Solution-phase hierarchical self-organization of ultralong Se nanowires into diverse macroarchitectures and their enhanced field emission.
A simple solution-phase route was developed for the large-scale synthesis of self-organized, closely packed ultralong single crystalline Se nanowire superstructures with diverse morphologies and macroscopic dimensions even extending over several millimeters. The hierarchical architectures of self-organized Se nanowires were formed by reducing H2SeO4 with a bisubstituted aniline, such as 3,5-dimethoxyaniline, 2,5-dimethoxyaniline, 2,6-dimethoxyaniline, and 2-methoxy-5-nitroaniline under solvothermal conditions. Scanning electron microscopy studies show 100% morphological yield and morphological uniformity of the self-organized hierarchical architectures. Based on the dependence of the Se nanostructures on the synthetic conditions, especially the molecular structures of reductants and solvent, we proposed a plausible mechanism to account for the formation of the distinctive morphologies of the self-organized nanowire architectures. The field emission characteristics of the Se nanowires synthesized using 2,6-dimethoxyaniline and 2-methoxy-5-nitroaniline as the reductants are studied. These well-aligned Se nanowires show very low turn-on field (Eto) and threshold field (Ethr) as well as high emission current densities under low applied electric fields, which are superior to most of the one-dimensional (1D) nanostructures reported previously, due to their exceptional aspect ratios (>20 000) and sharp tips in combination with the nature of low band gap and high conductivity of Se. Furthermore, the Se nanowire emitters exhibit good emission current stability with small fluctuations (typically, less than 3%) over a period of 1000 min.


Transthoracic Doppler echocardiography during a military mission in a French role II in Mali: is it useful to learn this practice?
Ultrasound is now recognized as a key tool in the practice of medicine in isolated situations. This study aims to evaluate the impact of transthoracic echocardiography (TTE) in a military mission when performed by a trained military practitioner (MP). We conducted a 2-month retrospective observational study on the use of TTE in a French medical complex in Mali with a mission that included providing a medical aid to the population. All patients were included. Every ultrasound performed by the MP was listed, and the epidemiologic data, indication for the exam and results were collected for each TTE. A total of 349 patients were included, 16 were war-wounded patients and 333 came for a general medical consultation. In all, 153 ultrasounds were performed, including 48 TTEs. Sixteen TTEs were performed to evaluate injuries in war-wounded patients. During the 333 medical consultations, 32 TTEs were realized. The indications were dyspnoea (10), heart murmur (7), acute chest pain (5) and assessment of heart disease (10). TTE permitted a direct positive diagnosis for 18 patients: 7 with acute heart failure and 11 with morphologic problems. The normality of the exam was a supplementary argument to exclude a cardiac implication for eight patients. TTE can provide important information with a direct impact on the management of patients. Faced with cardiac emergencies, an adapted training can be proposed for the MP. Thereby, the transfer of conventional cardiac views could facilitate the advice of a cardiologist.


Quantitative Proteomic Analysis of Human Airway Cilia Identifies Previously Uncharacterized Proteins of High Abundance.
Cilia are essential to many diverse cellular processes. Although many major axonemal components have been identified and studied, how they interact to form a functional axoneme is not completely understood. To further our understanding of the protein composition of human airway cilia, we performed a semiquantitative analysis of ciliary axonemes using label-free LC/MSE, which identified over 400 proteins with high confidence. Tubulins were the most abundant proteins identified, with evidence of 20 different isoforms obtained. Twelve different isoforms of axonemal dynein heavy chain were also identified. Absolute quantification of the nontubulin components demonstrated a greater than 75-fold range of protein abundance (RSPH9;1850 fmol vs CCDC103;24 fmol), adding another level of complexity to axonemal structure. Of the identified proteins, ∼70% are known axonemal proteins. In addition, many previously uncharacterized proteins were identified. Unexpectedly, several of these, including ERICH3, C1orf87, and CCDC181, were present at high relative abundance in the cilia. RT-PCR analysis and immunoblotting confirmed cilia-specific expression for eight uncharacterized proteins, and fluorescence microscopy demonstrated unique axonemal localizations. These studies have provided the first quantitative analysis of the ciliary proteome and have identified and characterized several previously unknown proteins as major constituents of human airway cilia.


Aspartame ingestion and headaches: a randomized crossover trial.
To examine whether ingestion of aspartame is associated with headaches, we conducted a double-blind crossover study using volunteers with self-identified headaches after using aspartame. Of the 32 subjects randomized to receive aspartame (approximately 30 mg/kg/d) and placebo in a two-treatment, four-period crossover design, 18 completed the full protocol, seven completed part of the protocol before withdrawing due to adverse effects, three withdrew for other reasons, two were lost to follow-up, one was withdrawn due to noncompliance, and one withdrew and gave no reason. Each experimental period was 7 days long. Subjects reported headaches on 33% of the days during aspartame treatment, compared with 24% on placebo treatment (p = 0.04). Subjects who were "very sure" prior to the study that aspartame triggered some of their headaches reported larger treatment differences (aspartame = 0.37 headache-days, placebo = 0.18 headache-days; p < 0.001) than subjects who were "somewhat sure" (aspartame = 0.29 headache-days, placebo = 0.22 headache-days; p = 0.51) or "not sure" (aspartame = 0.33 headache-days, placebo = 0.39 headache-days; p = 0.51). There was no significant treatment difference in the length or intensity of headaches or in the occurrence of side effects associated with the headaches. This experiment provides evidence that, among individuals with self-reported headaches after ingestion of aspartame, a subset of this group report more headaches when tested under controlled conditions. It appears that some people are particularly susceptible to headaches caused by aspartame and may want to limit their consumption.


Cu(aq)+/Cu(aq)2+ redox reaction exhibits strong nonlinear solvent response due to change in coordination number.
We have carried out extensive Born-Oppenheimer molecular dynamics simulations to characterize the structure and energetics of the Cu(+)/Cu(2+) redox pair. Our simulations support recent experimental evidence suggesting that Cu(2+) adopts a 5-fold coordination in aqueous solution and not the traditionally assumed octahedral coordination. Cu(+) forms a linear dihydrate structure with a third water molecule occasionally binding in the equatorial plane. We show that the change in ligand coordination number from 2 for aqueous Cu(+) to 5 for aqueous Cu(2+) leads to marked deviations from the linear response assumption underlying Marcus theory of oxidation. The diabatic free energy curves deviate from parabolic behavior and the reorganization free energies for Cu(+) and Cu(2+) are asymmetric and differ by 1.0 eV. The calculated reorganization free energies can semiquantitatively explain the exceptionally small electron self-exchange rate between Cu(+) and Cu(2+) in aqueous solution.


Thieno analogues of RNA nucleosides: a detailed theoretical study.
We use first-principles density functional theory calculations to investigate the structural, energetic, bonding aspects, and optical properties of recently synthesized thieno-analogues of RNA nucleosides. The results are compared against the findings obtained for both the natural nucleosides as well as available experimental data. We find that the modified nucleosides form the hydrogen bonded Watson-Crick (WC) base pairing with similar H-bonding energy as obtained for the natural nucleosides. We have calculated and compared the charge transfer integrals for the H-bonded natural and thieno-modified nucleosides. We find that the thieno modification of these nucleosides strongly affects the charge transfer integrals due to the difference in extent of orbital delocalization in these two types of nucleosides. We also find that the degree of reduction of charge transfer integrals is larger for the H-bonded A-U pair than in the G-C pair. We also focus on the optical absorption properties of these thieno-modified nucleosides and their WC H-bonded base pairs in gas phase as well as with implicit water. Our calculated results show that the low energy peaks in the absorption spectra mainly arise because of the π-π* electronic transition for both the nucleosides, and the observed red shift for thieno-nucleosides compared to natural nucleosides are consistent with the calculated decrease in electronic gaps. Our results demonstrate that the thieno modification of natural nucleosides significantly modifies their electronic and optical properties, although the basic structural and bonding aspects remained the same. It also gives a microscopic understanding of the experimentally observed optical behaviors.


Non-invasive endothelial function testing and the risk of adverse outcomes: a systematic review and meta-analysis.
We performed a systematic review and meta-analysis to understand the role of flow-mediated dilatation (FMD) of the brachial artery (BA) and peripheral arterial tonometry (PAT) in predicting adverse events, including cardiovascular (CV) events and all-cause mortality. FMD of the BA and PAT are non-invasive measures of endothelial function. Impairment of endothelial function is associated with increased CV events. While FMD is the more widely used and studied technique, PAT offers several advantages. The purpose of this systematic review and meta-analysis is to determine whether brachial FMD and PAT are independent risk factors for future CV events and mortality. Multiple electronic databases were searched for articles relating FMD or PAT to CV events. Data were extracted on study characteristics, study quality, and study outcomes. Relative risks (RRs) from individual studies were combined and a pooled multivariate RR was calculated. Thirty-six studies for FMD were included in the systematic review, of which 32 studies consisting of 15, 191 individuals were meta-analysed. The pooled RR of CV events and all-cause mortality per 1% increase in brachial FMD, adjusting for potential confounders, was 0.90 (0.88-0.92). In contrast, only three studies evaluated the prognostic value of PAT for CV events, and the pooled RR per 0.1 increase in reactive hyperaemia index was 0.85 (0.78-0.93). Brachial FMD and PAT are independent predictors of CV events and all-cause mortality. Further research to evaluate the prognostic utility of PAT is necessary to compare it with FMD as a non-invasive endothelial function test in clinical practice.


Identification of sympatric cryptic species of Aedes albopictus subgroup in Vietnam: new perspectives in phylosymbiosis of insect vector.
The Aedes (Stegomyia) albopictus subgroup includes 11 cryptic species of which Ae. albopictus is the most widely distributed. Its global expansion associated with a documented vector competence for several emerging arboviruses raise obvious concerns in the recently colonized regions. While several studies have provided important insights regarding medical importance of Ae. albopicus, the investigations of the other sibling species are scarce. In Asia, indigenous populations within the Ae. albopictus subgroup can be found in sympatry. In the present study, we aimed to describe and compare molecular, morphological and bacterial symbionts composition among sympatric individuals from the Ae. albopictus subgroup inhabiting a Vietnamese protected area. Based on morphological structure of the cibarial armarture, we identified a cryptic species in the forest park at Bù Gia Mập in the south-eastern region of Vietnam. Analysis of nuclear (ITS1-5.8S-ITS2) and mitochondrial (cox1, nad5) markers confirmed the divergence between the cryptic species and Ae. albopictus. Analysis of midgut bacterial microbiota revealed a strong similarity among the two species with a notable difference; contrary to Ae. albopictus, the cryptic species did not harbour any Wolbachia infection. These results could reflect either a recent invasion of Wolbachia in Ae. albopictus or alternatively a loss of this symbiont in the cryptic species. We argue that neglected species of the Ae. albopictus subgroup are of main importance in order to estimate variation of host-symbionts interactions across evolution.


