Activated KrasG¹²D is associated with invasion and metastasis of pancreatic cancer cells through inhibition of E-cadherin.
Pancreatic cancer (PC) harbours an activated point mutation (Kras(G12D)) in the Kras proto-oncogene that has been demonstrated to promote the development of PC. This study was designed to investigate the effect of the oncogenic Kras(G12D) allele on aggressiveness and metastatic potential of PC cells. We silenced the oncogenic Kras(G12D) allele expression in CD18/HPAF and ASPC1 cell lines by stable expression of shRNA specific to the Kras(G12D)allele. The Kras(G12D) knockdown cells exhibited a significant decrease in motility (P<0.0001), invasion (P<0.0001), anchorage-dependent (P<0.0001) and anchorage-independent growth (P<0.0001), proliferation (P<0.005) and an increase in cell doubling time (P<0.005) in vitro and a decrease in the incidence of metastases upon orthotopic implantation into nude mice. The knockdown of the Kras(G12D) allele led to a significant increase in the expression of E-cadherin (mRNA and protein) both in vitro and in vivo. This was associated with a decrease in the expression of phoshpo-ERK-1/2, NF-κB and MMP-9, and transcription factors such as δEF1, Snail and ETV4. Furthermore, the expression of several proteins involved in cell survival, invasion and metastasis was decreased in the Kras(G12D) knockdown cells. The results of this study suggest that the Kras(G12D) allele promotes metastasis in PC cells partly through the downregulation of E-cadherin.


Selective suppression of lymphomas by functional loss of Hsf1 in a p53-deficient mouse model for spontaneous tumors.
A hallmark in the pathogenesis of cancer is the increased expression of heat shock proteins (Hsps) and other molecular chaperones observed in many tumor types, which is considered to be an adaptive response to enhance tumor cell survival. Heat shock transcription factor 1 (Hsf1) is a major transactivator of Hsp induction and has been proposed to affect tumor initiation and progression, regulating expression of Hsps and other molecular targets. In this report, we provide direct in vivo evidence that Hsf1 plays a critical role in the evolution of spontaneous tumors arising in p53(-/-) mice. Thus, loss of Hsf1 function did not prolong tumor-free survival, but surprisingly altered the spectrum of tumors that arose in p53(-/-) mice. Tumor development is rapid in p53(-/-) mice, which predominantly (about 70%) succumb to lymphomas. In contrast, hsf1(-/-)p53(-/-) mice rarely develop lymphomas (<8%), but succumb to other tumor types including testicular carcinomas and soft tissue sarcomas. Our findings suggest that an increase in p53-independent apoptotic cell death in association with altered cytokine signaling and suppressed production of inflammatory factors in hsf1(-/-) mice may contribute to selective lymphoma suppression. In conclusion, the data presented here link the loss of Hsf1-dependent function to decreased susceptibility to spontaneous lymphomagenesis, which may have implications for cancer prevention and therapy.


[Medical resonance imaging (MRI)--the technology, the regulation and the utilization pattern in Israel].
Medical resonance imaging (MRI) is a technology for imaging and diagnosis of tissues and organs which does not use ionizing radiation. It was developed in the 1960's and 1970's and has been in clinical use since the 1980's. Over the last two decades there has been a substantial increase in utilization of MRI due to: improvements in imaging technology and image processing, the development of new indications for its use, and the increase in availability and accessibility of MRI in several medical fields. However, there is also overutilization of this technology due to: the use of imaging as a substitute for regular physical examinations, repeated examinations for the same medical reason, "defensive" medicine, and due to the public's desire for sophisticated examinations. These issues are all responsible for the increased use of MRI. MRI is an expensive technology and therefore, cost-lowering medical and economic mechanisms are employed to Limit its use. Until recently there were ten MRI scanners in Israel and this review presents their utilization patterns. The number of MRI scanners will double in the coming years. This may improve accessibility in different regions of the country, shorten waiting times, and improve medical diagnosis due to implementation for new indications. An international comparison showed that the number of MRI scanners in Israel is lower than the average number of MRI scanners in OECD countries. However, the utilization of MRI scanners in Israel is high relative to other OECD countries, indicating the high level of efficiency of the Israeli healthcare system.


The duration of mitosis and daughter cell size are modulated by nutrients in budding yeast.
The size of nearly all cells is modulated by nutrients. Thus, cells growing in poor nutrients can be nearly half the size of cells in rich nutrients. In budding yeast, cell size is thought to be controlled almost entirely by a mechanism that delays cell cycle entry until sufficient growth has occurred in G1 phase. Here, we show that most growth of a new daughter cell occurs in mitosis. When the rate of growth is slowed by poor nutrients, the duration of mitosis is increased, which suggests that cells compensate for slow growth in mitosis by increasing the duration of growth. The amount of growth required to complete mitosis is reduced in poor nutrients, leading to a large reduction in cell size. Together, these observations suggest that mechanisms that control the extent of growth in mitosis play a major role in cell size control in budding yeast.


Nonequilibrium velocity fluctuations and energy amplification in planar Couette flow.
In this paper we investigate intrinsic thermally excited nonequilibrium velocity fluctuations in laminar planar Couette flow. For this purpose we have complemented the solution of the stochastic Orr-Sommerfeld equation for the intensity of the fluctuations of the wall-normal velocity, presented in a previous publication, with a solution of the stochastic Squire equation for the intensity of the fluctuations of the wall-normal vorticity. We have obtained exact solutions of these equations without boundary conditions and solutions in a Galerkin approximation when appropriate boundary conditions are included. These results enable us to make a quantitative assessment of the intensity of these nonequilibrium fluctuations, as well as of the related energy amplification, which are always present, even in the absence of any externally imposed noise.


Powered metaphyseal stapler: an effective and simplified internal fixation system used in multiple types of podiatric surgery.
The multiplicity of types of usage of the powered stapler system in podiatric surgery were explored. The stapler system reduces surgical time and trauma, especially with complex reconstructive and repair procedures. The expedited surgical procedures along with minimized surgical trauma and comfortably implanted staples improved healing rate and less postoperative pain. The important criteria and indications for the usage of powered stapler fixation were reviewed. This relatively new system offers an effective alternative for internal fixation in the foot and ankle.


Rapid methods for the study of both stable and unstable plasmids in Pseudomonas.
Rapid methods for the analysis of degradative plasmids in Pseudomonas are described. Bacterial lysates prepared with alkaline sodium dodecyl sulphate were vigorously stirred in the presence of antifoam agent. Samples were subjected to agarose gel electrophoresis to detect plasmid DNA. After a short period of centrifugation on a sucrose gradient, the lysates yielded plasmid DNA of sufficient purity for restriction endonuclease digestion without further treatment. The methods have proved most useful in the extraction of previously undetected plasmid DNA, some of which appears to be unstable.


Dynamic, contrast-enhanced perfusion MRI in mouse gliomas: correlation with histopathology.
The aim of this study was to develop an MRI protocol to evaluate the growth and vascularity of implanted GL261 mouse gliomas on a 7T microimaging system. Both conventional T(1)- and T(2)-weighted imaging and dynamic, contrast-enhanced T(2)*-weighted imaging were performed on 34 mice at different stages of tumor development. MRI measurements of relative cerebral blood volume (rCBV) were compared to histological assessments of microvascular density (MVD). Enhancement on postcontrast T(1)-weighted images was compared to histological assessments of Evan's blue extravasation. Conventional T(2)-weighted and postcontrast T(1)-weighted images demonstrated tumor growth characteristics consistent with previous descriptions of GL261 glioma. Furthermore, measurements of rCBV from MRI data were in good agreement with histological measurements of MVD from the same tumors. Postcontrast enhancement on T(1)-weighted images was observed at all stages of GL261 glioma progression, even before evidence of angiogenesis, indicating that the mechanism of conventional contrast enhancement in MRI does not require neovascularization. These results provide quantitative support for MRI approaches currently used to assess human brain tumors, and form the basis for future studies of angiogenesis in genetically engineered mouse brain tumor models.


Erythema caused by a localised skin infection with Arthrobacter mysorens.
Skin erythemas of unknown origin are a frequent reason for consulting the general practitioner or dermatologist. Here we report a case of an erythema resembling the erythema migrans manifestation of Lyme disease, but with atypical symptoms like persistent pruritus. The patient had no history of a recent tick-bite but displayed a positive serology for an advanced stage of Lyme borreliosis, which stood in contrast to the clinical manifestation of erythema migrans as a symptom of early Lyme disease. Three skin swabs and soil samples, collected in the area where the patient possibly acquired the infection, were examined by bacterial and fungal culture methods. Microorganisms were identified by using 16 S rRNA gene sequencing and bioinformatics. The patient and soil isolates were compared by employing RAPD analysis. The serum samples of the patient were examined by immunoblotting. Arthrobacter mysorens, a soil bacterium, was isolated from the collected skin and soil samples. The identity of both isolates was determined by molecular fingerprinting methods. A. mysorens was proven to be causative for the erythema by direct isolation from the affected skin and a positive serology, thus explaining the atypical appearance of the erythema compared to erythema migrans caused by Borrelia infection. Infections with A. mysorens might be underreported and microbiological diagnostic techniques should be applied in cases of patients with unclear erythemas, resembling erythema migrans, without a history of tick bites.


Influence of motivation on control hierarchy in the human frontal cortex.
The frontal cortex mediates cognitive control and motivation to shape human behavior. It is generally observed that medial frontal areas are involved in motivational aspects of behavior, whereas lateral frontal regions are involved in cognitive control. Recent models of cognitive control suggest a rostro-caudal gradient in lateral frontal regions, such that progressively more rostral (anterior) regions process more complex aspects of cognitive control. How motivation influences such a control hierarchy is still under debate. Although some researchers argue that both systems work in parallel, others argue in favor of an interaction between motivation and cognitive control. In the latter case it is yet unclear how motivation would affect the different levels of the control hierarchy. This was investigated in the present functional MRI study applying different levels of cognitive control under different motivational states (low vs high reward anticipation). Three levels of cognitive control were tested by varying rule complexity: stimulus-response mapping (low-level), flexible task updating (mid-level), and sustained cue-task associations (high-level). We found an interaction between levels of cognitive control and motivation in medial and lateral frontal subregions. Specifically, flexible updating (mid-level of control) showed the strongest beneficial effect of reward and only this level exhibited functional coupling between dopamine-rich midbrain regions and the lateral frontal cortex. These findings suggest that motivation differentially affects the levels of a control hierarchy, influencing recruitment of frontal cortical control regions depending on specific task demands.


