Perceptions and experiences of taking oral medications for the treatment of Type 2 diabetes mellitus: a systematic review and meta-synthesis of qualitative studies.
To explore patients' perceptions and experiences of taking oral medications for the pharmacological management of Type 2 diabetes mellitus. Cinahl, EMBASE, Medline and PsycINFO databases were searched in 2014 to identify qualitative studies exploring patients' perceptions or experiences of taking medications for the management of Type 2 diabetes. Key concepts and themes were extracted and synthesized using meta-ethnography. Eight studies were included. Primary study findings were synthesized to develop three higher-order constructs that moved beyond the results of individual studies. The first construct, Medications for diabetes: a necessary evil, outlines how patients' negative perceptions of medication risks co-exist with a resounding view that medications are beneficial. Passive patients but active experimenters highlights the contrast between patients' passive acceptance of medication prescriptions and the urge to actively experiment and adjust doses to optimize medication use in daily life. Finally, Taking oral medication for Type 2 diabetes: a unique context describes features specific to the Type 2 diabetes medication experience, including lack of symptoms and the perceived relationship between medication and diet, which may influence adherence. Medication-taking for Type 2 diabetes is a unique adherence context, which requires the development of condition-specific interventions. The present findings indicate patients understand the need for medications but adjust dosage and timing in their daily lives. This review suggests providers should acknowledge patient preferences in the development of management strategies, and highlights an opportunity to direct the motivation evident in patients' experimentation towards potentially more beneficial medication-taking behaviours.


Association of iron depletion with menstruation and dietary intake indices in pubertal girls: the healthy growth study.
The aim of the present study was to investigate the associations of iron depletion (ID) with menstrual blood losses, lifestyle, and dietary habits, in pubertal girls. The study sample comprised 1222 girls aged 9-13 years old. Biochemical, anthropometrical, dietary, clinical, and physical activity data were collected. Out of 274 adolescent girls with menses, 33.5% were found to be iron depleted (defined as serum ferritin < 12 μg/L) compared to 15.9% out of 948 girls without menses. Iron-depleted girls without menses were found to have lower consumption of poultry (P = 0.017) and higher consumption of fruits (P = 0.044) and fast food (P = 0.041) compared to their peers having normal iron status. Multivariate logistic regression analysis showed that girls with menses were 2.57 (95% CI: 1.37, 4.81) times more likely of being iron depleted compared to girls with no menses. Iron depletion was found to be associated with high calcium intake, high consumption of fast foods, and low consumption of poultry and fruits. Menses was the only factor that was found to significantly increase the likelihood of ID in these girls. More future research is probably needed in order to better understand the role of diet and menses in iron depletion.


Hepatocyte-derived Snail1 propagates liver fibrosis progression.
Chronic exposure of the liver to hepatotoxic agents initiates an aberrant wound healing response marked by proinflammatory, as well as fibrotic, changes, leading to compromised organ structure and function. In a variety of pathological states, correlative links have been established between tissue fibrosis and the expression of transcription factors associated with the induction of epithelial-mesenchymal cell transition (EMT) programs similar to those engaged during development. However, the role played by endogenously derived, EMT-associated transcription factors in fibrotic states in vivo remains undefined. Using a mouse model of acute liver fibrosis, we demonstrate that hepatocytes upregulate the expression of the zinc finger transcriptional repressor, Snail1, during tissue remodeling. Hepatocyte-specific ablation of Snail1 demonstrates that this transcription factor plays a key role in liver fibrosis progression in vivo by triggering the proximal genetic programs that control multiple aspects of fibrogenesis, ranging from growth factor expression and extracellular matrix biosynthesis to the ensuing chronic inflammatory responses that characterize this class of pathological disorders.


A hierarchy in functional muscle roles at the knee is influenced by sex and anterior cruciate ligament deficiency.
Sex-related neuromuscular differences have been linked to greater risk of anterior cruciate ligament injuries in females. Despite this, it remains unclear if sex-related differences are present after injury. This study sought to determine if sex differences are present in the functional roles of knee joint muscles in an anterior cruciate ligament deficient population. An isometric, weight-bearing, force-generation protocol required injured and healthy males and females to modulate ground reaction forces. Electromyography was used to classify the functional role of 10 lower limb muscles in their contribution to knee joint stability during various loading directions. These roles were compared between the four groups at 12 loading directions using a directional analysis. Functional muscle roles were different between groups, except for injured males and healthy females. Healthy males had either joint actuators or specific joint stabilisers, but no general stabilisers; the vastus medialis and lateralis of injured males and healthy females were classified as general stabilisers while injured females added the gluteus medialis and medial gastrocnemius as general stabilisers. A population-based hierarchy in functional muscle roles was discovered. Healthy males demonstrated the most specific muscle roles, which can be viewed as more adaptive to variable loading conditions. The more generalised stabilisation strategies seen in injured males and females would alter joint loading which may be detrimental to the knee joint health over time. In summary, (1) these injuries alter muscle roles; (2) these alterations are sex-specific; (3) rehabilitation might be optimised if sex-differences are considered.


Alterations in left ventricular curvature and principal strains in dilated cardiomyopathy with functional mitral regurgitation.
Functional mitral regurgitation (FMR) is increasingly recognized as a left ventricular (LV) disease. Dilated cardiomyopathy (DCM) is commonly accompanied by FMR and reduction of LV torsion. Therapeutic targets for DCM include LV size reduction, altered LV shape, elimination of MR, and increasing LV torsion. It was hypothesized that, in addition to increasing LV size, DCM with FMR would alter normal LV shape and reduce and alter the direction of principal strains across the LV wall. This hypothesis was tested by measuring changes in epicardial and endocardial 2-D principal strains and regional radii of curvature accompanying tachycardia-induced cardiomyopathy in ovine hearts. Radio-opaque marker arrays were implanted into the left ventricle of eight sheep, including one subepicardial triangle and one subendocardial triangle in the anterior wall of the left ventricle. At one week postoperatively, biplane videofluoroscopy was used to determine marker dynamics. Rapid ventricular pacing was then instituted until FMR and signs of heart failure developed, and fluoroscopy was repeated. Circumferential LV radii of curvature were determined from marker triplets. DCM changed the normal epicardial oval LV cross-section to a more circular configuration. The endocardium maintained its normal circular shape as the left ventricle dilated. Deformations of the triangles from end-diastole to end-systole were determined, and the magnitude and direction of 2-D principal strains calculated. DCM was associated with decreased magnitude of both epicardial (-0.095 +/- 0.055 versus -0.040 +/- 0.032, p = 0.006) and endocardial (-0.117 +/- 0.047 versus -0.073 +/- 0.037, p = 0.023) principal strains. DCM reduced the angle of epicardial but not endocardial principal strain. DCM with FMR is associated with LV dilation, circularization of the normally oval equatorial circumferential LV epicardium, transmural reduction in principal strain, and decrease in angle of principal epicardial strain. These changes contribute to a reduction in the net torsional moment and may guide the development of reverse remodeling procedures for the dilated, failing ventricle with FMR.


The role of transient dynamics in biological pest control: insights from a host-parasitoid community.
1. Identifying natural enemies that can maintain pests at low abundances is a priority in biological control. Here, we show that experiments combined with models generate new insights into identifying effective control agents prior to their release in the field. Using a host-parasitoid community (the harlequin bug and its egg parasitoids) as a model system, we report three key findings. 2. The interplay between the host's self-limitation and the parasitoids' saturating functional response causes the long-term (steady-state) outcomes for pest suppression to differ from those of short-term (transient) dynamics. When the bug's self-limitation is moderately strong, the parasitoid with the higher attack rate and conversion efficiency (Ooencyrtus) achieves greater host suppression in the long term, but its longer handling time causes long periods of transient dynamics during which the bug can reach high abundances; when the bug's self-limitation is weak, host fluctuations amplify over time and Ooencyrtus fails at host suppression altogether. In contrast, the parasitoid with the lower attack rate and conversion efficiency but the shorter handling time (Trissolcus) induces only weak transient fluctuations of short duration and can maintain the host at low abundances regardless of the strength of the bug's self-limitation. 3. Release of multiple enemy species can compromise host suppression if an enemy that induces stronger transient fluctuations excludes one that induces weaker fluctuations. For instance, Ooencyrtus excludes Trissolcus despite having a longer handling time because of its higher conversion efficiency. The model correctly predicts the time to exclusion observed in experiments, suggesting that it captures the key biological features of the host-parasitoid interaction. 4. Intraspecific interference reduces long-term pest suppression but improves short-term pest control by reducing the magnitude and duration of transient fluctuations. 5. These results highlight the importance of transient dynamics in pest suppression. Pests are unlikely to be strongly self-limited because they attack crop monocultures. Hence, pest fluctuations are likely to dominate short-term dynamics even when the long-term outcome is a stable equilibrium. The tendency to induce strong transient fluctuations (e.g. through a long handling time) is therefore a crucial consideration when identifying effective pest control agents.


Respiratory cancer mortality among workers employed in thermoelectric power plants.
A historical cohort study of 406 workers was undertaken to evaluate the possible health hazards of employment in traditional electric power plants with particular regard to cancer mortality. The total mortality was below that expected [observed 40, standardized mortality ratio (SMR) 87] on the basis of national rates. Cancer mortality was slightly increased (SMR 112), mainly because of an excess of respiratory cancer (observed 9, SMR 171, 90% CI 89-299). Lung cancer deaths were higher than expected among those less than 60 years of age and among those with a duration of exposure and a latency period since first employment of over 10 years (observed 7, SMR 184). Furthermore, the increase was more pronounced among maintenance workers and workers in general services. Previous data indicated that there had been past exposure to some known respiratory carcinogens (ie, asbestos, polycyclic aromatic hydrocarbons). This study suggests that a possible lung cancer risk from traditional electricity generating plants should be considered and further studied.


Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles.
To test the hypothesis that butorphanol or morphine induces antinociception with minimal respiratory depression in conscious red-eared slider turtles. Prospective crossover study. 37 adult male and female red-eared slider turtles (Trachemys scripta). Antinociception (n = 27 turtles) and respiratory (10 turtles) experiments were performed. Infrared heat stimuli were applied to the plantar surface of turtle limbs. Thermal withdrawal latencies were measured before and at intervals after SC administration of physiologic saline (0.9% NaCl) solution, butorphanol tartrate (2.8 or 28 mg/kg [1.27 or 12.7 mg/lb]), or morphine sulfate (1.5 or 6.5 mg/kg [0.68 or 2.95 mg/lb]). Ventilation was assessed in freely swimming turtles before and after SC administration of saline solution, butorphanol (28 mg/kg), or morphine (1.5 mg/kg). For as long as 24 hours after injection of saline solution or either dose of butorphanol, thermal withdrawal latencies among turtles did not differ. Low- and high-dose morphine injections increased latencies significantly by 8 hours. Ventilation was not altered by saline solution administration, was temporarily depressed by 56% to 60% for 1 to 2 hours by butorphanol (28 mg/kg) administration, and was significantly depressed by a maximum of 83 +/- 9% at 3 hours after morphine (1.5 mg/kg) injection. Butorphanol and morphine depressed ventilation by decreasing breathing frequency. Although widely used in reptile species, butorphanol may not provide adequate antinociception for invasive procedures and caused short-term respiratory depression in red-eared slider turtles. In contrast, morphine apparently provided antinociception but caused long-lasting respiratory depression.


Protection of sound enamel and artificial enamel lesions against demineralisation: caries infiltrant versus adhesive.
To compare the protective potential of a conventional adhesive, a caries infiltrant and a combination of both against acidic challenge in vitro. One-hundred-and-fifty discs from bovine lower central incisors were fabricated. Seventy-five samples remained untreated, whereas the other half was subjected to a demineralisation process (14 days, acidic buffer, and pH 5) to create artificial enamel lesions. Specimens were then radioactively irradiated, and each 15 sound and demineralised specimens were treated with a caries infiltrant (Icon, DMG), an unfilled adhesive (Heliobond, IvoclarVivadent) or a combination of infiltrant and adhesive. Specimens treated with the adhesive followed by a flowable composite (TetricEvoFlow, IvoclarVivadent) served as positive control, while untreated specimens served as negative control. All samples were then subjected to lactic acid for 3 weeks at pH 4. Loss of apatite was determined using the radiochemical method of liquid scintillation. Data were statistically analysed by Kruskal-Wallis-test, one-way ANOVA and Scheffe's post hoc tests (p ≤.05). In both sound enamel and artificial caries lesions, untreated specimens showed the highest rate of apatite loss, whereas enamel treated with the adhesive and the flowable composite showed almost complete protection surface against dissolution. The caries infiltrant, the adhesive and the combination of both were able to decrease enamel dissolution, but the adhesive and the combination of adhesive and infiltrant were more effective than the infiltrant alone. Within the limitations of this in vitro study, the application of an adhesive (alone or in combination with the caries infiltrant) is more effective to protect enamel dissolution than the infiltrant alone.


Snowmelt and early to mid-growing season water availability augment tree growth during rapid warming in southern Asian boreal forests.
Boreal forests are facing profound changes in their growth environment, including warming-induced water deficits, extended growing seasons, accelerated snowmelt, and permafrost thaw. The influence of warming on trees varies regionally, but in most boreal forests studied to date, tree growth has been found to be negatively affected by increasing temperatures. Here, we used a network of Pinus sylvestris tree-ring collections spanning a wide climate gradient the southern end of the boreal forest in Asia to assess their response to climate change for the period 1958-2014. Contrary to findings in other boreal regions, we found that previously negative effects of temperature on tree growth turned positive in the northern portion of the study network after the onset of rapid warming. Trees in the drier portion did not show this reversal in their climatic response during the period of rapid warming. Abundant water availability during the growing season, particularly in the early to mid-growing season (May-July), is key to the reversal of tree sensitivity to climate. Advancement in the onset of growth appears to allow trees to take advantage of snowmelt water, such that tree growth increases with increasing temperatures during the rapidly warming period. The region's monsoonal climate delivers limited precipitation during the early growing season, and thus snowmelt likely covers the water deficit so trees are less stressed from the onset of earlier growth. Our results indicate that the growth response of P. sylvestris to increasing temperatures strongly related to increased early season water availability. Hence, boreal forests with sufficient water available during crucial parts of the growing season might be more able to withstand or even increase growth during periods of rising temperatures. We suspect that other regions of the boreal forest may be affected by similar dynamics.


The rhombotin gene family encode related LIM-domain proteins whose differing expression suggests multiple roles in mouse development.
The rhombotin (RBTN1 or Ttg-1) gene was first identified at a chromosome translocation in a T-cell acute leukaemia and later used to isolate two related genes (RBTN2 or Ttg-2 and RBTN3). Complete characterization of these genes in man and mouse shows that all three encode cysteine-rich proteins with typical LIM domains. RBTN1 and RBTN3-derived proteins have 98% identity in the LIM domains but are located on separate chromosomes in man and in mouse while RBTN1 and RBTN2, both located on human chromosome 11p but are on separate chromosomes in mouse, are only 48% identical in this part of the protein. The exon organization of RBTN1 and RBTN3 genes are similar, both having an intron, absent from the RBTN2 gene, in the LIM2-encoding region. The remarkable similarity between rbtn-1 and rbtn-3 proteins is parallelled in their expression patterns in mouse development, since both genes show high expression in restricted areas of the brain, but little lymphoid expression. rbtn-2 expression, however, is more ubiquitous. This gene shows a low level of thymus expression but high expression in fetal liver, adult spleen and B-cell lines, consistent with a role in B-cell development. These results suggest multiple cellular targets for the action of these proteins during development.


Mechanisms of nondisjunction: facts and perspectives.
An ordered segregation requires distinct processes of differentiation within the germ cell for recognition and segregation of homologous chromosomes/chromatids. These include synchronous maturation of the nucleus and cytoplasm, chromosome pairing and assembly at the metaphase plate, and movement within the spindle; all of them may be under direct/indirect regulatory control by the surrounding somatic compartments. Interference, e.g., by hormonal alterations at any of these steps, may alter the normal program of differentiation, thus increasing the risk of chromosomal malsegregation. Hence, many different causative mechanisms may exist which basically, nevertheless, act via (a) nonsegregation, (b) chance segregation, both during meiosis 1 and 2, or (c) presegregation during meiosis 1. In our animal models of the Djungarian hamster and the NMRI/Han mouse strain, we are analyzing the mechanisms of nondisjunction and presegregation during meiosis 1 in oocytes, as well as during aging of the females, by the application of hormones (gonadotrophins and steroids) and specific microtubular inhibitors (colchicine and methylbenzimidazolcarbamate). We suggest that chromosomes play a relatively passive role, although chromosomal properties, e.g., length, chiasma number, NORs, and position within the spindle, may provide an individual risk for each bivalent to be affected by nondisjunction. Failures in the endocrine control of follicular and germ cell maturation are considered to be primary causes for nondisjunction in young and aging oocytes. The understanding of the differentiation processes resulting in the maturation of follicles "at risk" may provide us with the tool to prevent the generation of aneuploidy in man.


Oxidative Stress Associated with Chilling Injury in Immature Fruit: Postharvest Technological and Biotechnological Solutions.
Immature, vegetable-like fruits are produced by crops of great economic importance, including cucumbers, zucchini, eggplants and bell peppers, among others. Because of their high respiration rates, associated with high rates of dehydration and metabolism, and their susceptibility to chilling injury (CI), vegetable fruits are highly perishable commodities, requiring particular storage conditions to avoid postharvest losses. This review focuses on the oxidative stress that affects the postharvest quality of vegetable fruits under chilling storage. We define the physiological and biochemical factors that are associated with the oxidative stress and the development of CI symptoms in these commodities, and discuss the different physical, chemical and biotechnological approaches that have been proposed to reduce oxidative stress while enhancing the chilling tolerance of vegetable fruits.


Ageing and Parkinson's disease: substantia nigra regional selectivity.
The micro-architecture of the substantia nigra was studied in control cases of varying age and patients with parkinsonism. A single 7 mu section stained with haematoxylin and eosin was examined at a specific level within the caudal nigra using strict criteria. The pars compacta was divided into a ventral and a dorsal tier, and each tier was further subdivided into 3 regions. In 36 control cases there was a linear fallout of pigmented neurons with advancing age in the pars compacta of the caudal substantia nigra at a rate of 4.7% per decade. Regionally, the lateral ventral tier was relatively spared (2.1% loss per decade) compared with the medial ventral tier (5.4%) and the dorsal tier (6.9%). In 20 Parkinson's disease (PD) cases of varying disease duration there was an exponential loss of pigmented neurons with a 45% loss in the first decade. Regionally, the pattern was opposite to ageing. Loss was greatest in the lateral ventral tier (average loss 91%) followed by the medial ventral tier (71%) and the dorsal tier (56%). The presymptomatic phase of PD from the onset of neuronal loss was estimated to be about 5 yrs. This phase is represented by incidental Lewy body cases: individuals who die without clinical signs of PD or dementia, but who are found to have Lewy bodies at post-mortem. In 7 cases cell loss was confined to the lateral ventral tier (average loss 52%) congruent with the lateral ventral selectivity of symptomatic PD. It was calculated that at the onset of symptoms there was a 68% cell loss in the lateral ventral tier and a 48% loss in the caudal nigra as a whole. The regional selectivity of PD is relatively specific. In 15 cases of striatonigral degeneration the distribution of cell loss was similar, but the loss in the dorsal tier was greater than PD by 21%. In 14 cases of Steele-Richardson-Olszewski syndrome (SRO) there was no predilection for the lateral ventral tier, but a tendency to involve the medial nigra and spare the lateral. These findings suggest that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of PD.


The effects of allitridin on the expression of transcription factors T-bet and GATA-3 in mice infected by murine cytomegalovirus.
This study was designed to investigate the effects of allitridin on the expression of transcription factors T-bet and GATA-3 in mice infected by murine cytomegalovirus (MCMV). A BALB/c mouse model system of MCMV infection was established. Twenty mice were allocated randomly into an allitridin-treated group (n = 10) and a placebo control group (n = 10). The same dose (25 mg/kg/day) and regimen of allitridin were used in the treated group in the 24 hours after virus infection; the same volume of saline solution was injected in placebo control mice. In an additional blank control group (n = 10), the same volume of saline solution was injected. The expression levels of the transcription factors T-bet and GATA-3 were measured by reverse transcription-polymerase chain reaction. The expression levels of the T helper (Th) 1 cytokine interferon-gamma (IFN-gamma) and the Th2 cytokine interleukin (IL)-10 in supernatant of spleen cell culture were measured by enzyme-linked immunosorbent assay. MCMV infection markedly down-modulated the expression of IFN-gamma and T-bet and significantly up-modulated the expression of IL-10 and GATA-3. Allitridin induced significantly (P < .01) increased expression of the transcription factor T-bet and the Th1 cytokine IFN-gamma and markedly (P < .01) decreased expression of the transcription factor GATA-3 and the Th2 cytokine IL-10. Thus MCMV infection could lead to disequilibrium of Th1/Th2 cytokine expression: The level of the Th1 cytokine IFN-gamma was decreased significantly, and Th2 cytokine IL-10 was overexpressed markedly. Allitridin could up-regulate the expression of T-bet and IFN-gamma and inhibit the expression of GATA-3 and IL-10 in MCMV-infected mice, indicating a Th1 dominant state, which should enhance the specific cellular immune reactions against cytomegalovirus (CMV) and be helpful for clearance of CMV from the host.


