor were unchanged in Pink1 knockout, but both were increased in DJ-1 knockout rats. The densities of D2 and D3 receptors, determined by mathematical analysis of binding of radioligands [(3)H]WC-10 and [(3)H]raclopride, were significantly increased in both knockout models. These distinctive changes in the expression of dopamine presynaptic markers and receptors in the striatum may reflect different compensatory regulation of dopamine system in DJ-1 versus Pink1 knockout rat models of familial PD.


Expression of fetal isoforms of actin after transplantation injury.
Trauma and injury to transplanted organs in the early post-transplant period are significant factors that affect long-term graft survival. Fetal isoforms of actin are integral members of the immediate early gene family and are expressed in response to free radical injury. We therefore studied actin gene expression in heart transplantation to determine if reperfusion injury activates fetal isoforms of actins. Heterotopic cardiac transplantations were performed in mice. mRNA was extracted from allo- and isografted hearts as well as from normal hearts and spleen. Northern hybridization with actin cDNA to alpha and beta/gamma actin mRNA was performed and analyzed by densitometry. The beta/gamma actin gene expression in the transplanted hearts was found to be significantly elevated within 48 h after transplantation. Analysis of beta/gamma actin gene expression in isografts substantiates the possibility of de novo increase in actin expression. Our studies demonstrate for the first time that fetal isoforms of actin are induced in the allograft heart after transplantation.