Sinus floor augmentation with simultaneous implant placement using Choukroun's platelet-rich fibrin as the sole grafting material: a radiologic and histologic study at 6 months.
Sinus augmentation with simultaneous implant placement without bone graft material is a hotly debated technique. This technique could be improved and secured by the use of an autologous leukocyte- and platelet-rich fibrin (PRF) (Choukroun's technique) concentrate. The objectives of this study were to assess the relevance of PRF clots and membranes as the sole filling material during a lateral sinus lift with immediate implantation using radiologic and histologic analyses in a case series. Twenty-five sinus elevations with simultaneous implantation were performed on 20 patients with Choukroun's PRF as the sole filling biomaterial. For each patient, a presurgical exam and a 6-month post-surgical radiologic exam were performed with a panoramic x-ray and three-dimensional volumetric computed radiography (VCR) to evaluate the subsinus residual bone height and the final bone gain around the implants. In nine patients, 6 months after the sinus lift, bone biopsies were collected on the buccal wall of the alveolar ridge at the level of the osteotomy window, and evaluated by histomorphometry. In this study, 41 implants from three different systems with different screw designs (Biomet 3I Nanotite, MIS Seven, Intra-Lock Ossean) were placed. All implants were inserted in residual bone height between 1.5 and 6 mm (mean +/- SD: 2.9 +/- 0.9 mm). The final bone gain was always very significant (between 7 and 13 mm [mean +/- SD: 10.1 +/- 0.9 mm]). No implant was lost. After radiologic analyses, the position of the final sinus floor was always in the continuation of the end of the implant. All biopsies showed well organized and vital bone. From a radiologic and histologic point of view at 6 months after surgery, the use of PRF as the sole filling material during a simultaneous sinus lift and implantation stabilized a high volume of natural regenerated bone in the subsinus cavity up to the tip of the implants. Choukroun's PRF is a simple and inexpensive biomaterial, and its systematic use during a sinus lift seems a relevant option, particularly for the protection of the Schneiderian membrane.


Effect of insulin on renal potassium metabolism.
The effect of insulin on renal potassium excretion was examined by employing the euglycemic insulin clamp technique in combination with renal clearance measurements. While euglycemia was maintained, insulin was infused at rates of 4.8 (n = 7) and 12 (n = 5) mU X kg-1 X min-1. Steady-state plasma insulin levels of 164 +/- 8 and 370 +/- 15 microU/ml were achieved in the low- and high-dose studies, respectively. Base-line plasma potassium concentration declined progressively by a mean of 0.14 +/- 0.09 (P less than 0.05) and 0.40 +/- 0.05 meq/liter (P less than 0.01) during the low- and high-dose insulin infusion protocols. Urinary potassium excretion did not change significantly from base line with either insulin dose. Because the decline in plasma potassium concentration could have masked a stimulatory effect of insulin on UKV, six rats received a 12-mU X kg-1 X min-1 euglycemic insulin clamp in combination with an exogenous potassium infusion to maintain the plasma potassium concentration constant at the basal level (4.03 +/- 0.03 vs. 4.05 +/- 0.05 meq/l). Under these conditions of normokalemia, insulin augmented UKV 2.4-fold, from 0.20 +/- 0.05 to 0.48 +/- 0.04 meq/l (P less than 0.001).


Male Youth Perceptions of Violent Extremism: towards a Test of Rational Choice Theory.
Understanding how people perceive the pros and cons of risky behaviors such as terrorism or violent extremism represents a first step in developing research testing rational choice theory aiming to explain and predict peoples' intentions to engage in, or support, these behaviors. Accordingly, the present study provides a qualitative, exploratory analysis of a sample of 57 male youths' perceptions of the benefits and drawbacks of: (a) accessing a violent extremist website, (b) joining a violent extremist group, and (c) leaving such a group. Youth perceived significantly more drawbacks than benefits of joining a violent extremist group (p = .001, d = .46) and accessing a violent extremist website (p = .001, d = .46). The perceived benefits of engagement referred to gaining knowledge/awareness, being part of a group/similar people, and fighting the enemy/for a cause. The drawbacks referred to being exposed to negative material and emotions, having violent/criminal beliefs and behaviors, and getting in trouble with the law. The perceived benefits of disengagement referred to no longer committing illegal acts, and regaining independence/not being manipulated. The drawbacks referred to exposing oneself to harm and reprisal. These findings provide an insight into how male youth think about (dis)engagement in violent extremism, and can inform future quantitative research designed to explain and predict (dis)engagement in violent extremism. Eventually, such research may inform the development of evidence-based prevention and intervention strategies.


Genetic dissection of the degradation pathways for the mycotoxin fusaric acid in Burkholderia ambifaria T16.
Fusaric acid (FA) is an important virulence factor produced by several Fusarium species. These fungi are responsible for wilt and rot diseases in a diverse range of crops. FA is toxic for animals, humans and soil-borne microorganisms. This mycotoxin reduces the survival and competition abilities of bacterial species able to antagonize Fusarium spp., due to its negative effects on viability and the production of antibiotics effective against these fungi. FA biodegradation is not a common characteristic among bacteria, and the determinants of FA catabolism have not been identified so far in any microorganism. In this study, we identified genes, enzymes, and metabolic pathways involved in the degradation of FA in the soil bacterium Burkholderia ambifaria T16. Our results provide insights into the catabolism of a pyridine-derivative involved in plant pathogenesis by a rhizosphere bacterium.


A New Phylogenetic Framework for the Animal-Adapted Mycobacterium tuberculosis Complex.
Tuberculosis (TB) affects humans and other animals and is caused by bacteria from the Mycobacterium tuberculosis complex (MTBC). Previous studies have shown that there are at least nine members of the MTBC infecting animals other than humans; these have also been referred to as ecotypes. However, the ecology and the evolution of these animal-adapted MTBC ecotypes are poorly understood. Here we screened 12,886 publicly available MTBC genomes and newly sequenced 17 animal-adapted MTBC strains, gathering a total of 529 genomes of animal-adapted MTBC strains. Phylogenomic and comparative analyses confirm that the animal-adapted MTBC members are paraphyletic with some members more closely related to the human-adapted Mycobacterium africanum Lineage 6 than to other animal-adapted strains. Furthermore, we identified four main animal-adapted MTBC clades that might correspond to four main host shifts; two of these clades are hypothesized to reflect independent cattle domestication events. Contrary to what would be expected from an obligate pathogen, MTBC nucleotide diversity was not positively correlated with host phylogenetic distances, suggesting that host tropism in the animal-adapted MTBC seems to be driven by contact rates and demographic aspects of the host population rather by than host relatedness. By combining phylogenomics with ecological data, we propose an evolutionary scenario in which the ancestor of Lineage 6 and all animal-adapted MTBC ecotypes was a generalist pathogen that subsequently adapted to different host species. This study provides a new phylogenetic framework to better understand the evolution of the different ecotypes of the MTBC and guide future work aimed at elucidating the molecular mechanisms underlying host range.


Bortezomib Facilitates Reparative Dentin Formation after Pulp Access Cavity Preparation in Mouse Molar.
The aim of this study was to evaluate in vitro and ex vivo roles of bortezomib, a proteasome inhibitor that binds to the active site of the 26S proteasome, in tertiary dentin formation. We established pulpal access cavity preparation that was treated with or without bortezomib before direct pulp capping with a calcium hydroxide-based material. We also analyzed bone morphogenetic protein (Bmp)- and Wnt-related signaling molecules using quantitative real-time polymerase chain reaction. In the short-term observation period, the bortezomib-treated pulp specimens showed the period-altered immunolocalization patterns of nestin, CD31, and myeloperoxidase, whereas the control specimens did not. The bortezomib-treated group showed a complete dentin bridge with very few irregular tubules after 42 days. The micro-computed tomographic images showed more apparent dentin bridge structures in the treated specimens than were in the controls. Quantitative real-time polymerase chain reaction analysis showed up-regulated Bmp and Wnt. These findings revealed that treatment with 1 μmol/L bortezomib induced reparative dentin formation that facilitated the maintenance of the integrity of the remaining pulpal tissue via early vascularization and regulation of Bmp and Wnt signaling.


Longitudinal associations of physical activity with inflammatory markers in US adults with and without type 1 diabetes.
To investigate the longitudinal associations of different levels of moderate-to-vigorous physical activity (MVPA) with C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), and fibrinogen. We conducted longitudinal analyses with data from the Coronary Artery Calcification in T1D (CACTI) cohort, which included individuals with type 1 diabetes (T1D, n = 563) and without diabetes mellitus (non-DM, n = 692) with ∼ 3 years follow-up. Individuals were divided into groups to perform two analyses: 1) those who performed any MVPA and those who were sedentary (0 mins/week) and 2) those who performed 1-149 mins/week, ≥150 mins/week, or who were sedentary. Mixed effect models with an unstructured covariance structure were applied. Compared to sedentary individuals, any MVPA was associated with a -2.96 % decrease in fibrinogen (p-value = 0.0043) and a -11.23 % decrease in PAI-1 (p-value = 0.0007) in combined analyses. Stratified analyses found 1-149 mins/week and ≥ 150 mins/week were associated with significant decreases in fibrinogen, -5.31 % and -3.44 %, respectively, in those with T1D. Both the non-DM and T1D groups had significant decreases in PAI-1 associated with ≥ 150 mins/week (-9.11 % and -16.96 %, respectively). Our findings highlight that meeting ≥ 150 mins/week of MVPA is inversely associated with inflammatory markers linked with increased CVD risk.


Capturing the dynamics of small populations: A retrospective assessment using long-term data for an island reintroduction.
The art of population modelling is to incorporate factors essential for capturing a population's dynamics while otherwise keeping the model as simple as possible. However, it is unclear how optimal model complexity should be assessed, and whether this optimal complexity has been affected by recent advances in modelling methodology. This issue is particularly relevant to small populations because they are subject to complex dynamics but inferences about those dynamics are often constrained by small sample sizes. We fitted Bayesian hierarchical models to long-term data on vital rates (survival and reproduction) for the toutouwai Petroica longipes population reintroduced to Tiritiri Matangi, a 220-ha New Zealand island, and quantified the performance of those models in terms of their likelihood of replicating the observed population dynamics. These dynamics consisted of overall growth from 33 (±0.3) to 160 (±6) birds from 1992-2018, including recoveries following five harvest events for further reintroductions to other sites. We initially included all factors found to affect vital rates, which included inbreeding, post-release effects (PRE), density-dependence, sex, age and random annual variation, then progressively removed these factors. We also compared performance of models where data analysis and simulations were done simultaneously to those produced with the traditional two-step approach, where vital rates are estimated first then fed into a separate simulation model. Parametric uncertainty and demographic stochasticity were incorporated in all projections. The essential factors for replicating the population's dynamics were density-dependence in juvenile survival and PRE, i.e. initial depression of survival and reproduction in translocated birds. Inclusion of other factors reduced the precision of projections, and therefore the likelihood of matching observed dynamics. However, this reduction was modest when the modelling was done in an integrated framework. In contrast, projections were much less precise when done with a two-step modelling approach, and the cost of additional parameters was much higher under the two-step approach. These results suggest that minimization of complexity may be less important than accounting for covariances in parameter estimates, which is facilitated by integrating data analysis and population projections using Bayesian methods.