Cytoplasmic free Ca2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes.
Egress of Plasmodium falciparum, from erythrocytes at the end of its asexual cycle and subsequent parasite invasion into new host cells, is responsible for parasite dissemination in the human body. The egress pathway is emerging as a coordinated multistep programme that extends in time for tens of minutes, ending with rapid parasite extrusion from erythrocytes. While the Ca2+ regulation of the invasion of P. falciparum in erythrocytes is well established, the role of Ca2+ in parasite egress is poorly understood. This study analysed the involvement of cytoplasmic free Ca2+ in infected erythrocytes during the multistep egress programme of malaria parasites. Live-cell fluorescence microscopy was used to image parasite egress from infected erythrocytes, assessing the effect of drugs modulating Ca2+ homeostasis on the egress programme. A steady increase in cytoplasmic free Ca2+ is found to precede parasite egress. This increase is independent of extracellular Ca2+ for at least the last two hours of the cycle, but is dependent upon Ca2+ release from internal stores. Intracellular BAPTA chelation of Ca2+ within the last 45 minutes of the cycle inhibits egress prior to parasitophorous vacuole swelling and erythrocyte membrane poration, two characteristic morphological transformations preceding parasite egress. Inhibitors of the parasite endoplasmic reticulum (ER) Ca2+-ATPase accelerate parasite egress, indicating that Ca2+ stores within the ER are sufficient in supporting egress. Markedly accelerated egress of apparently viable parasites was achieved in mature schizonts using Ca2+ ionophore A23187. Ionophore treatment overcomes the BAPTA-induced block of parasite egress, confirming that free Ca2+ is essential in egress initiation. Ionophore treatment of immature schizonts had an adverse effect inducing parasitophorous vacuole swelling and killing the parasites within the host cell. The parasite egress programme requires intracellular free Ca2+ for egress initiation, vacuole swelling, and host cell cytoskeleton digestion. The evidence that parasitophorous vacuole swelling, a stage of unaffected egress, is dependent upon a rise in intracellular Ca2+ suggests a mechanism for ionophore-inducible egress and a new target for Ca2+ in the programme liberating parasites from the host cell. A regulatory pathway for egress that depends upon increases in intracellular free Ca2+ is proposed.


Excess mortality related to seasonal influenza and extreme temperatures in Denmark, 1994-2010.
In temperate zones, all-cause mortality exhibits a marked seasonality, and one of the main causes of winter excess mortality is influenza. There is a tradition of using statistical models based on mortality from respiratory illnesses (Pneumonia and Influenza: PI) or all-cause mortality for estimating the number of deaths related to influenza. Different authors have applied different estimation methodologies. We estimated mortality related to influenza and periods with extreme temperatures in Denmark over the seasons 1994/95 to 2009/10. We applied a multivariable time-series model with all-cause mortality as outcome, activity of influenza-like illness (ILI) and excess temperatures as explanatory variables, controlling for trend, season, age, and gender. Two estimates of excess mortality related to influenza were obtained: (1) ILI-attributable mortality modelled directly on ILI-activity, and (2) influenza-associated mortality based on an influenza-index, designed to mimic the influenza transmission. The median ILI-attributable mortality per 100,000 population was 35 (range 6 to 100) per season which corresponds to findings from comparable countries. Overall, 88% of these deaths occurred among persons ≥ 65 years of age. The median influenza-associated mortality per 100,000 population was 26 (range 0 to 73), slightly higher than estimates based on pneumonia and influenza cause-specific mortality as estimated from other countries. Further, there was a tendency of declining mortality over the years. The influenza A(H3N2) seasons of 1995/96 and 1998/99 stood out with a high mortality, whereas the A(H3N2) 2005/6 season and the 2009 A(H1N1) influenza pandemic had none or only modest impact on mortality. Variations in mortality were also related to extreme temperatures: cold winters periods and hot summers periods were associated with excess mortality. It is doable to model influenza-related mortality based on data on all-cause mortality and ILI, data that are easily obtainable in many countries and less subject to bias and subjective interpretation than cause-of-death data. Further work is needed to understand the variations in mortality observed across seasons and in particular the impact of vaccination against influenza.


Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro.
Dendritic cells are morphologically distinct cells isolated in vitro from peripheral lymphoid organs of mice. They have a buoyant density of less than 1.082 and can be enriched 7-20-fold by isopycnic centrifugation in albumin columns. Surface adherence of enriched populations may yield cultures containing 50% dendritic cells-preparations which can then be studied in more detail. By functional tests, dendritic cells do not represent morphological variants of either lymphocytes or macrophages. They lack lymphocyte surface differentiation markers and do not exhibit the endocytic capacities of macrophages. In tissue culture, they do not differentiate into macrophages. Dendritic cells have a low labeling index in vitro (1.5-2.5%) following administration of [(3)H]thymidine, and this property distinguishes them from large lymphocytes and promonocytes. Dendritic cells also do not possess the functional properties of other types of reticular cells proposed to exist in lymphoid organs, i.e., they do not synthesize collagen-like macromolecules, they are not stem cells for erythroid and myeloid colony formation, and they do not retain antigens or immune complexes on their cell surface. Dendritic cells thus represent a novel cell type on both functional and morphological grounds.


Familiarity-based stimulus generalization of conditioned suppression.
We report that stimulus novelty/familiarity is able to modulate stimulus generalization and discuss the theoretical implications of novelty/familiarity coding. Rats in Skinner boxes received clicker → shock pairings before generalization testing to a tone. Before clicker training, different groups of rats received preexposure treatments designed to systematically modulate the clicker and the tone's novelty and familiarity. Rats whose preexposure matched novelty/familiarity (i.e., either both or neither clicker and tone were preexposed) showed enhanced suppression to the tone relative to rats whose preexposure mixed novelty/familiarity (i.e., only clicker or tone was preexposed). This was not the result of sensory preconditioning to clicker and tone. (PsycINFO Database Record


Characterization of the distal tail fiber locus and determination of the receptor for phage AR1, which specifically infects Escherichia coli O157:H7.
Phage AR1 is similar to phage T4 in several essential genes but differs in host range. AR1 infects various isolates of Escherichia coli O157:H7 but does not infect K-12 strains that are commonly infected by T4. We report here the determinants that confer this infection specificity. In T-even phages, gp37 and gp38 are components of the tail fiber that are critical for phage-host interaction. The counterparts in AR1 may be similarly important and, therefore, were characterized. The AR1 gp37 has a sequence that differs totally from those of T2 and T4, except for a short stretch at the N terminus. The gp38 sequence, however, has some conservation between AR1 and T2 but not between AR1 and T4. The sequences that are most closely related to the AR1 gp37 and gp38 are those of phage Ac3 in the T2 family. To identify the AR1-specific receptor, E. coli O157:H7 was mutated by Tn10 insertion and selected for an AR1-resistant phenotype. A mutant so obtained has an insertion occurring at ompC that encodes an outer membrane porin. To confirm the role of OmpC in the AR1 infection, homologous replacement was used to create an ompC disruption mutant (RM). When RM was complemented with OmpC originated from an O157:H7 strain, but not from K-12, its AR1 susceptibility was fully restored. Our results suggest that the host specificity of AR1 is mediated at least in part through the OmpC molecule.


Usefulness of coronary pressure measurement for functional evaluation of drug-eluting stent restenosis.
Despite the widespread adoption of drug-eluting stent (DES) implantation, the optimal treatment of DES failures remains challenging. The present study evaluated the relation between quantitative angiography and the fractional flow reserve (FFR) in restenotic lesions after DES implantation and the efficacy of FFR in determining whether to treat these lesions. To assess their functional significance, the coronary pressure-derived FFR was measured in 50 DES restenotic lesions (49 patients). Additional intervention was performed in lesions with a FFR <0.8. Major adverse cardiac events were assessed at 12 months after the reintervention procedure. The mean percent diameter stenosis (%DS) was 58 ± 13%. Of the 50 lesions, 20 (40%) were deferred without additional intervention. The FFR and %DS had a negative correlation (r = -0.61, p <0.001). However, when only the lesions with diffuse-type restenosis (15 lesions) were analyzed, the degree of correlation decreased (r = -0.56, p = 0.12). Although most lesions (89%) with a %DS of ≥70 had significant functional ischemia, among 41 lesions with a %DS <70, only 20 (49%) had demonstrated functional patency. The incidence of adverse events during the 12 months of follow-up after FFR-guided treatment was 18.0% (23.3% in the FFR <0.80 group and 10.0% in FFR ≥0.80 group). In conclusion, a discrepancy was found between functional ischemia measured by the FFR and the angiographic %DS, in particular, in moderate- or diffuse-type restenotic lesions after DES implantation. The outcome of FFR-guided deferral in patients with DES in-stent restenosis seems favorable.


The influence of smoking and homocysteine on subclinical atherosclerosis is modified by the connexin37 C1019T polymorphism - The Cardiovascular Risk in Young Finns Study.
A polymorphism C1019T on the connexin37 (Cx37) gene has been found to associate with coronary artery disease. There are conflicting results on which allele confers risk, and the possibility of interactions between the polymorphism and risk factors has been raised. In this study, we examined interactions between the Cx37 polymorphism and common risk factors and their associations to early vascular parameters of atherosclerosis: carotid artery intima-media thickness (IMT), and carotid artery compliance (CAC) and brachial artery flow mediated dilatation (FMD). A population of 1440 healthy young adults from the Cardiovascular Risk in Young Finns Study was studied. The subjects were genotyped and their cardiovascular risk factor and ultrasound data gathered in 2001 were used for the statistical analyses. In the whole population, homocysteine in subjects with the TT genotype was found to be associated with higher FMD values (p for interaction 0.038) and remained so in three different adjusted models (p for interaction 0.022-0.038). In women with the CC genotype, smoking was found to be associated with higher FMD values and the smoking-by-genotype interaction remained significant in three adjusted models (p for interaction 0.001-0.041). In women with TT genotype, the effect of smoking was opposite, i.e., FMD values for smokers were lower compared to non-smokers. In men, physical activity interacted with Cx37 on CAC in the CT and TT genotypes (p for interaction 0.011). No significant interactions were found to predict IMT. The effect of smoking and homocysteine levels on arterial endothelial functions and elasticity were modified by the allelic variation of the Cx37 gene. These data suggest that variation in the connexin gene may modify effects risk factors have on vascular function.


