Effect of prolapse repair on voiding and bladder overactivity.
To determine the effects of repair of pelvic organ prolapse (POP) on detrusor overactivity, overactive bladder (OAB) symptoms and voiding function. Understanding the cause of OAB in women with prolapse gives us more insight into the cause of detrusor overactivity and OAB in general. Understanding the different causes involved in OAB will allow us to target our treatments more effectively. This review discusses the evidence linking OAB and prolapse. Relevant studies or review articles were identified by performing a literature search using PubMed and MEDLINE. Prolapse and OAB may occur by chance together, but epidemiological studies support a link between OAB and prolapse. Also, POP repair (surgical correction or a ring pessary placement) is associated with improvement or resolution of OAB symptoms and detrusor overactivity. For these reasons, there seems to be a causal link between prolapse and OAB. The cause of OAB and detrusor overactivity is not fully understood, but theories relate to myogenic, neurogenic and obstructive elements. The most commonly accepted pathophysiology when prolapse is involved is that of increased bladder outlet obstruction or resistance. This is supported when the correction of POP improves voiding function, which is associated with a reduction in OAB. POP repair (surgery/ring pessary) has a positive effect on the resolution of OAB, detrusor overactivity and voiding dysfunction, providing a theory for a causal effect between the conditions. Larger prospective observational studies are needed.


Contrast harmonic imaging characterization of canine splenic lesions.
Although B-mode ultrasound is very sensitive for the detection of splenic lesions, its specificity is low. Contrast harmonic imaging is used successfully to differentiate benign from malignant liver lesions in humans and dogs. Contrast harmonic imaging could be useful to differentiate benign and malignant splenic lesions in dogs. Sixty dogs (clinical patients) with splenic abnormalities detected during abdominal ultrasonography. A prospective study was performed with a Philips ATL 5000 unit for contrast pulse inversion harmonic imaging (mechanical index: 0.08, contrast medium: SonoVue). Perfusion was assessed subjectively and quantitatively. Cytology or histology identified 27 benign (hyperplasia, extramedullary hematopoiesis, hematoma) and 29 malignant (hemangiosarcoma, malignant lymphoma, malignant histiocytosis, mesenchymal tumors without classification, mast cell tumors, and others) lesions and 4 normal spleens. Except for 1 benign nodule, extensive to moderate hypoechogenicity was only seen in malignant lesions during wash-in, at peak enhancement, and during wash-out (P= .0001, odds ratios: 37.9 [95% CI 4.5-316.5], 66.4 [95% CI 8.0-551.1], and 36.9 [95% CI 4.4-308.4]). Although all but 1 benign lesion enhanced well and were mildly hypo-, iso-, or hyperechoic in comparison with the normal spleen during all blood pool phases, marked enhancement occurred both in benign as well as in malignant splenic lesions. Quantitative perfusion values did not differ significantly between benign and malignant lesions. Moderate to extensive hypoechogenicity clearly identifies canine splenic malignant lesions. In nodules with marked enhancement, contrast harmonic ultrasound is of limited value and histology is needed.


Schwann Cells Accelerate Osteogenesis via the Mif/CD74/FOXO1 Signaling Pathway In Vitro.
Schwann cells have been found to promote osteogenesis by an unclear molecular mechanism. To better understand how Schwann cells accelerate osteogenesis, RNA-Seq and LC-MS/MS were utilized to explore the transcriptomic and metabolic response of MC3T3-E1 to Schwann cells. Osteogenic differentiation was determined by ALP staining. Lentiviruses were constructed to alter the expression of Mif (macrophage migration inhibitory factor) in Schwann cells. Western blot (WB) analysis was employed to detect the protein expression. The results of this study show that Mif is essential for Schwann cells to promote osteogenesis, and its downstream CD74/FOXO1 is also involved in the promotion of Schwann cells on osteogenesis. Further, Schwann cells regulate amino acid metabolism and lipid metabolism in preosteoblasts. These findings unveil the mechanism for Schwann cells to promote osteogenesis where Mif is a key factor.


Introduction to Laser Ablation Video Supplement.
Laser ablation (also known as laser interstitial thermal therapy [LITT]) has emerged as an important new technology for treating various disorders of the brain and spine. As with any new or emerging technology, there is a learning curve for its optimal use, and video tutorials can be important learning tools to help bridge gaps in knowledge for those who wish to become more familiar with laser ablation. In this special supplement to Neurosurgical Focus, videos illustrate laser ablation's use in the treatment of epilepsy and failed radiosurgery, as well as technical aspects of performing these procedures in eloquent brain and in the spine. We hope that these videos will enable you to enhance your understanding of the evolving use of laser ablation for disorders of the brain or spine. It is the editors' sincere hope that this will be helpful either in your own practice or in determining whether to refer to a neurosurgical colleague experienced in this field.


Phytochrome Regulation of Flowering in the Long-Day Plant, Hyoscyamus niger.
A daylength extension with incandescent light is more effective in promoting flowering of long-day plants like Hyoscyamus niger than fluorescent light. A low phytochrome photoequilibrium (Pfr/P(tot)), attained by a far-red irradiation at the close of long days under fluorescent light, also promotes flowering. Moreover, if flower initiation processes are initiated by several long days, a low phytochrome photoequilibrium at the end of short, postinduction photoperiods also enhances flowering. The initiation phase of flowering requires Pfr to be present whereas the development phase proceeds more rapidly in the absence of Pfr. Spectral dependence studies, therefore, could be misinterpreted if the initiation and development stages are combined into a single audit of flowering.


Rediscovering the joy of food: the need for long-term review of swallowing ability in stroke patients.
Stroke is commonly associated with dysphagia, which may necessitate the use of enteral feeding best provided by a percutaneous endoscopic gastrostomy (PEG) tube. Resolution of dysphagia complicating stroke is observed in the days, weeks and months following the event. This may allow the resumption of a normal diet, and cessation of enteral feeding. However at the time dysphagia resolves many patients--with enteral feeding still in place--will have been discharged from facilities where expert speech and language therapy is available to assess recovery of swallow. We report three cases of patients with dysphagia following stroke who benefited from long term review of swallowing ability. We then discuss the benefits of such follow-up, and how it might best be achieved in the community.


The role of dopaminergic and serotonergic systems in neurodevelopmental disorders: a focus on epilepsy and seizure susceptibility.
The embryonic development of the vertebrate Central Nervous System (CNS) requires the induction of transcription factors regulating the expression of specific subsets of genes in restricted CNS regions. Among these transcription factors, homeobox-containing proteins play a crucial role, and altered expression of these factors can impact the embryonic as well as adult CNS functions. Importantly, the homeobox-containing genes Otx2, Engrailed-1 (En1), and Engrailed-2 (En2) have been described to crucially regulate differentiation of dopaminergic and serotonergic neurons during vertebrate CNS development. Dopaminergic and serotonergic neurons, located in midbrain and hindbrain regions respectively, diffusely innervate several forebrain areas including limbic system, contributing in regulating several physiological functions. Understanding the embryonic development of these neuronal populations is crucial to elucidate their physiological function including brain excitability in the adult brain. New evidence is emerging about the impact of an altered embryonic development of dopamine and serotonin neurons onto seizure susceptibility in the adult life. In this mini-review, we summarized our kainic acid (KA) induced seizure susceptibility in adult mutant mouse lines with targeted manipulation of Otx2, En1, and En2 genes. Our results demonstrated that altered development of dopamine (DA) neurons does not interfere with KA seizure susceptibility, while increased serotonin (5-hydroxytryptamine, 5-HT) hyperinnervation leads to resistance to KA-induced seizure. We propose that developmental alterations of serotonergic but not dopaminergic circuits play a crucial role in controlling seizure susceptibility in the adult life.


Current Approaches to Fertility Preservation.
The 5 principal reasons a patient may consider fertility preservation are: treatment for cancer that may affect fertility, treatment for nonmalignant medical conditions that may affect fertility, planned indications, planned gender-affirming hormone therapy or surgery, or in the setting of genetic conditions that may increase the risks of premature ovarian insufficiency or early menopause. This paper will focus on describing who may consider preserving their fertility, how to provide the best clinical evaluation of those seeking fertility preservation, and current and future fertility preservation techniques. Last, we will highlight a need to continue to expand access to fertility preservation technologies.


Erythropoiesis: Paroxysmal Cold Haemoglobinuria: A Clinico-Pathological Study of Patients with a Positive Donath-Landsteiner Test.
52 patients (30 male, 22 female) with paroxysmal cold haemoglobinuria (PCH) were identified by critically examining the records of all cases with Donath-Landsteiner antibodies seen over a 37 year period. Although ages ranged from 1-82 years, PCH was much commoner in young children; the median age at presentation was 5 and the peak incidence, 0.4 per year per 100,000 of the population at risk, was in the 4 years and under group. 44 patients had acute transient PCH, 3 chronic non-syphilitic PCH and 1 chronic syphilitic PCH; 4, in whom the positive Donath-Landsteiner tests were incidental findings, could not be classified. Acute PCH typically presented in young children as sudden onset of malaise, haemoglobinuria and pallor, often associated with mild jaundice - all 30 patients who were 13 or younger had this type. There was usually a history of a recent viral type infection, most commonly of the upper respiratory tract. The occurrence of acute PCH had no obvious relation to exposure to cold. Dramatic and rapid falls in haemoglobin level were common, often accompanied initially by relative or absolute reticulocytopenia. The illness was severe, but the prognosis was generally good and the majority of patients had completely recovered within one month, some requiring no treatment. In approximately 68% of patients, blood transfusion was needed; the P blood group was not taken into account, but the patients were kept warm throughout. Steroids (usually prednisolone) were given in many cases; but since there was no evidence to support their benefit, it was recommended that they were stopped as soon as the diagnosis was confirmed. Chronic non-syphilitic PCH was much rarer; the patients had a characteristic presentation of severe systemic symptoms (paroxysms) and haemoglobinuria brought on by exposure to cold. The clinical manifestations varied in intensity between individuals; at the extreme, severe debility was experienced over many years. Warmth and avoidance of cold were an effective treatment, though in a severely afflicted patient, an attack could be precipitated by relatively little exposure to cold. With chronic syphilitic PCH there was the added need to treat the specific infection. The direct antiglobulin test was almost always positive (50 out of 51 cases tested), with C3d coating the red cells. The Donath-Landsteiner antibodies were of IgG class, but this was rarely demonstrated unless direct antiglobulin tests were carried out at 4 degrees C. The antibodies showed the classical anti-P specificity in 27 of the 30 patients tested; other specificities were unusual. Although acting much better as haemolysins, Donath-Landsteiner antibodies could also cause weak agglutination at room temperature. This was paralleled in vivo by predominantly intravascular haemolysis with an extravascular component. Diagnosis was usually easy when PCH was suspected, though in some patients Donath-Landsteiner tests did not become positive until more sensitive techniques involving papainised red cells or two-stage procedures were employed. Of particular interest was the association in some cases with lymphoproliferative disorders, collagen disease, myelodysplastic syndrome, delayed haemolytic transfusion reaction and other types of autoimmune haemolytic anaemia. In one patient, an aetiological relationship was confirmed by a saline extract of lymphoma tissue behaving as a strong Donath-Landsteiner antibody with the same anti-P specificity as the serum. 4 patients had other types of autoimmune haemolysis concomitant with, but distinct from, the PCH; in 3 cases this was cold haemagglutinin disease and in one it was warm type autoimmune haemolytic anaemia.


