Development of a Model of Holistic Reflection to facilitate transformative learning in student midwives.
Reflective practice is considered an essential aspect of personal and professional development, and critical reflection is considered the cornerstone of being an accountable and autonomous practitioner. Tertiary education should lay the foundations of lifelong learning by ensuring students develop into critically reflective and reflexive practitioners, who demonstrate self-awareness and an ability to reflect on personal values and beliefs and their impact on the wider healthcare system. This level of reflective practice is essential to effect change at both an individual and societal level. Reflection should therefore be embedded into education programs as a learning, teaching and assessment strategy. The aim of this paper is to describe a structured Model of Holistic Reflection embedded within an Australian Bachelor of Midwifery Program. The paper firstly outlines the theoretical and conceptual underpinnings of the newly developed model. Secondly describes the six integrated and inter-dependant phases of the model. The aim of developing the Holistic Reflective Model was to produce a sound educational tool to assist midwifery students to progressively build reflexivity and reflective practice. Furthermore, provide midwifery academics with an educational resource to facilitate development of reflective and critical thinking skills in students. The specific intention was to promote deep personal and transformative learning across an entry to practice program. This paper highlights a number of ways the model can be embedded within the curriculum to support the scaffolded development of critical reflection and reflexivity required to facilitate transformative learning. While evaluation is required the model may have transferability to other disciplines.


A Framework for Studying the Heterogeneity of Risk Factors in Math Anxiety.
Math anxiety is a prevalent disorder which affects many people worldwide. Here, we draw together ample evidence to suggest a dynamic developmental bio-psycho-social model. The model highlights the complex pathways towards the development of math anxiety, with a focus on dynamism. That is, math anxiety is viewed here as a dynamic interplay between environmental (parenting style, as well as social style including teachers' attitude, instruction strategies and wider social effects) and intrinsic factors (i.e., neuro-cognitive and genetic predispositions, including brain malfunctions, heritability, predisposition towards general anxiety) and basic numerical cognition and affective factors. The model predicts that the dynamic interplay between these factors can either prevent or promote math anxiety's effects on the development of heterogeneous symptoms. Considering the universal nature of math anxiety, a systematic description of the vulnerability factors that contribute to the development of math anxiety is vital. Such information may be of particular value in informing the design of preventive interventions as well as of specific intervention tools.


Measured Glomerular Filtration Rate at Dialysis Initiation and Clinical Outcomes of Indian Peritoneal Dialysis Patients.
The optimal time for dialysis initiation remains controversial. Studies have failed to show better outcomes with early initiation of hemodialysis; even a few had shown increased adverse outcomes including poorer survival. Few studies have examined the same in patients on peritoneal dialysis (PD). Measured glomerular filtration rate (mGFR) not creatinine-based estimated GFR is recommended as the measure of kidney function in end-stage renal disease (ESRD) patients. The objective of this observational study was to compare the outcomes of Indian patients initiated on PD with different residual renal function (RRF) as measured by 24-h urinary clearance method. A total of 352 incident patients starting on chronic ambulatory PD as the first modality of renal replacement therapy were followed prospectively. Patients were categorized into three groups as per mGFR at the initiation of PD (≤5, >5-10, and >10 ml/min/1.73 m2). Patient survival and technique survival were compared among the three groups. Patients with GFR of ≤5 ml/min/1.73 m2 (hazard ratio [HR] - 3.42, 95% confidence interval [CI] - 1.85-6.30, P = 0.000) and >5-10 ml/min/1.73 m2 (HR - 2.16, 95% CI - 1.26-3.71, P = 0.005) had higher risk of mortality as compared to those with GFR of >10 ml/min/1.73 m2. Each increment of 1 ml/min/1.73 m2 in baseline GFR was associated with 10% reduced risk of death (HR - 0.90, 95% CI - 0.85-0.96, P = 0.002). Technique survival was poor in those with an initial mGFR of ≤5 ml/min/1.73 m2 as compared to other categories. RRF at the initiation was also an important factor predicting nutritional status at 1 year of follow-up. To conclude, initiation of PD at a lower baseline mGFR is associated with poorer patient and technique survival in Indian ESRD patients.


A swordless knight: epidemiology and molecular characteristics of the blaKPC-negative sequence type 258 Klebsiella pneumoniae clone.
In June 2010, a bla(KPC)-negative, ertapenem-resistant ST-258 Klebsiella pneumoniae strain was isolated from a patient in the Laniado Medical Center (LMC). Our aims were (i) to describe its molecular characteristics and resistance mechanisms and (ii) to assess whether the bla(KPC)-negative ST-258 K. pneumoniae clone spreads as efficiently as its KPC-producing isogenic strain. In a prospective study, surveillance of all ertapenem-resistant, carbapenemase-negative K. pneumoniae (ERCNKP) isolates was conducted from June 2010 to May 2011 at LMC (314 beds) and from July 2008 to December 2010 at the Tel Aviv Sourasky Medical Center (TASMC) (1,200 beds). Molecular typing was done by arbitrarily primed PCR, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). A total of 8 of 42 (19%) ERCNKP isolates in LMC and 1 of 32 (3.1%) in TASMC belonged to the ST-258 clone. These strains carried the bla(CTX-M-2) or the bla(CTX-M-25) extended-spectrum β-lactamase (ESBL) gene. Sequencing of the ompK genes showed a frameshift mutation in the ompK35 gene. The fate of the bla(KPC)-carrying plasmid, pKpQIL, was determined by S1 analysis and by PCR of the Tn4401 transposon, repA, and the truncated bla(OXA-9). Plasmid analysis of the ERCNKP ST-258 isolates showed variability in plasmid composition and absence of the Tn4401 transposon and the pKpQIL plasmid. In addition, the ST-258 clone was identified in 35/35 (100%) of KPC-producing K. pneumoniae isolates but in none of 62 ertapenem-susceptible K. pneumoniae isolates collected in the two centers. Our results suggest that ERCNKP ST-258 evolved by loss of the bla(KPC)-carrying plasmid pKpQIL. ERCNKP ST-258 appears to have low epidemic potential.


[Effect of beta-adrenergic blocker propranolol during reflex renal degeneration induced by sciatic nerve transection].
We present the data on functional status of the mineralocorticoid receptor system in rat kidney in the course of renal reflex degeneration induced by sciatic nerve transection at the background of both renal denervation and injections of beta blocker propranolol. According to the status of renal mineralocorticoid receptors, simultaneous blocking of both neural and humoral pathological stimuli incoming to the kidney after the nerve injury to a higher extent inhibited cytochemical changes in the organ as compared to blocking the neural transmission alone. We propose that both the central neural transmission and humoral mechanisms control the activity of the molecular structures responsible for aldosterone reception in renal tubular cells.


The southern corn leaf blight epidemic.
A dramatic shift in the genetics of host-parasite interaction and balance occurred in the U.S. corn crop in the 1970 growing season. Southern corn leaf blight incited by Helminthosporium maydis Nisikado & Miyake evolved from a minor disease that causes an average annual loss of less than 1 percent, to one that caused more than the 12 percent average expected from all diseases of corn in the United States. In 1970 the losses to corn leaf blight approaches 710 million bushels. Reserves of corn and other grains ease the impact on the economy and food supplies but there are important domestic and foreign effects of the loss. The epidemic illustrates the vulnerability of our food crops to pests. Sources of genetic resistance to the new race of Helminthosporium maydis are available. The seed industry estimates that for 1971 enough resistant and partially resistant seed to plant about one-half of the crop may be available. Adequate supplies are expected in 1972. Sustained research programs are essential in protecting our food supplies from potential losses of catastrophe magnitude. Several professional groups, including the American Phytopathological Society and the Entomological Society of America, have urged that a program and facilities be established for the study of exotic pests that threaten our agriculture so that controls may be found before the pests are here. Such a program would be desirable but covers only one aspect of the problem. What is really needed is an overall strengthening of research on crop pests.


The withdrawal of benztropine mesylate in chronic schizophrenic patients.
In this double-blind, four-week study, 28 chronic schizophrenic patients receiving neuroleptic medication plus the antiparkinsonian drug, benztropine mesylate, were either switched to placebo or maintained on benztropine. Patients withdrawn from benztropine reliably increased their overall scores on the Wechsler Memory Scale in comparison with the drug group. Sub-test scores suggest that deficits in attention and concentration were induced by treatment with benztropine. Psychotic decompensation appeared to develop simultaneously with extrapyramidal symptoms (EPS) in some patients, but only 14.2 per cent of the placebo group experienced extrapyramidal symptoms severe enough to require resumption of benztropine therapy. It is suggested that antiparkinsonian agents should be prescribed only if and when EPS occur.


Comparative evolution of Alzheimer disease, vascular dementia, and mixed dementia.
To compare the evolution of Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia by cognitive domain. The University of Western Ontario Dementia Study, which is a registry of cases of dementia seen for secondary and tertiary assessment in a university memory disorders clinica with extensive follow-up data and histopathological confirmation of clinical diagnoses. One hundred twenty-nine patients with definite or probable AD, 12 patients with definite or probable VaD, and 36 patients with definite or probable mixed dementia. Patients were grouped as having an early, moderate, or advanced stage of disease according to the extended scale for dementia (ESD). The ESD was subdivided into cognitive domains, and the domain scores were compared for each stage of disease by diagnostic category with the use of a 2-way analysis of variance with repeated measures. As expected, the scores in all domains decreased significantly with increasing severity. There was a significant difference in the decline in memory among the diagnostic groups (P = .02) that was mostly attributable to the difference between AD and mixed dementia (P = .03), with the difference between AD and VaD only approaching significance (P = .06). There was a similar finding for praxis. The interaction between diagnosis (AD and VaD) and severity was significant only for memory (P = .02), showing a less severe memory deficit at onset but a proportionately more rapid progression in VaD and arithmetic ability (AD and mixed dementia [P = .03]). Alzheimer disease, VaD, and mixed dementia evolve similarly as assessed using cognitive domains obtained by subdivision of the ESD in a patient population derived from a memory clinic and by analyzing VaD as a single entity. Only memory impairment evolves differently between AD and VaD, with this depending on the severity. Memory is more severely impaired in the early stage of AD; however, with increasing severity of dementia, memory impairment in VaD accelerates and catches up with AD at the level of moderate impairment. The differences between AD and mixed dementia are greater than those between mixed dementia and VaD, suggesting an important role for the ischemic component of mixed dementia. Simple neuropsychological tools (eg, the ESD) may be incapable of distinguishing between AD and VaD, and more focused instruments may be required. Inherent bias in case selection may prevent extrapolation of these results to VaD in general, but the neuropsychological criteria for VaD may need to vary, depending on the severity.


