Assessing temporal processing of facial emotion perception with transcranial magnetic stimulation.
The ability to process facial expressions can be modified by altering the spatial frequency of the stimuli, an effect that has been attributed to differential properties of visual pathways that convey different types of information to distinct brain regions at different speeds. While this effect suggests a potential influence of spatial frequency on the processing speed of facial emotion, this hypothesis has not been examined directly. We addressed this question using a facial emotion identification task with photographs containing either high spatial frequency (HSF), low spatial frequency (LSF), or broadband spatial frequency (BSF). Temporal processing of emotion perception was manipulated by suppressing visual perception with a single-pulse transcranial magnetic stimulation (TMS), delivered to the visual cortex at six intervals prior to (forward masking) or following (backward masking) stimulus presentation. Participants performed best in the BSF, followed by LSF, and finally HSF condition. A spatial frequency by forward/backward masking interaction effect demonstrated reduced performance in the forward masking component in the BSF condition and a reversed performance pattern in the HSF condition, with no significant differences between forward and backward masking in the LSF condition. Results indicate that LSF information may play a greater role than HSF information in emotional processing, but may not be sufficient for fast conscious perception of emotion. As both LSF and HSF filtering reduced the speed of extracting emotional information from faces, it is possible that intact BSF faces have an inherent perceptual advantage and hence benefit from faster temporal processing.


Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents.
Parasitic infections cause a myriad of responses in their mammalian hosts, on immune as well as on metabolic level. A multiplex panel of cytokines and metabolites derived from four parasite-rodent models, namely, Plasmodium berghei-mouse, Trypanosoma brucei brucei-mouse, Schistosoma mansoni-mouse, and Fasciola hepatica-rat were statistically coanalyzed. (1)H NMR spectroscopy and multivariate statistical analysis were used to characterize the urine and plasma metabolite profiles in infected and noninfected animals. Each parasite generated a unique metabolic signature in the host. Plasma cytokine concentrations were obtained using the 'Meso Scale Discovery' multi cytokine assay platform. Multivariate data integration methods were subsequently used to elucidate the component of the metabolic signature which is associated with inflammation and to determine specific metabolic correlates with parasite-induced changes in plasma cytokine levels. For example, the relative levels of acetyl glycoproteins extracted from the plasma metabolite profile in the P. berghei-infected mice were statistically correlated with IFN-gamma, whereas the same cytokine was anticorrelated with glucose levels. Both the metabolic and the cytokine data showed a similar spatial distribution in principal component analysis scores plots constructed for the combined murine data, with samples from all infected animals clustering according to the parasite species and whereby the protozoan infections (P. berghei and T. b. brucei) grouped separately from the helminth infection (S. mansoni). For S. mansoni, the main infection-responsive cytokines were IL-4 and IL-5, which covaried with lactate, choline, and d-3-hydroxybutyrate. This study demonstrates that the inherently differential immune response to single- and multicellular parasites not only manifests in the cytokine expression, but also consequently imprints on the metabolic signature, and calls for in-depth analysis to further explore direct links between immune features and biochemical pathways.


Atypical glandular cells in conventional cervical smears: incidence and follow-up.
Atypical glandular cells on cervical smears are often associated with clinically significant uterine lesions. The frequency and accuracy of AGC-NOS (i.e. atypical glandular cells, not otherwise specified) diagnoses, regardless of the gland cell type or the degree of suspicion, and their outcome were investigated. From January 1, 1990 to December 31, 1999 a total of 261 patients had an AGC-NOS diagnosis made by conventional cervical Papanicolaou smear interpretation representing 0.05% of all Pap-smears analyzed at the national level. 191 (73.2%) patients had a subsequent histological examination, 8 samples were not representative by origin and were excluded. Out of 183 AGC-NOS diagnosed, 56.3% (103/183) were associated with tissue-proven precancerous and/or cancerous lesions, 44% being of endocervical and 56% of endometrial origin. 75% of all AGC-patients were asymptomatic. 66.7% (6/9) of the patients with subsequent invasive endocervical adenocarcinoma (AC) and 56% (28/50) of those patients with invasive endometrial AC were without clinical symptoms. 3 patients out of 9 with an invasive endocervical AC were 35 years of age or less. 10.1% and 12.3% of all 'new' tissue-proven invasive endocervical or endometrial AC respectively recorded by the national Morphologic Tumour Registry (MTR) were first identified by a cytological AGC-NOS diagnosis. Our findings emphasize the importance of the cytological AGC-category even in the absence of a precise origin or cell type specification. 56% of the AGC-diagnoses being associated with significant cancerous or precancerous conditions, a complete and careful evaluation is required.


Antiproliferative activity of 8-methoxypsoralen on DU145 prostate cancer cells under UVA and blue light.
The use of photoactivatable 8-methoxypsoralen (8-MOP) as potential focal treatment towards prostate cancer cells is proposed here. Our results, obtained on isolated DNA and DU145 cells, indicate that blue light, besides UVA, is able to activate 8-MOP. When compared to UVA, blue light irradiation led to a modulation of the extent and the types of 8-MOP-DNA damage, specially cross-links, coupled to a still valuable antiproliferative effect. Our data suggest that the proapototic activity of 8-MOP is related not only to DNA damage and reactive oxygen species generation but also to the modulation of cell signalling pathways. In particular, a different activation of p38 and p44/42 mitogen-activated protein kinases was detected depending on the light wavelengths.


Variation of bispectral index under TIVA with propofol in a paediatric population.
In this prospective observational study, we aim to explore the relationship between age and bispectral index (BIS) values at different plasma concentrations of propofol. Fifty children aged from 3 to 15 yr were included. Anaesthesia was induced using a target-controlled infusion of propofol with the Kataria pharmacokinetic model together with a bolus of remifentanil followed by a continuous infusion rate at 0.2 microg kg(-1) min(-1). Target plasma propofol concentration was initially stabilized to 6 microg ml(-1) and continued for 6 min. The target was then decreased and stabilized to 4 microg ml(-1) and then to 2 microg ml(-1). BIS values, plasma propofol concentration, and EEG were continuously recorded. In order to explore the relationship between variations in propofol concentration and the EEG bispectrum, we used a multiple correspondence analysis (MCA). Results are shown in median (range). We found no statistical difference between BIS values with propofol 6 microg ml(-1) [23 (12-40)] and 4 microg ml(-1) [28 (9-67)]. At 2 microg ml(-1), BIS was significantly different [52 (24-71)], but a significant correlation between the age of children and BIS values was found (r2=0.66; P<0.01). There was little change in children's position between 6 and 4 microg ml(-1) in the structure model of the MCA. From 4 to 2 microg ml(-1), the position of children moved only on axis 2. These results showed the difficulty to interpret BIS values because of the absence of significant change for higher plasma propofol concentration variation or because of the link with age for the lower plasma concentration.


Differential effects of rhythmic auditory stimulation and neurodevelopmental treatment/Bobath on gait patterns in adults with cerebral palsy: a randomized controlled trial.
To investigate the effects of rhythmic auditory stimulation (RAS) on gait patterns in comparison with changes after neurodevelopmental treatment (NDT/Bobath) in adults with cerebral palsy. A repeated-measures analysis between the pretreatment and posttreatment tests and a comparison study between groups. Human gait analysis laboratory. Twenty-eight cerebral palsy patients with bilateral spasticity participated in this study. The subjects were randomly allocated to either neurodevelopmental treatment (n = 13) or rhythmic auditory stimulation (n = 15). Gait training with rhythmic auditory stimulation or neurodevelopmental treatment was performed three sessions per week for three weeks. Temporal and kinematic data were analysed before and after the intervention. Rhythmic auditory stimulation was provided using a combination of a metronome beat set to the individual's cadence and rhythmic cueing from a live keyboard, while neurodevelopmental treatment was implemented following the traditional method. Temporal data, kinematic parameters and gait deviation index as a measure of overall gait pathology were assessed. Temporal gait measures revealed that rhythmic auditory stimulation significantly increased cadence, walking velocity, stride length, and step length (P < 0.05). Kinematic data demonstrated that anterior tilt of the pelvis and hip flexion during a gait cycle was significantly ameliorated after rhythmic auditory stimulation (P < 0.05). Gait deviation index also showed modest improvement in cerebral palsy patients treated with rhythmic auditory stimulation (P < 0.05). However, neurodevelopmental treatment showed that internal and external rotations of hip joints were significantly improved, whereas rhythmic auditory stimulation showed aggravated maximal internal rotation in the transverse plane (P < 0.05). Gait training with rhythmic auditory stimulation or neurodevelopmental treatment elicited differential effects on gait patterns in adults with cerebral palsy.


An apocalyptic vision of ageing in China: Old age care for the largest elderly population in the world.
According to the National Bureau of Statistics of China, by 2010 the number of people aged 60 or over had reached 178 million in China or 13% of its population. With the largest elderly population in the world in absolute numbers, China faces a challenge of providing care for the elderly both in the present and the future. Unlike old age pensions and health protection for the elderly, in Chinese society elderly care had never been considered to be a social problem but rather the individual family's responsibility. After the turn of the millennium, as the repercussions of increasingly ageing demographics, the results of the One-Child Policy and drastic changes in traditional family structures gradually became more apparent, this issue of elderly care has increasingly become one of the most pressing concerns for the ageing society. As there is little existing research on this particular topic, this article aims to shed light on elderly care in China, focusing on the care of elderly needing assistance with activities of daily living, since this group of elderly are most in need of care, their numbers having risen to 33 million in 2010. This article argues it is urgent for China to switch from informal family-based elderly care to the state's formal long-term care, illustrates that a model of social insurance (e.g. as in Germany) is advocated by many Chinese scholars and points out the ways in which it is different from both the commercialized models (e.g. as in the USA) and state organized "Beveridge" models (e.g. as in Sweden).


Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.
Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors.