Automatic testing of electrooptical systems.
The ever-increasing demand for test equipment which can interface with a computer or which can perform operationally in a completely automatic mode has had a large effect on the somewhat futuristic question: "How do we test electrooptical systems automatically?" This paper is developed to give information about the systems currently in operation, the techniques required for automation of these systems, the present problem areas of design, and a look at new techniques for future electrooptical systems testing.


Expanding the role of the stroke nurse: a pragmatic clinical trial.
This paper reports a study evaluating whether expanding a specialist nursing role to provide outreach education and support to stroke patients and carers after discharge from hospital is effective in promoting recovery. Building therapeutic relationships with patients and carers is a key component of the nursing role in stroke rehabilitation, although this is limited by the constraints of service organization. A pragmatic randomized controlled trial was undertaken. Patients with a diagnosis of stroke were randomized to receive continued support from a stroke nurse (n = 87) or usual care and follow-up (n = 89) after discharge from hospital. Patients were recruited from two hospitals in the north-west of England from November 1999 to April 2001. Patient dependence (Barthel Index), general health (Nottingham Health Profile), activities of living (Frenchay Activity of Living Index), depression (Beck Depression Inventory) and carer strain (Carer Strain Index) were assessed at 3 and 12 months after stroke. The continued intervention of a stroke nurse after discharge was associated with improved patient perceptions of general health at 12 months (median difference 42.6, P = 0.012), and in particular reduced negative emotional reaction (P = 0.037) and perceived social isolation (P = 0.002). In addition, the intervention reduced carer strain at 3 months (P = 0.045), and reduced deterioration in physical dependence from 3 to 12 months (P = 0.049). The provision of continued intervention from a stroke nurse after discharge from hospital, focusing on education and support, has tangible benefits for patients and carers.


Influence of Helminthosporium maydis, Race T, Toxin on Potassium Uptake in Maize Roots: II. Sensitivity of Development of the Augmented Uptake Potential to Toxin and Inhibitors of Protein Synthesis.
Basal K(+) uptake in the root midzone region (cm 2 + 3 + 4) of N and T cytoplasmic versions of each of four maize inbreds was equally sensitive to the toxin(s) of Helminthosporium maydis, race T. Basal K(+) uptake in the root apex (0-1 cm) and augmented K(+) uptake in the root midzone were more toxin-sensitive in inbreds W64A(T) and Mo17(T) than in inbreds W64A(N) and Mo17(N). This differential response of N and T cytoplasms to toxins was not found for corresponding cytoplasms of inbreds WF9 and B37.Development of the augmented K(+) uptake rate in midzone segments of W64A(T) was blocked by a toxin concentration which did not affect augmentation development in W64A(N). Augmentation development was more toxin-sensitive in T than in N cytoplasmic versions of all inbreds tested. Fertility-restoring nuclear loci decreased but did not eliminate the toxin sensitivity of augmentation developments as observed in root midzones of inbred A619(T). Chloramphenicol-and/or cycloheximide-sensitive protein synthesis was required for augmentation development, but not for expression of either basal or augmented K(+) uptake.


Self-assembly of kagome lattices, entangled webs and linear fibers with vibrating patchy particles in two dimensions.
A vibrating version of patchy particles in two dimensions is introduced to study self-assembly of kagome lattices, disordered networks of looping structures, and linear arrays. Discontinuous molecular dynamics simulations in the canonical ensemble are used to characterize the molecular architectures and thermodynamic conditions that result in each of those morphologies, as well as the time evolution of lattice formation. Several versions of the new model are tested and analysed in terms of their ability to produce kagome lattices. Due to molecular flexibility, particles with just attractive sites adopt a polarized-like configuration and assemble into linear arrays. Particles with additional repulsive sites are able to form kagome lattices, but at low temperature connect as entangled webs. Abundance of hexagonal motifs, required for the kagome lattice, is promoted even for very small repulsive sites but hindered when the attractive range is large. Differences in behavior between the new flexible model and previous ones based on rigid bodies offer opportunities to test and develop theories about the relative stability, kinetics of formation and mechanical response of the observed morphologies.


Winery by-products as a valuable source for natural antihypertensive agents.
Hypertension (HTN) is one of the leading causes of death in the world. Agri-food by-products are emerging as a novel source of natural antihypertensive agents allowing for their valorization and making food and agricultural industries more environmentally friendly. In this regard, wine making process generates large amounts of by-products rich in phenolic compounds that have shown potential to exert several beneficial effects including antihypertensive properties. The aim of this study was to review the blood pressure-lowering effects of winery by-products. In addition, molecular mechanisms involved in their bioactivity were also evaluated. Among the winery by-products, grape seed extracts have widely shown antihypertensive properties in both animal and human studies. Moreover, recent evidence suggests that grape stem, skin and pomace and wine lees may also have great potential to manage HTN, although more studies are needed in order to confirm their potential in humans. Improvement of endothelial dysfunction and reduction of oxidative stress associated with HTN are the main mechanisms involved in the blood pressure-lowering effects of these by-products.


A High-Performance WSe2 /h-BN Photodetector using a Triphenylphosphine (PPh3 )-Based n-Doping Technique.
The effects of triphenylphosphine (PPh3 )-based n-doping and hexagonal boron nitride (h-BN) insertion on a tungsten diselenide (WSe2 ) photodetector are systematically studied, and a very high performance WSe2 /h-BN heterostucture-based photodetector is demonstrated with a record photoresponsivity (1.27 × 10(6) A W(-1) ) and temporal photoresponse (rise time: 2.8 ms, decay time: 20.8 ms) under 520 nm wavelength and 5 pW power laser illumination.


Determining the intermolecular structure in the S0 and S1 states of the phenol dimer by rotationally resolved electronic spectroscopy.
The rotationally resolved UV spectra of the electronic origins of five isotopomers of the phenol dimer have been measured. The complex spectra are analyzed using a fitting strategy based on a genetic algorithm. The intermolecular geometry parameters have been determined from the inertial parameters for both electronic states and compared to the results of ab initio calculations. In the electronic ground state, a larger hydrogen-bond length than in the ab initio calculations is found together with a smaller tilt angle of the aromatic rings, which shows a more pronounced dispersion interaction. In the electronically excited state, the hydrogen-bond length decreases, as has been found for other hydrogen-bonded clusters of phenol, and the two aromatic rings are tilted less toward each other.


Best Probability Density Function for Random Sampled Data.
The maximum entropy method is a theoretically sound approach to construct an analytical form for the probability density function (pdf) given a sample of random events. In practice, numerical methods employed to determine the appropriate Lagrange multipliers associated with a set of moments are generally unstable in the presence of noise due to limited sampling. A robust method is presented that always returns the best pdf, where tradeoff in smoothing a highly varying function due to noise can be controlled. An unconventional adaptive simulated annealing technique, called funnel diffusion, determines expansion coefficients for Chebyshev polynomials in the exponential function.


Streptococcus mutans-associated bacteria in dental plaque of severe early childhood caries.
Streptococcus mutans (S. mutans) is a potential pathogenic bacteria of dental caries. However, the level of S. mutans is low in some children with severe early childhood caries (SECC). To evaluate the effect of S. mutans level on dental microbiome and cariogenesis. The oral microbiota was compared between caries-free group (CF) and SECC group.16S rRNA gene sequencing was used for S. mutans level bacterial community analysis. The candidate bacteria that were closely related with S. mutans abundance were identified and confirmed by absolute quantitative real-time PCR in clinical dental plaque samples from CF and SECC groups. Through in-depth analysis of dental plaque microorganism, Leptotrichia, Selenomonas and Prevotella_7 were found in the S. mutans-low group (p < 0.05) and Porphyromonas, Selenomonas_3 were found in the S. mutans-high group (p < 0.05). Through quantitative real-time PCR, Leptotrichia, Selenomonas and Prevotella_7 were identified as the potential biomarkers of SECC when S. mutans was at a low level. Leptotrichia, Selenomonas and Prevotella_7 are identified as potential biomarkers in SECC with a low abundance or without S. mutans. Our study may shed light on the understanding of caries occurrence in SECC with low abundance of S. mutans. S. mutans, Streptococcus mutans; CF, caries-free; SECC, severe early childhood caries; ECC, early childhood caries; rRNA, ribosome RNA; qPCR, Quantitative real-time PCR; OTUs, operational taxonomic units; ANOVA, analysis of variance; LDA, Linear discriminant analysis; LEfSe, Linear discriminant analysis effect size; COG, Groups of proteins; NMDS, Non-MetricMulti-Dimensional Scaling; IL-1β, interleukin -1β; IL-6, interleukin-6; IL-8, interleukin-8; IL-10, interleukin-10.