Linear-accelerator-based modified radiosurgical treatment of pituitary tumors in cats: 11 cases (1997-2008).
Determine the efficacy and safety of a linear-accelerator-based single fraction radiosurgical approach to the treatment of pituitary tumors in cats. Retrospective study. Eleven client-owned cats referred for treatment of pituitary tumors causing neurological signs, or poorly controlled diabetes mellitus (DM) secondary either to acromegaly or pituitary-dependent hyperadrenocortism. Cats underwent magnetic resonance imaging (MRI) of the brain to manually plan radiation therapy. After MRI, modified radiosurgery was performed by delivering a single large dose (15 or 20 Gy) of radiation while arcing a linear-accelerator-generated radiation beam around the cat's head with the pituitary mass at the center of the beam. Eight cats were treated once, 2 cats were treated twice, and 1 cat received 3 treatments. Treated cats were evaluated for improvement in endocrine function or resolution of neurological disease by review of medical records or contact with referring veterinarians and owners. Improvement in clinical signs occurred in 7/11 (63.6%) of treated cats. Five of 9 cats with poorly regulated DM had improved insulin responses, and 2/2 cats with neurological signs had clinical improvement. There were no confirmed acute or late adverse radiation effects. The overall median survival was 25 months (range, 1-60), and 3 cats were still alive. Single fraction modified radiosurgery is a safe and effective approach to the treatment of pituitary tumors in cats.


Interlaboratory Validation of Small-Scale Solubility and Dissolution Measurements of Poorly Water-Soluble Drugs.
The purpose of this study was to investigate the interlaboratory variability in determination of apparent solubility (Sapp) and intrinsic dissolution rate (IDR) using a miniaturized dissolution instrument. Three poorly water-soluble compounds were selected as reference compounds and measured at multiple laboratories using the same experimental protocol. Dissolution was studied in fasted-state simulated intestinal fluid and phosphate buffer (pH 6.5). An additional 6 compounds were used for the development of an IDR measurement guide, which was then validated with 5 compounds. The results clearly showed a need for a standardized protocol including both the experimental assay and the data analysis. Standardization at both these levels decreased the interlaboratory variability. The results also illustrated the difficulties in performing disc IDR on poorly water-soluble drugs because the concentrations reached are typically below the limit of detection. The following guidelines were established: for compounds with Sapp >1 mg/mL, the disc method is recommended. For compounds with Sapp <100 μg/mL, IDR is recommended to be performed using powder dissolution. Compounds in the interval 100 μg/mL to 1 mg/mL can be analyzed with either of these methods.


What determines the frequency of fast network oscillations with irregular neural discharges? I. Synaptic dynamics and excitation-inhibition balance.
When the local field potential of a cortical network displays coherent fast oscillations ( approximately 40-Hz gamma or approximately 200-Hz sharp-wave ripples), the spike trains of constituent neurons are typically irregular and sparse. The dichotomy between rhythmic local field and stochastic spike trains presents a challenge to the theory of brain rhythms in the framework of coupled oscillators. Previous studies have shown that when noise is large and recurrent inhibition is strong, a coherent network rhythm can be generated while single neurons fire intermittently at low rates compared to the frequency of the oscillation. However, these studies used too simplified synaptic kinetics to allow quantitative predictions of the population rhythmic frequency. Here we show how to derive quantitatively the coherent oscillation frequency for a randomly connected network of leaky integrate-and-fire neurons with realistic synaptic parameters. In a noise-dominated interneuronal network, the oscillation frequency depends much more on the shortest synaptic time constants (delay and rise time) than on the longer synaptic decay time, and approximately 200-Hz frequency can be realized with synaptic time constants taken from slice data. In a network composed of both interneurons and excitatory cells, the rhythmogenesis is a compromise between two scenarios: the fast purely interneuronal mechanism, and the slower feedback mechanism (relying on the excitatory-inhibitory loop). The properties of the rhythm are determined essentially by the ratio of time scales of excitatory and inhibitory currents and by the balance between the mean recurrent excitation and inhibition. Faster excitation than inhibition, or a higher excitation/inhibition ratio, favors the feedback loop and a much slower oscillation (typically in the gamma range).


Reduced polymorphism in the Kelch propeller domain in Plasmodium vivax isolates from Cambodia.
Polymorphism in the ortholog gene of the Plasmodium falciparum K13 gene was investigated in Plasmodium vivax isolates collected in Cambodia. All of them were Sal-1 wild-type alleles except two (2/284, 0.7%), and P. vivax K12 polymorphism was reduced compared to that of the P. falciparum K13 gene. Both mutant allele isolates had the same nonsynonymous mutation at codon 552 (V552I) and were from Ratanak Kiri province. These preliminary data should encourage additional studies for associating artemisinin or chloroquine resistance and K12 polymorphism.


Zinc oxide nanoparticles impair bacterial clearance by macrophages.
The extensive development of nanoparticles (NPs) and their widespread employment in daily life have led to an increase in environmental concentrations of substances that may pose a biohazard to humans. The aim of this work was to examine the effects of zinc oxide nanoparticles (ZnO-NPs) on the host's pulmonary immune system response to nontypeable Haemophilus influenzae (NTHi) infection. A murine infection model was employed to assess pulmonary inflammation and bacterial clearance in response to exposure to ZnO-NPs. The molecular mechanisms underlying ZnO-NP-impaired macrophage activation were investigated. Treatment with ZnO-NPs impaired macrophage activation, leading to a delay in NTHi clearance in the bronchial alveolar lavage fluids and lungs. Exposure to ZnO-NPs followed by NTHi challenge decreased levels of nitric oxide compared with NTHi infection alone. The effects of ZnO-NPs involved downregulation of NTHi-activated expression of inducible nitric oxide synthase and the translocation of active NF-kB into the nucleus. These results demonstrate that exposure to ZnO-NPs can impair innate immune responses and attenuate macrophage responses to bacterial infection.


Calcium-dependent mechanical oscillations occur spontaneously in unstimulated mammalian cardiac tissues.
In quiescent rat ventricular myocardium, bathed in solution of 2 mM Ca++ or less, it has been previously demonstrated that spontaneous microscopic oscillatory cell motion is present and interacts with an incident laser beam to produce scattered light intensity fluctuations which can be monitored to quantify the underlying motion. The present study shows that scattered light intensity fluctuations are not present under any conditions in frog atrial or ventricular preparations, but do occur in each type of mammalian cardiac tissue studied in the unstimulated state. The magnitude of scattered light intensity fluctuations in mammalian tissues varies with species and cellular Ca++ loading. In some tissues, e.g., rabbit or ferret ventricle, either an increase in the Ca++ concentration in the perfusate [( Ca++]e), reduction of perfusate Na+ concentration [( Na+]e), or addition of cardiac glycosides was required to elicit scattered light intensity fluctuations; in other tissues, however, e.g., the canine Purkinje fiber, atria, and ventricle, and guinea pig atria, scattered light intensity fluctuations were present at 2 mM [Ca++]e in the absence of experimental Ca++ loading. Scattered light intensity fluctuations were not affected by LaCl3, or verapamil, and were reversibly abolished by caffeine. When the pCa in the myofilament space is kept constant in detergent "skinned" fibers, scattered light intensity fluctuations are not present during contractile activation. We conclude: that scattered light intensity fluctuations are due to spontaneous intracellular Ca++ oscillations that require a functional sarcoplasmic reticulum; that the potential to exhibit these oscillations is a fundamental property of mammalian excitable cardiac cells; and that, in many mammalian tissues, these oscillations are present in the unstimulated state, even in the absence of experimental perturbations to enhance cell Ca++ loading.


Regulation of neuromuscular transmission by neurotrophins.
Motor units comprise a motoneuron and the muscle fibers it innervates. Neuromuscular transmission is tightly regulated to match the activity of individual motor units. Activity-dependent release of neuromodulators at the neuromuscular junction (NMJ) determines the efficacy of transmission. The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) are produced by motoneurons and muscle fibers, and their release by skeletal muscle is regulated by muscle activity. BDNF and NT-4 enhance both spontaneous and evoked synaptic transmission at NMJs via activation of the tyrosine kinase receptor B (TrkB). Improvements in neuromuscular transmission may result from increased release of synaptic vesicles, either by presynaptic alterations in Ca(2+) transients or facilitated vesicular exocytosis. In fact, BDNF potentiates intracellular Ca(2+) release presynaptically and BDNF-induced TrkB activation also results in phosphorylation of synapsin I via mitogen activated protein kinase, which increases the number of synaptic vesicles available for release. Neurotrophins may also regulate synaptic transmission at the NMJ by increasing local release of neuregulin or other nerve-derived modulators. We review recent studies on the regulation of neuromuscular transmission, the motor unit-specific properties of NMJs and the effects of neurotrophins on synaptic efficacy at the NMJ.


Free-space folded-path optical programmable logic array.
A new method to realize a medium-scale, free-space optical programmable logic array is proposed. By using either a two-dimensional optical spatial light modulator or an array of one-dimensional spatial light modulators inside a lens-based multiple-beam-path cavity, an array of optical multiple-variable logic product terms is generated. This device, together with a programmable multiple-variable OR matrix, can be used to implement any Boolean combinatorial logic operations. For an optical binary combinatorial logic computation, the proposed method efficiently uses three-dimensional space and optical elements. Preliminary experimental results obtained using an inexpensive liquid-crystal television are included.


