DNA-RNA hybrids at DSBs interfere with repair by homologous recombination.
DNA double-strand breaks (DSBs) are the most harmful DNA lesions and their repair is crucial for cell viability and genome integrity. The readout of DSB repair may depend on whether DSBs occur at transcribed versus non-transcribed regions. Some studies have postulated that DNA-RNA hybrids form at DSBs to promote recombinational repair, but others have challenged this notion. To directly assess whether hybrids formed at DSBs promote or interfere with the recombinational repair, we have used plasmid and chromosomal-based systems for the analysis of DSB-induced recombination in Saccharomyces cerevisiae. We show that, as expected, DNA-RNA hybrid formation is stimulated at DSBs. In addition, mutations that promote DNA-RNA hybrid accumulation, such as hpr1∆ and rnh1∆ rnh201∆, cause high levels of plasmid loss when DNA breaks are induced at sites that are transcribed. Importantly, we show that high levels or unresolved DNA-RNA hybrids at the breaks interfere with their repair by homologous recombination. This interference is observed for both plasmid and chromosomal recombination and is independent of whether the DSB is generated by endonucleolytic cleavage or by DNA replication. These data support a model in which DNA-RNA hybrids form fortuitously at DNA breaks during transcription and need to be removed to allow recombinational repair, rather than playing a positive role.


Effects of hyperbaric oxygen and hyperbaric air on the survival of island skin flaps.
The effects of hyperbaric air and oxygen on skin survival were studied in acute 8 X 8 cm neurovascular island flaps in rats. Skin flaps treated with hyperbaric 8% oxygen (equivalent to room air at standard pressure) exhibited no improvement in skin survival. Skin flaps treated with hyperbaric air (21% oxygen) and hyperbaric 100% oxygen exhibited significant increases in survival.


Biocompatibility studies of polyurethane electrospun membranes based on arginine as chain extender.
Electrospun polymers are an example of multi-functional biomaterials that improve the material-cellular interaction and aimed at enhancing wound healing. The main objective of this work is to fabricate electrospun polyurethane membranes using arginine as chain extender (PUUR) in order to test the fibroblasts affinity and adhesion on the material and the polymer toxicity. Polyurethane membranes were prepared in two steps: (i) the polyurethane synthesis, and ii) the electrospinning process. The membranes were characterized by scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy, gel permeation chromatography, and differential scanning calorimetry techniques. The evaluation of PUUR as a scaffolding biomaterial for growing and developing of cells on the material was realized by LIVE/DEAD staining. The results show that the fluorescent surface area of human fibroblasts (hFB), was greater in control dense membranes made from Tecoflex than in electrospun and dense PUUR. From SEM analysis, the electrospun membranes show relatively uniform attachment of cells with a well-spread shape, while Tecoflex dense membranes show a non-proliferating round shape, which is attributed to the fiber's structure in electrospun membranes. The cell morphology and the cell attachment assay results reveal the well spreading of hFB cells on the surface of electrospun PUUR membranes which indicates a good response related to cell adhesion.


Pulsed Ultrasound-Mediated Enhancement on Transscleral and Transconjunctival Fluorescein Sodium Delivery to Rabbit Eye In Vivo.
Purpose: To investigate the efficacy and safety of pulsed ultrasound (PUS) in enhancing fluorescein sodium (NaF) transport to the rabbit eye through the transscleral and transconjunctival routes in vivo. Methods: PUS and NaF were applied onto the supratemporal sclera/conjunctiva of healthy rabbit eyes. PUS (1 MHz, 2.37 W/cm2, 30% duty cycle, 5-min application time) was performed 3 times with a 5-min interval. In the same process, NaF was administered to the eye without PUS in the control. NaF concentrations in the vitreous and retina-choroid were determined by fluorescence measurement. The safety of PUS application was assessed based on temperature and intraocular pressure measurements, clinical observations, electroretinography, histology, and Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling assay. Results: In comparison to the control, higher NaF concentrations were found in the retina-choroid following transscleral (2.45-fold) and transconjunctival (2.97-fold) PUS applications (P < 0.05). NaF concentrations in the vitreous were 3.15 and 5.86 times greater in transscleral and transconjunctival PUS applications, respectively, compared with those obtained without PUS application (P < 0.05), and NaF level in the vitreous after transconjunctival PUS application was 2.61 times that of transscleral PUS application (P < 0.05). Ocular findings were transient and mild conjunctival injection, with no other structural and functional changes in PUS-treated eyes. Conclusions: PUS treatment can improve transscleral and transconjunctival delivery of NaF efficiently and safely. Transscleral and transconjunctival PUS applications offer potential clinical benefit in increasing drug penetration to the posterior segments of the eye for the noninvasive treatment of ocular diseases.


Expression and synthesis of murine immune response-associated (Ia) antigens by brain cells.
This paper provides biochemical and histochemical evidence that a fraction of murine brain cells express and synthesize Ia (Immune response-associated) antigens. Both I-A and I-E subregion products are detected on frozen sections of mouse brains by immunoperoxidase staining. Most of these Ia-bearing cells are located in white matter tracts and appear to be intrafascicular oligodendrocytes. In contrast, cells in the gray matter rarely display detectable Ia antigens on their cell surfaces. Specificity of the staining was confirmed by absorption studies. Biochemical evidence for the active synthesis of Ia antigens by brain cells was obtained by immunoprecipitation of [3H]leucine/tyrosine-labeled, NP-40-extracted cell lysates with monoclonal anti-Ia reagent. Both the alpha and beta subunits of Ia antigens were identified by NaDodSO4 electrophoresis. By contrast, anti-mu serum failed to precipitate any product, thus eliminating contaminant B lymphocytes as a source of Ia antigens.


[Experiences with the eradication of the bovine herpes virus 1 in Lower Saxony].
In this paper first the general cascade of animal disease eradication from the voluntary control programme up to culling of infected animals is described. Afterwards the development of the eradication of Bovine Herpes Virus in Lower Saxony is illustrated. Obvious the number of farms which are not eradicating decreases since the testing on BHV1 is obligate in Germany. In 2004 60% of the cattle holdings were free from BHV1. At least the measures which will be taken in Lower Saxony to increase the success of eradication are explained.


Nocturnal asthma: mechanisms and management.
Nocturnal asthma, defined as an exacerbation of asthma at night, is associated with increases in symptoms and need for medication, increased airway responsiveness and worsening of lung function. Nighttime worsening of asthma has been recognized since the 5th century A.D. and is believed to be quite common, affecting a majority of asthmatics. The mechanisms of nocturnal asthma are intimately related to circadian rhythms, which influence inflammatory cells and mediators, hormone levels and cholinergic tone. Patients with nocturnal asthma symptoms may have greater nighttime activation of inflammatory cells and mediators, lower levels of epinephrine and increased vagal tone. In addition, underlying differences in the glucocorticoid receptor and b- receptors in these patients may diminish their ability to respond to therapy. While sleep appears to play a role in the pathophysiology of nocturnal asthma, it is not essential to it. Selective timing of medication can increase its efficacy and reduce its toxicity. Available therapy includes inhaled and oral corticosteroids, sustained-release theophylline, long-acting b-agonists, leukotriene- modifying agents and anticholinergic medication. The definition, epidemiology, potential mechanisms and management of nocturnal asthma are discussed in this review.


Extension of the growing season increases vegetation exposure to frost.
While climate warming reduces the occurrence of frost events, the warming-induced lengthening of the growing season of plants in the Northern Hemisphere may actually induce more frequent frost days during the growing season (GSFDs, days with minimum temperature < 0 °C). Direct evidence of this hypothesis, however, is limited. Here we investigate the change in the number of GSFDs at latitudes greater than 30° N using remotely-sensed and in situ phenological records and three minimum temperature (Tmin) data sets from 1982 to 2012. While decreased GSFDs are found in northern Siberia, the Tibetan Plateau, and northwestern North America (mainly in autumn), ~43% of the hemisphere, especially in Europe, experienced a significant increase in GSFDs between 1982 and 2012 (mainly during spring). Overall, regions with larger increases in growing season length exhibit larger increases in GSFDs. Climate warming thus reduces the total number of frost days per year, but GSFDs nonetheless increase in many areas.


[Psychiatric emergency department of the Pinel hospital center].
According to objective expressed by 1992's decree about psychiatric's emergency, Philippe Pinel's hospital in Amiens have emergency ward since march 1994. Computing activity within hospital allow to surround characteristics of patients who come to psychiatric's hospital emergency, 2,122 patients have been examined in 1995, either 6 a day. 220 were consultations, 1,920 were admittance to hospital. Among these 2,122 patients, 20.5% don't know mental hospital, 19% don't know psychiatry, 40% have a relapse and 20% where hospitalized but without met again a doctor. On the average, one hour was dedicated to patient in 1995. On a level with sociocultural, men are 59%, which 26% between 30 and 39 years, and 25% between 40 and 49 years. Among the patients, 69% live alone, and 12% have social difficulty. Patients are sent by General Hospital (27%), general practitioners (24%, but this number grow in 1996), and various psychiatric institutions (10%). The main symptoms are: sadness and depression (40%), anxiety (37%), sleep disruption (31%), alcoholism (23%), bodily symptoms (16%), attempt to suicide (15%), social problems (14%). After observation, diagnosis are: psychosis (30%), neurosis (23%), alcoholism (19%), "anti-social" personality (10%), and drug addiction (7%). Among these 2,122 patients in 1995, 90.5% (1920) are sent to hospital, which 72% with their assent, and 28% under constraint. Consultations (9.5%) are sent to psychiatric's institution (43%), general hospital (35%), and psychiatrist (6%). In conclusion, computing activity within psychiatric's emergency could enable best reception, guidance, and collaboration with social or medical colleague.


Gastrointestinal motility problems in the elderly patient.
Statistics abound demonstrating the aging of the population, and this comes as no news to physicians caring for an increasing number of elderly patients. This group experiences the expected age-related physiologic declines, including systems critical to integrative functions such as immunologic, neurologic, and metabolic systems. Although an increased prevalence of several common gastrointestinal disorders occurs in the elderly person, aging per se appears to have less direct effect on most gastrointestinal functions, in large part because of the functional reserve of the gastrointestinal tract. Although irritable bowel symptoms decrease with aging, there seems to be an increase in many gastrointestinal disorders of function and motility. The gastroenterologist will frequently encounter elderly patients with complaints of dysphagia, anorexia, dyspepsia, and disorders of colonic function. Understanding age-related changes in gastrointestinal physiology and effects of common comorbid illnesses enhances the ability to evaluate and treat these common, troublesome symptoms.


