Biodiversity conservation adaptation to climate change: Protecting the actors or the stage.
To be able to protect biodiversity in coming decades, conservation strategies need to consider what sites will be important for species not just today but also in the future. Different methods have been proposed to identify places that will be important for species in the future. Two of the most frequently used methods, ecological niche modeling and climate resilience, have distinct aims. The former focuses on identifying the suitable environmental conditions for species, thus protecting the "actor," namely, the species, whereas the latter seeks to safeguard the "stage," or the landscape in which species occur. We used the two methods to identify climate refugia for 258 forest vertebrates under short- and long-term climatic changes in a biodiversity hotspot, the Appalachian ecoregion of the United States. We also evaluated the spatial congruence of the two approaches for a possible conservation application, that of protecting 30% of the Appalachian region, in line with recent national and international policy recommendations. We detected weak positive correlations between resilience scores and baseline vertebrate richness, estimated with ecological niche models for historical (baseline) climatic conditions. The correlations were stronger for amphibians and mammals than for birds and reptiles. Under climate change scenarios, the correlations between estimated vertebrate richness and resilience were also weakly positive; a positive correlation was detected only for amphibians. Locations with estimated future gain of suitable climatic conditions for vertebrates showed low correlation with resilience. Overall, our results indicate that climate resilience and ecological niche modeling approaches capture different characteristics of projected distributional changes of Appalachian vertebrates. A climate resilience (the stage) approach could be more effective in safeguarding species with low dispersal abilities, whereas an ecological niche modeling (the actor) approach could be more suitable for species with long-distance dispersal capacity because they may be more broadly impacted by climate and less sensitive to geophysical features captured by a climate resilience approach.


Plaque morphology and distribution in patients with and without myocardial bridge - an intravascular ultrasound study.
Myocardial bridging (MB) is a common congenital cardiovascular anomaly. There are reported associations of MB with different clinical presentations like effort angina, acute coronary syndromes (ACS) and sudden cardiac death. Acceleration of atherosclerosis in proximal vessel is reported in patients with MB, while bridged segments are reported to be free of atherosclerosis. We assessed patients who underwent intravascular ultrasound (IVUS) guided percutaneous intervention (PCI) of left anterior descending (LAD) artery. Plaque characteristics derived from IVUS analysis were compared between those who displayed myocardial bridge versus those who did not harbour the anomaly. One hundred and forty-seven (147) patients underwent IVUS guided PCI. Incidence of MB was 44/147 (29.9%). Mean age of patients who had MB {+} was higher (62.1 ± 10.3 vs. 57.8 ± 11.2 (p = .03). 142/147 (96.6%) patients presented with ACS. ST elevation myocardial infarction (STEMI) was the most common presenting diagnosis (110/147 to 74.8%). There were no differences in qualitative plaque characteristics - attenuated plaque, calcification or calcium score between two groups. Plaque burden and length of the lesion in the proximal vessel were not different. Among patients with MB {+}, atheromatous extension to segments underlying the bridge was seen in 31/44 (70.5%) cases. In a series of patients who presented with advanced clinical atherosclerosis, plaque characteristics were not different in patients who harboured myocardial bridge vs. those who did not have the anomaly. Atheromatous involvement was seen extending into bridged segment contrary to previous reports.


Statistical learning of higher-order temporal structure from visual shape sequences.
In 3 experiments, the authors investigated the ability of observers to extract the probabilities of successive shape co-occurrences during passive viewing. Participants became sensitive to several temporal-order statistics, both rapidly and with no overt task or explicit instructions. Sequences of shapes presented during familiarization were distinguished from novel sequences of familiar shapes, as well as from shape sequences that were seen during familiarization but less frequently than other shape sequences, demonstrating at least the extraction of joint probabilities of 2 consecutive shapes. When joint probabilities did not differ, another higher-order statistic (conditional probability) was automatically computed, thereby allowing participants to predict the temporal order of shapes. Results of a single-shape test documented that lower-order statistics were retained during the extraction of higher-order statistics. These results suggest that observers automatically extract multiple statistics of temporal events that are suitable for efficient associative learning of new temporal features.


Guidelines for the prevention and treatment of pressure ulcers.
An 'all-in-one' guideline on pressure ulcer prevention and management in primary and secondary care was published last year by the National Institute for Health and Clinical Excellence (NICE 2005a). The guideline is published in two parts. The first part is The Management of Pressure Ulcers in Primary and Secondary Care (Royal College of Nursing (RCN) and NICE 2005). The second part concerns pressure ulcer risk assessment and prevention, including the use of pressure-relieving devices (NICE 2003). A quick reference guide (NICE 2005b) summarises the recommendations made in both parts and is the focus of this article.


lncRNA-PVT1 Facilitates Invasion Through Upregulation of MMP9 in Nonsmall Cell Lung Cancer Cell.
Lung cancer is the most common solid tumor around the world. It has been reported that upregulation of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (lncRNA-PVT1) is closely associated with tumor metastasis. However, the function and underlying molecular mechanism of lncRNA-PVT1 in nonsmall cell lung cancer (NSCLC) invasion remain unknown. In this study, we found that overexpression of lncRNA-PVT1 promoted the invasive ability of NSCLC cells, whereas silence of lncRNA-PVT1 suppressed cell invasion. Furthermore, we found that lncRNA-PVT1 upregulated MMP9 expression in a post-transcriptional manner. Specifically, lncRNA-PVT1 directly interacted with miR-200a and miR-200b, which suppressed MMP9 expression. Taken together, lncRNA-PVT1 functions as a competitive endogenous RNA to regulate MMP9 expression through competitively binding the common microRNAs, miR-200a and miR-200b. These findings suggest that lncRNA-PVT1 could predispose NSCLC patients to metastases and may serve as a promising target for antimetastatic therapies.


Syringomyelia presenting as paroxysmal arm posturing resembling seizures.
A 9-year-old female presented with daily episodes of medically refractory paroxysmal bilateral arm posturing, which had long been thought to be epileptic seizures. She also had other types of episodes, including daily staring spells and infrequent generalized tonic-clonic convulsions. Neurologic examination was normal except for delayed cognitive development. The results of previous electroencephalograms (EEG) were normal, and magnetic resonance imaging of the head revealed a Chiari I malformation. Video EEG monitoring revealed no EEG changes during the attacks, and magnetic resonance imaging of the spine revealed a large cervical syrinx associated with the Chiari malformation. The episodes of paroxysmal bilateral dystonic arm posturing resolved after surgical intervention for the syrinx. This report illustrates that cervical cord disease is an unusual although potentially treatable condition to be considered in the differential diagnosis of paroxysmal episodes with dystonic movements of the arms, even in the absence of other physical findings of myelopathy.


[Factors related to screening of hepatitis C virus in general medicine].
Despite the high prevalence of hepatitis C in France ( approximately 1.2%), a large proportion of people infected with hepatitis C virus (HCV) are not known aware of their status. The objective of this study was to investigate the factors related to screening in general medicine. Three hundred and one general practitioners were interviewed by phone in South-Eastern France about their HCV screening practices, knowledge of the epidemic, of the natural course of the disease, and opinions about health care for people infected with HCV. While general practitioners often offered HCV screening to intravenous drug users, screening for people who had received blood transfusion, and identification of risk factors among patients were not satisfactory. Multivariate analysis showed that certain characteristics in general practitioners were negatively and independently related to the frequency of HCV screening, especially: general practitioners older than 40 (odds-ratio: 3.12), general practitioners who did not care for intravenous drug users (odds-ratio: 2.24) and did not prescribe human immunodeficiency virus tests (odds-ratio: 5.55). Other characteristics such as awareness of the course of hepatitis C and health care were also associated with HCV screening. Conversely knowledge of the size of the epidemic was not related to better HCV screening practices. Our study shows that knowledge about the size of the epidemic and the natural history of hepatitis C, HCV screening practices and investigation of risk factors among patients are not satisfactory among South-eastern French general practitioners. Although HCV screening and health care must be improved among intravenous drug users, hepatitis C should not be considered as a disease of injecting drug users only by general practitioners and the population. Efforts should be made so that hepatitis C is recognized as a global public health issue, and training of general practitioners should be improved to investigate risk factors and offer HCV screening instead of merely dramatizing the situation.


Aerobic Bacteriological Study of Acute Exacerbations of Chronic Obstructive Pulmonary Disease.
The natural history of chronic obstructive pulmonary disease is characterized by frequent exacerbations. Majority of exacerbations are infectious and bacteria responsible for 30-50% of these cases. The purpose of this study was to determine the bacteriology of acute exacerbations of chronic obstructive pulmonary disease in hospitalized patients in our institution and their antibiotic susceptibility pattern to formulate cost effective antibiotic strategy and reducing the emergence of drug resistance. One hundred and seven clinically diagnosed cases of acute exacerbations of chronic obstructive pulmonary disease admitted in medicine, tuberculosis and chest wards were selected for the study. Direct gram stain was done for all sputum samples. The suitable sputum samples were cultured. Identification of organism and antimicrobial susceptibility testing was done by standard microbiological techniques. Our study showed growth of pathogenic organisms in 41.12% cases. Males (67.29%) are more affected than females (32.71%). Gram negative bacilli were more isolated than gram positive cocci. The commonest isolate was Klebsiella pneumoniae 15 (38.46%), followed by Staphylococcus aureus 9 (23.08%), Streptococcus species 6 (15.39%), Pseudomonas aeruginosa 4 (10.26%), E.coli 2 (5.13%), Acinetobacter species 2 (5.13%) and Enterobacter species 1(2.56%). The antibiotic susceptibility reveals that vancomycin, linezolid, azithromycin and clarithromycin were most effective drugs for gram positive cocci, meropenem & piperacillin-tazobactam for gram negative bacilli and amikacin & levofloxacin for both gram positive cocci & gram negative bacilli. In developing country like India acute exacerbations of chronic obstructive pulmonary disease is common in adults more than 50 years of age due to smoking habits and high indoor pollution. This leads to a major impact on the quality of life of patients with the condition. They are a major cause of hospital admission and health care utilization.