Magnetic particle-based ultrasensitive biosensors for diagnostics.
The process of sensitive and accurate detection of small quantities of disease biomarkers is critical for the clinical diagnosis of disease. In this regard, magnetic particles (MPs) have been widely used because of their unique magnetic properties allowing for efficient target capture, enrichment and convenient separation. These properties, coupled with great signal amplification, have enabled MP-based biosensors to achieve ultrasensitivities. Over the past few years, several ultrasensitive MP-based biosensors suitable for early clinical diagnostics have been reported. This article highlights some of the most recent developments, with a focus on MP-based ultrasensitive assays that use an antibody or aptamer as the target-binding agent, and that utilize efficient signal amplification/readout strategies.


Heavy burden of intestinal parasite infections in Kalena Rongo village, a rural area in South West Sumba, eastern part of Indonesia: a cross sectional study.
Intestinal parasitic infections (IPIs) are one of the major public health problems, especially in the rural area of developing countries with low socio-economic status and poor sanitation. The study was aimed to determine the prevalence of IPIs among the inhabitants of a rural area in South West Sumba, eastern part of Indonesia. A cross-sectional study was done in Kalena Rongo village, South West Sumba in April 2014. Stool samples were collected and examined for IPIs using direct smear method. Faecal samples were collected from 424 of 473 inhabitants of the village, age 2 months to 80 years. About 95.5 % (405/424) of the participants had any IPIs. The most prevalent parasites found were Ascaris lumbricoides 65.8 % (279/424), Trichuris trichiura 60.4 % (256/424), hookworms 53.5 % (227/424), Blastocystis hominis 34.4 % (146/424), Entamoeba histolytica 17.9 % (76/424), and Giardia lamblia 4.5 % (19/424). The villagers used no latrine and defecated in their backyard. Clean water sources were scarce and far from the village. In Kalena Rongo village, the rural area in eastern part of Indonesia, the finding of IPIs was conspicuous and therefore expressed the poor hygiene and absence of proper sanitation in the area. Integrated efforts, such as improving infrastructure to provide clean water source and educating the inhabitants for appropriate hygienic lifestyle are needed.


Seroprevalence of fasciolosis and the difference of fasciolosis between rural area and city center in Isparta, Turkey.
To investigate the seroprevalence of fasciolosis and the possible causes of differences between rural and city center. We undertook a multi-stage sampling analysis of data from Isparta, Turkey, between March and June 2004. Four hundred and fifteen individuals participants from Isparta center and 171 from Asagi Gokdere village were included in the study. Fasciola hepatica (F. hepatica) specific antibodies were analyzed using excretory-secretory (ES)-enzyme-linked immunosorbent assay (ELISA) method. Fasciola hepatica antibodies were detected as positive in 10 (2.4%) of 415 people whose sera were collected from the city center and 16 (9.3%) of 171 people from Asagi Gokdere village. The positivity rates between village and city center were found statistically significant. A statistical difference was noted for fasciolosis positivity between individuals who have ingested water cress and who have not. Fasciolosis was not detected in the individuals who used to wash vegetables with water containing vinegar. Most of the patients in this region reported consumption of uncooked or unwashed water cress. Watering channel is one of the major risk factors of fasciolosis. Therefore, it is essential to determine the watering systems in this region. Moreover, ES-ELISA would be useful in investigating the laboratory diagnosis of fasciolosis.


Avoidant/restrictive food intake disorder: A systematic scoping review of the current literature.
Avoidant/restrictive food intake disorder (ARFID) was recently introduced to psychiatric nosology to describe a group of patients who have avoidant or restrictive eating behaviours that are not motivated by a body image disturbance or a desire to be thinner. This scoping review aimed to systematically assess the extent and nature of the ARFID literature, to identify gaps in current understanding, and to make recommendations for further study. Following an extensive database search, 291 unique references were identified. When matched against pre-determined eligibility criteria, 78 full-text publications from 14 countries were found to report primary, empirical data relating to ARFID. This literature was synthesised and categorised into five subject areas according to the central area of focus: diagnosis and assessment, clinical characteristics, treatment interventions, clinical outcomes, and prevalence. The current evidence base supports ARFID as a distinct clinical entity, but there is a limited understanding in all areas. Several possible avenues for further study are indicated, with an emphasis placed on first parsing this disorder's heterogeneous presentation. A better understanding of the varied mechanisms which drive food avoidance and/or restriction will inform the development of targeted treatment interventions, refine screening tools and impact clinical outcomes.


Intraoperative Injection of Botulinum Toxin A into Orbicularis Oculi Muscle for the Treatment of Crow's Feet.
The purpose of this investigation was to evaluate the degree of efficacy of eliminating crow's feet by means of direct injection of botulinum toxin A into orbicularis oculi muscles under direct surgical vision during either blepharoplasty or face lift operations. Eighteen patients were injected with Botox A-14 in each orbicularis oculi muscle. Dilution was obtained by adding 4 ml of preservative-free saline to 100 IU of Botox A. Doses ranged from 15 to 50 IU in each muscle, varying according to the severity of wrinkles and intensity of muscle contraction. In 10 patients (56 percent), the Botox was injected throughout the outer surface of both orbicularis oculi dissected during a face-lift operation. In eight other patients (44 percent), the toxin was injected into the inner surface of both orbicularis oculi exposed during classic blepharoplasty procedures. Most authors have demonstrated that the effect produced by transcutaneous Botox lasts between 4 and 6 months; the paralysis obtained by direct muscular injection was effective for 9 months in 14 patients (78 percent) and 10 months in the other 4 patients (22 percent). Results were documented by means of preinjection and postinjection photographs, videotapes, and electromyographs. Neither local nor general adverse effects were noted. The improvement obtained in crow's feet was satisfactory to the patient and to us. The use of Botox intraoperatively permitted at the same time not only the treatment of crow's feet by paralysis of orbicularis oculi muscles but also the correction of senile changes in the lids and face by means of either blepharoplasty or face-lift operations.


Transcriptional regulation of the raffinose family oligosaccharides pathway in Sorghum bicolor reveals potential roles in leaf sucrose transport and stem sucrose accumulation.
Bioenergy sorghum hybrids are being developed with enhanced drought tolerance and high levels of stem sugars. Raffinose family oligosaccharides (RFOs) contribute to plant environmental stress tolerance, sugar storage, transport, and signaling. To better understand the role of RFOs in sorghum, genes involved in myo-inositol and RFO metabolism were identified and relative transcript abundance analyzed during development. Genes involved in RFO biosynthesis (SbMIPS1, SbInsPase, SbGolS1, SbRS) were more highly expressed in leaves compared to stems and roots, with peak expression early in the morning in leaves. SbGolS, SbRS, SbAGA1 and SbAGA2 were also expressed at high levels in the leaf collar and leaf sheath. In leaf blades, genes involved in myo-inositol biosynthesis (SbMIPS1, SbInsPase) were expressed in bundle sheath cells, whereas genes involved in galactinol and raffinose synthesis (SbGolS1, SbRS) were expressed in mesophyll cells. Furthermore, SbAGA1 and SbAGA2, genes that encode neutral-alkaline alpha-galactosidases that hydrolyze raffinose, were differentially expressed in minor vein bundle sheath cells and major vein and mid-rib vascular and xylem parenchyma. This suggests that raffinose synthesized from sucrose and galactinol in mesophyll cells diffuses into vascular bundles where hydrolysis releases sucrose for long distance phloem transport. Increased expression (>20-fold) of SbAGA1 and SbAGA2 in stem storage pith parenchyma of sweet sorghum between floral initiation and grain maturity, and higher expression in sweet sorghum compared to grain sorghum, indicates these genes may play a key role in non-structural carbohydrate accumulation in stems.


Out of the mouths of plants: the molecular basis of the evolution and diversity of stomatal development.
Stomata are microscopic valves on the plant epidermis that played a critical role in the evolution of land plants. Studies in the model dicot Arabidopsis thaliana have identified key transcription factors and signaling pathways controlling stomatal patterning and differentiation. Three paralogous Arabidopsis basic helix-loop-helix proteins, SPEECHLESS (SPCH), MUTE, and FAMA, mediate sequential steps of cell-state transitions together with their heterodimeric partners SCREAM (SCRM) and SCRM2. Cell-cell signaling components, including putative ligands, putative receptors, and mitogen-activated protein kinase cascades, orient asymmetric cell divisions and prevent overproduction and clustering of stomata. The recent availability of genome sequence and reverse genetics tools for model monocots and basal land plants allows for the examination of the conservation of genes important in stomatal patterning and differentiation. Studies in grasses have revealed that divergence of SPCH-MUTE-FAMA predates the evolutionary split of monocots and dicots and that these proteins show conserved and novel roles in stomatal differentiation. By contrast, specific asymmetric cell divisions in Arabidopsis and grasses require unique molecular components. Molecular phylogenetic analysis implies potential conservation of signaling pathways and prototypical functions of the transcription factors specifying stomatal differentiation.


A Twofold Approach in Loss Reduction of KTa0.5Nb0.5O3 Ferroelectric Layers for Low-Loss Tunable Devices at Microwaves.
Ferroelectric oxide films are attractive to design and fabricate reconfigurable and miniaturized planar devices operating at microwaves due to the large electric field dependence of their dielectric permittivity. In particular, KTa1-xNbxO3 (KTN) ferroelectric material presents a high tunability under moderate dc bias electric field. However, its intrinsic dielectric loss strongly contributes to the global loss of the related devices and limits their application areas at microwaves. In this paper, a twofold approach is investigated to reduce the device loss. The intrinsic loss of KTN is first reduced by doping the ferroelectric material with a low-loss dielectric material, namely, MgO. Second, the doped ferroelectric films are confined using an original laser microetching process. Both routes have been implemented here to provide a synergic effect on the total insertion loss of the microwave test device, namely, a coplanar waveguide stub resonator. The experimental data demonstrate a decrease of the intrinsic loss by a factor of ~2 and a decrease of the global loss by a factor of ~4 with a frequency tunability close to 10% at ~10 GHz under a moderate biasing (80 kV/cm).


