[Combined antiretroviral therapy for prevention of vertical HIV-1 transmission].
A 25-year old woman with rapid HIV disease progression had been receiving zidovudine (ZDV) for two years, when she became pregnant. She had a high viral load and carried out zidovudine-resistant viral strains. For these reasons, and with the main objective to maximally reduce viremia, the association of DDI to ZDV was introduced a few weeks before delivery. The virological follow-up for one year has confirmed the lack of HIV infection in the child. Combined antiretroviral therapy during the last weeks of pregnancy might be considered for the prevention of vertical transmission of HIV in cases of high risk of newborn infection, without adding relevant toxicity.


2-Substituted 1,4-Naphthoquinones in [6 + 4]-Cycloaddition with 8,8-Dicyanoheptafulvene.
This study demonstrates that classical lowest unoccupied molecular orbital reactivity of 2-substituted 1,4-naphthoquinones is possible to be reversed by deprotonation and application of the resulting dienolate as a 4π component in the higher-order [6 + 4]-cycloaddition proceeding in a completely pericyclic manner. 8,8-Dicyanoheptafulvene was shown to be an efficient 6π component in the developed reaction opening the access to functionalized cycloadducts in a diastereoselective manner by employing organocatalytic activation. Attempts to introduce enantioselective version of the developed higher-order cycloaddition were also undertaken.


Heat generation by irradiated complex composite nanostructures.
Heating of irradiated metallic e-beam generated nanostructures was quantified through direct measurements paralleled by novel model-based numerical calculations. By comparing discs, triangles, and stars we showed how particle shape and composition determines the heating. Importantly, our results revealed that substantial heat is generated in the titanium adhesive layer between gold and glass. Even when the Ti layer is as thin as 2 nm it absorbs as much as a 30 nm Au layer and hence should not be ignored.


Ambipolar Discotic Liquid Crystals Built Around Platinum Diimine-Dithiolene Cores.
Platinum diimine dithiolene complexes bearing mesogenic groups on one or both ligands have been prepared through an original ligand metathesis reaction to introduce the dithiolene ligand. The neutral diimine ligands, the intermediate platinum dichloride diimine complexes, and the target compounds were characterized by a combination of electronic (electrochemistry, absorption and emission spectroscopy, DFT calculations) and structural (SAXS, DSC) tools. Several novel liquid crystalline platinum diimine-dithiolene were identified over a large temperature range, and the systems were endowed with ambipolar properties, associated with the high reversibility of both oxidation and reduction processes.


Space radiation-associated lung injury in a murine model.
Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to (137)Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u (56)Fe ions, or 350 MeV/u (28)Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy (56)Fe or (28)Si ions markedly decreased sphingosine-1-phosphate levels and Akt- and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dose-dependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions.


Suitability of the cingulate cortex for neural control.
Recent neuroprosthetic work has focused on the motor cortex as a source of voluntary control signals. However, the motor cortex can be damaged in upper motor neuron degenerative diseases such as primary lateral sclerosis and amyotrophic lateral sclerosis. The possibility exists that prefrontal areas may also be used in neuroprosthetic devices. Here, we report the use of the cingulate cortex in a neuroprosthetic model. Seven rats were able to significantly modulate spiking activity in the cingulate cortex in order to receive reward. Furthermore, experiments with single neurons provide evidence that the cingulate cortex neuronal modulation is highly flexible and thus useful for a neuroprosthetic device.


Keokuk County rural health study: self-reported use of agricultural chemicals and protective equipment.
The Keokuk County Rural Health Study is a population-based study of an agricultural community in Iowa. The study includes in-depth evaluations of respiratory disease, injury, and other health outcomes in relation to environmental and occupational exposures. This article reports descriptive findings on pesticide use from among the 1191 participants completing occupational surveys. Fifty-one percent (612) of respondents (farmers and non-farmers) had applied insecticides including lawn and garden chemicals at home during the past year. Thirty-three percent (395) of respondents had personally mixed or applied farm chemicals during their life. One-hundred and four had a current pesticide applicator's license. Information on the specific types of pesticides and protective measures used was obtained for the 144 individuals who had mixed or applied pesticides on farms within the previous year. Of these individuals, 67% worked with fertilizers, 49% used herbicides, 48% used crop insecticides, 28% used crop storage insecticides, 45% applied livestock insecticides, and 9% worked with fungicides. The use of personal protective equipment such as gloves, aprons, and respirators varied depending on the chemical. A substantial proportion did not use gloves even for mixing. Thirty-five percent reported at least one suspected work-related symptom after working with pesticides during the previous year. The lack of differences in protective equipment use between applicators who have completed pesticide applicator training courses and those who have not suggests a need to develop more effective training methods. The increased use of protective equipment when applying odorous agrochemicals suggests that addition of an odorant to more toxic pesticides may be a successful intervention strategy.


Immunolocalization of entactin, a sulfated basement membrane component, in rodent tissues, and comparison with GP-2 (laminin).
Entactin is a sulfated glycoprotein in the extracellular basement membrane like matrix produced by M1536-B3 cells, a mouse endodermal line derived from an embryonal carcinoma. It has a molecular weight of 158,000 and is chemically and immunologically distinguishable from GP-2 (laminin) and fibronectin. Antibodies produced against entactin and GP-2 react with subepithelial and vascular basement membranes in rat lung, liver, spleen, and kidney and mouse placenta and kidney when examined by light microscopy. Both antibodies yield staining around the marginal sinus of the white pulp of the spleen. Antientactin reacts with basement membrane and mesangium in rat glomeruli, and anti-GP2 does not. Ultrastructurally, staining in kidneys is strongest at epithelial or endothelial cell membranes bordering basement membranes, with only moderate staining of the basement membrane proper. Intracellular staining is not present. The location of entactin suggests that it has a role in the interaction of cells with extracellular matrix, possibly in adhesion. Lack of intracellular staining suggests that the tissues studied are not actively producing entactin or GP-2 and that these substances may be fairly stable in adult organisms.


Interactions over time between cereal leaf beetle (Coleoptera: Chrysomelidae) and larval parasitoid Tetrastichus julis (Hymenoptera: Eulophidae) in Utah.
The phenology of parasitism of the cereal leaf beetle, Oulema melanopus (L.) (Coleoptera: Chrysomelidae) by Tetrastichus julis (Walker) (Hymenoptera: Eulophidae) was studied in small grain fields from 2000 to 2005 in northern Utah, after release and redistribution of the partially bivoltine larval parasitoid during the 1990s. Host larvae first occurred in May, with peak infestation typically occurring in early to mid-June. Parasitism by overwintering females of T. julis was highest among earliest developing beetle larvae. Thereafter, rates of parasitism fell to low levels (5-10% or less) by the latter half of June, when heat accumulation had reached 280-350 degree-days (based on a minimum threshold of 8.9 degrees C). With the emergence of second generation parasitoids, rates of parasitism rose to levels approaching 100% among the relatively few late-developing larvae of O. inelanopus. Clear and consistent differences over the years were not observed among different crops of small grains (barley, wheat, or oats) either in the phenology and intensity of beetle infestation, or in the rate of parasitism of beetle larvae. The rate of parasitism was especially high in 2005, and an increase in the minimum level of parasitism (observed each year at mid-season) was apparent over the course of the study. These results indicate that the parasitoid has become well established and seems to be continuing to increase in its impact on O. melanopus in northern Utah, despite a relatively hostile environment of crop management, wherein most fields are plowed and disked annually.


Comparative pharmacokinetics of borneol in cerebral ischemia-reperfusion and sham-operated rats.
This study was designed to investigate the pharmacokinetics of borneol in the pathological conditions of stroke and evaluate the pharmacokinetic differences of borneol caused by stroke after oral administration of borneol and Xingnaojing (XNJ). The rats were divided into two groups, ischemia-reperfusion (IR) and sham-operated (SO) rats. Each group contained two subgroups: pure borneol and XNJ subgroups. After administration with the same dosages of borneol 162.0 mg/kg, plasma samples were collected. The cerebral ischemia-reperfusion model was created by reversible middle cerebral artery occlusion (MCAO). The blood samples were collected punctually after oral administration and a specific gas chromatographic system-flame ionization detector (GC-FID) method was developed and employed to determine the level of borneol in the plasma. The pharmacokinetic parameters were analyzed using non-compartmental methods with Kinetica. After administration of borneol, the maximum plasma concentration (Cmax) and area under the curve (AUC) values in stroke rats significantly increased by 302% and 275%, respectively, compared with the SO rats, and the same phenomenon appeared after administration of XNJ. In the rats with the same physiological conditions, the Cmax and AUC had higher values in the borneol subgroup (P<0.05). These results suggest that the pathological damages of ischemia-reperfusion have a significant impact on the pharmacokinetic traits of borneol and that there are some components in XNJ inhibiting the absorption of borneol.


Determination of chlorpromazine in the blood and brain of mice by high performance liquid chromatography combined with electrochemical detection.
A simple and sensitive procedure was developed for determining the concentration of chlorpromazine (CPZ) in the blood and brain of mice with promethazine as the internal standard. The procedure involves (1) primary extraction by a mixture of heptane and isoamyl alcohol (99:1) in an alkaline condition and (2) determination by means of high performance liquid chromatography with electrochemical detection. The detection limit of CPZ was 0.5 ng for one chromatographic injection. The drug was detectable in a 100 microliters sample of the blood by 6 hr after an intravenous injection of 0.25 mg/kg. The concentration of CPZ was about 40 times higher in the brain compared with that in the blood. The biological half life was estimated to be 87 and 65 min, in the blood and brain, respectively. The proposed method is also applicable for the determination of other phenothiazine derivatives and effective for pharmacokinetic study of the compounds in clinics and laboratories.