Down cancer alley: the lived experience of health and environmental suffering in Louisiana's chemical corridor.
With the massive Gulf oil spill of 2010, there has been intensified concern about the impacts of industrial contamination on physical environments, human health, and social well-being. Based on ethnographic research in a primarily African American town in an area of Southern Louisiana colloquially known as the Chemical Corridor because of the large number of local chemical manufacturing plants, this article engages arguments made by Auyero and Swistun concerning the uncertainties and confusions that emerge when official or empowered pronouncements about the health impacts of living near waste-generating factories conflict with the everyday experience of perceived health-related contamination in an impoverished community. The article seeks to address gaps in our understanding of how communities conceive of environmental health risk, what their sources of information and level of knowledge about this issue are, and how they handle potential conflict between access to needed employment and the local presence of industrial polluters.


Experiential contributions to social dominance in a rat model of fragile-X syndrome.
Social withdrawal is one phenotypic feature of the monogenic neurodevelopmental disorder fragile-X. Using a 'knockout' rat model of fragile-X, we examined whether deletion of the Fmr1 gene that causes this condition would affect the ability to form and express a social hierarchy as measured in a tube test. Male fragile-X 'knockout' rats living together could successfully form a social dominance hierarchy, but were significantly subordinate to wild-type animals in mixed group cages. Over 10 days of repeated testing, the fragile-X mutant rats gradually showed greater variance and instability of rank during their tube-test encounters. This affected the outcome of future encounters with stranger animals from other cages, with the initial phenotype of wild-type dominance lost to a more complex picture that reflected, regardless of genotype, the prior experience of winning or losing. Our findings offer a novel insight into the complex dynamics of social interactions between laboratory living groups of fragile-X and wild-type rats. Even though this is a monogenic condition, experience has an impact upon future interactions with other animals. Gene/environment interactions should therefore be considered in the development of therapeutics.


Role of Epidermal Growth Factor-Triggered PI3K/Akt Signaling in the Migration of Medulloblastoma-Derived Cells.
Medulloblastoma (MB) is the most common brain cancer diagnosed among children. The cellular pathways that regulate MB invasion in response to environmental cues remain incompletely understood. Herein, we examine the migratory response of human MB-derived Daoy cells to different concentration profiles of Epidermal Growth Factor (EGF) using a microfluidic system. Our findings provide the first quantitative evidence that EGF concentration gradients modulate the chemotaxis of MB-derived cells in a dose-dependent manner via the EGF receptor (EGF-R). Data illustrates that higher concentration gradients caused increased number of cells to migrate. In addition, our results show that EGF-induced receptor phosphorylation triggered the downstream activation of phosphoinositide-3 kinase (PI3K)/Akt pathway, while its downstream activation was inhibited by Tarceva (an EGF-R inhibitor), and Wortmannin (a PI3K inhibitor). The treatment with inhibitors also severely reduced the number of MB-derived cells that migrated towards increasing EGF concentration gradients. Our results provide evidence to bolster the development of anti-migratory therapies as viable strategies to impede EGF-stimulated MB dispersal.


Adipokinetic hormone enhances laminarin and bacterial lipopolysaccharide-induced activation of the prophenoloxidase cascade in the African migratory locust, Locusta migratoria.
Lom-AKH-I enhances the activation in vivo of prophenoloxidase in the haemolymph of the African migratory locust, Locusta migratoria, in response to challenge with laminarin. AKH does not influence the speed or initial magnitude of the phenoloxidase response to laminarin, but prolongs the period of activation of the enzyme in a dose-dependent manner. Injections of preparations of bacterial lipopolysaccharide (LPS) do not activate prophenoloxidase in vivo, but co-injection of Lom-AKH-I with commercial preparations of LPS from Klebsiella pneumoniae, Escherichia coli, or Shigella flexneri (but not one from Pseudomonas aeroginosa) results in dose-dependent increases in the levels of phenoloxidase that persist in the haemolymph for several hours. It is argued that the effects of AKH on phenoloxidase activation in locusts described here are, at least in part, related directly to changes in lipid metabolism brought about by the hormone.


Human fetal kidney morphometry during gestation and the relationship between weight, kidney morphometry and plasma active renin concentration at birth.
1. This study was designed to examine the changes in kidney morphometry during gestation in fetuses that were either appropriate or small for gestational age and the relationship between umbilical vein plasma active renin and kidney morphometry. 2. Serial ultrasound measurements of various morphometric and renal indices were performed in a cohort of 87 singleton fetuses from 22 to 38 weeks gestation. Blood was collected from the umbilical vein at delivery and active renin was measured from the plasma based on angiotensinogen I generated during incubation with plasma and ox renin substrate. 3. Growth in the longitudinal plane of fetal kidneys was similar in the small- and appropriate-for-gestational age groups; however, growth in the anterio-posterior, transverse and circumference planes of the kidneys was significantly slower in the small-for-gestational-age group after 26 weeks gestation. Differences in growth rate in the two groups were most marked between 26 and 34 weeks and persisted until delivery when the anterior-posterior diameter was significantly larger (P < 0.00001) in the appropriate-for-gestational-age group (26.1 +/- 2.5 mm compared with 19.8 +/- 2.6 mm). The mean umbilical vein active plasma renin concentration at delivery was significantly higher (P < 0.05) in the small-for-gestation-age group (274.4 +/- 32.9 mu-units/ml plasma) than in the appropriate-for-gestational-age group (164.9 +/- 28.3 mu-units/ml plasma). In addition, there were statistically significant inverse correlations between renin concentration and birthweight (r = -0.55, P < 0.001) and between renin concentration and kidney anterior-posterior diameter (r = -0.67, P < 0.001). 4. Fetal renal growth was slower in small than in appropriate-for-gestational-age fetuses. The period of 26-34 weeks gestation was that during which maximum fetal renal growth occurred. Umbilical vein plasma renin levels were higher in small-for-gestational-age fetuses. The findings of slow fetal renal growth rate and associated high renin concentrations seen in small-for-gestational-age fetuses could be implicated in an irreversible reno-vascular pathology leading to adult hypertension. We suggest that 26 to 34 weeks could be the "critical period' during which the insult that leads to in-utero programming for the development of adult hypertension occurs.


Ethylzingerone, a Novel Compound with Antifungal Activity.
Preservatives increase the shelf life of cosmetic products by preventing growth of contaminating microbes, including bacteria and fungi. In recent years, the Scientific Committee on Consumer Safety (SCCS) has recommended the ban or restricted use of a number of preservatives due to safety concerns. Here, we characterize the antifungal activity of ethylzingerone (hydroxyethoxyphenyl butanone [HEPB]), an SCCS-approved new preservative for use in rinse-off, oral care, and leave-on cosmetic products. We show that HEPB significantly inhibits growth of Candida albicans, Candida glabrata, and Saccharomyces cerevisiae, acting fungicidally against C. albicans Using transcript profiling experiments, we found that the C. albicans transcriptome responded to HEPB exposure by increasing the expression of genes involved in amino acid biosynthesis while activating pathways involved in chemical detoxification/oxidative stress response. Comparative analyses revealed that C. albicans phenotypic and transcriptomic responses to HEPB treatment were distinguishable from those of two widely used preservatives, triclosan and methylparaben. Chemogenomic analyses, using a barcoded S. cerevisiae nonessential mutant library, revealed that HEPB antifungal activity strongly interfered with the biosynthesis of aromatic amino acids. The trp1Δ mutants in S. cerevisiae and C. albicans were particularly sensitive to HEPB treatment, a phenotype rescued by exogenous addition of tryptophan to the growth medium, providing a direct link between HEPB mode of action and tryptophan availability. Collectively, our study sheds light on the antifungal activity of HEPB, a new molecule with safe properties for use as a preservative in the cosmetic industry, and exemplifies the powerful use of functional genomics to illuminate the mode of action of antimicrobial agents.


Proteomic Analysis of Vitreous Humor in Retinal Vein Occlusion.
To analyze the protein profile of human vitreous of untreated patients with retinal vein occlusion (RVO). Sixty-eight vitreous humor (VH) samples (44 from patients with treatment naïve RVO, 24 controls with idiopathic floaters) were analyzed in this clinical-experimental study using capillary electrophoresis coupled to mass spectrometer and tandem mass spectrometry. To define potential candidate protein markers of RVO, proteomic analysis was performed on RVO patients (n = 30) and compared with controls (n = 16). To determine validity of potential biomarker candidates in RVO, receiver operating characteristic (ROC) was performed by using proteome data of independent RVO (n = 14) and control samples (n = 8). Ninety-four different proteins (736 tryptic peptides) could be identified. Sixteen proteins were found to be significant when comparing RVO and control samples (P = 1.43E-05 to 4.48E-02). Five proteins (Clusterin, Complement C3, Ig lambda-like polypeptide 5 (IGLL5), Opticin and Vitronectin), remained significant after using correction for multiple testing. These five proteins were also detected significant when comparing subgroups of RVO (central RVO, hemi-central RVO, branch RVO) to controls. Using independent samples ROC-Area under the curve was determined proving the validity of the results: Clusterin 0.884, Complement C3 0.955, IGLL5 1.000, Opticin 0.741, Vitronectin 0.786. In addition, validation through ELISA measurements was performed. The results of the study reveal that the proteomic composition of VH differed significantly between the patients with RVO and the controls. The proteins identified may serve as potential biomarkers for pathogenesis induced by RVO.


The marine actinomycete genus Salinispora: a model organism for secondary metabolite discovery.
This review covers the initial discovery of the marine actinomycete genus Salinispora through its development as a model for natural product research. A focus is placed on the novel chemical structures reported with reference to their biological activities and the synthetic and biosynthetic studies they have inspired. The time line of discoveries progresses from more traditional bioassay-guided approaches through the application of genome mining and genetic engineering techniques that target the products of specific biosynthetic gene clusters. This overview exemplifies the extraordinary biosynthetic diversity that can emanate from a narrowly defined genus and supports future efforts to explore marine taxa in the search for novel natural products.


Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment.
Osteoblasts and endothelium constitute functional niches that support haematopoietic stem cells in mammalian bone marrow. Adult bone marrow also contains adipocytes, the number of which correlates inversely with the haematopoietic activity of the marrow. Fatty infiltration of haematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia. To explore whether adipocytes influence haematopoiesis or simply fill marrow space, we compared the haematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. Here we show, by flow cytometry, colony-forming activity and competitive repopulation assay, that haematopoietic stem cells and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 'fatless' mice, which are genetically incapable of forming adipocytes, and in mice treated with the peroxisome proliferator-activated receptor-gamma inhibitor bisphenol A diglycidyl ether, which inhibits adipogenesis, marrow engraftment after irradiation is accelerated relative to wild-type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone-marrow microenvironment, and indicate that antagonizing marrow adipogenesis may enhance haematopoietic recovery in clinical bone-marrow transplantation.


