Does host plant quality affect the oviposition decisions of an omnivore?
Optimal oviposition theory predicts a positive relationship between female preference for oviposition hosts and offspring performance. Interspecies effects on oviposition preference have been widely investigated, especially for herbivores. However, intraspecies variation, such as nitrogen content, might also influence female preference for oviposition hosts and subsequent offspring performance. To evaluate this possibility, we investigated the oviposition preference of a zoophytophagous omnivore and the development and survival of its nymphs on a single species of host plant that varied in nitrogen content. In choice and no-choice experiments without prey, female omnivores were allowed to oviposit on plants that had been fertilized using 4 rates of nitrogen fertilizer (39, 78, 156, and 311 mg/L nitrogen) for 72 h. After 72 h, the most females were found on tomato plants receiving high concentrations of nitrogen fertilizer and more eggs were laid on those plants. First instar nymphs developed more rapidly on high-nitrogen plants and third instar nymphs developed faster on low-nitrogen plants. Plant nitrogen did not affect nymph survival to the adult stage, or the probability of survival over time. Although female omnivores did discriminate between potential oviposition hosts based on plant nitrogen, their choices did not significantly impact nymph development or survival. This is the first study to show that intraspecies variation in nitrogen content between plants affects the oviposition preference of female omnivores, but not offspring performance.


Eye tracking and gating system for proton therapy of orbital tumors.
A new motion-based gated proton therapy for the treatment of orbital tumors using real-time eye-tracking system was designed and evaluated. We developed our system by image-pattern matching, using a normalized cross-correlation technique with LabVIEW 8.6 and Vision Assistant 8.6 (National Instruments, Austin, TX). To measure the pixel spacing of an image consistently, four different calibration modes such as the point-detection, the edge-detection, the line-measurement, and the manual measurement mode were suggested and used. After these methods were applied to proton therapy, gating was performed, and radiation dose distributions were evaluated. Moving phantom verification measurements resulted in errors of less than 0.1 mm for given ranges of translation. Dosimetric evaluation of the beam-gating system versus nongated treatment delivery with a moving phantom shows that while there was only 0.83 mm growth in lateral penumbra for gated radiotherapy, there was 4.95 mm growth in lateral penumbra in case of nongated exposure. The analysis from clinical results suggests that the average of eye movements depends distinctively on each patient by showing 0.44 mm, 0.45 mm, and 0.86 mm for three patients, respectively. The developed automatic eye-tracking based beam-gating system enabled us to perform high-precision proton radiotherapy of orbital tumors.


Fast all-optical flip-flop based on a single distributed feedback laser diode.
Since there is an increasing demand for fast networks and switches, the electronic data processing imposes a severe bottleneck and all-optical processing techniques will be required in the future. All-optical flip-flops are one of the key components because they can act as temporary memory elements. Several designs have already been demonstrated but they are often relatively slow or complex to fabricate. We demonstrate experimentally fast flip-flop operation in a single DFB laser diode which is one of the standard elements in today's telecommunication industry. Injecting continuous wave light in the laser diode, a bistability is obtained due to the spatial hole burning effect. We can switch between the two states by using pulses with energies below 200 fJ resulting in flip-flop operation with switching times below 75 ps and repetition rates of up to 2 GHz.


Activities of hexokinase, phosphofructokinase, fructose bisphosphatase and 2-oxoglutarate dehydrogenase in muscle of normal subjects and very ill surgical patients.
1. The activities of hexokinase, phosphofructokinase, fructose bisphosphatase and 2-oxoglutarate dehydrogenase have been measured in the vastus lateralis and rectus abdominus muscle of normal human subjects and in very ill surgical patients. 2. The activities of these enzymes in the muscle of control subjects were similar to the pattern seen in the skeletal muscle of other mammals and lower vertebrates. 3. Fructose bisphosphatase and phosphofructokinase activities were significantly lower in the muscle of ill patients although the depression of the activity of fructose bisphosphatase was much greater than that of phosphofructokinase in both muscle types of ill patients. 4. The maximum rate of cycling in the fructose 6-phosphate--fructose, 1,6-diphosphate cycle may be altered in the ill. 5. This decreased cycling may have a direct influence on the sensitivity of glycolysis to regulators such as the adenine nucleotides and may reduce the ability to maintain body temperature. 6. Increased glycogen synthesis in these muscles may indicate that the role of fructose bisphosphatase is unlikely to be solely in glycogen resynthesis.


Dissociation of renal nerve and excretory responses to volume expansion in prehypertensive Dahl salt-sensitive and Dahl salt-resistant rats.
Prehypertensive Dahl salt-sensitive rats on low sodium diet have impaired baroreceptor and cardiopulmonary receptor function as compared with Dahl salt-resistant control rats. We tested whether these abnormalities influenced the ability of conscious prehypertensive Dahl salt-sensitive rats to excrete a moderate intravenous isotonic saline volume load (0.9% NaCl, 3% body weight i.v.). During control, 30-minute volume expansion, and 2-hour recovery periods, arterial blood pressure and heart rate did not change. Glomerular filtration rate and renal plasma flow remained stable throughout control and recovery. The amount of the volume load excreted as either water or sodium was the same for Dahl salt-sensitive and Dahl salt-resistant rats with either denervated or innervated kidneys. The time course of water and sodium excretion was similar in Dahl salt-sensitive and Dahl salt-resistant rats. Renal sympathetic nerve activity, however, showed different patterns. Although the initial decrease in renal sympathetic nerve activity during volume expansion was similar for both groups, Dahl salt-sensitive rats exhibited a prompt return of renal sympathetic nerve activity to control levels, whereas renal sympathetic nerve activity in Dahl salt-resistant rats remained decreased throughout the recovery period. The rapid recovery of renal sympathetic nerve activity to control levels after volume expansion in Dahl salt-sensitive rats supports the concept of impaired cardiopulmonary receptor function in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation.
Biological mechanisms of tissue regeneration are often complex, involving the tightly coordinated spatial and temporal presentation of multiple factors. We investigated whether spatially compartmentalized and sequential delivery of factors can be used to pattern new blood vessel formation. A porous bi-layered poly(lactide-co-glycolide) (PLG) scaffold system was used to locally present vascular endothelial growth factor (VEGF) alone in one spatial region, and sequentially deliver VEGF and platelet-derived growth factor (PDGF) in an adjacent region. Scaffolds were implanted in severely ischemic hindlimbs of SCID mice for 2 and 6 weeks, and new vessel formation was quantified within the scaffolds. In the compartment delivering a high dose of VEGF alone, a high density of small, immature blood vessels was observed at 2 weeks. Sequential delivery of VEGF and PDGF led to a slightly lower blood vessel density, but vessel size and maturity were significantly enhanced. Results were similar at 6 weeks, with continued remodeling of vessels in the VEGF and PDGF layer towards increased size and maturation. Spatially localizing and temporally controlling growth factor presentation for angiogenesis can create spatially organized tissues.


Use and attitudes of obstetricians toward 3 high-risk interventions in MFMU Network hospitals.
We sought to evaluate the frequency of, and factors associated with, the use of 3 evidence-based interventions: antenatal corticosteroids for fetal lung maturity, progesterone for prevention of recurrent preterm birth, and magnesium sulfate for fetal neuroprotection. A self-administered survey was conducted from January through May 2011 among obstetricians from 21 hospitals that included 30 questions regarding their knowledge, attitudes, and practice of the 3 evidence-based interventions and the 14-item short version of the Team Climate for Innovation survey. Frequency of use of each intervention was ascertained from an obstetrical cohort of women between January 2010 and February 2011. A total of 329 obstetricians (74% response rate) who managed 16,946 deliveries within the obstetrical cohort participated in the survey. More than 90% of obstetricians reported that they incorporated each intervention into routine practice. Actual frequency of administration in women eligible for the treatments was 93% for corticosteroids, 39% for progesterone, and 71% for magnesium sulfate. Provider satisfaction with quality of treatment evidence was 97% for corticosteroids, 82% for progesterone, and 57% for magnesium sulfate. Obstetricians perceived that barriers to treatment were most frequent for progesterone (76%), 30% for magnesium sulfate, and 17% for corticosteroids. Progesterone use was more frequent among patients whose provider reported the quality of the evidence was above average to excellent compared with poor to average (42% vs 25%, respectively; P < .001), and they were satisfied with their knowledge of the intervention (41% vs 28%; P = .02), and was less common among patients whose provider reported barriers to hospital or pharmacy drug delivery (31% vs 42%; P = .01). Corticosteroid administration was more common among patients who delivered at hospitals with 24 hours a day-7 days a week maternal-fetal medicine specialist coverage (93% vs 84%; P = .046), CONCLUSION: Obstetricians in Maternal-Fetal Medicine Units Network hospitals frequently use these evidence-based interventions; however, progesterone use was found to be related to their assessment of evidence quality. Neither progesterone nor the other interventions were associated with overall climate of innovation within a hospital as measured by the Team Climate for Innovation. National Institutes of Health Consensus Conference Statements may also have an impact on use; there is such a statement for antenatal corticosteroids but not for progesterone for preterm prevention or magnesium sulfate for fetal neuroprotection.


[Morphofunctional Changes of Spleen After Hemostasis by Nonequilibrium Plasma].
Heavy bleeding is developed in case of spleen injury. It often leads to death. At present the search and development of new methods for hemostasis of spleen bleeding continues. An innovative method is coagulation of nonequilibrium plasma. Our aim was to study the effect of nonequilibrium plasma on the morphofunctional state of the spleen. The non-randomized study by type of "case-control" was conducted. The experiment was carried out on 45 male rabbits weighing 3000-3200 g. 1st group (control; n = 5)--intact animals without surgery; 2nd group (experimental, n = 40)--animals after atypical resection of the spleen and hemostasis by nonequilibrium plasma. The volume of blood loss, FBC, histological data, splenogram analysis data were assessed at defined periods (60 min, 3rd, 5th, 7th, 14th, 30th, 90th, 180th days) after surgery. They were compared with data of the control group. The volume of blood loss during the resection of the spleen with hemostasis by nonequilibrium plasma was 16.6 [15.98; 17.22] ml. Increase of neutrophil to 38 [24; 39] (control group 17[13, 18], p = 0.009), monocytes to 15 [14, 18] (control group 8 [6, 11], p = 0.036) is revealed in the FBC in the early period after hemostasis with nonequilibrium plasma. It is reduced to the norm on 30 day. Histological examination revealed leukocyte infiltration, edema, microvascular stasis, dilatation of vessels in the early period. At long-term period structure of the organ is normalized. Splenogramm analysis revealed a statistically significant (p = 0.023) decrease in the relative number of small lymphocytes by 28% in animals after hemostasis with nonequilibrium plasma as compared to control (23.3 [179; 26.7] versus 30.8 [29.25; 34.3] respectively). treatment of bleeding surface by plasma flow for 1.5-2 min is required order to achieve effective hemostasis during surgery of spleen injuries in the experiment. After coagulation there is minimal damage of the spleen parenchyma, which manifests itself as activation reaction. At long-term period parenchyma ofthe spleen completely regenerates with theformation of cicatrical tissue that does not affect thefunctioning of organ.


