The relationship between maternal-infant antibody levels and vertical transmission of HIV-1 infection.
This study assesses the predictive value of the ratio of HIV-1 antibodies in the newborn at birth to that in the mother for perinatally transmitted infection confirmed subsequently by age 18 months. The ratio of HIV-1 (EIA) antibody levels in the baby at birth to that in the seropositive mother after the first trimester (sequenstration index SI) was available in 114 of a perinatal cohort of 137 infants. We related this ratio to the HIV infection status of the children by 18 months, HIV-1 DNA PCR and HIV-specific IgA antibody detection at birth, between 3 and 6 months, and morbidity and mortality. Thirty-five of the 137 (26 per cent) children were diagnosed as infected by 18 months. The mean (SD) HIV SI was 1.57 (0.88) in 29 infected and 0.83 (0.42) in 85 uninfected infants (P < 0.0001). Sensitivity and specificity of a threshold SI of 1.27 (mean +/- 2 SD of uninfected group) for the prediction of perinatal HIV-1 infection were 41 and 98 per cent, respectively. The reason for the higher SI in the infected babies is the combination of lower antibody titres in the transmitting mothers with raised levels in the infected babies. A similar analysis of antibody ratios showed no statistical differences for measles and tetanus (P > 0.1) between HIV infected and uninfected groups. There was a tendency to increased morbidity (Pearson's correlation coefficient r = 0.31) and more severe disease in those with higher HIV-1 SI. Three of 17 (18 per cent) peripheral blood samples from infected children at birth were PCR positive; all had SI's above the threshold. Overall sensitivity and specificity of PCR were 85 per cent each. Eleven of the 29 infected children were HIV-1 specific IgA positive at birth; six (64 per cent) of these had an SI > 1.27. This simple SI of HIV-1 EIA antibodies at birth is comparable to elaborate techniques in its power to predict perinatally acquired infection. It may be a cheap, reliable and rapid screening test for vertically transmitted HIV-1 infection.


Reoperations on the aortic valve combined with replacement of the ascending aorta.
To review the experience with reoperations on the aortic valve combined with replacement of the ascending aorta. From 1991 to 2000, 237 patients underwent reoperations on the aortic valve combined with replacement of the ascending aorta. The study consisted of 188 men and 49 women, with a mean age of 51 years. The operation was urgent or emergent in 44% of cases. Many patients (42%) were in New York Heart Association Class IV, and 24 had active infective endocarditis. The ascending aorta was replaced previously in 46 patients, while the remaining patients had aneurismal dilation. An aortic valve sparing operation was performed in 14 patients and aortic valve replacement in 223. The ascending aorta was replaced in all patients as follows: as a composite graft in 166 and supracoronary in 71. Mechanical valves were used in 145 (61%) patients. The operative mortality was 9%. Postoperative complications were common and 30% of patients suffered an adverse event (death or complication). No independent predictor of operative mortality could be identified but urgent/emergent surgery, advanced functional class, infective endocarditis, coronary artery disease, and replacement of the transverse aortic arch were associated with higher operative mortality by chi-square analysis. The survival at 5 years was 74%+/-4% for patients who had composite replacement of the aortic valve and ascending aorta. Reoperations on the aortic valve combined with replacement of the ascending aorta can be performed with acceptable operative risk and good mid-term survival.


The focus on chemicals alone in human-dominated ecosystems is inappropriate.
As the earth's human population continues to increase, megacities rapidly expand, and agriculture tries to meet their needs, ecosystems are increasingly dominated by humans. This domination, of course, equates to increased loadings of eroded soils, nutrients, and chemicals, along with more degraded habitat. Governments will continue to struggle to address these conflicting issues and must adapt into more effective and efficient management modes. The traditional focus on using chemical-specific guidelines as the foundation of environmental protection and restoration no longer is sufficient and must move to a more realistic and effective approach. Improving environmental quality in aquatic systems to near an appropriate reference condition cannot occur without removing habitat and flow stressors, which in turn will be tied to removal of runoff loadings of soils, nutrients, and chemical pollutants. These issues cannot be resolved without a strategically designed, advanced weight-of-evidence approach to prioritize those stressors. This approach should subsequently improve the effectiveness and cost-benefit of site remediation and restoration. Integr Environ Assess Manag 2017;13:568-572. © 2017 SETAC.


Influence of absorption-edge properties on subpicosecond intrinsic laser-damage threshold at 1053 nm in hafnia and silica monolayers.
Owing to their relatively high resistance to laser-induced damage, hafnia and silica are commonly used in multilayered optical coatings in high-power laser facilities as high- and low-refractive-index materials, respectively. Here, we quantify the laser-induced-damage threshold (LIDT) at 1053 nm in the short-pulse regime of hafnia and silica monolayers deposited by different fabrication methods, including electron-beam evaporation, plasma ion-assisted deposition and ion-assisted deposition. The results demonstrate that nominally identical coatings fabricated by different deposition techniques and/or vendors can exhibit significantly different damage thresholds. A correlation of the LIDT performance of each material with its corresponding absorption edge is investigated. Our analysis indicates a weak correlation between intrinsic LIDT and the optical gap of each material (Tauc gap) but a much better correlation when considering the spectral characteristics in the Urbach tail spectral range. Spectrophotometry and photothermal absorption were used to provide evidence of the correlation between the strength of the red-shifted absorption tail and reduced LIDT at 1053 nm.


Neural basis of smoking-induced relief of craving and negative affect: Contribution of nicotine.
Smoking-induced relief of craving and withdrawal promotes continued cigarette use. Understanding how relief is produced and the role of nicotine in this process may facilitate development of new smoking-cessation therapies. As the US Food and Drug Administration considers setting a standard for reduced nicotine content in cigarettes to improve public health, knowledge of how nicotine contributes to relief also can inform policy. We assessed effects of nicotine using resting state functional magnetic resonance imaging (MRI) and behavioral assessments of craving and negative affect. Twenty-one young (18-25 years old) daily smokers underwent overnight abstinence on 4 days. On each of the following mornings, they self-rated their cigarette craving and negative affect and underwent resting-state functional MRI (fMRI) before and after smoking a cigarette that delivered 0.027, 0.110, 0.231, or 0.763 mg of nicotine. Functional connectivity between the anterior insula and anterior cingulate cortex (ACC) and between the nucleus accumbens and orbitofrontal cortex (OFC) was assessed. Smoking reduced craving, negative affect, and nucleus accumbens-OFC connectivity irrespective of nicotine dose, with positive correlations of the effects on behavioral and connectivity measures. Only the highest nicotine dose (0.763 mg) reduced right anterior insula-ACC connectivity; this reduction was positively correlated with the behavioral effects of the 0.763-mg dose only. While nicotine-based therapies may act on right anterior insula-ACC functional circuits to facilitate smoking cessation, non-nicotine (eg, the conditioned and sensorimotor) aspects of smoking may promote cessation by reducing OFC-accumbens connectivity to alleviate withdrawal.


Endolymphatic sac drainage for intractable vertigo (method and experiences).
This paper describes a method of endolymphatic sac decompression and drainage. The method emphasizes widely exposing dura, avoiding skeletonization of the posterior semicircular canal and draining the sac via a T tube. The results of this procedure in 75 patients, including statistics in 46 ears are discussed. In patients with unilateral disease good results were obtained in control of vertigo in 94 percent of patients and significant improvement in cochlear function in over 30 percent.


Dissecting the old Mediterranean durum wheat genetic architecture for phenology, biomass and yield formation by association mapping and QTL meta-analysis.
Association mapping was used to identify genome regions affecting yield formation, crop phenology and crop biomass in a collection of 172 durum wheat landraces representative of the genetic diversity of ancient local durum varieties from the Mediterranean Basin. The collection was genotyped with 1,149 DArT markers and phenotyped in Spanish northern and southern locations during three years. A total of 245 significant marker trait associations (MTAs) (P<0.01) were detected. Some of these associations confirmed previously identified quantitative trait loci (QTL) and/or candidate genes, and others are reported for the first time here. Eighty-six MTAs corresponded with yield and yield component traits, 70 to phenology and 89 to biomass production. Twelve genomic regions harbouring stable MTAs (significant in three or more environments) were identified, while five and two regions showed specific MTAs for northern and southern environments, respectively. Sixty per cent of MTAs were located on the B genome and 29% on the A genome. The marker wPt-9859 was detected in 12 MTAs, associated with six traits in four environments and the mean across years. To refine QTL positions, a meta-analysis was performed. A total of 477 unique QTLs were projected onto a durum wheat consensus map and were condensed to 71 meta-QTLs and left 13 QTLs as singletons. Sixty-one percent of QTLs explained less than 10% of the phenotypic variance confirming the high genetic complexity of the traits analysed.


Nonlinear approach to difference imaging in diffuse optical tomography.
Difference imaging aims at recovery of the change in the optical properties of a body based on measurements before and after the change. Conventionally, the image reconstruction is based on using difference of the measurements and a linear approximation of the observation model. One of the main benefits of the linearized difference reconstruction is that the approach has a good tolerance to modeling errors, which cancel out partially in the subtraction of the measurements. However, a drawback of the approach is that the difference images are usually only qualitative in nature and their spatial resolution can be weak because they rely on the global linearization of the nonlinear observation model. To overcome the limitations of the linear approach, we investigate a nonlinear approach for difference imaging where the images of the optical parameters before and after the change are reconstructed simultaneously based on the two datasets. We tested the feasibility of the method with simulations and experimental data from a phantom and studied how the approach tolerates modeling errors like domain truncation, optode coupling errors, and domain shape errors.


Two new sympatric troglobitic freshwater flatworms (Platyhelminthes: Dugesiidae) from a hotspot of subterranean biodiversity in the Neotropics.
The Areias System, situated in the Atlantic Forest, is considered a hotspot of troglobitic diversity in Brazil. Herein we describe two new sympatric, troglobitic species of Girardia occurring in this system. Both species show minute eyes; one of them has a whitish body, and the other scattered, fine pigmentation over the dorsal surface. Regarding the copulatory apparatus, one of the species shows a bulbar cavity with multiple diverticula and a bursal canal of the angled type, whereas the other has a single, ovoid bulbar cavity and a smoothly curved bursal canal, among other distinguishing features. Thus, each species can be differentiated by a unique combination of features in its external morphology and copulatory apparatus. Both present a restricted distribution, occurring in a group of pools in travertine rock formed by water from the epikarst. The morphological features of both species and this sampling location indicate that both species are stygobionts.