Paracentral acute middle maculopathy in the immediate postoperative of cataract surgery.
This case report identified paracentral acute middle maculopathy as the cause of severe and irreversible vision loss after cataract surgery. Cataract surgeons should be aware of known risk factors for the development of paracentral acute middle maculopathy. In those patients, extra care regarding anesthesia, intraocular pressure, and some other aspects of cataract surgery must be taken. Paracentral acute middle maculopathy is currently understood as a clinical sign evident on spectral-domain optical coherence tomography, and it is probably evidence of deep ischemic insult to the retina. It should be a differential diagnosis in cases of marked low vision acuity associated with no fundus abnormalities in the immediate postoperative period, as demonstrated in the presented case.


Egr-1 activation by cancer-derived extracellular vesicles promotes endothelial cell migration via ERK1/2 and JNK signaling pathways.
Various mammalian cells, including cancer cells, shed extracellular vesicles (EVs), also known as exosomes and microvesicles, into surrounding tissues. These EVs play roles in tumor growth and metastasis by promoting angiogenesis. However, the detailed mechanism of how cancer-derived EVs elicit endothelial cell activation remains unknown. Here, we provide evidence that early growth response-1 (Egr-1) activation in endothelial cells is involved in the angiogenic activity of colorectal cancer cell-derived EVs. Both RNA interference-mediated downregulation of Egr-1 and ERK1/2 or JNK inhibitor significantly blocked EV-mediated Egr-1 activation and endothelial cell migration. Furthermore, lipid raft-mediated endocytosis inhibitor effectively blocked endothelial Egr-1 activation and migration induced by cancer-derived EVs. Our results suggest that Egr-1 activation in endothelial cells may be a key mechanism involved in the angiogenic activity of cancer-derived EVs. These findings will improve our understanding regarding the proangiogenic activities of EVs in diverse pathological conditions including cancer, cardiovascular diseases, and neurodegenerative diseases.


Comparative analysis of the pathogenic mechanisms associated with the G8363A and A8296G mutations in the mitochondrial tRNA(Lys) gene.
Two mutations (G8363A and A8296G) in the mtDNA (mitochondrial DNA) tRNA(Lys) gene have been associated with severe mitochondrial diseases in a number of reports. Their functional significance, however, remains unknown. We have already shown that homoplasmic cybrids harbouring the A8296G mutation display normal oxidative phosphorylation, although the possibility of a subtle change in mitochondrial respiratory capacity remains an open issue. We have now investigated the pathogenic mechanism of another mutation in the tRNA(Lys) gene (G8363A) by repopulating an mtDNA-less human osteosarcoma cell line with mitochondria harbouring either this genetic variant alone or an unusual combination of the two mutations (A8296G+G8363A). Cybrids homoplasmic for the single G8363A or the A8296G+G8363A mutations have defective respiratory-chain enzyme activities and low oxygen consumption, indicating a severe impairment of the oxidative phosphorylation system. Generation of G8363A cybrids within a wild-type or the A8296G mtDNA genetic backgrounds resulted in an important alteration in the conformation of the tRNA(Lys), not affecting tRNA steady-state levels. Moreover, mutant cybrids have an important decrease in the proportion of amino-acylated tRNA(Lys) and, consequently, mitochondrial protein synthesis is greatly decreased. Our results demonstrate that the pathogenicity of the G8363A mutation is due to a change in the conformation of the tRNA that severely impairs aminoacylation in the absence of changes in tRNA stability. The only effect detected in the A8296G mutation is a moderate decrease in the aminoacylation capacity, which does not affect mitochondrial protein biosynthesis.


Intraventricular infusion of the selective sigma-agonist 1,3-di-ortho-tolylguanidine (DTG) mitigates ischaemic brain damage in the hippocampus.
Experimental evidence suggests that neuronal pharmacologic sites termed sigma (sigma) may be related, but not identical to PCP sites in the ion channel linked to NMDA excitatory receptors. These receptors may play a role in schizophreniform psychoses, and clinical trials of putative sigma-ligands have begun. Because of this, and because of the relationship of sigma-ligands to NMDA receptors, we studied the effect of the most selective presently available sigma-ligand on ischaemic neuronal death throughout the rat brain after transient forebrain ischaemia. Ventricular delivery of DTG at 0.5 mumol/h via an osmotic minipump was chosen to allow continuous access of the drug to brain tissue, control animals receiving artificial CSF. After one week survival, selective neuronal necrosis was reduced in the hippocampus, but not in the neocortex or striatum, contrasting with our previous findings in this model with pure NMDA antagonists. The results indicate that ischaemic neuronal necrosis in the hippocampus may be mitigated by sigma-agonists, possibly via an interaction with NMDA receptors.


Adipose tissue linoleic acid as a criterion of adherence to a modified diet.
In elderly, institutionalized men on a diet of high linoleic acid content, there was little correlation after 1 yr between adipose tissue linoleic acid concentration and dining room attendance. The correlation improved thereafter, with a correlation coefficient of +0.81 after 5 yr and +0.74 after 6 yr.


Cognitive Impairment Early After Initiating Maintenance Hemodialysis: A Cross Sectional Study.
Abnormalities in cognitive function are almost universal in patients receiving hemodialysis (HD) and are associated with worse quality of life, impaired decision making, increased healthcare utilization and mortality. While cognitive impairment in the HD population is increasingly recognized, it is unclear how quickly it develops after starting HD. This was a cross-sectional study of a cohort of low dialysis vintage HD patients (<12 months). We used the validated Cambridge Brain Science (CBS) battery of web-based tests to evaluate cognition compared to age- and sex matched controls across three cognitive domains: verbal processing, reasoning and short-term memory. Forty-nine HD patients were included in this study; 43 completed the full battery of tests. The average scores for HD patients were consistently below the age and sex-matched controls. Fifty-five percent of HD patients had cognitive impairment in verbal skills, 43% in reasoning and 18% in short-term memory. There is a high prevalence of CI evident early after starting HD, with the largest deficits seen in reasoning and verbal processing. These deficits may be attributable to the HD treatment itself. Further studies are needed to characterize the natural history of CI in this patient population and to test interventions aimed at preventing or slowing its progression.


Low pre-albumin but not thiamine predicts cognitive deficits in adolescents post-Fontan and healthy controls.
Low pre-albumin, body mass index, and thiamine levels have been associated with poor nutritional status and cognitive/memory deficits in adult heart failure patients. However, the relationship of these nutritional/dietary intake biomarkers to cognition has not been assessed in adolescents post-Fontan procedure and healthy controls. This is a cross-sectional study. Adolescents (14-21 years of age) post-Fontan completion were recruited from paediatric cardiology clinics and controls from the community. The Montreal Cognitive Assessment was administered (normal ≥ 26), and blood draw (thiamine [normal 70-110 nmol/L] and pre-albumin levels [adolescent normal 23-45 mg/dL]) and the Thiamine Food Frequency Questionnaire were completed by all participants. Seventy subjects, 40 post-Fontan (mean age 16 ± 1.6, female 51%, Hispanic 44%, hypoplastic left heart syndrome 26%) and 30 controls (mean age 16.8 ± 1.9, female 52%, Hispanic 66%), were participated. Post-Fontan group had lower median total cognitive scores (23 versus 29, p < 0.001), pre-albumin levels (23 versus 27, p = 0.013), and body mass index (20 versus 24, p = 0.027) than controls. Post-Fontan group had higher thiamine levels than controls (127 versus 103, p = 0.033). Lower pre-albumin levels (< 23) and underweight body mass index were associated with abnormal total cognitive scores (p = 0.030). Low pre-albumin level (p = .038) was an independent predictor of worse cognition. Lower pre-albumin was an independent predictor for worse cognition in adolescents post-Fontan. Lower pre-albumin levels may reflect chronic liver changes or protein-losing enteropathy seen in Fontan physiology. These findings highlight the possibility for nutrition-induced cognitive changes.


Axial and transverse stiffness measures of cochlear outer hair cells suggest a common mechanical basis.
The function of the hearing organ is based on mechanical processes occurring at the cellular level. The mechanical properties of guinea-pig isolated sensory cells were investigated using two different techniques. The stiffness of the outer hair cells along the longitudinal axis was measured by compressing the cell body using stiffness-calibrated quartz fibres. For cells with a mean length of 69 micron, the mean axial compression stiffness was 1. 1+/-0.8 mN/m (+/-SD). There was an inverse relation between stiffness and cell length. The stiffness of the cell membrane perpendicular to the longitudinal axis of the sensory cell was measured by indenting the cell membrane with a known force. The mean lateral indentation stiffness was 3.3+/-1.5 mN/m (+/-SD) for cells with a mean length of 64 microm. Longer cells were less stiff than short cells. Modelling the hair cell as a shell with bending resistance, finite element calculations demonstrated that the axial compression stiffness correlated well with the lateral indentation stiffness, and that a simple isotropic model is sufficient to explain the experimental observations despite the different stress strain states produced by the two techniques. The results imply that the two different stiffness properties may originate from the same cytoskeletal structures. It is suggested that the mechanical properties of the outer hair cells are designed to influence the sound-induced motion of the reticular lamina. In such a system, stiffness changes of the outer hair cell bodies could actively control the efficiency of the mechanical coupling between the basilar membrane and the important mechanoelectrical transduction sites at the surface of the hearing organ.


Effective zero-thickness model for a conductive membrane driven by an electric field.
The behavior of a conductive membrane in a static (dc) electric field is investigated theoretically. An effective zero-thickness model is constructed based on a Robin-type boundary condition for the electric potential at the membrane, originally developed for electrochemical systems. Within such a framework, corrections to the elastic moduli of the membrane are obtained, which arise from charge accumulation in the Debye layers due to capacitive effects and electric currents through the membrane and can lead to an undulation instability of the membrane. The fluid flow surrounding the membrane is also calculated, which clarifies issues regarding these flows sharing many similarities with flows produced by induced charge electro-osmosis (ICEO). Nonequilibrium steady states of the membrane and of the fluid can be effectively described by this method. It is both simpler, due to the zero thickness approximation which is widely used in the literature on fluid membranes, and more general than previous approaches. The predictions of this model are compared to recent experiments on supported membranes in an electric field.


