The Zinc-Finger protein ZCCHC3 inhibits LINE-1 retrotransposition.
Long-interspersed element 1 (LINE-1) is an autonomous non-LTR retrotransposon. Its replication can cause mutation and rearrangement of host genomic DNA, which may result in serious genetic diseases. Host cells therefore developed defense strategies to restrict LINE-1 mobilization. In this study, we reported that CCHC-type zinc-finger protein ZCCHC3 can repress LINE-1 retrotransposition, and this activity is closely related to its zinc-finger domain. Further studies show that ZCCHC3 can post-transcriptionally diminish the LINE-1 RNA level. The association of ZCCHC3 with both LINE-1 RNA and ORF1 suggests that ZCCHC3 interacts with LINE-1 RNP and consequently causes its RNA degradation. These data demonstrate collectively that ZCCHC3 contributes to the cellular control of LINE-1 replication.


Autofluorescence reveals menstrual phase in the endometrium.
Tissue contains fluorophores that autofluoresce without additional dye or photosensitizer with the appropriate light excitation. This technique has been widely applied for discrimination between normal and precancerous tissue. The aim of this study was to explore the capability and reliability of autofluorescence phase determination in samples of human endometrium. A total of 70 measurement sites from 31 endometrial tissue samples from hysterectomy were enrolled. Xenon light (330 nm) was directed at the endometrial tissue and the resultant autofluorescence intensity recorded. Spectra were then grouped according to the proliferative and secretory phase, with multivariant analysis, partial least square (PLS) and analysis of variance (ANOVA) used for evaluation of the statistical significance of phase determination. Both proliferative and secretory autofluorescence spectra showed a similar characteristic triple-peak curve shape pattern, however, each of the intensities at the three peaks between the two phases varied markedly (p < 0.01). PLS analysis confirmed that collagen, NADH and FAD autofluorescence were the principle determinants of endometrial spectrum; the sensitivity and specificity of phase determination by autofluorescent was 100% and 97%, respectively. Autofluorescence measurement provides real-time information on endometrial phase status and, based on our results, it appears reasonable to suggest that it may be promising as a clinical tool for prompt phase interpretation.


Antigenic relationships among sheep pox, goat pox and contagious pustular dermatitis viruses.
Antigenic relationships among sheep pox, goat pox and contagious pustular dermatitis (CPD) viruses were determined by serological techniques using soluble antigens partially purified by DEAE-cellulose chromatography. Homologous antigen-antibody reactions were characterized by the presence of 7 precipitation lines with sheep pox and of 5 ones each with goat pox and CPD viruses. The nature of cross-reactions of sheep pox, goat pox and CPD virus soluble antigens with corresponding sera suggested that sheep pox virus shared 3 soluble antigenic components with goat pox and either 3 or 4 ones with CPD virus. Goat pox virus shared either 2 or 3 soluble antigenic components with CPD virus. Cross-neutralization tests revealed an one-way cross of goat pox virus with sheep pox and CPD viruses, respectively. The results showed that the 3 viruses in question share common soluble antigenic components.


VAMOS--ventilator assisted model for off-pump surgery.
Introduction of innovative cardiac procedures mostly depends on extensive evaluation using laboratory animal models. Avoiding living creatures in the experimental setup where possible without loss of reliability would be progressive from a logistical as wells as an ethical perspective. Hearts of meat-production animals (pigs) were removed without structural damage. Two tracheotomy tubes (length 35 mm, diameter 10 mm) were inserted into aortic and pulmonal positions. The atrial inflow had to be ligated. The ventilation tubes were joined to a respirator. The "ventilation" frequency was limited to a maximum of 100/min, "inspiration" volume at 100 ml and ventilation pressure at up to 60 mbar. "Air beats" triggered by the frequency of the respirator occurred in the ventilated heart. Insufflation and deflation generated movement that was almost the same as physiological action. Air-animation of the heart using a standard respirator is an easily conducted alternative to extensive and expensive laboratory experiments for development and quality control of new devices or techniques without compromising the scientific value of results and without using living animals.


The pentoxifylline experience: exercise testing reconsidered.
This paper critically reviews the methodology used in clinical trials in chronic occlusive arterial disease (COAD) stage II (intermittent claudication) patients. The reasons for choosing internationally accepted standard treadmill settings as well as its limitations are discussed. Emphasis is put on the discussion of valid trial endpoints such as hemodynamic surrogates and clinically oriented parameters. Reasons for a spontaneous and treatment-unrelated improvement in claudication distance are elucidated, and variables which may be used for the definition of patient subsamples showing a high frequency of a pronounced treatment response (treatment responder populations) are presented. The magnitude of claudication distance improvement that might be considered clinically relevant is discussed in the light of the European Union guidelines for clinical trials in COAD patients. Results achieved with pentoxifylline are presented in context with all variables mentioned above.


Predicting local field potentials with recurrent neural networks.
We present a Recurrent Neural Network using LSTM (Long Short Term Memory) that is capable of modeling and predicting Local Field Potentials. We train and test the network on real data recorded from epilepsy patients. We construct networks that predict multi-channel LFPs for 1, 10, and 100 milliseconds forward in time. Our results show that prediction using LSTM outperforms regression when predicting 10 and 100 millisecond forward in time.


Releasing the brakes of plant growth: how GAs shutdown DELLA proteins.
Bioactive gibberellins (GAs) are tetracyclic diterpenoid plant hormones that promote important processes of plant growth and development, such as seed germination, growth through elongation, and floral transition. Thus, mutant plants that are affected in GA biosynthesis or signalling exhibit altered seed germination and, at the adult stage, are dwarf and dark green and also show delayed flowering. The components of the GA metabolism and signalling pathways are reviewed here and recent findings regarding the regulation and possible mode of action of DELLA proteins are discussed.


Scrub typhus in Himalayas.
Himachal Pradesh state of India is situated in the outer Himalayan ranges. During the rainy season, several cases of acute febrile illness of unknown origin occurred. Orientia tsutsugamushi was identified as the causative agent by microimmunofluorescence and PCR. Two new genotypes of O. tsutsugamushi were identified in the region.


Versatile Movements of Liquid Metal Droplet under Electrostatic Actuation in Alkaline Solutions.
The gallium-based eutectic liquid metal alloys exhibit unique properties of deformability, excellent electrical conductivity and low vapour pressure. The liquid metal-based circuits' element or actuator have drawn considerable attention in stretchable electronics and microelectromechanical (MEMS) actuators. Yet, the motion of the liquid metal within the electrolyte needs to be precisely regulated to satisfy application requirements. Herein, we investigated the locomotion of liquid metal within the alkaline aqueous solution under electrostatic actuation. The relationship between the travelling speed of the liquid metal slug and the relative influential parameters, such as the voltage amplitude and frequencies of the applied electric field, electrolyte concentration, electrodes distance and the liquid metal volume, were experimentally characterized. A travelling speed up to 20.33 mm/s was obtained at the applied voltage of 4 Vpp at 150 Hz at 6 V DC offset. Finally, the frequency-dependent liquid metal marble movements were demonstrated, namely oscillation and forward locomotion while oscillating. The oscillation frequency was determined by the frequency of the applied alternate current (AC) signal. The remarkable transportation and oscillating characteristic of the liquid metal marble under the electrostatic actuation may present potentials towards the development of flexible electronics and reconfigurable structures.


p58, a Cytoskeletal Protein, Is Associated With Muscle Cell Determinants in Ascidian Eggs.
The theory that p58, a cytoskeletal protein, has an important role in ascidian muscle cell development was tested by altering normal distributions of orange-pigmented myoplasm in Boltenia villosa embryos and determining if muscle development is correlated with the presence of p58. Removal of the animal region of fertilized Boltenia eggs resulted in the redistribution of myoplasm into the anterior endoderm cells of the embryo. Despite alterations in the normal distribution of myoplasm, these embryos developed into larvae. However, when four-celled embryos that exhibited altered distributions of pigmented myoplasm were stained with NN18, an antibody that stains p58, a maximum of two blastomeres were stained, as in control embryos. Compression of Boltenia embryos at the four-celled stage caused the myoplasm to be partitioned into four blastomeres of an eight-celled embryo, instead of into two blastomeres. Compressed and cleavage-arrested eight-celled embryos developed myosin and muscle actin RNA in a maximum of four blastomeres, compared to a maximum of two blastomeres in control embryos. When compressed eight-celled embryos were stained with NN18, p58 was present in a maximum of four blastomeres. These results support the idea that the cytoskeletal protein p58 is associated with muscle cell determinants in ascidian eggs.


In vivo inhibitory effect of a conjugate of immunoglobulin G and melphalan, K18, on human tumors transplanted in nude mice.
Various human tumor lines, including gastric, colonic, esophageal, pancreatic, lung and breast cancer, were transplanted in nude mice, and the effect of K18 (IgG conjugated melphalan) on them was assessed and compared with that of melphalan. Melphalan (1 mg/kg) or K18 (100 mg/kg) were administered to mice for 28 days. The tumor growth was significantly inhibited in 5 out of 6 tumors by both agents, although only the esophageal line was insensitive to both agents. Significant loss of body weight was observed in mice after treatment. K18 had no influence on body weight. These results suggested that K18 may be useful in cancer chemotherapy.


Proliferative characteristics of epithelial cells in the pregnant rat uterus.
In the pregnant rat, killed at about mid gestation and 1 h after injection of tritiated thymidine, 40% of the cells in the epithelium lining the uterine lumen at the implantation site were labelled. Between implantation sites fewer than 20% of the surface epithelial cells were labelled. A series of rats was given tritiated thymidine on day 12 of pregnancy and killed at intervals in the next 30 h. A percentage labelled mitoses analysis of the epithelium between implantation sites (interconceptual) and within the implantation site (conceptual) showed that cells in either region spent 7 h in DNA synthesis and 1-5 h in the G2 + 1/2 MITOSIS PHASES. The epithelial cells in the conceptual region spent 1-5 h in the G1 + 1/2 MITOSIS PHASES WHEREAS CELLS IN INTERCONCEPTual regions spent at least 11-5 h in these phases. The average cycle times of cells in conceptual regions was 10 h: in interconceptual regions minimum cycle time was 20 h and the average appeared to be considerably longer. The grain count of the epithelial cells in the conceptual region was rapidly reduced during the 30 h after injection of tritiated thymidine suggesting successive rounds of cell division. In contrast the grain count distribution of cells in interconceptual regions changed only slowly during this time. The percentage of labelled epithelial cells was determined in the animals killed up to 30 h after injection of tritiated thymidine. In both conceptual and interconceptual regions these percentages increased initially as labelled cells produced labelled progeny. In the conceptual region the increase was not maintained after 7 h as cells initially in G1 divided to give unlabelled progeny. In the interconceptual region the increase in the percentage of labelled cells continued for 14 h; thereafter the percentage did not significantly alter. The interpretation of these results is discussed in relation to the differences in the kinetic characteristics of the epithelial cells in the two regions and in relation to the morphology of the epithelium lining the uterus during pregnancy.


Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting.
Human Ku70/Ku80 protein is known to influence HIV-1 replication. One of the possible reasons may be the protection of integrase from proteasomal degradation by Ku70 subunit. We demonstrated that recombinant HIV-1 integrase and Ku70 form a stable complex, while no interaction of Ku70 with integrase from prototype foamy virus was observed. By analyzing protein subdomains we determined two binding sites in the structure of both Ku70 and integrase: the 51-160 a.a. region of integrase interacts with residues 251-438 of Ku70, whereas Ku70 N-terminal domain (1-250 a.a.) contacts an α6-helix in the 200-220 a.a. integrase region. Single substitutions within integrase (E212A or L213A) block the interaction with Ku70 thus indicating that the binding site formed by the 200-220 a.a. integrase region is crucial for complex formation. E212A/L213A substitutions decreased the integrase capacity to bind Ku70 in HEK293T cells. A conjugate of 2'-ОMe-GGUUUUUGUGU oligonucleotide with eosin is shown by molecular modeling to shield integrase residues E212/L213 and is effective in blocking complex formation of Ku70 with integrase what makes the complex between α6-helix and Ku70(1-250) a possible target for drug development.


Activation of the human T-cell leukemia virus type I long terminal repeat by 12-O-tetradecanoylphorbol-13-acetate and by tax (p40x) occurs through similar but functionally distinct target sequences.
One potent transcriptional activator of human T-cell leukemia virus type I (HTLV-I) is virally encoded protein Tax (p40x). p40x trans-activates HTLV-I through the long terminal repeat (LTR) by using a triply repeated 21-base-pair sequence as the target. In this report we have characterized the induction of the HTLV-I LTR by 12-O-tetradecanoylphorbol-13-acetate (TPA). By assaying progressively deleted mutations in the HTLV-I LTR, we have delimited a 60-base-pair sequence in the LTR which is capable of conferring TPA responsiveness, but not p40x responsiveness, to heterologous promoters in a position-independent fashion. This HTLV-I TPA-responsive element is specifically recognized by preexisting factors from uninfected cells. We show that activation of this sequence by phorbol ester does not require de novo cellular protein synthesis. When the HTLV-I LTR was simultaneously activated by both Tax and TPA, an additive effect was seen. This suggests the use of distinct regulatory pathways by the two respective trans-activators.


Self-Calibration of an Industrial Robot Using a Novel Affordable 3D Measuring Device.
This work shows the feasibility of calibrating an industrial robot arm through an automated procedure using a new, low-cost, wireless measuring device mounted on the robot's flange. The device consists of three digital indicators that are fixed orthogonally to each other on an aluminum support. Each indicator has a measuring accuracy of 3 µm. The measuring instrument uses a kinematic coupling platform which allows for the definition of an accurate and repeatable tool center point (TCP). The idea behind the calibration method is for the robot to bring automatically this TCP to three precisely-known positions (the centers of three precision balls fixed with respect to the robot's base) and with different orientations of the robot's end-effector. The self-calibration method was tested on a small six-axis industrial robot, the ABB IRB 120 (Vasteras, Sweden). The robot was modeled by including all its geometrical parameters and the compliance of its joints. The parameters of the model were identified using linear regression with the least-square method. Finally, the performance of the calibration was validated with a laser tracker. This validation showed that the mean and the maximum absolute position errors were reduced from 2.628 mm and 6.282 mm to 0.208 mm and 0.482 mm, respectively.


Mixed lymphocyte culture responses in rabbits undergoing corneal grafting and topical cyclosporine treatment.
Using a vascularized cornea rabbit model closely resembling human high-risk keratoplasty, corneal allografts were performed on three groups of animals that were paired and tested preoperatively by mixed lymphocyte cultures (MLCs). The three groups were group A, unmodified controls with clear corneas; group B, untreated animals with vascularized corneas; and group C, animals treated with topical cyclosporine (CSA) with vascularized corneas. The MLC results were expressed as stimulation indices (SIs) and divided into low (SI < or = 20) and high (SI > 20) responders and were correlated with final outcome of grafts using survival analysis estimates. In group A, five of 13 (38.5%) grafts rejected, the chance of failure depending on the degree of MLC mismatch between donor and recipient (p = 0.02). All allografts in group B rejected regardless of the degree of mismatch. In group C, seven of 12 (58.3%) grafts rejected, indicating that topical CSA significantly improved survival (p = 0.003) compared with group B. Grafts with mild degrees of MLC mismatch (low responders) survived better (p = 0.0003) than did higher degrees of MLC mismatch (high responders), all of which rejected despite treatment. Our results indicate that both corneal vascularization and the degree of donor-recipient matching play important roles in determining corneal graft survival.


Photoconductive detection of tetrahedrally coordinated hydrogen in ZnO.
In this Letter we apply an innovative experimental approach, which allows us to improve the sensitivity of detecting local vibrational modes (LVMs) even in highly absorbing spectral regions. This photoconductive technique allowed us to confirm a recent suggestion of a new multicenter bond for hydrogen in ZnO [A. Janotti and C. G. Van de Walle, Nature Mater. 6, 44 (2007)]. The two LVMs of the hydrogen substituting oxygen in ZnO are identified at 742 and 792 cm(-1). The modes belong to a nondegenerated A(1) and a twofold degenerated E representations of the C(3v) point group. The tetrahedral coordination of the hydrogen atom is the result of a newly detected multicenter bond for defects in solids.


Effect of Electroacupuncture at Wushu Acupoints of the Cardiopulmonary Meridian on the Autophagy in Rats with Acute Myocardial Ischemia.
Wushu acupoints are the five acupoints distributed below the human elbow and knee joint. They are all located on the same meridian and divided into five categories: Jing, Ying, Shu, Jing, and He. It has been shown that electroacupuncture (EA) at Shenmen point of heart meridian can improve acute myocardial ischemia (AMI) early. However, it is still unclear if all the Wushu acupoints of the heart meridian can improve AMI. Hence, this study emphasizes Wushu acupoints of heart meridian, compares them with Wushu acupoints of lung meridian, and studies the therapeutic effect of EA at Wushu acupoints on AMI and its possible mechanism. It also discusses the specificity of the heart meridian to heart disease. The AMI model is established by ligation of the left anterior descending coronary artery. The detection methods like the physiological recorder, TTC staining, ELISA, and so forth were used to determine the ECG, myocardial infarct size, serum myocardial enzymes, and myocardial tissue-related protein expression in rats. The heart rate (HR) and ST segment along with creatine kinase (CK), creatine kinase isoenzymes (CK-MB), lactate dehydrogenase (LDH), and myocardial infarctions increased after the induction with AMI. Furthermore, the expressions of PINK1 and Parkin protein also showed an increase. However, EA at Wushu acupoints in the heart meridian can reverse the above changes, whereas EA at the lung meridian exhibits limited effect. It is depicted that the heart meridian has a relatively specific relationship with the heart in a diseased state.


The distribution of infection with Propionibacterium acnes is equal in patients with cervical and lumbar disc herniation.
Cervical and back pains are important clinical problems affecting human populations globally. It is suggested that Propionibacterium acnes (P. acnes) is associated with disc herniation. The aim of this study is to evaluate the distribution of P. acnes infection in the cervical and lumbar disc material obtained from patients with disc herniation. A total of 145 patients with mean age of 45.21 ± 11.24 years who underwent micro-discectomy in cervical and lumbar regions were enrolled into the study. The samples were excited during the operation and then cultured in the anaerobic incubations. The cultured P. acnes were detected by 16S rRNA-based polymerase chain reaction. In this study, 145 patients including 25 cases with cervical and 120 cases with lumbar disc herniation were enrolled to the study. There was no significant difference in the age of male and female patients (p = 0.123). P. acnes infection was detected in nine patients (36%) with cervical disc herniation and 46 patients (38.3%) with lumbar disc herniation and no significant differences were reported in P. acnes presence according to the disc regions (p = 0.508.). Moreover, there was a significant difference in the presence of P. acnes infection according to the level of lumbar disc herniation (p = 0.028). According to the results, the presence of P. acnes is equal in patients with cervical and lumbar disc herniation. There was a significant difference in the distribution of P. acnes infection according to level of lumbar disc herniation. II.


Validation of the laparoscopically stapled approach as a standard technique for left lateral segment liver resection.
Left lateral sectionectomy (LLS) is the most common type of anatomic laparoscopic liver resection performed, accounting for 20 % of all laparoscopic hepatectomies. Because there has been no standardized surgical technique for laparoscopic left lateral sectionectomy (LLLS), we offer an established operation: laparoscopically stapled left lateral sectionectomy (LSLLS). Our aim was to perform a case-controlled study of LSLLS with traditional (without vascular staplers) laparoscopic left lateral sectionectomy (TLLLS), validating the standardization and reproducibility of LSLLS. From February 2009 to December 2011, a total of 49 LSLLSs were performed. The results were compared with 33 cohort-matched TLLLSs from an earlier time period. Ordered sample cluster analysis was used to determine the learning curve of LSLLS based on the operating time and blood loss. All LSLLS were performed successfully. There were no conversions to laparotomy or hand-assisted laparoscopic resection. Two endoscopic linear staplers were used in each case. Despite a higher hospital cost ($10,892 ± $944 vs. $8,962 ± $943, p < 0.05), LSLLS compared favorably with TLLLS regarding operating time (103 ± 21 vs. 151 ± 32 min, p < 0.05) and blood loss (70.8 ± 41.6 vs. 173.3 ± 131.1 ml, p < 0.05). No specific complications related to laparoscopy were observed. Ordered sample cluster analysis demonstrated a learning curve of 18 cases for LSLLS. This study demonstrates the standardization and reproducibility of LSLLS. We therefore propose LSLLS as the standard technique for lesions located in the left lateral section of the liver.