Molecular-level insights into the self-assembly driven enantioselective recognition process.
The importance of the orientation of functional groups in a chiral environment on enantioselective recognition has been demonstrated. Orientation controlled interactions of functional groups in (R)/(S)-MA lead to a visually differentiable morphology with an arginine-based gelator. The crucial role of various molecular-level interactions discriminating the enantioselective self-assembly has been established using different analytical techniques, crystal structure analysis, and DFT calculations.


PEACE of mind: Guidelines for enhancing psychological support for medical students.
This article was migrated. The article was marked as recommended. The prevalence of mental illness among medical students is high and this continues to be the case in spite of interventions and of providing students with access to mental health services. In this article we present the basic literature on the issue and the reasons why mental illness still prevails among medical students, and we propose the PEACE model for approaching the issue at multiple and interconnected levels, providing examples of relevant actions.


GPs, violence and work performance - 'just part of the job?'.
This study explored the impact of work related violence on general practitioners' work performance. A postal survey of 1000 randomly selected GPs about work related violence. Those GPs reporting incidents of work related violence in the past 12 months were asked to write about its effect on them in response to an open question. Eighty-five GPs responded. Seventy-three percent of GPs who had experienced work related violence answered an open question about its effect on their work performance. The effect was negative for most, respondents citing poor concentration, difficulty listening to patients, rumination and intrusive thoughts when in an enclosed space in subsequent consultations, particularly in consultations with the patient who had perpetrated the violence, or their families or coworkers, or with similar patients. General practitioners have reported that work related violence has a continuing impact on their work performance. Future research should include psychometric testing of cognitive functioning and mental health testing to quantify this.


Vascular muscle cell depolarization and activation in renal arteries on elevation of transmural pressure.
The goal of this study was to define some of the cellular and ionic mechanisms of smooth muscle cell activation in dog renal arteries exposed to physiological levels of transmural pressure. Isolated interlobular arteries were cannulated and connected to a pressure reservoir to allow manipulation of transmural pressure in 20-mmHg increment steps from 20 to 120 mmHg. As transmural pressure was increased, vascular smooth muscle exhibited a linear depolarization from an average resting potential of -57 +/- 2 mV at 20 mmHg to -38 +/- 2.4 mV at 120 mmHg. Spontaneous action potentials could often be recorded at pressures greater than 80 mmHg. These appeared to occur primarily at bifurcation points of branching arteries. Vascular smooth muscle depolarization and action potentials occurring in response to increases in transmural pressure were associated with a maintenance of internal diameter of the vessel segments despite increases in transmural pressure in the range between 60 and 120 mmHg. The "pressure-induced" activation of vascular smooth muscle contraction and spontaneous action potentials of small renal arteries at higher transmural pressures were blocked on Ca2+ channel inhibition with verapamil (10(-6) M). These data document a membrane ionic mechanism (probably increased Ca2+ influx) for pressure-induced myogenic activation of isolated renal arteries. It is interesting that the contraction of these vessels occurs over the pressure range in which autoregulation of renal blood flow normally occurs. The physiological significance of these responses needs to be determined.


The xenoestrogen bisphenol A induces growth, differentiation, and c-fos gene expression in the female reproductive tract.
The xenoestrogen bisphenol A (BPA) has been shown to mimic estrogen both in vivo and in vitro. BPA stimulates PRL secretion and the expression of a PRL regulating factor from the posterior pituitary in the estrogen-sensitive Fischer 344 rat (F344), but not in Sprague-Dawley (SD) rats. The goal of the present studies was to examine the in vivo actions of BPA on the reproductive tract. The specific objectives were 1) to characterize the short term effects of BPA on cell proliferation and c-fos expression in the uterus and vagina, and 2) to compare the effects of prolonged exposure to low doses of BPA on the reproductive tract of F344 and SD rats. Treatment with single high doses of BPA induced cell proliferation in the uterus and vagina of ovariectomized F344 rats, as determined by bromodeoxyuridine immunostaining. This proliferation was dose dependent (from 37.5-150 mg/kg) and followed a time course similar to that of estradiol (E2). Quantitative RT-PCR revealed that both BPA and E2 increased c-fos messenger RNA levels in the uterus 14- to 16-fold within 2 h, which returned to basal levels after 6 h. In the vagina, BPA-induced c-fos expression remained elevated for up to 6 h, compared with the transient increase caused by E2. Treatment of F344 rats for 3 days with continuous release capsules that supplied a much lower dose of BPA (approximately 0.3 mg/kg x day) resulted in hypertrophy, hyperplasia, and mucus secretion in the uterus and hyperplasia and cornification of the vaginal epithelium. The reproductive tract of SD rats did not respond to this treatment paradigm with BPA. These studies demonstrate that 1) the molecular and morphological alterations induced by BPA in the uterus and vagina are nearly identical to those induced by estradiol; 2) the vagina appears to be especially sensitive to the estrogenic actions of BPA; 3) the reproductive tract of the inbred F344 rat appears more sensitive to BPA than that of the outbred SD rat; and 4) continuous exposure to microgram levels of BPA is sufficient for exerting estrogenic actions.


Ivermectin lipid-based nanocarriers as novel formulations against head lice.
The use of pyrethroids to control the human head louse, Pediculus humanus capitis De Geer (Anoplura: Pediculidae), has suffered considerable loss of efficacy due to the evolution of resistance. Thus, the development of efficiently insecticide delivery systems is imperative for the control of head lice. We studied the insecticidal activity of ivermectin-loaded lipid nanocapsules (IVM-LNC) against permethrin-resistant head lice from Argentina. The LNC, prepared by a phase inversion procedure, were characterized in terms of size, surface potential, and physical stability. These nanoparticles were nearly spherical with mean diameters of 55 nm and narrow size distribution (PI ≤ 0.2). The KT50 mortality values of head lice after exposure to two IVM-LNC formulations (0.11 and 0.28%) were significantly smaller (5 and 3 h, respectively) compared to those exposed only to LNC control group (8 h). This investigation showed the effectiveness in the encapsulation of ivermectin (IVM) into stable LNC dispersion with a potential clinical activity against head lice.


Cost-Effectiveness of Initiating Antiretroviral Therapy at Different Points in TB Treatment in HIV-TB Coinfected Ambulatory Patients in South Africa.
Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment improves survival in TB-HIV coinfected patients. In patients with CD4 counts <50 cells per cubic millimeter, there is a substantial clinical and survival benefit of early ART initiation. The purpose of this study was to assess the costs and cost-effectiveness of starting ART at various time points during TB treatment in patients with CD4 counts ≥50 cells per cubic millimeter. In the SAPiT trial, 642 HIV-TB coinfected patients were randomized to 3 arms: receiving ART within 4 weeks of starting TB treatment (early treatment arm; Arm-1), after the intensive phase of TB treatment (late treatment arm; Arm-2), or after completing TB treatment (sequential arm; Arm-3). Direct health care costs were measured from a provider perspective using a micro-costing approach. The incremental cost per death averted was calculated using the trial outcomes. For patients with CD4 count ≥50 cells per cubic millimeter, median monthly variable costs per patient were US $116, US $113, and US $102 in Arm-1, Arm-2 and Arm-3, respectively. There were 12 deaths in 177 patients in Arm-1, 8 deaths in 180 patients in the Arm-2, and 19 deaths in 172 patients in Arm-3. Although the costs were lower in Arm-3, it had a substantially higher mortality rate. The incremental cost per death averted associated with moving from Arm-3 to Arm-2 was US $4199. There was no difference in mortality between Arm-1 and Arm-2, but Arm-1 was slightly more expensive. Initiation of ART after the completion of the intensive phase of TB treatment is cost-effective for patients with CD4 counts ≥50 cells per cubic millimeter.


CD4-independent use of the CCR5 receptor by sequential primary SIVsm isolates.
CD4-independence has been taken as a sign of a more open envelope structure that is more accessible to neutralizing antibodies and may confer altered cell tropism. In the present study, we analyzed SIVsm isolates for CD4-independent use of CCR5, mode of CCR5-use and macrophage tropism. The isolates have been collected sequentially from 13 experimentally infected cynomolgus macaques and have previously been shown to use CCR5 together with CD4. Furthermore, viruses obtained early after infection were neutralization sensitive, while neutralization resistance appeared already three months after infection in monkeys with progressive immunodeficiency. Depending whether isolated early or late in infection, two phenotypes of CD4-independent use of CCR5 could be observed. The inoculum virus (SIVsm isolate SMM-3) and reisolates obtained early in infection often showed a pronounced CD4-independence since virus production and/or syncytia induction could be detected directly in NP-2 cells expressing CCR5 but not CD4 (CD4-independent-HIGH). Conversely, late isolates were often more CD4-dependent in that productive infection in NP-2/CCR5 cells was in most cases weak and was revealed only after cocultivation of infected NP-2/CCR5 cells with peripheral blood mononuclear cells (CD4-independent-LOW). Considering neutralization sensitivity of these isolates, newly infected macaques often harbored virus populations with a CD4-independent-HIGH and neutralization sensitive phenotype that changed to a CD4-independent-LOW and neutralization resistant virus population in the course of infection. Phenotype changes occurred faster in progressor than long-term non-progressor macaques. The phenotypes were not reflected by macrophage tropism, since all isolates replicated efficiently in macrophages. Infection of cells expressing CCR5/CXCR4 chimeric receptors revealed that SIVsm used the CCR5 receptor in a different mode than HIV-1. Our results show that SIVsm isolates use CCR5 independently of CD4. While the degree of CD4 independence and neutralization sensitivity vary over time, the ability to productively infect monocyte-derived macrophages remains at a steady high level throughout infection. The mode of CCR5 use differs between SIVsm and HIV-1, SIVsm appears to be more flexible than HIV-1 in its receptor requirement. We suggest that the mode of CCR5 coreceptor use and CD4-independence are interrelated properties.