Oscillatory dynamics of vasoconstriction and vasodilation identified by time-localized phase coherence.
We apply wavelet-based time-localized phase coherence to investigate the relationship between blood flow and skin temperature, and between blood flow and instantaneous heart rate (IHR), during vasoconstriction and vasodilation provoked by local cooling or heating of the skin. A temperature-controlled metal plate (approximately 10 cm2) placed on the volar side of the left arm was used to provide the heating and cooling. Beneath the plate, the blood flow was measured by laser Doppler flowmetry and the adjacent skin temperature by a thermistor. Two 1 h datasets were collected from each of the ten subjects. In each case a 30 min basal recording was followed by a step change in plate temperature, to either 24 °C or 42 °C. The IHR was derived from simultaneously recorded ECG. We confirm the changes in the energy and frequency of blood flow oscillations during cooling and heating reported earlier. That is, during cooling, there was a significant decrease in the average frequency of myogenic blood flow oscillations (p < 0.05) and the myogenic spectral peak became more prominent. During heating, there was a significant (p < 0.05) general increase in spectral energy, associated with vasodilation, except in the myogenic interval. Weak phase coherence between temperature and blood flow was observed for unperturbed skin, but it increased in all frequency intervals as a result of heating. It was not significantly affected by cooling. We also show that significant (p < 0.05) phase coherence exists between blood flow and IHR in the respiratory and myogenic frequency intervals. Cooling did not affect this phase coherence in any of the frequency intervals, whereas heating enhanced the phase coherence in the respiratory and myogenic intervals. This can be explained by the reduction in vascular resistance produced by heating, a process where myogenic mechanisms play a key role. We conclude that the mechanisms of vasodilation and vasoconstriction, in response to temperature change, are oscillatory in nature and are independent of central sources of variability.


Satellite DNA in Paphiopedilum subgenus Parvisepalum as revealed by high-throughput sequencing and fluorescent in situ hybridization.
Satellite DNA is a rapidly diverging, largely repetitive DNA component of many eukaryotic genomes. Here we analyse the evolutionary dynamics of a satellite DNA repeat in the genomes of a group of Asian subtropical lady slipper orchids (Paphiopedilum subgenus Parvisepalum and representative species in the other subgenera/sections across the genus). A new satellite repeat in Paphiopedilum subgenus Parvisepalum, SatA, was identified and characterized using the RepeatExplorer pipeline in HiSeq Illumina reads from P. armeniacum (2n = 26). Reconstructed monomers were used to design a satellite-specific fluorescent in situ hybridization (FISH) probe. The data were also analysed within a phylogenetic framework built using the internal transcribed spacer (ITS) sequences of 45S nuclear ribosomal DNA. SatA comprises c. 14.5% of the P. armeniacum genome and is specific to subgenus Parvisepalum. It is composed of four primary monomers that range from 230 to 359 bp and contains multiple inverted repeat regions with hairpin-loop motifs. A new karyotype of P. vietnamense (2n = 28) is presented and shows that the chromosome number in subgenus Parvisepalum is not conserved at 2n = 26, as previously reported. The physical locations of SatA sequences were visualised on the chromosomes of all seven Paphiopedilum species of subgenus Parvisepalum (2n = 26-28), together with the 5S and 45S rDNA loci using FISH. The SatA repeats were predominantly localisedin the centromeric, peri-centromeric and sub-telocentric chromosome regions, but the exact distribution pattern was species-specific. We conclude that the newly discovered, highly abundant and rapidly evolving satellite sequence SatA is specific to Paphiopedilum subgenus Parvisepalum. SatA and rDNA chromosomal distributions are characteristic of species, and comparisons between species reveal that the distribution patterns generate a strong phylogenetic signal. We also conclude that the ancestral chromosome number of subgenus Parvisepalum and indeed of all Paphiopedilum could be either 2n = 26 or 28, if P. vietnamense is sister to all species in the subgenus as suggested by the ITS data.


Microvascular pressures and resistances in the left ventricular subepicardium and subendocardium.
These experiments tested the hypothesis that differences in the distribution of subepicardial and subendocardial microvascular resistances may alter the transmural distributions of microvascular pressures. Isolated blood- and physiological saline-perfused porcine hearts were surgically incised to enable exposure of the subendocardial and subepicardial microcirculations. Microvascular pressures were measured during cardiac arrest and maximal vasodilation at various perfusion pressures to formulate relations between perfusion pressure and microvascular pressure in the different subendocardial (both free wall and papillary muscle) and subepicardial segments. Measurements of arteriolar and venular pressures in both myocardial regions were performed in comparably sized vessels (80-120 microns in diameter). At a coronary perfusion pressure of 100 mm Hg, subendocardial arteriolar and venular pressures were 60 +/- 4 and 33 +/- 3 mm Hg, respectively. In contrast, at the same coronary perfusion pressure, arteriolar and venular pressures in the subepicardial microcirculation averaged 80 +/- 6 and 22 +/- 3 mm Hg, respectively (p less than 0.05 versus subendocardium). At all levels of coronary perfusion pressure, arteriolar pressures were significantly lower in the subendocardium than in the subepicardium (p less than 0.05). Venular pressures were also higher in the subendocardial microcirculation than in the subepicardial microcirculation at all but the lowest perfusion pressure (p less than 0.05). The relative distribution of resistances in arteries, microvessels, and veins was also different between the subepicardium and subendocardium. Specifically, in the subendocardium, arterial and venous resistances were higher, percentage-wise, but microvascular resistance was proportionately lower than that in the subepicardium (p less than 0.05). From these data, it is concluded that the distribution of microvascular resistances and pressures is different during maximal vasodilation in the subepicardial and subendocardial microcirculations of the left ventricle. It is also speculated that differences in autoregulatory capacity and vulnerability to ischemia may be partially related to unequal distribution of microvascular resistances across the wall of the left ventricle.


Syntaxin 3B is essential for the exocytosis of synaptic vesicles in ribbon synapses of the retina.
Ribbon synapses of the vertebrate retina are specialized synapses that release neurotransmitter by synaptic vesicle exocytosis in a manner that is proportional to the level of depolarization of the cell. This release property is different from conventional neurons, in which the release of neurotransmitter occurs as a short-lived burst triggered by an action potential. Synaptic vesicle exocytosis is a calcium regulated process that is dependent on a set of interacting synaptic proteins that form the so-called SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) complex. Syntaxin 3B has been identified as a specialized SNARE molecule in ribbon synapses of the rodent retina. However, the best physiologically-characterized neuron that forms ribbon-style synapses is the rod-dominant or Mb1 bipolar cell of the goldfish retina. We report here the molecular characterization of syntaxin 3B from the goldfish retina. Using a combination of reverse transcription (RT) polymerase chain reaction (PCR) and immunostaining with a specific antibody, we show that syntaxin 3B is highly enriched in the plasma membrane of bipolar cell synaptic terminals of the goldfish retina. Using membrane capacitance measurements we demonstrate that a peptide derived from goldfish syntaxin 3B inhibits synaptic vesicle exocytosis. These experiments demonstrate that syntaxin 3B is an important factor for synaptic vesicle exocytosis in ribbon synapses of the vertebrate retina.


Salt-induced cluster formation of gold nanoparticles followed by stopped-flow SAXS, DLS and extinction spectroscopy.
In this work we investigate the salt-induced cluster formation of monodisperse, spherical gold nanoparticles possessing negative surface charge. Time dependent dynamic light scattering was used to determine the critical coagulation concentration and to study the kinetics of cluster growth. Cryo-TEM as well as small angle X-ray scattering allowed to obtain insights into the cluster morphology at various salt concentrations. The time dependent cluster growth was monitored by stopped-flow small angle X-ray scattering experiments and UV-Visible extinction measurements simultaneously. Our results reveal the transition from reaction limited cluster aggregation (RLCA) at low salt concentrations to diffusion limited cluster aggregation (DLCA) at high salt concentrations. We were able to correlate changes of the plasmon resonance position of the gold nanoparticles to the cluster size. By comparison to theoretical calculations using Mie theory, we found indication that stronger resonance shifts during cluster growth can be related to smaller inter-particle spacings.


Deformation of the rodent optic nerve head and peripapillary structures during acute intraocular pressure elevation.
PURPOSE. To evaluate the effect of acutely elevated intraocular pressure (IOP) on retinal thickness and optic nerve head (ONH) structure in the rat eye by spectral domain-optical coherence tomography (SD-OCT). METHODS. Fourteen adult male Brown-Norway rats were studied under anesthesia (ketamine/xylazine/acepromazine, 55:5:1 mg/kg intramuscularly). Both eyes were imaged by SD-OCT on two baseline occasions several weeks before and again 2 and 4 weeks after the acute IOP imaging session. During the acute IOP session, SD-OCT imaging was performed 10 minutes after IOP was manometrically set at 15 mm Hg and then at 10, 30, and 60 minutes after IOP had been elevated to 50 mm Hg (n = 8) and again 10 and 30 minutes after IOP had been lowered back to 15 mm Hg (recovery). In two additional groups, IOP elevation was set to 70 mm Hg (n = 4) or 40 mm Hg (n = 2). Acute IOP results are reported for a pattern of 49 horizontal B-scans spanning a 20° square and follow-up results for peripapillary circular B-scans. Retinal and retinal nerve fiber layer (RNFL) thicknesses were measured with custom software by manual image segmentation. Friedman and Dunn's tests were used to assess acute and longer-term effects of acute IOP elevation. RESULTS. Acute IOP elevation to 50 mm Hg caused rapid (within seconds) deformation of the ONH and peripapillary structures, including posterior displacement of the ONH surface and outward bowing of peripapillary tissue; retinal thickness decreased progressively from 10 to 30 to 60 minutes by 16%, 18%, and 20% within the area of Bruch's membrane opening (BMO; P < 0.0001) by 8%, 9%, and 11% within the central 10° (excluding the BMO; P < 0.0001) but only by 1%, 2%, and 2.4% beyond the central 10° (P < 0.0001). Recovery was progressive and nearly complete by 30 minutes. Acute IOP elevation to 40 and 70 mm Hg produced similar structural changes, but 70 mm Hg also interfered with retinal blood flow. There were no changes in peripapillary retinal or RNFL thickness (P = 0.08 and P = 0.16, respectively) measured 2 and 4 weeks after acute elevation to 50 mm Hg. CONCLUSIONS. Acute IOP elevation in the rodent eye causes rapid, reversible posterior deformation of the ONH and thinning of the peripapillary retina, with only minimal retinal thinning beyond 5° of the ONH. No permanent changes in peripapillary retinal or RNFL thickness (for up to 1 month of follow-up) were caused by 60 minutes of IOP elevation to 50 mm Hg.