Bacteria and virus removal effectiveness of ceramic pot filters with different silver applications in a long term experiment.
In 2012 more than 4 million people used a ceramic pot filter (CPF) as household water treatment system for their daily drinking water needs. In the normal production protocol most low cost filters are impregnated with a silver solution to enhance the microbial removal efficiency. The aim of this study was to determine the role of silver during the filtration and subsequent storage. Twenty-two CPFs with three different silver applications (non, only outside and both sides) were compared in a long-term loading experiment with Escherichia coli (K12 and WR1) and MS2 bacteriophages in natural challenge water under highly controlled laboratory circumstances. No significant difference in Log Removal Values were found between the filters with different silver applications. The results show that the storage time in the receptacle is the dominant parameter to reach E. coli inactivation by silver, and not the contact time during the filtration phase. The hypothesis that the absence of silver would enhance the virus removal, due to biofilm formation on the ceramic filter element, could not be confirmed. The removal effectiveness for viruses is still of major concern for the CPF. This study suggests that the ceramic pot filter characteristics, such as burnt material content, do not determine E. coli removal efficacies, but rather the contact time with silver during storage is the dominant parameter to reach E. coli inactivation.


Expert medico-legal reports: The relationship between levels of consistency and judicial outcomes in asylum seekers in the Netherlands.
If asylum applicants need to prove that they have been persecuted in their home country, expert judgment of the psychological and physical consequences of torture may support the judicial process. Expert medico-legal reports can be used to assess whether the medical complaints of the asylum seeker are consistent with their asylum account. It is unclear which factors influence medical expert judgement about the consistency between an asylum seeker's symptoms and story, and to what extent expert medico-legal reports are associated with judicial outcomes. We analysed 97 medico-legal reports on traumatised asylum seekers in the Netherlands. First, we evaluated the impact of trauma-related and other variables on experts' judgments of the consistency of symptoms and story. Second, we evaluated the effect of experts' judgments of symptom-story consistency on subsequent judicial outcomes. Gender, receipt of mental health care and trauma-related variables were associated with symptom story consistency. Positive asylum decisions were predicted by expert judgments about the presence of physical signs and symptoms of torture, and ill-treatment and their consistency with the refugee's story, but not psychological symptoms. These results suggest that standardised procedures for the documenting of medical evidence by independent experts can improve judicial decision quality and the need to improve psychological and psychiatric assessments.


Prospective full-term-derived pluripotent amniotic fluid stem (AFS) cells.
Amniotic fluid (AF) serves as an excellent alternative source of pluripotent stem cells, as they are not bound with ethical issues and the stem cells are more primitive than adult stem (AS) cells. Hence, they have higher potential. Here we aim to isolate and characterize pluripotent stem cells from mid-term and full-term pregnant rat amniotic fluid. The results demonstrate the evidence of heterogeneous population of cells in the amniotic fluid and some of the cells morphology shows similarity with ES cells.


Impact of nanodroplets on cone-textured surfaces.
Molecular dynamics simulations have been performed to study the dynamics of nanodroplets impacting on a flat superhydrophobic surface and surfaces covered with nanocone structures. We present a panorama of nanodroplet behaviors for a wide range of impact velocities and different cone geometrics, and develop a model to predict whether a nanodroplet impacting onto cone-textured surfaces will touch the underlying substrate during impact. The advantages and disadvantages of applying nanocone structures to the solid surface are revealed by the investigations into restitution coefficient and contact time. The effects of nanocone structures on droplet bouncing dynamics are probed using momentum analysis rather than conventional energy analysis. We further demonstrate that a single Weber number is inadequate for unifying the dynamics of macroscale and nanoscale droplets on cone-textured surfaces, and propose a combined dimensionless number to address it. The extensive findings of this study carry noteworthy implications for engineering applications, such as nanoprinting and nanomedicine on functional patterned surfaces, providing fundamental support for these technologies.


Carbon nanodots as ligand exchange probes in Au@C-dot nanobeacons for fluorescent turn-on detection of biothiols.
Au nanoparticle-carbon dot core-shell (Au@C-dot) nanocomposite was synthesized in aqueous medium at room temperature using the carbon dots as reducing agents themselves. The carbon nanodots also function as an effective stabilizer by forming a thin layer surrounding Au nanoparticles (Au NPs) similar to self-assembled monolayers. Ligand exchange with thiol containing biomolecules resulted in the release of carbon dots from the Au NP surface leading to an enhancement of fluorescence. Simultaneously the agglomeration of Au NPs stimulated by the interaction of biothiols led to changes in the surface plasmon properties of Au NPs. A detailed spectroscopic investigation revealed a combination of static and dynamic quenching being involved in the process. Thus, the Au nanoparticle-carbon dot composite could be used as a dual colorimetric and fluorometric sensor for biothiols ranging from amino acids, peptides, proteins, enzymes etc. with a detection limit of 50 nM.


Morphometric analysis of pulpal myelinated nerve fibers in human teeth with chronic periodontitis and root sensitivity.
The reasons why root sensitivity occurs in some periodontally diseased teeth are still unknown. It is possible that root sensitivity may be related to changes of intradental myelinated nerve fibers, which are responsible for dentine sensitivity. The aim of this study was to define the pattern of myelinated nerve fiber changes in the pulps of teeth with and without root sensitivity in the presence of chronic periodontitis. A total of 33 cross-sectioned human dental pulp specimens were collected from noncarious, intact, permanent teeth sensitive to electric and thermal (cold) stimulus (10 hypersensitive teeth with chronic periodontitis (HTPP group), 15 nonsensitive teeth with chronic periodontitis (NTPP group), and 8 nonsensitive teeth with healthy periodontium (control group)). The morphometric parameters were estimated using light microscopy and image-analyzing computer program Image-Pro Plus. The means of myelinated nerve fiber density, fiber and axon diameter, area, perimeter, length, width, g ratio, index of circularity, and myelin sheath thickness in NTPP group significantly differed from HTPP group and the control group teeth (p<0.001). The great reduction in the density of myelinated nerve fibers in NTPP group was accompanied by unequal decrease in the number of very large-diameter myelinated nerve fibers. The mean values of morphometric parameters of all myelinated nerve fibers in HTPP group were almost the same as those in the control teeth, and no significant difference was observed. The findings of the present study suggest that the reason for enhanced root sensitivity has likely nothing to do with changes of the innervation of myelinated nerves in the dental pulp. While, decreased sensitivity of periodontally diseased teeth may be related to the degeneration of myelinated nerve fibers in the pulp.


Molecular characteristics of serum visfatin and differential detection by immunoassays.
There are controversial results concerning the association of visfatin with obesity and diabetes. We aimed to characterize molecular features of visfatin, to assess visfatin detection by different immunoassays, and evaluate the association with human obesity and glucose metabolism. Distinct preparations of human visfatin (recombinant, endogenously expressed from human adipocytes, and overexpressed in COS-7 cells) were readily identified by three currently available immunoassays. However, direct comparison of native human serum samples did reveal great discrepancies between these assays and complete lack of correlation. To specify putative molecular isoforms of visfatin, we fractionated iodine-125-labeled recombinant visfatin spiked into human serum and supernatants of visfatin-overexpressing COS-7 cells by size exclusion chromatography. We obtained a distinct peak at approximately 100 kDa that was confirmed by subsequent Western blotting of the fractions and is equivalent to the molecular mass of the dimer. Only one of the immunoassays detected a similar peak in native human size exclusion chromatography serum fractions, whereas the others detected a peak at more than 500 kDa or did not show any distinct peak. We did not observe any differences in visfatin serum levels between lean or obese patients. In addition, there was no correlation between visfatin serum levels with visfatin mRNA expression in sc or visceral fat and with parameters of glucose metabolism. Differences in the qualitative and quantitative detection of visfatin by immunoassays need to be considered in clinical association studies and may explain the conflicting observations with respect to a putative relation of circulating visfatin to human obesity or insulin resistance.


The Application of Intravascular Ultrasound to Evaluate Pulmonary Vascular Properties and Mortality in Patients with Pulmonary Arterial Hypertension.
The aim of this study was to explore the application of intravascular ultrasound (IVUS) to evaluate pulmonary vascular properties and mortality in patients with pulmonary arterial hypertension (PAH). Patients (n = 51) with systolic pulmonary artery pressures ≥ 40 mm Hg on echocardiography were prospectively enrolled. All patients underwent right-heart catheterization and IVUS and were divided into three groups: PAH associated with connective tissue diseases (group 1, n = 25), PAH due to other causes (group 2, n = 15), and patients with connective tissue diseases without pulmonary hypertension (group 3, n = 11). PAH groups (groups 1 and 2) were divided into distal (n = 22) and proximal (n = 18) remodeling subtypes on the basis of IVUS results. All patients were followed (19 ± 10 months) to compare the differences among clinical variables, pulmonary vascular properties, and survival rates. A total of 408 segments of pulmonary arteries were studied. The PAH groups demonstrated a greater mean wall thickness than group 3 (P < .01 for all). Pulmonary vascular mechanical properties, including compliance, distensibility, elastic modulus, and stiffness index β, were found to be worse in the PAH groups than in group 3 (P < .01 for all), but they tended to be better in group 1 than in group 2. An inverse exponential association was found between pulmonary vascular mechanical properties and hemodynamics, with R(2) values ranging from 0.54 to 0.78 (P < .001). In the PAH groups, the mortality in group 1 was similar to that in group 2 (12% vs 13%, P > .05), while the distal remodeling subtype had higher mortality than the proximal remodeling subtype (23% vs 0%, P < .05). IVUS is useful in PAH assessment by evaluating pulmonary vascular properties and predicting mortality. The classification of the proximal and distal remodeling type of PAH may be proposed to predict mortality and evaluate the prognosis of patients with PAH in clinical practice.


Biochemical networks with uncertain parameters.
The modelling of biochemical networks becomes delicate if kinetic parameters are varying, uncertain or unknown. Facing this situation, we quantify uncertain knowledge or beliefs about parameters by probability distributions. We show how parameter distributions can be used to infer probabilistic statements about dynamic network properties, such as steady-state fluxes and concentrations, signal characteristics or control coefficients. The parameter distributions can also serve as priors in Bayesian statistical analysis. We propose a graphical scheme, the 'dependence graph', to bring out known dependencies between parameters, for instance, due to the equilibrium constants. If a parameter distribution is narrow, the resulting distribution of the variables can be computed by expanding them around a set of mean parameter values. We compute the distributions of concentrations, fluxes and probabilities for qualitative variables such as flux directions. The probabilistic framework allows the study of metabolic correlations, and it provides simple measures of variability and stochastic sensitivity. It also shows clearly how the variability of biological systems is related to the metabolic response coefficients.