The ulcus-syndrome in cod (Gadus morhua). IV. Transmission experiments with two viruses isolated from cod and Vibrio anguillarum.
Vibrio anguillarum is a serious fish pathogenic bacterium, but it was not found capable of producing the ulcus-syndrome by different inoculation methods in cod. It was possible to transmit the ulcus-syndrome from cod with the papulo-vesicular stage to apparently healthy cod, when they were kept in the same aquarium. Scarification and inoculation with ground papule material lead to development of the ulcus-syndrome. Inoculation of rhabdovirus failed to produce the ulcus-syndrome. Intracardial inoculation of an icosahedral virus suspension could produce the initial papulo-vesicular stage of the ulcus-syndrome in 13 out of 57 inoculated cod (23%). In another experiment 8 out of 36 (22%) inoculated cod developed the ulcus-syndrome and 1 out of 24 (4%) in the control group developed the ulcus-syndrome. In a third experiment 20 inoculated cod failed to develop the ulcus-syndrome. In a number of other cases where the icosahedral virus probably was present in the inoculation material the ulcus-syndrome was also produced, but with a lower frequency. It is indicated, that the isolated icosahedral virus plays a role in the pathogenesis of the ulcus-syndrome in cod, and that Vibrio anguillarum is important for the further progress of the disease.


Evasion of Immunity to Plasmodium falciparum: Rosettes of Blood Group A Impair Recognition of PfEMP1.
The ABO blood group antigens are expressed on erythrocytes but also on endothelial cells, platelets and serum proteins. Notably, the ABO blood group of a malaria patient determines the development of the disease given that blood group O reduces the probability to succumb in severe malaria, compared to individuals of groups A, B or AB. P. falciparum rosetting and sequestration are mediated by PfEMP1, RIFIN and STEVOR, expressed at the surface of the parasitized red blood cell (pRBC). Antibodies to these antigens consequently modify the course of a malaria infection by preventing sequestration and promoting phagocytosis of pRBC. Here we have studied rosetting P. falciparum and present evidence of an immune evasion mechanism not previously recognized. We find the accessibility of antibodies to PfEMP1 at the surface of the pRBC to be reduced when P. falciparum forms rosettes in blood group A RBC, as compared to group O RBC. The pRBC surrounds itself with tightly bound normal RBC that makes PfEMP1 inaccessible to antibodies and clearance by the immune system. Accordingly, pRBC of in vitro cloned P. falciparum devoid of ABO blood group dependent rosetting were equally well detected by anti-PfEMP1 antibodies, independent of the blood group utilized for their propagation. The pathogenic mechanisms underlying the severe forms of malaria may in patients of blood group A depend on the ability of the parasite to mask PfEMP1 from antibody recognition, in so doing evading immune clearance.


Toxicity and bioaccumulation of biosolids-borne triclosan in terrestrial organisms.
Triclosan (TCS) is a common constituent of personal care products and is frequently present in biosolids. Application of biosolids to land transfers significant amounts of TCS to soils. Because TCS is an antimicrobial and is toxic to some aquatic organisms, concern has arisen that TCS may adversely affect soil organisms. The objective of the present study was to investigate the toxicity and bioaccumulation potential of biosolids-borne TCS in terrestrial micro- and macro-organisms (earthworms). Studies were conducted in two biosolids-amended soils (sand, silty clay loam), following U.S. Environmental Protection Agency (U.S. EPA) guidelines. At the concentrations tested herein, microbial toxicity tests suggested no adverse effects of TCS on microbial respiration, ammonification, and nitrification. The no observed effect concentration for TCS for microbial processes was 10 mg/kg soil. Earthworm subchronic toxicity tests showed that biosolids-borne TCS was not toxic to earthworms at the concentrations tested herein. The estimated TCS earthworm lethal concentration (LC50) was greater than 1 mg/kg soil. Greater TCS accumulation was observed in earthworms incubated in a silty clay loam soil (bioaccumulation factor [BAF] = 12 ± 3.1) than in a sand (BAF = 6.5 ± 0.84). Field-collected earthworms had a significantly smaller BAF value (4.3 ± 0.7) than our laboratory values (6.5-12.0). The BAF values varied significantly with exposure conditions (e.g., soil characteristics, laboratory vs field conditions); however, a value of 10 represents a reasonable first approximation for risk assessment purposes.


Constrained acquisition of ink spreading curves from printed color images.
Today's spectral reflection prediction models are able to predict the reflection spectra of printed color images with an accuracy as high as the reproduction variability allows. However, to calibrate such models, special uniform calibration patches need to be printed. These calibration patches use space and have to be removed from the final product. The present contribution shows how to deduce the ink spreading behavior of the color halftones from spectral reflectances acquired within printed color images. Image tiles of a color as uniform as possible are selected within the printed images. The ink spreading behavior is fitted by relying on the spectral reflectances of the selected image tiles. A relevance metric specifies the impact of each ink spreading curve on the selected image tiles. These relevance metrics are used to constrain the corresponding ink spreading curves. Experiments performed on an inkjet printer demonstrate that the new constraint-based calibration of the spectral reflection prediction model performs well when predicting color halftones significantly different from the selected image tiles. For some prints, the proposed image based model calibration is more accurate than a classical calibration.


High Expression of N-Acetylgalactosaminyl-transferase 1 (GALNT1) Associated with Invasion, Metastasis, and Proliferation in Osteosarcoma.
BACKGROUND Osteosarcoma (OS) is very common worldwide, and the mechanisms underlying its development remain unclear. This study aims to identify key genes promoting the reproduction, invasion, and transfer of osteosarcoma cells. MATERIAL AND METHODS Gene expression profile data (GSE42352 and GSE42572) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes were calculated using R software. Gene ontology and enriched pathway analysis of mRNAs were analyzed by using FunRich. Verification of the genes was conducted by using quantitative real-time polymerase chain reaction and western blot analyses to measure gene expression. Transwell and wound-healing assays were performed on osteosarcoma cells after knockdown to detect whether the genes enhanced the aggressiveness of osteosarcoma. RESULTS In total, 34 genes were selected after filtering. Kyoto Encyclopedia of Genes and Genomes enrichment analysis demonstrated that the genes were enriched in multiple tumor pathways. N-acetylgalactosaminyltransferase 1 (GALNT1) was identified for further study, and its expression was higher in osteosarcoma cells than in human osteoblasts. The invasion ability of cells was significantly decreased after gene knockdown. CONCLUSIONS Through the use of microarray and bioinformatics analysis, differentially expressed genes were selected and a complete gene network was constructed. Our findings provide new biomarkers for the treatment and prognosis of osteosarcoma. These biomarkers may contribute to the discovery of new therapeutic targets for clinical application.


Male Stress Incontinence Grading Scale (MSIGS) for Evaluation of Men with Post-Prostatectomy Incontinence: A Pilot Study.
We developed an objective clinical grading scale to characterize post-prostatectomy incontinence (PPI) and evaluated its use as a tool to facilitate male anti-incontinence procedure selection. Between September 2014 and July 2015, we prospectively implemented a novel Male Stress Incontinence Grading Scale (MSIGS) to stratify PPI patients based on incontinence severity. Patients included were those referred for PPI who had no prior anti-incontinence surgery. During the initial outpatient consultation, each patient was prospectively assigned an incontinence grade score of 0 through 4 based on the consensus of 2 examiners performing a standing cough test (SCT). All patients refrained from voiding for at least 60 minutes prior to the SCT. Men with mild SUI (MSIGS grades 0-2) were offered AdVance sling surgery while those with heavier SUI (MSIGS grades 3-4) were offered artificial urinary sphincter (AUS). MSIGS grade was correlated to patient-reported pads-per-day (PPD), and patient-reported outcomes of anti-incontinence surgery were assessed. Of 62 consecutive new PPI patients, 20 were graded as mild based on SCT [five (8%) grade 0, 10 (16%) grade 1, five (8%) grade 2] while 42 were graded as moderate-severe [10 (16%) grade 3, 32 (52%) grade 4]. MSIGS grade demonstrated a strong correlation with preoperative PPD (r=0.74). Among the 53 patients who underwent surgical intervention for PPI, 14 with mild SUI were treated with AdVance® male urethral sling (MSIGS grade 0, 1, or 2) while 39 more severe cases received AUS (MSIGS grade 3 or 4). Patient-reported improvement was high overall (median 95%) and similar for sling and AUS patients (95% and 96.5% respectively, p=0.596). The median time from radical prostatectomy to anti-incontinence surgery was 5.4 years (range 1-20). The Male Stress Incontinence Grading Scale provides a rapid, simple, non-invasive, objective assessment of PPI severity which strongly correlates with patient-reported pads-per-day and appears to facilitate anti-incontinence surgical procedure selection.


Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens.
Actomyosin-based contractility acts on cadherin junctions to support tissue integrity and morphogenesis. The actomyosin apparatus of the epithelial zonula adherens (ZA) is built by coordinating junctional actin assembly with Myosin II activation. However, the physical interaction between Myosin and actin filaments that is necessary for contractility can induce actin filament turnover, potentially compromising the contractile apparatus itself. We now identify tension-sensitive actin assembly as one cellular solution to this design paradox. We show that junctional actin assembly is maintained by contractility in established junctions and increases when contractility is stimulated. The underlying mechanism entails the tension-sensitive recruitment of vinculin to the ZA. Vinculin, in turn, directly recruits Mena/VASP proteins to support junctional actin assembly. By combining strategies that uncouple Mena/VASP from vinculin or ectopically target Mena/VASP to junctions, we show that tension-sensitive actin assembly is necessary for junctional integrity and effective contractility at the ZA. We conclude that tension-sensitive regulation of actin assembly represents a mechanism for epithelial cells to resolve potential design contradictions that are inherent in the way that the junctional actomyosin system is assembled. This emphasizes that maintenance and regulation of the actin scaffolds themselves influence how cells generate contractile tension.


