Biochar does not attenuate triclosan's impact on soil bacterial communities.
Triclosan, a broad-spectrum antimicrobial, has been widely used in pharmaceutical and personal care products. It undergoes limited degradation during wastewater treatment and is present in biosolids, most of which are land applied in the United States. This study assessed the impact of triclosan (0-100 mg kg-1) with and without biochar on soil bacterial communities. Very little 14C-triclosan was mineralized to 14CO2 (<7%) over the course of the study (42 days). While biochar (1%) significantly lowered mineralization of triclosan, analysis of 16S rRNA gene sequences revealed that biochar impacted very few OTUs and did not alter the overall structure of the community. Triclosan, on the other hand, significantly affected bacterial diversity and community structure (alpha diversity, ANOVA, p < 0.001; beta diversity, AMOVA, p < 0.01). Dirichlet multinomial mixtures (DMM) modeling and complete linkage clustering (CLC) revealed a dose-dependent impact of triclosan. Non-Parametric Metastats (NPM) analysis showed that 150 of 734 OTUs from seven main phyla were significantly impacted by triclosan (adjusted p < 0.05). Genera harboring opportunistic pathogens such as Flavobacterium were enriched in the presence of triclosan, as was Stenotrophomonas. The latter has previously been implicated in triclosan degradation via stable isotope probing. Surprisingly, Sphingomonads, which include well-characterized triclosan degraders were negatively impacted by even low doses of triclosan. Analyses of published genomes showed that triclosan resistance determinants were rare in Sphingomonads which may explain why they were negatively impacted by triclosan in our soil.


A Sophisticated Architecture Is Indeed Necessary for the Implementation of Health in All Policies but not Enough Comment on "Understanding the Role of Public Administration in Implementing Action on the Social Determinants of Health and Health Inequities".
In this commentary, I argue that beyond a sophisticated supportive architecture to facilitate implementation of actions on the social determinants of health (SDOH) and health inequities, the Health in All Policies (HiAP) project faces two main barriers: lack of awareness within policy networks on the social determinants of population health, and a tendency of health actors to neglect investing in other sectors' complex problems.


Acting mechanisms of Lentinan in human--II. Enhancement of non-specific cell-mediated cytotoxicity as an interferon inducer.
The immunopotentiator "Lentinan" augmented the cell-mediated cytotoxicity in humans. (a) The activation of killer T cells by the mixed lymphocyte culture was accelerated only when responder cells were mixed with both a suboptimum number of stimulator cells and Lentinan. (b) The interferon level in the peripheral blood circulation of cancer patients was elevated in 12 h following Lentinan administration, and natural killer activity of peripheral mononuclear cells was enhanced in 48 h. These data indicate that Lentinan favorably affects the host mechanisms of man.


Isoniazid treatment of Mycobacterium bovis in cattle as a model for human tuberculosis.
Cattle infected with Mycobacterium bovis spoligotype 9 were treated with Isoniazid (INH) from three to 14 weeks post infection, rested for fourweeks to allow INH depletion and then challenged with M. bovis spoligotype 35. Post mortem examination (PME) 35 weeks after the initial infection showed partial protection against infectious challenge following INH-attenuated infection compared with the spoligotype 35 challenge controls. Antigen-specific IFN-gamma responses decreased over time with INH therapy, following a similar pattern to that observed in the treatment of M. tuberculosis infection in humans. Following cessation of therapy, specific IFN-gamma responses increased more strongly in those calves that were visibly lesioned at PME. IFN-gamma responses were also used to identify two antigens, TB10.4 and Acr2, that induced anamnestic responses in INH-treated, re-challenged calves, suggesting a role for both antigens in protective immunity. Specific IL-10 responses were observed in all calves following treatment with INH suggesting a role for IL-10 in the resolution of infection.


From childhood maltreatment to adult inflammation: Evidence for the mediational status of social anxiety and low positive affect.
Prior work has established a robust association between childhood maltreatment and systemic inflammatory activation later in life; however, the mechanisms involved in this process remain incompletely understood. The purpose of this investigation was to examine potential mechanistic roles for social anxiety (SA) symptoms and low positive affect (PA) in the path from childhood maltreatment to elevations in circulating interleukin (IL)-6, a common biomarker of inflammatory activation. In addition, building on prior work establishing linkages between mindful awareness and reductions in systemic inflammation, we examined the potential role of trait mindfulness as a moderator of the relationships among childhood maltreatment, SA, low PA, and IL-6. A serial mediation model utilizing a large epidemiologic dataset (final N = 527) supported our central hypothesis that the direct effect of childhood maltreatment on IL-6 was fully serially statistically mediated by SA symptoms and low PA (but not high negative affect). Additionally, results indicated that individuals falling in the upper versus lower quartiles of SA symptoms demonstrated significantly elevated concentrations of IL-6, a finding that has not been previously reported. Trait mindfulness moderated the association between low PA and IL-6, to the exclusion of any paths related to negative affect. Additionally, results indicated that the effect of child maltreatment on IL-6 bypasses SA to indirectly impact IL-6 via negative affect. Overall, we conclude that childhood maltreatment and SA symptoms have a significant influence on IL-6, albeit indirectly via low PA, and the influence of PA on IL-6 may be uniquely susceptible to influence by individual differences in mindfulness.


Dopaminergic and norepinephrinergic modulation of endogenous event-related potentials: A systematic review and meta-analysis.
Event-related potentials (ERPs) represent the cortical processing of sensory, motor or cognitive functions invoked by particular events or stimuli. A current theory posits that the catecholaminergic neurotransmitters dopamine (DA) and norepinephrine (NE) modulate a number of endogenous ERPs during various cognitive processes. This manuscript aims to evaluate a leading neurotransmitter hypothesis with a systematic overview and meta-analysis of pharmacologic DA and NE manipulation of specific ERPs in healthy subjects during executive function. Specifically, the frontally-distributed P3a, N2, and Ne/ERN (or error-related negativity) are supposedly modulated primarily by DA, whereas the parietally-distributed P3b is thought to be modulated by NE. Based on preceding research, we refer to this distinction between frontally-distributed DA-sensitive and parietally-distributed NE-sensitive ERP components as the Extended Neurobiological Polich (ENP) hypothesis. Our systematic review and meta-analysis indicate that this distinction is too simplistic and many factors interact with DA and NE to influence these specific ERPs. These may include genetic factors, the specific cognitive processes engaged, or elements of study design, i.e. session or sequence effects or data-analysis strategies.


Disease-focused or integrated treatment: diabetes and depression.
This article reviewed the literature on the adverse health outcomes of the coexistence of diabetes and depression, the challenges of treating coexisting diabetes and depression in a fragmented health care system, and the need for integrated care as a strategy to improve the quality of care for patients who have complex medical illnesses (eg, patients who have coexisting diabetes and depression).


Role of genotype G hepatitis B virus mixed infection on the progression of hepatic fibrosis in HIV positive patients over 5 years of follow-up.
Due to common routes of transmission, HIV and HBV are frequently found as concomitant infections. The dynamic of liver disease in co-infected patients is important to understand for appropriate clinical management. Conflicting data surround the role played by genotype-G HBV (HBV-G) during the course of HIV co-infection. This study aims to assess, using non-invasive methods, liver disease progression in HIV-HBV genotype-G co-infected patients. Co-infected patients with residual HBV replication (n=125) were screened for HBV-G infection by specific real-time PCR. The impact of HBV-G on liver fibrosis progression, as assessed by a non invasive biomarker (Fibrotest), was evaluated first, by a cross sectional analysis comparing fibrosis between HBV-G (n=23) and non-G (n=55) infected patients and second, by a longitudinal study performed over a 5 year period. Selected patients were mostly male (90%), with homogenous characteristics between the HBV-G and non-G infected groups, in terms of age, known duration of HIV disease, immune and virological status and duration of HIV/HBV treatment. HBV-G infected patients were exclusively from Western Europe with homosexual intercourses (83%) as principal risk of transmission. Cross sectional analysis revealed comparable liver disease severity distribution between HBV-G and non-G infected patients. Co-infection with other hepatitis viruses and low CD4-nadir, but not HBV-G co-infection, were associated with a 5-year risk of fibrosis progression. This study suggests that HBV-G infection is not significantly associated with a more severe liver disease and does not have a deleterious impact on fibrosis progression in efficiently treated HIV-HBV co-infected patients.


Comparing the pregnancy rates of one versus two intrauterine inseminations (IUIs) in male factor and idiopathic infertility.
To compare the effectiveness of double IUI with single IUI in male factor and idiopathic infertility patients undergoing controlled ovarian hyperstimulation (COH). A prospective randomized study of 1257 COH-IUI cycles was performed. Total 1270 patients with mild or moderate male factor infertility (n = 776) and idiopathic infertility (n = 494) were enrolled in this study, and 767 with male factor infertility and 490 with idiopathic infertility completed clomiphene citrate (CC)/human menopausal gonadotrophin (hMG) COH cycles and IUI. Categorized on the basis of the causes of infertility (male factor, M; idiopathic infertility, I), patients were randomized into one of the following groups: Single IUI group (M(1)/I(1)) received single insemination 34 h post hCG administration, and double IUI group (M(2)/I(2)) received two inseminations 18-24 and 36-48 h post hCG injection, respectively. The overall pregnancy rates were 15.43%. Pregnancy rate for single and double IUI group was 11.06 and 19.87% (p < 0.05), respectively. There was a significant statistical difference in cycle fecundity between M(1) and M(2) group (11.34% vs. 24.93%, p < 0.05), and between I(2) and M(2) group (11.93% vs. 24.93%, p < 0.05), but there was no significant difference between I(1) and I(2) (10.53% vs. 11.93%, p > 0.05). Double IUI increases the pregnancy rate significantly in patients with male factor infertility, and single IUI acts as efficient as double IUI in patients with idiopathic infertility.


[The system of evaluating the specialty of pediatrics in the Instituto Mexicano del Seguro Social].
A system of evaluation applied to pediatric residents at the Mexican Institute of Social Security (IMSS) is presented. Historical precedents; deficiencies and modifications of the system are commented. Also institutional system of evaluation is described, with emphasis in education strategies: teaching-attendance-research. Usefulness of knowledge tests, supervision, and assessment of evaluation, are mentioned. Finally extrainstitutional evaluation strategies are considered.