Serum cholesterol levels in children are associated with dietary fat and fatty acid intake.
Recent studies in adults suggest that individual dietary fatty acids differ markedly in their effects on serum lipids and lipoprotein levels. However, these associations have rarely been studied in children. To assess, using regression procedures, the associations in children between specific fatty acids and nonfasting serum lipids and cholesterol after controlling for total energy and total fat intake, The sample consisted of 1,182 children who participated in the Child and Adolescent Trial for Cardiovascular Health. The sample was equally distributed across 4 sites (Louisiana, Texas, Minnesota, California). The sample was 48% boys; 71% white, 15% Hispanic-American, 10% African-American, 2% Asian, and 2% from other or unspecified racial/ethnic heritage. In this randomized multicenter trial with 56 intervention and 40 control elementary schools, food record-assisted 24-hour dietary recalls and serum lipid measurements were collected for each child at baseline (3rd grade) and at the 5th grade follow-up. Repeated-measures analysis of variance was used to evaluate the association between nutrient composition of the diet and serum lipids. Independent dietary variables included amount and type of fat, individual fatty acids, protein, carbohydrate, and fiber. The dependent variables were the absolute values of serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) both at baseline (3rd grade) and at follow-up (5th grade). Increased total fat (b=0.053; P<.03) was associated with increased TC in the model when energy was held constant, whereas increased carbohydrate was associated with decreased TC (b=-0.021, P<.02) and HDL-C (b=-0.010, P<.005) levels. Increased total protein (b=0.017, P<.05) was associated with increased HDL-C when energy was held constant. Saturated fat (b=0.004, P<.04), unsaturated fat (b=0.004, P<.03), and myristic fatty acid (b=0.021, P<.01) all increased TC in the model when total fat and total energy were held constant. We conclude that using a modeling approach, the effect of diet on serum lipids in children is similar to that observed in adults. Total fat and saturated fat were positively associated with TC and HDLC levels, saturated fat was positively associated with TC, and carbohydrate was inversely associated with both TC and HDL-C. In the statistical model, substitution of unsaturated fatty acids, monounsaturated fatty acids, or oleic acid for saturated fat, while holding total fat and energy constant, slightly lowered TC. In contrast, substitution of total fat for carbohydrate in the model increased TC and, thus, did not seem to be associated with an apparent health advantage except for HDL-C elevating effects. However, consumption of individual fats tends to be highly correlated, and we were unable to determine if these biological effects were operating independently.


Start-up of a multi-stage system for biogas production and solid waste treatment in low-tech countries.
Vegetable fruit garden wastes were treated anaerobically using a multistage Dranco system. The digesters were composed of three 50 L vessels kept in mesophilic conditions. They were operating at 14.5-17% TS. By controlling the pH in the system, the start-up for biogas production was shortened to 60 days. The pH correction was a buffering which enhanced methanogenic activity in the digesters. With a loading rate of 4.1 kg VS/m3 reactor/day, the production of biogas was 5 m3/m3 reactor/ day, and 60-70% methane content. This allowed making a multisystem by starting every 3 weeks with new vessels in order to maintain biogas production, to be used in industries or in local communities in low-tech countries. The designed model was started in Kinshasa (Congo) where a project is expected to treat one ton of solid waste on a daily basis, for a production of 100 m3 biogas. This cost effectiveness of the system is demonstrated and presents the opportunity for biowaste treatment coupled with environmental protection and substantial energy recovery.


Some aspects of allogeneic stem cell transplantation in patients with myelodysplastic syndrome: advances and controversy.
Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid disorders. MDS remains a disease of elderly patients; moreover, the incidence of high risk MDS is proportionally greater in elderly patients, with increased frequency of secondary acute myeloid leukemia, as well as adverse cytogenetic abnormalities. Allogeneic stem cell transplantation is a therapeutic approach with known curative potential for patients with MDS that allows the achievement of long-term disease control. Numerous controversies still exist regarding transplantation in MDS: timing of transplantation, disease status at transplantation and comorbidity, conditioning intensity, pretransplant therapy, and stem cell source. Various transplant modalities of different intensities and alternative donor sources are now in use. Current advances in transplant technology are allowing the consideration of older patients. This should result in a greater number of older patients benefiting from this potentially curative treatment modality. Despite advances in transplantation technology, there is still considerable morbidity and mortality associated with this approach. Nevertheless, with the introduction of reduced-intensity conditioning and thereby reduced early mortality, transplant numbers in MDS patients have significantly increased. Moreover, recent new developments with innovative drugs, including hypomethylating agents, have extended the therapeutic alternatives for MDS patients. Hypomethylating agents allow the delay of allogeneic stem cell transplantation by serving as an effective and well-tolerated means to reduce disease burden.


Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress.
Human pluripotent stem cells (hPSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have a well-orchestrated program for differentiation and self-renewal. However, the structural features of unique proteostatic-maintaining mechanisms in hPSCs and their features, distinct from those of differentiated cells, in response to cellular stress remain unclear. We evaluated and compared the morphological features and stress response of hPSCs and fibroblasts. Compared to fibroblasts, electron microscopy showed simpler/fewer structures with fewer networks in the endoplasmic reticulum (ER) of hPSCs, as well as lower expression of ER-related genes according to meta-analysis. As hPSCs contain low levels of binding immunoglobulin protein (BiP), an ER chaperone, thapsigargin treatment sharply increased the gene expression of the unfolded protein response. Thus, hPSCs with decreased chaperone function reacted sensitively to ER stress and entered apoptosis faster than fibroblasts. Such ER stress-induced apoptotic processes were abolished by tauroursodeoxycholic acid, an ER-stress reliever. Hence, our results revealed that as PSCs have an underdeveloped structure and express fewer BiP chaperone proteins than somatic cells, they are more susceptible to ER stress-induced apoptosis in response to stress.


Initial testing of dasatinib by the pediatric preclinical testing program.
Dasatinib, a dual inhibitor of the src and abl tyrosine kinases, was recently approved by the Federal Drug Administration for the treatment of imatinib mesylate-resistant chronic myeloid leukemia. Dasatinib was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro panel at concentrations ranging from 0.1 nM to 1.0 microM and was tested in vivo at a dose of 50 mg/kg administered orally twice daily 5 days per week for 4 weeks for the solid tumor xenografts and once daily for the acute lymphoblastic leukemia (ALL) xenografts. Dasatinib was selectively active against the cell lines of the PPTP in vitro panel, reaching an IC(50) in 6 of the 22 lines. The most sensitive were the AML line Kasumi-1, which has a gain-of-function c-Kit mutation (Asn822Lys), and the rhabdoid tumor line CHLA-266 (IC(50) approximately 10 nM for each). In the in vivo panel, dasatinib induced significant differences in EFS distribution in 8 of 32 (25%) solid tumor models and 3 of 7 ALL models. Using the time to event activity measure, dasatinib had intermediate activity against 1 of 27 (4%) evaluable solid tumor xenografts and 3 of 7 ALL xenografts. One xenograft in the ALL panel, a Philadelphia chromosome positive (Ph(+)) ALL xenograft, demonstrated a complete response. Dasatinib was active at low nanomolar concentrations against a small subset of the PPTP's in vitro panel. Dasatinib had limited in vivo activity against the PPTP solid tumor xenografts, but was highly active against a Ph(+) ALL xenograft and also had anti-leukemia activity against two other xenografts.


Magnetoresistance in Organic Spin Valves Based on Acid-Exfoliated 2D Covalent Organic Frameworks Thin Films.
Covalent organic frameworks (COFs), as a burgeoning class of crystalline porous materials, have made significant progress in their application to optoelectronic devices such as field-effect transistors, memristors, and photodetectors. However, the insoluble features of microcrystalline two-dimensional (2D) COF powders limit development of their thin film devices. Additionally, the exploration of spin transport properties in this category of π-conjugated skeleton materials remains vacant thus far. Herein, an imine-linked 2D Py-Np COF nanocrystalline powder was synthesized by Schiff base condensation of 4,4',4'',4'''-(pyrene-1,3,6,8-tetrayl)tetraaniline and naphthalene-2,6-dicarbaldehyde. Then, we prepared a large-scale free-standing Py-Np COF film via a top-down strategy of chemically assisted acid exfoliation. Moreover, high-quality COF films acted as active layers were transferred onto ferromagnetic La0.67 Sr0.33 MnO3 (LSMO) electrodes for the first attempt to fabricate organic spin valves (OSVs) based on 2D COF materials. This COF-based OSV device with a configuration of LSMO/Py-Np COF/Co/Au demonstrated a remarkable magnetoresistance (MR) value up to -26.5 % at 30 K. Meanwhile, the MR behavior of the COF-based OSVs exhibited a highly temperature dependence and operational stability. This work highlights the enormous application prospects of 2D COFs in organic spintronics and provides a promising approach for developing electronic and spintronic devices based on acid-exfoliated COF thin films.


Velopharyngeal impairment in the orthodontic population.
This article provides information concerning cleft palate teams and questions one might consider in identifying the best referral for patients manifesting velopharyngeal impairment. A discussion of the impact of velopharyngeal impairment on speech performance is followed by presentation of a variety of simple evaluative tasks that can assist the clinician in identifying patients who would benefit from referral to a cleft palate team. Finally, information is presented concerning the potential speech sequelae of maxillary advancement surgery.


Nanomechanically Visualizing Drug-Cell Interaction at the Early Stage of Chemotherapy.
A detailed understanding of chemotherapy is determined by the response of cell to the formation of the drug-target complex and its corresponding sudden or eventual cell death. However, visualization of this early but important process, encompassing the fast dynamics as well as complex network of molecular pathways, remains challenging. Herein, we report that the nanomechanical traction force is sensitive enough to reflect the early cellular response upon the addition of chemotherapeutical molecules in a real-time and noninvasive manner, due to interactions between chemotherapeutic drug and its cytoskeleton targets. This strategy has outperformed the traditional cell viability, cell cycle, cell impendence as well as intracellular protein analyses, in terms of fast response. Furthermore, by using the nanomechanical traction force as a nanoscale biophysical marker, we discover a cellular nanomechanical change upon drug treatment in a fast and sensitive manner. Overall, this approach could help to reveal the hidden mechanistic steps in chemotherapy and provide useful insights in drug screening.


