The self-adjusting file instrumentation results in less debris extrusion apically when compared to WaveOne and ProTaper NEXT.
The present ex vivo study aimed to evaluate the debris extrusion after instrumenting the root canals by three different files systems. Sixty extracted human mandibular premolars with single canals were selected and randomly divided into three groups (n = 20) for instrumentation with three different files. Group 1: WaveOne (primary) single reciprocating file (WO; Dentsply Maillefer, Ballaigues, Switzerland) (25/08), Group 2: Self-adjusting file (SAF; ReDent-Nova, Ra'anana, Israel) (1.5 mm), and Group 3: ProTaper NEXT X1 and X2 (PTN; Dentsply Tulsa Dental, Tulsa, OK) (25/06). Debris extruding by instrumentation were collected into pre-weighed Eppendorf tubes. These tubes were then stored in an incubator at 70°C for 5 days. The tubes were then weighed to obtain the final weight, with the extruded debris. Statistical analysis for the debris extruded apically was performed using one-way analysis of variance and post hoc Tukey's test. The statistical analysis showed a significant difference between all the three groups tested (P < 0.01). The following post hoc Tukey's test confirmed that Group 2 (SAF) exhibited significantly least (P < 0.01) debris extrusion between the three groups tested. The SAF resulted in significantly less extrusion of debris when compared to reciprocating WO and rotary PTN.


Laser radar cross-section estimation from high-resolution image data.
A methodology for the estimation of ladar cross sections from high-resolution image data of geometrically complex targets is presented. Coherent CO(2) laser radar was used to generate high-resolution amplitude imagery of a UC-8 Buffalo test aircraft at a range of 1.3 km at nine different aspect angles. The average target ladar cross section was synthesized from these data and calculated to be sigma(T) = 15.4 dBsm, which is similar to the expected microwave radar cross sections. The aspect angle dependence of the cross section shows pronounced peaks at nose on and broadside, which are also in agreement with radar results. Strong variations in both the mean amplitude and the statistical distributions of amplitude with the aspect angle have also been observed. The relative mix of diffuse and specular returns causes significant deviations from a simple Lambertian or Swerling II target, especially at broadside where large normal surfaces are present.


Random Forest Refinement of the KECSA2 Knowledge-Based Scoring Function for Protein Decoy Detection.
Knowledge-based potentials generally perform better than physics-based scoring functions in detecting the native structure from a collection of decoy protein structures. Through the use of a reference state, the pure interactions between atom/residue pairs can be obtained through the removal of contributions from ideal-gas state potentials. However, it is a challenge for conventional knowledge-based potentials to assign different importance factors to different atom/residue pairs. In this work, via the use of the "comparison" concept, Random Forest (RF) models were successfully generated using unbalanced data sets that assign different importance factors to atom pair potentials to enhance their ability to identify native proteins from decoy proteins. Individual and combined data sets consisting of 12 decoy sets were used to test the performance of the RF models. We find that RF models increase the recognition of native structures without affecting their ability to identify the best decoy structures. We also created models using scrambled atom types, which create physically unrealistic probability functions in order to test the ability of the RF algorithm to create useful models based on inputted scrambled probability functions. From this test, we find that we are unable to create models that are of similar quality relative to the unscrambled probability functions. Next, we created uniform probability functions where the peak positions are the same as the original, but each interaction has the same peak height. Using these uniform potentials, we were able to recover models as good as the ones using the full potentials suggesting all that is important in these models are the experimental peak positions. The KECSA2 potential along with all codes used in this work are available at https://github.com/JunPei000/protein_folding-decoy-set .


Triacylglycerol-rich lipoprotein margination: a potential surrogate for whole-body lipoprotein lipase activity and effects of eicosapentaenoic and docosahexaenoic acids.
Margination occurs when blood borne particles attach to the vessel wall. Triacylglycerol-rich lipoprotein (TRL) particles marginate when they bind to endothelial lipoprotein lipase (LpL). This study was undertaken to determine whether TRL margination reflects in vivo LpL activity and whether n-3 fatty acids affect fasting and fed TRL margination. Healthy subjects (n = 33) began with a 4-wk, placebo (olive oil; 4 g/d) run-in period and were then randomly assigned to 4 wk of treatment with 4 g/d of ethyl esters of either safflower oil (SAF; control), eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA). Margination volume (MV) was calculated by subtracting true from apparent plasma volume. MVs were 3 times as great during the fasting state as during the fed state (P < 0.0001). In both the fasting and the fed states, MV was significantly correlated with plasma triacylglycerol and TRL half-lives. In the fed state, MV was also correlated with preheparin LpL, whereas in the fasting state it was not. There was no significant correlation between preheparin LpL and postheparin LpL in the fasting state. Relative to SAF, EPA and DHA supplementation resulted in higher MVs by 64% and 53% (both P < 0.001), respectively, in the fasting state, without significantly reducing fasting triacylglycerol concentrations. In the fed state, DHA doubled the MV (P < 0.05), whereas EPA had no significant effect. The correlations between MV and TRL half-lives and preheparin LpL suggest that MV could be a reflection of whole-body LpL binding capacity. The increases in MVs with EPA and DHA supplementation suggest that these fatty acids may increase the amount of endothelial-bound LpL or its affinity for TRL.


New Insights About Albumin and Liver Disease.
Decompensated liver cirrhosis has a dismal prognosis, with an overall survival of 2-4 years, which is worse than for many oncological diseases. Albumin is an important tool in the management of patients with cirrhosis, since it decreases for less than half the risk for post-paracentesis cardiocirculatory dysfunction and mortality associated with spontaneous bacterial infection, as well as, it triplicates the response to terlipressin in patients with hepatorenal syndrome. Recently, research on albumin has been a hot topic, with important new insights such as the characterization of the pleiotropic effects of albumin (which surpass its oncotic properties) and the concept of effective albumin concentration. In fact, patients with liver cirrhosis present posttranslational modifications on albumin that compromises its function. Those modified albumin forms were proved to have prognostic value and its knowledge may change the paradigm of albumin treatment. In this review, we critically summarize the latest evidence on the potential benefits of albumin in patients with end-stage liver disease.


Effect of a thrombopoietin receptor agonist on use of intravenous immune globulin in patients with immune thrombocytopenia.
Thrombopoietin receptor agonists are new treatments for patients with chronic immune thrombocytopenia (ITP). How one of these agent, romiplostim, has impacted practice patterns, especially the use of intravenous immune globulin (IVIG), has not been evaluated outside of clinical trials. This was a retrospective cohort study of adult ITP patients treated with romiplostim in four Canadian centers. Patients had primary or secondary ITP and were followed for 1 year before starting weekly romiplostim treatment. We compared IVIG use, clinical outcomes, and cost before and after romiplostim. Twenty-nine patients with ITP received romiplostim. Median age was 54 years (interquartile range [IQR], 45-63 years) and patients had a median of two prior ITP treatments (IQR, 1-4) including splenectomy (n = 7). Median platelet (PLT) count was 23 × 10(9) before and 124 × 10(9) after romiplostim. Median duration of romiplostim treatment was 3.7 months. Patients used a median of two IVIG infusions per year before and 0.7 per year after starting romiplostim (p = 0.16). For patients who received weekly romiplostim for at least 1 month (n = 19), IVIG infusions were three (IQR, 1-5) per year before and 0.7 (IQR, 0.4-1.6) per year after romiplostim. Results were squewed by two high IVIG users. Nineteen (66%) patients discontinued romiplostim treatment during follow-up because of lack of response (n = 8), sustained response (n = 5), toxicities (n = 4), or response to splenectomy (n = 2). Overall health care costs were similar before and after romiplostim when concomitant treatments, nursing resources, and hospitalizations were considered. Romiplostim was associated with improved PLT counts and fewer IVIG infusions for most ITP patients. In practice, romiplostim was generally not continued long term and was cost neutral for overall ITP management.


Femtosecond laser writing of optical edge filters in fused silica optical waveguides.
The positional alignment of femtosecond laser written Bragg grating waveguides within standard and coreless optical fiber has been exploited to vary symmetry and open strong optical coupling to a high density of asymmetric cladding modes. This coupling was further intensified with tight focusing of the laser pulses through an oil-immersion lens to control mode size against an asymmetric refractive index profile. By extending this Bragg grating waveguide writing into bulk fused silica glass, strong coupling to a continuum of radiation-like modes facilitated a significant broadening to over hundreds of nanometers bandwidth that blended into the narrow Bragg resonance to form into a strongly isolating (43 dB) optical edge filter. This Bragg resonance defined exceptionally steep edge slopes of 136 dB/nm and 185 dB/nm for unpolarized and linearly polarized light, respectively, that were tunable through the 1450 nm to 1550 nm telecommunication band.


Constraints on muscular performance: trade-offs between power output and fatigue resistance.
An important functional and evolutionary constraint on the physical performance of vertebrates is believed to be the trade-off between speed and endurance capacity. However, despite the pervasiveness of physiological arguments, most studies have found no evidence of the trade-off when tested at the whole-animal level. We investigated the existence of this trade-off at the whole-muscle level, the presumed site of this physiological conflict, by examining inter-individual variation in both maximum power output and fatigue resistance for mouse extensor digitorum longus (EDL) muscle using the work-loop technique. We found negative correlations between several measures of in vitro maximum power output and force production with fatigue resistance for individual mouse EDL muscles, indicating functional trade-offs between these performance parameters. We suggest that this trade-off detected at the whole-muscle level has imposed an important constraint on the evolution of vertebrate physical performance.


N-acetylcysteineamide protects against manganese-induced toxicity in SHSY5Y cell line.
Manganese (Mn) is an essential trace element required for normal cellular functioning. However, overexposure of Mn can be neurotoxic resulting in the development of manganism, a syndrome that resembles Parkinson׳s disease. Although the pathogenetic basis of this disorder is unclear, several studies indicate that it is mainly associated with oxidative stress and mitochondrial energy failure. Therefore, this study is focused on (1) investigating the oxidative effects of Mn on neuroblastoma cells (SHSY5Y) and (2) elucidating whether a novel thiol antioxidant, N-acetylcysteineamide (NACA), provides any protection against Mn-induced neurotoxicity. Reactive oxygen species (ROS) were highly elevated after the exposure, indicating that mechanisms that induce oxidative stress were involved. Measures of oxidative stress parameters, such as glutathione (GSH), malondialdehyde (MDA), and activities of glutathione reductase (GR) and glutathione peroxidase (GPx) were altered in the Mn-treated groups. Loss of mitochondrial membrane potential, as assessed by flow cytometry and decreased levels of ATP, indicated that cytotoxicity was mediated through mitochondrial dysfunction. However, pretreatment with NACA protected against Mn-induced toxicity by inhibiting lipid peroxidation, scavenging ROS, and preserving intracellular GSH and mitochondrial membrane potential. NACA can potentially be developed into a promising therapeutic option for Mn-induced neurotoxicity. This article is part of a Special Issue entitled SI: Metals in neurodegeneration.


Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5.
There is intense interest in induction and characterization of strain-transcending neutralizing Ab against antigenically variable human pathogens. We have recently identified the human malaria parasite Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) as a target of broadly neutralizing Abs, but there is little information regarding the functional mechanism(s) of Ab-mediated neutralization. In this study, we report that vaccine-induced polyclonal anti-PfRH5 Abs inhibit the tight attachment of merozoites to erythrocytes and are capable of blocking the interaction of PfRH5 with its receptor basigin. Furthermore, by developing anti-PfRH5 mAbs, we provide evidence of the following: 1) the ability to block the PfRH5-basigin interaction in vitro is predictive of functional activity, but absence of blockade does not predict absence of functional activity; 2) neutralizing mAbs bind spatially related epitopes on the folded protein, involving at least two defined regions of the PfRH5 primary sequence; 3) a brief exposure window of PfRH5 is likely to necessitate rapid binding of Ab to neutralize parasites; and 4) intact bivalent IgG contributes to but is not necessary for parasite neutralization. These data provide important insight into the mechanisms of broadly neutralizing anti-malaria Abs and further encourage anti-PfRH5-based malaria prevention efforts.


Organ formation in Drosophila: specification and morphogenesis of the salivary gland.
The Drosophila salivary gland has emerged as an outstanding model system for the process of organ formation. Many of the component steps, from initial regional specification through cell specialization and morphogenesis, are known and many of the genes required for these different processes have been identified. The salivary gland is a relatively simple organ; the entire gland comprises of only two major cell types, which derive from a single contiguous primordium. Salivary cells cease dividing once they are specified, and organ growth is achieved simply by an increase in size of individual cells, thus eliminating concerns about the potential unequal distribution of determinants during mitosis. Drosophila salivary glands form by the same cellular mechanisms as organs in higher organisms, including regulated cell shape changes, cell intercalation and directed cell migration. Thus, learning how these events are coordinated for tissue morphogenesis in an organism for which the genetic and molecular tools are unsurpassed should provide excellent paradigms for dissecting related processes in the more intricate organs of more complicated species.


Transforming growth factor beta increases ecto-nucleoside triphosphate pyrophosphatase activity of human bone-derived cells.
Inorganic pyrophosphate (PPi) may be involved in the regulation of mineralization. The cell surface enzyme, ecto-NTP pyrophosphatase, could be a major source of extracellular PPi in bone, and agents that influence its activity in osteoblasts may modulate bone mineralization. We studied the effects of serum on the ecto-NTP pyrophosphatase activity of cultured human osteoblast-like cells. Enzyme activity was lowered when the concentration of fetal calf serum (FCS) was reduced from 10 to 2.5% (vol/vol) for 48 h, and a further decrease in activity was observed after 96 h. Relative to enzyme activity in cells cultured in serum-free medium for 96 h, adult human platelet-poor plasma (HPPP; 2.5-10% vol/vol) induced a small increase, similar concentrations of adult human serum (HS) induced much larger increases, and charcoal-depleted FCS was ineffective. In an attempt to identify the factor(s) present in serum that influence ecto-NTP pyrophosphatase activity, we examined transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF). PDGFs AA, AB, and BB (0.1-10 ng/ml) were ineffective, but both TGF-beta 1 and TGF-beta 2 increased enzyme activity. The increase was dose dependent between 0.001 and 10 ng/ml, was enhanced in the presence of 2% vol/vol FCS, and was not potentiated by PDGF or by 1,25-(OH)2D3. Furthermore, the increase was independent of cell density and was blocked by inhibitors of protein and RNA synthesis. Ecto-NTP pyrophosphatase of subject-matched human dermal fibroblasts was unaffected by TGF-beta (10 ng/ml), suggesting that modulation of activity by the growth factor may be tissue specific. Alkaline phosphatase (ALP) probably serves to hydrolyze extracellular PPi in bone. In contrast to effects on NTP pyrophosphatase activity is osteoblast-like cells, TGF-beta 1 and TGF-beta 2 (0.001-10 ng/ml) decreased ALP activity dose dependently after 72 h. By inducing opposing changes in ecto-NTP pyrophosphatase and ALP activities, TGF-beta may increase extracellular PPi concentrations in osseous tissues and consequently modulate bone mineral properties in vivo.


Dendritic cell vaccine for recurrent high-grade gliomas in pediatric and adult subjects: clinical trial protocol.
Although there have been significant advances in understanding the basic pathogenesis of glioblastoma multiforme, the median survival of patients has changed little in the past 25 years. Recent studies have suggested that immune modulation through dendritic cell (DC) vaccines may stimulate the immune system against tumor antigens and potentially increase survival. To determine whether the use of adjuvant vaccination with autologous DCs (matured in situ after being loaded with tumor cell lysate derived from autologous refractory gliomas) is safe, feasible, and beneficial for adult and pediatric patients with recurrent high-grade gliomas. The study design is a single-center, nonrandomized, open phase I clinical trial. A total of 20 patients with malignant gliomas will be enrolled preoperatively over 2 years. Patients will be given adjuvant vaccination with autologous DCs loaded with tumor lysate after maximal safe surgical resection. Using topical imiquimod before vaccination, it is anticipated that the immune response in vaccinated patients and potentially Overall survival will be greater than that demonstrated in the literature. We anticipate that there will be minimal side effects (minor dermatitis) associated with this treatment. In the current trial, we assess immune response, safety, and survival using a novel vaccine protocol developed in Belgium that seems to markedly increase survival of certain subjects. Nevertheless, larger randomized clinical studies need to be performed to evaluate fully the efficacy of this therapy for both recurrent and newly diagnosed glioblastoma.


Giardiasis in patients with dyspeptic symptoms.
To investigate the prevalence of giardiasis in patients with dyspeptic symptoms. Clinical records of consecutive patients who attended Gastroenterology Department at Aga Khan University Hospital from January 2000 to June 2003 and had esophagogastroduodenoscopy (EGD) with duodenal biopsies and international classification of diseases 9th revision with clinical modifications (ICD-9-CM) coded with giardiasis were studied. Two hundred and twenty patients fulfilled the above criteria. There were 44% (96/220) patients who were giardiasis positive, 72% (69/96) of them were males and 28% (27/96) of them were females. There were 65% (81/124) males and 35% (43/124) females who were giardiasis negative. The mean age of patients with giardiasis was 28+/-17 years, while that of giardiasis negative patients was 40+/-18 years (P<0.001). In patients with giardiasis, abdominal pain was present in 71% (68/96) of patients (P = 0.02) and diarrhea in 29% (28/96) (P = 0.005); duodenitis in 25% (24/96) on EGD (P = 0.006) and in 68% (65/96) on histopathology (P = 0.002). Giardiasis occurs significantly in young people with abdominal pain, while endoscopic duodenitis is seen in only 25% of giardiasis positive cases, which supports routine duodenal biopsy.


Spatial and temporal trends in PCBs in sediment along the lower Rhône River, France.
Despite increasingly strict control of polychlorinated biphenyl (PCB) releases in France since the mid-1970s, PCB contamination of fish recently has emerged as a major concern in the lower Rhône River basin. We measured PCB concentrations in Rhône sediment to evaluate the effects of PCB releases from major urban and industrial areas, sediment redistribution by large floods, and regulatory controls on PCB trends from 1970 to present. Profiles of PCBs (the sum of seven indicator PCB congeners) were reconstructed from sediment cores collected from an off-river rural reference site and from three depositional areas along the Rhône upstream and downstream from the city of Lyon, France. Core chronology was determined from radionuclide profiles and flood deposits. PCB concentrations increased progressively in the downstream direction, and reached a maximum concentration in 1991 of 281 μg/kg at the most downstream site. At the rural reference site and at the upstream Rhône site, PCB concentrations peaked in the 1970s (maximum concentration of 13 and 78 μg/kg, respectively) and have decreased exponentially since then. PCB concentrations in the middle and downstream cores were elevated into the early 1990s, decreased very rapidly until 2000, and since then have remained relatively stable. Congener profiles for three time windows (1965-80, 1986-93, and 2000-08) were similar in the three sediment cores from the Rhône and different from those at the rural reference site. The results indicate that permitted discharges from a hazardous-waste treatment facility upstream from Lyon might have contributed to high concentrations into the 1980-90s, but that industrial discharges from the greater Lyon area and tributaries to the Rhône near Lyon have had a greater contribution since the 1990s. There is little indication that PCB concentration in sediments downstream from Lyon will decrease over at least the short term.


Dietary inclusion of diallyl disulfide, yucca powder, calcium fumarate, an extruded linseed product, or medium-chain fatty acids does not affect methane production in lactating dairy cows.
Two similar experiments were conducted to assess the effect of diallyl disulfide (DADS), yucca powder (YP), calcium fumarate (CAFU), an extruded linseed product (UNSAT), or a mixture of capric and caprylic acid (MCFA) on methane production, energy balance, and dairy cow performance. In experiment 1, a control diet (CON1) and diets supplemented with 56 mg of DADS/kg of dry matter (DM), 3g of YP/kg of DM, or 25 g of CAFU/kg of DM were evaluated. In experiment 2, an inert saturated fat source in the control diet (CON2) was exchanged isolipidically for an extruded linseed source (100g/kg of DM; UNSAT) or a mixture of C8:0 and C10:0 (MCFA; 20.3g/kg of DM). In experiment 2, a higher inclusion level of DADS (200mg/kg of DM) was also tested. Both experiments were conducted using 40 lactating Holstein-Friesian dairy cows. Cows were adapted to the diet for 12 d and were subsequently kept in respiration chambers for 5 d to evaluate methane production, diet digestibility, energy balance, and animal performance. Feed intake was restricted to avoid confounding effects of possible differences in ad libitum feed intake on methane production. Feed intake was, on average, 17.5 and 16.6 kg of DM/d in experiments 1 and 2, respectively. None of the additives reduced methane production in vivo. Methane production in experiment 1 was 450, 453, 446, and 423 g/d for CON1 and the diets supplemented with DADS, YP, and CAFU, respectively. In experiment 2, methane production was 371, 394, 388, and 386 g/d for CON2 and the diets supplemented with UNSAT, MCFA, and DADS, respectively. No effects of the additives on energy balance or neutral detergent fiber digestibility were observed. The addition of MCFA increased milk fat content (5.38% vs. 4.82% for control) and fat digestibility (78.5% vs. 59.8% for control), but did not affect milk yield or other milk components. The other products did not affect milk yield or composition. Results from these experiments emphasize the need to confirm methane reductions observed in vitro with in vivo data.