Interaction of γ-conglutin from Lupinus albus with model phospholipid membranes: Investigations on structure, thermal stability and oligomerization status.
Interaction with model phospholipid membranes of lupin seed γ-conglutin, a glycaemia-lowering protein from Lupinus albus seeds, has been studied by means of Fourier-Transform infrared spectroscopy at p2H 7.0 and at p2H 4.5. The protein maintains the same secondary structure both at p2H 7.0 and at p2H 4.5, but at p2H 7.0 a higher 1H/2H exchange was observed, indicating a greater solvent accessibility. The difference in Tm and TD1/2 of the protein at the abovementioned p2H's has been calculated around 20 °C. Infrared measurements have been then performed in the presence of DMPG and DOPA at p2H 4.5. DMPG showed a little destabilizing effect while DOPA exerted a great stabilizing effect, increasing the Tm of γ-conglutin at p2H 4.5 of more than 20 °C. Since γ-conglutin at p2H 4.5 is in the monomeric form, the interaction with DOPA likely promotes the oligomerization even at p2H 4.5. Interaction between DMPG or DOPA and γ-conglutin has been confirmed by turbidity experiments with DMPC:DMPG or DOPC:DOPA SUVs. Turbidity data also showed high-affinity binding of γ-conglutin to anionic SUVs made up with DOPA. The molecular features outlined in this study are relevant to address the applicative exploitation and to delineate a deeper comprehension of the natural functional role of γ-conglutin.


Comparison of three serologic techniques for detection of antibody to Mycoplasma pulmonis.
A comparison of three micro-assay detection systems for naturally occurring and experimentally induced rat antibody to Mycoplasma pulmonis was performed. The micro-enzyme linked immunoabsorbent assay was found superior to counter immunoelectrophoresis or complement fixation techniques when comparing sensitivity, duration of antibody response, or technical requirements. The primary immune response was routinely detected at 3 weeks after antigen exposure when using the enzyme linked or complement fixation assays.


Normal and leukaemic human haemopoietic cells in diffusion chamber. A morphological and functional CFU-C study.
Leukaemic human bone marrow and peripheral blood cells were cultured for 25 d in diffusion chambers implanted into cyclophosphamide treated mice. Normal bone marrow cells were cultured simultaneously. These cells were studied both morphologically and functionally (CFU-C). The leukaemic cells behaved heterogeneously, 2 groups being distinguishable in accordance with their initial in vitro growth pattern (1: no growth or microcluster growth. 2: macrocluster growth). Group I showed progressive cellular death with a diminution of granulocytic progenitors and the appearance of a predominantly macrophagic population. This behaviour resembled that of the control group. The initial microcluster growth pattern remained identical throughout the entire culture period. Group 2, after considerable cellular death up to d 5, showed an explosive proliferation of the granulocytic progenitors and incomplete differentiation (up to myelocyte). The initial macrocluster growth pattern remained identical.


[Survey and anslysis of infection rate of dog rabies in the regions with high incidence of human rabies].
To investigate the situation of dog rabies and analyze it's relationship with human rabies. In Guizhou, Guangxi and Hunan provinces which suffered from rabies most heavily, one or two cities were selected respectively from regions with high-, middle-, low-incidence rate of human rabies as investigation spots where Dogs' brain specimens were collected and detected with both direct immunofluorescence assay (IFA) and RT-PCR. A total of 2887 specimens were collected and 66 of these were positive for IFA and RT-PCR. Therefore, the rate of positive specimens was 2.3%. However, there was not a close relationship in the incidence rate of dog rabies and human rabies. Dog's infection situation of rabies contributed to the severe epidemic of human rabies.


Conditional robustness analysis for fragility discovery and target identification in biochemical networks and in cancer systems biology.
The study of cancer therapy is a key issue in the field of oncology research and the development of target therapies is one of the main problems currently under investigation. This is particularly relevant in different types of tumor where traditional chemotherapy approaches often fail, such as lung cancer. We started from the general definition of robustness introduced by Kitano and applied it to the analysis of dynamical biochemical networks, proposing a new algorithm based on moment independent analysis of input/output uncertainty. The framework utilizes novel computational methods which enable evaluating the model fragility with respect to quantitative performance measures and parameters such as reaction rate constants and initial conditions. The algorithm generates a small subset of parameters that can be used to act on complex networks and to obtain the desired behaviors. We have applied the proposed framework to the EGFR-IGF1R signal transduction network, a crucial pathway in lung cancer, as an example of Cancer Systems Biology application in drug discovery. Furthermore, we have tested our framework on a pulse generator network as an example of Synthetic Biology application, thus proving the suitability of our methodology to the characterization of the input/output synthetic circuits. The achieved results are of immediate practical application in computational biology, and while we demonstrate their use in two specific examples, they can in fact be used to study a wider class of biological systems.


Reduction of medication errors in a pediatric cardiothoracic intensive care unit.
Medication errors resulting in patient harm were reduced from 33 in 2010 to 3 in 2011, 6 in 2012, and 4 in 2013 by initiating the following quality improvement interventions: multidisciplinary cardiothoracic intensive care unit quality committee, nursing education, shift change medication double check, medication error huddles, safety systems checklist, distraction-free zone to enter orders, and medication bar coding.


A Light-Induced Vinylogous Nazarov-Type Cyclization.
The first examples of a photochemically induced vinylogous Nazarov-type cyclization forming a cycloheptadienone core are described. The reaction can be included in a three-step cascade consisting of a photochemical isoxazole-azirine ring contraction, cobalt(II)-catalyzed ring expansion, and the photochemical cyclization. Furthermore, the first representative of the hitherto unknown 1-azatricyclo[18.104.22.168(2,6)]hexanes has been identified as a side product of the azirine formation.


Layer- and subregion-specific electrophysiological and morphological changes of the medial prefrontal cortex in a mouse model of neuropathic pain.
Chronic neuropathic pain constitutes a serious public health problem, but the disease mechanisms are only partially understood. The involvement of different brain regions like the medial prefrontal cortex has already been established, but the comparison of the role of different subregions and layers is still inconclusive. In the current study, we performed patch-clamp recordings followed by anatomical reconstruction of pyramidal cells from different layers of the prelimbic and infralimbic subregions of the medial prefrontal cortex in neuropathic (spared nerve injury, SNI) and control mice. We found that in the prelimbic cortex, layer 2/3 pyramidal cells from SNI mice exhibited increased excitability compared to sham controls, whereas prelimbic layer 5 pyramidal neurons showed reduced excitability. Pyramidal cells in both layer 2/3 and layer 5 of the infralimbic subregion did not change their excitability, but layer 2/3 pyramidal cells displayed increased dendritic length and branching. Our findings support the view that chronic pain is associated with subregion- and layer-specific changes in the medial prefrontal cortex. They therefore provide new insights into the mechanisms underlying the chronification of pain.


Polygamy: a cultural trait and maternal and child health.
This study indicates that it is probable that the cultural trait of polygamy was instituted as an adaptive measure in a particular ecology within a particular tribal group. Polygamy perpetuated because of its positive contribution to maternal and child health. The study further indicates that it is also probable that monogamy as a foreign cultural trait and its introduction without concomitant changes in other spheres of the ecosystem (biophysical and social environment) must have produced a negative effort on maternal and child health. The particular ecosystem is described and its effects on maternal and child health are pointed out.


Visceral Adipose Tissue: A New Target Organ in Virus-Induced Type 1 Diabetes.
Type 1 diabetes (T1D) is a proinflammatory pathology that leads to the specific destruction of insulin producing β-cells and hyperglycaemia. Much of the knowledge about type 1 diabetes (T1D) has focused on mechanisms of disease progression such as adaptive immune cells and the cytokines that control their function, whereas mechanisms linked with the initiation of the disease remain unknown. It has been hypothesized that in addition to genetics, environmental factors play a pivotal role in triggering β-cell autoimmunity. The BioBreeding Diabetes Resistant (BBDR) and LEW1.WR1 rats have been used to decipher the mechanisms that lead to virus-induced T1D. Both animals develop β-cell inflammation and hyperglycemia upon infection with the parvovirus Kilham Rat Virus (KRV). Our earlier in vitro and in vivo studies indicated that KRV-induced innate immune upregulation early in the disease course plays a causal role in triggering β-cell inflammation and destruction. Furthermore, we recently found for the first time that infection with KRV induces inflammation in visceral adipose tissue (VAT) detectable as early as day 1 post-infection prior to insulitis and hyperglycemia. The proinflammatory response in VAT is associated with macrophage recruitment, proinflammatory cytokine and chemokine upregulation, endoplasmic reticulum (ER) and oxidative stress responses, apoptosis, and downregulation of adipokines and molecules that mediate insulin signaling. Downregulation of inflammation suppresses VAT inflammation and T1D development. These observations are strikingly reminiscent of data from obesity and type 2 diabetes (T2D) in which VAT inflammation is believed to play a causal role in disease mechanisms. We propose that VAT inflammation and dysfunction may be linked with the mechanism of T1D progression.


Old and modern antibiotic structures with potential for today's infections.
Due to the lack of new antibiotics with efficacy against the ESKAPE and other resistant microbes, coupled to the demise of major pharmaceutical company antibiotic discovery programs, due to a number of factors but mainly ROI calculations and the lack of efficacy of combinatorial chemistry as a substitute, the search for novel antibiotics may well have moved to the utilization of older structures with significant synthetic chemistry input. This short review demonstrates how modern synthetic chemistry, when applied to either modification of current resistant antibiotics such as glycopeptides, or production of novel peptidic agents based on natural product sourced antimicrobial peptides (AMPs) and other potential initial peptide-based agents from genomic searches and baiting techniques, have produced active agents of significant utility. In addition, synthetic chemistry practitioners have now shown that they can produce bioactive molecules of greater than 800 Daltons in kilogram quantities under cGMP conditions.


Forward-looking intravascular ultrasonography: in vitro imaging of normal and atherosclerotic human arteries.
Inadequate guidance of angioplasty devices limits the endoluminal treatment of high grade atherosclerotic stenoses and total occlusions. Conventional intraluminal ultrasound systems (IVUS) enable lateral cross-sectional imaging of tomographic sections of the vessel wall, but do not offer imaging in front of the catheter. This study describes our initial experience with a forward-looking intravascular ultrasound (FL-IVUS) system (Echoeye, EchoCath, Inc., Princeton, NJ). The acoustic beam from a 25.5 MHz piezoelectric transducer on a 7.5 Fr catheter is mechanically rotated in a forward-looking spiral fashion at 300 cycles/second. Sixty-four axially aligned, cross-sectional, real time images are obtained from a truncated, 60 degree conical volume located 5 to 10 mm from the catheter tip. Luminal dimensions (n = 51) of human cadaveric femoral arteries (cast in agar and submerged in saline) measured by the FL-IVUS were compared to histologic cross-sections of the vessel with a correlation of r = 0.92. FL-IVUS accurately imaged the narrowing lumen in front of total occlusions and the geometry at vessel branches, and identified the location of lesions and the shape and morphology of vessel wall thickness. The 7.5 Fr FL-IVUS over-estimated luminal dimensions in vessels larger than 5 mm. We conclude that FL-IVUS imaging shows promise as a new, accurate method for identifying and characterizing high grade atherosclerotic stenoses and total occlusions, and expands the current capabilities of conventional IVUS systems.