Language and speech perception of young children with bimodal fitting or bilateral cochlear implants.
This paper compares language development and speech perception of children with bimodal fitting (a cochlear implant in one ear and a hearing aid in the opposite ear) or bilateral cochlear implantation. Participants were children enrolled in the Longitudinal Outcomes of Children with Hearing Impairment study. Language development was assessed at 3 years of age using standardized tests. Speech perception was evaluated at 5 years of age. Speech was presented from a frontal loudspeaker, and babble noise was presented either from the front or from both sides. On average, there was no significant difference in language outcomes between 44 children with bimodal fitting and 49 children with bilateral cochlear implants; after controlling for a range of demographic variables. Earlier age at cochlear implant activation was associated with better outcomes. Speech perception in noise was not significantly different between children with bimodal fitting and those with bilateral cochlear implants. Compared to normal-hearing children, children with cochlear implants required a better signal-to-noise ratio to perform at the same level, but demonstrated spatial release from masking of a similar magnitude. This population-based study found that language scores for children with bilateral implants were higher than those with bimodal fitting or those with unilateral implants, but neither reached significance level.


Honokiol inhibits sphere formation and xenograft growth of oral cancer side population cells accompanied with JAK/STAT signaling pathway suppression and apoptosis induction.
Eliminating cancer stem cells (CSCs) has been suggested for prevention of tumor recurrence and metastasis. Honokiol, an active compound of Magnolia officinalis, had been proposed to be a potential candidate drug for cancer treatment. We explored its effects on the elimination of oral CSCs both in vitro and in vivo. By using the Hoechst side population (SP) technique, CSCs-like SP cells were isolated from human oral squamous cell carcinoma (OSCC) cell lines, SAS and OECM-1. Effects of honokiol on the apoptosis and signaling pathways of SP-derived spheres were examined by Annexin V/Propidium iodide staining and Western blotting, respectively. The in vivo effectiveness was examined by xenograft mouse model and immunohistochemical tissue staining. The SP cells possessed higher stemness marker expression (ABCG2, Ep-CAM, Oct-4 and Nestin), clonogenicity, sphere formation capacity as well as tumorigenicity when compared to the parental cells. Treatment of these SP-derived spheres with honokiol resulted in apoptosis induction via Bax/Bcl-2 and caspase-3-dependent pathway. This apoptosis induction was associated with marked suppression of JAK2/STAT3, Akt and Erk signaling pathways in honokiol-treated SAS spheres. Consistent with its effect on JAK2/STAT3 suppression, honokiol also markedly inhibited IL-6-mediated migration of SAS cells. Accordingly, honokiol dose-dependently inhibited the growth of SAS SP xenograft and markedly reduced the immunohistochemical staining of PCNA and endothelial marker CD31 in the xenograft tumor. Honokiol suppressed the sphere formation and xenograft growth of oral CSC-like cells in association with apoptosis induction and inhibition of survival/proliferation signaling pathways as well as angiogenesis. These results suggest its potential as an integrative medicine for combating oral cancer through targeting on CSCs.


Comparison of faecal monitoring and area under the curve techniques to determine iron absorption in humans using stable isotope labelling.
The objective of the study was to compare faecal monitoring and area under the curve (AUC) techniques for measuring iron absorption from a stable isotope label. Nine healthy female subjects (age: 33+/-8 yr) were recruited to take part in the study. After an overnight fast, each subject received a 5 mg dose of highly enriched Fe-57 and all faecal samples were collected for 10 days post-dose to allow for estimation of iron absorption by the faecal monitoring method (geometric mean: 25%). Serial blood samples (12 in total) were also collected from each volunteer for 6h post-dose to estimate iron absorption by the well-validated area under the plasma iron concentration curve (AUC) method (geometric mean: 18%). The faecal monitoring method yields higher iron absorption results compared to AUC. This discrepancy may be due to the steps involved in faecal processing where systematic errors are likely to take place and also to the lack of complete faecal recovery associated with issues of cleanliness and hygiene when passing stools. Both of these lead to losses of the unabsorbed isotope and to an overestimate of iron absorption.


HIV-infected adolescents with hemophilia: adaptation and coping. The Hemophilia Behavioral Intervention Evaluation Project.
It is estimated that 70% of individuals with factor VIII deficiency hemophilia who received blood products before 1985 are infected with human immunodeficiency virus (HIV). The goal of the current study was to assess how adolescents with hemophilia cope with reminders of their HIV status, because adaptation is likely to have implications for these individuals' quality of life and adherence to safer sex recommendations. Participants included 297 HIV-positive adolescents with hemophilia who were recruited from 11 sites across the United States. Adolescents reported on the use and effectiveness of strategies for coping with reminders of their HIV status. A significant degree of distress was reported in response to such reminders, with anger being the most commonly reported emotion. Although a wide variety of coping strategies had been tried, participants reported using resignation (80.9%), self-calming (78.8%), and distraction (76.4%) most frequently in their attempts to cope with reminders of HIV. Self-blame (3.6%), engaging in risky behaviors (22.2%), thinking about sex (25.4%), and drug/alcohol use (29.1%) were used least. These adolescents tended to rate more active cognitive and behavioral coping strategies (eg, cognitive restructuring, seeking social support, physical activity) as most effective, whereas passive strategies (eg, wishful thinking, blaming others) were reported to be least helpful. Those individuals who reported being distressed by reminders of HIV endorsed most of the coping strategies significantly more often than the nondistressed group, although ineffective strategies were commonly chosen. Sexually active adolescents were more likely than their abstinent peers to cope by thinking about sex, engaging in risky behaviors, or using alcohol and drugs. In this population of adolescents who have known their serostatus for several years, distress about everyday reminders of HIV appears to be associated with ineffective coping strategies.


Dark adaptation and falls in the elderly.
The human eye is capable of adjusting to wide variations in light intensity by altering the pupil size and the sensitivity of the retina to light. Falls are one of the commonest problems of old age, and the causes are multifactorial. As falls often occur at night, this study was designed to compare dark adaptation in groups of elderly fallers and non-fallers. Twenty-two female patients in a geriatric assessment ward were included in the study and classified as 'fallers' or 'non-fallers'. A full ophthalmic examination was performed on each subject, and dark adaptation measured, in a single-blind fashion, using the Friedmann visual field analyser; following initial bleaching of the retinal photoreceptors, the room was placed in total darkness and retinal sensitivity measured every minute for 20 min. The values, expressed as log filter density, were plotted against duration of time in the dark. The mean values at 5 min were 0.9 in the fallers and 1.4 in the non-fallers (p less than 0.02 unpaired t test) and at 20 min 2.2 and 3.2, respectively (p less than 0.04). These results indicate reduced retinal sensitivity and hence impaired dark adaptation in the falling group. Lighting levels in the homes of many old people have been shown to be inadequate. Impaired dark adaptation may leave an elder person virtually blind for a minute or more on moving from a bright room to a darker area. The provision of night lights in the homes of recurrent fallers may offset the influence of impaired dark adaptation.


The fast is positive, now what? Derivation of a clinical decision rule to determine the need for therapeutic laparotomy in adults with blunt torso trauma and a positive trauma ultrasound.
The object of this study was to derive a clinical decision rule for therapeutic laparotomy among adult blunt trauma patients with a positive abdominal ultrasound for trauma (FAST) examination. We retrospectively reviewed the trauma registry and medical records of all critical trauma patients who underwent a FAST examination in the emergency department (ED) in a university Level I trauma center over a 3-year period. Blunt trauma patients aged >16 years who had a positive FAST examination (defined as the presence of intraperitoneal fluid) were eligible. We selected seven clinical and ultrasound variables available during ED resuscitation for analysis: age, presence of an episode of hypotension (systolic blood pressure <90 torr in the ED), presence of abdominal tenderness, chest injury, pelvic fracture, femur fracture, and FAST fluid location (right upper quadrant [RUQ] only; RUQ plus other location; other location only). The primary outcome variable was whether a laparotomy was performed and whether this laparotomy was needed to provide the definitive surgical intervention ("therapeutic laparotomy"). We analyzed the variables using binary recursive partitioning analysis to create a decision rule. There were 2336 FAST examinations performed during the study period, resulting in 230 (9.8%) positive examinations in patients meeting inclusion criteria. There were 135 patients who had therapeutic laparotomies and 95 who did not need laparotomy. The groups were similar in baseline characteristics. In the recursive partitioning analysis, the first node in the decision tree was the presence of fluid in the RUQ. Of the 144 patients with RUQ fluid, 105 (73%, 95% confidence interval [CI] 64%-80%) required therapeutic laparotomy. Of the 86 patients without RUQ fluid, 30 (35%, 95% CI 25%-46%) nevertheless required therapeutic laparotomies, and the variables blood pressure, femur fracture, abdominal tenderness, and age further divided these patient into high- and low-risk groups. Of the 12 patients without RUQ fluid who had normal blood pressures, no femur fractures, no abdominal tenderness, and were aged 60 years and younger, none (95% CI 0%-22%) required therapeutic laparotomy. In conclusion, given a positive FAST examination, the presence of fluid in the RUQ is an important predictor of the need for therapeutic laparotomy. In the absence of fluid in the RUQ, there are other clinical variables that may allow for the development of a clinical decision rule regarding the need for therapeutic laparotomy.


Cue combination anisotropies in contour integration: The role of lower spatial frequencies.
The combination of local orientation collinearity and spatial frequency contrast in contour integration was studied in two experiments using a 2AFC contour detection and discrimination task. Target contours were defined by local orientation collinearity, spatial frequency contrast between contour and background elements, or both cues. Experiments differed in the source of spatial frequency contrast by manipulating the spatial frequency of either contour or background elements. Cue summation gains, defined as the performance benefit of double cue conditions over single cue conditions, were evaluated and tested against the predictions derived from probability summation and linear summation. Summation gains were generally stronger than linear summation and tended to increase with the single-cue performance level until limited by ceiling effects. Cue summation was particularly large when contour elements exhibited a lower spatial frequency than background elements, regardless of the absolute spatial frequency ranges. The highly effective integration of lower spatial frequency contours in cluttered surrounds is discussed in the context of recent findings on high-level neural representations of contour integration as well as feature synergy.