Sleep disordered breathing and pregnancy.
Many changes in the respiratory system occur during pregnancy, particularly during the third trimester, which can alter respiratory function during sleep, increasing the incidence and severity of sleep disordered breathing. These changes include increased ventilatory drive and metabolic rate, reduced functional residual capacity and residual volume, increased alveolar-arterial oxygen gradients, and changes in upper airway patency. The clinical importance of these changes is indicated by the increased incidence of snoring during pregnancy, which is likely also to reflect an increased incidence of obstructive sleep apnoea/hypopnoea syndrome. For the respiratory physician asked to review a pregnant patient, the possibility of sleep disordered breathing should always be considered. This review first examines the normal physiological changes of pregnancy and their relationship to sleep disordered breathing, and then summarises the current knowledge of sleep disordered breathing in pregnancy.


Pointwise plucking of suspended carbon nanotubes.
Vibration of nanotubes/wires is significant for fundamental and applied researches. However, it remains challenging to control the vibration with point-level precision. Herein, individual suspended carbon nanotubes are plucked point by point to vibrate in scanning electron microscope with the electron beam as a nanoscale pointer. The vibration is directly imaged, and its images fit well with simulations from the plucking mechanism. This demonstrates a new way to manipulate the nanotube vibration with unprecedented precision.


Safety and biocompatibility of carbohydrate-functionalized polyanhydride nanoparticles.
Carbohydrate functionalization of nanoparticles allows for targeting of C-type lectin receptors. This family of pattern recognition receptors expressed on innate immune cells, such as macrophages and dendritic cells, can be used to modulate immune responses. In this work, the in vivo safety profile of carbohydrate-functionalized polyanhydride nanoparticles was analyzed following parenteral and intranasal administration in mice. Polyanhydride nanoparticles based on 1,6-bis-(p-carboxyphenoxy)hexane and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane were used. Nanoparticle functionalization with di-mannose (specifically carboxymethyl-α-D-mannopyranosyl-(1,2)-D-mannopyranoside), galactose (specifically carboxymethyl-β-galactoside), or glycolic acid induced no adverse effects after administration based on histopathological evaluation of liver, kidneys, and lungs. Regardless of the polymer formulation, there was no evidence of hepatic or renal damage or dysfunction observed in serum or urine samples. The histological profile of cellular infiltration and the cellular distribution and kinetics in the lungs of mice administered with nanoparticle treatments followed similar behavior as that observed in the lungs of animals administered with saline. Cytokine and chemokine profiles in bronchoalveolar lavage fluid indicated surface chemistry dependence on modest secretion of IL-6, IP-10, and MCP-1; however, there was no evidence of any deleterious histopathological changes. Based on these analyses, carbohydrate-functionalized nanoparticles are safe for in vivo applications. These results provide foundational information towards the evaluation of the capabilities of these surface-modified nanoparticles as vaccine delivery formulations.


[Effects of puerarin on expression of apelin and its receptor of 2K1C renal hypertension rats].
To examine the change of puerarin on the expression of apelin and its receptor of the two-kidney, one-clip (2K1C) rats. Tirty male Sprague-Dawley rats were randomly divided into normal control group (C), model group (M) and puerarin group (P). The mean of carotid arterial pressure (mCAP), mean of left ventricular end diastolic pressure (LVEDP), and the weight ratio of left ventricular mass (left ventricle plus septum) to bodyweight (LVM/BW) were measured to evaluate the model of 2K1C renal hypertension. The concentrations of apelin in the plasma and left ventricle (LV) were measured with radioimmunoassay. Apelin mRNA and APJ mRNA expressed in the LV were examined by reverse transcription-polymerase chain reaction (RT-PCR). The peptides of apelin and APJ expressed in the LV were detected with immunohistochemistry (IHC). Compared with C group, the mCAP, LVEDP and LVM/BW of M group were higher 36.58%, 333.8% and 20.24%, respectively (P<0.05, P<0.01, P<0.01). Compared with M group, LVEDP and LVM/BW of P group were lower 65.24% and 13.12%, respectively (both P<0.05). However mCAP was of no significant difference between these two groups. The levels of apelin-36 in the plasma and LV of M group were respectively higher 18.56% and 207.38% than those of C group (both P<0.05), while ones of P group were lower 24.21% and 49.40% than those of M group (both P<0.05). The expressions of apelin mRNA and APJ mRNA at left ventricle tissues of 2K1C rats were higher 77.66% and 119.00% (both P<0.05) than those of C group. The ones of P group were lower 27.40% and 45.66% than those of M group (both P<0.01). The IHC results indicate that the expressions of apelin and APJ peptides at left ventricle tissues of 2K1C rats were higher 129.51% and 154.1% (both P<0.01) than those of C group, respectively. Whereas the ones of P group were lower 65.36% and 62.87% than those of M group (both P<0.01). Through regulating apelin/APJ system puerarin has protective effect on the development of left ventricular hypertrophy by renal hypertension.


Live cell imaging of neuronal growth cone motility and guidance in vitro.
The neuronal growth cone, a highly motile structure at the tip of neuronal processes, is an excellent model system for studying directional cell movements. While biochemical and genetic approaches unveiled molecular interactions between ligand, receptor, signaling, and cytoskeleton-associated proteins controlling axonal growth and guidance, in vitro live cell imaging has emerged as a crucial approach for dissecting cellular mechanisms of growth cone motility and guidance. Important insights into these mechanisms have been gained from studies using the large growth cones elaborated by Aplysia californica neurons, an outstanding model system for live cell imaging for a number of reasons. Identified neurons can be isolated and imaged at room temperature. Aplysia growth cones are five to ten times larger than growth cones from other species, making them suitable for quantitative high-resolution imaging of cytoskeletal protein dynamics and biophysical approaches. Lastly, protein, RNA, fluorescent probes, and small molecules can be microinjected into the neuronal cell body for localization and functional studies. This chapter describes culturing of Aplysia bag cell neurons, live cell imaging of neuronal growth cones using differential interference contrast and fluorescent speckle microscopy as well as the restrained bead interaction assay to induce adhesion-mediated growth cone guidance in vitro.


System for rapid assessment of pneumonia and influenza-related mortality-Ohio, 2009-2010.
Rapid mortality surveillance is critical for state emergency preparedness. To enhance timeliness during the 2009-2010 influenza A H1N1 pandemic, the Ohio Department of Health activated a drop-down menu within Ohio's Electronic Death Registration System for reporting of pneumonia- or influenza-related deaths approximately 5 days postmortem. We used International Classification of Diseases-Tenth Revision (ICD-10) codes, available 2-3 months postmortem as the standard, and assessed their agreement with drop-down-menu codes for pneumonia- or influenza-related deaths. Among 56 660 Ohio deaths during September 2009-March 2010, agreement was 97.9% for pneumonia (κ = 0.85) and 99.9% for influenza (κ = 0.79). Sensitivity was 80.2% for pneumonia and 73.9% for influenza. Drop-down menu coding enhanced timeliness while maintaining high agreement with ICD-10 codes.


Diffuse corneal abrasion after ocular exposure to laundry detergent pod.
Although ocular injury from alkaline household cleaning products is well described, there is less known about the significance and extent of injury with ocular exposure to detergent pods. We report a 12-month-old with diffuse corneal abrasion caused by ocular contact with a laundry detergent pod. In addition to the known risks with aspiration with detergent pods, the potential for severe ocular injury is important for parents and clinicians to recognize. Children with ocular exposure to detergent pods should seek immediate medical care.


Local cerebral glucose utilization in fetal and neonatal sheep.
The newborn mammalian brain of several species has been shown to have a lower average rate of energy metabolism and a narrower range of rates in its various components than is found in maturity. In a further study of cerebral energy metabolism during development, we have employed the [14C]deoxyglucose method for measuring local cerebral glucose utilization in fetal and neonatal sheep. After establishing the lumped constant to be 0.40 and finding the rate constants for the kinetic behavior of deoxyglucose in plasma and brain to be close to those in other species, we measured the rates of glucose utilization in 44 regions of the brain. The rates were low and homogeneous in midgestation, except for those of brain stem nuclei of the auditory and vestibular systems and those of the hippocampus which were relatively high. In the last 7 wk, local rates rose approximately threefold. After birth there was a further average increase of 50% above full-term levels. The study shows that cerebral energy metabolism rises in most structures during prenatal maturation, a time when sensory stimulation is at a relatively low level and behavioral responses are minimal.


Birth-weight status of newborns and its relationship with other anthropometric parameters in a public maternity hospital in Dhaka, Bangladesh.
According to the World Health Organization, birth-weight of less than 2,500 g is considered low birth-weight since below this value birth-specific infant mortality begins to rise rapidly. In Bangladesh, the prevalence of low birth-weight is unacceptably high. To screen low-birth-weight babies, simple anthropometric parameters can be used in rural areas where 80-90% of deliveries take place. A sample of 316 newborn singleton babies were studied in a government maternity hospital in Dhaka city to examine the birth-weight status of newborns and to identity the relationship between birth-weight and other anthropometric parameters of newborns. The mean birth-weight was 2,889 +/- 468 g, and 15.18% were low-birth-weight (<2,500 g) babies. All key anthropometric parameters of the newborns significantly correlated with one another (p<0.001). The best cut-offs for detecting low-birth-weight and normal-weight babies were <10 cm (odds ratio=17.4), <30.5 cm (odds ratio=25.0) and <33 cm (odds ratio=19.4), respectively, for mid-upper arm circumference (MUAC), chest circumference, and head circumference. The sensitivity and specificity were best for chest circumference (83.3% and 83.6% respectively). At lower cut-off points of <9 cm, <29.5 cm, and <32 cm, respectively, for MUAC, chest circumference, and head circumference, high-risk babies could be identified with a minimum number of false-positive cases. Chest circumference was the best detector of birth-weight with a correlation-coefficient of just above 0.84, followed by MUAC with a correlation-coefficient of just below 0.84. Based on the findings of the study, it is recommended to use <29.5 and 29.5 to <30.5 cm for chest circumference to identify 'high-risk' and 'at high-risk' newborns respectively.