[Anti-leukotrienes in allergic diseases in children].
In the paper a review is presented of current literature on the use of antileukotrienes in the treatment of allergic diseases in children. Recent reports suggest a role of cysteinyl leukotrienes in the development of inflammatory reaction in the airways, including bronchial remodelling.


Molecular Origin of the Reinforcement Effect and Its Strain-Rate Dependence in Polymer Nanocomposite Glass.
We investigate the molecular origin of mechanical reinforcement in a polymer nanocomposite (PNC) under a glass state via molecular dynamics simulations. The strength of the PNC system is found to be reinforced mainly via reduced plastic deformations of the nanoparticle neighborhood (NN). Such a reinforcement effect is found to decay with an increase in the strain rate. The Arrhenius-Eyring relation is used to analyze its origin. The amplitude of the reinforcement is found to be determined by the difference between the energy barrier (ΔE) for the activation of NN and the work (W) done by the applied stress to conquer that barrier. A larger strain rate is found to result in a larger W and, hence, a weaker reinforcement effect. Such a strain-rate dependence is verified in the experimental tensile tests of a poly(vinyl alcohol)/SiO2 composite system. These results not only provide a new understanding of the molecular origin of the reinforcement effect in the PNC system, but also pave the way for a better design of the PNC material properties.


[CYTOKINE PROFILE IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION WITH AND WITHOUT COMPLICATIONS].
The aim of this study was to evaluate the prognostic role of the cytokine profile in patients with ST segment elevation myocardial infarction (STEMI). In the present paper we studied cytokines IL-6, IL-1β, IL-10, TNFα and CRP in 81 patients with different course of STEMI. In patients with complicated course of STEMI a significant increase in the concentration of IL-6, IL-10, FNOα, CRP was recorded on the 1st, 7th and 14th days compared with control group of healthy subjects and a group of patients with uncomplicated STEMI. Concentrations of TNFα>35.49 pg/ml, IL-6>33.37 pg/ml, IL-10>34 pg/ml, CRP>10.84 mg/l on day 1 may suggest cardiovascular complications in STEMI patients within 1 year after the onset of the disease. We have not found reliable prognostic levels of IL-1β, as the concentration of this cytokine remained within the accepted normal range.. It is concluded that initially elevated levels of CRP l, TNFα, IL-6, IL-10 in the blood make it possible to identify groups of patients with myocardial infarction with ST-segment elevation at high risk of cardiovascular events throughout the year.


Characterizing white matter damage in rat spinal cord with quantitative MRI and histology.
ABSTRACT Diffusion tensor imaging (DTI) and quantitative T(2) magnetic resonance imaging (MRI) were used to characterize ex vivo the white matter damage at 3 and 8 weeks following dorsal column transection (DC Tx) injury at the cervical level C5 of rat spinal cords. Luxol Fast Blue (LFB) and myelin basic protein (MBP) staining was used to assess myelin damage, and neurofilament-H in combination with neuron specific beta-III-tubulin (NF/Tub) staining was used to assess axonal damage. Average values of myelin water fraction (MWF), fractional anisotropy (FA), longitudinal diffusivity (D(long)), transverse diffusivity (D(trans)), and average diffusivity (D(ave)) were calculated in the fasciculus gracilis, fasciculus cuneatus, and the dorsal corticospinal tract (CST) 5 mm cranial, as well as 5 and 10 mm caudal to injury and correlated with histology. These tracts were selected as these contain bundles of parallel ascending and descending axons in very circumscribed areas with little intermingling of other axonal populations. Axonal and myelin degeneration occur cranial to injury in the funiculus gracilis and caudal to injury in the CST. Both MWF and D(trans) showed significant correlation with LFB staining at 3 weeks (0.64 and -0.49, respectively) and 8 weeks post-injury (0.88 and -0.71, respectively). Both D(long) and FA correlated significantly with NF/Tub staining at 3 weeks post-injury (0.78 and 0.64, respectively), while only D(long) displayed significant correlation 8 weeks post-injury (0.58 and 0.33, respectively). This study demonstrates that quantitative MRI can accurately characterize white matter damage in DC Tx model of injury in rat spinal cord.


Immunohistochemical staining, laser capture microdissection, and filter-aided sample preparation-assisted proteomic analysis of target cell populations within tissue samples.
An important problem involves isolating subpopulations of cells defined by protein markers in clinical tissue samples for proteomic studies. We describe a method termed Immunohistochemical staining, laser capture microdissection (LCM) and filter-aided sample preparation (FASP)-Assisted Proteomic analysis of Target cell populations within tissue samples (ILFAPT). The principle of ILFAPT is that a target cell population expressing a protein of interest can be lit up by immunohistochemical staining and isolated from tissue sections using LCM for FASP and proteomic analysis. Using this method, we isolated a small population of CD90(+) stem-like cells from glioblastoma multiforme tissue sections and identified 674 high-confidence (false discovery rate < 0.01) proteins from 32 nL of CD90(+) cells by LC-MS/MS using an Orbitrap Elite mass spectrometer. We further quantified the relative abundance of proteins identified from equal volumes of LCM-captured CD90(+) and CD90(-) cells, where 109 differentially expressed proteins were identified. The major group of these differentially expressed proteins was relevant to cell adhesion and cellular movement. This ILFAPT method has demonstrated the ability to provide in-depth proteome analysis of a very small specific cell population within tissues. It can be broadly applied to the study of target cell populations within clinical specimens.


Membrane tension controls adhesion positioning at the leading edge of cells.
Cell migration is dependent on adhesion dynamics and actin cytoskeleton remodeling at the leading edge. These events may be physically constrained by the plasma membrane. Here, we show that the mechanical signal produced by an increase in plasma membrane tension triggers the positioning of new rows of adhesions at the leading edge. During protrusion, as membrane tension increases, velocity slows, and the lamellipodium buckles upward in a myosin II-independent manner. The buckling occurs between the front of the lamellipodium, where nascent adhesions are positioned in rows, and the base of the lamellipodium, where a vinculin-dependent clutch couples actin to previously positioned adhesions. As membrane tension decreases, protrusion resumes and buckling disappears, until the next cycle. We propose that the mechanical signal of membrane tension exerts upstream control in mechanotransduction by periodically compressing and relaxing the lamellipodium, leading to the positioning of adhesions at the leading edge of cells.


Repair of Morgagni hernia and ventricular septal defect through sternotomy.
We report a case of Morgagni hernia occupying the anterior mediastinum and right hemithorax in a male infant with Down syndrome, who also had a perimembranous ventricular septal defect. Through a median sternotomy, the hernia sac was freed from the right pleura, and the pericardium was opened to reduce its contents (colon) into the abdomen. The diaphragmatic defect was closed with Prolene mesh and the hernia sac was used to reinforce the diaphragmatic defect. Finally, the pericardium was opened and the ventricular septal defect was closed with a polytetrafluoroethylene patch through a right atriotomy after instituting cardiopulmonary bypass.


Multilayer CuO@NiO Hollow Spheres: Microwave-Assisted Metal-Organic-Framework Derivation and Highly Reversible Structure-Matched Stepwise Lithium Storage.
A unique CuO@NiO microsphere with three-layer ball-in-ball hollow morphology is successfully synthesized by Cu-Ni bimetallic organic frameworks. The beforehand facile microwave-assisted production of the Ni organic framework sphere is used as the template to induce the morphology control of bimetallic oxides. Designed by the controlled surface cationic exchange reactions between Cu and Ni ions, there is an elemental gradient (decreased amount of CuO but increased amount of NiO) from the shell to the core of the microsphere product. This ternary metal oxide hollow structure is found to be very suitable for solving the critical volume expansion problem, which is critical for all high-capacity metal oxide electrodes for lithium ion batteries. A reversible larger-than-theoretical capacity of 1061 mAh·g(-1) can be retained after a repetitive 200 cycles without capacity fading compared to the initial cycle. These excellent electrochemical properties are ascribed to the step-by-step lithium insertion reactions induced by the matched CuO@NiO composition from the shell to the core and facilitated lithium/electron diffusion and accommodated volume change in the porous bimetallic oxides microsphere with a multiple-layer yolk-shell nanostructure.


Estimation of potassium and magnesium flows in animal production in Dianchi Lake basin, China.
The objectives of this study were to estimate and evaluate potassium (K) and magnesium (Mg) budgets and flows of animal production in the basin of Dianchi Lake, China. Feed sampling and farmer interviews were conducted in field surveys. The supplies of K and Mg from local and external feeds and the retention, production and excretion of animals were calculated individually for dairy cows, fattening pigs, breeding sows, and broilers and laying hens. The K and Mg flows on a regional level were estimated using the individual budgets. At the individual level, in dairy cattle, the K and Mg supplied from local feeds accounted for large parts of the total nutrient intakes, whereas in the other animal categories most of the K and Mg in the feeds depended on external resources. Our findings also suggested that excessive Mg intake resulted in high Mg excretion and low use efficiency in dairy cattle and fattening pigs. At the regional level, the K and Mg amounts of manure produced and applied in the area (K: 339 and Mg: 143 t/year) exceeded those used as local feeds. Our results imply the animal production potentially increased the K and Mg loads in the regional agriculture system.


Cardiovascular adverse reactions during antidepressant treatment: a drug surveillance report of German-speaking countries between 1993 and 2010.
Antidepressants (ADs) are known to have the potential to cause various cardiovascular adverse drug reactions (ADRs). The tricyclic antidepressants (TCAs) were first revealed to be a possible source of cardiovascular ADRs. In recent years, newer classes of ADs were also suggested to have a higher risk of cardiovascular adverse effects. In particular, the selective serotonin reuptake inhibitors (SSRIs) were suspected to have the potential to induce QTc interval prolongation, and therefore increase the risk of ventricular arrhythmia. This descriptive study is based on the continuous pharmacovigilance program of German-speaking countries (Austria, Germany, and Switzerland), the Arzneimittelsicherheit in der Psychiatrie (AMSP), which assesses severe ADRs occurring in clinical routine situations. Of 169,278 psychiatric inpatients treated with ADs between 1993 and 2010, 198 cases of cardiovascular ADRs (0.12%) were analyzed. Our study showed that the incidence rates of cardiovascular ADRs were highest during treatment with monoamine oxidase inhibitors (0.27%), TCAs (0.15%), and serotonin noradrenaline reuptake inhibitors (0.14%); the risk of occurring during treatment with SSRIs (0.08%) was significantly lower. The noradrenergic and specific serotonergic AD mirtazapine (0.07%) had a significantly lower risk of cardiovascular ADRs than all other ADs. Severe hypotension was the most frequent ADR, followed by hypertension, arrhythmia, and in some rare cases heart failure. Despite certain limitations due to the AMSP study design, our observations on cardiovascular ADRs can contribute to a better knowledge of the cardiovascular risk profiles of antidepressants in the clinical routine setting. However, prospective studies are needed to verify our findings.