Effect of vaccination on children's learning achievements: findings from the India Human Development Survey.
Beyond the prevention of illness and death, vaccination may provide additional benefits such as improved educational outcomes. However, there is currently little evidence on this question. Our objective was to estimate the effect of childhood vaccination on learning achievements among primary school children in India. We used cohort data from the India Human Development Survey. Vaccination status and confounders were measured among children who were at least 12 months old at baseline in 2004-2005. In 2011-2012, the same children completed basic reading, writing and math tests. We estimated the effect of full vaccination during childhood on learning achievements using inverse probability of treatment-weighted logistic regression models and results reported on the risk difference scale. The propensity score included 33 potential community-, household-, mother- and child-level confounders as well as state fixed effects. Among the 4877 children included in our analysis, 54% were fully vaccinated at baseline, and 54% could read by the age of 8-11 years. The estimated effect of full vaccination on learning achievements ranged from 4 to 6 percentage points, representing relative increases ranging from 6% to 12%. Bias analysis suggested that our observed effects could be explained by unmeasured confounding, but only in the case of strong associations with the treatment and outcome. These results support the hypothesis that vaccination has lasting effects on children's learning achievements. Further work is needed to confirm findings and elucidate the potential mechanisms linking vaccines to educational outcomes.


Use of the polymerase chain reaction for Salmonella detection.
A primer set of oligonucleotides (S18 and S19) from the ompC gene of Salmonella has been evaluated for specific detection of Salmonella by polymerase chain reaction (PCR). This primer set successfully amplified 40 Salmonella serovars (60 isolates), but not 24 non-Salmonella bacteria (42 isolates) that have been tested so far. The uniqueness of these primer sequences was also confirmed. The sensitivity of PCR detection in extracted chromosomal DNA for Salm. typhimurium was 1 pg. The sensitivity for boiled whole bacteria was 400 cells. The detection of Salm. typhimurium in ground beef samples required 4-6 h enrichment with an initial inocula of 100 bacteria.


Applying biomarkers to clinical practice: a guide for utilizing procalcitonin assays.
Prudent use of antimicrobial therapies is an important component in decreasing bacterial resistance. Procalcitonin (PCT) is a novel biomarker proposed as both a diagnostic and prognostic agent for use in various severe infections. Elevated PCT levels have a high sensitivity and specificity for diagnosing infections. This biomarker has been studied as an aid to identify patients requiring antimicrobial initiation, stratify infections according to severity and guide therapy durations. Two commercially available tests are approved for use in the USA. Other biomarkers have been studied for similar indications, but are subject to elevation from chronic inflammatory conditions and medications. The advantage of PCT over other biomarkers is due to the limited disease states and drug therapies that may interfere with this assay. PCT has been studied extensively for use in patients with severe sepsis and septic shock, as well as in lower respiratory tract infections. Decreased antimicrobial utilization without an increase in patient morbidity and mortality has been illustrated through numerous studies using PCT algorithms. Determining the utility of PCT in practice requires a comprehensive evaluation of the impact this biomarker has on outcomes to the patient and healthcare system, as well as examining convenience and cost factors. PCT can be used to assist clinicians in initiating and guiding antimicrobial therapies for specific patient populations, as an adjunct to other diagnostic tools. Further studies examining long-term outcomes of PCT are needed to determine the effect of this intervention on resistance patterns and overall prescribing trends.


Thymidylate kinase from Acetabularia. I. Properties of the enzyme.
The occurrence of a dTMP kinase as well as a dTDP kinase in Acetabularia mediterranea has been demonstrated. A test system was developed by which it was possible to estimate the enzyme activity in an individual Acetabularia cell or even in a cell fragment. The enzyme catalyses the phosphorylation of dTMP in the presence of ATP. In the test system described, dTTP is formed as well as dTDP. This indicates that there is also a dTDP kinase present in the enzyme preparation. Characteristics of the enzyme such as pH optima at pH 7.0 and 8.75, a temperature optimum at 45 degrees C, a Km value of 3.3 X 10(-6) M and a high specificity for ATP were established. In homogenates that were preserved at -70 degrees C the enzyme activity was retained even after many weeks. Freezing at -70 degrees C and then thawing resulted in an increase in enzyme activity. The enzyme was inhibited by low concentrations of dTTP. After centrifugation of homogenates the greater part of the enzyme activity was found in the sediment. From the observation that purified chloroplast preparations contained most of the dTMP kinase activity, and that chlorophyll and enzyme activity cosedimented in a linear sucrose gradient, it was concluded that the enzyme is located in the chloroplasts.


Motor speech effects in subthalamic deep brain stimulation for Parkinson's disease.
A motor speech disorder or dysarthria commonly arises in patients with Parkinson's disease (PD). The impact of subthalamic nucleus (STN) deep brain stimulation (DBS) on motor speech and the potential of intraoperative motor speech testing to predict outcomes are unknown. This study examined 1) the types and prevalence of motor speech changes observed with STN DBS and their relation to the preoperative condition, 2) the ability of intraoperative testing to predict postoperative changes in motor speech, and 3) the spatial relationship between stimulation sites producing maximal motor improvement, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and maximal motor speech deterioration. Comprehensive preoperative, intraoperative, and postoperative motor speech/dysarthria evaluations were performed in consecutive patients with advanced idiopathic PD who underwent STN DBS surgery in the period from 2011 to 2016. Preoperative type of dysarthria and overall dysarthria severity rating along with intraoperative motor speech testing results were evaluated as predictors of postoperative change. Atlas-independent, fully individualized field modeling was used to identify stimulation sites associated with maximal MDS-UPDRS motor improvement and motor speech deterioration. Forty-three patients with PD treated with STN DBS were prospectively studied. Improved MDS-UPDRS motor scores and worsened dysarthria were demonstrated by a subset of patients (16/43). Preoperative dysarthria characteristics did not predict postoperative deterioration. Intraoperative assessment of motor speech strongly predicted postoperative outcomes (OR 4.4, p = 0.02). Sites of maximal MDS-UPDRS motor improvement and worsened dysarthria were distinct. Worsened dysarthria was associated with capsular stimulation, anterior and ventral to the site of maximal MDS-UPDRS motor improvement. The predictive reliability of intraoperative motor speech testing, together with the identification of distinct stimulation sites for motor speech impairment and improved MDS-UPDRS motor function, raise the possibility that DBS lead repositioning or reprogramming could reduce adverse effects on motor speech without impacting MDS-UPDRS motor outcomes in patients undergoing STN DBS.


Babinski's signe de l'eventail: a turning point in the history of neurology.
The Babinski sign is a finding known since the start of the teachings of physical diagnosis by almost all medical students. This reflex is an incredibly helpful phenomenon that enables physicians to distinguish between central and the peripheral nervous system diseases right at the bedside. Yet, most students as well as physicians remain oblivious to the remarkable history behind the Babinski sign and what it means to evolutional history of the modern neurological exam. We intend to study the birth of the "signe de l'eventail" (the fanning sign) and how it transformed medical diagnosis as we practice it today. An extensive search was conducted through the Internet to identify historical documents referring to Babinski and other physicians who also observed the phenomenon as early as the 17th and 18th century. We also conducted a search through medical journals that examined the Babinski sign and its history. The Babinski reflex had been observed much earlier than 1896, when Babinski referred to his finding for the first time. The reflex had been reported in the literature as far back as 1784 and afterwards reobserved several times before Babinski. However, it was Babinski who first offered an interpretation of the reflex and suggested that it was related to an organic disruption in the central nervous system. By identifying the sign, Babinski separated himself from Charcot in the sense of creating a new tradition in neurology where the findings in a neurological exam were of far more importance than just a plain history as his mentor had relied upon. Babinski was not only responsible for suggesting the significance of such sign, but also transformed the role that physical diagnosis plays in modern medicine, where physical examination is key in revealing underlying pathology.


Compensatory control and the appeal of a structured world.
People are motivated to perceive themselves as having control over their lives. Consequently, they respond to events and cognitions that reduce control with compensatory strategies for restoring perceived control to baseline levels. Prior theory and research have documented 3 such strategies: bolstering personal agency, affiliating with external systems perceived to be acting on the self's behalf, and affirming clear contingencies between actions and outcomes within the context of reduced control (here termed specific structure). We propose a 4th strategy: affirming nonspecific structure, or seeking out and preferring simple, clear, and consistent interpretations of the social and physical environments. Formulating this claim suggests that people will respond to reduced control by affirming structured interpretations that are unrelated to the control-reducing condition, and even those that entail otherwise adverse outcomes (e.g., pessimistic health prospects). Section 1 lays the conceptual foundation for our review, situating the proposed phenomenon in the literatures on control motivation and threat-compensation mechanisms. Section 2 reviews studies that have demonstrated that trait and state variations in perceived control predict a wide range of epistemic structuring tendencies, including pattern recognition and causal reasoning. We posit that these tendencies reflect a common desire for a structured understanding of one's environment. Accordingly, a new meta-analysis spanning the reviewed studies (k = 55) revealed that control reduction predicts nonspecific structure affirmation with a moderate effect size (r = .25). Section 3 reviews research on individual differences and situational moderators of this effect. The discussion addresses the interplay of compensatory control strategies and practical implications.


Digging into Lipid Membrane Permeation for Cardiac Ion Channel Blocker d-Sotalol with All-Atom Simulations.
Interactions of drug molecules with lipid membranes play crucial role in their accessibility of cellular targets and can be an important predictor of their therapeutic and safety profiles. Very little is known about spatial localization of various drugs in the lipid bilayers, their active form (ionization state) or translocation rates and therefore potency to bind to different sites in membrane proteins. All-atom molecular simulations may help to map drug partitioning kinetics and thermodynamics, thus providing in-depth assessment of drug lipophilicity. As a proof of principle, we evaluated extensively lipid membrane partitioning of d-sotalol, well-known blocker of a cardiac potassium channel Kv11.1 encoded by the hERG gene, with reported substantial proclivity for arrhythmogenesis. We developed the positively charged (cationic) and neutral d-sotalol models, compatible with the biomolecular CHARMM force field, and subjected them to all-atom molecular dynamics (MD) simulations of drug partitioning through hydrated lipid membranes, aiming to elucidate thermodynamics and kinetics of their translocation and thus putative propensities for hydrophobic and aqueous hERG access. We found that only a neutral form of d-sotalol accumulates in the membrane interior and can move across the bilayer within millisecond time scale, and can be relevant to a lipophilic channel access. The computed water-membrane partitioning coefficient for this form is in good agreement with experiment. There is a large energetic barrier for a cationic form of the drug, dominant in water, to cross the membrane, resulting in slow membrane translocation kinetics. However, this form of the drug can be important for an aqueous access pathway through the intracellular gate of hERG. This route will likely occur after a neutral form of a drug crosses the membrane and subsequently re-protonates. Our study serves to demonstrate a first step toward a framework for multi-scale in silico safety pharmacology, and identifies some of the challenges that lie therein.