Spin Probe Determination of Molecular Orientation Distribution and Rotational Mobility in Liquid Crystals: Model-Free Approach.
A model-free approach for simulation of EPR spectra of nitroxide spin probes in liquid-crystalline materials was suggested and used to obtain parameters of molecular orientation and rotational mobility. The developed method is based on experimental recording and numerical simulation of the angular dependence of EPR spectra, which is shown to be much more informative in comparison with a single EPR spectrum. Quantitative spectral simulations considering both local orientational ordering and distribution of local directors in the sample were used for discrimination of models of rotational mobility and orientational alignment. The method was applied for detailed quantitative characterization of axial, orthorhombic, and low-symmetry non-orthorhombic molecular orientation distributions. It is shown that the ordinarily used model of rotational diffusion in a mean-field potential is suitable for the description of molecular mobility and orientational ordering only for relatively low sample temperatures and low-mobility probe molecules with large sizes. In cases of high molecular mobility, the more realistic jump mechanism of molecular moves can be approximately described as quasi-librations. For ordered liquid crystals it was found that mostly the order parameters up to rank 12-14 are essential and easily determined. When well-aligned materials are described, the order parameters up to 18th rank or even higher become meaningful. Both molecular and sample biaxiality is analyzed and quantitatively characterized. The local molecular ordering and sample orientational alignment are quantitatively characterized separately.


Pelvic Synovial Sarcoma Clinically Masquerading as an Ovarian Malignancy.
Background: Synovial sarcoma, a malignant mesenchymal tumor, commonly involves the extremities and is rarely found in the pelvis. Cytology with a biphasic pattern can suggest the diagnosis of synovial sarcoma. Case Report: A 32-year-old female presented with complaints of abdominal distension. She was initially evaluated in another hospital where she underwent ultrasound-guided fine needle aspiration cytology (FNAC) of the abdominal mass. The mass was diagnosed as ovarian adenocarcinoma, and the patient underwent 3 cycles of chemotherapy. After 3 months, she was referred to our institute for surgical excision of the mass. Contrast-enhanced computed tomography of the abdomen suggested a well-circumscribed, heterogeneous, solid-cystic mass in the left adnexal region measuring 13.9 × 10 × 9.1 cm and compressing the adjacent structures. No previous radiologic investigations were available. We reviewed the FNAC slide from the outside hospital and made a preliminary diagnosis of biphasic synovial sarcoma. The patient underwent debulking surgery consisting of panhysterectomy with excision of the pelvic mass. Microscopic examination of the pelvic mass showed a biphasic tumor composed of epithelial and mesenchymal components, suggestive of synovial sarcoma. The immunohistochemistry profile supported the morphologic diagnosis. Bilateral ovaries were unremarkable. The patient received 4 cycles of adjuvant chemotherapy and is presently asymptomatic. Conclusion: Although primary pelvic synovial sarcoma is a rare occurrence, this case illustrates that synovial sarcoma can be diagnosed or at least suspected on FNAC. Because of the importance of adjuvant chemotherapy, synovial sarcoma must be high on the list of differential diagnoses of high-grade intra-abdominal masses.


An improved theoretical model for thermal diffusion coefficient in liquid hydrocarbon mixtures: Comparison between experimental and numerical results.
Thermal diffusion or Soret effect is a phenomenon of mass transport in fluid mixtures driven by temperature gradients. In this paper, we have studied thermal diffusion coefficients for different binary n-alkane mixtures (equal mass fraction) through both theoretical and experimental methods. The theoretical model is based on the irreversible thermodynamics. Particularly, the nonequilibrium thermodynamic property tau is examined and remodeled with a consideration of vapor-liquid equilibrium in binary mixtures. The experimental method is based on the thermogravitational technique. The new model provides a good agreement with the experimental data from this study and in the literature.


Determination of 3,5,6-trichloro-2-pyridinol, phoxim and chlorpyrifos-methyl in water samples using a new pretreatment method coupled with high-performance liquid chromatography.
A novel low-density solvent-based vortex-assisted surfactant-enhanced-emulsification liquid-liquid microextraction with the solidification of floating organic droplet method coupled with high-performance liquid chromatography was developed for the determination of 3,5,6-trichloro-2-pyridinol, phoxim and chlorpyrifos-methyl in water samples. In this method, the addition of a surfactant could enhance the speed of the mass transfer from the sample solution into the extraction solvent. The extraction solvent could be dispersed into the aqueous by the vortex process. The main parameters affecting the extraction efficiency were investigated and the optimum conditions were established as follows: 80 μL 1-undecanol as extraction solvent, 0.2 mmol/L of Triton X-114 selected as the surfactant, the vortex time was fixed at 60 s with the vortex agitator set at 3000 rpm, the concentration of acetic acid in sample solution was 0.4% v/v and 1.0 g addition of NaCl. Under the optimum conditions, the enrichment factors were from 172 to 186 for the three analytes. The linear ranges were from 0.5 to 500 μg/L with a coefficient of determination (r(2) ) of between 0.9991 and 0.9995. Limits of detections were varied between 0.05 and 0.12 μg/L. The relative standard deviations (n = 6) ranged from 0.26 to 2.62%.


Establishment of the model of motorcyclist ejection injury.
To establish the device and model of motorcyclist ejection injury. Based on our laboratory devices, a motorcyclist ejection injury simulation system was developed. A total of 18 pigs were approved by the local animal experimentation and ethics committee to serve as the motorcyclist substitutes. In this ejection motion, the animal rode freely at the motor driver seat and was straightly accelerated by means of our custom motorcyclist ejection injury simulation system. When it was speeded up to the preset velocity (v equal to 30, 40 or 50 km/h) at the preset position, the animal was ejected forward. Pathological and dynamic analyses were conducted, accompanied with the high-speed photograph, acceleration/velocity signal test, gross observation and light microscope examination as well as the abbreviated injury score-injury severity score (AIS-ISS) scale. The high-speed photograph indicated that during the ejection procedure the motorcycle was first arrested and decelerated suddenly, and then the motorcycle driver was ejected forward, accompanied with the rotation motion in the air. Finally, the head, shoulder and thorax of the ejected animal impacted directly on the hard ground. Varying degrees of injury focusing on the liver, heart, lung and spleen were found. There existed a significant positive correlation between ISS and the ejection velocity of the motorcycle drivers (ISS equal to 16.7+/-2.9 for 30 km/h, 25.0+/-0.0 for 40 km/h and 37.3+/-1.0 for 50 km/h). The detailed injury characteristics were as follows: for the mildly injured animals, there were interlobar gaps or leaf gaps and lobar surface blood coagulation blocks in the liver, and mild lung hemorrhage; for the severely injured animals, there were liver comminuted laceration, moderate lung hemorrhage and heart injury. Animals suffering from the most severe injuries died half an hour later. The new injury model stated in this paper has a high stability and good repeatability, and is likely to be helpful to deeply investigate the injury mechanisms and protection countermeasures of motorcyclist ejection injury.


Harnessing electronic healthcare data for wound care research: Standards for reporting observational registry data obtained directly from electronic health records.
The United States Food and Drug Administration will consider the expansion of coverage indications for some drugs and devices based on real-world data. Real-world data accrual in patient registries has historically been via manual data entry from the medical chart at a time distant from patient care, which is fraught with systematic error. The efficient automated transmission of data directly from electronic health records is replacing this labor-intensive paradigm. However, real-world data collection is unfamiliar. The potential sources of bias arising from the source of data and data accrual, documentation, and aggregation have not been well defined. Furthermore, the technological aspects of data acquisition and transmission are less transparent. We explore opportunities for harnessing direct-from-electronic health record registry reporting and propose the ABCs of Registries (Analysis of Bias Criteria of Registries), which are an evaluation framework for publications to minimize potential bias of real-world data obtained directly from an electronic health record method. These standards are based on a point-of-care data documentation process using a common definitional framework and data dictionaries. By way of example, we describe a wound registry obtained directly from electronic health records. This qualified clinical data registry minimizes bias by ensuring complete and accurate point-of-care data capture, standardizes usual care linked to quality reporting, and prevents post-hoc vetting of outcomes. The resulting data are of high quality and integrity and can be used for comparative effectiveness research in wound care. In this way, the effort needed to succeed with the Quality Payment Program is leveraged to obtain the real-world data needed for comparative effectiveness research.


Chemokine Expression in Murine RPE/Choroid in Response to Systemic Viral Infection and Elevated Levels of Circulating Interferon-γ.
To examine how circulating immune mediators in vivo may affect gene and protein expression at the RPE/choroid interface. Young mice were systemically infected with lymphocytic choriomeningitis virus (LCMV) or continuously infused with IFN-γ. RPE/choroid was isolated and analyzed with whole-transcriptome gene expression microarrays. Selected gene expression findings were validated at the protein level. Both the systemic immune activation from virus infection and the sterile systemically increased level of IFN-γ resulted in increased expression of chemokine ligands, chemokine receptors, and early complement components in isolates of RPE/choroid. These findings were largely absent from LCMV-infected mice deficient in either the interferon α/β receptor or IFN-γ. Together, these findings demonstrate that acute systemic immune activation results in a local response at the RPE/choroid interface that may include chemokine-dependent recruitment of inflammatory cells and engagement of the complement system. This may represent a link between the systemic low-grade inflammation and the retinal pathology observed in several multifactorial entities such as aging, AMD, and diabetes.


Evaluation of the antioxidant capacity and phenolic content of three Thymus species.
Thymus species are known to have significant amounts of phenolic and flavonoid compounds and exhibit strong antioxidant activities. This work was designed to evaluate the antioxidant activities of three endemic Iranian Thymus species (including T. daenensis, T. kotschyanus, and T. pubescens) in different test systems [namely DPPH() (2,2'-diphenyl-1-picrylhydrazyl), ABTS(+) [2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid], and linoleic acid/β-carotene bleaching assays] to determine the total phenolic and flavonoid contents of the species (assayed by colorimetric techniques) and to study the possible composition-activity relationship. All the tested plants exhibited concentration-dependent antioxidant and free radical scavenging activities. T. pubescens showed the highest free radical scavenging activities in both DPPH() and ABTS(+) methods, while T. daenensis and T. kotschyanus were the most active species in the β-carotene bleaching inhibition test. Alternatively, T. pubescens exhibited a significantly higher level of the total flavonoid content compared with those of the other species, while no significant statistically differences were found among the tested plants regarding the total phenolic content. In addition, significant correlations were found between the flavonoid content and DPPH()/ABTS(+) radical scavenging activities, but not between the β-carotene bleaching inhibition system and the flavonoid content.