Precise fluorophore lifetime mapping in live-cell, multi-photon excitation microscopy.
Fluorophore excited state lifetime is a useful indicator of micro-environment in cellular optical molecular imaging. For quantitative sensing, precise lifetime determination is important, yet is often difficult to accomplish when using the experimental conditions favored by live cells. Here we report the first application of temporal optimization and spatial denoising methods to two-photon time-correlated single photon counting (TCSPC) fluorescence lifetime imaging microscopy (FLIM) to improve lifetime precision in live-cell images. The results demonstrated a greater than five-fold improvement in lifetime precision. This approach minimizes the adverse effects of excitation light on live cells and should benefit FLIM applications to high content analysis and bioimage informatics.


Both CD4+ and CD8+ T cell epitopes fused to heat shock cognate protein 70 (hsc70) can function to eradicate tumors.
Vaccination with heat shock proteins (HSP) protects mice from challenge with the tumor from which the HSP were isolated. The antigenicity of HSP vaccination is thought to result from HSP-associated endogenous major histocompatibility complex class I peptides or their precursors. The vaccination effect can be achieved in an adjuvant-free manner and is mediated by CD8(+) T cells, indicating that HSP can act as a natural adjuvant and cross-prime T cells in vivo. We previously devised a recombinant vaccine composed of a CD8(+) T cell epitope fused to the carboxyl-terminus of hsc70 and demonstrated efficient generation of antigen-specific cytotoxic T lymphocyte (CTL) after vaccination with a few micrograms of the hsc70-CTL epitope fusion protein. The present study aimed to determine if the fusion protein vaccine could control tumor growth in vivo and whether simultaneous fusion of a CD4(+) T cell epitope to the amino terminus of the hsc70-CTL epitope would be a more potent vaccine compared to the CTL epitope alone. Ovalbumin (OVA)-derived 8 mer peptide, OVA(257-264), and 16mer peptide, OVA(265-280), were used as CD8(+) and CD4(+) T cell epitopes, respectively. Vaccination with hsc70-OVA(257-264) generated peptide specific CTL more effectively than a peptide plus incomplete Freund's adjuvant combination, and suppressed growth of OVA expressing EL4 (E.G7) and B16 melanoma tumor cells. Addition of OVA(265-280) to the amino-terminus of hsc70-OVA(257-264) (OVA(265-280)-hsc70-OVA(257-264)) enhanced the generation of the OVA(257-264)-specific CTL population, leading to better eradication of MO5 lung metastasis compared to hsc70-OVA(257-264). Our results suggest that fusion of both CD4(+) and CD8(+) T cell epitopes to hsc70 enhances tumor immunity beyond the effect of the CD8(+) T cell epitope alone.


Identification of hemoglobin variants by top-down mass spectrometry using selected diagnostic product ions.
Hemoglobin disorder diagnosis is a complex procedure combining several analytical steps. Due to the lack of specificity of the currently used protein analysis methods, the identification of uncommon hemoglobin variants (proteoforms) can become a hard task to accomplish. The aim of this work was to develop a mass spectrometry-based approach to quickly identify mutated protein sequences within globin chain variants. To reach this goal, a top-down electron transfer dissociation mass spectrometry method was developed for hemoglobin β chain analysis. A diagnostic product ion list was established with a color code strategy allowing to quickly and specifically localize a mutation in the hemoglobin β chain sequence. The method was applied to the analysis of rare hemoglobin β chain variants and an (A)γ-β fusion protein. The results showed that the developed data analysis process allows fast and reliable interpretation of top-down electron transfer dissociation mass spectra by nonexpert users in the clinical area.


Simultaneous exposure of rats to dioxin and carbon monoxide reduces the xenobiotic but not the hypoxic response.
Aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor-1alpha (HIF-1alpha) are conditionally regulated transcription factor subunits that form heterodimeric complexes with their common partner, AhR nuclear translocator (ARNT/HIF-1beta). Whereas the environmentally toxic compound 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD) initiates the trans-activation activity of AhR:ARNT/HIF-1beta, hypoxic exposure stabilizes HIF-1alpha and functionally activates the HIF-1alpha:ARNT/HIF-1beta complex. To analyze a possible crosstalk between these two pathways in vivo, rats were given dioxin orally and/or were exposed to carbon monoxide (CO), causing functional anemia. We found that exposure to CO inhibited the xenobiotic response while dioxin application had no significant negative impact on hypoxia-mediated gene transcription.


Evolution of leaf warbler songs (Aves: Phylloscopidae).
Songs in passerine birds are important for territory defense and mating. Speciation rates in oscine passerines are so high, due to cultural evolution, that this bird lineage makes up half of the extant bird species. Leaf warblers are a speciose Old-World passerine family of limited morphological differentiation, so that songs are even more important for species delimitation. We took 16 sonographic traits from song recordings of 80 leaf warbler taxa and correlated them with 15 potentially explanatory variables, pairwise, and in linear models. Based on a well-resolved molecular phylogeny of the same taxa, all pairwise correlations were corrected for relatedness with phylogenetically independent contrasts and phylogenetic generalized linear models were used. We found a phylogenetic signal for most song traits, but a strong one only for the duration of the longest and of the shortest element, which are presumably inherited instead of learned. Body size of a leaf warbler species is a constraint on song frequencies independent of phylogeny. At least in this study, habitat density had only marginal impact on song features, which even disappeared through phylogenetic correction. Maybe most leaf warblers avoid the deterioration through sound propagation in dense vegetation by singing from exposed perches. Latitudinal (and longitudinal) extension of the breeding ranges was correlated with most song features, especially verse duration (longer polewards and westwards) and complexity (lower polewards). Climate niche or expansion history might explain these correlations. The number of different element types per verse decreases with elevation, possibly due to fewer resources and congeneric species at higher elevations.


Polarity of uncertainty representation during exploration and exploitation in ventromedial prefrontal cortex.
Environments furnish multiple information sources for making predictions about future events. Here we use behavioural modelling and functional magnetic resonance imaging to describe how humans select predictors that might be most relevant. First, during early encounters with potential predictors, participants' selections were explorative and directed towards subjectively uncertain predictors (positive uncertainty effect). This was particularly the case when many future opportunities remained to exploit knowledge gained. Then, preferences for accurate predictors increased over time, while uncertain predictors were avoided (negative uncertainty effect). The behavioural transition from positive to negative uncertainty-driven selections was accompanied by changes in the representations of belief uncertainty in ventromedial prefrontal cortex (vmPFC). The polarity of uncertainty representations (positive or negative encoding of uncertainty) changed between exploration and exploitation periods. Moreover, the two periods were separated by a third transitional period in which beliefs about predictors' accuracy predominated. The vmPFC signals a multiplicity of decision variables, the strength and polarity of which vary with behavioural context.


Intense secondary aerosol formation due to strong atmospheric photochemical reactions in summer: observations at a rural site in eastern Yangtze River Delta of China.
High pollution episodes of PM2.5 and O3 were frequently observed at a rural site (N31.0935º, E120.978°) in eastern Yangtze River Delta (YRD) in summer. To study the impacts of photochemical reactions on secondary aerosol formation in this region, we performed real-time measurements of the mass concentration and composition of PM2.5, particle size distribution (13.6~736.5 nm), concentrations of gas pollutants including O3, SO2, NO2, CO, non-methane hydrocarbons (NMHC)), and nitrate radical in 2013. During the sampling period, the average concentration of PM2.5 was 76.1 (± 16.5) μg/m(3), in which secondary aerosol species including sulfate, nitrate, ammonium, and secondary organic aerosol (SOA) accounted for ~ 62%. Gas-phase oxidation of SO2 was mainly responsible for a fast increase of sulfate (at 1.70 μg/m(3)/h) in the morning. Photochemical production of nitric acid was intense during daytime, but particulate nitrate concentration was low in the afternoon due to high temperature. At night, nitrate was mainly formed through the hydrolysis of NO3 and/or N2O5. The correlations among NMHC, Ox (= O3 + NO2), and SOA suggested that a combination of high emission of hydrocarbons and active photochemical reactions led to the rapid formation of SOA. In addition, several new particle formation and fast growth events were observed despite high ambient aerosol loading. Since the onset of new particle events was accompanied by a rapid increase of H2SO4 and SOA, enhanced formation of sulfate and SOA driven by photochemical oxidation likely promoted the formation and growth of new particles. Together, our results demonstrated that strong atmospheric photochemical reactions enhanced secondary aerosols formation and led to the synchronous occurrence of high concentrations of PM2.5 and O3 in a regional scale. These findings are important for better understanding the air pollution in summer in YRD.


Ambulatory monitoring of bladder and detrusor pressure during natural filling.
We have developed a system to perform fully ambulatory monitoring studies of the bladder. Bladder and rectal pressures are recorded during natural filling of the bladder for up to 6 hours. This system has been evaluated in 19 studies performed on 15 patients. The mean duration of the studies was 3 hours 51 minutes (standard deviation +/- 1 hour 3 minutes) and the mean number of voids per patient was 3.8 +/- 2.2. Visual inspection of the recorded data showed that subtraction of the rectal trace from the bladder trace provided a useful detrusor trace when subjects were ambulant as well as resting. When ambulant, movement caused typical peak-to-peak pressure variability in the bladder and rectal traces of approximately 30 +/- 20 cm. water (mean and standard deviation of peak-to-peak pressure for typical ambulant 5-minute sections for each patient), which after subtraction was reduced on the detrusor trace to 10 +/- 5 cm. water. The equivalent figures when resting were 9 +/- 5 cm. water, subtracting to less than 5 cm. water for the detrusor. Further measurements also were calculated for the whole of each trace. The system provided good quality recordings and should prove useful in future evaluations of natural fill urodynamic studies.