Proteogenomics of Candida tropicalis--An Opportunistic Pathogen with Importance for Global Health.
The frequency of Candida infections is currently rising, and thus adversely impacting global health. The situation is exacerbated by azole resistance developed by fungal pathogens. Candida tropicalis is an opportunistic pathogen that causes candidiasis, for example, in immune-compromised individuals, cancer patients, and those who undergo organ transplantation. It is a member of the non-albicans group of Candida that are known to be azole-resistant, and is frequently seen in individuals being treated for cancers, HIV-infection, and those who underwent bone marrow transplantation. Although the genome of C. tropicalis was sequenced in 2009, the genome annotation has not been supported by experimental validation. In the present study, we have carried out proteomics profiling of C. tropicalis using high-resolution Fourier transform mass spectrometry. We identified 2743 proteins, thus mapping nearly 44% of the computationally predicted protein-coding genes with peptide level evidence. In addition to identifying 2591 proteins in the cell lysate of this yeast, we also analyzed the proteome of the conditioned media of C. tropicalis culture and identified several unique secreted proteins among a total of 780 proteins. By subjecting the mass spectrometry data derived from cell lysate and conditioned media to proteogenomic analysis, we identified 86 novel genes, 12 novel exons, and corrected 49 computationally-predicted gene models. To our knowledge, this is the first high-throughput proteomics study of C. tropicalis validating predicted protein coding genes and refining the current genome annotation. The findings may prove useful in future global health efforts to fight against Candida infections.


Profitable solutions to climate, oil, and proliferation.
Protecting the climate is not costly but profitable (even if avoided climate change is worth zero), mainly because saving fuel costs less than buying fuel. The two biggest opportunities, both sufficiently fast, are oil and electricity. The US, for example, can eliminate its oil use by the 2040s at an average cost of $15 per barrel ($2000), half by redoubled efficiency and half by alternative supplies, and can save three-fourths of its electricity more cheaply than operating a thermal power station. Integrative design permits this by making big energy savings cheaper than small ones, turning traditionally assumed diminishing returns into empirically observed expanding returns. Such efficiency choices accelerate climate-safe, inexhaustible, and resilient energy supply-notably the "micropower" now delivering about a sixth of the world's electricity and 90% of its new electricity. These cheap, fast, market-financeable, globally applicable options offer the most effective, yet most underestimated and overlooked, solutions for climate, proliferation, and poverty.


SAMQA: error classification and validation of high-throughput sequenced read data.
The advances in high-throughput sequencing technologies and growth in data sizes has highlighted the need for scalable tools to perform quality assurance testing. These tests are necessary to ensure that data is of a minimum necessary standard for use in downstream analysis. In this paper we present the SAMQA tool to rapidly and robustly identify errors in population-scale sequence data. SAMQA has been used on samples from three separate sets of cancer genome data from The Cancer Genome Atlas (TCGA) project. Using technical standards provided by the SAM specification and biological standards defined by researchers, we have classified errors in these sequence data sets relative to individual reads within a sample. Due to an observed linearithmic speedup through the use of a high-performance computing (HPC) framework for the majority of tasks, poor quality data was identified prior to secondary analysis in significantly less time on the HPC framework than the same data run using alternative parallelization strategies on a single server. The SAMQA toolset validates a minimum set of data quality standards across whole-genome and exome sequences. It is tuned to run on a high-performance computational framework, enabling QA across hundreds gigabytes of samples regardless of coverage or sample type.


Nucleophile selection for the endonuclease activities of human, ovine, and avian retroviral integrases.
Retroviral integrases catalyze four endonuclease reactions (processing, joining, disintegration, and nonspecific alcoholysis) that differ in specificity for the attacking nucleophile and target DNA sites. To assess how the two substrates of this enzyme affect each other, we performed quantitative analyses, in three retroviral systems, of the two reactions that use a variety of nucleophiles. The integrase proteins of human immuno- deficiency virus type 1, visna virus, and Rous sarcoma virus exhibited distinct preferences for water or other nucleophiles during site-specific processing of viral DNA and during nonspecific alcoholysis of nonviral DNA. Although exogenous alcohols competed with water as the nucleophile for processing, the alcohols stimulated nicking of nonviral DNA. Moreover, different nucleophiles were preferred when the various integrases acted on different DNA targets. In contrast, the nicking patterns were independent of whether integrase was catalyzing hydrolysis or alcoholysis and were not influenced by the particular exogenous alcohol. Thus, although the target DNA influenced the choice of nucleophile, the nucleophile did not affect the choice of target sites. These results indicate that interaction with target DNA is the critical step before catalysis and suggest that integrase does not reach an active conformation until target DNA has bound to the enzyme.


Substrate-induced closing of the active site revealed by the crystal structure of pantothenate synthetase from Staphylococcus aureus.
Pantothenate synthetase (PS, EC 188.8.131.52) is the last enzyme in the pantothenate biosynthesis pathway, a metabolic pathway identified as a potential target for new antimicrobials. PS catalyzes the ATP-dependent condensation of pantoate and beta-alanine to form pantothenate. Here we report the overexpression, purification, enzyme assay, and tertiary structure of PS from Staphylococcus aureus. PS activity was experimentally confirmed, indicating a k(cat) value comparable to those of enzymes from other organisms. The structures of the apoenzyme and the reaction intermediate (pantoyl adenylate; PA) complex were determined by X-ray crystallography to resolutions of 2.5 and 1.85 A, respectively. Structural analysis indicated that the apoenzyme adopts an open and relatively mobile structure, while the complex structure is closed and entirely rigid. Structural comparison of the apoenzyme and the complex revealed how S. aureus PS undergoes open/close conformational change, and also determined the key interactions with the adenine ring of PA for a hinge bending domain closure. In the complex structure, PA and acetate are bound in the active site. We suggest that the acetate mimics the substrate beta-alanine. Therefore, the complex structure seems to represent a catalytic state poised for in-line nucleophilic attack on PA. These data also offer an alternative strategy for designing novel compounds that selectively inhibit PS activity.


Glyphosate inhibits melanization of Cryptococcus neoformans and prolongs survival of mice after systemic infection.
Cryptococcus neoformans is a major fungal pathogen and is a relatively common cause of life-threatening meningoencephalitis. Glyphosate is a widely used herbicide that inhibits the synthesis of aromatic amino acids via the shikimate acid pathway. This study investigated the effects of glyphosate on C. neoformans growth, melanization, and murine infection. C. neoformans was relatively resistant to glyphosate, requiring concentrations >250 microg/mL for inhibition. Melanization of C. neoformans in the presence of L-dopa was inhibited by subinhibitory concentrations of glyphosate. Glyphosate inhibited autopolymerization of L-dopa and oxidation of L-epinephrine by cryptococcal cells, which is mediated by a laccase. Administration of glyphosate to mice infected with C. neoformans delayed melanization of yeast cells in vivo and prolonged average mouse survival. The results suggest that inhibition of melanization in vivo may facilitate control of C. neoformans infection.


Vanadium, cobalt, zinc, and rubidium are associated with markers of inflammation and oxidative stress in a Greek population with obesity.
The prevalence of obesity is rising globally, with negative effects on the socioeconomic system. As a result of its drivers which include low-grade chronic inflammation, oxidative stress, and fatty acid metabolism, this phenotype develops metabolic anomalies that exacerbate its pathogenesis. It has been discovered that metals and metalloids have substantial effects on both the immune system and metabolism and are influenced by factors connected to obesity. Although there is a known connection between metals, obesity, and related metabolic disorders, it is still under research. We determined the plasma levels of 16 metals and metalloids in 76 individuals with obesity and investigated the relationships with inflammatory and oxidative stress biomarkers in order to clarify the processes by which metals/metalloids exhibit their effects. After adjusting for age, gender, BMI, physical activity level, smoking, the existence of metabolic abnormalities, and dietary intake of the corresponding metal, regression analysis revealed the following statistically significant associations; vanadium was negatively associated with oxLDL (Beta ± SE= -0.014 ± 0.005, p=0.007), zinc was negatively associated with leptin (Beta ± SE= -12.390 ± 5.226, p=0.025), cobalt was associated negatively with adiponectin (Beta ± SE= -0.030 ± 0.012, p=0.001) and positively with MPO (Beta ± SE= 0.002 ± 0.001, p=0.023), and rubidium was negatively associated with oxLDL (Beta ± SE= -1.139 ± 0.411, p=0.008) and positively with MPO (Beta ± SE= 0.324 ± 0.102, p=0.003). The aforementioned associations highlight the need for further research, demonstrating the importance of inflammation and oxidative stress in the association between metals/metalloids and obesity-related metabolic abnormalities.


The role of annexin A4 in cancer.
Annexin A4 (ANXA4) is a member of the annexin family that binds to both calcium ions and phospholipids. Studies indicate that ANXA4 modulates membrane permeability and membrane trafficking, participates in cellular growth and apoptosis, enhances tumor invasion and promotes anti-tumor drug resistance. The overexpression of ANXA4 has been identified in various clinical epithelial tumors including: lung, gastric, colorectal, pancreatic, gallbladder, breast, renal, ovarian, laryngeal, and prostate cancers. In addition, upregulation and nuclear translocation of ANXA4 have been observed in the progression of colorectal cancer and ovarian serous carcinoma. Knockdown of ANXA4 attenuated migration in ovarian cancer and breast cancer cells. In contrast, knockdown of ANXA4 increased susceptibility to platinum in ovarian cancer and malignant mesothelioma cells. It is conceivable that ANXA4 is an indicator for tumor development, invasion, chemo-resistance, poor outcomes of cancer patients, and may be a potential target for therapeutic intervention.


Calcium, phosphorus, and magnesium concentrations in plasma during first week of life and their relation to type of milk feed.
Serial changes in plasma levels of calcium, phosphorus, magnesium, alkaline phosphatase, and total proteins have been investigated in 138 healthy, term Caucasian infants. Blood samples were obtained for each infant from cord blood and on day 1 and day 6. The infants were studied in three groups according to whether they were breast fed, received 'Ostermilk No. 1' or 'Cow and Gate V' formulas. Levels of calcium, phosphorus, magnesium, alkaline phosphatase, and total proteins did not differ between the groups at birth or on day 1. By day 6 calcium levels were higher and phosphorus levels lower in the breast-fed infants compared with either of the artificially-fed groups. Phosphorus levels were lower in the V Formula group compared with the Ostermilk group but the mean calcium levels of these two groups did not differ significantly. However, only 2-8% of the V Formula group developed hypocalcaemia compared with 18-2% of the Ostermilk group. The only infant developing clinical tetany belonged to the group fed Ostermilk. Evidence is also given which suggests that those infants with low calcium levels on day 1 who were fed the high-solute milk tended to show a fall in calcium by day 6. This did not apply to the two other groups. It is concluded that the use of adapted cows' milk preparations for infant feeding should lead to a reduction in the incidence of neonatal tetany.