Comparison of urokinase and video-assisted thoracoscopic surgery for treatment of childhood empyema.
Despite increasing incidence and morbidity, little evidence exists to inform the best management approach in childhood empyema. To compare chest drain with intrapleural urokinase and primary video-assisted thoracoscopic surgery (VATS) for the treatment of childhood empyema. Children were prospectively randomized to receive either percutaneous chest drain with intrapleural urokinase or primary VATS. The primary outcome was the number of hospital days after intervention. Secondary end points were number of chest drain days, total hospital stay, failure rate, radiologic outcome at 6 mo, and total treatment costs. Sixty children were recruited. The two groups were well matched for demographics; baseline characteristics; and hematologic, biochemical, and bacteriologic parameters. No significant difference was found in length of hospital stay after intervention between the two groups: VATS (median [range], 6 [3-16] d) versus urokinase (6 [4-25] d) (p = 0.311; 95% confidence interval, -2 to 1). No difference was demonstrated in total hospital stay: VATS versus urokinase (8 [4-17] d and 7 [4-25] d) (p = 0.645); failure rate: 5 (16.6%); and radiologic outcome at 6 mo after intervention in both groups. The mean (median) treatment costs of patients in the urokinase arm US dollars 9,127 (US dollars 6,914) were significantly lower than those for the VATS arm US dollars 11,379 (US dollars 10,146) (p < 0.001). There is no difference in clinical outcome between intrapleural urokinase and VATS for the treatment of childhood empyema. Urokinase is a more economic treatment option compared with VATS and should be the primary treatment of choice. This study provides an evidence base to guide the management of childhood empyema.


Magnetically modified single and turbostratic stacked graphenes from tris(2,2'-bipyridyl) iron(II) ion-exchanged graphite oxide.
Loading of graphite oxide (GO) with tris(2,2'-bipyridyl) iron(II) ions and subsequent calcination affords a novel graphene-based composite with magnetic and electrically conductive properties. The pH of the starting aqueous suspension and the washing procedure play a crucial role in the successful immobilization of the iron precursor, which is mainly governed by ion exchange. The complex is intercalated between the graphene oxide layers, where it adopts a distorted conformation. Rapid heating of this solid results in the deflagration of GO and the formation of ultrafine ( d = 2-14 nm) Fe2O3 particles with maghemite as the dominant phase. The superparamagnetic maghemite crystals are dispersed uniformly in the high-surface-area diamagnetic matrix built up from single or turbostratic stacked graphenes.


Patellar taping in the treatment of patellofemoral pain. A prospective randomized study.
The purpose of this prospective study was to evaluate the efficacy of a patellar taping program in the conservative management of patellofemoral pain. Twenty-five patients with patellofemoral pain were randomized into two groups. One group underwent a standard physical therapy program for patellofemoral pain. The other group underwent the same physical therapy program, but use of a patellar taping technique was added to this program. Results of a subjective visual analog scale and changes in isokinetic strength and electromyographic activity of the quadriceps muscle were analyzed. Both the tape and no-tape groups experienced a statistically significant decrease in symptoms (P < 0.05), but no difference in improvement of patellofemoral pain was noted between the groups. Likewise, both groups demonstrated significant improvement in quadriceps muscle isokinetic strength (P < 0.05) and activity (P < 0.001), but no difference in improvement was noted between groups. The results of this study suggest no beneficial effect of adding a patellar taping program to a standard physical therapy program in the conservative treatment of patellofemoral pain. Larger prospective studies are warranted to support this opinion.


Establishment of a new cell-based assay to measure the activity of sweeteners in fluorescent food extracts.
Taste receptors have been defined at the molecular level in the past decade, and cell-based assays have been developed using cultured cells heterologously expressing these receptors. The most popular approach to detecting the cellular response to a tastant is to measure changes in intracellular Ca(2+) concentration using Ca(2+)-sensitive fluorescent dyes. However, this method cannot be applied to food-derived samples that contain fluorescent substances. To establish an assay system that would be applicable to fluorescent samples, we tested the use of Ca(2+)-sensitive photoproteins, such as aequorin and mitochondrial clytin-II, as Ca(2+) indicators in a human sweet taste receptor assay. Using these systems, we successfully detected receptor activation in response to sweetener, even when fluorescent compounds coexisted. This luminescence-based assay will be a powerful tool to objectively evaluate the sweetness of food-derived samples even at an industry level.


A "single-sample concept" (SSC): a new approach to the combinatorial chemistry of inorganic materials.
Combinatorial estimations show that, within an unreacted ceramic sample prepared by mixing N different starting materials MxOy with average particle size approximately 1 microm, there are about 10(12) grains per cubic centimeter, sufficient for local reactions to occur that may produce a larger number of product oxides than presently accessible by 2D plate techniques. The "single-sample concept" (SSC) is proposed for performing property-directed syntheses for the preparation of ferri-/ferromagnetic or superconducting compounds. Because of the magnetic properties of the products, libraries of product grains can be sorted by means of magnetic separation techniques. For materials with a large magnetization, the separation efficiency is so high that traces of products can be isolated. The SSC concept was tested experimentally to prepare Fe-based oxides (N=17, 24, 30). The large yields (<75 wt %, N=17) of product grains agree with the literature data, which indicate that 3d metal magnetic oxide phases (Tc>300 K) are most probably Fe oxides. In combination with magnetic separation techniques, SSC seems particularly adapted for exploring the solid-state chemistry of metallic lead elements that form ferri-/ferromagnetic or superconducting oxide phases difficult to detect systematically within the large phase space of theoretically existing compounds.


Regulation of gamma-aminobutyric acid synthesis in the brain.
gamma-Aminobutyric acid (GABA) is synthesized in brain in at least two compartments, commonly called the transmitter and metabolic compartments, and because regulatory processes must serve the physiologic function of each compartment, the regulation of GABA synthesis presents a complex problem. Brain contains at least two molecular forms of glutamate decarboxylase (GAD), the principal synthetic enzyme for GABA. Two forms, termed GAD65 and GAD67, are the products of two genes and differ in sequence, molecular weight, interaction with the cofactor, pyridoxal 5'-phosphate (pyridoxal-P), and level of expression among brain regions. GAD65 appears to be localized in nerve terminals to a greater degree than GAD67, which appears to be more uniformly distributed throughout the cell. The interaction of GAD with pyridoxal-P is a major factor in the short-term regulation of GAD activity. At least 50% of GAD is present in brain as apoenzyme (GAD without bound cofactor; apoGAD), which serves as a reservoir of inactive GAD that can be drawn on when additional GABA synthesis is needed. A substantial majority of apoGAD in brain is accounted for by GAD65, but GAD67 also contributes to the pool of apoGAD. The apparent localization of GAD65 in nerve terminals and the large reserve of apoGAD65 suggest that GAD65 is specialized to respond to short-term changes in demand for transmitter GABA.(ABSTRACT TRUNCATED AT 250 WORDS)


Cell Imaging Counting as a Novel Ex Vivo Approach for Investigating Drug-Induced Hepatotoxicity in Zebrafish Larvae.
Drug-induced liver injury (DILI) is the most common reason for failures during the drug development process and for safety-related withdrawal of drugs from the pharmaceutical market. Therefore, having tools and techniques that can detect hepatotoxic properties in drug candidates at an early discovery stage is highly desirable. In this study, cell imaging counting was used to measure in a fast, straightforward, and unbiased way the effect of paracetamol and tetracycline, (compounds known to cause hepatotoxicity in humans) on the amount of DsRed-labeled hepatocytes recovered by protease digestion from Tg(fabp10a:DsRed) transgenic zebrafish. The outcome was in general comparable with the results obtained using two reference methods, i.e., visual analysis of liver morphology by fluorescence microscopy and size analysis of fluorescent 2D liver images. In addition, our study shows that administering compounds into the yolk is relevant in the framework of hepatotoxicity testing. Taken together, cell imaging counting provides a novel and rapid tool for screening hepatotoxicants in early stages of drug development. This method is also suitable for testing of other organ-related toxicities subject to the organs and tissues expressing fluorescent proteins in transgenic zebrafish lines.


B-cell subsets in patients with transient hypogammaglobulinemia of infancy, partial IgA deficiency, and selective IgM deficiency.
The pathogenesis of some primary humoral immunodeficiencies, such as transient hypogammaglobulinemia of infancy (THI) and immunoglobulin (Ig) A deficiency, remains unknown and can render diagnosis problematic. In the present study, we used flow cytometry to analyze peripheral blood B-cell subsets in patients with THI and unclassified hypogammaglobulinemia (UCH), partial IgA deficiency, and selective IgM deficiency. The study population comprised 41 patients with hypogammaglobulinemia (THI, 18; UCH, 23), 16 patients with partial IgA deficiency, and 16 patients with selective IgM deficiency who were admitted to Ankara University Department of Pediatric Immunology-Allergy between January 2010 and April 2011, as well as 29 healthy controls. B-cell subsets were examined according to the EUROclass classification. Age at diagnosis in the hypogammaglobulinemia group ranged between-14 months and 13 years (median, 26 months). Naive B-cell percentages were significantly higher and activated B-cell values lower in the THI patients than in the UCH patients and age-matched healthy controls. Nonswitched (IgM+CD27+IgD+) memory B-cell values were found to be significantly lower in patients with selective IgM deficiency than in healthy controls. No significant differences in B-cell subsets were found in patients with partial IgA deficiency. Previous reports show that reduced class-switched memory B cell values are associated with CVID, THI, and selective IgA deficiency. Our findings did not support these reports. Furthermore, we observed that naive B cell values were higher in patients with THI. A maturation defect could play a role in the pathogenesis of THI.


Postnatal changes in the mammalian respiratory network as revealed by the transverse brainstem slice of mice.
1. Spontaneous rhythmic activity in hypoglossal (XII) rootlets is generated at all postnatal stages from postnatal day (P) 0 to P22 in the transverse brainstem slice of mice containing the pre-Bötzinger complex (PBC). The PBC is known to be a region essential for respiratory rhythm generation. It contains neurones generating periodic bursts that occur in synchrony with rhythmic XII activity. This synchrony indicates that the rhythmic PBC activity generated by the transverse slice is the central respiratory rhythm. 2. The strength of coupling between XII bursts and PBC bursts decreased during early postnatal development. In younger mice (P0-4) each burst in XII rootlets corresponded to one burst in the PBC. In older mice (P5-18) one burst in XII rootlets occurred only every third to fourth burst in PBC neurones. 3. Cycle length and burst duration of rhythmic XII activity did not change significantly during the first three postnatal weeks. However, the pattern of XII bursts changed from decrementing (P0-7) to bell shaped (P8-18) while the rate of rise of XII bursts decreased significantly. 4. The rate of rise of rhythmic depolarizations in neurones of the PBC discharging in phase with XII bursts ('inspiratory neurones') decreased with postnatal development. During interburst intervals, membrane potentials of neurones of older mice (P6-18) were characterized by waves of synaptic input that were not observed in neonatal animals (P0-5). 5. Blockade of glycine receptors by strychnine increased the frequency of rhythmic XII activity in neonatal and older mice (P0-22). Although in expiratory PBC neurones glycinergic transmission was blocked at 10 microM strychnine, in inspiratory PBC neurones and XII rootlets even higher concentrations of up to 50 microM strychnine failed to abolish rhythmic activity.