Optimal use of sampled tissue sections for estimating the number of hepatocellular foci.
Statistical techniques were applied to computer-simulated data to evaluate the importance of various factors that may affect the estimation of the number of hepatocellular foci from foci transections. The simulations were modeled after mouse foci for which three-dimensional size distributions and densities were determined from serial section reconstructions. The foci had been induced in male C57BL/6 X C3H F1 mice at 20 and 28 weeks after a single injection, in infancy, of diethylnitrosamine. In an earlier report, we had shown that the number of foci per cu cm could be accurately estimated from profiles using a conditional estimator when the investigator is unable to identify profiles smaller than a certain size (epsilon). In the present study, emphasis was placed on assessing the value of step serial sections in order to make optimal use of the small tissue samples in mouse liver. Since all mathematical estimators of N3 are based on measurement of sampled profiles (n2') and ultimately derive from the fundamental relationship. N3' = N2'/2mu, (where N3' is the number of foci per cu cm, N2' is the number of profiles per sq cm, and mu, is the average adjusted focus radius), the relative importance of N2' and mu, on the conditional estimator was evaluated. This was accomplished by comparing the errors resulting from use of the conditional estimator with those resulting from use of two other estimators. The latter two estimators consisted of a "sampled focus estimator," which used sampled intact foci to estimate N3, and a "reference estimator," which used profiles from foci with a mu, that was known. Additionally, in order to provide a stable variance for the conditional estimator, we adopted a simple smoothing procedure. As expected, none of the estimators showed any significant bias. However, somewhat surprising was the finding that the standard deviations from use of all three estimators were almost identical. Consequently, it appears that the variance resulting from application of the smoothed conditional estimator to large sets of profile data is not due to difficulty in estimating mu epsilon. In these instances, the faulty estimates of N2' resulted almost entirely from the variability in sampling foci from tissue blocks which constituted only about 1/25 of the liver volume. In addition, the ability to reduce the error in estimating the number of foci by increasing the number of profiles was also evaluated. We simulated a sectioning protocol for the 28-week mouse livers in which the distances between the 5-micron-thick step sections in a 1-mm block of liver were progressively decreased from 1000 to 50 micron.(ABSTRACT TRUNCATED AT 400 WORDS)


Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy.
Many idiopathic epilepsy syndromes have a characteristic age dependence, the underlying molecular mechanisms of which are largely unknown. Here we propose a mechanism that can explain that epileptic spells in benign familial neonatal-infantile seizures occur almost exclusively during the first days to months of life. Benign familial neonatal-infantile seizures are caused by mutations in the gene SCN2A encoding the voltage-gated Na(+) channel Na(V)1.2. We identified two novel SCN2A mutations causing benign familial neonatal-infantile seizures and analysed the functional consequences of these mutations in a neonatal and an adult splice variant of the human Na(+) channel Na(V)1.2 expressed heterologously in tsA201 cells together with beta1 and beta2 subunits. We found significant gating changes leading to a gain-of-function, such as an increased persistent Na(+) current, accelerated recovery from fast inactivation or altered voltage-dependence of steady-state activation. Those were restricted to the neonatal splice variant for one mutation, but more pronounced for the adult form for the other, suggesting that a differential developmental splicing does not provide a general explanation for seizure remission. We therefore analysed the developmental expression of Na(V)1.2 and of another voltage-gated Na(+) channel, Na(V)1.6, using immunohistochemistry and real-time reverse transcription-polymerase chain reaction in mouse brain slices. We found that Na(V)1.2 channels are expressed early in development at axon initial segments of principal neurons in the hippocampus and cortex, but their expression is diminished and they are gradually replaced as the dominant channel type by Na(V)1.6 during maturation. This finding provides a plausible explanation for the transient expression of seizures that occur due to a gain-of-function of mutant Na(V)1.2 channels.


Moyamoya disease associated with midaortic syndrome.
We report a 1-year-old girl who presented moyamoya disease associated with midaortic syndrome. She had been treated for cardiac failure and severe hypertension due to midaortic syndrome until she suffered seizure and repeated cerebral ischemic attack. Cerebral angiography revealed stenosis of the bilateral internal carotid artery at its terminal portion. She was successfully treated with encephaloduroarteriosynangiosis, and ischemic attack ceased postoperatively. This is the first report of moyamoya disease with midaortic syndrome. Although cerebral ischemic attack has been effectively managed by encephaloduroarteriosynangiosis, renovascular hypertension is still difficult to control.


Major role of positive selection in the evolution of conservative segments of Drosophila proteins.
Slow evolution of conservative segments of coding and non-coding DNA is caused by the action of negative selection, which removes new mutations. However, the mode of selection that affects the few substitutions that do occur within such segments remains unclear. Here, we show that the fraction of allele replacements that were driven by positive selection, and the strength of this selection, is the highest within the conservative segments of Drosophila protein-coding genes. The McDonald-Kreitman test, applied to the data on variation in Drosophila melanogaster and in Drosophila simulans, indicates that within the most conservative protein segments, approximately 72 per cent (approx. 80%) of allele replacements were driven by positive selection, as opposed to only approximately 44 per cent (approx. 53%) at rapidly evolving segments. Data on multiple non-synonymous substitutions at a codon lead to the same conclusion and additionally indicate that positive selection driving allele replacements at conservative sites is the strongest, as it accelerates evolution by a factor of approximately 40, as opposed to a factor of approximately 5 at rapidly evolving sites. Thus, random drift plays only a minor role in the evolution of conservative DNA segments, and those relatively rare allele replacements that occur within such segments are mostly driven by substantial positive selection.


Should Positive Claims of Conscience Receive the Same Protection as Negative Claims of Conscience? Clarifying the Asymmetry Debate.
In the debate over clinicians' conscience, there is a greater ethical, legal, and scholarly focus on negative, rather than positive, claims of conscience. This asymmetry produces a seemingly unjustified double standard with respect to clinicians' conscience under the law. For example, a Roman Catholic physician working at a secular institution may refuse to provide physician-aid-in-dying on the basis of conscience, but a secular physician working at a Roman Catholic institution may not insist on providing physician-aid-in-dying on the basis of conscience. This article outlines arguments against this asymmetry and critiques them for failing to distinguish between positive claims of conscience as positive or negative rights. I suggest the asymmetry debate should be focused on whether positive claims of conscience as positive rights ought to enjoy the same protections as negative claims of conscience. Clarifying the debate in this way helps elucidate some of the best reasons for the asymmetry, which these arguments have not addressed. This article does not take a definitive position on whether the asymmetry is justified, but attempts to bring some focus to the debate by directing arguments against the asymmetry to address the significant differences between positive claims of conscience as positive rights and negative claims of conscience.


The inhibition of mammalian target of rapamycin (mTOR) in improving inflammatory response after traumatic brain injury.
Traumatic brain injury (TBI) provokes primary and secondary damage on endothelium and brain parenchyma, leading neurons die rapidly by necrosis. The mammalian target of rapamycin signalling pathway (mTOR) manages numerous aspects of cellular growth, and it is up-regulated after moderate to severe traumatic brain injury (TBI). Currently, the significance of this increased signalling event for the recovery of brain function is unclear; therefore, we used two different selective inhibitors of mTOR activity to discover the functional role of mTOR inhibition in a mouse model of TBI performed by a controlled cortical impact injury (CCI). Treatment with KU0063794, a dual mTORC1 and mTORC2 inhibitor, and with rapamycin as well-known inhibitor of mTOR, was performed 1 and 4 hours subsequent to TBI. Results proved that mTOR inhibitors, especially KU0063794, significantly improved cognitive and motor recovery after TBI, reducing lesion volumes. Also, treatment with mTOR inhibitors ameliorated the neuroinflammation associated with TBI, showing a diminished neuronal death and astrogliosis after trauma. Our findings propose that the involvement of selective mTORC1/2 inhibitor may represent a therapeutic strategy to improve recovery after brain trauma.


Grafting materials and methods in reconstructive ear surgery.
The evolution of tympanic membrane grafting over the past 20 years has been based on biologic tissues of mesodermal origin which contain a collagen matrix. The dominant theme of this evolution has been the modification of these collagen membranes by physical and chemical agents to achieve a more ideal graft. The graft material and the operation should be suited to specific problems. Current operative techniques and graft materials are discussed. It is believed that there will be continued modification and manipulation of collagen in the future to achieve a more ideal graft for tympanic membrane restoration.


Polymer Composite with Carbon Nanofibers Aligned during Thermal Drawing as a Microelectrode for Chronic Neural Interfaces.
Microelectrodes provide a direct pathway to investigate brain activities electrically from the external world, which has advanced our fundamental understanding of brain functions and has been utilized for rehabilitative applications as brain-machine interfaces. However, minimizing the tissue response and prolonging the functional durations of these devices remain challenging. Therefore, the development of next-generation microelectrodes as neural interfaces is actively progressing from traditional inorganic materials toward biocompatible and functional organic materials with a miniature footprint, good flexibility, and reasonable robustness. In this study, we developed a miniaturized all polymer-based neural probe with carbon nanofiber (CNF) composites as recording electrodes via the scalable thermal drawing process. We demonstrated that in situ CNF unidirectional alignment can be achieved during the thermal drawing, which contributes to a drastic improvement of electrical conductivity by 2 orders of magnitude compared to a conventional polymer electrode, while still maintaining the mechanical compliance with brain tissues. The resulting neural probe has a miniature footprint, including a recording site with a reduced size comparable to a single neuron and maintained impedance that was able to capture neural activities. Its stable functionality as a chronic implant has been demonstrated with the long-term reliable electrophysiological recording with single-spike resolution and the minimal tissue response over the extended period of implantation in wild-type mice. Technology developed here can be applied to basic chronic electrophysiological studies as well as clinical implementation for neuro-rehabilitative applications.


The rapid urease test in the diagnosis of Helicobacter pylori infection.
With the increasing recognition of the importance of H. pylori in gastrointestinal disease, there is a need for a reliable, efficient and yet inexpensive diagnostic test. The performance of the rapid urease test (RUT) as an endoscopy suite diagnostic test was compared to the established methods of culture, histology and Gram stain of tissue smear, in 274 gastric biopsy samples. Histology had the highest sensitivity of 99.3% followed by the RUT (96.6%). Culture and Gram stain of tissue smear had 100% specificity, while the rapid urease test had 99.2% specificity. The RUT had a positive predictive value of 99.3% and a negative predictive value of 96.2%. The RUT is an inexpensive, rapid and reliable diagnostic test of H. pylori infection.