Strophanthidin-sensitive sodium fluxes in metabolically poisoned frog skeletal muscle.
Strophanthidin-sensitive and insensitive unidirectional fluxes of Na were measured in fog sartorius muscles whose internal Na levels were elevated by overnight storage in the cold. ATP levels were lowered, and ADP levels raised, by metabolic poisoning with either 2,4-dinitrofluorobenzene or iodoacetamide. Strophanthidin-sensitive Na efflux and influx both increased after poisoning, while strophanthidin-insensitives fluxes did not. The increase in efflux did not require the presence of external K but was greatly attenuated when Li replaced Na as the major external cation. Membrane potential was not markedly altered by 2,4-dinitrofluorobenzene. These observations indicate that the sodium pump of frog skeletal muscle resembles that of squid giant axon and human erythrocyte in its ability to catalyze Na-Na exchange to an extent determined by intracellular ATP/ADP levels.


In vitro activity of selected antibiotics against anaerobes.
Testing antibiotics for their activity against microorganisms is fraught with problems. The various methods and media yield different results, and controversy exists as to which is the most reliable. The technique used in our laboratory has shown wide differences in the susceptibility patterns of Bacteroides strains and other anaerobes to different antibiotics. Particularly with respect to the third-generation cephalosporins, reliable clinical data are needed to determine which in vitro tests most accurately predict clinical efficacy.


Studies on chiral interactions of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane and the corresponding N-hydroxy metabolites with cytochrome P-450.
The stereoselective pharmacological behavior and metabolism of the potent psychotomimetic amine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane have led to an investigation of the interactions of the racemic amine, its enantiomers, and the corresponding N-hydroxy metabolites with rabbit liver microsomal cytochrome P-450. An examination of the formation of cytochrome P-450 metabolic intermediate complexes with these species suggests that N-oxidation of the pharmacologically active (R)-amine in inhibited by the S enantiomer. Additionally, metabolic intermediate complex formation [favored by the (R)-amine] appears to be associated with loss of microsomal mixed function N-oxidase activity. The results have led to the prediction that N-hydroxylation of pure (R)-amine may be a qualitatively more important pathway than that observed with racemic amine even though this biotransformation may be suicidal.


Motif trap: a rapid method to clone motifs that can target proteins to defined subcellular localisations.
We have developed a rapid procedure termed Motif Trap (MT) to identify protein motifs that are able to target proteins to a distinct subcellular localisation in eukaryotic cells. By expressing random DNA fragments fused to green fluorescent protein (GFP), individual cells with the GFP localisation of interest are readily isolated allowing for the expressed DNA fragments to be cloned by RT-PCR. These can then be used to identify the corresponding full-length cDNAs. Using MT, we have identified patterns of GFP localisation which correspond to every major organelle and compartment. We have shown that MT is useful to identify new sequences that determine subcellular localisation as well as known targeting motifs.


Frontotemporal Lobar Degeneration (FTLD): Review and Update for Clinical Neurologists.
Frontotemporal Dementia (FTD) is a heterogeneous group of disorders and the second most frequent cause of early onset dementia making it the highest number of inherited cases. FTD is characterized by considerable variability in clinical, genetic and histopathologic features. Patients may present symptoms ranging from behavioural disturbances to different language disorders, with or without motor neuron disorders or associated parkinsonism. Atrophy in frontal and temporal lobes is the most relevant radiological finding. In the last 10 years, the knowledge of this clinical entity has undergone remarkable changes both genetically and histopathologically, which have served to establish more consistent clinical criteria. Until now, 10 genes causative of FTLD have been described and up to four different proteins causative of atrophy have been detected in aggregates. This review is mostly addressed to clinicians and aims to provide basic knowledge of these neurodegenerative disorders and clarify the complex FTD scenario.


Phylogenetic lineages in the Capnodiales.
The Capnodiales incorporates plant and human pathogens, endophytes, saprobes and epiphytes, with a wide range of nutritional modes. Several species are lichenised, or occur as parasites on fungi, or animals. The aim of the present study was to use DNA sequence data of the nuclear ribosomal small and large subunit RNA genes to test the monophyly of the Capnodiales, and resolve families within the order. We designed primers to allow the amplification and sequencing of almost the complete nuclear ribosomal small and large subunit RNA genes. Other than the Capnodiaceae (sooty moulds), and the Davidiellaceae, which contains saprobes and plant pathogens, the order presently incorporates families of major plant pathological importance such as the Mycosphaerellaceae, Teratosphaeriaceae and Schizothyriaceae. The Piedraiaceae was not supported, but resolves in the Teratosphaeriaceae. The Dissoconiaceae is introduced as a new family to accommodate Dissoconium and Ramichloridium. Lichenisation, as well as the ability to be saprobic or plant pathogenic evolved more than once in several families, though the taxa in the upper clades of the tree lead us to conclude that the strictly plant pathogenic, nectrotrophic families evolved from saprobic ancestors (Capnodiaceae), which is the more primitive state.


The determination of magnesium in human blood plasma by 31P magnetic resonance spectroscopy using a macrocyclic reporter ligand.
The ligand 1,4,7-triazacyclononane-1,4,7-tris(methylene methylphosphinic acid), NOTMP, was used to measure free MgII levels in blood plasma by 31P MRS. Separate resonances were observed for the free ligand and the MgII complex and the ratio of their resonance areas was used to evaluate the free, ionized MgII concentration, [Mg]free. The CaII and the ZnII complexes gave rise to separate resonances in the 31P spectrum in an aqueous sample. In human blood plasma samples, however, these resonances were never observed thus excluding the interference of these metal ions. Heparin, up to 150 units/ml, had no influence on the Mg-NOTMP equilibrium. The 31P MRS methodology was applied to twenty human blood plasma samples. Total MgII ([Mg]total), as measured by atomic absorption spectroscopy, averaged 0.85 +/- 0.12 mM while free ionized MgII ([Mg]free) measured by 31P MRS was 0.66 +/- 0.09 mM. The 31P MRS method gave inherently larger values for free ionized MgII than that reported by ion-selective electrodes (ISE). This was traced to a redistribution of existing plasma MgII species after the addition of about 2 mM of NOTMP. Calculations using existing thermodynamic data show that the ionized MgII concentration (iMg) and the concentration of MgII weakly complexed to small anions (Mg(comp)) both drop after the addition of NOTMP, with Mg(comp) dropping to negligible levels. Thus, the 31P MRS method appears to be less sensitive to variations in the concentration of weakly binding anions (bicarbonate, carbonate, chloride, lactate, phosphate, etc.) than the ISE method. Our data indicates that the difference between Mg(total), as measured by atomic absorption spectroscopy, and Mg(free), as measured by 31P MRS, provides an direct estimate of the protein bound MgII fraction.


Genome-Wide Association Mapping of Major Root Length QTLs Under PEG Induced Water Stress in Wheat.
Roots are vital plant organs that determine adaptation to various soil conditions. The present study evaluated a core winter wheat collection for rooting depth under PEG induced early stage water stress and non-stress growing conditions. Analysis of phenotypic data indicated highly significant (p < 0.01) variation among genotypes. Broad sense heritability of 59 and 73% with corresponding genetic gains of 7.6 and 9.7 (5% selection intensity) were found under non-stress and stress conditions, respectively. The test genotypes were grouped in to three distinct clusters using unweighted pair group method with arithmetic mean (UPGMA) clustering based on maximum Euclidian distance. The first three principal components gave optimum mixed linear model for genome wide association study (GWAS). Linkage disequilibrium (LD) analysis showed significant LD (p < 0.05) amongst 15% of total marker pairs (25,125). Nearly 16% of the significant LDs were among inter chromosomal marker pairs. GWAS revealed five significant root length QTLs spread across four chromosomes. None of the identified QTLs were common between the two growing conditions. Stress specific QTLs, combined explaining 31% of phenotypic variation were located on chromosomes 2B (wPt6278) and 3B (wPt1159). Similarly, two of the three QTLs (wPt0021 and wPt8890) identified under the non-stress condition were found on chromosomes 3B and 5B, respectively. The B genome showed significant importance in controlling root growth both under stress and non-stress conditions. The identified markers can potentially be validated and used for marker assisted selection.


Solitary fibrous tumor in the round ligament of the liver: a fortunate intraoperative discovery.
Solitary fibrous tumors (SFTs) are mesenchymal neoplasms of fibroblastic origin, most commonly found in the pleura. Numerous extrathoracic locations have been reported during the last 2 decades. Herein, we report the first case of an SFT in the round ligament of the liver. A 46-year-old Caucasian man presented with a 12-month history of abdominal pain. An ultrasonography-guided microbiopsy first revealed a desmoid tumor. After failure of first- and second-line medical treatments (celecoxib and tamoxifen, then imatinib), histological reexamination was suspicious for a low-grade sarcoma. MRI was also suspicious for a malignant process. Hence, surgery was decided. Laparotomy found a huge and well-limited tumor that, unexpectedly, was appended to the round ligament of the liver and free from any other intra-abdominal contact. The tumor was easily removed. Excision was monobloc and macroscopically complete. Histological analysis diagnosed an SFT arising from the round ligament of the liver. No adjuvant treatment was given. Ten months after surgery, the patient is alive without any signs or symptoms of relapse. This is the first report of SFT arising from the round ligament of the liver. It illustrates the difficulty in diagnosing such tumors. Whilst diagnosis of SFT is rare, it should be kept in mind to allow early diagnosis and complete surgical resection, which provide the best chance for recovery.