Oscillatory network markers of subcallosal cingulate deep brain stimulation for depression.
Identifying functional biomarkers related to treatment success can aid in expediting therapy optimization, as well as contribute to a better understanding of the neural mechanisms of the treatment-resistant depression (TRD) and subcallosal cingulate deep brain stimulation (SCC-DBS). Magnetoencephalography data were obtained from 16 individuals with SCC-DBS for TRD and 25 healthy subjects. The first objective of the study was to identify region-specific oscillatory modulations that both (i) discriminate individuals with TRD (with SCC-DBS OFF) from healthy controls, and (ii) discriminate TRD treatment responders from non-responders (with SCC-DBS ON). The second objective of this work was to further explore the effects of stimulation intensity and frequency on oscillatory activity in the identified brain regions of interest. Oscillatory power analyses led to the identification of brain regions that differentiated responders from non-responders based on modulations of increased alpha (8-12 Hz) and decreased gamma (32-116 Hz) power within nodes of the default mode, central executive, and somatomotor networks, Broca's area, and lingual gyrus. Within these nodes, it was also found that low stimulation frequency had stronger effects on oscillatory modulation than increased stimulation intensity. The identified functional network biomarkers implicate modulation of TRD-related activity in brain regions involved in emotional control/processing, motor control, and the interaction between speech, vision, and memory, which have all been implicated in depression. These electrophysiological biomarkers have the potential to be used as functional proxies for therapy optimization. Additional stimulation parameter analyses revealed that oscillatory modulations can be strengthened by increasing stimulation intensity or reducing frequency, which may represent potential avenues of direction in non-responders.


Physical, morphological and functional differences between ph 5.8 and 7.4 aggregates of the Alzheimer's amyloid peptide Abeta.
The Alzheimer's amyloid peptide Abeta(1-40) generates a turbid, Congo re-binding aggregation reaction product within minutes when incubated in the pH range 5 to 6. At pH 7.4, Abeta forms little or no aggregate in this time frame, requiring hours or days, rather than minutes, to complete fibril formation. The pH 5.8 aggregates are not amyloid fibrils, but rather appear in electron micrographs as a mixture of larger particles of different morphologies. These aggregates differ from classical fibrils by a number of other measures. Per mass of peptide aggregated, the pH 5.8 product binds less Congo red and thioflavin T than does aggregate grow in unstirred reactions at pH 7.4. Both the pH 5.8 and 7.4 aggregates exhibit light scattering at 90 degrees. However, while the pH 5.8 aggregate is visible in suspension by the light microscopy, and exhibits turbidity at 405 nm, the fibrils grown at pH 7.4 in an unstirred reaction are transparent. The two aggregate types do not interconvert in pH shift experiments. Most dramatically, and in contrast to fibrils grown at pH 7.4, the turbid aggregate generated at pH 5.8 is incapable of seeding fibril growth at pH 7.4. Although proteolytic processing of betaAPP to generate Abeta probably takes place in a low pH compartment of the cell, our results suggest that fibril formation is not likely to be initiated in such an environment.


Racial and ethnic differences in albuminuria in individuals with estimated GFR greater than 60 mL/min/1.73 m(2): results from the Kidney Early Evaluation Program (KEEP).
Albuminuria is an important marker for chronic kidney disease and progression to end-stage renal disease in the general population; understanding racial and ethnic differences can help inform efforts to reduce health disparities. We sought to estimate independent associations of race/ethnicity with albuminuria to determine whether observed differences were attributable to known kidney disease risk factors. This cross-sectional study included 64,161 Kidney Early Evaluation Program (KEEP) participants, 2000-2008, with estimated glomerular filtration rate > or = 60 mL/min/1.73 m(2), not on regular dialysis therapy, and without a previous kidney transplant. Albuminuria (urine albumin-creatinine ratio > or = 30 mg/g) was examined by self-reported race and ethnicity. Covariates were age, sex, educational level, body mass index, diabetes status or glucose level, hypertension status or blood pressure measurement, smoking status, health insurance status, and geographic region. Albuminuria prevalences were 8% (n = 2,303) in whites, 11% (n = 2,310) in African Americans, 9% (n = 730) in Hispanics, 10% (n = 381) in Asians, and 15% (n = 344) in American Indians/Alaska Natives. Compared with whites, odds of albuminuria were higher for all groups after multivariate adjustment. Odds were highest for American Indians/Alaska Natives (adjusted OR, 1.93; 95% CI, 1.70-2.20), then Asians (adjusted OR, 1.42; 95% CI, 1.26-1.61), African Americans (adjusted OR, 1.38; 95% CI, 1.29-1.47), and Hispanics (adjusted OR, 1.19; 95% CI, 1.08-1.31). In the KEEP study population, albuminuria prevalence was higher in African Americans, Hispanics, Asians, and American Indians/Alaska Natives than in non-Hispanic whites, suggesting a need for screening for early detection of kidney damage, especially in people at increased risk, in the community primary care setting.


Tumor cells-derived exosomal noncoding RNAs in cancer angiogenesis: Molecular mechanisms and prospective.
Exosomes, heterogeneous, membrane-bound nanoparticles that originated from eukaryotic cells, contribute to intracellular communication by transferring various biomolecules both on their surface and as internal cargo. One of the most significant current discussions on cancer progression is noncoding RNAs cargo of exosomes, which can regulate angiogenesis in tumor. A growing body of evidence shows that exosomes from tumor cells contain various microRNAs, long noncoding RNAs, and circular RNAs that can promote tumor progression by inducing angiogenesis. However, some noncoding RNAs may inhibit cancer angiogenesis. Targeting angiogenic noncoding RNA of exosomes may serve as a hopeful implement for cancer therapy. In this review, we discuss the latest knowledge of the roles of exosomal noncoding RNAs in tumor angiogenesis Understanding the biology of exosomal noncoding RNAs can help scientists plan exosomes-based innovations for the treatment of cancer angiogenesis and cancer biomarkers.


Psychological issues in craniofacial care: state of the art.
This article is an extensive review of the psychological literature on cleft lip and palate and other craniofacial anomalies. Issues of parental acceptance, social competence, self-concept, emotional adjustment, and cognitive functioning are examined. Cumulative research suggests that many children with craniofacial conditions develop in a typical manner and do not experience psychological problems. However, a significant number of children (30% to 40% in most studies) experience difficulties with internalizing and/or externalizing problems, learning disorders, and social competence. A multifactorial model for examining the domains that are related to both psychological risk and protection is recommended. The need for multicenter studies that are prospective and clinically relevant is emphasized.


Comparison of the opinion of students and teachers concerning medical education programmes in Switzerland.
Three medical schools in Switzerland (Geneva, Lausanne and Bern) have recently started to implement a problem-based learning community-oriented reform. It seemed worthwhile to attempt to identify the opinion of those who would be concerned (teachers and students) before any changes were made. Data were collected through interviews and questionnaires on the seven following themes: (i) community-oriented education; (ii) professional profile; (iii) learner-centred education; (iv) teachers' educational competence; (v) coveritis; (vi) problem-based learning; and (vii) programme evaluation. The opinions of teachers and students were also compared with the position taken by specialists in medical education. The aim of this article was to present the key finding of this complex research. Interested readers are invited to refer to the full report.


Requirement for BSF-1 in the induction of antigen-specific B cell proliferation by a thymus-dependent antigen and carrier-reactive T cell line.
We report here a role of B cell stimulatory factor 1 (BSF-1) in the induction of antigen-specific proliferation of affinity-purified small B lymphocytes by a thymus-dependent antigen and a carrier-reactive T cell line. By using an ovalbumin-reactive T cell line (designated Hen-1), which does not produce BSF-1 following activation, it was possible to demonstrate that the antigen-specific proliferative response of trinitrophenyl (TNP)-binding B cells to TNP-ovalbumin required exogenous BSF-1 in addition to direct interaction with irradiated Hen-1 T cells. The activation obtained under these conditions was highly efficient, being sensitive to antigen doses as low as 0.001 microgram/ml. The addition of saturating amounts of BSF-1 did not alter the antigen-specificity or the requirements for hapten-carrier linkage or major histocompatibility complex-restricted T-B interaction in this system. The involvement of BSF-1 was confirmed by the ability of 11B11 anti-BSF-1 antibody to specifically suppress the response of TNP-binding B cells to TNP-ovalbumin, BSF-1, and irradiated Hen-1 T cells. Finally, this response was augmented by addition of the monokine interleukin 1. These data indicate that the proliferative response of small B cells to the thymus-dependent antigen and carrier-reactive T cell line used in our experiments can be regulated by the same factors that govern B cell proliferation induced by thymus-independent type 2 antigens or anti-IgM antibodies.