Evaluation of auto-regulated inspiratory support during rebreathing and acute lung injury in pigs.
Auto-regulated inspiratory support mode (ARIS) is an original closed-loop pressure-support system that regulates the slope ("A") and the initial level ("B") of the applied inspiratory pressure, in order to achieve an optimal minute ventilation under constrained respiratory frequency, tidal volume, and maximum inspiratory airway pressure. The servo-controlled design results in a more or less decreasing applied pressure. The aim of this study was to evaluate the ARIS behavior, compared with pressure-support ventilation at a constant applied pressure. ARIS and pressure-support ventilation were randomly applied to 2 pig models of increasing ventilatory demand induced by a rebreathing test (n = 6), and of altered lung compliance induced by bronchoalveolar lavage (n = 6). The breathing pattern, work of breathing, and blood gas values were compared. ARIS automatically increased the mean inspiratory airway pressure in both groups. This increase was obtained in the rebreathing group by increasing "B" (35 +/- 3.5 cm H2O vs 42.8 +/- 2.5 cm H2O) and in the lung-injury group by decreasing the absolute value of "A" (25 +/- 5.5 cm H2O/s vs 14.7 +/- 8.6 cm H2O/s). There were significant differences (p < 0.05) between ARIS and pressure-support ventilation. In the rebreathing group, tidal volume was 692 +/- 63 mL versus 606 +/- 96 mL, work of breathing was 1.17 +/- 0.45 J/L versus 1.44 +/- 0.27 J/L, and P(aCO2) was 54 +/- 9 mm Hg versus 63 +/- 7 mm Hg. In the lung-injury group, respiratory frequency was 25 +/- 4 breaths/min versus 42 +/- 10 breaths/min, tidal volume was 477 +/- 67 mL versus 300 +/- 63 mL, work of breathing was 0.54 +/- 0.3 J/L versus 0.99 +/- 0.45 J/L, and P(aCO2) was 36 +/- 8 mm Hg versus 53 +/- 15 mm Hg. The ARIS servo control operates correctly, maintaining efficient ventilation facing an increase in respiratory demand or a decrease in respiratory system compliance.


Three-Dimensional Networks of S-Doped Fe/N/C with Hierarchical Porosity for Efficient Oxygen Reduction in Polymer Electrolyte Membrane Fuel Cells.
Reasonable design and synthesis of Fe/N/C-based catalysts is one of the most promising way for developing precious metal-free oxygen reduction reaction (ORR) catalysts in acidic mediums. Herein, we developed a highly active metal-organic framework-derived S-doped Fe/N/C catalyst [S-Fe/Z8/2-aminothiazole (2-AT)] prepared by thermal treatment. The S-Fe/Z8/2-AT catalyst with uniform S-doping possesses a three-dimensional macro-meso-micro hierarchically porous structure. Moreover, the chemical composition and structural features have been well-optimized and characterized for such S-Fe/Z8/2-AT catalysts; and their formation mechanism was also revealed. Significantly, applying the optimal S-Fe/Z8/2-AT catalysts into electrocatalytic test exhibits remarkable ORR catalytic activity with a half-wave potential of 0.82 V (vs reversible hydrogen electrode) and a mass activity of 18.3 A g-1 at 0.8 V in 0.1 M H2SO4 solution; the polymer electrolyte membrane fuel cell test also confirmed their excellent catalytic activity, which gives a maximal power density as high as 800 mW cm-2 at 1 bar. A series of designed experiments disclosed that the favorable structural merits and desirable chemical compositions of S-Fe/Z8/2-AT catalysts are critical factors for efficient electrocatalytic performance. The work provides a new approach to open an avenue for accurately controlling the composition and structure of Fe/N/C catalysts with highly activity for ORR.


Energetic costs of diving and thermal status in European shags (Phalacrocorax aristotelis).
Diving is believed to be very costly in cormorants (Phalacrocoracidae) when compared with other avian divers because of their poor insulation and less-efficient foot propulsion. It was therefore suggested that cormorants might employ a behavioural strategy to reduce daily energy expenditure by minimizing the amount of time spent in water. However, European shags (Phalacrocorax aristotelis) have been observed to spend up to 7 h day(-1) diving in water of around 5-6 degrees C. To gain a better understanding of the energetic requirements in European shags, we measured their metabolic rates when resting in air/water and during shallow diving using respirometry. To investigate the effects of water temperature and feeding status on metabolic rate, birds dived at water temperatures ranging from 5 to 13 degrees C in both post-absorptive and absorptive states. In parallel with respirometry, stomach temperature loggers were deployed to monitor body temperature. Basal metabolic rate (BMR) was almost identical to allometric predictions at 4.73 W kg(-1). Metabolic rate when resting on water, during diving and after feeding was significantly elevated when compared with the resting-in-air rate. During diving, the metabolic rate of post-absorptive shags increased to 22.66 W kg(-1), which corresponds to 4.8x BMR. Minimum cost of transport (COT) was calculated at 17.8 J kg(-1) m(-1) at a swim speed of 1.3 m s(-1). Feeding before diving elevated diving metabolic rate by 13% for up to 5 h. There was a significant relationship between diving metabolic rate and water temperature, where metabolic rate increased as water temperature declined. Thermal conductance when resting in air at 10-19 degrees C was 2.05 W m(-2) degrees C(-1) and quadrupled during diving (7.88 W m(-2) degrees C(-1)). Stomach temperature when resting in air during the day was 40.6 degrees C and increased during activity. In dive trials lasting up to 50 min, stomach temperature fluctuated around a peak value of 42.0 degrees C. Hence, there is no evidence that European shags might employ a strategy of regional hypothermia. The energetic costs during shallow diving in European shags are considerably lower than has previously been reported for great cormorants (Phalacrocorax carbo) and are comparable to other foot-propelled divers. The lower dive costs in shags might be the consequence of a more streamlined body shape reducing hydrodynamic costs as well as a greater insulative plumage air layer (estimated to be 2.71 mm), which reduces thermoregulatory costs. The latter might be of great importance for shags especially during winter when they spend extended periods foraging in cold water.


Five New Glycoside Constituents from the Roots of Gentiana crassicaulis Duthie ex Burk.
Three undescribed glycoside constituents, macrophyllosides E-G and a pair of iridoid glycosides genticrasides A/B, together with eleven known glycoside compounds were isolated from the roots of Gentiana crassicaulis Duthie ex Burk. Their structures were identified by means of spectra analysis and data comparison with previous literatures. Interestingly, the glucose moieties in macrophylloside E and F possess free anomeric hydroxy groups. Genticrasides A/B, identified as a pair of iridoid originated lactones, have not been reported from Gentianaceae family up to now. The anti-inflammatory effects of selected compounds were also evaluated through the nitric oxide (NO) production inhibition in lipopolysaccharides (LPS)-induced RAW264.7 macrophage cells. In which, macrophyllosides G and D showed NO inhibitory activities with rates of 76.14±4.02 % and 52.44±8.29 % at 100 μg/mL.


Autonomic function after botulinum toxin type A or B: a double-blind, randomized trial.
To compare autonomic effects of botulinum toxin (BTX), we randomized patients with cervical dystonia to receive either BTX-A or BTX-B in a double-blind manner. Efficacy and physiologic questionnaire measures of autonomic function were assessed at baseline and 2 weeks after injection. Patients treated with BTX-B had less saliva production (p < 0.01) and greater severity of constipation (p = 0.037) than those treated with BTX-A, but did not differ in other tests of autonomic functions.


Reducing Limitation in Probe Design: The Development of a Diazirine-Compatible Suzuki-Miyaura Cross Coupling Reaction.
Access to high quality photoaffinity probe molecules is often constrained by synthetic limitations related to diazirine installation. A survey of recently published photoaffinity probe syntheses identified the Suzuki-Miyaura (S-M) coupling reaction, ubiquitous in drug discovery, as being underutilized to incorporate diazirines. To test whether advances in modern cross-coupling catalysis might enable efficient S-M couplings tolerant of the diazirine moiety, a fragment-based screening approach was employed. A model S-M coupling reaction was screened under various conditions in the presence of an aromatic diazirine fragment. This screen identified reaction conditions that gave good yields of S-M coupling product while minimally perturbing the diazirine reporter fragment. These conditions were found to be highly scalable and exhibited broad scope when applied to a chemistry informer library of 24 pharmaceutically relevant aryl boron pinacol esters. Furthermore, these conditions were used to synthesize a known diazirine-containing probe molecule with improved synthetic efficiency.


Mitochondrial microsatellite instability of colorectal cancer stroma.
Mitochondrial microsatellite instability (mtMSI) and mutations of mitochondrial DNA has been reported in cancer epithelia of carcinomas. However, mtMSI in cancer stroma has not yet been identified in human cancers. In this study, we attempted to determine if mtMSI occurs in the cancer stroma of sporadic colorectal cancers, and if the stromal mtMSI has any correlations with stromal nuclear MSI (nMSI) and cancer epithelial mtMSI. Nine microsatellite sequences within the D-loop and 5 coding genes for mtMSI, and 9 microsatellites for nMSI were analyzed in the microdissected cancer epithelia and adjacent stromas of 48 sporadic colorectal cancers. Overall, 23 somatic mitochondrial DNA alterations were detected in 15 cancer epithelia (31.2%) and 5 stromas (10.4%). The mutations consisted of 19 D-loop mtMSI alterations, and 1 missense and 3 framshift mutations of repeat sequences within the coding genes. All of the 5 stromal genetic alterations showed D-loop mtMSI. In regards to other MSI status, the stromal mtMSI had no association with stromal nMSI or epithelial mtMSI, either. These findings indicate that in addition to the cancer epithelia the cancer stroma harbor mtMSI, and suggest a possible role of stromal mtMSI in the pathogenesis of colorectal cancers. Furthermore, the data suggest that stromal mtMSI may occur independently of stromal nMSI and epithelial mtMSI in sporadic colorectal cancers.


Age patterns of mortality and cause-of-death structures in Sweden, Japan, and the United States.
This paper uses a new standard model of adult mortality to compare the mortality patterns of Swedes, Japanese, and U.S. whites between 1950 and 1985. It examines changes in the age patterns of mortality and the cause-of-death structures within the populations, and the relationships between those two factors. As Japan has reached a level of mortality similar to that in Sweden, the age patterns of mortality in the two populations have become more similar despite distinct differences in causes of death. The United States has a cause-of-death structure similar to that of Sweden, but the age pattern of mortality is very different. High mortality in the middle age range in the United States results in approximately a one-year loss of life expectancy at age 45 in comparison with Sweden.