Fumonisin detection and analysis of potential fumonisin-producing Fusarium spp. in asparagus (Asparagus officinalis L.) in Zhejiang Province of China.
Fumonisins are mycotoxins produced by a number of Fusarium species, including several pathogens of asparagus plants. China is one of the largest asparagus producers in the world. In this study, we analysed the contamination of fumonisins and fumonisin-producing fungi in asparagus spear samples from Zhejiang Province, the major asparagus production province in China. The asparagus did not contain a detectable level of fumonisins. However, the recovery of Fusarium in asparagus was 72.7%, including F. proliferatum (40.9%), F. oxysporum (22.7%), F. acuminatum (4.55%) and F. equesti (4.55%). A multiplex PCR targeting the internal transcribed spacer sequence (ITS), translation elongation factor 1-alpha (TEF), and key biosynthetic genes FUM1 and FUM8, was used to simultaneously determine the identity and the biosynthetic ability of the fungal isolates. Fungal isolates containing the FUM genes also produced fumonisins in cultures, ranging from 28 to 4204 microg g(-1). F. proliferatum was the only fumonisin-producing Fusarium species in asparagus. Although no fumonisin contamination was detected in asparagus in the current survey, we found that the majority of samples contained Fusarium spp. Because F. proliferatum is a high fumonisin-producing species, potential health risks for human consumption of asparagus exist, if the appropriate environmental conditions are present for this fungus.


Heterogeneous persister cells formation in Acinetobacter baumannii.
Bacterial persistence is a feature that allows susceptible bacteria to survive extreme concentrations of antibiotics and it has been verified in a number of species, such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus spp., Mycobacterium spp. However, even though Acinetobacter baumannii is an important nosocomial pathogen, data regarding its persistence phenotype are still lacking. Therefore, the aim of this study was to evaluate the persistence phenotype in A. baumannii strains, as well as its variation among strains after treatment with polymyxin B and tobramycin. Stationary cultures of 37 polymyxin B-susceptible clinical strains of A. baumannii were analyzed for surviving cells after exposure to 15 µg/mL of polymyxin B for 6 h, by serial dilutions and colony counting. Among these, the 30 tobramycin-susceptible isolates also underwent tobramycin treatment at a concentration of 160 µg/mL and persister cells occurrence was evaluated equally. A high heterogeneity of persister cells formation patterns among isolates was observed. Polymyxin B-treated cultures presented persister cells corresponding from 0.0007% to 10.1% of the initial population and two isolates failed to produce detectable persister cells under this condition. A high variability could also be observed when cells were treated with tobramycin: the persister fraction corresponded to 0.0003%-11.84% of the pre-treatment population. Moreover, no correlation was found between persister subpopulations comparing both antibiotics among isolates, indicating that different mechanisms underlie the internal control of this phenotype. This is the first report of persister cells occurrence in A. baumannii. Our data suggest that distinct factors regulate the tolerance for unrelated antibiotics in this species, contrasting the multi-drug tolerance observed in other species (eg. dormancy-mediated tolerance). Supporting this observation, polymyxin B--an antibiotic that is believed to act on non-dividing cells as well--failed to eradicate persister cells in the majority of the isolates, possibly reflecting a disconnection between persistence and dormancy.


Enabling time resolved microscopy with random Raman lasing.
Optical imaging of fast events and processes is essential for understanding dynamics of complex systems. A bright flash of illuminating light is required to acquire sufficient number of photons for superior image quality. Laser pulses can provide extreme brightness and are typically employed to achieve high temporal resolution; however, the high degree of coherence associated with the lasing process degrades the image quality with speckle formation. Random lasers are low-coherence sources of stimulated emission and do not suffer from speckle, but are rather broadband and have a relatively low output power limiting the scope of their potential applications. In this report, we demonstrate the use of random Raman lasing as a novel imaging light source with unprecedented brightness for a speckle-free and narrowband light source. We showcase the advantages of a random Raman laser to image the nanosecond scale dynamics of cavitation formation in water and quantitatively compare these images to those taken with incoherent fluorescent emission and coherent laser light as illumination source.


5-Nitroisoxazoles in SNAr reactions: access to polysubstituted isoxazole derivatives.
An efficient protocol for the straightforward functionalization of the isoxazole ring via the reactions of aromatic nucleophilic substitution of the nitro group with various nucleophiles has been elaborated. The method features excellent chemical yields, easy operability of the reaction, mild reaction conditions and a broad scope of both 5-nitroisoxazoles and nucleophiles. A synthetic approach to 3,5- and 3,4,5-substituted isoxazoles via the sequential functionalization of the isoxazole ring has been developed based on the excellent regioselectivity of the reaction of 3,5-dinitroisoxazoles with nucleophiles.


Biomarker Displacement Activation: A General Host-Guest Strategy for Targeted Phototheranostics in Vivo.
Activatable phototheranostics is highly appealing to meet the demand of precision medicine. However, although it displays efficacy in the construction of activatable photosensitizers (PSs), direct covalent decoration still shows some inevitable issues, such as complex molecular design, tedious synthesis, possible photoactivity changes, and potential toxicity. Herein, we propose a novel concept of biomarker displacement activation (BDA) using host-guest strategy. To exemplify BDA, we engineered a PS-loaded nanocarrier by utilizing a macrocyclic amphiphile, where the fluorescence and photoactivity of PS were completely annihilated by the complexation of macrocyclic receptor (OFF state). When nanocarriers were accumulated into tumor tissues via the enhanced permeability and retention effect, the overexpressed biomarker adenosine triphosphates displaced PSs, accompanied by their fluorescence and photoactivity recovered (ON state). These reinstallations are unattainable in normal tissues, allowing us to concurrently achieve selective tumor imaging and targeted therapy in vivo. Compared with widely used covalent approach, the present BDA strategy provides the following advantages: (1) employment of approved PSs without custom covalent decoration; (2) traceless release of PSs with high fidelity by biomarker displacement; (3) adaptability to different PSs for establishing a universal platform and promised facile combination of diverse PSs to enhance photon utility in light window. Such a host-guest BDA strategy is easily amenable to other ensembles and targets, so that versatile biomedical applications can be envisaged.


IL-10 inhibition of human prostate PC-3 ML cell metastases in SCID mice: IL-10 stimulation of TIMP-1 and inhibition of MMP-2/MMP-9 expression.
The molecular mechanism by which IL-10 inhibits metastases was examined using a SCID mouse model. Human PC-3 ML subclones normally metastasize to the lumbar vertebrae (approximately 70% mice injected, n = 14/20) following intravenous injection in severe combined immunodeficient (SCID) mice. IL-10 treatment of the PC-3 ML cells (15 ng/ml for 36 h) and the SCID mice (0.03 mg/kg/day for 30 days) reduced the number of metastases to 5% of the mice (n = 1/20). More importantly, following discontinuation of IL-10 treatment on day 30, the mice remained tumor-free and mouse survival rates increased dramatically (from < 30% in untreated mice) to about 85% in IL-10-treated mice. IL-10 did not appear to alter the growth rates or colony-forming ability of the PC-3 ML cells in vitro. Likewise, the growth of subcutaneous tumors and established bone marrow metastases was not inhibited by IL-10 treatment of the SCID mice. However IL-10 may inhibit the production of matrix metalloproteases (MMP) and prevent the establishment of metastasis. We therefore examined the influence of IL-10 on PC-3 ML production of MMP-2/MMP-9 and the tissue inhibitors of metalloproteinases (TIMP-1/2). Enzyme-linked immunosandwich assays (ELISAs) revealed that IL-10 (15 ng/ml for 36 h) treatment of the PC-3 ML cells down-regulated MMP-2 and MMP-9 while up-regulating TIMP-1 (not TIMP-2) expression. Likewise, IL-10-treated mice exhibited similar changes in TIMP-1 and MMP-2/MMP-9 expression. The IL-10 effects were blocked by IL-10 receptor antibodies. In comparison to IL-10, IL-4 failed to influence metastasis or the expression of TIMP-1, TIMP-2, MMP-2 and MMP-9 by PC-3 ML cells. We suggest that IL-10-regulated increases in the molar ratio of TIMP-1/MMP-9 and TIMP-2/MMP-2 might inhibit processes critical to the establishment of bone marrow metastasis.


Patterns of neuropsychological impairment in MCI patients with small subcortical infarcts or hippocampal atrophy.
We investigated whether MCI patients with hippocampal atrophy or multiple subcortical infarcts demonstrate neuropsychological patterns and markers considered typical of Alzheimer's disease (AD) and of vascular dementia (VD), respectively. An extensive neuropsychological battery, including tests of memory, visual-spatial and executive functions, language, attention, praxis and psychomotor speed, was administered to 36 mild cognitive impairment (MCI) patients with hippocampal atrophy and 41 MCI patients with multiple subcortical infarcts. Both groups of MCI patients were very mildly impaired and well matched in terms of MMSE scores. A clear, disproportionately severe, episodic memory disorder was observed in MCI patients with hippocampal atrophy. A less specific neuropsychological profile, consisting of impairment on an Action Naming task that is sensitive to frontal lobe lesions, was observed in MCI patients with multiple subcortical infarcts. In MCI patients, a disproportionately severe episodic memory impairment strongly points to an Alzheimer's type brain pathology, whereas the prevalence of executive deficits and other frontal lobe symptoms are a much weaker diagnostic marker of small vessel subcortical disease.