Mouse Ovary Transplantation.
Ovary transplantation is a useful technique when there is a valuable female mouse (e.g., transgenic, unique allele) that is ill, not breeding, or cannot breed naturally. The ovaries from the valuable female are transplanted into a histocompatible wild-type female recipient whose ovaries have been surgically removed. The donor ovaries can then function in the wild-type recipient to generate oocytes that will be ovulated and can be fertilized after natural matings. The donor ovaries can be cut into smaller pieces and each piece can be transplanted into separate females. Newborn ovaries or cryorecovered ovaries can also be transplanted. The removal of the recipient ovary leaves the surrounding bursal membrane intact, providing a convenient sac to insert and hold the donor ovary or ovarian fragments.


Note: An improved 3D imaging system for electron-electron coincidence measurements.
We demonstrate an improved imaging system that can achieve highly efficient 3D detection of two electrons in coincidence. The imaging system is based on a fast frame complementary metal-oxide semiconductor camera and a high-speed waveform digitizer. We have shown previously that this detection system is capable of 3D detection of ions and electrons with good temporal and spatial resolution. Here, we show that with a new timing analysis algorithm, this system can achieve an unprecedented dead-time (<0.7 ns) and dead-space (<1 mm) when detecting two electrons. A true zero dead-time detection is also demonstrated.


Cytostatic activity of alveolar macrophages from smokers and nonsmokers: role of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha.
Several functions of alveolar macrophages (AM) are modified by cigarette smoking. AM are the first line of defense in bronchoalveolar spaces and could be depressed in their cytotoxicity to tumor cells in smokers. An assay using A549 cells (human lung adenocarcinoma) as target cells was performed to assess cytostasis mediated by AM and their supernatants (SN) from healthy smokers (n = 8) and nonsmokers (n = 6). Contact-mediated cytostasis was decreased in AM of smokers (n = 8) relative to nonsmokers (n = 6) (22.9 +/- 5.7% versus 42.7 +/- 6.0% [+/- SEM], P < 0.04) and increased after lipopolysaccharide (LPS) stimulation in both groups (34.5 +/- 5.3% versus 46.8 +/- 5.2%, NS). Cytostasis induced by SN from nonstimulated AM was low in both groups and was still lower in smokers after LPS exposure (19.3 +/- 4.5% versus 34.5 +/- 4.8%, P < 0.04). Among cytotoxic factors produced by macrophages, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) may play an important role in cytostasis. Recombinant human (rH) IL-1 beta and rHTNF alpha had a moderate cytostatic activity, which was additive, whereas rHIL-6 had no significant activity on A549 cells. Bioactive IL-1 beta, IL-6, and TNF alpha were therefore measured in macrophage SN. Their levels tended to be lower in smokers than in nonsmokers and were much increased after LPS stimulation. Levels of the three cytokines were also found to correlate with each other; furthermore, a good correlation between cytokine levels in SN and cytostasis was observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Cervical Cancer Screening in Iranian Women: Healthcare Practitioner Perceptions and Views
Background: Although regular screening for cervical cancer with the Papanicolaou test is an important element for reducing the incidence and mortality of cervical cancer, the actual screening program in Iranian women is not sufficiently comprehensive at present. The purpose of this study was to explore healthcare provider perceptions of factors affecting cervical cancer screening in Iranian women. Methods: In this qualitative study performed from September 2015 to August 2016 in Hamadan, Iran, we conducted semi-structured in depth interviews with 14 healthcare providers selected purposefully. All interviews were recorded, transcribed and analyzed according to a conventional thematic analysis approach. MAXQDA10 software was employed for data analysis. Results: Four themes were extracted from data: "Inefficient management of cervical cancer screening process, Personal and professional characteristics of health care providers, Individual barriers and facilitators, Need for health system authorities to pay attention". Conclusion: Increased official attention to screening, and identifying challenges and providing strategies based on these challenges will help in achieving a successful screening program. It is necessary to attend to professional features of medical science students and increase the skills of interaction with clients in addition to academic training. Efforts should be made to increase trust in healthcare providers regarding the Pap test and receptiveness of society to this screening modality through informing the public, with encouragement through the media.


Geranyl Phenyl Ethers from the New Zealand Liverwort Trichocolea hatcheri
Methyl 4-(geranyloxy)-3-hydroxybenzoate (6), previously unreported, has been identified from the New Zealand liverwort Trichocolea hatcheri. Four new related 3-hydroxybenzoates 7-10 were also found, with a carbonyl at C-5 of the geranyl group and various double bond arrangements. Two known geranyl phenyl ethers 1 and 3, found in other Trichocolea species, were also identified.


The curvature calculation mechanism based on simple cell model.
A conclusion has not yet been reached on how exactly the human visual system detects curvature. This paper demonstrates how orientation-selective simple cells can be used to construct curvature-detecting neural units. Through fixed arrangements, multiple plurality cells were constructed to simulate curvature cells with a proportional output to their curvature. In addition, this paper offers a solution to the problem of narrow detection range under fixed resolution by selecting an output value under multiple resolution. Curvature cells can be treated as concrete models of an end-stopped mechanism, and they can be used to further understand "curvature-selective" characteristics and to explain basic psychophysical findings and perceptual phenomena in current studies.


Use of Sacrificial Nanoparticles to Remove the Effects of Shot-noise in Contact Holes Fabricated by E-beam Lithography.
Nano-patterns fabricated with extreme ultraviolet (EUV) or electron-beam (E-beam) lithography exhibit unexpected variations in size. This variation has been attributed to statistical fluctuations in the number of photons/electrons arriving at a given nano-region arising from shot-noise (SN). The SN varies inversely to the square root of a number of photons/electrons. For a fixed dosage, the SN is larger in EUV and E-beam lithographies than for traditional (193 nm) optical lithography. Bottom-up and top-down patterning approaches are combined to minimize the effects of shot noise in nano-hole patterning. Specifically, an amino-silane surfactant self-assembles on a silicon wafer that is subsequently spin-coated with a 100 nm film of a PMMA-based E-beam photoresist. Exposure to the E-beam and the subsequent development uncover the underlying surfactant film at the bottoms of the holes. Dipping the wafer in a suspension of negatively charged, citrate-capped, 20 nm gold nanoparticles (GNP) deposits one particle per hole. The exposed positively charged surfactant film in the hole electrostatically funnels the negatively charged nanoparticle to the center of an exposed hole, which permanently fixes the positional registry. Next, by heating near the glass transition temperature of the photoresist polymer, the photoresist film reflows and engulfs the nanoparticles. This process erases the holes affected by SN but leaves the deposited GNPs locked in place by strong electrostatic binding. Treatment with oxygen plasma exposes the GNPs by etching a thin layer of the photoresist. Wet-etching the exposed GNPs with a solution of I2/KI yields uniform holes located at the center of indentations patterned by E-beam lithography. The experiments presented show that the approach reduces the variation in the size of the holes caused by SN from 35% to below 10%. The method extends the patterning limits of transistor contact holes to below 20 nm.


NASICON-Structured LiZr2(PO4)3 Surface Modification Improves Ionic Conductivity and Structural Stability of LiCoO2 for a Stable 4.6 V Cathode.
Lithium cobalt oxide (LCO) as a classic layered oxide cathode for lithium-ion batteries is limited by the cutoff voltage, which only delivers about half of the theoretical capacity (∼4.2 V, 140 mA h g-1). Recently, raising the cutoff voltage to 4.6 V has been considered to further improve its specific capacity. However, LCO suffers from serious phase transition of O3 to H1-3, which leads to dramatic volume change and loss of cobalt, finally resulting in rapid capacity decay. In this work, we introduce the NASICON-structured LiZr2(PO4)3 (LZP), an ion conductor for lithium ion, to modify the surface of LCO by a wet-chemical method. Such a surface modification improves lithium-ion diffusion between the interface of LCO and electrolyte and restrains the O3 to H1-3 phase transition. As a result, the optimized LCO with 1 wt % coating (denoted as LCO@LZP-1%) demonstrates enhanced electrochemical performance in both half-cell and full-cell. To be specific, LCO@LZP-1% delivers a high specific capacity of 161.3 mA h g-1 and increases the capacity retention from 37.8 to 75.1% within 100 cycles. Importantly, the full-cell assembled by LCO@LZP-1% and artificial graphite can exhibit an outstanding energy density of 345.5 W h kg-1 (based on the total mass of cathode and anode).


Modulation of potassium conductances optimizes fidelity of auditory information.
Potassium channels in auditory neurons are rapidly modified by changes in the auditory environment. In response to elevated auditory stimulation, short-term mechanisms such as protein phosphorylation and longer-term mechanisms such as accelerated channel synthesis increase the amplitude of currents that promote high-frequency firing. It has been suggested that this allows neurons to fire at high rates in response to high sound levels. We have carried out simple simulations of the response to postsynaptic neurons to patterns of neurotransmitter release triggered by auditory stimuli. These demonstrate that the amplitudes of potassium currents required for optimal encoding of a low-amplitude auditory signal differ from those for louder sounds. Specifically, the cross-correlation of the output of a neuron with an auditory stimulus is improved by increasing potassium currents as sound amplitude increases. Temporal fidelity for low-frequency stimuli is improved by increasing potassium currents that activate at negative potentials, while that for high-frequency stimuli requires increases in currents that activate at positive membrane potentials. These effects are independent of the firing rate. Moreover, levels of potassium currents that maximize the fidelity of the output of an ensemble of neurons differ from those that maximize fidelity for a single neuron. This suggests that the modulatory mechanisms must coordinate channel activity in groups of neurons or an entire nucleus. The simulations provide an explanation for the modulation of the intrinsic excitability of auditory brainstem neurons by changes in environmental sound levels, and the results may extend to information processing in other neural systems.


Factors associated with coverage of iodine deficiency disorders by control programs in an endemic area in West Sumatra, Indonesia.
In order to ascertain the coverage and to identify factors determining the success of an iodine deficiency disorders (IDD) control program in West Sumatra, Indonesia, a cross-sectional study among 495 school children aged 6-15 years in a subdistrict of an endemic goitre area was conducted. Coverage of iodine capsule distribution was 27%. Forty-eight percent of the households used iodized salt with an appropriate concentration (>= 40 p.p.m.). Factors associated with not taking idodine capsules among children were: mother's lack of knowledge about the iodine capsule (OR 13.3, 95% CI 7.4-24.1) and mother's education level (OR 1.89, 95% CI 1.05-3.39). For unsatisfactory use of iodized salt in a household, the only predictor was family monthly income. Odds ratios and 95% CI for moderate and high family income were 2.42 (1.39-4.21) and 2.22 (1.4-3.54), respectively. We concluded that for coverage in an IDD control program, supplementation and fortification alone were not enough. Education had an impact on coverage of the supplementation. Furthermore, iodization of salt needs further improvement in relation to quality control. Finally, the program neglected high-income groups. These pitfalls should be corrected.