[Chemiluminescence in the peroxidase oxidation of luminol with hydrogen peroxide in various media].
The effects of culture media of various compositions on chemiluminescence developing in peroxidase oxidation of luminol with hydrogen peroxide were under study. The findings evidence that the presence of carbonate and bicarbonate ions in the medium results in a two-staged chemiluminescence kinetics and in more intensive chemiluminescence in the peroxidase-luminol-hydrogen peroxide system. This fact has brought the authors to a conclusion that carbonate and bicarbonate-containing media are more effective for the detection of low peroxidase concentrations by the chemiluminescence technique.


Expectile Neural Networks for Genetic Data Analysis of Complex Diseases.
The genetic etiologies of common diseases are highly complex and heterogeneous. Classic methods, such as linear regression, have successfully identified numerous variants associated with complex diseases. Nonetheless, for most diseases, the identified variants only account for a small proportion of heritability. Challenges remain to discover additional variants contributing to complex diseases. Expectile regression is a generalization of linear regression and provides complete information on the conditional distribution of a phenotype of interest. While expectile regression has many nice properties, it has rarely been used in genetic research. In this paper, we develop an expectile neural network (ENN) method for genetic data analyses of complex diseases. Similar to expectile regression, ENN provides a comprehensive view of relationships between genetic variants and disease phenotypes, which can be used to discover variants predisposing to sub-populations. We further integrate the idea of neural networks into ENN, making it capable of capturing non-linear and non-additive genetic effects (e.g., gene-gene interactions). Through simulations, we showed that the proposed method outperformed an existing expectile regression when there exist complex genotype-phenotype relationships. We also applied the proposed method to the data from the Study of Addiction: Genetics and Environment (SAGE), investigating the relationships of candidate genes with smoking quantity.


Bioinduced Room-Temperature Methanol Reforming.
Imitating nature's approach in nucleophile-activated formaldehyde dehydrogenation, air-stable ruthenium complexes proved to be exquisite catalysts for the dehydrogenation of formaldehyde hydrate as well as for the transfer hydrogenation to unsaturated organic substrates at loadings as low as 0.5 mol %. Concatenation of the chemical hydrogen-fixation route with an oxidase-mediated activation of methanol gives an artificial methylotrophic in vitro metabolism providing methanol-derived reduction equivalents for synthetic hydrogenation purposes. Moreover, for the first time methanol reforming at room temperature was achieved on the basis of this bioinduced dehydrogenation path delivering hydrogen gas from aqueous methanol.


Noncovalent Interaction- and Steric Effect-Controlled Regiodivergent Selectivity in Dimeric Manganese-Catalyzed Hydroarylation of Internal Alkynes: A Computational Study.
Selective hydroarylation of internal alkynes catalyzed by a dimeric manganese complex provides a powerful strategy for the construction of multisubstituted alkenes. In this work, density functional theory (DFT) calculations and experimental studies were carried out to explore the mechanism and origin of regiodivergent hydroarylation of internal alkynes reported by our group. The results demonstrate that this reaction first proceeds via a bimetallic mechanism to generate the active catalyst that subsequently undergoes a monometallic mechanism to run the three-stage catalytic cycle: alkyne migratory insertion, protonation, and active catalyst regeneration. Alkyne migratory insertion is considered as the regioselectivity-determining step. Energy decomposition analyses on insertion transition states suggest that the interaction between the substrate and catalyst is mainly responsible for the observed exclusive γ-selectivity of 1a, while the deformation of these two sections induced by the sterically hindered phenyl group and aryl group accounts for the complete β-position arylation of 1e. The decrease of γ-selectivity with the regulation of a tertiary alcohol motif in 1a originates from the reduced noncovalent interaction. The computational results provide important insights into the origin of regiodivergent selectivities and useful information for further designing and adjusting the strategy in Mn-catalyzed alkyne hydroarylation.


[Studies on anti-inflammatory and immune effects of moxibustion].
An animal model of adjuvant arthritis in rats was established, and the effects of anti-inflammatory and immune regulation of moxibustion at "Shenshu" point were investigated. The results showed that it could lighten a local inflammatory reaction, eliminate swelling of the metatarsal and reduce it's girth, prevent or reduce the polyarthritises, maintain the weight and shorten the course of the disease. The results also showed that moxibustion could recover and promote the effects of the Concanavalin A (ConA) inducing splenic lymphocyte proliferation in rats, promote interleukin 2 (IL-2) production, decrease IL-1 contents. The indexes mentioned above were significantly different as compared with contral group. Above results indicated that moxibustion had directly anti-inflammatory and subsidence of swelling effects, through enhancing the ability of immune response the immune functions were lightened and regulated. Therefore, the anti-inflammatory and immune and anti-allergy effects of body were enhanced.


Mucosal immunity and gastrointestinal antigen processing.
The intestine is the largest lymphoid organ in the body by virtue of lymphocyte numbers and quantity of immunoglobulin produced. This is largely related to the enormous antigen load to which these cells are exposed on a daily basis. However, despite this, the mucosa-associated lymphoid tissue appears to be regulated by unique mechanisms, and this is reflected in specific phenomena (oral tolerance, controlled or physiologic inflammation) as well as unusual lymphoid populations (intraepithelial lymphocytes) that respond to alternative pathways of activation. This, coupled with the existence of novel antigen-presenting cells (intestinal epithelial cells) sets the scene for distinct immune responses. It is these distinct regulatory factors that support immunosuppression or tolerance rather than active immunity at a site juxtaposed to the external environment. This review defines these novel interactions and suggests how alteration in normal function may result in allergic or inflammatory responses. A clearer understanding of mucosal immunoregulation may lead to new therapeutic approaches for these diseases.


Permeability of the suberized mestome sheath in winter rye.
Mestome sheath cells of winter rye (Secale cereale L. cv Puma) deposit suberized lamellae in their secondary cell walls. Histochemical tests including acid digestion and staining with Sudan IV and Chelidonium majus root extract were used to detect the presence of suberin in the primary cell wall. There was no evidence of a Casparian band between adjacent mestome sheath cells. Fluorescent dye techniques were used to trace solute movement through the rye leaf apoplast. Calcofluor white M2R, a fluorescent dye which binds to cell walls as it moves apoplastically, proved to be too limited in its mobility in leaves to test mestome sheath permeability. Trisodium 3-hydroxy-5,8,10 pyrene trisulfonate, a fluorescent dye which is mobile in the apoplast, moved easily up the vascular bundles in the transpiration stream, and diffused outward from the veins to the epidermal cell walls within minutes of reaching a particular level in the leaf. We conclude that the suberized mestome sheath of rye leaves is freely permeable to solutes moving apoplastically through radial primary cell walls.


What emotion dimensions can affect working memory performance in healthy adults? A review.
Due to the critical roles of emotion and working memory in our daily activities, a great deal of attention has been given to how emotion influences working memory performance. Although the association between emotion and working memory is relatively well established, whether mood enhances or impairs working memory performance remains controversial. The present review provides a relatively representative overview of the research on the effect of different dimensions of emotion on working memory among healthy adults spanning a 30-year period. The findings show that the valence, arousal and motivational dimensions of emotion could all exert an impact on working memory performance. The impact of emotion on working memory might be modulated by task relevance, emotion type, working memory paradigms and individual differences. The vast majority of the studies regarding the effect of emotion on working memory performance focused on the impact of negatively valenced affect and yielded highly contradictory findings. The impacts of arousal and motivation on working memory have been less explored, and inconsistent findings have also been reported. Possible explanations are discussed. Considerable research on the effect of certain dimensions of emotion on working memory has suffered from a lack of control of other emotional dimensions, and different aspects of working memory have been investigated by various paradigms. Directions for further studies should include the exploration of specific dimensions of emotion on different aspects of working memory, with the other dimensions being well controlled.


Design of an Extreme Low Cutoff Frequency Highpass Frontend for CMOS ISFET via Direct Tunneling Principle.
In this work, ISFET frontends utilising the direct tunneling current to eliminate trapped charge are proposed. The principle has been investigated and verified via silicon-imitated ISFET first, where silicon capacitors are used to imitate the passivation ones. Because the dominant tunneling components depend on the potential difference between Gate and Drain terminals, a source-follower structure could itself perform a highpass filter with time constant at 10-100 seconds level. Additionally, a time-constant regulation mechanism is presented by feeding the output signal back to the drain terminal of ISFETs, achieving a regulation factor over 50, namely from 4.7 seconds to 243.4 seconds in our implementation. Afterwards in chemical test, proposed ISFETs have been verified in terms of unit passivation capacitance, linearity, noise and sensitivity for ISFETs with 3 different top metal areas. It is found that approximately 30.12 mV/pH sensitivity can be achieved, and for the first time we managed to derive the relation between chemical flicker noise and sensing metal area.


Huge biatrial primary cardiac B-cell lymphoma resulting in bilateral atrioventricular valve obstruction.
We report the case of a 48-year-old man with a clinical syndrome caused by both pulmonary and systemic venous congestion. Echocardiography indicated a huge tumor occupying both dilated atria almost completely, seeming to invade from the atrial septum. A test for HIV was negative. Our primary diagnosis was a biatrial myxoma. Urgent surgery was performed disclosing large cell B-cell primary cardiac lymphoma. The patient died 8 days later. Primary cardiac lymphoma is extremely rare in immunocompetent patients. Its rarity and heterogenous clinical presentation make diagnosis difficult. As tissue characterization is still beyond the capabilities of currently available echocardiography, a combination of examinations are indicated, when the clinical condition is relatively stable, in order to reach the exact diagnosis.


Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins.
1) To investigate which neutrophil-derived proteins in feces most accurately reflect disease activity in inflammatory bowel disease. 2) To examine the extracellular release of these proteins by activated neutrophils and their stability in feces by in vitro study. We studied 41 patients (91 samples) with ulcerative colitis (UC), 34 patients (105 samples) with Crohn's disease (CD), and 25 control subjects. Fecal levels of lactoferrin (Lf), polymorphonuclear neutrophil elastase (PMN-E), myeloperoxidase (MPO), and lysozyme (Lys) were measured by ELISA. We also measured fecal hemoglobin (Hb) and alpha 1-antitrypsin (alpha 1-AT), useful markers of disease activity in UC and CD, respectively. For the in vitro study, blood samples were stimulated with phorbol myristate acetate or latex beads. For the assessment of stability, homogenized stool samples were stored at 4 degrees C, 25 degrees C, and 37 degrees C for various periods. 1) Fecal Lf, PMN-E, MPO, and Lys concentrations were significantly increased in the active phase of the disease compared to the inactive phase in both UC and CD. 2) Fecal Lf, PMN-E, MPO, and Lys concentrations correlated significantly with fecal Hb concentration in UC, whereas fecal Lf, PMN-E, and MPO concentrations correlated significantly with alpha 1-AT concentration in CD. In UC, fecal Lf, PMN-E, MPO, and Lys concentrations were high in 15, 9, 14, and 14 samples, respectively, of 25 samples with normal Hb concentration. In CD, fecal Lf, PMN-E, and MPO concentrations were high in 19, 10, and 16 samples, respectively, of 30 samples with normal alpha 1-AT concentration. 3) The extracellular release of Lf was the most efficient and this molecule was the most stable in feces. Both our clinical and our in vitro studies suggested that Lf is the most suitable of these proteins to use as neutrophil-derived fecal marker of inflammation for clinical application.


The mechanism of photosynthetic water splitting.
Oxygenic photosynthesis, which provides the biosphere with most of its chemical energy, uses water as its source of electrons. Water is photochemically oxidized by the protein complex photosystem II (PSII), which is found, along with other proteins of the photosynthetic light reactions, in the thylakoid membranes of cyanobacteria and of green plant chloroplasts. Water splitting is catalyzed by the oxygen-evolving complex (OEC) of PSII, producing dioxygen gas, protons and electrons. O(2) is released into the atmosphere, sustaining all aerobic life on earth; product protons are released into the thylakoid lumen, augmenting a proton concentration gradient across the membrane; and photo-energized electrons pass to the rest of the electron-transfer pathway. The OEC contains four manganese ions, one calcium ion and (almost certainly) a chloride ion, but its precise structure and catalytic mechanism remain unclear. In this paper, we develop a chemically complete structure of the OEC and its environment by using molecular mechanics calculations to extend and slightly adjust the recently-obtained X-ray crystallographic model with reference to this structure and to some important recent experimental results.


Elution of viruses by ionic and nonionic surfactants.
The ionic and nonionic surfactants sodium dodecyl sulfate and Triton X-100, respectively, eluted two viruses, phi X174 and PRD1, which were adsorbed to the ionic and nonionic binding membranes cationic polysulfone and nitrocellulose, respectively. Results indicated that complete elution was readily achieved only when combinations of surfactants and binding membranes were matched (i.e., ionic-ionic or nonionic-nonionic).


Ratchet effect of a dimer with broken friction symmetry in a symmetric potential.
The one-dimensional overdamped Brownian motion of a dimer consisting of two harmonically interacting components is considered. Both components are coupled to the same heat bath and feel the same spatially periodic symmetric potential, whose amplitude is modulated periodically in time. The friction coefficients may differ between dimer components, thus breaking the dynamical symmetry of the system. In the absence of any external bias, a ratchet effect (directed transport) arises generically. Two accurate approximations for the dimer's velocity and diffusion coefficient are obtained for weak and strong couplings. The velocity of the system can be maximized for each direction by adding an optimal amount of noise and by tuning the driving frequency to an optimal value. Furthermore, there exist two optimal coupling strengths at which the velocity is the largest.


Advances in Biosynthesis, Regulation, and Function of Apple Cuticular Wax.
A layer of cuticular wax is deposited on the surface of terrestrial plants, which reduces the damage caused by environmental stress and maintains growth in a relatively stable internal environment. Apple cuticular wax is an important part of the fruit epidermis that plays an essential role in apple development, storage, and adaptation to environmental stress. The formation of cuticular wax has been described at the transcriptional, post-transcriptional, and translational levels in Arabidopsis, whereas less research has been performed on apple cuticular wax. Here, we provide a brief overview of how apple cuticular wax is formed, as well as its structure, composition, and function. An association among the environment, genes, and apple cuticular wax deposition was revealed. Cuticular wax prevents fruit rust from occurring on apple. Taken together, a detailed understanding of apple cuticular wax is discussed. The results will act as a reference for extending the storage period and increasing the commodity value of apple.


KeaA, a Dictyostelium Kelch-domain protein that regulates the response to stress and development.
The protein kinase YakA is responsible for the growth arrest and induction of developmental processes that occur upon starvation of Dictyostelium cells. yakA- cells are aggregation deficient, have a faster cell cycle and are hypersensitive to oxidative and nitrosoative stress. With the aim of isolating members of the YakA pathway, suppressors of the death induced by nitrosoative stress in the yakA- cells were identified. One of the suppressor mutations occurred in keaA, a gene identical to DG1106 and similar to Keap1 from mice and the Kelch protein from Drosophila, among others that contain Kelch domains. A mutation in keaA suppresses the hypersensitivity to oxidative and nitrosoative stresses but not the faster growth phenotype of yakA- cells. The growth profile of keaA deficient cells indicates that this gene is necessary for growth. keaA deficient cells are more resistant to nitrosoative and oxidative stress and keaA is necessary for the production and detection of cAMP. A morphological analysis of keaA deficient cells during multicellular development indicated that, although the mutant is not absolutely deficient in aggregation, cells do not efficiently participate in the process. Gene expression analysis using cDNA microarrays of wild-type and keaA deficient cells indicated a role for KeaA in the regulation of the cell cycle and pre-starvation responses. KeaA is required for cAMP signaling following stress. Our studies indicate a role for kelch proteins in the signaling that regulates the cell cycle and development in response to changes in the environmental conditions.


The effect of postlaminectomy spinal instability on the outcome of lumbar spinal stenosis patients.
Between 1986 and 1990, 37 of 72 patients undergoing decompressive lumbar laminectomy with medial facetectomy for lumbar stenosis at The Ohio State University were seen in follow-up at a mean of 31 months (range, 14-63 months) after their laminectomy and were evaluated by questionnaire, detailed neurologic examination, and static and dynamic lumbar radiographs. Thirteen patients who had undergone fusion or who had extenuating medical circumstances were excluded, leaving 24 patients for whom laminectomy was the sole treatment for lumbar stenosis. Postoperatively, normal walking improved from 4 to 45% of patients, sensory deficits decreased from 63 to 25%, and ability to perform most or all desired activities increased from 25 to 70%. Urinary function was unchanged. Thirteen patients (54%) showed radiographic signs of instability. All patients who were declared radiographically stable could walk without a prosthetic aid or normally; 62% of the unstable patients required aid for walking. All of the patients with a poor ambulatory outcome were radiographically unstable. Compared with stable patients, unstable patients had a significant (p < 0.01) decrease in their ambulatory ability. There was a clear correlation between the degree of listhesis and postoperative ambulatory status (p < 0.01). The unstable patients with a poor ambulatory outcome followed one of three clinical courses: improvement with later deterioration, improvement with a plateau at a poor functional level, or failure to improve from a poor functional level. In conclusion, (a) although instability did not necessarily preclude a good outcome, a poor ambulatory outcome was always associated with instability; (b) laminectomy can effectively ameliorate the symptoms of lumbar stenosis; however, there is a subset of patients in whom laminectomy is associated with instability and a poor clinical course.


CD44hiCD24lo mammosphere-forming cells from primary breast cancer display resistance to multiple chemotherapeutic drugs.
It has been widely suggested that mammosphere-forming cells from tumor cell lines or primary tumors represent the population of cancer stem cells (CSCs), which is supposed to lead to the failure of routine chemotherapy and the recurrence of the disease. However, it is still difficult to obtain CSCs from primary breast cancer for further investigation. We performed a modified culture system to generate mammosphere-forming cells derived from freshly isolated human breast cancer samples and the breast cancer cell line MCF-7. Cancer stem cell-like phenotypes such as CD44 and CD24 were measured by flow cytometry while alkaline phosphatase (AP) and mammaglobin (MGB1) expression was evaluated immunohistochemically. The expression levels of Klf4, Nanog, Oct4, Sox2 and mdr1 genes were analyzed by quantitative real‑time PCR. Resistance to chemotherapeutic drugs was detected through the apoptosis assay upon drug treatments together with the detection of drug-resistant gene mdr1. The results revealed that we successfully obtained mammosphere‑forming cells from the primary breast cancer in conditioned medium after 14 days of culture. Mammosphere-forming cells from primary breast cancer displayed a CD44hiCD24lo phenotype as well as positive AP and MGB1 reactivity. Stem cell-related genes such as Klf4, Nanog and Oct4 were detectably expressed in these cells. These cells formed tumor-like structures in the lymph nodes of nude mice, which were morphologically and histologically similar to breast cancer. Compared to the breast cancer cell line MCF-7 or mammosphere-forming cells from MCF-7 cells, the mammosphere-forming cells from the primary breast cancer exhibited resistance to three of four first-line chemotherapeutic drugs investigated through the induction of apoptosis, which was largely associated with the increased expression of drug-resistant gene mdr1 upon drug treatment. In conclusion, mammosphere-forming cells generated from the primary breast cancer exhibit CSC-like properties together with multiple drug resistance. Determination of the sensitivity of these primary cancer-derived mammosphere-forming cells to chemotherapeutic drugs may thus provide useful instructions for individualized therapy against the recurrence of breast cancer in the future.


