Physiopathologic mechanisms involved in mare endometrosis.
Endometrosis is a degenerative chronic process, characterized by paramount fibrosis development in mare endometrium. This condition is one of the major causes of subfertility/infertility in mares. As in other organs, fibrosis might be a pathologic sequel of many chronic inflammatory diseases. However, aetiology and physiopathologic mechanisms involved in endometrial fibrosis are still controversial. This review presents new hypotheses based on our newest data. As the first line of innate immune defence, systemic neutrophils arrive in the uterus at mating or in the presence of pathogens. A novel paradigm is that neutrophils cast out their DNA in response to infectious stimuli and form neutrophil extracellular traps (NETs). We have shown that bacterial strains of Streptococcus zooepidemicus, Escherichia coli or Staphylococcus capitis, known to cause endometritis in mares were able to induce NETs release in vitro by equine PMN to different extents. An intriguing dilemma is the dual action of NETs. While NETs play a desirable role fighting micro-organisms in mare uterus, they may also contribute to endometrial fibrosis. A long-term in vitro exposure of mare endometrium explants to NETs components (myeloperoxidase, elastase and cathepsin G) up-regulated fibrosis markers TGFβ and Tissue inhibitor of metalloproteinase (TIMP-1). Also, pro-fibrotic cytokines regulated collagen deposition and fibrosis. Changes in expression of connective tissue growth factor (CTGF), interleukins (IL)1-α, IL-1β, IL-6 and receptors in endometrium with different degrees of fibrosis and/or inflammation were observed. A putative role of CTGF, IL and NETs components in endometrosis development should be considered. Additionally, we speculate that in sustained endometritis in mares, prostaglandins may not only cause early luteolysis or early pregnancy loss, but may also be related to endometrial fibrosis pathogenesis by stimulating collagen deposition.


Kittens reared in a unidirectional environment: evidence for a critical period.
1. Kittens were reared in the dark from birth except for a period each day when they were put inside a stationary transparent cylinder, around which a drum with vertical black and white stripes on the inside, rotated in one direction. After the end of the period of exposure, we recorded a sample of single cells from their visual cortices, and analysed each cell for direction and orientation sensitivity and other properties. 2. Two kittens were placed inside the drum, rotating rightward, for 2 hr each seekday from 3 1/2 to 7 weeks of age. A greater proportion of the directionally sensitive cells in their cortices showed a preference for rightward movement. 3. Six other kittens were placed inside the drug for 1 hr each weekday from 2 to 12 weeks of age with the drum rotating leftward up to a particular changeover age, then rightward until 12 weeks. The changeover point occurred at 21, 26, 28, 33, 35 and 51 days for different kittens. A changeover earlier than 4 weeks of age led to a preponderance of cells preferring rightward movement. A changeover later than 5 weeks of age led to a preponderance of cells preferring leftward movement. Comparison of these results with others on monocular deprivation suggests that the peak of the critical period for directional deprivation may occur earlier than the peak of the critical period for monocular deprivation. 4. None of the samples of cells showed a preponderance of cells specific for vertical orientations. It is unclear whether this negative effect resulted from the presence of some horizontal contours during exposure, or some more fundamental cause.


Reconstruction of a severely atrophic maxilla using a Le Fort I downgraft and dental implants: clinical report.
A 55-year-old woman developed chronic infections of the maxillary sinuses with osteomyelitis resulting in extensive bone destruction and atrophy from a failed subperiosteal implant. After surgical removal of the subperiosteal implant, extensive debridement of the maxilla, and long-term antibiotic therapy, maxillary reconstruction was initiated. A Le Fort I osteotomy and downgraft was performed, and a posterior iliac bone graft was harvested and grafted to reconstruct the severely atrophic maxilla. In a later surgical procedure, maxillary and mandibular implants were placed. Implant-retained overdentures were fabricated to restore function and esthetics.


Improving x-ray fluorescence signal for benchtop polychromatic cone-beam x-ray fluorescence computed tomography by incident x-ray spectrum optimization: a Monte Carlo study.
To develop an accurate and comprehensive Monte Carlo (MC) model of an experimental benchtop polychromatic cone-beam x-ray fluorescence computed tomography (XFCT) setup and apply this MC model to optimize incident x-ray spectrum for improving production/detection of x-ray fluorescence photons from gold nanoparticles (GNPs). A detailed MC model, based on an experimental XFCT system, was created using the Monte Carlo N-Particle (MCNP) transport code. The model was validated by comparing MC results including x-ray fluorescence (XRF) and scatter photon spectra with measured data obtained under identical conditions using 105 kVp cone-beam x-rays filtered by either 1 mm of lead (Pb) or 0.9 mm of tin (Sn). After validation, the model was used to investigate the effects of additional filtration of the incident beam with Pb and Sn. Supplementary incident x-ray spectra, representing heavier filtration (Pb: 2 and 3 mm; Sn: 1, 2, and 3 mm) were computationally generated and used with the model to obtain XRF/scatter spectra. Quasimonochromatic incident x-ray spectra (81, 85, 90, 95, and 100 keV with 10 keV full width at half maximum) were also investigated to determine the ideal energy for distinguishing gold XRF signal from the scatter background. Fluorescence signal-to-dose ratio (FSDR) and fluorescence-normalized scan time (FNST) were used as metrics to assess results. Calculated XRF/scatter spectra for 1-mm Pb and 0.9-mm Sn filters matched (r ≥ 0.996) experimental measurements. Calculated spectra representing additional filtration for both filter materials showed that the spectral hardening improved the FSDR at the expense of requiring a much longer FNST. In general, using Sn instead of Pb, at a given filter thickness, allowed an increase of up to 20% in FSDR, more prominent gold XRF peaks, and up to an order of magnitude decrease in FNST. Simulations using quasimonochromatic spectra suggested that increasing source x-ray energy, in the investigated range of 81-100 keV, increased the FSDR up to a factor of 20, compared to 1 mm Pb, and further facilitated separation of gold XRF peaks from the scatter background. A detailed MC model of an experimental benchtop XFCT system has been developed and validated. In exemplary calculations to illustrate the usefulness of this model, it was shown that potential use of quasimonochromatic spectra or judicious choice of filter material/thickness to tailor the spectrum of a polychromatic x-ray source can significantly improve the performance of benchtop XFCT, while considering trade-offs between FSDR and FNST. As demonstrated, the current MC model is a reliable and powerful computational tool that can greatly expedite the further development of a benchtop XFCT system for routine preclinical molecular imaging with GNPs and other metal probes.


Anxiolytic Effect of Cedrol on Behavior and Brain Neurotransmitter Levels of Female Mice.
Cedrol has been reported to be effective in reducing anxiety of male mice. The limited application of females in animal models of anxiety makes it difficult to systematically investigate new drug substitutes with potential anxiolytic activity. In the present study, we investigated the behavioral response of female ICR mice to cedrol after intraperitoneal (i.p.) administration using the elevated plus maze (EPM) and the light-dark box (LDB) test, followed by determination of neurochemical changes in brain. The data suggested that cedrol at dose of 1200-1600 mg·kg-1 exhibited anxiolytic activity on the female mice, as reflected by greater percentage of entries into the open arms and time spent in the open arms in the EPM, and greater transitions between chambers and percentage of time spent in the light chamber in the LDB. Cedrol increased the level of 5-hydroxytryptamine (5-HT), decreased the level of dopamine (DA), reduced the ratio of 5-hydroxyindoleacetic acid (5-HIAA)/5-HT and increased the ratio of 3,4-dihydroxyphenyl acetic acid (DOPAC)/DA, compared with the control group, indicative of an anxiolytic-like effect on female mice via the 5-HTnergic or DAnergic pathways.


Anticonvulsant effect of A1 but not A2A adenosine receptors of piriform cortex in amygdala-kindled rats.
In this study, the effect of A1 and A2A adenosine receptor activity of the piriform cortex (PC) on amygdala-kindled seizures was investigated in rats. Animals were kindled by daily electrical stimulation of the amygdala. In fully kindled rats, N6-cyclohexyladenosine (CHA, a selective A1 agonist), 8-cyclopentyl-1,3-dimethylxanthine (CPT, a selective A1 antagonist), CGS21,680 hydrochloride (CGS, a selective A2A agonist), and ZM241,385 (ZM, a selective A2A antagonist) were microinjected bilaterally into the PC. Rats were stimulated 5 min post-drug microinjection and seizure parameters were measured. Results showed that intra-PC CHA (10 and 100 micromol/L) decreased the duration of both afterdischarge and stage 5 seizure and significantly increased the latency to stage 4 seizure. Intra-PC CPT increased afterdischarge and stage 5 seizure duration at the dose of 20 micromol/L. The anticonvulsant effect of CHA (100 micromol/L) was eliminated by CPT (10 micromol/L) pretreatment. On the other hand, neither intra-PC CGS nor ZM had a significant effect on kindled seizures. These results suggest that activity of A1, but not A2A, receptors of the PC have anticonvulsant effects on kindled seizures elicited from electrical stimulation of the amygdala.


First documented case of Aeromonas veronii biovar sobria infection in northern Europe.
The first Scandinavian case of Aeromonas veronii biovar sobria infection, an episode of peritonitis in a patient suffering from a cirrhotic liver and an earlier unrecognized appendiceal cancer, is described.


A genetic variant in cytoskeleton motors amplifies susceptibility to leukoaraiosis in hypertensive smokers: gene-environmental interactions behind vascular white matter demyelinization.
One of the most frequent causes of an age-associated cognitive decline is the vascular white matter demyelinization of the brain referred to as leukoaraiosis (LA). The wide range of severity of the cognitive decline caused by LA can have numerous deleterious effects on the quality of life, leading overall to far-reaching public health problems. Besides clinical risk factors such as hypertension and advanced age, genetic susceptibility factors are presumed to be of great importance in the development of LA. The protein kinesin, which is the main motor protein in the trafficking system of the mitochondria, can undergo functional damage under the circumstances of chronic hypoxia. This may give rise to a slowly developing metabolic crisis in the glia cells, a phenomenon hypothesized to account for the evolution of LA. Setting out from this assumption, we examined how the kinesin light-chain 1 (KNS2) G56836C single nucleotide polymorphism in intron 13 affects the susceptibility to LA. This genetic variant was found to be associated with cognitive disturbances and neurodegeneration, and it was presumed to affect the function of kinesin. The association analysis of the above genetic variant was performed in 229 patients with LA and 264 neuroimaging alteration-free controls. The KNS2 56836CC variant increased the risk of LA 7.76-fold in hypertensive smokers as compared with those not carrying this variant. This finding may be useful in everyday clinical practice by indicating the need for stricter preventive measures in CC carriers.