Colorectal Cancer Prevention in Inflammatory Bowel Disease: A Systematic Analysis of the Overall Quality of Guideline Recommendations.
Owing to the increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD), numerous societies developed preventative guidelines. We aimed to assess the overall quality of CRC prevention guidelines in IBD. A systematic search was performed in multiple databases to identify all guidelines pertaining to CRC prevention in IBD in September 2020. All guidelines were reviewed for conflicts of interest (COIs)/funding, recommendation quality/strength, external guideline review, use of patient representation, and plans for update-as per Institute of Medicine standards. In addition, recommendations were compared amongst societies. One hundred forty-nine recommendations from 14 different guidelines/societies were included. Not all guidelines provided recommendations on key elements surrounding (1) screening initiation and surveillance, (2) screening modality, (3) pharmacological chemoprevention, (4) dysplasia management and follow-up, and (5) molecular marker use. Only 71% of guidelines disclosed COIs, 43% reported industry funding, 14% were externally reviewed, 7% included patient representation, and 36% had plans for update. Of the total recommendations, 7.4%, 23.5%, and 69.1% were based on high,- moderate-, and low-quality evidence, respectively. Additionally, 20.1% of recommendations were strong, 14.1%, were weak/conditional, and 65.8% did not provide a strength. The proportion of high-quality evidence (P = 0.34) and strong recommendations (P = 0.57) did not significantly differ across societies. Many guidelines do not provide recommendations on key aspects of CRC prevention in IBD. Over 90% of recommendations are based on low- to moderate-quality evidence; therefore, further studies on CRC prevention in IBD are needed to improve the overall quality of evidence.


Proteasome in action: substrate degradation by the 26S proteasome.
Ubiquitination is the major criteria for the recognition of a substrate-protein by the 26S proteasome. Additionally, a disordered segment on the substrate - either intrinsic or induced - is critical for proteasome engagement. The proteasome is geared to interact with both of these substrate features and prepare it for degradation. To facilitate substrate accessibility, resting proteasomes are characterised by a peripheral distribution of ubiquitin receptors on the 19S regulatory particle (RP) and a wide-open lateral surface on the ATPase ring. In this substrate accepting state, the internal channel through the ATPase ring is discontinuous, thereby obstructing translocation of potential substrates. The binding of the conjugated ubiquitin to the ubiquitin receptors leads to contraction of the 19S RP. Next, the ATPases engage the substrate at a disordered segment, energetically unravel the polypeptide and translocate it towards the 20S catalytic core (CP). In this substrate engaged state, Rpn11 is repositioned at the pore of the ATPase channel to remove remaining ubiquitin modifications and accelerate translocation. C-termini of five of the six ATPases insert into corresponding lysine-pockets on the 20S α-ring to complete 20S CP gate opening. In the resulting substrate processing state, the ATPase channel is fully contiguous with the translocation channel into the 20S CP, where the substrate is proteolyzed. Complete degradation of a typical ubiquitin-conjugate takes place over a few tens of seconds while hydrolysing tens of ATP molecules in the process (50 kDa/∼50 s/∼80ATP). This article reviews recent insight into biochemical and structural features that underlie substrate recognition and processing by the 26S proteasome.


Performance on the Test of Memory Malingering in children with neurological conditions.
Despite increasing interest in the use of performance validity tests with youth, relatively little is known about how children and adolescents with neurological diagnoses perform on these measures. The purpose of this study was to examine performance on the Test of Memory Malingering (TOMM) in a general pediatric neurologic sample. Data were obtained from 266 consecutive patients (mean age = 13.0, SD = 3.7, range = 5-18) referred for a neuropsychological assessment in a tertiary care pediatric hospital. As part of a broader neuropsychological battery, patients were administered the TOMM. In this sample, 94% of children passed the TOMM. Pass rate was 87% for 5-7 year-olds but was ≥ 90% for all other ages. Children with a history of stroke had the lowest pass rate (86%), with other diagnostic groups scoring ≥ 90%, including epilepsy, traumatic brain injury, and hydrocephalus. Lower TOMM performance was related to slower processing speed and weaker memory performance. The results support using the TOMM with children and adolescents who have neurological diagnoses. Caution may still be warranted when interpreting scores in those who are younger and/or who have more significant cognitive difficulty.


Virulence genes of the phytopathogen Rhodococcus fascians show specific spatial and temporal expression patterns during plant infection.
The phytopathogenic bacterium Rhodococcus fascians provokes shoot meristem formation and malformations on aerial plant parts, mainly at the axils. The interaction is accompanied by bacterial colonization of the plant surface and tissues. Upon infection, the two bacterial loci required for full virulence, fas and att, were expressed only at the sites of symptom development, although their expression profiles differed both spatially and temporally. The att locus was expressed principally in bacteria located on the plant surface at early stages of infection. Expression of the fas locus occurred throughout infection, mainly in bacteria that were penetrating, or had penetrated, the plant tissues and coincided with sites of meristem initiation and proliferation. The implications for the regulation of virulence genes of R. fascians during plant infection are discussed.


Medically induced euthyroid hypothyroxinemia may extend survival in compassionate need cancer patients: an observational study.
Clinical studies have shown that interventional lowering of serum free thyroxine (FT4) may be associated with extended survival in patients with some terminal cancers. The report of success with this approach in glioblastoma multiforme caused involvement of the author (A.H.) in the prospective consultative management of 23 end-stage solid tumor patients in whom hypothyroxinemia was induced to prolong life. Patients were self-referred or recommended by attending physicians to the author (A.H.) and had advanced cancers of the brain, ovary, lung, pancreas, salivary gland, and breast or had mesothelioma or soft-tissue sarcoma. Hypothyroxinemia was achieved in euthyroid patients by using methimazole, with the addition of 3,3',5-triiodo-L-thyronine (L-T3) to prevent hypothyroidism and suppress endogenous thyrotropin (TSH). In patients with pre-existent primary hypothyroidism, T3 administration was substituted for T4 replacement. Serum FT4 and TSH concentrations were serially monitored to enable adjustments to drug therapy and prevent clinical hypothyroidism. Survival was measured from the date of hypothyroxinemia induction with T3 or methimazole plus T3. Outcomes were compared with the odds of death based on the Surveillance Epidemiology and End Results and American Joint Committee on Cancer databases and literature reports. The survival time of 83% (19 of 23) of patients exceeded the 20% expected 1-year survival for this hypothyroxinemic, end-stage cancer group. The difference between actual and expected survival was significant. Although this is an uncontrolled observational experience with frank limitations, compassionate medical induction of hypothyroxinemia should be considered for patients with advanced cancers to whom other avenues of treatment are closed.


Phase I study of O6-benzylguanine and temozolomide administered daily for 5 days to pediatric patients with solid tumors.
This pediatric phase I trial of O6-benzylguanine (O6BG) and temozolomide (TMZ) on a daily schedule for 5 days, every 28 days was performed to determine the maximum-tolerated dose of TMZ when given with a biologically active dose of O6BG and to define the toxicity profile of the combination in children with solid tumors. Patients < or = 21 years old with refractory solid tumors were eligible. O6BG was administered intravenously over 60 minutes daily for 5 days. TMZ was administered orally 30 minutes after completion of each O6BG infusion. Starting doses of O6BG and TMZ were 60 mg/m2/d and 28 mg/m2/d, respectively. O6BG was escalated to 90 and 120 mg/m2/d; TMZ was subsequently escalated to 40, 55, 75, and 100 mg/m2/d. Cycles were repeated every 28 days. Forty-one patients were enrolled; 32 patients were assessable for toxicity. The combination of O6BG and TMZ was tolerable at TMZ doses less than half of the conventional dose of 200 mg/m2/d. Myelosuppression occurred sporadically at all dose levels and was the dose-limiting toxicity (DLT) at 100 mg/m2/d of TMZ combined with 120 mg/m2/d O6BG. Nonhematologic toxicities were generally mild. Evidence of antitumor activity was observed at 120 mg/m2/d O6BG combined with TMZ doses of 55 mg/m2/d and above. The recommended doses of O6BG administered with TMZ on a 5-day schedule in children are 120 mg/m2/d of O6BG and 75 mg/m2/d of TMZ. Evidence of activity was observed at these doses. Myelosuppression was the DLT.


A Potential Red-Emitting Phosphor BaZrGe3O9:Eu3+ for WLED and FED Applications: Synthesis, Structure, and Luminescence Properties.
A variety of Eu3+-activated BaZrGe3O9 phosphors was synthesized via solid-state reaction. The phase formation of BaZrGe3O9:Eu3+ samples was verified by powder X-ray diffraction analysis, while Rietveld refinement method was used to confirm the crystal structure. The electronic structure and characteristic photoluminescence as well as cathodoluminescence properties were researched in detail. The samples show strong absorption at 394 nm, which matches well with the commercial near-ultraviolet chips. Under 394 nm excitation, the phosphors exhibit the characteristic emissions of Eu3+ ions consistent with the 5D0-7FJ transitions. Then we investigated the thermal stability detailedly. The temperature-dependent photoluminescence emission spectra suggest that the obtained phosphors have favorable thermal stability. A white light-emitting diode (WLED) lamp with low correlated color temperature and good color render index was fabricated with blue-emitting BaMgAl10O17:Eu2+, green-emitting Sr2SiO4:Eu2+ (commercial), and red-emitting BaZrGe3O9:Eu3+ phosphors in near-ultraviolet light-emitting diodes (λmax = 395 nm) as well. Furthermore, the phosphor also exhibits red emission with high resistance and high current saturation under low voltage electron bombardment. It has better degradation resistance than the commercial Y2O3:Eu phosphor. All the results manifest that the Ba0.88Eu0.08ZrGe3O9 phosphor can be an eligible red-emitting phosphor candidate for WLEDs and field-emission displays.


Reelin expression in human liver of patients with chronic hepatitis C infection.
Reelin is a secreted extracellular glycoprotein that plays a critical role during brain development. Several studies have described Reelin expression in hepatic stellate cells of the human liver. In order to investigate the possible role of Reelin in the process of hepatic fibrogenesis, in this study we investigated Reelin expression in the liver tissue of patients infected with the Hepatitis C Virus (HCV). On this basis, Reelin expression was analysed by immunohistochemistry during liver biopsies of 81 patients with HCV-related chronic hepatitis. A Knodell score was used to stage liver fibrosis. Hepatic stellate cells/myofibroblast immunohistochemical markers (CRBP-1, alpha-SMA) were also evaluated. As further confirmed by co-localization experiments (Reelin +CRBP-1), Reelin protein was expressed by hepatic stellate cells/myofibroblasts, and a significant positive correlation was found between Reelin expression and the stage of liver fibrosis (P=0.002). Moreover, Reelin correlated with CRBP-1 positive cells (P=0.002), but not with alpha-SMA, suggesting that Reelin should not be regarded as a marker of hepatic stellate cells/myofibroblasts differentiation but rather as a functional protein expressed during some phases of liver fibrosis. Furthermore, Disabled-1 (Dab1), a Reelin adaptor protein, was expressed in cells of ductular reaction suggesting a paracrine role for Reelin with regards these elements. In conclusion, Reelin was expressed by human hepatic stellate cells/myofibroblasts and the number of these cells increased significantly in the lobule as the liver fibrosis progressed, suggesting a role for Reelin in the activation of hepatic stellate cells/myofibroblasts during liver injury. Reelin may potentially be incorporated into liver injury evaluations in combination with other histological data.