Non-genetic impact factors on chronological lifespan and stress resistance of baker's yeast.
Survival under nutrient limitation is an essential feature of microbial cells, and it is defined by the chronological lifespan. We summarize recent findings, illustrating how crucial the choice of the experimental setup is for the interpretation of data in this field. Especially the impact of oxygen supply differs depending on the culture type, highlighting the differences of alternatives like the retentostat to classical batch cultures. Finally the importance of culture conditions on cell aging and survival in biotechnological processes is highlighted.


[Developmental tendencies of public health services on Polish lands before and after 1918].
On the basis of the up to now historic-medical researches we can state that sanitarian legislation of the repacious states (Austria, Prussia, Russia) had a decisive influence on public health services development on Polish lands in XIX century. In the elaboration of the polish services project, actively participated the medical Association of Cracow and Warsaw. The presented approaches realizes in the liberated polish State, considered the desire for health services administration union, as well as underlined the decisive role of the urban and district self-government in the organization of health care services. In the multisectorial structure of medical care, public health services-state and self-governed, were rendering services for the whole of population. Some of the important achievements were: accessibility to the public of numerous medical care units, declination of mortality coefficient because of acute and social infective diseases, wide range of preventive activities, etc.


Single-section quantum well mode-locked laser for 400 Gb/s SSB-OFDM transmission.
Successful use of a single-section quantum well (QW) passively mode-locked laser (MLL) as a comb source for optical interconnects is demonstrated for the first time. Sixteen comb lines spaced by 37.6 GHz are modulated using 25 Gb/s compatible single sideband orthogonal frequency division multiplexed (SSB-OFDM) signals and transmitted over 50 km of standard single-mode fiber with bit error ratio below the 7% forward error correction limit. The system performance, analyzed on the basis of the relative intensity noise of the device, reveal the suitability of single-section QW MLLs as inexpensive comb sources for inter- and intra-data center communication scenarios.


Diagnostic possibilities for the nuchal evoked potential.
As a response to stimulation of the arm nerves an evoked potential can be recorded in the posterior neck region in man. This nuchal evoked potential (NEP) was recorded in three selected patients with A) cervical rib, B) syringomyelia, and C) prolapse of cervical intervertebral disc. Patients A and C had low-amplitudic NEPs with increased latencies when the affected side was stimulated and "normal" NEPs when the unaffected side was stimulated. Patient B had grossly abnormal, polyphasic NEPs (regardless of the side stimulated) but the simultaneously recorded somatosensory evoked potential was "normal". No systematic differences in the parameters of the NEP due to different recording locations on the neck could be observed.


Properties of twitch motor units of the ankle extensor muscles in the bullfrog Rana catesbeiana.
A study of the mechanical properties of the twitch motor units in the ankle extensor muscles of bullfrogs was undertaken to expand our view of the diversity of motor unit properties among vertebrates. Two muscles were chosen that represent a wide range of extensor function: the plantaris longus (PL) is a large muscle providing most of the force for ankle extension in hopping and swimming, and the tibialis posticus (TP) is relatively small and may act as an ankle stabilizer or be primarily postural in function. Both muscles have highly fatigable motor units, but also some (especially in TP) low or non-fatigable ones. Mean tetanic tensions of motor units in both muscles are relatively large as compared with those of mammals but are especially large in PL. No clear correlations were found between contraction times and either motor unit tetanic tensions or fatigability, nor did the motor units fall into clearly defined types based on any functional parameters. Overall contraction and relaxation times are slow compared with those of mammals and are somewhat slow compared to those of other frogs; unlike results from earlier studies, the large units of PL are slower than the small units of TP. This results in PL units reaching fused tetani at lower stimulus frequencies. The twitch/tetanus and force/frequency ratios in PL motor units are much larger than those of TP, giving PL units greater relative forces at lower stimulus rates. These results are discussed in the context of motor unit function.


Tyrosine phosphorylation of recombinant hirudin increases affinity to thrombin and antithrombotic activity.
Thrombin is one of the key enzymes of the blood coagulation system and a promising target for the development of anticoagulants. One of the most specific natural thrombin inhibitors is hirudin, contained in the salivary glands of medicinal leeches. The medicinal use of recombinant hirudin is limited because of the lack of sulfation on Tyr63, resulting in a 10-fold decrease in activity compared to native (sulfated) hirudin. In the present work, a set of hirudin derivatives was tested for affinity to thrombin: phospho-Tyr63, Tyr63(carboxymethyl)Phe, and Tyr63Glu mutants, which mimic Tyr63 sulfation and Gln65Glu mutant and lysine-succinylated hirudin, which enhance the overall negative charge of hirudin, as well as sulfo-hirudin and desulfo-hirudin as references. Using steered molecular dynamics simulations with subsequent umbrella sampling, phospho-hirudin was shown to exhibit the highest affinity to thrombin among all hirudin analogs, including native sulfo-hirudin; succinylated hirudin was also prospective. Phospho-hirudin exhibited the highest antithrombotic activity in in vitro assay in human plasma. Taking into account the modern methods for obtaining phospho-hirudin and succinylated hirudin, they are prospective as anticoagulants in clinical practice.


Differential processing of stromal-derived factor-1alpha and stromal-derived factor-1beta explains functional diversity.
The chemokine stromal-derived factor-1 (SDF-1), which is constitutively expressed in most tissues as SDF-1alpha and SDF-1beta resulting from alternative gene splicing, regulates hematopoiesis, lymphocyte homing, B-lineage cell growth, and angiogenesis. Because SDF-1alpha and SDF-1beta are constitutively and ubiquitously expressed, their degradation must serve an important regulatory role. Here we show that SDF-1alpha and SDF-1beta are secreted as full-length molecules. When exposed to human serum, full-length SDF-1alpha (1-68) undergoes processing first at the COOH terminus to produce SDF-1alpha 1-67 and then at the NH2 terminus to produce SDF-1alpha 3-67. By contrast, full-length SDF-1beta (1-72) is processed only at the NH2 terminus to produce SDF-1beta 3-72. CD26/dipeptidyl peptidase is responsible for serum cleavage of SDF-1alpha and SDF-1beta at the NH2 terminus. Serum processing of SDF-1alpha at the COOH terminus, which has not been previously reported, reduces the ability of the polypeptide to bind to heparin and to cells and to stimulate B-cell proliferation and chemotaxis. The additional processing at the NH2 terminus renders both forms of SDF-1 unable to bind to heparin and to activate cells. The differential processing of SDF-1alpha and SDF-1beta provides biologic significance to the existence of 2 splice forms of the chemokine and adds a tool to precisely regulate SDF-1's biologic activity by changes in specific activity.


Bound Phosphorus and Growth of Phytoplankton.
No correlation was found between phytoplankton pulses in four North Carolina ponds and variations in bound phosphorus. It is concluded that the interaction of a complex of chemical and physical factors produces both seasonal fluctuations and sporadic blooms of phytoplankton.


[A multi-center clinical observation on safety and efficacy of a plasma derived coagulator factor Ⅷ for treatment of patients with hemophilia A].
To evaluate the efficacy and safety of homemade plasma derived coagulation factor Ⅷ in patients with hemophilia A. Patients with congenital hemophilia A who met the inclusive and exclusive criteria were enrolled in the study after informed consent. The doses of factor Ⅷ were calculated according to the weight, disease severity etc. FⅧ activity and infusion efficacy value at 10 min and 60 min after infusion were recorded, as well as adverse events and validity rating according to the improvement of clinical syndromes. Viral infections including HBV, HCV, HIV and FⅧ inhibitor were determined after 3 and 6 months. A total of 65 patients were enrolled in this study, all of whom were evaluable for drug safety. Treatment efficacy was evaluated in 60 patients and 57 cases completed the trial finally. In this 57 cases, most (52/57) subjects were of middle and severe hemophilia A mainly characterized by joint bleeding. Overall response rate of acute bleeding events was classified as "excellent" (70.00%) or "better" (30.00%). The non-responder was 0. FⅧ activity and infusion efficiency value of first administration after 10 min and 60 min improved significantly [10 min: (123.66±47.54)%; 60 min: (108.05±43.24)%]. The incidence of adverse events was 1.54%. Neither allergic reaction nor reactivation of HBV, HCV, HIV was detected after treatment of 3 and 6 months. No FⅧ inhibitor negative patients converted to positive during follow-up. This homemade plasma derived coagulation factor Ⅷ is safe and effective for the treatment of acute bleeding in patients with hemophilia A.


Perception of histamine-induced itch elicited in three different skin regions.
In order to investigate whether any regional difference in itch perception exists in experimentally induced pruritus, various concentrations of histamine (1, 3.3, 10, 33 and 100 micrograms/ml) were injected intradermally in three different skin regions in 15 healthy subjects. The regions were 1) the volar aspect of the forearm, 2) the lateral aspect of the upper arm and 3) the upper back at scapular level. Itch perception (itch latency, itch duration, maximal itch intensity, 'total itch index') and flare reactions were studied. A significant dose-response relationship was shown in each of the three regions for all itch variables, except itch latency, and for the flare reactions. However, no significant regional difference in itch perception was observed. The flare reaction showed a regional variation, with significantly smaller flares on the forearm than in the other two regions.


Prospective Evaluation of Postural Control and Gait in Pediatric Patients with Cancer After a 4-Week Inpatient Rehabilitation Program.
The aim of the study was to investigate the effects of a 4-wk inpatient rehabilitation program on postural control and gait in pediatric patients with cancer. Eighty-eight patients with brain tumors (n = 59) and bone/soft tissue sarcomas (n = 29) were evaluated. Postural control was assessed examining the velocity of the center of pressure and single-leg stance time on a pressure distribution platform. Walk ratio, a measure of neuromotor control, was used to evaluate intervention effects on gait. Repeated measures analysis of variance showed improvements in postural control measures, indicated by a decrease in velocity of center of pressure of -0.4 cm/sec (F1,80 = 7.175, P = 0.009, ηp = 0.082) and increase in single-leg stance time (mean [median] = 1.1 [2.6] sec, respectively; F1,80 = 12.617, P = 0.001, ηp = 0.136). Walk ratio increased by 0.2 mm/steps per min (F1,82 = 3.766, P = 0.056, ηp = 0.044). Mean changes in dependent variables did not differ between both patient groups (P > 0.05). The results indicate benefits of an inpatient rehabilitation program comprising standard physical therapy as well as aquatic and hippo therapy on postural control and gait after treatment of pediatric patients with cancer.