Holt-Oram syndrome revisited. Two patients in the same family.
Holt-Oram syndrome was first described in 1960 as an association of familial heart disease and musculoskeletal abnormalities. The most important findings include atrial septal defects, atrioventricular conduction abnormalities, vascular hypoplasia, and upper limb musculoskeletal deformities. We report two patients with this syndrome in the same family and discuss the variability of the musculoskeletal abnormalities and their association with the cardiac morphologic defects. Both patients in this study had associated eosinophilia, which has not been reported in the literature.


Anionic, Cationic, and Nonionic Surfactants in Atmospheric Aerosols from the Baltic Coast at Askö, Sweden: Implications for Cloud Droplet Activation.
Recent analyses of atmospheric aerosols from different regions have demonstrated the ubiquitous presence of strong surfactants and evidenced surface tension values, σ, below 40 mN m(-1), suspected to enhance the cloud-forming potential of these aerosols. In this work, this approach was further improved and combined with absolute concentration measurements of aerosol surfactants by colorimetric titration. This analysis was applied to PM2.5 aerosols collected at the Baltic station of Askö, Sweden, from July to October 2010. Strong surfactants were found in all the sampled aerosols, with σ = (32-40) ± 1 mN m(-1) and concentrations of at least 27 ± 6 mM or 104 ± 21 pmol m(-3). The absolute surface tension curves and critical micelle concentrations (CMC) determined for these aerosol surfactants show that (1) surfactants are concentrated enough in atmospheric particles to strongly depress the surface tension until activation, and (2) the surface tension does not follow the Szyszkowski equation during activation but is nearly constant and minimal, which provides new insights on cloud droplet activation. In addition, both the CMCs determined and the correlation (R(2) ∼ 0.7) between aerosol surfactant concentrations and chlorophyll-a seawater concentrations suggest a marine and biological origin for these compounds.


A genetic basis for molecular asymmetry at vertebrate electrical synapses.
Neural network function is based upon the patterns and types of connections made between neurons. Neuronal synapses are adhesions specialized for communication and they come in two types, chemical and electrical. Communication at chemical synapses occurs via neurotransmitter release whereas electrical synapses utilize gap junctions for direct ionic and metabolic coupling. Electrical synapses are often viewed as symmetrical structures, with the same components making both sides of the gap junction. By contrast, we show that a broad set of electrical synapses in zebrafish, Danio rerio, require two gap-junction-forming Connexins for formation and function. We find that one Connexin functions presynaptically while the other functions postsynaptically in forming the channels. We also show that these synapses are required for the speed and coordination of escape responses. Our data identify a genetic basis for molecular asymmetry at vertebrate electrical synapses and show they are required for appropriate behavioral performance.


False-positive DNA probe test for Legionella species associated with a cluster of respiratory illnesses.
Between 11 November 1986 and 28 February 1987, legionellosis was diagnosed in 23 patients at one hospital with a recently marketed Legionella-specific DNA probe for respiratory secretions. Only 10 of the 23 probe-positive patients showed findings typical of Legionella pneumonia, including a temperature of greater than or equal to 100.5 degrees F (approximately 38.1 degrees C) and radiographic evidence of pneumonia. No differences were found in the results of laboratory studies, demographic features, or underlying risk factors for these 10 probe-positive patients when compared with the 13 probe-positive patients with nonpneumonic illnesses. A case-control study comparing probe-positive and -negative patients failed to identify any different features of disease or epidemiologic characteristics. Probes of repeat specimens of sputum were still positive 2 to 13 weeks after the initial test in 5 (50%) of the 10 probe-positive patients. The clinical features in most patients were atypical for legionellosis, and the diagnosis could not be confirmed by traditional laboratory tests performed on duplicate specimens processed at the Centers for Disease Control. This report emphasizes the need for clinical microbiology laboratories to confirm test results from new procedures by accepted diagnostic methods.


[The influence of digoxin treatment on the statistical distribution of R-R intervals in atrial fibrillation].
Functional refraction of atrio-ventricular node and the phenomenon of concealed conduction are basic factors which determine the frequency of ventricular beats as well as the duration of R-R intervals in atrial fibrillation. R-R intervals may be ordered according to their size and presented graphically in the form of histograms. The morphology of histograms depends on the ability of A-V node. Digoxin influences the morphology of histograms of R-R intervals, which may have a diagnostic value and become a therapeutic indicator. The purpose of the study was to evaluate the correlation between the morphology of histograms and digoxin serum concentration, as well as the clinical treatment with digoxin. In the study a classification was used which divided R-R intervals into 4 types and several sub-types. The study covers 91 patients treated with digoxin upon whom 161 histograms were made. Two groups of patients were studied: A-patients in whom digoxin concentration was determined, B-patients in whom treatment with digoxin was evaluated on the basis of their clinical condition. The study confirmed a hypothesis that treatment with digoxin causes specific changes in the statistical distribution of R-R intervals even though no strict correlation was found between the direction of these changes and the digoxin serum concentration. The dependence, however, was observed between histograms of R-R intervals in atrial fibrillation and the clinical course of treatment with digoxin.


Phase II trial of a combination of cyclosphamide, vincristine, and methotrexate in advanced colorectal carcinoma.
Twenty patients with advanced colon cancer were treated with a combination of low-dose weekly cyclophosphamide, vincristine, and methotrexate (COM) after demonstrated progression of disease with 5-fluorouracil (5-FU). Four patients (20%) had partial responses with a median survival of 15 months, six (30%) had disease stabilization for 3--16 months (median survival, 8 months), and ten progressed with a median survival of 5.5 months. All four partial responses and five of six stabilizations occurred in patients with a performance status of 0 or 1. COM appeared well-tolerated and at least as effective as alternative secondary chemotherapy following 5-FU failure.


Margin status after loop electrosurgical excision procedure (LEEP) and laser excision in patients with high-grade cervical neoplasia.
Early management of high-grade cervical intraepithelial neoplasia is one of the key steps in cervical cancer prevention after vaccination and screening. It relies on lesion removal by surgical excision, and the French National Cancer Institute (INCa) in 2016 recommend using a Loop Electro Excision Procedure (LEEP). However, the laser excision method seems to be as effective with similar rates of negative excision margins and postoperative clearance of HPV. The main objective of our study was to compare the laser excision method to LEEP by evaluating the quality of the surgical margins. We also studied factors associated with the status of the margins and the depth of cones. We conducted a retrospective unicentric study between 2009 and 2017. Two hundred and thirty-one patients were included: 154 laser excisions and 77 LEEP. Negative surgical margin was achieved in 69.5% of laser excisions and 72.7% of LEEP (p= 0.649). Concerning factors predicting margin status, only a greater cone depth was associated with negative margins (OR: 0.91 (95%CI: 0.84, 0.89); p = 0.02). The surgical technique was not found to be associated with the status of the margins (OR: 0.85 (95%CI: 0.46,1.56); p = 0.61). Concerning factors predicting cone depth, only the LEEP was associated with a shorter cone depth (OR: 0.24 (95%CI: 0.08, 0.69); p 0.008). Significant results are based on univariate analysis. No difference was found between the two technics concerning the rate of negative margins. However, LEEP seems to be associated with shorter cone depth in this study.


Descriptive Epidemiology of Lymphoma in Northern Iran: Results from the Golestan Registry 2004-2013.
There is currently little known about the epidemiology of lymphomas in Iran. The aim of this paper is to describe the geographic and time variations in incidence rates of lymphomas in the Golestan province between 2004 and 2013. The Golestan Population-based Cancer Registry (GPCR) routinely registers primary cancer patients from all sources (e.g. pathology centers, hospitals, etc.) throughout the Golestan province. We obtained data on newly-diagnosed lymphomas in Golestan during 2004-2013 from the GPCR dataset. Crude rates and age standardized incidence (ASR) rates (per 100000) of lymphomas were estimated, joinpoint regression was used to quantify incidence trends and average annual percent changes (AAPCs) were calculated. In total, 898 new cases of lymphoma were registered in the GPCR during 2004-2013. The ASR of Hodgkin lymphoma (HL) was 1.5 and 1.1 in males and females, respectively, while corresponding non-Hodgkin lymphoma (NHL) rates were greater, at 6.5 and 3.4 in males and females, respectively. Our results indicated a significant difference in the trends of HL between males (AAPC = -3.2) and females (AAPC = 3.6, P value = 0.001). The incidence rates of lymphoma were considerably higher in the urban population (ASR = 7.3) compared to those residing in rural areas (ASR = 5.3, P value = 0.054). We also found higher incidence rates for both HL and NHL in the western parts of the Golestan province. The incidence rates of lymphoma in the Golestan province are relatively high and vary geographically, with a higher incidence observed in the western area. Such differences may reflect unknown lifestyle and environmental determinants linked to ethnic susceptibility differing between the two areas.


Tyrosine phosphorylation and invasion mechanisms in Eimeria tenella.
The role of signal transduction mechanisms with regard to the host cell invasion mechanics used by apicomplexans appears to have been overlooked: indeed, it is obvious that a signal must be transduced from the surface of an invading parasite to an intracellular location within it once the parasite makes contact with a host cell for the invasion process to be initiated. Data outlined in this communication show strong evidence for the role of tyrosine phosphorylation in the molecular mechanics and control of invasion of host cells when set within the context of the available literature, as detailed in this study.


Diagnosis and management of pancreatic cancer.
Pancreatic cancer remains the fourth leading cause of cancer-related deaths in the United States. Risk factors include family history, smoking, chronic pancreatitis, obesity, diabetes mellitus, heavy alcohol use, and possible dietary factors. Because more than two-thirds of adenocarcinomas occur in the head of the pancreas, abdominal pain, jaundice, pruritus, dark urine, and acholic stools may be presenting symptoms. In symptomatic patients, the serum tumor marker cancer antigen 19-9 can be used to confirm the diagnosis and to predict prognosis and recurrence after resection. Pancreas protocol computed tomography is considered standard for the diagnosis and staging of pancreatic cancer. Although surgical resection is the only potentially curative treatment for pancreatic ductal adenocarcinomas, less than 20% of surgical candidates survive five years. The decision on resectability requires multidisciplinary consultation. Pancreatic resections should be performed at institutions that complete at least 15 of the surgeries annually. Postoperatively, use of gemcitabine or fluorouracil/leucovorin as adjuvant chemotherapy improves overall survival by several months. However, more than 80% of patients present with disease that is not surgically resectable. For patients with locally advanced or metastatic disease, chemoradiotherapy with gemcitabine or irinotecan provides clinical benefit and modest survival improvement. Palliation should address pain control, biliary and gastric outlet obstruction, malnutrition, thromboembolic disease, and depression.


