Prognostic factors in children with acute lymphoblastic leukemia. Part I: Univariate analysis. Children's Cancer and Leukemia Study Group.
The pretreatment characteristics of 158 children with previously untreated acute lymphoblastic leukemia diagnosed April 1972 to June 1978 were analyzed for their ability to predict prognosis. The children were treated according to therapeutic protocols 721, 745 and 765, by members of the Japanese Children's Cancer and Leukemia Study Group. A univariate analysis was performed to determine the relationship between the characteristics and the duration of the patients' survival. The following characteristics were analyzed: initial white blood cell (WBC) count, age at diagnosis, initial hemoglobin level, initial platelet count, sex, organomegaly, and treatment regimen that was provided. Favorable prognosis was exhibited only by those patients with initial WBC counts of less than 50,000/mm3, with age at onset between 2 and 6 years, without splenomegaly, and with hemoglobin levels between 5 and 10 g/dl. The most significant contributions among the various individual prognostic factors were initial WBC count (p less than 0.001) and the age at diagnosis (p less than 0.01).


Monitoring follicular development in cattle by real-time ultrasonography: a review.
The application of real-time ultrasonography to monitoring ovarian function in mammals has advanced the understanding of follicular dynamics and its regulation. Follicular development is a wave-like sequence of organised events. The waves consist of the synchronous growth of small (4 to 5 mm) antral follicles, followed by the selection and growth of one dominant follicle which achieves the largest diameter and suppresses the growth of the subordinate follicles. In the absence of luteal regression, the dominant follicle eventually regresses (becomes atretic) and a new follicular wave begins. The dominant follicle regulates the growth of the subordinate follicles, because the appearance of the next wave is accelerated if the dominant follicle is ablated, and delayed if the lifespan of the dominant follicle is prolonged. During bovine oestrous cycles, two or three successive waves emerge, on average, on the day of ovulation (day 0) and day 10 for two-wave cycles, and on days 0, 9 and 16 for three-wave cycles. During the oestrous cycle there are thus two or three successive dominant follicles, and the last of these ovulates. Ovarian folliculogenesis is a complex process involving interactions between pituitary gonadotrophins, ovarian steroids and non-steroidal factors. Subtle changes in the hormonal milieu regulate folliculogenesis and the emergence of a follicular wave is preceded by a small increase in the concentration of plasma follicle-stimulating hormone. The mechanisms that promote the selection of a dominant follicle have not been elucidated, but considerable progress has been made in understanding follicular development and its regulation. Most treatments designed to control the development of follicular waves have been based on the physical or hormonal removal of the suppressive effect of the dominant follicle, and the consequent controlled induction of the emergence of a new follicular wave. The studies reviewed here describe current methods for regulating the bovine ovarian cycle, interesting models for future studies, and information that may be used for improving reproductive efficiency.


Induction of oxidative stress in brain of glutaryl-CoA dehydrogenase deficient mice by acute lysine administration.
In the present work we evaluated a variety of indicators of oxidative stress in distinct brain regions (striatum, cerebral cortex and hippocampus), the liver, and heart of 30-day-old glutaryl-CoA dehydrogenase deficient (Gcdh(-/-)) mice. The parameters evaluated included thiobarbituric acid-reactive substances (TBA-RS), 2-7-dihydrodichlorofluorescein (DCFH) oxidation, sulfhydryl content, and reduced glutathione (GSH) concentrations. We also measured the activities of the antioxidant enzymes glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD) and glucose-6-phosphate dehydrogenase (G6PD). Under basal conditions glutaric (GA) and 3-OH-glutaric (3OHGA) acids were elevated in all tissues of the Gcdh(-/-) mice, but were essentially absent in WT animals. In contrast there were no differences between WT and Gcdh(-/-) mice in any of the indicators or oxidative stress under basal conditions. Following a single intra-peritoneal (IP) injection of lysine (Lys) there was a moderate increase of brain GA concentration in Gcdh(-/-) mice, but no change in WT. Lys injection had no effect on brain 3OHGA in either WT or Gcdh(-/-) mice. The levels of GA and 3OHGA were approximately 40% higher in striatum compared to cerebral cortex in Lys-treated mice. In the striatum, Lys administration provoked a marked increase of lipid peroxidation, DCFH oxidation, SOD and GR activities, as well as significant reductions of GSH levels and GPx activity, with no alteration of sulfhydryl content, CAT and G6PD activities. There was also evidence of increased lipid peroxidation and SOD activity in the cerebral cortex, along with a decrease of GSH levels, but to a lesser extent than in the striatum. In the hippocampus only mild increases of SOD activity and DCFH oxidation were observed. In contrast, Lys injection had no effect on any of the parameters of oxidative stress in the liver or heart of Gcdh(-/-) or WT animals. These results indicate that in Gcdh(-/-) mice cerebral tissue, particularly the striatum, is at greater risk for oxidative stress than peripheral tissues following Lys administration.


The Effects of Quassinoid-Rich Eurycoma longifolia Extract on Bone Turnover and Histomorphometry Indices in the Androgen-Deficient Osteoporosis Rat Model.
Male osteoporosis is associated with higher rates of disability and mortality. Hence the search for suitable intervention and treatment to prevent the degeneration of skeletal health in men is necessary. Eurycoma longifolia (EL), a traditional plant with aphrodisiac potential may be used to treat and prevent male osteoporosis. The skeletal protective effect of quassinoid-rich EL extract, which has a high content of eurycomanone, has not been studied. This study aimed to determine whether EL could prevent skeletal deteriorations in gonadal hormone-deficient male rats. Ninety-six male Sprague⁻Dawley rats were randomly assigned to baseline, sham-operated (Sham), orchidectomised or chemically castrated groups. Chemical castration was achieved via subcutaneous injection of degarelix at 2 mg/kg. The orchidectomised and degarelix-castrated rats were then divided into negative control groups (ORX, DGX), testosterone-treated groups (intramuscular injection at 7 mg/kg weekly) (ORX + TES, DGX + TES), and EL-supplemented groups receiving daily oral gavages at doses of 25 mg/kg (ORX + EL25, DGX + EL25), 50 mg/kg (ORX + EL50, DGX + EL50), and 100 mg/kg (ORX + EL100, DGX + EL100). Following 10 weeks of treatment, the rats were euthanized and their blood and femora were collected. Bone biochemical markers, serum testosterone, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa β-ligand (RANKL) levels and histomorphometric indices were evaluated. Quassinoid-rich EL supplementation was found to reduce degenerative changes of trabecular structure by improving bone volume, trabecular number, and separation. A reduction in the percentage of osteoclast and increase in percentage of osteoblast on bone surface were also seen with EL supplementation. Dynamic histomorphometric analysis showed that the single-labeled surface was significantly decreased while the double-labeled surface was significantly increased with EL supplementations. There was a marginal but significant increase in serum testosterone levels in the ORX + EL25, DGX + EL50, and DGX + EL100 groups compared to their negative control groups. Quassinoid-rich EL extract was effective in reducing skeletal deteriorations in the androgen-deficient osteoporosis rat model.


Microemulsion-based gel of terbinafine for the treatment of onychomycosis: optimization of formulation using D-optimal design.
The aim of the present investigation was to evaluate microemulsion as a vehicle for dermal drug delivery and to develop microemulsion-based gel of terbinafine for the treatment of onychomycosis. D-optimal mixture experimental design was adopted to optimize the amount of oil (X(1)), Smix (mixture of surfactant and cosurfactant; X(2)) and water (X(3)) in the microemulsion. The formulations were assessed for globule size (in nanometers; Y(1)) and solubility of drug in microemulsion (in milligrams per milliliter; Y(2)). The microemulsion containing 5.75% oil, 53.75% surfactant-cosurfactant mixture and 40.5% water was selected as the optimized batch. The globule size and solubility of the optimized batch were 18.14 nm and 43.71 mg/ml, respectively. Transmission electron microscopy showed that globules were spherical in shape. Drug containing microemulsion was converted into gel employing 0.75% w/w carbopol 934P. The optimized gel showed better penetration and retention in the human cadaver skin as compared to the commercial cream. The cumulative amount of terbinafine permeated after 12 h was 244.65 ± 18.43 μg cm(-2) which was three times more than the selected commercial cream. Terbinafine microemulsion in the gel form showed better activity against Candida albicans and Trichophyton rubrum than the commercial cream. It was concluded that drug-loaded gel could be a promising formulation for effective treatment of onychomycosis.


Validation of a method for measuring sperm quality and quantity in reproductive toxicity tests with pair-breeding male fathead minnows (Pimephales promelas).
The fathead minnow (Pimephales promelas) is an OECD-proposed test species routinely used in reproductive toxicity trials with suspected endocrine-disrupting compounds (EDCs). The basic fecundity, endocrinology, and histopathology of reproductively active male and female fathead minnows has been well characterized, but there are few studies of the utility of male sperm concentration and motility as endpoints for use in reproductive trials. The purpose of this study was to (1) characterize the baseline sperm concentration and motility of pair-breeding male fathead minnows over their spawning cycle and (2) determine whether a repeated and nondestructive sperm sampling protocol would influence the baseline fecundity of the fish. Pair-breeding male fathead minnows that underwent sampling for milt three times a week for 4 weeks exhibited no significant changes in milt volume, sperm concentration, or motility parameters up to 6 days after each spawning event. The repeated sperm sampling procedure did, however, cause a significant lowering of spawning frequencies, although this decline did not correlate with effects on fecundity as there were no significant changes in the mean total numbers of eggs laid, fertilization, and hatching successes. This study confirmed the presence of a stable background of sperm concentration and motility parameters of pair-breeding male fathead minnows under reference conditions. The absence of any inherent "cycling" in the magnitude of these parameters over the spawning period suggests that sperm concentration and motility could be useful measures of male reproductive toxicity at the termination of tests in which pair-breeding males are at varying days post spawn.