Impact of frailty on outcomes after discharge in older surgical patients: a prospective cohort study.
Frailty is a state of vulnerability to diverse stressors. We assessed the impact of frailty on outcomes after discharge in older surgical patients. We prospectively followed patients 65 years of age or older who underwent emergency abdominal surgery at either of 2 tertiary care centres and who needed assistance with fewer than 3 activities of daily living. Preadmission frailty was defined according to the Canadian Study of Health and Aging Clinical Frailty Scale as "well" (score 1 or 2), "vulnerable" (score 3 or 4) or "frail" (score 5 or 6). We assessed composite end points of 30-day and 6-month all-cause readmission or death by multivariable logistic regression. Of 308 patients (median age 75 [range 65-94] yr, median Clinical Frailty Score 3 [range 1-6]), 168 (54.5%) were classified as vulnerable and 68 (22.1%) as frail. Ten (4.2%) of those classified as vulnerable or frail received a geriatric consultation. At 30 days after discharge, the proportions of patients who were readmitted or had died were greater among vulnerable patients (n = 27 [16.1%]; adjusted odds ratio [OR] 4.60, 95% confidence interval [CI] 1.29-16.45) and frail patients (n = 12 [17.6%]; adjusted OR 4.51, 95% CI 1.13-17.94) than among patients who were well (n = 3 [4.2%]). By 6 months, the degree of frailty independently and dose-dependently predicted readmission or death: 56 (33.3%) of the vulnerable patients (adjusted OR 2.15, 95% CI 1.01-4.55) and 37 (54.4%) of the frail patients (adjusted OR 3.27, 95% CI 1.32-8.12) were readmitted or had died, compared with 11 (15.3%) of the patients who were well. Vulnerability and frailty were prevalent in older patients undergoing surgery and unlikely to trigger specialized geriatric assessment, yet remained independently associated with greater risk of readmission for as long as 6 months after discharge. Therefore, the degree of frailty has important prognostic value for readmission. ClinicalTrials.gov, no. NCT02233153.


Sustained acclimatization in Chilean mine workers subjected to chronic intermittent hypoxia.
Farias, Jorge G., Jorge Osorio, Gustavo Soto, Julio Brito, Patricia Siques, and Juan G. Reyes. Sustained acclimatization in Chilean mine workers subjected to chronic intermittent hypoxia. High Alt. Med. Biol. 7:302-306, 2006--We wanted to know if sea-level mine workers exposed previously to chronic intermittent hypoxia reached a steady acclimatization at 36 months under hypobaric hypoxia. An intermittently exposed group of mine workers (IE, n = 25) were subjected to submaximal exercise (100 W) at 4500 m. Their systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and hemoglobin oxygen saturation (HbSatO(2)) were monitored. Two comparison groups of unacclimatized sea-level workers (n = 17) were studied. A nonexposed group (NE) performed 5 min of submaximal exercise at sea level. Some kind of exercise was performed both by an acutely exposed group (AE) and IE group at 4500 m. No statistical differences were found for HR, SBP, and DBP (p > 0.05) during exercise between IE and AE groups. Resting HbSatO(2) of IE (87 +/- 6%) was lower than NE (97 +/- 3%) (p < 0.05), but was higher than AE (82 +/- 4%) (p < 0.05). In the exercise condition, HbSatO(2) of IE (85 +/- 5%) was lower than NE (95 +/- 3%) (p < 0.05), but was higher than AE (76 +/- 2%) (p < 0.05). These responses were maintained through the 6 months of the study period. Thus, mine workers subjected to intermittent hypobaric condition for 3 years showed a good degree of acclimatization that was maintained through time.


Cryptic Diversity of Malassezia pachydermatis from Healthy and Diseased Domestic Animals.
Malassezia pachydermatis is part of the normal cutaneous microbiota of wild and domestic carnivores. However, under certain conditions this yeast can overproliferate and cause several diseases in its host, mainly otitis and dermatitis in dogs. The aim of this study was to conduct a molecular characterization of M. pachydermatis isolates from healthy and diseased domestic animals, in order to assess the molecular diversity and phylogenetic relationship within this species. The large subunit (LSU) and the internal transcribed spacer (ITS) of ribosomal RNA, chitin synthase 2 (CHS2) and β-tubulin genes from sixteen strains isolated from dogs, cats, a goat, a pig and a horse were sequenced. A different number of types of sequences were identified for each target gene, including some types described for the first time. Five sequence types were characterized for the LSU, eleven for the ITS region, nine for CHS2 and eight for β-tubulin. A multilocus analysis was performed including the four genes, and the resulting phylogenetic tree revealed fifteen genotypes. Genotypes were distributed in two well-supported clades. One clade comprised strains isolated from different domestic animals and a strongly supported cluster constituted by strains isolated from cats. The second clade included strains isolated mainly from dogs and an outlier strain isolated from a horse. No apparent association could be observed between the health status of the animal hosts and concrete strains. The multilocus phylogenetic analysis is a useful tool to assess the intraspecific variation within this species and could help understand the ecology, epidemiology and speciation process of M. pachydermatis.


Treatment of Large Bone Defects with a Vascularized Periosteal Flap in Combination with Biodegradable Scaffold Seeded with Bone Marrow-Derived Mononuclear Cells: An Experimental Study in Rats.
The surgical treatment of large bone defects continues to pose a major challenge in modern trauma and orthopedic surgery. In this study we test the effectiveness of a tissue engineering approach, using three-dimensional (3D) β-tricalcium phosphate (β-TCP) scaffolding plus bone marrow-derived mononuclear cells (BM-MNCs), combined with a vascularized periosteal flap, in a rat femur critical size defect model. Eighty rats were randomly allocated into four equal groups. Under general anesthesia, critical size defects were created on their femurs and were treated with (1) Vascularized periosteal flap alone, (2) Vascularized periosteal flap+β-TCP scaffolding, (3) Vascularized periosteal flap+β-TCP scaffolding+ligated vascular pedicle, and (4) Vascularized periosteal flap+β-TCP scaffolding+BM-MNCs. After 4 and 8 weeks animals were euthanized and the bone defects were harvested for analysis of new bone formation, vascularization, and strength using histology, immunohistology, micro-CT, and biomechanical testing, respectively. Group 1: (P. flap) Increase in new bone formation and vascularization. Group 2: (P. flap+scaffold) Increase in new bone formation and vascularization. Group 3: (P. flap+scaffold+ligated vascular pedicle) No new bone formation and no vascularization. Group 4: (P. flap+scaffold+BM-MNCs) A significant (p < 0.05) increase was seen in new bone formation, vascularization, and strength in bones treated with flaps, scaffold, and BM-MNCs, when compared with the other treatment groups. Combining a vascularized periosteal flap with tissue engineering approach (β-TCP scaffolding and BM-MNC) results in significantly improved bone healing in our rat femur critical size bone defect model.


Intuition: concept analysis of a group phenomenon.
Intuition as a group phenomenon is clarified through the process of concept analysis using the analytical process outlined by Walker and Avant. Intuition as a respectable characteristic of creative and powerful groups is based on uses of the concept; identification of attributes, antecedents, and consequences; construction of various cases; and identification of empirical referents. Suggestions for applications in nursing education, nursing administration, and professional organizations follow.


Freedom to Speak Up.
University Hospitals of Morecambe Bay NHS Foundation Trust is the first NHS Trust in the country to launch an app to make raising concerns easier.


[Modified FLAG regimen in the management of refractory acute myeloid leukemia].
To evaluate the therapeutic effect of modified FLAG regimen in the management of refractory acute myeloid leukemia (AML). Sixteen patients with refractory AML were divided into two groups. In modified FLAG regimen group (n=10), the patients received fludarabine (Flu, 50 mg/d, VDx5 d) and Ara-c (200 mg/d, VDx5 or 7 d). The regimen for classic FLAG group (n=6) consisted of Flu (50 mg/d, VDx5d), Ara-C (500 or 1,000 mg/d, VDx5d) and G-CSF (300 microg/d, x5 d, subcutaneously injected 4-6 hours before chemotherapy). Each patient received subcutaneous G-CSF (300 microg/d) when the white blood cell count was lower than 1.0x10(9)/L till the condition was corrected. The total complete remission(CR) rate of the 16 patients was 50% (8/16). Seven patients in modified group achieved CR (70%) and only one of the classic group did (17%, P<0.05). Episodes of infections were lower in modified group than in the classic group (50% vs 83%). Modified FLAG regimen is more likely than classic FLAG regimen to achieve CR and reduce infections in patients with refractory AML.


Medical image quality metrics for foveated model observers.
Purpose: A recently proposed model observer mimics the foveated nature of the human visual system by processing the entire image with varying spatial detail, executing eye movements, and scrolling through slices. The model can predict how human search performance changes with signal type and modality (2D versus 3D), yet its implementation is computationally expensive and time-consuming. Here, we evaluate various image quality metrics using extensions of the classic index of detectability expression and assess foveated model observers for search tasks. Approach: We evaluated foveated extensions of a channelized Hotelling and nonprewhitening matched filter model with an eye filter. The proposed methods involve calculating a model index of detectability ( d ' ) for each retinal eccentricity and combining these with a weighting function into a single detectability metric. We assessed different versions of the weighting function that varied in the required measurements of the human observers' search (no measurements, eye movement patterns, size of the image, and median search times). Results: We show that the index of detectability across eccentricities weighted using the eye movement patterns of observers best predicted human performance in 2D versus 3D search performance for a small microcalcification-like signal and a larger mass-like. The metric with a weighting function based on median search times was the second best predicting human results. Conclusions: The findings provide a set of model observer tools to evaluate image quality in the early stages of imaging system evaluation or design without implementing the more computationally complex foveated search model.