Corticocortical connection patterns reveal two distinct visual cortical areas bordering dorsal V2 in marmoset monkey.
The organization of the cortex located immediately anterior to the second visual area (V2), i.e., the third tier visual cortex, remains controversial, especially in New World primates. In particular, there is lack of consensus regarding the exact location and extent of the lower visual quadrant representation of the third visual area V3 (or ventrolateral posterior -VLP - of a different nomenclature). Microelectrode and connectional mapping studies have revealed the existence of an upper visual quadrant representation abutting dorsal V2 anteriorly, and bordered medially and laterally by representations of the lower visual quadrant. It remains unclear whether these lower field regions are both part of a single area V3, which is split into two patches by an interposed region of upper field representation, or whether they are the lower field representations of two different areas, the dorsomedial area (DM) and area V3/VLP, respectively. To address this question, we quantitatively analyzed the patterns of corticocortical afferent connections labeled by tracer injections targeted to these two lower field regions in the dorsal aspect of the third tier cortex. We found different inter-areal connectivity patterns arising from these two regions, strongly suggesting that they belong to two different visual areas. In particular, our results indicate that the dorsal aspect of the third tier cortex consists of two distinct areas: a full area DM, representing the lower quadrant medially, and the upper quadrant laterally, and the lower quadrant representation of V3/VLP, located laterally to upper field DM. DM is predominantly connected with areas of the dorsal visual stream, and V3/VLP with areas of the ventral stream. These results prompt further functional investigations of the third tier cortex, as previous studies of this cortical territory may have pooled response properties of two very different areas into a single area V3.


Therapeutic plasma exchange for perioperative management of patients with congenital factor XI deficiency.
Factor XI (FXI) deficiency (hemophilia C [HEM-C]) is a bleeding disorder with unpredictable severity that correlates poorly with FXI coagulation activity (FXI:C). It poses a perioperative hemostatic management challenge. For US patients with severe disease, fresh frozen plasma (FFP) or, in current use, thawed plasma is the most readily available option but comes with risk of volume overload. We report our experience of using therapeutic plasma exchange (TPE) as an alternative perioperative management strategy. A retrospective review of all HEM-C patients who underwent surgical procedures. Data were collected, including demographics, bleeding history, surgical site, perioperative hemostatic intervention, and outcome. Between July 1997 and September 2014, 28 HEM-C patients (12 men) were identified, 4 with severe disease (FXI:C <2% or excessive bleeding). Nineteen patients underwent 91 invasive procedures. For nearly 60% of the procedures, no periprocedural hemostatic intervention was provided; before 4 procedures (3 patients), 1 plasma volume TPE preoperatively with FFP was administered. Patient 1, a 28-year-old woman (FXI:C, 35%) with a history of excessive surgical bleeding, underwent 2 TPE procedures before laparoscopic pelvic biopsy and subsequent abdominal hysterectomy with salpingo-oophorectomy that increased her FXI:C to 48%. Patient 2, a 79-year-old man (FXI:C, <2%), had TPE before total hip arthroplasty, increasing his FXI:C to 24%. Patient 3, a 59-year-old man (FXI:C, <2%), had TPE before prostate laser enucleation, increasing his FXI:C to 46%. Patients 1 and 3 had mild reactions during TPE; no patient had evidence of volume overload. All patients had adequate intraoperative surgical hemostatic outcomes. TPE is an effective alternative presurgical hemostatic intervention in HEM-C with potentially lower risk of circulatory volume overload.


Allergenicity evaluation of fragrance mix and its ingredients by using ex vivo local lymph node assay-BrdU endpoints.
The present studies were performed to compare the differences between sensitization potency of fragrance mix and its ingredients (oak moss absolute, isoeugenol, eugenol, cinnamal, hydroxycitronellal, geraniol, cinnamic alcohol, alpha amyl cinnamal), by using ex vivo LLNA-BrdU ELISA. The SI and EC3 values were calculated and potency classification was found for the mixture and for each ingredients. TH1 cytokines (IL-2, IFN-γ) and TH2 cytokines (IL-4, IL-5) releases from lymph node cell culture were also investigated as contact sensitization endpoints. The EC3 values were calculated and the potency of contact sensitization were classified for fragrance mix, oak moss absolute, isoeugenol, eugenol, cinnamal, hydroxycitronellal, geraniol, cinnamic alcohol, alpha amyl cinnamal respectively: 4.4% (moderate), 3.4% (moderate), 0.88% (strong), 16.6% (weak), 1.91% (moderate), 9.77% (moderate), 13.1% (weak), 17.93% (weak), 7.74% (moderate). According to our results it should be concluded that exposure to fragrance mix does not constitute an evidently increased hazard compared to exposure to each of the eight fragrance ingredients separately. Cytokine analyses results indicate that both TH1 and TH2 cytokines are involved in the regulation of murine contact allergy and can be considered as useful endpoints.


Expression of transgenic FLIP on thyroid epithelial cells inhibits induction and promotes resolution of granulomatous experimental autoimmune thyroiditis in CBA/J mice.
Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by transfer of thyroglobulin-primed in vitro activated splenocytes. Thyroid lesions reach maximal severity 20 d later, and inflammation resolves or progresses to fibrosis by d 60, depending on the extent of thyroid damage at d 20. Depletion of CD8+ T cells inhibits G-EAT resolution. We showed that expression of Fas-associated death domain-like IL-1beta-converting enzyme inhibitory protein (FLIP) transgene (Tg) on thyroid epithelial cells (TECs) of DBA/1 mice had no effect on G-EAT induction but promoted earlier resolution of G-EAT. However, when CBA/J wild-type donor cells were transferred to transgenic CBA/J mice expressing FLIP on TECs, they developed less severe G-EAT than FLIP Tg- littermates. Both strains expressed similar levels of the FLIP Tg, but endogenous FLIP was up-regulated to a greater extent on infiltrating T cells during G-EAT development in DBA/1 compared with CBA/J mice. After transient depletion of CD8+ T cells, FLIP Tg+ and Tg- CBA/J recipients both developed severe G-EAT at d 20. Thyroid lesions in CD8-depleted Tg+ recipients were resolving by d 60, whereas lesions in Tg- littermates did not resolve, and most were fibrotic. FLIP Tg+ recipients had increased apoptosis of CD3+ T cells compared with Tg- recipients. The results indicate that transgenic FLIP expressed on TECs in CBA/J mice promotes G-EAT resolution, but induction of G-EAT is inhibited unless CD8+ T cells are transiently depleted.


Psychedelic Knowledge and Opinions in Psychiatrists at Two Professional Conferences: An Exploratory Survey.
Despite resurgent interest in psychedelic-assisted therapy, our insights into psychiatrists' knowledge and opinions about medicinal psychedelic applications are surprisingly narrow. Therefore, we anonymously surveyed psychiatrists attending psychedelic didactic presentations at two national meetings about these issues using a 26-item questionnaire. Response rate was 40.20% (106/264). Respondents were 41.73 ± 13.31 years old (range: 24-80) and 64.42% were male. They largely believed psychedelics show treatment promise and strongly supported federal funding for medicinal psychedelic research. The most common concerns were the lack of trained psychedelic-assisted therapy providers, the logistics of psychedelic-assisted therapy delivery, the administration of psychedelics for patients with contraindications, and diversion. The most desired psychedelic-related educational topics were potential benefits of psychedelic-assisted therapy, how to conduct psychedelic-assisted therapy, psychedelic pharmacology, and psychedelic side effects. Factors associated with increased belief in psychedelics' treatment potential included working primarily in research, scoring higher on a psychedelic knowledge test, and reporting less concern about psychedelics' addictive potential. Working primarily in research and consult-liaison psychiatry fellowship training were positively associated with support for medicinal psychedelic legalization, while increased concerns about addictive potential and attending psychiatrist status were negatively associated. Support for legalization of non-medicinal psychedelic use was negatively associated with age and positively associated with support for legalization of medicinal psychedelic use.


Electrochemical behavior of quinoxalin-2-one derivatives at mercury electrodes and its analytical use.
Derivatives of quinoxalin-2-one are interesting compounds with potential pharmacological activity. From this point of view, understanding of their electrochemical behavior is of great importance. In the present paper, a mechanism of electrochemical reduction of quinoxalin-2-one derivatives at mercury dropping electrode was proposed. Pyrazine ring was found to be the main electroactive center undergoing a pH-dependent two-electron reduction process. The molecule protonization of nitrogen in the position 4 precedes the electron acceptance forming a semiquinone radical intermediate which is relatively stable in acidic solutions. Its further reduction is manifested by separated current signal. A positive mesomeric effect of the nonprotonized amino group in the position 7 of the derivative III accelerates the semiquinone reduction yielding a single current wave. The suggested reaction mechanism was verified by means of direct current polarography, differential pulse, cyclic and elimination voltammetry, and coulometry with subsequent GC/MS analysis. The understanding of the mechanism was applied in developing of analytical method for the determination of the studied compounds.


Graying anatomy? Toward molecular tumor characterization.
Will anatomical tumor classification become history as we make way for molecular characterization in oncology? Howard McLeod, Fred Eshelman Distinguished Professor of Pharmacy and Professor of Medicine at the University of North Carolina (NC, USA), is internationally recognized for his work on the pharmacogenomic analysis of cancer treatments. Here, he offers Pharmacogenomics his perspectives on the prospects for practical implementation of PGx in clinical care and the corresponding timescales. He and colleagues have already identified specific genetic components of several drugs that have lead to the US FDA changing the drug package inserts to identify patient groups that are genetically predisposed to risk of severe side effects or inadequate benefit. He is currently working with the large national clinical trials groups--such as Cancer and Leukemia Group B--to confirm that findings from small institutional studies will actually translate into better therapy across the USA.