Novel HDAC inhibitors with radiosensitizing properties.
The members of the histone deacetylase (HDAC) family play important roles in various cellular processes, including transcriptional regulation, cell proliferation, differentiation and apoptosis. Inhibitors of histone deacetylases are emerging as an important new class of chemotherapeutic agents. As such, identifying stable and potent chemical HDAC inhibitory compounds is an important focus for translational research. Here we report the results of a rational drug design of novel HDAC inhibitors with potential for sensitizing cancer cells to radiation therapy. Over 60 HDAC inhibitor analogues incorporating a urea backbone and the hydroxamic acid end moiety were designed and screened. Six were found to confer 50% inhibition of HDAC enzyme activity at nanomolar concentrations. These candidate HDAC inhibitors inhibited cell proliferation at the ranges of IC50 10-50 microM in various cancer cells, including prostate (PC-3), breast (MCF-7) and head and neck squamous carcinoma (SQ-20B). Furthermore, radiation clonogenic survival assays revealed that these compounds possess radiosensitizing properties that are cell type-specific. The data support the further investigation of these HDAC inhibitors for use as sensitizing agents with potential for clinical application.


Effect of a specific iron chelating agent on animal models of inflammation.
Iron is an important catalyst of oxidative radical reactions and promotes the formation of the hydroxyl radical from the superoxide anion radical and hydrogen peroxide. The stimulatory effect of the hydroxyl radical on lipid peroxidation prompted the speculation that free iron may directly promote inflammation and that iron chelating agents may have useful anti-inflammatory properties. This hypothesis is tested in animal models of inflammation with a specific iron chelating agent, desferrioxamine. At low doses (6 . 6 mg/kg) intraperitoneal desferrioxamine stimulated the induction of acute foot pad swelling in rats by monosodium urate but at higher doses (above 200 mg/kg) it suppressed this inflammatory reaction. A similar anti-inflammatory effect was observed in carrageenan-induced foot pad swelling. In guinea-pigs in which a Glynn-Dumonde synovitis was induced with bovine gammaglobulin, desferrioxamine (100 mg/kg) stimulated the acute inflammatory induction phase of this chronic allergic monoarthritis model. Repeated administration of desferrioxamine (100 mg/kg) from the seventh to the twelfth day after intra-articular challenge with bovine gammaglobulin markedly depressed the chronic inflammatory phase. In-vitro experiments suggest that desferrioxamine inhibits iron-catalysed lipid peroxidation when it is poorly saturated with iron, but loses this effect when it is iron saturated. Such an effect may explain our results with desferrioxamine in the animal studies and suggests that effective iron chelation and its removal may modify the inflammatory process in man.


Characterization of the changes in eicosanoid profiles of activated macrophages treated with 20(S)-ginsenoside Rg3.
In this study, we used ultra-performance liquid chromatography coupled with tandem mass spectrometry to assess the levels of eicosanoids from RAW264.7 macrophages treated with lipopolysaccharides (LPS) and 20(S)-ginsenoside Rg3 (Rg3). The production of nitric oxide (NO) and the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were increased in inflammatory macrophages treated with LPS. Rg3 treatment, however, decreased the levels of NO, TNF-α, and IL-6 in activated macrophages. Eicosanoids, known as major metabolites correlated with inflammation, have pro- or anti-inflammatory activities. For a detailed characterization of the eicosanoids altered by treatment with LPS and Rg3, the eicosanoids were profiled by multiple reaction monitoring. A total of 69 macrophage eicosanoids were analyzed and the profiling dataset was statistically analyzed. Principal component and hierarchical cluster analyses differentiated control cells from cells treated with LPS, Rg3, or LPS+Rg3 for 12 or 24h. Furthermore, 18 differentially regulated eicosanoids were found between macrophages treated with LPS for 24h and those treated with LPS+Rg3 for 24h (fold change>2, p value<0.05). These results indicate that Rg3 alters eicosanoid metabolism in activated macrophages treated with LPS. Furthermore, we also identified several eicosanoids correlated with the anti-inflammatory activity of Rg3.


National Institutes of Health Funding for Tobacco Versus Harm From Tobacco.
Previously, the author documented that, even though tobacco-related diseases accounted for 20% of US deaths, in 1995 the National Institutes of Health (NIH) expended only 1.1% of its budget on tobacco research. The current analysis is a replication test of this result and adds other outcomes and comparisons. The author obtained NIH funding information for tobacco, alcohol, and drug use and for obesity for each year between 2007 and 2014 from Project Reporter and compared these to the total NIH budget and to measures of disease burden. NIH allocated $321 million for tobacco research in 2014. The percent of the NIH budget dedicated to tobacco was 1.3% in 2014 and has not changed since 1995; similar rates for alcohol, drug, and obesity problems in 2014 were 1.8%, 3.3%, and 3.8%. The ratio of spending to mortality from a risk factor was substantially less for tobacco compared to alcohol or obesity problems (0.07 vs. 0.60 and 0.30). These results replicate our earlier findings. Tobacco research continues to be underfunded at the NIH compared to its disease burden in the United States and to NIH funding for other behavioral risk factors.


Colon cancer secreted protein-2 (CCSP-2), a novel candidate serological marker of colon neoplasia.
Cancers of the colon and rectum are the second leading cause of cancer death among adult Americans. When detected at early stages, colon cancer is highly curable. Colonoscopy, an effective but invasive screening test, has been limited in its public acceptance. The goal of this study was to identify novel serum markers of colon cancers and precancerous colon adenomas as potential candidates for noninvasive detection of early colon neoplasms. Employing expression microarrays, we identified colon cancer secreted protein-2 (CCSP-2) as a novel transcript whose expression is generally absent in normal colon and other normal body tissues, but that is induced an average of 78-fold in Stage II, III, and IV colon cancers, as well as in colon adenomas and colon cancer cell lines. These findings were validated by real-time PCR analysis in an independent panel of colon cancer cases. Moreover, CCSP-2 was shown to encode a secreted protein that circulates stably and is detectable in the blood of mice bearing human cancer xenografts transfected with epitope-tagged CCSP-2. As a novel secreted protein that is markedly induced in colon adenomas and cancers, CCSP-2 is a novel candidate for development as a diagnostic serum marker of early stage colon cancer.


Representation of vestibular afferents in somatosensory thalamic nuclei of the squirrel monkey (Saimiri sciureus).
1. In awake squirrel monkeys the thalamus was investigated for neuronal responses to vestibular, auditory, visual, proprioceptive, and exteroceptive somatosensory stimulation. The vestibular representation in the thalamus was focused.2. Units responding to electrical vestibular stimulation were found to be scattered within thalamic nuclei receiving somatosensory afferents.3. Ventrobasal neurons have previously been considered place and modality specific. The present data suggest exceptions to this belief. Vestibular input converges with somatotopically organized proprioceptive afferents on neurons in the nucleus ventralis posterior lateralis, pars oralis (identical to nucleus ventralis intermedius), as well as in the posterior portion of the caudal part of the same nucleus. Convergence of both modalities was also found in other nuclei, mainly belonging to the posterior nuclear group, where auditory convergence was also demonstrated.4. Of the vestibular cells in the nucleus ventralis posterior lateralis, 23% projected to the sensorimotor cortex, some with collaterals to both pre- and postcentral gyri.


Synovial sarcoma of the vulva: a case report.
Contrary to its name, synovial sarcoma does not arise from the synovial membrane but from multipotent stem cells and can present in any part of the body. Very few cases of vulval synovial sarcoma have been reported in the literature; we report on such a presentation. These tumors can present as painless lumps, which must be completely excised to give the best prognosis. Therefore the diagnosis of synovial sarcoma should always be kept in mind in the management of vulval masses, especially in young patients. We report the case of a 28-year-old Caucasian woman with synovial sarcoma of the vulva. Complete excision was possible in this case. We have presented a rare case of synovial sarcoma of the vulva, which can be easily confused with lipoma of the vulva. The management of this tumor requires referral to a cancer centre, with a multidisciplinary approach.


Lymphoscintigraphy for malignant melanoma. Surgical considerations.
Lymphoscintigraphy using technetium-99m atimony sulfur colloid was performed in 22 patients with melanoma referred to Duke University Comprehensive Cancer Center in an attempt to identify patterns of regional lymphatic drainage. Scans from six patients revealed lower extremity lesions with three located below the knee, one in the popliteal space, and two others proximal to the knee joint. Despite the location of the primary, all scans but one showed initial drainage to the inguinal nodes bypassing the popliteal lymph node group. Of the three patients who had primary melanoma of the posterior scalp, the lymphatic drainage was directed to the posterior cervical nodes. No drainage to the parotid nodes or anterior neck nodes was visualized. The knowledge gained from lymphoscintigraphy resulted in posterior neck dissections instead of the standard anterior neck dissection and superficial parotidectomy. In areas of ambiguous lymphatic drainage from the trunk, radiocolloid scanning can identify areas at risk for developing metastatic disease. Six lesions within 5 cm of the midline demonstrated bilateral axillary or groin drainage in 83 per cent of the patients. For two lesions near Sappey's line colloidal uptake to the ipsilateral axilla and groin was the rule. After a 3-year follow-up, during which time 70 to 90 per cent of lymph node metastases are predicted to occur, no nodal metastases were ever documented in areas that did not show colloidal uptake. No correlation was found between amount of radiolabel in positive compared to negative nodes, although those nodes that were completely replaced by tumor contained no 99mTc activity and were negative on scanning.(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic dissection of Striga hermonthica (Del.) Benth. resistance via genome-wide association and genomic prediction in tropical maize germplasm.
Genome-wide association revealed that resistance to Striga hermonthica is influenced by multiple genomic regions with moderate effects. It is possible to increase genetic gains from selection for Striga resistance using genomic prediction. Striga hermonthica (Del.) Benth., commonly known as the purple witchweed or giant witchweed, is a serious problem for maize-dependent smallholder farmers in sub-Saharan Africa. Breeding for Striga resistance in maize is complicated due to limited genetic variation, complexity of resistance and challenges with phenotyping. This study was conducted to (i) evaluate a set of diverse tropical maize lines for their responses to Striga under artificial infestation in three environments in Kenya; (ii) detect quantitative trait loci associated with Striga resistance through genome-wide association study (GWAS); and (iii) evaluate the effectiveness of genomic prediction (GP) of Striga-related traits. An association mapping panel of 380 inbred lines was evaluated in three environments under artificial Striga infestation in replicated trials and genotyped with 278,810 single-nucleotide polymorphism (SNP) markers. Genotypic and genotype x environment variations were significant for measured traits associated with Striga resistance. Heritability estimates were moderate (0.42) to high (0.92) for measured traits. GWAS revealed 57 SNPs significantly associated with Striga resistance indicator traits and grain yield (GY) under artificial Striga infestation with low to moderate effect. A set of 32 candidate genes physically near the significant SNPs with roles in plant defense against biotic stresses were identified. GP with different cross-validations revealed that prediction of performance of lines in new environments is better than prediction of performance of new lines for all traits. Predictions across environments revealed high accuracy for all the traits, while inclusion of GWAS-detected SNPs led to slight increase in the accuracy. The item-based collaborative filtering approach that incorporates related traits evaluated in different environments to predict GY and Striga-related traits outperformed GP for Striga resistance indicator traits. The results demonstrated the polygenic nature of resistance to S. hermonthica, and that implementation of GP in Striga resistance breeding could potentially aid in increasing genetic gain for this important trait.