Quantification of membrane properties of trigeminal root ganglion neurons in guinea pigs.
Passive and active (voltage- and time-dependent) membrane properties of trigeminal root ganglion neurons of decerebrate guinea pigs have been determined using frequency-domain analyses of small-amplitude perturbations of membrane voltage. The complex impedance functions of trigeminal ganglion neurons were computed from the ratios of the fast Fourier transforms of the intracellularly recorded voltage response from the neuron and of the input current, which had a defined oscillatory waveform. The impedance magnitude functions and corresponding impedance locus diagrams were fitted with various membrane models such that the passive and active properties were quantified. The complex impedances of less than one-quarter of the 105 neurons which were investigated extensively could be described by the complex impedance function for a simple RC-electrical circuit. In such neurons, the voltage responses to constant-current pulses, using conventional bridge-balance techniques, could be fitted with single exponential curves, also suggesting passive membrane behavior. A nonlinear least-squares fit of the complex impedance function for the simple model to the experimentally observed complex impedance yielded estimates of the resistance of the electrode, and of input capacitance (range, 56 to 490 pF) and input resistance (range, 0.8 to 30 M omega) of the neurons. The majority of trigeminal ganglion neurons were characterized by a resonance in the 50- to 250-Hz bandwidth of their impedance magnitude functions. Such neurons when injected with "large" hyperpolarizing current pulses using bridge-balance techniques showed membrane voltage responses that "sagged" (time-dependent rectification). Also, repetitive firing commonly occurred with depolarizing current pulses; this characteristic of neurons with resonance in their impedance magnitude functions was not observed in neurons with "purely" passive membrane behavior. A nonlinear least-squares fit of a five-parameter impedance fitting function based on a membrane model to the impedance locus diagram of a neuron with resonance yielded estimates of its membrane properties: input capacitance, the time-invariant part of the conductance, the conductance activated by the small oscillatory input current, and the relaxation time constant for this conductance. The ranges of the estimates for input capacitance and input resistance were comparable to the ranges of corresponding properties derived for neurons exhibiting "purely" passive behavior.(ABSTRACT TRUNCATED AT 400 WORDS)


MS-325 EPIX.
EPIX is developing MS-325 (AngioMARK), an intravascular magnetic resonance contrast agent for use in the imaging of blood vessels and blood flow in patients with cardiovascular disease, including peripheral vascular disease (PVD). In June 1999, EPIX and Mallinckrodt began phase III trials of MS-325 for the detection of aortoiliac occlusive disease in patients with PVD or abdominal aortic aneurysm [328640]. NDAs for the peripheral and cardiac applications were expected in 1999 and 2000, respectively [275240], [325717]. MS-325 has also shown promise in demonstrating the presence of microscopic muscular dystrophy, as well as monitoring the effects of gene therapy in a mouse model of the disease [360974]. MS-325 is a stable complex of gadolinium and an organic chelating agent. It resembles approved agents in terms of stability, safety and elimination profile, but possesses novel chemical groups which allow it to bind reversibly to albumin. This retains the agent in the blood and, via a patented biophysical phenomenon, enhances the magnetic properties of the gadolinium ion approximately ten-fold.


Downregulation of glial glutamate transporters after dopamine denervation in the striatum of 6-hydroxydopamine-lesioned rats.
Overactivity of glutamatergic neurotransmission in the basal ganglia is known to be closely related to the onset and pathogenesis of Parkinson's disease. Glutamate homeostasis around glutamatergic synapses is tightly regulated by two groups of glutamate transporters: glial glutamate transporters GLT1 (EAAT2) and GLAST (EAAT1), and neuronal glutamate transporter EAAC1. In order to investigate the changes of glutamate transporters after the onset of Parkinson's disease, unilateral 6-hydroxydopamine-lesioned rat, an animal model of Parkinson's disease, was employed. By immunofluorescence and Western blot analyses, GLT1 and GLAST proteins were significantly reduced in the striatum with lesion. No change in GLT1 and GLAST protein was found in the substantia nigra. The reduction of GLT1 protein in the striatum was more prominent than that of GLAST protein (approximately 40% vs. 20%). In addition, EAAC1 protein was found to be increased in the substantia nigra pars reticulata of the lesioned rats but not in the striatum. The present results indicate that reductions of GLT1 and GLAST may impair glutamate homeostasis around glutamatergic synapses in the striatum and contribute to over-spills of glutamate in the system. An increase in the EAAC1 level in the substantia nigra pars reticulata may increase GABA synthesis and enhance GABAergic neurotransmission. These results indicate that there are differential and distinct modulations of glutamate transporters after dopamine denervation in the 6-hydroxydopamine-lesioned rat.


Acid and gastrin levels following pyloric-preserving pancreaticoduodenectomy.
Acid and gastrin production after pyloric-preserving pancreaticoduodenectomy was evaluated in six patients. Five patients had low-normal basal and stimulated acid output; the sixth patient was achlorhydric. Fasting gastrin levels were less than 90 to 105 pg/mL (normal range) in five patients, three of whom had stimulated gastrin levels that remained below this range. Two patients had stimulated gastrin levels of 510 pg/mL and 205 pg/mL, respectively, within 15 minutes of eating; however, both levels returned to normal by 120 minutes' time. The sixth patient had mildly elevated fasting (105 pg/mL) and stimulated gastrin levels (160 to 200 pg/mL) throughout the test period. The results suggest that pyloric-preserving pancreaticoduodenectomy does not lead to either gastric hyperacidity or persistent hypergastrinemia.


Synthesis and antiproliferative activity of 6-naphthylpterocarpans.
The Heck-oxyarylation of racemic 2-(1-naphthyl)- and 2-(2-naphthyl)-2H-chromene derivatives were carried out resulting diastereoselectively in (6S*,6aR*,11aR*)-6-(1-naphthyl)- and 6-(2-naphthyl)-pterocarpans as major products and bridged (6R*,12R*)-6,12-methanodibenzo[d,g][1,3]dioxocine derivatives as minor products. Antiproliferative activity of two 6-naphthylpterocarpans was identified by MTT assay against A2780 and WM35 human cancer cell lines with low micromolar IC50 values. The measured 0.80 and 3.51 μM IC50 values of the (6S*,6aR*,11aR*)-6-(1-naphthyl)pterocarpan derivative with 8,9-methylenedioxy substitution represent the best activities in the pterocarpan family. Enantiomers of the pterocarpan and dioxocine derivatives and their chiral 2-naphthylchroman-4-one and 2-naphthyl-2H-chromene precursors were separated by HPLC using chiral stationary phase. HPLC-ECD spectra were recorded and absolute configuration and low-energy solution conformations were determined by TDDFT-ECD calculations. Characteristic ECD transitions of the separated enantiomers were correlated with their absolute configuration.


Brief Adlerian psychodynamic psychotherapy: theoretical issues and process indicators.
Brief psychotherapy is gaining interest worldwide, because of its good cost/effectiveness ratio and proved efficacy. The aim of the paper was to describe the brief Adlerian psychodynamic psychotherapy (B-APP): a brief, psychodynamically oriented psychotherapy referring to the individual psychology (IP). The B-APP theory refers to the following paradigms: 1) the individual represents a psychosomatic unity integrated in the social context; 2) the individual needs to build and regulate the image of the self; 3) bond patterns regulate human relationships and represent the symbolic ''fil rouge'' connecting the elements of the life-style. Its objectives are: 1) an at least partial resolution of the focus problem; 2) a decrease or a non-increase of symptoms; 3) a global increase of quality of life. The results depend on intrapsychic and relational changes. Indications are more relative than absolute. The possibility of identifying a meaningful focus is fundamental. The treatment scheme includes 15 sessions subdivided into 5 phases. B-APP offers a technical approach to brief psychotherapy which is suitable in many fields of psychiatry and liaison medicine such as preventive interventions in at-risk subjects, somatopsychic disorders and liaison psychiatry, personality and eating disorders, and treatment of emotionally disturbed children. It was applied as psychotherapeutic approach in some clinical outcome studies about eating disorders and severe personality disorders displaying a good efficacy.


Enhanced antigen transport across rat tracheal epithelium induced by sensitization and mast cell activation.
Ag challenge to the apical surface of tracheal epithelium results in a rapid ion secretory response due to the activation of mast cells. The aim of this study was to examine the impact of sensitization and specific Ag challenge on the timing, route, and quantity of Ag transported across tracheal epithelium. After sensitization of rats to a model protein, HRP, tracheal tissues were excised and mounted in Ussing chambers. Tracheas from HRP-sensitized rats, but not naive or OVA-sensitized rats, responded to apical HRP challenge with a rise in short-circuit current (beginning at approximately 2 min). Photomicrographs of tissues fixed at 2 min showed that initial transepithelial HRP transport occurred via endosomes and was significantly enhanced in HRP-sensitized rats compared with both control groups. In addition, nonciliated cells, the proportion of which increased after sensitization, contained significantly more HRP than ciliated cells. The hypersensitivity response occurred only in HRP-sensitized and challenged rats and was associated with increased conductance of tracheal epithelium and overall flux of HRP across the tissue. This increased flux of Ag and elevated conductance was not observed in mast cell-deficient Ws/Ws rats. Photomicrographs of tissues fixed 90 min after challenge also showed HRP in the paracellular spaces between adjacent epithelial cells. We conclude that sensitization increases uptake of specific Ag initially via an endosomal transcellular pathway across tracheal epithelium and that, after the hypersensitivity reaction, mast cell-dependent recruitment of the paracellular pathway further augments Ag influx into airway tissue.


Women are more sensitive than men to prior trial events on the Stop-signal task.
Sexual dimorphism in the brain and cognition is a topic of widespread interest. Many studies of sex differences have focused on visuospatial and verbal abilities, but few studies have investigated sex differences in executive functions. We examined two key components of executive function - response inhibition and response monitoring - in healthy men (n = 285) and women (n = 346) performing the Stop-signal task. In this task, participants are required to make a key press to a stimulus, unless a tone is presented at some delay following the initial stimulus presentation; on these infrequent trials, participants are instructed to inhibit their planned response. Response inhibition was assessed with an estimate of the latency needed to inhibit a response (stop-signal reaction time), and response monitoring was measured by calculating the degree to which participants adjusted their reaction times based on the immediately preceding trial (e.g., speeding following correct trials and slowing following errors). There were no sex differences in overall accuracy or response inhibition, but women showed greater sensitivity to trial history. Women sped up more than men following correct 'Go' trials, and slowed down more than men following errors. These small but statistically significant effects (Cohen's d = 0.25-0.3) suggest more flexible adjustments in speed-accuracy trade-offs in women and greater cognitive flexibility associated with the responsive control of action.