The DARTS tool for assessing online medicines information.
The use of the Internet as a source of medicines information is increasing. However, the quality of online information is highly variable. Equipping Internet users to distinguish good quality information is the aim of a new five-item quality assessment tool (DARTS) that was developed by the Working Group on Information to Patients under the Pharmaceutical Forum established by the European Commission. The objective of this study was to investigate how people with depression assess the quality of online medicines information and to study their opinions about the DARTS tool in assisting in this process. Focus group discussions with Internet users were conducted in metropolitan Helsinki, Finland. Six focus group discussions (67-109 min duration) were conducted with people with depression (n = 29). The DARTS tool was used as a stimulus after open discussion in relation to the evaluation of the quality of Internet-based medicines information. The focus groups were digitally audiotaped and transcribed verbatim. The transcripts were thematically content analysed by two researchers. Focus group participants were generally critical of the information they retrieved. However, few participants systematically applied quality assessment criteria when retrieving online information. No participants had knowledge or experience of any quality assessment tools. The DARTS tool was perceived as being concise and easy to use and understand. Many participants indicated it would allay some of their concerns related to information quality and act as a reminder. While several participants felt the tool should not be any more extensive, some of them believed it should include a more in-depth explanation to accompany each of the quality criteria. The DARTS tool may act as a prompt for people with depression to assess the quality of online information they obtain. The five DARTS criteria may form the basis of a systematic approach to quality assessment and the tool may also act as a reminder of quality issues in general. Further studies are needed to assess the actual value of the DARTS tool as well as its value in relation to other quality assessment instruments.


Plasticity of the histamine H3 receptors after acute vestibular lesion in the adult cat.
After unilateral vestibular neurectomy (UVN) many molecular and neurochemical mechanisms underlie the neurophysiological reorganizations occurring in the vestibular nuclei (VN) complex, as well as the behavioral recovery process. As a key regulator, the histaminergic system appears to be a likely candidate because drugs interfering with histamine (HA) neurotransmission facilitate behavioral recovery after vestibular lesion. This study aimed at analyzing the post-lesion changes of the histaminergic system by quantifying binding to histamine H3 receptors (H3R; mediating namely histamine autoinhibition) using a histamine H3 receptor agonist ([(3)H]N-α-methylhistamine). Experiments were done in brain sections of control cats (N = 6) and cats submitted to UVN and killed 1 (N = 6) or 3 (N = 6) weeks after the lesion. UVN induced a bilateral decrease in binding density of the agonist [(3)H]N-α-methylhistamine to H3R in the tuberomammillary nuclei (TMN) at 1 week post-lesion, with a predominant down-regulation in the ipsilateral TMN. The bilateral decrease remained at the 3 weeks survival time and became symmetric. Concerning brainstem structures, binding density in the VN, the prepositus hypoglossi, the subdivisions of the inferior olive decreased unilaterally on the ipsilateral side at 1 week and bilaterally 3 weeks after UVN. Similar changes were observed in the subdivisions of the solitary nucleus only 1 week after the lesion. These findings indicate vestibular lesion induces plasticity of the histamine H3R, which could contribute to vestibular function recovery.


Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation.
In a randomized trial comparing mitral-valve repair with mitral-valve replacement in patients with severe ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI), survival, or adverse events at 1 year after surgery. However, patients in the repair group had significantly more recurrences of moderate or severe mitral regurgitation. We now report the 2-year outcomes of this trial. We randomly assigned 251 patients to mitral-valve repair or replacement. Patients were followed for 2 years, and clinical and echocardiographic outcomes were assessed. Among surviving patients, the mean (±SD) 2-year LVESVI was 52.6±27.7 ml per square meter of body-surface area with mitral-valve repair and 60.6±39.0 ml per square meter with mitral-valve replacement (mean changes from baseline, -9.0 ml per square meter and -6.5 ml per square meter, respectively). Two-year mortality was 19.0% in the repair group and 23.2% in the replacement group (hazard ratio in the repair group, 0.79; 95% confidence interval, 0.46 to 1.35; P=0.39). The rank-based assessment of LVESVI at 2 years (incorporating deaths) showed no significant between-group difference (z score=-1.32, P=0.19). The rate of recurrence of moderate or severe mitral regurgitation over 2 years was higher in the repair group than in the replacement group (58.8% vs. 3.8%, P<0.001). There were no significant between-group differences in rates of serious adverse events and overall readmissions, but patients in the repair group had more serious adverse events related to heart failure (P=0.05) and cardiovascular readmissions (P=0.01). On the Minnesota Living with Heart Failure questionnaire, there was a trend toward greater improvement in the replacement group (P=0.07). In patients undergoing mitral-valve repair or replacement for severe ischemic mitral regurgitation, we observed no significant between-group difference in left ventricular reverse remodeling or survival at 2 years. Mitral regurgitation recurred more frequently in the repair group, resulting in more heart-failure-related adverse events and cardiovascular admissions. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00807040.).


MEK inhibition preferentially suppresses anchorage-independent growth in osteosarcoma cells and decreases tumors in vivo.
Osteosarcoma is the most common high-grade malignancy of bone, and novel therapeutic options are urgently required. Previously, we developed mouse osteosarcoma AXT cells that can proliferate both under adherent and nonadherent conditions. Based on metabolite levels, nonadherent conditions were more similar to the in vivo environment than adherent conditions. A drug screen identified MEK inhibitors, including trametinib, that preferentially decreased the viability of nonadherent AXT cells. Trametinib inhibited the cell cycle and induced apoptosis in AXT cells, and both effects were stronger under nonadherent conditions. Trametinib also potently decreased viability in U2OS cells, but its effects were less prominent in MG63 or Saos2 cells. By contrast, MG63 and Saos2 cells were more sensitive to PI3K inhibition than AXT or U2OS cells. Notably, the combination of MAPK/ERK kinase (MEK) and PI3K inhibition synergistically decreased viability in U2OS and AXT cells, but this effect was less pronounced in MG63 or Saos2 cells. Therefore, signal dependence for cell survival and crosstalk between MEK-ERK and PI3K-AKT pathways in osteosarcoma are cell context-dependent. The activation status of other kinases including CREB varied in a cell context-dependent manner, which might determine the response to MEK inhibition. A single dose of trametinib was sufficient to decrease the size of the primary tumor and circulating tumor cells in vivo. Moreover, combined administration of trametinib and rapamycin or conventional anticancer drugs further increased antitumor activity. Thus, given optimal biomarkers for predicting its effects, trametinib holds therapeutic potential for the treatment of osteosarcoma.


Dose- and time-dependent effects of ethanolic extract of Mucuna pruriens Linn. seed on sexual behaviour of normal male rats.
According to Indian Systems of Medicine, Mucuna pruriens Linn., belonging to the leguminous family (Papilionaceae), were used for treating male sexual disorders since ancient times. In this study, the effects of ethanolic extracts of the Mucuna pruriens Linn. seed on general mating behaviour, libido and potency of normal male Wister albino rats were investigated and also compared with the standard reference drug, Sildenafil citrate. Animals were divided into one control group (Group I--received saline) and four experimental groups (Groups II-V). Experimental groups were divided on the basis of the dosage of extract to the animals as follows: 150 mg/kg body weight (Group I), 200mg/kg body weight (Group II) and 250 mg/kg body weight (Group IV) while Group V received Sildenafil citrate (5mg/kg body weight). Animals were fed PO with saline or extract or standard drug once in a day for 45 days. To analyse the mating behaviour, female rats with oestrus phase were used. The extract administered PO significantly increased the mounting frequency, intromission frequency and ejaculation latency, and decreased the mounting latency, intromission latency, post-ejaculatory interval and inter-intromission interval. The potency test significantly increased erections, quick flips, long flips and total reflex. Therefore, the results indicated that the ethanolic extracts of Mucuna pruriens Linn. seed produced a significant and sustained increase in the sexual activity of normal male rats at a particular dose (200mg/kg). When compared to control, all the drug-treated groups have shown drug-induced effects for a few parameters. However in Group II, there was an obvious enhancement in all parameters, without affecting the normal behaviour. When compared with the standard drug, the net effect of extract is even less than that in Group II. Therefore, the resulting aphrodisiac activity of the extract lends support to the claim that it has traditionally been used for the treatment of sexual disorders.


Single-neuron stability during repeated reaching in macaque premotor cortex.
Some movements that animals and humans make are highly stereotyped, repeated with little variation. The patterns of neural activity associated with repeats of a movement may be highly similar, or the same movement may arise from different patterns of neural activity, if the brain exploits redundancies in the neural projections to muscles. We examined the stability of the relationship between neural activity and behavior. We asked whether the variability in neural activity that we observed during repeated reaching was consistent with a noisy but stable relationship, or with a changing relationship, between neural activity and behavior. Monkeys performed highly similar reaches under tight behavioral control, while many neurons in the dorsal aspect of premotor cortex and the primary motor cortex were simultaneously monitored for several hours. Neural activity was predominantly stable over time in all measured properties: firing rate, directional tuning, and contribution to a decoding model that predicted kinematics from neural activity. The small changes in neural activity that we did observe could be accounted for primarily by subtle changes in behavior. We conclude that the relationship between neural activity and practiced behavior is reasonably stable, at least on timescales of minutes up to 48 h. This finding has significant implications for the design of neural prosthetic systems because it suggests that device recalibration need not be overly frequent, It also has implications for studies of neural plasticity because a stable baseline permits identification of nonstationary shifts.


[FeFe]- and [NiFe]-hydrogenase diversity, mechanism, and maturation.
The [FeFe]- and [NiFe]-hydrogenases catalyze the formal interconversion between hydrogen and protons and electrons, possess characteristic non-protein ligands at their catalytic sites and thus share common mechanistic features. Despite the similarities between these two types of hydrogenases, they clearly have distinct evolutionary origins and likely emerged from different selective pressures. [FeFe]-hydrogenases are widely distributed in fermentative anaerobic microorganisms and likely evolved under selective pressure to couple hydrogen production to the recycling of electron carriers that accumulate during anaerobic metabolism. In contrast, many [NiFe]-hydrogenases catalyze hydrogen oxidation as part of energy metabolism and were likely key enzymes in early life and arguably represent the predecessors of modern respiratory metabolism. Although the reversible combination of protons and electrons to generate hydrogen gas is the simplest of chemical reactions, the [FeFe]- and [NiFe]-hydrogenases have distinct mechanisms and differ in the fundamental chemistry associated with proton transfer and control of electron flow that also help to define catalytic bias. A unifying feature of these enzymes is that hydrogen activation itself has been restricted to one solution involving diatomic ligands (carbon monoxide and cyanide) bound to an Fe ion. On the other hand, and quite remarkably, the biosynthetic mechanisms to produce these ligands are exclusive to each type of enzyme. Furthermore, these mechanisms represent two independent solutions to the formation of complex bioinorganic active sites for catalyzing the simplest of chemical reactions, reversible hydrogen oxidation. As such, the [FeFe]- and [NiFe]-hydrogenases are arguably the most profound case of convergent evolution. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases.