Anticlastogenic effect of β-glucan, extracted from Saccharomyces cerevisiae, on cultured cells exposed to ultraviolet radiation.
β-glucan is an important polysaccharide due to its medicinal properties of stimulating the immune system and preventing chronic diseases such as cancer. The aim of the present study was to determine the anticlastogenic effect of β-glucan in cells exposed to ultraviolet radiation (UV). Chromosome aberration assay was performed in drug-metabolizing cells (HTC) and non drug-metabolizing cells (CHO-K1 and repair-deficient CHO-xrs5), using different treatment protocols. Continuous treatment (UV + β-glucan) was not effective in reducing the DNA damage only in CHO-xrs5 cells. However, the pre-treatment protocol (β-glucan before UV exposition) was effective in reducing DNA damage only in CHO-K1 cells. In post-treatment (β-glucan after UV exposition) did not show significative anticlastogenic effects, although there was a tendency toward prevention. The data suggest that β-glucan has more than one action mechanism, being capable of exerting desmutagenic as well as bio-antimutagenic action. The findings also suggest that the presence of the xenobiotic metabolizing system can reduce the chemopreventive capacity of β-glucan. Therefore, these results indicate that β-glucan from Saccharomyces cerevisiae can be used in the prevention and/or reduction of DNA damage.


Description of a new rare alpha-1 antitrypsin mutation in Naples (Italy): PI*M S-Napoli.
Alpha-1 antitrypsin deficiency is a rare and often underdiagnosed hereditary disorder, which mainly affects the Caucasian population. We report a case of a noncystic fibrosis bronchiectasis patient in the absence of emphysema associated with low serum alpha-1-antitrypsin (AAT) level, in the absence of the most common defective alleles associated with AAT deficiency (PI*S and PI*Z) but with a new mutation in heterozygosis. This mutation is characterized by the substitution in the coding region of exon 3, of a guanine (G) for a thymine (T), generating the replacement of a glutamine (Gln) by a histidine (His) in codon 212 (cod 212 GlnCAG > HisCAT), corresponds to a new S allelic variant. This mutation, never identified before, is called S-Napoli.


Management of lone star ticks (Acari: Ixodidae) in recreational areas with acaricide applications, vegetative management, and exclusion of white-tailed deer.
A project on management of lone star ticks, Amblyomma americanum (L.), at Land Between the Lakes, a Tennessee Valley Authority recreational area in Kentucky-Tennessee, during 1984-1988, demonstrated the effectiveness and economics of three control technologies. Acaricide applications (chlorpyrifos at 0.28 kg [AI]/ha), vegetative management (mowing and removal of 40% overstory and 90-100% of midstory, understory, and leaf litter), and host management (white-tailed deer exclusion from a 71-ha campground with a single-line fence) provided 75, 70, and 64% mean controls of all life stages of the lone star tick, respectively. Combinations of acaricide applications + vegetative management, acaricide applications + host management, and acaricide applications + vegetative management + host management produced 94, 89, and 96% mean control of all life stages, respectively. The costs of acaricide applications (two per year), vegetative management (two mowings per year), and white-tailed deer exclusion (single-line fence) were $45, $150, and $30/ha/yr, respectively. Results of this project are used to design management strategies that could be considered for use against lone star ticks in recreational areas.


Genomic Insights Into the Evolution and Demographic History of the SARS-CoV-2 Omicron Variant: Population Genomics Approach.
A thorough understanding of the patterns of genetic subdivision in a pathogen can provide crucial information that is necessary to prevent disease spread. For SARS-CoV-2, the availability of millions of genomes makes this task analytically challenging, and traditional methods for understanding genetic subdivision often fail. The aim of our study was to use population genomics methods to identify the subtle subdivisions and demographic history of the Omicron variant, in addition to those captured by the Pango lineage. We used a combination of an evolutionary network approach and multivariate statistical protocols to understand the subdivision and spread of the Omicron variant. We identified subdivisions within the BA.1 and BA.2 lineages and further identified the mutations associated with each cluster. We further characterized the overall genomic diversity of the Omicron variant and assessed the selection pressure for each of the genetic clusters identified. We observed concordant results, using two different methods to understand genetic subdivision. The overall pattern of subdivision in the Omicron variant was in broad agreement with the Pango lineage definition. Further, 1 cluster of the BA.1 lineage and 3 clusters of the BA.2 lineage revealed statistically significant signatures of selection or demographic expansion (Tajima's D<-2), suggesting the role of microevolutionary processes in the spread of the virus. We provide an easy framework for assessing the genetic structure and demographic history of SARS-CoV-2, which can be particularly useful for understanding the local history of the virus. We identified important mutations that are advantageous to some lineages of Omicron and aid in the transmission of the virus. This is crucial information for policy makers, as preventive measures can be designed to mitigate further spread based on a holistic understanding of the variability of the virus and the evolutionary processes aiding its spread.


Assessment of T- and B-lymphocytes and VEGF-A in acute pancreatitis.
Highlighting certain characteristics of T- and B-lymphocytes, as well as of vascular endothelial growth factor-A (VEGF-A) as a prognosis factors for patients suffering from acute pancreatitis, with the scope of establishing diagnosis and therapy. Pancreatic tissue samples were analyzed, originating from 21 patients deceased due to acute pancreatitis, between the years 2015 and 2016. The study group was subdivided into two subgroups by pathology duration. As control group, pancreatic tissue fragments were sampled from eight patients, deceased due to non-pancreatic acute surgical abdomen (NPASA). By analyzing the immunohistochemical expression of T-lymphocytes (immunomarked with the anti-CD3 antibody) and of B-lymphocytes (immunomarked with the anti-CD20 antibody), both on the tissue sections originating from the study patients, as well as the control group patients, we established that these were mostly present in the interstitium, following which the acini, less frequently in the islets, in general with B-lymphocytes being less present than T-lymphocytes. VEGF-A also tends to emerge in the acini periphery, at the border with the stromal connective tissue, while the islets are almost negative for VEGF-A. We can state that the decreased expression of T- and B-lymphocytes in normal pancreatic tissue, surrounding the necrosis areas, can be used as an aggravated prognosis factor for patients diagnosed with acute pancreatitis. Moreover, the increased immunohistochemical expression of VEGF-A can play an important role in tracking the evolution and pathology of acute pancreatitis.


Craniofacial osteoblast responses to polycaprolactone produced using a novel boron polymerisation technique and potassium fluoride post-treatment.
There is no ideal material for craniofacial bone repair at present. The aim of this study was to test the biocompatibility of polycaprolactone (PCL) synthesised by a novel method allowing control of molecular weight and degradation rate, with regard to it being used as matrix for a biodegradable composite for craniofacial bone repair. Human primary craniofacial cells were used, isolated from paediatric skull after surgery. Cell responses were analysed using various assays and antibody staining. Cells attached and spread on the PCL in a similar manner to the Thermanox controls as shown by phalloidin staining of F-actin. Cells maintained the osteoblast phenotype as demonstrated by alkaline phosphatase assay and antibody staining throughout the time points studied, up to 28 days. Cells proliferated on the PCL as shown by a DNA assay. Collagen-1 staining showed extensive production of a collagen-1 containing extracellular matrix, which was also shown to be mineralised by alizarin red staining. Short-term (up to 48 h) attachment studies and long-term (up to 28 days) expression of markers of the osteoblast phenotype have been demonstrated on the PCL. This new method of synthesising PCL shows biocompatibility characteristics that give it potential to be used for craniofacial bone repair.


Identification of a Mitochondria-Related Gene Signature to Predict the Prognosis in AML.
Mitochondria-related metabolic reprogramming plays a major role in the occurrence, development, drug resistance, and recurrence of acute myeloid leukemia (AML). However, the roles of mitochondria-related genes (MRGs) in the prognosis and immune microenvironment for AML patients remain largely unknown. In this study, by least absolute shrinkage and selection operator (LASSO) Cox regression analysis, 4 MRGs' (HPDL, CPT1A, IDH3A, and ETFB) signature was established that demonstrated good robustness in TARGET AML datasets. The univariate and multivariate Cox regression analyses both demonstrated that the MRG signature was a robust independent prognostic factor in overall survival prediction with high accuracy for AML patients. Based on the risk score calculated by the signature, samples were divided into high- and low-risk groups. Gene set enrichment analysis (GSEA) suggested that the MRG signature is involved in the immune-related pathways. Via immune infiltration analysis and immunosuppressive genes analysis, we found that MRG risk of AML patients was strikingly positively correlated with an immune cell infiltration and expression of critical immune checkpoints, indicating that the poor prognosis might be caused by immunosuppressive tumor microenvironment (TME). In summary, the signature based on MRGs could act as an independent risk factor for predicting the clinical prognosis of AML and could also reflect an association with the immunosuppressive microenvironment, providing a novel method for AML metabolic and immune therapy based on the regulation of mitochondrial function.


Proteinases and their inhibitors in liver cancer.
Proteinases are known to be involved in many cancer-related processes, particularly in the breakdown of extracellular matrix barriers in the course of tumor invasion and metastasis. In this review we summarize the current knowledge about the role of the most important matrix-degrading proteinases (cathepsins, matrix metalloproteinases, plasmin/plasminogen activators) and their respective inhibitors in liver cancer progression and metastasis.