Did You Hear That? Detecting Auditory Events with EEGNet.
The behavioural nature of pure-tone audiometry (PTA) limits those who can participate in the test, and therefore those who can access accurate hearing threshold measurements. Event Related Potentials (ERPs) from brain signals has shown limited utility on adult subjects, and a neural response that can consistently be identified as a result of pure-tone auditory stimulus has yet to be identified. The in doing so challenge is worsened by the nature of PTA, where stimulus amplitude decrease to a patient's lower threshold of hearing. We investigate whether EEGNet, a compact Convolutional Neural Network, could help in this domain. We trained EEGNet on a dataset collected whilst patients underwent a test designed to mimic a pure-tone audiogram, then assessed EEGNet performance in the detection task. For comparison, we also trained Support Vector Machines (SVMs) and Common Spatial Patterns + Linear Discriminant Analysis (CSPLDA) on the same task, with the same training paradigms. The results show that EEGNet is capable of detecting hearing events with 81.5% accuracy on unseen participants, outperforming SVMs by just over 5%. Whilst EEGNet outperformed SVMs and CSPLDA, it did not, however, always show a statistically significant improvement. Further analysis of EEGNet predictions revealed that, with sufficient test repetition, EEGNet has the potential to accurately ascertain hearing thresholds. The implication of these results is for a brain-signal based hearing test for those with physical or mental disabilities that limit their participation in a PTA. While this research is promising, future research will be needed to address the complexity of test setup, the duration of testing, and to further improve accuracy.


HSF1 is required for extra-embryonic development, postnatal growth and protection during inflammatory responses in mice.
HSF1 is the major heat shock transcriptional factor that binds heat shock element (HSE) in the promoter of heat shock proteins (Hsps) and controls rapid Hsp induction in cells subjected to various environmental stresses. Although at least four members of the vertebrate HSF family have been described, details of their individual physiological roles remain relatively obscure. To assess whether HSF1 exhibited redundant or unique in vivo functions, we created Hsf1(-/-) deficient mice. We demonstrate that homozygous Hsf1(-/-) mice can survive to adulthood but exhibit multiple phenotypes including: defects of the chorioallantoic placenta and prenatal lethality; growth retardation; female infertility; elimination of the 'classical' heat shock response; and exaggerated tumor necrosis factor alpha production resulting in increased mortality after endotoxin challenge. Because basal Hsp expression is not altered appreciably by the HSF1 null mutation, our findings suggest that this factor, like Drosophila Hsf protein, might be involved in regulating other important genes or signaling pathways. Our results establish direct causal effects for the HSF1 transactivator in regulating critical physiological events during extra-embryonic development and under pathological conditions such as sepsis to modulate pro-inflammatory responses, indicating that these pathways have clinical importance as therapeutic targets in humans.


Prevalence of Asthma in School Children on the Arizona-Sonora Border.
Mexican-born children living in the United States have a lower prevalence of asthma than other US children. Although children of Mexican descent near the Arizona (AZ)-Sonora border are genetically similar, differences in environmental exposures might result in differences in asthma prevalence across this region. The objective of this study was to determine if the prevalence of asthma and wheeze in these children varies across the AZ-Sonora border. The International Study of Asthma and Allergy in Children written and video questionnaires were administered to 1753 adolescents from 5 middle schools: Tucson (school A), Nogales, AZ (schools B, C), and Nogales, Sonora, Mexico (schools D, E). The prevalence of asthma and symptoms was compared, with analyses in the AZ schools limited to self-identified Mexican American students. Compared with the Sonoran reference school E, the adjusted odds ratio (OR) for asthma was significantly higher in US schools A (OR 4.89, 95% confidence interval [CI] 2.72-8.80), B (OR 3.47, 95% CI 1.88-6.42), and C (OR 4.12, 95% CI 1.78-9.60). The adjusted OR for wheeze in the past year was significantly higher in schools A (OR 2.19, 95% CI 1.20-4.01) and B (OR 2.67, 95% CI 1.42-5.01) on the written questionnaire and significantly higher in A (OR 2.13, 95% CI 1.22-3.75), B (OR 1.95, 95% CI 1.07-3.53), and Sonoran school D (OR 2.34, 95% CI 1.28-4.30) on the video questionnaire compared with school E. Asthma and wheeze prevalence differed significantly between schools and was higher in the United States. Environmental factors that may account for these differences could provide insight into mechanisms of protection from asthma.


Imaging features of CNS involvement in AIDS.
Patients with acquired immunodeficiency syndrome (AIDS) are the subjects of a large part of routine neuroradiological work in the Western world currently. The World Health Organization announced that Turkish authorities had reported a cumulative total of 2544 HIV cases from 1985 to 2006, of whom 623 had developed AIDS and 140 had died. It is estimated that approximately one-third of AIDS patients develop neurological complications. The spectrum of diseases affecting the central nervous system (CNS) in AIDS patients comprises predominantly opportunistic infections and primary CNS lymphoma. Although to a lesser degree when compared with Western countries, the incidence of AIDS and related neurological diseases are on the rise also in Turkey. Therefore radiologists should recognize HIV-associated problems and their imaging features. In this review, we focus on imaging features of more common CNS diseases in HIV-seropositive patients. This essay has been prepared using radiological studies of the patients who had been managed in our hospital which is a tertiary care center with a highly motivated medical team for this peculiar disease in the years between 2002 and 2008.


Social functioning after traumatic brain injury.
To determine the relationship between adult-onset traumatic brain injury (TBI) and social functioning including employment, social relationships, independent living, recreation, functional status, and quality of life 6 months or longer after injury. Not applicable. Systematic review of the published, peer-reviewed literature. Not applicable. Fourteen primary and 25 secondary studies were identified that allowed comparison to controls for adults who were at least 6 months post-TBI. TBI decreases the probability of employment after injury in those who were workers before their injury, lengthens the timing of their return if they do return to work, and decreases the likelihood that they will return to the same position. Those with moderate and severe TBI are clearly affected, but there was insufficient evidence of a relationship between unemployment and mild TBI. Penetrating head injury sustained in wartime is clearly associated with increased unemployment. TBI also adversely affects leisure and recreation, social relationships, functional status, quality of life, and independent living. Although there is a dose-response relationship between severity of injury and social outcomes, there is insufficient evidence to determine at what level of severity the adverse effects are demonstrated. TBI clearly has adverse effects on social functioning for adults. While some consequences might arise from injuries to other parts of the body, those with moderate to severe TBI have more impaired functioning than do those with other injuries alone.


Density-dependent habitat selection of spawning Chinook salmon: broad-scale evidence and implications.
An extensive body of theory suggests that density-dependent habitat selection drives many fundamental ecological processes. The ideal free distribution and the ideal despotic distribution make contrasting predictions about the effect of total population size on relative abundances among habitats. Empirical assessment of these habitat selection models is uncommon because data must be collected over large temporal and spatial scales. I ask whether fluctuation in Chinook salmon (Oncorhynchus tshawytscha) spawner population size through time leads to different relative densities over space. Twenty-six years of monitoring data on spawning Chinook salmon across the entire coast of Oregon, USA, were used to evaluate models that make contrasting statements about the interactions of a latent population abundance parameter with physical habitat characteristics. There is strong information-theoretic support for models that include terms that allow the spatial variation in density to change as population size changes through time. Analysis of the best model reveals nonlinear isodars, which suggests a 'despotic' or 'preemptive' distribution of individuals across habitats, indicating that dominant or early-arriving individuals exclude others from breeding sites. This finding has implications for genetic dynamics, population dynamics and conservation metrics of these highly valued fish. The novel application of modelling techniques used here to assess mechanisms of habitat selection from observational data can be used in the emerging field of eco-evolutionary dynamics.


Vascular tumors simulating occlusive disease.
Two cases of vascular tumors of large vessels with intraluminal growth simulating venous thrombosis and arterial occlusive disease are reported. One was a borderline malignant epithelioid hemangioendothelioma of the femoral vein and the other a malignant epithelioid angiosarcoma of the carotid artery. Immunohistochemical studies permitted to classify the tumors. Treatment consisted in surgical resection. No recurrence and no metastasis are noted at 24 months. Uncertainty regarding biological behaviour of vascular tumors and treatment persists.


[Triglyceride lipase activity and fatty acid transport in physical endurance in rats adapted to the muscular activity].
Aerobic training led to enhancement of lipase activity in type IIA type muscles. Still more obvious changes were found in rats trained to aerobic swimming with maximal intensity. In latter activity, a rise of the fatty acid-binding protein (FABP) was revealed in types I and IIA skeletal muscles. These adaptive changes led to enhancement of lipid metabolism. It was also shown that the FABP content decreased after physical exercise more obviously in the trained animals due, probably, to their substance turnover enhancement.


Msb4p, a protein involved in Cdc42p-dependent organization of the actin cytoskeleton, is a Ypt/Rab-specific GAP.
Ypt/Rab proteins of the Ras superfamily are regulators of protein transport in exo- and endocytosis. Like Ras and Rho proteins, they have a slow intrinsic GTPase activity that can be accelerated by several orders of magnitude by GTPase-activating proteins (GAP). Here we describe a new member of a family of Ypt/Rab-specific GAPs, Msb4p/Gyp4p, that shares with other Gyp family members significant homology in the catalytic domain, recently identified in Gyp1p and Gyp7p. Purified Msb4p/Gyp4p acts primarily on Sec4p, Ypt6p and Ypt7p and might have a role in polarized secretion.