Asbestos-related increase in pulmonary levels of vasoactive intestinal peptide (VIP).
Vasoactive intestinal peptide (VIP), leucine-enkephalin (Leu-Enk), dynorphin (Dyn), neurotensin (NT) and substance P (SP) were measured by radioimmunoassay in lung and bronchoalveolar lavage (BAL) fluids of sham operated control rats and rats exposed to asbestos (5 and 10 mg, single intratracheal injections) for 3 and 6 months. Among these peptides, VIP, Leu-Enk and Dyn were the most abundant with 6 to 25 pmoles per g of lung tissue as compared with 0.95 to 1.2 pmoles per g for the other neuropeptides. In the presence of asbestos, VIP levels were selectively increased up to 2.7 times in lung tissue and 4.3 times in BAL fluids. On high pressure liquid chromatography (HPLC), the immunoreactive VIP coeluted with synthetic VIP. It is concluded that this selective increase may be involved in the pathogenesis of asbestos-related diseases. Exposure to asbestos causes chronic inflammatory reactions in the lung which may lead to fibrosis (1) and increase the incidence of pleuropulmonary cancers (2). Little is known concerning the biochemical changes responsible for the deleterious effects of asbestos on pulmonary functions. Previous studies have documented the vast complexity and diversity of lung biochemistry including its ability to metabolize lipids, inactivate certain enzymes and produce physiologically active amines (3-6). Recently, the lung has been recognized as an important source of peptidergic substances. VIP and SP were reported to be localized in nerve terminals of the main airways and in axons of the parasympathetic conducts (7-11). Other neuropeptides including bombesin (12, 13), calcitonin (13, 14) and Leu-Enk (13) were also detected in the lung. However, these latter peptides were mainly confined to diffuse granule-containing cells also known as APUD cells (amine precursor uptake and decarboxylation cells) (15). The role of these neuropeptides in normal lung function and in pulmonary diseases is unknown. However, it has recently been demonstrated that APUD cells proliferate in the rat lung following asbestos inhalation (16) and lung exposure to carcinogens (17, 18). In addition, Moody et al. (19) and Sorenson et al. (20) have observed high levels of bombesin in human cell lines derived from small-cell lung carcinoma. It was then of particular interest to verify if lung exposure to asbestos can induce some changes in the levels of various neuropeptides. In the present study, we report that VIP is significantly increased in the lungs and BAL fluids of rats exposed to asbestos while no significant change in the levels of Leu-Enk, Dyn, NT and SP is observed.


Who will be readmitted? Evaluation of the laparoscopic hysterectomy readmission score in a gynecologic oncology population undergoing robotic-assisted hysterectomy.
The laparoscopic hysterectomy readmission score (LHRS) was created to identify patients for whom same day discharge (SDD) after minimally invasive hysterectomy (MIH) may not be advisable and includes diabetes, chronic obstructive pulmonary disease, disseminated cancer, chronic steroid use, bleeding disorder, length of surgery, and any postoperative complication prior to discharge. We evaluated the performance of the score at predicting readmission in a gynecologic oncology population, and additionally sought to determine if any factors known prior to surgery could replace those that are not known until the time of surgery (operative time and postoperative complication). This was a single-institution retrospective cohort study of women undergoing robotic hysterectomy by a gynecologic oncologist in 2018. Associations between pre-operative, operative and post-operative factors and 30-day readmission, SDD and postoperative complications were assessed using logistic regression. The 30-day readmission rate among the 423 women in the cohort was 4.5% and 1.9% in those undergoing SDD. Readmission rates by LHRS were: score 1 (4.9%), score 2 (7.8%), score 3 (13.6%), score 4 (16.7%). Patients with a LHRS of ≥3 had higher odds of readmission compared to those with a lower score (OR 4.20, p = 0.02). Infectious morbidity accounted for the majority of postoperative complications, emergency room visits and readmissions. We did not identify preoperative factors to replace the intra- and post-operative factors used in the score. The readmission rate following MIH is low, and a LHRS of ≥3 is associated with increased risk of readmission. Our findings support the applicability of the LHRS to a gynecologic oncology population; addressing risk factors for postoperative infection or closer follow up for patients with a LHRS ≥3 could reduce postoperative readmissions.


Persistence and convergence of ecosystems: an analysis of some second order difference equations.
Three second order difference equation models are analyzed and numerical solutions computed. It is shown that two concepts of ecosystem stability, the local property of convergence and the global property of persistence, do not coincide, and that the exislity are obtained and shown as parameter space diagrams. Examples of solution trajectories representative of different regions of this space are computed and discussed. A wide range of oscillatory behavior, as noted in recent papers by several authors, results. In addition, the erratic nature of regions of convergence to stable solutions is discussed.


Antidepressant-Like Effects of Chaihu Shugan Powder () on Rats Exposed to Chronic Unpredictable Mild Stress through Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis.
To investigate the antidepressant-like effects of Chaihu Shugan Powder (CSP, ) and to explore its underlying mechanisms. Thirty-two Sprague-Dawley rats were randomly divided into control (CON), chronic unpredictable mild stress (CUMS), fluoxetine (FLU), and CSP groups, 8 rats in each group. All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model. The open field test (OFT), forced swimming test (FST), and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues. The mRNA and protein levels of glucose-regulated protein (GRP) 78, spliced X-box-binding protein (XBP)-1, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and c-Jun N-terminal kinase (JNK) in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis, respectively. Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats, as revealed by enhanced time and distance in the center of the OFT (P<0.05), an increased preference for sucrose, and longer swimming time and shorter immobility time during the FST (all P<0.05). In addition, CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons (P<0.05). The mRNA and protein expression levels of GRP78, spliced XBP-1, and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins (all P<0.05), whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats. CSP can improve depression-like behavior in rats exposed to CUMS, possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.


1H NMR in a quasi-one-dimensional zig-zag spin chain of hambergite, Be2BO3(OH).
One-dimensional spin chains are important testbeds for the investigation of quantum many-body systems. Here, we introduce a new quasi-one-dimensional chain of spin-1/2 1H nuclei in hambergite (Be2BO3(OH)) crystal. The distinctive feature of hambergite is the zig-zag arrangement of the spins in the chains compared to the systems reported earlier. A single crystal of hambergite was investigated experimentally using 1H nuclear magnetic resonance at different orientations in the external magnetic field. The experimental spectra were compared with the Van Vleck's second moments calculated from the structural data. For the orientation of the chain along the external magnetic field the resonance resembles that of the linear spin chains and the calculated contributions to the second moment from spins within one chain of hambergite amount to 96%. For other orientations the spectra demonstrate features specific to the zig-zag chain. Our results show that 1H nuclei in hambergite crystals could serve a good model of a well-isolated zig-zag spin chain.


Conscious contents as reflexive processes: Evidence from the habituation of high-level cognitions.
Reflexes are often insuppressible, predictable, and susceptible to external control. In contrast, conscious thoughts have been regarded as whimsical, 'offline,' and shielded from external control. Recent advances suggest that conscious thoughts are more reflex-like and susceptible to external control than previously thought. In one paradigm, high-level conscious thoughts (subvocalizations) are triggered by external control, as a function of external stimuli and experimenter-induced action sets. It has been hypothesized that these conscious contents are activated involuntarily and in a reflex-like manner. If such is the case, then these activations should possess a well-known property of the reflex: habituation. Accordingly, we found that involuntary high-level cognitions (subvocalizations) habituated (i.e., were less likely to arise) after repeated stimulation. As in the case of the habituation of a reflex, this novel effect was stimulus-specific. We discuss the implications of this finding for theories about consciousness and about psychopathological phenomena involving undesired, involuntary cognitions.


From classified to commonplace: the trajectory of the hydrogen bomb 'secret'.
The secret of the hydrogen bomb went from being an icon of nuclear secrecy to something that could be widely reproduced on the Internet and in children's textbooks. The rise and fall of the H-bomb secret reveals both changing attitudes towards state secrecy in general and the contingent nature of secrecy, depending on an imagined threat as guidance.


Renal cell carcinoma with intracaval tumor thrombus extending to the diaphragm: ultrasonography and surgical management.
We describe the successful management of a patient with intracaval extension of renal cell carcinoma to the level of the diaphragm. Ultrasonography delineated clearly the upper extent of the tumor thrombus and revealed no invasion of the vena caval wall at or above the entrance of the main hepatic veins. To prevent severe hypotension caused by intrapericardial control of the inferior vena cava, the aorta was clamped temporarily just above the celiac axis. The tumor was removed completely en bloc with the thrombus. Blood loss was minimal and the patient recovered promptly.


Motor deficits in 16-month-old male and female 3xTg-AD mice.
Motor deficits are some of the most prevalent non-cognitive symptoms of Alzheimer's disease (AD) with patients showing impairments in speech, gait and fine motor skills. We investigated motor behaviour in 16-month-old male and female 3xTg-AD mice and their B6129SF2 wildtype (WT) controls. The 3xTg-AD mice develop extracellular Aβ plaques and tau tangles in the hippocampus and motor cortex between 6 and 9 months of age. Previously we showed that at 6 months of age, 3xTg-AD mice performed better on tests of motor coordination and motor learning than WT mice. The aim of our experiment was to use a battery of motor behaviour tests to determine if this superior motor performance was present in older mice. On the Rotarod, the aged 3xTg-AD mice showed better motor coordination and learning than WT mice. Although females performed better than males, this sex difference was confounded by body weight as females weighed less than males. There were no significant genotype or sex differences on the wire hang or grid suspension tasks, nor in stride length or stride width, but 3xTg-AD mice performed worse than WT mice on the balance beam. In comparison to the 6-month-old mice, an age-related decline in most aspects of motor behaviour was apparent. These results indicate that different sub-domains of motor function are affected differently in the 3xTg-AD mice and that aging does not have the same effect on all motor behaviours.


Hearing preservation surgery for cochlear implantation--hearing and quality of life after 2 years.
To study the benefits of hearing preservation surgery in cochlear implantation after 2 years. A retrospective cohort study. Performed at a single academic institution between 2008 and 2010 Thirteen patients (1 bilateral): 43% male and 57% female subjects. Mean age at surgery was 51 years (range, 32-72 yr). Average duration of deafness was 25 years (range, 5-62 yr). Hearing preservation cochlear implantation surgery performed with the Med-El FlexEAS electrode. Pure tone thresholds, speech perception in quiet and noise and quality of life (Abbreviated Profile of Hearing Aid Benefit [APHAB] and Glasgow Hearing Aid Benefit [GHABP Scales] up to and including 2 years after surgery. At the first postoperative audiogram, the hearing preservation rate was 100% (complete (42.9%), partial (50%), and minimal (7.1%)). After 24 months, the breakdown was complete (25%), partial (12.5%), minimal (37.5%) and complete loss (12.5%). There was a trend in improvement in all areas of APHAB) with significant improvements in the background noise and reverberation categories as well as the global scores. The GHABP scores showed high levels of use, benefit, and low levels of residual disease. Hearing preservation can be achieved in the short term but deteriorates with time over the medium term at a rate greater than that can be expected with the natural progression of the disease. Patients show benefits in speech outcomes and quality of life regardless of whether hearing preservation was achieved in the medium term.