Director precession and nonlinear waves in nematic liquid crystals under elliptic shear
Elliptic shear applied to a homeotropically oriented nematic above the electric bend Freedericks transition (FT) generates slow precession of the director. The character of the accompanying nonlinear waves changes from diffusive phase waves to dispersive ones exhibiting spirals and spatiotemporal chaos as the FT is approached from above. An exact solution of the flow alignment equations captures the observed precession and predicts its reversal for non-flow-aligning materials. The FT transforms into a Hopf bifurcation opening the way to understand the wave phenomena.


Perinatal Hypophosphatasia in a Premature Infant.
A premature male infant was delivered at 32 weeks' gestation due to category-2 fetal tracing after preterm labor. The physical exam showed shortened and bowed long bones, with calvarium felt in small area of the head. Serum alkaline phosphatase was very low on admission. Extensive metaphyseal abnormalities, bowing of long bones, and poor ossification of all bones were noted on skeletal survey (radiography). Based on ultrasound evidence of "bowing" and long bone fractures at 26 weeks, amniocentesis was performed that later diagnosed hypophosphatasia by genetic testing while ruling out osteogenesis imperfecta. Although ventilated initially, the infant gradually improved with enzyme replacement therapy (ERT) and was extubated to noninvasive ventilation for 6 weeks. Following clinical deterioration with hypoxic respiratory failure secondary to sepsis at 4 months of age, he succumbed to severe pulmonary hypertension, likely secondary to chronic lung disease and prolonged ventilation. Early diagnosis allowed timely initiation of appropriate therapy. Radiological improvement with the therapy showed promising results in this rare disease. Despite specific novel therapy being available, variability in presentation dictates prognosis in this previously universally fatal condition. The potential unknown effects of ERT on pulmonary vascular remodeling need further investigation.


Differences in estrogen modulation of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-1 expression in cultured fibroblasts from continent and incontinent women.
The purpose of this study was to investigate the effect of increasing estrogen concentrations on metalloproteinase and tissue inhibitors of metalloproteinase protein expressions in cultured pelvic fibroblasts that were obtained from continent and incontinent women. Periurethral vaginal wall tissues were taken from four stress incontinent and three continent premenopausal women who underwent gynecologic surgery for benign indications. Protein was extracted from these tissues, and Western blot analysis was performed to document that fibroblasts from continent and incontinent women differed with respect to metalloproteinase and tissue inhibitors of metalloproteinase production. One age-matched tissue pair was prepared for fibroblast culture. Cells were cultured with increasing concentrations of estradiol (0-500 pg/mL). Extracellular metalloproteinase and tissue inhibitors of metalloproteinase were assessed semiquantitatively with Western blotting. Periurethral vaginal tissues from incontinent women expressed less tissue inhibitors of metalloproteinase when compared with tissue from the control subjects; there was no difference in the expression of cleaved, active metalloproteinase protein. Tissue inhibitors of metalloproteinase expression from fibroblasts of continent women significantly increased with increasing estradiol concentrations (0-100 pg/mL, P <.05). No significant dose response was seen in fibroblasts from an incontinent woman. Metalloproteinase expression was not altered by increasing estradiol concentrations in fibroblasts from either continent or incontinent women. This preliminary in vitro study suggested that, in fibroblasts that were derived from the continent woman, tissue inhibitors of metalloproteinase protein production increases with increasing estrogen levels and that, in stress incontinent fibroblasts, no similar increase occurs. Neither group demonstrated a change in metalloproteinase production in response to varying estrogen levels, which suggests that estrogen may inhibit collagen degradation in continent women by increasing tissue inhibitors of metalloproteinase production but exerts a reduced inhibitory effect on collagenolysis in women with stress urinary incontinence.


The response of dorsal horn neurones of the cat to intraarterial bradykinin and noxious radiant heat.
In chloralose-anaesthetized or decerebrate cats intra-arterially administered bradykinin (BKN) and noxious radiant heat were tested on dorsal horn neurones characterized according to their responses to natural stimuli. Of the 28 neurones which were excited only to non-noxious forms of stimuli, BKN affected 4 while noxious radiant heat was ineffective. BKN also affected relatively few of the nociceptor-driven neurones (18 of 60) and most of these were inhibited, while noxious radiant heat excited the majority of these cells (47 of 60). Therefore, under our experimental conditions, noxious radiant heat would appear to be a more effective and specific noxious stimulus than BKN.


Resistance to Clopidogrel among Iranian Patients Undergoing Angioplasty Intervention.
To study the resistance to standard dosage of clopidogrel among Iranian patients following percutaneous coronary intervention measured by platelet aggregation test. Patients undergoing percutaneous coronary intervention in Imam Hussein Medical center, Tehran, Iran, who were under treatment with aspirin, but had no history of clopidogrel usage, entered the study. Patients received standard dosage of clopidogrel (Plavix(®), Sanofi, France, 600 mg loading dose and 75 mg/day afterward). Platelet aggregation was measured using light transmission aggregometer. The response to the drug was categorized as complete resistance (platelet aggregation decreased less than 10%), intermediate resistance (platelet aggregation decreased between 10 to 30%) and complete response (platelet aggregation decreased to 30% or more). All patients were evaluated for major adverse cardio vascular events one month after the angioplasty based on MACE criteria by phone contact. Thirty-one patients with a mean age of 59 ± 13 entered the study. Sixty-five percent of patients showed complete response to clopidogrel (95% CI: 45% to 81%), 22% showed intermediate resistance (95% CI: 10-41%) and 13% showed complete resistance (95% CI: 4-30%). One month after the angioplasty, no major adverse cardiovascular event was recorded. Based on our findings, it seems that there is no major difference between Iranian population and other studies regarding the resistance to clopidogrel. Due to the limited number of participants in our study, further investigations with higher number of patients are recommended to more precisely calculate the percentage of resistance among Iranian patients.


Obesity and weight loss result in increased adipose tissue ABCG1 expression in db/db mice.
The prevalence of obesity has reached epidemic proportions and is associated with several co-morbid conditions including diabetes, dyslipidemia, cancer, atherosclerosis and gallstones. Obesity is associated with low systemic inflammation and an accumulation of adipose tissue macrophages (ATMs) that are thought to modulate insulin resistance. ATMs may also modulate adipocyte metabolism and take up lipids released during adipocyte lipolysis and cell death. We suggest that high levels of free cholesterol residing in adipocytes are released during these processes and contribute to ATM activation and accumulation during obesity and caloric restriction. Db/db mice were studied for extent of adipose tissue inflammation under feeding conditions of ad libitum (AL) and caloric restriction (CR). The major finding was a marked elevation in epididymal adipose ABCG1 mRNA levels with obesity and CR (6-fold and 16-fold, respectively) over that seen for lean wild-type mice. ABCG1 protein was also elevated for CR as compared to AL adipose tissue. ABCG1 is likely produced by cholesterol loaded ATMs since this gene is not highly expressed in adipocytes and ABCG1 expression is sterol mediated. Our data supports the concept that metabolic changes in adipocytes due to demand lipolysis and cell death lead to cholesterol loading of ATMs. Based on finding cholesterol-loaded peritoneal leukocytes with elevated levels of ABCG1 in CR as compared to AL mice, we suggest that pathways for cholesterol trafficking out of adipose tissue involve ATM egress as well as ABCG1 mediated cholesterol efflux. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).


Population Dynamics of Salmonella enterica within Beef Cattle Cohorts Followed from Single-Dose Metaphylactic Antibiotic Treatment until Slaughter.
Antibiotic use in cattle can select for multidrug-resistant Salmonella enterica, which is considered a serious threat by the U.S. Centers for Disease Control and Prevention. A randomized controlled longitudinal field trial was designed to determine the long-term effects of a single dose of ceftiofur or tulathromycin on Salmonella population characteristics in cattle feces and peripheral lymph nodes and on hides. A total of 134 beef cattle from two sources were divided among 12 pens, with cattle in each of the 3-pen blocks receiving a single dose of either ceftiofur or tulathromycin or neither (control) on day 0. Fecal samples were collected before treatment (day 0) and repeatedly following treatment until slaughter (day 99+). Hide and lymph node samples were collected at slaughter age. Salmonella prevalence, phenotypic antimicrobial resistance, serotype, and phylogenetic relationships were examined. Multilevel mixed logistic regression models indicated no significant effects (P ≥ 0.218) of metaphylactic antibiotics on the prevalence of Salmonella across sample types. However, there was a significant time effect observed, with prevalence increasing from spring through the midsummer months (P < 0.0001) in feces. The majority of Salmonella isolates were pansusceptible to a panel of 14 antibiotics both before and after treatment. Highly prevalent Salmonella serotypes were Salmonella enterica serovar Montevideo, Salmonella enterica serovar Anatum, Salmonella enterica serovar Cerro, and Salmonella enterica serovar Lubbock across all sample types. Strong pen and cattle source serotype clustering effects were observed among Salmonella isolates originating from fecal, lymph node, and hide samples; however, the potential role of Salmonella isolates from the pen environment prior to animal placement was not assessed in this study.IMPORTANCESalmonella is a leading bacterial foodborne pathogen, causing a significant number of human infections and deaths every year in the United States. Macrolides and 3rd-generation cephalosporins play critical roles in the treatment of human salmonellosis. Use of these antibiotics in beef cattle can select for resistant bacteria that may enter the food chain or spread from the farm via manure. There is a lack of longitudinal research concerning the long-term effects of metaphylactic antibiotic administration. Here, we assessed Salmonella population dynamics during the feeding period until slaughter following single-dose antibiotic treatment. We found no long-term effects of antibiotic use early in the cattle-feeding period on Salmonella prevalence and antimicrobial resistance at slaughter. We identified the pens in which cattle were housed as the factor that contributed most to Salmonella serotypes being shared; importantly, the dominant strain in each pen changed repeatedly over the entire feeding period.


Optimal color filters in the presence of noise.
The effect of noise on the number of effective channels (color filters) used to record a color image is investigated. Transmittances of color filters are calculated that minimize the mean square error that occurs when estimating, from the recorded data, the colors in the image under a collection of viewing illuminants. Since the results indicate that a significant improvement in color correction accuracy is achieved by using four channels, there is good reason to consider using four-tuples for representation of colorimetric information.