Do African American Patients Treated with Radical Cystectomy for Bladder Cancer have Worse Overall Survival? Accounting for Pathologic Staging and Patient Demographics Beyond Race Makes a Difference.
Background: It is estimated that 74,000 men and women in the United States will be diagnosed with bladder cancer and 16,000 will die from the disease in 2015. The incidence of bladder cancer in Caucasian males is double that of African American males, but African American men and women have worse survival. Although factors contributing to this disparity have been analyzed, there is still great uncertainty as to why this disparity exists. Objective: To evaluate whether the disparities in bladder cancer survival after radical cystectomy for transitional cell carcinoma (TCC) of the bladder amongst African American (AA) and Caucasian patients is attributable to patient demographics, year of diagnosis, and/or tumor characteristics. Methods: Using Surveillance, Epidemiology, and End Results Program (SEER) data from 1973-2011, African American and Caucasian patients treated with a radical cystectomy for TCC of the bladder were identified. Primary outcomes were all-cause and cancer-specific mortality. Differences in survival between African Americans and Caucasian patients were assessed using chi-square tests for categorical variables and Student's t-tests for continuous variables. Cox proportional hazards regression was used to measure the hazard ratio for African Americans compared to Caucasians for all-cause and cancer-specific mortality. In addition, coarsened matching techniques within narrow ranges, were used to match African American and Caucasian patients on the basis of age, sex, and cancer stage. Following matching, differences in all-cause and cancer-specific mortality were again assessed using a stratified Cox proportional hazards model, using the matching strata for the regression strata. Results: The study cohort consisted of 21,406 African American and Caucasian patients treated with radical cystectomy for bladder urothelial cancer, with 6.2% being African American and 73.9% male. African American patients had worse all-cause and cancer-specific mortality in the univariable analysis (all-cause: HR: 1.23; 95% CI 1.15-1.32, p < 0.001); bladder-cancer specific: HR 1.21; 95% CI 1.11-1.33; p < 0.001). However, after accounting for sex, age, year of diagnosis, marital status, region of treatment, and stage at cystectomy, all-cause mortality was significant (HR 1.20; 95% CI 1.12-1.29; p < 0.0001), but not bladder-cancer specific mortality (HR 1.09; 95% CI 1.00-1.20; p < 0.053). Predictors of bladder cancer specific mortality were age, sex, stage of disease, and marital status. The matched analysis yielded a roughly 1 : 15 match, with 22,511 Caucasians being matched to 1,509 African American patients. In the matched analysis, African Americans had increased all-cause mortality (HR 1.17; 95% CI 1.09-1.26; p < 0.0001), but bladder-cancer specific mortality was no longer significant (HR 1.08; 95% CI 0.99-1.18; p < 0.102). Conclusions: African Americans who undergo a cystectomy are more likely to die, but not necessarily solely because of bladder cancer. Although African American patients have worse all-cause and cancer-specific mortality in univariable models, after controlling for sex, age, year of diagnosis, marital status, region of treatment, and stage at cystectomy, African American patients still have worse overall survival, but equivalent bladder-cancer specific survival. Differences in age, sex, and stage at diagnosis explain some, but not all of the differences in survival.


The cathelicidins LL-37 and rCRAMP are associated with pathogenic events of arthritis in humans and rats.
In rheumatoid arthritis (RA), neutrophil granulocytes fuel inflammation and damage tissue in the joint by releasing cytotoxic agents, antimicrobial peptides, proteases and other inflammatory mediators. The human cathelicidin LL-37 has recently been implicated in the development of systemic lupus erythematosus and psoriasis. To elucidate if antimicrobial peptides (AMPs) contribute to the pathogenesis of arthritis. Expression of LL-37 was determined in synovial membranes from patients with arthritis and control subjects. Expression of the rat cathelicidin rCRAMP and defensins was characterised in joints, blood and secondary lymphoid organs during pristane-induced arthritis (PIA) in rats and in a transfer model of PIA induced by CD4 T cells. Serum samples of rats with arthritis were tested for IgG and IgM autoantibodies against rCRAMP by immunoblot and for interferon (IFNα) by ELISA. Cathelicidins are strongly upregulated in RA synovial membranes and in joints from rats with arthritis as compared with healthy joints. Expression was most prominent in neutrophil granulocytes and macrophages/osteoclasts. Cathelicidin expression is also upregulated in the blood and spleen of pristane-injected rats, with strongest expression detected in activated CD62L- cells coexpressing granulocyte and monocyte markers. Pristane injection caused accumulation of low-density granulocytes in the blood. After pristane injection, the increased expression of rCRAMP coincided with higher levels of cell death, raised levels of interferon (IFN)α and development of autoantibodies. Our results show strong upregulation of cathelicidins and β-defensins coinciding with pathological events of arthritis. Higher expression and release of AMPs might contribute to development and/or maintenance of disease by systemic or local mechanisms.


Quantitative connection between polyglutamine aggregation kinetics and neurodegenerative process in patients with Huntington's disease.
Despite enormous progress in elucidating the biophysics of aggregation, no cause-and-effect relationship between protein aggregation and neurodegenerative disease has been unequivocally established. Here, we derived several risk-based stochastic kinetic models that assess genotype/phenotype correlations in patients with Huntington's disease (HD) caused by the expansion of a CAG repeat. Fascinating disease-specific aspects of HD include the polyglutamine (polyQ)-length dependence of both age at symptoms onset and the propensity of the expanded polyQ protein to aggregate. In vitro, aggregation of polyQ peptides follows a simple nucleated growth polymerization pathway. Our models that reflect polyQ aggregation kinetics in a nucleated growth polymerization divided aggregate process into the length-dependent nucleation and the nucleation-dependent elongation. In contrast to the repeat-length dependent variability of age at onset, recent studies have shown that the extent of expansion has only a subtle effect on the rate of disease progression, suggesting possible differences in the mechanisms underlying the neurodegenerative process. Using polyQ-length as an index, these procedures enabled us for the first time to establish a quantitative connection between aggregation kinetics and disease process, including onset and the rate of progression. Although the complexity of disease process in HD, the time course of striatal neurodegeneration can be precisely predicted by the mathematical model in which neurodegeneration occurs by different mechanisms for the initiation and progression of disease processes. Nucleation is sufficient to initiate neuronal loss as a series of random events in time. The stochastic appearance of nucleation in a cell population acts as the constant risk of neuronal cell damage over time, while elongation reduces the risk by nucleation in proportion to the increased extent of the aggregates during disease progression. Our findings suggest that nucleation is a critical step in gaining toxic effects to the cell, and provide a new insight into the relationship between polyQ aggregation and neurodegenerative process in HD.


DNA Primer Extension with Cyclopropenylated 7-Deaza-2'-deoxyadenosine and Efficient Bioorthogonal Labeling in Vitro and in Living Cells.
A deoxyadenosine triphosphate (dATP) analogue for DNA labeling was synthesized with the 1-methylcyclopropene (1MCP) group at the 7-position of 7-deaza-2'-deoxyadenosine and applied for primer extension experiments. The real-time kinetic data reveals that this 1MCP-modified dATP analogue is incorporated into DNA much faster than that of the similarly 1MCP-modified deoxyuridine triphosphate (dUTP) analogue. The postsynthetic fluorescent labeling of these oligonucleotides works efficiently according to PAGE analysis, and can be applied for immobilization of a functional antibody on a surface. Site-specific labeling at two different positions in DNA was achieved and the bioorthogonality of the postsynthetic fluorescent labeling was demonstrated in living HeLa cells.


First Report of the Pear Trellis Rust Fungus, Gymnosporangium sabinae, on Pyrus calleryana ('Bradford' and 'Chanticleer') and P. communis in New York State.
Owing to their relative disease resistance and showy spring flowers, cultivars of Callery pear (Pyrus calleryana) are commonly planted ornamental and streetside trees in New York state and elsewhere in the U.S. Over the past 2 years, we collected a leaf rust on P. calleryana 'Bradford' or 'Chanticleer' (also known as 'Cleveland Select') from Hempstead (Nassau County), East Moriches and Riverhead (Suffolk Co.), Rochester (Monroe Co.), and Staten Island (Richmond Co.), NY. Leaf samples were collected in June and August 2010 and 2011; adaxial surface lesions resembled infection by fungi in the genus Gymnosporangium (Pucciniales). Lesions were yellow- to red-orange with irregular red to purple margins, 1 to 3.5 cm in any one dimension, and contained 20 to 45 black, subepidermal spermogonia. Hypertrophied plant tissue was evident on the abaxial surface below the spermagonia, but aecia were absent. Genomic DNA was extracted from rust-infected tissue on P. calleryana 'Bradford' (East Moriches, Hempstead, Rochester, and Staten Island) and 'Chanticleer' (Riverhead), and the D1/D2 domain of the 28s ribosomal DNA was PCR-amplified using primers 4 and 11 (3) and sequenced. Partial 28s rDNA sequences (GenBank Accession Nos. JN969962 to JN969966) were either identical or nearly so (99%) to that of the trellis rust fungus, G. sabinae (AF426209 and AY512845). G. sabinae produces aecia with conspicuous balanoid peridia from August to November or until leaf drop; both characteristics are unique to the genus (1). We therefore monitored rust-infected Callery pears in Riverhead as well as a common pear (P. communis) in Ithaca, NY, for the appearance of aecia in 2011. The telial state of G. sabinae on taxa in the genus Juniperus sect. Sabina (e.g., J. sabina and J. virginiana) was not observed within the vicinity of affected pears. In late September, aecia of G. sabinae with morphological features identical to those described by Kerns (1) and Yun et al. (4) were collected from a P. calleryana in Riverhead (Cornell Plant Pathology Herbarium; CUP-067943) and a P. communis in Ithaca (CUP-067943): aecia roestelioid, hypophyllous; periderium balanoid, apex intact and conic, cancellate along the sides; aeciospores brown, globoid to broadly ellipsoid, 22.5 to 28.2 × 25.1 to 32.4 μm, walls 3.3 to 4.7 μm thick. A native of Eurasia and North Africa, G. sabinae was first identified in North America on common pear in 1960 in British Columbia and California (2). Thereafter, the fungus was collected on Callery pear in northern Washington in 1988 and recently, in Michigan in 2009 (4). To our knowledge, this is the first report of G. sabinae on P. calleryana 'Bradford' and 'Chanticleer' as well as P. communis in New York and the new records represent a large (>800 km) eastward expansion of the distribution of the pathogen in the U.S. The geographic locations of affected trees described herein suggest that the trellis rust fungus is well-established across New York, and has spread undetected since its introduction. Given the widespread planting of Callery pear and occurrence of susceptible Juniperus spp. in urban landscapes of New York, G. sabinae has the potential to become a perennial problem where epidemiological conditions permit host alternation. References: (2) F. Kerns. A revised taxonomic account of Gymnosporangium, 1973. (4) A. McCain. Plant Dis. Rep. 45:151, 1961. (1) G. Van der Auwera et al. FEBS Lett. 338:133, 1994. (3) H. Yun et al. Plant Dis. 93:841, 2009.