Comparing ECT data of two different inpatient clinics: propofol or thiopental?
This study compares the data of (modified) electroconvulsive theraphy (ECT) applications from two different inpatient clinics in Turkey: Kocaeli Derince Training and Research Hospital (Clinic-I) and Kocaeli University (Clinic-II). Recorded files of patients from the two clinics were compared in terms of ECT indications, number and duration of seizures, and anesthetic agents used (propofol vs. thiopental). ECT applications occurring between January 2011 and January 2013 were included in the study. A total of 86 patients (9.5% of the inpatients) received ECT in Clinic-I and 103 patients (21.1% of the inpatients) in Clinic-II during the period studied. The yearly ECT rate (treated person rate per 10,000 per year) was 0.59/10,000 for Kocaeli (Turkey) as a whole. The overall number of ECT applications was 539 in Clinic-I and 999 in Clinic-II, and the average number of ECT sessions for each patient was 6.4 ± 2.33 in Clinic-I and 9.69 ± 4.66 in Clinic-II. The majority of indications were depressive disorders and insufficient response to medicine. Patients in the clinic which utilized thiopental as the anesthetic agent experienced more cardiovascular and respiratory side effects than the one which used propofol. The number of ECT sessions required was greater for patients with schizoaffective disorder than for others. The administration of ECT was considered to be a reliable method of treatment in these clinics. With respect to specific anesthetic agents, propofol was found to have less hemodynamic side effects and shorter seizure durations than thiopental.


Vitamin D, parathyroid hormone and the metabolic syndrome in middle-aged and older European men.
Low serum 25-hydroxyvitamin D (25(OH)D) and elevated parathyroid hormone (PTH) levels have been linked to insulin resistance, the metabolic syndrome (MetS) and its components. Data in healthy, community-dwelling Europeans are lacking, and previous studies have not excluded subjects receiving drug treatments that may distort the relationship between 25(OH)D/PTH and MetS. The aim of our analysis was to examine the association of 25(OH)D and PTH with Adult Treatment Panel III-defined MetS in middle-aged and older European men. This was a population-based, cross-sectional study of 3369 men aged 40-79 years enrolled in the European Male Ageing Study. After exclusion of subjects with missing data, 3069 men with a mean (+/-s.d.) age of 60+/-11 years were included in the analysis. Age-adjusted 25(OH)D levels were inversely associated with waist circumference, systolic blood pressure (BP), triglycerides, and glucose (all P<0.01). Age-adjusted PTH levels were only associated with waist and diastolic BP (both P<0.05). After adjusting for age, centre, season and lifestyle factors the odds for MetS decreased across increasing 25(OH)D quintiles (odds ratios 0.48 (95% confidence intervals 0.36-0.64) highest versus lowest quintile; P(trend)<0.001). This relationship was unchanged after adjustment for PTH, but was attenuated after additional adjustment for homoeostasis model assessment of insulin resistance (0.60 (0.47-0.78); P(trend)<0.001). There was no association between PTH and MetS. Our results demonstrate an inverse relationship between 25(OH)D levels and MetS, which is independent of several confounders and PTH. The relationship is partly explained by insulin resistance. The clinical significance of these observations warrants further study.


Prevalence of impaired glucose regulation in Europe: a meta-analysis.
Impaired glucose regulation represents an opportunity to prevent Type 2 diabetes mellitus. It is important to have a clear understanding of the prevalence of this condition in order to be able to plan interventions and health care provision. This paper presents a meta-analysis of literature assessing the prevalence of impaired glucose regulation in the general population of developed countries in Europe. Five electronic databases were systematically searched in March 2014 to identify English language articles with general population samples aged 18 and over from developed countries in Europe. Values for the measures of interest were combined using a random effects model and analysis of the effects of moderator variables was carried out. A total of 5594 abstracts were screened, with 46 studies included in the review. Overall prevalence of impaired glucose regulation was 22.3%. Mean prevalence of impaired glucose tolerance was 11.4% (10.1-12.8) and did not differ by gender. Sample age, diagnostic criteria and country were found to have a significant univariate effect on prevalence of impaired glucose tolerance but only diagnostic criteria remained significant in multivariate analysis. Mean prevalence of impaired fasting glucose was significantly higher in men at 10.1% (7.9-12.7) compared with 5.9% in women (4-8.7). The only moderator variable with a significant effect on impaired fasting glucose prevalence was country. This meta-analysis shows a moderate prevalence of impaired glucose regulation in developed Europe with over one in five people meeting the criteria for either impaired glucose tolerance, impaired fasting glucose or both.


Noninvasive vaccination against infectious diseases.
The development of a successful vaccine, which should elicit a combination of humoral and cellular responses to control or prevent infections, is the first step in protecting against infectious diseases. A vaccine may protect against bacterial, fungal, parasitic, or viral infections in animal models, but to be effective in humans there are some issues that should be considered, such as the adjuvant, the route of vaccination, and the antigen-carrier system. While almost all licensed vaccines are injected such that inoculation is by far the most commonly used method, injection has several potential disadvantages, including pain, cross contamination, needlestick injury, under- or overdosing, and increased cost. It is also problematic for patients from rural areas of developing countries, who must travel to a hospital for vaccine administration. Noninvasive immunizations, including oral, intranasal, and transcutaneous administration of vaccines, can reduce or eliminate pain, reduce the cost of vaccinations, and increase their safety. Several preclinical and clinical studies as well as experience with licensed vaccines have demonstrated that noninvasive vaccine immunization activates cellular and humoral immunity, which protect against pathogen infections. Here we review the development of noninvasive immunization with vaccines based on live attenuated virus, recombinant adenovirus, inactivated virus, viral subunits, virus-like particles, DNA, RNA, and antigen expression in rice in preclinical and clinical studies. We predict that noninvasive vaccine administration will be more widely applied in the clinic in the near future.


"I Felt Like It Was God's Hands Putting the Needles In": A Qualitative Analysis of the Experience of Acupuncture for Chronic Pain in a Low-Income, Ethnically Diverse, and Medically Underserved Patient Population.
To examine the experience of patients from a low-income, ethnically diverse medically underserved population receiving acupuncture for chronic pain. Qualitative analysis using inductive thematic analysis of interviews with participants from an acupuncture trial. Four community health centers in the Bronx, New York. Thirty-seven adults with chronic neck or back pain or osteoarthritis who participated in a previous acupuncture trial. Up to 14 weekly acupuncture treatments. Pain and quality of life were examined in the original trial; this study examines qualitative outcomes. The themes grouped naturally into three domains of the acupuncture experience: the decision-making process, the treatment experience, and the effect of acupuncture on health. Regarding decision-making, important factors were a willingness to try something new even if you do not necessarily "believe" in it or have specifically positive expectations; a sense that medications were not working for their pain, that they also caused significant adverse effects, and that natural strategies might be preferable; and a feeling of desperation. Cost and access were significant barriers to acupuncture treatment. Regarding the process of acupuncture, the open and personal communication with the acupuncturist was an important factor, as were the sense that the process of acupuncture related to a natural process of healing or correction within the body and that part of making acupuncture successful required being open to the power of the mind to generate a positive outcome. Regarding the effect of treatment, notable aspects were the deep sense of rest and relaxation participants reported during treatment as well as the benefit they experienced for conditions other than pain. The themes that emerged in this ethnically diverse, low-income population were very similar to those that have emerged over the past decade of qualitative research on the acupuncture experience in other patient populations.


Levamisole-adulterated cocaine: what about in European countries?
A wide variety of somatic complications is reported or expected among cocaine users because of the adulterant levamisole. Most of the reports come from North America. To update the data on levamisole-adulterated cocaine in European countries, we present here a synthesis of data on samples seized by the police with the detection of levamisole, the amount of levamisole in cocaine samples, European drug information reports, and clinical cases. Although there is a variation in the percentage of levamisole in cocaine samples between European countries, the trend is an increase of these percentages. As in North America, levamisole is becoming the most common cocaine adulterant. First European cases of complications secondary to the use of adulterated cocaine with levamisole were skin necrosis, vasculitis, and agranulocytosis. Levamisole postmortem data concerned two cases of complications leading to death, possibly related to levamisole or its metabolite (acute coronary syndrome, pulmonary hypertension). Even if it is difficult to have a global European view with comparable data, levamisole is present in European cocaine specimens and can lead to severe adverse health effects. However data on the prevalence of toxicity related to levamisole-adulterated cocaine abuse are missing.


Comparison of adult, embryonic, and dystrophic myosin heavy chains from chicken muscle by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and peptide mapping.
Chicken myosin heavy chains from adult fast white muscle fibers (both normal and dystrophic), adult slow red fibers, and embryonic presumptive fast white fibers were compared by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and by peptide mapping. The heavy chain of slow red myosin migrated electrophoretically more slowly than the heavy chains of the other myosins and differed markedly from them in its peptide maps. The heavy chain of dystrophic fast white myosin was similar to its normal counterpart by peptide mapping but showed slight differences. The peptide map of the heavy chain of embryonic presumptive fast white myosin had the general features of that of the heavy chain of fast white, not slow red, fibers but contained definite differences from the former. The results are consistent with the existence of a separate gene for the heavy chain of embryonic presumptive fast white myosin.