Psychosocial stimulation interventions for children with severe acute malnutrition: a systematic review.
The WHO Guidelines for the inpatient treatment of severely malnourished children include a recommendation to provide sensory stimulation or play therapy for children with severe acute malnutrition (SAM). This systematic review was performed to synthesize evidence around this recommendation. Specifically, the objective was to answer the question: "In children with severe acute malnutrition, does psychosocial stimulation improve child developmental, nutritional, or other outcomes?" A review protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO 2016: CRD42016036403). MEDLINE, Embase, CINAHL, and PsycINFO were searched with terms related to SAM and psychosocial stimulation. Studies were selected if they applied a stimulation intervention in children with SAM and child developmental and nutritional outcomes were assessed. Findings were presented within a narrative synthesis and a summary of findings table. Quality of the evidence was evaluated using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Only two studies, both non-randomized controlled trials, met the selection criteria for this review. One was conducted in Jamaica (1975) with a follow-up period of 14 years; the other was done in Bangladesh (2002) with a six-month follow-up. At the individual study level, each of the included studies demonstrated significant differences in child development outcomes between intervention and control groups. Only the study conducted in Bangladesh demonstrated a clinically significant increase in weight-for-age z-scores in the intervention group compared to the control group. The evidence supporting the recommendation of psychosocial stimulation for children with SAM is not only sparse, but also of very low quality across important outcomes. High-quality trials are needed to determine the effects of psychosocial stimulation interventions on outcomes in children with SAM.


[High frequency oscillatory ventilation in the newborn infant].
The objective of this study was to determine the effectivity, results and complications after application of HFOV in a group of newborns with serious respiratory distress. Between February and October 1995, HFOV was required by 18 newborns in the NICU of the Hospital "La Fe" of Valencia, as ventilatory rescue therapy because of the failure of conventional ventilation in 10 cases (group A) and serious air leaks in 8 cases (group B). We used pure HFOV without superimposed cycles of conventional IMV following a high volume-high pressure strategy. Among the lung pathology, RDS was most frequent (11/18). Twenty-four hours after beginning HFOV, a decrease of the FiO2 was obtained in group A from 0.89 to 0.4 and in group B from 0.7 to 0.4. Oxygenation, ventilation, OI and a/AO2 ration also improved. In the group with conventional ventilation failure, this improvement was significant for all parameters in the first two hours after the start of HFOV (p < 0.01). In the group with air leaks, all parameters improved at two hours, but this change was significant only for oxygenation (p < 0.01). Four newborns died (22%) in the first month. HFOV is an effective and secure ventilatory method when conventional ventilation fails or serious air leaks occur. Important improvement in oxygenation and ventilation is obtained during the first two hours and it is possible to decrease the oxygen requirements at 24 hours after the start of HFOV.


Novel microemulsion of tanshinone IIA, isolated from Salvia miltiorrhiza Bunge, exerts anticancer activity through inducing apoptosis in hepatoma cells.
Natural product Tanshinone IIA (TanIIA) induces apoptosis and differentiation in hepatocellular carcinoma (HCC) cells, but its clinical use is limited due to poor water solubility and lack of appropriate formulations for drug delivery. In this study, we capsulated TanIIA into a microemulsion (ME) that was composed of phospholipid, ethyl oleate, glycerol and pluronic F68. We then determined the anticancer effects and mechanisms of action for TanIIA ME with in vitro and in vivo HCC models. The mRNA and protein levels of apoptosis-related molecules (Bcl-2, Bax and caspase-3) were analyzed in murine hepatoma H22 cells and H22 tumor-bearing mice by flow cytometry, RT-PCR and immunofluorescence staining. Compared with the groups treated with empty ME and drug solution, the mRNA levels of Bax and caspase-3 were up-regulated, and the mRNA and protein levels of Bcl-2 were down-regulated in H22 cells treated with TanIIA ME in a dose-dependent manner. The mRNA and protein levels of Bax and caspase-3 were up-regulated and the Bcl-2 levels were also down-regulated in animals treated with TanIIA ME in a dose-dependent manner. Our results suggest that as a novel drug delivery system, microemulsion enhances the antitumor effects of TanIIA.


Real-time PCR-based determination of gene copy numbers in Pichia pastoris.
Pichia pastoris is a preferred host for heterologous protein production. Expression cassettes are usually integrated into the genome of this methylotrophic yeast. This manuscript describes a method for fast and reliable gene copy number determinations for P. pastoris expression strains. We believe that gene copy number determinations are important for all researchers working with P. pastoris and also many other research groups using similar gene integration techniques for the transformation of other yeasts. The described method uses real-time PCR to quantify the integrated expression cassettes. Similar methods were employed previously for other host systems such as animal and plant cells but no such method comparing different detection methods and describing details for yeast analysis by quantitative PCR is known to us, especially for methylotrophic yeasts such as P. pastoris. Neglecting gene copy numbers can easily lead to false interpretations of experimental results from codon optimization or promoter studies and co-expression of helper proteins as demonstrated in an application example, which is also described here.


The energy response of LiF, film and a chemical dosemeter to high energy photons and electrons.
The physical responses of LiF, film and a chemical dosemeter in high energy photon and electron beams has been studied. It is shown that the response for film and the chemical dosemeter does not change significantly up to 42 MeV, while for LiF it decreases by about 10%. Analysis of calculations and measurements showed that this decrease could not be explained by existing theories.


Histopathologic changes in anti-angiotensin II type 1 receptor antibody-positive kidney transplant recipients with acute rejection and no donor specific HLA antibodies.
To determine the association of antibodies against angiotensin II type 1 receptor (AT1R Ab) and histopathologic changes seen in patients with kidney allograft rejection and negative donor specific HLA antibodies (DSA). Stored sera from 27 patients who had biopsy-proven rejection in the absence of DSA were tested for AT1R Ab. Biopsy slides of all patients were re-examined and classified according to Banff 2013 criteria. Histopathologic changes were compared between AT1R positive and negative patients. 75% of patients with positive pre-transplant AT1R Ab had antibody mediated rejection (AMR) compared to 37% of AT1R Ab-negative patients. A trend towards increased interstitial inflammation was observed in the AT1R Ab positive group (p=0.08). More patients in the AT1R Ab positive group had microcirculation inflammation (88% vs 58% with glomerulitis scores ≥1; 75% vs 58% with peritubular capillaritis scores ≥1). In kidney transplant recipients with rejection and no DSA, a higher incidence of AMR and worse inflammation scores are observed in the presence of positive pre-transplant AT1R antibodies.


Does facial sebum excretion really affect the development of acne?
It is generally accepted that the severity of acne is correlated with facial sebum secretion. However, previous studies on the relation between seborrhoea and the development of acne did not consider topographical differences in facial sebum secretion and used relatively vague acne severity grading systems. To elucidate the relation between topographical variations in facial sebum secretion and the severity of acne in women. Forty-six female controls and 46 women with acne were included in this study. The Sebumeter was used to measure facial sebum secretion in the following facial areas: forehead, nose, chin, and right and left cheek. We counted noninflammatory comedones and inflammatory acne lesions in the same areas. We compared sebum secretion between patients with acne and controls, and analysed the relation between the quantity of sebum secreted and the number of acne lesions. Sebum secretions in the whole face and in the T- and U-zones (areas of high and low sebum secretion, respectively) were higher in patients with acne than in controls. There was no correlation between sebum quantity and acne lesion count in most facial regions. Increased levels of facial sebum secretion were observed in patients with acne. Our findings indicate that increased sebum levels do not directly cause development of acne lesions.


Nasal polyposis in patients with asthma and allergic rhinitis.
This study aimed to determine the prevalence of nasal polyps in patients with allergic rhinitis and with asthma, and also to assess the impact of this condition on these disorders. Cross-sectional study. The presence of nasal polyps was assessed by rhinoscopy and endoscopic examination. Nasal polyps were detected in 60 out of 250 patients (24 per cent) with documented asthma or allergic rhinitis. There was a statistically significant correlation between asthma severity and nasal polyposis prevalence (p = 0.007), but not between allergic rhinitis severity and nasal polyposis prevalence (p = 0.081). The prevalence of nasal polyps increased significantly with increasing patient age and rhinitis or asthma duration. The prevalence of nasal polyps in patients with allergic rhinitis or asthma was higher than previously reported. Given this high prevalence of nasal polyposis, nasal examination and concomitant treatment of this disorder are recommended.


Transcription of exogenous and endogenous deoxyribonucleic acid templates in cold-shocked Bacillus subtilis.
Ribonucleic acid (RNA) synthesis was examined in cold-shocked Bacillus subtilis cells. The cells were grown to mid-log stage, harvested, and cold shocked. RNA synthesis was monitored by the incorporation of [3H]uridine triphosphate or [alpha 32P]adenosine triphosphate into trichloroacetic acid-precipitable material in the presence of all four nucleoside triphosphates. The inhibition of RNA synthesis in cold-shocked cells by lipiarmycin, ethidium bromide, rifampin. or streptolydigin was analyzed using mutant or wild-type cells. Also examined were the effects of temperature, salt concentration, and the addition of polyamines or highly phosphorylated nucleotides. In ultraviolet-irradiated and cold-shocked cells, RNA wynthesis decreased to low levels. The addition of exogenous phi 29 or TSP-1 template to these cells caused a 13- to 20-fold increase in RNA synthesis, as monitored by trichloroacetic acid-precipitable counts. RNA synthesized in the presence of phi 29 deoxyribonucleic acid (DNA) hybridizes mainly to EcoRI fragments A and C of phi 29 DBA, These two fragments direct transcription by purified RNA polymerase in vitro and hybridize to early phi 29 DNA produced in vivo. Our results with TSP-1 DNA in this system indicated that the RNA produced hybridizes to the same fragments as early RNA produced in vivo. Plasmic pUB110 DNA was not transcribed in this system.


Oxygen- and Nitrogen-Enriched 3D Porous Carbon for Supercapacitors of High Volumetric Capacity.
Efficient utilization and broader commercialization of alternative energies (e.g., solar, wind, and geothermal) hinges on the performance and cost of energy storage and conversion systems. For now and in the foreseeable future, the combination of rechargeable batteries and electrochemical capacitors remains the most promising option for many energy storage applications. Porous carbonaceous materials have been widely used as an electrode for batteries and supercapacitors. To date, however, the highest specific capacitance of an electrochemical double layer capacitor is only ∼200 F/g, although a wide variety of synthetic approaches have been explored in creating optimized porous structures. Here, we report our findings in the synthesis of porous carbon through a simple, one-step process: direct carbonization of kelp in an NH3 atmosphere at 700 °C. The resulting oxygen- and nitrogen-enriched carbon has a three-dimensional structure with specific surface area greater than 1000 m(2)/g. When evaluated as an electrode for electrochemical double layer capacitors, the porous carbon structure demonstrated excellent volumetric capacitance (>360 F/cm(3)) with excellent cycling stability. This simple approach to low-cost carbonaceous materials with unique architecture and functionality could be a promising alternative to fabrication of porous carbon structures for many practical applications, including batteries and fuel cells.