Low dose evaluation of the antiandrogen flutamide following a Mode of Action approach.
The dose-response characterization of endocrine mediated toxicity is an on-going debate which is controversial when exploring the nature of the dose-response curve and the effect at the low-end of the curve. To contribute to this debate we have assessed the effects of a wide range of dose levels of the antiandrogen flutamide (FLU) on 7-week male Wistar rats. FLU was administered by oral gavage at doses of 0, 0.001, 0.01, 0.1, 1 and 10mg/kg/day for 28 days. To evaluate the reproducibility, the study was performed 3 times. The molecular initiating event (MIE; AR antagonism), the key events (LH increase, Leydig cell proliferation and hyperplasia increases) and associated events involved in the mode of action (MOA) of FLU induced testicular toxicity were characterized to address the dose response concordance. Results showed no effects at low doses (<0.1mg/kg/day) for the different key events studied. The histopathological changes (Leydig cell hyperplasia) observed at 1 and 10mg/kg/day were associated with an increase in steroidogenesis gene expression in the testis from 1mg/kg/day, as well as an increase in testosterone blood level at 10mg/kg/day. Each key event dose-response was in good concordance with the MOA of FLU on the testis. From the available results, only monotonic dose-response curves were observed for the MIE, the key events, associated events and in effects observed in other sex related tissues. All the results, so far, show that the reference endocrine disruptor FLU induces threshold effects in a standard 28-day toxicity study on adult male rats.


Respiratory mechanics of horses measured by conventional and forced oscillation techniques.
Respiratory mechanics were compared using conventional and forced oscillation techniques in six conscious horses and a mechanical model of the equine respiratory system. The parameters calculated from conventional airflow and esophageal pressure measurements were pulmonary resistance and dynamic compliance. The impedance of the respiratory system was measured at 1, 2, and 3 Hz with the forced oscillation technique, and respiratory system resistance, compliance, inertance, and resonant frequency were calculated. Pulmonary resistance was 1.0 +/- 0.3 cmH2O.l-1.s, and pulmonary dynamic compliance was 2.4 +/- 0.6 l/cmH2O. With the use of the forced oscillation system, respiratory resistance was 1.61 +/- 0.50 cmH2O.l-1.s at 1 Hz, compliance was 0.195 +/- 0.075 l/cmH2O, inertance was 0.026 +/- 0.0095 cmH2O.l-1.s2, and resonant frequency was 2.40 +/- 0.25 Hz. Data collected from a model of the respiratory system showed a close correlation between resistance and compliance measured with the two systems. This study demonstrates that the forced oscillation technique is a useful method for noninvasive measurement of respiratory mechanics in horses.


Rare Osteochondroma Associated with Natural Mortality of a Wild White-Tailed Deer ( Odocoileus virginianus).
Within a 6-mo period, a radio-collared, white-tailed deer ( Odocoileus virginianus) doe from Delaware, US, developed a fatal head mass consistent with osteochondroma. We suspected a retroviral etiology, but test results were negative. Population implications were not suspected, but this case is concerning as these tumors are not thought to cause mortality.


Safety and antigenicity of typhoid-Shigella sonnei vaccine (strain 5076-1C).
The form-1 antigen of Shigella sonnei was transferred to the avirulent Salmonella typhi strain 21a and the resulting 5076-1C transconjugate strain was tested for safety and immunogenicity as a candidate oral vaccine. The transconjugant strain was shown to be well tolerated and safe in 19 human volunteers who were fed from 1 X 10(7) to 1 X 10(10) organisms. Only two of 10 volunteers tested had developed a rise in antibody titer to the lipopolysaccharide of the hybrid 5076-1C strain.


Prognostic value of angiogenesis evaluated with high-frequency and color Doppler sonography for preoperative assessment of melanomas.
The aim of our study was to confirm the value of high-frequency and color Doppler sonography in evaluating the metastatic potential of melanomas. Sixty-nine histologically proven melanomas in 67 patients were prospectively studied before surgical resection. A morphologic study was performed with a 20-MHz probe. The maximal thickness of tumors was measured and compared with the Breslow index. A color Doppler sonographic analysis of neovascularization was performed with a 13-MHz probe to depict intratumoral vessels. Of the 69 melanomas, 65 were depicted on sonography. Tumor thickness ranged from 0.26 to 8.0 mm as measured by sonography and from 0.15 to 8.0 mm according to the Breslow index. Sonographic measurements correlated strongly with the Breslow index (r > 0.96). Surgical reexcision was necessary in 33 tumors with a Breslow index exceeding 1 mm, but reexcision could have been avoided in 31 of these cases had the initial surgical planning been based on high-frequency sonographic measurements. Among the 62 patients studied with color Doppler sonography, intratumoral vessels were depicted on color Doppler sonography in 21 melanomas, all of which were thicker than 2 mm. The median follow-up was 40 months. Eleven patients developed metastases, and all except one had a vascularized melanoma. In the univariate analyses, neovascularization visualized with sonography and the Breslow index were both significantly linked to the occurrence of metastases (p < 0.0001). In the multivariate Cox proportional hazards regression analysis, neovascularization was the only significant parameter. This study confirms that prognostic value of angiogenesis evaluated with color Doppler sonography could be used to identify melanomas with a high metastatic potential.


Laparoscopic incisional and ventral hernia repair in a district general hospital.
The laparoscopic approach to repairing ventral and incisional hernias has gained increasing popularity worldwide. We reviewed the experience of laparoscopic ventral hernia repair at a district general hospital in the UK with particular reference to patients with massive defects (diameter ≥15cm) and the morbidly obese. A total of 144 patients underwent laparoscopic ventral (incisional or umbilical/paraumbilical) hernia repair between April 2007 and September 2012. The prevalence of conversion to open surgery was 2.8%. The prevalence of postoperative complications was 3.5%. Median postoperative follow-up was 30.2 months. A total of 5.6% cases suffered late complications and 2.8% developed recurrence. Thirty-four patients underwent repair of defects ≥10cm in diameter with a prevalence of recurrence of 5.6%. Sixteen patients underwent repair of 'massive' incisional hernia (diameter ≥15cm) with a prevalence of recurrence of 12.5%. Sixteen patients with a body mass index (BMI) ≥40kg/m(2) (range, 40-61kg/m(2)) underwent laparoscopic repair with a prevalence of recurrence of 6.3% (p>0.05 vs BMI <40kg/m(2)). Laparoscopic ventral hernia repair can be carried out safely with a low prevalence of recurrence. It may have advantages in morbidly obese patients in whom open repair would represent a significant undertaking. Laparoscopic ventral hernia repair may be used in cases of large and massive hernias, in which the risk of recurrence increases but is comparable with open repair and associated with low morbidity.


Therapeutic equivalence of generic imipenem/cilastatin for therapy of infections at Siriraj Hospital.
Several generic imipenem/cilastatin formulations have been approved by Thai FDA and a generic imipenem/cilastatin (Yungjin) has been available in SirirajHospital since 2007. Since imipenem/cilastatin is usually given to the patients with serious hospital-acquired infections, the generic imipenem/cilastatin must be therapeutically equivalent to the original imipenem/cilastatin. The objective of the study was to compare effectiveness and safety of generic imipenem/cilastatin with original imipenem/cilastatin for therapy of infections in hospitalized patients at Siriraj Hospital. Medical records of adult hospitalized patients at Siriraj Hospital who received imipenem/cilastatin at least 48 hours during June 2007 to September 2008 were reviewed. The effectiveness data of 300 patients who received original imipenem/cilastatin were compared with those of 300 patients who received generic imipenem/cilastatin in order to determine if a difference in composite favorable outcome of both formulations was within 10%. The demographics, clinical features of infections, site of infections, type of causative organisms and concomitant antibiotics of the patients in both groups were not significantly different. The overall favorable outcomes in the original imipenem/cilastatin and the generic imipenem/cilastatin groups were 65% and 58.7% respectively (absolute difference 6.3%, 95% CI -1.4% to 14%). Cure rates of infections in the original imipenem/cilastatin and the generic imipenem/cilastatin groups were 35% and 28.7% respectively (absolute difference 6.3%, 95% CI -1.1% to 13.7%). Super-infection rates in the original imipenem/cilastatin and the generic imipenem/cilastatin groups were 4.7% and 9% respectively (absolute difference -4.3%, 95% CI -8.5% to 0.3%). Mortality due to infections in the original imipenem/cilastatin and the generic imipenem/cilastatin groups were 18.3% and 21.3% respectively (absolute difference -3%, 95% CI -9.4% to 3.4%). Overall mortality in the original imipenem/cilastatin and the generic imipenem/cilastatin groups were 35.3% and 43% respectively (absolute difference -7.7%, 95% CI -15.3% to 0.1%). The occurrence of adverse events in the patients in both groups was not significantly different. Although the point estimate of composite favorable outcome of the patients who received generic imipenem/cilastatin (Yungjin) was < 10% of those who received original imipenem/cilastatin (Tienam), generic imipenem/cilastatin showed a trend for therapeutic non-equivalence to original imipenem/cilastatin because the upper limits of 95% confidence interval of differences of several important clinical outcomes were more than 10%.


Reduced Face Preference in Infancy: A Developmental Precursor to Callous-Unemotional Traits?
Children with callous-unemotional (CU) traits, a proposed precursor to adult psychopathy, are characterized by impaired emotion recognition, reduced responsiveness to others' distress, and a lack of guilt or empathy. Reduced attention to faces, and more specifically to the eye region, has been proposed to underlie these difficulties, although this has never been tested longitudinally from infancy. Attention to faces occurs within the context of dyadic caregiver interactions, and early environment including parenting characteristics has been associated with CU traits. The present study tested whether infants' preferential tracking of a face with direct gaze and levels of maternal sensitivity predict later CU traits. Data were analyzed from a stratified random sample of 213 participants drawn from a population-based sample of 1233 first-time mothers. Infants' preferential face tracking at 5 weeks and maternal sensitivity at 29 weeks were entered into a weighted linear regression as predictors of CU traits at 2.5 years. Controlling for a range of confounders (e.g., deprivation), lower preferential face tracking predicted higher CU traits (p = .001). Higher maternal sensitivity predicted lower CU traits in girls (p = .009), but not boys. No significant interaction between face tracking and maternal sensitivity was found. This is the first study to show that attention to social features during infancy as well as early sensitive parenting predict the subsequent development of CU traits. Identifying such early atypicalities offers the potential for developing parent-mediated interventions in children at risk for developing CU traits.


[Theoretical-experimental study of the process of phage lysis].
The mathematical model of phagolytic process is proposed, taking into account the preexponential phase in the growth of the biomass of bacteria and phages. This phase seems to be connected with the existence of biological inertia in the synthesis of phage and bacterial proteins. Proceeding from the comparison with experiments on E. coli and the corresponding phage, the numerical values of the constants of the model were determined by one of the optimization methods. The comparison of theoretical calculations with the results of experimental studies showed that this mathematical model correctly described the dynamics of phagolysis both in qualitative and quantitative aspects.