Cumulative Incidence of Cancer Among Persons With HIV in North America: A Cohort Study.
Cancer is increasingly common among persons with HIV. To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status. Cohort study. North American AIDS Cohort Collaboration on Research and Design during 1996 to 2009. 86 620 persons with HIV and 196 987 uninfected adults. Cancer type-specific cumulative incidence by age 75 years and calendar trends in cumulative incidence and hazard rates, each by HIV status. Cumulative incidences of cancer by age 75 years for persons with and without HIV, respectively, were as follows: Kaposi sarcoma, 4.4% and 0.01%; non-Hodgkin lymphoma, 4.5% and 0.7%; lung cancer, 3.4% and 2.8%; anal cancer, 1.5% and 0.05%; colorectal cancer, 1.0% and 1.5%; liver cancer, 1.1% and 0.4%; Hodgkin lymphoma, 0.9% and 0.09%; melanoma, 0.5% and 0.6%; and oral cavity/pharyngeal cancer, 0.8% and 0.8%. Among persons with HIV, calendar trends in cumulative incidence and hazard rate decreased for Kaposi sarcoma and non-Hodgkin lymphoma. For anal, colorectal, and liver cancer, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (-9% per year), allowing greater opportunity to be diagnosed. Despite decreasing hazard rate trends for lung cancer, Hodgkin lymphoma, and melanoma, cumulative incidence trends were not seen because of the compensating effect of the declining mortality rate. Secular trends in screening, smoking, and viral co-infections were not evaluated. Cumulative cancer incidence by age 75 years, approximating lifetime risk in persons with HIV, may have clinical utility in this population. The high cumulative incidences by age 75 years for Kaposi sarcoma, non-Hodgkin lymphoma, and lung cancer support early and sustained antiretroviral therapy and smoking cessation.


Macrophage invasion does not contribute to muscle membrane injury during inflammation.
Previous observations have shown that neutrophil invasion precedes macrophage invasion during muscle inflammation and that peak muscle injury is observed at the peak of ED1+ macrophage invasion. We tested the hypothesis that neutrophil invasion causes subsequent invasion by ED1+ macrophages and that ED1+ macrophages then contribute significantly to muscle membrane injury during modified muscle use. Rat hindlimbs were unloaded for 10 days followed by reloading by normal ambulation to induce inflammation. Membrane injury was measured by assaying Evans blue-bound serum protein influx through membrane lesions. Muscle neutrophil populations increased significantly during the first 2 h of reloading but ED1+ macrophages did not increase until 24 h. Neutrophil invasion was uncoupled from subsequent macrophage invasion by reloading rat hindlimbs for 2 h to cause neutrophil invasion, followed by resuspension for hours 2-24. This produced similar increases in neutrophil concentration as measured in muscles continuously reloaded for 24 h without causing an increase in macrophages. However, resuspension did not reduce the extent of muscle damage compared with that occurring in muscles that were reloaded continuously for 24 h. Thus, muscle invasion by neutrophils is not sufficient to cause invasion by ED1+ macrophages. In addition, muscle membrane injury that occurs during reloading is independent of invasion by ED1+ macrophages.


Optimising the mandatory reporting process for drivers admitted to an inpatient stroke rehabilitation unit.
Ontario physicians are legally obligated to report patients who may be medically unfit to drive to the Ministry of Transportation of Ontario (MTO). Currently at Toronto Rehabilitation Institute (TRI), there are no standardised processes for MTO reporting, resulting in inconsistent communication regarding driving with patients and between healthcare providers, redundant assessments and ultimately reduced patient satisfaction. TRI received 10 patient complaints regarding the driving reporting process in the 5 years prior to this project and a large number of patients were not being reported appropriately. The project aim was to use Lean Methods to achieve 100% reporting and optimise communication and education of drivers admitted to a 23-bed inpatient stroke rehabilitation unit. Interventions included process mapping, identification of wasteful steps and implementation of a standard work. Chart audits before and after implementation were performed. Value stream process mapping identified inconsistent reporting procedures and lack of use of the government-issued driver reporting form. Following implementation of standard work processes, use of the MTO Medical Conditions Report Form increased from 0% to 100%. Indication of whether drivers were reported to the MTO in Physical Medicine & Rehabilitation consultation notes increased from 50% to 91%. Identifying reported drivers in the discharge summary, of which patients receive a copy at the time of discharge, increased from 0% to 90%. Physician satisfaction with the new standard work process was qualitatively assessed to be high, with no negative impacts reported. Lean methodology was effective for increasing the usage of the MTO Medical Conditions Report Form, documenting driver status in the initial Physical Medicine & Rehabilitation consultation and indicating MTO reporting status in the discharge summary. Communication between healthcare providers regarding patients' driving status has been successfully standardised, resulting in improved coordination of care and a reduction in patient complaints to zero in the 14 months since implementation.


Raising standards in pathology: the accreditation process in the United Kingdom.
The accreditation scheme established by Clinical Pathology Accreditation (UK) Ltd has been in formal operation since 1992. So far, 933 laboratories have been inspected, nearly two-thirds of all laboratories in the UK. Of these, 73% are fully accredited, 24% have outstanding conditions requiring correction, and 3% have been referred. Inspectors have identified some regional and specialty differences, most notably in histopathology and cytology. The second cycle of inspection visits is underway. Most UK departments of pathology have embraced the concept of accreditation with relative enthusiasm and there has been strong support from professional bodies, specialist societies, health service managers, the independent sector and government departments.


HIF-1 in cancer therapy: two decade long story of a transcription factor.
Oxygen (O2) homeostasis is an indispensable requirement of eukaryotes. O2 concentration in cellular milieu is defined as normoxia (∼21% O2), physoxia (∼1-13% O2) or hypoxia (∼0.1-1% O2). Hypoxia, a striking micro-environmental feature in tumorigenesis, is countered by tumor cells via induction of O2 governed transcription factor, hypoxia inducible factor-1 (HIF-1). Post discovery, HIF-1 has emerged as a promising anticancer therapeutic target during the last two decades. Recent reports have highlighted that enhanced levels of HIF-1 correlate with tumor metastasis leading to poor patient prognosis. A systematic search in PubMed and SciFinder for the literature on HIF-1 biology and therapeutic importance in cancer was carried out. This review highlights the initial description as well as the recent insights into HIF-1 biology and regulation. We have focused on emerging data regarding varied classes of HIF-1 target genes affecting various levels of crosstalk among tumorigenic pathways. We have emphasized on the fact that HIF-1 acts as a networking hub coordinating activities of multiple signaling molecules influencing tumorigenesis. Emerging evidences indicate role of many HIF-induced proteomic and genomic alterations in malignant progression by mediating a myriad of genes stimulating angiogenesis, anaerobic metabolism and survival of cancer cells in O2-deficient microenvironment. Better understanding of the crucial role of HIF-1 in carcinogenesis could offer promising new avenues to researchers and aid in elucidating various open issues regarding the use of HIF-1 as an anticancer therapeutic target. In spite of large efforts in this field, many questions still remain unanswered. Hence, future investigations are necessary to devise, assess and refine methods for translating previous research efforts into novel clinical practices in cancer treatment.


Epstein-Barr virus seroepidemiology in China.
Since 1978 more than 300,000 sera from normal individuals were screened serologically in NPC high risk areas and prospective studies were carried out. Many patients were diagnosed in early stage. For example, in Wuzhou city, 20,726 persons over 40 years of age were screened; 1,138 persons were found to have IgA VCA antibody. Among them 18 NPC cases were detected; an additional 21 NPC patients were found within 5 year follow-up studies. Altogether there were 39 NPC patients. As compared to the patients in outpatient clinics, the frequency of NPC in stage I increased from 1.7% to 38.5% and in early stage (I + II) increased from 32% to 92.3%. IgA VCA antibody can be detected 5 years before the diagnosis of NPC in early stage was made. The detection rate of NPC from IgA VCA antibody-positive persons is 38-374 times the incidence rate of NPC in the general population of the same age group. Follow-up studies on the change of IgA VCA antibody titer in antibody-positive and antibody-negative groups were also carried out for years. 10.9% of antibody-positive individuals became antibody negative and 5.4% seronegative persons converted to positive within 4 years. Eighty-eight per cent of NPC patients were detected in the group of no change of antibody titer or in the group of increasing antibody titer. No NPC patients were found in the original antibody negative group.


[Tuberculosis annual report 2009 --series 10. Treatment outcome and TB deaths].
Evaluation of the treatment outcome by the cohort analysis method is an important part of tuberculosis (TB) control. In the Japanese TB surveillance system, the treatment outcome is automatically classified by computer according to a pre-set algorithm, so the treatment outcome is evaluated very rigidly. In the case of new sputum smear positive pulmonary TB cases (n = 8,999) newly notified in 2008, the patients' treatment outcomes based on the annual report 2009 database were as follows: "success," which combined "cured" and "completed," was 47.7%, "died" was 19.1%, "failed" was 1.1%, "defaulted" was 3.8%, "transferred out" was 2.8%, "on treatment after 12 months" was 11.8% and "not evaluated" was 13.6%. In addition to evaluation of the treatment outcome by the cohort method, the proportion of deaths was observed among all forms of TB patients (n = 24,571) who were newly registered in 2008. In total, 17.3% of all forms of TB cases died within one year after the beginning of treatment. The proportion corresponding to this was 23.7% for new sputum smear positive pulmonary TB and 23.5% for re-treatment sputum smear positive pulmonary TB. Among the new sputum smear positive pulmonary TB patients (n = 2,136) who died within one year after the beginning of treatment, 37.0% of them died within one month after the beginning of treatment, 51.6% died within two months and 61.9% died within three months.


Barrett's esophagus with adenocarcinoma in scleroderma.
The gastrointestinal manifestations of scleroderma are varied. Esophageal problems are common especially in patients with Raynaud's phenomenon. An adenocarcinoma complicating a Barrett's esophagus was identified in a patient with the CREST variant of scleroderma. The significance of this association and its relationship to chronic reflux esophagitis is discussed. Patients with scleroderma should be considered to be at an increased risk of developing this premalignant condition of the esophagus.


Serosurvey for Influenza Virus Subtypes H3N8 and H3N2 Antibodies in Free-Ranging Canids in Pennsylvania, USA.
Canine influenza virus (CIV) subtypes H3N8 and H3N2 are endemic among domestic dog ( Canis lupus familiaris ) populations in the northeastern US. Infection of free-ranging carnivores with influenza virus has been sporadically reported. Generalist mesocarnivores that exploit anthropogenic, peri-urban habitats share a wide interface with domestic dogs that allows for the transmission of infectious disease. To investigate the potential exposure of free-ranging canids to CIV in Pennsylvania, US, serum samples were obtained from freshly killed coyotes ( Canis latrans, n=67), grey foxes ( Urocyon cinereoargenteus, n=8), and red foxes ( Vulpes vulpes, n=5) from 24 counties. Animals were harvested during the January-February 2017 hunting season. We failed to detect antibodies to CIV subtypes H3N2 and H3N8 by using hemagglutination inhibition assays validated for domestic dogs. Results suggest CIV was not endemic in free-ranging canid populations in Pennsylvania or that prevalence was too low to be detected by our limited sample size.