ADAPTATIONS TO ENVIRONMENTAL OXYGEN LEVELS IN INFAUNAL AND EPIFAUNAL SEA ANEMONES.
1. Aerobic metabolism in Haloclava producta, a burrowing sea anemone, is largely or wholly dependent upon the oxygen supply in the water overlying its burrow. 2. This superficial water is brought through the burrow by an irrigation cycle of peristaltic waves. About 33% of the oxygen in the irrigation current is withdrawn by the animal. 3. Externally H. producta is exceedingly vermiform, studded with numerous thin walled hollow blisters and body surface area largely consists of the columnar body wall. M. senile, in comparison, is more robust, relatively smooth walled, and most of its total surface area is tentacular. Internally, the body wall of H. producta is an order of magnitude thinner than that of M. senile, and H. producta has fewer and smaller mesenterial septa and longitudinal retractors. 4. These morphological considerations suggest that vermiformicity and simplicity of internal organization are adaptive to low or unstable oxygen environments. The modifications associated with H. producta are not uniquely actinian, and are paralleled in completely unrelated phyla; thus they may represent a general mode or pattern of adaptation to burrow existence. 5. The morphological adaptations seem to be correlated with efficient use of the oxygen in the irrigation current, and with rapid restoration of internal pO2's following transient periods of anoxia. 6. H. producta is much more resistant to prolonged anoxia than M. senile, and it has a lower oxygen consumption rate at air saturation. 7. After exposure to anoxia, both species show a compensatory increase in the fraction of dissolved oxygen which they can remove from a closed system. 8. After exposure to anoxia, both species show an increased rate of oxygen consumption (both in relative and absolute terms) over wide ranges of oxygen concentration. 9. Different individuals of M. senile have very different absolute metabolic response curves to diminishing oxygen concentration, but all individuals examined showed the same relative decrease in oxygen consumption rate over a given change in oxygen concentration. This relative change is independent of acclimation temperature, experimental temperature, weight and previous exposure to anoxia. Different individuals of H. producta also have different absolute metabolic response curves to diminishing oxygen concentration, but a single relative response comparable to that in M. senile does not exist.


Navigation and thermophotovoltaic activity by hornets at different light conditions: the influence of UVB blockers.
The aim of the present investigation was two-fold: a) to observe the homing of the Oriental hornet, Vespa orientalis (Hymenoptera, Vespinae) from different distances; and b) to study the photothermoelectric activity of hornet cuticle obtained from the subjects of goal (a) and kept frozen for a number of days prior to its testing. In both the above mentioned phases of the investigation, an attempt was made to assess how the covering of the hornets' cuticle with Ultra Violet B (UVB) blockers affects their activity as compared to the control. Flying hornets were observed to return to the nest from distances of up to 7 km, once they had learned the way back. However, covering of the cuticle with UVB blockers increases the percentage of 'non-returners' to nearly 100%. Covering the cuticle completely or partly with a number of UVB blockers (except for Sisley) proves lethal for the hornets within 24 hours. A statistical model on homing is proposed of the effect of range, of covering with UVB blockers and covering ocelli with Tippex. In the wing of the hornet there is increase in the electric current with rise in the temperature and decrease in the current upon drop of the temperature, but light has no effect on this alar (wing) current. Contrariwise, the body cuticle of the hornet responds to both temperature and illumination in terms of its electric current. Coating of the cuticle with UVB blockers causes in the wing (under all conditions of illumination) and in the cuticle (only in the dark) a moderation in the amplitude of the photothermoelectric current.


Speciation of iron in river water using a specific catalytic determination and size fractionation.
A comprehensive speciation scheme was proposed for the speciation of iron in river water (0.45 microm filtrate). The speciation was based on the catalytic determination of reactive iron as Fe3+ and Fe(III)Li/(3 -in)+, where i = 1 or 2 for a unidentate and i = 1 for a bidentate ligand, Ln-. The scheme incudes size fractionation and acid decomposition of the sample and determination of the coexisting species. The proposed scheme was applied to natural and artificial samples and acidified preparations of these. Resulting fractionation patterns of reactive and unreactive iron and of coexisting humic acid were useful for the characterization of iron species in the natural samples. The reactive iron in the molecular weight (Mr) > or = 10(4) fraction was associated with humic iron aggregates and estimated as iron complexed with them. The unreactive iron in this fraction dissociated in 0.1 M HCI and was estimated as iron in the aggregates of iron(III) hydroxide (s) and humic iron. From the fractionation results of the artificial sample, the reactive and unreactive iron in the Mr < 10(3) fraction may be formed by complexing simple anions like F- and C2O4(2-) at their naturally-occurring concentration levels. The fractionation results also suggested that humic acid and Si contributed to the formation of reactive and unreactive iron in the Mr > or = 10(4) fraction.


Molecular determinants of the inhibition of human Kv1.5 potassium currents by external protons and Zn(2+).
Using human Kv1.5 channels expressed in HEK293 cells we assessed the ability of H+o to mimic the previously reported action of Zn(2+) to inhibit macroscopic hKv1.5 currents, and using site-directed mutagenesis, we addressed the mechanistic basis for the inhibitory effects of H(+)(o) and Zn(2+). As with Zn(2+), H(+)(o) caused a concentration-dependent, K(+)(o)-sensitive and reversible reduction of the maximum conductance (g(max)). With zero, 5 and 140 mM K(+)(o) the pK(H) for this decrease of g(max) was 6.8, 6.2 and 6.0, respectively. The concentration dependence of the block relief caused by increasing [K(+)](o) was well fitted by a non-competitive interaction between H(+)(o) and K(+)(o), for which the K(D) for the K(+) binding site was 0.5-1.0 mM. Additionally, gating current analysis in the non-conducting mutant hKv1.5 W472F showed that changing from pH 7.4 to pH 5.4 did not affect Q(max) and that charge immobilization, presumed to be due to C-type inactivation, was preserved at pH 5.4. Inhibition of hKv1.5 currents by H+o or Zn(2+) was substantially reduced by a mutation either in the channel turret (H463Q) or near the pore mouth (R487V). In light of the requirement for R487, the homologue of Shaker T449, as well as the block-relieving action of K(+)(o), we propose that H(+) or Zn(2+) binding to histidine residues in the pore turret stabilizes a channel conformation that is most likely an inactivated state.


Combined Application of Quantitative Susceptibility Mapping and Diffusion Kurtosis Imaging Techniques to Investigate the Effect of Iron Deposition on Microstructural Changes in the Brain in Parkinson's Disease.
Brain iron deposition and microstructural changes in brain tissue are associated with Parkinson's disease (PD). However, the correlation between these factors in Parkinson's disease has been little studied. This study aimed to use quantitative susceptibility mapping combined with diffusion kurtosis imaging to investigate the effects of iron deposition on microstructural tissue alterations in the brain. Quantitative susceptibility mapping and diffusion kurtosis imaging were performed on 24 patients with early PD, 13 patients with advanced PD, and 25 healthy controls. The mean values of magnetic susceptibility and diffusion kurtosis were calculated for the bilateral substantia nigra, red nucleus, putamen, globus pallidus, and caudate nucleus, and compared between the groups. Correlation analyses between the diffusion kurtosis of each nucleus and its magnetic susceptibility parameters in PD patients and healthy controls were performed. The study found a significant increase in iron deposition in the substantia nigra, red nucleus, putamen and globus pallidus, bilaterally, in patients with PD. Mean kurtosis values were increased in the substantia nigra but decreased in the globus pallidus; axial kurtosis values were decreased in both the substantia nigra and red nucleus; radial kurtosis values were increased in the substantia nigra but showed an opposite trend in the globus pallidus and caudate nucleus. In the substantia nigra of patients with PD, magnetic susceptibility was positively correlated with mean and radial kurtosis values, and negatively correlated with axial kurtosis. None of these correlations were significantly different in the control group. In the putamen, magnetic susceptibility was positively correlated with mean, axial, and radial kurtosis only in patients with advanced-stage PD. Our study provides new evidence for brain iron content and microstructural alterations in patients with PD. Iron deposition may be a common mechanism for microstructural alterations in the substantia nigra and putamen of patients with PD. Tracking the dynamic changes in iron content and microstructure throughout the course of PD will help us to better understand the dynamics of iron metabolism and microstructural alterations in the pathogenesis of PD and to develop new approaches to monitor and treat PD.


[Method of coherent optical processing of bronchograms].
The problem of space filtration of bronchi images is solved by using as a model a tube filled with a contrast substance. The effects of bronchi wall lesions on the images after filtering are analysed. Some results of bronchogram processing using a hybrid optoelectronic device are presented.


Near-Zero Temperatures Arrest Movement of the Diaheliotropic Malva sylvestris.
In the present study, the diaheliotropic leaf movement pattern of Malva sylvestris in relation to the impact of low temperature is presented. Seasonal measurements of movement characteristics along with important aspects of plant function, such as chlorophyll content, water potential, PSII photochemistry, and phenological parameters were performed on plants in their natural environment. During the study period, low winter temperatures and a 10-day freezing event gave insights into the plant's response to harsh environmental conditions and the effect of the latter on leaf movement profile. Plant growth was significantly inhibited during low-temperature periods (leaf shedding) and the photosynthetic performance was seriously depressed, as judged by in vivo chlorophyll a fluorescence. Additionally, the diaheliotropic leaf movement pattern was arrested. Temperature rise in March triggered new leaf burst and expansion, enhancement of the photosynthetic performance, and the recovery of the diaheliotropic movement. The daily and seasonal profiles of the water potential were synergistically shaped by leaf movement and climatic conditions. We conclude that diaheliotropism of M. sylvestris is a dynamic process that coordinates with the prevailing temperatures in ecosystems like the studied one, reaching a full arrest under near-zero temperatures to protect the photosynthetic apparatus from over-excitation and prevent photoinhibition.