The Effects of Fiscal Decentralisation on Publicly Provided Services and Labour Market.
This paper studies how fiscal decentralization affects local services. It explores a 1993 reform that increased the fiscal autonomy of Italian municipalities by replacing government transfers with revenues from a local property tax. Our identification leverages cross-municipal variation in the degree of decentralization that stems from differences in the average age of buildings caused by bombings during WWII. Decentralization reduced local spending but expanded municipal services, such as nursery schools. These effects are larger in areas with greater political competition. The paper also investigates how the reform affected labor markets. Decentralization increased female labor supply-probably through expanded availability of nursery schools- thereby reducing the gender gap in employment.


The amnesiac gene product is expressed in two neurons in the Drosophila brain that are critical for memory.
Mutations in the amnesiac gene in Drosophila affect both memory retention and ethanol sensitivity. The predicted amnesiac gene product, AMN, is an apparent preproneuropeptide, and previous studies suggest that it stimulates cAMP synthesis. Here we show that, unlike other learning-related Drosophila proteins, AMN is not preferentially expressed in mushroom bodies. Instead, it is strongly expressed in two large neurons that project over all the lobes of the mushroom bodies, a finding that suggests a modulatory role for AMN in memory formation. Genetically engineered blockade of vesicle recycling in these cells abbreviates memory as in the amnesiac mutant. Moreover, restoration of amn gene expression to these cells reestablishes normal olfactory memory in an amn deletion background. These results indicate that AMN neuropeptide release onto the mushroom bodies is critical for normal olfactory memory.


Polytobacco use among a nationally-representative sample of black high school students.
Studies of the patterns of polytobacco use have increased. However, understanding the patterns of using multiple tobacco products among Black adolescents is minimal. This study identified the patterns of polytobacco use among U.S. Black adolescents. Latent class analysis (LCA) was used to identify patterns of adolescent polytobacco use among a representative sample of Black youth from the 2017 Youth Risk Behavior Survey (n = 2782). Ever and recent (past 30 day) use of cigarettes, electronic cigarettes, cigars, and dip or chewing tobacco were used as latent class indicators. Multinomial regression was conducted to identify the association if smoking adjusting for sex, age, grade, and marijuana use. Most students were in the 9th grade (29%), e-cigarette users (21%) and were current marijuana users (25%). Three profiles of tobacco use were identified: Class 1: Non-smokers (81%), Class 2: E-cigarette Users (14%), and Class 3: Polytobacco Users (5%). Black adolescent Polytobacco users were the smallest class, but had the highest conditional probabilities of recent cigarette use, e-cigarette use, ever smoking cigars or chewing tobacco. Ever and current use of marijuana were associated with increased odds of being in the e-cigarette user versus non-smoker group, and current marijuana use was associated with increased odds of polytobacco use (aOR = 24.61, CI = 6.95-87.11). Findings suggests the need for targeted interventions for reducing tobacco use and examining the unique effects of polytobacco use on Black adolescents. Findings confirm a significant association of marijuana use with tobacco use.


Plastid genome-based phylogeny pinpointed the origin of the green-colored plastid in the dinoflagellate Lepidodinium chlorophorum.
Unlike many other photosynthetic dinoflagellates, whose plastids contain a characteristic carotenoid peridinin, members of the genus Lepidodinium are the only known dinoflagellate species possessing green alga-derived plastids. However, the precise origin of Lepidodinium plastids has hitherto remained uncertain. In this study, we completely sequenced the plastid genome of Lepidodinium chlorophorum NIES-1868. Our phylogenetic analyses of 52 plastid-encoded proteins unite L. chlorophorum exclusively with a pedinophyte, Pedinomonas minor, indicating that the green-colored plastids in Lepidodinium spp. were derived from an endosymbiotic pedinophyte or a green alga closely related to pedinophytes. Our genome comparison incorporating the origin of the Lepidodinium plastids strongly suggests that the endosymbiont plastid genome acquired by the ancestral Lepidodinium species has lost genes encoding proteins involved in metabolism and biosynthesis, protein/metabolite transport, and plastid division during the endosymbiosis. We further discuss the commonalities and idiosyncrasies in genome evolution between the L. chlorophorum plastid and other plastids acquired through endosymbiosis of eukaryotic photoautotrophs.


Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning.
Remote ischemic preconditioning reduces myocardial infarction (MI) in animal models. We tested the hypothesis that the systemic protection thus induced is effective when ischemic preconditioning is administered during ischemia (PerC) and before reperfusion and examined the role of the K(+)-dependent ATP (K(ATP)) channel. Twenty 20-kg pigs were randomized (10 in each group) to 40 min of left anterior descending coronary artery occlusion with 120 min of reperfusion. PerC consisted of four 5-min cycles of lower limb ischemia by tourniquet during left anterior descending coronary artery occlusion. Left ventricular (LV) function was assessed by a conductance catheter and extent of infarction by tetrazolium staining. The extent of MI was significantly reduced by PerC (60.4 +/- 14.3 vs. 38.3 +/- 15.4%, P = 0.004) and associated with improved functional indexes. The increase in the time constant of diastolic relaxation was significantly attenuated by PerC compared with control in ischemia and reperfusion (P = 0.01 and 0.04, respectively). At 120 min of reperfusion, preload-recruitable stroke work declined 38 +/- 6% and 3 +/- 5% in control and PerC, respectively (P = 0.001). The force-frequency relation was significantly depressed at 120 min of reperfusion in both groups, but optimal heart rate was significantly lower in the control group (P = 0.04). There were fewer malignant arrhythmias with PerC during reperfusion (P = 0.02). These protective effects of PerC were abolished by glibenclamide. Intermittent limb ischemia during myocardial ischemia reduces MI, preserves global systolic and diastolic function, and protects against arrhythmia during the reperfusion phase through a K(ATP) channel-dependent mechanism. Understanding this process may have important therapeutic implications for a range of ischemia-reperfusion syndromes.


National five-year examination of inequalities and trends in emergency hospital admission for violence across England.
To examine relationships between violence, age (0-74 years), and deprivation, and to explore in which communities, age groups, and gender the potential for transmission of violent tendencies between individuals is greatest. Five year (2004/2005 to 2008/2009) ecological study of emergency admissions resulting from violence (n=170074) into all English hospitals using trend and logistic regression analyses. Hospital admissions for violence peak as individuals achieve legal adulthood (18 years). Risks of admission increase exponentially with increasing quintile of deprivation of residence, with odds overall being 5.5 times higher in the poorest quintile compared with the richest. The greatest absolute difference in violence admissions by deprivation quintile is seen in males aged 18 (218/100 000, richest; 698/100 000, poorest). However, the highest deprivation rate ratios (quintile 5:1) are seen at ages 0-10 years in both sexes and at all ages after 40 years in males (40-58 years, females). In males aged 17-19 years, violence accounts for 20% of the entire gap between wealthiest and poorest quintiles in all cause emergency hospital admissions. Analyses identify four lifetime periods for violence: up to 10 years (prepubescent), 11-20 years (adolescence), 21-45 years (younger adults), and over 45 years (older adults). While violence is most common in adolescence, its concentration in poorer areas during prepubescence and in younger adulthood (parenting age) suggests that poorer children are exposed to much more aggressive communities. This is likely to contribute to the disproportionate escalation in violence they experience during adolescence. Effective interventions to prevent such escalations are available and need to be implemented particularly in poor communities.


Super electron donor-mediated reductive transformation of nitrobenzenes: a novel strategy to synthesize azobenzenes and phenazines.
The transformation of nitrobenzenes into azobenzenes by pyridine-derived super electron donor 2 is described. This method provides an efficient synthesis of azobenzenes because of not requiring the use of expensive transition-metals, toxic or flammable reagents, or harsh conditions. Moreover, when using 2-fluoronitrobenzenes as substrates, phenazines were found to be obtained. The process affords a novel synthesis of phenazines.


Prevalence of eating disorders and disordered eating in Western Asia: a systematic review and meta-Analysis.
This study aimed to systematically synthesize and appraise existing literature on the prevalence of eating disorders and disordered eating in Western Asia. A systematic literature search of major English and Arabic databases, i.e., PubMed/Medline, EMBASE, PsychInfo, Web of Science and Scopus (English), Al-Manhal (Arabic) and grey literature was done to obtain the prevalence of disordered eating and eating disorders in Western Asia. The literature search was conducted on June 12th, 2020, and included papers from 1990-2020. Out of the 249 unduplicated original studies reviewed, 27 were included in the final meta-analysis. Data were then categorized according to the tools used to identify the presence of disordered eating or eating disorders. The pooled prevalence of disordered eating as solicited by both the Eating Attitudes Scale 26 and the Eating Attitudes Scale 40 (N = 11841) was 22.07%, the Sick, Control, One stone, Fat, Food Questionnaire (n = 3160) was 22.28% and the Eating Disorder Examination-Questionnaire (n = 425) was 7.95%. The pooled prevalence obtained from those studies using semi-structured interviews for anorexia nervosa (n = 118190) was 1.59%, bulimia nervosa (n = 118513) was 2.41% and the estimated prevalence of Eating Disorder Not Otherwise Specified (EDNOS) (n = 118087) was 3.51%. Although the prevalence rate of eating disorders solicited using semi-structured interviews appeared to parallel the international range, the overall prevalence rate of disordered eating appeared to be slightly higher than the global rates of prevalence. A significant number of the suspected/detected cases of disordered eating appear to fulfill the criteria for EDNOS. This study is classified as evidence obtained from systematic reviews and meta-analyses (i.e. Level 1).


CK2 phosphorylation of XRCC1 facilitates dissociation from DNA and single-strand break formation during base excision repair.
CK2 phosphorylates the scaffold protein XRCC1, which is required for efficient DNA single-strand break (SSB) repair. Here, we express an XRCC1 protein (XRCC1(ckm)) that cannot be phosphorylated by CK2 in XRCC1 mutated EM9 cells and show that the role of this post-translational modification gives distinct phenotypes in SSB repair and base excision repair (BER). Interestingly, we find that fewer SSBs are formed during BER after treatment with the alkylating agent dimethyl sulfate (DMS) in EM9 cells expressing XRCC1(ckm) (CKM cells) or following inhibition with the CK2 inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT). We also show that XRCC1(ckm) protein has a higher affinity for DNA than wild type XRCC1 protein and resides in an immobile fraction on DNA, in particular after damage. We propose a model whereby the increased affinity for DNA sequesters XRCC1(ckm) and the repair enzymes associated with it, at the repair site, which retards kinetics of BER. In conclusion, our results indicate that phosphorylation of XRCC1 by CK2 facilitates the BER incision step, likely by promoting dissociation from DNA.