Complete Genome Sequence of Ovine Mycobacterium avium subsp. paratuberculosis Strain JIII-386 (MAP-S/type III) and Its Comparison to MAP-S/type I, MAP-C, and M. avium Complex Genomes.
Mycobacterium avium (M. a.) subsp. paratuberculosis (MAP) is a worldwide-distributed obligate pathogen in ruminants causing Johne's disease. Due to a lack of complete subtype III genome sequences, there is not yet conclusive information about genetic differences between strains of cattle (MAP-C, type II) and sheep (MAP-S) type, and especially between MAP-S subtypes I, and III. Here we present the complete, circular genome of MAP-S/type III strain JIII-386 (DE) closed by Nanopore-technology and its comparison with MAP-S/type I closed genome of strain Telford (AUS), MAP-S/type III draft genome of strain S397 (U.S.), twelve closed MAP-C strains, and eight closed M.-a.-complex-strains. Structural comparative alignments revealed clearly the mosaic nature of MAP, emphasized differences between the subtypes and the higher diversity of MAP-S genomes. The comparison of various genomic elements including transposases and genomic islands provide new insights in MAP genomics. MAP type specific phenotypic features may be attributed to genes of known large sequence polymorphisms (LSPSs) regions I-IV and deletions #1 and #2, confirmed here, but could also result from identified frameshifts or interruptions of various virulence-associated genes (e.g., mbtC in MAP-S). Comprehensive core and pan genome analysis uncovered unique genes (e.g., cytochromes) and genes probably acquired by horizontal gene transfer in different MAP-types and subtypes, but also emphasized the highly conserved and close relationship, and the complex evolution of M.-a.-strains.


Planetary heat flow measurements.
The year 2005 marks the 35th anniversary of the Apollo 13 mission, probably the most successful failure in the history of manned spaceflight. Naturally, Apollo 13's scientific payload is far less known than the spectacular accident and subsequent rescue of its crew. Among other instruments, it carried the first instrument designed to measure the flux of heat on a planetary body other than Earth. The year 2005 also should have marked the launch of the Japanese LUNAR-A mission, and ESA's Rosetta mission is slowly approaching comet Churyumov-Gerasimenko. Both missions carry penetrators to study the heat flow from their target bodies. What is so interesting about planetary heat flow? What can we learn from it and how do we measure it?Not only the Sun, but all planets in the Solar System are essentially heat engines. Various heat sources or heat reservoirs drive intrinsic and surface processes, causing 'dead balls of rock, ice or gas' to evolve dynamically over time, driving convection that powers tectonic processes and spawns magnetic fields. The heat flow constrains models of the thermal evolution of a planet and also its composition because it provides an upper limit for the bulk abundance of radioactive elements. On Earth, the global variation of heat flow also reflects the tectonic activity: heat flow increases towards the young ocean ridges, whereas it is rather low on the old continental shields. It is not surprising that surface heat flow measurements, or even estimates, where performed, contributed greatly to our understanding of what happens inside the planets. In this article, I will review the results and the methods used in past heat flow measurements and speculate on the targets and design of future experiments.


Protecting posted genes: social networking and the limits of GINA.
The combination of decreased genotyping costs and prolific social media use is fueling a personal genetic testing industry in which consumers purchase and interact with genetic risk information online. Consumers and their genetic risk profiles are protected in some respects by the 2008 federal Genetic Information Nondiscrimination Act (GINA), which forbids the discriminatory use of genetic information by employers and health insurers; however, practical and technical limitations undermine its enforceability, given the everyday practices of online social networking and its impact on the workplace. In the Web 2.0 era, employers in most states can legally search about job candidates and employees online, probing social networking sites for personal information that might bear on hiring and employment decisions. We examine GINA's protections for online sharing of genetic information as well as its limitations, and propose policy recommendations to address current gaps that leave employees' genetic information vulnerable in a Web-based world.


Global agricultural intensification during climate change: a role for genomics.
Agriculture is now facing the 'perfect storm' of climate change, increasing costs of fertilizer and rising food demands from a larger and wealthier human population. These factors point to a global food deficit unless the efficiency and resilience of crop production is increased. The intensification of agriculture has focused on improving production under optimized conditions, with significant agronomic inputs. Furthermore, the intensive cultivation of a limited number of crops has drastically narrowed the number of plant species humans rely on. A new agricultural paradigm is required, reducing dependence on high inputs and increasing crop diversity, yield stability and environmental resilience. Genomics offers unprecedented opportunities to increase crop yield, quality and stability of production through advanced breeding strategies, enhancing the resilience of major crops to climate variability, and increasing the productivity and range of minor crops to diversify the food supply. Here we review the state of the art of genomic-assisted breeding for the most important staples that feed the world, and how to use and adapt such genomic tools to accelerate development of both major and minor crops with desired traits that enhance adaptation to, or mitigate the effects of climate change.


Dendritic polyglycerol sulfate as a novel platform for paclitaxel delivery: pitfalls of ester linkage.
In this study, dendritic polyglycerol sulfate (dPGS) is evaluated as a delivery platform for the anticancer, tubulin-binding drug paclitaxel (PTX). The conjugation of PTX to dPGS is conducted via a labile ester linkage. A non-sulfated dendritic polyglycerol (dPG) is used as a control, and the labeling with an indocarbocyanine dye (ICC) renders multifunctional conjugates that can be monitored by fluorescence microscopy. The conjugates are characterized by (1)H NMR, UV-vis measurements, and RP-HPLC. In vitro cytotoxicity of PTX and dendritic conjugates is evaluated using A549 and A431 cell lines, showing a reduced cytotoxic efficacy of the conjugates compared to PTX. The study of uptake kinetics reveals a linear, non saturable uptake in tumor cells for dPGS-PTX-ICC, while dPG-PTX-ICC is hardly taken up. Despite the marginal uptake of dPG-PTX-ICC, it prompts tubulin polymerization to a comparable extent as PTX. These observations suggest a fast ester hydrolysis and premature drug release, as confirmed by HPLC measurements in the presence of plasma enzymes.


Development of a glycoproteomic strategy to detect more aggressive prostate cancer using lectin-immunoassays for serum fucosylated PSA.
Prostate-specific antigen (PSA) is commonly used as a serum biomarker for the detection of prostate cancer. However, levels of PSA in serum do not reliably distinguish aggressive prostate cancer from non-aggressive disease. Therefore, there is an urgent need for biomarkers that can differentiate aggressive prostate cancers from non-aggressive phenotypes. Fucosylation is one of the glycosylation-based protein modifications. Previously we demonstrated increased levels of serum fucosylated PSA in patients with aggressive prostate cancer using lectin selection followed by PSA immunoassay. We developed two lectin-immunoassays, Lens culinaris agglutinin (LCA) and Aleuria aurantia lectin (AAL) followed by clinical PSA immunoassay and investigated the levels of PSA and its fucosylated glycoforms in serum specimens from prostate cancer patients with different Gleason scores. First, we developed standard curves for lectins enrichment, which were applied to lectin-immunoassay for fucosylated PSA-LCA and PSA-AAL quantification in serum samples. Our results showed that both LCA- and AAL-immunoassays detected elevated fucosylated PSA and were correlated with higher Gleason scores but only AAL-immunoassay detected an increased percentage of fucosylated PSA in patient serum with higher Gleason scores. We have developed quantitative lectin-immunoassays for serum fucosylated PSA. Our data demonstrated that fucosylated PSA-AAL, % fucosylated PSA-AAL and fucosylated PSA-LCA levels could be effective biomarkers to differentiate aggressive prostate cancer [especially Gleason 7 (4 + 3) or above] from non-aggressive disease. We believe that application of these lectin-immunoassays to a larger patient population is needed to evaluate the clinical utilities of fucosylated PSA using AAL-PSA and LCA-PSA for aggressive prostate cancer.


Characteristics of low-speed vehicle run-over events in children: an 11-year review.
The purpose of this study was to investigate the characteristics associated with fatal and non-fatal low-speed vehicle run-over (LSVRO) events in relation to person, incident and injury characteristics, in order to identify appropriate points for intervention and injury prevention. Data on all known LSVRO events in Queensland, Australia, over 11 calendar years (1999-2009) were extracted from five different databases representing the continuum of care (prehospital to fatality) and manually linked. Descriptive and multivariate analyses were used to analyse the sample characteristics in relation to demographics, health service usage, outcomes, incident characteristics, and injury characteristics. Of the 1641 LSVRO incidents, 98.4% (n=1615) were non-fatal, and 1.6% were fatal (n=26). Over half the children required admission to hospital (56%, n=921); mean length of stay was 3.4 days. Younger children aged 0-4 years were more frequently injured, and experienced more serious injuries with worse outcomes. Patterns of injury (injury type and severity), injury characteristics (eg, time of injury, vehicle type, driver of vehicle, incident location), and demographic characteristics (such as socioeconomic status, indigenous status, remoteness), varied according to age group. Almost half (45.6%; n=737) the events occurred outside major cities, and approximately 10% of events involved indigenous children. Parents were most commonly the vehicle drivers in fatal incidents. While larger vehicles such as four-wheel drives (4WD) were most frequently involved in LSVRO events resulting in fatalities, cars were most frequently involved in non-fatal events. This is the first study, to the authors' knowledge, to analyse the characteristics of fatal and non-fatal LSVRO events in children aged 0-15 years on a state-wide basis. Characteristics of LSVRO events varied with age, thus age-specific interventions are required. Children living outside major cities, and indigenous children, were over-represented in these data. Further research is required to identify the burden of injury in these groups.


Observations on the macroscopic digestive anatomy of the Himalayan tahr (Hemitragus jemlahicus).
We measured macroscopic anatomical parameters of the digestive tract of 12 female Himalayan tahrs. According to morphological criteria used sensu Hofmann for the classification of ruminants into feeding types - in particular the reticuloruminal capacity measured as wet content weights, the ruminal pillar thickness, the reticular honeycomb structure, the size of the omasum and the size of the parotid glands - tahrs can be classified as predominantly grazing ruminants. As reported in other ruminant species, the length of the large intestine was a more constant parameter over a range of body weights than that of the small intestine. The weight of the parotid glands scaled to metabolic body weight.