Can tert-butylhydroquinone improve the healing of extracted tooth socket in rats?
Tooth extraction causes an open wound in the soft and hard tissues. During the inflammatory phase of the healing process, a large amount of free radicals are produced and cause oxidative stress, which leads to tissue damage and delayed wound healing. Thus, in this study, we evaluated the effect of tert-butylhydroquinone (TBHQ), as an antioxidant, on the healing process of tooth sockets in rats. To conduct this experimental study, male Wistar rats (n = 42) were divided into two groups. In each case, one upper second molar was extracted under general anesthesia. After the extraction, the tooth sockets of the experimental group were treated with a 0.02% TBHQ solution (0.1 ml) while the same volume of distilled water placed in the sockets of the control group. On days 3, 7, and 21 postoperatively, 7 rats from each group were euthanized, and histological slides were prepared from their tooth sockets. The prepared slides were examined histopathologically using a light microscope and compared using an independent two-sample t-test. The significance level was set at 0.05. In the experimental group, a statistically significant (P = 0.003) increase in granulation tissue was observed on day 3, in comparison to the control group. The extent of bony trabeculation was also significantly higher in the TBHQ-treated group than in the control group on day 21 (P < 0.001). Considering the limitations of an experimental study, it can be concluded that TBHQ may enhance the healing of the hard tissue in the tooth sockets.


Energy intake: its relationship to colon cancer risk.
A case-control study was conducted to assess the role of diet in the etiology of colon cancer. Diet was measured by means of a comprehensive quantifiable food frequency history instrument in 246 cases and 484 controls drawn from the general population of Utah. Each subject's diet was described by major nutrient groups and total energy based on the nutritional content of foods reported. Cases reported higher daily food intake 5 years preceding diagnosis than controls [men, rate ratio (RR) = 2.5; women, RR = 3.6], as measured by total energy content of the diet. Higher risk of colon cancer with increasing energy intake was independent of stage of disease at diagnosis and obesity, as measured by body mass. Fat, protein, and carbohydrate intake all had elevated RRs but could not be assessed as risk factors independent of energy intake because of their strong correlations with total calories. Due to the higher energy intake of the cases, odds ratios for the daily intake of dietary fiber and vitamins A and C were also greater than 1. However, adjusting for caloric intake removed this effect, and dietary fiber showed a weak protective effect. Total energy intake must be evaluated before attempting to assign a causal role to any food or nutrient that may be postulated to play a role in colon cancer.


Bond Behavior of Plain Bars in Concrete under Reversed Cyclic Loading.
Plain bars with a diameter of 10 mm are widely used in reinforced concrete buildings, and the bond behavior between the bars and concrete has an essential effect on the seismic performance of concrete structures. Thus, to assess the safety of old buildings and repaired buildings with normal concrete, it was necessary to further investigate the bond performance of the plain bars in the concrete. The bonding tests under monotonic and reversed cyclic loading were carried out on the specimens reinforced with plain bars, and the influences of concrete grade and embedment length on the bond behavior were taken into consideration. The results indicate the maximum bond stress under reversed cyclic loading is less than that under monotonic loading, and this is the same for corresponding slip for the same test parameters. The concrete compressive strength positively affects the maximum bond stress, whereas the embedment length has a negative effect. Based on the elasticity analysis and test data fitting, the expressions of bond stress at characteristic points on the bond stress-slip curves were carried out. Consequently, the bond stress-slip model was established, which could be applied to calculate the bond stress-slip relationships under monotonic and reversed cyclic loading. By comparison between the test curves and proposed model, a good agreement is observed, which indicates that the proposed model can be used to predict the bond stress-slip curve of plain bars in concrete.


Structural Studies of Predicted Ligand Binding Sites and Molecular Docking Analysis of Slc2a4 as a Therapeutic Target for the Treatment of Cancer.
Presently, many studies have focused on exploring in silico approaches in the identification and development of alternative therapy for the treatment and management of cancer. Solute carrier family-2-member-4-gene (Slc2a4) which encodes glucose transporter 4 protein (GLUT4), has been identified as a promising therapeutic target for cancer. Though Slc2a4 is known to play a major regulatory role in the pathophysiology of type 2 diabetes, emerging evidence suggests that successful pharmacological inhibition of this protein may lead to the development of a novel drug candidate for the treatment of cancer. In this study, Slc2a4 protein sequence was retrieved and analysed using in silico approaches, and we identified seven putative antimicrobial peptides (AMPs; RAB1-RAB7) as anti-cancer. The structures of the protein and AMPs were modelled using I-TASSER server, and the overall quality of the Slc2a4 model was validated using PROCHECK. Subsequently, the probable motifs and active site of the protein were forecasted. Also, the molecular interaction between the AMPs and Slc2a4 was ascertained using PatchDock. The result revealed that, all the AMPs are good Slc2a4 inhibitors with RAB1 having the highest binding affinity of 12,392 and binding energy of -39.13 kcal/mol. Hence, this study reveals that all the generated AMPs can serve as therapeutic drug in treating cancer by inhibiting Slc2a4 which is responsible for the production of energy for cancer cells during angiogenesis. This is the first report on AMPs as inhibitors of Slc2a4 for the treatment of cancer.


The triangular relationship between traditional Chinese medicines, intestinal flora, and colorectal cancer.
Over the past decade, colorectal cancer has reported a higher incidence in younger adults and a lower mortality rate. Recently, the influence of the intestinal flora in the initiation, progression, and treatment of colorectal cancer has been extensively studied, as well as their positive therapeutic impact on inflammation and the cancer microenvironment. Historically, traditional Chinese medicine (TCM) has been widely used in the treatment of colorectal cancer via promoted cancer cell apoptosis, inhibited cancer metastasis, and reduced drug resistance and side effects. The present research is more on the effect of either herbal medicine or intestinal flora on colorectal cancer. The interactions between TCM and intestinal flora are bidirectional and the combined impacts of TCM and gut microbiota in the treatment of colon cancer should not be neglected. Therefore, this review discusses the role of intestinal bacteria in the progression and treatment of colorectal cancer by inhibiting carcinogenesis, participating in therapy, and assisting in healing. Then the complex anticolon cancer effects of different kinds of TCM monomers, TCM drug pairs, and traditional Chinese prescriptions embodied in apoptosis, metastasis, immune suppression, and drug resistance are summarized separately. In addition, the interaction between TCM and intestinal flora and the combined effect on cancer treatment were analyzed. This review provides a mechanistic reference for the application of TCM and intestinal flora in the clinical treatment of colorectal cancer and paves the way for the combined development and application of microbiome and TCM.


Clinical and Radiologic Predictive Factors of Rib Fractures in Outpatients With Chest Pain.
To identify the clinical and radiologic predictive factors of rib fractures in stable adult outpatients presenting with chest pain and to determine the utility of dedicated rib radiographs in this population of patients. Following Institutional Review Board approval, we performed a retrospective review of 339 consecutive cases in which a frontal chest radiograph and dedicated rib series had been obtained for chest pain in the outpatient setting. The frontal chest radiograph and dedicated rib series were sequentially reviewed in consensus by two fellowship-trained musculoskeletal radiologists blinded to the initial report. The consensus interpretation of the dedicated rib series was used as the gold standard. Multiple variable logistic regression analysis assessed clinical and radiological factors associated with rib fractures. Fisher exact test was used to assess differences in medical treatment between the 2 groups. Of the 339 patients, 53 (15.6%) had at least 1 rib fracture. Only 20 of the 53 (37.7%) patients' fractures could be identified on the frontal chest radiograph. The frontal chest radiograph had a sensitivity of 38% and specificity of 100% when using the rib series as the reference standard. No pneumothorax, new mediastinal widening or pulmonary contusion was identified. Multiple variable logistic regression analysis of clinical factors associated with the presence of rib fractures revealed a significant association of trauma history (odds ratio 5.7 [p < 0.05]) and age ≥40 (odds radio 3.1 [p < 0.05]). Multiple variable logistic regression analysis of radiographic factors associated with rib fractures in this population demonstrated a significant association of pleural effusion with rib fractures (odds ratio 18.9 [p < 0.05]). Patients with rib fractures received narcotic analgesia in 47.2% of the cases, significantly more than those without rib fractures (21.3%, p < 0.05). None of the patients required hospitalization. In the stable outpatient setting, rib fractures have a higher association with a history of minor trauma and age ≥40 in the adult population. Radiographic findings associated with rib fractures include pleural effusion. The frontal chest radiograph alone has low sensitivity in detecting rib fractures. The dedicated rib series detected a greater number of rib fractures. Although no patients required hospitalization, those with rib fractures were more likely to receive narcotic analgesia.


Structural and mechanistic insights into the inhibition of respiratory syncytial virus polymerase by a non-nucleoside inhibitor.
The respiratory syncytial virus polymerase complex, consisting of the polymerase (L) and phosphoprotein (P), catalyzes nucleotide polymerization, cap addition, and cap methylation via the RNA dependent RNA polymerase, capping, and Methyltransferase domains on L. Several nucleoside and non-nucleoside inhibitors have been reported to inhibit this polymerase complex, but the structural details of the exact inhibitor-polymerase interactions have been lacking. Here, we report a non-nucleoside inhibitor JNJ-8003 with sub-nanomolar inhibition potency in both antiviral and polymerase assays. Our 2.9 Å resolution cryo-EM structure revealed that JNJ-8003 binds to an induced-fit pocket on the capping domain, with multiple interactions consistent with its tight binding and resistance mutation profile. The minigenome and gel-based de novo RNA synthesis and primer extension assays demonstrated that JNJ-8003 inhibited nucleotide polymerization at the early stages of RNA transcription and replication. Our results support that JNJ-8003 binding modulates a functional interplay between the capping and RdRp domains, and this molecular insight could accelerate the design of broad-spectrum antiviral drugs.


Integration of longitudinal electronic records in a large healthcare enterprise: the U.S. Veterans Health Administration experience.
The U.S. Veterans Health Administration (VHA) provides care to some 5.2 million patients spread across the continental United States, Alaska, Hawaii, Puerto Rico, and the Philippines. Sites of care include 157 medical centers, nearly 900 outpatient clinics, long-term facilities, and home care. Over the last 10 years, major changes in the nature of VHA healthcare have imposed a requirement for longitudinal electronic health records and integration of those records across the enterprise at the point of care. VHA has now evolved through three generations of applications that support such integration. This paper reports on the VHA experience, points out lessons learned, and outlines future directions for electronic health record integration in VHA.


Complement Inhibitor Therapy for Myasthenia Gravis.
Complement activation as a driver of pathology in myasthenia gravis (MG) has been appreciated for decades. The terminal complement component [membrane attack complex (MAC)] is found at the neuromuscular junctions of patients with MG. Animals with experimental autoimmune MG are dependent predominantly on an active complement system to develop weakness. Mice deficient in intrinsic complement regulatory proteins demonstrate a significant increase in the destruction of the neuromuscular junction. As subtypes of MG have been better defined, it has been appreciated that acetylcholine receptor antibody-positive disease is driven by complement activation. Preclinical assessments have confirmed that complement inhibition would be a viable therapeutic approach. Eculizumab, an antibody directed toward the C5 component of complement, was demonstrated to be effective in a Phase 3 trial with subsequent approval by the Federal Drug Administration of the United States and other worldwide regulatory agencies for its use in acetylcholine receptor antibody-positive MG. Second- and third-generation complement inhibitors are in development and approaching pivotal efficacy evaluations. This review will summarize the history and present the state of knowledge of this new therapeutic modality.