Repeated multiphasic screening examinations: evaluating the process.
There are sound clinical and epidemiological reasons to promote and emphasize early detection efforts and disease prevention services. A large body of scientific literature supports the notion that detection and intervention early in the course of many diseases is beneficial both to the afflicted individual and to society at large. Several publications deal with the evaluation of multiphasic screening examinations (MSE) as a tool for simultaneous early detection and prevention of multiple risk factors and various diseases. Usually, this technology is evaluated based on data from a single (cross-sectional) comprehensive screening study. However, frequently MSE are performed periodically, resulting in repeated test results of the same individuals. The health impact of such repeated (longitudinal) MSE has not been studied extensively. Similarly, many of the unique theoretical, technical, and epidemiological features characteristic of consecutive (periodical) comprehensive screening examinations are not well-documented. The purpose of this study was to compare the test results of two MSE, performed 3.5 years apart, in order to demonstrate certain characteristics of multiphasic health testing (MHT) technology related to repeated (longitudinal) multiphasic examination of the same individuals.


Electrosensitization Increases Antitumor Effectiveness of Nanosecond Pulsed Electric Fields In Vivo.
Nanosecond pulsed electric fields are emerging as a new modality for tissue and tumor ablation. We previously reported that cells exposed to pulsed electric fields develop hypersensitivity to subsequent pulsed electric field applications. This phenomenon, named electrosensitization, is evoked by splitting the pulsed electric field treatment in fractions (split-dose treatments) and causes in vitro a 2- to 3-fold increase in cytotoxicity. The aim of this study was to show the benefit of split-dose treatments for in vivo tumor ablation by nanosecond pulsed electric field. KLN 205 squamous carcinoma cells were embedded in an agarose gel or grown subcutaneously as tumors in mice. Nanosecond pulsed electric field ablations were produced using a 2-needle probe with a 6.5-mm interelectrode distance. In agarose gel, splitting a pulsed electric field dose of 300, 300-ns pulses (20 Hz, 4.4-6.4 kV) in 2 equal fractions increased cell death up to 3-fold compared to single-train treatments. We then compared the antitumor effectiveness of these treatments in vivo. At 24 hours after treatment, sensitizing tumors by a split-dose pulsed electric field exposure (150 + 150, 300-ns pulses, 20 Hz, 6.4 kV) caused a 4- and 2-fold tumor volume reduction as compared to sham and single-train treatments, respectively. Tumor volume reduction that exceeds 75% was 43% for split-dose-treated animals compared to only 12% for single-dose treatments. The difference between the 2 experimental groups remained statistically significant for at least 1 week after the treatment. The results show that electrosensitization occurs in vivo and can be exploited to assist in vivo cancer ablation.


The Effects of Occupational Stress, Work-Centrality, Self-Efficacy, and Job Satisfaction on Intent to Quit Among Long-Term Care Workers in Korea.
A large and growing population of elderly Koreans with chronic conditions necessitates an increase in long-term care. This study is aimed at investigating the effects of occupational stress, work-centrality, self-efficacy, and job satisfaction on intent to leave among long-term care workers in Korea. We tested the hypothesized structural equation model predicting the intention to quit among long-term care workers in Korea. Survey data were collected from 532 long-term care workers in Seoul, Korea. Results showed that occupational stress was positively associated with intention to leave the job. The study also identified several possible mediators (self-efficacy, work-centrality, job satisfaction) in the relationship between stress and intent to quit. Evidence-based stress management interventions are suggested to help the workers better cope with stressors. Mentoring programs should also be considered for new workers.


A novel role for phagocytosis-like uptake in herpes simplex virus entry.
It is becoming increasingly clear that herpesviruses can exploit the endocytic pathway to infect cells, yet several important features of this process remain poorly defined. Using herpes simplex virus-1 (HSV-1) as a model, we demonstrate that endocytosis of the virions mimic many features of phagocytosis. During entry, HSV-1 virions associated with plasma membrane protrusions followed by a phagocytosis-like uptake involving rearrangement of actin cytoskeleton and trafficking of the virions in large phagosome-like vesicles. RhoA GTPase was activated during this process and the mode of entry was cell type-specific. Clathrin-coated vesicles had no detectable role in virion trafficking as Eps15 dominant-negative mutants failed to affect HSV-1 uptake. Binding and fusion of the virion envelope with the phagosomal membrane is likely facilitated by clustering of nectin-1 (or HVEM) in phagosomes, which was observed in infected cells. Collectively, our data suggests a novel mode of uptake by which the virus can infect both professional and nonprofessional phagocytes.


[Clinical and morphological parallels in the validation of surgical treatment of nephrotuberculosi].
To Study clinical and morphological variants of kidney tuberculosis (KTB), for grounding a tactics of surgical treatment. There were 107 examined patients (patients with cavitary lesions of kidneys: cavernous and multi-cavernous), operated in different phases of KTB. There were 56 men (52,3%) and women - 51(47,7%). The mean age of patients was 57,6 years (23-84 years). All the patients had a complex examination, including X-ray and ultrasound investigations, computer tomography ( was performed selectively), bacteriological examinations of urine and morphological examinations of removed kidneys or their parts. Surgical interventions were as follows: open surgery nephrectomy 86/107 (80,4%), open organ-sparing surgery (resections of kidneys) 21/107 ( 19,6%). Mycobacterium tuberculosis were revealed by cultural method in 68,6% of cases in patients with cavernous KTB and in 76,3% of cases in patients with multi-cavernous KTB. In appliance with pathomorphological results of presented specimens, there were revealed 3 groups, each one with its own properties of cavern wall. I group (74 specimens) - stage of active progressing KTB, II group (20 specimens) - stage of intermediate activity, III group (13 specimens) - stage of healed caverns. Performed morphological investigations allowed us grounded a rational tactics of surgical treatment. It was defined that the longer specific anti-TB therapy was carried out the less frequency of TB progression we would have. However when it presented isolated cavitary lesion (isolated cavern), the performance of adequate and long courses of chemotherapy is not worth to do. Only surgical interventions (resection of infected tissue) with the anti-TB therapy allowed to reach the satisfactory results in treatment of KTB.


The use of a bioactive bone cement containing apatite-wollastonite glass-ceramic filler and bisphenol-a-glycidyl methacrylate resin for acetabular fixation in total hip arthroplasty: long-term follow-up results of a clinical trial.
In the 1990s, a bioactive bone cement (BABC) containing apatite-wollastonite glass-ceramic (AW-GC) powder and bisphenol-a-glycidyl methacrylate resin was developed at our hospital. In 1996, we used BABC to fix the acetabular component in primary total hip arthroplasty (THA) in 20 patients as part of a clinical trial. The purpose of this study was to investigate the long-term results of primary THA using BABC. A total of 20 patients (three men and 17 women) with a mean age of 57.4 years (40 to 71), a mean body weight of 52.3 kg (39 to 64), and a mean body mass index (BMI) of 23.0 kg/m2 (19.8 to 28.6) were evaluated clinically and radiologically. Survival analyses were undertaken, and wear analyses were carried out using a computer-aided method. The mean follow-up was 17.6 years (1.5 to 21.1). Radiological loosening occurred in four sockets with aseptic loosening at a mean of 7.8 years (1.5 to 20.7). Kaplan-Meier survival analyses using revision of the acetabular component, radiological loosening of the acetabular component, and the worst-case scenario with revision of the acetabular component to include the two patients lost to follow-up as endpoints yielded survival rates of 94.7%, 84.4%, and 85.0% at ten years, and 70.0%, 84.4%, and 62.8% at 20 years, respectively. Wear analysis revealed a mean linear wear rate of 0.068 mm per year. The long-term results of primary THAs using BABC were unsatisfactory. Its brittle nature and poor handling properties need to be improved before it becomes an alternative method of fixing the acetabular component in cemented THA. Cite this article: Bone Joint J 2019;101-B:787-792.


The Sensitivity of Grating-Based SPR Sensors with Wavelength Interrogation.
In this paper, we derive the analytical expression for the sensitivity of grating-based surface plasmon resonance (SPR) sensors working in wavelength interrogation. The theoretical analysis shows that the sensitivity increases with increasing wavelength and is saturated beyond a certain wavelength for Au and Ag gratings, while it is almost constant for Al gratings in the wavelength range of 500 to 1000 nm. More importantly, the grating period (P) and the diffraction order (m) dominate the value of sensitivity. Higher sensitivity is possible for SPR sensors with a larger grating period and lower diffraction order. At long wavelengths, a simple expression of P/|m| can be used to estimate the sensor sensitivity. Moreover, we perform experimental measurements of the sensitivity of an SPR sensor based on an Al grating to confirm the theoretical calculations.


Hyperamylasemia in critically injured patients.
We found that in traumatic shock patients without pancreatic injury, hyperamylasemia occurs in high frequency [49 of 61 (80%)]. Isoenzyme studies of 19 of these patients revealed 18 of them (94%) to have the salivary type of hyperamylasemia. Further, based on the results of the present study, the salivary gland as the organ of origin and the permeability of its cell membranes are suggested as the mechanism for traumatic hyperamylasemia.


Increased pulse wave velocity in subclinical hypothyroidism.
Subclinical hypothyroidism affects 5-15% of the general population and is associated with increased morbidity from cardiovascular disease. Brachial-ankle pulse wave velocity (baPWV) is a parameter of arterial stiffening and a good independent predictor for the presence of coronary artery disease. This study was performed to assess whether subclinical hypothyroidism might cause enhanced baPWV. baPWV was examined in subclinical hypothyroid patients (n = 50) and normal control subjects (n = 50). Diastolic blood pressure (DBP), a main risk factor for cardiovascular disease, and baPWV were both significantly higher in subclinical hypothyroid patients than normal subjects. baPWV was significantly positively correlated with age and systolic, diastolic, and pulse pressure and significantly negatively correlated with pulse rate in both subclinical hypothyroid patients and normal subjects. In contrast, there was no significant correlation of baPWV with free T3, free T4, TSH, total, high-density lipoprotein- and low-density lipoprotein-cholesterol, and the preejection time to ejection time ratio. A comparison of individual values of baPWV and DBP and regression slopes in two groups revealed that baPWV values increase to a larger extent than the increase in DBP in subclinical hypothyroid patients. In both groups, stepwise regression analysis showed a significant and independent association of DBP with baPWV. The present study demonstrated significant increases of baPWV and DBP in subclinical hypothyroid patients. Furthermore, the results suggest that increased DBP might be one of the main factors responsible for increased arterial stiffening in subclinical hypothyroid patients.