Cross-correlation of EMG reveals widespread synchronization of motor units during some slow movements in intact cats.
It is commonly assumed that the motor units comprising a single mammalian muscle will be recruited asynchronously at subtetanic firing rates to produce smoothly modulated force output. However, electromyograms from certain neck muscles, recorded by implanted bipolar "patch" electrodes having large contacts, often exhibited a rhythmic clustering of spike activity whose patterns suggested that motor-unit firing was synchronized both within and across muscles. We have developed a computerized processing system that digitizes EMG activity and calculates auto- and cross-correlation products of selected segments. The presence or absence of synchronization caused by neural mechanisms can be identified and differentiated from that due to the rhythmicity of the behavior itself (e.g. shaking) or due to cross-talk, according to the shapes of the resultant correlograms. These methods have so far been applied to the study of hindlimb and neck muscle EMG during various natural motor behaviors, but they provide a general, quantitative tool for the study of an important aspect of motor control that may be overlooked by conventional sampling and smoothing techniques.


Surrogate nutrition markers, malnutrition, and adequacy of nutrition support.
Surrogate nutrition markers are used to assess adequacy of nourishment and to define malnutrition despite evidence that fails to link nourishment, surrogate markers, and outcomes. Markers such as serum levels of albumin, prealbumin, transferrin, and IGF-1 and delayed hypersensitivity and total lymphocyte count may be valid to help stratify risk. However, it is not appropriate to consider these as markers of adequacy of nourishment in the sick patient.


Persistent and emerging pollutants assessment on aquaculture oysters (Crassostrea gigas) from NW Portuguese coast (Ria De Aveiro).
The study aim was to determine a range of relevant persistent and emerging pollutants in oysters produced in an aquaculture facility located in an important production area, to assure their safety for human consumption. Pollutants, including 16 PAHs, 3 butyltins (BTs), 29 flame retardants (FRs, including organophosphate and halogenated FRs), 35 pesticides (including 9 pyrethroid insecticides) and 13 personal care products (PCPs, including musks and UV filters), were determined in oysters' tissues collected during one year in four seasonal sampling surveys. The seasonal environmental pollution on the production site was evaluated by water and sediment analysis. Furthermore, oysters' nutritional quality was also assessed and related with the consumption of healthy seafood, showing that oysters are a rich source of protein with low fat content and with a high quality index all year around. Results showed that most analysed pollutants were not detected either in oyster tissues or in environmental matrixes (water and sediments). The few pollutants detected in oyster tissues, including both regulated and non-legislated pollutants, such as a few PAHs (fluorene, phenanthrene, anthracene, fluoranthene, pyrene and indenopyrene), FRs (TPPO, TDCPP, DCP, BDE-47, BDE-209 and Dec 602) and PCPs (galaxolide, galaxolidone, homosalate and octocrylene), were present at low levels (in the ng/g dw range) and did not represent a significant health risk to humans. The observed seasonal variations related to human activities (e.g. tourism in summer) highlights the need for environmental protection and sustainable resource exploration for safe seafood production.


Inhibition of cathepsin activity in a cell-based assay by a light-activated ruthenium compound.
Light-activated inhibition of cathepsin activity was demonstrated in a cell-based assay. Inhibitors of cathepsin K, Cbz-Leu-NHCH2 CN (2) and Cbz-Leu-Ser(OBn)-CN (3), were caged within the complexes cis-[Ru(bpy)2 (2)2 ]Cl2 (4) and cis-[Ru(bpy)2 (3)2 ](BF4 )2 (5) (bpy=2,2'-bipyridine) as 1:1 mixtures of Δ and Λ stereoisomers. Complexes 4 and 5 were characterized by (1) H NMR, IR, and UV/Vis spectroscopies and electrospray mass spectrometry. Photochemical experiments confirm that 4 releases two molecules of 2 upon exposure to visible light for 15 min, whereas release of 3 by 5 requires longer irradiation times. IC50 determinations against purified cathepsin K under light and dark conditions with 4 and 5 confirm that inhibition is enhanced from 35- to 88-fold, respectively, upon irradiation with visible light. No apparent toxicity was observed for 4 in the absence or presence of irradiation in bone marrow macrophage (BMM) or PC3 cells, as determined by MTT assays, at concentrations up to 10 μM. Compound 5 is well tolerated at lower concentrations (<1 μM), but does show growth-inhibitory effects at higher concentrations. Confocal microscopy experiments show that 4 decreases intracellular cathepsin activity in osteoclasts with light activation. These results support the further development of caged nitrile-based inhibitors as chemical tools for investigating spatial aspects of proteolysis within living systems.


Steroidal MRA Across the Spectrum of Renal Function: A Pooled Analysis of RCTs.
Mineralocorticoid receptor antagonists (MRAs) are underused in patients with kidney dysfunction, and their efficacy among patients with chronic kidney disease (CKD) is uncertain. The goal of this study was to analyze the efficacy and safety of steroidal MRAs across the spectrum of estimated glomerular filtration rates (eGFRs) in randomized controlled trials. The study included patients with heart failure (HF) or myocardial infarction and advanced CKD who participated in the RALES (Randomized Aldactone Evaluation Study), EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure), TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) in the Americas, and EPHESUS (Eplerenone Post-AMI Heart Failure Efficacy and Survival Study) trials. This study used individual patient data meta-analysis using Cox models stratified by trial with treatment-by-eGFR interaction terms. eGFR was recalculated by using the Chronic Kidney Disease Epidemiology Collaboration creatinine formula. A total of 12,700 patients were included, of whom 331 (2.6%) had an eGFR ≤30 mL/min/1.73 m2 (mean eGFR: 26.8 ± 3.2 mL/min/1.73 m2). Patients with advanced CKD had higher annualized event rates for all studied outcomes: placebo event rate for the composite of cardiovascular death or HF hospitalization was ∼3-fold higher in patients with eGFR ≤30 compared with those with eGFR >90 mL/min/1.73 m2: 41.6 vs 14.6 events per 100 person-years. MRAs (vs placebo) reduced the composite of cardiovascular death or HF hospitalization, but the effect was attenuated as eGFR decreased: the corresponding HRs by eGFR categories were: HR for >90 mL/min/1.73 m2: 0.62 (95% CI: 0.49-0.78); HR for 61-90 mL/min/1.73 m2: 0.69 (95% CI: 0.61-0.77); HR for 46-60 mL/min/1.73 m2: 0.84 (95% CI: 0.74-0.95); HR for 31-45 mL/min/1.73 m2: 0.79 (95% CI: 0.68-0.91); and HR for ≤30 mL/min/1.73 m2: 0.96 (95% CI: 0.70-1.32) (treatment-by-eGFR interaction P for trend = 0.033). Investigator-reported hyperkalemia and worsening renal function were more frequent (2- to 3-fold) among MRA users, and hyperkalemia was more frequent as eGFR decreased (treatment-by-eGFR interaction P for trend = 0.002). Steroidal MRAs reduced HF hospitalizations and mortality across a wide range of eGFR. However, declining benefit and worsening safety may limit their use in patients with lower eGFR, particularly those with levels ≤30 mL/min/1.73 m2.


Defining the Systemic Inflammatory Response Syndrome in Equine Neonates.
Defining and describing the systemic inflammatory response syndrome (SIRS) and sepsis facilitated recognition and investigation of the complex disease processes involving the host response to infection and trauma. Over the years a variety of definitions of SIRS have been examined and applied to numerous research studies to improve critical care in both human and veterinary clinical practice. This article summarizes the history of the development of the SIRS definition, outlines the pathophysiologic processes that are involved in SIRS, and provides a specific definition for use in foal medicine.


Expression of fear-conditioning is accompanied by increased paired-pulse depression within the amygdala.
Fear-conditioning is a model of fear learning and anxiety. The lateral nucleus of the amygdala (LA) provides a critical link for relaying thalamic and cortical auditory information to the rest of the amygdala during the fear conditioning process. Alterations in excitatory synaptic transmission in the thalamic to LA pyramidal cells was studied using whole-cell patch clamp recordings in brain slices from fear-conditioned animals. Following paired stimulation of the thalamic afferents, paired-pulse depression (PPD) could be recorded at 200-ms to 2-s intervals. Increasing transmitter release by decreasing the Mg2+/Ca2+ ratio enhanced PPD suggesting that PPD is reflective of changes in release probability. Analysis of the pairs of composite, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic currents (EPSCs) showed that there was no correlation between EPSC pairs suggesting that PPD may be mediated through a release-independent mechanism of presynaptic origin. However, AMPA and NMDA receptor mediated PPD had a different time course and magnitude suggesting postsynaptic factors may be involved in PPD. After fear-conditioning PPD of the composite and AMPA receptor-mediated EPSCs was enhanced suggesting that neurotransmitter release may be increased in learned fear. The NMDA receptor-mediated PPD was however not altered in fear-conditioned animals. The differences in response of AMPA and NMDA receptor-mediated PPD suggest that postsynaptic mechanisms may also be involved in the expression of fear conditioning.


Melatonin reduces the endoplasmic reticulum stress and polyubiquitinated protein accumulation induced by repeated anesthesia exposure in Caenorhabditis elegans.
Endoplasmic reticulum (ER) stress has been linked to anesthesia-induced neurotoxicity, but melatonin seems to play a protective role against ER stress. Synchronized Caenorhabditis elegans were exposed to isoflurane during the developmental period; melatonin treatment was used to evaluate its role in preventing the defective unfolded protein response (UPR) and ER-associated protein degradation (ERAD). The induced expression of hsp-4::GFP by isoflurane was attenuated in the isoflurane-melatonin group. Isoflurane upregulated the expression of ire-1, whereas melatonin did not induce ire-1 expression in C. elegans even after isoflurane exposure. With luzindole treatment, the effect of melatonin on the level of ire-1 was significantly attenuated. The reduced expression of sel-1, sel-11, cdc-48.1, and cdc-48.2 due to isoflurane was restored by melatonin, although not up to the level of the control group. The amount of polyubiquitinated proteins was increased in the isoflurane group; however, melatonin suppressed its accumulation, which was significantly inhibited by a proteasome inhibitor, MG132. The chemotaxis index of the isoflurane-melatonin group was improved compared with the isoflurane group. Melatonin may be a potential preventive molecule against defective UPR and ERAD caused by repeated anesthesia exposure. The ire-1 branch of the UPR and ERAD pathways can be the target of melatonin to reduce anesthesia-induced ER stress.