Inter-laboratory variation in DNA damage using a standard comet assay protocol.
There are substantial inter-laboratory variations in the levels of DNA damage measured by the comet assay. The aim of this study was to investigate whether adherence to a standard comet assay protocol would reduce inter-laboratory variation in reported values of DNA damage. Fourteen laboratories determined the baseline level of DNA strand breaks (SBs)/alkaline labile sites and formamidopyrimidine DNA glycosylase (FPG)-sensitive sites in coded samples of mononuclear blood cells (MNBCs) from healthy volunteers. There were technical problems in seven laboratories in adopting the standard protocol, which were not related to the level of experience. Therefore, the inter-laboratory variation in DNA damage was only analysed using the results from laboratories that had obtained complete data with the standard comet assay protocol. This analysis showed that the differences between reported levels of DNA SBs/alkaline labile sites in MNBCs were not reduced by applying the standard assay protocol as compared with the laboratory's own protocol. There was large inter-laboratory variation in FPG-sensitive sites by the laboratory-specific protocol and the variation was reduced when the samples were analysed by the standard protocol. The SBs and FPG-sensitive sites were measured in the same experiment, indicating that the large spread in the latter lesions was the main reason for the reduced inter-laboratory variation. However, it remains worrying that half of the participating laboratories obtained poor results using the standard procedure. This study indicates that future comet assay validation trials should take steps to evaluate the implementation of standard procedures in participating laboratories.


Music intervention to relieve anxiety and pain in adults undergoing cardiac surgery: a systematic review and meta-analysis.
Previous studies have reported beneficial effects of perioperative music on patients' anxiety and pain. We performed a systematic review and meta-analysis of randomised controlled trials investigating music interventions in cardiac surgery. Five electronic databases were systematically searched. Primary outcomes were patients' postoperative anxiety and pain. Secondary outcomes were hospital length of stay, opioid use, vital parameters and time on mechanical ventilation. PRISMA guidelines were followed and PROSPERO database registration was completed (CRD42020149733). A meta-analysis was performed using random effects models and pooled standardised mean differences (SMD) with 95% confidence intervals were calculated. Twenty studies were included for qualitative analysis (1169 patients) and 16 (987 patients) for meta-analysis. The first postoperative music session was associated with significantly reduced postoperative anxiety (SMD = -0.50 (95% CI -0.67 to -0.32), p<0.01) and pain (SMD = -0.51 (95% CI -0.84 to -0.19), p<0.01). This is equal to a reduction of 4.00 points (95% CI 2.56 to 5.36) and 1.05 points (95% CI 0.67 to 1.41) on the State-Trait Anxiety Inventory and Visual Analogue Scale (VAS)/Numeric Rating Scale (NRS), respectively, for anxiety, and 1.26 points (95% CI 0.47 to 2.07) on the VAS/NRS for pain. Multiple days of music intervention reduced anxiety until 8 days postoperatively (SMD = -0.39 (95% CI -0.64 to -0.15), p<0.01). Offering recorded music is associated with a significant reduction in postoperative anxiety and pain in cardiac surgery. Unlike pharmacological interventions, music is without side effects so is promising in this population.


Ion transport in the intestine.
In recent years, the field of intestinal physiology has witnessed significant progress in our understanding of the expression and function of ion transport proteins and their genes under physiological and pathophysiological conditions. This review will present some of these most recent advances in the small intestinal ion transport mechanisms. One of the new and exciting aspects of this field has been the integration of function and structure of several intestinal transport processes. This is well exemplified by the discussed intricacies of intestinal bicarbonate secretion as well as the role of scaffolding PDZ proteins interacting with several transporters. We also discuss some of the most recent data pointing to the role of ion transporters in the pathogenesis of inflammation-associated diarrhea and their potential role in the maintenance of epithelial integrity. Mouse models deficient in some of the key genes encoding ion transporters and their adapter proteins continue to provide important clues into intestinal transport processes. Several of the new in-vivo findings revise or complement past paradigms, many of which were derived from in-vitro approaches. New data on the interdependent functions of multiple transporters, as exemplified here by intestinal bicarbonate secretion, increase the complexity of the intestinal ion transport mechanisms and continue to contribute to a more integrated view of the transport phenomena in the gut. Data from patients and mouse models of intestinal inflammation also increase our understanding of the pathophysiology of inflammation-associated diarrhea.


[Comparative study of the antiviral activity of natural double-stranded RNAs in experimental tick-borne encephalitis].
A comparative study of the antiviral effect of interferon inducers from the group of natural double-stranded RNAs (yeast plasmid dsRNA, phage phi 6 and phage f2 dsRNAs was carried out on the model of experimental tick-borne encephalitis. The possibility of inducing up to 60% protection against 10 LD50 of TBE virus by prophylactic inoculation of interferon inducers alone was demonstrated. The therapeutic effect was observed only with yeast dsRNA (30% protection when the inducer was administered 4 hours after virus infection of mice). The prophylactic effect of inoculation of interferon inducers (yeast dsRNA and f2 dsRNA) to immune mice correlated with the protective effect of inducers alone. At the same time, the therapeutic effect of inoculation of yeast dsRNA to immune animals (4 hours after TBE virus, 40% protection) was more marked. In the therapeutic use of f2 dsRNA for pre-immunized animals a synergetic effect of the preparation was observed (56.7% protection in 4 hours and 26.7% protection 24 hours postinfection).


[Hindlimb antigravity muscles' reaction in male and female rats to the deficit of functional loading].
Histological and histomorphometric comparison of the antigravity muscles of rats of both sexes was performed following 30-d unloading of their hind limbs by head-down suspension. It was shown that growth rate of control males was higher as compared to control females. This is attributed to the synergic effects of somatotropin and testosterone on metabolism and growth of males and only somatotropin in females. Load deprivation of the hind limbs inhibited body mass gain in all animals; however, this inhibition was twice as great in males. Increase of the soleus and gastrocnemius in the control males in this experiment was slightly ahead of the muscle mass gain in the females. The histomorphometric investigation of the cross-section area of myofibers did not reveal differences between males and females either in the control or suspension. No difference was found in percent of various types of fibers in the control males and females. In the soleus of the suspended rats, a part of slow fibers had transformed into fast ones without any sex-related particularities. The conclusion was made that despite the significant difference in the hormonal profile, the reaction of males and females to insufficient weight loading of the antigravity muscles was alike.


Derivation and validation of automated electronic search strategies to identify pertinent risk factors for postoperative acute lung injury.
To develop and validate time-efficient automated electronic search strategies for identifying preoperative risk factors for postoperative acute lung injury. This secondary analysis of a prospective cohort study included 249 patients undergoing high-risk surgery between November 1, 2005, and August 31, 2006. Two independent data-extraction strategies were compared. The first strategy used a manual review of medical records and the second a Web-based query-building tool. Web-based searches were derived and refined in a derivation cohort of 83 patients and subsequently validated in an independent cohort of 166 patients. Agreement between the 2 search strategies was assessed with percent agreement and Cohen κ statistics. Cohen κ statistics ranged from 0.34 (95% confidence interval, 0.00-0.86) for amiodarone to 0.85 for cirrhosis (95% confidence interval, 0.57-1.00). Agreement between manual and automated electronic data extraction was almost complete for 3 variables (diabetes mellitus, cirrhosis, H(2)-receptor antagonists), substantial for 3 (chronic obstructive pulmonary disease, proton pump inhibitors, statins), moderate for gastroesophageal reflux disease, and fair for 2 variables (restrictive lung disease and amiodarone). Automated electronic queries outperformed manual data collection in terms of sensitivities (median, 100% [range, 77%-100%] vs median, 87% [range, 0%-100%]). The specificities were uniformly high (≥ 96%) for both search strategies. Automated electronic query building is an iterative process that ultimately results in accurate, highly efficient data extraction. These strategies may be useful for both clinicians and researchers when determining the risk of time-sensitive conditions such as postoperative acute lung injury.


Freezable and non-freezable water content of cataractous human lenses.
Twenty-nine cataractous human lenses between the ages of 36 and 93 were investigated. The total water content of cortex and nucleus were obtained by vacuum dehydration. The freezable water content was measured by differential scanning calorimetry. The non-freezable water content was obtained by difference. To measure the extent that syneresis contributes to cataract formation, an excess function was designed. The excess function represents the changes that occur, for example, in non-freezable water content due to cataractogenesis. It is calculated as the difference between the non-freezable water content of a normal lens and that of a cataractous lens of the same age. On the average, there is 7% less non-freezable water in the cortex of a cataractous lens than in the cortex of a normal lens. The corresponding number for the nucleus is 9%. This represents 29 and 36% changes, respectively, in the cortex and nucleus due to syneresis during cataractogenesis.


Identification of Late Embryogenesis Abundant (LEA) protein putative interactors using phage display.
Arabidopsis thaliana seeds without functional SEED MATURATION PROTEIN1 (SMP1), a boiling soluble protein predicted to be of intrinsic disorder, presumed to be a LATE EMBRYOGENESIS ABUNDANT (LEA) family protein based on sequence homology, do not enter secondary dormancy after 3 days at 40 °C. We hypothesized that SMP1 may protect a heat labile protein involved in the promotion of secondary dormancy. Recombinant SMP1 and GmPM28, its soybean (Glycine max), LEA4 homologue, protected the labile GLUCOSE-6-PHOSPHATE DEHYROGENASE enzyme from heat stress, as did a known protectant, Bovine Serum Albumin, whether the LEA protein was in solution or attached to the bottom of microtiter plates. Maintenance of a biological function for both recombinant LEA proteins when immobilized encouraged a biopanning approach to screen for potential protein interactors. Phage display with two Arabidopsis seed, T7 phage, cDNA libraries, normalized for transcripts present in the mature, dehydrated, 12-, 24-, or 36-h imbibed seeds, were used in biopans against recombinant SMP1 and GmPM28. Phage titer increased considerably over four rounds of biopanning for both LEA proteins, but not for BSA, at both 25 and at 41 °C, regardless of the library used. The prevalence of multiple, independent clones encoding portions of specific proteins repeatedly retrieved from different libraries, temperatures and baits, provides evidence suggesting these LEA proteins are discriminating which proteins they protect, a novel finding. The identification of putative LEA-interacting proteins provides targets for reverse genetic approaches to further dissect the induction of secondary dormancy in seeds in response to heat stress.