T'ain't what you say, it's the way that you say it--left insula and inferior frontal cortex work in interaction with superior temporal regions to control the performance of vocal impersonations.
Historically, the study of human identity perception has focused on faces, but the voice is also central to our expressions and experiences of identity [Belin, P., Fecteau, S., & Bedard, C. Thinking the voice: Neural correlates of voice perception. Trends in Cognitive Sciences, 8, 129-135, 2004]. Our voices are highly flexible and dynamic; talkers speak differently, depending on their health, emotional state, and the social setting, as well as extrinsic factors such as background noise. However, to date, there have been no studies of the neural correlates of identity modulation in speech production. In the current fMRI experiment, we measured the neural activity supporting controlled voice change in adult participants performing spoken impressions. We reveal that deliberate modulation of vocal identity recruits the left anterior insula and inferior frontal gyrus, supporting the planning of novel articulations. Bilateral sites in posterior superior temporal/inferior parietal cortex and a region in right middle/anterior STS showed greater responses during the emulation of specific vocal identities than for impressions of generic accents. Using functional connectivity analyses, we describe roles for these three sites in their interactions with the brain regions supporting speech planning and production. Our findings mark a significant step toward understanding the neural control of vocal identity, with wider implications for the cognitive control of voluntary motor acts.


Novel combined miniature optical coherence tomography ultrasound probe for in vivo intravascular imaging.
We have developed a miniature integrated optical coherence tomography (OCT) ultrasound (US) probing system for intravascular imaging applications. In the OCT probe, the light coming out of a single mode fiber is focused by a gradient-index lens and then reflected by a right-angle prism from the side of the probe into the sample. It was combined with a 35 MHz PMN-PT side-viewing ultrasound transducer to obtain the ultrasound image as well. The OCT and ultrasound probes were integrated as a single probe to obtain OCT and ultrasound images simultaneously. The integrated probe has an outer diameter of 0.69 mm which, to our knowledge, is the smallest integrated OCT-US probe reported. Fast data acquisition and processing was implemented for real-time imaging. In vitro OCT and US images of human coronary artery with pathology, as well as in vivo images of normal rabbit abdominal aorta, were obtained using the integrated OCT-US probe to demonstrate its capability.


The correlation between insulin resistance and the visceral fat to skeletal muscle ratio in middle-aged women.
Central obesity with visceral fat accumulation and the amount of skeletal muscle mass may influence insulin sensitivity via its capacity for glucose load uptake. We investigated the relationships among the following metabolic variables: ratio of fat area to skeletal muscle area (VMR), percent ideal body weight, body mass index, waist-to-hip circumference (WHR) and visceral fat to subcutaneous fat ratio (VSR) in 114 nondiabetic middle-aged women. Anthropometric parameters, lipid profiles and sex hormone- binding globulin were measured. Visceral and subcutaneous fat areas at the umbilical level and the skeletal muscle area at the mid-thigh level were measured and computed. 75-gram OGTT tests were performed, along with measuring plasma glucose, insulin and free fatty acid levels, according to which area under the curve of glucose (Glu-AUC), insulin (Ins-AUC), free fatty acid (FFA-AUC) and glucose/insulin ratio (GIR=Glu- AUC/Ins-AUC), were calculated. 1) Triglyceride was more correlated with VSR than VMR. 2) The independent anthropometric parameters for each metabolic variable were In conclusion, VMR for Ins-AUC, WHR for Glu-AUC and total cholesterol, and VSR for triglyceride. 3) For subjects with higher VMR, age, Ins-AUC and triglyceride were significantly higher. 4) Subjects with higher VMR were older and showed higher Ins-AUC and lower GIR than the subjects with lower VMR. In conclusion, VMR is an anthropometric parameter that reflects insulin resistance concerning glucose metabolism, and VSR is thought to be a good parameter that that reflects the serum lipid levels. Further prospective studies are necessary to reevaluate the visceral fat vs. skeletal muscle relationship.


Vitamin B12 deficiency in the elderly.
Vitamin B12 deficiency is estimated to affect 10%-15% of people over the age of 60, and the laboratory diagnosis is usually based on low serum vitamin B12 levels or elevated serum methylmalonic acid and homocysteine levels. Although elderly people with low vitamin B12 status frequently lack the classical signs and symptoms of vitamin B12 deficiency, e.g. megaloblastic anemia, precise evaluation and treatment in this population is important. Absorption of crystalline vitamin B12 does not decline with advancing age. However, compared with the younger population, absorption of protein-bound vitamin B12 is decreased in the elderly, owing to a high prevalence of atrophic gastritis in this age group. Atrophic gastritis results in a low acid-pepsin secretion by the gastric mucosa, which in turn results in a reduced release of free vitamin B12 from food proteins. Furthermore, hypochlorhydria in atrophic gastritis results in bacterial overgrowth of the stomach and small intestine, and these bacteria may bind vitamin B12 for their own use. The ability to absorb crystalline vitamin B12 remains intact in older people with atrophic gastritis. The 1998 recommended daily allowance for vitamin B12 is 2.4 micrograms, but elderly people should try to obtain their vitamin B12 from either supplements or fortified foods (e.g. fortified ready-to-eat breakfast cereals) to ensure adequate absorption from the gastrointestinal tract. Because the American food supply is now being fortified with folic acid, concern is increasing about neurologic exacerbation in individuals with marginal vitamin B12 status and high-dose folate intake.


Direct oral anticoagulants in the treatment of acute venous thromboembolism: a systematic review and meta-analysis.
Acute venous thromboembolism (VTE) is a common disease associated to significant morbidity and mortality. We systematically reviewed and meta-analysed clinical outcomes with direct oral anticoagulants (DOAC: dabigatran, rivaroxaban, apixaban or edoxaban) for treatment of acute VTE. We used MEDLINE and CENTRAL, clinical trials registers, conference proceedings, and websites of regulatory agencies to identify randomised clinical trials of DOAC compared with conventional treatment [parenteral anticoagulant followed by a vitamin K antagonist (VKA)] for acute VTE. Two investigators independently extracted data. Relative risk of recurrent VTE, bleeding events, deaths and a net clinical endpoint (composite of recurrent VTE, major bleeding, and death) were estimated using a random effect meta-analysis (RevMan software). Six trials including 27,127 patients were selected. The risk of recurrent VTE was similar with the DOAC and standard treatment (relative risk 0.91, 95% confidence interval 0.79 to 1.06). The DOAC reduced the risk of major bleeding in comparison with standard treatment (0.62, 0.45 to 0.85) (absolute risk difference, -0.6%; 95% confidence interval -1.0% to -0.3%), but there was heterogeneity across trials in the relative risk of bleeding. No between treatment differences were found in the relative risk of all-cause mortality (0.98, 0.84 to 1.14). The DOAC and conventional treatment differed on the net clinical endpoint (0.85, 0.75 to 0.97). Subgroup analyses in relevant subgroups (index pulmonary embolism, heparin lead-in, age, gender, renal function, presence of cancer), as well as sensitivity analyses, were consistent with the main analysis. The DOAC seem as effective as, and probably safer than standard treatment of acute VTE. The relative efficacy and safety of the DOAC was consistent across a wide range of patients.


Ectopic pregnancy among American Indian and Alaska Native women, 2002-2009.
To examine rates of ectopic pregnancy (EP) among American Indian and Alaska Native (AI/AN) women aged 15-44 years seeking care at Indian Health Service (IHS), Tribal, and urban Indian health facilities during 2002-2009. We used 2002-2009 inpatient and outpatient data from the IHS National Patient Information Reporting System to identify EP-associated visits and obtain the number of pregnancies among AI/AN women. Repeat visits for the same EP were determined by calculating the interval between visits; if more than 90 days between visits, the visit was considered related to a new EP. We identified 229,986 pregnancies among AI/AN women 15-44 years receiving care at IHS-affiliated facilities during 2002-2009. Of these, 2,406 (1.05 %) were coded as EPs, corresponding to an average annual rate of 10.5 per 1,000 pregnancies. The EP rate among AI/AN women was lowest in the 15-19 years age group (5.5 EPs per 1,000 pregnancies) and highest among 35-39 year olds (18.7 EPs per 1,000 pregnancies). EP rates varied by geographic region, ranging between 6.9 and 24.4 per 1,000 pregnancies in the Northern Plains East and the East region, respectively. The percentage of ectopic pregnancies found among AI/AN women is within the national 1-2 % range. We found relatively stable annual rates of EP among AI/AN women receiving care at IHS-affiliated facilities during 2002-2009, but considerable variation by age group and geographic region. Coupling timely diagnosis and management with public health interventions focused on tobacco use and sexually transmitted diseases may provide opportunities for reducing EP and EP-associated complications among AI/AN women.


A dual-template imprinted polymer-modified carbon ceramic electrode for ultra trace simultaneous analysis of ascorbic acid and dopamine.
A dual-template imprinted polymer film containing dispersed multiwalled carbon nanotubes was exploited in the fabrication of a typical, reproducible, and rugged carbon ceramic electrode, adopting "surface grafting from" approach for the growth of a nanometer thin coating on its surface. For this, chloro groups were first introduced at the exterior surface of silica-carbon composite electrode through sol-gel modification using (3-chloropropyl)-trimethoxysilane, followed by an iniferter (sodium diethyl dithiocarbamate) initiated photopolymerization of functional monomer (2,4,6-trisacrylamido-1,3,5-triazine), mixed templates (ascorbic acid and dopamine), and cross-linker (ethylene glycol dimethacrylate), in the presence of multiwalled carbon nanotubes. The modified sensor was validated for the simultaneous analysis of ascorbic acid and dopamine in aqueous, blood serum, cerebrospinal fluid, and pharmaceutical samples, using differential pulse anodic stripping voltammetric technique. The oxidation peak potentials for both analytes were found to be well apart approximately by 300 mV, which was large enough to allow selective and sensitive analysis of one in the presence of other, without any cross reactivity, interferences and false-positives. The detection limits realized by the proposed sensor, under optimized conditions, were found to be as low as 2.24 ng mL(-1) for ascorbic acid and 0.21 ng mL(-1) for dopamine (S/N=3). Such stringent limits could be considered suitable for the primitive diagnosis of several chronic diseases, in clinical settings.