The role of bacterial phytotoxins in inhibiting the eukaryotic proteasome.
The ubiquitin-26S proteasome degradation system (UPS) plays a pivotal role in almost all aspects of plant life, including defending against pathogens. Although the proteasome is important for plant immunity, it has been found to be also exploited by pathogens using effectors to increase their virulence. Recent work on the XopJ effector and syringolin A/syrbactins has highlighted host proteasome inhibition as a virulence strategy of pathogens. This review will focus on these recent developments.


The topography of transmembrane segment six is altered during the catalytic cycle of P-glycoprotein.
Structural evidence has demonstrated that P-glycoprotein (P-gp) undergoes considerable conformational changes during catalysis, and these alterations are important in drug interaction. Knowledge of which regions in P-gp undergo conformational alterations will provide vital information to elucidate the locations of drug binding sites and the mechanism of coupling. A number of investigations have implicated transmembrane segment six (TM6) in drug-P-gp interactions, and a cysteine-scanning mutagenesis approach was directed to this segment. Introduction of cysteine residues into TM6 did not disturb basal or drug-stimulated ATPase activity per se. Under basal conditions the hydrophobic probe coumarin maleimide readily labeled all introduced cysteine residues, whereas the hydrophilic fluorescein maleimide only labeled residue Cys-343. The amphiphilic BODIPY-maleimide displayed a more complex labeling profile. The extent of labeling with coumarin maleimide did not vary during the catalytic cycle, whereas fluorescein maleimide labeling of F343C was lost after nucleotide binding or hydrolysis. BODIPY-maleimide labeling was markedly altered during the catalytic cycle and indicated that the adenosine 5'-(beta,gamma-imino)triphosphate-bound and ADP/vanadate-trapped intermediates were conformationally distinct. Our data are reconciled with a recent atomic scale model of P-gp and are consistent with a tilting of TM6 in response to nucleotide binding and ATP hydrolysis.


Comprehensive cardiopulmonary assessment in α mannosidosis.
α Mannosidosis is an extremely rare, progressive, and complex lysosomal storage disease, characterized by mental retardation, hearing impairment, coarse facial features, skeletal abnormalities, and pulmonary involvement. While bone marrow transplantation has been the only therapeutic option to date, nowadays new treatment options are being explored, which may affect pulmonary and exercise capacity. To assess cardiopulmonary involvement in patients with α mannosidosis by pulmonary function tests, cardiopulmonary exercise testing, and low irradiation chest computed tomography (CT). Five patients aged 11 to 28 years were followed in our Respiratory-Metabolic Clinic. All five had pulmonary symptoms and received inhaled therapy. Three patients underwent bone marrow transplantation. Parenchymal lung disease was evident in 3/5 chest CT tests. Pulmonary function tests were abnormal in all patients and showed obstructive/restrictive impairment with air trapping. All five patients showed reduced peak oxygen uptake (median 23.1; range 20.4-32.2 mL/minute/kg, median %predicted 62; range %predicted 59-79). Pulmonary involvement is a known complication in this rare disease. Comprehensive cardiopulmonary evaluation is feasible among these patients and may help in assessing disease progression and response to new treatment modalities.


Application of the social action theory to understand factors associated with risky sexual behavior among individuals in residential substance abuse treatment.
Risky sexual behavior (RSB) is a leading cause of HIV/AIDS, particularly among urban substance users. Using the social action theory, an integrative systems model of sociocognitive, motivational, and environmental influences, as a guiding framework, the current study examined (1) environmental influences, (2) psychopathology and affect, (3) HIV-related attitudes and knowledge, and (4) self-regulatory skills/deficits as factors associated with event-level condom use (CU) among a sample of 156 substance users residing at a residential substance abuse treatment center (M age = 41.85; SD = 8.59; 75% male). RSB was assessed using event-level measurement of CU given its advantages for improved accuracy of recall and ability for an examination of situational variables. A logistic regression predicting event-level CU indicated the significant contribution of partner type (environmental influences), less favorable attitudes towards condoms (HIV-related attitudes and knowledge), and higher levels of risk-taking propensity (self-regulatory skills/deficits) in predicting greater likelihood of not having used a condom at one's most recent sexual encounter. This study contributes to the literature examining HIV risk behaviors among substance users within a theory-driven model of risk.


Structural characterization of dissolved organic matter: a review of current techniques for isolation and analysis.
Natural dissolved organic matter (DOM) in aquatic systems plays many environmental roles: providing building blocks and energy for aquatic biota, acting as a sunscreen in surface water, and interacting with anthropogenic compounds to affect their ultimate fate in the environment. Such interactions are a function of DOM composition, which is difficult to ascertain due to its heterogeneity and the co-occurring matrix effects in most aquatic samples. This review focuses on current approaches to the chemical structural characterization of DOM, ranging from those applicable to bulk samples and in situ analyses (UV-visible spectrophotometry and fluorescence spectroscopy) through the concentration/isolation of DOM followed by the application of one or more analytical techniques, to the detailed separation and analysis of individual compounds or compound classes. Also provided is a brief overview of the main techniques used to characterize isolated DOM: mass spectrometry (MS), nuclear magnetic resonance mass spectrometry (NMR) and Fourier transform infrared spectroscopy (FTIR).


Advances in quantitative trait analysis in yeast.
Understanding the genetic mechanisms underlying complex traits is one of the next frontiers in biology. The budding yeast Saccharomyces cerevisiae has become an important model for elucidating the mechanisms that govern natural genetic and phenotypic variation. This success is partially due to its intrinsic biological features, such as the short sexual generation time, high meiotic recombination rate, and small genome size. Precise reverse genetics technologies allow the high throughput manipulation of genetic information with exquisite precision, offering the unique opportunity to experimentally measure the phenotypic effect of genetic variants. Population genomic and phenomic studies have revealed widespread variation between diverged populations, characteristic of man-made environments, as well as geographic clusters of wild strains along with naturally occurring recombinant strains (mosaics). Here, we review these recent studies and provide a perspective on how these previously unappreciated levels of variation can help to bridge our understanding of the genotype-phenotype gap, keeping budding yeast at the forefront of genetic studies. Not only are quantitative trait loci (QTL) being mapped with high resolution down to the nucleotide, for the first time QTLs of modest effect and complex interactions between these QTLs and between QTLs and the environment are being determined experimentally at unprecedented levels using next generation techniques of deep sequencing selected pools of individuals as well as multi-generational crosses.


A proteomic analysis of ataxia telangiectasia-mutated (ATM)/ATM-Rad3-related (ATR) substrates identifies the ubiquitin-proteasome system as a regulator for DNA damage checkpoints.
ATM (ataxia telangiectasia-mutated) and ATR (ATM-Rad3-related) are proximal checkpoint kinases that regulate DNA damage response (DDR). Identification and characterization of ATM/ATR substrates hold the keys for the understanding of DDR. Few techniques are available to identify protein kinase substrates. Here, we screened for potential ATM/ATR substrates using phospho-specific antibodies against known ATM/ATR substrates. We identified proteins cross-reacting to phospho-specific antibodies in response to DNA damage by mass spectrometry. We validated a subset of the candidate substrates to be phosphorylated in an ATM/ATR-dependent manner in vivo. Combining with a functional checkpoint screen, we identified proteins that belong to the ubiquitin-proteasome system (UPS) to be required in mammalian DNA damage checkpoint control, particularly the G(1) cell cycle checkpoint, thus revealing protein ubiquitylation as an important regulatory mechanism downstream of ATM/ATR activation for checkpoint control.


Optimal localization of diffusion sources in complex networks.
Locating sources of diffusion and spreading from minimum data is a significant problem in network science with great applied values to the society. However, a general theoretical framework dealing with optimal source localization is lacking. Combining the controllability theory for complex networks and compressive sensing, we develop a framework with high efficiency and robustness for optimal source localization in arbitrary weighted networks with arbitrary distribution of sources. We offer a minimum output analysis to quantify the source locatability through a minimal number of messenger nodes that produce sufficient measurement for fully locating the sources. When the minimum messenger nodes are discerned, the problem of optimal source localization becomes one of sparse signal reconstruction, which can be solved using compressive sensing. Application of our framework to model and empirical networks demonstrates that sources in homogeneous and denser networks are more readily to be located. A surprising finding is that, for a connected undirected network with random link weights and weak noise, a single messenger node is sufficient for locating any number of sources. The framework deepens our understanding of the network source localization problem and offers efficient tools with broad applications.


Prolonged overall survival of patients with leptomeningeal carcinomatosis from nonsmall cell lung cancer.
Leptomeningeal metastasis (LM) carries a devastating prognosis. Treatment selection is limited for patients with LM. We introduced to use nimotuzumab (also known as h-R3) for treating LM of nonsmall cell lung cancer. Here, we report two patients in our treatment who had prolonged overall survival over 1 year each. The pressure of cerebrospinal fluid of the patients decreased remarkably after intrathecal therapy. Symptoms of the patients had been improved quickly after one or two times of intrathecal therapy. Nimotuzumab was well tolerated used in intrathecal therapy.


Parallel sets: interactive exploration and visual analysis of categorical data.
Categorical data dimensions appear in many real-world data sets, but few visualization methods exist that properly deal with them. Parallel Sets are a new method for the visualization and interactive exploration of categorical data that shows data frequencies instead of the individual data points. The method is based on the axis layout of parallel coordinates, with boxes representing the categories and parallelograms between the axes showing the relations between categories. In addition to the visual representation, we designed a rich set of interactions. Parallel Sets allow the user to interactively remap the data to new categorizations and, thus, to consider more data dimensions during exploration and analysis than usually possible. At the same time, a metalevel, semantic representation of the data is built. Common procedures, like building the cross product of two or more dimensions, can be performed automatically, thus complementing the interactive visualization. We demonstrate Parallel Sets by analyzing a large CRM data set, as well as investigating housing data from two US states.