Biomechanical Comparison of INTERTAN Nail and Gamma3 Nail for Intertrochanteric Fractures.
To compare the biomechanical stabilities of Gamma3 nail and INTERTAN nail (ITN) for stable (AO/OTA 31A1.1) and unstable (AO/OTA 31A2.2) femoral intertrochanteric fracture. Twenty-four synthetic femora were randomly divided into four groups. After internal fixation (Gamma3 nail or ITN) had been implanted, stable and unstable intertrochanteric fracture models were produced. A cyclic testing protocol with increasing loads was performed for both stable and unstable intertrochanteric fracture models, and then torsional test and axial compression failure test were conducted. Stiffness, failure load, torque, and fragment displacement were recorded. For stable fracture model: fragment displacement in ITN group were smaller than Gamma3 nail group (Gamma3 nail: 1.66 ± 0.13 mm; ITN: 1.55 ± 0.1 mm); stiffness (Gamma3 nail: 1142.6 ± 161.1 N/mm, ITN: 1159.3 ± 203.5 N/mm, P = 0.872) and failure load (Gamma3 nail: 5715.42 ± 616.34 N, ITN: 5690.27 ± 625.59 N, P = 0. 951) of the two nails were similar after cyclic test; torque of the ITN group was larger than the Gamma3 nail group. For unstable fracture model: fragment displacement in ITN group was significantly smaller than in the Gamma3 nail group when the axial load was larger than 800 N (Gamma3 nail: 3.59 ± 0.19 mm; ITN: 2.93 ± 0.28 mm); ITN group showed a significantly higher failure load than Gamma3 nail group (Gamma3 nail: 2942.77 ± 573.4 N, ITN: 3672.3 ± 790.5 N, P = 0. 011); torque was significantly higher for the ITN group compared to the Gamma3 nail group for three different angles. Both ITN and Gamma3 nail can maintain sufficient biomechanical stability for stable intertrochanteric fractures, but ITN was a better choice for unstable intertrochanteric fractures.


Dissemination of fusidic acid resistance among Staphylococcus aureus clinical isolates.
A significant trend towards increased fusidic acid (FA) resistance among Staphylococcus aureus with increased duration of use is of concern. The aim of the present study is to investigate the dissemination of fusidic acid resistance among Staphylococcus aureus clinical isolates. The susceptibility of S. aureus isolates to antimicrobial agents was determined by disc-diffusion method. The minimal inhibitory concertrations(MICs) of fusidic acid and vacomycin for fusidic acid-resisitant isolates were determined by ager dillution method. FA resistance determinants were determined by PCR and DNA sequencing. SCCmec typing, spa typing and multi-locus sequence typing were used for the determination of molecular characteristics for S. aureus isolates. A total of 392 non-duplicate S. aureus isolates including 181 methicillin-resistant S. aureus (MRSA) isolates, which were isolated from the clinical specimens of patients at a Chinese tertiary hospital from January, 2012 to September, 2013, were collected for investigating FA resistance. Among 392 S. aureus clinical isolates tested, 56 (14.3%) with FA MIC values ranging from 2 μg/ml to ≥128 μg/ml were resistant to FA. The proportions of FA resistance among MRSA and MSSA isolates were 27.1% (49/181) and 3.3% (7/211). There was a trend of rapidly increased FA resistance among S. aureus and MRSA isolates from 5.2% and 8.9% in 2012 to 24.9% and 45.1% in 2013. Acquired FA resistance gene, fusB, was present in 73.2% (41/56) of FA-resistant S. aureus isolates. fusC and fusA mutation were not found in any of tested isolates. A total of 9 sequence types (STs) and 12 spa types were identified among the 56 FA-resistant S. aureus isolates. ST5 accounting for 66.1% (37/56) was the most prevalent ST. The majority (92.9%, 52/56) of the isolates tested belonged to clonal complex 5(CC5). t2460 was the most prevalent spa type, accounting for 67.9% (38/56) . ST5-MRSA- II-t2460 was predominant clone, accounting for 75.5% (37/49) of FA-resistant MRSA isolates and 66.1% (37/56) of FA-resistant S. aureus isolates. Five of 7 FA-resistant MSSA isolates belonged to ST630-MSSA. Increased FA resistance among S. aureus isolates was found in China. fusB was predominant FA resistance determinant. The spread of CC5 clone, especially novel ST5-MRSA- II-t2460 clone with high-level resistance to FA, was responsible for the increase of FA resistance.


Development outcomes of Thai children with cleft lip/palate at 5-years-old.
To measure the development outcomes among Thai children with non-syndromic cleft lip and/or palate (CLP) treated at the Tawanchai Center 5 years after birth. Using a developmental screening test, Thai children with CLP were followed-up at the center. Nearly two-thirds (62.5%) of 24 Thai children with CLP had delayed development. Eight of the children had more than one delayed category and 13 both "delayed" and "caution". Delayed language, personal, social and fine motor skills occurred in 54.2%, 20.8% (5/24) and 20.8% (5/24) of cases, respectively. An understanding of the incidence of the different types of delays will help our center to improve our treatment standards and place more emphasis on psychosocial and development outcomes.


Early marginal microleakage in Class II resin composite restorations.
The aim of this study was to evaluate in vitro the early marginal microleakage around conventional and sandwich Class II (MOD) restorations. Ten different combinations of dentin bonding agents, glass-ionomer cements, and posterior resin composites were used. Class II cavities were prepared in freshly extracted third molars whose root surfaces had previously been coated. All gingival margins were prepared at the cementum-enamel junction. Teeth were filled by use of a multi-incremental technique, finished with discs, and immediately immersed in 2% erythrosin B for 12 h at 37 degrees C. Three transverse sections were made at 0.5 mm, 2 mm, and 3.5 mm over the cementum-enamel margin and evaluated under a stereomicroscope. Microleakage was scored linearly along the dentin/enamel-restoration interface. Sections at the cementum-enamel level showed significantly higher microleakage than the other two. Significant differences were observed between the various combinations of materials. Early marginal microleakage in Class II restorations depends not only on filling technique and on dentin bonding systems but also on the resin composite. Glass-ionomer cements significantly reduce early marginal microleakage in Class II restorations.


In vivo bile acid uptake from terminal ileum in cystic fibrosis.
The cause(s) of excessive fecal bile acid loss in cystic fibrosis (CF) has not yet been fully determined, but in vitro studies have suggested that a primary mucosal defect in ileal bile acid uptake may be of importance. To examine this mechanism in vivo, the terminal ileal uptakes of taurocholate and glycocholate were determined using a marker-perfusion technique in three CF infants and four controls. Normal and CF ileal conditions were stimulated by varying the taurocholate:glycocholate concentration ratio (normal 1:1, CF 1:4) and pH (normal 7.8, CF 6.0) of the perfusate. The mean bile acid uptake under normal perfusate conditions was not significantly different in CF subjects (taurocholate 0.124 mumol/min/cm ileum +/- SD 0.127, glycocholate 0.117 mumol/min/cm ileum +/- 0.114), and controls (0.142 +/- 0.164 and 0.115 +/- 0.120 respectively). Similarly, under CF conditions, bile acid uptake values in CF subjects and controls were similar. The results are not consistent with deranged ileal bile acid reabsorption being a major cause of fecal bile acid loss in CF.


Applications of catastrophe theory to optometry.
Catastrophe theory, a recently developed area of mathematics, is used to model two aspects of visual behavior. Visual behavior measured in a patient undergoing phorometry and the visual behavior of some patients with anomalous retinal correspondence undergoing the Walraven technique are characterized as catastrophes.


Chemokine receptor CCR6 expression level and aggressiveness of prostate cancer.
CCR6 is expressed in various tumors and has been implicated in the process of tumor progression and metastasis. Its chemokine ligand, CCL20, is present in different tissues including lymph nodes, but also the normal prostate. This study was performed to investigate a potential relationship between CCR6 and CCL20 expression and features of human prostate cancer (PCA) at time of primary treatment. Immunohistochemistry was used to detect CCR6 and CCL20 expression in archival tissue blocks of 80 PCA cases of various tumor grades and stages. Evaluation was semiquantitatively by visual scoring and quantitatively by digital image analysis (DIA). CCR6 and CCL20 expression was compared with Gleason score, stage, perineural invasion, nodal metastasis, age, and preoperative serum prostate-specific antigen (PSA) level by univariate and multivariate analyses. Staining intensity of CCR6 in tumor cells varied considerably, with it being: weak in 21 tumors (26.2%), intermediate in 44 (55.0%), and strong in 15 (18.8%), with 3.6-log differences in DIA measurements. CCL20 expression was absent in eight tumors (10.0%), weak in 41 (51.2%), intermediate in 23 (28.8%), and strong in eight (10.0%). CCR6 and CCL20 expression did not correlate. CCR6 expression was associated with T-category (P < 0.0005), Gleason score (P = 0.003), and lymph node metastasis (P = 0.002). Expression levels of CCR6 in PCA were associated with clinical and pathologic features of more advanced and aggressive prostate cancer. Thus, CCR6 may directly or indirectly be involved in tumor progression and should be evaluated as novel candidate target molecule for specific treatment interventions.


Spatial and temporal analysis of estuarine bacterioneuston and bacterioplankton using culture-dependent and culture-independent methodologies.
Bacterioneuston may play a key role in water-air exchange of gases and in processing organic matter and pollutants that accumulate at the sea-surface microlayer (SML). However, the phylogenetic diversity of bacterioneuston has been poorly characterized. We analyzed 24 samples each from the SML and underlying water (UW) at three sites in the Ria de Aveiro estuary, Portugal. Cultivation and culture-independent techniques were used to compare bacterioneuston and bacterioplankton. Culturable heterotrophic bacteria were enriched in the SML. The culturable community was dominated by Psychrobacter and Acinetobacter. The presence of high numbers of Psychrobacter was a notable result. Differences were confined to a few genera overrepresented in UW samples (Kocuria, Agrococcus and Vibrio). 16S rDNA DGGE profiles were highly stable in terms of number and position of bands between sampling sites and dates but cluster analysis revealed a slight tendency for grouping according to sampled layer. SML-specific DGGE bands affiliated with Actinobacteria, Cyanobacteria, Gammaproteobacteria and Bacteroidetes. Low similarity between nucleotide sequences of DGGE-bands and previously reported sequences suggest the occurrence of SML-specific populations. Enrichment of SML for Pseudomonas and Aeromonas was questioned and the diversity of both communities was analyzed. Consistent differences between SML and UW aeromonads communities were not identified. In terms of Pseudomonas, a culturable operational taxonomic unit was consistently overrepresented within SML samples. Taken together, our results indicate that the similarity between SML and UW communities depends on spatial and temporal factors.