Sexually Dimorphic Regulation of EET Synthesis and Metabolism: Roles of Estrogen.
Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid via cytochrome P450 (CYP)/epoxygenase and are hydrolyzed by soluble epoxide hydrolase (sEH). Circulating and tissue levels of EETs are controlled by CYP (EET synthesis) and sEH (EET degradation). Therefore, both increases in CYP activity and decreases in sEH expression potentiate EET bioavailability, responses that prevail in the female sex as a function of estrogen. This mini review, based on subtitles listed, briefly summarizes studies focusing specifically on (1) female-specific potentiation of CYP/epoxygenase activity to compensate for the endothelial dysfunction; and (2) estrogen-dependent downregulation of sEH expression, which yields divergent actions in both systemic and pulmonary circulation, respectively. Estrogen-Potentiating EET Synthesis in Response to Endothelial Dysfunction: This section summarizes the current understanding regarding the roles of estrogen in facilitating EET synthesis in response to endothelial dysfunction. In this regard, estrogen recruitment of EET-driven signaling serves as a back-up mechanism, which compensates for NO deficiency to preserve endothelium-dependent vasodilator responses and maintain normal blood pressure. Estrogen-Dependent Downregulation of Ephx2/sEH Expression: This section focuses on molecular mechanisms responsible for the female-specific downregulation of sEH expression. Roles of EETs in Systemic Circulation, as a Function of Estrogen-Dependent Downregulation of sEH: This section summarizes studies conducted on animals that are either deficient in the Ephx2 gene (sEH-KO) or have been treated with sEH inhibitors (sEHIs), and exhibit EET-mediated cardiovascular protections in the cerebral, coronary, skeletal, and splanchnic circulations. In particular, the estrogen-inherent silencing of the Ephx2 gene duplicates the action of sEH deficiency, yielding comparable adaptations in attenuated myogenic vasoconstriction, enhanced shear stress-induced vasodilation, and improved cardiac contractility among female WT mice, male sEH-KO and sEHI-treated mice. Roles of Estrogen-Driven EET Production in Pulmonary Circulation: This section reviews epidemiological and clinical studies that provide the correlation between the polymorphism, or mutation of gene(s) involving estrogen metabolism and female predisposition to pulmonary hypertension, and specifically addresses an intrinsic causation between the estrogen-dependent downregulation of Ephx2 gene/sEH expression and female-susceptibility of being pulmonary hypertensive, a topic that has never been explored before. Additionally, the issue of the "estrogen paradox" in the incidence and prognosis of pulmonary hypertension is discussed.


Raising yield potential in wheat.
Recent advances in crop research have the potential to accelerate genetic gains in wheat, especially if co-ordinated with a breeding perspective. For example, improving photosynthesis by exploiting natural variation in Rubisco's catalytic rate or adopting C(4) metabolism could raise the baseline for yield potential by 50% or more. However, spike fertility must also be improved to permit full utilization of photosynthetic capacity throughout the crop life cycle and this has several components. While larger radiation use efficiency will increase the total assimilates available for spike growth, thereby increasing the potential for grain number, an optimized phenological pattern will permit the maximum partitioning of the available assimilates to the spikes. Evidence for underutilized photosynthetic capacity during grain filling in elite material suggests unnecessary floret abortion. Therefore, a better understanding of its physiological and genetic basis, including possible signalling in response to photoperiod or growth-limiting resources, may permit floret abortion to be minimized for a more optimal source:sink balance. However, trade-offs in terms of the partitioning of assimilates to competing sinks during spike growth, to improve root anchorage and stem strength, may be necessary to prevent yield losses as a result of lodging. Breeding technologies that can be used to complement conventional approaches include wide crossing with members of the Triticeae tribe to broaden the wheat genepool, and physiological and molecular breeding strategically to combine complementary traits and to identify elite progeny more efficiently.


Anatomy of a "black eye": a newly described fascial system of the lower eyelid.
The anatomy of a black eye is examined in a series of cadaver dissections in which a previously unreported fascial system of the lower eyelid is identified. This fascia originates at the orbital rim, and is in continuity with the orbital septum and with the periosteum of the orbital floor and anterior maxillary wall. This fascia contributes to the thickened area along the orbital rim called the arcus marginale. At the level of the orbicularis oculi muscle, this fascia was noted microscopically to fuse with a fibrous septa of the superficial cheek fat. This creates one long continuous membrane from the orbital rim above to the cheek skin below. Dye injection techniques show that this membrane is impermeable and traps injected dye in the same place where a black eye forms. After periorbital injury, extravasated hemoglobin pigment is confined to the area above the cutaneous insertion of this membrane. This fascial system has been named the septum malaris: malar describes its origin along the orbital rim of the cheek, and septum further describes the partitioning nature of this ultra-thin membrane.


iactA of Listeria ivanovii, although distantly related to Listeria monocytogenes actA, restores actin tail formation in an L. monocytogenes actA mutant.
A gene homologous to the actA gene of Listeria monocytogenes was cloned from Listeria ivanovii (strain CLIP257) by chromosome walking starting from the ilo gene that encodes the pore-forming toxin ivanolysin. The nucleotide sequence revealed that this gene, named iactA, encodes a protein of 1,044 amino acids (IactA) comprising a central region with seven highly conserved tandem proline-rich repeats of 47 amino acids. Although IactA and ActA share an overall similar structure, these two proteins are only distantly related. Like ActA, IactA migrates aberrantly on sodium dodecyl sulfate gels. When expressed in an L. monocytogenes actA deletion mutant strain, iactA restored actin polymerization.


Cecropia peltata L(Cecropiaceae) has wound-healing potential: a preclinical study in a Sprague Dawley rat model.
The plant Cecropia peltata is used in traditional medicine to treat a variety of disorders. The objective of the study presented in this report was to screen the extracts of this plant leaf for its wound-healing properties based on its traditional use for wound healing. Aqueous and ethanol extracts were prepared for topical and oral administration. The dose studied was 150 mgkg(-1)day(-1) for 10 days, using the excision wound model in rats. Carboxymethyl cellulose (1%) was used as control in topical and oral route studies. Animals were randomized to treatment or control, the experiment being done with prior ethical approval from the university. Wound areas were measured. On day 11, tissue was excised to determine the contents of protein, hydroxyproline, and hexosamine. Wound areas reduced statistically significantly in all treatment groups compared to respective controls (P < .001). Biochemistry and tissue histology outcomes were consistent with changes in the treatment groups. No differences were detected within the treatment groups. The study permits the conclusion that Crecopia peltata has wound-healing potential.


Role of etelcalcetide in the management of secondary hyperparathyroidism in hemodialysis patients: a review on current data and place in therapy.
Secondary hyperparathyroidism (sHPT) is a frequently occurring severe complication of advanced kidney disease. Its clinical consequences include extraskeletal vascular and valvular calcifications, changes in bone metabolism resulting in renal osteodystrophy, and an increased risk of cardiovascular morbidity and mortality. Calcimimetics are a cornerstone of parathyroid hormone (PTH)-lowering therapy, as confirmed by the recently updated 2017 Kidney Disease: Improving Global Outcomes chronic kidney disease - mineral and bone disorder clinical practice guidelines. Contrary to calcitriol or other vitamin D-receptor activators, calcimimetics reduce PTH without increasing serum-calcium, phosphorus, or FGF23 levels. Etelcalcetide is a new second-generation calcimimetic that has been approved for the treatment of sHPT in adult hemodialysis patients. Whereas the first-generation calcimimetic cinacalcet is taken orally once daily, etelcalcetide is given intravenously thrice weekly at the end of the hemodialysis session. Apart from improving drug adherence, etelcalcetide has proven to be more effective in lowering PTH when compared to cinacalcet, with an acceptable and comparable safety profile. The hope for better gastrointestinal tolerance with intravenous administration did not come true, as etelcalcetide did not significantly mitigate the adverse gastrointestinal effects associated with cinacalcet. Enhanced adherence and strong reductions in PTH, phosphorus, and FGF23 could set the stage for a future large randomized controlled trial to demonstrate that improved biochemical control of mineral metabolism with etelcalcetide in hemodialysis patients translates into cardiovascular and survival benefits and better health-related quality of life.


Outcomes and Predictive Factors After Cataract Surgery in Patients With Neovascular Age-related Macular Degeneration. The Fight Retinal Blindness! Project.
To evaluate outcomes and predictive factors of visual acuity (VA) change after cataract surgery in patients being treated for neovascular age-related macular degeneration (nAMD). Retrospective, matched case-control study. We studied eyes undergoing cataract surgery that had been tracked since they first started treatment for nAMD. These eyes were compared with a cohort of unoperated phakic eyes being treated for nAMD (3 per case) matched for treatment duration before cataract surgery, baseline VA, age, and length of follow-up. We included 124 patients that had cataract surgery and 372 matched controls. The mean (95% confidence interval) VA gained was 10.6 letters (7.8, 13.2; P < .001) 12 months after surgery; 26.0% had gained ≥3 lines and 1.6% had lost ≥3 lines of VA. Visual acuity (mean [standard deviation]) 12 months after surgery was higher in eyes that had cataract extraction compared with controls (65.8 [17.1] vs 61.3 [20.8] letters, respectively, P = .018). The proportion of visits where the choroidal neovascular (CNV) lesion was graded active and the mean number of injections were similar before and after surgery (P = .506 and P = .316, respectively), whereas both decreased in the control group, suggesting that surgery modestly increased the level of activity of the CNV lesion. Mean [SD] VA prior to surgery was lower in eyes that gained ≥15 letters compared with eyes that gained 0-14 letters (40.2 [21.4] vs 62.1 [15.1], P < .001). Patients undergoing cataract surgery within the first 6 months of anti-VEGF therapy were more likely to lose rather than gain vision (20.8% lost vision vs 12.8% and 4.4% gaining ≥15 or 0-14 letters respectively, P = .023). Age, receiving an injection at least 2 weeks before surgery, and the CNV lesion type had no discernible association with VA outcomes. We found evidence of a modest effect of cataract surgery on CNV lesion activity in eyes being treated for nAMD. Despite this, visual outcomes were reassuringly good. Cataract surgery within 6 months of starting treatment for nAMD should be avoided if possible.