Expression of GARP Is Increased in Tumor-Infiltrating Regulatory T Cells and Is Correlated to Clinicopathology of Lung Cancer Patients.
Regulatory T cells (Tregs) are immunosuppressive T cells that play an important role in immune homeostasis. Multiple markers have been associated with the characterization, as well as function of Tregs. Recently, glycoprotein A repetitions predominant (GARP), a transmembrane protein containing leucine-rich repeats, has been found to be highly expressed on the surface of activated Tregs. GARP maintains Tregs' regulatory function and homeostasis through the activation and secretion of transforming growth factor β. In this study, we investigated the expression of GARP in Tregs from the peripheral blood (PB) and tumor tissues of lung cancer patients. The association between the proportion and expression level of GARP on Tregs and the clinicopathological factors of lung cancer patients was also analyzed. Results showed that in the tumor tissues of patients with lung cancer, GARP expression was increased in Tregs and was associated with lymph node metastasis, distant metastasis, and clinical stage. Furthermore, the infiltrating Tregs from early stage patients exhibited higher GARP expression than that from advanced cancer patients, which indicated that GARP might be an early prognostic biomarker. In vitro coculture studies demonstrated that human lung cancer cell lines might induce the expression of GARP in Tregs by certain mechanisms. Overall, this research demonstrated the potential value of GARP in Tregs definition and cancer immunotherapy.


PIF1 directly and indirectly regulates chlorophyll biosynthesis to optimize the greening process in Arabidopsis.
Plants depend on light signals to modulate many aspects of their development and optimize their photosynthetic capacity. Phytochromes (phys), a family of photoreceptors, initiate a signal transduction pathway that alters expression of a large number of genes to induce these responses. Recently, phyA and phyB were shown to bind members of a basic helix-loop-helix family of transcription factors called phy-interacting factors (PIFs). PIF1 negatively regulates chlorophyll biosynthesis and seed germination in the dark, and light-induced degradation of PIF1 relieves this negative regulation to promote photomorphogenesis. Here, we report that PIF1 regulates expression of a discrete set of genes in the dark, including protochlorophyllide oxidoreductase (POR), ferrochelatase (FeChII), and heme oxygenase (HO3), which are involved in controlling the chlorophyll biosynthetic pathway. Using ChIP and DNA gel-shift assays, we demonstrate that PIF1 directly binds to a G-box (CACGTG) DNA sequence element present in the PORC promoter. Moreover, in transient assays, PIF1 activates transcription of PORC in a G-box-dependent manner. These data strongly suggest that PIF1 directly and indirectly regulates key genes involved in chlorophyll biosynthesis to optimize the greening process in Arabidopsis.


Preparation and characterisation of tetrandrine nanosuspensions and in vitro estimate antitumour activity on A549 lung cancer cell line.
Aim: The aim of this study was to improve solubility and antitumour ability in vitro of tetrandrine (Tet) via preparing nanosuspensions (NSs).Methods: The Tet-NSs were prepared by wet media milling. The Tet-CCS-NS was prepared with croscarmellose sodium (CCS) as single stabiliser. The Tet-HACC-TPGS-NS was manufactured with D-α-tocopheryl polyethylene glycol 1,000 succinate (TPGS) and hydroponically trimethyl ammonium chloride chitosan (HACC) as combined stabilisers. Physicochemical properties of the NSs such as particle size, surface morphologies, crystallinity and molecular interactions were investigated. In addition, the in vitro dissolution and antitumour activities using A549 human lung cancer cells were evaluated.Results: The mean particle sizes and Zeta potential of freshly prepared Tet-CCS-NS, Tet-HACC-TPGS-NS were 469.1 ± 14nm and 157.3 ± 5nm, -29.4 ± 0.26 mV and 23.3 ± 0.36 mV, respectively. In comparison to pure Tet, the cumulative dissolution of Tet-NSs were increased by 4 ∼ 5 times in 2 h. In vitro antitumour studies on Tet- NSs in A549 cells, the cell survival rate of the Tet-NSs at high concentration (30-50µg/ml) were less than 10% within 48 h. Meanwhile, Tet-NSs were revealed to induce A549 cells apoptosis and promote cell uptake.Conclusion: The present study has proved that the Tet-NSs can increase Tet solubility as well as improve Tet antitumour activity in vitro.


Cardioprotective effect of nesfatin-1 against isoproterenol-induced myocardial infarction in rats: Role of the Akt/GSK-3β pathway.
The present study was designed to evaluate the cardioprotective effects of nesfatin-1, a novel peptide with anorexigenic properties, in rats with isoproterenol (ISO)-induced myocardial infarction (MI), and to further investigate the role of Akt/GSK-3β signaling pathway in the protective effect of nesfatin-1. To induce MI, ISO was subcutaneously injected into the rats for two consecutive days at a dosage of 85mg/kg/day. ISO-induced myocardial damage was indicated by elevated levels of cardiac specific troponin-T, enhanced myocardial expression of proinflammatory cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α), and increased number of cells with apoptotic and necrotic appearance in the myocardial tissue. Levels of p-Akt/Akt and p-GSK-3β/GSK-3β significantly decreased in heart tissue after ISO-induced MI. However, intraperitoneal administration of nesfatin-1 (10μg/kg/day) elicited a significant cardioprotective activity by lowering the levels of cardiac troponin-T and proinflammatory cytokines, indicating the protective effect of nesfatin-1 against ISO-induced MI. The biochemical findings were further confirmed by histopathological examination, which was demonstrated by reduced number of apoptotic and necrotic cells. Moreover, expressions of p-Akt/Akt and p-GSK-3β/GSK-3β in the myocardium of MI group rats were significantly increased by nesfatin-1 administration, suggesting that nesfatin-1, which appears to possess anti-apoptotic and anti-inflammatory properties, may confer protection against ISO-induced MI via an Akt/GSK-3β-dependent mechanism.


Nalorphine as a stimulus in drug discrimination learning: assessment of the role of mu- and kappa-receptor subtypes.
Using the conditioned taste aversion baseline of drug discrimination learning, animals were trained to discriminate nalorphine from distilled water. In subsequent generalization tests, the mu-opiate agonist morphine substituted for the nalorphine stimulus in a dose-dependent manner, while the kappa-opiate agonist U50,488H and the mu-opiate antagonists naloxone and naltrexone failed to do so. That the mu-agonist morphine substituted for the nalorphine stimulus while a kappa-agonist and mu-antagonists failed to substitute indicate that the discriminative control that was established with nalorphine in the present study was mu-agonist receptor-mediated. The basis for this selective control by the mu-receptor subtype may be related to the relative salience of receptor activity in opiate-naive animals. The present results suggest that discriminative control by compounds with activity at multiple receptor sites is not uniformly mediated by specific activity at all of those sites. The specific site mediating discriminative control appears to be a function of the specific training drug.


Acute urinary retention: risks and management.
Acute urinary retention (AUR) secondary to benign prostatic hyperplasia has in the past represented an immediate indication for surgery, and today most patients failing to void after an attempt at catheter removal still undergo surgery. The concept that this disease is in fact progressive in nature is slowly being accepted. Descriptive and analytical epidemiological data have shown that the incidence rate per 1000 person-years is less variable in the community than previously assumed; however, the risk is cumulative and increases with advancing age. The risk for patients diagnosed with benign prostatic hyperplasia is naturally higher, and analytical epidemiology has identified several strong risk factors, the most important one being serum prostate-specific antigen (PSA). In addition, prostate volume, maximum flow rate, and symptom severity should be considered when counseling patients presenting with lower urinary tract symptoms and clinical benign prostatic hyperplasia who are considering a course of watchful waiting. Efforts toward primary prevention of AUR should be directed to patients at increased risk, ie, those who are older and have more severe symptoms, larger glands, and higher PSA values. Risk reduction with finasteride has been demonstrated, and alpha-blockers have been shown to aid patients in achieving spontaneous voiding after an episode of AUR.


Effect of converting enzyme inhibition with captopril on baroreflex sensitivity.
Clinical and experimental data suggest that both Captopril and angiotensin II (AII) reduce baroreflex responsiveness, and the main action of this converting enzyme inhibitor (CEI) seems clear to suppress AII synthesis. The aim of this work is to investigate this striking similarity of effects. We have verified that CEI (4 mg/kg) originates tachycardia significantly lower (P less than 0.001) than that produced in response to a similar hypotension elicited by an unspecific vasodilator: sodium nitroprusside (10-45 micrograms/kg min). CEI SQ 20881 has been reported to increase plasma vasopressin concentrations (AVP); this peptide is also known to modify baroreflex responses and has a small direct negative chronotropic effect. However, our determinations of AVP do not show any difference between the control group and the group treated with Captopril (4.78 +/- 0.87 and 5.26 +/- 0.19 pg/ml respectively). On the other hand, although CEI did not modify the rapid responses of heart rate (HR) to changes of mean arterial pressure (MAP), the decrease of MAP induced by nitroprusside was higher in the group treated with Captopril than in control group; it could mean a baroreflex ability decrease to buffer the hypotension. However, AII elicited a strong impairment of both rapid responses of HR and the buffering of hypotension produced by NP, these actions being suggested as centrally mediated. These results could indicate that the suppression of peripheral AII synthesis and therefore, the lack of pre- and postjunctional sympathetic potentiation owing to this hormone, is responsible for the absence of tachycardia under Captopril treatment.


Trauma-induced filtering bleb formation and blebitis 40 years following a penetrating eye injury.
A 49-year-old man presented to the emergency eye clinic with a 3-week history of redness, irritation and blurred vision in his right eye, with a noticeable lesion superotemporally on the conjunctiva. He had a previous ocular history of penetrating glass injury in the right eye at the age of 9 years (40 years ago), of which no surgical intervention was performed at that time, as his parents did not seek medical attention. Slit lamp examination revealed a thin, conjunctival cystic bleb at 10 o'clock position with surrounding conjunctival injection and chemosis at close proximity to the site of previous ocular trauma. Investigations confirmed a diagnosis of trauma-induced filtering bleb with blebitis (bleb inflammation). The patient was treated with a combination of steroid and antibiotic drops for duration of 2 weeks. Subsequent follow-up revealed marked improvement of symptoms with reduced inflammation. Patient is being monitored regularly to prevent recurrence of blebitis and bleb associated complications.


[Effect of nylestriol on bone remodeling in ovariectomized rats].
To clarify the effects of nylestriol on microarchitecture and interleukin-6 (IL-6) mRNA expression in tibial bone in ovariectomized rats. 30 female rats were randomly allocated into 3 groups: sham, OVX and nylestriol-treated group. Nylestriol-treated group were ovariectomized, then fed with nylestriol for 3 months and the bone mineral density (BMD) was measured in lumbar vertebra by dual energy x-ray absorptiometry. After sacrifice of the animal, bone histomorphometric parameters were measured to study the changes in bone microarchitecture, and RT-PCR was performed to detect the expression of IL-6 mRNA in bone tissue. BMD was significantly reduced, while IL-6 mRNA level elevated in the OVX group compared with the sham group. Static histomorphometric data showed that the trabecular bone volume, mean trabecular plate thickness and density were reduced while the mean trabecular plate space elevated remarkably in the OVX group in comparison with that in the sham group. As for dynamic parameters, trabecular osteoid surface, tetracyclin labeled surface and bone turnover rate were increased while osteoid maturation rate decreased significantly in the OVX group compared with the sham group. BMD, IL-6 mRNA expression and bone histomorphometric parameters were improved in nylestriol-treated rats. Nylestriol plays an important role in maintaining bone volume and improving bone microarchitecture by markedly inhibiting bone turnover and bone resorption, which might be to some degree attributed to reduced IL-6 expression.