Sensitive targeted quantification of ERK phosphorylation dynamics and stoichiometry in human cells without affinity enrichment.
Targeted mass spectrometry is a promising technology for site-specific quantification of posttranslational modifications. However, a major constraint is the limited sensitivity for quantifying low-abundance PTMs, requiring the use of affinity reagents for enrichment. Herein, we demonstrate the direct site-specific quantification of ERK phosphorylation isoforms (pT, pY, pTpY) and their relative stoichiometry using a sensitive targeted MS approach termed high-pressure, high-resolution separations with intelligent selection, and multiplexing (PRISM). PRISM provides effective enrichment of target peptides into a given fraction from complex mixture, followed by selected reaction monitoring quantification. Direct quantification of ERK phosphorylation in human mammary epithelial cells (HMEC) was demonstrated from as little as 25 μg tryptic peptides from whole cell lysates. Compared to immobilized metal-ion affinity chromatography, PRISM provided ∼10-fold higher signal intensities, presumably due to the better peptide recovery of PRISM. This approach was applied to quantify ERK phosphorylation dynamics in HMEC treated by different doses of epidermal growth factor at both the peak activation (10 min) and steady state (2 h). The maximal ERK activation was observed with 0.3 and 3 ng/mL doses for 10 min and 2 h time points, respectively. The dose-response profiles of individual phosphorylated isoforms showed that singly phosphorylated pT-ERK never increases significantly, while the increase of pY-ERK paralleled that of pTpY-ERK. This data supports for a processive, rather than distributed model of ERK phosphorylation. The PRISM-SRM quantification of protein phosphorylation illustrates the potential for simultaneous quantification of multiple PTMs.


Spontaneous eye lesions in laboratory animals: incidence in relation to age.
Examination of the eye in experiments designed to test the toxicity of drugs or chemicals is of considerable importance and the investigator must have a clear idea of the spontaneous eye changes he can expect in the test species. We have attempted to review the literature relating to commonly used laboratory animals--the rat, mouse, and dog as well as the hamster--but as there is still only a handful of workers that publish their findings, the literature is not fully comprehensive. Our own unpublished data have been used to try and provide a more complete account. There is, therefore, a considerable need for further work in this area and, in the future, newer techniques such as electron microscopy and histochemistry can help us in the understanding of the pathogenesis of age-related changes in laboratory animals.


Secretin/secretin receptor signaling mediates biliary damage and liver fibrosis in early-stage primary biliary cholangitis.
Primary biliary cholangitis (PBC) primarily targets cholangiocytes and is characterized by liver fibrosis and biliary proliferation. Activation of the secretin (Sct)/secretin receptor (SR) axis, expressed only by cholangiocytes, increases biliary proliferation, liver fibrosis, and bicarbonate secretion. We evaluated the effectiveness of SR antagonist treatment for early-stage PBC. Male and female dominant-negative TGF-β receptor II (dnTGF-βRII) (model of PBC) and wild-type mice at 12 wk of age were treated with saline or the SR antagonist, Sec 5-27, for 1 wk. dnTGF-βRII mice expressed features of early-stage PBC along with enhanced Sct/SR axis activation and Sct secretion. dnTGF-βRII mice had increased biliary proliferation or senescence, inflammation, and liver fibrosis. In dnTGF-βRII mice, there was increased microRNA-125b/TGF-β1/TGF-β receptor 1/VEGF-A signaling. Human early-stage PBC patients had an increase in hepatobiliary Sct and SR expression and serum Sct levels. Increased biliary Sct/SR signaling promotes biliary and hepatic damage during early-stage PBC.-Kennedy, L., Francis, H., Invernizzi, P., Venter, J., Wu, N., Carbone, M., Gershwin, M. E., Bernuzzi, F., Franchitto, A., Alvaro, D., Marzioni, M., Onori, P., Gaudio, E., Sybenga, A., Fabris, L., Meng, F., Glaser, S., Alpini, G. Secretin/secretin receptor signaling mediates biliary damage and liver fibrosis in early-stage primary biliary cholangitis.


Void Content, Tensile, Vibration and Acoustic Properties of Kenaf/Bamboo Fiber Reinforced Epoxy Hybrid Composites.
This study aims to investigate the void content, tensile, vibration and acoustic properties of kenaf/bamboo fiber reinforced epoxy hybrid composites. The composites were made using the hand lay-up method. The weight ratios of kenaf/bamboo were 30:70, 50:50 and 70:30. Further, kenaf and bamboo composites were fabricated for the purpose of comparison. The hybridization of woven kenaf/bamboo reduced the void content. The void contents of hybrid composites were almost similar. An enhancement in elongation at break, tensile strength and modulus of hybrid composites was observed until a kenaf/bamboo ratio of 50:50. Kenaf/bamboo (50:50) hybrid composite displays the highest elongation at break, tensile strength and modulus compared to the other hybrid composites which are 2.42 mm, 55.18 MPa and 5.15 GPa, respectively. On the other hand, the highest natural frequency and damping factors were observed for Bamboo/Kenaf (30:70) hybrid composites. The sound absorption coefficient of composites were measured in two conditions: without air gap and with air gap (10, 20, 30 mm). The sound absorption coefficient for testing without air gap was less than 0.5. Introducing an air gap improved the sound absorption coefficient of all composites. Hence, hybrid kenaf/bamboo composites exhibited less void content, as well as improved tensile, vibration and acoustic properties.


Worth a glance: using eye movements to investigate the cognitive neuroscience of memory.
Results of several investigations indicate that eye movements can reveal memory for elements of previous experience. These effects of memory on eye movement behavior can emerge very rapidly, changing the efficiency and even the nature of visual processing without appealing to verbal reports and without requiring conscious recollection. This aspect of eye movement based memory investigations is particularly useful when eye movement methods are used with special populations (e.g., young children, elderly individuals, and patients with severe amnesia), and also permits use of comparable paradigms in animals and humans, helping to bridge different memory literatures and permitting cross-species generalizations. Unique characteristics of eye movement methods have produced findings that challenge long-held views about the nature of memory, its organization in the brain, and its failures in special populations. Recently, eye movement methods have been successfully combined with neuroimaging techniques such as fMRI, single-unit recording, and magnetoencephalography, permitting more sophisticated investigations of memory. Ultimately, combined use of eye-tracking with neuropsychological and neuroimaging methods promises to provide a more comprehensive account of brain-behavior relationships and adheres to the "converging evidence" approach to cognitive neuroscience.


Guillain-Barré syndrome: natural history and prognostic factors: a retrospective review of 106 cases.
Guillain-Barre syndrome (GBS) is characterized by acute onset and progressive course, and is usually associated with a good prognosis. However, there are forms of poor prognosis, needing ventilatory support and major deficits at discharge. With this study we try to identify the factors associated with a worse outcome. 106 cases of GBS admitted in our hospital between years 2000-2010 were reviewed. Epidemiological, clinical, therapeutical and evolutionary data were collected. At admission 45% had severe deficits, percentage which improves throughout the evolution of the illness, with full recovery or minor deficits in the 87% of patients at the first year review. Ages greater than 55 years, severity at admission (p < 0.001), injured cranial nerves (p = 0.008) and the needing of ventilator support (p = 0.003) were associated with greater sequels at the discharge and at the posterior reviews in the following months. 17% required mechanical ventilation (MV). Values < 250 L/min in the Peak Flow-test are associated with an increased likelihood of requiring MV (p < 0.001). Older age, severe deficits at onset, injured cranial nerves, requiring MV, and axonal lesion patterns in the NCS were demonstrated as poor prognostic factors. Peak Flow-test is a useful predictive factor of respiratory failure by its easy management.


The human stress response.
The human stress response has evolved to maintain homeostasis under conditions of real or perceived stress. This objective is achieved through autoregulatory neural and hormonal systems in close association with central and peripheral clocks. The hypothalamic-pituitary-adrenal axis is a key regulatory pathway in the maintenance of these homeostatic processes. The end product of this pathway - cortisol - is secreted in a pulsatile pattern, with changes in pulse amplitude creating a circadian pattern. During acute stress, cortisol levels rise and pulsatility is maintained. Although the initial rise in cortisol follows a large surge in adrenocorticotropic hormone levels, if long-term inflammatory stress occurs, adrenocorticotropic hormone levels return to near basal levels while cortisol levels remain raised as a result of increased adrenal sensitivity. In chronic stress, hypothalamic activation of the pituitary changes from corticotropin-releasing hormone-dominant to arginine vasopressin-dominant, and cortisol levels remain raised due at least in part to decreased cortisol metabolism. Acute elevations in cortisol levels are beneficial to promoting survival of the fittest as part of the fight-or-flight response. However, chronic exposure to stress results in reversal of the beneficial effects, with long-term cortisol exposure becoming maladaptive, which can lead to a broad range of problems including the metabolic syndrome, obesity, cancer, mental health disorders, cardiovascular disease and increased susceptibility to infections. Neuroimmunoendocrine modulation in disease states and glucocorticoid-based therapeutics are also discussed.


The Molecular Basis of Viral Inhibition of IRF- and STAT-Dependent Immune Responses.
The antiviral innate immunity is the first line of host defense against virus infections. In mammalian cells, viral infections initiate the expression of interferons (IFNs) in the host that in turn activate an antiviral defense program to restrict viral replications by induction of IFN stimulated genes (ISGs), which are largely regulated by the IFN-regulatory factor (IRF) family and signal transducer and activator of transcription (STAT) family transcription factors. The mechanisms of action of IRFs and STATs involve several post-translational modifications, complex formation, and nuclear translocation of these transcription factors. However, many viruses, including human immunodeficiency virus (HIV), Zika virus (ZIKV), and herpes simplex virus (HSV), have evolved strategies to evade host defense, including alteration in IRF and STAT post-translational modifications, disturbing the formation and nuclear translocation of the transcription complexes as well as proteolysis/degradation of IRFs and STATs. In this review, we discuss and summarize the molecular mechanisms by which how viral components may target IRFs and STATs to antagonize the establishment of antiviral host defense. The underlying host-viral interactions determine the outcome of viral infection. Gaining mechanistic insight into these processes will be crucial in understanding how viral replication can be more effectively controlled and in developing approaches to improve virus infection outcomes.


TGFB1 induces fetal reprogramming and enhances intestinal regeneration.
The gut epithelium has a remarkable ability to recover from damage. We employed a combination of high-throughput sequencing approaches, mouse genetics, and murine and human organoids and identified a role for TGFB signaling during intestinal regeneration following injury. At 2 days following irradiation (IR)-induced damage of intestinal crypts, a surge in TGFB1 expression is mediated by monocyte/macrophage cells at the location of damage. The depletion of macrophages or genetic disruption of TGFB signaling significantly impaired the regenerative response. Intestinal regeneration is characterized by the induction of a fetal-like transcriptional signature during repair. In organoid culture, TGFB1 treatment was necessary and sufficient to induce the fetal-like/regenerative state. Mesenchymal cells were also responsive to TGFB1 and enhanced the regenerative response. Mechanistically, pro-regenerative factors, YAP/TEAD and SOX9, are activated in the epithelium exposed to TGFB1. Finally, pre-treatment with TGFB1 enhanced the ability of primary epithelial cultures to engraft into damaged murine colon, suggesting promise for cellular therapy.