Ionic Conductivity of K-ion Glassy Solid Electrolytes of K2S-P2S5-KOTf System.
Ternary glassy electrolytes containing K2S as a glass modifier and P2S5 as a network former are synthesized by introducing a new type of complex and asymmetric salt, potassium triflate (KOTf), to obtain unprecedented K+ ion conductivity at ambient temperature. The glasses are synthesized using a conventional quenching technique at a low temperature. In general, alkali ionic glassy electrolytes of ternary systems, specifically for Li+ and Na+ ion conductivity, have been studied with the addition of halide salts or oxysalts such as M2SO4, M2SiO4, M3PO4 (M = Li or Na), etc. We introduce a distinct and complex salt, potassium triflate (KOTf) with asymmetric anion, to the conventional glass modifier and former to synthesize K+-ion-conducting glassy electrolytes. Two series of glassy electrolytes with a ternary system of (0.9-x)K2S-xP2S5-0.1KOTf (x = 0.15, 0.30, 0.45, 0.60, and 0.75) and z(K2S-2P2S5)-yKOTf (y = 0.05, 0.10, 0.15, 0.20, and 0.25) on a straight line of z(K2S-2P2S5) are studied for their K+ ionic conductivities by using electrochemical impedance spectroscopy (EIS). The composition 0.3K2S-0.6P2S5-0.1KOTf is found to have the highest conductivity among the studied glassy electrolytes at ambient temperature with the value of 1.06 × 10-7 S cm-1, which is the highest of all pure K+-ion-conducting glasses reported to date. Since the glass transition temperatures of the glasses are near 100 °C, as demonstrated by DSC, temperature-dependent conductivities are studied within the range of 25 to 100 °C to determine the activation energies. A Raman spectroscopic study shows the variation in the structural units PS43-, P2S74-, and P2S64- of the network former for different glassy electrolytes. It seems that there is a role of P2S74- and P2S64- in K+-ion conductivity in the glassy electrolytes because the spectroscopic results are compatible with the composition-dependent, room-temperature conductivity trend.


Factors associated with successful mentor matching in an intervention study of youth violence.
One challenge of conducting intervention studies is ensuring that study participants are exposed to the intervention. For example, in our randomized controlled trial of Take Charge!, a mentor-implemented and research-informed violence prevention program that partners with one-on-one community-based mentoring agencies, only 50% of intervention youth with fight-related injuries were successfully matched with a mentor. We examined the differences between matched (n = 49) and unmatched (n = 49) youth with regard to demographics, time from injury to study enrollment, perceived seriousness of injury, belief that future injury can be avoided, and household chaos. Youth who were successfully matched with a mentor were more likely to perceive the injury as very serious or somewhat serious compared with unmatched youth (95.9% vs. 79.6%, p = .028). All other factors were not significantly associated with successful mentor matching. Future violence prevention interventions should consider youth perceptions as a factor that may influence the completion of desired interventions.


Role of Atypical Chemokines and Chemokine Receptors Pathways in the Pathogenesis of COPD.
Chronic obstructive pulmonary disease (COPD) represents a heightened inflammatory response in the lung generally resulting from tobacco smoking-induced recruitment and activation of inflammatory cells and/or activation of lower airway structural cells. Several mediators can modulate activation and recruitment of these cells, particularly those belonging to the chemokines (conventional and atypical) family. There is emerging evidence for complex roles of atypical chemokines and their receptors (such as high mobility group box 1 (HMGB1), antimicrobial peptides, receptor for advanced glycosylation end products (RAGE) or toll-like receptors (TLRs)) in the pathogenesis of COPD, both in the stable disease and during exacerbations. Modulators of these pathways represent potential novel therapies for COPD and many are now in preclinical development. Inhibition of only a single atypical chemokine or receptor may not block inflammatory processes because there is redundancy in this network. However, there are many animal studies that encourage studies for modulating the atypical chemokine network in COPD. Thus, few pharmaceutical companies maintain a significant interest in developing agents that target these molecules as potential antiinflammatory drugs. Antibody-based (biological) and small molecule drug (SMD)-based therapies targeting atypical chemokines and/or their receptors are mostly at the preclinical stage and their progression to clinical trials is eagerly awaited. These agents will most likely enhance our knowledge about the role of atypical chemokines in COPD pathophysiology and thereby improve COPD management.


Analysis of subtelomeric virulence gene families in Plasmodium falciparum by comparative transcriptional profiling.
The Plasmodium falciparum genome is equipped with several subtelomeric gene families that are implicated in parasite virulence and immune evasion. Members of these families are uniformly positioned within heterochromatic domains and are thus subject to variegated expression. The best-studied example is that of the var family encoding the major parasite virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 undergoes antigenic variation through switches in mutually exclusive var gene transcription. var promoters function as crucial regulatory elements in the underlying epigenetic control strategy. Here, we analysed promoters of upsA, upsB and upsC var, rifA1-type rif, stevor, phist and pfmc-2tm genes and investigated their role in endogenous gene transcription by comparative genome-wide expression profiling of transgenic parasite lines. We find that the three major var promoter types are functionally equal and play an essential role in singular gene choice. Unlike var promoters, promoters of non-var families are not silenced by default, and transcription of non-var families is not subject to the same mode of mutually exclusive transcription as has been observed for var genes. Our findings identified a differential logic in the regulation of var and other subtelomeric virulence gene families, which will have important implications for our understanding and future analyses of phenotypic variation in malaria parasites.


Ground and excited states of zinc phthalocyanine, zinc tetrabenzoporphyrin, and azaporphyrin analogs using DFT and TDDFT with Franck-Condon analysis.
The electronic structure of eight zinc-centered porphyrin macrocyclic molecules are investigated using density functional theory for ground-state properties, time-dependent density functional theory (TDDFT) for excited states, and Franck-Condon (FC) analysis for further characterization of the UV-vis spectrum. Symmetry breaking was utilized to find the lowest energy of the excited states for many states in the spectra. To confirm the theoretical modeling, the spectroscopic result from zinc phthalocyanine (ZnPc) is used to compare to the TDDFT and FC result. After confirmation of the modeling, five more planar molecules are investigated: zinc tetrabenzoporphyrin (ZnTBP), zinc tetrabenzomonoazaporphyrin (ZnTBMAP), zinc tetrabenzocisdiazaporphyrin (ZnTBcisDAP), zinc tetrabenzotransdiazaporphyrin (ZnTBtransDAP), and zinc tetrabenzotriazaporphyrin (ZnTBTrAP). The two latter molecules are then compared to their phenylated sister molecules: zinc monophenyltetrabenzotriazaporphyrin (ZnMPTBTrAP) and zinc diphenyltetrabenzotransdiazaporphyrin (ZnDPTBtransDAP). The spectroscopic results from the synthesis of ZnMPTBTrAP and ZnDPTBtransDAP are then compared to their theoretical models and non-phenylated pairs. While the Franck-Condon results were not as illuminating for every B-band, the Q-band results were successful in all eight molecules, with a considerable amount of spectral analysis in the range of interest between 300 and 750 nm. The π-π(∗) transitions are evident in the results for all of the Q bands, while satellite vibrations are also visible in the spectra. In particular, this investigation finds that, while ZnPc has a D4h symmetry at ground state, a C4v symmetry is predicted in the excited-state Q band region. The theoretical results for ZnPc found an excitation energy at the Q-band 0-0 transition of 1.88 eV in vacuum, which is in remarkable agreement with published gas-phase spectroscopy, as well as our own results of ZnPc in solution with Tetrahydrofuran that are provided in this paper.


Fenton process on single and mixture components of phenothiazine pharmaceuticals: Assessment of intermediaries, fate, and preliminary ecotoxicity.
Pharmaceuticals do not occur isolated in the environment but in multi-component mixtures and may exhibit antagonist, synergistic or additive behavior. Knowledge on this is still scarce. The situation is even more complicated if effluents or potable water is treated by oxidative processes or such transformations occur in the environment. Thus, determining the fate and effects of parent compounds, metabolites and transformation products (TPs) formed by transformation and degradation processes in the environment is needed. This study investigated the fate and preliminary ecotoxicity of the phenothiazine pharmaceuticals, Promazine (PRO), Promethazine (PRM), Chlorpromazine (CPR), and Thioridazine (THI) as single and as components of the resulting mixtures obtained from their treatment by Fenton process. The Fenton process was carried out at pH7 and by using 0.5-2mgL-1 of [Fe2+]0 and 1-12.5mgL-1 of [H2O2]0 at the fixed ratio [Fe2+]0:[H2O2]0 of 1:10 (w:w). No complete mineralization was achieved. Constitutional isomers and some metabolite-like TPs formed were suggested based on their UHPLC-HRMSn data. A degradation pathway was proposed considering interconnected mechanisms such as sulfoxidation, hydroxylation, N-dealkylation, and dechlorination steps. Aerobic biodegradation tests (OECD 301 D and OECD 301 F) were applied to the parent compounds separately, to the mixture of parent compounds, and for the cocktail of TPs present after the treatment by Fenton process. The samples were not readily biodegradable. However, LC-MS analysis revealed that abiotic transformations, such hydrolysis, and autocatalytic transformations occurred. The initial ecotoxicity tested towards Vibrio fischeri as individual compounds featured a reduction in toxicity of PRM and CPR by the treatment process, whereas PRO showed an increase in acute luminescence inhibition and THI a stable luminescence inhibition. Concerning effects of the mixture components, reduction in toxicity by the Fenton process was predicted by concentration addition and independent action models.


Shift-and-add tomosynthesis of a finger joint by X-ray dark-field imaging: difference due to tomographic angle.
A tomogram of a finger joint showing articular cartilage was generated based on X-ray dark-field imaging (XDFI) using the shift-and-add tomosynthesis algorithm. The experiment was performed at beamline 14B of the Photon Factory in Tsukuba, Japan, using synchrotron X-rays from a vertical wiggler. The incident X-ray energy was 36.0 keV. The X-ray optics for XDFI comprised two Si crystals: an asymmetric cut Si (220) monochromator-collimator and a 1.1-mm thick Si (220) Laue-case analyzer. The object was an intact cadaveric proximal interphalangeal joint fixed in formalin. Raw projection data were acquired by XDFI in a total of 41 views through an angle of 20 degrees in 0.5 degrees increments. The object and detector were synchronously rotated such that the fulcrum plane in the object and detector plane remained parallel. The X-ray dose for one piece of raw projection data was set to one-eleventh of that for one standard projection image by XDFI. Eleven views through an angle of 10 degrees in increments of 1 degrees of all 41 appropriately shifted raw projection data were added to produce arbitrary tomograms parallel to the fulcrum plane. We obtained a clear tomogram of the finger joint including the articular cartilage with the moderate artifact peculiar to tomosynthesis. Consequently, arbitrary tomograms can be obtained for the same X-ray dose as that received for one standard projection image by XDFI. The fact that an inner structure such as articular cartilage, which is invisible to conventional X-ray imaging methods, has been visualized on a tomogram with preserved refraction-enhanced contrast, is of considerable significance to clinical medicine.