Outcome of a latex avoidance program in a high-risk population for latex allergy - a five-year follow-up study.
Children with a shunted hydrocephalus are at highest risk for developing an immediate type allergy to latex. Limited data are available for preventive or therapeutical approaches. To evaluate the effectiveness of latex avoidance, with special regard to status of sensitization and compliance. In 1995, 131 children with a shunted hydrocephalus were screened for sensitization to latex by skin prick test and determination of specific IgE. Patients and parents were instructed on latex-avoiding strategies. Hospital physicians, family doctors and dentists were advised to perform further surgical and other medical interventions under latex-free conditions. In 2000, 100 of these 131 patients were re-evaluated according to the same testing procedures. Special attention was directed at the extent prophylaxis had been performed. In 1995, 30/100 patients re-evaluable in 2000 proved sensitized to latex, 70 had negative testing results. In 2000, 64/70 patients were still negative, six had meanwhile developed latex-specific IgE. Seven out of thirty subjects with former positive testing had changes within the same RAST-class, 20 showed a decline of at least one RAST-class, whereas in three cases an increase of latex-specific IgE was found. However, only 34 patients, mainly those being already sensitized, had thoroughly followed both medical and private prophylaxis. Within this group, 16 subjects (47.1%) had improved and another nine (26.5%) were still negative. Only three (8.8%) already previously sensitized patients presented with a further increase of latex-specific IgE. Medical prevention contributed more to the outcome than home prevention. No statistically significant correlation with latex-avoidance was observed, however, in previously unsensitized subjects. Underlying disease, atopy, number of operations, and age did not prove as significant variables. Secondary prevention results in a decrease of specific IgE in latex-sensitized patients with hydrocephalus. This is due to medical more than home prophylaxis. Sensitization obviously occurs mainly in early childhood, thus primary prevention remains to be the main target.


Dosimetry of 125I sources in a low-density material using scaling.
One may apply O'Connor's scaling theorem to dose measurements with brachytherapy sources in order to overcome the difficulties associated with the need for high spatial accuracy. This possibility has been evaluated by measuring the dose distribution around 125I sources in a low-density styrofoam phantom and comparing it with the dose distributions in water and solid water. Some generalization of the scaling theorem is proposed to allow for the minor differences in atomic composition between styrofoam and water, and the distances are scaled according to the ratio of the linear attenuation coefficients, instead of the physical densities, of the two media. The validity of this application of the scaling theorem has also been tested using Monte Carlo calculations. The results indicate that the scaling of the styrofoam measurements to water is a useful approximation in brachytherapy dosimetry.


Value of the Petromeatal Angle in Predicting Outcome of Translabyrinthine Resection of Vestibular Schwannomas.
Factors associated with extent of tumor resection (EOR) and facial nerve outcomes include tumor size, anterior extension of the tumor, patient age, and surgical approach. To check whether preoperative measurement of the petromeatal (PMA), petroclival (PCA), and petrous-petrous (PPA) angles can help in predicting EOR, facial nerve outcome, and cerebrospinal fluid (CSF) leak occurrence in patients undergoing vestibular schwannoma (VS) surgery via the translabyrinthine approach (TLA). A total of 75 patients were included in this retrospective study. Preoperative magnetic resonance imaging constructive interface in steady state and postcontrast T1-weighted sequences through the internal acoustic meatus were used to measure the PMA, PCA, and PPA. There was a statistically significant association between tumor size and EOR; every additional cm in tumor size decreases the odds of gross-total (GTR)/near-total (NTR) resection by 524% (P = .0000355).After controlling for tumor size, the logistic models revealed a significant effect of the angles on EOR. For example, in a patient with a 2-cm VS, every additional degree in PMA, PCA, and PPA increases the odds of GTR/NTR by 2.3% (P = .0000571), 4.05% (P = .0000397), and 0.37% (P = .0000438), respectively.After adjusting for tumor size, sex, and age, the effect of PMA on the occurrence of an immediate postoperative facial nerve deficit and CSF leak indicated a trend towards significance (P = .0581 and P = .0568, respectively). More obtuse petrous bone angles, namely PMA, PCA, and PPA, are good predictors of GTR or NTR in patients undergoing VS surgery via TLA and may be associated with better facial nerve outcomes and lower CSF leak occurrences.


The building of the neocortex with non-hyperpolarizing neurotransmitters.
The development of the neocortex requires the synergic action of several secreted molecules to achieve the right amount of proliferation, differentiation, and migration of neural cells. Neurons are well known to release neurotransmitters (NTs) in adult and a growing body of evidences describes the presence of NTs already in the embryonic brain, long before the generation of synapses. NTs are classified as inhibitory or excitatory based on the physiological responses of the target neuron. However, this view is challenged by the fact that glycine and GABA NTs are excitatory during development. Many reviews have described the role of nonhyperpolarizing GABA at this stage. Nevertheless, a global consideration of the inhibitory neurotransmitters and their downstream signaling during the embryonic cortical development is still needed. For example, taurine, the most abundant neurotransmitter during development is poorly studied regarding its role during cortical development. In the light of recent discoveries, we will discuss the functions of glycine, GABA, and taurine during embryonic cortical development with an emphasis on their downstream signaling. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1023-1037, 2017.


Effects of Granulated Lactose Characteristics and Lubricant Blending Conditions on Tablet Physical Properties in Direct Powder Compression.
Lactose is an excipient used extensively for bulking, diluting, and molding active pharmaceutical ingredients in tablet manufacturing. Particularly, granulated lactose (GL) intended for direct powder compression has distinct properties due to differences in manufacturing methods. It contributes to handling blended powders for tableting and tablet quality. In this study, we aimed to compare the functions of different forms of GL added as excipients during direct powder compression on the tablet properties and the effect of magnesium stearate (Mg-S) used as a lubricant on each type of GL. Different GL types obtained using different manufacturing methods (agitated granulation, GL-AG; spray-dried granulation, GL-SD; fluidized bed granulation, GL-FB) were blended with maize starch, low-substituted hydroxypropyl cellulose, and paracetamol in a V-type blender for 10 min. Mg-S was added at varying amounts (0.1, 1.0, and 2.0%) and blending times (5, 10, and 30 min) for the nine types of blended powders for tableting formulation. The powders were tableted, and the tablets were evaluated for weight and drug loading variations, tensile strength, friability, and disintegration time. When tablets with the same blending conditions were compared, the tensile strength and disintegration time were in the order of GL-FB > GL-SD > GL-AG. For each GL, we analyzed the effects of changes in the added amount of Mg-S and blending time using contour plots, evaluated the effects of blending conditions on tablet properties, and determined the target tablet properties. We investigated the optimization of the lubricant blending conditions to obtain suitable tablets.


Cerebral abscess associated with stranding in a dolphin.
A captive Atlantic bottlenosed dolphin (Tursiops truncatus) was examined after being found beached in the shallows of its lagoon enclosure. An abscess was found in the right cerebral hemisphere, and Staphylococcus aureus was isolated from the lesion. Histopathologic examination of the brain revealed a pyogenic meningoencephalitis.


Meta-analysis on the effectiveness of extra time as a test accommodation for transitioning adolescents with learning disabilities: more questions than answers.
The accommodation of students with learning disabilities (LD) on mandatory high stakes tests continues to heighten concern over the equity and effectiveness of current practices. As students transition from high school, they are required to complete timed graduation tests and postsecondary entrance examinations. The most common accommodation accessed by transitioning adolescents with LD is extended time. In order to inform test accommodation practices, a meta-analysis was conducted to address whether test scores from accommodated (i.e., extended time only) and standard test administrations are comparable for transitioning adolescents with LD as compared to their normally achieving peers. The results of the meta-analyses raised more questions than answers and highlighted the need for future research in this area.


Amino acid side chain interaction with chelate-liganded crosslinked dextran, agarose and TSK gel. A mini review of recent work.
Protein adsorption and retention data collected from recent chromatographic studies on hydrophilic gels substituted with chelate-bonded metal ions are discussed. Attempts are made to interpret the adsorption behavior in terms of molecular events caused by the affinity for the immobilized metal ions.


Motivation and Behaviors Related to Sport Specialization in College Baseball Players.
Early sport specialization is a growing concern among youth sports athletes, particularly in baseball. Motivation to participate in sports is an important factor in determining which sports youth athletes participate in and why. The purpose of this study was to qualitatively investigate youth sport participation behaviors and motivations of college baseball players. Qualitative Study. Online Teleconference. We conducted 25 semi-structured interviews with college baseball athletes who were classified as either high-level (n=8), moderate-level (n=9), or low-level specialists (n=8) prior to college. Participants completed an individual semi-structured interview to develop an understanding of the participants' youth and high school sports experiences and associated motivations to participate in those experiences. A framework analysis approach was used to analyze transcript data to identify themes among the three specialization groups. From our interview analysis, six overall themes emerged among the groups: (1) Motivation, (2) Stress, (3) Quitting, (4) Barriers, (5) Facilitators of Success, and (6) Future Directions. Moderate and high-level specialists described higher levels of passion, participating in deliberate practice, higher levels of performance-related stress, and a desire to quit sports more than low-level specialists. None of the groups described parents as an overbearing external motivator to participate in sports at an early age. Participants who were classified as low-, moderate-, and high-level specialists described different experiences related to their motivation, stress levels, desire to quit, barriers to participating in baseball, facilitators of success, and their overall future career goals after completing baseball. This information may be useful for parents, coaches, and health care professionals to better communicate the benefits and risks associated with sport specialization to youth athletes. Future research is needed to determine if differences in motivation levels exist in younger populations.