Why did I do that? Explaining actions activated outside of awareness.
We review the latest research investigating how people explain their own actions when they have been activated nonconsciously. We will discuss evidence that when nonconsciously activated behavior is unexpected (e.g., norm- violating, against self -standards), negative affect arises and triggers confabulations aimed to explain the behavior. Nonconsciously activated behaviors may provide a window into everyday confabulation of (erroneous) explanations for behavior, which may also affect self-knowledge. Implications for self-concept formation and intentionality are discussed.


Psychosocial variables associated with teenage pregnancy.
This study investigated whether psychosocial factors differentiate sexually active teenagers who become pregnant from those who do not. Data were collected from 64 unmarried adolescents who attended a suburban health clinic for a pregnancy test or for contraceptive care. Thirty-nine percent of the sample had been or were now pregnant, and 61% had never been pregnant. Each teenager completed a questionnaire and three self-report measures (Life Events Checklist, Self-Worth, Health Locus of Control) prior to her medical visit. Information about family, medical, and psychosocial history was obtained from chart review. When girls who had positive pregnancy tests, and sexually active girls who had never been pregnant were compared, no significant differences emerged on socioeconomic status, race, religion, age or psychological variables. However, when adolescents with a previous or current history of pregnancy (N = 25) were compared with girls who had never been pregnant (N = 39), using the Mann Whitney test, two significant differences were found: adolescents with a history of pregnancy had first intercourse at the mean age of 15 rather than 16 (p < .02) and scored higher than never-pregnant teenagers on the "Powerful Other" Health Locus of Control subscale, a measure of strong belief in external control by others (p < .01). No significant differences were detected between the groups for self-worth or life events perceived as stressful during the past year. These data indicate that in a middle-class suburban population of sexually active teenagers, earlier age at first intercourse and the influence of powerful others are important variables associated with pregnancy.


Body image disturbance in body dysmorphic disorder and eating disorders. Obsessions or delusions?
At this time, the question posed by this article's title--body image disturbance in body dysmorphic disorder and eating disorders: obsessions or delusions?--is probably best answered "both." Both disorders appear to be characterized by obsessional and delusional thinking. In addition, it is likely that their nondelusional and delusional variants constitute a single disorder encompassing a spectrum of insight, with the entire spectrum characterized by obsessional thinking. This view represents a considerable departure from DSM-III-R, in which the psychotic disorders were encapsulated in a separate section of the manual and considered different disorders from their nonpsychotic variants. The one exception was the mood disorders, which were acknowledged to have psychotic variants that were classified in the manual's "nonpsychotic" section. In DSM-IV, on the basis of emerging empirical evidence about the dimensional nature of the psychotic/nonpsychotic boundary, the dichotomy between delusional and nondelusional disorders is less clear. The double coding allowed for BDD acknowledges that BDD and its delusional disorder variant may constitute a single disorder; that allowed for OCD acknowledges that OCD may be delusional. With regard to eating disorders, however, DSM-IV is surprisingly silent, perhaps because delusional preoccupations are less common than in BDD. These issues also may apply to other disorders. Like BDD, hypochondriasis is classified as a somatoform disorder, with its delusional variant a type of delusional disorder, somatic type. Do the delusional and nondelusional variants of hypochondriasis constitute the same disorder? Do other types of somatic delusional disorder, such as parasitosis and olfactory reference syndrome (the belief that one emits a foul body odor) have nondelusional variants? It is likely that a number of disorders span a spectrum from delusional to nondelusional thinking, with unlimited shades of gray in between. Future research may indicate that obsessional disorders such as BDD, anorexia, OCD, and hypochondriasis, as well as other disorders such as major depression, should have qualifiers or subtypes--for example, "with good insight," "with poor insight," and "with delusional (or psychotic) thinking"--with an implied continuum of insight embraced by a single disorder. Such an approach, which scatters psychosis throughout the nomenclature, ultimately may be shown to be a more valid and clinically useful classification approach. Answers to these questions will not only improve our classification system but also may have important treatment implications. For example, the preliminary finding that delusional BDD responds preferentially to SRIs but not to neuroleptic agents contradicts conventional wisdom about the treatment of psychosis.(ABSTRACT TRUNCATED AT 400 WORDS)


pCEST: Positive contrast using Chemical Exchange Saturation Transfer.
Chemical Exchange Saturation Transfer (CEST) contrast utilizes selective pre-saturation of a small pool of exchanging protons and subsequent detection of the decrease in bulk water signal. The CEST contrast is negative and requires detection of small signal change in the presence of a strong background signal. Here we develop a Positive CEST (pCEST) detection scheme utilizing the analogous nature of the CEST and off-resonance T(1)(ρ) experiments and exploring increased apparent relaxation rates in the presence of the selective pre-saturation. pCEST leads to the positive contrast, i.e., increased signal intensity as the result of the presence of the agent and RF pre-saturation. Simultaneously substantial background suppression is achieved. The contrast can be switched "ON" and "OFF", similar to the original CEST.


Advances in flow cytometry for sperm sexing.
This review presents the key technological developments that have been implemented in the 20 years since the first reports of successful measurement, sorting, insemination and live births using flow cytometry as a proven physical sperm separation technique. Since the first reports of sexed sperm, flow technology efforts have been largely focused on improving sample throughput by increasing the rate at which sperm are introduced to the sorter, and on improving measurement resolution, which has increased the proportion of cells that can be reliably measured and sorted. Today, routine high-purity sorting of X- or Y-chromosome-bearing sperm can be achieved at rates up to 8000 s(-1) for an input rate of 40,000 X- and Y-sperms(-1). With current protocols, straws of sex-sorted sperm intended for use in artificial insemination contain approximately 2 x 10(6)sperm. The sort rate of 8000 sperms(-1) mentioned above corresponds to a production capacity of approximately 14 straws of each sex per hour per instrument.


Proton and Multinuclear Spectroscopy of the Pediatric Brain.
Magnetic resonance spectroscopy (MRS) is a valuable adjunct to structural brain imaging. State-of-the-art MRS has benefited greatly from recent technical advancements. Neurometabolic alterations in pediatric brain diseases have implications for diagnosis, prognosis, and therapy. Herein, the authors discuss MRS technical considerations and applications in the setting of various pediatric disease processes including tumors, metabolic diseases, hypoxic/ischemic encephalopathy/stroke, epilepsy, demyelinating disease, and infection.


Saturable [D-Ala2, D-Leu5]-enkephalin transport into cholinergic synaptic vesicles.
Incubation of cholinergic synaptic vesicles purified from the electric organ of Torpedo ocellata with radiolabeled [D-Ala2, D-Leu5]-enkephalin results in its accumulation in the vesicles. Kinetic analysis of the initial rates of uptake reveals temperature-dependent saturation kinetics which are best fitted by a single transport system (KT = 12 +/- 2 microM and Vmax = 0.85 +/- 0.24 pmol/mg protein per min). The specific rates and extents of [3H]-[D-Ala2, D-Leu5]-enkephalin uptake, like those of [3H]acetylcholine uptake, are highest in the purified synaptic vesicles fraction. These findings suggest that Torpedo cholinergic synaptic vesicles contain an opioid peptide transporter. The physiological significance of this transporter is discussed in view of the recent observation that Torpedo nerve terminals contain an endogenous enkephalin-like peptide and presynaptic opiate receptors.


Prognostic criteria in idiopathic pulmonary hemosiderosis in children.
An epidemiologic survey was undertaken of 30 children in whom idiopathic pulmonary hemosiderosis (IPH) had been identified. In determining the prognostic significance of various parameters, a clinical severity score was used. This included the year of onset of IPH, fever, difficulty in breathing, the severity of the anemia, the roentgenographic findings and therapeutic modalities such as transfusions, administration of steroids, antibiotic treatment and splenectomy. Eighteen patients had died. The results of this investigation suggest that: (1) The severity of the disease at its onset does not determine the survival; (2) Females survived longer; (3) Young age of the patients at the onset of IPH seems to carry a less favorable prognosis; (4) The common therapeutic modalities in use have not proved to be beneficial. We believe that some environmental insult to the developing lung in genetically predisposed persons may contribute to a higher morbidity in the younger patients.


Early Formation of Serum Advanced Glycation End-Products in Children with Type 1 Diabetes Mellitus: Relationship with Glycemic Control.
To quantify serum advanced glycation end-products (AGEs) at the onset of type 1 diabetes mellitus and to determine their potential usefulness as retrospective indicators of glycemic balance. Carboxymethyllysine (CML) and pentosidine concentrations were determined by liquid chromatography-tandem mass spectrometry in 3 groups of children with type 1 diabetes mellitus: group (Gr) 1, subjects included at disease onset (n = 36); Gr2, subjects with diabetes of 5 years duration (n = 48); Gr3, subjects with diabetes of 10 years duration and in control subjects (n = 33). Hemoglobin A1c (HbA1c) values were recorded over the entire course of treatment for assessing long-term glycemic balance. Serum AGE concentrations were increased in all groups of subjects with diabetes compared with control subjects, but were highest in Gr1 (for CML: 0.155, 0.306, 0.219, and 0.224 mmol/mol Lys in control, Gr1, Gr2, and Gr3 subjects, respectively; for pentosidine: 312, 492, 365, and 403 nmol/mol Lys, respectively). AGE concentrations were closely correlated with HbA1c values (r = 0.78 for CML; r = 0.49 for pentosidine). In Gr2 and Gr3, the overall glycemic balance estimated by average HbA1c values was positively correlated with CML and pentosidine concentrations, especially in the first year of follow-up. Our results indicate that AGE concentrations are elevated in serum at the time of diabetes mellitus diagnosis, suggesting that the deleterious role of AGEs in the development of long-term complications should be taken into account even at the initial stages of the disease. Moreover, in some circumstances, AGEs could serve as surrogate markers of HbA1c for monitoring glycemic control.