Rasip1 is essential to blood vessel stability and angiogenic blood vessel growth.
Cardiovascular function depends on patent, continuous and stable blood vessel formation by endothelial cells (ECs). Blood vessel development initiates by vasculogenesis, as ECs coalesce into linear aggregates and organize to form central lumens that allow blood flow. Molecular mechanisms underlying in vivo vascular 'tubulogenesis' are only beginning to be unraveled. We previously showed that the GTPase-interacting protein called Rasip1 is required for the formation of continuous vascular lumens in the early embryo. Rasip1(-/-) ECs exhibit loss of proper cell polarity and cell shape, disrupted localization of EC-EC junctions and defects in adhesion of ECs to extracellular matrix. In vitro studies showed that Rasip1 depletion in cultured ECs blocked tubulogenesis. Whether Rasip1 is required in blood vessels after their initial formation remained unclear. Here, we show that Rasip1 is essential for vessel formation and maintenance in the embryo, but not in quiescent adult vessels. Rasip1 is also required for angiogenesis in three models of blood vessel growth: in vitro matrix invasion, retinal blood vessel growth and directed in vivo angiogenesis assays. Rasip1 is thus necessary in growing embryonic blood vessels, postnatal angiogenic sprouting and remodeling, but is dispensable for maintenance of established blood vessels, making it a potential anti-angiogenic therapeutic target.


Separate pathways for p53 induction by ionizing radiation and N-(phosphonoacetyl)-L-aspartate.
The tumor suppressor gene product, p53, appears to be a significant participant in signaling pathways that mediate cellular responses to cytotoxic stresses. In particular, p53 appears to be a critical determinant of whether the cell lives or dies and how it progresses through the cell cycle after the cytotoxic exposure. Many of the molecular details for these signaling pathways remain to be elucidated, and whether all cytotoxic signals utilize the same pathway to increase p53 expression is not clear. Here, we demonstrate the existence of cell types in which the induction of p53 and associated G1 arrest by the antimetabolite, N-(phosphonoacetyl)-L-aspartate (PALA), is defective, whereas p53 induction and G1 arrest induced by ionizing radiation are intact. These observations demonstrate the existence of genetic defects that can alter p53 induction and associated cellular outcomes after some, but not all, cytotoxic insults and suggest distinct pathways of p53 induction by PALA and ionizing radiation.


Neuronal activity in prepositus nucleus correlated with eye movement in the alert cat.
1. In nine alert chronically prepared cats the activity of 177 neurons was recorded in the prepositus nucleus during either spontaneous eye movement or that induced by natural vestibular and optokinetic stimulation. 2. In 116 cells, eye position and/or eye velocity was precisely and unequivocally encoded whatever the origin of the eye movement. These cells were separated into different populations according to the eye movement variable encoded and the directionality of the neuronal response. The firing rates of the remaining 61 cells were loosely related to eye movements because a variety of discharge patterns were observed during identical eye movements. In the latter case, some other unmeasured variable (e.g., neck or visual) was suggested to be encoded in the firing frequency. 3. Discharge rate changed before the eyes began to move and reached a new steady level during fixation following a saccade into a particular direction of the orbit. The ondirection was horizontal for 59% of the neurons, vertical for 17%, and oblique for 24%. 4. Regardless of their preferred direction, the discharge rate in 19% of the neurons was closely proportional to eye position. The range in sensitivity was from 1.1 to 7.5 spikes X s-1/deg. Weak velocity responses were occasionally observed during the slow phase of vestibular and optokinetic nystagmus including during saccades. This class of neurons exhibited a very regular interspike interval for a given position of fixation. Since mainly eye position was encoded, these cells were called position neurons. 5. Other prepositus neurons showed both position and velocity sensitivity during saccades and fixation. Their firing rate encoded eye position over the same range as above and also coded velocity during the slow phase of vestibular and optokinetic nystagmus. Depending on the weighting between the position and velocity proportionality constants, these neurons were classified into position-velocity (48%) or velocity-position (33%) groups. 6. The distribution of the above responses led to the conclusion that the prepositus nucleus plays a role in vertical and horizontal spatial integration. The predominance of horizontal activity suggested that the nucleus may be a significant site underlying genesis of horizontal eye position.


[Changes in the wave composition of evoked potentials during treatment of endogenous depression].
Evoked potentials (EPs) were studied in patients with endogenic depression prior to and during the therapy. It was found that a reduction in the maximum amplitude of EPs reflecting the initial severity of depression could not serve as an indicator of its time-course in the treatment by tricyclic antidepressants. In contrast, the newly identified electrophysiological sign of endogenic depression, a number of EP waves, shifted toward normalization in the process of the treatment parallelled by a decrease in the severity of the depressive syndrome.


Neuroplastic Sensorimotor Resting State Network Reorganization in Children With Hemiplegic Cerebral Palsy Treated With Constraint-Induced Movement Therapy.
Using resting state functional magnetic resonance imaging (MRI), we aim to understand the neurologic basis of improved function in children with hemiplegic cerebral palsy treated with constraint-induced movement therapy. Eleven children including 4 untreated comparison subjects diagnosed with hemiplegic cerebral palsy were recruited from 3 clinical centers. MRI and clinical data were gathered at baseline and 1 month for both groups, and 6 months later for the case group only. After constraint therapy, the sensorimotor resting state network became more bilateral, with balanced contributions from each hemisphere, which was sustained 6 months later. Sensorimotor resting state network reorganization after therapy was correlated with a change in the Quality of Upper Extremity Skills Test score at 1 month (r = 0.79, P = .06), and Canadian Occupational Performance Measure scores at 6 months (r = 0.82, P = .05). This clinically correlated resting state network reorganization provides further evidence of the neuroplastic mechanisms underlying constraint-induced movement therapy.


Pediatric Phalanx Fractures.
Phalangeal fractures are extremely common in the pediatric and adolescent populations. The incidence of phalangeal fractures peaks in children ages 10 to 14 years, corresponding to the age in which children begin contact sports. Younger children are more likely to experience crush injuries, whereas older children often sustain phalangeal fractures during sports. The physis is particularly susceptible to fracture because of the biomechanically weak nature of the physis compared with the surrounding ligaments and bone. Phalangeal fractures are identified through a thorough physical examination and are subsequently confirmed with radiographic evaluation. Management of pediatric phalangeal fractures is dependent on the age of the child, the severity of the injury, and the degree of fracture displacement. Nondisplaced fractures are often managed nonsurgically with immobilization, whereas unstable, displaced fractures may require surgery, which is often a closed rather than open reduction and percutaneous pinning.


Preparation, Characterization, and In Vitro Pharmacodynamics and Pharmacokinetics Evaluation of PEGylated Urolithin A Liposomes.
Urolithin A (Uro-A), a metabolite of ellagitannins in mammals' intestinal tract, displays broad biological properties in preclinical models, including anti-oxidant, anti-inflammatory, and anti-tumor effects. However, the clinical application of Uro-A is restricted because of its low aqueous solubility and short elimination half-life. Our purpose was to develop a delivery system to improve the bioavailability and anti-tumor efficacy of Uro-A. To achieve this goal, urolithin A-loaded PEGylated liposomes (Uro-A-PEG-LPs) were prepared for the first time and its physicochemical properties and anti-tumor efficacy in vitro were evaluated. The morphology of Uro-A-PEG-LPs displayed a uniform sphere under transmission electron microscope. The particle size, polydispersity index, zeta potential, and encapsulation efficiency of Uro-A-PEG-LPs were 122.8 ± 7.4 nm, 0.25 ± 0.16, - 25.5 ± 2.3 mV, and 94.6 ± 1.6%, respectively. Moreover, Uro-A-PEG-LPs possessed higher stability and could be stably stored at 4°C for a long time. In vitro release characteristics indicated that Uro-A-PEG-LPs possessed superior sustained release properties. The results of confocal laser scanning microscopy experiment showed that the coumarin 6-loaded PEGylated liposomes (C6-PEG-LPs) have superior cellular uptake than that of conventional liposomes. In addition, in vitro tests demonstrated that Uro-A-PEG-LPs elevated cytotoxicity and pro-apoptotic effect in human hepatoma cells comparing with free Uro-A. Furthermore, the results of pharmacokinetic experiments showed that the t1/2, AUC0-t, and MRT0-t of Uro-A-PEG-LPs increased to 4.58-fold, 2.33-fold, and 2.43-fold than those of free Uro-A solution, respectively. Collectively, these manifested that PEGylated liposomes might be a potential delivery system for Uro-A to prolonging in vivo circulation time, promoting cellular uptake, and enhancing its anti-tumor efficacy.


Upregulation of myocardial Annexin A5 in hypertensive heart disease: association with systolic dysfunction.
To investigate whether Annexin A5 (AnxA5) is related to hypertensive heart disease (HHD) and whether this relation is dependent of apoptosis. Hypertensives without cardiac abnormalities (stage A), with left ventricular hypertrophy (LVH) (stage B), and with LVH and clinical manifestations of chronic HF (stage C), were studied. AnxA5 was quantified in endomyocardial biopsies by real time RT-PCR, Western blot, and immunohistochemistry, and apoptosis by DNA fragmentation, caspase-3 activation, and PARP and Bax/Bcl-2 ratios. Plasma AnxA5 was measured by ELISA in samples from the coronary sinus and the antecubital vein. Although AnxA5 mRNA did not change, myocardial and plasma AnxA5 were increased in hypertensives stages B and C compared with normotensives and hypertensives stage A. Myocardial AnxA5 was inversely correlated with parameters assessing systolic function in all hypertensives, this association being independent of apoptosis. Myocardial AnxA5 was directly correlated with plasma AnxA5. Plasma AnxA5 was inversely correlated with systolic function in all hypertensives. This cross-sectional study shows that myocardial AnxA5 upregulation is associated with HHD and impairment of systolic function in hypertensive patients, this association being independent of apoptosis. Plasma AnxA5 can be a marker of myocardial AnxA5 upregulation and systolic dysfunction in patients with HHD.