A Learnable Counter-condition Analysis Framework for Functional Connectivity-based Neurological Disorder Diagnosis.
To understand the biological characteristics of neurological disorders with functional connectivity (FC), recent studies have widely utilized deep learning-based models to identify the disease and conducted post-hoc analyses via explainable models to discover disease-related biomarkers. Most existing frameworks consist of three stages, namely, feature selection, feature extraction for classification, and analysis, where each stage is implemented separately. However, if the results at each stage lack reliability, it can cause misdiagnosis and incorrect analysis in afterward stages. In this study, we propose a novel unified framework that systemically integrates diagnoses (i.e., feature selection and feature extraction) and explanations. Notably, we devised an adaptive attention network as a feature selection approach to identify individual-specific disease-related connections. We also propose a functional network relational encoder that summarizes the global topological properties of FC by learning the inter-network relations without pre-defined edges between functional networks. Last but not least, our framework provides a novel explanatory power for neuroscientific interpretation, also termed counter-condition analysis. We simulated the FC that reverses the diagnostic information (i.e., counter-condition FC): converting a normal brain to be abnormal and vice versa. We validated the effectiveness of our framework by using two large resting-state functional magnetic resonance imaging (fMRI) datasets, Autism Brain Imaging Data Exchange (ABIDE) and REST-meta-MDD, and demonstrated that our framework outperforms other competing methods for disease identification. Furthermore, we analyzed the disease-related neurological patterns based on counter-condition analysis.


Enhanced transformation of tnt by tobacco plants expressing a bacterial nitroreductase.
The manufacture, disposal, and detonation of explosives have resulted in the pollution of large tracts of land and groundwater. Historically, 2,4,6-trinitrotoluene (TNT) is the most widely used military explosive and is toxic to biological systems and recalcitrant to degradation. To examine the feasibility of enhancing the ability of plants to detoxify the explosive TNT, we created transgenic tobacco (Nicotiana tabacum) constitutively expressing the nsfI nitroreductase gene from Enterobacter cloacae. The product of TNT reduction by the nitroreductase was found to be 4-hydroxylamino-2,6-dinitrotoluene (4-HADNT). Characterization of the transgenic lines in sterile, aqueous conditions amended with TNT demonstrated that these plants were able to remove all of the TNT from the medium at an initial concentration of 0.5 mM (113 mg L(-1)) TNT. In contrast, growth was suppressed in wild-type plants at 0.1 mM (23 mg L(-1)). Following uptake, transgenic seedlings transformed TNT predominantly to 4-HADNT and its high levels appeared to correlate with enhanced tolerance and transformation of TNT. Transformation products of TNT were subsequently conjugated to plant macromolecules to a greater degree in transgenic tobacco, indicating enhanced detoxification compared to the wild type.


Cardiorespiratory response to physical exercise and psychological variables in panic disorder.
To investigate the possible influence of psychological variables on cardiorespiratory responses and perceived exertion of patients with Panic Disorder (PD) during a submaximal exercise test. Ten outpatients with PD and 10 matched healthy subjects walked up on a treadmill slope at a speed of 4 km/h in order to reach 65% of their maximum heart rate. Cardiorespiratory variables were continuously recorded. Before the exercise, the state and trait anxiety (State-Trait Anxiety Inventory scores), fear of physical sensations (Body Sensation Questionnaire scores), and fear of autonomic arousal (Anxiety Sensitivity Index scores) were assessed; during the exercise, levels of anxiety (VAS-A) and exertion (Borg Scale CR 10) were measured. Compared to controls, patients reached earlier the target HR and the ventilatory threshold, showed lower oxygen consumption, higher HR and lower within-subject standard deviations of HR (a measure of cardiac variability). Exertion was also higher, and there was a significant correlation between breathing frequency, tidal volume and HR. No significant associations were found between cardiorespiratory response, perceived exertion, and psychological variables in patients with PD. Although patients with PD presented poor cardiorespiratory fitness and were required to spend more effort during physical exercise, this did not appear to be related to the psychological variables considered. Further studies with larger groups are warranted.


Analysis of the fate of systemically administered liposomes and implications for their use in drug delivery.
Functional and ultrastructural studies of liposomes injected i.v. into inbred C57BL/6N mice were performed to determine whether free liposomes can traverse capillaries. In the liver and spleen, organs with discontinuous (sinusoidal) capillaries, ultrastructural and cell fractionation studies revealed that small (300- to 800-A diameter), sonicated, unilamellar liposomes were more efficient in penetrating liver sinusoids to interact with hepatocytes than were large (0.5- to 10-micrometers) multilamellar liposomes. Ultrastructural studies of the behavior of liposomes in the continuous capillaries of the lungs revealed that circulating phagocytic cells engulf the liposomes in the capillaries. Transcapillary migration of free liposomes was not observed. We conclude that free liposomes are unable to extravasate to reach the alveoli for subsequent engulfment by alveolar macrophages. Instead, liposomes in the lung capillaries are engulfed by circulating blood phagocytes which subsequently migrate to the alveoli to become alveolar macrophages. Experiments on the recruitment of blood monocytes into the lungs subjected to whole- or partial-body X-radiation confirmed that transfer of i.v.-injected liposomes to the alveolar compartment was mediated by blood monocytes. The inability of liposomes to escape from continuous capillaries and their rapid uptake by circulating and fixed phagocytic cells calls into question the feasibility of using liposomes to "target" drugs to cells in extravascular tissues.


A comparative analysis of alternative approaches for quantifying nonlinear dynamics in cardiovascular system.
Heart rate variability (HRV) analysis has emerged as an important research topic to evaluate autonomic cardiac function. However, traditional time and frequency-domain analysis characterizes and quantify only linear and stationary phenomena. In the present investigation, we made a comparative analysis of three alternative approaches (i.e., wavelet multifractal analysis, Lyapunov exponents and multiscale entropy analysis) for quantifying nonlinear dynamics in heart rate time series. Note that these extracted nonlinear features provide information about nonlinear scaling behaviors and the complexity of cardiac systems. To evaluate the performance, we used 24-hour HRV recordings from 54 healthy subjects and 29 heart failure patients, available in PhysioNet. Three nonlinear methods are evaluated not only individually but also in combination using three classification algorithms, i.e., linear discriminate analysis, quadratic discriminate analysis and k-nearest neighbors. Experimental results show that three nonlinear methods capture nonlinear dynamics from different perspectives and the combined feature set achieves the best performance, i.e., sensitivity 97.7% and specificity 91.5%. Collectively, nonlinear HRV features are shown to have the promise to identify the disorders in autonomic cardiovascular function.


The temporal influence of a heroin shortage on pregnant drug users and their newborn infants in Sydney, Australia.
Heroin availability and purity decreased precipitously in Australian markets between 2000 and 2001. This led to increased use of non-opiate drugs in the general community but whether pregnant drug users and their newborn infants were affected remains unknown. To determine if perinatal drug exposure and outcomes are affected by changes in street drug availability. Retrospective review was carried out of known drug-exposed mothers delivering live-born infants at the Royal Hospital for Women, Randwick, Australia (n = 316). Study periods were divided into preshortage (A = 1998-2000, n = 79), shortage (B = 2001-2002, n = 92) and post-shortage (C = 2003-2006, n = 122) periods. Cannabis-only users were excluded (n = 23). The percentage of confined women who admitted to using heroin decreased significantly (65%(A) vs 34%(B), P < 0.01) as did women on methadone programmes (90%(A), 80%(B), 75%(C), P = 0.024). The use of cocaine (7% (A) vs 33% (B), P = 0.031) and amphetamines (4% (A) vs 22% (C), P = 0.01), tripled. Most infants were born full-term and healthy but the duration of infant hospitalisation increased significantly from (median [interquartile range]) 8 [10, 38](A) to 13 [7, 23](C) days (P < 0.01). Approximately 50% of infants required withdrawal treatment but more needed phenobarbitone as an adjunct to morphine during the shortage (4/80 (0.5%) vs 15/93 (16%), P = 0.026), probably because of increased exposure to non-opiate drugs. The types of drugs used by pregnant drug users follow street trends and may affect infant hospitalisation and withdrawal treatment. Of concern is the rise in amphetamine-use and there needs to be increased vigilance for similar trends, especially in previously unidentified drug users.


Biocompatibility, Bioactivity, and Antibacterial Behaviour of Cerium-Containing Bioglass®.
The main reason for the increased use of dental implants in clinical practice is associated with aesthetic parameters. Implants are also presented as the only technique that conserves and stimulates natural bone. However, there are several problems associated with infections, such as peri-implantitis. This disease reveals a progressive inflammatory action that affects the hard and soft tissues surrounding the implant, leading to implant loss. To prevent the onset of this disease, coating the implant with bioactive glasses has been suggested. In addition to its intrinsic function of promoting bone regeneration, it is also possible to insert therapeutic ions, such as cerium. Cerium has several advantages when the aim is to improve osseointegration and prevent infectious problems with dental implant placement. It promotes increased growth and the differentiation of osteoblasts, improves the mechanical properties of bone, and prevents bacterial adhesion and proliferation that may occur on the implant surface. This antibacterial effect is due to its ability to disrupt the cell wall and membrane of bacteria, thus interfering with vital metabolic functions such as respiration. In addition, its antioxidant effect reverses oxidative stress after implantation in bone. In this work, Bioglass 45S5 with CeO2 with different percentages (0.25, 0.5, 1, and 2 mol%) was developed by the melt-quenching method. The materials were analyzed in terms of morphological, structural, and biological (cytotoxicity, bioactivity, and antibacterial activity) properties. The addition of cerium did not promote structural changes to the bioactive glass, which shows no cytotoxicity for the Saos-2 cell line up to 25 mg/mL of extract concentration for all cerium contents. For the maximum cerium concentration (2 mol%) the bioactive glass shows an evident inhibitory effect for Escherichia coli and Streptococcus mutans bacteria. Furthermore, all samples showed the beginning of the deposition of a CaP-rich layer on the surface of the material after 24 h.


Alternative Markers of Performance in Simulation: Where We Are and Where We Need To Go.
This article on alternative markers of performance in simulation is the product of a session held during the 2017 Academic Emergency Medicine Consensus Conference "Catalyzing System Change Through Health Care Simulation: Systems, Competency, and Outcomes." There is a dearth of research on the use of performance markers other than checklists, holistic ratings, and behaviorally anchored rating scales in the simulation environment. Through literature review, group discussion, and consultation with experts prior to the conference, the working group defined five topics for discussion: 1) establishing a working definition for alternative markers of performance, 2) defining goals for using alternative performance markers, 3) implications for measurement when using alternative markers, identifying practical concerns related to the use of alternative performance markers, and 5) identifying potential for alternative markers of performance to validate simulation scenarios. Five research propositions also emerged and are summarized.