A safety study of transumbilical single incision versus conventional laparoscopic surgery for colorectal cancer: study protocol for a randomized controlled trial.
Single-incision laparoscopic surgery (SILS) is an emerging minimally invasive surgery to reduce abdominal incisions. However, despite the increasing clinical application of SILS, no evidence from large-scale, randomized controlled trials is available for assessing the feasibility, short-term safety, oncological safety, and potential benefits of SILS compared with conventional laparoscopic surgery (CLS) for colorectal cancer. This is a single-center, open-label, noninferiority, randomized controlled trial. A total of 198 eligible patients will be randomly assigned to transumbilical single incision plus one port laparoscopic surgery (SILS plus one) group or to a CLS group at a 1:1 ratio. Patients ranging in age from 18 to 80 years with rectosigmoid cancer diagnosed as cT1-4aN0-2 M0 and a tumor size no larger than 5 cm are considered eligible. The primary endpoint is early morbidity, as evaluated by an independent investigator. Secondary outcomes include operative outcomes (operative time, estimated blood loss, and incision length), pathologic outcomes (tumor size, length of proximal and distal resection margins, and number of harvested lymph nodes), postoperative inflammatory and immune responses (white blood cells [WBC], neutrophil percentage [NE %], C-reactive protein [CRP], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]), postoperative recovery (time to first ambulation, flatus, liquid diet, soft diet, and duration of hospital stay), pain intensity, body image and cosmetic assessment, 3-year disease free survival (DFS), and 5-year overall survival (OS). Follow-up visits are scheduled for 1 and 3 months after surgery, then every 3 months for the first 2 years and every 6 months for the next 3 years. This trial will provide valuable clinical evidence for the objective assessment of the feasibility, safety, and potential benefits of SILS plus one compared with CLS for the radical resection of rectosigmoid cancer. The hypothesis is that SILS plus one is feasible for the radical resection of rectosigmoid cancer and offers short-term safety and long-term oncological safety comparable to that of CLS, and that SILS plus one offers better cosmetic results and faster convalescence compared to CLS. ClinicalTrials.gov: NCT02117557 (registered on 16 April 2014).


Saying the 'S' word in public.
The mechanism by which self-reactive, peripheral lymphocytes are prevented from causing overt autoimmune disease is the subject of much debate. A recent meeting examined the evidence to support a role for T-cell mediated suppression in maintenance of peripheral tolerance.


Acute cerebral stroke imaging and brain perfusion with the use of high-concentration contrast media.
Acute cerebral stroke remains a major cause of death among adults and the emergence of new therapies has created a need for early and rapid imaging at a time when conventional CT is either normal or demonstrates subtle abnormalities that are easy to misinterpret. Perfusion CT uses the temporal changes in cerebral and blood attenuation during a rapid series of images acquired without table movement following an intravenous bolus of contrast medium to generate images of mean transit time (MTT) cerebral blood volume (CBV) and perfusion. Reduced perfusion with preserved CBV is indicative of reversible ischaemia, whereas a matched reduction in perfusion and CBV implies infarction. The CT perfusion imaging can positively identify patients with non-haemorrhagic stroke in the presence of a normal conventional CT, provide an indication as to prognosis and potentially select those patients for whom thrombolysis is appropriate. Perfusion CT offers a powerful adjunct to MDCT based imaging of cerebrovascular disease, but further clinical validation is required.


[Case of metastatic intraocular malignant lymphoma with neovascular glaucoma].
It is relatively rare to encounter a case of neovascular glaucoma induced by malignant lymphoma metastasized into the eyeball. A 79-year-old woman initially visited our ophthalmology clinic with the chief complaint of blurring of vision in the left eye which was affected by neovascular glaucoma. She had a history of systemic malignant lymphoma, first diagnosed from skin biopsy and treated to complete remission 3 years previously. A metastatic brain lesion, detected 2 months before her initial visit to our clinic, was cured by radiotherapy. By ultrasound biomicroscopy (UBM) we detected abnormal thickening of the temporal half of the ciliary body of her left eye. Cytological examination of the aqueous humor revealed invasion by malignant cells of presumed lymphocyte origin. Radiation therapy to the left eye normalized the intraocular pressure in a week, followed by a reduction in the neovascularization of the iris and the thickening of the ciliary body. This case showed that metastatic malignant lymphoma in the eye could result in neovascular glaucoma and that UBM is useful to detect and to observe lesions in the iris and ciliary body.


Types of Generalization: Introduction to Special Section of Perspectives on Psychological Science on Cultural Psychology.
Cultural psychology represents one of the broadest types of generalization of psychological findings. We all need to pay attention to cultural findings because many of our most treasured "truisms" fail to generalize when looked at across cultural contexts.


Effect of Er,Cr:YSGG pretreatment on bond strength of fiber posts to root canal dentin using a self-adhesive resin cement.
The weak link in the adhesive luting of fiber posts to root canal dentin is at the cement-dentin interface. The aim of the present study was to evaluate the effect of Er,Cr:YSGG laser irradiation on push-out bond strength of fiber posts cemented to root canal dentin using a self-adhesive cement. A total of 30 sound human maxillary central incisors were equally divided into two groups after root canal treatment, decoronation and preparation of the post space. Teeth of group 1 were treated with the Er,Cr:YSGG laser, and teeth of group 2 (control) received no laser treatment. After cementation of fiber posts with Maxcem self-adhesive cement, 3-mm cervical, middle and apical sections were prepared from the roots. Then a push-out test was performed using a universal testing machine at a strain rate of 0.5 mm/min. Data were analyzed using two-way ANOVA and the Bonferroni test. Statistical significance was defined as P < 0.05. There was a significant difference in the mean bond strength values between groups 1 and 2 (P = 0.001), but there were no significant differences between the various root parts (P = 0.14). In addition, the cumulative effects of dentin treatment type and various root parts were not statistically significant (P = 0.41). The mean bond strength in the laser group was significantly higher than in the control group (P = 0.001, post hoc Bonferroni test).The failure mode was evaluated under a stereomicroscope at × 20 magnification.


Post-pyelonephritic renal scars are not associated with high voiding pressures.
The aim of this study was to evaluate whether renal scars and vesicoureteral reflux (VUR) are associated with bladder dysfunction in children after first clinical pyelonephritis. Sixty-four children were evaluated with urodynamics and voiding cystourethrography at a median of 8 weeks after their first episode of clinical pyelonephritis. All patients had ultrasonography and dimercaptosuccinic acid (DMSA) scintigraphy during the infection. After 2 years, DMSA scintigraphy was repeated in 58 patients. Re-infections were recorded. Overactive detrusor was found in 27 (42%) patients. There was no significant difference in the incidence of overactive detrusor between boys and girls. The maximal voiding pressure was higher in boys (median 92.5, range 48-191 cmH(2)O) than in girls (median 82, range 37-150 cmH(2)O) (P=0.0117). Thirty-one (48%) patients had renal defects in scintigraphy during the infection. Ultimately, 12 patients (21%) developed renal scars; 11 patients (17%) had VUR. Renal defects in DMSA scintigraphy and the presence of VUR were not associated with overactive detrusor or high voiding pressures. Overactive detrusor is a common finding after first episode of pyelonephritis. The dysfunction may explain the development of urinary tract infections in some children. There were no differences in the incidence of overactive detrusor or voiding pressures in patients with and without VUR, or in those with and without renal defects on DMSA scintigraphy. Urodynamic study is not a primary investigation in pyelonephritic children.


Oral Administration of Succinoglycan Riclin Improves Diet-Induced Hypercholesterolemia in Mice.
Epidemiological studies have demonstrated that hypercholesterolemia is associated with an elevated risk of atherosclerosis and cardiovascular diseases. In addition to the available cholesterol-lowering drugs, nutritionally balanced diets containing functional foods have attracted much interest as potential candidates to improve hypercholesterolemia. In the study, we demonstrated that dietary succinoglycan riclin effectively alleviated diet-induced hypercholesterolemia. Compared with the high-cholesterol-diet (HCD) group, the high-riclin group significantly decreased levels of the serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and hepatic cholesterol (34, 40, and 51%, respectively), consequently improving hepatic steatosis and reducing proinflammatory cytokine expressions. 1H nuclear magnetic resonance (NMR)-based lipidomics and metabolomics analyses revealed that the riclin group partially reversed metabolic profile changes induced by the HCD, approaching that of the normal diet (ND) group. Riclin has no direct effects on cholesterol metabolism-related gene expression among the three HCD model groups. Basically, riclin increased the solution viscosity and interfered in the process of bile acid-cholesterol emulsification, decreasing cholesterol digestion and promoting cholesterol and bile acid excretion in the feces. These results suggested potential therapeutic utility of succinoglycan riclin as a food additive for people suffering from hypercholesterolemia and related diseases.


The role of long non-coding RNA HCG18 in cancer.
The incidence of cancer is increasing worldwide and is becoming the most common cause of death. Identifying new biomarkers for cancer diagnosis and prognosis is important for developing cancer treatment strategies and reducing mortality. Long non-coding RNAs (lncRNAs) are non-coding, single-stranded RNAs that play an important role as oncogenes or tumor suppressors in the occurrence and development of human tumors. Abnormal expression of human leukocyte antigen complex group 18 (HCG18) is observed in many types of cancer, and its imbalance is closely related to cancer progression. HCG18 regulates cell proliferation, invasion, metastasis, and anti-apoptosis through a variety of mechanisms. Therefore, HCG18 is a potential tumor biomarker and therapeutic target. However, the therapeutic significance of HCG18 has not been well studied, and future research may develop new intervention strategies to combat cancer. In this study, we reviewed the biological function, mechanism, and potential clinical significance of HCG18 in various cancers to provide a reference for future research.


Enzymatic O-methylation of catechol estrogens in red blood cells: differences in animal species and strains.
Enzymatic O-methylation of catechol estrogens in red blood cells has been investigated with respect to species difference. In the presence of S-adenosylmethionine, 2- or 4-hydroxyestradiol (2-OHE2 or 4-OHE2) was incubated with blood lysate obtained from rats (five strains), guinea pigs, mice, rabbits, dogs, monkeys, and humans, respectively. The yielded guaiacols and unchanged substrate were determined by gas chromatography/mass spectrometry in a selected ion monitoring mode employing the corresponding 2H4-labeled compounds as internal standards. The total amounts of guaiacols formed from 2-OHE2 and 4-OHE2 were different, being the highest (79.6% and 38.1%) in monkeys and the lowest (5.1% and 1.9%) in humans. The ratios of isomeric guaiacols formed from 4-OHE2 (4Me/3Me) were 7.6-71, while those from 2-OHE2 (2Me/3Me) were 1.4-3.2. Thus, marked differences in O-methylation of catechol estrogens were observed among animal species, but no significant strain difference was detected in rats.