Mobile gene cassettes: a fundamental resource for bacterial evolution.
Horizontal gene transfer increases genetic diversity in prokaryotes to a degree not allowed by the limitations of reproduction by binary fission. The integron/gene cassette system is one of the most recently characterized examples of a system that facilitates horizontal gene transfer. This system, discovered in the context of multidrug resistance, is recognized in a clinical context for its role in allowing pathogens to adapt to the widespread use of antibiotics. Recent studies suggest that gene cassettes are common and encode functions relevant to many adaptive traits. To estimate the diversity of mobile cassettes in a natural environment, a molecular technique was developed to provide representative distributions of cassette populations at points within a sampling area. Subsequently, statistical methods analogous to those used for calculating species diversity were employed to assess the diversity of gene cassettes within the sample area in addition to gaining an estimate of cassette pool size. Results indicated that the number of cassettes within a 5x10-m sample area was large and that the overall mobile cassette metagenome was likely to be orders of magnitude larger again. Accordingly, gene cassettes appear to be capable of mobilizing a significant genetic resource and consequently have a substantial impact on bacterial adaptability.


Decreased IL-27 expression in association with an increased Th17 response in Vogt-Koyanagi-Harada disease.
IL-27 has emerged as an important regulator of proinflammatory T-cell responses in animal models. We investigated the pathophysiological role of IL-27 in Vogt-Koyanagi-Harada (VKH) disease. IL-27P28 and EBI3 mRNA expression in peripheral blood mononuclear cells (PBMCs) were assayed by RT-PCR. Cytokines in the serum and supernatants of PBMCs, naïve CD4(+) T cells and DC-T cocultures were assayed by ELISA. Flow cytometry was used to evaluate the frequencies of IL-17-producing CD4(+) T cells. The active VKH patients showed a decreased IL-27P28 mRNA expression in PBMCs and lower IL-27 expression in the serum and supernatants of PBMCs, but higher Th17 cells in PBMCs. EBI3 mRNA expression was not different among the groups tested. Stimulation of naïve CD4(+) T cells under Th17 polarizing conditions showed a higher Th17 cell differentiation in active VKH patients. IL-27 significantly inhibited Th17 cell differentiation. IL-27-treated DCs showed a significant inhibition on Th17 differentiation. There was a significant defect in the Tr1 cell induction as measured by IL-10 in active VKH patients. Treatment with corticosteroids and cyclosporine A (CsA) resolved the intraocular inflammation in association with an upregulation of IL-27 and a downregulation of IL-17. In vitro experiments showed that corticosteroids, but not CsA, significantly upregulated the expression of IL-27. The present study suggests that decreased IL-27 expression may result in a higher Th17 in active VKH patients, which may promote the autoimmune response observed in these patients. Manipulation of IL-27 may offer a novel target for treatment of this disease.


Trajectories of Health-Related Quality of Life in Coronary Artery Disease.
Health-related quality of life (HRQOL) assessment is an important health outcome for measuring the efficacy of treatments and interventions for coronary artery disease (CAD). HRQOL is known to improve over the first year after interventions for CAD, but there is limited knowledge of the changes in HRQOL beyond 1 year. We investigated heterogeneity in long-term trajectories of HRQOL in patients with CAD. Data were obtained from 6226 patients identified from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease with at least 1-vessel CAD who underwent their first catheterization between 2006 and 2009. HRQOL was assessed using the Seattle Angina Questionnaire, a 19-item disease-specific measure of HRQOL for patients with CAD. Group-based trajectory analysis was used to identify various subgroups of Seattle Angina Questionnaire trajectories over time while adjusting for missing data through a longitudinal multiple imputation model. Multinomial logistic regression was used to identify the predictors of differences among the identified subgroups. Our analysis revealed significant improvements in HRQOL across all the 5 domains of Seattle Angina Questionnaire overtime for the whole data. Multitrajectory analyses revealed 4 HRQOL trajectory subgroups including high (25.1%), largely increased (32.3%), largely decreased (25.0%), and low (17.6%) trajectories. Age, sex, body mass index, diabetes mellitus, previous history of myocardial infarction, smoking, depression, anxiety, type of treatment received, and perceived social support were significant predictors of differences among these trajectory subgroups. This study highlights variations in longitudinal trajectories of HRQOL in patients with CAD. Despite overall improvements in HRQOL, about a quarter of our cohort experienced a significant decline in their HRQOL over the 5-year period. Understanding these HRQOL trajectories may help personalize prognostic information, identify patients and HRQOL domains on which clinical interventions are most beneficial, and support treatment decisions for patients with CAD.


Role of lipooligosaccharide in the attachment of Moraxella catarrhalis to human pharyngeal epithelial cells.
The goal of this study was to determine the role of lipooligosaccharide in the attachment of Moraxella catarrhalis to human pharyngeal epithelial cells. Strain 2951 and its P(k) mutant strain 2951 galE were used in this study. This study suggests that the P(k) epitope of LOS is not an adhesin for M. catarrhalis, but plays a crucial role by its surface charge in the initial stage of attachment.


Purification by affinity chromatography of 2,4-dienoyl-CoA reductases from bovine liver and Escherichia coli.
1. Dye-ligand chromatography using immobilized Cibacron blue F3GA (blue Sepharose CL-6B) and Procion red HE3B (Matrex gel red A) as matrices and general ligand chromatography employing immobilized 2',5'-ADP (2',5'-ADP-Sepharose 4B) and immobilized 3',5'-ADP (3',5'-ADP-Agarose) were employed for purification of NADPH-dependent 2-enoyl-CoA reductase and 2,4-dienoyl-CoA reductase from bovine liver (formerly called 4-enoyl-CoA reductase [Kunau, W. H. and Dommes, P. (1978) Eur. J. Biochem. 91, 533-544], as well as 2,4-dienoyl-CoA reductase from Escherichia coli. 2. The NADPH-dependent 2-enoyl-CoA reductase from bovine liver mitochondria was separated from 2,4-dienoyl-CoA reductase by dye-ligand chromatography (Matrex gel red A/KCl gradient) as well as by general ligand affinity chromatography (2',5'-ADP-Sepharose 4B/NADP gradient). The enzyme was obtained in a highly purified form. 3. The NADPH-dependent 2,4-dienoyl-CoA reductase from bovine liver mitochondria was purified to homogeneity using blue Sepharose CL-6B, Matrex gel red A, and 2',5'-ADP-Sepharose 4B chromatography. 4. The bacterial 2,4-dienoyl-CoA reductase was completely purified by ion-exchange chromatography on DEAE-cellulose followed by a single affinity chromatography step employing 2',5'-ADP-Sepharose 4B and biospecific elution from the column with a substrate, trans,trans-2,4-decadienoyl-CoA. 5. The application of dye-ligand and general ligand affinity chromatography for purification of NADPH-dependent 2,4-dienoyl-CoA reductases taking part in the beta-oxidation of unsaturated fatty acids is discussed. It is concluded that making use of coenzyme specificity for binding and substrate specificity for elution is essential for obtaining homogeneous enzyme preparations.


Tumour volume measurement in head and neck cancer.
Tumour volume is a significant prognostic factor in the treatment of malignant head and neck tumours. Studies of laryngeal and pharyngeal tumours have shown tumour volume to be an important predictor for tumour recurrence. Some studies (for instance nasopharyngeal carcinoma) have shown through multivariate modelling that tumour volume is a dominant covariate that overwhelms T stage, N stage and stage group. The results of these studies have prompted several investigators to suggest the inclusion of tumour volume as an additional prognostic factor in future revisions of the TNM staging system. This paper briefly reviews the TNM system as a staging tool, the measurement of tumour volume and how tumour volume could possibly be incorporated in the system or used as an additional prognostic factor.


[The importance of fetal echocardiography in the detection and management of congenital cardiac malformations].
Using present-day high-resolution ultrasound scanners, it is possible to visualize and study the heart during the different stages of fetal growth in patients at risk of some forms of congenital heart disease. Detailed anatomical knowledge of cardiac structures combined with the accurate interpretation of echocardiographic images made during fetal development enable early diagnosis of particular forms of congenital disease that have serious pathophysiologic consequences. In addition, it also becomes possible to select the most appropriate nature and timing of delivery, and to organize early treatment for the newborn. Any decision taken on how to treat a fetus in which a congenital cardiac abnormality has been identified must be taken by a multidisciplinary team. This will help in coordinating the measures that must be taken after delivery and, in the near future, in implementing intrauterine surgery. Fetal echocardiography is establishing itself as a valuable tool in the management of the various types of congenital malformation, which together comprise the main cause of death among the newborn. In addition, the technique can be used to confirm and broaden our knowledge of the natural history of cardiac malformations, which are the most common congenital malformations. There is no doubt that the application and understanding of this imaging technology will increase the survival rate of newborns with specific congenital cardiac abnormalities, and will have a significant impact on long-term clinical outcome and quality of life in these patients.


Impact of Temporal Visual Flicker on Spatial Contrast Sensitivity in Myopia.
To investigate whether short-term exposure to high temporal frequency full-field flicker has an impact on spatial visual acuity in individuals with varying degrees of myopia. Thirty subjects (evenly divided between control and experimental groups) underwent a 5-min exposure to full-field flicker. The flicker rate was lower than critical flicker frequency (CFF) for the experimental group (12.5 Hz) and significantly higher than CFF for the controls (60 Hz). Spatial contrast sensitivity function (CSF) was measured before and immediately after flicker exposure. We examined whether the post flicker CSF parameters were different from the pre-exposure CSF values in either of the subject groups. Additionally, we examined the relationship between the amount of CSF change from pre to post timepoints and the degree of subjects' myopia. The CSF parameters included peak frequency, peak sensitivity, bandwidth, truncation, and area under log CSF (AULCSF). There was no significant difference of all five pre-exposure CSF parameters between the two groups at baseline (P = 0.333 ∼ 0.424). Experimental group subjects exhibited significant (P < 0.005) increases in peak sensitivity and AULCSF, when comparing post-exposure results to pre-exposure ones. Controls showed no such enhancements. Furthermore, the extent of these changes in the experimental group was correlated significantly with the participants' refractive error (P = 0.005 and 0.018, respectively). Our data suggest that exposure to perceivable high-frequency flicker (but, not to supra-CFF frequencies) enhances important aspects of spatial contrast sensitivity, and these enhancements are correlated to the degree of myopia. This finding has implications for potential interventions for cases of modest myopia.