Willingness to Use Safe Consumption Spaces among Opioid Users at High Risk of Fentanyl Overdose in Baltimore, Providence, and Boston.
Safe consumption spaces (SCS) are evidence-based interventions that reduce drug-related morbidity and mortality operating in many countries. However, SCS are yet to be widely implemented in the USA despite the escalating overdose epidemic. The aim of this multi-city study was to identify the factors associated with willingness to use a SCS among people who use drugs (PWUD) in Baltimore, Providence, and Boston, stratified by injection drug use status. Our secondary aim was to characterize the anticipated barriers to accessing SCS if they were to be implemented in these cities. PWUD were invited to complete a cross-sectional survey in 2017. The analysis was restricted to 326 opioid users (i.e., heroin, fentanyl, and non-medical opioid pill use). The majority (77%) of participants expressed willingness to use a SCS (Baltimore, 78%; Providence, 68%; Boston. 84%). Most respondents were male (59%), older than 35 years (76%), non-white (64%), relied on public/semi-public settings to inject (60%), had a history of overdose (64%), and recently suspected fentanyl contamination of their drugs (73%). A quarter (26%) preferred drugs containing fentanyl. Among injectors, female gender, racial minority status, suspicion of drugs containing fentanyl, and drug use in public/semi-public settings were associated with higher willingness to use a SCS; prior arrest was associated with lower willingness. Among non-injectors, racial minority status, preference for fentanyl, and drug use in public/semi-public settings were associated with higher willingness, whereas recent overdose held a negative association. The most commonly anticipated barriers to accessing a SCS in the future were concerns around arrest (38%), privacy (34%), confidentiality/trust/safety (25%), and cost/time/transportation (16%). These data provide evidence of high SCS acceptability among high-risk PWUD in the USA, including those who prefer street fentanyl. As SCS are implemented in the USA, targeted engagement efforts may be required to reach individuals exposed to the criminal justice system.


Diagnosis of periprosthetic infection following total hip arthroplasty--evaluation of the diagnostic values of pre- and intraoperative parameters and the associated strategy to preoperatively select patients with a high probability of joint infection.
The correct diagnosis of a prosthetic joint infection (PJI) is crucial for adequate surgical treatment. The detection may be a challenge since presentation and preoperative tests are not always obvious and precise. This prospective study was performed to evaluate a variety of pre- and intraoperative investigations. Furthermore a detailed evaluation of concordance of each preoperative diagnosis was performed, together with a final diagnosis to assess the accuracy of the pre-operative assumption of PJI. Between 01/2005 and 02/2007, a prospective analysis was performed in 50 patients, who had a two stage revision because of assumed PJI. Based on clinical presentation, radiography, haematological screening, or early failure, infection was assumed and a joint aspiration was performed. Depending upon these findings, a two stage revision was performed, with intra-operative samples for culture and histological evaluation obtained. Final diagnosis of infection was based upon the interpretation of the clinical presentation and the pre- and intraoperative findings. In 37 patients a positive diagnosis of PJI could be made definitely. The histopathology yielded the highest accuracy (0.94) in identification of PJI and identified 35 of 37 infections (sensitivity 0.94, specificity 0.94, positive-/negative predictive value 0.97/0.86). Intra-operative cultures revealed sensitivities, specificities, positive-/negative predictive values and accuracy of 0.78, 0.92, 0.96, 0.63 and 0.82. These values for blood screening tests were 0.95, 0.62, 0.88, 0.80, and 0.86 respectively for the level of C-reactive protein, and 0.14, 0.92, 0.83, 0.29 and, 0.34 respectively for the white blood-cell count. The results of aspiration were 0.57, 0.5, 0.78, 0.29, and 0.54. The detection of PJI is still a challenge in clinical practice. The histopathological evaluation emerges as a highly practical diagnostic tool in detection of PJI. Furthermore, we found a discrepancy between the pre-operative suspicion of PJI and the final post-operative diagnosis, resulting in a slight uncertainty in whether loosening is due to bacterial infection or not. The variation in accuracy of the single tests may influence the detection of PJI. Diagnostic Level I.


The state of UK pediatric anesthesia: a survey of National Health Service activity.
This secondary analysis of the 2013 United Kingdom National Health Service (NHS) Anaesthesia Activity Survey of the Fifth National Audit Project (of the Royal College of Anaesthetists and Association of Anaesthetists of Great Britain and Ireland) shows pediatric anesthesia activity in detail. A local coordinator (LC) in every NHS hospital collected data on patients undergoing any procedure managed by an anesthetist. Questionnaires had 30 question categories. Each LC was randomized to a 2-day period. The pediatric age groups were infants, (<1 year), preschool age (1-5 year), and school age children (6-15 year). The median questionnaire return rate was 98%. The annual caseload was estimated to be 486 900 children: 36 500 infants, 184 700 preschool age, and 265 800 school age children. Almost 90% of children (1-15 year) were ASA 1 or 2 and the substantial majority underwent routine nonurgent ear nose and throat, dental, orthopaedics, or general surgery procedures; 65% were 'day cases'. One in six children were managed outside operating theater sites compared with one in 12 adults. Forty one per cent was in district general hospitals. Almost all ASA 4 and 5 children (89%) and infants (92%) were managed in specialist hospitals. 'Awake' cases and sedation accounted for only 2% of cases. There were notable differences in demography and anesthetic care compared with adults and between different age groups of children. These data enable analysis of the current state of UK pediatric anesthetic practice and highlight differences between pediatric and adult services.


Host Preference of Mating Type in Pseudoperonospora cubensis, the Downy Mildew Causal Agent of Cucurbits.
The A2 mating type of Pseudoperonospora cubensis was first discovered in Israel in May 2010 on butternut gourd (Cucurbita moschata) (1). We monitored the occurrence of the A2 mating type of P. cubensis in isolates collected during May 2010 through September 2012 from downy mildew-infected cucurbit crops growing along the coastal plain of Israel. Mating type was determined by oospore production in melon leaf discs co-inoculated with sporangia of a test isolate mixed with sporangia of A1 or A2 tester isolates (2). The A1 and A2 tester isolates were maintained at 14°C (14 h light/day) by repeated inoculation of detached leaves of cucumber and pumpkin, respectively. The 29 isolates that were collected from cucumber (Cucumis sativum) were all A1. Of the 33 isolates collected from pumpkin (Cucurbita maxima), squash (C. pepo), or butternut gourd (C. moschata), 88% were A2 and 12% were A1. The host preference of mating type in P. cubensis was monitored at Bar-Ilan University farm during April to July 2012, among about 800 plants of eight cucurbit species (~100 plants per species) that were grown side-by-side in three adjacent net-houses (two 6 × 50 m and one 6 × 100 m) and exposed to natural infection. Downy mildew developed on cucumber, melon, pumpkin, squash, and butternut gourd, but not on watermelon, sponge gourd (Luffa cylindrica), or Momordica balsamina. Three-hundred and three isolates of P. cubensis were collected and tested for mating type: 123 from cucumber, 53 from melon, 30 from pumpkin, 48 from butternut gourd, and 41 from squash. The cucumber isolates expressed A1, A2, and A1A2 at a ratio of 94.3%, 3.3%, and 2.4%, respectively; the melon isolates 58.5%, 26.4%, and 15.1%; the pumpkin isolates 0%, 96.7%, and 3.3%; the butternut isolate 7.3%, 87.3%, and 5.5%; and the squash isolates 2.4%, 97.6%, and 0%, respectively. A1A2 isolates produce oospores when crossed with either A1 or A2 tester isolates. This is the first evidence suggesting a preference of A1 isolates to Cucumis spp. and of A2 isolates to Cucurbita spp. similar preference was recently observed among Chinese isolates of this pathogen (unpublished data). The mechanism(s) controlling this preference is not known. Classical genetics is currently employed to P. cubensis in order to understand if it derives from true linkage. The practical implication for downy mildew management is that growing cucumber/melon in close proximity to pumpkin/squash/butternut gourd should be avoided as it may enhance oospore production in nature. Oospores in soil were recently shown to serve as a primary source of downy mildew infection in cucumber (3). References: (1) Y. Cohen, A. E. Rubin, and M.Galperin. Plant Dis. 95:874, 2011; (2) Y. Cohen and A. E. Rubin. Eur. J. Plant Pathol. 132:577, 2012; (3) Y. J. Zhang et al. J. Phytopathol. 160:469, 2012.


Facial hirsutism treated with the normal-mode ruby laser: results of a 12-month follow-up study.
Fifty-one patients of skin type I to IV with facial hirsutism received treatment with the normal-mode ruby laser (950-micros pulse; 4-mm spot; mean fluence, 49 J/cm(2); maximum fluence, 66 J/cm(2)). For each patient, one site was treated once only, and a second site was treated 4 times at 4-week intervals. After 48 weeks, 46 patients were available for assessment. After a single treatment, hair counts were reduced to a mean of 45% at 4 weeks (pretreatment median of 63 hairs down to 26), increased to 80% (median, 51 hairs) at 12 weeks, were 65% (median, 41 hairs) at 24 weeks, and were 59% (median, 35 hairs) at 48 weeks. Four weeks after 3 treatments, the hair counts had reduced to a mean of 30% (pretreatment median of 68 hairs down to 15). Twelve weeks after 4 treatments, the hair counts had increased to 45% (median, 24 hairs) and were 39% after 36 weeks (median, 22.5 hairs). No anesthesia was needed. Treatment tolerance improved with consecutive visits, allowing higher fluences to be used. Hyperpigmentation developed in 9 patients, which had faded completely in 8 patients at the end of the study. One patient showed hypopigmentation. Depressions in the skin below the jaw line developed in 5 patients, which resolved completely within 4 to 32 weeks. We conclude that normal-mode ruby laser treatment is well tolerated and leads to significant improvement of facial hirsutism, which is maintained for at least 48 weeks. Repeated treatments result in greater clinical effects.


Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes.
Tobacco smoking continues to be a leading cause of preventable death. Recent research has underscored the important role of specific cholinergic nicotinic receptor subunit (CHRN) genes in risk for nicotine dependence and smoking. To detect and characterize the influence of genetic variation on vulnerability to nicotine dependence, we analyzed 226 SNPs covering the complete family of 16 CHRN genes, which encode the nicotinic acetylcholine receptor (nAChR) subunits, in a sample of 1,050 nicotine-dependent cases and 879 non-dependent controls of European descent. This expanded SNP coverage has extended and refined the findings of our previous large-scale genome-wide association and candidate gene study. After correcting for the multiple tests across this gene family, we found significant association for two distinct loci in the CHRNA5-CHRNA3-CHRNB4 gene cluster, one locus in the CHRNB3-CHRNA6 gene cluster, and a fourth, novel locus in the CHRND-CHRNG gene cluster. The two distinct loci in CHRNA5-CHRNA3-CHRNB4 are represented by the non-synonymous SNP rs16969968 in CHRNA5 and by rs578776 in CHRNA3, respectively, and joint analyses show that the associations at these two SNPs are statistically independent. Nominally significant single-SNP association was detected in CHRNA4 and CHRNB1. In summary, this is the most comprehensive study of the CHRN genes for involvement with nicotine dependence to date. Our analysis reveals significant evidence for at least four distinct loci in the nicotinic receptor subunit genes that each influence the transition from smoking to nicotine dependence and may inform the development of improved smoking cessation treatments and prevention initiatives.


Pancreatic neuroendocrine tumors: radiographic calcifications correlate with grade and metastasis.
Studies to identify preoperative prognostic variables for pancreatic neuroendocrine tumor (PNET) have been inconclusive. Specifically, the prevalence and prognostic significance of radiographic calcifications in these tumors remains unclear. From 1998 to 2009, a total of 110 patients with well-differentiated PNET underwent surgical resection at our institution. Synchronous liver metastases present in 31 patients (28%) were addressed surgically with curative intent. Patients with high-grade PNET were excluded. The presence of calcifications in the primary tumor on preoperative computed tomography was recorded and correlated with clinicopathologic variables and overall survival. Calcifications were present in 16% of patients and were more common in gastrinomas and glucagonomas (50%), but never encountered in insulinomas. Calcified tumors were larger (median size 4.5 vs. 2.3 cm, P=0.04) and more commonly associated with lymph node metastasis (75 vs. 35%, P=0.01), synchronous liver metastasis (62 vs. 21%, P<0.01), and intermediate tumor grade (80 vs. 31%, P<0.01). On multivariate analysis of factors available preoperatively, calcifications (P=0.01) and size (P<0.01) remained independent predictors of lymph node metastasis. Overall survival after resection was significantly worse in the presence of synchronous liver metastasis (5-year, 64 vs. 86%, P=0.04), but not in the presence of radiographic calcifications. Calcifications on preoperative computed tomography correlate with intermediate grade and lymph node metastasis in well-differentiated PNET. This information is available preoperatively and supports the routine dissection of regional lymph nodes through formal pancreatectomy rather than enucleation in calcified PNET.


Roles of GRK2 in cell signaling beyond GPCR desensitization: GRK2-HDAC6 interaction modulates cell spreading and motility.
G protein-coupled receptor kinase 2 (GRK2) is a ubiquitous, essential protein kinase that is emerging as an integrative node in many signaling networks. Moreover, changes in GRK2 abundance and activity have been identified in several inflammatory, cardiovascular disease, and tumor contexts, suggesting that those alterations may contribute to the initiation or development of pathologies. GRKs were initially identified as key players in the desensitization and internalization of multiple G protein-coupled receptors (GPCRs), but GRK2 also phosphorylates several non-GPCR substrates and dynamically associates with a variety of proteins related to signal transduction. Ongoing research in our laboratory is aimed at understanding how specific GRK2 interactomes are orchestrated in a stimulus-, context-, or cell type-specific manner. We have recently identified an interaction between GRK2 and histone deacetylase 6 (HDAC6) that modulates cell spreading and motility. HDAC6 is a major cytoplasmic a-tubulin deacetylase that is involved in cell motility and adhesion. GRK2 dynamically and directly associates with and phosphorylates HDAC6 to stimulate its a-tubulin deacetylase activity at specific cellular localizations, such as the leading edge of migrating cells, thus promoting local tubulin deacetylation and enhanced motility. GRK2-HDAC6-mediated regulation of tubulin acetylation also modulates cellular spreading. This GRK2-HDAC6 functional interaction may have important implications in pathological contexts related to epithelial cell migration.


A Flatworm from the Genus Waminoa (Acoela: Convolutidae) Associated with Bleached Corals in Western Australia.
A flatworm isolated from bleached colonies of the coral Coscinaraea marshae at Rottnest Island, Western Australia, is described using a combination of morphological and molecular systematics. This flatworm shares morphological features characteristic of the genus Waminoa (Acoelomorpha: Acoela), including the presence of two algal symbionts, but appears to have genital regions different from those of other described species of Waminoa. The design of new oligonucleotide primers enabled the amplification of partial 18S rDNA of the Rottnest Island acoel specimens, and phylogenetic analysis positioned them within Waminoa, confirming their placement in the genus. Furthermore, Waminoa specimens from Rottnest Island grouped into a sister clade to Waminoa brickneri, indicating that the morphological and genetic differences observed are most likely intraspecific and due to geographic variation. As such, we name these Rottnest Island specimens W. cf. brickneri, but highlight that key differences warrant further exploration before assignment to this species can be confirmed. This is the first acoel flatworm described from Western Australia and contributes to our understanding of the diversity and evolutionary relationship of the Acoela.


Relation of Low Normal Left Ventricular Ejection Fraction to Heart Failure Hospitalization in Blacks (From the Jackson Heart Study).
There is no clear consensus on a lower cutoff value for normal left ventricular ejection fraction (EF) and the prognostic implications of low normal EF (LNEF) are poorly understood, particularly in Blacks. Therefore, we investigated the association of LNEF and incident heart failure (HF) in a community-based cohort of Blacks. We studied 3,669 participants (mean age 54 years, 63% women) of the Jackson Heart Study without prevalent HF or coronary heart disease (CHD). Participants were divided into three groups: (1) Reduced EF (<50%), (2) LNEF (≥50%, <55%), and (3) Normal EF (≥55%). There were 197 cases of incident HF hospitalizations over a median follow-up of 10 years (interquartile range 9.4 to 10). After adjustment for conventional risk factors and incident CHD, the LNEF group had a higher rate of incident HF hospitalization than the Normal EF group (HR 1.58, 95% CI 1.04 to 2.38, p<0.05). Furthermore, this relation remained statistically significant after additionally adjusting for LV mass index but was not significant after adjusting for LV diastolic dysfunction grade. In participants with LNEF with incident HF, 63% developed HF with reduced EF and 37% developed HF with preserved EF. In conclusion, LNEF is associated with higher risk of incident HF hospitalization in comparison with normal EF in a community-based cohort of Blacks. In those with LNEF who went on to develop HF, most cases were HF with reduced EF. These findings suggest that strategies are needed for risk stratification and management to improve outcomes in patients with LNEF.


What are the neural origins of choice variability?
Two recent studies examine neural activity predictive of upcoming choices during value-guided choice. Their results may be cast in light of a competitive winner-take-all decision network. This viewpoint places certain decision variables not as features of the environment to be encoded, but as emergent properties of network activity.


The characterization of ESBL genes in Escherichia coli and Klebsiella pneumoniae causing nosocomial infections in Vietnam.
Extended-spectrum β-lactamases (ESBLs) are enzymes capable of hydrolyzing oxyimino-β-lactams and inducing resistance to third generation cephalosporins. The genes encoding ESBLs are widespread and generally located on highly transmissible resistance plasmids. We aimed to investigate the complement of ESBL genes in E. coli and Klebsiella pneumoniae causing nosocomial infections in hospitals in Ho Chi Minh City, Vietnam. Thirty-two non-duplicate isolates of E. coli and Klebsiella pneumoniae causing nosocomial infections, isolated between March and June 2010, were subjected to antimicrobial susceptibility testing. All isolates were PCR-amplified to detect the blaSHV, blaTEM and blaCTX-M ESBL genes and subjected to plasmid analysis. We found that co-resistance to multiple antimicrobials was highly prevalent, and we report the predominance of the blaCTX-M-15 and blaCTX-M-27 genes, located on highly transmissible plasmids ranging from 50 to 170 kb in size. Our study represents a snap shot of ESBL-producing enteric bacteria causing nosocomial infections in this setting. We suggest that antimicrobial resistance in nosocomial E. coli and Klebsiella pneumoniae is rampant in Vietnam and ESBL organisms are widespread. In view of these data and the dramatic levels of antimicrobial resistance reported in Vietnam we advocate an urgent review of antimicrobial use in the Vietnamese healthcare system.


The effect of treadmill exercise on gait efficiency during overground walking in adults with cerebral palsy.
To investigate the effect of treadmill walking exercise as a treatment method to improve gait efficiency in adults with cerebral palsy (CP) and to determine gait efficiency during overground walking after the treadmill walking exercise. Fourteen adults with CP were recruited in the experimental group of treadmill walking exercise. A control group of 7 adults with CP who attended conventional physical therapy were also recruited. The treadmill walking exercise protocol consisted of 3-5 training sessions per week for 1-2 months (total 20 sessions). Gait distance, velocity, VO2, VCO2, O2 rate (mL/kg·min), and O2 cost (mL/kg·m) were assessed at the beginning and at the end of the treadmill walking exercise. The parameters were measured by KB1-C oximeter. After the treadmill walking exercise, gait distance during overground walking up to 6 minutes significantly increased from 151.29±91.79 to 193.93±79.01 m, and gait velocity increased from 28.09±14.29 to 33.49±12.69 m/min (p<0.05). Energy efficiency evaluated by O2 cost during overground walking significantly improved from 0.56±0.36 to 0.41±0.18 mL/kg·m (p<0.05), whereas O2 rate did not improve significantly after the treadmill walking exercise. On the other hand, gait velocity and O2 cost during overground walking were not significantly changed in the control group. Treadmill walking exercise improved the gait efficiency by decreased energy expenditure during overground walking in adults with CP. Therefore, treadmill walking exercise can be an important method for gait training in adults with CP who have higher energy expenditure.


Antireflection effect of femtosecond laser-induced periodic surface structures on silicon.
Following direct femtosecond laser pulse irradiation, we produce a unique grating structure over a large area superimposed by finer nanostructures on a silicon wafer. We study, for the first time, the antireflection effect of this femtosecond laser-induced periodic surface structures (FLIPSSs) in the wavelength range of 250 - 2500 nm. Our study shows that the FLIPSSs suppress both the total hemispherical and specular polarized reflectance of silicon surface significantly over the entire studied wavelength range. The total polarized reflectance of the processed surface is reduced by a factor of about 3.5 in the visible and 7 in the UV compared to an untreated sample. The antireflection effect of the FLIPSS surface is broadband and the suppression stays to the longest wavelength (2500 nm) studied here although the antireflection effect in the infrared is weaker than in the visible. Our FLIPSS structures are free of chemical contamination, highly durable, and easily controllable in size.