Integrated network analysis of transcriptomic and proteomic data in psoriasis.
Psoriasis is complex inflammatory skin pathology of autoimmune origin. Several cell types are perturbed in this pathology, and underlying signaling events are complex and still poorly understood. In order to gain insight into molecular machinery underlying the disease, we conducted a comprehensive meta-analysis of proteomics and transcriptomics of psoriatic lesions from independent studies. Network-based analysis revealed similarities in regulation at both proteomics and transcriptomics level. We identified a group of transcription factors responsible for overexpression of psoriasis genes and a number of previously unknown signaling pathways that may play a role in this process. We also evaluated functional synergy between transcriptomics and proteomics results. We developed network-based methodology for integrative analysis of high throughput data sets of different types. Investigation of proteomics and transcriptomics data sets on psoriasis revealed versatility in regulatory machinery underlying pathology and showed complementarities between two levels of cellular organization.


A primer on the methods and applications for contrast echocardiography in clinical imaging.
Contrast echocardiography is broadly described as a variety of techniques whereby the blood pool on cardiac ultrasound is enhanced with encapsulated gas-filled microbubbles or other acoustically active nano- or microparticles. The development of this technology has occurred primarily in response to the need improve current diagnostic applications of echocardiography such as the need to better define left ventricular cavity volumes, regional wall motion, or the presence or absence of masses and thrombi. A secondary reason for the development of contrast echocardiography has been to expand the capabilities of echocardiography. These new applications include myocardial perfusion imaging for detection of ischemia and viability, perfusion imaging of masses/tumors, and molecular imaging. The ability to fill all of these current and future clinical roles has been predicated on the ability to produce robust contrast signal which, in turn, has relied on technical innovation with regards to the microbubble contrast agents and the ultrasound imaging paradigms. In this review, we will discuss the basics of contrast echocardiography including the composition of microbubble contrast agents, the unique imaging methods used to optimize contrast signal-to-noise ratio, and the clinical applications of contrast echocardiography that have made a clinical impact.


Aspects of Sustainability: Cooperation, Job Satisfaction, and Burnout among Swiss Psychiatrists.
Greater sustainability in mental health services is frequently demanded but seldom analyzed. Levels of cooperation, job satisfaction, and burnout are indicators of social sustainability in this field and are of particular importance to medical staff. Because registered psychiatrists play a central role, we assessed the status quo and interactions between these three factors among registered psychiatrists in Switzerland. A postal survey with three standardized questionnaires about cooperation, job satisfaction, and burnout was conducted among all registered psychiatrists in the German-speaking part of Switzerland (n = 1485). Addresses were provided by the Swiss Medical Association. Response rate was 23.7% (n = 352), yielding a largely male sample (62.8%; n = 218) aged 55.5 ± 8.7 years old. Quantity (47 ± 56.2 contacts over 3 months) and duration (91.1 ± 101.6 min per week) of cooperation was found to be diverse depending on the stakeholder. Quality of cooperation was greatest in general practitioners (81.5%) while it was worst in community mental health providers (54.9%). Overall job satisfaction was assessed rather high (3.7 ± 0.8), and burnout rates were below crucial values (Emotional Exhaustion, 2.9 ± 0.8; Depersonalization, 1.9 ± 0.5). Both were positively influenced by cooperation. The strongest correlation was found between job satisfaction and burnout, and both had significant inverse relationships in all dimensions. To foster sustainability in outpatient mental health care regarding cooperation, job satisfaction, and burnout, personal aspects such and age or years of registration, organizational aspects, such as networking and practice setting, as wells as supportive aspects such as psychotherapy, and self-help groups, must be considered. Quality of cooperation should be reinforced in particular. Because Integrated and Managed Care models cover several of these factors, the models should be more strongly embedded in health care systems.


The relation between body semantics and spatial body representations.
The present study addressed the relation between body semantics (i.e. semantic knowledge about the human body) and spatial body representations, by presenting participants with word pairs, one below the other, referring to body parts. The spatial position of the word pairs could be congruent (e.g. EYE / MOUTH) or incongruent (MOUTH / EYE) with respect to the spatial position of the words' referents. In addition, the spatial distance between the words' referents was varied, resulting in word pairs referring to body parts that are close (e.g. EYE / MOUTH) or far in space (e.g. EYE / FOOT). A spatial congruency effect was observed when subjects made an iconicity judgment (Experiments 2 and 3) but not when making a semantic relatedness judgment (Experiment 1). In addition, when making a semantic relatedness judgment (Experiment 1) reaction times increased with increased distance between the body parts but when making an iconicity judgment (Experiments 2 and 3) reaction times decreased with increased distance. These findings suggest that the processing of body-semantics results in the activation of a detailed visuo-spatial body representation that is modulated by the specific task requirements. We discuss these new data with respect to theories of embodied cognition and body semantics.


Hypertension and smoking are associated with reduced regional left ventricular function in asymptomatic: individuals the Multi-Ethnic Study of Atherosclerosis.
This study sought to test the hypothesis that reduced regional left ventricular (LV) function is associated with traditional risk factors including hypertension, hypercholesterolemia, and smoking in asymptomatic individuals. Coronary artery disease is the main etiology of congestive heart failure in the U.S. and Europe. However, the relationship between risk factors for coronary artery disease and decreased myocardial function has not been studied systematically in asymptomatic individuals. The Multi-Ethnic Study of Atherosclerosis (MESA) is a cohort study designed to investigate the nature of atherosclerosis in asymptomatic individuals. A total of 1,184 participants (45 to 84 years old) underwent tagged cardiac magnetic resonance imaging. Regional LV function was quantified by analyzing peak systolic circumferential strain (Ecc) in regions corresponding to the left anterior descending (LAD), circumflex (LCX), and right coronary (RCA) territories. The association between risk factors and strains was studied using multiple linear regression. Higher diastolic blood pressure (DBP) was associated with lower Ecc (p < or = 0.002). The Ecc's in the LAD territory of participants with DBP <80, 80 to 84, 85 to 89, and > or =90 mm Hg were -15.6%, -14.8%, -14.2%, and -13.7%, respectively (p < 0.001). Similar results were documented in other territories and after multivariable analysis. Smokers had lower Ecc in the LAD and RCA regions compared with nonsmokers. Furthermore, dose response relationship between cigarette consumption measured in pack-years and regional LV dysfunction by Ecc was noted (p < or = 0.01 in LAD and RCA territories). Finally, combined diastolic hypertension and smoking was associated with a greater reduction of regional LV function. Higher diastolic blood pressure and smoking are associated with decreased regional LV function in asymptomatic individuals.


Hybrid Alginate-Protein-Coated Graphene Oxide Microcapsules Enhance the Functionality of Erythropoietin Secreting C2C12 Myoblasts.
The beneficial effect of combining alginate hydrogel with graphene oxide (GO) on microencapsulated C2C12-myoblast viability has recently been described. However, the commercially available GO lacks homogeneity in size, this parameter being of high relevance for the cell fate in two-dimensional studies. In three-dimensional applications the capacity of this material for binding different kinds of proteins can result in the reduction of de novo released protein that can effectively reach the vicinity of the microcapsules. Undoubtedly, this could be an important hurdle in its clinical use when combined with alginate-PLL microcapsules. Here, we demonstrate that the homogenization of GO nanoparticles is not a mandatory preparation step in order to get the best of this material upon cell microencapsulation. In fact, when the superficial area of these particles is increased, higher amounts of the therapeutic protein erythropoietin (EPO) are adsorbed on their surface. On the other hand, we have been able to improve even more the favorable effects of this graphene derivative on microencapsulated cell viability by forming a protein biocorona. These proteins block the potential binding sites of EPO and, therefore, enhance the amount of therapeutic drug that is released. Finally, we prove that these hybrid alginate-protein-coated GO-microcapsules are functional in vivo.


Switching to antipsychotic monotherapy vs. staying on antipsychotic polypharmacy in schizophrenia: A systematic review and meta-analysis.
While recent meta-analyses have reported the superiority of antipsychotic polypharmacy (APP) over antipsychotic monotherapy (APM) in schizophrenia, switching to APM can be beneficial in terms of side effects. To determine whether patients receiving APP should switch to APM or stay on APP, we conducted a systematic review and meta-analysis. Randomized controlled trials (RCTs) examining a switch from APP to APM vs. staying on APP were systematically selected from a previous meta-analysis comparing APP with APM in patients with schizophrenia. In addition, we conducted an updated systematic literature search using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Data on study discontinuation, relapse, psychopathology, neurocognition, extrapyramidal symptoms, and body weight/body mass index (BMI) were extracted and synthesized. A total of 6 RCTs involving 341 patients were included. All studies examined a switch from 2 antipsychotic agents to a single agent. Clozapine-treated patients were included in 3 studies. There was a significant difference in study discontinuation due to all causes in favor of staying on APP (N = 6, n = 341, RR = 2.28, 95% CI = 1.50-3.46, P < 0.001). There were no significant differences in relapse, any psychopathology, neurocognition, extrapyramidal symptoms, or body weight/BMI between the 2 groups. The quality of evidence was low to very low. The findings suggest that clinicians should closely monitor patient condition when switching to APM after receiving 2 antipsychotics. Given the low to very low overall quality of the evidence, the findings should be considered preliminary and inconclusive.


Oxford medial unicompartmental knee arthroplasty. A survival analysis of an independent series.
We describe the outcome of a series of 124 Oxford meniscal-bearing unicompartmental arthroplasties carried out for osteoarthritis of the medial compartment. They had been undertaken more than ten years ago in a non-teaching hospital in Sweden by three surgeons. All the knees had an intact anterior cruciate ligament, a correctable varus deformity and full-thickness cartilage in the lateral compartment. Thirty-seven patients had died; the mean time since operation for the remainder was 12.5 years (10.1 to 15.6). Using the endpoint of revision for any cause, the outcome for every knee was established. Six had been revised (4.8%). At ten years there were 94 knees still at risk and the cumulative survival rate was 95.0% (95% confidence interval 90.8 to 99.3). This figure is similar to that reported by the designers of the prosthesis and to the best published results for independent series of total knee replacement. If patients are selected appropriately, this implant is a reliable treatment for anteromedial osteoarthritis of the knee.