[Mental disease, existence of diagnostic, use of psychotropic medication: differences by autonomous communities under the national health survey 2006].
Most of the studies on psychological distress in Spain have been conducted in small geographical areas or specific population groups. However, there are no studies that provide representative data for each Autonomous Community (AC). The objectives of this paper are to determine, both in Spain and in the AC, the prevalence of psychological distress, diagnosis, use of psychoactive medication, social support and self-perceived health, as well as to study the association between psychological distress and the rest of the variables. Cross-sectional study, using data from the 2006 National Health Survey, that was completed by 29,478 persons. sociodemographics, psychological distress (GHQ-12), self-perceived health, mental disorder diagnosis, functional social support (Duke) and use and prescription of psychoactive medication. The prevalence of psychological distress in Spain was 20,1%; the highest prevalence was found in Canary Islands (28,2%) and the lowest in La Rioja (12,2%). Among those who presented psychological distress, 62,4% had never received a mental disorder diagnosis, and 71,6% had not used psychoactive medication in the last year. The highest prevalences of non-diagnosed cases (81,8%) and cases non-treated with psychoactive medication (83,1%) were found in La Rioja, whereas the lowest prevalences were found in Asturias. Eight percent of the persons who presented psychological distress had low social support and 63,8% reported bad self-perceived health. Psychological distress is a prevalent phenomenon, and more than half of the persons who suffer it receive neither a diagnosis nor psychoactive medication. Moreover, there are considerable differences between the AC.


Flavonoid-alkylphospholipid conjugates elicit dual inhibition of cancer cell growth and lipid accumulation.
Cancer development is often associated with lipid metabolic reprogramming, including aberrant lipid accumulation. We create novel paradigms endowed with dual functions of anticancer activity and inhibition of lipid accumulation by conjugating the natural product quercetin and synthetic alkylphospholipid drugs, and harnessing the biomedical effects of both. These conjugates offer fresh perspectives in the search for anticancer candidates.


Effect of silica coating on fracture strength of glass-infiltrated alumina ceramic cemented to dentin.
To examine the availability of sol-gel processed silica coating for alumina-based ceramic bonding, and determine which silica sol concentration was appropriate for silica coating. Sixty disks of In-Ceram alumina ceramic were fabricated and randomly divided into 5 main groups. The disks received 5 different surface conditioning treatments: Group Al, sandblasted; Group AlC, sandblasted + silane coupling agent applied; Groups Al20C, Al30C, and Al40C, sandblasted, silica coating via sol-gel process prepared using 20 wt%, 30 wt%, and 40 wt% silica sols, and then silane coupling agent applied. Before bonding, one-step adhesives were applied on pre-prepared ceramic surfaces of all groups. Then, 60 dentin specimens were prepared and conditioned with phosphoric acid and one-step adhesive. Ceramic disks of all groups were cemented to dentin specimens with dual-curing resin cements. Fracture strength was determined at 24 h and after 20 days of storage in water. Groups Al20C, Al30C, and Al40C revealed significantly higher fracture strength than groups Al and AlC. No statistically significant difference in fracture strength was found between groups Al and AlC, or among groups Al20C, Al30C, and Al40C. Fracture strength values of all the groups did not change after 20 days of water storage. Sol-gel processed silica coating can enhance fracture strength of In-Ceram alumina ceramic after bonding to dentin, and different silica sol concentrations produced the same effects. Twenty days of water storage did not decrease the fracture strength.


Subfamily relationships and clustering of rabbit C repeats.
C repeats constitute the predominant family of short interspersed repeats (SINEs) in the rabbit genome. Determination of the nucleotide sequence 5' to rabbit zeta-globin genes reveals clusters of C repeats, and analysis of these and other sequenced regions of rabbit chromosomes shows that the C repeats have a strong tendency to insert within or in close proximity to other C repeats. An alignment of 44 members of the C repeat family shows that they are composites of different sequences, including a tRNA-like sequence, a conserved central core, a stretch of repeating CT dinucleotides, and an A-rich tract. Cladograms generated by both parsimony and cluster analysis subdivide the C repeats into at least three distinct subfamilies. Nucleotides at sites diagnostic for subfamilies appear to have changed in a punctuated and progressive manner during evolution, indicating that a limited number of progenitors have given rise to new repeats in waves of dispersion. C repeats that insert into preexisting C repeats belong to subfamilies that are proposed to have been propagated more recently; hence, these data support the model of dispersion in successive waves. The divergence among the oldest group of C repeats is greater than that observed for the analogous Alu repeats in humans, indicating that rabbit C repeats have been propagating longer than human Alu repeats. The improved consensus sequence for these repeats is similar to that of the predominant artiodactyl SINE in both the tRNA-like region and a central region. Because members of different subfamilies cross-hybridize very poorly, hybridization data with representatives of each subfamily provide a new minimal estimate, 234,000, for the copy number of C repeats in the rabbit haploid genome, although it is likely that the actual value is closer to 1 million.


Future directions for resuscitation research. III. External cardiopulmonary resuscitation advanced life support.
This discussion about advanced cardiac life support (ACLS) reflects disappointment with the over 50% of out-of-hospital cardiopulmonary resuscitation (CPR) attempts that fail to achieve restoration of spontaneous circulation (ROSC). Hospital discharge rates are equally poor for in-hospital CPR attempts outside special care units. Early bystander CPR and early defibrillation (manual, semi-automatic or automatic) are the most effective methods for achieving ROSC from ventricular fibrillation (VF). Automated external defibrillation (AED), which is effective in the hands of first responders in the out-of-hospital setting, should also be used and evaluated in hospitals, inside and outside of special care units. The first countershock is most important. Biphasic waveforms seem to have advantages over monophasic ones. Tracheal intubation has obvious efficacy when the airway is threatened. Scientific documentation of specific types, doses, and timing of drug treatments (epinephrine, bicarbonate, lidocaine, bretylium) are weak. Clinical trials have failed so far to document anything statistically but a breakthrough effect. Interactions between catecholamines and buffers need further exploration. A major cause of unsuccessful attempts at ROSC is the underlying disease, which present ACLS guidelines do not consider adequately. Early thrombolysis and early coronary revascularization procedures should also be considered for selected victims of sudden cardiac death. Emergency cardiopulmonary bypass (CPB) could be a breakthrough measure, but cannot be initiated rapidly enough in the field due to technical limitations. Open-chest CPR by ambulance physicians deserves further trials. In searches for causes of VF, neurocardiology gives clues for new directions. Fibrillation and defibrillation thresholds are influenced by the peripheral sympathetic and parasympathetic nervous systems and impulses from the frontal cerebral cortex. CPR for cardiac arrest of the mother in advanced pregnancy requires modifications and outcome data. Until more recognizable critical factors for ROSC are identified, titrated sequencing of ACLS measures, based on physiologic rationale and sound judgement, rather than rigid standards, gives the best chance for achieving survival with good cerebral function.


Morphoproteomic Characterization of Lung Squamous Cell Carcinoma Fragmentation, a Histological Marker of Increased Tumor Invasiveness.
Accurate stratification of tumors is imperative for adequate cancer management. In addition to staging, morphologic subtyping allows stratification of patients into additional prognostic groups. In this study, we used an image-based computational method on pan-cytokeratin IHC stainings to quantify tumor fragmentation (TF), a measure of tumor invasiveness of lung squamous cell carcinoma (LSCC). In two independent clinical cohorts from tissue microarrays (TMA: n = 208 patients) and whole sections (WS: n = 99 patients), TF was associated with poor prognosis and increased risk of blood vessel infiltration. A third cohort from The Cancer Genome Atlas (TCGA: n = 335 patients) confirmed the poor prognostic value of TF using a similar human-based score on hematoxylin-eosin staining. Integration of RNA-seq data from TCGA and LC-MS/MS proteomics from WS revealed an upregulation of extracellular matrix remodeling and focal adhesion processes in tumors with high TF, supporting their increased invasive potential. This proposed histologic parameter is an independent and unfavorable prognostic marker that could be established as a new grading parameter for LSCC. Cancer Res; 77(10); 2585-93. ©2017 AACR.


The consequences of reducing transmission of Plasmodium falciparum in Africa.
Malaria transmission intensity in Africa varies over several log orders, from less than one infected bite per year to more than one thousand. In this review we examine the consequences in terms of age pattern, clinical spectrum and overall burden of disease and discuss the possible implications for interventions that reduce exposure to infected bites. With very low transmission intensity, all age groups are susceptible to severe malaria. With increasing transmission intensities, older children and adults suffer less severe disease and with high transmission rates the majority of severe cases occur in infants under one year of age. This pattern reflects the increasingly rapid acquisition of immune responses that limit the life-threatening effects of malaria with increasing exposure to the parasite. The clinical spectrum of severe malaria varies with transmission: with high transmission, severe malarial anaemia dominates and cerebral malaria is rare. As one moves towards lower transmission rates, cerebral malaria accounts for an increasingly large proportion of cases. Although the population risk of severe disease falls with age, the risk of death at an individual level may rise with age after an initial fall from very high case fatality rates in children aged under 6 months. Of central interest to malaria control is how the overall amount of disease in childhood varies with transmission. Data from a number of sources suggest that, with low transmission, the amount of malarial disease rises with increasing exposure but that this saturates relatively early. A key issue is whether the same pattern obtains for deaths, both those directly due to malaria and those from all causes. The methodological limitations of ecological comparisons between different areas are discussed before presenting a review of attempts to use this approach in Africa. This suggests that children living in areas of low malarial endemicity have all-cause mortality rates about half of those of children living in areas of moderate to high transmission. Deaths in the first year of life rise linearly with increasing exposure to malaria over a wide range of transmission intensities; by contrast all-cause mortality in children aged 0-4 years appears to saturate at relatively low transmission intensities. These data suggest that interventions that reduce exposure to malaria parasites, such as insecticide-treated bed nets (ITNs), will have the greatest chance of a sustained effect when used in areas where disease burdens are high but the frequency of parasite exposure is low-to-moderate. In conditions of high transmission, initial reductions in mortality may prove difficult to sustain as the reduced level of transmission may still lie on the part of the curve where mortality has saturated. However, at all levels of transmission the overall balance of benefits, including reduced load on families and health services from non-life-threatening malaria, favours the widespread introduction of ITNs in endemic areas of Africa.