Novel duplication on chromosome 16 (q12.1-q21) associated with behavioral disorder, mild cognitive impairment, speech delay, and dysmorphic features: case report.
We report on the 10-year follow-up and clinical, cytogenetic, and molecular investigation of a girl admitted for evaluation because of speech delay, learning difficulties, aggressive behavior, and dysmorphic facial features that included high forehead, round face, epicanthic folds, low-set dysplastic ears, flat nasal bridge, long flat philtrum, thin upper lip, small mouth, and short neck. The analysis of high-resolution GTG- and CTG-banding chromosomes suggested a de novo direct duplication of 16q12-q21 region and fluorescence in situ hybridization analysis with whole-chromosome specific 16 probe confirmed that the duplicated genetic material originated from the chromosome 16. Subsequently, array-based comparative genomic hybridization analysis with a≈75 kb resolution showed a 9.92 Mb gain on the long arm of chromosome 16 at bands q12.1 through q21. To the best of our knowledge, this is the first case of duplication 16q12.1q21 described in literature. Several genes within the duplicated region are possibly correlated with clinical features present in our patient. Clinical and cytogenetic findings were compared with the small number of reported patients with pure duplications 16q, partially overlapping the one in our patient. Clinical phenotype seems to be distinctive between the proximal-intermediate and intermediate-distal regions of the long arm of the chromosome 16. In particular, we observed a set of dysmorphic features that could present a characteristic dup 16q11.2-q13 phenotype. The present study illustrates the advantages of an integrative approach using both conventional and molecular techniques for the precise characterization and genotype-phenotype correlation in patients with dysmorphism, behavioral problems, and learning difficulties.


Clinical management of renal transplant patients with donor-specific alloantibody: the state of the art.
Our understanding of the role of DSA in both early and late renal allograft injury has advanced significantly over the past decade. Novel protocols have been developed that have led to improved outcomes both in overcoming a positive crossmatch and in the treatment of early AMR. Early experience with bortezomib and eculizumab are encouraging and suggest the possibility of validation in controlled clinical trials. While alloantibody remains an extremely difficult clinical problem and it is unclear if overcoming early hurdles will only be followed by another major hurdle of chronic antibody mediated injury. However, it is clear that significant advances have occurred and if future studies can be designed appropriately, then our ability to control alloantibody in sensitized patients will continue to improve.


Intraseasonal dynamics and dominant sequences in H3N2 influenza.
Long-term influenza evolution has been well studied, but the patterns of sequence diversity within seasons are less clear. H3N2 influenza genomes sampled from New York State over ten years indicated intraseasonal changes in evolutionary dynamics. Using the mean Hamming distance of a set of amino acid or nucleotide sequences as an indicator of its diversity, we found that influenza sequence diversity was significantly higher during the early epidemic period than later in the influenza season. Diversity was lowest during the peak of the epidemic, most likely due to the high prevalence of a single dominant amino acid sequence or very few dominant sequences during the peak epidemic period, corresponding with rapid expansion of the viral population. The frequency and duration of dominant sequences varied by influenza protein, but all proteins had an abundance of one distinct sequence during the peak epidemic period. In New York State from 1995 to 2005, high sequence diversity during the early epidemic suggested that seasonal antigenic drift could have occurred primarily in this period, followed by a clonal expansion of typically one clade during the peak of the epidemic, possibly indicating a shift to neutral drift or purifying selection.


Opioid-like adverse effects of tianeptine in male rats and mice.
Tianeptine is a mu-opioid receptor (MOR) agonist with increasing reports of abuse in human populations. Preclinical data regarding the abuse potential and other opioid-like adverse effects of tianeptine at supratherapeutic doses are sparse. The present study evaluated tianeptine in a rat model of abuse potential assessment and in mouse models of motor, gastrointestinal, and respiratory adverse effects. Abuse potential was assessed in adult male Sprague-Dawley rats using an intracranial self-stimulation (ICSS) procedure to determine effects of acute and repeated tianeptine on responding for electrical brain stimulation. Male ICR mice were used to determine the effects of tianeptine in assays of locomotor behavior and gastrointestinal motility. Male Swiss-Webster mice were monitored for respiratory changes using whole-body plethysmography. In rats, acute tianeptine produced weak and delayed evidence for abuse-related ICSS facilitation at an intermediate dose (10 mg/kg, IP) and pronounced, naltrexone-preventable ICSS depression at a higher dose (32 mg/kg, IP). Repeated 7-day tianeptine (10 and 32 mg/kg/day, IP) produced no increase in abuse-related ICSS facilitation, only modest tolerance to ICSS depression, and no evidence of physical dependence. In mice, tianeptine produced dose-dependent, naltrexone-preventable locomotor activation. Tianeptine (100 mg/kg, SC) also significantly inhibited gastrointestinal motility and produced naloxone-reversible respiratory depression. Tianeptine presents as a MOR agonist with resistance to tolerance and dependence in our ICSS assay in rats, and it has lower abuse potential by this metric than many commonly abused opioids. Nonetheless, tianeptine produces MOR agonist-like acute adverse effects that include motor impairment, constipation, and respiratory depression.


Sexual function and postpartum depression 6 months after attempted operative vaginal delivery according to fetal head station: A prospective population-based cohort study.
To evaluate the effect of the fetal head station at attempted operative vaginal delivery (aOVD), and specifically midpelvic or low aOVD, on female and male sexual function and symptoms of postpartum depression (PPD) at 6 months. Prospective population-based cohort study. 1,941 women with singleton term fetuses in vertex presentation with midpelvic or low aOVD between 2008 and 2013 in a tertiary care university hospital. Symptoms of female sexual dysfunction using the Pelvic Organ Prolapse/Urinary Incontinence/Sexual Function Short Form Questionnaire (PISQ-12), symptoms of PPD using the Edinburgh Postnatal Depression Scale (EPDS) score, symptoms of male sexual dysfunction using the International Index of Erectile Function (IIEF-15) and perineal pain were assessed 6 months after aOVD. We measured the association between midpelvic or low aOVD and symptoms of female and male sexual function and symptoms of PPD at 6 months using multiple regression and adjusting for demographics, and risk factors of sexual dysfunction, symptoms of PPD and perineal pain with adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). The study included 907 women (46.7%) who responded to the questionnaire; 18.4% (167/907) had midpelvic aOVD, and 81.6% (740/907) low. Most women (873/907 [96.3%]) of those with partners reported sexual activity at 6 months. No significant difference was observed for PISQ-12, EPDS, IIEF-15 scores and perineal pain between mid and low pelvic groups. Compared with low pelvic aOVD, midpelvic aOVD was not significantly associated with either female or male sexual dysfunction (p = 0.89 and p = 0.76, respectively), or maternal symptoms of PPD (p = 0.83). Perineal pain significantly increased the risk of male and female sexual dysfunction and maternal symptoms of PPD at 6 months (p = 0.02, p = 0.006, and p = 0.02, respectively). Midpelvic compared with low pelvic aOVD was not associated with an increase in sexual dysfunction, nor with symptoms of PPD at 6 months.


Characterization and analysis of finite-beam Bragg diffraction in a periodically poled lithium niobate electro-optic grating.
We report the study, both theoretical and experimental, of the finite-beam Bragg diffraction behavior of an electro-optic (EO) volume grating made of a periodically poled lithium niobate (PPLN) crystal. When a Gaussian laser beam is used, the experimental observations show that the diffraction characteristics of the PPLN EO Bragg device, including the diffraction mode pattern and diffraction efficiency, are closely related to the interaction beam size and applied voltage, which cannot be modeled properly by a simplified theory using the plane-wave approximation. In this work, we have developed a theoretical model for describing the diffraction behavior of a PPLN EO Bragg device based on the coupled-wave theory with the aid of the plane-wave decomposition method. Specifically, we found that it is the angular distribution (or the dephasing bandwidth) of the plane wave elements decomposed from the incident Gaussian beam and grating strength that determine the Bragg coupling behavior of the device. We also identified some other electro-optically induced effects in the PPLN grating as an important mechanism in affecting the diffraction performance of the present device, especially at high working voltages.


Benefit of heparin in peripheral venous and arterial catheters: systematic review and meta-analysis of randomised controlled trials.
To evaluate the effect of heparin on duration of catheter patency and on prevention of complications associated with use of peripheral venous and arterial catheters. Critical appraisal and meta-analysis of 26 randomised controlled trials that evaluated infusion of heparin intermittently or continuously. Thirteen trials of peripheral venous catheters and two of peripheral arterial catheters met criteria for inclusion. Data on the populations, interventions, outcomes, and methodological quality. For peripheral venous catheters locked between use flushing with 10 U/ml of heparin instead of normal saline did not reduce the incidence of catheter clotting and phlebitis or improve catheter patency. When heparin was given as a continuous infusion at 1 U/ml the risk of phlebitis decreased (relative risk 0.55; 95% confidence interval 0.39 to 0.77), the duration of patency increased, and infusion failure was reduced (0.88; 0.72 to 1.07). Heparin significantly prolonged duration of patency of radial artery catheters and decreased the risk of clot formation (0.51; 0.42 to 0.61). Use of intermittent heparin flushes at doses of 10 U/ml in peripheral venous catheters locked between use had no benefit over normal saline flush. Infusion of low dose heparin through a peripheral arterial catheter prolonged the duration of patency but further study is needed to establish its benefit for peripheral venous catheters.