Array comparative genomic hybridization reveals unbalanced gain of the MYCN region in Wilms tumors.
Wilms tumor (WT) is one of the most common solid tumors in childhood. It is characterized by a nonrandom pattern of chromosomal aberrations whose clinical significance is still uncertain. To gain further insight into different genetic events and their corresponding biological role, conventional cytogenetics and array comparative genomic hybridization (array CGH) were performed on 13 tumor samples. In two of these, array CGH revealed, together with other aberrations, a low-level amplification and an unbalanced gain in the region of chromosome bands 2p23 approximately p24 that encompass the MYCN gene. Both events were confirmed with a MYCN-specific fluorescence in situ hybridization probe, which showed a signal pattern consistent with a small homogenous staining region in one case. In addition, mRNA expression levels for MYCN were determined by quantitative reverse-transcriptase polymerase chain reaction and revealed that gain of chromosomal material was reflected in enhanced levels of MYCN mRNA in both tumors, whereby also additional tumors showed increased MYCN expression. Therefore, our findings suggest that WT is an additional childhood tumor where MYCN gain might play an important role in tumor development.


[Diagnostic value of right thoracic ECG recording in detection of pulmonary hypertension in chronic obstructive respiratory disease].
There are many electrocardiographic criteria of pulmonary hypertension and cor pulmonale. These criteria are generally highly specific but not sensitive. Therefore many patients with pulmonary hypertension remain undetected. The aim of this study was to delineate a sensitive as well as a specific ECG parameter for noninvasive prediction of pulmonary hypertension under special consideration of the right thoracic leads. 75 patients were included in this study, 62 male and 13 female, mean age 62.7 +/- 9.5 years. All presented with chronic obstructive lung disease known since 12.1 +/- 9.7 years. The underlying disease had been confirmed clinically and by body plethysmography. Laboratory and lung function data showed a high air way resistance with a mean value of 6.8 +/- 3.3 cm H2O/l/s and a high intrathoracic gas volume of 149.1% of the expected value. The severity of hypoxemia was variable but generally moderate with a PaO2 of 65.3 +/- 11.6 mm Hg on average. All patients applied aerosols with ipratropiumbromid, fenoterol and glucocorticoids. 92% additionally received aminophylline and 87.0% oral glucocorticoids. Diuretics and glycosides were prescribed in 50.0% and 34.8% respectively. The four right thoracic ECG leads Vr3 to Vr6 were recorded in addition to the common twelve leads I to III, a VR, aVL, aVF and V1 to V6. A modified Sokolow-Lyon-Index (SIm) as a sum of amplitudes of R in lead Vr3 and S in lead V6 and the combination of SIm with PaO2 (SIm-PaO2, n = 44) according to the formula SIm + 0.02 (100--PaO2%) were established. Additionally a right heart catherization by Swan-Ganz technique was performed. The mean values of hemodynamic data demonstrated a constellation of precapillary pulmonary hypertension with high PAPm and pulmonary resistance and low pulmonary capillary wedge pressure (26.4 +/- 12.9 mm Hg, 396.0 +/- 294.0 dyn.s./cm5 and 8.7 +/- 4.2 mm Hg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Apolipoprotein A1 polymorphisms and risk of coronary artery disease: a meta-analysis.
It has been reported that APOA1 -75G/A polymorphism might be associated with susceptibility to coronary artery disease (CAD). Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between APOA1-75G/A polymorphism and the risk of CAD. A systematic search of studies on the association of single nucleotide polymorphisms (SNP) with susceptibility to CAD was conducted. A total of 9 case-control studies (1864 cases and 1196 controls) on the APOA1-75G/A polymorphism were included. We observed no statistically significant association between APOA1 -75G/A polymorphism and risk of CAD under the dominant genetic model (AA + AG vs. GG: OR = 1.03, 95% CI: 0.65-1.66), allelic contrast (A vs. G: OR = 0.88, 95% CI: 0.58-1.32), heterozygote model (AG vs. GG: OR = 1.24, 95% CI: 0.81-1.89) or homozygote model (AA vs. GG: OR = 0.52, 95% CI: 0.26-1.05). Significant heterogeneity between individual studies appears in all five models, but a strong association under the recessive genetic model (AA vs. AG + GG: OR = 0.51, 95% CI: 0.28-0.92). In the subgroup analysis by Hardy-Weinberg equilibrium (HWE; the presence or absence of HWE in controls), significantly decreased CAD risk and no significant heterogeneity were observed among controls consistent with HWE. Overall, the APOA1 A allele is one of the protective factors of CAD. A stronger association between APOA1-75G/A polymorphisms and CAD risk was present in the studies consistent with HWE. The minor allele of the APOA1-75G/A polymorphism is a protective factor for CAD, especially in the studies consistent with HWE.


Evidence for environment-dependent introgression of adaptive genes between two red oak species with different drought adaptations.
Introgression of adaptive alleles between hybridizing species is likely an important mechanism to generate new genetic variation for adaptation to rapidly changing environmental conditions. Oaks provide a model for the study of adaptive gene introgression because environmental selection maintains high interspecific differentiation at a few outlier loci and species-specific adaptations despite recurrent interspecific gene flow. Previously, we identified a CONSTANS-like gene under strong divergent selection between drought-tolerant Quercus ellipsoidalis and drought-averse Quercus rubra. Neighboring (parapatric) populations of both species were fixed for alternate alleles, Q. ellipsoidalis for allele 138 and Q. rubra for allele 141. In this study, we analyzed introgression of these outlier alleles in sympatric and in parapatric Q. rubra/Q. ellipsoidalis populations. We found evidence that environmental selection affected the level and direction of outlier allele introgression. Thus, in the face of symmetric interspecific gene flow, outlier allele introgression was asymmetric and introgression of allele 138 into Q. rubra was consistently higher than introgression of allele 141 into Q. ellipsoidalis in sympatric populations, but the opposite pattern was found in parapatric populations. Furthermore, the rate of introgression of outlier alleles between species in sympatric stands was related to soil quality (i.e., soil water holding capacity, nutrient availability). This pattern suggests that introgression of adaptive genes between these two red oak species is strongly affected by environmental selection and is an important mechanism for species' adaptation to changing environmental conditions in a changing climate.


Benign prostatic hyperplasia: does prostate size matter?
Recent studies and analyses have confirmed that baseline prostate volume is related to progression of benign prostatic hyperplasia (BPH) as well as to negative outcomes related to BPH, such as acute urinary retention (AUR) and need for surgery, and can also predict response to therapy. Other investigations have determined that prostate-specific antigen (PSA) level has good predictive value for assessing prostate volume. Strong evidence exists that baseline serum PSA level, like baseline prostate volume, predicts future prostate growth. Randomized placebo-controlled finasteride trials have shown that men with larger prostate volumes and higher PSA levels experience a clinically significant response to therapy compared with those with smaller prostate volumes and lower PSA levels. It has also been demonstrated that men with larger prostate glands and higher PSA levels are at increased risk for AUR and BPH-related surgery but that finasteride reduces these risks. Moreover, doxazosin and finasteride, alone and in combination, have been shown to significantly reduce BPH clinical progression.


Lamivudine versus Entecavir for Newly Diagnosed Hepatitis B Virus-Related Hepatocellular Carcinoma.
Antiviral therapy is a key component in the management of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. However, whether the potent drug entecavir is more effective than a less potent drug, such as lamivudine, in HBV-related HCC is not clear. A retrospective cohort of 451 newly diagnosed, HBV-related HCC patients without antiviral therapy at diagnosis, who started antiviral therapy with either entecavir (n=249) or lamivudine (n=202), were enrolled. The median survival was longer for the entecavir group than for the lamivudine group, and lamivudine use (vs entecavir) was an independent factor for mortality (hazard ratio [HR], 1.49; p=0.002). Lamivudine use (vs entecavir) was an independent risk factor for new-onset hepatic decompensation (HR, 1.67; p=0.010) in 318 patients without previous hepatic decompensation, and it was also an independent risk factor for recurrence after curative therapy (HR, 1.84; p=0.002) in 117 patients who received curative therapy. The findings were similar in a propensity score-matched cohort. Overall survival, decompensation-free survival, and recurrence-free survival were better in the entecavir-treated patients than in the lamivudine treated-patients, indicating that the potent antiviral drug should be the preferred choice in HBV-related HCC patients.


LSTMAtU-Net: A Precipitation Nowcasting Model Based on ECSA Module.
Precipitation nowcasting refers to the use of specific meteorological elements to predict precipitation in the next 0-2 h. Existing methods use radar echo maps and the Z-R relationship to directly predict future rainfall rates through deep learning methods, which are not physically constrained, but suffer from severe loss of predicted image details. This paper proposes a new model framework to effectively solve this problem, namely LSTMAtU-Net. It is based on the U-Net architecture, equipped with a Convolutional LSTM (ConvLSTM) unit with the vertical flow direction and depthwise-separable convolution, and we propose a new component, the Efficient Channel and Space Attention (ECSA) module. The ConvLSTM unit with the vertical flow direction memorizes temporal changes by extracting features from different levels of the convolutional layers, while the ECSA module innovatively integrates different structural information of each layer of U-Net into the channelwise attention mechanism to learn channel and spatial information, thereby enhancing attention to the details of precipitation images. The experimental results showed that the performance of the model on the test dataset was better than other examined models and improved the accuracy of medium- and high-intensity precipitation nowcasting.


Molecular probe for identification of medically important Candida species and Torulopsis glabrata.
A cloned DNA fragment from Candida albicans containing the gene for the protein actin was used to probe the molecular structure of the actin gene of several medically important yeasts (C. albicans, Candida stellatoidea, Candida tropicalis, Candida pseudotropicalis, Candida krusei, Candida parapsilosis, Candida guilliermondii, and Torulopsis glabrata). Whole-cell DNA from each species was digested with restriction endonucleases, electrophoresed on agarose gels, and transferred to nitrocellulose. Radioactively labeled C. albicans actin gene was hybridized to the DNA fragments on the nitrocellulose. The C. albicans probe produced a strong signal with all of the Candida DNAs tested, indicating considerable conservation of this gene. In addition, the actin genes of all of the species tested were found to have no internal EcoRI or SalI restriction sites. With the exception of C. guilliermondii, all of the species tested had a single internal HindIII recognition site. However, the location of flanking restriction sites was found to be species specific. For all of the enzymes tested, the locations of the flanking restriction sites in C. albicans and C. stellatoidea were identical; all of the other strains yielded fragments clearly distinct from one another. These differences provide a molecular tool for the differentiation of medically important Candida species.