A simple ball milling method for the preparation of p-CuO/n-ZnO nanocomposite photocatalysts with high photocatalytic activity.
The p-n junction photocatalyst, p-CuO/n-ZnO, was prepared via ball milling of ZnO and CuO nanoparticles in water. The structural, optical, and surface properties of the p-n junction photocatalyst p-CuO/n-ZnO were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-Vis spectroscopy, and Zeta potential analyzer. The Photocatalytic activity of the photocatalyst was evaluated via photocatalytic oxidation of Methylene Blue (MB) in the presence of UV light. This study demonstrates a novel p-n junction oxide photocatalyst p-CuO (wt. 10%)/n-ZnO having superior photocatalytic activity (PCA) for the degradation of model dye under the illumination of UV-Vis light. The MB solution was only PCA, degraded by 100% within 15 min by the use of CuO (wt. 10%)/ZnO photocatalyst. Effectivley 365% increase in degradation rate constant was noticed for CuO (10 Wt.%)/ZnO nanocomposite as compared to that of pure ZnO nanoparticles. The enhanced PCA is anticipated from the presence of many micro p-n junctions formed between ZnO-CuO nanoparticles upon ball milling, which helps in efficient electron/hole pair charge separation upon excitation. The study highlights the fact that PCA of p-n junction CuO/ZnO photocatalyst can be effectively tuned by manipulating the interface of the heterostructure and by adjusting the parameters affecting the PCA. The result obtained from PCA is further verified by the zeta potential study.


Establishing the psychometric properties of 2 self-reported outcome measures of elbow pain and function: A systematic review.
Systematic review. The Patient-Rated Elbow Evaluation (PREE) and the self-report section of the American Shoulder and Elbow Surgeons-elbow form (pASES-e) are 2 patient-reported outcome measures (PROMs) commonly used to assess pain and disability arising from elbow disorders. To systematically review and summarize the quality and content of the evidence that is available on the psychometric properties of the PREE and pASES-e. We systematically searched the online databases PubMed, EMBASE, ProQuest, Scopus, Cumulative Index to Nursing and Allied Health Literature, UptoDate, ProQuest Dissertations & Theses, and Google Scholar. Ninety-one articles were retrieved, and after screening, 9 were included in the final analysis. Data extraction and quality appraisal was performed by 2 independent raters. Descriptive synthesis of the reviewed studies was completed. Seven of the 9 studies had a quality score of 75% or higher. Agreement between the raters was good (kappa, 0.81). Both the PROMs did not demonstrate any floor and ceiling effects except for the satisfaction subscale of the pASES-e. Factor analysis revealed multidimensionality in the function subscale for both the PROMs. Construct validity was good with correlations above 0.70. Both were highly reliable with interclass correlation coefficient of >0.90. They were also highly responsive with an effect size and standardized response mean above 1. The minimal clinical important difference was not estimated for either measures. This study concluded that strong clinical measurement properties exist for both the PREE and the pASES-e. We identified gaps in the current evidence for both the ASES-e and the PREE. Future studies need to calculate clinically important estimates like MCID, SEM, and others; and provide clear and specific conclusions. The PREE and pASES-e have been established to be valid, reliable, and sensitive to change in both clinical and research settings based on high-quality evidence.


Reduced infant birthweight consequent upon maternal exposure to severe life events.
To investigate the association between maternal exposure to severe life events and fetal growth (birthweight and small for gestational age). Stress has been associated with adverse pregnancy outcome. Mothers of 1.38 million singleton live births in Denmark between January 1, 1979 and December 31, 2002 were linked to information on their spouses, parents, siblings, and older children. Exposure was defined as death or serious illness in a relative during pregnancy or in the 6 months before conception. Linear regression was used to examine the effect of exposure on birthweight. Log-linear binomial regression was used to assess the effect of exposure on small for gestational age. Death of a relative during pregnancy or in the 6 months before conception reduced birthweight by 27 g (adjusted estimate -27 g, 95% Confidence Interval (CI) = -33, -22). There was a significant association between maternal exposure to death of a relative and risk of a baby weighing below the 10th percentile (adjusted relative risk (RR) = 1.17, 95% CI = 1.13, 1.22) and 5th percentile (adjusted RR = 1.22, 95% CI = 1.15, 1.29). Mothers exposed to severe life events before conception or during pregnancy have babies with significantly lower birthweight. If this association is causal, the potential mechanisms of stress-related effects on birthweight include changes in lifestyle due to the exposure and stress-related dysregulation of the hypothalamic-pituitary-adrenal axis during pregnancy.


Changes in quality of life and the cost-utility associated with cochlear implantation in patients with large vestibular aqueduct syndrome.
A group of 20 patients with large vestibular aqueduct syndrome was identified at the Indiana University School of Medicine. The major objective of this study was to explore the improvements in quality of life associated with cochlear implantation in patients with large vestibular aqueduct syndrome, as well as the cost-utility of cochlear implantation in this group. A total of 70 patients were identified with large vestibular aqueduct syndrome through analysis of thin-section computed tomography of the temporal bone over the past 6 years at this medical center. Data collected from the medical records for each patient included demographic data, hearing-related statistics, implantation data, and audiometric data. Sixteen children and adults with large vestibular aqueduct syndrome had undergone cochlear implantation before the beginning of this study, and the remaining 54 children and adults were identified as undergoing treatment of progressive or fluctuant sensorineural hearing loss. Health utility indexes used in this analysis were taken through the use of the Ontario Health Utility Index, Mark III. The range of costs used for cost-utility analysis was derived from the costs of cochlear implantation at this medical center, as well as from costs associated with implantation published in the medical literature. Participants were selected from the total population of patients with large vestibular aqueduct syndrome at this center who were postlingually deafened and who currently had severe hearing loss. Two groups were formed. These groups comprised either cochlear implant patients with large vestibular aqueduct syndrome or patients with large vestibular aqueduct syndrome currently using hearing aids. Ten of the 16 cochlear implant patients and 10 of the remaining 54 patients with large vestibular aqueduct syndrome met these criteria. Mark III health utility indexes were distributed to patients in each group and scored. Those health utility indexes not completed by the patients were scored by proxy, using the audiologist at this center who was the most familiar with the patient. Changes in quality of life associated with cochlear implantation were derived by comparison of the health utility index results of the two groups. Cost-utility measures were then made using discounted costs per quality-of-life years (QALYs) (5%), and a sensitivity analysis was performed that evaluated changes in scoring done by proxy. The cost-utility results were then compared with the cost-utilities derived from similar studies and associated with other disease states. Although both groups of patients had significant hearing loss, the hearing aid group had a better mean pure-tone average. The mean pure-tone average for the hearing aid group was 70.8 dB (SD 24.4), and the mean pure-tone average for the cochlear implant group was 107.0 dB (SD 21.7). Seven of the 20 health utility indexes were scored by proxy. Results from the base case indicate a 0.20 gain in health utility from cochlear implantation (hearing aid = 0.62, cochlear implant = 0.82, p = 0.037), resulting in a discounted cost per QALY of $12,774. Sensitivity analysis of the proxy scoring indicated that decreasing the hearing score one level on the health utility index resulted in a gain in health utility with cochlear implantation of 0.15, resulting in a discounted cost per QALY of $17,832. A decrease of the hearing score by two levels on the health utility survey resulted in no significant gain in quality of life with cochlear implantation. This study found an improvement in quality of life associated with cochlear implantation in postlingually deafened patients with large vestibular aqueduct syndrome. By weighing this improvement in quality of life against the significant difference noted between the pure-tone averages of each group, further strength can be given to this conclusion. This gain in quality of life, as well as the results derived for the cost-utility of cochlear implantation, was similar to that in previous published studies of cochlear implantation in all types of patients. These results also indicate a favorable cost-utility when compared with published data about other disease states. As patients with large vestibular aqueduct syndrome progress to profound levels of hearing loss, these results indicate that cochlear implantation can be offered as a beneficial, life-improving therapy.


Selected noble-gas partition coefficients.
The Ostwald solubility of 41Ar, 127,133Xe, N13N and CH3 18F in water, saline, blood, plasma, lipids, benzene and bone were measured in vitro. In addition the bone-blood partition coefficients for these gases were determined. For 41Ar, the bone-blood partition function is found to be 1.1 +/- 0.3, whereas for xenon the bone-blood partition coefficient is 0.41 +/- 0.1.


Computed tomography (CT) venography using a multidetector CT prior to the percutaneous external jugular vein approach for an implantable venous-access port.
The objective of this study was to determine the success rate and complications of using the percutaneous approach of the external jugular vein (EJV) for placement of a totally implantable venous-access port (TIVAP) with a preoperative estimate of the detailed anatomical orientation of the cervical venous plexus using computed tomography venography (CT-V). A prospective cohort study of 45 patients in whom placement of a TIVAP was attempted via the right EJV was conducted. The preoperative anatomical estimation of the cervical venous plexus was performed with CT-V using a Multidetector Helical 16-section CT. The angulation between the right EJV and the right subclavian vein, anterior jugular vein, transverse cervical vein, and suprascapular vein was estimated. CT-V success was achieved in 45 of 45 patients (100 %). A plexus of veins under the clavicle was most commonly responsible for the insertion of the central venous catheter. The EJV approach resulted in a successful cannulation rate of 93 %. No initial complications of pneumothorax or carotid artery puncture occurred during insertion procedures. Late complications occurred in three patients. These included one port erosion (2 %), one catheter occlusion (2 %), and one wound hematoma (2 %). Catheter-related infections were observed in one patient (2 %). The percutaneous EJV approach with CT-V guidance is an optional method for patients with multiple central venous cannulations, those in hemodialysis, or those with long catheter indwelling periods.