Levels of annexin IV and V in the plasma of pregnant and postpartum women.
Annexin (Anx) V is pivotal in the maintenance of pregnancy by preventing the activation of blood coagulation. The homology of the amino acid sequence between Anx IV and Anx V is highest in Anx family proteins. However, little is known about the roles of Anx IV in pregnancy. The aim of this study is to clarify the roles of circulating Anx IV and Anx V in normal pregnancy. Subjects were non-pregnant women (n = 50), 120 pregnant women, and maternal subjects just after delivery (n = 53) or postpartum (n = 67). Anx IV in the plasma of non-pregnant women was at a concentration 20 times that of Anx V. The plasma levels of Anx IV suddenly increase after delivery, but Anx V levels remain low during this period. Anx IV and Anx V exert similar levels of anticoagulant activity. Anx IV protein was expressed on the basal surface of syncytiotrophoblasts; Anx V protein, on the apical surface of syncytiotrophoblasts. These results suggest that Anx IV enters the maternal bloodstream just after delivery and might play a role in preventing disseminated intravascular coagulopathy, and that Anx V helps to prevent clotting in the placenta during pregnancy.


Accuracy of Preoperative MDCT in Patients With Penetrating Abdominal and Pelvic Trauma.
This study aims to evaluate the overall diagnostic accuracy of preoperative multidetector computed tomography (MDCT) in penetrating abdominal and pelvic injuries (PAPI). We used our hospitals' trauma registry to retrospectively identify patients with PAPI from January 1, 2006, to December 31, 2016. Only patients who had a 64-MDCT scan at presentation and subsequently underwent laparotomy or laparoscopy were included in our study cohort. Each finding noted on MDCT was rated using a 5-point scale to indicate certainty of injury, with a score of 0 being definitive. Using surgical findings as the gold standard, the accuracy of radiology reports was analyzed in 2 ways. A κ statistic was calculated to evaluate each pair of values for absolute agreement, and ratings for all organ systems were analyzed using a repeated measures analysis of variance (ANOVA) to determine whether radiology and surgical findings were similar enough to be clinically meaningful. Qualitative review of the radiology and surgical reports focused on the gastrointestinal (GI) tract was conducted. Our cohort consisted of 38 males and 4 females with a median age of 29 years and a median injury severity score of 15.6. For this study, 12 different organ groups were categorized and analyzed. Of those organ groups, absolute agreement between MDCT and surgical findings was found only for liver and spleen (κ values ranging from 0.2 to 0.5). Additionally, the ANOVA revealed an interaction between finding type and organ system (F 1, 33 = 7.4, P < .001). The most clinically significant discrepancies between MDCT and surgical findings were for gallbladder, bowel, mesenteric, and diaphragmatic injuries. Qualitative review of the GI tract revealed that radiologists can detect significant findings such as presence of injury, however, localization and extent of injury pose a challenge. The detection of clinically significant injuries to solid organs in trauma patients with PAPI on 64-MDCT is adequate. However, detection of injury to the remaining organ groups on MDCT, especially bowel, mesentery, and diaphragm, remains a challenge.


Taxon-specific evolution of glandular kallikrein genes and identification of a progenitor of prostate-specific antigen.
In a previous study we demonstrated that repeated duplications of the tissue kallikrein gene (Klk1) had resulted in 24 paralogs in mouse. Here we demonstrate a different evolution of rat glandular kallikrein genes. Repeated duplications of an approximately 30-kb region, encompassing Klk1, Klk15, and Klk2-ps, resulted in 10 copies of each gene, but only the Klk1 paralogs are functional. The number of genes varies also between nonrodent mammals, e.g., there are probably no paralogs to KLK1 in cow and pig, whereas horse could have up to 5. In the dog, the gene encoding the prostatic arginine esterase was identified as an ortholog to the progenitor of the PSA and hK2 genes, and it carries the same conserved androgen-responsive elements directing prostate transcription as these genes. This is highly interesting with respect to animal models of benign prostate hyperplasia and prostate adenocarcinoma--diseases that have been described only in humans and dogs.


Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis.
Invasive candidiasis is an important cause of morbidity and mortality among patients with health care-associated infection. The echinocandins have potent fungicidal activity against most Candida species, but there are few data comparing the safety and efficacy of echinocandins in the treatment of invasive candidiasis. This was an international, randomized, double-blind trial comparing micafungin (100 mg daily) and micafungin (150 mg daily) with a standard dosage of caspofungin (70 mg followed by 50 mg daily) in adults with candidemia and other forms of invasive candidiasis. The primary end point was treatment success, defined as clinical and mycological success at the end of blinded intravenous therapy. A total of 595 patients were randomized to one the treatment groups and received at least 1 dose of study drug. In the modified intent-to-treat population, 191 patients were assigned to the micafungin 100 mg group, 199 to the micafungin 150 mg group, and 188 to the caspofungin group. Demographic characteristics and underlying disorders were comparable across the groups. Approximately 85% of patients had candidemia; the remainder had noncandidemic invasive candidiasis. At the end of blinded intravenous therapy, treatment was considered successful for 76.4% of patients in the micafungin 100 mg group, 71.4% in the micafungin 150 mg group, and 72.3% in the caspofungin group. The median time to culture negativity was 2 days in the micafungin 100 mg group and the caspofungin group, compared with 3 days in the micafungin 150 mg groups. There were no significant differences in mortality, relapsing and emergent infections, or adverse events between the study arms. Dosages of micafungin 100 mg daily and 150 mg daily were noninferior to a standard dosage of caspofungin for the treatment of candidemia and other forms of invasive candidiasis.


Changing environments or shifting paradigms? Strategic decision making toward water protection in Helsinki, 1850-2000.
The study examines the history of strategic decision-making concerning water protection in Helsinki, 1850-2000. We identified five major strategic decisions that occurred during the study period. The results indicate that strategic decision-making evolves in long-term policy cycles that last on average 20-30 years. New policy cycles are caused by paradigm shifts. Paradigms are shared and predominant ways of understanding reality that help when groups must act to solve common and complex environmental problems. However the internal structure and external dynamics of paradigms are contradictory. Although paradigms serve initially as means to redefine problems and find creative solutions, as time goes by each paradigm seems to become also a barrier that restricts the introduction of new ways of thinking and acting. The power of paradigms lies in the fact that they can be defined as scientific but also social, political, or cultural agreements depending on the context.


A Novel, Stable, Estradiol-Stimulating, Osteogenic Yam Protein with Potential for the Treatment of Menopausal Syndrome.
A novel protein, designated as DOI, isolated from the Chinese yam (Dioscorea opposita Thunb.) could be the first protein drug for the treatment of menopausal syndrome and an alternative to hormone replacement therapy (HRT), which is known to have undesirable side effects. DOI is an acid- and thermo-stable protein with a distinctive N-terminal sequence Gly-Ile-Gly-Lys-Ile-Thr-Thr-Tyr-Trp-Gly-Gln-Tyr-Ser-Asp-Glu-Pro-Ser-Leu-Thr-Glu. DOI was found to stimulate estradiol biosynthesis in rat ovarian granulosa cells; induce estradiol and progesterone secretion in 16- to 18-month-old female Sprague Dawley rats by upregulating expressions of follicle-stimulating hormone receptor and ovarian aromatase; counteract the progression of osteoporosis and augment bone mineral density; and improve cognitive functioning by upregulating protein expressions of brain-derived neurotrophic factor and TrkB receptors in the prefrontal cortex. Furthermore, DOI did not stimulate the proliferation of breast cancer and ovarian cancer cells, which suggest it could be a more efficacious and safer alternative to HRT.


Economic Evaluation of a Patient-Directed Music Intervention for ICU Patients Receiving Mechanical Ventilatory Support.
Music intervention has been shown to reduce anxiety and sedative exposure among mechanically ventilated patients. Whether music intervention reduces ICU costs is not known. The aim of this study was to examine ICU costs for patients receiving a patient-directed music intervention compared with patients who received usual ICU care. A cost-effectiveness analysis from the hospital perspective was conducted to determine if patient-directed music intervention was cost-effective in improving patient-reported anxiety. Cost savings were also evaluated. One-way and probabilistic sensitivity analyses determined the influence of input variation on the cost-effectiveness. Midwestern ICUs. Adult ICU patients from a parent clinical trial receiving mechanical ventilatory support. Patients receiving the experimental patient-directed music intervention received a MP3 player, noise-canceling headphones, and music tailored to individual preferences by a music therapist. The base case cost-effectiveness analysis estimated patient-directed music intervention reduced anxiety by 19 points on the Visual Analogue Scale-Anxiety with a reduction in cost of $2,322/patient compared with usual ICU care, resulting in patient-directed music dominance. The probabilistic cost-effectiveness analysis found that average patient-directed music intervention costs were $2,155 less than usual ICU care and projected that cost saving is achieved in 70% of 1,000 iterations. Based on break-even analyses, cost saving is achieved if the per-patient cost of patient-directed music intervention remains below $2,651, a value eight times the base case of $329. Patient-directed music intervention is cost-effective for reducing anxiety in mechanically ventilated ICU patients.


Genetic polymorphism of proline-rich human salivary proteins.
In randomly collected saliva samples from 120 Caucasians, 79 Blacks, and 40 Chinese, three phenotypes were observed by electrophoresis in alkaline slab polyacrylamide gels. The proteins showing polymorphism were identical with four previously characterized proline-rich proteins. Inheritance is controlled by two autosomal codominant alleles. The gene frequencies were for Caucasians, Pr(l)=0.73, Pr(2)=0.27; for Blacks, Pr(1)=0.80, Pr(2)=0.20; for Chinese, Pr(l)=0.84, Pr(2)=0.16.