Early post-treatment MRI predicts long-term hepatocellular carcinoma response to radiation segmentectomy.
Radiation segmentectomy using yttrium-90 plays an emerging role in the management of early-stage HCC. However, the value of early post-treatment MRI for response assessment is uncertain. We assessed the value of response criteria obtained early after radiation segmentectomy in predicting long-term response in patients with HCC. Patients with HCC who underwent contrast-enhanced MRI before, early, and 12 months after radiation segmentectomy were included in this retrospective single-center study. Three independent radiologists reviewed images at baseline and 1st follow-up after radiation segmentectomy and assessed lesion-based response according to mRECIST, LI-RADS treatment response algorithm (TRA), and image subtraction. The endpoint was response at 12 months based on consensus readout of two separate radiologists. Diagnostic accuracy for predicting complete response (CR) at 12 months based on the 1st post-treatment MRI was calculated. Eighty patients (M/F 60/20, mean age 67.7 years) with 80 HCCs were assessed (median size baseline, 1.8 cm [IQR, 1.4-2.9 cm]). At 12 months, 74 patients were classified as CR (92.5%), 5 as partial response (6.3%), and 1 as progressive disease (1.2%). Diagnostic accuracy for predicting CR was fair to good for all readers with excellent positive predictive value (PPV): mRECIST (range between 3 readers, accuracy: 0.763-0.825, PPV: 0.966-1), LI-RADS TRA (accuracy: 0.700-0.825, PPV: 0.983-1), and subtraction (accuracy: 0.775-0.825, PPV: 0.967-1), with no difference in accuracy between criteria (p range 0.053 to > 0.9). mRECIST, LI-RADS TRA, and subtraction obtained on early post-treatment MRI show similar performance for predicting long-term response in patients with HCC treated with radiation segmentectomy. Response assessment extracted from early post-treatment MRI after radiation segmentectomy predicts complete response in patients with HCC with high PPV (≥ 0.96). • Early post-treatment response assessment on MRI predicts response in patients with HCC treated with radiation segmentectomy with fair to good accuracy and excellent positive predictive value. • There was no difference in diagnostic accuracy between mRECIST, LI-RADS, and subtraction for predicting HCC response to radiation segmentectomy.


Goal-directed and stimulus-driven selection of internal representations.
Adaptive behavior relies on the selection of relevant sensory information from both the external environment and internal memory representations. In understanding external selection, a classic distinction is made between voluntary (goal-directed) and involuntary (stimulus-driven) guidance of attention. We have developed a task-the anti-retrocue task-to separate and examine voluntary and involuntary guidance of attention to internal representations in visual working memory. We show that both voluntary and involuntary factors influence memory performance but do so in distinct ways. Moreover, by tracking gaze biases linked to attentional focusing in memory, we provide direct evidence for an involuntary "retro-capture" effect whereby external stimuli involuntarily trigger the selection of feature-matching internal representations. We show that stimulus-driven and goal-directed influences compete for selection in memory, and that the balance of this competition-as reflected in oculomotor signatures of internal attention-predicts the quality of ensuing memory-guided behavior. Thus, goal-directed and stimulus-driven factors together determine the fate not only of perception, but also of internal representations in working memory.


Efficacy of mistletoe extract as a complement to standard treatment in advanced pancreatic cancer: study protocol for a multicentre, parallel group, double-blind, randomised, placebo-controlled clinical trial (MISTRAL).
Most pancreatic cancer patients present with advanced stage at diagnosis with extremely short expected survival and few treatment options. A multimodal palliative approach is necessary for symptom relief and optimisation of health-related quality of life. In a recent open-label trial of mistletoe extract for advanced pancreatic cancer patients not eligible for chemotherapy, promising results on improved overall survival and better health-related quality of life were reported. The objective of the present study is to assess the value of mistletoe extract as a complement to standard treatment (palliative chemotherapy or best supportive care) in advanced pancreatic cancer patients with regard to overall survival and health-related quality of life. The trial is prospective, randomised, double-blind, multicentre, parallel group and placebo-controlled. In total, 290 participants are randomly assigned to placebo or mistletoe extract given subcutaneously in increasing dosage from 0.01 to 20 mg three times per week for 9 months. Stratification is performed for site and palliative chemotherapy. Main inclusion criteria are advanced pancreatic cancer and Eastern Cooperative Oncology Group performance status 0 to 2; main exclusion criteria are life expectancy less than 4 weeks and neuroendocrine tumour of the pancreas. Two ancillary studies on sub-sets of participants are nested in the trial: a biomarker study collecting blood samples and a cross-sectional qualitative study with semi-structured face-to-face interviews. To our knowledge, this is the first placebo-controlled randomised trial assessing the impact of mistletoe extract as a complement to standard treatment on overall survival and health-related quality of life in patients with advanced pancreatic cancer. The presented trial with its two nested ancillary studies exploring biomarkers and patient experiences is expected to give new insights into the treatment of advanced pancreatic cancer. EU Clinical Trial Register, EudraCT Number 2014-004552-64 . Registered on 19 January 2016. ClinicalTrials.gov NCT02948309 . Registered on 28 October 2016.


Expression of oestrogen and progesterone receptors, Ki-67, p53 and BCL-2 proteins, cathepsin D, urokinase plasminogen activator and urokinase plasminogen activator-receptors in carcinomas of the female breast in an African population.
To determine the expression of oestrogen (ER) and progesterone receptor (PgR), Ki-67, p53, bcl-2 proteins and the proteolytic enzymes cathepsin D (CD), urokinase-plasminogen activator (uPA) and its receptor (uPA-R) in primary carcinomas of the breast from indigenous Tanzanian female patients by immunohistochemistry. Prospective cross-sectional study. Muhimbili Medical Centre, Dar es Salaam, Tanzania. Sixty patients admitted between 1995 and 1997. Markers were found to be expressed as follows: ER (33.3%), PgR (18.3%), p53 (30%), bcl-2 (43.5%) and the median proliferation rate of Ki-67 was 15%. Proportion of tumours positive for ER, PgR and bcl-2 initially decreased to 12 months disease duration, after which it increased. The observed proliferation rate approaches that reported in developed countries. p53 expression did not influence the proliferation rate nor did bcl-2 expression. ER, PgR and bcl-2 were strongly co-expressed. CD was predominantly expressed in stromal macrophages than in cancer cells. The low expression of ER and PgR and their strong co-expression with bcl-2 might negatively influence response to hormonal therapy. The influence of bcl-2 on tumour response to anti-cancer therapy in patients with long disease duration requires urgent clarification. Determination of CD in stromal macrophages rather than in cancer cells may have greater prognostic significance in patients of this region.


Diagnostic value of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 for acute kidney injury: a meta-analysis.
Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7), inducers of G1 cell cycle arrest, are two recently discovered good biomarkers for early diagnosis of acute kidney injury (AKI). To obtain a more robust performance measurement, the present meta-analysis was performed, pooling existing studies. Literature in the MEDLINE (via PubMed), Ovid, Embase, and Cochrane Library databases was systematically searched from inception to 12 October 2016. Studies that met the set inclusion and exclusion criteria were identified by two independent investigators. The diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was evaluated by pooled sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve analyses. The causes of heterogeneity were explored by sensitivity and subgroup analyses. A total of nine published and eligible studies assessing 1886 cases were included in this meta-analysis. Early diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was assessed using a random-effects model. Pooled sensitivity and specificity with corresponding 95% CIs were 0.83 (95% CI 0.79-0.87, heterogeneity I 2 = 68.8%) and 0.55 (95% CI 0.52-0.57, I 2 = 92.9%), respectively. Pooled positive LR, negative LR, and DOR were 2.37 (95% CI 1.87-2.99, I 2 = 82.6%), 0.30 (95% CI 0.21-0.41, I 2 = 43.4%), and 9.92 (95% CI 6.09-16.18, I 2 = 38.5%), respectively. The AUC estimated by SROC was 0.846 (SE 0.027) with a Q* value of 0.777 (SE 0.026). Sensitivity analysis indicated that one study significantly affected the stability of pooled results. Subgroup analysis showed that population setting and AKI threshold were the key factors causing heterogeneity in pooled sensitivity and specificity. On the basis of recent evidence, urinary [TIMP-2] × [IGFBP7] is an effective predictive factor of AKI. PROSPERO registration number: CRD42016051186 . Registered on 10 November 2016.


Frequency of Development of Aortic Valve Disease in Unrepaired Perimembranous Ventricular Septal Defects.
We sought to determine the natural history of aortic valve disease in patients with unrepaired perimembranous ventricular septal defects (pVSDs) and to identify echocardiographic parameters predictive of increased risk of surgical repair of pVSD because of aortic valve disease. We retrospectively analyzed all echocardiograms of patients with a diagnosis of pVSD at our institution from January 1999 to January 2015. All available echocardiographic data were collected. Patients were excluded if there was another structural cardiac anomaly other than bicuspid aortic valve, small patent foramen ovale, or ductus arteriosus. The prevalences of aortic valve prolapse and regurgitation, as well as aortic valve disease progression, were determined. A total of 2,114 echocardiograms from 657 patients with unrepaired pVSD were reviewed. Median age at the time of echocardiogram was 1.9 years (interquartile range [IQR] 0.2 to 5.4). Median duration of follow-up was 1.7 years (IQR 0.2 to 7.4). pVSD-associated aortic valve disease prompted surgical intervention in 1.5% (10 of 657) of patients. Median age at the time of surgery was 4.8 years (IQR 1.7 to 8.4). A pVSD-to-aortic annulus diameter ratio of 0.66 ± 0.05 was present in 90% (9 of 10) of patients who underwent surgical closure because of pVSD-associated aortic valve disease. In conclusion, pVSD-associated aortic valve disease is uncommon, and progression of aortic regurgitation is rare. These data suggest that the majority of patients with pVSD do not require frequent follow-up and that frequent follow-up can be saved for a subset with echocardiographic markers placing them at higher risk of aortic valve diseases.


Biochemical characterization of mitogen-activated protein (MAP) kinase activity in Toxoplasma gondii.
Mitogen-activated protein (MAP) kinase or extracellular signal-regulated kinase (ERK) are activated by many extracellular stimuli. In this study, we investigated whether MAP kinase and tyrosine kinases were involved in transducing signals in Toxoplasma gondii. Using anti-phosphotyrosine and anti-active ERK antibodies, we identified several phosphorylated proteins in Toxoplasma. In particular, phosphorylation of a 47 kDa and a 43 kDa protein increased strongly after calcium influx. MAP kinase activity, caused by calcium influx, was determined using either a specific synthetic peptide, or an in gel kinase assay. Conversely, calcium chelators (BAPTA and EGTA) and a calcium channel blocker (nifedipine) inhibited this activation. Also, a specific inhibitor of MAP kinase kinase (PD 098059) blocked MAP kinase activity. Three specific anti-MAP kinase antibodies recognized the 47 kDa and 43 kDa proteins, which were putatively identified as ERK1- and ERK2-homologs, respectively. These findings provide early evidence of signal transduction involving members of the MAP kinase family in T. gondii.