Yield of EBUS-TBNA for the diagnosis of sarcoidosis: impact of operator and cytopathologist experience.
Studies have reported a high diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of sarcoidosis. We sought to review the yield of EBUS-TBNA for the diagnosis of sarcoidosis at our institution over time, and examine factors that may influence this yield. Patients who underwent EBUS-TBNA for suspected sarcoidosis between December 2008 and November 2011 were identified. EBUS was performed without rapid on-site evaluation (ROSE) of samples. The final diagnosis was based on the results of all invasive diagnostic procedures and/or clinical follow-up. Logistic regression analysis was used to examine the effect of various factors on yield. 43 patients underwent 45 EBUS-TBNA procedures for suspected sarcoidosis. A total of 115 lymph nodes were sampled. The 21 G needle was used in 51% of procedures. The mean number of lymph node stations sampled was 2.6 (SD 0.7) and the mean number of needle passes per procedure was 7.8 (SD 2.0). Non-necrotising granulomatous inflammation was detected in EBUS-TBNA samples from 34/45 (76%) procedures. The overall diagnostic yield increased to 36/45 (80%) following a cytopathology review for this study. Needle gauge, number of lymph node stations sampled and number of needle passes were not associated with diagnostic yield. The yield of EBUS-TBNA increased significantly after the first 15 procedures performed for suspected sarcoidosis; the 2 additional cases diagnosed after the cytopathology review were part of this early experience. EBUS-TBNA is a valuable technique for the diagnosis of sarcoidosis when performed without ROSE. The yield of the procedure improved significantly over time, based on operator and cytopathologist experience.


[Cholera and environmental medicine in the manuscript "Cholera-morbus" (1832), by Antonio Correa de Lacerda (1777-1852)].
In the first half of the nineteenth century, the environmentalist paradigm dominated medical debate. In Brazil, it engendered the construction of a hygienist agenda that framed physicians' work and provided an interpretive key to public health-related issues The article addresses these and other questions from teh perspective of a text by Portuguese physician Antonio Correa de Lacerda who resided in Belém (Pará) and São Luís (Maranhão) between 1818 and 1852. Entitled "Cholera-morbus," the manuscript was written in 1832, the year the epidemic hit Paris. Lacerda calls on different areas of knowledge in his presentation of a coherent explanation of the disease, affording us a view of an anticontagionist interpretation grounded in anatomopathological practice. He likewise demonstrates how it was possible for a provincial doctor to produce original knowledge on the relation between climate, health, and culture, including the medicinal use of Amazon plants.


[Impact of admission blood glucose on prognosis of ST-segment elevation myocardial infarction patients with or without known diabetes].
To evaluate the impact of admission blood glucose level on 30-day mortality in ST-segment elevation acute myocardial infarction (STEMI) patients with or without known diabetes. This observational analysis enrolled 7446 Chinese STEMI patients hospitalized within 12 hours of symptom onset joining a global randomized controlled trial. The patients with or without known diabetes were divided into different groups by the admission blood glucose level: < 6.1 mmol/L (n = 2018), 6.1 to 7.7 mmol/L (n = 2170), 7.8 to 11.0 mmol/L (n = 1929), 11.1 to 13.0 mmol/L (n = 465), > 13.0 mmol/L (n = 864), the last three groups were defined as the hyperglycemia group. The 30-day mortality was analyzed. A substantial proportion of hyperglycemic patients did not have recognized diabetes. Insulin use during hospitalization in hyperglycemic patients without known diabetes was significantly lower than that in known diabetics with similar glucose levels. Incidence of 30-day mortality increased in proportion to increasing admission glucose levels in patients without known diabetes (glucose< 6.1 mmol/L 6.8%, 6.1 to 7.7 mmol/L 8.3%, glucose > 13.0 mmol/L 18.6%, P < 0.001). In patients with known diabetes, the 30-day mortality was 16.7% with admission glucose < 6.1 mmol/L and 8.2% with admission glucose 6.1 to 7.7 mmol/L, and 22.0% with admission glucose > 13.0 mmol/L (P < 0.001). Except in patients with admission glucose > 13.0 mmol/L, the 30-day mortality was significantly higher in patients without known diabetes than in patients with known diabetes at comparable admission glucose levels (all P < 0.05). Comparing with the known diabetic patients, admission hyperglycemia is common in STEMI patients without known diabetes and was associated with higher 30-day mortality compared to known diabetes patients with comparable admission glucose level with the exception of admission glucose level > 13.0 mmol/L.


Pmp-like proteins Pls1 and Pls2 are secreted into the lumen of the Chlamydia trachomatis inclusion.
The obligate intracellular pathogen Chlamydia trachomatis secretes effector proteins across the membrane of the pathogen-containing vacuole (inclusion) to modulate host cellular functions. In an immunological screen for secreted chlamydial proteins, we identified CT049 and CT050 as potential inclusion membrane-associated proteins. These acidic, nonglobular proteins are paralogously related to the passenger domain of the polymorphic membrane protein PmpC and, like other Pmp proteins, are highly polymorphic among C. trachomatis ocular and urogenital strains. We generated antibodies to these Pmp-like secreted (Pls) proteins and determined by immunofluorescence microscopy that Pls1 (CT049) and Pls2 (CT050) localized to globular structures within the inclusion lumen and at the inclusion membrane. Fractionation of membranes and cytoplasmic components from infected cells by differential and density gradient centrifugation further indicated that Pls1 and Pls2 associated with membranes distinct from the bulk of bacterial and inclusion membranes. The accumulation of Pls1 and, to a lesser extent, Pls2 in the inclusion lumen was insensitive to the type III secretion inhibitor C1, suggesting that this translocation system is not essential for Pls protein secretion. In contrast, Pls secretion and stability were sensitive to low levels of beta-lactam antibiotics, suggesting that a functional cell wall is required for Pls secretion from the bacterial cell. Finally, we tested the requirement for these proteins in Chlamydia infection by microinjecting anti-Pls1 and anti-Pls2 antibodies into infected cells. Coinjection of anti-Pls1 and -Pls2 antibodies partially inhibited expansion of the inclusion. Because Pls proteins lack classical sec-dependent secretion signals, we propose that Pls proteins are secreted into the inclusion lumen by a novel mechanism to regulate events important for chlamydial replication and inclusion expansion.


Predictors of Adherence Among Patients With Multiple Sclerosis Using the BETACONNECT® Autoinjector: A Prospective Observational Cohort Study.
Background: In patients with multiple sclerosis (MS), non-adherence to disease-modifying drug therapy is associated with an increased rate of MS relapses. Early identification of patients at risk of non-adherence would allow provision of timely and individualized support. The aim of the BETAPREDICT study was to investigate potential predictors of adherence in patients with MS in Germany treated with interferon β-1b (IFNβ-1b) using the BETACONNECT® autoinjector. Methods: BETAPREDICT was a national, multi-center, prospective, non-interventional, single-arm, 24-month cohort study of patients with relapsing-remitting MS or clinically isolated syndrome receiving IFNβ-1b via the BETACONNECT® autoinjector (ClinicalTrials.gov: NCT02486640). Injection data were captured by the autoinjector. The primary objective was to determine baseline predictors of compliance, persistence, and adherence to IFNβ-1b treatment after 12- and 24 months using multivariable-adjusted regression. Secondary objectives included evaluation of satisfaction with the autoinjector, injection site pain, vitamin and nutrient supplementation, clinical course, and patient-related outcome measures. Results: Of 165 patients enrolled, 153 were available for analysis (120 with autoinjector data). Seventy-two patients left the study prematurely. Compliance (N = 120), persistence (N = 153), and adherence (N = 120) at 24 months were 89.1, 53.6, and 41.7%, respectively. Compliance at 12- and 24 months was predicted by intake of vitamin D supplements and absence of specific injection site reactions. Positive predictors of persistence included age (at 12- and 24 months) and previous duration of treatment (at 12 months), while intake of vitamins/nutrients other than vitamin D was a negative predictor (at 12 months). Positive predictors of adherence at 24 months were age and being experienced with IFNβ-1b. Higher scores in specific SF-36 subscales were positive predictors of medication-taking behavior at 24 months. Satisfaction with the autoinjector was high at baseline and 24 months (median score: 9 out of 10). Conclusions: Compliance with IFNβ-1b treatment among participants still under observation remained high over a 24-month period, while persistence and adherence continuously declined. Multiple factors affected medication-taking behavior, including patient characteristics, treatment history, injection site reactions, patients' perception of their health and support programs. The importance of these factors may differ among patients according to their individual situation.


Age-related decline of visual processing components in change detection.
Previous research has suggested that an age-related decline in change detection may be due to older adults using a more conservative response criterion. However, this finding may reflect methodological limitations of the traditional change detection design, in which displays are presented continuously until a change is detected. Across 2 experiments, the authors assessed adult age differences in a version of change detection that required a response after each pair of pre- and postchange displays, thus reducing the potential contribution of response criterion. Older adults performed worse than younger adults, committing more errors and requiring a greater number of display cycles for correct detection. These age-related performance declines were substantially reduced after controlling statistically for elementary perceptual speed. Search strategy was largely similar for the 2 age groups, but perceptual speed was less successful in accounting for age-related variance in detectability when a more precise spatial localization of change was required (Experiment 2). Thus, the negative effect of aging in the present tasks lies in a reduction of detection efficiency due largely to processing speed, though some strategy-level effects may also contribute. (PsycINFO Database Record (c) 2010 APA, all rights reserved).


First taxonomic description of multivalvulidan myxosporean parasites from elasmobranchs: Kudoa hemiscylli n.sp. and Kudoa carcharhini n.sp. (Myxosporea: Multivalvulidae).
Myxosporean parasites are significant parasites of fishes not only for their apparent high diversity but also for their potential impact on fish health and/or marketability. Regardless, our knowledge of most myxosporeans, especially those found in elasmobranch hosts, is superficial. A study of multivalvulidan diversity in a range of elasmobranchs from Queensland, Western Australia and the Northern Territory (Australia) was conducted to address this knowledge gap. Specimens were collected from a total of 3 orders, 9 families and 31 species of elasmobranchs. Myxosporean infections referable to the genus Kudoa were discovered in host muscle and characterized morphologically and genetically. Both small subunit (SSU) and large subunit (LSU) rDNA sequences were used in molecular phylogenetic analyses. Kudoa spp. infected 27 of the 31 species of elasmobranchs examined, representing new records of this parasite genus in 26, of the 27, host species. Kudoids were observed in all 3 orders, and 7 out of the 9 families of elasmobranchs investigated. This paper reports the first 2 multivalvulidan species to be formally described from elasmobranchs, Kudoa hemiscylli n.sp. characterized from Hemiscyllium ocellatum (and 8 other host species) and Kudoa carcharhini n. sp. characterized from Carcharhinus cautus (and 2 other host species). Phylogenetic analyses revealed that kudoids from elasmobranchs form a separate lineage to those of teleosts, but are anchored within the overall kudoid clade.