[A case of advanced rectal cancer treated with leucovorin, fluorouracil, and oxaliplatin plus panitumumab preoperative chemotherapy].
A 58-year-old woman had a very large advanced rectal cancer( with wild-type K-RAS expression). Abdominal computed tomography( CT) revealed a space-occupying lesion in the pelvis and an enlarged lymph node. We established a diagnosis of unresectable rectal cancer and subsequently performed transverse colostomy. The patient received 6 courses of Leucovorin, fluorouracil, and oxaliplatin( mFOLFOX6) plus panitumumab( Pmab), 2 courses of simplified Leucovorin plus 5-fluorouraci(l sLV5-FU) plus Pmab, and 1 course of Pmab. The size of the primary tumor decreased remarkably after chemotherapy. Low anterior resection was performed. The pathological stage was T4a, N0, M1, Stage IVa. The results from this case suggest that mFOLFOX6 plus Pmab preoperative chemotherapy is a useful regimen for the treatment of locally advanced K-RAS wild-type rectal cancer.


Interleukin-1 receptor antagonist is associated with both lipid metabolism and inflammation in rheumatoid arthritis.
There is a relationship between cardiovascular morbidity, inflammatory activity, and changes in the lipid profile in rheumatoid arthritis (RA), although the mechanisms are not fully elaborated. Recent know-ledge that white adipose tissue (WAT) is a producer of immunologically and metabolically active substances gives another perspective to study. To evaluate the relationship between interleukin-1 receptor antagonist (IL-1Ra) and variables associated with WAT and inflammation in RA. Anthropometric, inflammatory and metabolic variables were assessed in 23 women with RA and 23 matched controls. Spearman, partial correlation and factor analyses were performed. Inflammatory markers were increased in patients. In both groups, IL-1Ra correlated with leptin independent of age and BMI. IL-1Ra also correlated with haptoglobin and apolipoprotein (Apo) B in patients and with soluble TNF receptor (sTNFR) 1 in controls. In factor analysis, three latent factors were identified among patients. The first loaded on IL-1Ra, leptin, BMI, ApoB and body fat content (BF%), the second loaded on IL1-Ra and sTNF-receptors and the third showed inverse loadings on ApoA-I together with loadings on ESR, haptoglobin, orosomucoid, BF% and BMI. IL-1Ra was associated with markers of inflammation and with fat-related factors in RA patients, suggesting a dualistic relationship of IL-1Ra in RA. IL-1Ra correlated independently with leptin in both patients and controls, indicating a relationship between inflammation and leptin.


Metallophilic interactions in silver(I) dicyanoaurate complexes.
This manuscript reports four new gold(I)-silver(I) complexes with 2-(2-pyridyl)-1,8-naphthyridine (pyNP) and terpyridine (terpy) as ancillary ligands, having formulae [Ag(pyNP)(Au(CN)2)]2 (1), [Ag2Au2(μ-CN)2(CN)2(pyNP)2] (2), [Ag2Au(μ-CN)2(terpy)2][Au(CN)2] (3) and [Ag4Au4(μ-CN)8(terpy)2(py)] (4). Complexes 1 and 2 are structural isomers obtained from different solvents. The Au(CN)2- anion is not coordinated and establishes intramolecular Au⋯Ag,Ag interactions in 1. In contrast, it is monocoordinated to silver atoms via a CN fragment in compound 2 and no metallophilic interaction is observed. In compound 3, one Au(CN)2 anion bridges two Ag(terpy) fragments. In this complex an infinite array of gold atoms is found, exhibiting aurophilic interactions of 3.415 Å. In complex 4 the 3D architecture observed in the crystal packing is driven by Au⋯Au and Au⋯Ag metallophilic interactions. All compounds have been structurally and vibrationally characterized to better understand the crystal forces. In addition, a solution chemistry study in different solvents by ESI-MS spectrometry was performed to comprehend the speciation and solvent effects. Finally, DFT calculations were carried out to analyze the Ag⋯Au interactions and also the π-stacking interactions that are relevant in the crystal packing of some structures. Special attention has been paid to the bifurcated nature of the Au⋯Ag,Ag interactions in compound 1 that has been analyzed theoretically using the quantum theory of atoms-in-molecules (QTAIM) and the Natural Bond Orbital (NBO) computational tools.


Subtle changes in motif positioning cause tissue-specific effects on robustness of an enhancer's activity.
Deciphering the specific contribution of individual motifs within cis-regulatory modules (CRMs) is crucial to understanding how gene expression is regulated and how this process is affected by sequence variation. But despite vast improvements in the ability to identify where transcription factors (TFs) bind throughout the genome, we are limited in our ability to relate information on motif occupancy to function from sequence alone. Here, we engineered 63 synthetic CRMs to systematically assess the relationship between variation in the content and spacing of motifs within CRMs to CRM activity during development using Drosophila transgenic embryos. In over half the cases, very simple elements containing only one or two types of TF binding motifs were capable of driving specific spatio-temporal patterns during development. Different motif organizations provide different degrees of robustness to enhancer activity, ranging from binary on-off responses to more subtle effects including embryo-to-embryo and within-embryo variation. By quantifying the effects of subtle changes in motif organization, we were able to model biophysical rules that explain CRM behavior and may contribute to the spatial positioning of CRM activity in vivo. For the same enhancer, the effects of small differences in motif positions varied in developmentally related tissues, suggesting that gene expression may be more susceptible to sequence variation in one tissue compared to another. This result has important implications for human eQTL studies in which many associated mutations are found in cis-regulatory regions, though the mechanism for how they affect tissue-specific gene expression is often not understood.


The Effects of the Putative Confession and Parent Suggestion on Children's Disclosure of a Minor Transgression.
This study examined the effects of the putative confession (telling the child that an adult "told me everything that happened and he wants you to tell the truth") on children's disclosure of a minor transgression after questioning by their parents. Children (N = 188; 4 - 7-year-olds) played with a confederate, and while doing so, for half of the children, toys broke. Parents then questioned their children about what occurred, and half of the parents were given additional scripted suggestive questions. Finally, children completed a mock forensic investigative interview. Children given the putative confession were 1.6 times more likely in free recall to disclose truthfully that toys had broken. Among children who failed to disclose during free recall, those who received the putative confession were 1.9 times more likely when asked yes/no questions to disclose true breakage. The putative confession did not decrease accuracy, and children who received the putative confession were 2.6 times less likely to report false toy play. Parent suggestion did not adversely affect the efficacy of the putative confession. The current study demonstrates that children are often quite reticent to disclose transgressions, and that the putative confession is a promising avenue for increasing children's comfort with disclosing and minimizing their tendency to report false details, even in the face of suggestive questioning by parents.


Stereocontrolled Synthesis of Amino-Substituted Carbocycles by Pd-Catalyzed Alkene Carboamination Reactions.
Amino-substituted alkylidenecyclopentanes were synthesized through a stereoselective intermolecular Pd-catalyzed alkene carboamination reaction between alkenyl triflates bearing a pendant alkene and exogenous amine nucleophiles. The reactions are effective with a range of different substrate combinations, and proceed with generally high diastereoselectivity. Use of (S)-tBuPhox as the ligand in reactions of achiral substrates provides enantioenriched products with up to 98.5:1.5 e.r.


Structural and Thermodynamic Model for the Activation of Cardiac Troponin.
Cardiac troponin is a regulatory protein complex located on the sarcomere that regulates the engagement of myosin on actin filaments. Low-molecular weight modulators of troponin that bind allosterically with the calcium ion have the potential to improve cardiac contractility in patients with reduced cardiac function. Here we propose an approach to the rational design of troponin modulators through the combined use of solution nuclear magnetic resonance and isothermal titration calorimetry methods. In contrast to traditional approaches limited to calcium and activator-bound troponin structures, here we analyzed the structural and thermodynamic impact of an activator in the context of the troponin functional cycle. This led us to propose a rationale for developing an efficacious troponin activator.


Phase II study of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) therapy for newly diagnosed patients with low- and low-intermediate risk, aggressive non-Hodgkin's lymphoma: final results of the Japan Clinical Oncology Group Study, JCOG9508.
The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone, known as CHOP therapy, has been established as the standard treatment for aggressive non-Hodgkin's lymphoma (NHL). Although patients categorized as low (L) and low-intermediate (L-I) risk using the International Prognostic Index have favorable prognoses in Western countries, the efficacy and safety of CHOP therapy has not been prospectively evaluated in Japan. We conducted a phase II study of CHOP in L and L-I risk Japanese patients, evaluating overall survival (OS) as the primary endpoint. A total of 213 patients were enrolled and treated with eight courses of CHOP. Efficacy was evaluated in 168 eligible patients (L risk, 87; L-I risk, 81). Five-year OS rates in all eligible, L, and L-I risk patients were 68 % [95 % confidence interval (CI): 61-76 %], 73 % (95 % CI: 63-82 %), and 64 % (95 % CI: 53-74 %), respectively. The major toxicity observed was grade 4 neutropenia (64 %). Grade 4 non-hematological toxicities were observed as follows: one case each of paralytic ileus, convulsions, hypoxemia due to interstitial pneumonia, and reactivated fulminant hepatitis B. These results show reasonable efficacy and safety of the CHOP regimen in Japanese patients with lower risk aggressive NHL (UMIN-CTR Number C000000053).


Photosensitivity and biosynthesis of indole compounds in the cells of the receptor line of the pineal organ of the pike.
The pineal organ of the pike is a functional photoreceptive organ in which a multiplicity of the cells of the receptor line (CRL i.e. typical and modified photoreceptors) was demonstrated. The CRL appeared to be (i) regionally distributed, (ii) photosensitive, and (iii) responsible for the storage of various indoles (melatonin and precursors), their levels showing light-dark fluctuations. It is strongly suggested that CRL are photoneuroendocrine transducers in which photoperiodic stimuli are converted into nervous (typical photoreceptors) and neurohumoral (all CRL) messages, displaying circadian variations. CRL appeared to be one of the components by which environmental lighting influences physiological and behavioral processes in fish.


Protein C activity and postoperative metabolic liver function after liver transplantation.
Protein C is a natural thrombin antagonist produced by hepatocytes. Its levels are low in liver failure and predispose patients to increased risk for thrombosis. Little is known about the relationship between protein C activity and hepatic function after orthotopic liver transplantation (OLT). We measured protein C activity of 41 patients undergoing liver transplantation by the Staclot method (normal range, 70%-130%) preoperatively and then daily on postoperative days (POD) 0-5. The mean protein C activity was low before OLT (34.3 ± 4.3%) and inversely correlated with the preoperative Model for End-Stage Liver Disease score (Spearman's r = -0.643; P < .0001). Mean activity increased significantly on POD 1 (58.9 ± 4.5%), and remained above preoperative levels through POD 5. Ten patients developed metabolic liver dysfunction defined by a serum total bilirubin >5 mg/dL on POD 7. These patients had significantly lower protein C activity from POD 3 (47.2 ± 9.6% vs 75.9 ± 5.8%; P = .01) to POD 5. Preoperative protein C activity correlated inversely with the severity of liver failure as indicated by preoperative MELD score. Protein C activity recovered rapidly in patients with good allograft function but remained significantly lower in patients who had limited metabolic function as evidenced by increased total bilirubin levels.