Warning signal words: connoted strength and understandability by children, elders, and non-native English speakers.
Signal words, such as DANGER, WARNING and CAUTION, are commonly used in sign and product label warnings for the purpose of conveying different levels of hazard. Previous research has focused on whether people's perceptions of connoted hazard are consistent with the levels suggested by design standards and guidelines. Most investigations have used college students to evaluate the terms; other populations who may be at greater risk have not been adequately studied. One purpose of the present research was to determine whether young children, the elderly, and non-native English speakers perceive similar connoted hazard levels from the terms as undergraduates and published guidelines. A second purpose was to assess the terms' comprehensibility using various metrics such as missing values (i.e. ratings left blank) and understandability ratings. A third purpose was to develop a list of potential signal words that probably would be understandable to members of special populations. In the first experiment, 298 fourth- to eighth-grade students and 70 undergraduates rated 43 potential signal words on how careful they would be after seeing each term. The undergraduates also rated the terms on strength and understandability. In the second experiment, 98 elders and 135 non-native English speakers rated the same set of terms. The rank ordering of the words was found to be consistent across the participant groups. In general, the younger students gave higher carefulness ratings than the undergraduates. The words that the younger children and the non-native English speakers frequently left blank were given lower understandability ratings. Finally, a short list of terms was derived that 95% or 99% of the youngest students (fourth- and fifth-graders) and 80% of the non-native English speakers understood. Implications of hazard communication are discussed.


Epigenetic remodeling in heart failure with preserved ejection fraction.
In this review, we critically address the role of epigenetic processing and its therapeutic modulation in heart failure with preserved ejection fraction (HFpEF). HFpEF associates with a poor prognosis and the identification of novel molecular targets and therapeutic approaches are in high demand. Emerging evidence indicates a key involvement of epigenetic signals in the regulation of transcriptional programs underpinning features of HFpEF. The growing understanding of chromatin dynamics has led to the development of selective epigenetic drugs able to reset transcriptional changes thus delaying or preventing the progression toward HFpEF. Epigenetic information in the setting of HFpEF can be employed to: (i) dissect novel epigenetic networks and chromatin marks contributing to HFpEF; (ii) unveil circulating and cell-specific epigenetic biomarkers; (iii) build predictive models by using computational epigenetics and deep machine learning; (iv) develop new chromatin modifying drugs for personalized management of HFpEF. Acquired epigenetic signatures during the lifetime can contribute to derail molecular pathways involved in HFpEF. A scrutiny investigation of the individual epigenetic landscape will offer opportunities to develop personalized epigenetic biomarkers and therapies to fight HFpEF in the decades to come.


Identification of domains directing specificity of coupling to G-proteins for the melanocortin MC3 and MC4 receptors.
The melanocortin receptors, MC3R and MC4R, are G protein-coupled receptors that are involved in regulating energy homeostasis. Using a luciferase reporter gene under the transcriptional control of a cAMP- responsive element (CRE), the coupling efficiency of the MC4R and MC3R to G-proteins was previously shown to be different. MC4R exhibited only 30-50% of the maximum activity induced by MC3R. To assess the role of the different MC3R and MC4R domains in G-protein coupling, several chimeric MC3R/MC4R receptors were constructed. The relative luciferase activities, which were assessed after transfecting the chimeric receptors into HEK 293T cells, showed that the i3 (3rd intracellular) loop domain has an essential role in the differential signaling of MC3R and MC4R. To reveal which amino acid residue was involved in the MC4R-specific signaling in the i3 loop, a series of mutant MC4Rs was constructed. Reporter gene analysis showed that single mutations of Arg(220) to Ala and Thr(232) to either Val or Ala increased the relative luciferase activities, which suggests that these specific amino acids, Arg(220) and Thr(232), in the i3 loop of MC4R play crucial roles in G-protein coupling and the subtype-specific signaling pathways. An examination of the inositol phosphate (IP) levels in the cells transfected with either MC3R or MC4R after being exposed to the melanocortin peptides revealed significant stimulation of IP production by MC3R but no detectable increase in IP production was observed by MC4R. Furthermore, none of the MC4R mutants displayed melanocortin peptide-stimulated IP production. Overall, this study demonstrated that MC3R and MC4R have distinct signaling in either the cAMP- or the inositol phospholipid-mediated pathway with different conformational requirements.


The covariant dissipation function for transient nonequilibrium states.
It has recently become apparent that the dissipation function, first defined by Evans and Searles [J. Chem. Phys. 113, 3503 (2000)], is one of the most important functions in classical nonequilibrium statistical mechanics. It is the argument of the Evans-Searles fluctuation theorem, the dissipation theorem, and the relaxation theorems. It is a function of both the initial distribution and the dynamics. We pose the following question: How does the dissipation function change if we define that function with respect to the time evolving phase space distribution as one relaxes from the initial equilibrium distribution toward the nonequilibrium steady state distribution? We prove that this covariant dissipation function has a rather simple fixed relationship to the dissipation function defined with respect to the initial distribution function. We also show that there is no exact, time-local, Evans-Searles nonequilibrium steady state fluctuation relation for deterministic systems. Only an asymptotic version exists.


Responses of superoxide dismutase and glutathione reductase activities in cotton leaf tissue exposed to an atmosphere enriched in oxygen.
Responses of superoxide dismutase (EC 184.108.40.206) and glutathione reductase (EC 22.214.171.124) activities were evaluated in leaf tissue from intact cotton plants (Cotton Branch 1697) which were exposed to 75% O(2), 350 microliters per liter CO(2) for 48 hours. Soluble protein was extracted from O(2)-treated and control tissue, and enzyme levels were determined. Superoxide dismutase activity in cotton leaf tissue was high (26 units per milligram protein) under normal conditions of 21% O(2), saturating light, and limiting CO(2), and neither qualitative nor quantitative differences in the cyanide-sensitive or -insensitive forms of the enzyme occurred in response to hyperoxic conditions. Glutathione reductase activity, however, was 2- to 3-fold higher in extracts from tissue exposed to 75% O(2). No increase in activity was observed for the peroxisomal enzymes, glycolate oxidase (EC 22.214.171.124) and catalase (EC 126.96.36.199). Results are consistent with an integrated pathway involving superoxide dismutase and glutathione reductase for protection of sensitive leaf components against detrimental effects of intermediate reduction products of O(2).


Nanoscale control of silica particle formation via silk-silica fusion proteins for bone regeneration.
The biomimetic design of silk/silica fusion proteins was carried out, combining the self assembling domains of spider dragline silk (Nephila clavipes) and silaffin derived R5 peptide of Cylindrotheca fusiformis that is responsible for silica mineralization. Genetic engineering was used to generate the protein-based biomaterials incorporating the physical properties of both components. With genetic control over the nanodomain sizes and chemistry, as well as modification of synthetic conditions for silica formation, controlled mineralized silk films with different silica morphologies and distributions were successfully generated; generating 3D porous networks, clustered silica nanoparticles (SNPs), or single SNPs. Silk serves as the organic scaffolding to control the material stability and multiprocessing makes silk/silica biomaterials suitable for different tissue regenerative applications. The influence of these new silk-silica composite systems on osteogenesis was evaluated with human mesenchymal stem cells (hMSCs) subjected to osteogenic differentiation. hMSCs adhered, proliferated, and differentiated towards osteogenic lineages on the silk/silica films. The presence of the silica in the silk films influenced osteogenic gene expression, with the upregulation of alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen type 1 (Col 1) markers. Evidence for early bone formation as calcium deposits was observed on silk films with silica. These results indicate the potential utility of these new silk/silica systems towards bone regeneration.


Health effects from hazardous waste incineration facilities: five case studies.
Environmental pollution, primarily from industrialization, has caused significant adverse effects to humans, animals, and the ecosystem. Attempts have been made to reduce and prevent these pollutants through better waste management practices. Incineration is one such practice, which seeks to prevent adverse health impacts to future generations by destroying waste today, without increasing risk to those living near incineration facilities in the process. As with any industrial process, however, proper design and operation are important requirements to ensure the facility can be operated safely. Any technology that cannot be managed safely should not be considered acceptable. This paper reviews the scientific basis of past allegations associated with the process of hazardous waste incineration. These five case studies, which have attracted considerable public attention, have not been shown to be scientifically accurate of factually based. This paper attempts to separate fact from fiction and to show some of the consistent inaccuracies that were repeated throughout all five studies. In reviewing the above cases and others in the literature, several common elements become apparent. 1. Most of the reports are based on single newspaper articles, activist newsletters, interviews with admittedly biased respondents, and other secondary or inappropriate sources of information that do not withstand scientific scrutiny. 2. Research studies are quoted incompletely or out of context. Often the original point made by the researcher is the exact opposite of the impression left by Costner and Thornton. 3. In four of five cases, no data were supplied to substantiate the claims. As an observation, where substantive research data do not exist to support allegations of adverse health effects, a tendency seems to be increasing over time to make allegations and then not provide supporting data. Because public damage is often done simply by making the allegation, this tactic appears to be effective. Thus, unsubstantiated allegations should not go unchallenged. 4. A relatively small group of people appears to be consistently generating most of the allegations. 5. The format of the allegations tends to be similar; often just the name of the facility changes. 6. Furthermore, these same few individuals tend to repeat the same allegations about the same facilities, even after the allegations have been long since proven incorrect. Despite the widespread prevalence of incineration facilities around the world and the millions of tons of waste destroyed in them each year, surprisingly few reports of adverse health effects exist in the scientific literature relative to other types of waste management practices. 7. The existing reports do not indicate that hazardous waste incineration has widespread potential for adverse health effects. However, as with all industrial processes, care must be taken to ensure that facilities are well designed and well operated to minimize or prevent adverse health effects. As with all environmental exposures, potential impacts on public health need to be addressed scientifically. Making a scientifically valid connection between operation of an incinerator and resulting disease within a population is a difficult undertaking, requiring the combined efforts of toxicologists, epidemiologists, chemists, physicians, and persons in other disciplines. Nevertheless, concerns regarding potential impacts of incineration must be addressed and communicated, both accurately and effectively, if the actual risks of incineration are to become widely understood.