Behavioral response and transmitter release during atonia elicited by medial medullary stimulation.
Activation of the medial medulla is responsible for rapid eye movement (REM) sleep atonia and cataplexy. Dysfunction can cause REM sleep behavior disorder and other motor pathologies. Here we report the behavioral effects of stimulation of the nucleus gigantocellularis (NGC) and nucleus magnocellularis (NMC) in unrestrained cats. In waking, 62% of the medial medullary stimulation sites suppressed muscle tone. In contrast, stimulation at all sites, including sites where stimulation produced no change or increased muscle tone in waking, produced decreased muscle tone during slow-wave sleep. In the decerebrate cat electrical stimulation of the NGC increased glycine and decreased norepinephrine (NE) release in the lumbar ventral horn, with no change in γ-aminobutyric acid (GABA) or serotonin (5-HT) release. Stimulation of the NMC increased both glycine and GABA release and also decreased both NE and 5-HT release in the ventral horn. Glutamate levels in the ventral horn were not changed by either NGC or NMC stimulation. We conclude that NGC and NMC play neurochemically distinct but synergistic roles in the modulation of motor activity across the sleep-wake cycle via a combination of increased release of glycine and GABA and decreased release of 5-HT and NE. Stimulation of the medial medulla that elicited muscle tone suppression also triggered rapid eye movements, but never produced the phasic twitches that characterize REM sleep, indicating that the twitching and rapid eye movement generators of REM sleep have separate brain stem substrates.


Correlation of preoperative MRI with the long-term outcomes of dorsal root entry zone lesioning for brachial plexus avulsion pain.
OBJECT Lesioning of the dorsal root entry zone (DREZotomy) is an effective treatment for brachial plexus avulsion (BPA) pain. The role of preoperative assessment with MRI has been shown to be unreliable for determining affected levels; however, it may have a role in predicting pain outcomes. Here, DREZotomy outcomes are reviewed and preoperative MRI is examined as a possible prognostic factor. METHODS A retrospective review was performed of an institutional database of patients who had undergone brachial plexus DREZ procedures since 1995. Preoperative MRI was examined to assess damage to the DREZ or dorsal horn, as evidenced by avulsion of the DREZ or T2 hyperintensity within the spinal cord. Phone interviews were conducted to assess the long-term pain outcomes. RESULTS Between 1995 and 2012, 27 patients were found to have undergone cervical DREZ procedures for BPA. Of these, 15 had preoperative MR images of the cervical spine available for review. The outcomes were graded from 1 to 4 as poor (no significant relief), good (more than 50% pain relief), excellent (more than 75% pain relief), or pain free, respectively. Overall, DREZotomy was found to be a safe, efficacious, and durable procedure for relief of pain due to BPA. The initial success rate was 73%, which declined to 66% at a median follow-up time of 62.5 months. Damage to the DREZ or dorsal horn was significantly correlated with poorer outcomes (p = 0.02). The average outcomes in patients without MRI evidence of DREZ or dorsal horn damage was significantly higher than in patients with such damage (3.67 vs 1.75, t-test; p = 0.001). A longer duration of pain prior to operation was also a significant predictor of treatment success (p = 0.004). CONCLUSIONS Overall, the DREZotomy procedure has a 66% chance of achieving meaningful pain relief on long-term follow-up. Successful pain relief is associated with the lack of damage to the DREZ and dorsal horn on preoperative MRI.


Making sense of professional enablers' involvement in laundering organized crime proceeds and of their regulation.
Money laundering has ascended the enforcement and criminological agenda in the course of this century, and has been accompanied by an increased focus on legal professionals as 'enablers' of crime. This article explores the dynamics of this enforcement, media and political agenda, and how the legal profession has responded in the UK and elsewhere, within the context of ignoring the difficulties of judging the effectiveness of anti money laundering. It concludes that legal responses are a function of their lobbying power, the determination of governments to clamp down on the toxic impacts of legal structures, and different legal cultures. However, it remains unclear what the effects on the levels and organization of serious crimes for gain are of controls on the professions.


Pre-operative traction for fractures of the proximal femur in adults.
Following a hip fracture, traction may be applied to the injured limb before surgery. To evaluate the effects of traction applied to the injured limb prior to surgery for a fractured hip. Different methods of applying traction (skin or skeletal) were considered. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (March 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to March 2006), EMBASE (1988 to 2006 Week 11), CINAHL (1982 to March 2006), the UK National Research Register (Issue 1, 2006), conference proceedings and reference lists of articles. All randomised or quasi-randomised trials comparing either skin or skeletal traction with no traction, or skin with skeletal traction for patients with an acute hip fracture prior to surgery. Both authors independently assessed trial quality and extracted data. Additional information was sought from all trialists. Wherever appropriate and possible, data were pooled. Ten randomised trials, mainly of moderate quality, involving a total of 1546 predominantly elderly patients with hip fractures, were identified and included in the review. Nine trials compared traction with no traction. Although limited data pooling was possible, overall this provided no evidence of benefit from traction, either in the relief of pain before surgery or ease of fracture reduction or quality of fracture reduction at time of surgery. One of these trials included both skin and skeletal traction groups. This trial and one other compared skeletal traction with skin traction and found no important differences between these two methods, although the initial application of skeletal traction was noted as being more painful and more costly. From the evidence available, the routine use of traction (either skin or skeletal) prior to surgery for a hip fracture does not appear to have any benefit. However, the evidence is also insufficient to rule out the potential advantages for traction, in particular for specific fracture types, or to confirm additional complications due to traction use. Further, high quality trials would be required to confirm or refute the absence of benefits of traction.


Reduced thoracolumbar fascia shear strain in human chronic low back pain.
The role played by the thoracolumbar fascia in chronic low back pain (LBP) is poorly understood. The thoracolumbar fascia is composed of dense connective tissue layers separated by layers of loose connective tissue that normally allow the dense layers to glide past one another during trunk motion. The goal of this study was to quantify shear plane motion within the thoracolumbar fascia using ultrasound elasticity imaging in human subjects with and without chronic low back pain (LBP). We tested 121 human subjects, 50 without LBP and 71 with LBP of greater than 12 months duration. In each subject, an ultrasound cine-recording was acquired on the right and left sides of the back during passive trunk flexion using a motorized articulated table with the hinge point of the table at L4-5 and the ultrasound probe located longitudinally 2 cm lateral to the midline at the level of the L2-3 interspace. Tissue displacement within the thoracolumbar fascia was calculated using cross correlation techniques and shear strain was derived from this displacement data. Additional measures included standard range of motion and physical performance evaluations as well as ultrasound measurement of perimuscular connective tissue thickness and echogenicity. Thoracolumbar fascia shear strain was reduced in the LBP group compared with the No-LBP group (56.4% ± 3.1% vs. 70.2% ± 3.6% respectively, p < .01). There was no evidence that this difference was sex-specific (group by sex interaction p = .09), although overall, males had significantly lower shear strain than females (p = .02). Significant correlations were found in male subjects between thoracolumbar fascia shear strain and the following variables: perimuscular connective tissue thickness (r = -0.45, p <.001), echogenicity (r = -0.28, p < .05), trunk flexion range of motion (r = 0.36, p < .01), trunk extension range of motion (r = 0.41, p < .01), repeated forward bend task duration (r = -0.54, p < .0001) and repeated sit-to-stand task duration (r = -0.45, p < .001). Thoracolumbar fascia shear strain was ~20% lower in human subjects with chronic low back pain. This reduction of shear plane motion may be due to abnormal trunk movement patterns and/or intrinsic connective tissue pathology. There appears to be some sex-related differences in thoracolumbar fascia shear strain that may also play a role in altered connective tissue function.


Implementation of the Code of Marketing of Breast-Milk Substitutes in Vietnam: Marketing Practices by the Industry and Perceptions of Caregivers and Health Workers.
The promotion of breastmilk substitutes (BMS) is an important barrier to successful breastfeeding. To examine the enactment and implementation of the Code of Marketing of Breast-Milk Substitutes (the Code) in Vietnam with a focus on marketing practices by the baby food industry and perceptions of caregivers, health workers, and policy makers. From May to July 2020, we conducted a mixed-method, cross-sectional study including a survey of 268 pregnant women and 726 mothers of infants aged 0-11 months and in-depth interviews with a subset of interviewed women (n = 39), policy makers, media executives, and health workers (n = 31). In the previous 30 days, two mothers (out of 726) participating in the quantitative survey reported that health workers had recommended BMS, at private hospitals in both cases. In-depth interviews with health workers showed that hospitals have internal procedures to prevent the promotion of BMS by health workers. However, companies employed representatives to promote products not covered under the Code (e.g., commercial milk formula for pregnant women) at antenatal care visits and by gaining contact information from women and using this information to promote BMS outside the hospital, often on social media. In the 30 days preceding the survey, one-fifth of pregnant women were exposed to promotions of commercial milk formula for pregnant women and 7.1% to promotions of BMS. Among mothers of infants, 7.3% and 10.7% of respondents with infants aged 0-5 and 6-11 months, respectively, were exposed to some form of BMS promotion in the past 30 days. Around the time of birth, parents commonly brought BMS to maternity facilities (52.5%) or purchased it nearby (35.4%). Although Vietnam has a strong regulatory environment for the protection, promotion, and support of breastfeeding, there are implementation, monitoring, and enforcement gaps. Stronger enforcement of national policies to regulate the presence of BMS industry representatives in health facilities-both public and private-and the promotion of BMS products on digital platforms are needed.


Bone mineral content in Polynesian and white New Zealand women.
The forearm bone mineral content of Polynesian and European women in New Zealand was measured to assess whether the inter-racial differences found in other populations also occurred in these two groups. The bone mineral content of the nondominant distal radius and ulna was measured by single photon absorptiometry in 123 European and 80 Polynesian women. The mean values were about 20% higher in Polynesians than in Europeans. The reason for this difference in bone mineral content is unknown but the findings do show that high bone density is not confined to African races and that inter-racial differences in bone mineral content may be more common than has been thought hitherto.