A novel approach in root coverage - Coronally repositioned flap with GTR membrane and frenotomy.
This case report describes a guided tissue regeneration (GTR) based root coverage procedure over maxillary central incisor using coronally advanced flap with simultaneously performed frenotomy. The patient was a 32-year-old female with chief complaint of gingival enlargement in relation to 11. Based on overall findings it was diagnosed as a case of inflammatory gingival enlargement. Vertical osseous defect along with Millers class I gingival recession was seen after initial therapy. GTR-based root coverage procedure using coronally advanced flap with simultaneously performed frenotomy was planned. Complete root coverage was achieved over the maxillary central incisor that initially presented with Miller's class I gingival recession along with radiographic bone fill of the osseous defect. This case report shows the possibility of applying GTR-based root coverage procedure using coronally advanced flap combined with frenotomy to treat Millers class I gingival recession.


Photophysical properties of the ReI and RuII complexes of a new C60-substituted bipyridine ligand.
The rhenium(I) and ruthenium(II) complexes of a fullerene-substituted bipyridine ligand have been prepared. Electrochemical studies indicate that some ground state electronic interaction between the fullerene subunit and the metal-complexed moiety are present in the Re(I) but not the Ru(II) complex. The photophysical properties have been investigated by steady-state and time-resolved UV/Vis-NIR luminescence spectroscopy and nanosecond laser flash photolysis in CH2Cl2 solution, and compared to those of the corresponding model compounds. Excitation of the methanofullerene moiety in the dyads does not lead to excited state intercomponent interactions. Instead, excitation of the metal-complexed unit shows that the lowest triplet metal-to-ligand-charge-transfer excited state ((3)MLCT) centered on the Re(I)- or Ru(II)-type unit is quenched with a rate constant of about 2.5 x 10(8) s(-1). The quenching is attributed to an electron-transfer (ElT) process leading to the reduction of the carbon sphere, as determined by luminescence spectroscopy for the Ru(II) dyad. Experimental detection of electron transfer in the Re(I) dyad is prevented due to the unfavorable absorption of the metal-complexed moiety relative to the fullerene unit. However, it can be postulated on the basis of energetic/kinetic arguments and by comparison with the Ru(II)-type array. The primary ElT process is followed by charge-recombination to give the lowest-lying fullerene triplet excited state (3C60) with quantitative yield, as determined by sensitized singlet oxygen luminescence experiments. Direct (3)MLCT-->3C60 triplet-triplet energy-transfer (EnT) does not successfully compete with ElT since it is highly exoergonic and located in the Marcus inverted region. The quantum yield of singlet oxygen sensitization (Phi(delta)) of the Re(I)-based dyad is found to be lower (0.80) than for the corresponding Ru(II) derivative (1.0). This is likely to be the consequence of different conformational structures for the two dyads, rather than a different yield of 3C60 formation.


Feline leukemia and RD-114 virus group-specific proteins: comparison of amino terminal sequence.
The major internal virion polypeptide from feline and RD-114 type C viruses has been subjected to amino terminal sequence analyses with the Beckman automated sequencer. These proteins, as well as their homologs in rat and mouse viruses, begin with the sequence prolylleucylarginyl (Pro-Leu-Arg). Virus RD-114 differs from conventional feline type C viruses that show about 80 percent relatedness based on calculation of the minimum number of base changes to give equivalent coding for the protein segments analyzed. In addition, insertion of a gap in the RD-114 sequence is necessary to maintain positional homology. The difference between RD-114 and feline leukemia virus appears as great as the difference between mouse type C viruses and either of these two viruses. Thus, even though current evidence suggests that RD-114 is of feline origin, the sequence differences between RD-114 and conventional feline virus group-specific proteins is well beyond that based on one or a few point mutations.


Cyclodextrin solubilization in hydrated reline: Resolving the unique stabilization mechanism in a deep eutectic solvent.
By complexing with hydrophobic compounds, cyclodextrins afford increased solubility and thermodynamic stability to hardly soluble compounds, thereby underlining their invaluable applications in pharmaceutical and other industries. However, common cyclodextrins such as β-cyclodextrin, suffer from limited solubility in water, which often leads to precipitation and formation of unfavorable aggregates, driving the search for better solvents. Here, we study the solvation of cyclodextrin in deep eutectic solvents (DESs), environmentally friendly media that possess unique properties. We focus on reline, the DES formed from choline chloride and urea, and resolve the mechanism through which its constituents elevate β-cyclodextrin solubility in hydrated solutions compared to pure water or dry reline. Combining experiments and simulations, we determine that the remarkable solubilization of β-cyclodextrin in hydrated reline is mostly due to the inclusion of urea inside β-cyclodextrin's cavity and at its exterior surfaces. The role of choline chloride in further increasing solvation is twofold. First, it increases urea's solubility beyond the saturation limit in water, ultimately leading to much higher β-cyclodextrin solubility in hydrated reline in comparison to aqueous urea solutions. Second, choline chloride increases urea's accumulation in β-cyclodextrin's vicinity. Specifically, we find that the accumulation of urea becomes stronger at high reline concentrations, as the solution transitions from reline-in-water to water-in-reline, where water alone cannot be regarded as the solvent. Simulations further suggest that in dry DES, the mechanism of β-cyclodextrin solvation changes so that reline acts as a quasi-single component solvent that lacks preference for the accumulation of urea or choline chloride around β-cyclodextrin.


Erythroferrone: the missing link in β-thalassemia?
In this issue of Blood, Kautz et al show that the ablation of the erythroid-derived factor erythroferrone (ERFE), which has been shown to be highly expressed in β-thalassemic mice, restores hepcidin levels and corrects iron overload. However, correction of hepcidin levels in those mice does not improve anemia of β-thalassemia.


Is Health Promotion a Journey or a Destination?
Recent data on our progress in workplace-based health promotion should keep us grounded as we consider whether we are on track to planned destinations. One recent survey suggests employees view worksite wellness as a valuable employee benefit but another survey suggests employees are dissatisfied with their employers' wellness offerings. What explains these differences? Is the program driven by a plan? Is the plan relevant to the company's priorities? Was the plan developed using participatory planning principles?" A participant centered health promotion initiative means deciding a destination and planning how to get there alongside those you aspire to serve. This approach is far more likely to lead to alternative routes and, often, untested sources of data for finding the way. The urgent opportunity for workplace-based program planners is that of strategic planning that is guided by a continuous review of credible metrics such as those offered in best practices scorecards.


Stomatal behavior of ozone-sensitive and -insensitive coneflowers (Rudbeckia laciniata var. digitata) in Great Smoky Mountains National Park.
* Morphological and physiological attributes were assessed to elucidate the underlying mechanisms of ozone (O(3)) sensitivity in a highly sensitive species, cutleaf coneflower (Rudbeckia laciniata var. digitata). * Foliage at the same height in the canopy on paired O(3)-sensitive and -insensitive cutleaf coneflowers was assessed for level of foliar symptoms, stomatal density, stomatal responsiveness to dynamic changes in light and leaf-to-air vapor pressure deficit (VPD), steady-state responses to light and CO(2), intrinsic transpirational efficiency, and plant water balance. * There were no morphological differences between the sensitivity types that might have contributed to greater O(3) uptake in sensitive individuals. Stomata of sensitive plants were less responsive than those of insensitive plants to experimentally increased and decreased light intensities, and to increased VPD. O(3)-insensitive plants had greater intrinsic transpirational efficiencies, greater maximum assimilation rates under saturating CO(2) and light, and greater carboxylation rates. * Different physiological attributes vary independently within an individual plant, which collectively confer sensitivity or insensitivity to O(3) injury.


Price discounting as a hidden risk factor of energy drink consumption.
Global consumption of caffeinated energy drinks (CED) has been increasing dramatically despite increasing evidence of their adverse health effects. Temporary price discounting is a rarely investigated but potentially powerful food marketing tactic influencing purchasing of CED. Using grocery transaction records generated by food stores in Montreal, we investigated the association between price discounting and purchasing of CED across socio-economic status operationalized by education and income levels in store neighbourhood. The outcome, log-transformed weekly store-level sales of CED, was modelled as a function of store-level percent price discounting, store- and neighbourhood-level confounders, and an interaction term between discounting and each of tertile education and income in store neighbourhood. The model was separately fit to transactions from supermarkets, pharmacies, supercentres, and convenience stores. There were 18,743, 12,437, 3965, and 49,533 weeks of CED sales from supermarkets, pharmacies, supercentres, and convenience stores, respectively. Percent price discounting was positively associated with log sales of CED for all store types, and the interaction between education and discounting was prominent in supercentres: -0.039 [95% confidence interval (CI): -0.051, -0.028] and -0.039 [95% CI: -0.057, -0.021], for middle- and high-education neighbourhoods relative to low-education neighbourhoods, respectively. Relative to low-income areas, the associations of discounting and log CED sales in supercentres for neighbourhoods with middle- and high-income tertile were 0.022 [95% CI: 0.010, 0.033] and 0.015 (95% CI: -0.001, 0.031), respectively. Price discounting is an important driver of CED consumption and has a varying impact across community education and income.


Live Imaging of the Drosophila Testis Stem Cell Niche.
Live imaging of adult tissue stem cell niches provides key insights into the dynamic behavior of stem cells, their differentiating progeny, and their neighboring support cells, but few niches are amenable to this approach. Here, we discuss a technique for long-term live imaging of the Drosophila testis stem cell niche. Culturing whole testes ex vivo for up to 18 h allows for tracking of cell-type-specific behaviors under normal and various chemically or genetically modified conditions. Fixing and staining tissues after live imaging allows for the molecular confirmation of cell identity and behavior. By using live imaging in intact niches, we can better uncover the cellular and molecular mechanisms that regulate stem cell function in vivo.