Influence of Na+-independent Cl--HCO3- exchange on the slow force response to myocardial stretch.
Previous work demonstrated that the slow force response (SFR) to stretch is due to the increase in calcium transients (Ca2+T) produced by an autocrine-paracrine mechanism of locally produced angiotensin II/endothelin activating Na+-H+ exchange. Although a rise in pHi is presumed to follow stretch, it was observed only in the absence of extracellular bicarbonate, suggesting pHi compensation through the Na+-independent Cl--HCO3- exchange (AE) mechanism. Because available AE inhibitors do not distinguish between different bicarbonate-dependent mechanisms or even between AE isoforms, we developed a functional inhibitory antibody against both the AE3c and AE3fl isoforms (anti-AE3Loop III) that was used to explore if pHi would rise in stretched cat papillary muscles superfused with bicarbonate after AE3 inhibition. In addition, the influence of this potential increase in pHi on the SFR was analyzed. In this study, we present evidence that cancellation of AE3 isoforms activity (either by superfusion with bicarbonate-free buffer or with anti-AE3Loop III) results in pHi increase after stretch and the magnitude of the SFR was larger than when AE was operative, despite of similar increases in [Na+]i and Ca2+T under both conditions. Inhibition of reverse mode Na+-Ca2+ exchange reduced the SFR to the half when the AE was inactive and totally suppressed it when AE3 was active. The difference in the SFR magnitude and response to inhibition of reverse mode Na+-Ca2+ exchange can be ascribed to a pHi-induced increase in myofilament Ca2+ responsiveness.


Novel strategy for improving the bioavailability of curcumin based on a new membrane transport mechanism that directly involves solid particles.
Amorphization has been widely recognized as a useful solubilization technique for poorly water-soluble drugs, such as curcumin. We have recently reported the novel finding that the membrane transport of curcumin was markedly enhanced when amorphous solid particles of curcumin came into direct contact with the lipid membrane surface, but this was not true for crystalline solid particles. The increase in the permeation of curcumin was found to be independent of the improvements in aqueous solubility brought about by amorphization. Thus, we have identified a novel membrane transport mechanism that directly involves solid particles. In addition, it might represent a novel strategy for improving the bioavailability of curcumin that does not focus on the aqueous solubility of the drug. In this study, the direct effects of the administration of amorphous nanoparticles of curcumin (ANC) on the in vivo intestinal absorption of curcumin were investigated. After the intraduodenal administration of a curcumin suspension, the area under the curve of the plasma concentration of curcumin increased in a manner that was dependent on the curcumin concentration of the suspension, while no significant absorption was observed from a saturated solution. This finding is consistent with the results from our in vitro transepithelial transport study. In the latter experiment, the bioavailability of curcumin was found to be 1-2%. The intrapulmonary insufflation of ANC powder resulted in a significant increase in the bioavailability of curcumin (it was two orders of magnitude higher than that seen after the application of a crystalline suspension). This was due to the ANC particles coming into contact with epithelial cells in a more efficient manner after the pulmonary application of the ANC powder than after the intestinal application of the ANC suspension. Therefore, the pulmonary insufflation of amorphous powder is a novel approach to improving the bioavailability of curcumin and might be a useful way of increasing the bioavailability of poorly water-soluble drugs, such as curcumin.


Pathology of gastrointestinal organs in a porcine model of cystic fibrosis.
Cystic fibrosis (CF), which is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), is characterized by multiorgan pathology that begins early in life. To better understand the initial stages of disease, we studied the gastrointestinal pathology of CFTR-/- pigs. By studying newborns, we avoided secondary changes attributable to environmental interactions, infection, or disease progression. Lesions resembling those in humans with CF were detected in intestine, pancreas, liver, gallbladder, and cystic duct. These organs had four common features. First, disease was accelerated compared with that in humans, which could provide a strategy to discover modifying factors. Second, affected organs showed variable hyperplastic, metaplastic, and connective tissue changes, indicating that remodeling was a dynamic component of fetal life. Third, cellular inflammation was often mild to moderate and not always present, which raises new questions as to the role of cellular inflammation in early disease pathogenesis. Fourth, epithelial mucus-producing cells were often increased, producing a striking accumulation of mucus with a layered appearance and resilient structure. Thus, mucus cell hyperplasia and mucus accumulation play prominent roles in early disease. Our findings also have implications for CF lung disease, and they lay the foundation for a better understanding of CF pathogenesis.


Nonalcoholic fatty liver disease, spleen and psoriasis: New aspects of low-grade chronic inflammation.
To investigate spleen status in psoriasis and its relationship with hepatic steatosis, Psoriasis Area and Severity Index, and insulin resistance. Seventy-nine psoriatic patients who were not suffering from any chronic inflammatory disease were retrospectively selected for inclusion in this study, and their complete medical records were accessed. An age- and sex-matched group of 80 non-psoriatic, obese patients was included as a control. The following relevant data were collected: age, sex, weight, height, body mass index, waist circumference, blood pressure, insulin resistance status, age at psoriasis onset, and severity of psoriasis. Abdominal ultrasonography was performed to determine spleen longitudinal diameter (SLD), and hepatic steatosis grade. The SLD of control obese patients was greater than that of psoriatic subjects (P = 0.013), but body mass index predicted the size of the spleen in psoriatic patients (P < 0.001). The SLD of psoriatic patients with normal weight was significantly reduced with respect to the overweight/obese psoriatic patients (P = 0.002). A multiple regression analysis revealed that body mass index was a unique predictor of the spleen size (P < 0.001). Finally, the disease duration predicted the spleen size in psoriatic subjects (P = 0.038). This study shows a correlation between the SLD and the duration of psoriasis.


How to treat Guyon's canal syndrome? Results from the European HANDGUIDE study: a multidisciplinary treatment guideline.
Although Guyon's canal syndrome is not highly prevalent, a considerable knowledge of anatomy is needed to localise and treat the pathology. Data on the effectiveness of interventions for this disorder are lacking. To achieve consensus on a multidisciplinary treatment guideline for this disorder based on experts' opinions. A European Delphi consensus strategy was initiated. In total, 35 experts (hand surgeons/hand therapists selected by the national member associations of their European federations and Physical Medicine and Rehabilitation physicians) participated in the Delphi consensus strategy. Each Delphi round consisted of a questionnaire, an analysis and a feedback report. After three Delphi rounds, consensus was achieved on the description, symptoms and diagnosis of Guyon's canal syndrome. The experts agreed that patients with this disorder should always receive instructions and that these instructions should be combined with another form of treatment. Instructions combined with splinting or with surgery were considered as suitable treatment options. Details on the use of instructions, splinting and surgery were described. Main factors for selecting one of the aforementioned treatment options were identified: severity and duration of the syndrome and previous treatments given. A relation between the severity/duration and choice of therapy was indicated by the experts and reported in the guideline. Although this disorder is less prevalent and not easy to diagnose, this guideline may contribute to better insight into and treatment of Guyon's canal syndrome.


Effect of multidisciplinary team treatment on outcomes of patients with gastrointestinal malignancy.
To evaluate the effect of multidisciplinary team (MDT) treatment modality on outcomes of patients with gastrointestinal malignancy in China. Data about patients with gastric and colorectal cancer treated in our center during the past 10 years were collected and divided into two parts. Part 1 consisted of the data collected from 516 consecutive complicated cases discussed at MDT meetings in Peking University School of Oncology (PKUSO) from December 2005 to July 2009. Part 2 consisted of the data collected from 263 consecutive cases of resectable locally advanced rectal cancer from January 2001 to January 2005. These 263 patients were divided into neoadjuvant therapy (NT) group and control group. Patients in NT group received MDT treatment, namely neoadjuvant therapy + surgery + postoperative adjuvant therapy. Patients in control group underwent direct surgery + postoperative adjuvant therapy. The outcomes in two groups were compared. The treatment strategy was altered after discussed at MDT meeting in 76.81% of gastric cancer patients and in 58.33% of colorectal cancer patients before operation. The sphincter-preservation and local control of tumor were better in NT group than in control group. The 5-year overall survival rate was also higher in NT group than in control group (77.23% vs 69.75%, P = 0.049). MDT treatment modality can significantly improve the outcomes of patients with gastrointestinal malignancy in China.


Transcriptome responses to heat stress in the nucleated red blood cells of the rainbow trout (Oncorhynchus mykiss).
The retention of a nucleus in the mature state of fish red blood cells (RBCs) and the ability to easily collect and manipulate blood in nonterminal experiments make blood an ideal tissue on which to study the cellular stress response in fish. Through the use of the cGRASP 16K salmonid microarray, we investigated differences in RBC global gene transcription in fish held under control conditions (11 degrees C) and exposed to heat stress (1 h at 25 degrees C followed by recovery at 11 degrees C). Repeated blood sampling (via a dorsal aorta cannula) enables us to examine the individual stress response over time. Samples were taken preheat stress (representing individual control) and at 4 and 24 h postheat stress (representing early and late transcriptional regulation). Approximately 3,000 microarray features had signal above threshold when hybridized with RBC RNA-derived targets, and cannulation did not have a detectable effect on RBC mRNA expression at the investigated time points. Genes involved in the stress response, immune response, and apoptosis were among those showing the highest dysregulation during both early and late transcriptional regulation. Additionally, genes related to the differentiation and development of blood cells were transcriptionally upregulated at the 24 h time point. This study provides a broader understanding of the mechanisms underpinning the stress response in fish and the discovery of novel genes that are regulated in a stress specific manner. Moreover, salmonid transcripts that are consistently dysregulated in blood in response to heat stress are potential candidates of nonlethal biomarkers of exposure to this particular stressor.


Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers.
Members of the POU and SOX transcription factor families exemplify the partnerships established between various transcriptional regulators during early embryonic development. Although functional cooperativity between key regulator proteins is pivotal for milestone decisions in mammalian development, little is known about the underlying molecular mechanisms. In this study, we focus on two transcription factors, Oct4 and Sox2, as their combination on DNA is considered to direct the establishment of the first three lineages in the mammalian embryo. Using experimental high-resolution structure determination, followed by model building and experimental validation, we found that Oct4 and Sox2 were able to dimerize onto DNA in distinct conformational arrangements. We demonstrate that the DNA enhancer region of their target genes is responsible for the correct spatial alignment of glue-like interaction domains on their surface. Interestingly, these surfaces frequently have redundant functions and are instrumental in recruiting various interacting protein partners.


Carbohydrate versus fat intake: differing patterns of macronutrient selection in two inbred mouse strains.
As a first step toward developing a mouse model to characterize genetic factors linked to the preferential intake of dietary carbohydrate or fat, we have identified two mouse strains that exhibit distinctly different patterns of macronutrient selection. Macronutrient selection was evaluated in AKR/J and SWR/J mice, two strains that have been characterized previously for their sensitivity to high-fat dietary obesity. Mice were adapted to a self-selection protocol in which separate carbohydrate, fat, and protein sources were simultaneously available. AKR/J mice ate 30% more calories than the SWR/J mice. Furthermore, strain comparisons revealed a significantly higher proportion of fat intake by the AKR/J mice (69 vs. 28%), and in the SWR/J mice a significantly higher intake of carbohydrate (62 vs. 24%). The mice were then returned to a standard chow diet for 10 wk. These mice subsequently were allowed to self-select from two composite energy diets (carbohydrate and protein, or fat and protein). Once again, AKR/J mice selected a greater proportion of energy from the fat/protein diet (85%) than did the SWR/J strain (32%). These findings suggest a possible relationship between sensitivity to dietary obesity and fat selection.


Contribution of aquatic products consumption to total human exposure to PAHs in Eastern China: The source matters.
Demand for aquatic products surges, due to the increasing concerns on high-quality nutrition and food security. Eastern China is the leading area in contributing significantly to both production and consumption of aquatic products from inland aquaculture, coastal fishing, and distant-water fishing. It is imperative to comprehensively assess the dietary risks of common chemical hazards, such as polycyclic aromatic hydrocarbons (PAHs) in aquatic products of these supply origins, and the contribution of aquatic product consumption to total human exposure. The observed body loads of total PAHs in the coastal aquatic products varied significantly, indicating an unstable food quality from the east coast of China. In the meantime, benzo[a]pyrene equivalent concentrations (BaPeq) exhibited the highest level in the aquatic products from inland farm ponds. High BaPeq, along with high consumption of inland aquaculture products, led to higher corresponding cumulative carcinogenic risks (ILCRs) than the other two kinds of products, which further indicate that the origins and consumption rates of the aquatic products do matter. Furthermore, it is confirmed that the consumption of aquatic products is an important contributor to the total daily exposure to PAHs, especially for children and pregnant women. Finally, it is necessary to apply practical remediation in aquaculture farm ponds to provide high-quality products, especially for the population groups of children and pregnant women, and alleviate the exposure and risk due to the PAHs in aquatic products.


Investigation of the Anxiolytic and Antidepressant Effects of Curcumin, a Compound From Turmeric (Curcuma longa), in the Adult Male Sprague-Dawley Rat.
As the use of herbal medications continues to increase in America, the potential interaction between herbal and prescription medications necessitates the discovery of their mechanisms of action. The purpose of this study was to investigate the anxiolytic and antidepressant effects of curcumin, a compound from turmeric (Curcuma longa), and its effects on the benzodiazepine site of the γ-aminobutyric acid receptor A (GABAA) receptor. Utilizing a prospective, between-subjects group design, 55 male Sprague-Dawley rats were randomly assigned to 1 of the 5 intraperitoneally injected treatment groups: vehicle, curcumin, curcumin + flumazenil, midazolam, and midazolam + curcumin. Behavioral testing was performed using the elevated plus maze, open field test, and forced swim test. A 2-tailed multivariate analysis of variance and least significant difference post hoc tests were used for data analysis. In our models, curcumin did not demonstrate anxiolytic effects or changes in behavioral despair. An interaction of curcumin at the benzodiazepine site of the GABAA receptor was also not observed. Additional studies are recommended that examine the anxiolytic and antidepressant effects of curcumin through alternate dosing regimens, modulation of other subunits on the GABAA receptor, and interactions with other central nervous system neurotransmitter systems.


Low-cost electronic-nose (LC-e-nose) systems for the evaluation of plantation and fruit crops: recent advances and future trends.
An electronic nose (e-nose) is a device designed to recognize and classify odors. The equipment is built around a series of sensors that detect the presence of odors, especially volatile organic compounds (VOCs), and generate an electric signal (voltage), known as e-nose data, which contains chemical information. In the food business, the use of e-noses for analyses and quality control of fruits and plantation crops has increased in recent years. Their use is particularly relevant due to the lack of non-invasive and inexpensive methods to detect VOCs in crops. However, the majority of reports in the literature involve commercial e-noses, with only a few studies addressing low-cost e-nose (LC-e-nose) devices or providing a data-oriented description to assist researchers in choosing their setup and appropriate statistical methods to analyze crop data. Therefore, the objective of this study is to discuss the hardware of the two most common e-nose sensors: electrochemical (EC) sensors and metal oxide sensors (MOSs), as well as a critical review of the literature reporting MOS-based low-cost e-nose devices used for investigating plantations and fruit crops, including the main features of such devices. Miniaturization of equipment from lab-scale to portable and convenient gear, allowing producers to take it into the field, as shown in many appraised systems, is one of the future advancements in this area. By utilizing the low-cost designs provided in this review, researchers can develop their own devices based on practical demands such as quality control and compare results with those reported in the literature. Overall, this review thoroughly discusses the applications of low-cost e-noses based on MOSs for fruits, tea, and coffee, as well as the key features of their equipment (i.e., advantages and disadvantages) based on their technical parameters (i.e., electronic and physical parts). As a final remark, LC-e-nose technology deserves significant attention as it has the potential to be a valuable quality control tool for emerging countries.


Emotion recognition in music changes across the adult life span.
In comparison with other modalities, the recognition of emotion in music has received little attention. An unexplored question is whether and how emotion recognition in music changes as a function of ageing. In the present study, healthy adults aged between 17 and 84 years (N=114) judged the magnitude to which a set of musical excerpts (Vieillard et al., 2008) expressed happiness, peacefulness, sadness and fear/threat. The results revealed emotion-specific age-related changes: advancing age was associated with a gradual decrease in responsiveness to sad and scary music from middle age onwards, whereas the recognition of happiness and peacefulness, both positive emotional qualities, remained stable from young adulthood to older age. Additionally, the number of years of music training was associated with more accurate categorisation of the musical emotions examined here. We argue that these findings are consistent with two accounts on how ageing might influence the recognition of emotions: motivational changes towards positivity and, to a lesser extent, selective neuropsychological decline.


Antiviral Effect of Agaricomycetes Mushrooms (Review).
This review presents data on the studied antiviral activities of Agaricomycetes mushrooms against the herpes, West Nile, influenza, human immunodeficiency, and hepatitis viruses, as well as orthopoxviruses, including the variola virus. Polysaccharides and other compounds (e.g., proteins, glycoproteins, terpenoids, melanins, nucleosides) exhibit antiviral activity against many viruses that are pathogenic in humans. Effective strains isolated from wild mushrooms in culture represent promising objects for the development of biotechnological drugs, including ones possessing antiviral activity. The data on antitumor and antiviral activities of compounds from the same mushroom species indicate the correlation of these properties. With regard to this connection, preparations of Basidiomycetes may have prophylactic value in preventing cancers with a viral etiology.


Influence of different breathing frequencies on the severity of inspiratory muscle fatigue induced by high-intensity front crawl swimming.
The aim of the present study was to assess the influence of 2 different breathing frequencies on the magnitude of inspiratory muscle fatigue after high-intensity front crawl swimming. The influence of different breathing frequencies on postexercise blood lactate ([La]) and heart rate (HR) was also examined. Ten collegiate swimmers performed 2 x 200-m front crawl swims at 90% of race pace with the following breathing frequencies: 1) 1 breath every second stroke (B2), and 2) 1 breath every fourth stroke (B4). Maximal inspiratory pressure (PImax) was measured at the mouth from residual volume before (baseline) and after swimming, in a standing position. The HR and [La] were assessed at rest and immediately at the cessation of swimming. The PImax decreased by 21% after B4 and by 11% after B2 compared with baseline (p < 0.05). The [La] was lower by 15% after B4 than after B2 (p < 0.05). The HR was not significantly different between B2 and B4. These data suggest that there is significant global inspiratory muscle fatigue after high-intensity swimming. Inspiratory muscle fatigue is, however, greater when breathing frequency is reduced during high-intensity front crawl swimming. Respiratory muscle training should be used to improve respiratory muscle strength and endurance in swimmers.


Molecular epidemiology of Campylobacter jejuni populations in dairy cattle, wildlife, and the environment in a farmland area.
We describe a cross-sectional study of the molecular epidemiology of Campylobacter jejuni in a dairy farmland environment, with the aim of elucidating the dynamics of horizontal transmission of C. jejuni genotypes among sources in the area. A collection of 327 C. jejuni isolates from cattle, wildlife, and environmental sources in a 100-km(2) area of farmland in northwest England was characterized by multilocus sequence typing. A total of 91 sequence types and 18 clonal complexes were identified. Clonal complexes ST-21, ST-45, and ST-61, which have been frequently associated with human disease, were the most commonly recovered genotypes in this study. In addition, widely distributed genotypes as well as potentially host-associated genotypes have been identified, which suggests that both restricted and interconnecting pathways of transmission may be operating in the dairy farmland environment. In particular, the ST-61 complex and the ST-21 complex were significantly associated with cattle. In contrast, complex strains ST-45, ST-952, and ST-677 were isolated predominantly from wild birds, wild rabbits, and environmental water. A considerable number of novel sequence types have also been identified, which were unassigned to existing clonal complexes and were frequently isolated from wildlife and environmental sources. The segregated distribution of genotypes among samples from different sources suggests that their transmission to humans is perhaps via independent routes. Insight into the dynamics and interactions of C. jejuni populations between important animal reservoirs and their surrounding environment would improve the identification of sources of Campylobacter infection and the design of control strategies.