Platelet glycoprotein IIb/IIIa antagonists: lessons learned from clinical trials and future directions.
Platelets play an important role in the pathophysiology of acute myocardial infarction, unstable angina, and ischemic stroke. The expression of the glycoprotein IIb/IIIa (alphaIIb/beta3 integrin) receptor on the surface of activated platelets constitutes the common pathway for platelet aggregation. Glycoprotein IIb/IIIa has low affinity for its soluble ligands (fibrinogen and von Willebrand factor) in resting platelets. In the setting of vascular injury, platelet activation occurs after binding of the glycoprotein Ib-IX-V receptor to von Willebrand factor in the extracellular matrix (at high shear rate) and binding of soluble agonists to specific platelet membrane receptors. The ensuing inside-out signaling increases several-fold the affinity and avidity of alphaIIb/beta3 for its ligands. High affinity ligand binding to alphaIIb/beta3 triggers outside-in signaling, causing microskeletal contraction and platelet retraction. The signaling pathways for inside-out and outside-in signaling are incompletely understood. Glycoprotein IIb/IIIa antagonists were developed under the premise that these agents would abrogate platelet aggregation while preserving platelet monolayer deposition at sites of injury. A number of parenteral and oral agents have been developed and evaluated in clinical trials. Three of them are approved in the United States and other countries: abciximab (ReoPro; the Fab fragment of a chimeric human-mouse antibody), eptifibatide (Integrelin; a cyclic heptapeptide), and tirofiban (Aggrastat; a tyrosine-derived nonpeptide molecule). The greatest clinical impact of these parenteral agents (used in conjunction with aspirin and heparin) has been in the prevention of ischemic complications after percutaneous coronary intervention. In contrast, oral agents have yielded disappointing results in the secondary prevention of acute coronary syndromes, and none of them are approved at present. Eptifibatide and tirofiban are specific for alphaIIb/beta3, whereas abciximab also exhibits cross-reactivity with the alphavbeta3 and alphaMbeta2 integrins. Although alphaIIb/beta3 is unique to platelets and megakaryocytes, alphavbeta3 is more widely distributed and mediates several functions, including endothelial cell migration, monocyte adhesion, angiogenesis, and inhibition of apoptosis. alphaMbeta2 mediates leukocyte-platelet interactions. In the percutaneous coronary intervention trials, abciximab has been more efficacious than the other parenteral agents, perhaps because of cross-reactivity with these other integrins, the pharmacodynamic profile of abciximab, or other effects. Other documented effects of abciximab include acute dethrombosis, reduction of thrombin generation, and improved flow in the coronary microcirculation after percutaneous coronary intervention. Abciximab is presently under evaluation in the treatment of acute ischemic stroke. Promising data have been obtained in experimental models of tumor angiogenesis and sickle cell anemia.


The effect of changes in iron redox state on the activity of enzymes sensitive to modification of SH groups.
Iron ions in micromolar concentrations induced a rapid and selective inhibition of the activity of skeletal muscle creatine kinase (CK), sarcoplasmic reticulum (SR) Ca(2+)-ATPase, and pyruvate kinase (PK). This effect of iron was dependent on the presence of adenine nucleotides and on the redox state of iron. Changing the redox state of the media created different Fe2+/Fe3+ ratios which selectively depressed different enzymes: depression of PK activity occurred when iron was predominantly in its reduced form and, consequently, when there was a high Fe2+/Fe3+ ratio; depression of SR Ca2+ uptake and SR Ca(2+)-ATPase activity occurred when the Fe2+/Fe3+ ratio was close to 1; depression of CK activity occurred when iron was predominantly in its oxidized form and the Fe2+/Fe3+ ratio was low. All iron-sensitive enzymes possessed sulfhydryl groups, accessible to N-ethylmaleimide (NEM), which were essential for their activity. The rate of inhibition of enzyme activity with NEM increased in the order PK < Ca(2+)-ATPase < CK. Iron-induced depression of CK and PK activities was reversible by dithiotreithol. Results suggest that changes in the redox state of cellular microenvironments, which inevitably occur during reperfusion of ischemic tissue or rapid increase in tissue oxygen consumption, may selectively depress the activity of several enzymes bearing SH groups that are sensitive to modifications and that are essential for their activity. Iron-induced depression of enzyme activity depends on the availability of iron bound to adenine nucleotides and possibly to other low molecular weight chelators and on the Fe2+/Fe3+ ratio generated by the induced redox change.


Tuning bacterial hydrodynamics with magnetic fields.
Magnetotactic bacteria are a group of motile prokaryotes that synthesize chains of lipid-bound, magnetic nanoparticles called magnetosomes. This study exploits their innate magnetism to investigate previously unexplored facets of bacterial hydrodynamics at surfaces. Through use of weak, uniform, external magnetic fields and local, micromagnetic surface patterns, the relative strength of hydrodynamic, magnetic, and flagellar force components is tuned through magnetic control of the bacteria's orientation. The resulting swimming behaviors provide a means to experimentally determine hydrodynamic parameters and offer a high degree of control over large numbers of living microscopic entities. The implications of this controlled motion for studies of bacterial motility near surfaces and for micro- and nanotechnology are discussed.


Entrepreneurial management technology for nursing professionals.
to validate entrepreneurial management technology for the nursing practice. methodological study, carried out based on the development of an entrepreneurial management technology, based on literature review and, later, content validation by 11 experts, recognized by their peers as entrepreneurs. The validation process took place through Delphi conferences, between June and September 2018. on the second round of Delphi conferences, at least 90% agreement was obtained on all items. In addition, all items were validated as pertinent and considered prospective and inducing of new thinking and acting among nursing professionals who wish to undertake and explore opportunities, goods, and services in the area. it was noted that the experts, in general, showed good adherence to the initiative and ease in validating the theoretical-conceptual dimension and the dimension of "Personal/professional qualities necessary for the performance of entrepreneurial management"; however, they had difficulty in validating the methodological steps.


Reaction of glycosyl isothiocynates with 3-indolylaminomethyl-ketone hydrochloride.
Reaction of glycosyl isothiocyanate la-c with 3-indolylaminomethylketone hydrochloride(2) yielded glycosylthiourea derivatives 3a-c. Cyclodehydration of 3a-c with acetic anhydride afforded 5-(indol-3-yl)-2-[N-per-O-acetyl-D-glycopyranosyl)amino]thiazoles 4a-c. Deacetylation of 4a-c gave 5-(indol-3-yl)-2-[N-(D-glycopyranosyl) amino] thiazoles 5a-c.


Biomarkers of Kidney Injury in Very-low-birth-weight Preterm Infants: Influence of Maternal and Neonatal Factors.
Acute kidney injury is an important cause of mortality in very-low-birth-weight (VLBW) preterm infants. As in the general population, the detection of renal damage cannot rely on the measurement of serum creatinine, since it has been demonstrated to be a weak predictor and a delayed indicator of kidney function deterioration. However, several candidate biomarkers have failed to prove sufficient specificity and sensitivity for a routine clinical use because of the poor awareness of their biological role. This study was aimed to investigate the impact of different maternal and neonatal conditions on several renal biomarkers in VLBW preterm infants during the first week of life. Preterm infants<32 weeks' gestation and <1500g were enrolled. We measured urinary biomarkers kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, epidermal growth factor (EGF) and osteopontin (OPN) on the 1st, 3rd, and 7th day after birth. Thirty-tree infants were included. The multivariate analysis showed a significant association between gestational age, the presence of patent ductus arteriosus, antenatal maternal hypertension and the levels of urinary biomarkers. There is a possible relation between early biomarkers of renal injury and antenatal, perinatal and post-natal characteristics in VLBW preterm infants during the first week of life.


Nonequilibrium molecular dynamics calculation of the thermal conductivity of amorphous polyamide-6,6.
The thermal conductivity of the amorphous phase of polyamide-6,6 is investigated by nonequilibrium molecular dynamics simulations. Two different algorithms are used, reverse nonequilibrium molecular dynamics and the dual-thermostat method. Particular attention is paid to the force field used. Four different models are tested, flexible and rigid bonds and all-atom and united-atom descriptions. They mainly differ in the number of high-frequency degrees of freedom retained. The calculated thermal conductivity depends systematically on the number of degrees of freedom of the model. This dependence is traced to the quantum nature of the fast molecular vibrations, which are incorrectly described by classical mechanics. The best agreement with experiment is achieved for a united-atom model with all bonds kept rigid. It could be shown that both the thermal conductivity and the heat capacity of a model show a similar (but not equal) dependence on its number of degrees of freedom. Hence, the computationally more convenient heat capacity can be used for force field optimization. A side result is the anisotropy of the thermal conductivity in stretched polyamide; heat conduction is faster parallel to the drawing direction than perpendicular to it.


Oxidative stress indices in Nigerian pesticide applicators and farmers occupationally exposed to organophosphate pesticides.
Reports have clearly indicated the role of oxidative stress in the pathogenesis of organophosphate pesticides (Op) toxicity. However, there is dearth of information on which group of the farm workers is more at risk of Op-induced oxidative stress. This study determined serum levels of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), myeloperoxidase (MPO), nitric oxide (NO), and serum activity of acetylcholinesterase (AChE) in farm workers exposed to Op. A total of 60 (30 pesticide applicators and 30 farmers) and 30 apparently healthy non-farmers who were nonexposed to Op (controls) were recruited into this study. Serum activity of AChE was determined using high performance liquid chromatography (HPLC), while serum levels of MDA, GSH, and NO and serum activities of CAT, MPO, GPx, and superoxide dismutase (SOD) were determined colorimetrically. Serum activities of AChE and CAT were significantly lower, whereas MPO activity was significantly higher in pesticide applicators compared with controls. Similarly, farmers had significantly reduced serum AChE activity and significantly raised MPO activity compared with controls. However, serum activities of AChE, CAT, and MPO were significantly lower, whereas mean level of MDA was significantly higher in pesticide applicators compared with farmers. This study shows that Op applicators are more exposed to oxidative stress than farmers, thus Op applicators require increased antioxidant supplements than farmers.


Evaluation of abrin induced nephrotoxicity by using novel renal injury markers.
Abrin is a potent plant toxin analogous to ricin that is derived from the seeds of Abrus precatorius plant. It belongs to the family of type II ribosome-inactivating proteins and causes cell death by irreversibly inactivating ribosomes through site-specific depurination. In this study we examined the in vivo nephrotoxicity potential of abrin toxin in terms of oxidative stress, inflammation, histopathological changes and biomarkers of kidney injury. Animals were exposed to 0.5 and 1.0 LD50 dose of abrin by intraperitoneal route and observed for 1, 3, and 7 day post-toxin exposure. Depletion of reduced glutathione and increased lipid peroxidation levels were observed in abrin treated mice. In addition, abrin also induced inflammation in the kidneys as observed through expression of MMP-9 and MMP-9/NGAL complex in abrin treated groups by using zymography method. Nephrotoxicity was also evaluated by western blot analysis of kidney injury biomarkers including Clusterin, Cystatin C and NGAL, and their results indicate severity of kidney injury in abrin treated groups. Kidney histology confirmed inflammatory changes due to abrin. The data generated in the present study clearly prove the nephrotoxicity potential of abrin.