Role of maternal thyroid hormones in the developing neocortex and during human evolution.
The importance of thyroid hormones during brain development has been appreciated for many decades. In humans, low levels of circulating maternal thyroid hormones, e.g., caused by maternal hypothyroidism or lack of iodine in diet, results in a wide spectrum of severe neurological defects, including neurological cretinism characterized by profound neurologic impairment and mental retardation, underlining the importance of the maternal thyroid hormone contribution. In fact, iodine intake, which is essential for thyroid hormone production in the thyroid gland, has been related to the expansion of the brain, associated with the increased cognitive capacities during human evolution. Because thyroid hormones regulate transcriptional activity of target genes via their nuclear thyroid hormone receptors (THRs), even mild and transient changes in maternal thyroid hormone levels can directly affect and alter the gene expression profile, and thus disturb fetal brain development. Here we summarize how thyroid hormones may have influenced human brain evolution through the adaptation to new habitats, concomitant with changes in diet and, therefore, iodine intake. Further, we review the current picture we gained from experimental studies in rodents on the function of maternal thyroid hormones during developmental neurogenesis. We aim to evaluate the effects of maternal thyroid hormone deficiency as well as lack of THRs and transporters on brain development and function, shedding light on the cellular behavior conducted by thyroid hormones.


R.JIVE for exploration of multi-source molecular data.
: The integrative analysis of multiple high-throughput data sources that are available for a common sample set is an increasingly common goal in biomedical research. Joint and individual variation explained (JIVE) is a tool for exploratory dimension reduction that decomposes a multi-source dataset into three terms: a low-rank approximation capturing joint variation across sources, low-rank approximations for structured variation individual to each source and residual noise. JIVE has been used to explore multi-source data for a variety of application areas but its accessibility was previously limited. We introduce R.JIVE, an intuitive R package to perform JIVE and visualize the results. We discuss several improvements and extensions of the JIVE methodology that are included. We illustrate the package with an application to multi-source breast tumor data from The Cancer Genome Atlas. R.JIVE is available via the Comprehensive R Archive Network (CRAN) under the GPLv3 license: https://cran.r-project.org/web/packages/r.jive/ email@example.com Supplementary data are available at Bioinformatics online.


Accuracy of fetal gender detection using a conventional nested PCR assay of maternal plasma in daily practice.
We have prospectively examined the diagnostic accuracy of a conventional multiplex polymerase chain reaction (PCR) analysis of maternal plasma for fetal gender determination in daily practice. Plasma DNAs were obtained from 168 pregnant women between five and 32 weeks of gestation. The 198-bp-specific sequence on Y-chromosome and the 261 bp ATL1-gene-specific sequence on X-chromosome were coamplified in a multiplex nested PCR manner. The results of fetal sex prediction were compared with routine analysis of fetal tissues and birth outcomes. The ATL1-specific sequences were detected in all cases but Y-chromosome-specific signals were observed in 95 of 97 plasma samples of women carrying male fetuses, leading to the sensitivity of 97.9, 100 and 100% for the first, second and third trimesters, respectively, and the specificity of 100% at all gestational stages. Therefore, fetal gender detection in maternal plasma with a conventional multiplex PCR assay is highly accurate in daily practice which should prove useful for non-invasive prenatal screening of sex-linked genetic disorders.


The validity of self-reported body mass index in a population-based osteoarthritis study.
Obesity is a well-known risk factor for osteoarthritis (OA). The majority of obesity research in OA is performed using self-reported BMI-data, however, its validity in persons with OA is unknown. The aim of this study was to compare the validity of self-reported body mass index (BMI) in persons with and without clinical osteoarthritis (OA) in a population-based survey. Height and weight were self-reported, and thereafter measured in 600 persons with and without clinical OA according to the American College of Rheumatology-criteria (knees, hips and/or hands). We compared the differences between measured and self-reported heights, weights and BMIs (kg/m2) for the two groups and explored whether demographic/clinical factors were associated with inaccurate reporting in the OA patients using multivariate linear regression analyses. Mean (SD) age was 64 (8.7) years and 412 (69%) were women. Participants with clinical OA (n = 449) underreported their BMI to a greater extent than participants without clinical OA (n = 151) [mean (SD) difference 1.34 (1.68) kg/m2 and 0.78 (1.40) kg/m2 (p = 0.000), respectively]. There was a strong dose-dependent association between higher measured BMI and greater underreporting of BMI in multivariate analyses (BMI 25-29.99 kg/m2: B = 0.40, 95% CI, 0.06, 0.77), BMI ≥ 30 kg/m2: B = 1.30, 95% CI, 0.86, 1.75) in the clinical OA patients. A higher age as well as the time interval from self-reported to measured BMI-data were associated with inaccurate reporting. Researchers using self-reported height and weight data should be aware of limited agreement with actual height and weight in overweight and obese individuals with clinical OA.


Distinct mechanisms of regulation by Ca2+/calmodulin of type 1 and 8 adenylyl cyclases support their different physiological roles.
Nine membrane-bound mammalian adenylyl cyclases (ACs) have been identified. Type 1 and 8 ACs (AC1 and AC8), which are both expressed in the brain and are stimulated by Ca(2+)/calmodulin (CaM), have discrete neuronal functions. Although the Ca(2+) sensitivity of AC1 is higher than that of AC8, precisely how these two ACs are regulated by Ca(2+)/CaM remains elusive, and the basis for their diverse physiological roles is quite unknown. Distinct localization of the CaM binding domains within the two enzymes may be essential to differential regulation of the ACs by Ca(2+)/CaM. In this study we compare in detail the regulation of AC1 and AC8 by Ca(2+)/CaM both in vivo and in vitro and explore the different role of each Ca(2+)-binding lobe of CaM in regulating the two enzymes. We also assess the relative dependence of AC1 and AC8 on capacitative Ca(2+) entry. Finally, in real-time fluorescence resonance energy transfer-based imaging experiments, we examine the effects of dynamic Ca(2+) events on the production of cAMP in cells expressing AC1 and AC8. Our data demonstrate distinct patterns of regulation and Ca(2+) dependence of AC1 and AC8, which seems to emanate from their mode of regulation by CaM. Such distinctive properties may contribute significantly to the divergent physiological roles in which these ACs have been implicated.


Smad-dependent and Smad-independent pathways in TGF-beta family signalling.
Transforming growth factor-beta (TGF-beta) proteins regulate cell function, and have key roles in development and carcinogenesis. The intracellular effectors of TGF-beta signalling, the Smad proteins, are activated by receptors and translocate into the nucleus, where they regulate transcription. Although this pathway is inherently simple, combinatorial interactions in the heteromeric receptor and Smad complexes, receptor-interacting and Smad-interacting proteins, and cooperation with sequence-specific transcription factors allow substantial versatility and diversification of TGF-beta family responses. Other signalling pathways further regulate Smad activation and function. In addition, TGF-beta receptors activate Smad-independent pathways that not only regulate Smad signalling, but also allow Smad-independent TGF-beta responses.


Fabrication of an Optical Waveguide-Mode-Field Compressor in Glass Using a Femtosecond Laser.
We report on fabrication of an optical waveguide-mode-field compressor in glass using a femtosecond laser. Our approach is based on building up a stress field within the waveguiding area which is realized by sandwiching the waveguide between a pair of laser-induced-modification-tracks. To induce an adiabatic conversion of the optical mode in the waveguide, the tracks are intentionally designed to be tapered along the waveguide. We show that our technique can allow for reducing the mode field size in a single mode waveguide from more than 10 μm to around 7 μm.


Stiffness of Hydrogels Regulates Cellular Reprogramming Efficiency Through Mesenchymal-to-Epithelial Transition and Stemness Markers.
The stiffness of hydrogels has been reported to direct cell fate. Here, we found that the stiffness of hydrogels promotes the reprogramming of mouse embryonic fibroblasts into induced pluripotent stem cells (iPSCs). We prepared cell culture substrates of various stiffnesses (0.1, 1, 4, 10, and 20 kPa) using a polyacrylamide hydrogel. We found that culture on a soft hydrogel plays an important role in inducing cellular reprogramming into iPSCs via activation of mesenchymal-to-epithelial transition and enhancement of stemness marker expression. These results suggest that physical signals at the interface between cell and substrate can be used as a potent regulator to promote cell fate changes associated with reprogramming into iPSCs, which may lead to effective and reproducible iPSC-production.


68Ga-DOTA-affibody molecule for in vivo assessment of HER2/neu expression with PET.
Overexpression of HER2/neu in breast cancer is correlated with a poor prognosis. It may vary between primary tumors and metastatic lesions and change during the treatment. Therefore, there is a need for a new means to assess HER2/neu expression in vivo. In this work, we used (68)Ga-labeled DOTA-Z(HER2:2891)-Affibody to monitor HER2/neu expression in a panel of breast cancer xenografts. DOTA-Z(HER2:2891)-Affibody molecules were labeled with (68)Ga. In vitro binding was characterized by a receptor saturation assay. Biodistribution and PET imaging studies were conducted in athymic nude mice bearing subcutaneous human breast cancer tumors with three different levels of HER2/neu expression. Nonspecific uptake was analyzed using non-HER2-specific Affibody molecules. Signal detected by PET was compared with ex vivo assessment of the tracer uptake and HER2/neu expression. The (68)Ga-DOTA-Z(HER2:2891)-Affibody probe showed high binding affinity to MDA-MB-361 cells (K (D) = 1.4 ± 0.19 nM). In vivo biodistribution and PET imaging studies demonstrated high radioactivity uptake in HER2/neu-positive tumors. Tracer was eliminated quickly from the blood and normal tissues, resulting in high tumor-to-blood ratios. The highest concentration of radioactivity in normal tissue was seen in the kidneys (227 ± 14%ID/g). High-contrast PET images of HER2/neu-overexpressing tumors were recorded as soon as 1 h after tracer injection. A good correlation was observed between PET imaging, biodistribution estimates of tumor tracer concentration, and the receptor expression. These results suggest that PET imaging using (68)Ga-DOTA-Z(HER2:2891)-Affibody is sensitive enough to detect different levels of HER2/neu expression in vivo.