Colorectal tumor-on-a-chip system: A 3D tool for precision onco-nanomedicine.
Awareness that traditional two-dimensional (2D) in vitro and nonrepresentative animal models may not completely emulate the 3D hierarchical complexity of tissues and organs is on the rise. Therefore, posterior translation into successful clinical application is compromised. To address this dearth, on-chip biomimetic microenvironments powered by microfluidic technologies are being developed to better capture the complexity of in vivo pathophysiology. Here, we describe a "tumor-on-a-chip" model for assessment of precision nanomedicine delivery on which we validate the efficacy of drug-loaded nanoparticles in a gradient fashion. The model validation was performed by viability studies integrated with live imaging to confirm the dose-response effect of cells exposed to the CMCht/PAMAM nanoparticle gradient. This platform also enables the analysis at the gene expression level, where a down-regulation of all the studied genes (MMP-1, Caspase-3, and Ki-67) was observed. This tumor-on-chip model represents an important development in the use of precision nanomedicine toward personalized treatment.


Frailty and the Prediction of Negative Health Outcomes: A Meta-Analysis.
Frailty is one of the most important concerns regarding our aging population. Evidence grows that the syndrome is linked to several important health outcomes. A general overview of frailty concepts and a comprehensive meta-analysis of their relation with negative health outcomes still lacks in literature, making it difficult for health care professionals and researchers to recognize frailty and the related health risks on the one hand and on the other hand to appropriately follow up the frailty process and take substantiated action. Therefore, this study aims to give an overview of the predictive value of the main frailty concepts for negative health outcomes in community-dwelling older adults. This review and meta-analysis assembles prospective studies regarding the relation between frailty and any potential health outcome. Frailty instruments were subdivided into frailty concepts, so as to make comprehensive comparisons. Odds ratios (ORs), hazard ratios (HRs), and relative risk (RR) scores were extracted from the studies, and meta-analyses were conducted in OpenMeta Analyst software. In total, 31 articles retrieved from PubMed, Web of Knowledge, and PsycInfo provided sufficient information for the systematic review and meta-analysis. Overall, (pre)frailty increased the likelihood for developing negative health outcomes; for example, premature mortality (OR 2.34 [1.77-3.09]; HR/RR 1.83 [1.68-1.98]), hospitalization (OR 1.82 [1.53-2.15]; HR/RR 1.18 [1.10-1.28]), or the development of disabilities in basic activities of daily living (OR 2.05 [1.73-2.44]); HR/RR 1.62 [1.50-1.76]). Overall, frailty increases the risk for developing any discussed negative health outcome, with a 1.8- to 2.3-fold risk for mortality; a 1.6- to 2.0-fold risk for loss of activities of daily living; 1.2- to 1.8-fold risk for hospitalization; 1.5- to 2.6-fold risk for physical limitation; and a 1.2- to 2.8-fold risk for falls and fractures. The analyses presented in this study can be used as a guideline for the prediction of negative outcomes according to the frailty concept used, as well as to estimate the time frame within which these events can be expected to occur.


Clinical implementation of quality of life instruments and prediction tools for localized prostate cancer: results from a national survey of radiation oncologists and urologists.
Although clinical guidelines recommend assessing quality of life, cancer aggressiveness and life expectancy for making localized prostate cancer treatment decisions, it is unknown whether instruments that objectively measure such outcomes have disseminated into clinical practice. In this context we determined whether quality of life and prediction instruments for prostate cancer have been adopted by radiation oncologists and urologists in the United States. Using a nationally representative mail survey of 1,422 prostate cancer specialists in the United States, we queried about self-reported clinical implementation of quality of life instruments, prostate cancer nomograms and life expectancy prediction tools in late 2011. The Pearson chi-square test and multivariate logistic regression were used to determine differences in the use of each instrument by physician characteristics. A total of 313 radiation oncologists and 328 urologists completed the survey for a 45% response rate. Although 55% of respondents reported using prostate cancer nomograms, only 27% and 23% reported using quality of life and life expectancy prediction instruments, respectively. On multivariate analysis urologists were less likely to use quality of life instruments than radiation oncologists (OR 0.40, p <0.001). Physicians who spent 30 minutes or more counseling patients were consistently more likely to use quality of life instruments (OR 2.57, p <0.001), prostate cancer nomograms (OR 1.83, p = 0.009) and life expectancy prediction tools (OR 1.85, p = 0.02) than those who spent less than 15 minutes. Although prostate cancer nomograms have been implemented into clinical practice to some degree, the use of quality of life and life expectancy tools has been more limited. Increased attention to implementing validated instruments into clinical practice may facilitate shared decision making for patients with prostate cancer.


Evidence for NHE3-mediated Na transport in sheep and bovine forestomach.
Na absorption across the cornified, multilayered, and squamous rumen epithelium is mediated by electrogenic amiloride-insensitive transport and by electroneutral Na transport. High concentrations of amiloride (>100 μM) inhibit Na transport, indicating Na(+)/H(+) exchange (NHE) activity. The underlying NHE isoform for transepithelial Na absorption was characterized by mucosal application of the specific inhibitor HOE642 for NHE1 and S3226 for NHE3 in Ussing chamber studies with isolated epithelia from bovine and sheep forestomach. S3226 (1 μM; NHE3 inhibitor) abolished electroneutral Na transport under control conditions and also the short-chain fatty acid-induced increase of Na transport via NHE. However, HOE642 (30 μM; NHE1 inhibitor) did not change Na transport rates. NHE3 was immunohistochemically localized in membranes of the upper layers toward the lumen. Expression of NHE1 and NHE3 has been previously demonstrated by RT-PCR, and earlier experiments with isolated rumen epithelial cells have shown the activity of both NHE1 and NHE3. Obviously, both isoforms are involved in the regulation of intracellular pH, pH(i). However, transepithelial Na transport is only mediated by apical uptake via NHE3 in connection with extrusion of Na by the basolaterally located Na-K-ATPase. The missing involvement of NHE1 in transepithelial Na transport suggests that the proposed "job sharing" in epithelia between these two isoforms probably also applies to forestomach epithelia: NHE3 for transepithelial transport and NHE1 for, among others, pH(i) and volume regulation.


SCORE Study report 1: baseline associations between central retinal thickness and visual acuity in patients with retinal vein occlusion.
To investigate the relationship between baseline center point retinal thickness measured by optical coherence tomography (OCT) and best-corrected visual acuity in eyes with macular edema associated with retinal vein occlusion and to investigate other factors associated with baseline visual acuity letter score. The Standard Care versus COrticosteroid for REtinal Vein Occlusion (SCORE) Study includes 2 multicenter, randomized clinical trials: one evaluating participants with central retinal vein occlusion (CRVO) and the other evaluating participants with branch retinal vein occlusion (BRVO). After omitting 17 participants with missing or unreliable OCT measurements, analyses proceeded with 665 enrolled SCORE Study participants (665 eyes), including 262 with CRVO and 403 with BRVO. At baseline, center point thickness was measured by OCT (Stratus OCT 3 [n=663] and OCT2 [n=2]; Carl Zeiss Meditech, Dublin, CA), and visual acuity was measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) methodology. Center point thickness and best-corrected E-ETDRS visual acuity letter score. The correlation coefficient for the association between baseline OCT-measured center point thickness and best-corrected E-ETDRS visual acuity letter score is -0.27 (95% confidence limit: -0.38 to -0.16) for participants in the CRVO trial and -0.28 (95% confidence limit: -0.37 to -0.19) in the BRVO trial. Regression modeling estimated the following decrease in baseline visual acuity letter score for every 100-microm increase in OCT-measured center point thickness: 1.7 letters (P=0.0007) for CRVO and 1.9 letters (P<0.0001) for BRVO. On the basis of multivariate regression models, baseline factors significantly associated (P<0.05, after adjusting for multiple testing) with baseline visual acuity letter score include age and duration of macular edema for CRVO participants and center point thickness and presence of cystoid spaces for BRVO participants. The correlation between OCT-measured center point thickness and visual acuity letter score is modest. OCT-measured center point thickness represents a useful tool for the detection and monitoring of macular edema in retinal vein occlusion, but it cannot reliably substitute for visual acuity measurements.


Plasma appearance and correlation between coffee and green tea metabolites in human subjects.
Coffee and green tea are two of the most widely consumed hot beverages in the world. Their respective bioavailability has been studied separately, but absorption of their respective bioactive phenolics has not been compared. In a randomised cross-over design, nine healthy subjects drank instant coffee and green tea. Blood samples were collected over 12 h and at 24 h to assess return to baseline. After green tea consumption, (-)-epigallocatechin (EGC) was the major catechin, appearing rapidly in the plasma; (-)-EGC gallate (EGCg) and (-)-epicatechin (EC) were also present, but (-)-EC gallate and C were not detected. Dihydroferulic acid and dihydrocaffeic acid were the major metabolites that appeared after coffee consumption with a long time needed to reach maximum plasma concentration, suggesting metabolism and absorption in the colon. Other phenolic acid equivalents (caffeic acid (CA), ferulic acid (FA) and isoferulic acid (iFA)) were detected earlier, and they peaked at lower concentrations. Summations of the plasma area under the curves (AUC) for the measured metabolites showed 1.7-fold more coffee-derived phenolic acids than green tea-derived catechins (P = 0.0014). Furthermore, we found a significant correlation between coffee metabolites based on AUC. Inter-individual differences were observed, but individuals with a high level of CA also showed a correspondingly high level of FA. However, no such correlation was observed between the tea catechins and coffee phenolic acids. Correlation between AUC and maximum plasma concentration was also significant for CA, FA and iFA and for EGCg. This implies that the mechanisms of absorption for these two classes of compounds are different, and that a high absorber of phenolic acids is not necessarily a high absorber of catechins.