Fluorescent vasotocin conjugate for identification of the target cells for brain actions of vasotocin.
The effects of neuropeptides on the brain are a major focus of neuroendocrine research, and little progress has been made in the identification of the target neurons for many neuropeptides. Arginine8-vasotocin (AVT) is a neurohypophyseal peptide present in nonmammalian vertebrates that controls many neural and behavioral functions. Here we describe synthesis and functional characterization of an AVT-Oregon green conjugate 1 (AVT-OG 1) that can be used in vivo to identify AVT target neurons. Application of AVT-OG 1 to the brainstem of an amphibian produces rapid, endosome-like internalization together with typical AVT-like neurophysiological effects. Thus, preparation of AVT-OG 1, which preserves the peptide's neurophysiological effects, is useful as a fluorescent marker for AVT target neurons. Consequently, AVT-OG 1 conjugate will have considerable utility for analyzing the neural actions of AVT in the intact brain.


Interaction of forskolin with the P-glycoprotein multidrug transporter.
Forskolin and 1,9-dideoxyforskolin, an analogue that does not activate adenylyl cyclase, were tested for their ability to enhance the cytotoxic effects of adriamycin in human ovarian carcinoma cells, SKOV3, which are sensitive to adriamycin and express low levels of P-glycoprotein, and a variant cell line, SKVLB, which overexpresses the P-glycoprotein and has the multidrug resistance (MDR) phenotype. Forskolin and 1,9-dideoxyforskolin both increased the cytotoxic effects of adriamycin in SKVLB cells, yet had no effect on SKOV3 cells. Two photoactive derivatives of forskolin have been synthesized, 7-O-[[2-[3-(4-azido-3- [125I]iodophenyl)propionamido]ethyl] carbamyl]-7-deacetylforskolin, 125I-7-AIPP-Fsk, and 6-O-[[2-[3-(4-azido-3- [125I]iodophenyl)propionamido]ethyl]carbamyl]forskolin, 125I-6-AIPP-Fsk, which exhibit specificity for labeling the glucose transporter and adenylyl cyclase, respectively (Morris et al., 1991). Both photolabels identified a 140-kDa protein in membranes from SKVLB cells whose labeling was inhibited by forskolin and 1,9-dideoxyforskolin. There was no specific labeling of proteins in membranes from the SKOV3 cells. The overexpressed 140-kDa protein in SKVLB membranes was identified as the P-glycoprotein by immunoblot analysis and immunoprecipitation using anti-P-glycoprotein antiserum. Total inhibition of photolabeling of the P-glycoprotein was observed with verapamil, nifedipine, diltiazem, and vinbalastine, and partial inhibition was observed with colchicine and cytochalasin B. Forskolin was less effective at inhibiting the photolabeling of the P-glycoprotein than 1,9-dideoxyforskolin or a lipophilic derivative of forskolin. The data are consistent with forskolin binding to the P-glycoprotein analogous to that of other chemosensitizing drugs that have been shown to partially reverse MDR.(ABSTRACT TRUNCATED AT 250 WORDS)


[Encapsulating peritoneal sclerosis in a patient who had previously been in peritoneal dialysis].
Encapsulating peritoneal sclerosis (EPS) is a rare but potentially fatal complication to long-term peritoneal dialysis (PD). We describe a case of EPS in a 58-year-old patient who had formerly had PD. The interdisciplinary approach for diagnosis and possible treatments in this condition is discussed.


Team learning in medical education: initial experiences at ten institutions.
In the midst of curricular reforms that frequently call for reducing lectures and increasing small-group teaching, there is a crisis in faculty time for teaching. This paper describes the initial experiences of ten institutions with team learning (TL), a teaching method which fosters small-group learning in a large-class setting. After initial pilot studies at one institution, nine additional institutions implemented TL in one or more courses. Within 18 months, TL has been used in 40 courses (from.5% to 100% of the time) and all ten institutions will increase its use next year. We surmise that this relatively rapid spread of TL into the medical curriculum is due to the sound pedagogy and efficiency of TL as well as the modest financial resources and support we have provided to partner institutions.


IL-2 receptor expression in autoimmune MRL-lpr/lpr mice. The expanded L3T4-, Lyt-2- population does not express p75 and cannot generate functional high-affinity IL-2 receptors.
Autoimmune MRL-lpr/lpr mice develop an SLE-like disease characterized by a profound lymphadenopathy within an L3T4-, Lyt-2- (DN), B220+ T-cell population. Despite its immature phenotype this subset expresses mature alpha beta TCR belonging predominantly to the V beta 8 gene family and appears to be identical to an activated form of a minor T cell population present in both the thymus and periphery of normal mice. However, the mechanisms underlying the greatly increased cellularity in lpr/lpr-bearing mice are not understood. In this study, the IL-2R expression of lpr/lpr T cells was examined to assess the contribution of IL-2-mediated division to their expansion. The lpr/lpr DN T cells lacked high-affinity IL-2R, even after stimulation, suggesting that IL-2-dependent proliferation plays no role in the expansion of these cells and demonstrating the existence of this unusual T cell phenotype in vivo.


The risk of spinal cord injury during the frozen elephant trunk procedure in acute aortic dissection.
The aim of the study was to access the extended occlusion of the intercostal arteries by a stent graft in the development of postoperative spinal cord injury during aortic arch surgery using the frozen elephant trunk technique. A total of 37 consecutive patients underwent total aortic arch surgery using the frozen elephant trunk technique between March 2012 and July 2017. The mean age of the patients was 54.7 ± 10.5 years. Type A and Type B aortic dissections were the indications for surgery. Moderate hypothermia and antegrade cerebral perfusion via the innominate artery were utilized. The mean diameter of the implanted stent graft was 27.7 ± 2 mm (range 24-30 mm). No permanent spinal cord injuries occurred. The distal edge of the stent graft was in the T7-T12 range. Its lower edge was implanted at the T9-T12 level in 25 (67.6%) cases. Preoperatively, the mean number of intercostal arteries was 10 ± 1 on the left side and 10 ± 2 on the right side (P = 0.59). Postoperatively, the mean number of open segmental arteries was 3 ± 2 on the left and 4 ± 1 on the right (P = 0.003). The frozen elephant trunk procedure is associated with the occlusion of most (two-thirds) of the intercostal arteries. Maintenance of adequate blood flow in the subclavian and iliac arteries is an integral prerequisite for a favourable outcome. The level of the deployment of the distal edge of the stent graft does not play a defining role.


The Beaumont behavioral intervention in a Chinese amyotrophic lateral sclerosis cohort.
The prevalence of behavior impairment (27.38%) in the Chinese amyotrophic lateral sclerosis (ALS) cohort is lower. We hypothesize that the screening scales used among studies might not be appropriate to diagnose behavioral disorders in ALS patients. So, we urgently need to find a behavior scale with a high detection rate designed specifically for ALS. This study aims to verify the Chinese translation of the Beaumont Behavioral Inventory (BBI) as an effective assessment in a Chinese ALS cohort. Ninety-eighty ALS patients and ninety-three healthy controls were included in this cross-sectional study. All participants took emotional state, overall cognitive, sleep quality and gastroenteric function, and behavioral evaluation. The BBI scores showed a strong association with the amyotrophic lateral sclerosis-Frontotemporal Dementia-Questionnaire (ALS-FTD-Q) (rs = 0.71, p < 0.001) as well as a moderate correlation with the Frontal Behavioral Inventory (FBI) (rs = 0.55, p < 0.001). High internal consistency was demonstrated in patients using BBI-after items (Cronbach's a = 0.89). When tested against clinical diagnoses, the optimal cutoff of total BBI score was identified at 5.5 (AUC = 0.95; SE = 0.02; 95% CI [0.91, 0.99]), the BBI reached optimal sensitivity and specificity values (91.5% and 87.2%). The BBI turned out to be more precise than the FBI (AUC = 0.76; SE = 0.05; 95% CI [0.66, 0.86]) and the ALS-FTD-Q (AUC = 0.84; SE = 0.04; 95% CI [0.77, 0.92]). The Chinese version of BBI is a quicker and more efficient instrument for assessing behavioral impairment in the ALS population in China.


Berberine suppresses TNF-alpha-induced MMP-9 and cell invasion through inhibition of AP-1 activity in MDA-MB-231 human breast cancer cells.
Invasion of cancer cell induced by matrix metalloproteinase-9 (MMP-9) is one of pivotal steps in cancer metastasis. Herein, we investigated how cell invasion was regulated by berberine (BBR), an isoquinoline derivative alkaloid compound, in MDA-MB-231 human breast cancer cells. The basal level of MMP-9 activity and expression was dose-dependently increased by TNF-alpha, while TNF-a-induced MMP-9 gelatinase activity and expression was decreased by BBR. To investigate regulatory mechanism of TNF-alpha-induced MMP-9 expression, we pretreated cells with UO126 (MEK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor), respectively. Interestingly, TNF-alpha-induced MMP-9 activity and expression was decreased by UO126 and SB203580, but not by SP600125. Therefore, we further examined the effects of BBR on TNF-alpha-induced AP-1 DNA binding activity which is a downstream target of ERK and p38. Our data showed that TNF-alpha-induced AP-1 DNA binding activity was inhibited by BBR. Finally, we investigated the effect of BBR on TNF-alpha-induced cell invasion. TNF-alpha-induced cell invasion was significantly decreased by BBR treatment. Taken together, we suggest that TNF-alpha-induced MMP-9 expression and cell invasion are decreased by BBR through the suppression of AP-1 DNA binding activity in MDA-MB-231 human breast cancer cells.


Deal breakers in the organ donation request process.
Organ donation consent rates have stagnated at about 50%, while the need for transplantable organs continues to increase. This article focuses on consent rates of families who make a donation decision for a deceased loved one, and how social marketing efforts to increase organ donation can be enhanced by better understanding the decision-making process these families use. Three categories of factors bear significantly on that decision which, if not addressed properly, will very likely result in a refusal to donate. These "deal breaker" categories include (1) family predisposition and family care, (2) requestor characteristics, and (3) request dynamics. Recommendations are made toward developing best practices protocols which roughly parallel promotion activities and the selling process utilized in commercial marketing for overcoming these barriers.