Human Gene Expression in Uncomplicated Plasmodium falciparum Malaria.
To examine human gene expression during uncomplicated P. falciparum malaria, we obtained three samples (acute illness, treatment, and recovery) from 10 subjects and utilized each subject's recovery sample as their baseline. At the time of acute illness (day 1), subjects had upregulation of innate immune response, cytokine, and inflammation-related genes (IL-1β, IL-6, TNF, and IFN-γ), which was more frequent with parasitemias >100,000 per μL and body temperatures ≥ 39°C. Apoptosis-related genes (Fas, BAX, and TP53) were upregulated acutely and for several days thereafter (days 1-3). In contrast, the expression of immune-modulatory (transcription factor 7, HLV-DOA, and CD6) and apoptosis inhibitory (c-myc, caspase 8, and Fas Ligand G) genes was downregulated initially and returned to normal with clinical recovery (days 7-10). These results indicate that the innate immune response, cytokine, and apoptosis pathways are upregulated acutely in uncomplicated malaria with concomitant downregulation of immune-modulatory and apoptosis inhibitory genes.


Neuropeptides in synovium of patients with rheumatoid arthritis and osteoarthritis.
The presence of neural elements in synovial tissue proper has earlier been suggested on the basis of nonspecific silver impregnation techniques and is now confirmed in a study based on specific demonstration of cytoskeletal neurofilaments and various neuropeptides. With both the neurofilament and neuropeptide antisera, nerves were seen predominantly in a perivascular location, there being fewer nerves freely in the stromal tissue. In the synovium of patients with rheumatoid arthritis (RA), free stromal nerves stained with neurofilament antiserum often lacked neuropeptide immunoreactivity, while this was not the case in normal synovium or synovial samples from patients with osteoarthritis (OA). Furthermore, the intensity of staining of neurotransmitter peptides was weaker in RA than in OA or normal synovial tissue. It is suggested that neurogenic inflammation may play a role in RA and that neuropeptide nerves possibly release their mediators in RA.


Resection of puncture site necrosis over an arteriovenous fistula: Endoclamp use for preservation of cannulation sites.
Skin necrosis overlying an arteriovenous fistula at the cannulation site is a common and potentially life-threatening problem, often associated with underlying aneurysm formation. Arteriovenous fistula-skin necrosis generally requires resection of surrounding skin margins and the underlying aneurysmal vessel wall, allowing repair with healthy tissue of the arteriovenous fistula in addition to closure of soft tissue and skin. In patients with insufficient fistula length, salvage of these arteriovenous fistulas may result in difficult or insurmountable cannulation issues leading to attempts at one-needle cannulation dialysis or, most often, catheter placement. Pre-existing stents or extensive calcification may add to the technical challenge of gaining proximal and/or distal control. We describe our technique for dealing with such arteriovenous fistula-skin necrosis lesions utilizing endo-occlusion with an angioplasty balloon for vascular control, allowing a limited incision and tissue resection with preservation of arteriovenous fistula cannulation length.


Comparing the Maryland Comprehensive Cancer Control Plan With Federal Cancer Prevention and Control Recommendations.
Since the introduction of the Affordable Care Act (ACA) in 2012, 11 million more Americans now have access to preventive services via health care coverage. Several prevention-related recommendations issued by the US Preventive Services Task Force (USPSTF), Centers for Disease Control and Prevention (CDC), and Advisory Committee on Immunization Practices (ACIP) are covered under the ACA. State cancer plans often provide prevention strategies, but whether these strategies correspond to federal evidence-based recommendations is unclear. The objective of this article is to assess whether federal evidence-based recommendations, including those covered under the ACA, are included in the Maryland Comprehensive Cancer Control Plan (MCCCP). A total of 19 federal recommendations pertaining to cancer prevention and control were identified. Inclusion of federal cancer-related recommendations by USPSTF, CDC, and ACIP in the MCCCP's goals, objectives, and strategies was examined. Nine of the federal recommendations were issued after the MCCCP's publication. MCCCP recommendations corresponded completely with 4 federal recommendations and corresponded only partially with 3. Reasons for partial correspondence included specification of less restrictive at-risk populations or different intervention implementers. Three federal recommendations were not mentioned in the MCCCP's goals, objectives, and strategies. Many cancer-related federal recommendations were released after the MCCCP's publication and therefore do not appear in the most current version. We recommend that the results of this analysis be considered in the update of the MCCCP. Our findings underscore the need for a periodic scan for changes to federal recommendations and for adjusting state policies and programs to correspond with federal recommendations, as appropriate for Marylanders.


Diastereoselective construction of tetracyclic chromanes via a triply annulative strategy.
A triple Michael/aldol cascade reaction has been established to construct tetracyclic chromanes in a diastereoselective fashion (≥5 : 1 dr). The polycyclic products were generated in 50-78% isolated yields under mild and metal-free conditions. Five reactive sites of enolate-tethered divinyl ketones were sequentially utilized to form four C-C bonds in a one-pot operation, leading to a construction of three new rings. Up to six consecutive stereocenters, including two quarternary stereogenic centers, were created in this domino process.


Hox9 genes and vertebrate limb specification.
Development of paired appendages at appropriate levels along the primary body axis is a hallmark of the body plan of jawed vertebrates. Hox genes are good candidates for encoding position in lateral plate mesoderm along the body axis and thus for determining where limbs are formed. Local application of fibroblast growth factors (FGFs) to the anterior prospective flank of a chick embryo induces development of an ectopic wing, and FGF applied to posterior flank induces an ectopic leg. If particular combinations of Hox gene expression determine where wings and legs develop, then formation of additional limbs from flank should involve changes in Hox gene expression that reflect the type of limb induced. Here we show that the same population of flank cells can be induced to form either a wing or a leg, and that induction of these ectopic limbs is accompanied by specific changes in expression of three Hox genes in lateral plate mesoderm. This then reproduces, in the flank, expression patterns found at normal limb levels. Hox gene expression is reprogrammed in lateral plate mesoderm, but is unaffected in paraxial mesoderm. Independent regulation of Hox gene expression in lateral plate mesoderm may have been a key step in the evolution of paired appendages.


Transcription factor YcjW controls the emergency H2S production in E. coli.
Prokaryotes and eukaryotes alike endogenously generate the gaseous molecule hydrogen sulfide (H2S). Bacterial H2S acts as a cytoprotectant against antibiotics-induced stress and promotes redox homeostasis. In E. coli, endogenous H2S production is primarily dependent on 3-mercaptopyruvate sulfurtransferase (3MST), encoded by mstA. Here, we show that cells lacking 3MST acquire a phenotypic suppressor mutation resulting in compensatory H2S production and tolerance to antibiotics and oxidative stress. Using whole genome sequencing, we identified a non-synonymous mutation within an uncharacterized LacI-type transcription factor, ycjW. We then mapped regulatory targets of YcjW and discovered it controls the expression of carbohydrate metabolic genes and thiosulfate sulfurtransferase PspE. Induction of pspE expression in the suppressor strain provides an alternative mechanism for H2S biosynthesis. Our results reveal a complex interaction between carbohydrate metabolism and H2S production in bacteria and the role, a hitherto uncharacterized transcription factor, YcjW, plays in linking the two.


Diagnosis of pericardial effusion by ultrasound.
A reliable method of determining the presence of a pericardial effusion has been evolved. Ultrasonic waves reflected from the posterior part of the anterior chest wall and from the anterior surface of the anterior myocardium and pericardium produce echoes separated from each other by a bare area. This bare area varies in width and the variation has the same periodicity as the cardiac cycle.


Sequence structure and intragenomic variability of ribosomal ITS2 in monozoic tapeworms of the genus Khawia (Cestoda: Caryophyllidea), parasites of cyprinid fish.
The sequence structure of the ribosomal internal transcribed spacer 2 (ITS2) was determined for six species of Khawia (Cestoda: Caryophyllidea), parasites of cyprinid fish in the Holarctic Region. Homologous intragenomic ITS2 structure was found in Khawia armeniaca, Khawia baltica, and Khawia rossittensis; whereas divergent intragenomic ITS2 copies were detected in Chinese, Japanese, and Slovak isolates of Khawia sinensis and in Khawia japonensis, both parasitic in common carp, and in Khawia saurogobii, recently described from Chinese lizard gudgeon in China. Despite distinct morphological differences between K. saurogobii and K. sinensis, both species display very high level of molecular homogeneity. Variation in number of short repetitive motifs [(GCCT)(n) (GCCC)(n)], [(GTG)(n)], [(ATAC)(n)], [ACGTGT (TCGTGT)(n)], [(GT)(n)], [(GT)(n)], and [(ACCT)(n) (GCCT)(n)] resulted in assortment of ITS2 sequences in four ITS2 variants in K. saurogobii from China, three in Chinese and Japanese isolates of K. sinensis, and five ITS2 variants in K. sinensis from Slovakia. In K. japonensis, the structure and arrangement of microsatellites was different from those of K. sinensis and K. saurogobii. The heterogeneity in the number of two microsatellite regions [(TG)(n); (TTG)(n)] divided ITS2 clones into two variants-first ITS2 variant (472 bp) with (TG)(5) and (TTG)(6), and second variant with (TG)(7) and (TTG)(2) (465 bp). Sequence identity of K. saurogobii with all but one (K. sinensis) congeneric species ranged between 49.5 and 69.2%, which corresponds to the interspecific differences. In contrast, sequence identity of K. saurogobii and K. sinensis (87.6-95.0%) failed into the range of intraspecific variation determined for K. sinensis samples. This close genetic similarity indicates that recently described K. saurogobii may have undergone morphological divergence as a result of ongoing sympatric speciation by host switching.


Multiplex real-time reverse transcription-PCR assay for determination of hepatitis C virus genotypes.
A variety of methods have been used to determine hepatitis C virus (HCV) genotypes. Because therapeutic decisions for chronic HCV-related hepatitis are made on the basis of genotype, it is important that genotype be accurately determined by clinical laboratories. Existing methods are often subjective, inaccurate, manual, time-consuming, and contamination prone. We therefore evaluated real-time reverse transcription-PCR (RT-PCR) reagents that have recently become commercially available (Abbott HCV Genotype ASR). The assay developed by our laboratory starts with purified RNA and can be performed in 4 to 5 h. An initial evaluation of 479 samples was done with a restriction fragment length polymorphism (RFLP) method and the RT-PCR assay, and discrepant samples were sequenced. An additional 1,200 samples were then tested, and data from all assays were used to evaluate the efficiency and specificity of each genotype-specific reaction. Good correlation between results by the two methods was seen. Discrepant samples included those indeterminate by the RT-PCR assay (n = 110) and a subset that were incorrectly called 2a by the RFLP method (n = 75). The real-time RT-PCR assay performed well with genotype 1, 2, and 3 samples. Inadequate numbers of samples were available to evaluate fully genotypes 4, 5, and 6. Analysis of each primer-probe set demonstrated that weak cross-reactive amplifications were common but usually did not interfere with the genotype determination. However, in about 1% of samples, two or more genotypes amplified at roughly equivalent amounts. Further studies are necessary to determine whether these mixed-genotype samples are true mixtures or a reflection of occasional cross-reactive amplifications.