Effect of transforming growth factor-beta on insulin-like growth factor 1- and dexamethasone-induced proliferation and differentiation in primary cultures of pig preadipocytes.
The purpose of this study was to examine the effects of a known inhibitor, transforming growth factor-beta1 (TGF-beta1) versus the known stimulators insulin-like growth factor-1 (IGF-1) and dexamethasone (DEX) on pig preadipocyte differentiation in serum and serum-free primary cultures. In cultures with serum, preadipocyte and nonpreadipocyte replication was increased (p < 0.02) by IGF-1 and by TGF-beta1 (p < 0.05; p < 0.001). IGF-1 (10 nM) enhanced preadipocyte differentiation (p < 0.05) in serum-supplemented (1% pig serum) cultures, whereas TGF-beta1 (15 pM) reduced preadipocyte differentiation (p < 0.01) in the presence and absence of IGF-1. Furthermore, GPDH (SN-glycerol-3-phosphate dehydrogenase) specific activity (marker that indicates differentiation) was decreased (p < 0.05) by adding TGF-beta1 to serum-free cultures, but TGF-beta1 had little effect in serum-supplemented cultures. DEX significantly enhanced GPDH activity and fat cell cluster number, whereas pretreatment with TGF-beta1 eliminated the DEX enhancement. We have shown for the first time that TGF-beta can decrease (p < 0.01) the cellular secretion of IGF-1 by pig adipose tissue cells and counter the effects of exogenous IGF-1. These studies indicate that TGF-beta1 may not inhibit adipocyte development in the initial growth phase, but may inhibit differentiation and/or hypertrophy (lipid filling) at a later stage of development.


Quantifying the Sustainability of Water Availability for the Water-Food-Energy-Ecosystem Nexus in the Niger River Basin.
Water, food, energy, and the ecosystems they depend on interact with each other in highly complex and interlinked ways. These interdependencies can be traced particularly well in the context of a river basin, which is delineated by hydrological boundaries. The interactions are shaped by humans interacting with nature, and as such, a river basin can be characterized as a complex, coupled socioecological system. The Niger River Basin in West Africa is such a system, where water infrastructure development to meet growing water, food, and energy demands may threaten a productive and vulnerable basin ecosystem. These dynamic interactions remain poorly understood. Trade-off analyses between different sectors and at different spatial scales are needed to support solution-oriented policy analysis, particularly in transboundary basins. This study assesses the impact of climate and human/anthropogenic changes on the water, energy, food, and ecosystem sectors and characterizes the resulting trade-offs through a set of generic metrics related to the sustainability of water availability. Results suggest that dam development can mitigate negative impacts from climate change on hydropower generation and also on ecosystem health to some extent.


Agreement of Cardiac Output Measurements between Bioreactance and Transthoracic Echocardiography in Preterm Infants during the Transitional Phase: A Single-Centre, Prospective Study.
Bioreactance cardiac output (CO) monitors are able to non-invasively and continuously monitor CO. However, as a novel tool to measure CO, it must be proven to be accurate and precise. To determine the agreement between CO measured with a bioreactance monitor and transthoracic echocardiography-derived left ventricular output parameters in preterm infants. This is a prospective observational study in 63 preterm neonates with non-invasive respiratory support, not requiring inotrope support. The infants underwent continuous bioreactance monitoring of CO and stroke volume (SV) and simultaneous transthoracic echocardiography every 6 h until 72 h of life. The agreement between bioreactance and transthoracic echocardiography, for both SV and CO, was poor. The percentage error was 67.5% for SV and 71.6% for CO. The mean error was 60.4% for SV and 69.8% for CO. Bias was affected by numerous variables. After correcting for time, CO and SV bias were significantly affected by the presence of an open patent ductus arteriosus and the level of CO. Bioreactance cannot be considered interchangeable with transthoracic echocardiography to measure CO in preterm infants during the transition phase. Agreement between bioreactance and other CO metrics should be assessed before concluding its accuracy or inaccuracy in neonates.


Local control of long bone giant cell tumour using curettage, burring and bone grafting without adjuvant therapy.
Giant cell tumour (GCT) is a benign, but aggressive, primary tumour of the bone. The recurrence rate after surgical treatment has been reported to be as high as 50%. Many surgical techniques have been employed in the treatment of this tumour. More aggressive interventions, such as en bloc resection and bulk allograft or prosthetic reconstruction, are generally understood to be associated with lower rates of local recurrence. However, because of lessened morbidity, intralesional techniques have come to be favoured for this condition. In addition to curettage, various adjuvant procedures and packing materials have been advocated in order to control and reconstruct long bone defects secondary to this neoplasm. We report our experience with 40 long bone GCT patients treated with curettage, burring, bone grafting and no adjuvants between 1997 and 2002. There was a local recurrence rate of 32.5%, with most recurrences noted within the first 30 months after surgery. Minor complications were found in 18% of patients. The risk of local recurrence in this study is acceptable (within the range that has been historically reported for curettage and bone grafting). In cases where more resources are available, the addition of adjuvant therapies, as noted in the recent literature, may be beneficial. The results of this study should be considered when designing multicenteric studies in the future.


Correlations between clinical findings and magnetization transfer imaging metrics of tissue damage in individuals with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
We obtained magnetization transfer imaging (MTI) scans from individuals with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (1) to investigate the presence, extent, and nature of pathology in white and gray matter outside proton density (PD)-visible lesions; (2) to quantify the degree of tissue damage occurring in lesions seen on PD-weighted scans; and (3) to correlate MTI-derived measures of disease burden with age, physical disability, and cognitive performance. Dual-echo, T1-weighted, and MTI scans of the brain were obtained from 33 individuals with CADASIL and 12 control subjects. Magnetization transfer ratio (MTR) values from PD-visible lesions, normal-appearing white matter (NAWM), and normal-appearing gray matter (NAGM) were measured. Histograms of MTR from the whole brain and normal-appearing brain tissue were also produced. All MTR values from NAWM and NAGM regions studied were significantly lower for individuals with CADASIL than for control subjects, with the exception of those obtained from the NAWM of the infratentorial structures and the NAGM of the occipital cortex. The average MTR from PD lesions in individuals with CADASIL was significantly lower than that from all the NAWM regions. Average MTR and peak location from whole-brain and normal-appearing brain tissue histograms were significantly lower for individuals with CADASIL than for control subjects. MTR values from NAWM were strongly correlated with the extent of macroscopic lesions and their average MTR. Apart from NAGM, average MTR from all other tissues studied significantly decreased with increasing age, physical disability, and cognitive impairment. PD lesions of individuals with CADASIL have variable degrees of tissue damage. Brain tissue outside PD abnormalities is also damaged. This study suggests that the extent and the severity of the brain tissue damage are critical factors in determining clinical status in CADASIL.


A CRISPR/Cas9-based strategy to simultaneously inactivate the entire ALS gene family in Candida orthopsilosis.
Aim: In this study, the CRISPR gene-editing approach was used to simultaneously inactivate all three members of the ALS gene family in the opportunistic pathogen Candida orthopsilosis. Materials & methods: Using a single gRNA and repair template, CRISPR-edited clones were successfully generated in a one-step process in both C. orthopsilosis reference and clinical strains. Results: The phenotypic characterization of the ALS triple-edited strains revealed no impact on growth in liquid or solid media. However, pseudohyphal formation and the ability to adhere to human buccal epithelial cells were significantly decreased in triple-edited clones. Conclusion: Our CRISPR/Cas9 system is a powerful tool for simultaneous editing of fungal gene families, which greatly accelerates the generation of multiple gene-edited Candida strains. Data deposition: Nucleotide sequence data are available in the GenBank databases under the accession numbers MK875971, MK875972, MK875973, MK875974, MK875975, MK875976, MK875977.


Transit time of swallowing after subtotal laryngectomy.
The aim of subtotal laryngeal surgery (Cricohyoidopexy = CHP and Cricohyoidoepiglottopexy = CHEP) is to create a simplified but functional neolarynx. The neolarynx permits the passage of air, the closure of the airway, and ensures phonation through the vibration of the cricoid and arytenoid mucosa; furthermore, it allows the recovery of swallowing, optimizing the closure of the neoglottis with the movement of the remaining arytenoids. The aim of the present study was to evaluate, on a long-term basis, the efficiency of the swallowing function comparing swallowing times in CHEP and CHP with and without functional neck dissection (FND). A radiological study was conducted on 48 patients selected from a group of 253, who underwent subtotal laryngectomies at the "G. Ferreri" Department of Otorhinolaryngology, Audiology and Phoniatrics of the University of Rome "La Sapienza". The selection of the 48 patients was carried out based on the following criteria: type of surgery, date of surgery (follow up of at least 12 months), patients who were not treated with radiotherapy before or after surgery, patients who were also examined with fibrolaryngoscopy and videofluoroscopy, patients not affected by motor deficits involving phonatory and swallowing regions (stroke, lesions of the central nervous system), negative follow up (no evidence of disease). The parameters for evaluating the functional recovery were the times the nasogastric tube and tracheotomy tube were kept in place. The functional recovery times of the groups thus formed were compared to one another Through videofluoroscopy the authors evaluated oral transit times (OTT) and pharyngeal transit times (PTT) as parameters of deglutition. The results consistently showed that swallowing time remains under one second as in individuals with normal swallowing functions. The study of deglutition times, conducted at least 12 months after surgery, does not show any substantial differences between CHEP and CHP with reference to pharyngeal transit and oral transit times.


Ultrastructural and morphological characteristics of human anterior cruciate ligament and hamstring tendons.
Hamstring tendons are a commonly used substitute for anterior cruciate ligament (ACL) reconstruction. Ligaments and tendons are similar in composition but the ACL is more complex than hamstring tendons in function and gross morphology, which are highly dependent on its structure and ultrastructure. The purpose of this study was to compare the morphology and ultrastructure of normal human ACL and hamstring tendons, including the cell type and arrangement, expression level of proteoglycans, diameter, and density of collagen fibrils. Twenty semitendinosus or gracilis tendons and 20 ACL specimens were harvested from patients with ACL rupture or osteoarthritis undergoing routine total knee arthroplasty. The specimens were examined histologically and the ultrastructure was observed using scanning and transmission electron microscopy. Semitendinosus and gracilis tendons showed a homogeneous arrangement of collagen fibers and cell type. They had lower fibril density and more widely distributed fibril diameters. In the ACL, there was a more complex arrangement of collagen fibers, distribution of proteoglycans and different cell types. Electronic microscopy demonstrated a combination of parallel, helical and nonlinear networks of ACL fibrils, and fibril diameters were smaller and more nonuniform. This study compared the anatomy of normal human ACL and hamstring tendons, which may provide a standard for evaluating hamstring tendons grafts after ACL reconstruction and may facilitate the application of hamstring tendons in clinical applications.


Gluten-sensitive recurrent aphthous stomatitis.
Twenty selected patients with recurrent aphthous stomatitis in whom celiac disease had been specifically excluded were placed on a gluten-free diet. Five patients (25%) showed a favorable response to gluten withdrawal and a positive gluten challenge. Jejunal morphology was normal in all patients indicating gluten sensitivity without enteropathy. Gluten withdrawal provides a further method of treating some patients with recurrent aphthous stomatitis.