Elastoma: clinical and histopathological aspects of a rare disease.
Elastoma is a connective tissue nevus characterized by changes in elastic fibers. It can be congenital or acquired, and is usually diagnosed before puberty. Associated with osteopoikilosis, it is known as Buschke-Ollendorff syndrome. Histopathology with specific staining for elastic fibers is critical for a diagnostic conclusion. This report describes the case of a 7-year-old male patient with lesions diagnosed as elastoma, with absence of bone changes in the radiological imaging. This study aims to report the clinical presentation and histological examination of such unusual disease.


Discovery and characterization of an inhibitory angiotensin receptor in the guinea-pig ileum.
Using nitrendipine to block the smooth muscle contractile effects of angiotensin II, it has been shown that the agonist produces a dose-related inhibitory effect on the electrically stimulated, longitudinal smooth muscle, myenteric plexus preparation from the guinea-pig. In the absence of stimulation, there is no detectable direct relaxant effect of angiotensin II on the preparation, even when it is partially contracted with carbachol, leading to the conclusion that the inhibitory effects of angiotensin are mediated via prejunctional receptors on the neuron. A number of angiotensin antagonists, including DUP753, saralasin, SKB108566 and several nonpeptide antagonists synthesized at ZENECA, have been investigated vs (1) the inhibitory effects of angiotensin II and (2) the direct contractile effects produced in unstimulated tissues in the absence of nitrendipine. A correlation curve comparing the results from the two sets of experiments gave a slope of 1.05 and a correlation coefficient of 0.99, providing very strong evidence that the two receptor systems are pharmacologically identical. The antagonists were further evaluated vs angiotensin II in the rat fundic strip in order to (1) determine whether there was any species variation in the receptor systems and (2) provide an example of a smooth muscle preparation uncomplicated by indirect effects of transmitters released by angiotensin, as has been reported in the guinea-pig ileum. An excellent correlation was obtained between the Ke values in the fundus and the guinea-pig ileum, indicating no difference in receptors between species or between neurons and smooth muscle.


Abnormal luminescent property of Mn(2+) in α-LiZnBO3:Mn(2+).
Mn(2+)-activated red phosphor α-LiZnBO3:Mn(2+) was synthesized by solid state reaction. ESR spectra prove that the doped ions are Mn(2+). The doped Mn(2+) ion is inclined to occupy Zn(2+) site, which is a tetrahedral coordination. The diffuse reflection spectra indicate that α-LiZnBO3:Mn(2+) has strong absorption in the range of 400-450 nm. Excited at 431 nm, an abnormal red emission band in the wavelength of 550-800 nm is observed, which is because of the strong crystal field induced by the distorted tetrahedral. The emission bands are centered at 647 nm, regardless of the excitation wavelength and Mn(2+) doping concentration. The temperature-dependent PL results reveal that α-LiZnBO3:Mn(2+) is thermally stable but the emission peak moves to shorter wavelength as temperature increases because of the decrease of the crystal field.


Chaetoceros pauciramosus sp. nov. (Bacillariophyceae), a Widely Distributed Brackish Water Species in the C. lorenzianus Complex.
To understand the diversity of the diatom genus Chaetoceros Ehrenberg, the C. lorenzianus complex was previously chosen as a model and three new species were described. In the present study, yet another new species, Chaetoceros pauciramosus sp. nov., was discovered from Chinese tropical waters and the temperate south-eastern Baltic Sea. In the latter locality it has been known since 2003 and identified as C. cf lorenzianus, and now found to comprise a dominating component of the autumn phytoplankton community. Vegetative cells and resting spores were examined by light and electron microscopy. The LSU and SSU of the nuclear rDNA were sequenced. The characters suggesting that C. pauciramosus belongs to C. lorenzianus complex are: 1) the vegetative cells contain four or more chloroplasts, 2) the cells have stiff setae and form regular straight chains, 3) the terminal setae differ in the direction from the intercalary setae. The relationship was well-supported by molecular phylogenetic analyses inferred from both LSU and SSU markers. The primary valve of the resting spore has two conical elevations, each with dichotomously branching processes, similar to other species in the C. lorenzianus complex. Each process forms a tree-like structure with the pointed distal tips which possess one or two thin spikes, that distinguishes C. pauciramosus from allied taxa. In the phylogenetic trees, Chaetoceros pauciramosus clustered with C. elegans, in agreement with their morphologically similar resting spores.


[Combined effect of intraperitoneally administered OK-432 and recombinant interleukin (rIL-2) against mouse tumors].
Combined effect of the streptococcal preparation, OK-432 and rIL-2, both administered intraperitoneally, was examined against Meth-A tumor, a syngeneic tumor of inbred BALB/c mice and an analysis of the effector cells also was performed. The combined treatment resulted in significant in vitro inhibition of tumor growth and increase in the length of survival of the Meth-A bearing mice. The spleen cells obtained from Meth-A bearing mice treated with both OK-432 and rIL-2 on the 12th day after the tumor transplantation were capable of lysing syngeneic Meth-A tumor cells in addition to NK-sensitive allogenic YAC-1 cells and LAK-sensitive EL-4 cells in vitro in a 4 hour 51Cr-release assay. Neither spleen cells obtained from the tumor bearing mice treated with OK-432 or rIL-2 alone, nor those obtained from normal mice treated with both agents, showed cytotoxic activity against Meth-A cells. The in vitro growth of NK-resistant allogenic P-388 was not inhibited by the spleen cells obtained from any treated mouse, with or without Meth-A tumor. In order to determine the effector subpopulation against Meth-A cells, the spleen cells obtained from the tumor-bearing mice treated with OK-432 and rIL-2 on the 12th day after tumor transplantation, were treated with either anti-Thy-1, 2 antibody plus complement, anti-asialo GM1 serum plus complement, or by adherence to a plastic plate or nylon wool column.(ABSTRACT TRUNCATED AT 250 WORDS)


Lung Cancer Incidence and Mortality with Extended Follow-up in the National Lung Screening Trial.
The National Lung Screening Trial (NLST) randomized high-risk current and former smokers to three annual screens with either low-dose computed tomography (LDCT) or chest radiography (CXR) and demonstrated a significant reduction in lung cancer mortality in the LDCT arm after a median of 6.5 years' follow-up. We report on extended follow-up of NLST subjects. Subjects were followed by linkage to state cancer registries and the National Death Index. The number needed to screen (NNS) to prevent one lung cancer death was computed as the reciprocal of the difference in the proportion of patients dying of lung cancer across arms. Lung cancer mortality rate ratios (RRs) were computed overall and adjusted for dilution effect, with the latter including only deaths with a corresponding diagnosis close enough to the end of protocol screening. The median follow-up times were 11.3 years for incidence and 12.3 years for mortality. In all, 1701 and 1681 lung cancers were diagnosed in the LDCT and CXR arms, respectively (RR = 1.01, 95% confidence interval [CI]: 0.95-1.09). The observed numbers of lung cancer deaths were 1147 (with LDCT) versus 1236 (with CXR) (RR = 0.92, 95% CI: 0.85-1.00). The difference in the number of patients dying of lung cancer (per 1000) across arms was 3.3, translating into an NNS of 303, which is similar to the original NNS estimate of around 320. The dilution-adjusted lung cancer mortality RR was 0.89 (95% CI: 0.80-0.997). With regard to overall mortality, there were 5253 (with LDCT) and 5366 (with CXR) deaths, for a difference across arms (per 1000) of 4.2 (95% CI: -2.6 to 10.9). Extended follow-up of the NLST showed an NNS similar to that of the original analysis. There was no overall increase in lung cancer incidence in the LDCT arm versus in the CXR arm.


Level of dietary iron, not type of dietary fat, is hyperlipidemic in copper-deficient rats.
This study was conducted to determine whether high dietary iron will negate the protective effect of unsaturated fat against hyperlipidemia. Forty-eight weanling, male Sprague Dawley rats were randomly assigned to eight dietary groups differing in the levels of copper and iron and type of dietary fat (saturated or unsaturated). The diets were either deficient (0.6 microg Cu/g) or adequate (6.8 microg Cu/g) copper and either adequate (53 microg Fe/g) or high (506 microg Fe/g) iron. All diets contained starch as the sole source of dietary carbohydrate. Regardless of the type of dietary fat, three copper-deficient rats fed the high levels of dietary iron died prematurely due to ruptured hearts. Surviving rats belonging to the copper deficiency and high-dietary iron regimen developed severe anemia, enlarged hearts and livers, and exhibited the highest levels of liver iron. These rats also developed hypercholesterolemia. Triglycerides were elevated by the consumption of high iron diets. Data show that levels of dietary iron, not the type of dietary fat, are potential inducers of hypertriglyceridemia. Data also show that the combination of high iron intake and dietary copper deficiency is responsible for elevating blood cholesterol.


Tissue-type plasminogen activator and plasminogen embedded in casein rule its degradation under physiological situations: manipulation with casein hydrolysate.
The aims of this study were to test the assumption that tissue-type plasminogen activator (t-PA) and plasminogen (PG) are closely associated with the casein micelle and form a functional complex that rules casein degradation. This assumption was essentially verified for bovine milk under conditions wherein the plasmin system was activated by treatment with casein hydrolysate. It was also shown that urokinase-type PA (u-PA), the second type of plasminogen activator present in milk, was not involved in casein degradation. In agreement with previous studies, we show that treatment with casein hydrolysate precipitously reduced mammary secretion, disrupted the tight junction integrity (increase in Na+ and decrease in K+ concentrations), induced hydrolysis of casein, and activated various elements of the innate and acquired immune system. In the present study, we have identified t-PA as the principal PA, which is responsible for the conversion of PG to plasmin. It was found that t-PA and plasminogen are present in freshly secreted milk (less than 10 min from its secretion), suggesting that they are secreted as a complex by the mammary gland epithelial cells. Further research is needed to provide the direct evidence to verify this concept.