A system for study of coronavirus mRNA synthesis: a regulated, expressed subgenomic defective interfering RNA results from intergenic site insertion.
A system that exploits defective interfering (DI) RNAs of mouse hepatitis virus (MHV) for deciphering the mechanisms of coronavirus mRNA transcription was developed. A complete cDNA clone of MHV DI RNA containing an inserted intergenic region, derived from the area of genomic RNA between genes 6 and 7, was constructed. After transfection of the in vitro-synthesized DI RNA into MHV-infected cells, replication of genomic DI RNA as well as transcription of the subgenomic DI RNA was observed. S1 nuclease protection experiments, sequence analysis, and Northern (RNA) blotting analysis revealed that the subgenomic DI RNA contained the leader sequence at its 5' end and that the body of the subgenomic DI RNA started from the inserted intergenic sequence. Two subgenomic DI RNAs were synthesized after inserting two intergenic sites into the MHV DI RNA. Metabolic labeling of virus-specific protein in DI RNA replicating cells demonstrated that a protein was translated from the subgenomic DI RNA, which can therefore be considered a functional mRNA. Transfection study of gel-purified genomic DI RNA and subgenomic DI RNA revealed that the introduction of the genomic DI RNA, but not subgenomic DI RNA, into MHV-infected cells was required for synthesis of the subgenomic DI RNA. A series of deletion mutations in the intergenic site demonstrated that the sequence flanking the consensus sequence of UCUAAAC affected the efficiency of subgenomic DI RNA transcription and that the consensus sequence was necessary but not sufficient for the synthesis of the subgenomic DI RNA.


Plasma concentrations of sVCAM-1 and severity of dengue infections.
Adhesion molecules are essential for the immune response. They are involved in the regulation of cell-to-cell contact, thereby enabling leukocytes to communicate. Circulating forms of adhesion molecules are found in the serum of healthy individuals. Raised levels have been associated with disease severity in HCV and other infections and thus appear to be good markers of endothelial damage. The levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and of sP and sL-selectin in the plasma of children hospitalised for dengue in French Polynesia were monitored. Studies from the 1996/1997 dengue-2 outbreak, showed that levels of sVCAM-1 increase steadily during the febrile period, peak on day 7, and then decline relatively rapidly. Disregarding the time frame within the febrile period, sVCAM-1 levels were always higher compared to controls. There was a significant association between sVCAM-1 levels and dengue haemorrhagic fever, a severe manifestation of dengue virus infection characterised by plasma leakage. No association was apparent between sVCAM-1 levels and primary vs. secondary dengue virus infections. Levels of sP-selectin and sL-selectin were significantly higher in primary compared with secondary infection but were not different in patients presenting with plasma leakage. Lastly, sVCAM-1 levels were significantly higher in an outbreak of severe disease in 1989/1990 (dengue-3) when compared to a non-severe outbreak in 1988/1989 (dengue-1) and a mild outbreak in 1996/1997 (dengue-2). The results suggested that levels of sVCAM-1 production might prove to be a useful marker in the management of severe dengue.


A virtual reality-integrated program for improving social skills in patients with schizophrenia: a pilot study.
Social skills training (SST) intervention has shown its efficacy to improve social dysfunction in patients with psychosis; however the implementation of new skills into patients' everyday functioning is difficult to achieve. In this study, we report results from the application of a virtual reality (VR) integrated program as an adjunct technique to a brief social skills intervention for patients with schizophrenia. It was predicted that the intervention would improve social cognition and performance of patients as well as generalisation of the learned responses into patient's daily life. Twelve patients with schizophrenia or schizoaffective disorder completed the study. They attended sixteen individual one-hour sessions, and outcome assessments were conducted at pre-treatment, post-treatment and four-month follow-up. The results of a series of repeated measures ANOVA revealed significant improvement in negative symptoms, psychopathology, social anxiety and discomfort, avoidance and social functioning. Objective scores obtained through the use of the VR program showed a pattern of learning in emotion perception, assertive behaviours and time spent in a conversation. Most of these gains were maintained at four-month follow-up. The reported results are based on a small, uncontrolled pilot study. Although there was an independent rater for the self-reported and informant questionnaires, assessments were not blinded. The results showed that the intervention may be effective for improving social dysfunction. The use of the VR program contributed to the generalisation of new skills into the patient's everyday functioning.


Reducing production of taste and odor by deep-living cyanobacteria in drinking water reservoirs by regulation of water level.
Abatement and control of algae, producing toxins and creating taste & odor (T&O) in drinking water sources, is a major challenge for water supply. In this study we proposed a strategy based on water level regulation for the control of odor-producing cyanobacteria in source water. Miyun Reservoir, the main surface water source for Beijing, has been suffering from 2-methylisoborneol (2-MIB) induced T&O problems caused by deep-living Planktothrix sp. since 2002. The biomass of deep-living Planktothrix in Miyun Reservoir was found to be mainly governed by the water depth above its sediment habitat. An algorithm for water level regulation aiming to minimize the risk for T&O in different types of reservoirs is proposed. The study demonstrates that risk for T&O can be minimized by increasing the water level in Miyun Reservoir. The high-risk area can be reduced by about 2.91% (0.61% to 5.76%) of surface area for each meter increase in the water level, when the water level is lower than 145m. More specifically, the water level needs to be raised to higher than 147.7ma.s.l. from 131.0m in order to obtain an acceptable risk level (ARL) of 10%. This management strategy to abate T&O problems is simpler and cheaper to implement compared to traditional physical, chemical and biological techniques. Moreover, it has no apparent negative impact on water quality and aquatic organisms.


Monitoring the condition of natural resources in US national parks.
The National Park Service has developed a long-term ecological monitoring program for 32 ecoregional networks containing more than 270 parks with significant natural resources. The monitoring program assists park managers in developing a broad-based understanding of the status and trends of park resources as a basis for making decisions and working with other agencies and the public for the long-term protection of park ecosystems. We found that the basic steps involved in planning and designing a long-term ecological monitoring program were the same for a range of ecological systems including coral reefs, deserts, arctic tundra, prairie grasslands, caves, and tropical rainforests. These steps involve (1) clearly defining goals and objectives, (2) compiling and summarizing existing information, (3) developing conceptual models, (4) prioritizing and selecting indicators, (5) developing an overall sampling design, (6) developing monitoring protocols, and (7) establishing data management, analysis, and reporting procedures. The broad-based, scientifically sound information obtained through this systems-based monitoring program will have multiple applications for management decision-making, research, education, and promoting public understanding of park resources. When combined with an effective education program, monitoring results can contribute not only to park issues, but also to larger quality-of-life issues that affect surrounding communities and can contribute significantly to the environmental health of the nation.


Anchors, scales and the relative coding of value in the brain.
People are alarmingly susceptible to manipulations that change both their expectations and experience of the value of goods. Recent studies in behavioral economics suggest such variability reflects more than mere caprice. People commonly judge options and prices in relative terms, rather than absolutely, and display strong sensitivity to exemplar and price anchors. We propose that these findings elucidate important principles about reward processing in the brain. In particular, relative valuation may be a natural consequence of adaptive coding of neuronal firing to optimise sensitivity across large ranges of value. Furthermore, the initial apparent arbitrariness of value may reflect the brains' attempts to optimally integrate diverse sources of value-relevant information in the face of perceived uncertainty. Recent findings in neuroscience support both accounts, and implicate regions in the orbitofrontal cortex, striatum, and ventromedial prefrontal cortex in the construction of value.


Propagation of action potentials from the soma to individual dendrite of cultured rat amacrine cells is regulated by local GABA input.
Retinal amacrine cells are interneurons that make lateral and vertical connections in the inner plexiform layer of the retina. Amacrine cells do not possess a long axon, and this morphological feature is the origin of their naming. Their dendrites function as both presynaptic and postsynaptic sites. Half of all amacrine cells are GABAergic inhibitory neurons that mediate lateral inhibition, and their light-evoked response consists of graded voltage changes and regenerative action potentials. There is evidence that the amount of neurotransmitter release from presynaptic sites is increased by spike propagation into the dendrite. Thus understanding of how action potentials propagate in dendrites is important to elucidating the extent and strength of lateral inhibition. In the present study, we used the dual whole cell patch-clamp technique on the soma and the dendrite of cultured rat amacrine cells and directly demonstrated that the action potentials propagate into the dendrites. The action potential in the dendrite was TTX sensitive and was affected by the local membrane potential of the dendrite. Propagation of the action potential was suppressed by local application of GABA to the dendrite. Dual dendrite whole cell patch-clamp recordings showed that GABA suppresses the propagation of action potentials in one dendrite of an amacrine cell, while the action potentials propagate in the other dendrites. It is likely that the action potentials in the dendrites are susceptible to various external factors resulting in the nonuniform propagation of the action potential from the soma of an amacrine cell.


Learning factorizations in estimation of distribution algorithms using affinity propagation.
Estimation of distribution algorithms (EDAs) that use marginal product model factorizations have been widely applied to a broad range of mainly binary optimization problems. In this paper, we introduce the affinity propagation EDA (AffEDA) which learns a marginal product model by clustering a matrix of mutual information learned from the data using a very efficient message-passing algorithm known as affinity propagation. The introduced algorithm is tested on a set of binary and nonbinary decomposable functions and using a hard combinatorial class of problem known as the HP protein model. The results show that the algorithm is a very efficient alternative to other EDAs that use marginal product model factorizations such as the extended compact genetic algorithm (ECGA) and improves the quality of the results achieved by ECGA when the cardinality of the variables is increased.


Meta-Analysis of Changes in Sleep Quality of Women with Breast Cancer before and after Therapy.
Cancer treatments may affect the sleep quality and even future quality of life of women with breast cancer. A meta-analysis was performed to understand the changes in the sleep quality of women with breast cancer during their treatment period. In a systematic literature review in compliance with the PRISMA guidelines, we searched for articles published between 2000 and 2018 in databases. A total of 12 study articles were included. The standardized mean differences of the pooling effect size of sleep quality between the period before treatment and 1-8 weeks, 9-16 weeks, 17-24 weeks, and 25-56 weeks after the commencement of treatment were -0.020, -0.162, 0.075, and 0.216, respectively. Although the differences were not statistically significant, in view of the heterogeneity among the studies, we conducted further analysis using a linear mixed effect model. The overall results indicated poorer sleep quality as time passed from the start of the first treatment (p = 0.014). The results of this study revealed that patients experienced better sleep quality in the initial months after the beginning of treatment; however, their sleep quality became poorer between 4 months to approximately 1 year after the beginning of treatment, compared with the sleep quality before treatment, and continued to decline rather than improve during the follow-up period.