[The SNPs analysis of encoding sequence of interacting factor gene in Chinese population].
To screen the variations of TG interacting factor(TGIF) gene in encoding sequence in Chinese high myopia patients and normal controls and to analyze the SNPs of TGIF gene encoding sequence in Chinese population. Genomic DNA was collected from 204 probands with high myopia and 112 unrelated persons without high myopia. The coding sequences of TGIF gene in 316 subjects were analyzed by using exon-by-exon PCR heteroduplex-SSCP analysis and sequencing. There were 3 types of SNP and one single nucleotide mutation in the coding sequence of TGIF gene: IVS-2 nt350 G --> T(36/204), codon140 CCA --> CCG; Pro140Pro codon163 CCG --> CTG;Pro163Leu and codon126 GTG --> GCG; Val126Ala(1/204). The SNPs of codon140 CCA --> CCG and codon163 CCG --> CTG were composed of 3 alleles and 5 genotypes in Chinese population which abide by Hardy-Weinberg law. There was no evidence to prove that mutations in the TGIF gene are responsible for the high myopia in Chinese. Three SNPs of coding sequence TGIF gene in Chinese population abide by Hardy-Weinberg law.


Serum alpha-CGRP levels are increased in COVID-19 patients with headache indicating an activation of the trigeminal system.
Headache is among the most frequent symptoms of acute COVID-19 infection. Its mechanisms remain obscure, but due to its migraine-like characteristics, the activation of the trigeminal system could account for its underlying pathophysiology. Our aim was to compare the serum levels of CGRP, as a theoretical marker of trigemino-vascular activation, in 25 COVID-19 inpatients with lung involvement experiencing headache, against 15 COVID-19 inpatients without headache and with those of 25 matched healthy controls with no headache history. Morning serum alpha-CGRP levels, as measured by ELISA (Abbexa, UK), were increased in COVID-19 patients with headache (55.2±34.3 pg/mL) vs. controls (33.9±14.0 pg/mL) (p < 0.01). Alpha-CGRP levels in COVID-19 patients without headache were also significantly increased (43.3 ± 12.8 pg/mL; p = 0.05) versus healthy controls, but were numerically lower (-28.2%; p = 0.36) as compared to COVID-19 patients with headache. CGRP levels are increased in COVID-19 patients experiencing headache in the acute phase of this disease, which could explain why headache frequently occurs in COVID-19 and strongly supports a role for trigeminal activation in the pathophysiology of headache in this viral infection.


To achieve stable spherical clusters: general principles and experimental confirmations.
General principles for designing stable highly symmetrical clusters are proposed. This approach takes advantage of both the extra stability of cage aromaticity and the good geometrical balance between the outer cage and the endohedral atom. The applicability of these design principles was confirmed by gas-phase experimental observations on group 14 element cages with endohedral Al's and also is illustrated by many literature examples of diverse systems.


Plasminogen activator production and enhanced development in medium containing plasminogen or plasmin by rabbit embryos in vitro.
A series of experiments was conducted to evaluate plasminogen activator production and effects of supplementing culture medium with plasminogen or plasmin on development of rabbit embryos in vitro. In Expt 1, 495 one- to two-cell embryos were cultured in Ham's F-12 with 15 mg BSA ml-1 containing 0, 30, 60 or 120 micrograms porcine plasminogen ml-1 or 0, 75, 150 or 300 micrograms rabbit plasminogen ml-1. Percentages of embryos developing to the expanded blastocyst, hatching blastocyst and hatched blastocyst stages were greater (P < 0.05) in medium with 120 micrograms porcine plasminogen ml-1 than in the absence of plasminogen. More (P < 0.05) embryos developed to the blastocyst, expanded blastocyst and hatching blastocyst stages in medium with 300 micrograms rabbit plasminogen ml-1 than in the absence of plasminogen. In Expt 2, 216 one- to two-cell embryos were cultured in medium with 0, 30, 60 or 120 micrograms porcine plasminogen ml-1 for 96 h, fixed and strained with haematoxylin and eosin, and the number of cells determined. No differences (P > 0.05) were observed in number of cells of morulae but blastocysts developing in medium with 120 micrograms porcine plasminogen ml-1 had more (P < 0.05) cells (109.9 +/- 10.4) than did blastocysts in medium with either 0 (69.4 +/- 14.6) or 30 micrograms porcine plasminogen ml-1 (73.3 +/- 12.2). In Expt 3, 144 one- to two-cell embryos were cultured in medium with 0, 13 or 45 micrograms porcine plasmin ml-1 or 120 micrograms porcine plasminogen ml-1.(ABSTRACT TRUNCATED AT 250 WORDS)


Beauty sleep: experimental study on the perceived health and attractiveness of sleep deprived people.
To investigate whether sleep deprived people are perceived as less healthy, less attractive, and more tired than after a normal night's sleep. Experimental study. Sleep laboratory in Stockholm, Sweden. 23 healthy, sleep deprived adults (age 18-31) who were photographed and 65 untrained observers (age 18-61) who rated the photographs. Participants were photographed after a normal night's sleep (eight hours) and after sleep deprivation (31 hours of wakefulness after a night of reduced sleep). The photographs were presented in a randomised order and rated by untrained observers. Difference in observer ratings of perceived health, attractiveness, and tiredness between sleep deprived and well rested participants using a visual analogue scale (100 mm). Sleep deprived people were rated as less healthy (visual analogue scale scores, mean 63 (SE 2) v 68 (SE 2), P<0.001), more tired (53 (SE 3) v 44 (SE 3), P<0.001), and less attractive (38 (SE 2) v 40 (SE 2), P<0.001) than after a normal night's sleep. The decrease in rated health was associated with ratings of increased tiredness and decreased attractiveness. Our findings show that sleep deprived people appear less healthy, less attractive, and more tired compared with when they are well rested. This suggests that humans are sensitive to sleep related facial cues, with potential implications for social and clinical judgments and behaviour. Studies are warranted for understanding how these effects may affect clinical decision making and can add knowledge with direct implications in a medical context.


Isolation and characterization of CspBI, a novel NotI isoschizomer from Corynebacterium species B recognizing 5'-GC/GGCCGC-3'.
Sixty-seven bacterial strains were surveyed for the presence of type II restriction endonucleases, especially concerning super-rare-cutting enzymes. Fourteen strains were found to contain specific enzymes. One of them CspBI from Corynebacterium species B was purified and characterized as an isoschizomer of NotI, which recognizes the palindromic octanucleotide sequence 5'-GC/GGCCGC-3' and cleaves at the position shown by the arrow. A comparison between the cleavage patterns on different DNAs, obtained with partially purified endonucleases from other detected producents including some strains of Corynebacterium, Cellulomonas and Rhizobium has shown that these enzymes do not belong to super-rare-cutting restriction endonucleases.


Trombone tongue: a new clinical sign for significant medullary compression at the craniovertebral junction. Case report.
The authors describe a previously unreported clinical sign that may indicate the onset of significant compression of the medulla oblongata in cases of craniovertebral junction abnormalities. This 17-year-old boy presented with mild bilateral leg weakness. Imaging studies revealed severe basilar invagination and a marked Chiari malformation. While awaiting surgery, his tongue developed an involuntary constant protrusion-intrusion repetitive motion. The onset of this so-named "trombone tongue" sign was followed shortly afterward by rapidly progressive spastic tetraparesis. After the authors performed a transmaxillary clivectomy, foramen magnum decompression, and occipitocervical fusion, they noted that the abnormal tongue motion promptly resolved and the tetraparesis gradually improved. The authors discuss their current understanding of the central control of tongue movements and present a hypothesis on the pathogenesis of trombone tongue based on the neuroanatomical basis of another abnormal tongue movement sign, lingual myoclonus.


[A comparison of some indices of innate and adaptive immunity in different types of schizophrenia].
Leukocyte elastase (LE) blood serum activity as an index of innate immunity and autoimmune reactions to brain antigens i.e. a level of autoantiboies to nerve growth factor (NGF) as an index of adaptive immunity were studied in patients with attack-like and slow progressive schizophrenia. Compared to controls, higher LE activity accompanied by a significant increase of autoantibodies to NGF titers was found in patients with attack-like schizophrenia. In slow progressive schizophrenia, only higher LE activity was detected. Correlations between immunological parameters and some clinical appearances (positive and negative disorders) and disease course peculiarities were revealed. The results suggest an involvement of different parts of immune system in pathophysiology of attack-like and slow progressive schizophrenia.


Lumbar pain with intracranial origin.
A 48-year-old woman presented low-back pain radiating to the lower right leg. Magnetic resonance imaging (MRI) of the lumbar spine revealed a L4-L5 subacute subdural hematoma (SDH). The patient had no general or local cause for this lumbar SDH, such as coagulation disorder, trauma, surgery, or lumbar puncture. She had a history of post-traumatic bilateral hemorrhagic contusions of the brain and intracranial SDH because of a fall occurring several months before the current problems. A downward migration of the cerebral SDH was found as only potential explanation of the lumbar SDH. The association between the intracranial and spinal hematomas is discussed.


Panic attacks. Psychologic response or medical illness?
Panic attacks are surprisingly common in the United States, costing our economy more than $100 million per year in disability benefits and health care expenses. However, diagnosis is difficult and consequently many patients are treated for other conditions. When an underlying disorder is determined to be present, treatment of that disorder may ameliorate attacks. If none is present, panic symptoms will respond to a variety of drugs. Behavioral therapy may be necessary in severe cases or as adjunctive therapy after attacks abate.


Psychiatric correlates of past incarceration in the national co-morbidity study replication.
Mental illness and substance abuse have been increasingly linked to criminal justice system involvement, but this relationship has mostly been by survey of prison populations and inferences of excess rates of disorder made by noting how these rates compare with national population-based surveys of mental disorders. The aim of this study is to examine associations between history of mental disorders, including substance misuse, with incarceration history within a single population-based data set. Data were from the National Comorbidity Survey Replication, a nationally representative household survey of respondents 18 years and older conducted between 5 February 2001 and 7 April 2003. Multivariate regression analysis showed the strongest independent risk factors for a history of incarceration were being male [odds ratio (OR) = 6.3; p < 0.001], past receipt of welfare payments (OR = 2.1; p < 0.001), longer than 1 week of past homelessness (OR = 2.1; p < 0.001), not being from the northeast of the USA (OR = 0.31; p < 0.001) and a lifetime substance abuse or dependence diagnosis (OR = 4.9; p < 0.001). With the exception of welfare payments, these measures were also independently associated with longer (27 + days) incarceration. The socioeconomic associates of incarceration history were unexpected, and in line with other, differently conducted studies. The fact that only substance misuse disorders of all those assessed were independently associated with incarceration history was a surprise, given the multiplicity of prison surveys, which have shown higher rates of other serious mental disorders. Although we were unable to include measures of schizophrenia or similar psychosis and used impulse control disorders as surrogates for personality disorder, absence of a relationship between depression and incarceration when measured in the same way and over the same time among those previously incarcerated and those not, raises questions about the weight that should be put on the existing epidemiological perspective of mental disorder among prisoners.