Psychophysiological triad and verbal system in the study of affect and emotion.
In this paper, emotion is dealt with as a complex theoretical term, whose empirical referents derive from physiological, behavioral and subjective discourses (psychophysiological triad). It is argued that the meaning of emotion terms is not exhausted by any of these discourses (or 'texts'), but by the complementary consideration of the three. In order to proceed psychophysiologically, any given text becomes context for the others, thus allowing for consensual validation of hypothetical constructs. The position delineated in this paper seeks to go beyond the usual correlational approach and is discussed in relation to other similar attempts. The pivotal position of language and the implications of content category (or meaning) analysis in the study of affect and emotion are illustrated.


DFT study on the interactions between Au(n) (n = 2...4) and adenine.
Binding of gold clusters with adenine was studied using density functional method (DFT). Geometries of neutral adenine with Au(n) (n = 2, 3 and 4) clusters were optimized using the B3LYP approach. The 6-31G+(d, p) basis set was used for adenine and the Stuttgart/Dresden effective core potential (ECP) basis set SDD was employed for the gold atom. Structural parameters and energy properties were discussed for the optimized complexes stabilized with the anchoring Au-N and the nonconventional Au...H-N hydrogen bond. The calculated interacting energy results show that the binding of Au(n) is the most strong at N3, whereas its binding at N6 displays relatively weaker stability. Furthermore, analysis of the charge distributions of the optimized complexes by using the natural bond orbital analysis indicates charge is transferred from the lone pair of nitrogen in adenine to the n* and sigma* orbitals of Au during the interaction between the Au(n) and adenine. The calculated second-order perturbation stabilization energies show that the interaction Au-N anchoring bond plays an important role compared with the nonconventional Au...H-N hydrogen bond.


Genetic parameters for claw disorders in Dutch dairy cattle and correlations with conformation traits.
Impaired claw health is one of the major problems causing production loss and reduced animal welfare in dairy cattle. In response, the Dutch Animal Health Service (GD) Ltd. initiated this study, in which claws of lactating and near-term cows and heifers in 430 herds were trimmed by hoof trimmers and the health status of the rear claws recorded. Only herds with >75% of the animals having feet trimmed were considered, resulting in records on 21,611 animals. Eight claw disorders were scored: digital dermatitis (DD), interdigital dermatitis/heel horn erosions (IDHE), sole hemorrhage (SH), chronic laminitis (CL), sole ulcer (SU), white line disease (WLD), interdigital hyperplasia (HYP), and interdigital phlegmona (IP). The prevalence varied from 0.6% (IP) to 39.9% (SH). More than 70% of the animals had at least one claw disorder. Conformation traits and locomotion were recorded once during the animal's first lactation by trained classifiers of the Royal Dutch Cattle Syndicate and completely independent of the moment of claw trimming. Heritabilities were estimated using a sire model, and ranged from <0.01 (IP) to 0.10 (DD and HYP). Genetic correlations of incidences of claw disorders with locomotion were variable, ranging from 0.13 (SH) to -0.91 (CL). Genetic correlations with the rear leg conformation traits were lower, ranging from 0.04 (ID with rear leg side view) to -0.69 (IP with rear leg rear view).


Structural and Catalytic Insight into the Unique Pentacyclic Triterpene Synthase TwOSC.
The oxidosqualene cyclase (OSC) catalyzed cyclization of the linear substrate (3S)-2,3-oxidosqualene to form diverse pentacyclic triterpenoid (PT) skeletons is one of the most complex reactions in nature. Friedelin has a unique PT skeleton involving a fascinating nine-step cation shuttle run (CSR) cascade rearrangement reaction, in which the carbocation formed at C2 moves to the other side of the skeleton, runs back to C3 to yield a friedelin cation, which is finally deprotonated. However, as crystal structure data of plant OSCs are lacking, it remains unknown why the CSR cascade reactions occur in friedelin biosynthesis, as does the exact catalytic mechanism of the CSR. In this study, we determined the first cryogenic electron microscopy structure of a plant OSC, friedelin synthase, from Tripterygium wilfordii Hook. f (TwOSC). We also performed quantum mechanics/molecular mechanics simulations to reveal the energy profile for the CSR cascade reaction and identify key residues crucial for PT skeleton formation. Furthermore, we semirationally designed two TwOSC mutants, which significantly improved the yields of friedelin and β-amyrin, respectively.


The effect of alcohol inhalation on the cardiovascular state of the rat.
Rats were exposed to alcohol vapors by an inhalation technique and blood pressure and its reactivity and platelet aggregation were measured. Acute exposure to alcohol levels which produced moderate blood alcohol concentration (BAC) was associated with increased vascular production of prostacyclin (PGI2) and plasma catecholamines, whereas platelet production of thromboxane (TXA2) decreased. Blood pressure is elevated in these animals, however, the platelet aggregating and pressor effects of noradrenaline (NE) were decreased. Chronic exposure to high BAC is associated with a dramatic reduction in vascular and platelet prostaglandin (PG) production and a marked increase in plasma catecholamine levels. Platelet aggregation decreased in these animals, however, the pressor effect of TXA2 and NE was significantly increased. The fatty acid precursors to PG were reduced by 50% in the lipid extracts of these preparations. These findings suggest that alterations in fatty acid metabolism may lead to a functional deficiency in PG production from dependent rats. Qualitative differences may exist between acute and chronic exposure with respect to the cardiovascular state. Locally produced PG and circulating catecholamines may mediate alcohol-induced alterations in vascular smooth muscle tone and platelet aggregation.


Mechanochemical Studies on Coupling of Hydrazines and Hydrazine Amides with Phenolic and Furanyl Aldehydes-Hydrazones with Antileishmanial and Antibacterial Activities.
Hydrazone compounds represent an important area of research that includes, among others, synthetic approaches and biological studies. A series of 17 hydrazones have been synthesized by mechanochemical means. The fragments chosen were phenolic and furanyl aldehydes coupled with 12 heterocyclic hydrazines or hydrazinamides. All compounds can be obtained quantitatively when operating on a planetary ball mill and a maximum reaction time of 180 min (6 cycles of 30 min each). Complete spectroscopic analyses of hydrazones revealed eight compounds (3-5, 8-11, 16) present in one geometric form, six compounds (1, 2, 13-15) present in two isomeric forms, and three compounds (6, 7, 12) where one rotation is restricted giving rise to two different forms. The single crystal X-ray structure of one of the hydrazones bearing the isoniazid fragment (8) indicates a crystal lattice consisting of two symmetry-independent molecules with different geometries. All compounds obtained were tested for anti-infectious and antibacterial activities. Four compounds (1, 3, 5 and 8) showed good activity against Mycobacterium tuberculosis, and one (7) was very potent against Staphylococcus aureus. Most interesting, this series of compounds displayed very promising antileishmanial activity. Among all, compound 9 exhibited an IC50 value of 0.3 µM on the Leishmania donovani intramacrophage amastigote in vitro model and a good selectivity index, better than miltefosine, making it worth evaluating in vivo.


New, potentially chelating NHC ligands; synthesis, complexation studies, and preliminary catalytic evaluation.
Two new N-heterocyclic carbene (NHC) ligands bearing 2-morpholino and 2-piperidinyl naphthyl wingtips were synthesised (2-SIMorNap and 2-SIPipNap). Nuclear magnetic resonance studies, in conjunction with crystal structures and derivatisation of the NHC salts using a chiral counteranion, revealed that the ligand wingtips are oriented anti with respect to each other. From the free carbene, palladium, ruthenium and iridium complexes were prepared. NHC-iridium dicarbonyl complexes were made in order to extract the TEP values for these ligands. The study showed that these NHC ligands are more electron-donating than normal, aryl-substituted NHCs. The palladium complexes were tested in representative Suzuki-Miyaura cross-coupling reactions and compared to the state of the art systems. Ruthenium-catalysed ring-closing metathesis with these ligands was also performed. It was found that Grubbs' 2nd generation catalyst incorporating 2-SIPipNap did not initiate at room temperature and required heating for RCM to occur.


Myocardial failure with altered response to adrenaline in endotoxin shock.
1 There is a growing concensus that myocardial performance in the early stages of experimental endotoxic and septic shock is relatively normal; however, recent reports have identified an intermediate phase of shock when myocardial dysfunction is clearly apparent.2 The mechanism of dysfunction has become a subject of intense investigation. A current view is that altered myocardial responsiveness to circulating catecholamines may play an important role in the dysfunction observed after endotoxin administration. The present studies, in which an isolated working heart preparation of the dog was used, were designed to test this hypothesis. This particular experimental preparation was selected to provide an adequate interpretation of results; cardiac output, afterload, and concentrations of adrenaline reaching the coronary vascular bed were controlled in all experiments. Responses to infusions of adrenaline were recorded in the ;steady-state' condition. Control (non-shocked) heart responses to adrenaline were highly reproducible in terms of inotropic, chronotropic and coronary vascular behaviour.3 Results from the study document myocardial dysfunction within 4-6 h following an LD(70) endotoxin administration on the basis of increased left ventricular end diastolic pressure (LVEDP), decreased cardiac power and myocardial efficiency, and depressed negative and positive dP/dt parameters.4 Findings suggest significantly altered responsiveness of the myocardium to infused adrenaline at rates of 1, 2, and 5 mug/min with concentrations between 10 and 1 ng/ml blood. LVEDP was elevated while calculated power and efficiency parameters remained significantly below control values during infusion of adrenaline in endotoxin-treated hearts. Depressions of responsiveness were interpreted to occur on the basis of failure to restore positive and negative dP/dt to normal values and depressed coronary blood flow responses during adrenaline administration. Increases in coronary flow were regularly less in experimental hearts than the controls. Heart rate responses to adrenaline in both failing and non-failing hearts were identical.5 In conclusion, it is suggested that myocardial contractile and relaxation characteristics and coronary vascular responses to adrenaline infusion are depressed in endotoxin shock during the period of demonstrated myocardial dysfunction. No distinct causal relationships were observed between the altered myocardial responsiveness and pathogenesis of heart dysfunction since myocardial dysfunction and altered responsiveness to adrenaline were generally observed together. Myocardial oedema formation after endotoxin as previously reported by this laboratory may bear a relationship to the depressed negative dP/dt response to adrenaline.