Characterization of Bacteriophage cd2, a Siphophage Infecting Carnobacterium divergens and a Representative Species of a New Genus of Phage.
Carnobacterium divergens is frequently isolated from natural environments and is a predominant species found in refrigerated foods, particularly meat, seafood, and dairy. While there is substantial interest in using C. divergens as biopreservatives and/or probiotics, some strains are known to be fish pathogens, and the uncontrolled growth of C. divergens has been associated with food spoilage. Bacteriophages offer a selective approach to identify and control the growth of bacteria; however, to date, few phages targeting C. divergens have been reported. In this study, we characterize bacteriophage cd2, which we recently isolated from minced beef. A detailed host range study reveals that phage cd2 infects certain phylogenetic groups of C. divergens. This phage has a latent period of 60 min and a burst size of ~28 PFU/infected cell. The phage was found to be acid and heat sensitive, with a complete loss of phage activity when stored at pH 2 or heated to 60°C. Electron microscopy shows that phage cd2 is a siphophage, and while it shares the B3 morphotype with a unique cluster of Listeria and Enterococcus phages, a comparison of genomes reveals that phage cd2 comprises a new genus of phage, which we have termed as Carnodivirus. IMPORTANCE Currently, very little is known about phages that infect carnobacteria, an important genus of lactic acid bacteria with both beneficial and detrimental effects in the food and aquaculture industries. This report provides a detailed characterization of phage cd2, a novel siphophage that targets Carnobacterium divergens, and sets the groundwork for understanding the biology of these phages and their potential use in the detection and biocontrol of C. divergens isolates.


Penicillium purpurogenum produces a family 1 acetyl xylan esterase containing a carbohydrate-binding module: characterization of the protein and its gene.
At least three acetyl xylan esterases (AXE I, II and III) are secreted by Penicillium purpurogenum. This publication describes more detailed work on AXE I and its gene. AXE I binds cellulose but not xylan; it is glycosylated and inactivated by phenylmethylsulphonyl fluoride, showing that it is a serine esterase. The axe1 gene presents an open reading frame of 1278 bp, including two introns of 68 and 61 bp; it codes for a signal peptide of 31 residues and a mature protein of 351 amino acids (molecular weight 36,693). AXE I has a modular structure: a catalytic module at the amino terminus belonging to family 1 of the carbohydrate esterases, a linker rich in serines and threonines, and a family 1 carboxy terminal carbohydrate binding module (CBM). The CBM is similar to that of AXE from Trichoderma reesei, (with a family 5 catalytic module) indicating that the genes for catalytic modules and CBMs have evolved separately, and that they have been linked by gene fusion. The promoter sequence of axe1 contains several putative sequences for binding of gene expression regulators also found in other family 1 esterase gene promoters. It is proposed that AXE I and II act in succession in xylan degradation; first, xylan is attacked by AXE I and other xylanases possessing CBMs (which facilitate binding to lignocellulose), followed by other enzymes acting mainly on soluble substrates.


Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy.
Mild micro-hepatic encephalopathy (MHE) is a severe complication of cirrhosis. At present, there are differences in the consistency of detection strategies and treatment directions for MHE. The characteristic changes in intestinal microbiota and serum metabolites in MHE patients and the possible relevant interaction mechanisms would inevitably affect the developmental direction of MHE. Therefore, the changes in the characteristics of intestinal microbiota and serum metabolites of MHE patients were determined, and the possible interactions between them were analyzed. Stool and serum tests were performed on both the MHE patients and healthy individuals. The 16S rRNA gene high-throughput sequencing and bioinformatics analyses were used to analyze the differences in intestinal microbiota in MHE patients. The serum metabolites were detected using liquid LC-MS/MS (liquid chromatography-mass spectrometry) technology, and the differences in the metabolic networks of blood metabolites in MHE patients were analyzed. A comprehensive bioinformatics analysis approach was adopted to identify the composition and characteristics of microbiota and serum metabolites and the possible correlation between them. The main characteristics of the structural imbalance in the intestinal microbiota of MHE patients included a decrease in the number of beneficial bacteria at the levels of phylum, class, order, family, and genus and an increase in the pathogenic bacteria, resulting in substantial changes in the relative abundances of bacteria in the intestinal microbiota. The main predicted functions that showed significant differences included chromosome, amino acid-related enzymes, methane metabolism, and arginine and proline metabolism. The detection of serum metabolites resulted in 10 different metabolites, including taurocholic acid, citrulline, d-phenyl-lactic acid, l-tyrosine, benzoate, phenylalanine, linoleic acid, eicosapedienic acid, alpha-dimorphecolic acid, and dehydroepiandrosterone. The subsequent metabolite pathways analysis showed differences in the metabolism of linoleic acid, phenyl-propane, caffeine, arginine, proline, glycine, serine, threonine, tyrosine, and pyrimidine compared to the control group. In summary, it seems that the changes in the microbiome that we have identified have resulted in corresponding changes to the serum metabolome. In turn, this may represent changes in the absorption of metabolites from the gut or reflect the changed metabolic capacity of the MHE liver or both. There were characteristic changes in the intestinal microbiota and serum metabolites in the MHE patients. There might be a related interaction mechanism between the two, which would provide evidence and direction for the detection and treatment strategies of MHE.


microRNA-146a as a biomarker for transmissible spongiform encephalopathy.
The pro-inflammatory, innate-immune system ribonucleic acid mediator microRNA-146a, constitutively expressed in the brain and central nervous system (CNS) of both the mouse and the human, is pathologically up-regulated in multiple transmissible spongiform encephalopathies (TSEs) to several times its basal level. miRNA-146a: (i) exists as a ~22-ribonucleotide (nt) single-stranded non-coding RNA (sncRNA) whose sequence is unique and highly selected over evolution; (ii) is brain-, CNS- and lymphoid-tissue enriched and exhibits a 100% RNA sequence homology between the mouse and the human; (iii) has been repeatedly shown to play critical immunological and pro-inflammatory roles in the onset and propagation of several human CNS disorders including progressive, incapacitating, and lethal neurological syndromes that include prion disease (PrD) and Alzheimer's disease (AD); (iv) is a fascinating molecular entity because it is representative of the smallest class of soluble, information-carrying, amphipathic sncRNA yet described; (v) has capability to be induced by cellular stressors and the pro-inflammatory transcription factor NF-kB (p50/p65); (vi) has capability to post-transcriptionally regulate multiple mRNAs and cellular processes in neurological health and disease; (vii) is upregulated in human host cells after viral invasion by single-stranded RNA (ssRNA) or double-stranded DNA (dsDNA) neurotropic viruses; and (viii) has an immense potential in neuro-degenerative disease therapeutics via anti-NF-kB and/or anti-miRNA-146a treatment strategies. In this short communication we provide for the first time evidence that miRNA-146a is a prominent sncRNA species in experimental murine prion disease, progressively increasing in the pre-symptomatic stages in C57BL/6J, SJL/J or Swiss Albino murine scrapie prion models. The highest miRNA-146a levels were quantified in these three different murine scrapie models exhibiting full symptomology of prion infection. The results suggest that miRNA-146a levels in the brain may be useful as an accessory diagnostic, prognostic or response-to-treatment biomarker to monitor the onset and development of PrD in experimental murine models that may also be extrapolated to be a relevant adjunct biomarker in human TSEs.


Dominant denitrifying bacteria are important hosts of antibiotic resistance genes in pig farm anoxic-oxic wastewater treatment processes.
The anoxic-oxic (A/O) wastewater treatment process that is widely used in pig farms in China is an important repository for antibiotic resistance genes (ARGs). However, the distribution of ARGs and their hosts in the A/O process has not been well characterized. In this study, the wastewaters in the anoxic and oxic tanks for A/O processes were collected from 38 pig farms. The concentrations of 20 subtypes of ARGs, 5 denitrification-related genes, 2 integrons, and bacterial community composition were investigated. Bacterial genome binning was performed using metagenome sequencing. In this study, 20 subtypes of ARGs and integrons were detected in all sampling sites. A total of 16 of the 20 subtypes of ARGs were detected with the highest abundance in anoxic tanks, and sul1 was detected with a maximum average abundance of 19.21 ± 0.24 log10 (copies/mL). Cooccurrence patterns were observed for some genes in the pig farm A/O process, such as sul1 and intl1, sul1 and tetG, and tetO and tetW. There was a significant cooccurrence pattern between the dominant denitrifying bacteria and some ARGs (blaTEM, ermB, tetC, tetH and tetQ), so the dominant denitrifying bacteria were considered to be potential ARG hosts. In addition, 170 highly abundant bacterial genome bins were assembled and further confirmed that the denitrifying bacteria Brachymonas, Candidatus Competibacter, Thiobacillus and Steroidobacter were the important ARG hosts in the pig farm A/O process, providing a useful reference for the surveillance and risk management of ARGs in pig farm wastewater.


The role of the amygdala and the basal ganglia in visual processing of central vs. peripheral emotional content.
In human cognition, most relevant stimuli, such as faces, are processed in central vision. However, it is widely believed that recognition of relevant stimuli (e.g. threatening animal faces) at peripheral locations is also important due to their survival value. Moreover, task instructions have been shown to modulate brain regions involved in threat recognition (e.g. the amygdala). In this respect it is also controversial whether tasks requiring explicit focus on stimulus threat content vs. implicit processing differently engage primitive subcortical structures involved in emotional appraisal. Here we have addressed the role of central vs. peripheral processing in the human amygdala using animal threatening vs. non-threatening face stimuli. First, a simple animal face recognition task with threatening and non-threatening animal faces, as well as non-face control stimuli, was employed in naïve subjects (implicit task). A subsequent task was then performed with the same stimulus categories (but different stimuli) in which subjects were told to explicitly detect threat signals. We found lateralized amygdala responses both to the spatial location of stimuli and to the threatening content of faces depending on the task performed: the right amygdala showed increased responses to central compared to left presented stimuli specifically during the threat detection task, while the left amygdala was better prone to discriminate threatening faces from non-facial displays during the animal face recognition task. Additionally, the right amygdala responded to faces during the threat detection task but only when centrally presented. Moreover, we have found no evidence for superior responses of the amygdala to peripheral stimuli. Importantly, we have found that striatal regions activate differentially depending on peripheral vs. central processing of threatening faces. Accordingly, peripheral processing of these stimuli activated more strongly the putaminal region, while central processing engaged mainly the caudate nucleus. We conclude that the human amygdala has a central bias for face stimuli, and that visual processing recruits different striatal regions, putaminal or caudate based, depending on the task and on whether peripheral or central visual processing is involved.