Flawed communications: Health professionals' experience of collaboration in the care of frail elderly patients.
Frail elderly patients who have multiple illnesses do not fare well in modern health care systems, mainly due to a lack of care planning and flawed communication between health professionals in different care organisations. This is especially noticeable when patients are discharged from hospital. The aim of this study was to explore health care professionals' experience of obstacles and opportunities for collaboration. Health professionals were invited to participate in three focus groups, each consisting of a hospital physician, a primary care physician, a hospital nurse, a primary care nurse, a municipal home care nurse or an assistant officer, a physical or occupational therapist and a patient or a family member representative. These individual people were then asked to discuss the obstacles and opportunities for communication between themselves and with the patients and their relatives when presented with the case report of a fictitious patient. Content analysis was used to identify categories. Several obstacles were identified for effective communication and care planning: insufficient communication with patients and relatives; delayed collaboration between care-givers; the lack of an adequate responsible person for care planning; and resources not being distributed according to the actual needs of patients. The absence of an overarching responsibility for the patient, beyond organisational borders, was a recurring theme. These obstacles could also be seen as opportunities. Obstacles for collaboration were found on three levels: societal, organisational and individual. As health care professionals are well aware of the problems and also see solutions, management for health care should support employees' own initiatives for changes that are of benefit in the care of frail elderly patients with multiple illnesses.


Low prevalence of Helicobacter pylori infection in Canadian children: a cross-sectional analysis.
The incidence and prevalence rates of childhood Helicobacter pylori infection vary greatly by nation, with infection rates of 8.9% to 72.8% reported in developed and developing countries, respectively. To date, few studies have assessed the prevalence of H pylori in Canadian children, with studies limited to Aboriginal communities and single tertiary care centres from Ontario and Quebec. To determine the prevalence of H pylori in consecutive children referred to three Canadian tertiary care academic centres for upper gastrointestinal (GI) endoscopy due to upper GI symptoms, and to determine the sensitivity and specificity of the carbon-13-labelled urea breath test, the rapid urease test and the H pylori stool monoclonal antigen test. Two hundred four patients were recruited. The prevalence of H pylori was 7.1%. Of the H pylori-positive patients, 41.7% were male, with a mean age of 10.3 years. Ethnic minorities accounted for 42% of the H pylori-positive patients. Consistent with previous observations, the sensitivity and specificity of the carbon-13-labelled urea breath test were 1.0 and 0.98, respectively. The sensitivity and specificity of the rapid urease test were 1.0 and 0.99, respectively. Stool samples were collected from 34 patients from one centre, with a sensitivity and specificity of 1.0 and 0.68, respectively. No defining symptoms of H pylori infection were evident and no peptic ulcer disease was demonstrated. H pylori infection rates in Canadian children with upper GI symptoms are low, and are lower than those reported for other developed countries. Further studies are required in Canada to determine the prevalence in the general population and specifically in the populations at risk.


Involvement of Plasmodium falciparum protein kinase CK2 in the chromatin assembly pathway.
Protein kinase CK2 is a pleiotropic serine/threonine protein kinase with hundreds of reported substrates, and plays an important role in a number of cellular processes. The cellular functions of Plasmodium falciparum CK2 (PfCK2) are unknown. The parasite's genome encodes one catalytic subunit, PfCK2α, which we have previously shown to be essential for completion of the asexual erythrocytic cycle, and two putative regulatory subunits, PfCK2β1 and PfCK2β2. We now show that the genes encoding both regulatory PfCK2 subunits (PfCK2β1 and PfCK2β2) cannot be disrupted. Using immunofluorescence and electron microscopy, we examined the intra-erythrocytic stages of transgenic parasite lines expressing hemagglutinin (HA)-tagged catalytic and regulatory subunits (HA-CK2α, HA-PfCK2β1 or HA-PfCK2β2), and localized all three subunits to both cytoplasmic and nuclear compartments of the parasite. The same transgenic parasite lines were used to purify PfCK2β1- and PfCK2β2-containing complexes, which were analyzed by mass spectrometry. The recovered proteins were unevenly distributed between various pathways, with a large proportion of components of the chromatin assembly pathway being present in both PfCK2β1 and PfCK2β2 precipitates, implicating PfCK2 in chromatin dynamics. We also found that chromatin-related substrates such as nucleosome assembly proteins (Naps), histones, and two members of the Alba family are phosphorylated by PfCK2α in vitro. Our reverse-genetics data show that each of the two regulatory PfCK2 subunits is required for completion of the asexual erythrocytic cycle. Our interactome study points to an implication of PfCK2 in many cellular pathways, with chromatin dynamics being identified as a major process regulated by PfCK2. This study paves the way for a kinome-wide interactomics-based approach to elucidate protein kinase function in malaria parasites.


Thermally-nucleated self-assembly of water and alcohol into stable structures at hydrophobic interfaces.
At the interface with solids, the mobility of liquid molecules tends to be reduced compared with bulk, often resulting in increased local order due to interactions with the surface of the solid. At room temperature, liquids such as water and methanol can form solvation structures, but the molecules remain highly mobile, thus preventing the formation of long-lived supramolecular assemblies. Here we show that mixtures of water with methanol can form a novel type of interfaces with hydrophobic solids. Combining in situ atomic force microscopy and multiscale molecular dynamics simulations, we identify solid-like two-dimensional interfacial structures that nucleate thermally, and are held together by an extended network of hydrogen bonds. On graphite, nucleation occurs above ∼35 °C, resulting in robust, multilayered nanoscopic patterns. Our findings could have an impact on many fields where water-alcohol mixtures play an important role such as fuel cells, chemical synthesis, self-assembly, catalysis and surface treatments.


Mouse genomic associations with in vitro sensitivity to simulated space radiation.
Exposure to ionizing radiation is considered by NASA to be a major health hazard for deep space exploration missions. Ionizing radiation sensitivity is modulated by both genomic and environmental factors. Understanding their contributions is crucial for designing experiments in model organisms, evaluating the risk of deep space (i.e. high-linear energy transfer, or LET, particle) radiation exposure in astronauts, and also selecting therapeutic irradiation regimes for cancer patients. We identified single nucleotide polymorphisms in 15 strains of mice, including 10 collaborative cross model strains and 5 founder strains, associated with spontaneous and ionizing radiation-induced in vitro DNA damage quantified based on immunofluorescent tumor protein p53 binding protein (53BP1) positive nuclear foci. Statistical analysis suggested an association with pathways primarily related to cellular signaling, metabolism, tumorigenesis and nervous system damage. We observed different genomic associations in early (4 and 8 h) responses to different LET radiation, while later (24 hour) DNA damage responses showed a stronger overlap across all LETs. Furthermore, a subset of pathways was associated with spontaneous DNA damage, suggesting 53BP1 positive foci as a potential biomarker for DNA integrity in mouse models. Our results suggest several mouse strains as new models to further study the impact of ionizing radiation and validate the identified genetic loci. We also highlight the importance of future human in vitro studies to refine the association of genes and pathways with the DNA damage response to ionizing radiation and identify targets for space travel countermeasures.


Anti-inflammatory and antioxidant therapies for chagasic myocarditis: a systematic review.
The aim of this review was to identify anti-inflammatory and antioxidant therapeutic agents and their effects on patients with chagasic myocarditis. A systematic review of the MEDLINE, EMBASE, WEB OF SCIENCE, SCOPUS, LILACS and CENTRAL databases (Cochrane Library) was carried out without language restrictions. The descriptors used were: 'Chagas cardiomyopathy', 'treatment', 'Chagas disease', 'anti-inflammatory agents', 'Trypanosoma cruzi' and 'antioxidants'. A total of 4,138 articles was identified, six of which were selected for data extraction. Of these, four were related to antioxidant therapy with vitamins C and E supplementation, and two using anti-inflammatory therapy. The studies were carried out in Brazil and were published between 2002 and 2017. Antioxidant therapy with vitamin C and E supplementation increases the activity of antioxidant enzymes and reduces the oxidative markers. There is no conclusive data to support the use of vitamin supplementation and anti-inflammatory therapy in the treatment of chagasic cardiomyopathy. However, the studies indicate the possibility of vitamin supplementation as a new approach to the treatment of Chagas disease. Antioxidant therapy was proven to be a viable alternative for attenuating the oxidative damage caused by chronic chagasic cardiopathy, leading to a better prognosis for patients.


Quantitative combination of natural anti-oxidants prevents metabolic syndrome by reducing oxidative stress.
Insulin resistance and abdominal obesity are present in the majority of people with the metabolic syndrome. Antioxidant therapy might be a useful strategy for type 2 diabetes and other insulin-resistant states. The combination of vitamin C (Vc) and vitamin E has synthetic scavenging effect on free radicals and inhibition effect on lipid peroxidation. However, there are few studies about how to define the best combination of more than three anti-oxidants as it is difficult or impossible to test the anti-oxidant effect of the combination of every concentration of each ingredient experimentally. Here we present a math model, which is based on the classical Hill equation to determine the best combination, called Fixed Dose Combination (FDC), of several natural anti-oxidants, including Vc, green tea polyphenols (GTP) and grape seed extract proanthocyanidin (GSEP). Then we investigated the effects of FDC on oxidative stress, blood glucose and serum lipid levels in cultured 3T3-L1 adipocytes, high fat diet (HFD)-fed rats which serve as obesity model, and KK-ay mice as diabetic model. The level of serum malondialdehyde (MDA) in the treated rats was studied and Hematoxylin-Eosin (HE) staining or Oil red slices of liver and adipose tissue in the rats were examined as well. FDC shows excellent antioxidant and anti-glycation activity by attenuating lipid peroxidation. FDC determined in this investigation can become a potential solution to reduce obesity, to improve insulin sensitivity and be beneficial for the treatment of fat and diabetic patients. It is the first time to use the math model to determine the best ratio of three anti-oxidants, which can save much more time and chemical materials than traditional experimental method. This quantitative method represents a potentially new and useful strategy to screen all possible combinations of many natural anti-oxidants, therefore may help develop novel therapeutics with the potential to ameliorate the worldwide metabolic abnormalities.