Efficacy and tolerability of an intraoral benzocaine patch in the relief of spontaneous toothache pain.
In this randomized, double-blind, placebo-controlled clinical trial, the effectiveness and tolerability of a novel intraoral benzocaine patch was evaluated in 60 patients who presented to the Dental School's emergency clinic with spontaneous toothache pain of at least a moderate intensity. Mucoadhesive patches, containing either 12 mg of benzocaine or a matching placebo, were applied approximately two millimeters apical to the mucogingival junction of the symptomatic tooth and remained in place for 60 minutes. Pain intensity (0-4 scale) and pain relief (0-4 scale) were recorded every five minutes through 30 minutes, and then every ten minutes through the 90-minute time point. The onset times of first perceptible and meaningful relief were recorded using two stopwatches. The occurrence of adverse events was also monitored. While the benzocaine patches were numerically superior to the placebo patches at all time points with respect to pain relief, PID (pain intensity difference) and their summed measures (TOTPAR and SPID scores), an analysis of covariance revealed no significant differences between treatments. Survival analysis indicated that the percentage of patients reporting meaningful pain relief by 30 minutes was significantly (p < 0.05) greater in the benzocaine group than in the placebo group (77% for benzocaine and 47% for placebo). The median onset times to first perceptible and meaningful relief were 5.4 and 18.1 minutes in the benzocaine group, and 7.8 and 30.4 minutes in the placebo group. Only two side effects (headache) were reported in the entire study. Although the results of the present study were promising, further research on this novel delivery system of benzocaine is warranted to firmly establish efficacy in patients with spontaneous toothache pain.


Human papillomavirus types 16, 18, and 31 serostatus and prostate cancer risk in the Prostate Cancer Prevention Trial.
Since human papillomavirus (HPV) infection was first identified as a risk factor for cervical cancer, several seroepidemiologic and tissue-based studies have investigated HPV in relation to prostate cancer, another common genitourinary malignancy, with mixed results. To further inform this potential association, we conducted a large, prospective investigation of HPV types 16, 18, and 31 in relation to risk of prostate cancer in the Prostate Cancer Prevention Trial. Cases were a sample of men diagnosed with prostate cancer after visit 2 or on their end-of-study biopsy (n = 616). Controls were men not diagnosed with prostate cancer during the trial or on their end-of-study biopsy (n = 616). Controls were frequency matched to cases by age, treatment arm, and family history of prostate cancer. Sera from visit 2 were tested for IgG antibodies against HPV types 16, 18, and 31. No associations were observed for weak or strong HPV-16 [odds ratio (OR), 0.94; 95% confidence interval (95% CI), 0.53-1.64 and OR, 1.07; 95% CI, 077-1.48, respectively], HPV-18 (OR, 0.75; 95% CI, 0.27-2.04 and OR, 0.87; 95% CI, 0.47-1.63, respectively), or HPV-31 seropositivity (OR, 0.76; 95% CI, 0.45-1.28 and OR, 1.15; 95% CI, 0.80-1.64, respectively) and risk of prostate cancer. Considering this finding in the context of the HPV and prostate cancer literature, HPV does not appear to be associated with risk of prostate cancer, at least by mechanisms proposed to date, and using epidemiologic designs and laboratory techniques currently available.


Machine Vision Systems in Precision Agriculture for Crop Farming.
Machine vision for precision agriculture has attracted considerable research interest in recent years. The aim of this paper is to review the most recent work in the application of machine vision to agriculture, mainly for crop farming. This study can serve as a research guide for the researcher and practitioner alike in applying cognitive technology to agriculture. Studies of different agricultural activities that support crop harvesting are reviewed, such as fruit grading, fruit counting, and yield estimation. Moreover, plant health monitoring approaches are addressed, including weed, insect, and disease detection. Finally, recent research efforts considering vehicle guidance systems and agricultural harvesting robots are also reviewed.


Estimation of inbreeding coefficients from genotypic data on multiple alleles, and application to estimation of clonality in malaria parasites.
Methods for estimating probability of identity by descent (f) are derived for data on numbers of genotypes at single loci and at pairs of loci with many alleles at each locus. The methods are general, but are specifically applied to data on genotype frequencies in zygotes of the malaria parasite sampled from its mosquito host in order to find the extent of outcrossing in the parasite and the degree of clonality in populations. It is assumed that zygotes are the outcome either of gametes of the same clone, in which they are identical at all loci, or are products of two random, unrelated clones. From the estimate of f an effective number of clones per human host can also be derived. For Plasmodium falciparum from a Tanzanian village, estimates of f are 0.33 from data on zygote frequencies at two multiallelic loci, indicating that two-thirds of zygotes produce recombinant type.


On acoustic reflection from sand-sized water-saturated granular media at MHz frequencies: Measurements, models and the role of speckle.
Acoustic reflection coefficients are reported for water-saturated granular media at frequencies from 1.2 to 2.0 MHz using a narrow-beam broadband transducer in a monostatic geometry at near-normal incidence. Natural sand and glass beads with median grain diameters ranging from 0.22 to 0.40 mm were used. For each granular medium, bed elevation and root-mean-square roughness were measured using side-on photographs of the sediment-water interface. The probability density distributions of the bed elevations are Gaussian. The roughness parameter is close to 1, indicating that the reflected pressure field is mainly due to coherent scattering. The probability distribution of the observed reflection coefficients is nearly Gaussian, consistent with the predictions from a coherent single-scattering model. The horizontal decorrelation length of the observed reflection coefficients is ∼4 mm, with no consistent dependence on either frequency or grain size, and approximately equal to 20% of the transducer diameter. This behaviour, which is reproduced by the single-scattering model, is due to speckle. The size/frequency-dependence of the reflection coefficients are well described by Eckart's [(1953). J. Acoust. Soc. Am. 25(3), 566-570] prediction for a rough surface with Gaussian-distributed surface elevations. Comparisons are made to previously reported reflection coefficient measurements.


General dental practitioners' perceptions of the West of Scotland Cancer Awareness Programme oral cancer campaign.
The 2003/04 West of Scotland Cancer Awareness Programme (WoSCAP) oral cancer campaign was designed to raise public awareness of the signs and symptoms of oral cancer. The objectives of this study were to explore general dental practitioners' (GDPs) awareness and perceptions of the campaign, and its impact on local dental practices. A self-completing questionnaire was sent to GDPs in the West of Scotland (N = 983) at the conclusion of the public awareness campaign. A response rate of 68.6% was achieved. Most dentists (92%) had heard of the campaign and a large percentage had displayed the promotional materials in their practice. The majority of respondents rated the campaign materials, including a television advertisement, in a very positive manner. Over 40% of dentists reported that, during the active phase of the campaign, patients had asked for information concerning the programme, and 66% indicated that registered patients had asked for advice regarding a specific lesion. Additionally, 41% of dentists reported non-registered patients had attended asking for advice regarding a 'worrying' lesion. Over 60% of dentists had referred a patient during the campaign and 40% of these practitioners indicated an increased referral rate during this period. Most respondents were positive in their assessment of the campaign and reported an increased awareness of oral cancer among patients.


Biochar-based fertilizer: Supercharging root membrane potential and biomass yield of rice.
Biochar-based compound fertilizers (BCF) and amendments have proven to enhance crop yields and modify soil properties (pH, nutrients, organic matter, structure etc.) and are now in commercial production in China. While there is a good understanding of the changes in soil properties following biochar addition, the interactions within the rhizosphere remain largely unstudied, with benefits to yield observed beyond the changes in soil properties alone. We investigated the rhizosphere interactions following the addition of an activated wheat straw BCF at an application rates of 0.25% (g·g-1 soil), which could potentially explain the increase of plant biomass (by 67%), herbage N (by 40%) and P (by 46%) uptake in the rice plants grown in the BCF-treated soil, compared to the rice plants grown in the soil with conventional fertilizer alone. Examination of the roots revealed that micron and submicron-sized biochar were embedded in the plaque layer. BCF increased soil Eh by 85 mV and increased the potential difference between the rhizosphere soil and the root membrane by 65 mV. This increased potential difference lowered the free energy required for root nutrient accumulation, potentially explaining greater plant nutrient content and biomass. We also demonstrate an increased abundance of plant-growth promoting bacteria and fungi in the rhizosphere. We suggest that the redox properties of the biochar cause major changes in electron status of rhizosphere soils that drive the observed agronomic benefits.


[Functional microscopic imaging of the thyroid gland with the help of analytical ion microscopy].
Secondary ion mass spectrometry (SIMS) microscopy provides a direct mapping of 127I in thyroid follicles. Thyroid tissue should be fixed and embedded in methacrylate resin, then cut in 3 microns-thick sections which are placed on a gold coverslip. The histological structure of the tissue is determined by the phosphorus ion (31P) which is present in large amounts in nuclei and phosphorylated molecules in the cytoplasm. An image processing system is used to superimpose images of 127I and 31P: this system allows measurement of local concentration of 127I in the follicular cell and follicular lumen compartments. A study in 8 subjects with normal thyroid glands showed that the level of 127I within follicular cells (430 +/- 250 micrograms/g; m +/- SE) was 6 to 7 times lower than the level in the follicular lumen (2.780 +/- 230 micrograms/g). In simple goiter (9 patients with macrofollicular adenomas), follicular lumen (346 +/- 17 micrograms/g) and cellular (68 +/- 6 micrograms/g) concentrations of 127I were decreased fivefold but the ratio of concentrations remained similar to that seen in normal tissue. In hyperfunctioning nodules (2 microfollicular and 3 macrofollicular adenomas), follicular cell and follicular lumen 127I levels varied widely and showed considerable overlap (2 to 16,000 micrograms/g and 1-21,000 micrograms/g, respectively). In benign cold nodules (1 microfollicular adenoma and 2 macrofollicular adenomas), follicular cell and follicular lumen 127I levels were barely detectable (3 +/- 0.6 micrograms/g and 6 +/- 0.7 micrograms/g respectively). In the 9 malignant nodules studied, no difference in 127I level profile was found with benign nodules.(ABSTRACT TRUNCATED AT 250 WORDS)