[Nursing care in ambulatory methadone programs. A comparative literature study between The Netherlands and The United States].
In this article, the results are discussed of a literature study on nursing care for heroin addicts in out-patient methadone maintenance clinics in the Netherlands and the United States. In the Netherlands, the most important aim of methadone maintenance is to limit the harm caused by heroin use. Community based methadone maintenance is the subject in several Dutch evaluation studies. Care is described in these studies, however the medical role is not distinguished from the nursing role and functions. Research variables are basic care assumptions and client satisfaction. In the USA, heroin misuse is considered a disease more than in the Netherlands. Nurses in the American methadone maintenance clinics have a more independent function compared with the nurses in the Netherlands. The main variables in the American studies on nursing care in the out-patient methadone maintenance clinics are the nursing process as well as the development and testing of nursing interventions. Further nursing research concerning the methadone maintenance clinics in the Netherlands is needed because the nursing contribution in maintaining and improving the basic health status of the heroin misuser is of vital importance. The American nursing research and the associated outcomes could be used as a guideline.


Some but not all benefits of intravenous immunoglobulin therapy after marrow transplantation appear to correlate with IgG trough levels.
Multiple benefits of intravenous immunoglobulin (IVIG) therapy after marrow transplantation have been reported, including decreased incidence of acute graft-versus-host disease (GVHD), infection, sepsis, cytomegalovirus (CMV) pneumonitis and platelet use. To test the hypothesis that the observed beneficial effects of IVIG are related to the serum IgG levels achieved, we followed IgG levels (pre-infusion, 1 h and 24 h post-infusion) in 45 consecutive marrow transplant recipients. IVIG 500 mg/kg was given weekly for six doses starting day -8 pre-transplant, then every other week for a total of 11 doses. Forty-one patients (22 allogeneic, 17 autologous, two syngeneic) were evaluable. Patients with acute GVHD had significantly lower serum IgG trough levels (less than 1200 mg/dl) noted at day +20 post-transplant and afterwards than patients without GVHD (greater than or equal to 1200 mg/dl). Pharmacokinetic modeling of the data indicates that IgG half-life between day -8 and day +6 may predict which recipients are at increased risk of acute GVHD. Allogeneic recipients in the group with trough levels less than 1200 mg/dl required more platelet transfusions. Although there was no significant difference in fungal infection rates or bacteremia, sepsis was noted in only two recipients (one allogeneic, one autologous), both with serum IgG trough levels less than 1200 mg/dl. In addition, three allogeneic recipients had cytomegalovirus pneumonitis, all in the group with lower IgG trough levels. Thus, while serum IgG trough levels less than 1200 mg/dl appear to be strongly associated with acute GVHD, low levels may also be associated with increased platelet utilization, with cytomegalovirus pneumonitis, and sepsis, but not with the overall incidence of infection.


Design of holographic structures using genetic algorithms.
We have developed a general technique using genetic algorithms to design photonic crystals to be fabricated by holographic lithography. In contrast to current analytical approaches that rely almost exclusively on symmetry considerations, this technique allows for high-fidelity approximations to real-space structures without limiting the search space to a prescribed set of symmetries. We have used this new technique to design a structure having a complete photonic band gap of 28%, the largest yet reported for holographic lithography.


Impact of the bidirectional relationship between communication and cognitive efficacy on orthopedic patient adherence behavior.
There is growing interest in patient autonomy, and communication between physicians and patients has become the essential cornerstone for improving the quality of healthcare services. Previous research has concentrated on the direct effect of physician-patient communication on service outcomes. In the present study, we examined the influence among constructs in the service process and the impact on healthcare outcomes. The present study used behavioral theory to expand the process aspect of the Donabedian healthcare service quality structure-process-outcome model to examine the impact of cognitive changes and communication feedback on patients' adherence behavior. In addition, the moderating effect of hospital facility levels is examined. A conceptual model was developed and tested using a questionnaire administered to patients in eight hospitals. A total of 397 respondents returned usable surveys, with a response rate of 92.11%. Structural equation modeling was used to analyze the data in two steps that involved a measurement model and a structural model. The former was applied to estimate the Cronbach's alphas, intercorrelations of factors, and descriptive statistics; the latter was used to test the hypothesized relationships of the constructs. The results identified three mediators of the healthcare process within the healthcare services framework: physician-patient communication, cognitive efficacy, and adherence behavior. Physician-patient communication influenced cognitive efficacy (β = 0.16, p < 0.001), and cognitive efficacy influenced physician-patient communication (β = 0.18, p < 0.001). The effect of this bidirectional relationship on adherence behavior was positive (β = 0.38, p < 0.001). The healthcare structure influenced healthcare outcomes via these three healthcare process constructs. The adherence behavior of patients who were treated in the medical center has greater influences by the structure and physician-patient communication than it was treated in the regional hospitals. This study revealed a complex pattern in relationships among process constructs for healthcare services. The findings of this study acknowledge the important potential interrelationships among the healthcare service constructs to improve the quality of healthcare outcomes. CRREC104107. Date: 22/01/2016. Prospectively Registered.


Benzodiazepines in the treatment of schizophrenia: a review and reappraisal.
Benzodiazepines, either alone or added to neuroleptics, have been studied extensively as treatments for schizophrenia, but no consensus regarding their efficacy has been reached. The authors review the double-blind trials in the literature and relate the findings to the neurobiology of benzodiazepine actions. The clinical review included all double-blind studies through 1989 that could be identified by means of Index Medicus and computer-assisted searches and by the cross-referencing of articles. The findings from the 14 studies of benzodiazepines used alone and the 16 studies of adjunctive therapy are presented separately. The studies reviewed suggest that 1) response is highly variable, and about one-third to one-half of patients improve; 2) benzodiazepines are potentially most useful as adjuncts to neuroleptics in the acute management of psychotic agitation, although actual antipsychotic effects have also been observed in some patients; 3) relatively higher doses of benzodiazepines may be associated with better response; and 4) therapeutic effects, when seen, develop rapidly but diminish after several weeks in some patients. The authors explore the neurobiological bases of benzodiazepine action, which presumably underlie their efficacy in schizophrenia and may help explain the variability of response. Future research on benzodiazepines in the treatment of schizophrenia should focus on features that predict response, the relation of dopamine or other neurotransmitter systems to therapeutic effects, the schizophrenic symptoms most amenable to benzodiazepine treatment, changes in neuroleptic dose during benzodiazepine augmentation, the role of benzodiazepines in maintenance therapy, and the optimal characteristics of benzodiazepine treatment.


pH-regulated anion antiport in nucleated mammalian cells.
The uptake of 36Cl- into cells was measured after preincubation in medium containing nigericin and KCl to allow control of the intracellular pH. When the pH was increased from pH 7.0 to pH 7.3 there was a 10-fold increase in the rate of 36Cl- uptake. The increase was half maximal at pH 7.15 in Vero and L-cells, whereas in phorbol 12-myristate 13-acetate-treated Vero cells the increase was half maximal at pH 6.9. Kinetic studies showed that in cells preincubated with nigericin and isotonic KCl, both at pH 7.0 and at pH 8.0, the Km for Cl- was 7 mM. In the two cases the Jmax was 1.7 X 10(8) Cl- ions X cell-1 X s-1 and 1.6 X 10(9) Cl- ions X cell-1 X s-1, respectively. Bicarbonate inhibited 36Cl- uptake with a Ki of 5-6 mM. Probably, the anion antiporter plays a role in the regulation of the intracellular pH.


JC virus early protein detection by immunohistochemistry in progressive multifocal leukoencephalopathy: a comparative study with in situ hybridization and polymerase chain reaction.
In situ hybridization (ISH) for JC virus (JCV) is generally applied for the diagnosis of progressive multifocal leukoencephalopathy (PML). To explore the usefulness of immunohistochemistry (IHC) for JCV early proteins, 14 paraffin-embedded postmortem brain specimens with histologic features compatible with PML were tested for the presence of JCV by means of DNA-DNA ISH with a biotinylated probe corresponding to the entire JCV genome, for JCV early proteins IHC with both PAb 2003 and anti-SV40 large T antigen monoclonal antibodies, and polymerase chain reaction (PCR) amplification of JCV virion protein 3 (VP3) and transcriptional control region (TCR) sequences. ISH was positive in 13 cases and IHC in all 14 cases, the number of IHC-positive cells generally being far in excess of ISH-positive cells. Of the 2 monoclonal antibodies used, PAb 2003 proved to be more sensitive than anti-SV40 large T antigen. Occasional neuronal nuclei were positive for JCV early proteins in 5 cases. As for PCR, VP3 was amplified in all 14 cases and TCR in 9 cases. Consequently, PAb 2003 IHC for JCV early proteins seems to be a powerful tool for viral demonstration in PML and may well become the diagnostic recourse of choice in this setting.


Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS): a randomised trial.
Extracranial carotid and vertebral artery dissection is an important cause of stroke, especially in young people. In some observational studies it has been associated with a high risk of recurrent stroke. Both antiplatelet drugs and anticoagulant drugs are used to reduce risk of stroke but whether one treatment strategy is more effective than the other is unknown. We compared their efficacy in the Cervical Artery Dissection in Stroke Study (CADISS), with the additional aim of establishing the true risk of recurrent stroke. We did this randomised trial at hospitals with specialised stroke or neurology services (39 in the UK and seven in Australia). We included patients with extracranial carotid and vertebral dissection with onset of symptoms within the past 7 days. Patients were randomly assigned (1:1) by an automated telephone randomisation service to receive antiplatelet drugs or anticoagulant drugs (specific treatment decided by the local clinician) for 3 months. Patients and clinicians were not masked to allocation, but investigators assessing endpoints were. The primary endpoint was ipsilateral stroke or death in the intention-to-treat population. The trial was registered with EUDract (2006-002827-18) and ISRN (CTN44555237). We enrolled 250 participants (118 carotid, 132 vertebral). Mean time to randomisation was 3·65 days (SD 1·91). The major presenting symptoms were stroke or transient ischaemic attack (n=224) and local symptoms (headache, neck pain, or Horner's syndrome; n=26). 126 participants were assigned to antiplatelet treatment versus 124 to anticoagulant treatment. Overall, four (2%) of 250 patients had stroke recurrence (all ipsilateral). Stroke or death occurred in three (2%) of 126 patients versus one (1%) of 124 (odds ratio [OR] 0·335, 95% CI 0·006-4·233; p=0·63). There were no deaths, but one major bleeding (subarachnoid haemorrhage) in the anticoagulant group. Central review of imaging failed to confirm dissection in 52 patients. Preplanned per-protocol analysis excluding these patients showed stroke or death in three (3%) of 101 patients in the antiplatelet group versus one (1%) of 96 patients in the anticoagulant group (OR 0·346, 95% CI 0·006-4·390; p=0·66). We found no difference in efficacy of antiplatelet and anticoagulant drugs at preventing stroke and death in patients with symptomatic carotid and vertebral artery dissection but stroke was rare in both groups, and much rarer than reported in some observational studies. Diagnosis of dissection was not confirmed after review in many cases, suggesting that radiographic criteria are not always correctly applied in routine clinical practice. Stroke Association.