Long non-coding RNA LINC00630 facilitates hepatocellular carcinoma progression through recruiting transcription factor E2F1 to up-regulate cyclin-dependent kinase 2 expression.
This study is aimed to investigate the role of long non-coding RNA 630 (LINC00630) in hepatocellular carcinoma (HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine LINC00630 expression in HCC cell lines and tissues. After LINC00630 was overexpressed or depleted in HCC cell lines, cell counting kit-8 (CCK-8) assay, BrdU assay, and flow cytometry were conducted for detecting HCC cell multiplication, apoptosis, and cell cycle progression. The catRAPID database was adopted to predict the binding relationship between LINC00630 and E2F transcription factor 1 (E2F1), and RNA pull-down and RNA immunoprecipitation (RIP) assays were carried out to verify this binding relationship. The binding of E2F1 to the cyclin-dependent kinase 2 (CDK2) promoter region was verified by dual-luciferase reporter gene assay and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assay. Western blotting was conducted to detect the protein expression of E2F1 and CDK2 in HCC cells. We report that LINC00630 expression was up-regulated in HCC and was significantly correlated with TNM stage and lymph node metastasis. LINC00630 overexpression facilitated HCC cell proliferation and cell cycle progression and inhibited the cell apoptosis, while LINC00630 knockdown had the opposite effects. LINC00630 directly bounds with E2F1. LINC00630 overexpression enhanced the binding of E2F1 to the CDK2 promoter region, thereby promoting CDK2 transcription, whereas knocking down LINC00630 inhibited CDK2 transcription. Collectively, LINC00630 promoted CDK2 transcription by recruiting E2F1 to the promoter region of CDK2, thereby promoting the malignant progression of HCC. Our data suggest that LINC00630 is a promising molecular target for HCC.


Use of checking systems in medicines administration with children and young people.
This study aimed to establish which policies are in place for checking medication administration in UK children's units and to discuss evidence to support the use of different checking processes. It involved a questionnaire survey (n=105) in 69 UK hospitals of children's nurses and pharmacists. In the hospitals surveyed, most administrations of oral and intravenous medications were checked by two registered children's nurses. Evidence suggests a role for single and double checking depending on risk assessment. Robust research is needed to further evaluate these processes.


Squamous cell carcinoma of the scrotum: A look beyond the chimneystacks.
Despite the low incidence, squamous cell carcinoma (SCC) remains the most common scrotal malignancy with a propensity for recurrence and metastasis. In recent years there has been a significant change in the epidemiology of scrotal SCC. Surgery is the mainstay of treatment for resectable disease. Sentinel lymph node dissection adapted from experience with penile SCC can reduce the morbidity of routine lymph node dissection. Emerging treatments for advanced and metastatic SCC are at the cusp of significantly changing management of this disease. We have performed a comprehensive review of scrotal SCC with a focus on these topics.


Improvement of photoluminescence and lasing properties in ZnO submicron spheres by elimination of surface-trapped state.
We report on the enhancement of photoluminescence and laser action behaviors of ZnO submicron spheres fabricated by a sol-gel process. As annealing temperature increases, intense ultraviolet excitonic emission at room temperature can be observed. Upon pulsed excitations, the lasing threshold gradually decreases as annealed temperature increases, which is consistent with the results of the ratio of surface-trapped exciton to donor-bound exciton emissions at low temperature. X-ray photoelectron spectroscopy confirmed that adsorbed OH bonds played a critical role in trapping species of exciton at the ZnO surface. The superior optical properties of high-annealing ZnO mainly result from the elimination of a surface-trapped state.


Remote access to closer care.
Some community nurses are reluctant to use new technology, fearing it will be difficult to use and will take them away from patients. A recent report reveals that new technologies, properly introduced, can transform care and save money. With the Department of Health determined to reduce unnecessary face-to-face contact between staff and patients, change is inevitable.


Carcinoma of the prostate: indigenous patterns.
Thirty-two cases of prostatic carcinoma were collected from a 13-year series containing approximately 15,000 surgical specimens removed from Igbo patients in Nigeria, West Africa. The growths were generally well-differentiated adenocarcinomas; latent carcinoma was found in a 72-year-old man. The peak incidence was in the seventh decade. The symptom that compelled admission was usually acute urine retention. Clinical diagnosis was often possible because of an advanced state of disease, indicating the need for health education. Prospective research in Igboland may help to explain the high incidence of prostatic carcinoma in American blacks whose forefathers were from this area and neighboring localities.


Cytotoxicity of a new uridine analog, 4-hydroxy-1-(beta-D-ribofuranosyl)-pyridazine-6-one, and its interaction with uridine kinase.
A new uridine analog, 4-hydroxy-1-(beta-D-ribonfuranosyl)-pyridazin-6-one (3-deaza-6-azaUrd), inhibited the growth of L1210 cells in culture, with a concentration to reduce growth rate to 50% of control of 7 X 10(-5) M. After treatment for 24 or 48 h with 5 X 10(-4) M 3-deaza-6-azaUrd, 80% of the cells were unable to resume growth when the analog was removed from the cultures; also, 99% of the cells were killed, as determined by colony formation in soft agar. Studies on the prevention of the cytotoxic effects of 5 X 10(-4) M 3-deaza-6-azaUrd showed that uridine or cytidine gave complete protection. 2'-Deoxycytidine also gave partial protection, but orotic acid or thymidine had no effect on the growth inhibition by 3-deaza-6-azaUrd. These results suggested that growth inhibition by 3-deaza-6-azaUrd might be due to interference in pyrimidine biosynthesis. Activation of 3-deaza-6-azaUrd to its 5'-phosphate derivative appeared to be catalyzed by uridine kinase. 3-Deaza-6-azaUrd was shown to complete with uridine for phosphorylation (Ki = 4.7 mM) and, therefore, to be a possible alternative substrate for uridine kinase from mouse kidney (Km for uridine = 82 microM). The enzyme was partially purified by streptomycin sulfate precipitation, ammonium sulfate fractionation, and gel filtration. This preparation was found to be free of pyrimidine nucleoside phosphorylase and uridine monophosphate kinase.


Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway.
Recombinant human-erythropoietin (rh-EPO) has therapeutic efficacy for premature infants with brain damage during the active rehabilitation and anti-inflammation. In the present study, we found that the rh-EPO was related to the promotion of neovascularization. Our aim was to investigate whether rh-EPO augments neovascularization in the neonatal rat model of premature brain damage through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. Postnatal day 5 (PD5), rats underwent permanent ligation of the right common carotid artery and were exposed to hypoxia for 2 h. All the rat pups were randomized into five groups as follows: (1) control group; (2) hypoxia-ischemic (HI) group; (3) HI + LY294002 group; (4) HI + rh-EPO group; and (5) HI + rh-EPO + LY294002 group. The phospho-Akt protein was tested 90 min after the whole operation, and CD34, vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor (VEGF) were also tested 2 days after the whole operation. In the hypoxic and ischemic zone of the premature rat brain, the rh-EPO induced CD34+ cells to immigrate to the HI brain zone (P < 0.05) and also upregulated the VEGFR2 protein expression (P < 0.05) and VEGF mRNA level (P < 0.05) through the PI3K/Akt (P < 0.05) signaling pathway when compared with other groups. The rh-EPO treatment augments neovascularization responses in the neonatal rat model of premature brain damage through the PI3K/Akt signaling pathway. Besides, the endogenous EPO may exist in the HI zone of rat brain and also has neovascularization function through the PI3K/Akt signaling pathway.


Connectivity mapping (ssCMap) to predict A20-inducing drugs and their antiinflammatory action in cystic fibrosis.
Cystic fibrosis (CF) lung disease is characterized by chronic and exaggerated inflammation in the airways. Despite recent developments to therapeutically overcome the underlying functional defect in the cystic fibrosis transmembrane conductance regulator, there is still an unmet need to also normalize the inflammatory response. The prolonged and heightened inflammatory response in CF is, in part, mediated by a lack of intrinsic down-regulation of the proinflammatory NF-κB pathway. We have previously identified reduced expression of the NF-κB down-regulator A20 in CF as a key target to normalize the inflammatory response. Here, we have used publicly available gene array expression data together with a statistically significant connections' map (sscMap) to successfully predict drugs already licensed for the use in humans to induce A20 mRNA and protein expression and thereby reduce inflammation. The effect of the predicted drugs on A20 and NF-κB(p65) expression (mRNA) as well as proinflammatory cytokine release (IL-8) in the presence and absence of bacterial LPS was shown in bronchial epithelial cells lines (16HBE14o-, CFBE41o-) and in primary nasal epithelial cells from patients with CF (Phe508del homozygous) and non-CF controls. Additionally, the specificity of the drug action on A20 was confirmed using cell lines with tnfαip3 (A20) knockdown (siRNA). We also show that the A20-inducing effect of ikarugamycin and quercetin is lower in CF-derived airway epithelial cells than in non-CF cells.


Label-Free and Homogenous Detection of Caspase-3-Like Proteases by Disrupting Homodimerization-Directed Bipartite Tetracysteine Display.
Caspase-3-like proteases (e.g., caspase-3 and caspase-7) constitute the core players of cell apoptosis, and their dysregulation has been linked to a number of human diseases, such as cancer and neurodegenerative disorders. However, the methods for measuring caspase-3-like proteases are often complex and time-consuming. Herein, we develop a label-free method to homogeneously detect caspase-3-like proteases in vitro and in complex cell lysate. This assay uses a modular peptide that contains a dimerization domain, a caspase-3/7 cleavage sequence, and a dicysteine motif as the activity sensor to detect caspase-3-like proteases. In the absence of caspase-3-like proteases, the homodimerization of modular peptide brings the dicysteine motif into close proximity and forms a particular configuration suitable for the binding to bisarsenical dye FlAsH-EDT2. The coordination of FlAsH-EDT2 to dimeric peptide forms a highly fluorescent FlAsH-peptide complex. In contrast, the cleavage of the modular peptide by caspase-3-like proteases removes the dicysteine motif from the peptide and abrogates the bipartite tetracysteine display, leading to the disappearance of fluorescence. As a result, the caspase-3-like proteases can be quantitatively evaluated by measuring the change in fluorescence. This assay may be carried out in a "mix-and-read" manner and is, thus, quite simple and convenient. Moreover, this assay is extremely specific and can measure caspase-3 protein down to 1.28 × 10-4 μg/mL. Importantly, the assay is compatible with complex biological samples and can measure both the activation and inhibition of intracellular caspase-3, thereby providing a new approach for the screening of caspase-targeted drugs and the diagnosis of apoptosis-associated diseases.