Prediction of nitrogen excretion from data on dairy cows fed a wide range of diets compiled in an intercontinental database: A meta-analysis.
Manure nitrogen (N) from cattle contributes to nitrous oxide and ammonia emissions and nitrate leaching. Measurement of manure N outputs on dairy farms is laborious, expensive, and impractical at large scales; therefore, models are needed to predict N excreted in urine and feces. Building robust prediction models requires extensive data from animals under different management systems worldwide. Thus, the study objectives were (1) to collate an international database of N excretion in feces and urine based on individual lactating dairy cow data from different continents; (2) to determine the suitability of key variables for predicting fecal, urinary, and total manure N excretion; and (3) to develop robust and reliable N excretion prediction models based on individual data from lactating dairy cows consuming various diets. A raw data set was created based on 5,483 individual cow observations, with 5,420 fecal N excretion and 3,621 urine N excretion measurements collected from 162 in vivo experiments conducted by 22 research institutes mostly located in Europe (n = 14) and North America (n = 5). A sequential approach was taken in developing models with increasing complexity by incrementally adding variables that had a significant individual effect on fecal, urinary, or total manure N excretion. Nitrogen excretion was predicted by fitting linear mixed models including experiment as a random effect. Simple models requiring dry matter intake (DMI) or N intake performed better for predicting fecal N excretion than simple models using diet nutrient composition or milk performance parameters. Simple models based on N intake performed better for urinary and total manure N excretion than those based on DMI, but simple models using milk urea N (MUN) and N intake performed even better for urinary N excretion. The full model predicting fecal N excretion had similar performance to simple models based on DMI but included several independent variables (DMI, diet crude protein content, diet neutral detergent fiber content, milk protein), depending on the location, and had root mean square prediction errors as a fraction of the observed mean values of 19.1% for intercontinental, 19.8% for European, and 17.7% for North American data sets. Complex total manure N excretion models based on N intake and MUN led to prediction errors of about 13.0% to 14.0%, which were comparable to models based on N intake alone. Intercepts and slopes of variables in optimal prediction equations developed on intercontinental, European, and North American bases differed from each other, and therefore region-specific models are preferred to predict N excretion. In conclusion, region-specific models that include information on DMI or N intake and MUN are required for good prediction of fecal, urinary, and total manure N excretion. In absence of intake data, region-specific complex equations using easily and routinely measured variables to predict fecal, urinary, or total manure N excretion may be used, but these equations have lower performance than equations based on intake.


Korean Nationwide Surveillance of Antimicrobial Resistance of bacteria in 1997.
Antimicrobial-resistant bacteria are known to be prevalent in tertiary-care hospitals in Korea. Twenty hospitals participated to this surveillance to determine the nationwide prevalence of resistance bacteria in 1997. Seven per cent and 26% of Escherichia coli and Klebsiella pneumoniae were resistant to 3rd-generation cephalosporin. Increased resistance rates, 19% of Acinetobacter baumannii to ampicillin/sulbactam, and 17% of Pseudomonas aeruginoa to imipenem, were noted. The resistance rate to fluoroquinolone rose to 24% in E. coli, 56% in A. baumannii and 42% in P. aeruginosa. Mean resistance rates were similar in all hospital groups: about 17% of P. aeruginosa to imipenem, 50% of Haemophilus influenzae to ampicillin, 70% of Staphylococcus aureus to methicillin, and 70% of pneumococci to penicillin. In conclusion, nosocomial pathogens and problem resistant organisms are prevalent in smaller hospitals too, indicating nosocomial spread is a significant cause of the increasing prevalence of resistant bacteria in Korea.


Salvage focal and salvage total cryoablation for locally recurrent prostate cancer after primary radiation therapy.
To present the oncological and functional outcomes of salvage focal (SFC) and salvage total (STC) cryoablation for recurrent prostate cancer (PCa) after failed primary radiotherapy. From March 2003 to August 2010, 50 men with biopsy-proven unilateral (n = 25) or bilateral (n = 25) radio-recurrent PCa underwent SFC or STC, respectively. Patients were assessed after treatment by prostate-specific antigen (PSA) testing, transrectal ultrasonography, biopsy and questionnaires. Biochemical failure (BF) was defined using the Phoenix criteria (PSA nadir + 2 mg/mL). Data were prospectively collected and retrospectively analysed. The median pre-cryoablation PSA level and Gleason score were, respectively, 2.8 ng/mL and 7 for SFC, and 3.9 ng/mL and 7 for STC. The median follow-up was 31 and 53 months (P = 0.004) for SFC and STC, respectively. Oncological outcomes were as follows: no patient died; one patient who underwent STC developed bone metastases; eight patients who underwent SFC and three who underwent STC had BF and the 5-year BF-free survival rates were 54 and 86%, respectively. In those patients without BF, the mean PSA decreased by 86% for SFC and 90% for STC within the first year and remained stable. Functional outcomes were as follows: new onset urinary incontinence occurred in three (13%) patients in the STC group, whereas no patient in the SFC group developed incontinence (P = 0.10); Two of seven patients in the SFC group retained postoperative potency, but none of the four potent patients in the STC group recovered potency postoperatively (P = 0.48); one (4%) patient in the STC group developed a recto-urethral fistula, but none occurred in the SFC group (P = 0.48). SFC and STC are feasible and safe with acceptable mid-term oncological outcomes. For carefully selected patients, SFC is an option that could be associated with lower treatment-related morbidity compared with STC. Although longer follow-up and more patient numbers are needed, our initial oncological and functional outcomes of SFC and STC are encouraging.


Dynamics of the skeletal muscle secretome during myoblast differentiation.
During recent years, increased efforts have focused on elucidating the secretory function of skeletal muscle. Through secreted molecules, skeletal muscle affects local muscle biology in an auto/paracrine manner as well as having systemic effects on other tissues. Here we used a quantitative proteomics platform to investigate the factors secreted during the differentiation of murine C2C12 skeletal muscle cells. Using triple encoding stable isotope labeling by amino acids in cell culture, we compared the secretomes at three different time points of muscle differentiation and followed the dynamics of protein secretion. We identified and quantitatively analyzed 635 secreted proteins, including 35 growth factors, 40 cytokines, and 36 metallopeptidases. The extensive presence of these proteins that can act as potent signaling mediators to other cells and tissues strongly highlights the important role of the skeletal muscle as a prominent secretory organ. In addition to previously reported molecules, we identified many secreted proteins that have not previously been shown to be released from skeletal muscle cells nor shown to be differentially released during the process of myogenesis. We found 188 of these secreted proteins to be significantly regulated during the process of myogenesis. Comparative analyses of selected secreted proteins revealed little correlation between their mRNA and protein levels, indicating pronounced regulation by posttranscriptional mechanisms. Furthermore, analyses of the intracellular levels of members of the semaphorin family and their corresponding secretion dynamics demonstrated that the release of secreted proteins is tightly regulated by the secretory pathway, the stability of the protein, and/or the processing of secreted proteins. Finally, we provide 299 unique hydroxyproline sites mapping to 48 distinct secreted proteins and have discovered a novel hydroxyproline motif.


Isolation of Mouse and Human Tumor-Associated Macrophages.
The tumor microenvironment is a complex network of cells that support tumor progression and malignancy. It has been demonstrated that tumor cells can educate the immune system to promote a tumor-friendly environment. Among all these immune cells, tumor-associated macrophages (TAMs) are well represented and their presence in mouse models has been shown to promote tumor progression and metastasis. These effects are through the stimulation of angiogenesis, enhancement of tumor cell invasion and intravasation, immunosuppression, and at the metastatic site tumor cell extravasation and growth. However, the precise mechanisms are not fully understood. Furthermore there is limited information on TAMs derived from human cancers. For this reason it is important to be able to extract TAMs from tumors in order to compare their phenotypes, functions, and transcriptomes with normal resident tissue macrophages. Isolation of these cells is challenging due to the lack of markers and standardized protocols. Here we show an optimized protocol for the efficient isolation and extraction of resident macrophages and TAMs from human and mouse tissues by using multicolor flow cytometry. These protocols allow for the extraction of thousands of macrophages in less than 5 h from tissues as small as half a gram. The isolated macrophages can then be used for both "omics" and in vitro studies.


WITHDRAWN: Multi-agent chemotherapy for early breast cancer.
There have been many randomised trials of adjuvant prolonged polychemotherapy among women with early breast cancer, and an updated overview of their results is presented. In this report, the Early Breast Cancer Trialists' Collaborative Group present their updated systematic overview (meta-analysis) of treatment with polychemotherapy. Trial identification procedures for the EBCTCG overviews have been described elsewhere. See under "EBCTCG" in the Breast Cancer Collaborative Review Group module. All randomised trials that began before 1990 and involved treatment groups that differed only with respect to the chemotherapy regimens that were being compared. In 1995, information was sought on each woman in any randomised trial that began before 1990 and involved treatment groups that differed only with respect to the chemotherapy regimens that were being compared. Analyses involved about 18,000 women in 47 trials of prolonged polychemotherapy versus no chemotherapy, about 6000 in 11 trials of longer versus shorter polychemotherapy, and about 6000 in 11 trials of anthracycline-containing regimens versus CMF (cyclophosphamide, methotrexate, and fluorouracil). For recurrence, polychemotherapy produced substantial and highly significant proportional reductions both among women aged under 50 at randomisation (35% [SD 4] reduction; 2p<0.00001) and among those aged 50-69 (20% [SD 3] reduction; 2p<0.00001); few women aged 70 or over had been studied. For mortality, the reductions were also significant both among women aged under 50 (27% [SD 5] reduction; 2p<0.00001) and among those aged 50-69 (11% [SD 3] reduction; 2p=0.0001). The recurrence reductions emerged chiefly during the first 5 years of follow-up, whereas the difference in survival grew throughout the first 10 years. After standardisation for age and time since randomisation, the proportional reductions in risk were similar for women with node-negative and node-positive disease. Applying the proportional mortality reduction observed in all women aged under 50 at randomisation would typically change a 10-year survival of 71% for those with node-negative disease to 78% (an absolute benefit of 7%), and of 42% for those with node-positive disease to 53% (an absolute benefit of 11%). The smaller proportional mortality reduction observed in all women aged 50-69 at randomisation would translate into smaller absolute benefits, changing a 10-year survival of 67% for those with node-negative disease to 69% (an absolute gain of 2%) and of 46% for those with node-positive disease to 49% (an absolute gain of 3%). The age-specific benefits of polychemotherapy appeared to be largely irrespective of menopausal status at presentation, oestrogen receptor status of the primary tumour, and of whether adjuvant tamoxifen had been given. In terms of other outcomes, there was a reduction of about one-fifth (2p=0.05) in contralateral breast cancer, which has already been included in the analyses of recurrence, and no apparent adverse effect on deaths from causes other than breast cancer (death rate ratio 0.89 [SD 0.09]). The directly randomised comparisons of longer versus shorter durations of polychemotherapy did not indicate any survival advantage with the use of more than about 3-6 months of polychemotherapy. By contrast, directly randomised comparisons did suggest that, compared with CMF alone, the anthracycline-containing regimens studied produced somewhat greater effects on recurrence (2p=0.006) and mortality (69% vs 72% 5-year survival; log-rank 2p=0.02). But this comparison is one of many that could have been selected for emphasis, the 99% CI reaches zero, and the results of several of the relevant trials are not yet available. Some months of adjuvant polychemotherapy (eg, with CMF or an anthracycline-containing regimen) typically produces an absolute improvement of about 7-11% in 10-year survival for women aged under 50 at presentation with early breast cancer, and of about 2-3% for those aged 50-69 (unless their prognosis is likely to be extremely good even without such treatment). Treatment decisions involve consideration not only of improvements in cancer recurrence and survival but also of adverse side-effects of treatment, and this report makes no recommendations as to who should or should not be treated.