[Multiple primary cancers of oral cavity and pharynx].
Multiple primary cancers were found in 23 of 68 patients (34%) with an index cancer in the oral cavity or pharyngeal area treated in our institute from June 1995 to July 1998. Four cases had triple primary cancers. All 68 cases underwent upper and lower gastrointestinal endoscopy as well as ultrasonography of the liver. Lung CT was performed in cases with abnormal findings on chest roentgenograms. Multiple cancers were found in 5 of 25 oral cavity cases (20%), 6 of 14 mesopharynx cases (43%) and 12 of 29 hypopharynx cases (41%). Nine of 23 cases (39%) were synchronous and 14 (61%) were metachronous. Eighteen of 27 (69%) secondary cancers occurred in the upper aerodigestive tract with an especially high incidence (22%) in the esophagus. Gastroendoscopy also revealed 7 neoplastic lesions, aside from cancers, with the total abnormal rate of 24% (24/68). Thus, gastroendoscopy is useful for the diagnosis of multiple primary cancers. The frequency of multiple primary cancers in males (33%) was not different from that in females (35%). The average age of multiple primary cancer patients (65.1 years) was a little higher than that of single cancer patient (62.7 years). Smoking or drinking was not related to the incidence of multiple cancers. The interval between the first and the second cancer in metachronous cancer cases was 25.5 months on average, and within 4 years in 71% (10/14) of the cases. This result suggests that close follow-up including endoscopy should be required for at least 4 years after treatment of oral or pharyngeal cancer. Radical treatment for each of the multiple cancer lesions was performed in 22 of 23 cases, and the mortality rate of multiple primary cancer cases was not significantly different from that of single cancer cases. Among 7 cases who died of disease, 5 cases died of distant metastasis, suggesting that control of distant metastasis is an important issue in the treatment of multiple primary cancers.


Identification of AglE, a second glycosyltransferase involved in N glycosylation of the Haloferax volcanii S-layer glycoprotein.
Archaea, like Eukarya and Bacteria, are able to N glycosylate select protein targets. However, in contrast to relatively advanced understanding of the eukaryal N glycosylation process and the information being amassed on the bacterial process, little is known of this posttranslational modification in Archaea. Toward remedying this situation, the present report continues ongoing efforts to identify components involved in the N glycosylation of the Haloferax volcanii S-layer glycoprotein. By combining gene deletion together with mass spectrometry, AglE, originally identified as a homologue of murine Dpm1, was shown to play a role in the addition of the 190-Da sugar subunit of the novel pentasaccharide decorating the S-layer glycoprotein. Topological analysis of an AglE-based chimeric reporter assigns AglE as an integral membrane protein, with its N terminus and putative active site facing the cytoplasm. These finding, therefore, contribute to the developing picture of the N glycosylation pathway in Archaea.


Metabolic syndrome before and after initiation of antiretroviral therapy in treatment-naive HIV-infected individuals.
Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease and diabetes, many of which are associated with HIV and antiretroviral therapy (ART). We examined prevalence and incidence of MetS and risk factors for MetS in ART-naive HIV-infected individuals starting ART. MetS, defined by the Adult Treatment Panel III criteria, was assessed at and after ART initiation in HIV-infected individuals who enrolled in selected AIDS Clinical Trials Group trials and were followed long-term after these trials as part of the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort. Cox proportional hazards models were used to examine risk factors of incident MetS. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CI) are reported. At ART initiation, the prevalence of MetS was 20%. After ART initiation, the incidence of MetS was 8.5 per 100 person-years. After adjusting for demographics and body mass index, the risk of MetS was decreased for CD4+ T-cell counts >50 cells per cubic millimeter (aHR = 0.62, 95% CI = 0.43 to 0.90 for CD4 >500), and the risk was increased for HIV-1 RNA >400 copies per milliliter (aHR = 1.55 (95% CI = 1.25 to 1.92) and use of a protease-inhibitor (PI)-based regimen [relative to no PI use, aHR = 1.25 (95% CI = 1.04 to 1.51) for any PI use]. In HIV-infected individuals on ART, virologic suppression and maintenance of high CD4+ T-cell counts may be potentially modifiable factors that can reduce the risk of MetS. The effect of MetS on the risk of cardiovascular disease and diabetes needs to be evaluated.


New Insights into Mechanical, Metabolic and Muscle Oxygenation Signals During and After High-Intensity Tethered Running.
High-intensity exercises including tethered efforts are commonly used in training programs for athletes, active and even sedentary individuals. Despite this, the knowledge about the external and internal load during and after this effort is scarce. Our study aimed to characterize the kinetics of mechanical and physiological responses in all-out 30 seconds (AO30) tethered running and up to 18 minutes of passive recovery. Additionally, in an innovative way, we investigated the muscle oxygenation in more or less active muscles (vastus lateralis and biceps brachii, respectively) during and after high-intensity tethered running by near-infrared spectroscopy - NIRS. Twelve physically active young men were submitted to AO30 on a non-motorized treadmill to determine the running force, velocity and power. We used wearable technologies to monitor the muscle oxygenation and heart rate responses during rest, exercise and passive recovery. Blood lactate concentration and arterial oxygen saturation were also measured. In a synchronized analysis by high capture frequency of mechanical and physiological signals, we advance the understanding of AO30 tethered running. Muscle oxygenation responses showed rapid adjustments (both, during and after AO30) in a tissue-dependence manner, with very low tissue saturation index observed in biceps brachii during exercise when compared to vastus lateralis. Significant correlations between peak and mean blood lactate with biceps brachii oxygenation indicate an important participation of less active muscle during and after high-intensity AO30 tethered running.


Comparison of Functional Ankle Motion Measures in Modern Dancers.
Ankle injuries are the most common lower extremity injury in dance and sports, often resulting in limitation of dorsiflexion or plantar flexion. Accurate assessment of any limitation in range of motion is an important factor in implementing effective preventative and rehabilitative regimens. Ankle range of motion has traditionally been quantified with goniometers. However, standard goniometry may not be an adequate method of assessing plantar flexion range of motion in dancers. An alternative technique using inclinometers to quantify ankle plantar flexion has been reported, but reliability and inter-instrument correlations for this method are limited. The dorsiflexion lunge distance method has been used to assess ankle dorsiflexion. Although shown to be reliable, this method has not been objectively correlated. The purpose of this study was to determine the most clinically appropriate tool for assessing functional ankle dorsiflexion and plantar flexion in dancers. The aims were to: 1. determine reliability of the weightbearing ankle dorsiflexion lunge method using inclinometer, goniometer, and distance; 2. assess the reliability of inclinometer and goniometer measurements of non-weightbearing active plantar flexion; 3. conduct inter-method and experienced versus novice rater correlations; and 4. determine if a relationship exists between dorsiflexion distance (cm) and dorsiflexion inclinometer angle (degrees) measurements. Twenty-six modern dancers (age: 20.2 ± 1.8 years) participated in the study. Four raters measured weightbearing dorsiflexion in a lunge position using a goniometer, two inclinometer placements, and a distance measurement. They also measured active ankle plantar flexion using an inclinometer placed on the anterior talonavicular joint and a goniometer placed at the lateral ankle. Intra- and inter-rater reliability and inter-method correlations were calculated with Intraclass Correlation Coefficients (ICC) and standard error of measurement (SEM). The relationship of dorsiflexion distance to angle was determined using grouped linear regression (p < 0.05). Dorsiflexion and plantar flexion intra- and inter-rater ICCs for inclinometer, goniometer, and distance ranged from 0.84 to 0.99. The SEM for angular measures ranged from 1° to 3°, and linear measures from 0.3 cm to 0.9 cm. Inter-method correlations ranged from 0.55 to 0.89. There were no differences between inclinometer and goniometer measurement dorsiflexion means. However, inclinometer plantar flexion values were greater than goniometric values (p < 0.001). Experienced raters recorded greater goniometric values compared to novice raters (p < 0.01). There was no consistent linear relationship between dorsiflexion lunge distance measure and inclinometer degrees. It is concluded that functional ankle DF in modern dancers is best quantified using an inclinometer (posterior placement) in the weightbearing lunge position. Non-weightbearing active ankle PF in modern dancers is best quantified with inclinometer placement on the dorsum of the foot. The distance method cannot be compared directly to angular measurement, is subject-specific, and cannot be used as a normative measure to compare DF range between subjects, populations, or age groups.


Maternal and neonatal outcomes in vacuum-assisted delivery with the Kiwi OmniCup and Malmström metal cup.
To evaluate the effects of different types of vacuum cups on maternal and neonatal outcomes following assisted vaginal delivery. A retrospective cohort study was undertaken of all vacuum-assisted deliveries performed over a period of 2 years. Patients were divided into two groups according to whether a Kiwi OmniCup (n = 230) or Malmström metal cup (n = 98) was used. Maternal outcomes included maternal genital tract injury and total blood loss. Neonatal outcomes included Apgar score, umbilical cord blood gases, neonatal scalp injury and time spent in the neonatal unit. Maternal or neonatal outcomes and failure rates did not differ between the two groups, however, the duration of the procedure and the fundal pressure maneuver was more frequent in the Malmström group. The results of this study suggest that the Kiwi OmniCup and Malmström metal cup vacuum extractors are safe and functionally effective for vacuum-assisted delivery.