[Prediction and treatment of peritoneal dissemination in gastric cancer].
In advanced gastric cancer, the frequency of relapses such as metastasis to the peritoneum is high. For this reason, prognostic and treatment methods were studied. In 457 cases in which diagnostic cytology was utilized, 36 (61%) of the 59 cases in which dissemination had been macroscopically observed (P 1) were positive. Moreover, 13 cases of P 0 were also positive. The prognosis of the positive cases was worse, but there was not a significant statistical difference between the positive and negative cases. Chemotherapy has become the most common treatment because of the appearance of new anticancer drugs. TS-1 and paclitaxel were repeatedly administered in 10 cases, and the median survival time was 17 months. These drugs were effective even in carcinoma of the peritoneum, and an improvement in the prognosis can be expected. Surgery was performed in 23 cases due to stenosis of the digestive tract, and in 21 cases the patients were able to eat after surgery. The median postoperative survival time was 7 months, and surgery improved the prognosis. The improved sensitivity of diagnostic cytology and the standardization of chemotherapy and surgery warrant further study.


Adaptive Cylindrical Wireless Metasurfaces in Clinical Magnetic Resonance Imaging.
The signal-to-noise ratio (SNR) is one of the most important criteria for evaluating the image quality in magnetic resonance imaging (MRI), and metasurfaces with unique electromagnetic properties provide a novel method for SNR improvement. However, their applications in clinical MRI are highly restricted by the inhomogeneous enhancement of the magnetic field and interference in the radio frequency (RF) transmitting field. In this study, an adaptive cylindrical wireless metasurface (ACWM) with homogeneous field enhancement and adaptive resonant modes is reported. The ACWM automatically switches its resonant modes between the partial (transmitting period) and whole (receiving period) resonance, which enables it to not only eliminate the interference in RF transmitting field, but also greatly enhance the SNR. Its adaptability also makes the ACWM applicable to all common clinical sequences without any modifications in the scan parameters. The SNR of MRI images of the human wrist, acquired with ACWM, is two to four times compared with the conventional coil. This work offers a practical control method to fill the scientific knowledge gaps between the preclinical research and medical applications for metasurfaces, and suggests a novel and powerful tool for diagnosing and evaluating human diseases.


Conserved gene regulatory module specifies lateral neural borders across bilaterians.
The lateral neural plate border (NPB), the neural part of the vertebrate neural border, is composed of central nervous system (CNS) progenitors and peripheral nervous system (PNS) progenitors. In invertebrates, PNS progenitors are also juxtaposed to the lateral boundary of the CNS. Whether there are conserved molecular mechanisms determining vertebrate and invertebrate lateral neural borders remains unclear. Using single-cell-resolution gene-expression profiling and genetic analysis, we present evidence that orthologs of the NPB specification module specify the invertebrate lateral neural border, which is composed of CNS and PNS progenitors. First, like in vertebrates, the conserved neuroectoderm lateral border specifier Msx/vab-15 specifies lateral neuroblasts in Caenorhabditis elegans Second, orthologs of the vertebrate NPB specification module (Msx/vab-15, Pax3/7/pax-3, and Zic/ref-2) are significantly enriched in worm lateral neuroblasts. In addition, like in other bilaterians, the expression domain of Msx/vab-15 is more lateral than those of Pax3/7/pax-3 and Zic/ref-2 in C. elegans Third, we show that Msx/vab-15 regulates the development of mechanosensory neurons derived from lateral neural progenitors in multiple invertebrate species, including C. elegans, Drosophila melanogaster, and Ciona intestinalis We also identify a novel lateral neural border specifier, ZNF703/tlp-1, which functions synergistically with Msx/vab-15 in both C. elegans and Xenopus laevis These data suggest a common origin of the molecular mechanism specifying lateral neural borders across bilaterians.


mTOR Inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons.
Abnormalities during brain development are thought to cause psychiatric illness and other neurodevelopmental disorders. However, developmental processes such as neurogenesis continue in restricted brain regions of adults, and disruptions of these processes could contribute to the phenotypes of neurodevelopmental disorders. As previously reported, we show that Disc1 knockdown specifically in adult-born dentate gyrus (DG) neurons results in increased mTOR signaling, hyperexcitability, and neuronal structure deficits. Disc1 knockdown also resulted in pronounced cognitive and affective deficits, which could be reversed when the affected DG neurons were inactivated. Importantly, reversing increases in mTOR signaling with an FDA-approved inhibitor both prevented and treated these behavioral deficits, even when associated structural deficits were not reversed. Our findings suggest that a component of the affective and cognitive phenotypes in neurodevelopmental disorders may be caused by disruptions in adult-born neurons. Consequently, treatments directed at this cell population may have a significant impact on these phenotypes.


Blood Lead Levels and Cause-Specific Mortality of Inorganic Lead-Exposed Workers in South Korea.
The objective of this study was to identify the association of blood lead level (BLL) with mortality in inorganic lead-exposed workers of South Korea. A cohort was compiled comprising 81,067 inorganic lead exposed workers working between January 1, 2000, and December 31, 2004. This cohort was merged with the Korean National Statistical Office to follow-up for mortality between 2000 and 2008. After adjusting for age and other carcinogenic metal exposure, all-cause mortality (Relative risk [RR] 1.36, 95% confidence interval [CI] 1.03-1.79), digestive disease (RR 3.23, 95% CI 1.33-7.86), and intentional self-harm (RR 2.92, 95% CI 1.07-7.81) were statistically significantly higher in males with BLL >20 μg/dl than of those with BLL ≤10μg/dl. The RR of males with BLL of 10-20 μg/dl was statistically higher than of those with BLL ≤10μg/dl in infection (RR 3.73. 95% CI, 1.06-13.06). The RRs of females with 10-20 μg/dl BLL was statistically significantly greater than those with BLL <10μg/dl in all-cause mortality (RR 1.93, 95% CI 1.16-3.20) and colon and rectal cancer (RR 13.42, 95% CI 1.21-149.4). The RRs of females with BLL 10-20 μg/dl (RR 10.45, 95% CI 1.74-62.93) and BLL ≥20 μg/dl (RR 12.68, 95% CI 1.69-147.86) was statistically significantly increased in bronchus and lung cancer. The increased suicide of males with ≥20 μg/dl BLLs, which might be caused by major depression, might be associated with higher lead exposure. Also, increased bronchus and lung cancer mortality in female workers with higher BLL might be related to lead exposure considering low smoking rate in females. The kinds of BLL-associated mortality differed by gender.


Corneal cooling and rehydration during photorefractive keratectomy to reduce postoperative corneal haze.
An increase in corneal temperature has been implicated in subepithelial haze after surface photorefractive keratectomy. We aimed to determine if cooling the cornea by means of hydration between ablations and immediately after final surface ablation in PRK reduces haze. One hundred five eyes of 61 patients with myopia ranging from -6.00 to -9.75 D were included. One of the surgeons irrigated with cool balanced salt solution between ablation passes and immediately at the end of the surface ablation while two others did not. Results of haze grading were analyzed at the end of 3 and 6 months and 1 year after PRK by an independent examiner. Haze was significantly reduced in those eyes in which irrigation (cooling) with balanced salt solution was performed intraoperatively and immediately after ablation. Cooling and rehydration of the cornea with chilled balanced salt solution between passes during PRK significantly reduces haze in patients with baseline myopia between -6.00 and -9.75 D.


Comparative Study of Xenobiotic-Free Media for the Cultivation of Human Limbal Epithelial Stem/Progenitor Cells.
The culture of human limbal epithelial stem/progenitor cells (LSCs) in the presence of animal components poses the risk of cross-species contamination in clinical applications. We quantitatively compared different xenobiotic-free culture media for the cultivation of human LSCs. LSCs were cultured from 2 × 2 mm limbal tissue explants on denuded human amniotic membrane with different xenobiotic-free culture media: CnT-Prime (CnT-PR) supplemented with 0%, 1%, 5%, and 10% human serum (HS), embryonic stem cell medium (ESCM) alone or in combination with the standard supplemented hormonal epithelium medium (SHEM, control) at a 1:1 dilution ratio, and modified SHEM (mSHEM), in which cholera toxin and dimethyl sulfoxide (DMSO) were removed, isoproterenol was added, and the epidermal growth factor concentration was reduced. Several parameters were quantified to assess the LSC phenotype: cell morphology, cell growth, cell size, outgrowth size, and expression of the undifferentiated LSC markers cytokeratin (K) 14, and p63α high-expressing (p63αbright) cells, a mature keratinocyte marker K12, epithelial marker pancytokeratin (PanK), and stromal cell marker vimentin (Vim). Compared with the standard SHEM control, CnT-PR base medium was associated with a lower cell growth and reduction in the proportion of stem cells generated regardless of the amount of HS supplemented (p < 0.05); ESCM resulted in an increased proportion of PanK-/Vim+ stromal cells (p < 0.05) and a decreased proportion of p63αbright cells (p < 0.05); mSHEM supported a similar cell growth (p > 0.05), increased the number of small cells (diameter ≤12 μm; p < 0.05), and provided a similar proportion of p63αbright cells (p > 0.05). Among all the conditions tested, mSHEM was the most efficient and consistent in supporting the LSC phenotype and growth.


Brief prevention for adolescent risk-taking behavior.
Despite widespread prevention efforts to decrease adolescent risk-taking, substance use and driving after drinking (DD) are prevalent in the United States. The current study compared the efficacy of an abbreviated version of Drug Abuse and Resistance Education (DARE-A) to a new Risk Skills Training Program (RSTP). Adolescent participation in drinking, drug use, DD and riding with a drunk driver was examined longitudinally. After baseline assessments, adolescents were randomly assigned to the RSTP. DARE-A or a no intervention control group and then completed 2-month post-test and 6-month follow-up assessments. Adolescents attended a mid-sized suburban high school. The sample (N = 300) was comprised of 58% females and the age range was 14-19 years. The RSTP was developed to target several risk behaviors and to examine the feasibility of conducting a brief personalized prevention program in a group setting. DARE-A focused on increasing knowledge and understanding the deleterious effects of substance use. Risk-taking behavior, perception of peer risk-taking and positive and negative alcohol expectancies were assessed. RSTP participants decreased participation in several risk behaviors at post-test, but reductions were not maintained at 6-month follow-up. The control and DARE-A groups increased their positive and decreased their negative alcohol expectancies. The control group increased their alcohol consumption. Results suggest that a brief, personalized, group prevention program is a feasible approach to reducing adolescent risk-taking. Strategies must be developed to solidify these positive changes so that they are longer-lasting.