Relationship between iron deficiency and cholestasis associated with parenteral nutrition.
In a study of 22 patients receiving total parenteral nutrition (TPN), we found that iron-deficient patients were less likely to develop cholestasis than patients with normal iron stores. The mean and S.D. of serum iron, total iron binding capacity and percent saturation in the 12 patients developing cholestasis were 12.7 +/- 5.2 micromol/L, 37.1 +/- 8.5 micromol/L and 37 +/- 24% whereas in the 10 patients who did not develop cholestasis, the values were 7.3 +/- 3.6 micromol/L, 54.8 +/- 17.9 micromol/L and 14 +/- 7% respectively. All differences were statistically significant. The relationship between iron stores and TPN-associated cholestasis deserves further study.


Immobilization of protein molecules on liposomes. Anchorage by artificially bound unsaturated hydrocarbon tails.
A method for the immobilization of trypsin, a hydrophilic nonmembrane protein, on a liposomal surface has been developed. The technique consists of covalent coupling of linoleoyl residues to the protein globules and consequent binding of linoleoyl trypsin to liposomes by a detergent dilution method. The immobilized protein preserved its biological functions: specific esterolytic catalytic activity and ability to bind to a macromolecular trypsin protein inhibitor. Liposomes carrying immobilized trypsin were able to sequester glucose with the same efficiency as liposomes without trypsin.


Separation and characterization of impurity P in azithromycin product.
Azithromycin is a macrolide antibiotic which is used to treat a wide variety of bacterial infections. Impurity P is one of the impurities in azithromycin product, which is registered in Pharmacopoeias of Europe and USA. However, to date, the structure of this impurity has still not been elucidated. In this work, we separated impurity P from azithromycin product using preparative chromatography and successfully identified its chemical structure using multiple analytical techniques. First, high-resolution ion trap-time-of-flight mass spectrometry (IT-TOF MS) was used to determine the accurate molecular mass ([M+H]+m/z 777.5121) and the chemical formula (C39H72N2O13) of the impurity. Second, Fourier transforming infrared spectroscopy (FT-IR), ultraviolet-visible absorption spectroscopy (UV-vis) and tandem mass spectrometry (MS/MS) analyses were performed to probe into the key functional groups of the impurity to aid the NMR analysis. Finally, the structure of the impurity was successfully resolved using multidimensional NMR. In addition, a mechanism for the formation of this impurity was proposed.


Benefit-Risk Assessment of Vaccines. Part II: Proposal Towards Consolidated Standards of Reporting Quantitative Benefit-Risk Models Applied to Vaccines (BRIVAC).
Quantitative benefit-risk models (qBRm) applied to vaccines are increasingly used by public health authorities and pharmaceutical companies as an important tool to help decision makers with supporting benefit-risk assessment (BRA). However, many publications on vaccine qBRm provide insufficient details on the methodological approaches used. Incomplete and/or inadequate qBRm reporting may affect result interpretation and confidence in BRA, highlighting a need for the development of standard reporting guidance. Our objective was to provide an operational checklist for improved reporting of vaccine qBRm. The consolidated standards of reporting quantitative Benefit-RIsk models applied to VACcines (BRIVAC) were designed as a checklist of key information to report in qBRm scientific publications regarding the assessed vaccines, the methodological considerations and the results and their interpretation. In total, 22 items and accompanying definitions, recommendations, explanations and examples were provided and divided into six main sections corresponding to the classic subdivisions of a scientific publication: title and abstract (items 1-2), introduction (items 3-4), methods (items 5-15), results (items 16-17), discussion (items 18-20) and other (items 21-22). The BRIVAC checklist is the first initiative providing an operational checklist for improved reporting of qBRm applied to vaccines in scientific articles. It is intended to assist authors, peer-reviewers, editors and readers in their critical appraisal. Future initiatives are needed to provide methodological guidance to perform qBRm while taking into account the vaccine specificities.


Theoretical studies on the tautomerism and intramolecular hydrogen shifts of 5-amino-tetrazole in the gas phase.
The tautomerism and intramolecular hydrogen shifts of 5-amino-tetrazole in the gas phase were studied in the present work. The minimum energy path (MEP) information of 5-amino-tetrazole was obtained at the CCSD(T)/6-311G**//MP2/6-311G** level of theory. The six possible tautomers of 1H, 4H-5-imino-tetrazole (a), 1H-5-amino-tetrazole (b), 2H-5-amino-tetrazole (c), 1H, 2H-5-imino-tetrazole (d), the mesoionic form (e) and 2H, 4H-5-imino-tetrazole (f) were investigated. Among these tautomers, there are 2 amino- forms, 3 imino- forms, and 1 mesoionic structure form. In all the tautomers, 2-H form (c) is the energetically preferred one in the gas phase. In the imino- tautomers, the energy value of the compound d is similar as that of the compound f but it is higher than the energy value of the compound a. The potential energetic surface (PES) and kinetics for five reactions have been investigated. Reaction 2 (b-->c) was hydrogen shifts only in which the 1-H and 2-H rearrangement. This means that the reaction 2 (b-->c) is energetically favorable having an activation barrier of 45.66 kcal.mol(-1) and the reaction energies (DeltaE) is only 2.67 kcal.mol(-1). However, the reaction energy barrier for tautomerism of reaction 1 (b-->e) is 54.90 kcal.mol(-1). Reaction 1 (b-->a), reaction 3 (c-->d), and reaction 5 (c-->f) were amino- -->imino- tautomerism reactions. The energy barriers of amino- -->imino- tautomerism reactions required are 59.39, 65.57, 73.61 kcal.mol(-1) respectively in the gas phase. The calculated values of rate constants using TST, TST/Eckart, CVT, CVT/SCT and CVT/ZCT methods using the optimized geometries obtained at the MP2/6-311G** level of theory show the variational effects are small over the whole temperature range, while tunneling effects are big in the lower temperature range for all tautomerism reactions.


The degenerative, regenerative mandibular condyle: facial asymmetry.
Studies of longitudinal cephalometric radiographs are presented for several patients with condylar fracture or hemifacial microsomia to illustrate condylar regeneration, presumably under functional influences. Implications of new condylar development and growth to facial and mandibular symmetry are presented. Clinical implications are introduced and the hypothesis of necessity of function for maintenance of relative facial symmetry is considered.


NMR data processing using iterative thresholding and minimum l(1)-norm reconstruction.
Iterative thresholding algorithms have a long history of application to signal processing. Although they are intuitive and easy to implement, their development was heuristic and mainly ad hoc. Using a special form of the thresholding operation, called soft thresholding, we show that the fixed point of iterative thresholding is equivalent to minimum l(1)-norm reconstruction. We illustrate the method for spectrum analysis of a time series. This result helps to explain the success of these methods and illuminates connections with maximum entropy and minimum area methods, while also showing that there are more efficient routes to the same result. The power of the l(1)-norm and related functionals as regularizers of solutions to underdetermined systems will likely find numerous useful applications in NMR.


Calcium oxide modification of activated sludge as a low-cost adsorbent: Preparation and application in Cd(II) removal.
In this study, a simple to produce, low-cost and environment-friendly sludge based adsorbent, prepared from municipal dewatered sludge and modified by calcium oxide (CaO), is described. The enhancement effect of CaO modification on the adsorption capacity and mechanical strength of sludge based adsorbents (CaO-SA), and the modification mechanism of CaO on activated sludge are discussed. Also, the Cd(II) adsorption conditions are optimized using surface optimization experiment. The results indicated that CaO had a good effect on improving the adsorption capacity and mechanical strength of the sludge-based adsorbent. The CaO-SA adsorbent showed best performance with respect to the mechanical strength and Cd(II) adsorption capacity when prepared under 5% CaO dosage and 60 °C drying temperature. CaO modification can increase the specific surface area and calcium ion content of the sludge-based adsorbent and remove the proton of the carboxylic acid in the sludge. The Box-Behnken experimental design results revealed that the importance of operating conditions for CaO-SA adsorption of Cd(II) can be arranged in the order of adsorption time > dosage> pH> temperature. The results also indicated that the interactions between adsorption time and CaO-SA dosage, adsorption time and pH, adsorption time and temperature are all important factors affecting the Cd(II) adsorption. The optimal conditions (adsorption time of 90 min, CaO-SA dosage of 1 g/L, pH of 5 and adsorption temperature of 40 °C) for CaO-SA to adsorb Cd(II) were obtained by surface optimization, at which the Cd(II) adsorption rate could reach a value of 99.74%.


Biomolecular recognition with a sensitivity-enhanced nanowire transistor biosensor.
In applications of silicon nanowire field-effect transistors (SiNW-FETs) as biosensors, the SiNW-FETs conventionally are all area modified (AAM), with receptors covering not only the minute SiNW surface area but also the relatively large surrounding substrate area. In this study, using a bottom-up technique, we successfully fabricated selective surface modified (SSM) SiNW-FETs with the receptors on the SiNW sensing surface only. In this approach, the strategy was to modify the SiNWs with a chemical linker of 3-aminopropyltrimethoxysilane (APTMS) prior to photolithographic fabrication of the device. The APTMS molecules modifying the SiNWs survived the harsh photolithographic processes, including coating with photoresist, washing with organic solvent, and thermal annealing. These SSM SiNW-FETs also exhibited desirable electrical characteristics such as ohmic contact and high transconductance. Using the biotin-avidin binding system, we showed that the faster response time and smaller sample requirements of the SSM SiNW-FETs, relative to the conventional AAM SiNW-FETs, clearly show that restricting the surface modification of the SiNW-FETs substantially improves their detection sensitivity. Detection with a SSM boronic acid-modified SiNW-FET of the dopamine released under high-K(+) buffer stimulation from living PC12 cells also demonstrates that SiNW-FETs can serve as highly sensitive biosensors for biomedical diagnosis. In binding affinity measurements with SiNW-FETs, the dissociation constants (Kd) of the biotin-avidin and dopamine-boronic acid complexes were determined to be 15 ± 1 fM and 33 ± 8 fM, respectively.