Degos cutaneous disease with features of connective tissue disease.
A 30-year-old woman was referred on April 2002 for a plaque that involved the internal aspect of the right leg, an erythema nodosum-like lesion on the lower extremities, and periarthritis on her left ankle. Subsequently, the patient developed anular, atrophic, growing, porcelain-white papules, with a thin rim of erythema and telangiectases over her upper and lower extremities. Clinically and histologically, these lesions were the characteristics of Degos disease. Despite arthritis and myositis that required treatment, low level C3 and C4, positive antinuclear antibodies, and elevated anticardiolipin antibodies only once, in a follow-up of 6 years the patient never developed a specific connective tissue disease or other systemic involvement. In conclusion, because clinical and histological findings of Degos disease might mimic connective tissue diseases, rheumatologists must be aware that this reaction pattern can be seen in a wide clinical spectrum of diseases.


Pulmonary metastasectomy from head and neck tumors.
Isolated pulmonary metastases from head and neck cancer occur in 20%-30% of patients affected by head and neck neoplasms. Surgical resection is well accepted as a standard approach to treat metastases from head and neck cancer isolated to the lungs. Many studies reported overall five-year survival ranging from 20% to 30%. The aim of this study is to determine demographics and clinical treatment-related variables associated with long-term (60-month) overall survival in patients with lung metastases undergoing pulmonary metastasectomy from head and neck tumors. A retrospective review was performed of patients who were admitted with lung metastases and underwent thoracotomy for resection after treatment of the primary tumor. Data were collected regarding primary tumor features, demographics, treatment, and outcome. Median follow-up time of all patients was 36.4 months (range: 0-288 months). The postoperative complication rate was 14.4%, and the 30-day mortality rate was 0%. The 60-month overall survival rate for all patients was 35.5%. Multivariate analysis identified the number of nodules at CT scan, the disease-free interval, and histological type as independent prognostic factors for overall survival. Lung metastasectomy is a safe and potentially curative procedure for patients with treated primary tumors. A select group of patients can achieve long-term survival after lung resection.


[Genetic Polymorphisms of 21 Autosomal STR Loci of Fujian Han Population].
To investigate the genetic polymorphisms of 21 autosomal STR loci of Fujian Han population and evaluate the forensic application value of GlobalFiler Express kit. Amplified with GlobalFiler Express kit, DNA samples were obtained from 741 unrelated individuals of Fujian Han population. The population genetics parameters of 21 autosomal STR loci were calculated. The 21 autosomal STR loci were found to be no deviation from Hardy-Weinberg equilibration (P > 0.05) and relatively abundant in high polymorphism. Heterozygosity ranged from 0.589 to 0.914, power of discrimination ranged from 0.754 to 0.992, polymorphic information content ranged from 0.520 to 0.940, and power of exclusion ranged from 0.278 to 0.825. The SE33 locus was the highest degree in polymorphism. The 21 STR loci of GlobalFiler Express kit have high value in discrimination power and can be useful in personal identification and paternity test in Fujian Han population.


Another type of diaphragmatic hernia to remember: parahiatal hernia.
Parahiatal hernia is a less common form of diaphragmatic hernia, with the defect lateral to the crus and oesophageal hiatus, and the unfamiliarity of this disease would cause confusion to general surgeons. In the present study, the literature on parahiatal hernia were reviewed, the clinical profile of this disease, as well as our own experience is presented and analysed. In the present study, a thorough identification of all published reports on parahiatal hernias was made, together with our own cases, the available data were summarized, analysed and discussed. A total of 27 cases of parahiatal hernias were identified since 1987. Among them, 19 cases were primary parahiatal hernias, and eight cases were secondary or acquired parahiatal hernias. None of the 27 cases were pre-operatively diagnosed, and the majority of them were pre-operatively diagnosed as paraoesophageal hernias. Detailed treatment data were available in 26 of the 27 cases. Three patients received open surgery, and 23 patients were treated with laparoscopic procedures. Suture repair was used in 12 cases, and 14 cases were repaired with mesh reinforcement. In addition, two cases underwent partial gastrectomy, stomach suture was performed in another two cases. Patients with parahiatal hernia have a high risk of developing hernia incarceration or gastric vovulus. Laparoscopic treatment of parahiatal hernia is feasible and safe in the majority cases. Surgeons should be aware of this disease when performing paraoesophageal hernia repair, as parahiatal hernias may occur with or without previous diaphragmatic surgery.


Health literacy.
Health literacy skills are cognitive and social skills which determine the motivation and ability of individuals to gain access to, understand, and use information in ways which promote and maintain good health'. Patients use these literacy skills to critically analyze information; to allow them to exert greater control over life events and situations. An understanding of health literacy is also important for those developing and delivering healthcare programmes, especially vaccination programmes, as both the information and the actions required to use the information are complex requiring sophisticated health literacy skills beyond the capacity of a significant proportion of the population. There are simple steps which can be taken to make the information in vaccination materials easier to understand and use. The complex concepts of reading and numeracy skills in relation to health will be discussed and strategies described which can improve access to healthcare information for all patients, whatever their literacy level.


Location of implant-retained fixed dentures affects oral health-related quality of life.
The effects of the locations of dental implants on treatment outcomes, as evaluated by oral health-related quality of life (OHRQoL) assessment, remain controversial. To investigate the association between the locations of dental implants and changes in OHRQoL. Sixty-eight subjects received implant treatment in the anterior or posterior region and completed the Oral Health Impact Profile (OHIP) questionnaire before and after treatment. Change in OHIP summary scores and the 4 dimension scores were calculated to evaluate the effects of implant treatment on OHRQoL. The mean Oro-facial Appearance score for the anterior group was significantly higher than that for the posterior group (10.4 ± 5.1 and 7.2 ± 3.8, respectively; P = .005; Effect size = 0.63) at baseline. All questionnaire scores were significantly improved following implant treatment in both groups, and no significant group differences were observed at follow-up. Regression analysis revealed a significant association between the locations of most anterior implants and changes in the Oro-facial Appearance score (adjusted R2 = 0.073; P = .015). Our results suggest that the locations of dental implants influence OHRQoL impairments and improvements after treatment. This information might be useful in clinical decision-making.


Neural inhibition can explain negative BOLD responses: A mechanistic modelling and fMRI study.
Functional magnetic resonance imaging (fMRI) of hemodynamic changes captured in the blood oxygen level-dependent (BOLD) response contains information of brain activity. The BOLD response is the result of a complex neurovascular coupling and comes in at least two fundamentally different forms: a positive and a negative deflection. Because of the complexity of the signaling, mathematical modelling can provide vital help in the data analysis. For the positive BOLD response, there are plenty of mathematical models, both physiological and phenomenological. However, for the negative BOLD response, no physiologically based model exists. Here, we expand our previously developed physiological model with the most prominent mechanistic hypothesis for the negative BOLD response: the neural inhibition hypothesis. The model was trained and tested on experimental data containing both negative and positive BOLD responses from two studies: 1) a visual-motor task and 2) a working-memory task in conjunction with administration of the tranquilizer diazepam. Our model was able to predict independent validation data not used for training and provides a mechanistic underpinning for previously observed effects of diazepam. The new model moves our understanding of the negative BOLD response from qualitative reasoning to a quantitative systems-biology level, which can be useful both in basic research and in clinical use.


Novel thrombo-resistant coating based on iron-polysaccharide complex multilayers.
The biocompatibility of iron-polysaccharide complexes has been well-documented. Herein, a stable thrombo-resistant coating was fabricated by consecutive adsorption of Fe (III) and polysaccharides including heparin (Hep) and dextran sulfate (DS) onto various surface by layer-by-layer self-assembly technique via both electrostatic interaction and chemical complexation process. The absorbance at 350 nm increased linearly with the number of Fe3+/Hep multilayer, indicating the formation of multilayer structure and the uniform coating. Compared with (Fe3+/Hep)10, the (Fe3+/DS/Fe3+/Hep)5 coating was more hydrophilic and stable due to the incorporation of DS. The activated partial thromboplastin time (APTT) and platelet adhesion assays showed that both (Fe3+/Hep)10 and (Fe3+/DS/Fe3+/Hep)5 coated surfaces were anticoagulant. The complexing with ferric ions did not compromise the catalytic capacity of heparin to promote antithrombin(III)-mediated thrombin inactivation. Chromogenic assays for heparin activity proved definitively that the inhibition of locally produced thrombin was contributed to the thromboresistance of the surface-bound heparin. The surface with Hep or DS as the outmost layer showed stronger anticoagulant activity than Fe3+, indicating that the outermost layer of the coating played a key role in anticoagulant activity. The utilization of dextran sulfate/heparin surfaces was more advantageous than merely the heparin surface for improving blood-contacting medical devices for long-term usage.


Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ dysfunction.
Multiple organ dysfunction syndrome (MODS) is a common complication of sepsis in mechanically ventilated patients with acute respiratory distress syndrome, but the links between mechanical ventilation and MODS are unclear. Our goal was to determine whether a minimally injurious mechanical ventilation strategy synergizes with low-dose endotoxemia to induce the activation of pro-inflammatory pathways in the lungs and in the systemic circulation, resulting in distal organ dysfunction and/or injury. We administered intraperitoneal Escherichia coli lipopolysaccharide (LPS; 1 microg/g) to C57BL/6 mice, and 14 hours later subjected the mice to 6 hours of mechanical ventilation with tidal volumes of 10 ml/kg (LPS + MV). Comparison groups received ventilation but no LPS (MV), LPS but no ventilation (LPS), or neither LPS nor ventilation (phosphate-buffered saline; PBS). Myeloperoxidase activity and the concentrations of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC were significantly increased in the lungs of mice in the LPS + MV group, in comparison with mice in the PBS group. Interestingly, permeability changes across the alveolar epithelium and histological changes suggestive of lung injury were minimal in mice in the LPS + MV group. However, despite the minimal lung injury, the combination of mechanical ventilation and LPS resulted in chemical and histological evidence of liver and kidney injury, and this was associated with increases in the plasma concentrations of KC, MIP-2, IL-6, and TNF-alpha. Non-injurious mechanical ventilation strategies interact with endotoxemia in mice to enhance pro-inflammatory mechanisms in the lungs and promote extra-pulmonary end-organ injury, even in the absence of demonstrable acute lung injury.