NOTCH3 signaling regulates MUSASHI-1 expression in metastatic colorectal cancer cells.
MUSASHI-1 (MSI-1) is a well-established stem cell marker in both normal and malignant colon cells and it acts by positively regulating the NOTCH pathway through inactivation of NUMB, a NOTCH signaling repressor. To date, the mechanisms of regulation of MSI-1 levels remain largely unknown. Here, we investigated the regulation of MSI-1 by NOTCH signaling in colorectal cancer cell lines and in primary cultures of colorectal cancer metastases. Stimulation by the NOTCH ligand DLL4 was associated with an increase of MSI-1 mRNA and protein levels, and this phenomenon was prevented by the addition of an antibody neutralizing NOTCH2/3 but not NOTCH1. Moreover, forced expression of activated NOTCH3 increased MSI-1 levels, whereas silencing of NOTCH3 by short hairpin RNA reduced MSI-1 levels in both colorectal cancer cells and CRC tumor xenografts. Consistent with these findings, enforced NOTCH3 expression or stimulation by DLL4 increased levels of activated NOTCH1 in colorectal cell lines. Finally, treatment of colorectal cancer cells with anti-NOTCH2/3 antibody increased NUMB protein while significantly reducing formation of tumor cell spheroids. This novel feed-forward circuit involving DLL4, NOTCH3, MSI-1, NUMB, and NOTCH1 may be relevant for regulation of NOTCH signaling in physiologic processes as well as in tumor development. With regard to therapeutic implications, NOTCH3-specific drugs could represent a valuable strategy to limit NOTCH signaling in the context of colorectal cancers overexpressing this receptor.


Treatment of Caenorhabditis elegans with Small Selenium Species Enhances Antioxidant Defense Systems.
Small selenium (Se) species play a key role in Se metabolism and act as dietary sources of the essential trace element. However, they are redox-active and trigger pro- and antioxidant responses. As health outcomes are strongly species-dependent, species-specific characteristics of Se compounds are tested in vivo. In the model organism Caenorhabditis elegans (C. elegans), immediate and sustained effects of selenite, selenomethionine (SeMet), and Se-methylselenocysteine (MeSeCys) are studied regarding their bioavailability, incorporation into proteins, as well as modulation of the cellular redox status. While all tested Se compounds are bioavailable, only SeMet persistently accumulates and is non-specifically incorporated into proteins. However, the protection toward chemically-induced formation of reactive species is independent of the applied Se compound. Increased thioredoxin reductase (TXNRD) activity and changes in mRNA expression levels of antioxidant proteins indicate the activation of cellular defense mechanisms. However, in txnrd-1 deletion mutants, no protective effects of the Se species are observed anymore, which is also reflected by differential gene expression data. Se species protect against chemically-induced reactive species formation. The identified immediate and sustained systemic effects of Se species give rise to speculations on possible benefits facing subsequent periods of inadequate Se intake.


Electrostatic deflections and electromechanical resonances of carbon nanotubes
Static and dynamic mechanical deflections were electrically induced in cantilevered, multiwalled carbon nanotubes in a transmission electron microscope. The nanotubes were resonantly excited at the fundamental frequency and higher harmonics as revealed by their deflected contours, which correspond closely to those determined for cantilevered elastic beams. The elastic bending modulus as a function of diameter was found to decrease sharply (from about 1 to 0.1 terapascals) with increasing diameter (from 8 to 40 nanometers), which indicates a crossover from a uniform elastic mode to an elastic mode that involves wavelike distortions in the nanotube. The quality factors of the resonances are on the order of 500. The methods developed here have been applied to a nanobalance for nanoscopic particles and also to a Kelvin probe based on nanotubes.


Comparison of predictability of epileptic seizures by a linear and a nonlinear method.
The performance of traditional linear (variance based) methods for the identification and prediction of epileptic seizures are contrasted with "modern" methods from nonlinear time series analysis. We note several flaws of design in demonstrations claiming to establish the efficacy of nonlinear techniques; in particular, we examine published evidence for precursor identification. We perform null hypothesis tests using relevant surrogate data to demonstrate that decreases in the correlation density prior to and during seizure may simply reflect increases in the variance.


First Report of Phaeomoniella chlamydospora on Vitis vinifera and French American Hybrids in Chile.
Phaeomoniella chlamydospora (W. Gams, Crous. M.J. Wingfield & L. Mugnai) Crous & Gams (= Phaeoacremonium chlamydosporum) was isolated during the growing seasons of 2003-2004 from roots, trunks, and cordons of grapevines, including cvs. Cabernet Sauvignon, Merlot, Pinot noir, Thompson seedless, Ruby seedless and root stock 3309C, and Kober 5BB, from 10 locations in V, VI, VII, and metropolitan regions of Chile. P. chlamydospora was isolated from 82% of samples from vines 2 to 18 years old that showed decline symptoms in the field. Isolates were identified on the basis of a previous description (1) and internal transcribed spacer (ITS1-5.8S-ITS2) rDNA sequences identical to those of P. chlamydospora isolated from Vitis vinifera (culture CBS 22995, GenBank Accession No. AF 197973). P. chlamydospora is established as a member of the petri and esca disease complex and as a pathogen of grapevines (2,3). Pathogenicity tests were completed by injecting into the pith of 50 single-node, rooted cuttings of Pinot noir and 3309C, approximately 20 μl of a 106 conidia per ml suspension, obtained from four isolates from Chile and one from California. Ten control cuttings of Pinot noir and 3309C were injected with an equal volume of sterile distilled water. Twenty-four weeks after inoculations, all P. chlamydospora-inoculated cuttings exhibited dark streaking of the vascular tissue extending 40 to 45 mm from the point of inoculation. The vascular streaking observed in inoculated plants was identical to symptoms observed in declining vines in the vineyard. No symptoms were observed in the controls. P. chlamydospora was isolated from the region of vascular streaking in 85% of inoculated cuttings. P. chlamydospora was not isolated from the water-treated controls. The reisolated P. chlamydospora was verified with means of morphological characters and polymerase chain reaction amplification with the species-specific primers (3). P. chlamydospora is widespread and readily isolated from declining grapevines in Chile and other grape growing regions of the world. To our knowledge, this is the first report of P. chlamydospora from the cultivars cited above in Chile. References: (1) M. Groenewald et al. Mycol. Res. 105:651, 2001. (2) L. sparapano et al. Phytopathol. Mediterr. (Suppl.)40:376, 2001. (3) S. Tegli et al. Phytopathol. Mediterr. 39:134, 2000.


Fetal microchimerisms in the mother: immunologic implications.
The previously held concept that the fetus is completely separated from the mother, especially by trophoblasts that line the outer layer of the placenta, has recently been questioned. It has recently been shown that fetal cells are detectable not only in the peripheral blood, but also in maternal skin and liver. Although the migration of fetal cells into the maternal circulation has been given a great deal of attention because of its implication in the prenatal diagnosis of genetic diseases, the potential role of such placental transfer of fetal cells in the pathogenesis of autoimmune diseases has only recently been considered. In patients with scleroderma, fetal cell-derived DNA was detected more frequently in the peripheral blood of patients than controls. This finding of a limited number of fetal cells in maternal tissues leading to microchimerism has been proposed to have a role in the induction of scleroderma. Although evidence for microchimerism has also been confirmed in a high frequency of liver tissues from patients with primary biliary cirrhosis (PBC), a similar high frequency was noted in control patients, which suggests that microchimerism by itself is unlikely to fully account for the pathogenesis of PBC. The finding of such a high frequency of fetal microchimerism in the liver suggests that this is a very common event, raising the possibility that the migration of fetal cells may be important in the induction and subsequent maintenance of tolerance against the fetus during pregnancy. In addition, it is clearly possible that such microchimerism could contribute to the pathogenesis of select autoimmune diseases.


Utility and tolerance of stress testing in geriatric patients.
To determine the sensitivity and specificity of stress testing in geriatric patients and to estimate the tolerance of these patients to exercise. A prospective study done in two populations with different ages. Cardiologists and a stress testing laboratory. Persons with ages above and under 65 years who were admitted in our center and submitted to stress testing and coronary angiography for suspicion of ischemic heart disease. All stress tests were performed on a Siemens Elama cicloergometer model 380-B adapted to a Hewlett Packard 1517 A ECG recorder. Our protocol started with an initial work load of 30 Watts with increments of other 30 Watts every three minutes. A 12 lead ECG was registered at rest, at maximum effort and in the recovery phase (approx. eight minutes after maximum effort). Three leads ECG's (V2, aVF, V5) were registered every three minutes. Stress finishing criteria were: symptom's limited, fatigue and maximum heart rate (220-age). Blood pressure was also controlled every three minutes during exercise and every two minutes during the recovery phase. Coronary angiographies were performed on a Siemens Cardoskop U (cine) using the Judkins technique. Left anterior oblique, right anterior oblique and postero anterior projections were used in all the procedures. Stress testing presents high sensitivity and low specificity in geriatric patients. A good tolerance to exercise was observed in this group of patients. A similar sensitivity was observed in the stress tests performed by patients with ages above and under 65 years. Sensitivity seems to be related to the severity of the coronary lesion. On the other hand stress testing presented a lower specificity in the geriatric patient. Finally, good tolerance to exercise was observed in patients older than 65 years.


Baseline Sensitivity and Cross-Resistance to Succinate-Dehydrogenase-Inhibiting and Demethylation-Inhibiting Fungicides in Didymella bryoniae.
Didymella bryoniae, which causes gummy stem blight (GSB) of watermelon, has a history of developing resistance to fungicides, most recently the succinate-dehydrogenase-inhibiting (SDHI) fungicide boscalid. To facilitate fungicide resistance monitoring, baseline sensitivity distributions were established for demethylation-inhibiting (DMI) fungicides tebuconazole and difenoconazole and the SDHI fungicide penthiopyrad, and reestablished for the SDHI fungicide boscalid. In all, 71 isolates with no known prior exposure to SDHIs or DMIs were used to determine the effective concentration at which mycelial growth was inhibited by 50% (EC50). EC50 values for boscalid, penthiopyrad, tebuconazole, and difenoconazole were 0.018 to 0.064, 0.015 to 0.057, 0.062 to 0.385, and 0.018 to 0.048 μg/ml, with median values of 0.032, 0.026, 0.118, and 0.031 μg/ml, respectively. Significant positive correlations between the sensitivity to penthiopyrad and boscalid (P < 0.0001, r = 0.75) and between tebuconazole and difenoconazole (P < 0.0001, r = 0.59) indicate a potential for cross-resistance between chemically related fungicides. In 2009, 103 isolates from fungicidetreated watermelon fields were tested for sensitivity to boscalid and penthiopyrad using a discriminatory concentration of 3.0 μg/ml. Of the isolates tested, 82 were insensitive and 14 were sensitive to both fungicides. Because of the significant potential for cross-resistance between closely related fungicides, growers will be advised not to use both SDHIs or both DMIs successively in the same fungicide spray program.