Molecular adsorbent recirculating system: albumin dialysis-based extracorporeal liver assist device.
Extracorporeal liver assist devices have been used for more than five decades to support patients with liver failure. Numerous modifications have been made to both biological as well as mechanical liver assist devices. Possibly, an ideal liver assist device would be one that would perform optimal detoxification and synthetic functions of the liver, be simple to set up and yet be cost-effective. An albumin dialysis-based device that uses a hybrid albumin-impregnated membrane to get rid of albumin-bound toxins that circulate in abundance in liver failure, called the molecular adsorbent recirculating system (MARS) has been in clinical use for nearly four years now. Results with the use of this device in both acute and acute-on-chronic liver failure have shown consistent improvement in biochemical profile, resolution of encephalopathy, correction in hemodynamics, reduction in intracranial pressure and some improvement in the synthetic function of the liver. In a number of studies, albeit of small sample size, survival advantage has also been observed. The timing of initiation of therapy with MARS, duration of treatment, frequency of sessions and 'maintenance therapy' are still some of the unresolved issues with the use of this device. Large multicentric trials on the use of this technique are expected to throw light on these issues and help optimize the potential of this liver assist device.


Risk indicators for talipes equinovarus in Washington State, 1987-1989.
To identify risk indicators for talipes equinovarus, we compared 175 case children with talipes equinovarus of unknown etiology identified through the Washington State Birth Defect Registry with 1,470 control children sampled from resident live births. Infant gender, maternal smoking, death of a preterm sibling, and marital status were independently related to talipes equinovarus in an analysis based on information from birth certificate records. The findings differed by infant gender. The prevalence odds ratio for maternal smoking was 2.6 (95% confidence interval: 1.6-4.0) in males and 1.4 (95% confidence interval:0.6-3.2) in females.


CONVERTING THE 'RIGHT TO LIFE' TO THE 'RIGHT TO PHYSICIAN-ASSISTED SUICIDE AND EUTHANASIA': AN ANALYSIS OF CARTER V CANADA (ATTORNEY GENERAL), SUPREME COURT OF CANADA.
In its landmark decision Carter v Canada (Attorney General), the Supreme Court of Canada ruled that the criminal prohibition on physician-assisted suicide and euthanasia for certain persons in certain circumstances violated their rights to life, liberty, and security of the person in sec. 7 of the Canadian Charter of Rights and Freedoms and thus was unconstitutional. The Supreme Court in effect overruled its earlier decision, Rodriguez v British Columbia (Attorney General), which upheld the prohibition as constitutionally valid, on the basis of changes in Charter jurisprudence and in the social facts since Rodriguez was decided. We argue that the Supreme Court's Carter decision shows conceptual disagreements with its Rodriguez decision concerning the nature and scope of the sec. 7-protected interests and the accompanying principles of fundamental justice. Not only do these conceptual differences have little to do with the changes that the Court in Carter invoked for 'revisiting' Rodriguez, the Court's articulation of the sec. 7 interests, particularly the right to life, and the principles of fundamental justice, especially the principle of over breadth, are problematic on their own terms. Furthermore, the way in which the Court dealt with evidence regarding abuses in permissive jurisdictions is also subject to criticism. We recommend that if, as now seems inevitable, legislation is introduced, it should mandate that assisted suicide and euthanasia be performed by specially licensed non-medical personnel and only on the authorization of a Superior Court judge. We also reject the key recommendations recently issued by the Provincial-Territorial Expert Advisory Group on Physician-Assisted Dying.


Transforming growth factor-β-induced secretion of extracellular vesicles from oral cancer cells evokes endothelial barrier instability via endothelial-mesenchymal transition.
During metastasis, cancer cells undergo epithelial-mesenchymal transition (EMT) in response to transforming growth factor-β (TGF-β), which is abundant in the tumor microenvironment, and acquire invasive and metastatic potentials. Metastasis to distant organs requires intravascular invasion and extravasation of cancer cells, which is accompanied by the disruption of the adhesion between vascular endothelial cells. Cancer cell-derived extracellular vesicles (EVs) have been suggested to induce the destabilization of normal blood vessels at the metastatic sites. However, the roles of EVs secreted from cancer cells that have undergone EMT in the destabilization of blood vessels remain to be elucidated. In the present study, we characterized EVs secreted by oral cancer cells undergoing TGF-β-induced EMT and elucidated their effects on the characteristics of vascular endothelial cells. Induction of EMT by TGF-β in human oral cancer cells was assessed using quantitative RT-PCR (qRT-PCR) and immunocytochemistry. Oral cancer cell-derived EVs were isolated from the conditioned media of oral cancer cells that were treated with or without TGF-β using ultracentrifugation, and characterized using nanoparticle tracking analysis and immunoblotting. The effects of EVs on human umbilical artery endothelial cells were examined by qRT-PCR, cellular staining, and permeability assay. The significant differences between means were determined using a t-test or one-way analysis of variance with Tukey's multiple comparisons test. Oral cancer cells underwent EMT in response to TGF-β as revealed by changes in the expression of epithelial and mesenchymal cell markers at both the RNA and protein levels. Oral cancer cells treated with TGF-β showed increased EV production and altered EV composition when compared with untreated cells. The EVs that originated from cells that underwent EMT by TGF-β induced endothelial-mesenchymal transition, which was characterized by the decreased and increased expression of endothelial and mesenchymal cell markers, respectively. EVs derived from oral cancer cells also induced intercellular gap formation which led to the loss of endothelial cell barrier stability. EVs released from oral cancer cells that underwent TGF-β-induced EMT target endothelial cells to induce vascular destabilization. Detailed characterization of oral cancer-derived EVs and factors responsible for EV-mediated vascular instability will lead to the development of agents targeting metastasis.


Can optical diagnosis of small colon polyps be accurate? Comparing standard scope without narrow banding to high definition scope with narrow banding.
To study the accuracy of using high definition (HD) scope with narrow band imaging (NBI) vs standard white light colonoscope without NBI (ST), to predict the histology of the colon polyps, particularly those < 1 cm. A total of 147 African Americans patients who were referred to Howard University Hospital for screening or, diagnostic or follow up colonoscopy, during a 12-mo period in 2012 were prospectively recruited. Some patients had multiple polyps and total number of polyps was 179. Their colonoscopies were performed by 3 experienced endoscopists who determined the size and stated whether the polyps being removed were hyperplastic or adenomatous polyps using standard colonoscopes or high definition colonoscopes with NBI. The histopathologic diagnosis was reported by pathologists as part of routine care. Of participants in the study, 55 (37%) were male and median (interquartile range) of age was 56 (19-80). Demographic, clinical characteristics, past medical history of patients, and the data obtained by two instruments were not significantly different and two methods detected similar number of polyps. In ST scope 89% of polyps were < 1 cm vs 87% in HD scope (P = 0.7). The ST scope had a positive predictive value (PPV) and positive likelihood ratio (PLR) of 86% and 4.0 for adenoma compared to 74% and 2.6 for HD scope. There was a trend of higher sensitivity for HD scope (68%) compare to ST scope (53%) with almost the same specificity. The ST scope had a PPV and PLR of 38% and 1.8 for hyperplastic polyp (HPP) compared to 42% and 2.2 for HD scope. The sensitivity and specificity of two instruments for HPP diagnosis were similar. Our results indicated that HD scope was more sensitive in diagnosis of adenoma than ST scope. Clinical diagnosis of HPP with either scope is less accurate compared to adenoma. Colonoscopy diagnosis is not yet fully matched with pathologic diagnosis of colon polyp. However with the advancement of both imaging and training, it may be possible to increase the sensitivity and specificity of the scopes and hence save money for eliminating time and the cost of Immunohistochemistry/pathology.


Retrospective Genotyping and Whole Genome Sequencing of a Canine Parvovirus Outbreak in Bangladesh.
Canine parvovirus 2 (CPV-2) outbreaks in close quarters such as kennels or shelters can cause substantial case fatality. Thirteen dead Labradors from a secluded kennel of security dogs presented with typical clinical signs and gross pathology of parvovirus infection. Whole genome shotgun sequencing from tissue-extracted genomic DNA detected new CPV-2a as the contributing antigenic variant. Further genotyping using polymerase chain reaction coupled with high-resolution melt assays (PCR-HRM) confirmed new CPV-2a infection in all deceased dogs. PCR-HRM of additional thirty-four clinically suspected dogs suggested that this variant is in wider community circulation, at least in the southeastern part of Bangladesh. We present complete genome sequence of the new CPV-2a variant circulating in the domestic canine population of Bangladesh.


Tissue culture specificity of the tobacco ASA2 promoter driving hpt as a selectable marker for soybean transformation selection.
This study was carried out to determine if the tobacco anthranilate synthase ASA2 2.3 kb promoter drives tissue culture specific expression and if it is strong enough to drive hpt (hygromycin phosphotransferase) gene expression at a level sufficient to allow selection of transformed soybean embryogenic culture lines. A number of transformed cell lines were selected showing that the promoter was strong enough. Northern blot analysis of plant tissues did not detect hpt mRNA in the untransformed control or in the ASA2-hpt plants except in developing seeds while hpt mRNA was detected in all tissues of the CaMV35S-hpt positive control line plants. However, when the more sensitive RT-PCR assay was used all tissues of the ASA2-hpt plants except roots and mature seeds were found to contain detectable hpt mRNA. Embryogenic tissue cultures initiated from the ASA2-hpt plants contained hpt mRNA detectable by both northern and RT-PCR analysis and the cultures were hygromycin resistant. Friable callus initiated from leaves of ASA2-hpt plants did in some cases contain hpt mRNA that was only barely detectable by northern hybridization even though the callus was very hygromycin resistant. Thus the ASA2 promoter is strong enough to drive sufficient hpt expression in soybean embryogenic cultures for hygromycin selection and only very low levels of expression were found in most plant tissues with none in mature seeds.


Priming DNA replication from triple helix oligonucleotides: possible threestranded DNA in DNA polymerases.
Triplex associate with a duplex DNA presenting the same polypurine or polypyrimidine-rich sequence in an antiparallel orientation. So far, triplex forming oligonucleotides (TFOs) are known to inhibit transcription, replication, and to induce mutations. A new property of TFO is reviewed here upon analysis of DNA breakpoint yielding DNA rearrangements; the synthesized sequence of the first direct repeat displays a skewed polypurine- rich sequence. This synthesized sequence can bind the second homologous duplex sequence through the formation of a triple helix, which is able to prime further DNA replication. In these case, the d(G)-rich Triple Helix Primers (THP) bind the homologous strand in a parallel manner, possibly via a RecA-like mechanism. This novel property is shared by all tested DNA polymerases: phage, retrovirus, bacteria, and human. These features may account for illegitimate initiation of replication upon single-strand breakage and annealing to a homologous sequence where priming may occur. Our experiments suggest that DNA polymerases can bind three instead of two polynucleotide strands in their catalytic centre.