Heat shock protein 90 and tyrosine kinase regulate eNOS NO* generation but not NO* bioactivity.
An increase in the association of heat shock protein 90 (HSP90) with endothelial nitric oxide (NO) synthase (eNOS) is well recognized for increasing NO (NO*) production. Despite the progress in this field, the mechanisms by which HSP90 modulates eNOS remain unclear due, in part, to the fact that geldanamycin (GA) redox cycles to generate superoxide anion (O(2)(-*) and the fact that inhibiting HSP90 with GA or radicicol (RAD) destabilizes tyrosine kinases that rely on the chaperone for maturation. In this report, we determine the extent to which these side effects alter vascular and endothelial cell function in physiologically relevant systems and in cultured endothelial cells. Vascular endothelial growth factor (VEGF)-stimulated vascular permeability, as measured by Evans blue leakage in the ears of male Swiss mice in vivo, and acetylcholine-induced vasodilation of isolated, pressurized mandibular arterioles from male C57BL6 mice ex vivo were attenuated by N(omega)-nitro-L-arginine methyl ester (L-NAME), GA, and RAD. Z-1[N-(2-aminoethyl)-N-(2-ammonoethyl)amino]diazen-1-ium-1,2-dioate (DETA-NONOate), a slow releasing NO. donor, increased vasodilation of arterioles pretreated with GA, RAD, and L-NAME equally well except at 10(-5) M, the highest concentration used, where vasodilation was greater in pressurized arterioles treated with L-NAME than in arterioles pretreated with GA or RAD alone. Both GA and RAD reduced NO* release from stimulated endothelial cell cultures and increased O(2)(-*) production in the endothelium of isolated aortas by an L-NAME-inhibitable mechanism. Pretreatment with RAD increased stimulated O(2)(-*) production from eNOS, whereas pretreatment with genistein (GE), a broad-spectrum tyrosine kinase inhibitor, did not; however, pretreatment with GE + RAD resulted in a super-induced state of uncoupled eNOS activity upon stimulation. These data suggest that the tyrosine kinases, either directly or indirectly, and HSP90-dependent signaling pathways act in concert to suppress uncoupled eNOS activity.


Target delineation in stereotactic body radiation therapy for recurrent head and neck cancer: a retrospective analysis of the impact of margins and automated PET-CT segmentation.
Few guidelines exist on stereotactic body radiation therapy (SBRT) treatment planning for recurrent head and neck cancer. We assessed the impact of retrospectively adding margins/automated PET volumes to the gross tumor volume (GTV) in patients with post-SBRT recurrences. We reviewed 89 patients with recurrent head and neck cancer treated with SBRT using no margin around the GTV. GTVs were recontoured with 1-5mm margins. PET-CT planned GTVs were also recontoured by adding PET-standardized uptake value (SUV)(3.5), SUV(4.5), SUV(40% max), and signal/background ratio (SBR) to the original GTV. We deformably registered recontoured GTVs to post-SBRT scans and assessed fraction of recurrence volume (RV) falling within the GTV, the "RV-GTV overlap." With non-PET-CT planning, median RV-GTV overlap increased from 11.7% to 48.2% using 5mm margins, and median GTV size increased by 41.8 cc (156%). With PET-CT planning, RV-GTV overlap increased from 45% to 93.6% using 5mm margins, and GTV size increased by 34.8 cc (140%). Adding SUV(3.5) and SBR increased RV-GTV overlap from 45% to 73.3% and 73.6%, with GTV size increases of 0.8 (3%) and 3.1 cc (11%), respectively. Recontouring increased recurrence coverage and also GTV size. Margins up to 5mm may reduce failures but could possibly increase toxicities. Automated PET contours may reduce near-miss failures with smaller increases in GTV size.


Mycobacterium avium-intracellulare otomastoiditis in a young AIDS patient: case report and review of the literature.
Mycobacterium avium-intracellulare (MAI) complex is a common opportunistic infection that generally occurs in patients with a CD4 cell count less than 75. Current recommendations for prophylaxis include using a macrolide once a week, while treatment usually requires a multidrug regimen. Disseminated MAI infections often occur in patients who are not compliant with prophylaxis or their highly active antiretroviral therapy (HAART). Many manifestations of MAI infection are well documented in human immunodeficiency virus (HIV) patients, including pulmonary and cutaneous manifestations, but other unusual manifestations such as pericarditis, pleurisy, peritonitis, brain abscess, otitis media, and mastoiditis are sporadically reported in the infectious diseases literature. This case report is of a 22-year-old female who contracted HIV at a young age and who was subsequently noncompliant with HAART, MAI prophylaxis, and prior treatment for disseminated MAI infection. Unsurprisingly, the patient developed recurrent disseminated MAI infection. The patient's presentation was atypical, as she developed severe otomastoiditis and posterior reversible encephalopathy syndrome. The posterior reversible encephalopathy syndrome was thought to be due to the disseminated MAI infection or to immune reconstitution inflammatory syndrome. The infection was confirmed to be secondary to MAI by culture of the mastoid bone. Microbiological analysis of the MAI strain cultured showed resistance to several first-line antibiotics used for prophylaxis against and treatment of MAI. This was likely due to the patient's chronic noncompliance. Otomastoiditis secondary to MAI is predominantly a pediatric disease and a rare entity in general. It has been reported in three case reports and one case series in pediatric patients, and now in this case report of an adult patient with HIV [corrected]. Improved clinician education in the diagnosis, treatment, and, most important, prevention of MAI and other opportunistic infections is needed. Greater HIV screening, appropriate HAART medication administration, and availability of infectious disease specialists is needed in at-risk populations to help prevent such serious infections. Patient education and greater access to care should serve to prevent medication nonadherence and to enhance affordability of HAART and prophylactic antibiotics.


A light-sectioning technique for contouring and measuring a child's face.
A contouring device for measuring the face (Cobb, 1972) was adopted and developed to make it suitable for use with children. Modifications were made to overcome incomplete facial coverage and lack of common head orientation by incorporating a method of optical head positioning which had been invented during the assessment of a stereophotogrammetric technique (Ainsworth and Joseph 1976). The precise alignment of a series of exposures with a common datum enables a set of contour maps to be processed by computer to produce three-dimensional measurements and sections of the complete face.


Effect of dietary protein and light restriction on body weight and semen production of breeder male turkeys.
The relationships of dietary protein, body weight gain, prebreeder light restriction, age at the start of semen production, and semen volume were studied. Large White breeder male turkeys were fed corn-soybean meal diets containing the following percentages of protein at different age intervals: Treatment A, 26% (8 to 12 weeks), 19% (13 to 18 weeks), 15% (19 to 52 weeks); Treatment B, 26% (8 to 12 weeks), 19% (13 to 18 weeks), 8% (19 to 52 weeks); Treatment C, 17% (8 to 28 weeks), 8% (29 to 52 weeks); Treatment D, 17% (8 to 18 weeks), 8% (19 to 52 weeks). Body weights at 18, 28, and 52 weeks of age were: Treatment A, 11.8, 20.8, and 21.7 kg; Treatment B, 11.4, 15.1, and 17.8 kg; Treatment C, 9.2, 20.0, and 20.7 kg; Treatment D, 9.1, 11.8, and 15.0 kg. The effects of 6 hr light: 18 hr dark (restricted light) were compared with 12 hr light: 12 hr dark (full light) during the prebreeder period (18 to 28 weeks of age). All turkeys received 14 hr light: 10 hr dark from 29 to 52 weeks of age. With full light, 50% of the turkeys were producing semen at 29 weeks and 100% at 32 weeks. With restricted light, 50% of the turkeys were producing semen at 32 weeks and 100% at 34 weeks. Turkeys fed Treatments A, B, C, and D reached 50% production at 28, 30, 29, and 32 weeks, respectively, and all turkeys were producing semen at 35 weeks. The average semen volume per ejaculate for weeks 34 to 52 were: .35, .34, .34, and .25 ml for Treatments A, B, C, and D, respectively; and .34 and .31 ml for full and restricted light, respectively. Treatments B and D reduced body weight gain after 18 weeks of age. However, Treatment B had better semen production than Treatment D. There was no advantage to restricted light during the prebreeder period.


[Value of anti-Müllerian hormone in predicting pregnant outcomes of polycystic ovary syndrome patients undergone assisted reproductive technology].
Objective: Explore the value of anti-Müllerian hormone (AMH) in predicting pregnant outcomes of polycystic ovary syndrome (PCOS) patients undergone assisted reproductive technology. Methods: The study totally recruited 1 697 patients who underwent the first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle in Sun Yat-sen Memorial Hospital from the January 2014 to December 2015. The patients were divided into two groups based on the age<35 (n=758) and ≥35 years old (n=939) , compare the basic data and pregnant outcomes of controlled ovarian hyerstimulation. Spearman correlation method was conducted to analyze the relations between AMH and clinical outcomes. The logistic regression method and partial correlation analysis were used to judge the main factors which determine pregnancy outcomes by controlled the confounding factors. The receiver operating characteristic curve (ROC) was used to evaluate the predictive sensitivity and specificity of AMH. Results: In the group of PCOS patient younger than 35 years, AMH were correlated with the number of antral follicles (r=0.388) and retrieved oocytes (r=0.235) . When the effect of total dosage and starting dosage of gonadotropin were controlled, AMH was still significantly associated with the number of retrieved oocytes (P<0.05) . AMH had no predictive value for the clinical pregnancy of PCOS patient younger than 35 years (area under ROC curve=0.481, P=0.768) . In the group of PCOS patient≥35 years old, AMH were correlated with the number of antral follicles (r=0.450) , retrieved oocytes (r=0.399) , available embryo (r=0.336) and high quality embryo (r=0.235) . When the effect of total dosage and starting dosage of gonadotropin were controlled, the correlations were still significant between those indexes (all P<0.05) . AMH had no predictive value for the clinical pregnancy of PCOS patient ≥35 years old (area under ROC curve=0.535, P=0.560) . However, the clinical pregnancy rate of the group of PCOS patient ≥35 years old was slightly higher than the control group (P=0.062) . Conclusions: AMH has no predictive value for the pregnancy outcome of PCOS patient. The pregnancy rate of PCOS patient ≥35 years old is slightly higher than the younger group, because the PCOS patient may have better ovarian reserve.