[Prophylaxis of vitamin D deficiency--Polish recommendations 2009].
Appropriate state procurement system for vitamin D is important not only for the proper functioning of the skeletal, maintaining calcium and phosphorus homeostasis, but also for a number of other organs and tissues in our body. In connection with the change in lifestyle including dietary habits change, the widespread use of UV filters and less outdoor activity, observed an increase in the percentage of vitamin D deficiency, both in population and developmental age and adults. Based on the results of recent scientific research team of experts provides recommendations for preventive Polish supply of vitamin D in infants, children, adolescents and adults, including pregnant women and nursing mothers.


Potential benefit of final kissing balloon inflation after single stenting for the treatment of bifurcation lesions--insights from optical coherence tomography observations.
Treatment of coronary bifurcation lesions using a single stenting strategy is preferable over that using a 2-stent technique. The benefit of final kissing inflation (FKI), however, has not been established. Seventy-two patients (76 lesions) with true bifurcation lesions treated with a single drug-eluting stent with FKI (n=33 lesions) or without FKI (non-FKI, n=43 lesions) were enrolled in this study. Optical coherence tomography (OCT) was performed at 6-12 months after implantation. Based on the OCT findings, the percentage of jailing struts (number of jailing struts/total number of struts at the bifurcation lesion) was calculated. Percentage of uncovered struts and frequency of thrombus attachment were each evaluated at the proximal, bifurcation, and distal segments. Major adverse cardiac events (MACE) were also evaluated. The percentage of jailing struts was significantly lower in the FKI than in the non-FKI group (5.8±6.2% vs. 17.3±6.1%, P<0.01). Thrombus attachment was less frequent in the FKI group (24.2% vs. 46.5%, P=0.046), especially at side-branch orifices (3.0% vs. 27.9%, P<0.001). The percentage of uncovered struts was lower in the FKI than non-FKI group at the proximal, bifurcation, and distal segments. The incidence of MACE was not different in this small cohort. FKI might reduce the frequency of subclinical thrombus possibly by reducing the number of jailing struts.


An Empirical Identification Issue of the Bifactor Item Response Theory Model.
Using the bifactor item response theory model to analyze data arising from educational and psychological studies has gained popularity over the years. Unfortunately, using this model in practice comes with challenges. One such challenge is an empirical identification issue that is seldom discussed in the literature, and its impact on the estimates of the bifactor model's parameters has not been demonstrated. This issue occurs when an item's discriminations on the general and specific dimensions are approximately equal (i.e., the within-item discriminations are similar in strength), leading to difficulties in obtaining unique estimates for those discriminations. We conducted three simulation studies to demonstrate that within-item discriminations being similar in strength creates problems in estimation stability. The results suggest that a large sample could alleviate but not resolve the problems, at least when considering sample sizes up to 4,000. When the discriminations within items were made clearly different, the estimates of these discriminations were more consistent across the data replicates than that observed when the discriminations within the items were similar. The results also show that the similarity of an item's discriminatory magnitudes on different dimensions has direct implications on the sample size needed in order to consistently obtain accurate parameter estimates. Although our goal was to provide evidence of the empirical identification issue, the study further reveals that the extent of similarity of within-item discriminations, the magnitude of discriminations, and how well the items are targeted to the respondents also play factors in the estimation of the bifactor model's parameters.


Effect of pH on the formation of lysosome-alginate beads for antimicrobial activity.
In this study, we developed lysosome-alginate beads for application as an oral drug delivery system (ODDS). The beads harboring lysosomes, which have antimicrobial activity, and various concentrations of alginate were characterized and optimized. For application as an ODDS, pH-dependent lysosome-alginate beads were generated, and the level of lysosome release was investigated by using antimicrobial tests. At low pH, lysosomes were not released from the lysosome-alginate beads; however, at neutral pH, similar to the pH in the intestine, lysosome release was confirmed, as determined by a high antimicrobial activity. This study shows the potential of such an ODDS for the in vivo treatment of infection with pathogens.


Ischemic mitral valve repair: correlations between the mechanisms of mitral regurgitation and left ventricular function prior to and following surgery.
To define the mechanisms of ischemic mitral regurgitation (MR) and its correlation with left ventricular (LV) function prior to and 1 year following mitral valve (MV) repair. Fifty-three patients (pts) underwent echocardiographic evaluation of the MR mechanism according to Carpentier's classification; quantification of MR and LV function. Forty-one, 5% of pts had Type I (annulus dilation), 20, 5% had Type II (commissural prolapse) and 38% had Type IIIb MR (predominant posterior leaflet restriction). Preoperative LV function was slightly better preserved in pts with Type II and IIIb MR. Despite similar MV repair efficiency intraoperatively, after 1 year Type I MR progressed vs the remaining types. LV function, including dimensions, ejection fraction and pulmonary artery pressure had a tendency to worsen in pts with Type I and markedly improved in Type II and IIIb MR. Ischemic MR of Type I is associated with more marked LV dysfunction preoperatively, its further deterioration and MR progression after MV repair. Type II and IIIb MR correlates with better preserved LV function preoperatively and its incremental improvement late after surgery.


[Basic studies on the potential changes in the eyelid elicited by flash stimulation, especially related to the adaptation of the eye].
In order to establish the most adequate method to lead the photically evoked lid potential changes, their physiological properties were studied from standpoint of dark or light adaptation, which is known to be due to the increase or decrease in the sensitiveness of the retina that is the receptor of the orbicularis oculi reflex. The photically evoked lid potential changes were obtained with the summation technique by the signal processor (7 T 0 8, SAN-EI, Tokyo) in normal subjects. In addition, the average summated responses of the photically evoked lid MV responses, the ERG, EOG and EEG were also recorded simultaneously and discussed polygraphically. The results obtained were as follows: The average evoked lid potential changes in healthy resting subjects with eyes closed were shown to be composed of early rapid component, initial slow component and late slow component, which corresponded to dominant rapid vibrations of the evoked lid MV responses, the a and b waves of ERG and the EOG, respectively. The electromyographic and electrooculographic components were observed to have peak latency of about 60 msec and 200 msec, respectively. The electromyographic and electrooculographic components were found to change corresponding to the level of cortical activity indicated by the EEG patterns. They were gradually suppressed in amplitude according to the decrease of cortical activity and disappeared in stage 2 of natural sleep, although the electroretinographic components remained. With the progress of dark adaptation after adapting from light to darkness, the electromyographic and electrooculographic components in addition to the electroretinographic component of the average lid potential changes were considerably increased in amplitude but hardly changed in peak latency.(ABSTRACT TRUNCATED AT 250 WORDS)


On the non-closure of particle backscattering coefficient in oligotrophic oceans.
Many studies have consistently found that the particle backscattering coefficient (bbp) in oligotrophic oceans estimated from remote-sensing reflectance (Rrs) using semi-analytical algorithms is higher than that from in situ measurements. This overestimation can be as high as ~300% for some oligotrophic ocean regions. Various sources potentially responsible for this discrepancy are examined. Further, after applying an empirical algorithm to correct the impact from Raman scattering, it is found that bbp from analytical inversion of Rrs is in good agreement with that from in situ measurements, and that a closure is achieved.


Identification of the gliogenic state of human neural stem cells to optimize in vitro astrocyte differentiation.
Human preclinical models are crucial for advancing biomedical research. In particular consistent and robust protocols for astrocyte differentiation in the human system are rare. We performed a transcriptional characterization of human gliogenesis using embryonic H9- derived hNSCs. Based on these findings we established a fast and highly efficient protocol for the differentiation of mature human astrocytes. We could reproduce these results in induced pluripotent stem cell (iPSC)-derived NSCs. We identified an increasing propensity of NSCs to give rise to astrocytes with repeated cell passaging. The gliogenic phenotype of NSCs was marked by a down-regulation of stem cell factors (e.g. SOX1, SOX2, EGFR) and an increase of glia-associated factors (e.g. NFIX, SOX9, PDGFRa). Using late passage NSCs, rapid and robust astrocyte differentiation can be achieved within 28 days. In published protocols it usually takes around three months to yield in mature astrocytes. The difficulty, expense and time associated with generating astrocytes in vitro represents a major roadblock for glial cell research. We show that rapid and robust astrocyte differentiation can be achieved within 28 days. We describe here by an extensive sequential transcriptome analysis of hNSCs the characterization of the signature of a novel gliogenic stem cell population. The transcriptomic signature might serve to identify the proper divisional maturity. This work sheds light on the factors associated with rapid NSC differentiation into glial cells. These findings contribute to understand human gliogenesis and to develop novel preclinical models that will help to study CNS disease such as Multiple Sclerosis.


High in vitro activity of fidaxomicin against Clostridium difficile isolates from a university teaching hospital in China.
Clostridium difficile infection (CDI) is a significant cause of morbidity and mortality in both the acute care setting and the wider healthcare system. The purpose of this study was to evaluate the in vitro activity of fidaxomicin against C. difficile isolates from a university teaching hospital in China. One hundred and one C. difficile isolates were collected and analyzed for toxin genes by multiplex PCR. The toxin gene positive strains were also typed by multilocus sequence typing (MLST) and PCR-ribotyping. The MICs of the isolates were determined against fidaxomicin, metronidazole, vancomycin, tigecycline and moxifloxacin, by the agar dilution method. All the 101 isolates exhibited low MICs to fidaxomicin (0.032-1 mg/L), metronidazole (0.125-1 mg/L), vancomycin (0.25-2 mg/L) and tigecycline (0.016-0.5 mg/L). Tigecycline showed the lowest geometric mean MIC value (0.041 mg/L), followed by fidaxomicin (0.227 mg/L), metronidazole (0.345 mg/L), and vancomycin (0.579 mg/L). About 35% of the strains (n = 35) were resistant to moxifloxacin, and the resistance rate to moxifloxacin for A-B+CDT- isolates (85.0%) was much higher than that of A+B+CDT- (15.7%) and A-B-CDT- (29.2%) isolates (P < 0.001). The MIC values of fidaxomicin, metronidazole, vancomycin and moxifloxacin against the 3 ST1 isolates were higher than for other STs. All the 28 moxifloxacin-resistant toxigenic isolates carried a mutation either in gyrA or/and gyrB. Fidaxomicin exhibited high antimicrobial activity against all C. difficile isolates tested, which shows promise as a new drug for treating Chinese CDI patients.