The Art of Medical Photography in Breast Surgery: Clinical, Intra-operative and Specimen Photography - Standards and Recommendations.
Medical visual documentation is an especially important source of information for medicine. Medical photography has become the main method of medical visual documentation. In breast surgery, as in all other medical branches, medical photography has a major role in education and patient follow-up. The published literature was reviewed for medical photography techniques. In co-operation with the University fine arts faculty photography unit, standards for clinical, intra-operative and specimen photography in breast surgery were analyzed and identified. As a result, we have made recommendations for obtaining high quality and academically more effective medical photographs in breast surgery.


Antitumor effects of melanin from Lachnum YM226 and its derivative in H22 tumor-bearing mice.
In the present study, we investigated the anti-tumor activities of the intracellular homogeneous melanin (LM) of Lachnum YM226 and its derivative (ALM) on liver cancer using murine H22 hepatocarcinoma model. The results showed that LM and ALM (50 and 200 mg kg-1) could effectively inhibit tumor growth of H22 tumour-bearing mice. The body weight, liver, spleen and thymus indices also improved in the LM and ALM treated groups. Moreover, the levels of alanine aminotransferase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), creatinine (CRE), blood urea nitrogen (BUN) and uric acid (UA) were lowered. Serum cytokines of interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were increased on LM and ALM administration, while LM and ALM significantly decreased the vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels. The H&E staining indicated that LM and ALM exhibited antitumor activity in vivo by promoting apoptosis and inhibiting angiogenesis. The anti-tumor effect of ALM was more significant than that of LM for the same dose. In summary, the findings demonstrated that LM and ALM might be promising candidates for the prevention and treatment of HCC.


Administration of rCTRP9 Attenuates Neuronal Apoptosis Through AdipoR1/PI3K/Akt Signaling Pathway after ICH in Mice.
Targeting neuronal apoptosis after intracerebral hemorrhage (ICH) may be an important therapeutic strategy for ICH patients. Emerging evidence indicates that C1q/TNF-Related Protein 9 (CTRP9), a newly discovered adiponectin receptor agonist, exerts neuroprotection in cerebrovascular disease. The aim of this study was to investigate the anti-apoptotic role of CTRP9 after experimental ICH and to explore the underlying molecular mechanisms. ICH was induced in mice via intrastriatal injection of bacterial collagenase. Recombinant CTRP9 (rCTRP9) was administrated intranasally at 1 h after ICH. To elucidate the underlying mechanisms, adiponectin receptor1 small interfering ribonucleic acid (AdipoR1 siRNA) and selective PI3 K inhibitor LY294002 were administered prior to rCTRP9 treatment. Western blots, neurofunctional assessments, immunofluorescence staining, and Fluoro-Jade C (FJC) staining experiments were performed. Administration of rCTRP9 significantly improved both short- and long-term neurofunctional behavior after ICH. RCTRP9 treatment significantly increased the expression of AdipoR1, PI3 K, p-Akt, and Bcl-2, while at the same time was found to decrease the expression of Bax in the brain, which was reversed by inhibition of AdipoR1 and PI3 K. The neuroprotective effect of rCTRP9 after ICH was mediated by attenuation of neuronal apoptosis via the AdipoR1/PI3K/Akt signaling pathway; therefore, rCTRP9 should be further evaluated as a potential therapeutic agent for ICH patients.


Interaction and functional cooperation of the cancer-amplified transcriptional coactivator activating signal cointegrator-2 and E2F-1 in cell proliferation.
Activating signal cointegrator-2 (ASC-2), a novel coactivator, is amplified in several cancer cells and known to interact with mitogenic transcription factors, including serum response factor, activating protein-1, and nuclear factor-kappaB, suggesting the physiological role of ASC-2 in the promotion of cell proliferation. Here, we show that the expression pattern of ASC-2 was correlated with that of E2F-1 for protein increases at G(1) and S phase. Furthermore, cells stably overexpressing ASC-2 had an increased cell proliferation profile. These results prompted us to examine the functional interaction of ASC-2 and E2F-1. Biochemical evidence of protein interaction indicated that the transactivation domain of E2F-1 interacted with the COOH-terminal region of ASC-2. The importance of the E2F-1-ASC-2 interaction was supported by the demonstration that the coexpression of ASC-2 and E2F-1 synergistically transactivated E2F-1-driven gene transcription and the acetylation of E2F-1 protein was necessary for ASC-2-mediated transcriptional coactivation. Interestingly, overexpression of ASC-2 increased the endogenous protein level of E2F-1 in cells, resulting from the prolonged protein stability of E2F-1. Taken together, these results suggest that the cancer-amplified transcriptional coactivator ASC-2 may promote cell proliferation through enhancement of E2F-1-dependent transactivation of the expression of genes associated with cell cycle progression that may be available to favor tumor growth in vivo.


Enhanced adaptive loop filter for motion compensated frame.
We propose an adaptive loop filter to remove the redundancy between current and motion compensated frames so that the residual signal is minimized, thus coding efficiency increases. The loop filter coefficients and offset are optimized for each frame or a set of blocks to minimize the total energy of the residual signal resulting from motion estimation and compensation. The optimized loop filter with offset is applied for the set of blocks where the filtering process gives coding gain based upon rate-distortion cost. The proposed loop filter is used for the motion compensated frame whereas the conventional adaptive interpolation filter (AIF) is applied to the reference frames to interpolate the subpixel values. Another conventional scheme adaptive loop filter (ALF), is used after deblocking filtering to enhance quality of reconstructed frames, not to minimize energy of residual signal. The proposed loop filter can be used in combination with the AIF and ALF. Experimental results show that proposed algorithm provides the averaged bit reduction of 8% compared to conventional H.264/AVC scheme. When the proposed scheme is combined with AIF and ALF, the coding gain increases even further.


Puerarin protects PC12 cells against beta-amyloid-induced cell injury.
beta-Amyloid protein (Abeta), a major protein component of brain senile plaques in Alzheimer's disease, is known to be directly responsible for the production of reactive oxygen species (ROS) and induction of apoptosis. In this study, the protective effect of puerarin, an isoflavone purified from the radix of the Chinese herb Pueraria lobata, on Abeta-induced rat pheochromocytoma (PC12) cultures was investigated. Although exposure of PC12 cells to 50 microM Abeta25-35 caused significant viability loss and apoptotic rate increase, pretreatment of the cells with puerarin for 24h reduced the viability loss and apoptotic rate. Puerarin (1 microM) significantly inhibited Abeta25-35-induced apoptosis of PC12 cells. Preincubation of the cell with puerarin also restored the ROS and mitochondrial membrane potential levels that had been altered as a result of Abeta25-35 treatment. Puerarin was also found to increase the Bcl-2/Bax ratio and reduce caspase-3 activation. These results suggest that puerarin could attenuate Abeta25-35-induced PC12 cell injure and apoptosis and could also promote the survival of PC12 cells. Therefore, puerarin may act as an intracellular ROS scavenger, and its antioxidant properties may protect against Abeta25-35-induced cell injury.


Acupuncture for insomnia.
Although conventional non-pharmacological and pharmacological treatments for insomnia are effective in many people, alternative therapies such as acupuncture are still widely practiced. However, it remains unclear whether the existing evidence is rigorous enough to support its use. To determine the efficacy and safety of acupuncture in people with insomnia. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, Dissertation Abstracts International, CINAHL, AMED (the Allied and Complementary Medicine Database), TCMLARS (Traditional Chinese Medical Literature Analysis and Retrieval System), National Center for Complementary and Alternative Medicine, the National Institute of Health Clinical Trials Database, the Chinese Acupuncture Trials Register, the Trials Register of the Cochrane Complementary Medicine Field, from inception to 2006, and the sleep bibliography, which is available at www.websciences.org/bibliosleep. We searched reference lists of retrieved articles, and contacted trial authors and experts in the field for information on ongoing/completed trials. Randomised controlled trials evaluating any form of acupuncture involving participants of any age with any type of insomnia were included. Included trials compared acupuncture with placebo or sham or no treatment, or acupuncture plus other treatments compared with the same other treatments. Trials that compared only acupuncture methods or compared acupuncture alone against other treatments alone were excluded, since they did not yield the net effect of acupuncture. Two review authors independently extracted data and assessed quality according to a set of criteria for risk of selection bias, performance bias, attrition bias and detection bias. Relative risk (RR) and standardised mean difference (SMD) with 95% confidence intervals were used for binary and continuous outcomes respectively. Data were combined in meta-analyses (on an intention-to-treat basis), where more than one trial without significant clinical heterogeneity presented the same outcome. Seven trials met the inclusion criteria. The studies included 590 participants with insomnia, of whom 56 dropped out. Participant age ranged from 15 to 98 years, and the duration of insomnia varied from 6 months to 19 years. Co-existing medical conditions contributing to insomnia included stroke, end-stage renal disease and pregnancy. Apart from conventional needle acupuncture, different variants of acupuncture such as acupressure, auricular magnetic and seed therapy, and transcutaneous electrical acupoint stimulation (TEAS) were evaluated. Meta-analysis was limited because of considerable heterogeneity between comparison groups and between outcome measures. Based on the findings from individual trials, the review suggested that acupuncture and acupressure may help to improve sleep quality scores when compared to placebo (SMD = -1.08, 95% CI = -1.86 to -0.31, p=0.006) or no treatment (SMD -0.55, 95% CI = -0.89 to -0.21, p=0.002). TEAS also resulted in better sleep quality score in one trial (SMD = -0.74, 95% CI = -1.22 to -0.26, p=0.003). However, the efficacy of acupuncture or its variants was inconsistent between studies for many sleep parameters, such as sleep onset latency, total sleep duration and wake after sleep onset. The combined result from three studies reporting subjective insomnia improvement showed that acupuncture or its variants was not more significantly effective than control (RR = 1.66, 95% CI = 0.68 to -4.03) and significant statistical heterogeneity was observed. Only one study reported an adverse event, with one out of 16 patients (6.3%) withdrawing from acupuncture because of pain. The small number of randomised controlled trials, together with the poor methodological quality and significant clinical heterogeneity, means that the current evidence is not sufficiently extensive or rigorous to support the use of any form of acupuncture for the treatment of insomnia. Larger high quality clinical trials employing appropriate randomisation concealment and blinding with longer follow-up are needed to further investigate the efficacy and safety of acupuncture for the treatment of insomnia.