[Study on absorbed components of Aconitum kusnezoffii under Yunnan Baiyao compatibility in effect of activating blood circulation and removing blood stasis].
Rat model of blood stasis syndrome was prepared by subcutaneous injecting of epinephrine hydrochlorid,then the model rats were administrated by Yunnan Baiyao for 15 days. Blood rheology,coagulation function and histopathology were chosen as indicators to evaluate the successful replication of blood stasis syndrome model and the treatment effect of Yunnan Baiyao. UPLC-Q-TOF-MS was used to rapidly analyze the serum samples of blood stasis syndrome rat after 15 days Yunnan Baiyao treatment,Progenesis QI software was employed to identify the alkaloids components. The results showed that Yunnan Baiyao reduced the plasma viscosity and whole blood viscosity of rats with blood stasis syndrome,prolonged thrombin and prothrombin time,reduced fibrinogen content,and effectively improved pathological state such as inflammatory cell infiltration,blood stasis,congestion and edema of various organs in rats with blood stasis syndrome. Seven alkaloids components from Aconitum kusnezoffii,including karacolidine,senbusine B,isotalatizidine,karakoline,denudatine,talatisamine and chasmanine were found in the rat serum after Yunnan Baiyao treatment. Based on the effectiveness of Yunnan Baiyao in the treatment of blood stasis syndrome induced by epinephrine hydrochloride in rats,alkaloids components from the root of A. kusnezoffii absorbed into blood after Yunnan Baiyao treatment were clarified rapidly and accurately with the help of UPLC-Q-TOF-MS. Karacolidine,senbusine B,isotalatizidine,karakoline,denudatine,talatisamine and chasmanine are the pharmacodynamic material basis of the root of A. kusnezoffii for activating blood circulation and removing blood stasis.


Who or what is the preembryo?
... The moral status -- and specifically the controversial issue of personhood -- is related to attainment of developmental individuality... This contrasts with the view that holds that personhood occurs earlier, at the point of genetic uniqueness. I believe that an embryo that has developed to the point where it can be one individual and one individual only, differs in moral status from a preembryo that has not, even if in many cases we may choose to treat them similarly... In view of the conviction that the preembryo is not yet a person and that its statistical potential for becoming such is small, it is not clear that nontherapeutic experiments can be excluded in principle. However, because the preembryo does have intrinsic potential...the preembryo should be treated as a person... Any exceptions from the prima facie duty to treat the preembryo as a person should be based on criteria established at the national level....


Management of ventilator-associated pneumonia caused by multiresistant bacteria.
The inappropriate choice of antibiotics (in nearly one third of episodes) is the most important risk factor for death. Traditionally, a narrow-spectrum drug was used first, and the most potent drugs were reserved for subsequent use. As multidrug resistance increases in the intensive care unit in patients treated for nosocomial pneumonia, costs, mortality, and morbidity are rising. Although methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii are frequently considered together, they have different virulence, risk factors and susceptibilities, requiring different antimicrobial choices. Assessment of clinical resolution should be differentiated in the presence of acute lung injury. In the absence of biochemical markers, oxygenation and core temperature should guide therapeutic decisions. As ventilator-associated pneumonia increases, empiric therapy should be based on local pathogen etiology and antibiotic resistant patterns. A new approach to consider is to start with a high-dose, broad-spectrum antibiotic and then tailor the individual therapy based on microbiological results and clinical resolution. With the use of broad-spectrum antibiotics available in empiric therapy tailored after reassessment of the patient, there is hope for reducing costs, length of stay and mortality whereas the emergence of resistance will be minimized.


Anticoagulant drugs: what is new?
Heparins and vitamin K antagonists have been the cornerstones of anticoagulation treatment for several decades. Despite their effectiveness, these agents have limitations which can include food and drug interactions and the need for monitoring. It follows that there is a need for new anticoagulants. There are numerous promising agents at various stages of evaluation. Those in the most advanced stages of development are the oral factor Xa and the thrombin inhibitors, which are the focus of this review.


A NAV2729-sensitive mechanism promotes adrenergic smooth muscle contraction and growth of stromal cells in the human prostate.
Voiding symptoms in benign prostatic hyperplasia (BPH) are driven by prostate smooth muscle contraction and prostate growth. Smooth muscle contraction in the prostate and other organs critically depends on activation of the small monomeric GTPase RhoA and probably Rac1. A role of another GTPase, ADP-ribosylation factor 6 (ARF6), for smooth muscle contraction has been recently suggested by indirect evidence but remains to be proven for any organ. Here, we report effects of NAV2729, an inhibitor with assumed specificity for ARF6, in human prostate tissues and cultured prostate stromal cells (WPMY-1). NAV2729 (5 μm) inhibited neurogenic and α1-adrenergic contractions of human prostate tissues. Contractions induced by endothelin-1, by the thromboxane A2 agonist U46619, or by high molar KCl were not inhibited. Correlation analyses suggested up-regulation of prostatic ARF6 expression with increasing degree of BPH, as ARF6 expression increased with the content of prostate-specific antigen (PSA) of prostate tissues. NAV2729 inhibited ARF6 activity but not other GTPases (ARF1, RhoA, Rac1) in prostate tissues and in WPMY-1 cells. Proliferation of WPMY-1 cells was inhibited concentration-dependently by NAV2726, as reflected by decreased viability, 5-ethynyl-2'-deoxyuridine (EdU) assay, colony formation assay, and expression of Ki-67. Silencing of ARF6 expression mimicked effects of NAV2729 on viability and in the EdU assay. Effects of NAV2729 on viability and proliferation were attenuated in cells with silenced ARF6 expression. Our findings suggest that a NAV2729-sensitive mechanism promotes adrenergic contraction and stromal cell growth in the human prostate, which is probably ARF6-mediated. Similar actions in other organs and urodynamic effects of NAV2729 appear possible.


Pathophysiology of diastolic hypertension.
Two different mechanisms for long-term vasoconstriction that sustain diastolic hypertension in the experimental and clinical forms of primary aldosteronism and renovascular hypertension can also be identified and quantified among patients with essential hypertension. The first is renin-independent, requires antecedent sodium retention, and appears related to abnormal membrane transport of calcium. This vasoconstriction is identified by low plasma renin and ionized calcium values and is correctable by sodium depletion or calcium channel or alpha-blockade. The second is renin-mediated but also involves an increase in cytosolic calcium. This mechanism is quantifiable by the plasma renin level and by the hypotensive response to an anti-renin-system drug (CEI inhibitor, saralasin, beta-blocker). At the very extremes of the range of plasma renin values encountered in hypertensive patients, one of the two mechanisms predominates, whereas in the medium range of renin values either or both mechanisms can be operative.


Relationship between allergy and bruxism in patients with myofascial pain-dysfunction syndrome.
The relationship between allergy and bruxism was examined in three groups: patients with myofascial pain-dysfunction, patients with organic disorders of the temporomandibular joint, and patients without temporomandibular joint disorders.


A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1.
Toll-like receptors (TLRs) play important roles in building innate immune and inducing adaptive immune responses. Associations of the TLR genes polymorphisms with disease susceptibility, which are the basis of molecular breeding for disease resistant animals, have been reported extensively. Retrotransposon insertion polymorphisms (RIPs), as a new type of molecular markers developed recently, have great potential in population genetics and quantitative trait locus mapping. In this study, bioinformatic prediction combined with PCR-based amplification was employed to screen for RIPs in porcine TLR genes. Their population distribution was examined, and for one RIP the impact on gene activity and phenotype was further evaluated. Five RIPs, located at the 3' flank of TLR3, 5' flank of TLR5, intron 1 of TLR6, intron 1 of TLR7, and 3' flank of TLR8 respectively, were identified. These RIPs were detected in different breeds with an uneven distribution among them. By using the dual luciferase activity assay a 192 bp endogenous retrovirus (ERV) in the intron 1 of TLR6 was shown to act as an enhancer increasing the activities of TLR6 putative promoter and two mini-promoters. Furthermore, real-time quantitative polymerase chain reaction (qPCR) analysis revealed significant association (p < 0.05) of the ERV insertion with increased mRNA expression of TLR6, the neighboring gene TLR1, and genes downstream in the TLR signaling pathway such as MyD88 (Myeloid differentiation factor 88), Rac1 (Rac family small GTPase 1), TIRAP (TIR domain containing adaptor protein), Tollip (Toll interacting protein) as well as the inflammatory factors IL6 (Interleukin 6), IL8 (Interleukin 8), and TNFα (Tumor necrosis factor alpha) in tissues of 30 day-old piglet. In addition, serum IL6 and TNFα concentrations were also significantly upregulated by the ERV insertion (p < 0.05). A total of five RIPs were identified in five different TLR loci. The 192 bp ERV insertion in the first intron of TLR6 was associated with higher expression of TLR6, TLR1, and several genes downstream in the signaling cascade. Thus, the ERV insertion may act as an enhancer affecting regulation of the TLR signaling pathways, and can be potentially applied in breeding of disease resistant animals.


Hyperosmotic stress induces immediate-early gene expression in ventricular adult cardiomyocytes.
Mammalian cells possessing osmosensors have long been described in brain and kidney. The genetic basis of the response to hyperosmotic stress has been well characterized in prokaryotes. In contrast, the genetic response of eukaryotic cells is poorly understood. Therefore we investigated the effect of hypertonic NaCl and sucrose solutions on the transcriptional activation of the immediate-early genes (IEGs) egr-1 and c-fos in isolated ventricular adult rat cardiomyocytes. We observed that even small increases in osmolarity to 315 +/- 5 mosmol/l and 370 +/- 8 mosmol/l by hypertonic NaCl solution resulted in dose-dependent induction of egr-1 (4-and 5-fold) and c-fos (3-and 4-fold), respectively. Hypertonic sucrose solution had the same effect on egr-1 and c-fos mRNA levels while increased sucrose concentration under isotonic conditions had no effect. Cardiomyocytes exposed to hypertonic media did not significantly shrink as shown by a cell length measurement. We conclude that isolated adult cardiomyocytes possess an osmoreceptor mechanism which is able to sense even slight changes in osmolarity and to translate these into a transcriptional response of the myocardial IEG program.


Surviving trees are key elements in the fate of ectomycorrhizal community after severe bark-beetle forest disturbance.
Bark beetle disturbances are a critical event in the life cycle of Norway spruce forests. However, our knowledge of their effects on ectomycorrhizal fungi (EMF), which play a key role in forest productivity and nutrient cycling, is still incomplete. Special attention has been paid to the dynamics and diversity of EMF communities in managed forests, but studies dealing with disturbed natural stands are underrepresented. We conducted a study in an unmanaged natural spruce forest in the Bohemian Forest (Czech Republic), which suffered severe forest dieback caused by bark beetle. Approximately a decade after the disturbance, the character of the forest structure in the study area (∼60 ha, 41 study plots) ranged from sites with open canopy and sparse tree cover to areas with dense spruce regeneration to patches of closed-canopy forest. We found that relative EMF abundance in soils was positively related to surviving tree and regeneration density. The number of surviving trees also positively affected species EMF richness and tended to support preservation of late-successional EMF species. Our results suggest that trees that survive bark beetle disturbance are key for the fate of the EMF community in natural forests.