The culture of affluence: psychological costs of material wealth.
Children of affluence are generally presumed to be at low risk. However, recent studies have suggested problems in several domains--notably, substance use, anxiety, and depression--and 2 sets of potential causes: pressures to achieve and isolation from parents. Recognizing the limited awareness of these issues, the objectives in this paper are to collate evidence on the nature of problems among the wealthy and their likely causes. The first half of the paper is focused on disturbances among affluent children and the second half is focused on characteristics of their families and neighborhoods. Widespread negative sentiments toward the rich are then discussed, and the paper concludes with suggestions for future work with families at the upper end of the socioeconomic spectrum.


Water channel pore size determines exclusion properties but not solute selectivity.
Aquaporins (AQPs) are a ubiquitous family of transmembrane water channel proteins. A subgroup of AQP water channels also facilitates transmembrane diffusion of small, polar solutes. A constriction within the pore, the aromatic/arginine (ar/R) selectivity filter, is thought to control solute permeability: previous studies on single representative water channel proteins suggest narrow channels conduct water, whilst wider channels permit passage of solutes. To assess this model of selectivity, we used mutagenesis, permeability measurements and in silico comparisons of water-specific as well as glycerol-permeable human AQPs. Our studies show that single amino acid substitutions in the selectivity filters of AQP1, AQP4 and AQP3 differentially affect glycerol and urea permeability in an AQP-specific manner. Comparison between in silico-calculated channel cross-sectional areas and in vitro permeability measurements suggests that selectivity filter cross-sectional area predicts urea but not glycerol permeability. Our data show that substrate discrimination in water channels depends on a complex interplay between the solute, pore size, and polarity, and that using single water channel proteins as representative models has led to an underestimation of this complexity.


The impact of positive airway pressure on cardiac status and clinical outcomes in patients with advanced heart failure and sleep-disordered breathing: a preliminary report.
Heart failure (HF) is a major public health problem associated with high rates of morbidity and mortality. Patients with HF exhibit a high prevalence of sleep-disordered breathing (SDB). We have investigated the long-term impact of positive airway pressure (PAP) therapy on heart function and clinical outcomes in patients with advanced HF and concomitant SDB. We assessed 18 patients with advanced HF (New York Heart Association (NYHA) functional classification III-IV) and concomitant SDB (diagnosed with polysomnography) either of obstructive or central type. Eleven patients who received PAP therapy (auto-titrating PAP or adaptive servo-ventilation) for 12 months were compared with seven patients who refused this therapy. All participants were assessed at both baseline and end of follow-up for NYHA functional status, left and right ventricular function, neurohormonal activation, and exercise tolerance. The rates of hospitalization, deaths, and the combination of both were also recorded. Patients treated with PAP achieved better functional status, higher left ventricular ejection fraction, improved longitudinal right ventricular contractile function, lower levels of b-type natriuretic peptide, and greater exercise performance compared to those who remained untreated. PAP-treated group had a significantly lower incidence of the prespecified combined end-point (i.e., hospital admissions and death) than the control group (87.5 vs. 18.2%, p = 0.013). Interestingly, the mortality rate was 28% (two out of seven patients) in the control group, while no deaths were recorded in the PAP-treated group. In this preliminary study, we found that treatment of SDB, irrespective of type, in stable patients with advanced HF receiving optimal medical therapy was associated with improvement in cardiac functional status, ventricular contraction, physical performance, and neurohormonal status, leading to better clinical outcomes.


[Evaluation of the clinical usefulness of super dynamic 99mTc-HM-PAO SPECT in ischemic cerebrovascular disease--detection of hypo- and hyperperfusion area].
The purpose of this study is to assess the clinical usefulness of super dynamic SPECT of 99mTc-HM-PAO. Six patients with unilateral occlusion of middle cerebral artery (MCA) or internal carotid artery (ICA) in the chronic phase, and 5 patients with subacute cerebral infarction were studied. We used a ring-type SPECT "HEADTOME." Two types of collimator were used: a high sensitivity (HS) collimator for super dynamic scan and a high resolution (HR) collimator for static scan. First, the intravenous constant infusion of 99mTc-HM-PAO (925-1480 MBq) for 1 minute was started. After 30 seconds from the beginning of the injection, we performed the 12 seconds/frame super dynamic SPECT for 2 minutes. Then, the static SPECT for 10 minutes was done. For semiquantitative analyses, differential percentage of regional activity between affected and non-affected hemispheres was calculated in the 6th frame image of super dynamic SPECT and static SPECT image. In all 6 patients with unilateral occlusion of MCA and ICA, super dynamic SPECT images showed the better contrast of low perfusion areas in comparison with the static SPECT images. In 5 patients with subacute cerebral infarction who showed focal hyperactivities on static SPECT, focal hyperactivities (hyperperfusion or hyperemia) were displayed in 3 cases, whereas, focal hypo- or isoactivities (hypo- or isoperfusion) were shown in 2 cases on super dynamic SPECT. However, all patients with subacute cerebral infarction showed hyperfixation on static SPECT as compared with super dynamic SPECT. Although the image quality on super dynamic SPECT is not as high as that on static SPECT, cerebral hemodynamics would be detected with less backdiffusion of 99mTc-HM-PAO from the brain to blood, and with less accumulation of hydrophilic components in subacute infarct region. In conclusion, super dynamic SPECT in early distribution of 99mTc-HM-PAO using dedicated SPECT device might be helpful to detect cerebral perfusion close to true cerebral blood flow distribution.


Atrial natriuretic peptide levels during development of chronic heart failure after myocardial infarction in rats.
Serum levels of atrial natriuretic peptide (ANP) are elevated in chronic heart failure presumably due to dilatation of the left atrium resulting from increases in intracardiac pressures. To define the time course of changes in serum ANP levels and to determine the relationship to left ventricular end-diastolic pressure, rats were subjected to coronary artery ligation to produce myocardial infarction and left ventricular failure. Atrial natriuretic peptide levels were measured weekly for four weeks thereafter. In rats with myocardial infarction and elevation of left ventricular end-diastolic pressure there was no change in ANP levels at 7 and 14 days. However, at day 21 and 28, ANP levels were elevated more than 3 fold. There was a correlation between ANP levels and left ventricular end-diastolic pressures. There was no correlation between ANP levels and right atrial pressures or serum sodium concentrations. We conclude that the chronic elevation of left ventricular end-diastolic pressure is required to produce an increase in ANP after myocardial infarction which results in chronic heart failure.


Outcome of alcohol septal ablation for obstructive hypertrophic cardiomyopathy.
The clinical efficacy of alcohol septal ablation for drug-refractory hypertrophic cardiomyopathy remains unclear. This study examines the outcome of alcohol septal ablation performed at a tertiary hypertrophic cardiomyopathy referral center. Among 601 patients with severely symptomatic obstructive hypertrophic cardiomyopathy referred for alcohol septal ablation or myectomy from 1998 to 2006, 138 patients (median age, 64 years; 39% men) chose to undergo ablation. Procedural complications included death in 1.4%, sustained ventricular arrhythmias in 3%, tamponade in 3%, and pacemaker implantation in 20%. This rate was higher than a combined complication rate of 5% in age- and gender-matched patients who had undergone septal myectomy at Mayo Clinic (P<0.0001). Four-year survival free of all mortality was 88.0% (95% confidence interval, 79.4 to 97.5%), which was similar to that of the age- and gender-matched patients who had undergone myectomy (P=0.18). Six patients had documented ventricular arrhythmias after ablation, 4 of whom had successful intervention. Four-year survival free of death and severe New York Heart Association class III/IV symptoms after septal ablation was 76.4%, and 71 patients (51%) became asymptomatic. Myectomy patients <or=65 years of age had significantly better survival free of death and severe symptoms (P=0.01). Alcohol septal ablation is an efficacious procedure if performed in an experienced institution and may resolve symptoms in a subset of patients with obstructive hypertrophic cardiomyopathy. However, the procedural complication rate exceeds that of myectomy. Patients 65 years of age have better symptom resolution with myectomy. No impairment in short-term survival was noted in this nonrandomized study, but the long-term outcome remains unknown.


Construction of a Shape-Diverse Fragment Set: Design, Synthesis and Screen against Aurora-A Kinase.
Historically, chemists have explored chemical space in a highly uneven and unsystematic manner. As an example, the shape diversity of existing fragment sets does not generally reflect that of all theoretically possible fragments. To assess experimentally the added value of increased three dimensionality, a shape-diverse fragment set was designed and collated. The set was assembled by both using commercially available fragments and harnessing unified synthetic approaches to sp3 -rich molecular scaffolds. The resulting set of 80 fragments was highly three-dimensional, and its shape diversity was significantly enriched by twenty synthesised fragments. The fragment set was screened by high-throughput protein crystallography against Aurora-A kinase, revealing four hits that targeted the binding site of allosteric regulators. In the longer term, it is envisaged that the fragment set could be screened against a range of functionally diverse proteins, allowing the added value of more shape-diverse screening collections to be more fully assessed.