Chemical Compositions of Eupatorium heterophyllum Leaf Samples from Yunnan and Sichuan Provinces of China-Isolation of 13 New Sesquiterpene Lactones.
Eight samples of Eupatorium heterophyllum leaves were collected at different locations in Yunnan and Sichuan provinces in China, and their chemical constituents were investigated. Thirteen previously undescribed sesquiterpene lactones-seven germacranolides, three eudesmanolides, two guaianolides, and a 2-norelemanolide-were isolated, and their structures were elucidated based on extensive spectroscopic analyses. The major constituents in the six samples from northwestern Yunnan and Sichuan are hiyodorilactones A and B, whereas that in the two samples from the region near Kunming, Yunnan is eupatoriopicrin. These results and previously reported results suggest the presence of locality-dependent intra-specific diversity in the chemical constituents of E. heterophyllum leaves.


Using volume-time curves with real-time three-dimensional echocardiography to analyze right ventricular function in patients with pneumoconiosis.
We evaluated right ventricular function in patients with pneumoconiosis using real-time three-dimensional echocardiography (RT3DE). A total of 80 consecutive patients were prospectively recruited, 44 of whom were diagnosed with pneumoconiosis, and the remaining 36 age- and gender-matched healthy volunteers served as the control group. All patients underwent both 2D and 3DE. The tricuspid regurgitation pressure (TRPG), right ventricular anterior wall thickness and range of motion, right ventricular posterior wall thickness and range of motion, right ventricular end-diastolic volume, right ventricular end-systolic volume, and right ventricular ejection fraction (RVEF) were measured. The RVEF of healthy volunteers ranged from 50 to 78%, while the RVEF of pneumoconiosis patients ranged from 29 to 73%. TRPG influenced RVEF by 77.3% (P = 0.006) and showed a negative correlation (r = -0.643, P < 0.01). Volume-time curves (VTC) of patients with pneumoconiosis showed more troughs (low stroke volumes) than the VTCs of normal subjects. Evaluation of right ventricular function in patients with pneumoconiosis using RT3DE can provide additional clinical information.


Evaluation of water treatment sludge for ameliorating acid mine waste.
This study investigated the liming effect of water treatment sludge on acid mine spoils. The study was conducted with sludge from a water purification plant along the Vaal River catchments in South Africa. The optimum application rate for liming acid spoils and the speed and depth with which the sludge reacted with the mine waste were investigated. Chemical analysis indicated that the sludge is suitable as a liming agent because of its alkaline pH (8.08), high bicarbonate concentration (183.03 mg L(-1)), and low salinity (electrical conductivity = 76 mS m(-1)). The high cation exchange capacity of 15.47 cmol(c) kg(-1) and elevated nitrate concentration (73.16 mg L(-1)) also increase its value as an ameliorative material. The soluble concentrations for manganese, aluminum, lead, and selenium were high at a pH of 5 although only selenium (0.83 mg L(-1)) warranted some concern. According to experimental results, the application of 10 Mg ha(-1) of sludge to acid gold tailings increased the leach water pH from 4.5 to more than 7.5 and also increased the medium pH from 2.4 to 7.5. The addition of sludge further reduced the solubility of iron, manganese, copper, and zinc in the ameliorated gold tailings, but increased the electrical conductivity. The liming tempo was highest in the coal discard profile that had a coarse particle size distribution and took the longest to move through the gold tailings that had a fine particle size distribution. Results from this study indicate that the water treatment sludge investigated is suitable as a liming agent for rehabilitation of acid mine waste.


Imaging to distinguish between viable and nonviable myocardium: pathophysiologic basis and importance of positron emission tomography.
One goal of strategies designed to restore nutritive perfusion in patients with left ventricular dysfunction attributable to coronary artery disease is salvage of reversibly ischemic myocardium in an effort to improve patients' left ventricular function, signs and symptoms, and survival. Accurate identification of patients likely to benefit from interventions such as coronary revascularization requires the differentiation of viable (reversibly dysfunctional) myocardium from nonviable (persistently dysfunctional) tissue. To date, no consensus has been reached regarding the best approach for achieving this differentiation. In this review, the pathophysiologic characteristics of viable and nonviable myocardium are summarized, and diagnostic methods that exploit these characteristics for the purposes of detecting viable myocardium are discussed. Emphasis is placed on approaches that use positron emission tomography because of its usefulness in quantifying those specific metabolic processes that support both tissue viability and the capacity for functional recovery.


Tandem carbon-carbon bond constructions via catalyzed cyanation/Brook rearrangement/C-acylation reactions of acylsilanes.
[reaction: see text] A tandem nucleophile-catalyzed cyanation/Brook rearrangement/C-acylation has been developed. Phase transfer cocatalysts facilitate cyanide-catalyzed reactions between acylsilanes and cyanoformates to afford protected tertiary carbinol products. A catalytic cycle is proposed involving cyanation of an acylsilane, [1,2]-Brook rearrangement, and C-acylation of the derived carbanion by a cyanoformate ester. The reaction offers an efficient method for the preparation of functionalized, unsymmetrical malonic acid derivatives.


Erp29 Attenuates Cigarette Smoke Extract-Induced Endoplasmic Reticulum Stress and Mitigates Tight Junction Damage in Retinal Pigment Epithelial Cells.
Endoplasmic reticulum protein 29 (ERp29) is a novel chaperone that was recently found decreased in human retinas with AMD. Herein, we examined the effect of ERp29 on cigarette smoke-induced RPE apoptosis and tight junction disruption. Cultured human RPE (HRPE) cells (ARPE-19) or mouse RPE eyecup explants were exposed to cigarette smoke extract (CSE) for short (up to 24 hours) or long (up to 3 weeks) periods. Expression of ERp29 was up- and downregulated by adenovirus and siRNA, respectively. Endoplasmic reticulum stress markers, apoptosis, and cell death, the expression and distribution of tight junction protein ZO-1, transepithelial electrical resistance (TEER), and F-actin expression were examined. Endoplasmic reticulum protein 29 was significantly increased by short-term exposure to CSE in ARPE-19 cells or eyecup explants but was reduced after 3-week exposure. Overexpression of ERp29 increased the levels of GRP78, p58(IPK), and Nrf-2, while reducing p-eIF2α and C/EBP homologous protein (CHOP), and protected RPE cells from CSE-induced apoptosis. In contrast, knockdown of ERp29 decreased the levels of p58(IPK) and Nrf2, but increased p-eIF2α and CHOP and exacerbated CSE-triggered cell death. In addition, overexpression of ERp29 attenuated CSE-induced reduction in ZO-1 and enhanced the RPE barrier function, as measured by TEER. Knockdown of ERp29 decreased the level of ZO-1 protein. These effects were associated with changes in the expression of cytoskeleton F-actin. Endoplasmic reticulum protein 29 attenuates CSE-induced ER stress and enhances cell viability and barrier integrity of RPE cells, and therefore may act as a protective mechanism for RPE survival and activity.


The complete mitochondrial genome of Boeseman's rainbowfish (Melanotaenia boesemani Allen & Cross, 1980).
In this study, the mitochondrial genome of Melanotaenia boesemani (Allen & Cross, 1980 ) (Atheriniformes: Melanotaeniidae) was sequenced for the first time. The assembled mitogenome consisting of 16 493 bp, includes 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs genes and 1 putative control region. The overall base composition of M. boesemani is 27.88% for A, 29.92% for C, 15.74% for G, 26.47% for T and shows 96% identities to Lake Kutubu rainbowfish, Melanotaenia lacustris. These data would provide useful molecular information for phylogenetic relationships within the family Melanotaeniidae species.


The role of unintended pregnancy in internalized stigma among women living with HIV in Kenya.
Kenya has successfully expanded HIV treatment, but HIV-related stigma and discrimination, and unintended pregnancy remain issues for many Kenyan women living with HIV. While HIV-related stigma can influence the health seeking behaviors of those living with HIV, less is known about how reproductive health outcomes influence internalized stigma among women living with HIV. Baseline data only were used in this analysis and came from an implementation science study conducted in Kenya from 2015 to 2017. The analytic sample was limited to 1116 women who are living with HIV, between 18 to 44 years old, and have ever experienced a pregnancy. The outcome variable was constructed from 7 internalized stigma statements and agreement with at least 3 statements was categorized as medium/high levels of internalized stigma. Unintended pregnancy, categorized as unintended if the last pregnancy was mistimed or unwanted, was the key independent variable. Univariate and multivariate logistic regression models were used to assess the association between unintended pregnancy and internalized stigma. Associations between internalized stigma and HIV-related discrimination and violence/abuse were also explored. About 48% agreed with at least one internalized stigma statement and 19% agreed with at least three. Over half of women reported that their last pregnancy was unintended (59%). Within the year preceding the survey, 52% reported experiencing discrimination and 41% reported experiencing violence or abuse due to their HIV status. Women whose last pregnancy was unintended were 1.6 times (95% CI 1.2-2.3) more likely to have medium/high levels of internalized stigma compared to those whose pregnancy was wanted at the time, adjusting for respondents' characteristics, experiences of discrimination, and experiences of violence and abuse. Women who experienced HIV-related discrimination in the past 12 months were 1.8 times (95% CI 1.3-2.6) more likely to have medium/high levels of internalized stigma compared to those who experienced no discrimination. Results suggest that unintended pregnancy is associated with internalized stigma. Integrated HIV and FP programs in Kenya should continue to address stigma and discrimination while increasing access to comprehensive voluntary family planning services for women living with HIV.


Coevolutionary genetic variation in the legume-rhizobium transcriptome.
Coevolutionary change requires reciprocal selection between interacting species, where the partner genotypes that are favoured in one species depend on the genetic composition of the interacting species. Coevolutionary genetic variation is manifested as genotype × genotype (G × G) interactions for fitness in interspecific interactions. Although quantitative genetic approaches have revealed abundant evidence for G × G interactions in symbioses, the molecular basis of this variation remains unclear. Here we study the molecular basis of G × G interactions in a model legume-rhizobium mutualism using gene expression microarrays. We find that, like quantitative traits such as fitness, variation in the symbiotic transcriptome may be partitioned into additive and interactive genetic components. Our results suggest that plant genetic variation had the largest influence on nodule gene expression and that plant genotype and the plant genotype × rhizobium genotype interaction determine global shifts in rhizobium gene expression that in turn feedback to influence plant fitness benefits. Moreover, the transcriptomic variation we uncover implicates regulatory changes in both species as drivers of symbiotic gene expression variation. Our study is the first to partition genetic variation in a symbiotic transcriptome and illuminates potential molecular routes of coevolutionary change.