Synthesis and Characterization of a New Bivalent Ligand Combining Caffeine and Docosahexaenoic Acid.
Caffeine is a promising drug for the management of neurodegenerative diseases such as Parkinson's disease (PD), demonstrating neuroprotective properties that have been attributed to its interaction with the basal ganglia adenosine A2A receptor (A2AR). However, the doses needed to exert these neuroprotective effects may be too high. Thus, it is important to design novel approaches that selectively deliver this natural compound to the desired target. Docosahexaenoic acid (DHA) is the major omega-3 fatty acid in the brain and can act as a specific carrier of caffeine. Furthermore, DHA displays properties that may lead to its use as a neuroprotective agent. In the present study, we constructed a novel bivalent ligand covalently linking caffeine and DHA and assessed its pharmacological activity and safety profile in a simple cellular model. Interestingly, the new bivalent ligand presented higher potency as an A2AR inverse agonist than caffeine alone. We also determined the range of concentrations inducing toxicity both in a heterologous system and in primary striatal cultures. The novel strategy presented here of attaching DHA to caffeine may enable increased effects of the drug at desired sites, which could be of interest for the treatment of PD.


Titanium mesh and autogenous iliac bone graft: treatment of a mandibular fracture delayed for one year.
In treatment of bone defects, transplantation of autogenous iliac bone and marrow give satisfactory results. Titanium mesh implants have also been used reconstruction of maxillofacial defects for years. Specifically, this technique of provides stabilization in ununited fractures of edentulous and atrophic mandibles, and facilitate bone grafting. This paper report the use of titanium mesh and autogenous iliac bone grafting in an ununited mandibular fracture one year after injury.


Children's pain assessment in northeastern Thailand: perspectives of health professionals.
Deficiencies in pain care within the developing world are starting to be realized. Children, in particular, are vulnerable, as preliminary studies suggest that these children receive less pain treatment because of health professionals' attitudes and beliefs. This article reports on some of the findings of the first study in a larger program of research aimed at improving pediatric pain care in Thailand. Improvements in practice are not simply the result of providing evidenced-based knowledge, but a complex process that includes the context of care. Given that little is known about the pain management experiences of Thai health professionals, including the challenges they face, we used focus groups to capture their stories. Data revealed a need for both updating pain knowledge and for supporting an increased use of appropriate practices. In this article, we focus on the issues concerning the assessment of pain resulting from underrecognizing children's pain and complex issues in communicating findings of children's pain.


Transumbilical single-incision laparoscopic distal pancreatectomy: preliminary experience and comparison to conventional multi-port laparoscopic surgery.
Single-incision laparoscopic surgery (SILS), which has been demonstrated to be safely applied on kinds of surgeries, may represent an improvement over conventional multi-port laparoscopic surgery. However, there are still few clinical experiences of SILS in pancreatic surgery until now. In this study, we will summarize our experience of transumbilical single-incision laparoscopic distal pancreatectomy (TUSI-LDP), and compare its related parameters with conventional multi-port laparoscopic distal pancreatectomy (C-LDP). A retrospective analysis was conducted for the patients who underwent C-LDP or TUSI-LDP in our department. The demographic data, operative parameters, and postoperative complications in the two groups were summarized and compared. Laparoscopic distal pancreatectomy was performed in a total of 21 cases, among which TUSI-LDP was performed in 14 cases. As far as the demographical results concerned, there were no significant differences between the two groups. The conversion to open surgery was conducted in one case in the TUSI-LDP group because of severe adhesion between pancreatic cyst and surrounding tissues, while in the C-LDP group the only one conversion was for the difficult detection of small lesion. The mean operating time and intraoperative blood loss in TUSI-LDP group was a little shorter (166.4 ± 57.4 versus 202.1 ± 122.5 minutes, p > 0.05, and 157.1 ± 162.4 versus 168.6 ± 157.4 ml, p > 0.05). The postoperative pain and post-operation lengths of hospital stay in the TUSI-LDP group were also less, though there was no significant statistical difference between the two groups. For the post-operation complications, in TUSI-LDP group the pancreatic leakage occurred in only one case, and ceased spontaneously with only a drain for 61 days. There were no other complications including postoperative hemorrhage, venous thrombosis, infections and so on in both groups. For the experienced laparoscopic surgeons, in selected patients, TUSI-LDP is a feasible technique, with excellent cosmetic effect, less postoperative pain and post-operation lengths of hospital stay. With the experience accumulated, the operating time and intraoperative blood loss of TUSI-LDP could also gradually reduce.


The Ecology of Agrobacterium vitis and Management of Crown Gall Disease in Vineyards.
Agrobacterium vitis is the primary causal agent of grapevine crown gall worldwide. Symptoms of grapevine crown gall disease include tumor formation on the aerial plant parts, whereas both tumorigenic and nontumorigenic strains of A. vitis cause root necrosis. Genetic and genomic analyses indicated that A. vitis is distinguishable from the members of the Agrobacterium genus and its transfer to the genus Allorhizobium was suggested. A. vitis is genetically diverse, with respect to both chromosomal and plasmid DNA. Its pathogenicity is mainly determined by a large conjugal tumor-inducing (Ti) plasmid characterized by a mosaic structure with conserved and variable regions. Traditionally, A. vitis Ti plasmids and host strains were differentiated into octopine/cucumopine, nopaline, and vitopine groups, based on opine markers. However, tumorigenic and nontumorigenic strains of A. vitis may carry other ecologically important plasmids, such as tartrate- and opine-catabolic plasmids. A. vitis colonizes vines endophytically. It is also able to survive epiphytically on grapevine plants and is detected in soil exclusively in association with grapevine plants. Because A. vitis persists systemically in symptomless grapevine plants, it can be efficiently disseminated to distant geographical areas via international trade of propagation material. The use of healthy planting material in areas with no history of the crown gall represents the crucial measure of disease management. Moreover, biological control and production of resistant grape varieties are encouraging as future control measures.


Allergic contact dermatitis from EMLA cream: concomitant sensitization to both local anesthetics lidocaine and prilocaine.
Local anesthetics are widely used drugs. In contrast to the local anesthetics of the ester group, the ones of the amide group (for example prilocaine and lidocaine) are considered to be rare sensitizers. Positive patch test results to both prilocaine and lidocaine in EMLA cream might indicate potential cross-reactivity.


Development of a stage-scanning system for high-resolution confocal STEM.
A stage-scanning system is composed of a specially designed transmission electron microscopy specimen holder equipped with a piezo-driven specimen stage, power supplier and control software. This system enables the specimen to be scanned three-dimensionally, and therefore confocal scanning transmission electron microscopy (STEM) can be performed with a fixed electron-optics configuration. It is demonstrated that stage-scanning confocal STEM images can be obtained with the lateral atomic resolution and the specimen can be moved three-dimensionally with high precision.


Interferometric Diffraction from Amorphous Double Films.
We explore the interference fringes that arise in diffraction patterns from double-layer amorphous samples where there is a substantial separation, up to about a micron, between two overlapping thin films. This interferometric diffraction geometry, where both waves have interacted with the specimen, reveals phase gradients within microdiffraction patterns. The rapid fading of the observed fringes as the magnitude of the diffraction vector increases confirms that displacement decoherence is strong in high-energy electron scattering from amorphous samples. The fading of fringes with increasing layer separation indicates an effective illumination coherence length of about 225 nm, which is consistent with the value of 270 nm expected for the heated Schottky field emitter source. A small reduction in measured coherence length is expected because of the additional energy spread induced in the beam after it passes through the first layer.


miR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis via Targeting the FOG2/PI3K Pathway.
Although expression of miR-200s is aberrant in liver fibrosis, its role in liver fibrogenesis still remains unknown. Here, we investigated the role of miR-200c in the activation of human hepatic stellate cells (HSCs) and induction of liver fibrosis. We engineered human HSCs (LX2 cell line) to stably express miR-200c (LX2-200c) or empty vector control (LX2-nc). miR-200c expression upregulated α-smooth muscle actin (SMA) and vimentin, enhanced HSCs growth and migration, increased expression of collagen type I (a main component of ECM) gene and secretion of epidermal growth factor (EGF), and upregulated the phosphorylation of Akt, a downstream effector of the PI3K pathway. As a target of miR-200s and inhibitor of PI3K pathway, FOG2 protein expression was significantly suppressed in LX2-200c cells. Moreover, LY294002, a highly selective inhibitor of PI3K, blocked phosphorylation of Akt and the effects of miR-200c. These data suggest that miR-200c activates HSCs in liver fibrosis possibly by downregulating FOG2 protein expression and upregulating PI3K/Akt signaling. Autocrine activation of EGF signaling may also be a mechanism of miR-200c-mediated HSCs activation. So miR-200c can be a potential marker for HSCs activation and liver fibrosis progression, as well as a potential target to attenuate liver fibrosis.


Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model.
Mesenchymal stem (stromal) cells (MSCs) mediate their immunoregulatory and tissue repair functions by secreting paracrine factors, including extracellular vesicles (EVs). In several animal models of human diseases, MSC-EVs mimic the beneficial effects of MSCs. Influenza viruses cause annual outbreaks of acute respiratory illness resulting in significant mortality and morbidity. Influenza viruses constantly evolve, thus generating drug-resistant strains and rendering current vaccines less effective against the newly generated strains. Therefore, new therapies that can control virus replication and the inflammatory response of the host are needed. The objective of this study was to examine if MSC-EV treatment can attenuate influenza virus-induced acute lung injury in a preclinical model. We isolated EVs from swine bone marrow-derived MSCs. Morphology of MSC-EVs was determined by electron microscopy and expression of mesenchymal markers was examined by flow cytometry. Next, we examined the anti-influenza activity of MSC-EVs in vitro in lung epithelial cells and anti-viral and immunomodulatory properties in vivo in a pig model of influenza virus. MSC-EVs were isolated from MSC-conditioned medium by ultracentrifugation. MSC-EVs were round-shaped and, similarly to MSCs, expressed mesenchymal markers and lacked the expression of swine leukocyte antigens I and II. Incubation of PKH-26-labeled EVs with lung epithelial cells revealed that MSC-EVs incorporated into the epithelial cells. Next, we examined the anti-influenza and anti-inflammatory properties of MSC-EVs. MSC-EVs inhibited the hemagglutination activity of avian, swine, and human influenza viruses at concentrations of 1.25-5 μg/ml. MSC-EVs inhibited influenza virus replication and virus-induced apoptosis in lung epithelial cells. The anti-influenza activity of MSC-EVs was due to transfer of RNAs from EVs to epithelial cells since pre-incubation of MSC-EVs with RNase enzyme abrogated the anti-influenza activity of MSC-EVs. In a pig model of influenza virus, intratracheal administration of MSC-EVs 12 h after influenza virus infection significantly reduced virus shedding in the nasal swabs, influenza virus replication in the lungs, and virus-induced production of proinflammatory cytokines in the lungs of influenza-infected pigs. The histopathological findings revealed that MSC-EVs alleviated influenza virus-induced lung lesions in pigs. Our data demonstrated in a relevant preclinical large animal model of influenza virus that MSC-EVs possessed anti-influenza and anti-inflammatory properties and that EVs may be used as cell-free therapy for influenza in humans.