Serum Oncomarkers in Patients with MPO-ANCA-Positive Vasculitis: Diagnostic and Prognostic Predictive Values for Interstitial Lung Disease.
To explore in myeloperoxidase-antineutrophil cytoplasmic autoantibody-associated vasculitis (MPO-AAV) the value of circulating oncomarkers in identifying interstitial lung disease (ILD) and predicting prognosis. Newly diagnosed MPO-AAV patients were evaluated retrospectively at a single center. The serum levels of carbohydrate antigen (CA) 19-9, CA125, cytokeratin fraction 21-1 (CYFRA21-1), carcinoembryonic antigen, squamous cell carcinoma antigen, and neuron-specific enolase were compared between patients with and without ILD. The strength of the oncomarkers in identifying ILD was assessed through logistic regression and receiver operating characteristic (ROC) curves. Correlation analysis was applied to detect the associations between oncomarkers and ILD severity. The significance of serum oncomarkers as prognosis predictors for MPO-AAV associated ILD was evaluated by survival analysis. 169 MPO-AAV patients were included and ILD was found in 101 patients. Serum CA125, CA19-9, and CYFRA21-1 were significantly higher in patients with ILD than those without ILD. The area under the ROC curve of CA19-9, CA125, and CYFRA21-1 for identifying ILD was 0.701, 0.660, and 0.711, respectively. A specificity of 98.5% for diagnosing ILD was found for CA19-9 at the recommended normal level. CA19-9 was positively correlated with HRCT fibrosis score (r = 0.498, p < 0.001) and CYFRA21-1 was correlated with ground-glass score (r = 0.316, p = 0.002). Both CA19-9 and CYFRA21-1 were independent risk factors for all-cause mortality in patients with ILD. Serum CA19-9 and CYFRA21-1 might be useful markers in the diagnosis, disease severity evaluation, and prognosis prediction of MPO-AAV-associated ILD.


Chromosome abnormalities in congenital heart disease.
Refinements in cytogenetic techniques have promoted progress in understanding the role that chromosome abnormalities play in the cause of congenital heart disease. To determine if mutations at specific loci cause congenital heart disease, irrespective of the presence of other defects, and to estimate the prevalence of chromosome abnormalities in selected conotruncal cardiac defects, we reviewed retrospectively cytogenetic and clinical databases at St. Louis Children's Hospital. Patients with known 7q11.23 deletion (Williams syndrome), Ullrich-Turner syndrome (UTS), and most autosomal trisomies were excluded from this analysis. Two groups of patients were studied. Over a 6.5-year period, 57 patients with chromosomal abnormalities and congenital heart disease were identified. Of these, 37 had 22q11 deletions; 5 had abnormalities of 8p; and 15 had several other chromosome abnormalities. The prevalence of chromosome abnormalities in selected conotruncal or aortic arch defects was estimated by analysis of a subgroup of patients from a recent 22-month period. Chromosome abnormalities were present in 12% of patients with tetralogy of Fallot, 26% in tetralogy of Fallot/pulmonary atresia, 44% in interrupted aortic arch, 12% in truncus arteriosus, 5% in double outlet right ventricle, and 60% in absent pulmonary valve. We conclude that chromosome analysis should be considered in patients with certain cardiac defects. Specifically, fluorescent in situ hybridization (FISH) analysis of 22q11 is indicated in patients with conotruncal defects or interrupted aortic arch. High resolution analysis should include careful evaluation of the 8p region in patients with either conotruncal or endocardial cushion defects.


Damage-Resistant Composites Using Electrospun Nanofibers: A Multiscale Analysis of the Toughening Mechanisms.
Today, fiber-reinforced polymer composites are a standard material in applications where a high stiffness and strength are required at minimal weight, such as aerospace structures, ultralight vehicles, or even flywheels for highly efficient power storage systems. Although fiber-reinforced polymer composites show many advantages compared to other materials, delamination between reinforcing plies remains a major problem limiting further breakthrough. Traditional solutions that have been proposed to toughen the interlaminar region between reinforcing plies have already reached their limit or have important disadvantages such as a high cost or the need for adapted production processes. Recently, electrospun nanofibers have been suggested as a more viable interlaminar toughening method. Although the expected benefits are numerous, the research on composite laminates enhanced with electrospun nanofibrous veils is still very limited. The work that has been done so far is almost exclusively focused on interlaminar fracture toughness tests with different kinds of nanofibers, where typically a trial and error approach has been used. A thorough understanding of the micromechanical fracture mechanisms and the parameters to obtain toughened composites has not been reported as of yet, but it is crucial to advance the research and design highly damage-resistant composites. This article provides such insight by analyzing the nanofiber toughening effect on three different levels for several nanofiber types. Only by combining the results from different levels, a thorough understanding can be obtained. These levels correspond to the hierarchical nature of a composite: the laminate, the interlaminar region, and the matrix resin. It is found that each level corresponds to certain mechanisms that result in a toughening effect. The bridging of microcracks by electrospun nanofibers is the main toughening mechanism resulting in damage resistance. Nevertheless, the way in which the nanofiber bridging mechanism expresses itself is different for each scale and dependent on parameters linked to a certain scale. The multiscale analysis of the toughening mechanisms reported in this paper is therefore crucial for understanding the behavior of nanofiber toughened composites, and as such allows for designing novel, damage-resistant, nanofiber-toughened materials.


Increment of growth factors in mouse skin treated with non-thermal plasma.
Non-thermal plasma (NTP) has several beneficial effects, and can be applied as a novel instrument for skin treatment. Recently, many types of NTP have been developed for potential medical or clinical applications, but their direct effects on skin activation remain unclear. In this study, the effect of NTP on the alteration of mouse skin tissue was analyzed. After NTP treatment, there were no signs of tissue damage in mouse skin, whereas significant increases in epidermal thickness and dermal collagen density were detected. Furthermore, treatment with NTP increased the expression of various growth factors, including TGF-α, TGF-β, VEGF, GM-CSF, and EGF, in skin tissue. Therefore, NTP treatment on skin induces the expression of growth factors without causing damage, a phenomenon that might be directly linked to epidermal expansion and dermal tissue remodeling.


In vitro inhibition of negative strand virus transcriptase activity by proteins soluble in acidic chloroform-methanol.
The effect of proteins soluble in acidic chloroform-methanol (ACMS proteins) on the transcriptase activity of virus ribonucleoproteins (RNPs) in vitro has been studied. Experiments with ACMS membrane (M) proteins from type A and B orthomyxoviruses, as well as from vesicular stomatitis virus, showed that inhibition of the viral RNP transcriptase activity occurred when they interacted with M proteins isolated from viruses of a different serotype, or even of a different family. The presence of ACMS proteins capable of inhibiting the transcriptase activity of orthomyxovirus RNP in vitro was also detected in human blood plasma and among proteins produced by human leukocytes. Determination of the minimum concentration of M protein inhibiting the RNP transcriptase activity, and analysis of the fowl plague virus M protein-RNP complex formed in the in vitro system, showed that the M protein was capable of inhibiting RNP transcriptase activity at a M:RNP ratio of 0.1 to 0.2:1.


Depth profiling of photothermal compound concentrations using phase sensitive optical coherence tomography.
A model that describes the concentration of photothermal (light-to-heat converters) compounds as a function of depth in a turbid medium is developed. The system consists of a pump laser (808 nm modulated at 400 Hz), which heats a photothermal compound, and a phase sensitive spectral domain optical coherence tomography system, which detects the changes in the optical path length of the sample induced by the temperature increase. The model is theoretically derived and the coefficients are empirically determined using solid homogeneous gel phantoms. The model is validated by reconstructing the concentration of a photothermal compound in thick single and double layer solid phantoms.


Unlocking the full potential of citric acid-synthesized carbon dots as a supercapacitor electrode material via surface functionalization.
This research paper investigates the effect of functionalizing the surfaces of citric acid-synthesized carbon dots (CDs) with hyperbranched bis(methylol)propionic acid (bis-MPA) polyester hydroxyl polymers (HBPs) on their performance as electrode materials in a supercapacitor. Two types of HBPs with 16 and 64 peripheral hydroxyl groups were used to functionalize the CDs' oxygen-enriched surface. Here, CDs were used as electrode materials for the first time in symmetric supercapacitors without a composite material, and how surface modification affects the capacitance performance of CDs was investigated. Our results showed that the functionalization of green-emitting CDs with HBP resulted in the successful passivation of surface defects, which improved their stability and prevented further oxidation. The CDs with HBP passivation exhibited excellent electrochemical performance, with a high specific capacitance of 32.08 F g-1 at 0.1 A g-1 and good rate capability, indicating a faster ion transport rate at high current densities. Experimental EPR spectra of functionalized and non-functionalized CDs reveal distinct changes in g-factor values and line widths, confirming the impact of dangling bonds and spin-orbit interactions. The observed broader linewidth indicates a wider range of electron spin resonances due to energy-level splitting induced by spin-orbit coupling. The excellent electrochemical performance of CDs with HBP passivation can be attributed to the presence of oxygen-containing surface functional groups such as hydroxyl and carboxyl groups on their surfaces, which enhance the conductivity and charge transfer reactions. These results suggest that functionalization with polar HBPs is a promising strategy to enhance the electrochemical performance of CDs in supercapacitor applications.


Guiding spatial arrangements of silver nanoparticles by optical binding interactions in shaped light fields.
We demonstrate assembly of spheroidal Ag nanoparticle clusters, chains and arrays induced by optical binding. Particles with diameters of 40 nm formed ordered clusters and chains in aqueous solution when illuminated by shaped optical fields with a wavelength of 800 nm; specifically, close-packed clusters were formed in cylindrically symmetric optical traps, and linear chains were formed in line traps. We developed a coupled-dipole model to calculate the optical forces between an arbitrary number of particles and successfully predicted the experimentally observed particle separations and arrangements as well as their dependence on the polarization of the incident light. This demonstrates that the interaction between these small Ag particles and light is well described by approximating the particles as point dipoles, showing that these experiments extend optical binding into the Rayleigh regime. For larger Ag nanoparticles, with diameters of approximately 100 nm, the optical-binding forces become comparable to the largest gradient forces in the optical trap, and the particles can arrange themselves into regular arrays or synthetic photonic lattices. Finally, we discuss the differences between our experimental observations and the point dipole theory and suggest factors that prevent the Ag nanoparticles from aggregating as expected from the theory.


[Effect of a single dose of hydrocortisone and adrenaline on the synthesis of nuclear proteins and DNA in the rat thymus].
Single injections of hydrocortisone and adrenaline low doses long before the rat killing induced a change in the level of thymic DNA and nuclear protein synthesis. The effect and direction of hormone activity were dependent on the day time and duration of hormone presence in the organism. Hydrocortisone in a dose of 10 mg/kg, injected at 11 o'clock, promoted thymic DNA synthesis, whereas adrenaline in a dose of 0.06 mg/kg, administered at 11 o'clock, inhibited DNA synthesis, stimulating it, when injected at 23 o'clock.