Molecular cloning, sequencing, and expression of the crr gene: the structural gene for IIIGlc of the bacterial PEP:glucose phosphotransferase system.
The phosphoenolpyruvate:glucose phosphotransferase system (PTS) of Salmonella typhimurium is involved both in glucose transport and in the regulation and synthesis of adenylate cyclase and several transport systems. The crr gene has been implicated in this regulating mechanism. A 9.6-kb segment of the S. typhimurium chromosome containing the crr gene was cloned in pAT153. The cloned fragment also complemented cysA mutations but did not contain a functional pts operon which is closely linked to the crr gene and codes for two enzymes of the PTS. Although cysA and crr have been reported to be located on opposite sides of ptsHI, our results suggest that the correct gene order is cysK-ptsHI-crr-cysA. Expression of crr plasmids in a maxicell system yielded two proteins which reacted with specific anti-serum against IIIGlc. The apparent mol. wts. in SDS-polyacrylamide gels were 20 000 and 21 000, the former corresponding to the major band of purified IIIGlc. Both forms were also observed in bacterial extracts and purified IIIGlc. The crr gene was localized on a 1-kb EcoRI-EcoRV fragment of the 9.6-kb insert and sequenced. It codes for a single protein (18 556 D) containing 169 amino acid residues and identified as IIIGlc.


Communication technology adoption among older adult veterans: the interplay of social and cognitive factors.
InTouch is an electronic communication platform designed to be accessible by computer-naive seniors. The present study explored the process of adoption and use of the application by seniors with and without mild cognitive impairment (MCI) through the lens of Social Cognitive Theory (SCT). We studied adoption and use of InTouch for social communication over a 12-week period in a 475-bed Veteran's care facility at Sunnybrook Health Sciences Centre in Toronto, Canada. Eleven older adult veterans participated, six of whom had MCI, as indicated by their Montreal Cognitive Assessment score. Veterans were partnered with volunteers, each was provided with an iPad with the InTouch application. Qualitative data were collected through interviews, field notes, and direct observation. Quantitative data were collected from data logging of the software and medical charts. Data types and sources were triangulated and examined through the lens of SCT. A total of 2361 messages (102 videos, 359 audios, 417 photos, 1438 texts) were sent by 10 of the 11 veterans over the 12-week study period. There was no apparent difference in extent of adoption or use, between participants with and without MCI. Participants used various resources and techniques to learn, provided that they felt motivated to connect with others using the app. This pilot illustrates both the accessibility of InTouch and the promise of using extrinsic motivators such as social bonding to promote learning in institutionalized older adults with and without cognitive impairment, whose intrinsic motivation and self-efficacy may well be suffering.


[Sixty years of mitral valve surgery].
On June 10, 1948, Charles Bailey, MD, operated successfully a mitral valve stenosis in Philadelphia and six days later, Dwight Harken, MD, performed the same operation in Boston, marking the onset of cardiovascular surgery. These successful operations were preceded by several failures and even deaths, that had to be overcome by both pioneers. This manuscript reviews several cases and situations that these surgeons had to face during the development of cardiovascular surgery, that changed the natural history of cardiac diseases. The history culminates with the successful mitral valve replacement, performed by Albert Starr using a mechanical valve designed by him and Lowell Edwards, a retired engineer whose primary interest was to develop an artificial heart. The first mitral commissurotomy in Chile was performed by Svante Tornvall, MD, and Pedro Uribe, MD, at van Buren Hospital in Valparaiso in December, 1950. The first mitral valve replacement was performed by Hugo Salvestrini, MD, in 1964 at the Catholic University Hospital.


Relationship between urinary excretion of modified nucleosides and rheumatoid arthritis process.
The levels of the five methylated nucleosides pseudouridine (psi-Urd), 1-methyladenosine (1-MeAdo), 4 acetylcytidine (4-AcCyd), 1 methylinosine (1-Melno) and 7 methylguanosine (7-MeGuo) resulting from RNA degradation were examined in the urine of rheumatoid arthritis (RA) patients. Of these five, 1-MeAdo and psi-Urd were correlated with the active phase of the disease, while two others (4-AcCyd and 1-Melno), which require further evaluation, appeared to be linked to the prognosis of the disease. As RNA turnover is closely associated with cell proliferation, including that of lymphocytes in RA, there may be a hitherto unsuspected benefit in measuring 1-MeAdo and psi-Urd as biochemical markers of RA disease activity.


Hepatic injuries resulting from chronic alcohol abuse identified by forensics.
Alcohol intake is largely spread all over the world, although it is well-known that it causes important changes of the liver, from liver steatosis, hepatitis to liver cirrhosis. The study we performed on 93 patients deceased in suspicious circumstances and brought to the Institute of Forensic Medicine, Iaşi, Romania, confirmed through the determination of Ethyl glucuronide, that these were alcohol consumers. The macroscopic analysis during necropsy highlighted the presence of alcoholic liver disease (ALD), while microscopy studies confirmed the macroscopic observations. The immunohistochemical studies showed the existence of a chronic liver inflammation, the transdifferentiation of stellate hepatic cells, the activation of Kupffer cells, important changes of the hepatic vascular network, hepatocyte necrosis, lipid loadings and the progression of liver fibrosis process.


The antioxidative properties of S-allyl cysteine not only influence somatic cells but also improve early embryo cleavage in pigs.
In vitro cultivation systems for oocytes and embryos are characterised by increased levels of reactive oxygen species (ROS), which can be balanced by the addition of suitable antioxidants. S-allyl cysteine (SAC) is a sulfur compound naturally occurring in garlic (Allium sativum), which is responsible for its high antioxidant properties. In this study, we demonstrated the capacity of SAC (0.1, 0.5 and 1.0 mM) to reduce levels of ROS in maturing oocytes significantly after 24 (reduced by 90.33, 82.87 and 91.62%, respectively) and 48 h (reduced by 86.35, 94.42 and 99.05%, respectively) cultivation, without leading to a disturbance of the standard course of meiotic maturation. Oocytes matured in the presence of SAC furthermore maintained reduced levels of ROS even 22 h after parthenogenic activation (reduced by 66.33, 61.64 and 57.80%, respectively). In these oocytes we also demonstrated a growth of early embryo cleavage rate (increased by 33.34, 35.00 and 35.00%, respectively). SAC may be a valuable supplement to cultivation media.


A community wide promotion of asthma self management: process evaluation.
During the months February through July 1991, a community wide promotion of asthma self-management was undertaken as a pilot study for the national launch of an asthma action plan developed by the Asthma Foundation of New Zealand in conjunction with the Royal New Zealand College of General Practitioners. A multidisciplinary team of hospital and community-based health workers was established, with the aim of educating and resourcing general practitioners, practice nurses and retail pharmacists to enable them to effectively promote and distribute the asthma action plan. 332 general practitioners and 148 retail pharmacists were surveyed through postal and telephone questionnaires at the completion of the promotion, to assess its impact on health professionals and to obtain feedback for the national promotion of the asthma action plan. 108 (73%) of pharmacists who responded and were involved with the promotion found their participation to be worthwhile, although some had difficulty allocating sufficient time to give detailed advice to patients. Of the 240 general practitioners who responded, 77% indicated that they had used the asthma action plan with their patients. They were positive about the use of the workshop format that had provided education and resources for the plan, and of those that had used the plan, 94% indicated that they would continue to promote the plan, or one similar. The promotion of the asthma action plan in Canterbury had a major impact on health professionals. The community-wide promotion might have had a greater impact on people with asthma had television advertising been used. The pilot project provided useful feedback for the Asthma Foundation in their preparation for the national launch.


Decree No. 88-86, 17 July 1986.
This Decree amends Article 92 of the Honduras Law of Agrarian Reform to provide that the Executive Directorate may, after analysis, transfer to rural peasants and peasant cooperatives and enterprises land at a cost less than the value of land expropriated in the same area, given its condition, including the quality of soil and infrastructure. Previously, Article 92 contained no provision for the modification of land prices. The value of all land transferred had to be the same as that of land expropriated in the same area.


Living donor liver transplantation in the USA.
Living donor liver transplant (LDLT) accounts for a small volume of the transplants in the USA. Due to the current liver allocation system based on the model for end-stage liver disease (MELD), LDLT has a unique role in providing life-saving transplantation for patients with low MELD scores and significant complications from portal hypertension, as well as select patients with hepatocellular carcinoma (HCC). Donor safety is paramount and has been a topic of much discussion in the transplant community as well as the general media. The donor risk appears to be low overall, with a favorable long-term quality of life. The latest trend has been a gradual shift from right-lobe grafts to left-lobe grafts to reduce donor risk, provided that the left lobe can provide adequate liver volume for the recipient.


Multicolor tunability and upconversion enhancement of fluoride nanoparticles by oxygen dopant.
The ability to manipulate the upconversion luminescence of lanthanide-ion doped fluoride upconversion nanoparticles (UCNPs) is particularly important and highly desired due to their wide applications in color displays, multiplexing bioassays and multicolor imaging. Here, we developed a strategy for simultaneously tuning color output and enhancing upconversion emission of Yb/Er doped fluoride UCNPs, based on adjusting the oxygen doping level. The synthesis of multicolored multifunctional NaGdF4:Yb,Er UCNPs was used as the model host system to demonstrate this protocol. Ammonium nitrate (NH4NO3) was used as the oxygen source and added into the reaction system at the beginning stage of nucleation and growth process of fluoride UCNPs, which facilitates the formation of enough oxygen atoms and the diffusion of these into the fluoride host matrix. The results revealed that multicolour output and upconversion enhancement mainly resulted from the variation of phonon energy and crystal field symmetry of the host lattice, respectively. This strategy can be further expanded to other fluoride host matrices. As an example of an application, multicolored UCNPs were used as a color converter in light emitting diodes, which can effectively convert near-infrared light into visible light. It is expected that these multicolored UCNPs will be promising for applications in multiplexing biodetection, bioimaging (optical and magnetic resonance imaging) and other optical technologies, and the present method for the control of O(2-) doping may also be used in other functional nanomaterials.