Synthesis, activity and metabolic stability of propan-2-one substituted tetrazolylalkanoic acids as dual inhibitors of cytosolic phospholipase A2α and fatty acid amide hydrolase.
The serine hydrolases cytosolic phospholipase A2α (cPLA2α) and fatty acid amide hydrolase (FAAH) are interesting targets for the development of new anti-inflammatory and analgesic drugs. Structural modifications of a potent dual inhibitor with a propan-2-one substituted tetrazolylpropionic acid moiety led to compounds with also nanomolar activity against both enzymes but better physicochemical properties. The structure-activity relationships showed that the variations had partially divergent effects on the inhibitory activity of the compounds towards cPLA2α and FAAH reflecting differences in the binding mode to the enzymes. Furthermore, the metabolic stability of the target structures was investigated in vitro.


CD28nullCD4+ T cells--characterization of an effector memory T-cell population in patients with rheumatoid arthritis.
CD4+ T cells lacking the costimulatory molecule CD28 have been described both in elderly individuals and in chronic inflammatory disorders, one being rheumatoid arthritis (RA). We, in this study, provide a comprehensive characterization of cell surface markers on and function of such CD28nullCD4+ T cells, as well as correlations with clinical parameters. We conclude that of all surface markers associated with these cells, only CD57 and CD11b are expressed on the majority of them. This CD28null population occurred in one-third of patients with RA and was independent of clinical characteristics. The population was persistent and expanded in peripheral blood, but was excluded from the joint in most patients. Functionally, CD28nullCD4+ T cells were potent effector memory cells with regard to their proliferation and cytokine-secretion profiles. This capacity correlated with a hitherto unpublished surface phenotype, the cells being uniformly CCR7- and CD43high. Moreover, a new terminally differentiated CD45RA+CCR7- population of CD4+ T cells was identified. We would like to suggest that in the unbalanced immune system of patients with autoimmune disease and chronic infection an expanded CD28nullCD4+ T-cell population able to secrete high levels of cytokines is likely to contribute to disease manifestations.


LRRK2 mutation alters behavioral, synaptic, and nonsynaptic adaptations to acute social stress.
Parkinson's disease (PD) risk is increased by stress and certain gene mutations, including the most prevalent PD-linked mutation LRRK2-G2019S. Both PD and stress increase risk for psychiatric symptoms, yet it is unclear how PD-risk genes alter neural circuitry in response to stress that may promote psychopathology. Here we show significant differences between adult G2019S knockin and wild-type (wt) mice in stress-induced behaviors, with an unexpected uncoupling of depression-like and hedonia-like responses in G2019S mice. Moreover, mutant spiny projection neurons in nucleus accumbens (NAc) lack an adaptive, stress-induced change in excitability displayed by wt neurons, and instead show stress-induced changes in synaptic properties that wt neurons lack. Some synaptic alterations in NAc are already evident early in postnatal life. Thus G2019S alters the magnitude and direction of behavioral responses to stress that may reflect unique modifications of adaptive plasticity in cells and circuits implicated in psychopathology in humans.NEW & NOTEWORTHY Depression is associated with Parkinson's disease (PD), and environmental stress is a risk factor for both. We investigated how LRRK2-G2019S PD mutation affects depression-like behaviors, synaptic function, and intrinsic neuronal excitability following stress. In response to stress, the mutation drives abnormal synaptic changes, prevents adaptive changes in intrinsic excitability, and leads to aberrant behaviors, thus defining new ways in which PD mutations derail adaptive plasticity in response to stress that may contribute to disease onset.


[Peritonitis caused by the rupture of an amebic abscess of the liver in childhood].
The peritonitis from the rupture of the amebic liver's abscess is a not rare complication of the hepatic amebiasis in the children, with a poor prognosis. The usual treatment is loaded with a high morbility and mortality. The AA show a therapeutic screen based on saucerization with debridment and on the installation of a disposal of peritoneal washing. The above mentioned treatment is looking at the recovery of the organ and consequently at the direct removal of the "primum movens" of the septic shock and generalized peritonitis.


Pulmonary edema associated with upper airway obstruction.
We retrospectively surveyed records of 153 patients with croup or epiglottitis. Thirty-four children required intubation of the trachea to relieve upper airway obstruction. In those requiring intubation, pulmonary edema occurred in four (12%) of 34. Review of 17 previously reported cases, along with our patients, demonstrated that onset of pulmonary edema due to upper airway obstruction usually follows intubation. A PaO2 below 50 mm Hg is observed in 38% and pneumothorax in 24% of all reported cases. Supplemental oxygen, positive end-expiratory pressure, mechanical ventilation, and chest tube drainage have prevented death despite these life-threatening complications.


Hormones and territorial behavior during breeding in snow buntings (Plectrophenax nivalis): an Arctic-breeding songbird.
We examined hormonal profiles and behavior associated with maintaining a single-purpose territory in an Arctic-breeding songbird-the snow bunting (Plectrophenax nivalis). Snow buntings differ from many other Arctic-breeding passerines by using nest cavities, an uncommon and defended resource, but not relying upon the surrounding territory for forage. Circulating levels of testosterone in males were high when territories were established and then decreased over the breeding season. LH secretion was enhanced in females while laying eggs, followed by detectable levels of estradiol during incubation. Both sexes showed equivalent corticosterone responses to the stress of being captured and held. Male snow buntings vigorously defended territories in response to a simulated territorial intrusion both when initiating breeding and when feeding young. Exogenous testosterone implants surprisingly inhibited physical aggression but enhanced singing when birds were feeding young, thus suggesting that song and physical aggression are mediated by different hormonal mechanisms at this time of year. Together, these results contrast with hormonal profiles and behavior in other Arctic-breeding passerines.


Interlaboratory method validation of capillary electrophoresis sodium dodecyl sulfate (CE-SDS) methodology for analysis of mAbs.
Capillary electrophoresis sodium dodecyl sulfate (CE-SDS) is an analytical method to assess the purity of proteins, commonly applied to monoclonal antibodies (mAbs) in the biopharmaceutical industry. To address the need to standardize the CE-SDS method in the pharmaceutical industry and to enhance the confidence in method transfer between laboratories operating different commercial capillary electrophoresis (CE) instrument platforms, an interlaboratory CE-SDS method validation was organized involving 13 laboratories in 13 companies on four different types of commercial capillary electrophoresis instruments. In the validation, a commercial mAb therapeutic was used as the sample. The validation process followed the analytical guidelines set by the ICH guidelines (International Conference for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use). The method's precision, accuracy, linearity and range, and limit of quantitation (LOQ) were validated in the study. Variations of all the parameters validated in the study passed the pre-set criteria defined at the beginning of the study. The definition was based on previously published works and the intended application purpose of the CE-SDS method for mAbs. The study proved that the CE-SDS method fits its intended application purpose as a size impurity assay and size heterogeneity characterization assay for mAb therapeutic products. This study is the first time a CE-SDS method is validated by multiple laboratories using different commercial CE instrument platforms and on a commercial mAb therapeutic. Its results will enhance the confidence of the biopharmaceutical industry to develop CE-SDS methods and transfer CE-SDS methods between different laboratories.


Acute ascending thrombosis of abdominal and suprarenal aorta.
We report the diagnostic and successful therapeutic images of an acute occlusion of the abdominal and suprarenal aorta. This lesion is a rare but catastrophic pathology which can cause severe ischemic manifestations, depending on the site of obstruction, with high rate of mortality even after treatment. In the majority of cases it represents a surgical emergency. Although the mechanism of the thrombosis has not been delineated, the proposed etiologies include propagation of thrombus from distal artery occlusion, cardiac thromboembolism, dislodgment of a mural thrombus, or coagulation disorders. Frequent risk factors include advanced atherosclerosis combined with a low flow state because of poor cardiac performance. The management of this condition includes immediate intervention with systemic heparinization, improvement of the cardiac condition, and surgical revascularization based on the clinical and anatomical presentation. In this case the authors highlight the importance of an early detection and early intervention to enhance survival rates and reduce morbidity.


Sex-specific splicing occurs genome-wide during early Drosophila embryogenesis.
Sex-specific splicing is an essential process that regulates sex determination and drives sexual dimorphism. Yet, how early in development widespread sex-specific transcript diversity occurs was unknown because it had yet to be studied at the genome-wide level. We use the powerful Drosophila model to show that widespread sex-specific transcript diversity occurs early in development, concurrent with zygotic genome activation. We also present a new pipeline called time2Splice to quantify changes in alternative splicing over time. Furthermore, we determine that one of the consequences of losing an essential maternally deposited pioneer factor called CLAMP (chromatin-linked adapter for MSL proteins) is altered sex-specific splicing of genes involved in diverse biological processes that drive development. Overall, we show that sex-specific differences in transcript diversity exist even at the earliest stages of development..


Reliability and validity of ratio developmental quotients from the Cattell Infant Intelligence Scale.
The test-retest reliability and predictive validity of developmental quotients (DQs) derived from the Cattell Infant Intelligence Scale as administered to children with mental retardation over 30 months of age was assessed. When DQs of 36 children assessed twice with the Cattell were compared, scores were highly correlated, with no significant difference between them, indicating impressive test score stability. When DQs of 47 youngsters assessed once with the Cattell and once with the Stanford-Binet, Form L-M, were compared, scores were significantly correlated but significantly discrepant. These results were compared to previous findings (Goldstein & Sheaffer, 1988) on the Bayley Scales of Infant Development as a predictor of Stanford-Binet IQ. The DQs derived from the Bayley were superior to Cattell DQs in predicting Stanford-Binet IQ.


Rayleigh-Taylor instability under a flat beam.
A theoretical and experimental study on the Rayleigh-Taylor instability of a thin liquid film is presented. The experiments were performed by coating the underside of a flat beam with uniform liquid film. The size of the beam is such that a linear arrangement of drops is formed allowing the measurement of the drops growth. The experimental growth of the drops has been compared to the results obtained from a stability analysis performed on the equation that controls the thickness evolution and an excellent agreement is found. In addition, both time and length scales of the phenomenon are established.