Structural studies of interactions between cardiac troponin I and actin in regulated thin filament using Förster resonance energy transfer.
The Ca(2+)-induced interaction between cardiac troponin I (cTnI) and actin plays a key role in the regulation of cardiac muscle contraction and relaxation. In this report we have investigated changes of this interaction in response to strong cross-bridge formation between myosin S1 and actin and PKA phosphorylation of cTnI within reconstituted thin filament. The interaction was monitored by measuring Förster resonance energy transfer (FRET) between the fluorescent donor 5-(iodoacetamidoethyl)aminonaphthalene-1-sulfonic acid (AEDANS) attached to the residues 131, 151, 160 167, 188, and 210 of cTnI and the nonfluorescent acceptor 4-(dimethylamino)phenylazophenyl-4'-maleimide (DABM) attached to cysteine 374 of actin. The FRET distance measurements showed that bound Ca(2+) induced large increases in the distances from actin to the cTnI sites, indicating a Ca(2+)-triggered separation of cTnI from actin. Strongly bound myosin S1 induced additional increases in these distances in the presence of bound Ca(2+). The two ligand-induced increases were independent of each other. These two-step changes in distances provide a direct link of structural changes at the interface between cTnI and actin to the three-state model of thin filament regulation of muscle contraction and relaxation. When cTnC was inactivated through mutations of key residues within the 12-residue Ca(2+)-binding loop, strongly bound S1 alone induced increases in the distances in spite of the fact that the filaments no longer bound regulatory Ca(2+). These results suggest bound Ca(2+) or strongly bound S1 alone can partially activate thin filament, but full activation requires both bound Ca(2+) and strongly bound S1. The distributions of the FRET distances revealed different structural dynamics associated with different regions of cTnI in different biochemical states. The second actin-binding region appears more rigid than the inhibitory/regulatory region. In the Mg(2+) state, the regulatory region appears more flexible than the inhibitory region, and in the Ca(2+) state the inhibitory region becomes more flexible. PKA phosphorylation of cTnI at Ser23 and Ser24 distance from actin to cTnI residue 131 by 2.2-5.2 A in different biochemical states and narrowed the distributions of the distances from actin to the inhibitory and regulatory regions of cTnI. The observed phosphorylation effects are likely due to an intramolecular interaction of the phosphorylated N-terminal segment and the inhibitory region of cTnI.


What makes a drug a primary mood stabilizer?
The term 'mood stabilizer' has been applied to a number of medications for the treatment of patients with bipolar disorder. The operational definition of the properties of a mood-stabilizing medication has varied according to the properties of specific medications and the clinical characteristics of the illness. Randomized controlled trials of agents accepted or proposed as mood stabilizers are reviewed to marshall the available evidence in support of this claim. In addition, potential pharmacological mechanisms underlying mood-stabilizing effects of established compounds are reviewed.


Typhoid fever in Hong Kong children.
Experience with typhoid fever in 111 children over a 5-year period was reviewed. There were 66 boys and 45 girls, ranging in age from 1 to 11.5 years. The symptoms of typhoid fever were quite non-specific. Fever was the most common presenting symptom (in 98.3%). Other common presenting features were diarrhoea (25.7%), constipation (22%), vomiting (21.1%), cough (25%), abdominal pain (27.5%), headache (9.2%), epistaxis, meningism and convulsions. Rose spots were detected in 20% of cases, occurring mainly during the first 2 weeks of illness. Significant Widal reactions were present in 84.7% of cases. Blood and stool cultures were positive in 57% and 44% of cases, respectively. Peripheral blood white cell counts were not found to be of great diagnostic value. Chloramphenicol remained the drug of choice in the treatment of typhoid fever. It was more effective than ampicillin or co-trimoxazole. Complications were uncommon, occurring in only two patients. There were two deaths; both were admitted late and in moribund state. Early diagnosis and treatment is vital in typhoid fever and, as the presenting features are non-specific, a high index of suspicion is required.


Hepatoprotective Effect of Camel Milk on Poloxamer 407 Induced Hyperlipidaemic Wistar Rats.
To investigate the effect of oral administration of camel milk on liver enzymes, total proteins and histology of poloxamer 407 induced hyperlipidaemic wistar rats. Thirty male wistar rats weighing between 150-200 g were randomly assigned into six groups of five each; group I: administered distilled water, group II: induced with P407, group III: induced with P407 and treated with atorvastatin (20 mg/kg) and groups IV, V and VI: induced with P407 and treated with camel milk 250 mg/kg, 500 mg/kg and 1000 mg/kg respectively. After three weeks, blood samples and liver tissues were collected for the determination of alkaline phospatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin, albumin/globulin ratio and histological studies respectively. All camel milk treated groups showed significant (p < 0.05) decrease in ALT and AST. Camel milk treated groups; 250 mg/kg and 1000mg/kg showed significant (p < 0.05) decrease in total protein, globulin with all camel milk treated groups having significant (p < 0.05) increase in A/G ratio. Histological examination of liver tissues showed that camel milk at a dose of 250 mg/kg had slight adipocytes infiltration. The results of our findings highlight the hepatoprotective effect of camel milk in poloxamer 407 induced hyperlipidaemic wistar rats.


Short-Segment Barrett's Esophagus and Adenocarcinoma.
Barrett's esophagus is a known risk factor for the development of adenocarcinoma of the esophagus and esophagogastric junction. Based on the length of the columnar segment at endoscopy, Barrett's esophagus has been arbitrarily separated into two broad categories: long-segment and short-segment. The rapid rise in the incidence of esophageal adenocarcinoma has generated sustained research interest in this lesion. Studies have shown that although the prevalence of short-segment Barrett's esophagus is higher than that of long-segment Barrett's esophagus, the risk of developing dysplasia and adenocarcinoma may actually be lower in those patients with short segment Barrett's esophagus. Nonetheless, both dysplasia and esophageal adenocarcinoma have been reported in patients with short-segment Barrett's esophagus, making this arbitrary distinction clinically unimportant. The current surveillance guidelines remain the same for both short- and long-segment Barrett's esophagus. Another key issue is differentiating short-segment Barrett's esophagus from intestinal metaplasia of the gastric cardia. The latter is distinct from esophageal intestinal metaplasia (ie, Barrett's esophagus) and probably does not warrant surveillance.


Mass casualty management: Jos University Teaching Hospital experience.
Three experiences of management of mass casualties in Jos University Teaching Hospital were analysed. Classification into minor, moderate and major mass casualties was done using multiple criteria of number of casualties, number of doctors required to contain the situation, number of nurses and paramedical staff, degree of distruption of hospital services and time required to handle the immediate stabilisation of the casualties. The classification recognises a category called "regional disaster" and attempts to enunciate a principle of initiation, mobilisation and co-ordination of management of such disasters among hospitals and human and material resources within the region. It is envisaged that coalescence of "regional disaster preparedness" would from the bedrock of national ambulance services system.


AT(1) and glutamatergic receptors in paraventricular nucleus support blood pressure during water deprivation.
Water deprivation activates sympathoexcitatory neurons in the paraventricular nucleus (PVN); however, the neurotransmitters that mediate this activation are unknown. To test the hypothesis that ANG II and glutamate are involved, effects on blood pressure (BP) of bilateral PVN microinjections of ANG II type 1 receptor (AT1R) antagonists, candesartan and valsartan, or the ionotropic glutamate receptor antagonist, kynurenate, were determined in urethane-anesthetized water-deprived and water-replete male rats. Because PVN may activate sympathetic neurons via the rostral ventrolateral medulla (RVLM) and because PVN disinhibition increases sympathetic activity in part via increased drive of AT1R in the RVLM, candesartan was also bilaterally microinjected into the RVLM. Total blockade of the PVN with bilateral microinjections of muscimol, a GABA(A) agonist, decreased BP more (P < 0.05) in water-deprived (-29 +/- 8 mmHg) than in water-replete (-7 +/- 2 mmHg) rats, verifying that the PVN is required for BP maintenance during water deprivation. PVN candesartan slowly lowered BP by 7 +/- 1 mmHg (P < 0.05). In water-replete rats, however, candesartan did not alter BP (1 +/- 1 mmHg). Valsartan also produced a slowly developing decrease in arterial pressure (-6 +/- 1 mmHg; P < 0.05) in water-deprived but not in water-replete (-1 +/- 1 mmHg) rats. In water-deprived rats, PVN kynurenate rapidly decreased BP (-19 +/- 3 mmHg), and the response was greater (P < 0.05) than in water-replete rats (-4 +/- 1 mmHg). Finally, as in PVN, candesartan in RVLM slowly decreased BP in water-deprived (-8 +/- 1 mmHg; P < 0.05) but not in water-replete (-3 +/- 1 mmHg) rats. These data suggest that activation of AT(1) and glutamate receptors in PVN, as well as of AT1R in RVLM, contributes to BP maintenance during water deprivation.


Wound, pressure ulcer and burn guidelines - 1: Guidelines for wounds in general, second edition.
The Japanese Dermatological Association prepared the clinical guidelines for the "Wound, pressure ulcer and burn guidelines", second edition, focusing on treatments. Among them, "Guidelines for wounds in general" is intended to provide the knowledge necessary to heal wounds, without focusing on particular disorders. It informs the basic principles of wound treatment, before explanations are provided in individual chapters of the guidelines. We updated all sections by collecting references published since the publication of the first edition. In particular, we included new wound dressings and topical medications. Additionally, we added "Question 6: How should wound-related pain be considered, and what should be done to control it?" as a new section addressing wound pain, which was not included in the first edition.