Harnessing root exudates for plant microbiome engineering and stress resistance in plants.
A wide range of abiotic and biotic stresses adversely affect plant's growth and production. Under stress, one of the main responses of plants is the modulation of exudates excreted in the rhizosphere, which consequently leads to alterations in the resident microbiota. Thus, the exudates discharged into the rhizospheric environment play a preponderant role in the association and formation of plant-microbe interactions. In this review, we aimed to provide a synthesis of the latest and most pertinent literature on the diverse biochemical and structural compositions of plant root exudates. Also, this work investigates into their multifaceted role in microbial nutrition and intricate signaling processes within the rhizosphere, which includes quorum-sensing molecules. Specifically, it explores the contributions of low molecular weight compounds, such as carbohydrates, phenolics, organic acids, amino acids, and secondary metabolites, as well as the significance of high molecular weight compounds, including proteins and polysaccharides. It also discusses the state-of-the-art omics strategies that unveil the vital role of root exudates in plant-microbiome interactions, including defense against pathogens like nematodes and fungi. We propose multiple challenges and perspectives, including exploiting plant root exudates for host-mediated microbiome engineering. In this discourse, root exudates and their derived interactions with the rhizospheric microbiota should receive greater attention due to their positive influence on plant health and stress mitigation.


Reversed Septal Curvature Is Associated With Nonsustained Ventricular Tachycardia in Hypertrophic Cardiomyopathy.
Sudden cardiac death (SCD) is associated with nonsustained ventricular tachycardia (NSVT) in patients with hypertrophic cardiomyopathy (HCM). Recently, differences regarding septal morphology have been reported, with an increased probability of sudden death in patients with HCM who had reverse septal curvature (RSC). This study aimed to examine the relation between RSC and NSVT in HCM. A total of 138 patients with HCM were enrolled. Of 138 patients, 47 (34.1%) were diagnosed with RSC and 42 patients (30.4%) had NSVT. Compared with the non-RSC group, those with RSC were much younger and had an increased incidence of NSVT, thicker septal thickness, larger mass, and a higher proportion of HCM or SCD family history. Furthermore, patients with RSC had a higher risk of SCD according to the European Society of Cardiology calculator (2.5 [1.6 to 4.6] vs 1.6 [1.1 to 2.3] [%/5 years], p <0.001). The multivariate analysis showed that RSC was a strong and independent risk factor for NSVT (odds ratio 2.756, 95% confidence interval 1.164 to 6.525, p = 0.021). In conclusion, the presence of RSC in patients with HCM is independently associated with NSVT. Further studies are needed to evaluate the role of RSC as a risk factor for SCD in this population.


Natural Functional Beverages as an Approach to Manage Diabetes.
Diabetes mellitus is a chronic disease, commonly associated with unhealthy habits and obesity, and it is becoming a serious health issue worldwide. As a result, new approaches to treat diabetes are required, and a movement towards more natural approaches is emerging. Consuming fruit and vegetables is advised to prevent diabetes since they contain several bioactive compounds. A simple and effective strategy to include them in the diets of diabetic and obese people is through beverages. This review aims to report the anti-diabetic potentials of different vegetable and fruit beverages. These functional beverages demonstrated in vitro potential to inhibit α-glucosidase and α-amylase enzymes and to improve glucose uptake. In vivo, beverage consumption showed a reduction of blood glucose, increase of insulin tolerance, improvement of lipid profile, control of obesity, and reduction of oxidative stress. This suggests the potential of vegetable- and fruit-based functional beverages to be used as a natural innovative therapy for the management of diabetes.


Nutritional assessment of charitable meal programmes serving homeless people in Toronto.
To assess the potential nutritional contribution of meals provided in a sample of community programmes for homeless individuals, to determine the effect of food donations on meal quality and to develop food-based guidance for meals that would meet adults' total nutrient needs. Toronto, Canada. An analysis of weighed meal records from eighteen programmes. The energy and nutrient contents of meals were compared to requirement estimates to assess contribution to total needs, given that homeless people have limited access to nutritious foods. Mixed linear modelling was applied to determine the relationship between the use of food donations and meal quality. The composition of meals that would meet adults' nutrient requirements was determined by constructing simulated meals, drawing on the selection of foods available to programmes. In all, seventy meals, sampled from eighteen programmes serving homeless individuals. On average, the meals contained 2.6 servings of grain products, 1.7 servings of meat and alternatives, 4.1 servings of vegetables and fruits and 0.4 servings of milk products. The energy and nutrient contents of most meals were below adults' average daily requirements. Most meals included both purchased and donated foods; the vitamin C content of meals was positively associated with the percentage of energy from donations. Increasing portion sizes improved the nutrient contribution of meals, but the provision of more milk products and fruits and vegetables was required to meet adults' nutrient requirements. The meals assessed were inadequate to meet adults' nutrient requirements. Improving the nutritional quality of meals requires additional resources.


Analysis of a horizontally transferred pathway involved in vitamin B6 biosynthesis from the soybean cyst nematode Heterodera glycines.
Heterodera glycines is an obligate plant parasite capable of biochemically and developmentally altering its host's cells in order to create a specialized feeding cell. Although the exact mechanism of feeding cell morphogenesis remains a mystery, the nematode's ability to manipulate the plant is thought to be due in part to horizontal gene transfers (HGTs). A bioinformatic screen of the nematode genome has revealed homologues of the genes SNZ and SNO, which comprise a metabolic pathway for the de novo biosynthesis of pyridoxal 5'-phosphate, the active form of vitamin B(6) (VB(6)). Analysis of the 2 genes, HgSNZ and HgSNO, show that they contain nematode-like introns, generate polyadenylated mRNAs, and map to the soybean cyst nematode genetic linkage map, indicating that they are part of the nematode genome. However, gene synteny, protein homology, and phylogenetic evidence suggest prokaryotic origin. This would represent the first case of the HGT of a complete pathway into a nematode or terrestrial animal. VB(6) acts as a cofactor in over 140 different enzymes, and recent studies point toward an important role as a potent quencher of reactive oxygen species. With H. glycines' penchant for acquiring parasitism genes through HGT along with the absence of this pathway in other land-based animals suggests a specific need for VB(6) which may involve the parasite-host interaction.


Acquisition and maintenance of resistance to viruses in eukaryotic phytoplankton populations.
Viruses are known to play a key role in the regulation of eukaryotic phytoplankton population densities; however, little is known about the mechanisms of how they interact with their hosts and how phytoplankton populations mediate their regulations. Viruses are obligate parasites that depend on host cell machinery for their dissemination in the environment (most of the time through host cell lysis that liberates many new particles). But viruses also depend on a reliable host population to carry on their replication before losing their viability. How do hosts cells survive when they coexist with their viruses? We show that clonal lines of three picoeukaryotic green algae (i.e. Bathycoccus sp., Micromonas sp., Ostreococcus tauri) reproducibly acquire resistance to their specific viruses following a round of infection. Our observations show that two mechanisms of resistance may operate in O. tauri. In the first resistant type, viruses can attach to their host cells but no new particles develop. In the second one, O. tauri acquires tolerance to its virus and releases these viruses consistently. These lines maintained their resistance over a 3-year period, irrespective of whether or not they were re-challenged with new viral inoculations. Co-culturing resistant and susceptible lines revealed resistance to be associated with reduced host fitness in terms of growth rate.


Childhood adversity and borderline personality disorder: a focus on adolescence.
This article explores recent research in the field of childhood exposure to trauma and the development of borderline personality disorder in adolescence. Adolescence is a critical period of development. Exposure to trauma, specifically sexual abuse, prior to and during puberty has specific implications for personality development and heightens risk for borderline personality disorder. Elevated symptom levels in adolescence are likely to decline across adulthood, but social and vocational impairments remain. Impulsivity, difficulties in emotion regulation, and suicidality may characterize adolescent expression of borderline personality disorder, whereas negative affect and functional impairment are more stable features of the disorder. Preliminary findings in treatment models for adults have potential for benefit among adolescence. Further research is required to examine treatment effectiveness and efficiency. Greater attention to low-income and middle-income nations, which are disproportionately affected by adversity, is needed to determine cross-cultural validity and the impact of trauma in adolescent populations.


Factors affecting the views and experiences of women living in the city centre of Manisa, Turkey, regarding domestic violence.
Domestic violence against women is an important social and public health problem worldwide resulting from unequal power relationships between men and women. The purpose of the present cross-sectional descriptive study was to determine the factors affecting the views and experiences of women living in the city centre of Manisa, Turkey, regarding domestic violence. The data were collected from a representative sample of women (n=873) in 2012. The socio-demographic questionnaire and the World Health Organization's Multi-country Study on Women's Health and Domestic Violence Against Women were used for data collection. The study results revealed that of the women, 14.8% were exposed to physical violence, 7.9% to sexual violence, 20.2% to emotional violence/abuse and 11.2% to economic violence/abuse within the last 12 months. Lower income level, lower social status, lower educational level, unemployment, being exposed to parental violence during childhood and being married to husbands exposed to parental violence during childhood were associated risk factors with domestic violence. The study results indicate that domestic violence against women is a common phenomenon in Manisa.


Comprehensive Transcriptional Profiling of the Gastrointestinal Tract of Ruminants from Birth to Adulthood Reveals Strong Developmental Stage Specific Gene Expression.
One of the most significant physiological challenges to neonatal and juvenile ruminants is the development and establishment of the rumen. Using a subset of RNA-Seq data from our high-resolution atlas of gene expression in sheep (Ovis aries) we have provided the first comprehensive characterization of transcription of the entire gastrointestinal (GI) tract during the transition from pre-ruminant to ruminant. The dataset comprises 164 tissue samples from sheep at four different time points (birth, one week, 8 weeks and adult). Using network cluster analysis we illustrate how the complexity of the GI tract is reflected in tissue- and developmental stage-specific differences in gene expression. The most significant transcriptional differences between neonatal and adult sheep were observed in the rumen complex. Comparative analysis of gene expression in three GI tract tissues from age-matched sheep and goats revealed species-specific differences in genes involved in immunity and metabolism. This study improves our understanding of the transcriptomic mechanisms involved in the transition from pre-ruminant to ruminant by identifying key genes involved in immunity, microbe recognition and metabolism. The results form a basis for future studies linking gene expression with microbial colonization of the developing GI tract and provide a foundation to improve ruminant efficiency and productivity through identifying potential targets for novel therapeutics and gene editing.