Failure of ubiquitin proteasome system: risk for neurodegenerative diseases.
The ubiquitin proteasome system (UPS) is the primary proteolytic quality control system in cells and has an essential function in the nervous system. UPS dysfunction has been linked to neurodegenerative conditions, including Alzheimer's, Parkinson's and Huntington's diseases. The pathology of neurodegenerative diseases is characterized by the abnormal accumulation of insoluble protein aggregates or inclusion bodies within neurons. The failure or dysregulation of the UPS prevents the degradation of misfolded/aberrant proteins, leading to deficient synaptic function that eventually affects the nervous system. In this review, we discuss the UPS and its physiological roles in the nervous system, its influence on neuronal function, and how UPS dysfunction contributes to the development of neurodegenerative diseases.


[A conceptual analysis of professional commitment].
Professional Commitment is an attitude, and it is the core and spirit of professionalism. In addition to increasing personal stability in the profession, it also enables individuals to reach their professional goals in general. Because nurses usually have more opportunities than other health care professionals to be in contact with patients, patients receive most of their information about health care from nurses. If nurses accept professional commitment as early as possible, the quality of patient-care will be improved. That is the reason why professional commitment is regarded as the hallmark of quality in professional care. This paper will use the conceptual analysis framework developed by Walker and Avant (1995) to examine and analyze professional commitment and establish its relationship with nursing. The authors hope that it can provide nurses with the opportunity to understand this concept more fully, to support their own profession, to raise the position of the nursing profession and to guarantee the health of the general public.


Phenotypic and Genetic Structure Support Gene Flow Generating Gene Tree Discordances in an Amazonian Floodplain Endemic Species.
Before populations become independent evolutionary lineages, the effects of micro evolutionary processes tend to generate complex scenarios of diversification that may affect phylogenetic reconstruction. Not accounting for gene flow in species tree estimates can directly impact topology, effective population sizes and branch lengths, and the resulting estimation errors are still poorly understood in wild populations. In this study, we used an integrative approach, including sequence capture of ultra-conserved elements (UCEs), mtDNA Sanger sequencing and morphological data to investigate species limits and phylogenetic relationships in face of gene flow in an Amazonian endemic species (Myrmoborus lugubris: Aves). We used commonly implemented species tree and model-based approaches to understand the potential effects of gene flow in phylogenetic reconstructions. The genetic structure observed was congruent with the four recognized subspecies of M. lugubris. Morphological and UCEs data supported the presence of a wide hybrid zone between M. l. femininus from the Madeira river and M. l. lugubris from the Middle and lower Amazon river, which were recovered as sister taxa by species tree methods. When fitting gene flow into simulated demographic models with different topologies, the best-fit model indicated these two taxa as non-sister lineages, a finding that is in agreement with the results of mitochondrial and morphological analyses. Our results demonstrated that failing to account for gene flow when estimating phylogenies at shallow divergence levels can generate topological uncertainty, which can nevertheless be statistically well supported, and that model testing approaches using simulated data can be useful tools to test alternative phylogenetic hypotheses.


From Anhydrous Zinc Oxide Nanoparticle Powders to Aqueous Colloids: Impact of Water Condensation and Organic Salt Adsorption on Free Exciton Emission.
Variations in the composition and structure of ZnO nanoparticle interfaces have a key influence on the materials' optoelectronic properties and are responsible for high number of discrepant results reported for ZnO-based nanomaterials. Here, we conduct a systematic study of the room-temperature photoluminescence of anhydrous ZnO nanocrystals, as synthesized in the gas phase and processed in water-free atmosphere, and of their colloidal derivatives in aqueous dispersions with varying amounts of organic salt admixtures. A free exciton band at hν = 3.3 eV is essentially absent in the anhydrous ZnO nanocrystal powders measured in vacuum or in oxygen atmosphere. Surface hydration of the nanoparticles during colloid formation leads to the emergence of the free exciton band at hν = 3.3 eV and induces a small but significant release in lattice strain as detected by X-ray diffraction. Most importantly, admixture of acetate or citrate ions to the aqueous colloidal dispersions not only allows for the control of the ζ-potential but also affects the intensity of the free exciton emission in a correlated manner. The buildup of negative charge at the solid-liquid interface, as produced by citrate adsorption, increases the free exciton emission. This effect is attributed to the suppression of electron trapping in the near-surface region, which counteracts nonradiative exciton recombination. Using well-defined ZnO nanoparticles as model systems for interface chemistry studies, our findings highlight water-induced key effects that depend on the composition of the aqueous solution shell around the semiconducting metal oxide nanoparticles.


Experimental hemichorea/hemiballismus in the monkey. Studies on the intracerebral site of action in a drug-induced dyskinesia.
Antagonists of the neurotransmitter gamma aminobutyric acid (GABA) were injected at seventy intracerebral sites in the conscious monkey. Injections located in or near to the subthalamic nucleus provoked involuntary movements of the contralateral limbs. These movements had the characteristics of chorea and, when severe, resembled hemiballismus as seen following subthalamic nucleus lesions in man and monkey. Localized injections of GABA antagonists into the medial segment of the globus pallidus were without observable effect on motor activity. These observations are discussed with regard to the role of GABA in subthalamopallidal relations. Injection of GABA antagonists at some other sites provoked different forms of dyskinesia. Injections in or near the zona incerta adjacent to the subthalamic nucleus induced torticollis and circling behaviour either in isolation or in addition to contralateral limb dyskinesia. Injections at some sites located in the lateral segment of the globus pallidus or in the putamen induced choreoathetoid or myoclonic movements, respectively.


Tethered spinal cord with double spinal lipomas.
Although lumbosacral lipoma is reported to occur in 4-8 of 100,000 patients, and 66% of lipomyelomeningoceles in young patients are accompanied by hypertrophic filum terminale, it is very rare to find two isolated spinal lipomas simultaneously. A 3 month-old baby girl was admitted to the hospital for a protruding, non-tender, soft, subcutaneous 2.5 cm mass of the lumbosacral area that had been present since birth. Simple radiography showed a spinal posterior arch defect from L3 to L5, and magnetic resonance imaging (MRI) demonstrated two isolated spinal lipomas, a transitional type from L3 to L5, and a terminal type below S1 without dural defect. The cornus medullaris was severely tethered descending to the S1, but there was no cerebellar or brain stem herniation on the MRI. We suggest that the presence of a combined spinal lipoma should be a point for careful differentiation in an infant with spinal lipoma.


Correlation between the rs7101 and rs1063169 polymorphisms in the FOS noncoding region and susceptibility to and prognosis of colorectal cancer.
The FOS gene is located on human chromosome 14q21-31 and encodes the nuclear oncoprotein c-Fos. This study analyzed the correlation between the FOS noncoding region rs7101 and rs1063169 polymorphisms and colorectal cancer susceptibility and prognosis. We analyzed the FOS genotypes in 432 colorectal cancer patients and 315 healthy subjects by PCR/Sanger sequencing. Survival was analyzed by Kaplan-Meier and Cox regression analysis. Western blot was used to detect the expression of c-Fos protein in cancer tissues and adjacent tissues in colorectal cancer patients with different genotypes. The presence of a T allele at rs7101 and a T allele at rs1063169 in FOS carried a higher risk of colorectal cancer [adjusted odds ratio (OR) = 1.237, 95% confidence interval (95% CI) = 1.131-1.346, P ≤ .001 and adjusted OR = 1.218, 95% CI = 1.111-1.327, P ≤ .001, respectively]. c-Fos protein levels were significantly higher in variant cancer tissues than in normal mucosa tissues (P < .05), and c-Fos proteins levels were also higher in homozygous variant cancer tissues than in heterozygous variant cancer tissues. The 3-year survival rate of patients with wild-type FOS was higher than that of patients with variant FOS (P < .05). The rs7101 and rs1063169 polymorphisms in the noncoding region of FOS are associated with the risk of developing colorectal cancer and the progression of colorectal cancer, which may be because the mutation enhances the expression of c-Fos protein to promote the incidence and development of colorectal cancer.


Determination of absolute amounts of heparin and of dextran sulfate in plasma in microgram quantities.
Heparin and dextran sulfates 8000 are separated from citrated plasma by absorption on epichlorohydrin triethanolamine cellulose columns followed by elution with 1.1 and 1.4 mol/L NaCl in 0.05 mol/L glycine-HCl buffer. The eluate is desalted with Sephadex G25-40, dried, and dissolved in water. A 1 microliters sample is applied to an agarose gel slide. After electrophoresis, the slide is fixed and stained with toluidine blue. The sulfated polysaccharide band(s) is identified by relative electrophoretic migration. The total amount of drug is estimated by matching its optical density with that of a band on one of a set of slides with graded amounts of heparin or dextran sulfate. The reaction with toluidine blue measures the total polyelectrolyte, not just the small proportion of the drug with anticoagulant activity. Pooled normal plasma showed a trace of chondroitin and no heparin. Recovery of heparin and hydrogenated dextran sulfate that was added to pooled normal plasma was complete (lowest concentration tested was 10 micrograms/ml); however, recovery for unhydrogenated dextran sulfate declined consistently by 9 micrograms/ml for concentrations below 50 micrograms/ml, setting a limit for its recovery. Plasma samples taken from patients for coagulation tests were examined by this procedure, and in so doing, steps were ascertained to improve the procedure for routine use. Results were compared with values for prothrombin time and activated partial thromboplastin times obtained on the same samples by the clinical laboratory. Because the procedure provides an independent parameter for measurement in patients who have received heparin therapy, insight into different patient responses to the drug is therefore possible. With minor modifications, the procedure can be used for heparans, dermatans, and chondroitins, because it allows identification and microscale quantitation on the basis of charge, molecular weight, and carbohydrate structure.


Factors Associated With Medication Use Among Individuals Living With Multiple Sclerosis.
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system causing neurological deterioration over time. The objective of this study was to examine the predictors associated with MS medication use. The categories that were investigated were various alternative treatments such as complementary/alternative medications (CAMs), rehabilitation therapy and psychotherapy services as well as comorbid health conditions. The Survey on Living with Neurological Conditions in Canada (SLNCC) 2011-2012 was used (N = 73 347) to carry out a logistic regression model. Individuals who did not take CAMs were more (OR = 5.44, 95% CI 1.37-9.29) likely to use medications for MS. Having a mood disorder was associated with greater use of MS medications (OR = 5.39, 95% CI 1.60-18.17) while back problems were associated with lower odds of medication use (OR = 0.38, 95% CI 0.15-0.98). These factors need to be taken into consideration when creating effective medication adherence interventions.